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Sample records for mouse mus musculus

  1. Aryl hydrocarbon hydroxlyase induction by benzo(a)anthracene: regulatory gene localized to the distal portion of mouse chromosome 17. [Mus musculus molossinus, M. m. castaneus

    SciTech Connect (OSTI)

    Legraverend, C.; Kaerenlampi, S.O.; Bigelow, S.W.; Lalley, P.A.; Kozak, C.A.; Womack, J.E.; Nebert, D.W.

    1984-07-01

    Aryl hydrocarbon (benzo(a)pyrene) hydroxylase inducibility by benzo(a)anthracene was studied in 29 somatic cell hybrid clones, developed by fusing mouse spleen or peritoneal cells from four different inbred strains with hypoxanthine phosphoribosyltransferase-deficient Chinese hamster E36 cells. Karyotype analysis plus 25 markers assigned to 16 autosomes and the X chromosome were examined. In 28 of the 29 clones, the presence or absence of inducibility is associated with the presence or absence, respectively, of mouse chromosome 17. Liver microsomal aryl hydrocarbon hydroxylase induction by 3-methylcholanthrene or benzo(a)anthracene was assessed in appropriate backcrosses with the Mus musculus molossinus, M.m. castaneus, MOR/Cv, Pl/J.SM/J and DBA/2J inbred strains and in 13 NX8 recombinant inbred lines. Twenty-seven biochemical genetic markers representing all but four autosomes were tested for possible linkage with the hydroxylase inducibility, and no linkage was found. The hepatic Ah receptor was quantitated in 26 BXD recombinant inbred lines; the Ah phenotype did not match exactly any of the more than 70 genes with established strain distribution patterns representing 12 autosomes and at least five unlinked markers. It is concluded that a major gene controlling aryl hydrocarbon hydroxylase inducibility by benzo(a)anthracene is located on chromosome 17.

  2. Mark Musculus named SAE fellow

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Mark Musculus named SAE fellow - Sandia Energy Energy Search Icon Sandia Home Locations Contact Us Employee Locator Energy & Climate Secure & Sustainable Energy Future Stationary Power Energy Conversion Efficiency Solar Energy Wind Energy Water Power Supercritical CO2 Geothermal Natural Gas Safety, Security & Resilience of the Energy Infrastructure Energy Storage Nuclear Power & Engineering Grid Modernization Battery Testing Nuclear Energy Defense Waste Management Programs

  3. Track recognition in 4 [mu]s by a systolic trigger processor using a parallel Hough transform

    SciTech Connect (OSTI)

    Klefenz, F.; Noffz, K.H.; Conen, W.; Zoz, R.; Kugel, A. . Lehrstuhl fuer Informatik V); Maenner, R. . Lehrstuhl fuer Informatik V Univ. Heidelberg . Interdisziplinaeres Zentrum fuer Wissenschaftliches Rechnen)

    1993-08-01

    A parallel Hough transform processor has been developed that identifies circular particle tracks in a 2D projection of the OPAL jet chamber. The high-speed requirements imposed by the 8 bunch crossing mode of LEP could be fulfilled by computing the starting angle and the radius of curvature for each well defined track in less than 4 [mu]s. The system consists of a Hough transform processor that determines well defined tracks, and a Euler processor that counts their number by applying the Euler relation to the thresholded result of the Hough transform. A prototype of a systolic processor has been built that handles one sector of the jet chamber. It consists of 35 [times] 32 processing elements that were loaded into 21 programmable gate arrays (XILINX). This processor runs at a clock rate of 40 MHz. It has been tested offline with about 1,000 original OPAL events. No deviations from the off-line simulation have been found. A trigger efficiency of 93% has been obtained. The prototype together with the associated drift time measurement unit has been installed at the OPAL detector at LEP and 100k events have been sampled to evaluate the system under detector conditions.

  4. Comparative mapping in the beige-satin region of mouse chromosome 13

    SciTech Connect (OSTI)

    Perou, C.M.; Pryor, R.; Kaplan, J.

    1997-01-15

    The proximal end of mouse chromosome (Chr) 13 contains regions conserved on human chromosomes 1q42-q44, 6p23-p21, and 7p22-p13. This region also contains mutations that may be models for human disease, including beige (human Chediak-Higashi syndrome). An interspecific backcross of SB/Le and Mus spretus mice was used to generate a molecular genetic linkage map of mouse chromosome 13 with an emphasis on the proximal region including beige (bg) and satin (sa). This map provides the gene order of the two phenotypic markers bg and sa relative to restriction fragment length polymorphisms and simple sequence length polymorphisms in 131 backcross animals. In parallel, we have created a physical map of the region using Nidogen (Nid) as a molecular starting point for cloning a YAC contig that was used to identify the beige gene. The physical map provides the fine-structure order of genes and anonymous DNA fragments that was not resolved by the genetic linkage mapping. The results show that the bg region of mouse Chr 13 is highly conserved on human Chr 1q42-q44 and provide a starting point for a complete functional analysis of the entire bg-sa interval. 37 refs., 4 figs., 1 tab.

  5. The mouse genome informatics and the mouse genome database

    SciTech Connect (OSTI)

    Maltais, L.J.; Blackburn, R.E.; Bradt, D.W.

    1994-09-01

    The Mouse Genome Database (MGD) is a centralized, comprehensive database of the mouse genome that includes genetic mapping data, comparative mapping data, gene descriptions, mutant phenotype descriptions, strains and allelic polymorphism data, inbred strain characteristics, physical mapping data, and molecular probes and clones data. Data in MGD are obtained from the published literature and by electronic transfer from laboratories working on large backcross panels of mice. MGD provides tools that enable the user to search the database, retrieve data, generate reports, analyze data, annotate records, and build genetic maps. The Encyclopedia of the Mouse Genome provides a graphic user interface to mouse genome data. It consists of software tools including: LinkMap, a graphic display of genetic linkage maps with the ability to magnify regions of high locus density: CytoMap, a graphic display of cytogenetic maps showing banded chromosomes with cytogenetic locations of genes and chromosomal aberrations; CATS, a catalog searching tool for text retrieval of mouse locus descriptions. These software tools provide access to the following data sets: Chromosome Committee Reports, MIT Genome Center data, GBASE reports, Mouse Locus Catalog (MLC), and Mouse Cytogenetic Mapping Data. The MGD is available to the scientific community through the World Wide Web (WWW) and Gopher. In addition GBASE can be accessed via the Internet.

  6. RAPID/Best Practices/Memorandums of Understanding (MOUs) | Open...

    Open Energy Info (EERE)

    Practices(Redirected from RAPIDBest PracticesMemorandums of Understanding (MOUs) for Interstate Transmission Projects)...

  7. Computational, Integrative, and Comparative Methods for the Elucidation of Genetic Coexpression Networks

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Baldwin, Nicole E.; Chesler, Elissa J.; Kirov, Stefan; Langston, Michael A.; Snoddy, Jay R.; Williams, Robert W.; Zhang, Bing

    2005-01-01

    Gene expression microarray data can be used for the assembly of genetic coexpression network graphs. Using mRNA samples obtained from recombinant inbred Mus musculus strains, it is possible to integrate allelic variation with molecular and higher-order phenotypes. The depth of quantitative genetic analysis of microarray data can be vastly enhanced utilizing this mouse resource in combination with powerful computational algorithms, platforms, and data repositories. The resulting network graphs transect many levels of biological scale. This approach is illustrated with the extraction of cliques of putatively co-regulated genes and their annotation using gene ontology analysis and cis -regulatory element discovery.more » The causal basis for co-regulation is detected through the use of quantitative trait locus mapping.« less

  8. Laboratory Memoranda of Understanding (MOUs) with Foreign Partners

    Broader source: Directives, Delegations, and Requirements [Office of Management (MA)]

    2012-05-14

    This memorandum establishes policy and procedures for any Memoranda of Understanding (MOUs) between DOE National Laboratories and any foreign entity, whether governmental or private.

  9. The Mouse House: a brief history of the ORNL mouse-genetics program, 1947-2009

    SciTech Connect (OSTI)

    Russell, Liane B

    2013-01-01

    The large mouse genetics program at the Oak Ridge National Lab is often re-membered chiefly for the germ-cell mutation-rate data it generated and their uses in estimating the risk of heritable radiation damage. In fact, it soon became a multi-faceted research effort that, over a period of almost 60 years, generated a wealth of information in the areas of mammalian mutagenesis, basic genetics (later enriched by molecular techniques), cytogenetics, reproductive biology, biochemistry of germ cells, and teratology. Research in the area of germ-cell mutagenesis explored the important physical and biological factors that affect the frequency and nature of induced mutations and made several unexpected discoveries, such as the major importance of the perigametic interval (the zygote stage) for the origin of spontaneous mutations and for the sensitivity to induced genetic change. Of practical value was the discovery that ethylnitrosourea was a supermutagen for point mutations, making high-efficiency mutagenesis in the mouse feasible worldwide. Teratogenesis findings resulted in recommendations still generally accepted in radiological practice. Studies supporting the mutagenesis research added whole bodies of information about mammalian germ-cell development and about molecular targets in germ cells. The early decision to not merely count but propagate genetic variants of all sorts made possible further discoveries, such as the Y-Chromosome s importance in mammalian sex determination and the identification of rare X-autosome translocations, which, in turn, led to the formulation of the single-active-X hypothesis and provided tools for studies of functional mosaicism for autosomal genes, male sterility, and chromosome-pairing mechanism. Extensive genetic and then molecular analyses of large numbers of induced specific-locus mutants resulted in fine-structure physical and correlated functional mapping of significant portions of the mouse genome and constituted a valuable

  10. Insights from Human/Mouse genome comparisons

    SciTech Connect (OSTI)

    Pennacchio, Len A.

    2003-03-30

    Large-scale public genomic sequencing efforts have provided a wealth of vertebrate sequence data poised to provide insights into mammalian biology. These include deep genomic sequence coverage of human, mouse, rat, zebrafish, and two pufferfish (Fugu rubripes and Tetraodon nigroviridis) (Aparicio et al. 2002; Lander et al. 2001; Venter et al. 2001; Waterston et al. 2002). In addition, a high-priority has been placed on determining the genomic sequence of chimpanzee, dog, cow, frog, and chicken (Boguski 2002). While only recently available, whole genome sequence data have provided the unique opportunity to globally compare complete genome contents. Furthermore, the shared evolutionary ancestry of vertebrate species has allowed the development of comparative genomic approaches to identify ancient conserved sequences with functionality. Accordingly, this review focuses on the initial comparison of available mammalian genomes and describes various insights derived from such analysis.

  11. Transgenic Mouse Model of Chronic Beryllium Disease

    SciTech Connect (OSTI)

    Gordon, Terry

    2009-05-26

    Animal models provide powerful tools for dissecting dose-response relationships and pathogenic mechanisms and for testing new treatment paradigms. Mechanistic research on beryllium exposure-disease relationships is severely limited by a general inability to develop a sufficient chronic beryllium disease animal model. Discovery of the Human Leukocyte Antigen (HLA) - DPB1Glu69 genetic susceptibility component of chronic beryllium disease permitted the addition of this human beryllium antigen presentation molecule to an animal genome which may permit development of a better animal model for chronic beryllium disease. Using FVB/N inbred mice, Drs. Rubin and Zhu, successfully produced three strains of HLA-DPB1 Glu 69 transgenic mice. Each mouse strain contains a haplotype of the HLA-DPB1 Glu 69 gene that confers a different magnitude of odds ratio (OR) of risk for chronic beryllium disease: HLA-DPB1*0401 (OR = 0.2), HLA-DPB1*0201 (OR = 15), HLA-DPB1*1701 (OR = 240). In addition, Drs. Rubin and Zhu developed transgenic mice with the human CD4 gene to permit better transmission of signals between T cells and antigen presenting cells. This project has maintained the colonies of these transgenic mice and tested the functionality of the human transgenes.

  12. Gain and frequency tuning within the mouse cochlear apex

    SciTech Connect (OSTI)

    Oghalai, John S.; Raphael, Patrick D.; Gao, Simon; Lee, Hee Yoon; Groves, Andrew K.; Zuo, Jian; Applegate, Brian E.

    2015-12-31

    Normal mammalian hearing requires cochlear outer hair cell active processes that amplify the traveling wave with high gain and sharp tuning, termed cochlear amplification. We have used optical coherence tomography to study cochlear amplification within the apical turn of the mouse cochlea. We measured not only classical basilar membrane vibratory tuning curves but also vibratory responses from the rest of the tissues that compose the organ of Corti. Basilar membrane tuning was sharp in live mice and broad in dead mice, whereas other regions of the organ of Corti demonstrated phase shifts consistent with additional filtering beyond that provided by basilar membrane mechanics. We use these experimental data to support a conceptual framework of how cochlear amplification is tuned within the mouse cochlear apex. We will also study transgenic mice with targeted mutations that affect different biomechanical aspects of the organ of Corti in an effort to localize the underlying processes that produce this additional filtering.

  13. Janus Experiments: Data from Mouse Irradiation Experiments 1972 - 1989

    DOE Data Explorer [Office of Scientific and Technical Information (OSTI)]

    The Janus Experiments, carried out at Argonne National Laboratory from 1972 to 1989 and supported by grants from the US Department of Energy, investigated the effects of neutron and gamma radiation on mouse tissues primarily from B6CF1 mice. 49,000 mice were irradiated: Death records were recorded for 42,000 mice; gross pathologies were recorded for 39,000 mice; and paraffin embedded tissues were preserved for most mice. Mouse record details type and source of radiation [gamma, neutrons]; dose and dose rate [including life span irradiation]; type and presence/absence of radioprotector treatment; tissue/animal morphology and pathology. Protracted low dose rate treatments, short term higher dose rate treatments, variable dose rates with a same total dose, etc. in some cases in conjunction with radioprotectors, were administered. Normal tissues, tumors, metastases were preserved. Standard tissues saved were : lung, liver, spleen, kidney, heart, any with gross lesions (including mammary glands, Harderian gland with eye, adrenal gland, gut, ovaries or testes, brain and pituitary, bone). Data are searchable and specimens can be obtained by request.

  14. The biology of novel animal genes: Mouse APEX gene knockout

    SciTech Connect (OSTI)

    MacInnes, M.; Altherr, M.R.; Ludwig, D.; Pedersen, R.; Mold, C.

    1997-07-01

    This is the final report of a one-year, Laboratory Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). The controlled breeding of novel genes into mice, including the gene knockout (KO), or conversely by adding back transgenes provide powerful genetic technologies that together suffice to determine in large part the biological role(s) of novel genes. Inbred mouse remains the best understood and most useful mammalian experimental system available for tackling the biology of novel genes. The major mammalian apurinic/apyrimidinic (AP) endonuclease (APE), is involved in a key step in the repair of spontaneous and induced AP sites in DNA. Efficient repair of these lesions is imperative to prevent the stable incorporation of mutations into the cellular genome which may lead to cell death or transformation. Loss or modulation of base excison repair activity in vivo may elevate the spontaneous mutation rate in cells, and may lead to a substantial increase in the incidence of cancer. Despite extensive biochemical analysis, however, the significance of these individual APE functions in vivo has not been elucidated. Mouse embryonic stem (ES) cells heterozygous for a deletion mutation in APE have been generated and whole animals containing the APE mutation have been derived from these ES cells. Animals homozygous for the APE null mutation die early in gestation, underscoring the biological significance of this DNA repair gene.

  15. Principles of regulatory information conservation between mouse and human

    SciTech Connect (OSTI)

    Cheng, Yong; Ma, Zhihai; Kim, Bong-Hyun; Wu, Weisheng; Cayting, Philip; Boyle, Alan P.; Sundaram, Vasavi; Xing, Xiaoyun; Dogan, Nergiz; Li, Jingjing; Euskirchen, Ghia; Lin, Shin; Lin, Yiing; Visel, Axel; Kawli, Trupti; Yang, Xinqiong; Patacsil, Dorrelyn; Keller, Cheryl A.; Giardine, Belinda; Kundaje, Anshul; Wang, Ting; Pennacchio, Len A.; Weng, Zhiping; Hardison, Ross C.; Snyder, Michael P.

    2014-11-19

    To broaden our understanding of the evolution of gene regulation mechanisms, we generated occupancy profiles for 34 orthologous transcription factors (TFs) in human–mouse erythroid progenitor, lymphoblast and embryonic stem-cell lines. By combining the genome-wide transcription factor occupancy repertoires, associated epigenetic signals, and co-association patterns, here we deduce several evolutionary principles of gene regulatory features operating since the mouse and human lineages diverged. The genomic distribution profiles, primary binding motifs, chromatin states, and DNA methylation preferences are well conserved for TF-occupied sequences. However, the extent to which orthologous DNA segments are bound by orthologous TFs varies both among TFs and with genomic location: binding at promoters is more highly conserved than binding at distal elements. Notably, occupancy-conserved TF-occupied sequences tend to be pleiotropic; they function in several tissues and also co-associate with many TFs. Lastly, single nucleotide variants at sites with potential regulatory functions are enriched in occupancy-conserved TF-occupied sequences.

  16. Principles of regulatory information conservation between mouse and human

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Cheng, Yong; Ma, Zhihai; Kim, Bong-Hyun; Wu, Weisheng; Cayting, Philip; Boyle, Alan P.; Sundaram, Vasavi; Xing, Xiaoyun; Dogan, Nergiz; Li, Jingjing; et al

    2014-11-19

    To broaden our understanding of the evolution of gene regulation mechanisms, we generated occupancy profiles for 34 orthologous transcription factors (TFs) in human–mouse erythroid progenitor, lymphoblast and embryonic stem-cell lines. By combining the genome-wide transcription factor occupancy repertoires, associated epigenetic signals, and co-association patterns, here we deduce several evolutionary principles of gene regulatory features operating since the mouse and human lineages diverged. The genomic distribution profiles, primary binding motifs, chromatin states, and DNA methylation preferences are well conserved for TF-occupied sequences. However, the extent to which orthologous DNA segments are bound by orthologous TFs varies both among TFs and withmore » genomic location: binding at promoters is more highly conserved than binding at distal elements. Notably, occupancy-conserved TF-occupied sequences tend to be pleiotropic; they function in several tissues and also co-associate with many TFs. Lastly, single nucleotide variants at sites with potential regulatory functions are enriched in occupancy-conserved TF-occupied sequences.« less

  17. GATA-1 directly regulates Nanog in mouse embryonic stem cells

    SciTech Connect (OSTI)

    Li, Wen-Zhong; Ai, Zhi-Ying; Wang, Zhi-Wei; Chen, Lin-Lin; Guo, Ze-Kun; Zhang, Yong

    2015-09-25

    Nanog safeguards pluripotency in mouse embryonic stem cells (mESCs). Insight into the regulation of Nanog is important for a better understanding of the molecular mechanisms that control pluripotency of mESCs. In a silico analysis, we identify four GATA-1 putative binding sites in Nanog proximal promoter. The Nanog promoter activity can be significantly repressed by ectopic expression of GATA-1 evidenced by a promoter reporter assay. Mutation studies reveal that one of the four putative binding sites counts for GATA-1 repressing Nanog promoter activity. Direct binding of GATA-1 on Nanog proximal promoter is confirmed by electrophoretic mobility shift assay and chromatin immunoprecipitation. Our data provide new insights into the expanded regulatory circuitry that coordinates Nanog expression. - Highlights: • The Nanog proximal promoter conceives functional element for GATA-1. • GATA-1 occupies the Nanog proximal promoter in vitro and in vivo. • GATA-1 transcriptionally suppresses Nanog.

  18. A Systematic Analysis of a Deep Mouse Epididymal Sperm Proteome

    SciTech Connect (OSTI)

    Chauvin, Theodore; Xie, Fang; Liu, Tao; Nicora, Carrie D.; Yang, Feng; Camp, David G.; Smith, Richard D.; Roberts, Kenneth P.

    2012-12-21

    Spermatozoa are highly specialized cells that, when mature, are capable of navigating the female reproductive tract and fertilizing an oocyte. The sperm cell is thought to be largely quiescent in terms of transcriptional and translational activity. As a result, once it has left the male reproductive tract, the sperm cell is essentially operating with a static population of proteins. It is therefore theoretically possible to understand the protein networks contained in a sperm cell and to deduce its cellular function capabilities. To this end we have performed a proteomic analysis of mouse sperm isolated from the cauda epididymis and have confidently identified 2,850 proteins, which is the most comprehensive sperm proteome for any species reported to date. These proteins comprise many complete cellular pathways, including those for energy production via glycolysis, ?-oxidation and oxidative phosphorylation, protein folding and transport, and cell signaling systems. This proteome should prove a useful tool for assembly and testing of protein networks important for sperm function.

  19. The gene encoding PBP74/CSA/motalin-1, a novel mouse hsp70, maps to mouse chromosome 18

    SciTech Connect (OSTI)

    Ohashi, Manabu; Oyanagi, Mitsuru; Kominami, Ryo

    1995-11-20

    The 70-kDa heat shock proteins (hsp70) function in folding of peptides and the assembly and disassembly of protein complexes. They are encoded by a multigene family comprising both heat-inducible and constitutively expressed genes. Different family members function in different organelles: hsp70 members such as hsp70 and hsc70 are present in the cytoplasm, BiP/GRP78 in the endoplasmic reticulum, and GRP75 in the mitochondria. PBP74/CSA/motalin-1 is a novel mouse hsp70 protein that was identified by three different groups. PBP74 was found to be a peptide-binding protein implicated in antigen processing. CSA is an antigen specific for the CM strain, and motalin-1 is a protein associated with cellular mortality. 10 refs., 1 fig.

  20. A developmentally plastic adult mouse kidney cell line spontaneously generates multiple adult kidney structures

    SciTech Connect (OSTI)

    Webb, Carol F.; Ratliff, Michelle L.; Powell, Rebecca; Wirsig-Wiechmann, Celeste R.; Lakiza, Olga; Obara, Tomoko

    2015-08-07

    Despite exciting new possibilities for regenerative therapy posed by the ability to induce pluripotent stem cells, recapitulation of three-dimensional kidneys for repair or replacement has not been possible. ARID3a-deficient mouse tissues generated multipotent, developmentally plastic cells. Therefore, we assessed the adult mouse ARID3a−/− kidney cell line, KKPS5, which expresses renal progenitor surface markers as an alternative cell source for modeling kidney development. Remarkably, these cells spontaneously developed into multicellular nephron-like structures in vitro, and engrafted into immunocompromised medaka mesonephros, where they formed mouse nephron structures. These data implicate KKPS5 cells as a new model system for studying kidney development. - Highlights: • An ARID3a-deficient mouse kidney cell line expresses multiple progenitor markers. • This cell line spontaneously forms multiple nephron-like structures in vitro. • This cell line formed mouse kidney structures in immunocompromised medaka fish kidneys. • Our data identify a novel model system for studying kidney development.

  1. A study of the first and second polar bodies in mouse oogenesis

    SciTech Connect (OSTI)

    Evsikov, A.V.; Evsikov, S.V.

    1995-05-01

    The possibility of using a polar body for biopsy of human oocytes and early embryos has recently been shown. Genetic analysis of polar bodies can also provide additional information about the mechanisms underlying oocyte maturation. The first polar body is extremely unstable: in mouse oocytes, it disintegrates within several hours. Thus, the possibilities for its analysis are limited. We obtained karyoplasts of mouse eggs that contained the metaphase II spindle. By using them as a model for the first polar body, we studied the causes of its rapid disintegration. The rates of disintegration of the karyoplasts treated with various inhibitors of the cytoskeleton indicate that disintegration of the first polar body may be due to interaction between the actin cytoskeleton, chromatin, and the plasma membrane. The second polar body is found in mouse embryos until the blastocyst stage. Fusion of the second polar body with the enucleated zygote allowed analysis of its chromosomes. 22 refs., 5 figs., 1 tab.

  2. Interpretation of the Moessbauer Spectra of the Magnetic Nanoparticles in Mouse Spleen

    SciTech Connect (OSTI)

    Chuev, Mikhail A.; Cherepanov, Valery M.; Polikarpov, Mikhail A.; Panchenko, Vladislav Y.; Deyev, Sergey M.; Mischenko, Iliya N.; Nikitin, Maxim P.

    2010-12-02

    We have developed a stochastic model for description of relaxation effects in the system of homogeneously magnetized single-domain particles and applied the model to the analysis of Moessbauer spectra of magnetic nanoparticles (Chemicell ARA) and mouse spleen after i.v. injection into animals. We estimate that the fraction of exogenous iron in nanoparticles in the mouse spleen 3 months after injection was 0.27{+-}0.03. The spectra of the residual nanoparticles in the spleen had almost the same isomer shift but smaller mean hyperfine magnetic field values indicating decrease in the magnetic anisotropy energy (size) of the particles compared to the initial ones in the course of biodegradation. Concentration of ferritin-like iron was about three-fold higher than that in the spleen of untreated animals showing ferritin-like forms in the mouse spleen.

  3. Characterization of the Mouse Brain Proteome Using Global Proteomic Analysis Complemented with Cysteinyl-Peptide Enrichment

    SciTech Connect (OSTI)

    Wang, Haixing H.; Qian, Weijun; Chin, Mark H.; Petyuk, Vladislav A.; Barry, Richard C.; Liu, Tao; Gritsenko, Marina A.; Mottaz, Heather M.; Moore, Ronald J.; Camp, David G.; Khan, Arshad H.; Smith, Desmond; Smith, Richard D.

    2006-02-01

    Given the growing interest in applying genomic and proteomic approaches for studying the mammalian brain using mouse models, we hereby present for the first time a comprehensive characterization of the mouse brain proteome. Preparation of the whole brain sample incorporated a highly efficient cysteinyl-peptide enrichment (CPE) technique to complement a global enzymatic digestion method. Both the global and the cysteinyl-enriched peptide samples were analyzed by SCX fractionation coupled with reversed phase LC-MS/MS analysis. A total of 48,328 different peptides were confidently identified (>98% confidence level), covering 7792 non-redundant proteins (~34% of the predicted mouse proteome). 1564 and 1859 proteins were identified exclusively from the cysteinyl-peptide and the global peptide samples, respectively, corresponding to 25% and 31% improvements in proteome coverage compared to analysis of only the global peptide or cysteinyl-peptide samples. The identified proteins provide a broad representation of the mouse proteome with little bias evident due to protein pI, molecular weight, and/or cellular localization. Approximately 26% of the identified proteins with gene ontology (GO) annotations were membrane proteins, with 1447 proteins predicted to have transmembrane domains, and many of the membrane proteins were found to be involved in transport and cell signaling. The MS/MS spectrum count information for the identified proteins was used to provide a measure of relative protein abundances. The mouse brain peptide/protein database generated from this study represents the most comprehensive proteome coverage for the mammalian brain to date, and the basis for future quantitative brain proteomic studies using mouse models.

  4. Automated whole-genome multiple alignment of rat, mouse, and human

    SciTech Connect (OSTI)

    Brudno, Michael; Poliakov, Alexander; Salamov, Asaf; Cooper, Gregory M.; Sidow, Arend; Rubin, Edward M.; Solovyev, Victor; Batzoglou, Serafim; Dubchak, Inna

    2004-07-04

    We have built a whole genome multiple alignment of the three currently available mammalian genomes using a fully automated pipeline which combines the local/global approach of the Berkeley Genome Pipeline and the LAGAN program. The strategy is based on progressive alignment, and consists of two main steps: (1) alignment of the mouse and rat genomes; and (2) alignment of human to either the mouse-rat alignments from step 1, or the remaining unaligned mouse and rat sequences. The resulting alignments demonstrate high sensitivity, with 87% of all human gene-coding areas aligned in both mouse and rat. The specificity is also high: <7% of the rat contigs are aligned to multiple places in human and 97% of all alignments with human sequence > 100kb agree with a three-way synteny map built independently using predicted exons in the three genomes. At the nucleotide level <1% of the rat nucleotides are mapped to multiple places in the human sequence in the alignment; and 96.5% of human nucleotides within all alignments agree with the synteny map. The alignments are publicly available online, with visualization through the novel Multi-VISTA browser that we also present.

  5. Mapping of the NEP receptor tyrosine kinase gene to human chromosome 6p21.3 and mouse chromosome 17C

    SciTech Connect (OSTI)

    Edelhoff, S.; Disteche, C.M.; Sweetser, D.A.

    1995-01-01

    The mouse receptor tyrosine kinase (RTK) NEP, also called Ptk-3, is widely expressed, with high levels in proliferating neuroepithelia of mouse embryos. The recently described human discoidin domain receptor (DDR) has a predicted amino acid sequence 93% identical to that of murine NEP and may be its human homologue. We have mapped the gene encoding NEP in human and mouse by fluorescence in situ hybridization using a mouse cDNA probe. The NEP/Nep gene maps to human chromosome 6p21.3 and mouse chromosome 17C, respectively. This places the NEP/Nep gene at, or near, the major histocompatibility (MHC) locus-HLA in human and H2 in mouse, respectively. Based on its pattern of expression during development, NEP and Nep represent candidate genes for several MHC-linked developmental abnormalities in human and mouse. 19 refs., 1 fig.

  6. Human-mouse comparative genomics: successes and failures to reveal functional regions of the human genome

    SciTech Connect (OSTI)

    Pennacchio, Len A.; Baroukh, Nadine; Rubin, Edward M.

    2003-05-15

    Deciphering the genetic code embedded within the human genome remains a significant challenge despite the human genome consortium's recent success at defining its linear sequence (Lander et al. 2001; Venter et al. 2001). While useful strategies exist to identify a large percentage of protein encoding regions, efforts to accurately define functional sequences in the remaining {approx}97 percent of the genome lag. Our primary interest has been to utilize the evolutionary relationship and the universal nature of genomic sequence information in vertebrates to reveal functional elements in the human genome. This has been achieved through the combined use of vertebrate comparative genomics to pinpoint highly conserved sequences as candidates for biological activity and transgenic mouse studies to address the functionality of defined human DNA fragments. Accordingly, we describe strategies and insights into functional sequences in the human genome through the use of comparative genomics coupled wit h functional studies in the mouse.

  7. Thalidomide induced early gene expression perturbations indicative of human embryopathy in mouse embryonic stem cells

    SciTech Connect (OSTI)

    Gao, Xiugong Sprando, Robert L.; Yourick, Jeffrey J.

    2015-08-15

    Developmental toxicity testing has traditionally relied on animal models which are costly, time consuming, and require the sacrifice of large numbers of animals. In addition, there are significant disparities between human beings and animals in their responses to chemicals. Thalidomide is a species-specific developmental toxicant that causes severe limb malformations in humans but not in mice. Here, we used microarrays to study transcriptomic changes induced by thalidomide in an in vitro model based on differentiation of mouse embryonic stem cells (mESCs). C57BL/6 mESCs were allowed to differentiate spontaneously and RNA was collected at 24, 48, and 72 h after exposure to 0.25 mM thalidomide. Global gene expression analysis using microarrays revealed hundreds of differentially expressed genes upon thalidomide exposure that were enriched in gene ontology (GO) terms and canonical pathways associated with embryonic development and differentiation. In addition, many genes were found to be involved in small GTPases-mediated signal transduction, heart development, and inflammatory responses, which coincide with clinical evidences and may represent critical embryotoxicities of thalidomide. These results demonstrate that transcriptomics in combination with mouse embryonic stem cell differentiation is a promising alternative model for developmental toxicity assessment. - Highlights: • Studied genomic changes in mouse embryonic stem cells upon thalidomide exposure • Identified gene expression changes that may represent thalidomide embryotoxicity • The toxicogenomic changes coincide well with known thalidomide clinical outcomes. • The mouse embryonic stem cell model is suitable for developmental toxicity testing. • The model has the potential for high-throughput screening of a multitude of compounds.

  8. Sulfur mustard induces an endoplasmic reticulum stress response in the mouse ear vesicant model

    SciTech Connect (OSTI)

    Chang, Yoke-Chen; Wang, James D.; Svoboda, Kathy K.; Casillas, Robert P.; Laskin, Jeffrey D.; Gordon, Marion K.; Gerecke, Donald R.

    2013-04-15

    The endoplasmic reticulum (ER) stress response is a cell survival pathway upregulated when cells are under severe stress. Severely damaged mouse ear skin exposed to the vesicant, sulfur mustard (bis-2-chloroethyl sulfide, SM), resulted in increased expression of ER chaperone proteins that accompany misfolded and incorrectly made proteins targeted for degradation. Time course studies with SM using the mouse ear vesicant model (MEVM) showed progressive histopathologic changes including edema, separation of the epidermis from the dermis, persistent inflammation, upregulation of laminin ?2 (one of the chains of laminin-332, a heterotrimeric skin glycoprotein required for wound repair), and delayed wound healing from 24 h to 168 h post exposure. This was associated with time related increased expression of the cell survival ER stress marker, GRP78/BiP, and the ER stress apoptosis marker, GADD153/CHOP, suggesting simultaneous activation of both cell survival and non-mitochondrial apoptosis pathways. Dual immunofluorescence labeling of a keratinocyte migration promoting protein, laminin ?2 and GRP78/BIP, showed colocalization of the two molecules 72 h post exposure indicating that the laminin ?2 was misfolded after SM exposure and trapped within the ER. Taken together, these data show that ER stress is induced in mouse skin within 24 h of vesicant exposure in a defensive response to promote cell survival; however, it appears that this response is rapidly overwhelmed by the apoptotic pathway as a consequence of severe SM-induced injury. - Highlights: ? We demonstrated ER stress response in the mouse ear vesicant model. ? We described the asymmetrical nature of wound repair in the MEVM. ? We identified the distribution of various ER stress markers in the MEVM.

  9. A mouse model of mitochondrial complex III dysfunction induced by myxothiazol

    SciTech Connect (OSTI)

    Davoudi, Mina; Kallijrvi, Jukka; Marjavaara, Sanna; Kotarsky, Heike; Hansson, Eva; Leven, Per; Fellman, Vineta

    2014-04-18

    Highlights: Reversible chemical inhibition of complex III in wild type mouse. Myxothiazol causes decreased complex III activity in mouse liver. The model is useful for therapeutic trials to improve mitochondrial function. - Abstract: Myxothiazol is a respiratory chain complex III (CIII) inhibitor that binds to the ubiquinol oxidation site Qo of CIII. It blocks electron transfer from ubiquinol to cytochrome b and thus inhibits CIII activity. It has been utilized as a tool in studies of respiratory chain function in in vitro and cell culture models. We developed a mouse model of biochemically induced and reversible CIII inhibition using myxothiazol. We administered myxothiazol intraperitoneally at a dose of 0.56 mg/kg to C57Bl/J6 mice every 24 h and assessed CIII activity, histology, lipid content, supercomplex formation, and gene expression in the livers of the mice. A reversible CIII activity decrease to 50% of control value occurred at 2 h post-injection. At 74 h only minor histological changes in the liver were found, supercomplex formation was preserved and no significant changes in the expression of genes indicating hepatotoxicity or inflammation were found. Thus, myxothiazol-induced CIII inhibition can be induced in mice for four days in a row without overt hepatotoxicity or lethality. This model could be utilized in further studies of respiratory chain function and pharmacological approaches to mitochondrial hepatopathies.

  10. Radiation-Induced Alterations in Mouse Brain Development Characterized by Magnetic Resonance Imaging

    SciTech Connect (OSTI)

    Gazdzinski, Lisa M.; Cormier, Kyle; Lu, Fred G.; Lerch, Jason P.; Department of Medical Biophysics, University of Toronto, Toronto ; Wong, C. Shun; Department of Medical Biophysics, University of Toronto, Toronto; Department of Radiation Oncology, University of Toronto, Toronto ; Nieman, Brian J.

    2012-12-01

    Purpose: The purpose of this study was to identify regions of altered development in the mouse brain after cranial irradiation using longitudinal magnetic resonance imaging (MRI). Methods and Materials: Female C57Bl/6 mice received a whole-brain radiation dose of 7 Gy at an infant-equivalent age of 2.5 weeks. MRI was performed before irradiation and at 3 time points following irradiation. Deformation-based morphometry was used to quantify volume and growth rate changes following irradiation. Results: Widespread developmental deficits were observed in both white and gray matter regions following irradiation. Most of the affected brain regions suffered an initial volume deficit followed by growth at a normal rate, remaining smaller in irradiated brains compared with controls at all time points examined. The one exception was the olfactory bulb, which in addition to an early volume deficit, grew at a slower rate thereafter, resulting in a progressive volume deficit relative to controls. Immunohistochemical assessment revealed demyelination in white matter and loss of neural progenitor cells in the subgranular zone of the dentate gyrus and subventricular zone. Conclusions: MRI can detect regional differences in neuroanatomy and brain growth after whole-brain irradiation in the developing mouse. Developmental deficits in neuroanatomy persist, or even progress, and may serve as useful markers of late effects in mouse models. The high-throughput evaluation of brain development enabled by these methods may allow testing of strategies to mitigate late effects after pediatric cranial irradiation.

  11. Application of the optically stimulated luminescence (OSL) technique for mouse dosimetry in micro-CT imaging

    SciTech Connect (OSTI)

    Vrigneaud, Jean-Marc; Courteau, Alan; Oudot, Alexandra; Collin, Bertrand; Ranouil, Julien; Morgand, Loïc; Raguin, Olivier; Walker, Paul; Brunotte, François

    2013-12-15

    Purpose: Micro-CT is considered to be a powerful tool to investigate various models of disease on anesthetized animals. In longitudinal studies, the radiation dose delivered by the micro-CT to the same animal is a major concern as it could potentially induce spurious effects in experimental results. Optically stimulated luminescence dosimeters (OSLDs) are a relatively new kind of detector used in radiation dosimetry for medical applications. The aim of this work was to assess the dose delivered by the CT component of a micro-SPECT (single-photon emission computed tomography)/CT camera during a typical whole-body mouse study, using commercially available OSLDs based on Al{sub 2}O{sub 3}:C crystals.Methods: CTDI (computed tomography dose index) was measured in micro-CT with a properly calibrated pencil ionization chamber using a rat-like phantom (60 mm in diameter) and a mouse-like phantom (30 mm in diameter). OSLDs were checked for reproducibility and linearity in the range of doses delivered by the micro-CT. Dose measurements obtained with OSLDs were compared to those of the ionization chamber to correct for the radiation quality dependence of OSLDs in the low-kV range. Doses to tissue were then investigated in phantoms and cadavers. A 30 mm diameter phantom, specifically designed to insert OSLDs, was used to assess radiation dose over a typical whole-body mouse imaging study. Eighteen healthy female BALB/c mice weighing 27.1 ± 0.8 g (1 SD) were euthanized for small animal measurements. OLSDs were placed externally or implanted internally in nine different locations by an experienced animal technician. Five commonly used micro-CT protocols were investigated.Results: CTDI measurements were between 78.0 ± 2.1 and 110.7 ± 3.0 mGy for the rat-like phantom and between 169.3 ± 4.6 and 203.6 ± 5.5 mGy for the mouse-like phantom. On average, the displayed CTDI at the operator console was underestimated by 1.19 for the rat-like phantom and 2.36 for the mouse

  12. Cell-autonomous progeroid changes in conditional mouse models for repair endonuclease XPG deficiency

    SciTech Connect (OSTI)

    Barnhoorn, Sander; Uittenboogaard, Lieneke M.; Jaarsma, Dick; Vermeij, Wilbert P.; Tresini, Maria; Weymaere, Michael; Menoni, Hervé; Brandt, Renata M. C.; de Waard, Monique C.; Botter, Sander M.; Sarker, Altaf H.; Jaspers, Nicolaas G. J.; van der Horst, Gijsbertus T. J.; Cooper, Priscilla K.; Hoeijmakers, Jan H. J.; van der Pluijm, Ingrid; Niedernhofer, Laura J.

    2014-10-09

    As part of the Nucleotide Excision Repair (NER) process, the endonuclease XPG is involved in repair of helix-distorting DNA lesions, but the protein has also been implicated in several other DNA repair systems, complicating genotype-phenotype relationship in XPG patients. Defects in XPG can cause either the cancer-prone condition xeroderma pigmentosum (XP) alone, or XP combined with the severe neurodevelopmental disorder Cockayne Syndrome (CS), or the infantile lethal cerebro-oculo-facio-skeletal (COFS) syndrome, characterized by dramatic growth failure, progressive neurodevelopmental abnormalities and greatly reduced life expectancy. Here, we present a novel (conditional) Xpg-/- mouse model which—in a C57BL6/FVB F1 hybrid genetic background—displays many progeroid features, including cessation of growth, loss of subcutaneous fat, kyphosis, osteoporosis, retinal photoreceptor loss, liver aging, extensive neurodegeneration, and a short lifespan of 4–5 months. We show that deletion of XPG specifically in the liver reproduces the progeroid features in the liver, yet abolishes the effect on growth or lifespan. In addition, specific XPG deletion in neurons and glia of the forebrain creates a progressive neurodegenerative phenotype that shows many characteristics of human XPG deficiency. Our findings therefore exclude that both the liver as well as the neurological phenotype are a secondary consequence of derailment in other cell types, organs or tissues (e.g. vascular abnormalities) and support a cell-autonomous origin caused by the DNA repair defect itself. In addition they allow the dissection of the complex aging process in tissue- and cell-type-specific components. Moreover, our data highlight the critical importance of genetic background in mouse aging studies, establish the Xpg-/- mouse as a valid model for the severe form of human XPG patients and segmental accelerated aging, and strengthen the link between DNA damage and aging.

  13. Cell-autonomous progeroid changes in conditional mouse models for repair endonuclease XPG deficiency

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Barnhoorn, Sander; Uittenboogaard, Lieneke M.; Jaarsma, Dick; Vermeij, Wilbert P.; Tresini, Maria; Weymaere, Michael; Menoni, Hervé; Brandt, Renata M. C.; de Waard, Monique C.; Botter, Sander M.; et al

    2014-10-09

    As part of the Nucleotide Excision Repair (NER) process, the endonuclease XPG is involved in repair of helix-distorting DNA lesions, but the protein has also been implicated in several other DNA repair systems, complicating genotype-phenotype relationship in XPG patients. Defects in XPG can cause either the cancer-prone condition xeroderma pigmentosum (XP) alone, or XP combined with the severe neurodevelopmental disorder Cockayne Syndrome (CS), or the infantile lethal cerebro-oculo-facio-skeletal (COFS) syndrome, characterized by dramatic growth failure, progressive neurodevelopmental abnormalities and greatly reduced life expectancy. Here, we present a novel (conditional) Xpg-/- mouse model which—in a C57BL6/FVB F1 hybrid genetic background—displays manymore » progeroid features, including cessation of growth, loss of subcutaneous fat, kyphosis, osteoporosis, retinal photoreceptor loss, liver aging, extensive neurodegeneration, and a short lifespan of 4–5 months. We show that deletion of XPG specifically in the liver reproduces the progeroid features in the liver, yet abolishes the effect on growth or lifespan. In addition, specific XPG deletion in neurons and glia of the forebrain creates a progressive neurodegenerative phenotype that shows many characteristics of human XPG deficiency. Our findings therefore exclude that both the liver as well as the neurological phenotype are a secondary consequence of derailment in other cell types, organs or tissues (e.g. vascular abnormalities) and support a cell-autonomous origin caused by the DNA repair defect itself. In addition they allow the dissection of the complex aging process in tissue- and cell-type-specific components. Moreover, our data highlight the critical importance of genetic background in mouse aging studies, establish the Xpg-/- mouse as a valid model for the severe form of human XPG patients and segmental accelerated aging, and strengthen the link between DNA damage and aging.« less

  14. Sertad1 encodes a novel transcriptional co-activator of SMAD1 in mouse embryonic hearts

    SciTech Connect (OSTI)

    Peng, Yin; Zhao, Shaomin; Song, Langying; Wang, Manyuan; Jiao, Kai

    2013-11-29

    Highlights: •SERTAD1 interacts with SMAD1. •Sertad1 is expressed in mouse embryonic hearts. •SERTAD1 is localized in both cytoplasm and nucleus of cardiomyocytes. •SERTAD1 enhances expression of BMP target cardiogenic genes as a SMAD1 co-activator. -- Abstract: Despite considerable advances in surgical repairing procedures, congenital heart diseases (CHDs) remain the leading noninfectious cause of infant morbidity and mortality. Understanding the molecular/genetic mechanisms underlying normal cardiogenesis will provide essential information for the development of novel diagnostic and therapeutic strategies against CHDs. BMP signaling plays complex roles in multiple cardiogenic processes in mammals. SMAD1 is a canonical nuclear mediator of BMP signaling, the activity of which is critically regulated through its interaction partners. We screened a mouse embryonic heart yeast two-hybrid library using Smad1 as bait and identified SERTAD1 as a novel interaction partner of SMAD1. SERTAD1 contains multiple potential functional domains, including two partially overlapping transactivation domains at the C terminus. The SERTAD1-SMAD1 interaction in vitro and in mammalian cells was further confirmed through biochemical assays. The expression of Sertad1 in developing hearts was demonstrated using RT-PCR, western blotting and in situ hybridization analyses. We also showed that SERTAD1 was localized in both the cytoplasm and nucleus of immortalized cardiomyocytes and primary embryonic cardiomyocyte cultures. The overexpression of SERTAD1 in cardiomyocytes not only enhanced the activity of two BMP reporters in a dose-dependent manner but also increased the expression of several known BMP/SMAD regulatory targets. Therefore, these data suggest that SERTAD1 acts as a SMAD1 transcriptional co-activator to promote the expression of BMP target genes during mouse cardiogenesis.

  15. DNA repair decline during mouse spermiogenesis results in the accumulation of heritable DNA damage

    SciTech Connect (OSTI)

    Marchetti, Francesco; Marchetti, Francesco; Wryobek, Andrew J

    2008-02-21

    The post-meiotic phase of mouse spermatogenesis (spermiogenesis) is very sensitive to the genomic effects of environmental mutagens because as male germ cells form mature sperm they progressively lose the ability to repair DNA damage. We hypothesized that repeated exposures to mutagens during this repair-deficient phase result in the accumulation of heritable genomic damage in mouse sperm that leads to chromosomal aberrations in zygotes after fertilization. We used a combination of single or fractionated exposures to diepoxybutane (DEB), a component of tobacco smoke, to investigate how differential DNA repair efficiencies during the three weeks of spermiogenesis affected the accumulation of DEB-induced heritable damage in early spermatids (21-15 days before fertilization, dbf), late spermatids (14-8 dbf) and sperm (7- 1 dbf). Analysis of chromosomalaberrations in zygotic metaphases using PAINT/DAPI showed that late spermatids and sperm are unable to repair DEB-induced DNA damage as demonstrated by significant increases (P<0.001) in the frequencies of zygotes with chromosomal aberrations. Comparisons between single and fractionated exposures suggested that the DNA repair-deficient window during late spermiogenesis may be less than two weeks in the mouse and that during this repair-deficient window there is accumulation of DNA damage in sperm. Finally, the dose-response study in sperm indicated a linear response for both single and repeated exposures. These findings show that the differential DNA repair capacity of post-meioitic male germ cells has a major impact on the risk of paternally transmitted heritable damage and suggest that chronic exposures that may occur in the weeks prior to fertilization because of occupational or lifestyle factors (i.e, smoking) can lead to an accumulation of genetic damage in sperm and result in heritable chromosomal aberrations of paternal origin.

  16. DNA Repair Decline During Mouse Spermiogenesis Results in the Accumulation of Heritable DNA Damage

    SciTech Connect (OSTI)

    Marchetti, Francesco; Marchetti, Francesco; Wyrobek, Andrew J.

    2007-12-01

    The post-meiotic phase of mouse spermatogenesis (spermiogenesis) is very sensitive to the genomic effects of environmental mutagens because as male germ cells form mature sperm they progressively lose the ability to repair DNA damage. We hypothesized that repeated exposures to mutagens during this repair-deficient phase result in the accumulation of heritable genomic damage in mouse sperm that leads to chromosomal aberrations in zygotes after fertilization. We used a combination of single or fractionated exposures to diepoxybutane (DEB), a component of tobacco smoke, to investigate how differential DNA repair efficiencies during the three weeks of spermiogenesis affected the accumulation of DEB-induced heritable damage in early spermatids (21-15 days before fertilization, dbf), late spermatids (14-8 dbf) and sperm (7-1 dbf). Analysis of chromosomal aberrations in zygotic metaphases using PAINT/DAPI showed that late spermatids and sperm are unable to repair DEB-induced DNA damage as demonstrated by significant increases (P<0.001) in the frequencies of zygotes with chromosomal aberrations. Comparisons between single and fractionated exposures suggested that the DNA repair-deficient window during late spermiogenesis may be less than two weeks in the mouse and that during this repair-deficient window there is accumulation of DNA damage in sperm. Finally, the dose-response study in sperm indicated a linear response for both single and repeated exposures. These findings show that the differential DNA repair capacity of post-meioitic male germ cells has a major impact on the risk of paternally transmitted heritable damage and suggest that chronic exposures that may occur in the weeks prior to fertilization because of occupational or lifestyle factors (i.e, smoking) can lead to an accumulation of genetic damage in sperm and result in heritable chromosomal aberrations of paternal origin.

  17. Characterization of a panel of somatic cell hybrids for regional mapping of the mouse X chromosome

    SciTech Connect (OSTI)

    Avner, P.; Arnaud, D.; Amar, L.; Cambrou, J.; Winking, H.; Russell, L.B.

    1987-08-01

    A panel of five hybrid cell lines containing mouse X chromosomes with various deletions has been obtained by fusing splenocytes from male mice carrying one of a series of reciprocal X-autosome translocations with the azaguanine-resistant Chinese hamster cell line CH3g. These hybrids have been extensively characterized by using the allozymes hypoxanthine/guanine phosphoribosyltransferase (encoded by the Hprt locus) and ..cap alpha..-galactosidase (Ags) and a series of 11 X-chromosome-specific DNA probes whose localization had been previously established by linkage studies. Such studies have established the genetic breakpoints of the T(X;12)13R1 and T(X;2)14R1 X-autosome translocations on the X chromosome and provided additional information as to the X-chromosome genetic breakpoints of the T(X;16)16H, T(X;4)7R1, and T(X;7)6R1 translocations. The data establish clearly that both the T(X;7)5RI and T(X;12)13R1 X-chromosome breakpoints are proximal to Hprt, the breakpoint of the former being more centromeric, lying as it does in the 9-centimorgan interval between the ornithine transcarbamoylase (Otc) and DXPas7 (M2C) loci. These five hybrid cell lines provide, with the previously characterized EBS4 hybrid cell line, a nested series of seven mapping intervals distributed along the length of the mouse X chromosome. Their characterization not only allows further correlation of the genetic and cytological X-chromosome maps but also should permit the rapid identification of DNA probes specific for particular regions of the mouse X chromosome.

  18. Pointright: a system to redirect mouse and keyboard control among multiple machines

    DOE Patents [OSTI]

    Johanson, Bradley E.; Winograd, Terry A.; Hutchins, Gregory M.

    2008-09-30

    The present invention provides a software system, PointRight, that allows for smooth and effortless control of pointing and input devices among multiple displays. With PointRight, a single free-floating mouse and keyboard can be used to control multiple screens. When the cursor reaches the edge of a screen it seamlessly moves to the adjacent screen and keyboard control is simultaneously redirected to the appropriate machine. Laptops may also redirect their keyboard and pointing device, and multiple pointers are supported simultaneously. The system automatically reconfigures itself as displays go on, go off, or change the machine they display.

  19. Control Board Digital Interface Input Devices – Touchscreen, Trackpad, or Mouse?

    SciTech Connect (OSTI)

    Thomas A. Ulrich; Ronald L. Boring; Roger Lew

    2015-08-01

    The authors collaborated with a power utility to evaluate input devices for use in the human system interface (HSI) for a new digital Turbine Control System (TCS) at a nuclear power plant (NPP) undergoing a TCS upgrade. A standalone dynamic software simulation of the new digital TCS and a mobile kiosk were developed to conduct an input device study to evaluate operator preference and input device effectiveness. The TCS software presented the anticipated HSI for the TCS and mimicked (i.e., simulated) the turbine systems’ responses to operator commands. Twenty-four licensed operators from the two nuclear power units participated in the study. Three input devices were tested: a trackpad, mouse, and touchscreen. The subjective feedback from the survey indicates the operators preferred the touchscreen interface. The operators subjectively rated the touchscreen as the fastest and most comfortable input device given the range of tasks they performed during the study, but also noted a lack of accuracy for selecting small targets. The empirical data suggest the mouse input device provides the most consistent performance for screen navigation and manipulating on screen controls. The trackpad input device was both empirically and subjectively found to be the least effective and least desired input device.

  20. Arsenic- and cadmium-induced toxicogenomic response in mouse embryos undergoing neurulation

    SciTech Connect (OSTI)

    Robinson, Joshua F.; Yu, Xiaozhong; Moreira, Estefania G.; Hong, Sungwoo; Faustman, Elaine M.

    2011-01-15

    Arsenic (As) and cadmium (Cd) are well-characterized teratogens in animal models inducing embryotoxicity and neural tube defects (NTDs) when exposed during neurulation. Toxicological research is needed to resolve the specific biological processes and associated molecular pathways underlying metal-induced toxicity during this timeframe in gestational development. In this study, we investigated the dose-dependent effects of As and Cd on gene expression in C57BL/6J mouse embryos exposed in utero during neurulation (GD8) to identify significantly altered genes and corresponding biological processes associated with embryotoxicity. We quantitatively examined the toxicogenomic dose-response relationship at the gene level. Our results suggest that As and Cd induce dose-dependent gene expression alterations representing shared (cell cycle, response to UV, glutathione metabolism, RNA processing) and unique (alcohol/sugar metabolism) biological processes, which serve as robust indicators of metal-induced developmental toxicity and indicate underlying embryotoxic effects. Our observations also correlate well with previously identified impacts of As and Cd on specific genes associated with metal-induced toxicity (Cdkn1a, Mt1). In summary, we have identified in a quantitative manner As and Cd induced dose-dependent effects on gene expression in mouse embryos during a peak window of sensitivity to embryotoxicity and NTDs in the sensitive C57BL/6J strain.

  1. Sulforaphane induces phase II detoxication enzymes in mouse skin and prevents mutagenesis induced by a mustard gas analog

    SciTech Connect (OSTI)

    Abel, E.L.; Boulware, S.; Fields, T.; McIvor, E.; Powell, K.L.; DiGiovanni, J.; Vasquez, K.M.; MacLeod, M.C.

    2013-02-01

    Mustard gas, used in chemical warfare since 1917, is a mutagenic and carcinogenic agent that produces severe dermal lesions for which there are no effective therapeutics; it is currently seen as a potential terrorist threat to civilian populations. Sulforaphane, found in cruciferous vegetables, is known to induce enzymes that detoxify compounds such as the sulfur mustards that react through electrophilic intermediates. Here, we observe that a single topical treatment with sulforaphane induces mouse epidermal levels of the regulatory subunit of glutamate-cysteine ligase, the rate-limiting enzyme in glutathione biosynthesis, and also increases epidermal levels of reduced glutathione. Furthermore, a glutathione S-transferase, GSTA4, is also induced in mouse skin by sulforaphane. In an in vivo model in which mice are given a single mutagenic application of the sulfur mustard analog 2-(chloroethyl) ethyl sulfide (CEES), we now show that therapeutic treatment with sulforaphane abolishes the CEES-induced increase in mutation frequency in the skin, measured four days after exposure. Sulforaphane, a natural product currently in clinical trials, shows promise as an effective therapeutic against mustard gas. -- Highlights: ► Sulforaphane induces increased levels of glutathione in mouse skin. ► Sulforaphane induces increased levels of GSTA4 in mouse skin. ► Sulforaphane, applied after CEES-treatment, completely abolishes CEES-mutagenesis. ► The therapeutic effect may suggest a long biological half-life for CEES in vivo.

  2. Enhanced BMP signaling results in supernumerary tooth formation in USAG-1 deficient mouse

    SciTech Connect (OSTI)

    Murashima-Suginami, Akiko; Takahashi, Katsu Sakata, Tomoko; Tsukamoto, Hiroko; Sugai, Manabu; Yanagita, Motoko; Shimizu, Akira; Sakurai, Takeshi; Slavkin, Harold C.; Bessho, Kazuhisa

    2008-05-16

    Uterine sensitization associated gene-1 (USAG-1) is a BMP antagonist, and also modulates Wnt signaling. We previously reported that USAG-1 deficient mice have supernumerary teeth. The supernumerary maxillary incisor appears to form as a result of the successive development of the rudimentary upper incisor. USAG-1 abrogation rescued apoptotic elimination of odontogenic mesenchymal cells. We confirmed that BMPs were expressed in both the epithelium and mesenchyme of the rudimentary incisor at E14 and E15. BMP signaling in the rudimentary maxillary incisor, assessed by expressions of Msx1 and Dlx2 and the phosphorylation of Smad protein, was significantly enhanced. Wnt signaling as demonstrated by the nuclear localization of {beta}-catenin was also up-regulated. Inhibition of BMP signaling rescues supernumerary tooth formation in E15 incisor explant culture. Based upon these results, we conclude that enhanced BMP signaling results in supernumerary teeth and BMP signaling was modulated by Wnt signaling in the USAG-1 deficient mouse model.

  3. Automatic analysis of flow cytometric DNA histograms from irradiated mouse male germ cells

    SciTech Connect (OSTI)

    Lampariello, F.; Mauro, F.; Uccelli, R.; Spano, M.

    1989-01-01

    An automatic procedure for recovering the DNA content distribution of mouse irradiated testis cells from flow cytometric histograms is presented. First, a suitable mathematical model is developed, to represent the pattern of DNA content and fluorescence distribution in the sample. Then a parameter estimation procedure, based on the maximum likelihood approach, is constructed by means of an optimization technique. This procedure has been applied to a set of DNA histograms relative to different doses of 0.4-MeV neutrons and to different time intervals after irradiation. In each case, a good agreement between the measured histograms and the corresponding fits has been obtained. The results indicate that the proposed method for the quantitative analysis of germ cell DNA histograms can be usefully applied to the study of the cytotoxic and mutagenic action of agents of toxicological interest such as ionizing radiations.18 references.

  4. Phosphorylated SAP155, the spliceosomal component, is localized to chromatin in postnatal mouse testes

    SciTech Connect (OSTI)

    Eto, Ko; Sonoda, Yoshiyuki; Jin, Yuji; Abe, Shin-ichi

    2010-03-19

    SAP155 is an essential component of the spliceosome and its phosphorylation is required for splicing catalysis, but little is known concerning its expression and regulation during spermatogenesis in postnatal mouse testes. We report that SAP155 is ubiquitously expressed in nuclei of germ and Sertoli cells within the seminiferous tubules of 6- and 35-day postpartum (dpp) testes. Analyses by fractionation of testes revealed that (1) phosphorylated SAP155 was found in the fraction containing nuclear structures at 6 dpp in amounts much larger than that at other ages; (2) non-phosphorylated SAP155 was detected in the fraction containing nucleoplasm; and (3) phosphorylated SAP155 was preferentially associated with chromatin. Our findings suggest that the active spliceosome, containing phosphorylated SAP155, performs pre-mRNA splicing on chromatin concomitant with transcription during testicular development.

  5. A simple, low-cost, data logging pendulum built from a computer mouse

    SciTech Connect (OSTI)

    Gintautas, Vadas; Hubler, Alfred

    2009-01-01

    Lessons and homework problems involving a pendulum are often a big part of introductory physics classes and laboratory courses from high school to undergraduate levels. Although laboratory equipment for pendulum experiments is commercially available, it is often expensive and may not be affordable for teachers on fixed budgets, particularly in developing countries. We present a low-cost, easy-to-build rotary sensor pendulum using the existing hardware in a ball-type computer mouse. We demonstrate how this apparatus may be used to measure both the frequency and coefficient of damping of a simple physical pendulum. This easily constructed laboratory equipment makes it possible for all students to have hands-on experience with one of the most important simple physical systems.

  6. Metastable primordial germ cell-like state induced from mouse embryonic stem cells by Akt activation

    SciTech Connect (OSTI)

    Yamano, Noriko; Kimura, Tohru; Watanabe-Kushima, Shoko; Shinohara, Takashi; Nakano, Toru; Department of Pathology, Medical School, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871

    2010-02-12

    Specification to primordial germ cells (PGCs) is mediated by mesoderm-induction signals during gastrulation. We found that Akt activation during in vitro mesodermal differentiation of embryonic stem cells (ESCs) generated self-renewing spheres with differentiation states between those of ESCs and PGCs. Essential regulators for PGC specification and their downstream germ cell-specific genes were expressed in the spheres, indicating that the sphere cells had commenced differentiation to the germ lineage. However, the spheres did not proceed to spermatogenesis after transplantation into testes. Sphere cell transfer to the original feeder-free ESC cultures resulted in chaotic differentiation. In contrast, when the spheres were cultured on mouse embryonic fibroblasts or in the presence of ERK-cascade and GSK3 inhibitors, reversion to the ESC-like state was observed. These results indicate that Akt signaling promotes a novel metastable and pluripotent state that is intermediate to those of ESCs and PGCs.

  7. MONICA: a compact, portable dual gamma camera system for mouse whole-body imaging

    SciTech Connect (OSTI)

    Choyke, Peter L.; Xia, Wenze; Seidel, Jurgen; Kakareka, John W.; Pohida, Thomas J.; Milenic, Diane E.; Proffitt, James; Majewski, Stan; Weisenberger, Andrew G.; Green, Michael V.

    2010-04-01

    Introduction We describe a compact, portable dual-gamma camera system (named "MONICA" for MObile Nuclear Imaging CAmeras) for visualizing and analyzing the whole-body biodistribution of putative diagnostic and therapeutic single photon emitting radiotracers in animals the size of mice. Methods Two identical, miniature pixelated NaI(Tl) gamma cameras were fabricated and installed ?looking up? through the tabletop of a compact portable cart. Mice are placed directly on the tabletop for imaging. Camera imaging performance was evaluated with phantoms and field performance was evaluated in a weeklong In-111 imaging study performed in a mouse tumor xenograft model. Results Tc-99m performance measurements, using a photopeak energy window of 140 keV?10%, yielded the following results: spatial resolution (FWHM at 1 cm), 2.2 mm; sensitivity, 149 cps (counts per seconds)/MBq (5.5 cps/μCi); energy resolution (FWHM, full width at half maximum), 10.8%; count rate linearity (count rate vs. activity), r2=0.99 for 0?185 MBq (0?5 mCi) in the field of view (FOV); spatial uniformity, <3% count rate variation across the FOV. Tumor and whole-body distributions of the In-111 agent were well visualized in all animals in 5-min images acquired throughout the 168-h study period. Conclusion Performance measurements indicate that MONICA is well suited to whole-body single photon mouse imaging. The field study suggests that inter-device communications and user-oriented interfaces included in the MONICA design facilitate use of the system in practice. We believe that MONICA may be particularly useful early in the (cancer) drug development cycle where basic whole-body biodistribution data can direct future development of the agent under study and where logistical factors, e.g., limited imaging space, portability and, potentially, cost are important.

  8. Flavanone silibinin treatment attenuates nitrogen mustard-induced toxic effects in mouse skin

    SciTech Connect (OSTI)

    Jain, Anil K.; Tewari-Singh, Neera; Inturi, Swetha; Kumar, Dileep; Orlicky, David J.; Agarwal, Chapla; White, Carl W.; Agarwal, Rajesh

    2015-05-15

    Currently, there is no effective antidote to prevent skin injuries by sulfur mustard (SM) and nitrogen mustard (NM), which are vesicating agents with potential relevance to chemical warfare, terrorist attacks, or industrial/laboratory accidents. Our earlier report has demonstrated the therapeutic efficacy of silibinin, a natural flavanone, in reversing monofunctional alkylating SM analog 2-chloroethyl ethyl sulfide-induced toxic effects in mouse skin. To translate this effect to a bifunctional alkylating vesicant, herein, efficacy studies were carried out with NM. Topical application of silibinin (1 or 2 mg) 30 min after NM exposure on the dorsal skin of male SKH-1 hairless mice significantly decreased NM-induced toxic lesions at 24, 72 or 120 h post-exposure. Specifically, silibinin treatment resulted in dose-dependent reduction of NM-induced increase in epidermal thickness, dead and denuded epidermis, parakeratosis and microvesication. Higher silibinin dose also caused a 79% and 51%reversal in NM-induced increases in myeloperoxidase activity and COX-2 levels, respectively. Furthermore, silibinin completely prevented NM-induced H2A.X phosphorylation, indicating reversal of DNA damage which could be an oxidative DNA damage as evidenced by high levels of 8-oxodG in NM-exposed mouse skin that was significantly reversed by silibinin. Together, these findings suggest that attenuation of NM-induced skin injury by silibinin is due to its effects on the pathways associated with DNA damage, inflammation, vesication and oxidative stress. In conclusion, results presented here support the optimization of silibinin as an effective treatment of skin injury by vesicants. - Highlights: • Silibinin treatment attenuated nitrogen mustard (NM)-induced skin injury. • Silibinin affects pathways associated with DNA damage, inflammation and vesication. • The efficacy of silibinin could also be associated with oxidative stress. • These results support testing and optimization of

  9. Technical Note: Immunohistochemical evaluation of mouse brain irradiation targeting accuracy with 3D-printed immobilization device

    SciTech Connect (OSTI)

    Zarghami, Niloufar Jensen, Michael D.; Talluri, Srikanth; Dick, Frederick A.; Foster, Paula J.; Chambers, Ann F.; Wong, Eugene

    2015-11-15

    Purpose: Small animal immobilization devices facilitate positioning of animals for reproducible imaging and accurate focal radiation therapy. In this study, the authors demonstrate the use of three-dimensional (3D) printing technology to fabricate a custom-designed mouse head restraint. The authors evaluate the accuracy of this device for the purpose of mouse brain irradiation. Methods: A mouse head holder was designed for a microCT couch using CAD software and printed in an acrylic based material. Ten mice received half-brain radiation while positioned in the 3D-printed head holder. Animal placement was achieved using on-board image guidance and computerized asymmetric collimators. To evaluate the precision of beam localization for half-brain irradiation, mice were sacrificed approximately 30 min after treatment and brain sections were stained for γ-H2AX, a marker for DNA breaks. The distance and angle of the γ-H2AX radiation beam border to longitudinal fissure were measured on histological samples. Animals were monitored for any possible trauma from the device. Results: Visualization of the radiation beam on ex vivo brain sections with γ-H2AX immunohistochemical staining showed a sharp radiation field within the tissue. Measurements showed a mean irradiation targeting error of 0.14 ± 0.09 mm (standard deviation). Rotation between the beam axis and mouse head was 1.2° ± 1.0° (standard deviation). The immobilization device was easily adjusted to accommodate different sizes of mice. No signs of trauma to the mice were observed from the use of tooth block and ear bars. Conclusions: The authors designed and built a novel 3D-printed mouse head holder with many desired features for accurate and reproducible radiation targeting. The 3D printing technology was found to be practical and economical for producing a small animal imaging and radiation restraint device and allows for customization for study specific needs.

  10. Cell-specific oxidative stress and cytotoxicity after wildfire coarse particulate matter instillation into mouse lung

    SciTech Connect (OSTI)

    Williams, Keisha M.; Franzi, Lisa M.; Last, Jerold A.

    2013-01-01

    Our previous work has shown that coarse particulate matter (PM{sub 10-2.5}) from wildfire smoke is more toxic to lung macrophages on an equal dose (by mass) basis than coarse PM isolated from normal ambient air, as evidenced by decreased numbers of macrophages in lung lavage fluid 6 and 24 hours after PM instillation into mouse lungs in vivo and by cytotoxicity to a macrophage cell line observed directly in vitro. We hypothesized that pulmonary macrophages from mice instilled with wildfire coarse PM would undergo more cytotoxicity than macrophages from controls, and that there would be an increase in oxidative stress in their lungs. Cytotoxicity was quantified as decreased viable macrophages and increased percentages of dead macrophages in the bronchoalveolar lavage fluid (BALF) of mice instilled with wildfire coarse PM. At 1 hour after PM instillation, we observed both decreased numbers of viable macrophages and increased dead macrophage percentages as compared to controls. An increase in free isoprostanes, an indicator of oxidative stress, from control values of 28.1 3.2 pg/mL to 83.9 12.2 pg/mL was observed a half-hour after PM instillation. By 1 hour after PM instillation, isoprostane values had returned to 30.4 7.6 pg/mL, not significantly different from control concentrations. Lung sections from mice instilled with wildfire coarse PM showed rapid Clara cell responses, with decreased intracellular staining for the Clara cell secretory protein CCSP 1 hour after wildfire PM instillation. In conclusion, very rapid cytotoxicity occurs in pulmonary macrophages and oxidative stress responses are seen 0.51 hour after wildfire coarse PM instillation. These results define early cellular and biochemical events occurring in vivo and support the hypothesis that oxidative stress-mediated macrophage toxicity plays a key role in the initial response of the mouse lung to wildfire PM exposure. -- Highlights: ? We studied very early events (0.51 hour) after giving

  11. Strain-dependent Damage in Mouse Lung After Carbon Ion Irradiation

    SciTech Connect (OSTI)

    Moritake, Takashi; Proton Medical Research Center, University of Tsukuba, Tsukuba ; Fujita, Hidetoshi; Yanagisawa, Mitsuru; Nakawatari, Miyako; Imadome, Kaori; Nakamura, Etsuko; Iwakawa, Mayumi; Imai, Takashi

    2012-09-01

    Purpose: To examine whether inherent factors produce differences in lung morbidity in response to carbon ion (C-ion) irradiation, and to identify the molecules that have a key role in strain-dependent adverse effects in the lung. Methods and Materials: Three strains of female mice (C3H/He Slc, C57BL/6J Jms Slc, and A/J Jms Slc) were locally irradiated in the thorax with either C-ion beams (290 MeV/n, in 6 cm spread-out Bragg peak) or with {sup 137}Cs {gamma}-rays as a reference beam. We performed survival assays and histologic examination of the lung with hematoxylin-eosin and Masson's trichrome staining. In addition, we performed immunohistochemical staining for hyaluronic acid (HA), CD44, and Mac3 and assayed for gene expression. Results: The survival data in mice showed a between-strain variance after C-ion irradiation with 10 Gy. The median survival time of C3H/He was significantly shortened after C-ion irradiation at the higher dose of 12.5 Gy. Histologic examination revealed early-phase hemorrhagic pneumonitis in C3H/He and late-phase focal fibrotic lesions in C57BL/6J after C-ion irradiation with 10 Gy. Pleural effusion was apparent in C57BL/6J and A/J mice, 168 days after C-ion irradiation with 10 Gy. Microarray analysis of irradiated lung tissue in the three mouse strains identified differential expression changes in growth differentiation factor 15 (Gdf15), which regulates macrophage function, and hyaluronan synthase 1 (Has1), which plays a role in HA metabolism. Immunohistochemistry showed that the number of CD44-positive cells, a surrogate marker for HA accumulation, and Mac3-positive cells, a marker for macrophage infiltration in irradiated lung, varied significantly among the three mouse strains during the early phase. Conclusions: This study demonstrated a strain-dependent differential response in mice to C-ion thoracic irradiation. Our findings identified candidate molecules that could be implicated in the between-strain variance to early

  12. PR-Set7 is degraded in a conditional Cul4A transgenic mouse model of lung cancer

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Wang, Yang; Xu, Zhidong; Mao, Jian -Hua; Hsieh, David; Au, Alfred; Jablons, David M.; Li, Hui; You, Lian

    2015-06-01

    Background and objective. Maintenance of genomic integrity is essential to ensure normal organismal development and to prevent diseases such as cancer. PR-Set7 (also known as Set8) is a cell cycle regulated enzyme that catalyses monomethylation of histone 4 at Lys20 (H4K20me1) to promote chromosome condensation and prevent DNA damage. Recent studies show that CRL4CDT2-mediated ubiquitylation of PR-Set7 leads to its degradation during S phase and after DNA damage. This might occur to ensure appropriate changes in chromosome structure during the cell cycle or to preserve genome integrity after DNA damage. Methods. We developed a new model of lung tumor developmentmore » in mice harboring a conditionally expressed allele of Cul4A. We have therefore used a mouse model to demonstrate for the first time that Cul4A is oncogenic in vivo. With this model, staining of PR-Set7 in the preneoplastic and tumor lesions in AdenoCre-induced mouse lungs was performed. Meanwhile we identified higher protein level changes of γ-tubulin and pericentrin by IHC. Results. The level of PR-Set7 down-regulated in the preneoplastic and adenocarcinomous lesions following over-expression of Cul4A. We also identified higher levels of the proteins pericentrin and γ-tubulin in Cul4A mouse lungs induced by AdenoCre. Conclusion. PR-Set7 is a direct target of Cul4A for degradation and involved in the formation of lung tumors in the conditional Cul4A transgenic mouse model.« less

  13. Multi-walled carbon nanotube-induced gene expression in the mouse lung: Association with lung pathology

    SciTech Connect (OSTI)

    Pacurari, M.; Qian, Y.; Porter, D.W.; Wolfarth, M.; Wan, Y.; Luo, D.; Ding, M.; Castranova, V.; Guo, N.L.

    2011-08-15

    Due to the fibrous shape and durability of multi-walled carbon nanotubes (MWCNT), concerns regarding their potential for producing environmental and human health risks, including carcinogenesis, have been raised. This study sought to investigate how previously identified lung cancer prognostic biomarkers and the related cancer signaling pathways are affected in the mouse lung following pharyngeal aspiration of well-dispersed MWCNT. A total of 63 identified lung cancer prognostic biomarker genes and major signaling biomarker genes were analyzed in mouse lungs (n = 80) exposed to 0, 10, 20, 40, or 80 {mu}g of MWCNT by pharyngeal aspiration at 7 and 56 days post-exposure using quantitative PCR assays. At 7 and 56 days post-exposure, a set of 7 genes and a set of 11 genes, respectively, showed differential expression in the lungs of mice exposed to MWCNT vs. the control group. Additionally, these significant genes could separate the control group from the treated group over the time series in a hierarchical gene clustering analysis. Furthermore, 4 genes from these two sets of significant genes, coiled-coil domain containing-99 (Ccdc99), muscle segment homeobox gene-2 (Msx2), nitric oxide synthase-2 (Nos2), and wingless-type inhibitory factor-1 (Wif1), showed significant mRNA expression perturbations at both time points. It was also found that the expression changes of these 4 overlapping genes at 7 days post-exposure were attenuated at 56 days post-exposure. Ingenuity Pathway Analysis (IPA) found that several carcinogenic-related signaling pathways and carcinogenesis itself were associated with both the 7 and 11 gene signatures. Taken together, this study identifies that MWCNT exposure affects a subset of lung cancer biomarkers in mouse lungs. - Research Highlights: > Multi-Walled Carbon Nanotubes affect lung cancer biomarkers in mouse lungs. > The results suggest potentially harmful effects of MWCNT exposure on human lungs. > The results could potentially be used for

  14. Uranyl nitrate inhibits lactate gluconeogenesis in isolated human and mouse renal proximal tubules: A {sup 13}C-NMR study

    SciTech Connect (OSTI)

    Renault, Sophie; Faiz, Hassan; Gadet, Rudy; Ferrier, Bernard; Martin, Guy; Baverel, Gabriel; Conjard-Duplany, Agnes

    2010-01-01

    As part of a study on uranium nephrotoxicity, we investigated the effect of uranyl nitrate in isolated human and mouse kidney cortex tubules metabolizing the physiological substrate lactate. In the millimolar range, uranyl nitrate reduced lactate removal and gluconeogenesis and the cellular ATP level in a dose-dependent fashion. After incubation in phosphate-free Krebs-Henseleit medium with 5 mM L-[1-{sup 13}C]-, or L-[2-{sup 13}C]-, or L-[3-{sup 13}C]lactate, substrate utilization and product formation were measured by enzymatic and NMR spectroscopic methods. In the presence of 3 mM uranyl nitrate, glucose production and the intracellular ATP content were significantly reduced in both human and mouse tubules. Combination of enzymatic and NMR measurements with a mathematical model of lactate metabolism revealed an inhibition of fluxes through lactate dehydrogenase and the gluconeogenic enzymes in the presence of 3 mM uranyl nitrate; in human and mouse tubules, fluxes were lowered by 20% and 14% (lactate dehydrogenase), 27% and 32% (pyruvate carboxylase), 35% and 36% (phosphoenolpyruvate carboxykinase), and 39% and 45% (glucose-6-phosphatase), respectively. These results indicate that natural uranium is an inhibitor of renal lactate gluconeogenesis in both humans and mice.

  15. Swept source optical coherence tomography for in vivo imaging and vibrometry in the apex of the mouse cochlea

    SciTech Connect (OSTI)

    Lee, Hee Yoon; Raphael, Patrick D.; Oghalai, John S.; Ellerbee, Audrey K.; Applegate, Brian E.

    2015-12-31

    Cochlear amplification has been most commonly investigated by measuring the vibrations of the basilar membrane in animal models. Several different techniques have been used for measuring these vibrations such as laser Doppler vibrometry, miniature pressure sensors, low coherence interferometry, and spectral-domain optical coherence tomography (SD-OCT). We have built a swept-source OCT (SS-OCT) system, which is similar to SD-OCT in that it is capable of performing both imaging and vibration measurements within the mouse cochlea in vivo without having to open the bone. In vivo 3D images of a mouse cochlea were obtained, and the basilar membrane, tectorial membrane, Reissner’s membrane, tunnel of Corti, and reticular lamina could all be resolved. We measured vibrations of multiple structures within the mouse cochlea to sound stimuli. As well, we measured the radial deflections of the reticular lamina and tectorial membrane to estimate the displacement of the outer hair cell stereocilia. These measurements have the potential to more clearly define the mechanisms underlying the linear and non-linear processes within the mammalian cochlea.

  16. Transport of N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine, a metabolite of trichloroethylene, by mouse multidrug resistance associated protein 2 (Mrp2)

    SciTech Connect (OSTI)

    Tsirulnikov, Kirill; Abuladze, Natalia; Koag, Myong-Chul; Newman, Debra; Bondar, Galyna; Zhu Quansheng; Dekant, Wolfgang; Faull, Kym; Kurtz, Ira

    2010-04-15

    N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine (Ac-DCVC) and S-(1,2-dichlorovinyl)-L-cysteine (DCVC) are the glutathione conjugation pathway metabolites of a common industrial contaminant and potent nephrotoxicant trichloroethylene (TCE). Ac-DCVC and DCVC are accumulated in the renal proximal tubule where they may be secreted into the urine by an unknown apical transporter(s). In this study, we explored the hypothesis that the apical transport of Ac-DCVC and/or DCVC may be mediated by the multidrug resistance associated protein 2 (Mrp2, ABCC2), which is known to mediate proximal tubular apical ATP-dependent transport of glutathione and numerous xenobiotics and endogenous substances conjugated with glutathione. Transport experiments using membrane vesicles prepared from mouse proximal tubule derived cells expressing mouse Mrp2 utilizing ATPase assay and direct measurements of Ac-DCVC/DCVC using liquid chromatography/tandem mass-spectrometry (LC/MS/MS) demonstrated that mouse Mrp2 mediates ATP-dependent transport of Ac-DCVC. Expression of mouse Mrp2 antisense mRNA significantly inhibited the vectorial basolateral to apical transport of Ac-DCVC but not DCVC in mouse proximal tubule derived cells endogenously expressing mouse Mrp2. The results suggest that Mrp2 may be involved in the renal secretion of Ac-DCVC.

  17. Thalidomide Ameliorates Inflammation and Vascular Injury but Aggravates Tubular Damage in the Irradiated Mouse Kidney

    SciTech Connect (OSTI)

    Scharpfenecker, Marion; Floot, Ben; Russell, Nicola S.; Coppes, Rob P.; Stewart, Fiona A.

    2014-07-01

    Purpose: The late side effects of kidney irradiation include vascular damage and fibrosis, which are promoted by an irradiation-induced inflammatory response. We therefore treated kidney-irradiated mice with the anti-inflammatory and angiogenesis-modulating drug thalidomide in an attempt to prevent the development of late normal tissue damage and radiation nephropathy in the mouse kidney. Methods and Materials: Kidneys of C57Bl/6 mice were irradiated with a single dose of 14 Gy. Starting from week 16 after irradiation, the mice were fed with thalidomide-containing chow (100 mg/kg body weight/day). Gene expression and kidney histology were analyzed at 40 weeks and blood samples at 10, 20, 30, and 40 weeks after irradiation. Results: Thalidomide improved the vascular structure and vessel perfusion after irradiation, associated with a normalization of pericyte coverage. The drug also reduced infiltration of inflammatory cells but could not suppress the development of fibrosis. Irradiation-induced changes in hematocrit and blood urea nitrogen levels were not rescued by thalidomide. Moreover, thalidomide worsened tubular damage after irradiation and also negatively affected basal tubular function. Conclusions: Thalidomide improved the inflammatory and vascular side effects of kidney irradiation but could not reverse tubular toxicity, which probably prevented preservation of kidney function.

  18. 1H NMR metabolomics study of metastatic melanoma in C57BL/6J mouse spleen

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Wang, Xuan; Hu, Mary Y.; Feng, Ju; Liu, Maili; Hu, Jian Z.

    2014-04-03

    Melanoma is a malignant tumor of melanocytes. Although extensive investigations have been done to study metabolic changes in primary melanoma in vivo and in vitro, little effort has been devoted to metabolic profiling of metastatic tumors in organs other than lymph nodes. In this work, NMR-based metabolomics combined with multivariate data analysis is used to study metastatic B16-F10 melanoma in C57BL/6J mouse spleen. Principal Component Analysis (PCA), an unsupervised multivariate data analysis method, is used to detect possible outliers, while Orthogonal Projection to Latent Structure (OPLS), a supervised multivariate data analysis method, is employed to find important metabolites responsible formore » discriminating the control and the melanoma groups. Two different strategies, i.e., spectral binning and spectral deconvolution, are used to reduce the original spectral data before statistical analysis. Spectral deconvolution is found to be superior for identifying a set of discriminatory metabolites between the control and the melanoma groups, especially when the sample size is small. OPLS results show that the melanoma group can be well separated from its control group. It is found that taurine, glutamate, aspartate, O-Phosphoethanolamine, niacinamide ,ATP, lipids and glycerol derivatives are decreased statistically and significantly while alanine, malate, xanthine, histamine, dCTP, GTP, thymidine, 2'-Deoxyguanosine are statistically and significantly elevated. Furthermore, these significantly changed metabolites are associated with multiple biological pathways and may be potential biomarkers for metastatic melanoma in spleen.« less

  19. X-ray scatter imaging of hepatocellular carcinoma in a mouse model using nanoparticle contrast agents

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Rand, Danielle; Derdak, Zoltan; Carlson, Rolf; Wands, Jack R.; Rose-Petruck, Christoph

    2015-10-29

    Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide and is almost uniformly fatal. Current methods of detection include ultrasound examination and imaging by CT scan or MRI; however, these techniques are problematic in terms of sensitivity and specificity, and the detection of early tumors (<1 cm diameter) has proven elusive. Better, more specific, and more sensitive detection methods are therefore urgently needed. Here we discuss the application of a newly developed x-ray imaging technique called Spatial Frequency Heterodyne Imaging (SFHI) for the early detection of HCC. SFHI uses x-rays scattered by an object to form anmore » image and is more sensitive than conventional absorption-based x-radiography. We show that tissues labeled in vivo with gold nanoparticle contrast agents can be detected using SFHI. We also demonstrate that directed targeting and SFHI of HCC tumors in a mouse model is possible through the use of HCC-specific antibodies. As a result, the enhanced sensitivity of SFHI relative to currently available techniques enables the x-ray imaging of tumors that are just a few millimeters in diameter and substantially reduces the amount of nanoparticle contrast agent required for intravenous injection relative to absorption-based x-ray imaging.« less

  20. DIFFERENTIAL SENSITIVITY OF MALE GERM CELLS TO MAINSTREAM AND SIDESTREAM TOBACCO SMOKE IN THE MOUSE

    SciTech Connect (OSTI)

    Polyzos, Aris; Schmid, Thomas Ernst; Pina-Guzman, Belem; Quintanilla-Vega, Betzabet; Marchetti, Francesco

    2009-03-13

    Cigarette smoking in men has been associated with increased chromosomal abnormalities in sperm and with increased risks for spontaneous abortions, birth defects and neonatal death. Little is known, however, about the reproductive consequences of paternal exposure to second-hand smoke. We used a mouse model to investigate the effects of paternal exposure to sidestream (SS) smoke, the main constituent of second-hand smoke, on the genetic integrity and function of sperm, and to determine whether male germ cells were equally sensitive to mainstream (MS) and SS smoke. A series of sperm DNA quality and reproductive endpoints were investigated after exposing male mice for two weeks to MS or SS smoke. Our results indicated that: (i) only SS smoke significantly affected sperm motility; (ii) only MS smoke induced DNA strand breaks in sperm; (iii) both MS and SS smoke increased sperm chromatin structure abnormalities; and (iv) MS smoke affected both fertilization and the rate of early embryonic development, while SS smoke affected fertilization only. These results show that MS and SS smoke have differential effects on the genetic integrity and function of sperm and provide further evidence that male exposure to second-hand smoke, as well as direct cigarette smoke, may diminish a couple's chance for a successful pregnancy and the birth of a healthy baby.

  1. X-ray scatter imaging of hepatocellular carcinoma in a mouse model using nanoparticle contrast agents

    SciTech Connect (OSTI)

    Rand, Danielle; Derdak, Zoltan; Carlson, Rolf; Wands, Jack R.; Rose-Petruck, Christoph

    2015-10-29

    Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide and is almost uniformly fatal. Current methods of detection include ultrasound examination and imaging by CT scan or MRI; however, these techniques are problematic in terms of sensitivity and specificity, and the detection of early tumors (<1 cm diameter) has proven elusive. Better, more specific, and more sensitive detection methods are therefore urgently needed. Here we discuss the application of a newly developed x-ray imaging technique called Spatial Frequency Heterodyne Imaging (SFHI) for the early detection of HCC. SFHI uses x-rays scattered by an object to form an image and is more sensitive than conventional absorption-based x-radiography. We show that tissues labeled in vivo with gold nanoparticle contrast agents can be detected using SFHI. We also demonstrate that directed targeting and SFHI of HCC tumors in a mouse model is possible through the use of HCC-specific antibodies. As a result, the enhanced sensitivity of SFHI relative to currently available techniques enables the x-ray imaging of tumors that are just a few millimeters in diameter and substantially reduces the amount of nanoparticle contrast agent required for intravenous injection relative to absorption-based x-ray imaging.

  2. Chromosomal mosaicism in mouse two-cell embryos after paternal exposure to acrylamide

    SciTech Connect (OSTI)

    Marchetti, Francesco; Bishop, Jack; Lowe, Xiu; Wyrobek, Andrew J

    2008-10-14

    Chromosomal mosaicism in human preimplantation embryos is a common cause ofspontaneous abortions, however, our knowledge of its etiology is limited. We used multicolor fluorescence in situ hybridization (FISH) painting to investigate whether paternally-transmitted chromosomal aberrations result in mosaicism in mouse 2-cell embryos. Paternal exposure to acrylamide, an important industrial chemical also found in tobacco smoke and generated during the cooking process of starchy foods, produced significant increases in chromosomally defective 2-cell embryos, however, the effects were transient primarily affecting the postmeiotic stages of spermatogenesis. Comparisons with our previous study of zygotes demonstrated similar frequencies of chromosomally abnormal zygotes and 2-cell embryos suggesting that there was no apparent selection against numerical or structural chromosomal aberrations. However, the majority of affected 2-cell embryos were mosaics showing different chromosomal abnormalities in the two blastomeric metaphases. Analyses of chromosomal aberrations in zygotes and 2-cell embryos showed a tendency for loss of acentric fragments during the first mitotic division ofembryogenesis, while both dicentrics and translocations apparently underwent propersegregation. These results suggest that embryonic development can proceed up to the end of the second cell cycle of development in the presence of abnormal paternal chromosomes and that even dicentrics can persist through cell division. The high incidence of chromosomally mosaic 2-cell embryos suggests that the first mitotic division of embryogenesis is prone to missegregation errors and that paternally-transmitted chromosomal abnromalities increase the risk of missegregation leading to embryonic mosaicism.

  3. Requirement of B-Raf, C-Raf, and A-Raf for the growth and survival of mouse embryonic stem cells

    SciTech Connect (OSTI)

    Guo, Wenjing; Hao, Baixia; Wang, Qian; Lu, Yingying; Yue, Jianbo

    2013-11-01

    Extracellular signal-regulated kinases (ERKs) have been implicated to be dispensable for self-renewal of mouse embryonic stem (ES) cells, and simultaneous inhibition of both ERK signaling and glycogen synthase kinase 3 (GSK3) not only allows mouse ES cells to self-renew independent of extracellular stimuli but also enables more efficient derivation of naïve ES cells from mouse and rat strains. Interestingly, some ERKs stay active in mouse ES cells which are maintained in regular medium containing leukemia inhibitory factor (LIF) and bone morphogenetic protein (BMP). Yet, the upstream signaling for ERK activation and their roles in mouse ES cells, other than promoting or priming differentiation, have not been determined. Here we found that mouse ES cells express three forms of Raf kinases, A-Raf, B-Raf, and C-Raf. Knocking-down each single Raf member failed to affect the sustained ERK activity, neither did A-Raf and B-Raf double knockdown or B-Raf and C-Raf double knockdown change it in ES cells. Interestingly, B-Raf and C-Raf double knockdown, not A-Raf and B-Raf knockdown, inhibited the maximal ERK activation induced by LIF, concomitant with the slower growth of ES cells. On the other hand, A-Raf, B-Raf, and C-Raf triple knockdown markedly inhibited both the maximal and sustained ERK activity in ES cells. Moreover, Raf triple knockdown, similar to the treatment of U-0126, an MEK inhibitor, significantly inhibited the survival and proliferation of ES cells, thereby compromising the colony propagation of mouse ES cells. In summary, our data demonstrate that all three Raf members are required for ERK activation in mouse ES cells and are involved in growth and survival of mouse ES cells. - Highlights: ●Mouse ES (mES) cells express all three Raf members, A-Raf, B-Raf, and C-Raf. ●Leukemia inhibitory factor (LIF) temporally activates ERKs in mES cells. ●B-Raf and C-Raf are required for LIF-induced maximal ERKs activity in mES cells. ●All Raf members are

  4. Curine inhibits eosinophil activation and airway hyper-responsiveness in a mouse model of allergic asthma

    SciTech Connect (OSTI)

    Ribeiro-Filho, Jaime; Calheiros, Andrea Surrage; Vieira-de-Abreu, Adriana; Moraes de Carvalho, Katharinne Ingrid; Silva Mendes, Diego da; Melo, Christianne Bandeira; Martins, Marco Aurlio; Silva Dias, Celidarque da; Piuvezam, Mrcia Regina; and others

    2013-11-15

    Allergic asthma is a chronic inflammatory airway disease with increasing prevalence around the world. Current asthma therapy includes drugs that usually cause significant side effects, justifying the search for new anti-asthmatic drugs. Curine is a bisbenzylisoquinoline alkaloid that modulates calcium influx in many cell types; however, its anti-allergic and putative toxic effects remain to be elucidated. Our aim was to investigate the effects of curine on eosinophil activation and airway hyper-responsiveness (AHR) and to characterize its potential toxic effects. We used a mouse model of allergic asthma induced by sensitization and challenge with ovalbumin (OVA) to evaluate the anti-allergic effects of oral treatment with curine. The oral administration of curine significantly inhibited eosinophilic inflammation, eosinophil lipid body formation and AHR in animals challenged with OVA compared with animals in the untreated group. The curine treatment also reduced eotaxin and IL-13 production triggered by OVA. Verapamil, a calcium channel antagonist, had similar anti-allergic properties, and curine pre-treatment inhibited the calcium-induced tracheal contractile response ex-vivo, suggesting that the mechanism by which curine exerts its effects is through the inhibition of a calcium-dependent response. A toxicological evaluation showed that orally administered curine did not significantly alter the biochemical, hematological, behavioral and physical parameters measured in the experimental animals compared with saline-treated animals. In conclusion, curine showed anti-allergic activity through mechanisms that involve inhibition of IL-13 and eotaxin and of Ca{sup ++} influx, without inducing evident toxicity and as such, has the potential for the development of anti-asthmatic drugs. - Highlights: Curine is a bisbenzylisoquinoline alkaloid from Chondrodendron platyphyllum. Curine inhibits eosinophil influx and activation and airway hyper-responsiveness. Curine

  5. Paraoxonase 2 (PON2) in the mouse central nervous system: A neuroprotective role?

    SciTech Connect (OSTI)

    Giordano, Gennaro; Cole, Toby B.; Furlong, Clement E.; Costa, Lucio G.

    2011-11-15

    The aims of this study were to characterize the expression of paraoxonase 2 (PON2) in mouse brain and to assess its antioxidant properties. PON2 levels were highest in the lung, intestine, heart and liver, and lower in the brain; in all tissues, PON2 expression was higher in female than in male mice. PON2 knockout [PON2{sup -/-}] mice did not express any PON2, as expected. In the brain, the highest levels of PON2 were found in the substantia nigra, the nucleus accumbens and the striatum, with lower levels in the cerebral cortex, hippocampus, cerebellum and brainstem. A similar regional distribution of PON2 activity (measured by dihydrocoumarin hydrolysis) was also found. PON3 was not detected in any brain area, while PON1 was expressed at very low levels, and did not show any regional difference. PON2 levels were higher in astrocytes than in neurons isolated from all brain regions, and were highest in cells from the striatum. PON2 activity and mRNA levels followed a similar pattern. Brain PON2 levels were highest around birth, and gradually declined. Subcellular distribution experiments indicated that PON2 is primarily expressed in microsomes and in mitochondria. The toxicity in neurons and astrocytes of agents known to cause oxidative stress (DMNQ and H{sub 2}O{sub 2}) was higher in cells from PON2{sup -/-} mice than in the same cells from wild-type mice, despite similar glutathione levels. These results indicate that PON2 is expressed in the brain, and that higher levels are found in dopaminergic regions such as the striatum, suggesting that this enzyme may provide protection against oxidative stress-mediated neurotoxicity.

  6. Tunicamycin-induced unfolded protein response in the developing mouse brain

    SciTech Connect (OSTI)

    Wang, Haiping; Wang, Xin; Ke, Zun-Ji; Comer, Ashley L.; Xu, Mei; Frank, Jacqueline A.; Zhang, Zhuo; Shi, Xianglin; Luo, Jia

    2015-03-15

    Accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) causes ER stress, resulting in the activation of the unfolded protein response (UPR). ER stress and UPR are associated with many neurodevelopmental and neurodegenerative disorders. The developing brain is particularly susceptible to environmental insults which may cause ER stress. We evaluated the UPR in the brain of postnatal mice. Tunicamycin, a commonly used ER stress inducer, was administered subcutaneously to mice of postnatal days (PDs) 4, 12 and 25. Tunicamycin caused UPR in the cerebral cortex, hippocampus and cerebellum of mice of PD4 and PD12, which was evident by the upregulation of ATF6, XBP1s, p-eIF2α, GRP78, GRP94 and MANF, but failed to induce UPR in the brain of PD25 mice. Tunicamycin-induced UPR in the liver was observed at all stages. In PD4 mice, tunicamycin-induced caspase-3 activation was observed in layer II of the parietal and optical cortex, CA1–CA3 and the subiculum of the hippocampus, the cerebellar external germinal layer and the superior/inferior colliculus. Tunicamycin-induced caspase-3 activation was also shown on PD12 but to a much lesser degree and mainly located in the dentate gyrus of the hippocampus, deep cerebellar nuclei and pons. Tunicamycin did not activate caspase-3 in the brain of PD25 mice and the liver of all stages. Similarly, immature cerebellar neurons were sensitive to tunicamycin-induced cell death in culture, but became resistant as they matured in vitro. These results suggest that the UPR is developmentally regulated and the immature brain is more susceptible to ER stress. - Highlights: • Tunicamycin caused a development-dependent UPR in the mouse brain. • Immature brain was more susceptible to tunicamycin-induced endoplasmic reticulum stress. • Tunicamycin caused more neuronal death in immature brain than mature brain. • Tunicamycin-induced neuronal death is region-specific.

  7. Isoniazid suppresses antioxidant response element activities and impairs adipogenesis in mouse and human preadipocytes

    SciTech Connect (OSTI)

    Chen, Yanyan; Xue, Peng; Hou, Yongyong; Zhang, Hao; Zheng, Hongzhi; Zhou, Tong; Qu, Weidong; Teng, Weiping; Zhang, Qiang; Andersen, Melvin E.; Pi, Jingbo

    2013-12-15

    Transcriptional signaling through the antioxidant response element (ARE), orchestrated by the Nuclear factor E2-related factor 2 (Nrf2), is a major cellular defense mechanism against oxidative or electrophilic stress. Here, we reported that isoniazid (INH), a widely used antitubercular drug, displays a substantial inhibitory property against ARE activities in diverse mouse and human cells. In 3T3-L1 preadipocytes, INH concentration-dependently suppressed the ARE-luciferase reporter activity and mRNA expression of various ARE-dependent antioxidant genes under basal and oxidative stressed conditions. In keeping with our previous findings that Nrf2-ARE plays a critical role in adipogenesis by regulating expression of CCAAT/enhancer-binding protein ? (C/EBP?) and peroxisome proliferator-activated receptor ? (PPAR?), suppression of ARE signaling by INH hampered adipogenic differentiation of 3T3-L1 cells and human adipose-derived stem cells (ADSCs). Following adipogenesis induced by hormonal cocktails, INH-treated 3T3-L1 cells and ADSCs displayed significantly reduced levels of lipid accumulation and attenuated expression of C/EBP? and PPAR?. Time-course studies in 3T3-L1 cells revealed that inhibition of adipogenesis by INH occurred in the early stage of terminal adipogenic differentiation, where reduced expression of C/EBP? and C/EBP? was observed. To our knowledge, the present study is the first to demonstrate that INH suppresses ARE signaling and interrupts with the transcriptional network of adipogenesis, leading to impaired adipogenic differentiation. The inhibition of ARE signaling may be a potential underlying mechanism by which INH attenuates cellular antioxidant response contributing to various complications. - Highlights: Isoniazid suppresses ARE-mediated transcriptional activity. Isoniazid inhibits adipogenesis in preadipocytes. Isoniazid suppresses adipogenic gene expression during adipogenesis.

  8. Methoxychlor reduces estradiol levels by altering steroidogenesis and metabolism in mouse antral follicles in vitro

    SciTech Connect (OSTI)

    Basavarajappa, Mallikarjuna S. Craig, Zelieann R. Hernandez-Ochoa, Isabel Paulose, Tessie Leslie, Traci C. Flaws, Jodi A.

    2011-06-15

    The organochlorine pesticide methoxychlor (MXC) is a known endocrine disruptor that affects adult rodent females by causing reduced fertility, persistent estrus, and ovarian atrophy. Since MXC is also known to target antral follicles, the major producer of sex steroids in the ovary, the present study was designed to test the hypothesis that MXC decreases estradiol (E{sub 2}) levels by altering steroidogenic and metabolic enzymes in the antral follicles. To test this hypothesis, antral follicles were isolated from CD-1 mouse ovaries and cultured with either dimethylsulfoxide (DMSO) or MXC. Follicle growth was measured every 24 h for 96 h. In addition, sex steroid hormone levels were measured using enzyme-linked immunosorbent assays (ELISA) and mRNA expression levels of steroidogenic enzymes as well as the E{sub 2} metabolic enzyme Cyp1b1 were measured using qPCR. The results indicate that MXC decreased E{sub 2}, testosterone, androstenedione, and progesterone (P{sub 4}) levels compared to DMSO. In addition, MXC decreased expression of aromatase (Cyp19a1), 17{beta}-hydroxysteroid dehydrogenase 1 (Hsd17b1), 17{alpha}-hydroxylase/17,20-lyase (Cyp17a1), 3{beta} hydroxysteroid dehydrogenase 1 (Hsd3b1), cholesterol side-chain cleavage (Cyp11a1), steroid acute regulatory protein (Star), and increased expression of Cyp1b1 enzyme levels. Thus, these data suggest that MXC decreases steroidogenic enzyme levels, increases metabolic enzyme expression and this in turn leads to decreased sex steroid hormone levels. - Highlights: > MXC inhibits steroidogenesis > MXC inhibits steroidogenic enzymes > MXC induces metabolic enzymes

  9. Comparative mapping of DNA markers from the familial Alzheimer disease and Down syndrome regions of human chromosome 21 to mouse chromosomes 16 and 17

    SciTech Connect (OSTI)

    Cheng, S.V.; Nadeau, J.H.; Tanzi, R.E.; Watkins, P.C.; Jagadesh, J.; Taylor, B.A.; Haines, J.L.; Sacchi, N.; Gusella, J.F. )

    1988-08-01

    Mouse trisomy 16 has been proposed as an animal model of Down syndrome (DS), since this chromosome contains homologues of several loci from the q22 band of human chromosome 21. The recent mapping of the defect causing familial Alzheimer disease (FAD) and the locus encoding the Alzheimer amyloid {beta} precursor protein (APP) to human chromosome 21 has prompted a more detailed examination of the extent of conservation of this linkage group between the two species. Using anonymous DNA probes and cloned genes from human chromosome 21 in a combination of recombinant inbred and interspecific mouse backcross analyses, the authors have established that the linkage group shared by mouse chromosome 16 includes not only the critical DS region of human chromosome 21 but also the APP gene and FAD-linked markers. Extending from the anonymous DNA locus D21S52 to ETS2, the linkage map of six loci spans 39% recombination in man but only 6.4% recombination in the mouse. A break in synteny occurs distal to ETS2, with the homologue of the human marker D21S56 mapping to mouse chromosome 17. Conservation of the linkage relationships of markers in the FAD region suggests that the murine homologue of the FAD locus probably maps to chromosome 16 and that detailed comparison of the corresponding region in both species could facilitate identification of the primary defect in this disorder. The break in synteny between the terminal portion of human chromosome 21 and mouse chromosome 16 indicates, however, that mouse trisomy 16 may not represent a complete model of DS.

  10. UVB light upregulates prostaglandin synthases and prostaglandin receptors in mouse keratinocytes

    SciTech Connect (OSTI)

    Black, Adrienne T.; Gray, Joshua P.; Shakarjian, Michael P.; Mishin, Vladimir; Laskin, Debra L.; Heck, Diane E.; Laskin, Jeffrey D.

    2008-10-01

    Prostaglandins belong to a class of cyclic lipid-derived mediators synthesized from arachidonic acid via COX-1, COX-2 and various prostaglandin synthases. Members of this family include prostaglandins such as PGE{sub 2}, PGF{sub 2{alpha}}, PGD{sub 2} and PGI{sub 2} (prostacyclin) as well as thromboxane. In the present studies we analyzed the effects of UVB on prostaglandin production and prostaglandin synthase expression in primary cultures of undifferentiated and calcium-differentiated mouse keratinocytes. Both cell types were found to constitutively synthesize PGE{sub 2}, PGD{sub 2} and the PGD{sub 2} metabolite PGJ{sub 2}. Twenty-four hours after treatment with UVB (25 mJ/cm{sup 2}), production of PGE{sub 2} and PGJ{sub 2} increased, while PGD{sub 2} production decreased. This was associated with increased expression of COX-2 mRNA and protein. UVB (2.5-25 mJ/cm{sup 2}) also caused marked increases in mRNA expression for the prostanoid synthases PGDS, mPGES-1, mPGES-2, PGFS and PGIS, as well as expression of receptors for PGE{sub 2} (EP1 and EP2), PGD{sub 2} (DP and CRTH2) and prostacyclin (IP). UVB was more effective in inducing COX-2 and DP in differentiated cells and EP1 and IP in undifferentiated cells. UVB readily activated keratinocyte PI-3-kinase (PI3K)/Akt, JNK and p38 MAP signaling pathways which are known to regulate COX-2 expression. While inhibition of PI3K suppressed UVB-induced mPGES-1 and CRTH2 expression, JNK inhibition suppressed mPGES-1, PGIS, EP2 and CRTH2, and p38 kinase inhibition only suppressed EP1 and EP2. These data indicate that UVB modulates expression of prostaglandin synthases and receptors by distinct mechanisms. Moreover, both the capacity of keratinocytes to generate prostaglandins and their ability to respond to these lipid mediators are stimulated by exposure to UVB.

  11. Inducible bilirubin oxidase: A novel function for the mouse cytochrome P450 2A5

    SciTech Connect (OSTI)

    Abu-Bakar, A'edah; Arthur, Dionne Maioha; Cooperative Research Centre for Contamination Assessment and Remediation of the Environment, Adelaide ; Aganovic, Simona; Ng, Jack C.; Cooperative Research Centre for Contamination Assessment and Remediation of the Environment, Adelaide ; Lang, Matti A.; Department of Pharmaceutical Biosciences, Uppsala University, Biomedical Centre, Box 578, S-751 23 Uppsala

    2011-11-15

    We have previously shown that bilirubin (BR), a breakdown product of haem, is a strong inhibitor and a high affinity substrate of the mouse cytochrome P450 2A5 (CYP2A5). The antioxidant BR, which is cytotoxic at high concentrations, is potentially useful in cellular protection against oxygen radicals if its intracellular levels can be strictly controlled. The mechanisms that regulate cellular BR levels are still obscure. In this paper we provide preliminary evidence for a novel function of CYP2A5 as hepatic 'BR oxidase'. A high-performance liquid chromatography/electrospray ionisation mass spectrometry screening showed that recombinant yeast microsomes expressing the CYP2A5 oxidise BR to biliverdin, as the main metabolite, and to three other smaller products with m/z values of 301, 315 and 333. The metabolic profile is significantly different from that of chemical oxidation of BR. In chemical oxidation the smaller products were the main metabolites. This suggests that the enzymatic reaction is selective, towards biliverdin production. Bilirubin treatment of primary hepatocytes increased the CYP2A5 protein and activity levels with no effect on the corresponding mRNA. Co-treatment with cycloheximide (CHX), a protein synthesis inhibitor, resulted in increased half-life of the CYP2A5 compared to cells treated only with CHX. Collectively, the observations suggest that the CYP2A5 is potentially an inducible 'BR oxidase' where BR may accelerate its own metabolism through stabilization of the CYP2A5 protein. It is possible that this metabolic pathway is potentially part of the machinery controlling intracellular BR levels in transient oxidative stress situations, in which high amounts of BR are produced. -- Highlights: Black-Right-Pointing-Pointer CYP2A5 metabolizes bilirubin to biliverdin and dipyrroles. Black-Right-Pointing-Pointer Bilirubin increased the hepatic CYP2A5 protein and activity levels. Black-Right-Pointing-Pointer Bilirubin does not change the hepatic CYP2A5

  12. Transient inhibition of cell proliferation does not compromise self-renewal of mouse embryonic stem cells

    SciTech Connect (OSTI)

    Wang, Ruoxing; Guo, Yan-Lin

    2012-10-01

    Embryonic stem cells (ESCs) have unlimited capacity for self-renewal and can differentiate into various cell types when induced. They also have an unusual cell cycle control mechanism driven by constitutively active cyclin dependent kinases (Cdks). In mouse ESCs (mESCs). It is proposed that the rapid cell proliferation could be a necessary part of mechanisms that maintain mESC self-renewal and pluripotency, but this hypothesis is not in line with the finding in human ESCs (hESCs) that the length of the cell cycle is similar to differentiated cells. Therefore, whether rapid cell proliferation is essential for the maintenance of mESC state remains unclear. We provide insight into this uncertainty through chemical intervention of mESC cell cycle. We report here that inhibition of Cdks with olomoucine II can dramatically slow down cell proliferation of mESCs with concurrent down-regulation of cyclin A, B and E, and the activation of the Rb pathway. However, mESCs display can recover upon the removal of olomoucine II and are able to resume normal cell proliferation without losing self-renewal and pluripotency, as demonstrated by the expression of ESC markers, colony formation, embryoid body formation, and induced differentiation. We provide a mechanistic explanation for these observations by demonstrating that Oct4 and Nanog, two major transcription factors that play critical roles in the maintenance of ESC properties, are up-regulated via de novo protein synthesis when the cells are exposed to olomoucine II. Together, our data suggest that short-term inhibition of cell proliferation does not compromise the basic properties of mESCs. -- Highlights: Black-Right-Pointing-Pointer Inhibition of Cdks slows down mESCs proliferation. Black-Right-Pointing-Pointer mESCs display remarkable recovery capacity from short-term cell cycle interruption. Black-Right-Pointing-Pointer Short-term cell cycle interruption does not compromise mESC self-renewal. Black

  13. Evidence for the evolutionary origin of human chromosome 21 from comparative gene mapping in the cow and mouse

    SciTech Connect (OSTI)

    Threadgill, D.S.; Womack, J.E. ); Kraus, J.P. ); Krawetz, S.A. )

    1991-01-01

    To determine the extent of conservation between bovine syntenic group U10, human chromosome 21 (HSA 21), and mouse chromosome 16(MMU 16), 11 genes were physically mapped by segregation analysis in a bovine-hamster hybrid somatic cell panel. The genes chosen for study span MMU 16 and represent virtually the entire q arm of HSA 21. Because the somatostatin gene (SST), an HSA 3/MMU 16 locus, was previously shown to be in U10, the transferrin gene (TF), an HSA 3/MMU 9 marker, was also mapped to determine whether U10 contains any HSA 3 genes not represented on MMU 16. With the exception of the protamine gene PRM1 (HSA 16/MMU 16), all of the genes studies were syntenic on bovine U10. Thus, all homologous loci from HSA 21 that have been studied in the cow are on a single chromosome. The bovine homolog of HSA 21 also carries several HSA 3 genes, two of which have homologous loci on MMU 16. The syntenic association of genes from the q arm of HSA 3 with HSAS 21 genes in two mammalian species, the mouse and the cow, indicates that HSA 21 may have evolved from a larger ancestral mammalian chromosome that contained genes now residing on HSA 3. Additionally, the syntenic association of TF with SST in the cow permits the prediction that the rhodopsin gene (RHO) is proximal to TF on HSA 3q.

  14. Stepwise renal lineage differentiation of mouse embryonic stem cells tracing in vivo development

    SciTech Connect (OSTI)

    Nishikawa, Masaki; Yanagawa, Naomi; Kojima, Nobuhiko; Yuri, Shunsuke; Hauser, Peter V.; Jo, Oak D.; Yanagawa, Norimoto

    2012-01-13

    Highlights: Black-Right-Pointing-Pointer We induced renal lineages from mESCs by following the in vivo developmental cues. Black-Right-Pointing-Pointer We induced nephrogenic intermediate mesoderm by stepwise addition of factors. Black-Right-Pointing-Pointer We induced two types of renal progenitor cells by reciprocal conditioned media. Black-Right-Pointing-Pointer We propose the potential role of CD24 for the enrichment of renal lineage cells. -- Abstract: The in vitro derivation of renal lineage progenitor cells is essential for renal cell therapy and regeneration. Despite extensive studies in the past, a protocol for renal lineage induction from embryonic stem cells remains unestablished. In this study, we aimed to induce renal lineages from mouse embryonic stem cells (mESC) by following in vivo developmental stages, i.e., the induction of mesoderm (Stage I), intermediate mesoderm (Stage II) and renal lineages (Stage III). For stage I induction, in accordance with known signaling pathways involved in mesoderm development in vivo, i.e., Nodal, bone morphogenic proteins (BMPs) and Wnt, we found that the sequential addition of three factors, i.e., Activin-A (A), a surrogate for Nodal signaling, during days 0-2, A plus BMP-4 (4) during days 2-4, and A4 plus lithium (L), a surrogate for Wnt signaling, during days 4-6, was most effective to induce the mesodermal marker, Brachyury. For stage II induction, the addition of retinoic acid (R) in the continuous presence of A4L during days 6-8 was most effective to induce nephrogenic intermediate mesodermal markers, such as Pax2 and Lim1. Under this condition, more than 30% of cells were stained positive for Pax2, and there was a concomitant decrease in the expression of non-mesodermal markers. For stage III induction, in resemblance to the reciprocal induction between ureteric bud (UB) and metanephric mesenchyme (MM) during kidney development, we found that the exposure to conditioned media derived from UB and MM cells was

  15. Suppression of somatic expansion delays the onset of pathophysiology in a mouse model of Huntington’s Disease

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Budworth, Helen; Harris, Faye R.; Williams, Paul; Lee, Do Yup; Holt, Amy; Pahnke, Jens; Szczesny, Bartosz; Acevedo-Torres, Karina; Ayala-Peña, Sylvette; McMurray, Cynthia T.; et al

    2015-08-06

    Huntington’s Disease (HD) is caused by inheritance of a single disease-length allele harboring an expanded CAG repeat, which continues to expand in somatic tissues with age. The inherited disease allele expresses a toxic protein, and whether further somatic expansion adds to toxicity is unknown. We have created an HD mouse model that resolves the effects of the inherited and somatic expansions. We show here that suppressing somatic expansion substantially delays the onset of disease in littermates that inherit the same disease-length allele. Furthermore, a pharmacological inhibitor, XJB-5-131, inhibits the lengthening of the repeat tracks, and correlates with rescue of motormore » decline in these animals. The results provide evidence that pharmacological approaches to offset disease progression are possible.« less

  16. Suppression of somatic expansion delays the onset of pathophysiology in a mouse model of Huntington’s Disease

    SciTech Connect (OSTI)

    Budworth, Helen; Harris, Faye R.; Williams, Paul; Lee, Do Yup; Holt, Amy; Pahnke, Jens; Szczesny, Bartosz; Acevedo-Torres, Karina; Ayala-Peña, Sylvette; McMurray, Cynthia T.; McKinnon, Peter

    2015-08-06

    Huntington’s Disease (HD) is caused by inheritance of a single disease-length allele harboring an expanded CAG repeat, which continues to expand in somatic tissues with age. The inherited disease allele expresses a toxic protein, and whether further somatic expansion adds to toxicity is unknown. We have created an HD mouse model that resolves the effects of the inherited and somatic expansions. We show here that suppressing somatic expansion substantially delays the onset of disease in littermates that inherit the same disease-length allele. Furthermore, a pharmacological inhibitor, XJB-5-131, inhibits the lengthening of the repeat tracks, and correlates with rescue of motor decline in these animals. The results provide evidence that pharmacological approaches to offset disease progression are possible.

  17. The crystal structure of a partial mouse Notch-1 ankyrin domain: Repeats 4 through 7 preserve an ankyrin fold

    SciTech Connect (OSTI)

    Lubman, Olga Y.; Kopan, Raphael; Waksman, Gabriel; Korolev, Sergey (Birbeck); (St. Louis-MED); (WU-MED)

    2010-07-20

    Folding and stability of proteins containing ankyrin repeats (ARs) is of great interest because they mediate numerous protein-protein interactions involved in a wide range of regulatory cellular processes. Notch, an ankyrin domain containing protein, signals by converting a transcriptional repression complex into an activation complex. The Notch ANK domain is essential for Notch function and contains seven ARs. Here, we present the 2.2 {angstrom} crystal structure of ARs 4-7 from mouse Notch 1 (m1ANK). These C-terminal repeats were resistant to degradation during crystallization, and their secondary and tertiary structures are maintained in the absence of repeats 1-3. The crystallized fragment adopts a typical ankyrin fold including the poorly conserved seventh AR, as seen in the Drosophila Notch ANK domain (dANK). The structural preservation and stability of the C-terminal repeats shed a new light onto the mechanism of hetero-oligomeric assembly during Notch-mediated transcriptional activation.

  18. Differential gene expression profiling of mouse skin after sulfur mustard exposure: Extended time response and inhibitor effect

    SciTech Connect (OSTI)

    Gerecke, Donald R. Chen Minjun; Isukapalli, Sastry S.; Gordon, Marion K.; Chang, Y.-C.; Tong Weida; Androulakis, Ioannis P.; Georgopoulos, Panos G.

    2009-01-15

    Sulfur mustard (HD, SM), is a chemical warfare agent that within hours causes extensive blistering at the dermal-epidermal junction of skin. To better understand the progression of SM-induced blistering, gene expression profiling for mouse skin was performed after a single high dose of SM exposure. Punch biopsies of mouse ears were collected at both early and late time periods following SM exposure (previous studies only considered early time periods). The biopsies were examined for pathological disturbances and the samples further assayed for gene expression profiling using the Affymetrix microarray analysis system. Principal component analysis and hierarchical cluster analysis of the differently expressed genes, performed with ArrayTrack showed clear separation of the various groups. Pathway analysis employing the KEGG library and Ingenuity Pathway Analysis (IPA) indicated that cytokine-cytokine receptor interaction, cell adhesion molecules (CAMs), and hematopoietic cell lineage are common pathways affected at different time points. Gene ontology analysis identified the most significantly altered biological processes as the immune response, inflammatory response, and chemotaxis; these findings are consistent with other reported results for shorter time periods. Selected genes were chosen for RT-PCR verification and showed correlations in the general trends for the microarrays. Interleukin 1 beta was checked for biological analysis to confirm the presence of protein correlated to the corresponding microarray data. The impact of a matrix metalloproteinase inhibitor, MMP-2/MMP-9 inhibitor I, against SM exposure was assessed. These results can help in understanding the molecular mechanism of SM-induced blistering, as well as to test the efficacy of different inhibitors.

  19. A Novel mouse model of enhanced proteostasis: Full-length human heat shock factor 1 transgenic mice

    SciTech Connect (OSTI)

    Pierce, Anson; Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, 78229; The Department of Veteran's Affairs, South Texas Veterans Health Care System, San Antonio, Texas, 78284 ; Wei, Rochelle; Halade, Dipti; Yoo, Si-Eun; Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, 78229 ; Ran, Qitao; Richardson, Arlan; Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, 78229; The Department of Veteran's Affairs, South Texas Veterans Health Care System, San Antonio, Texas, 78284

    2010-11-05

    Research highlights: {yields} Development of mouse overexpressing native human HSF1 in all tissues including CNS. {yields} HSF1 overexpression enhances heat shock response at whole-animal and cellular level. {yields} HSF1 overexpression protects from polyglutamine toxicity and favors aggresomes. {yields} HSF1 overexpression enhances proteostasis at the whole-animal and cellular level. -- Abstract: The heat shock response (HSR) is controlled by the master transcriptional regulator heat shock factor 1 (HSF1). HSF1 maintains proteostasis and resistance to stress through production of heat shock proteins (HSPs). No transgenic model exists that overexpresses HSF1 in tissues of the central nervous system (CNS). We generated a transgenic mouse overexpressing full-length non-mutant HSF1 and observed a 2-4-fold increase in HSF1 mRNA and protein expression in all tissues studied of HSF1 transgenic (HSF1{sup +/0}) mice compared to wild type (WT) littermates, including several regions of the CNS. Basal expression of HSP70 and 90 showed only mild tissue-specific changes; however, in response to forced exercise, the skeletal muscle HSR was more elevated in HSF1{sup +/0} mice compared to WT littermates and in fibroblasts following heat shock, as indicated by levels of inducible HSP70 mRNA and protein. HSF1{sup +/0} cells elicited a significantly more robust HSR in response to expression of the 82 repeat polyglutamine-YFP fusion construct (Q82YFP) and maintained proteasome-dependent processing of Q82YFP compared to WT fibroblasts. Overexpression of HSF1 was associated with fewer, but larger Q82YFP aggregates resembling aggresomes in HSF1{sup +/0} cells, and increased viability. Therefore, our data demonstrate that tissues and cells from mice overexpressing full-length non-mutant HSF1 exhibit enhanced proteostasis.

  20. Dioxin exposure reduces the steroidogenic capacity of mouse antral follicles mainly at the level of HSD17B1 without altering atresia

    SciTech Connect (OSTI)

    Karman, Bethany N., E-mail: bklement@illinois.edu; Basavarajappa, Mallikarjuna S., E-mail: mbshivapur@gmail.com; Hannon, Patrick, E-mail: phannon2@illinois.edu; Flaws, Jodi A., E-mail: jflaws@illinois.edu

    2012-10-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent ovarian toxicant. Previously, we demonstrated that in vitro TCDD (1 nM) exposure decreases production/secretion of the sex steroid hormones progesterone (P4), androstenedione (A4), testosterone (T), and 17?-estradiol (E2) in mouse antral follicles. The purpose of this study was to determine the mechanism by which TCDD inhibits steroidogenesis. Specifically, we examined the effects of TCDD on the steroidogenic enzymes, atresia, and the aryl hydrocarbon receptor (AHR) protein. TCDD exposure for 48 h increased levels of A4, without changing HSD3B1 protein, HSD17B1 protein, estrone (E1), T or E2 levels. Further, TCDD did not alter atresia ratings compared to vehicle at 48 h. TCDD, however, did down regulate the AHR protein at 48 h. TCDD exposure for 96 h decreased transcript levels for Cyp11a1, Cyp17a1, Hsd17b1, and Cyp19a1, but increased Hsd3b1 transcript. TCDD exposure particularly lowered both Hsd17b1 transcript and HSD17B1 protein. However, TCDD exposure did not affect levels of E1 in the media nor atresia ratings at 96 h. TCDD, however, decreased levels of the proapoptotic factor Bax. Collectively, these data suggest that TCDD exposure causes a major block in the steroidogenic enzyme conversion of A4 to T and E1 to E2 and that it regulates apoptotic pathways, favoring survival over death in antral follicles. Finally, the down?regulation of the AHR protein in TCDD exposed follicles persisted at 96 h, indicating that the activation and proteasomal degradation of this receptor likely plays a central role in the impaired steroidogenic capacity and altered apoptotic pathway of exposed antral follicles. -- Highlights: ? TCDD disrupts steroidogenic enzymes in mouse antral follicles. ? TCDD particularly affects the HSD17B1 enzyme in mouse antral follicles. ? TCDD does not affect atresia ratings in mouse antral follicles. ? TCDD decreases levels of the proapoptitic factor Bax in mouse antral follicles. ? TCDD down

  1. Ortho-aminoazotoluene activates mouse constitutive androstane receptor (mCAR) and increases expression of mCAR target genes

    SciTech Connect (OSTI)

    Smetanina, Mariya A.; Pakharukova, Mariya Y.; Kurinna, Svitlana M.; Dong, Bingning; Hernandez, Juan P.; Moore, David D.; Merkulova, Tatyana I.

    2011-08-15

    2'-3-dimethyl-4-aminoazobenzene (ortho-aminoazotoluene, OAT) is an azo dye and a rodent carcinogen that has been evaluated by the International Agency for Research on Cancer (IARC) as a possible (class 2B) human carcinogen. Its mechanism of action remains unclear. We examined the role of the xenobiotic receptor Constitutive Androstane Receptor (CAR, NR1I3) as a mediator of the effects of OAT. We found that OAT increases mouse CAR (mCAR) transactivation in a dose-dependent manner. This effect is specific because another closely related azo dye, 3'-methyl-4-dimethyl-aminoazobenzene (3'MeDAB), did not activate mCAR. Real-time Q-PCR analysis in wild-type C57BL/6 mice revealed that OAT induces the hepatic mRNA expression of the following CAR target genes: Cyp2b10, Cyp2c29, Cyp3a11, Ugt1a1, Mrp4, Mrp2 and c-Myc. CAR-null (Car{sup -/-}) mice showed no increased expression of these genes following OAT treatment, demonstrating that CAR is required for their OAT dependent induction. The OAT-induced CAR-dependent increase of Cyp2b10 and c-Myc expression was confirmed by Western blotting. Immunohistochemistry analysis of wild-type and Car{sup -/-} livers showed that OAT did not acutely induce hepatocyte proliferation, but at much later time points showed an unexpected CAR-dependent proliferative response. These studies demonstrate that mCAR is an OAT xenosensor, and indicate that at least some of the biological effects of this compound are mediated by this nuclear receptor. - Highlights: > The azo dye and mouse carcinogen OAT is a very effective mCAR activator. > OAT increases mCAR transactivation in a dose-dependent manner. > OAT CAR-dependently increases the expression of a specific subset of CAR target genes. > OAT induces an unexpectedly deferred, but CAR-dependent hepatocyte proliferation.

  2. 2,6-Dithiopurine, a nucleophilic scavenger, protects against mutagenesis in mouse skin treated in vivo with 2-(chloroethyl) ethyl sulfide, a mustard gas analog

    SciTech Connect (OSTI)

    Boulware, Stephen; Fields, Tammy; McIvor, Elizabeth; Powell, K. Leslie; Abel, Erika L.; Vasquez, Karen M.; MacLeod, Michael C.

    2012-09-01

    Sulfur mustard [bis(2-chloroethyl)sulfide, SM] is a well-known DNA-damaging agent that has been used in chemical warfare since World War I, and is a weapon that could potentially be used in a terrorist attack on a civilian population. Dermal exposure to high concentrations of SM produces severe, long-lasting burns. Topical exposure to high concentrations of 2-(chloroethyl) ethyl sulfide (CEES), a monofunctional analog of SM, also produces severe skin lesions in mice. Utilizing a genetically engineered mouse strain, Big Blue, that allows measurement of mutation frequencies in mouse tissues, we now show that topical treatment with much lower concentrations of CEES induces significant dose- and time-dependent increases in mutation frequency in mouse skin; the mutagenic exposures produce minimal toxicity as determined by standard histopathology and immunohistochemical analysis for cytokeratin 6 and the DNA-damage induced phosphorylation of histone H2AX (γ-H2AX). We attempted to develop a therapeutic that would inhibit the CEES-induced increase in mutation frequency in the skin. We observe that multi-dose, topical treatment with 2,6-dithiopurine (DTP), a known chemical scavenger of CEES, beginning 1 h post-exposure to CEES, completely abolishes the CEES-induced increase in mutation frequency. These findings suggest the possibility that DTP, previously shown to be non-toxic in mice, may be useful as a therapeutic agent in accidental or malicious human exposures to SM. -- Highlights: ► 200 mM 2-(chloroethyl) ethyl sulfide (CEES) induces mutations in mouse skin. ► This dose of CEES is not overtly toxic, as assayed by histopathology. ► 2,6-Dithiopurine (DTP), applied after CEES-treatment, abolishes CEES-mutagenesis. ► This supports the idea that sulfur mustards exhibit long biological half-lives.

  3. A novel rabbit anti-hepatocyte growth factor monoclonal neutralizing antibody inhibits tumor growth in prostate cancer cells and mouse xenografts

    SciTech Connect (OSTI)

    Yu, Yanlan; Chen, Yicheng; Ding, Guoqing; Wang, Mingchao; Wu, Haiyang; Xu, Liwei; Rui, Xuefang; Zhang, Zhigen

    2015-08-14

    The hepatocyte growth factor and its receptor c-Met are correlated with castration-resistance in prostate cancer. Although HGF has been considered as an attractive target for therapeutic antibodies, the lack of cross-reactivity of monoclonal antibodies with human/mouse HGFs is a major obstacle in preclinical developments. We generated a panel of anti-HGF RabMAbs either blocking HGF/c-Met interaction or inhibiting c-Met phosphorylation. We selected one RabMAb with mouse cross-reactivity and demonstrated that it blocked HGF-stimulated downstream activation in PC-3 and DU145 cells. Anti-HGF RabMAb inhibited not only the growth of PC-3 cells but also HGF-dependent proliferation in HUVECs. We further demonstrated the efficacy and potency of the anti-HGF RabMAb in tumor xenograft mice models. Through these in vitro and in vivo experiments, we explored a novel therapeutic antibody for advanced prostate cancer. - Highlights: • HGF is an attractive target for castration-refractory prostate cancer. • We generated and characterized a panel of anti-HGF rabbit monoclonal antibodies. • More than half of these anti-HGF RabMAbs was cross-reactive with mouse HGF. • Anti-HGF RabMAb blocks HGF-stimulated phosphorylation and cell growth in vitro. • Anti-HGF RabMAb inhibits tumor growth and angiogenesis in xenograft mice.

  4. Glomerular-specific imprinting of the mouse Gs{alpha} gene: How does this relate to hormone resistance in Albright hereditary osteodystrophy?

    SciTech Connect (OSTI)

    Williamson, C.M.; Dutton, E.R.; Seymour, A.

    1996-09-01

    The gene for alpha-stimulating guanine-nucleotide binding polypeptide, Gnas, has been considered as a candidate for the imprinting effects ascribed to distal mouse Chromosome (Chr) 2. Its human homologue (GNAS1) appears, from clinical and biochemical studies of patients with Albright hereditary ostodystrophy, to be paternally imprinted. GNAS1 maps to 20q13, a region that shows linkage conservation with distal mouse Chr 2. We have mapped Gnas within the imprinting region on distal Chr 2 by linkage analysis. To establish if Gnas is imprinted, we have looked for expression differences in tissues taken from mice carrying maternal duplication/paternal deficiency for distal Chr 2 (MatDp2) and its reciprocal (PatDp2). RNA in situ hybridization revealed high levels of Gnas mRNA in glomeruli of PatDp2 embryos at late gestation and lower levels in glomeruli of MatDp2 embryos. These results strongly suggest that Gnas is maternally imprinted and suggest that the mouse gene may be imprinted in a manner opposite the predicted in human. 42 refs., 4 figs.

  5. Combination Effect of Regulatory T-Cell Depletion and Ionizing Radiation in Mouse Models of Lung and Colon Cancer

    SciTech Connect (OSTI)

    Son, Cheol-Hun; Bae, Jae-Ho; Shin, Dong-Yeok; Lee, Hong-Rae; Jo, Wol-Soon; Yang, Kwangmo; Park, You-Soo

    2015-06-01

    Purpose: To investigate the potential of low-dose cyclophosphamide (LD-CTX) and anti-CD25 antibody to prevent activation of regulatory T cells (Tregs) during radiation therapy. Methods and Materials: We used LD-CTX and anti-CD25 monoclonal antibody as a means to inhibit Tregs and improve the therapeutic effect of radiation in a mouse model of lung and colon cancer. Mice were irradiated on the tumor mass of the right leg and treated with LD-CTX and anti-CD25 antibody once per week for 3 weeks. Results: Combined treatment of LD-CTX or anti-CD25 antibody with radiation significantly decreased Tregs in the spleen and tumor compared with control and irradiation only in both lung and colon cancer. Combinatorial treatments resulted in a significant increase in the effector T cells, longer survival rate, and suppressed irradiated and distal nonirradiated tumor growth. Specifically, the combinatorial treatment of LD-CTX with radiation resulted in outstanding regression of local and distant tumors in colon cancer, and almost all mice in this group survived until the end of the study. Conclusions: Our results suggest that Treg depletion strategies may enhance radiation-mediated antitumor immunity and further improve outcomes after radiation therapy.

  6. Convergence of bone morphogenetic protein and laminin-1 signaling pathways promotes proliferation and colony formation by fetal mouse pancreatic cells

    SciTech Connect (OSTI)

    Jiang Fangxu . E-mail: jiang@wehi.edu.au; Harrison, Leonard C.

    2005-08-01

    We previously reported that bone morphogenetic proteins (BMPs), members of the transforming growth factor superfamily, together with the basement membrane glycoprotein laminin-1 (Ln-1), promote proliferation of fetal pancreatic cells and formation of colonies containing peripheral insulin-positive cells. Here, we further investigate the cross-talk between BMP and Ln-1 signals. By RT-PCR, receptors for BMP (BMPR) (excepting BMPR-1B) and Ln-1 were expressed in the fetal pancreas between E13.5 and E17.5. Specific blocking antibodies to BMP-4 and -6 and selective BMP antagonists partially inhibited colony formation by fetal pancreas cells. Colony formation induced by BMP-6 and Ln-1 was completely abolished in a dose-dependent manner by blocking Ln-1 binding to its {alpha}{sub 6} integrin and {alpha}-dystroglycan receptors or by blocking the Ln-1 signaling molecules, phosphatidyl-inositol-3-kinase (P13K) and MAP kinase kinase-1. These results demonstrate a convergence of BMP and Ln-1 signaling through P13K and MAP kinase pathways to induce proliferation and colony formation in E15.5 fetal mouse pancreatic cells.

  7. Crystal Structure of Staphylococcal Enterotoxin G (SEG) in Complex with a Mouse T-cell Receptor Beta Chain

    SciTech Connect (OSTI)

    Fernandez, M.M.; Robinson, H.; Cho, S.; De Marzi, M. C.; Kerzic, M. C.; Mariuzza, R. A.; Malchiodi, E. L.

    2011-01-14

    Superantigens (SAgs) are bacterial or viral toxins that bind MHC class II (MHC-II) molecules and T-cell receptor (TCR) in a nonconventional manner, inducing T-cell activation that leads to inflammatory cytokine production, which may result in acute toxic shock. In addition, the emerging threat of purpura fulminans and community-associated meticillin-resistant Staphylococcus aureus emphasizes the importance of a better characterization of SAg binding to their natural ligands that may allow the development of reagents to neutralize their action. The three-dimensional structure of the complex between a mouse TCR {beta} chain (mV{beta}8.2) and staphylococcal enterotoxin G (SEG) at 2.0 {angstrom} resolution revealed a binding site that does not conserve the 'hot spots' present in mV{beta}8.2-SEC2, mV{beta}8.2-SEC3, mV{beta}8.2-SEB, and mV{beta}8.2-SPEA complexes. Analysis of the mV{beta}8.2-SEG interface allowed us to explain the higher affinity of this complex compared with the others, which may account for the early activation of T-cells bearing mV{beta}8.2 by SEG. This mode of interaction between SEG and mV{beta}8.2 could be an adaptive advantage to bestow on the pathogen a faster rate of colonization of the host.

  8. Metastatic Melanoma Induced Metabolic Changes in C57BL/6J Mouse Stomach Measured by 1H NMR Spectroscopy

    SciTech Connect (OSTI)

    Hu, M; Wang, Xiliang

    2014-12-05

    Melanoma is a malignant tumor of melanocytes with high capability of invasion and rapid metastasis to other organs. Malignant melanoma is the most common metastatic malignancy found in gastrointestinal tract (GI). To the best of our knowledge, previous studies of melanoma in gastrointestinal tract are all clinical case reports. In this work, 1H NMR-based metabolomics approach is used to investigate the metabolite profiles differences of stomach tissue extracts of metastatic B16-F10 melanoma in C57BL/6J mouse and search for specific metabolite biomarker candidates. Principal Component Analysis (PCA), an unsupervised multivariate data analysis method, is used to detect possible outliers, while Orthogonal Projection to Latent Structure (OPLS), a supervised multivariate data analysis method, is employed to evaluate important metabolites responsible for discriminating the control and the melanoma groups. Both PCA and OPLS results reveal that the melanoma group can be well separated from its control group. Among the 50 identified metabolites, it is found that the concentrations of 19 metabolites are statistically and significantly changed with the levels of O-phosphocholine and hypoxanthine down-regulated while the levels of isoleucine, leucine, valine, isobutyrate, threonine, cadaverine, alanine, glutamate, glutamine, methionine, citrate, asparagine, tryptophan, glycine, serine, uracil, and formate up-regulated in the melanoma group. These significantly changed metabolites are associated with multiple biological pathways and may be potential biomarkers for metastatic melanoma in stomach.

  9. Metastatic Melanoma Induced Metabolic Changes in C57BL/6J Mouse Stomach Measured by 1H NMR Spectroscopy

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Hu, M; Wang, Xiliang

    2014-12-05

    Melanoma is a malignant tumor of melanocytes with high capability of invasion and rapid metastasis to other organs. Malignant melanoma is the most common metastatic malignancy found in gastrointestinal tract (GI). To the best of our knowledge, previous studies of melanoma in gastrointestinal tract are all clinical case reports. In this work, 1H NMR-based metabolomics approach is used to investigate the metabolite profiles differences of stomach tissue extracts of metastatic B16-F10 melanoma in C57BL/6J mouse and search for specific metabolite biomarker candidates. Principal Component Analysis (PCA), an unsupervised multivariate data analysis method, is used to detect possible outliers, while Orthogonalmore » Projection to Latent Structure (OPLS), a supervised multivariate data analysis method, is employed to evaluate important metabolites responsible for discriminating the control and the melanoma groups. Both PCA and OPLS results reveal that the melanoma group can be well separated from its control group. Among the 50 identified metabolites, it is found that the concentrations of 19 metabolites are statistically and significantly changed with the levels of O-phosphocholine and hypoxanthine down-regulated while the levels of isoleucine, leucine, valine, isobutyrate, threonine, cadaverine, alanine, glutamate, glutamine, methionine, citrate, asparagine, tryptophan, glycine, serine, uracil, and formate up-regulated in the melanoma group. These significantly changed metabolites are associated with multiple biological pathways and may be potential biomarkers for metastatic melanoma in stomach.« less

  10. Fourier Transform Infrared Imaging Showing Reduced Unsaturated Lipid Content in the Hippocampus of a mouse Model of Alzheimer's Disease

    SciTech Connect (OSTI)

    Leskovjan, A.C.; Kretlow, A.; Miller, L.M.

    2010-04-01

    Polyunsaturated fatty acids are essential to brain functions such as membrane fluidity, signal transduction, and cell survival. It is also thought that low levels of unsaturated lipid in the brain may contribute to Alzheimer's disease (AD) risk or severity. However, it is not known how accumulation of unsaturated lipids is affected in different regions of the hippocampus, which is a central target of AD plaque pathology, during aging. In this study, we used Fourier transform infrared imaging (FTIRI) to visualize the unsaturated lipid content in specific regions of the hippocampus in the PSAPP mouse model of AD as a function of plaque formation. Specifically, the unsaturated lipid content was imaged using the olefinic {double_bond}CH stretching mode at 3012 cm{sup -1}. The axonal, dendritic, and somatic layers of the hippocampus were examined in the mice at 13, 24, 40, and 56 weeks old. Results showed that lipid unsaturation in the axonal layer was significantly increased with normal aging in control (CNT) mice (p < 0.01) but remained low and relatively constant in PSAPP mice. Thus, these findings indicate that unsaturated lipid content is reduced in hippocampal white matter during amyloid pathogenesis and that maintaining unsaturated lipid content early in the disease may be critical in avoiding progression of the disease.

  11. Metabolite signatures in hydrophilic extracts of mouse lungs exposed to cigarette smoke revealed by 1H NMR metabolomics investigation

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Hu, Jian Z.; Wang, Xuan; Feng, Ju; Webb-Robertson, Bobbie-Jo M.; Waters, Katrina M.; Tilton, Susan C.; Pounds, Joel G.; Corley, Richard A.; Liu, Maili; Hu, Mary Y.

    2015-05-12

    Herein, 1H-NMR metabolomics are carried out to evaluate the changes of metabolites in lungs of mice exposed to cigarette smoke. It is found that the concentrations of adenosine derivatives (i.e. ATP, ADP and AMP), inosine and uridine are significantly fluctuated in the lungs of mice exposed to cigarette smoke compared with those of controls regardless the mouse is obese or regular weight. The decreased ATP, ADP, AMP and elevated inosine predict that the deaminases in charge of adenosine derivatives to inosine derivatives conversion are altered in lungs of mice exposed to cigarette smoke. Transcriptional analysis reveals that the concentrations ofmore » adenosine monophosphate deaminase and adenosine deaminase are different in the lungs of mice exposed to cigarette smoke, confirming the prediction from metabolomics studies. We also found, for the first time, that the ratio of glycerophosphocholine (GPC) to phosphocholine (PC) is significantly increased in the lungs of obese mice compared with regular weight mice. The ratio of GPC/PC is further elevated in the lungs of obese group by cigarette smoke exposure. Since GPC/PC ratio is a known biomarker for cancer, these results may suggest that obese group is more susceptible to lung cancer when exposed to cigarette smoke.« less

  12. Histone deacetylase inhibitor valproic acid promotes the induction of pluripotency in mouse fibroblasts by suppressing reprogramming-induced senescence stress

    SciTech Connect (OSTI)

    Zhai, Yingying; Chen, Xi; Yu, Dehai; Li, Tao; Cui, Jiuwei; Wang, Guanjun; Hu, Ji-Fan; Li, Wei

    2015-09-10

    Histone deacetylase inhibitor valproic acid (VPA) has been used to increase the reprogramming efficiency of induced pluripotent stem cell (iPSC) from somatic cells, yet the specific molecular mechanisms underlying this effect is unknown. Here, we demonstrate that reprogramming with lentiviruses carrying the iPSC-inducing factors (Oct4-Sox2-Klf4-cMyc, OSKM) caused senescence in mouse fibroblasts, establishing a stress barrier for cell reprogramming. Administration of VPA protected cells from reprogramming-induced senescent stress. Using an in vitro pre-mature senescence model, we found that VPA treatment increased cell proliferation and inhibited apoptosis through the suppression of the p16/p21 pathway. In addition, VPA also inhibited the G2/M phase blockage derived from the senescence stress. These findings highlight the role of VPA in breaking the cell senescence barrier required for the induction of pluripotency. - Highlights: • Histone deacetylase inhibitor valproic acid enhances iPSC induction. • Valproic acid suppresses reprogramming-induced senescence stress. • Valproic acid downregulates the p16/p21 pathway in reprogramming. • This study demonstrates a new mechanistic role of valproic acid in enhancing reprogramming.

  13. Population genomics of the Anthropocene: Urbanization is negatively associated with genome-wide variation in white-footed mouse populations

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Munshi-South, Jason; Zolnik, Christine P.; Harris, Stephen E.

    2016-02-11

    Urbanization results in pervasive habitat fragmentation and reduces standing genetic variation through bottlenecks and drift. Loss of genomewide variation may ultimately reduce the evolutionary potential of animal populations experiencing rapidly changing conditions. In this study, we examined genomewide variation among 23 white-footed mouse (Peromyscus leucopus) populations sampled along an urbanization gradient in the New York City metropolitan area. Genomewide variation was estimated as a proxy for evolutionary potential using more than 10000 single nucleotide polymorphism (SNP) markers generated by ddRAD-Seq. We found that genomewide variation is inversely related to urbanization as measured by percent impervious surface cover, and to amore » lesser extent, human population density. We also report that urbanization results in enhanced genomewide differentiation between populations in cities. There was no pattern of isolation by distance among these populations, but an isolation by resistance model based on impervious surface significantly explained patterns of genetic differentiation. Isolation by environment modeling also indicated that urban populations deviate much more strongly from global allele frequencies than suburban or rural populations. Lastly, this study is the first to examine loss of genomewide SNP variation along an urban-to-rural gradient and quantify urbanization as a driver of population genomic patterns.« less

  14. Synergistic regulation of the mouse orphan nuclear receptor SHP gene promoter by CLOCK-BMAL1 and LRH-1

    SciTech Connect (OSTI)

    Oiwa, Ako; Kakizawa, Tomoko . E-mail: tkaki@hsp.md.shinshu-u.ac.jp; Miyamoto, Takahide; Yamashita, Koh; Jiang, Wei; Takeda, Teiji; Suzuki, Satoru; Hashizume, Kiyoshi

    2007-02-23

    Small heterodimer partner (SHP; NR0B2) is an orphan nuclear receptor and acts as a repressor for wide variety of nuclear hormone receptors. We demonstrated here that mouse SHP mRNA showed a circadian expression pattern in the liver. Transient transfection of the mSHP promoter demonstrated that CLOCK-BMAL1, core circadian clock components, bound to E-box (CACGTG), and stimulated the promoter activity by 4-fold. Liver receptor homologue-1 (LRH-1; NR5A2) stimulated the mSHP promoter, and CLOCK-BMAL1 synergistically enhanced the LRH-1-mediated transactivation. Interestingly, SHP did not affect the CLOCK-BMAL1-mediated promoter activity, but strongly repressed the synergistic activation of CLOCK-BMAL1 and LRH-1. Furthermore, in vitro pull-down assays revealed the existence of direct protein-protein interaction between LRH-1 and CLOCK. In summary, this study shows that CLOCK-BMAL1, LRH-1 and SHP coordinately regulate the mSHP gene to generate the circadian oscillation. The cyclic expression of mSHP may affect daily activity of other nuclear receptors and contribute to circadian liver functions.

  15. Final Report of project entitled "A metabolomics and mouse models approach to study inflammatory and immune responses to radiation"

    SciTech Connect (OSTI)

    Fornace, Albert J.; Li, Henghong

    2013-12-02

    The three-year project entitled ?A Metabolomics and Mouse Models Approach to Study Inflammatory and Immune Responses to Radiation? was initiated in September 2009. The overall objectives of this project were to investigate the acute and persistent effects of low dose radiation on T cell lymphocyte function and physiology, as well the contributions of these cells to radiation-induced inflammatory responses. Inflammation after ionizing radiation (IR), even at low doses, may impact a variety of disease processes, including infectious disease, cardiovascular disease, cancer, and other potentially inflammatory disorders. There were three overall specific aims: 1. To investigate acute and persistent effects of low dose radiation on T cell subsets and function; 2. A genetic approach with mouse models to investigate p38 MAPK pathways that are involved in radiation-induced inflammatory signaling; 3. To investigate the effect of radiation quality on the inflammatory response. We have completed the work proposed in these aims. Below are our major accomplishments: ? Our data show that T cells from low dose irradiated animals have lower proliferation potency and cytokine production upon T cell receptor (TCR) stimulation. This effect was observed as early as 4 hours after radiation, and lasted up to two weeks. ? Using our ultraperformance liquid chromatography coupled with highly sensitive time-of-flight mass spectrometry (UPLC-QTOF) metabolomics method, we demonstrated the global changes of metabolites in T cells upon TCR stimulation in a time-dependent pattern. ? We found that the TCR activation induced metabolome changes are remarkably altered in a dose-dependent manner after radiation. At a dose of 0.5 Gy and above, IR mitigated TCR activation induced metabolome changes while at the dose of as low as 0.1Gy IR had a mild stimulatory effect on some of the metabolome changes. ? We revealed the mechanism for how radiation affects T cell activation by showing that the energy

  16. Studies of Secondary Melanoma on C57BL/6J Mouse Liver Using 1H NMR Metabolomics

    SciTech Connect (OSTI)

    Feng, Ju; Isern, Nancy G.; Burton, Sarah D.; Hu, Jian Z.

    2013-10-31

    NMR metabolomics, consisting of solid state high resolution (hr) magic angle spinning (MAS) 1H NMR (1H hr-MAS), liquid state high resolution 1H-NMR, and principal components analysis (PCA) has been used to study secondary metastatic B16-F10 melanoma in C57BL/6J mouse liver . The melanoma group can be differentiated from its control group by PCA analysis of the absolute concentrations or by the absolute peak intensities of metabolites from either 1H hr-MAS NMR data on intact liver tissues or liquid state 1H-NMR spectra on liver tissue extracts. In particular, we found that the absolute concentrations of alanine, glutamate, creatine, creatinine, fumarate and cholesterol are elevated in the melanoma group as compared to controls, while the absolute concentrations of succinate, glycine, glucose, and the family of linear lipids including long chain fatty acids, total choline and acylglycerol are decreased. The ratio of glycerophosphocholine to phosphocholine is increased by about 1.5 fold in the melanoma group, while the absolute concentration of total choline is actually lower in melanoma mice. These results suggest the following picture in secondary melanoma metastasis: Linear lipid levels are decreased by beta oxidation in the melanoma group, which contributes to an increase in the synthesis of cholesterol, and also provides an energy source input for TCA cycle. These findings suggest a link between lipid oxidation, the TCA cycle and the hypoxia-inducible factors (HIF) signal pathway in tumor metastases. Thus this study indicates that the metabolic profile derived from NMR analysis can provide a valuable bio-signature of malignancy and cell hypoxia in metastatic melanoma.

  17. Geraniin suppresses RANKL-induced osteoclastogenesis in vitro and ameliorates wear particle-induced osteolysis in mouse model

    SciTech Connect (OSTI)

    Xiao, Fei; Zhai, Zanjing; Jiang, Chuan; Liu, Xuqiang; Li, Haowei; Qu, Xinhua; Ouyang, Zhengxiao; Fan, Qiming; Tang, Tingting; Qin, An; Gu, Dongyun

    2015-01-01

    Wear particle-induced osteolysis and subsequent aseptic loosening remains the most common complication that limits the longevity of prostheses. Wear particle-induced osteoclastogenesis is known to be responsible for extensive bone erosion that leads to prosthesis failure. Thus, inhibition of osteoclastic bone resorption may serve as a therapeutic strategy for the treatment of wear particle induced osteolysis. In this study, we demonstrated for the first time that geraniin, an active natural compound derived from Geranium thunbergii, ameliorated particle-induced osteolysis in a Ti particle-induced mouse calvaria model in vivo. We also investigated the mechanism by which geraniin exerts inhibitory effects on osteoclasts. Geraniin inhibited RANKL-induced osteoclastogenesis in a dose-dependent manner, evidenced by reduced osteoclast formation and suppressed osteoclast specific gene expression. Specially, geraniin inhibited actin ring formation and bone resorption in vitro. Further molecular investigation demonstrated geraniin impaired osteoclast differentiation via the inhibition of the RANKL-induced NF-κB and ERK signaling pathways, as well as suppressed the expression of key osteoclast transcriptional factors NFATc1 and c-Fos. Collectively, our data suggested that geraniin exerts inhibitory effects on osteoclast differentiation in vitro and suppresses Ti particle-induced osteolysis in vivo. Geraniin is therefore a potential natural compound for the treatment of wear particle induced osteolysis in prostheses failure. - Highlights: • Geraniin suppresses osteoclasts formation and function in vitro. • Geraniin impairs RANKL-induced nuclear factor-κB and ERK signaling pathway. • Geraniin suppresses osteolysis in vivo. • Geraniin may be used for treating osteoclast related diseases.

  18. BENZO[a]PYRENE DIOL EPOXIDE PERTURBATION OF CELL CYCLE KINETICS OF SYNCHRONIZED MOUSE LIVER EPITHELIAL CELLS

    SciTech Connect (OSTI)

    Pearlman, A.L.; Navsky, B.N.; Bartholomew, J.C

    1980-07-01

    A cell cycle synchronization system is described for the analysis of the perturbation of cell cycle kinetics and the cycle-phase specificity of chemicals and other agents. We used the system to study the effects of ({+-})r-7, t-8-dihydroxy-t-9, 10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BaP diol epoxide) upon the cell cycle of mouse liver epithelial cells(NMuLi). BaP diol epoxide(0.6 uM) was added to replated cultures of NMuLi cells that had been synchronized in various stages of the cell cycle by centrifugal elutriation. DNA histograms were obtained by flow cytometry as a function of time after replating. The data were analyzed by a computer modeling routine and reduced to a few graphs illustrating the 'net effects' of the BaP diol epoxide relative to controls. BaP diol epoxide slowed S-phase traversal in all samples relative to their respective control. Traversal through G{sub 2}M was also slowed by at least 50%. BaP diol epoxide had no apparent effect upon G{sub 1} traversal by cycling cells, but delayed the recruitment of quiescent G{sub 0} cells by about 2 hrs. The methods described constitute a powerful new approach for probing the cell cycle effects of a wide variety of agents. The present system appears to be extremely sensitive and capable of characterizing the action of agents on each phase of the cell cycle. The methods are automatable and would allow for the assay and possible differential characterization of mutagens and carcinogens.

  19. Inhibition of Vascular Endothelial Growth Factor A and Hypoxia-Inducible Factor 1α Maximizes the Effects of Radiation in Sarcoma Mouse Models Through Destruction of Tumor Vasculature

    SciTech Connect (OSTI)

    Lee, Hae-June; Yoon, Changhwan; Park, Do Joong; Kim, Yeo-Jung; Schmidt, Benjamin; Lee, Yoon-Jin; Tap, William D.; Eisinger-Mathason, T.S. Karin; Choy, Edwin; Kirsch, David G.; Simon, M. Celeste; and others

    2015-03-01

    Purpose: To examine the addition of genetic or pharmacologic inhibition of hypoxia-inducible factor 1α (HIF-1α) to radiation therapy (RT) and vascular endothelial growth factor A (VEGF-A) inhibition (ie trimodality therapy) for soft-tissue sarcoma. Methods and Materials: Hypoxia-inducible factor 1α was inhibited using short hairpin RNA or low metronomic doses of doxorubicin, which blocks HIF-1α binding to DNA. Trimodality therapy was examined in a mouse xenograft model and a genetically engineered mouse model of sarcoma, as well as in vitro in tumor endothelial cells (ECs) and 4 sarcoma cell lines. Results: In both mouse models, any monotherapy or bimodality therapy resulted in tumor growth beyond 250 mm{sup 3} within the 12-day treatment period, but trimodality therapy with RT, VEGF-A inhibition, and HIF-1α inhibition kept tumors at <250 mm{sup 3} for up to 30 days. Trimodality therapy on tumors reduced HIF-1α activity as measured by expression of nuclear HIF-1α by 87% to 95% compared with RT alone, and cytoplasmic carbonic anhydrase 9 by 79% to 82%. Trimodality therapy also increased EC-specific apoptosis 2- to 4-fold more than RT alone and reduced microvessel density by 75% to 82%. When tumor ECs were treated in vitro with trimodality therapy under hypoxia, there were significant decreases in proliferation and colony formation and increases in DNA damage (as measured by Comet assay and γH2AX expression) and apoptosis (as measured by cleaved caspase 3 expression). Trimodality therapy had much less pronounced effects when 4 sarcoma cell lines were examined in these same assays. Conclusions: Inhibition of HIF-1α is highly effective when combined with RT and VEGF-A inhibition in blocking sarcoma growth by maximizing DNA damage and apoptosis in tumor ECs, leading to loss of tumor vasculature.

  20. Development of a phase-sensitive Fourier domain optical coherence tomography system to measure mouse organ of Corti vibrations in two cochlear turns

    SciTech Connect (OSTI)

    Ramamoorthy, Sripriya; Zhang, Yuan; Jacques, Steven; Petrie, Tracy; Wang, Ruikang; Nuttall, Alfred L.

    2015-12-31

    In this study, we have developed a phase-sensitive Fourier-domain optical coherence tomography system to simultaneously measure the in vivo inner ear vibrations in the hook area and second turn of the mouse cochlea. This technical development will enable measurement of intra-cochlear distortion products at ideal locations such as the distortion product generation site and reflection site. This information is necessary to un-mix the complex mixture of intra-cochlear waves comprising the DPOAE and thus leads to the non-invasive identification of the local region of cochlear damage.

  1. Flavin-containing monooxygenase-3: Induction by 3-methylcholanthrene and complex regulation by xenobiotic chemicals in hepatoma cells and mouse liver

    SciTech Connect (OSTI)

    Celius, Trine; Pansoy, Andrea; Matthews, Jason; Okey, Allan B.; Henderson, Marilyn C.; Krueger, Sharon K.; Williams, David E.

    2010-08-15

    Flavin-containing monooxygenases often are thought not to be inducible but we recently demonstrated aryl hydrocarbon receptor (AHR)-dependent induction of FMO mRNAs in mouse liver by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (Celius et al., Drug Metab Dispos 36:2499, 2008). We now evaluated FMO induction by other AHR ligands and xenobiotic chemicals in vivo and in mouse Hepa1c1c7 hepatoma cells (Hepa-1). In mouse liver, 3-methylcholanthrene (3MC) induced FMO3 mRNA 8-fold. In Hepa-1 cells, 3MC and benzo[a]pyrene (BaP) induced FMO3 mRNA > 30-fold. Induction by 3MC and BaP was AHR dependent but, surprisingly, the potent AHR agonist, TCDD, did not induce FMO3 mRNA in Hepa-1 cells nor did chromatin immunoprecipitation assays detect recruitment of AHR or ARNT to Fmo3 regulatory elements after exposure to 3MC in liver or in Hepa-1 cells. However, in Hepa-1, 3MC and BaP (but not TCDD) caused recruitment of p53 protein to a p53 response element in the 5'-flanking region of the Fmo3 gene. We tested the possibility that FMO3 induction in Hepa-1 cells might be mediated by Nrf2/anti-oxidant response pathways, but agents known to activate Nrf2 or to induce oxidative stress did not affect FMO3 mRNA levels. The protein synthesis inhibitor, cycloheximide (which causes 'superinduction' of CYP1A1 mRNA in TCDD-treated cells), by itself caused dramatic upregulation (> 300-fold) of FMO3 mRNA in Hepa-1 suggesting that cycloheximide prevents synthesis of a labile protein that suppresses FMO3 expression. Although FMO3 mRNA is highly induced by 3MC or TCDD in mouse liver and in Hepa-1 cells, FMO protein levels and FMO catalytic function showed only modest elevation.

  2. TH-E-BRF-07: Raman Spectroscopy for Radiation Treatment Response Assessment in a Lung Metastases Mouse Model

    SciTech Connect (OSTI)

    Devpura, S; Barton, K; Brown, S; Siddiqui, F; Chetty, I; Sethi, S; Klein, M

    2014-06-15

    Purpose: Raman spectroscopy is an optical spectroscopic method used to probe chemical information about a target tissue. Our goal was to investigate whether Raman spectroscopy is able to distinguish lung tumors from normal lung tissue and whether this technique can identify the molecular changes induced by radiation. Methods: 4T1 mouse breast cancer cells were implanted subcutaneously into the flanks of 6 Balb/C female mice. Four additional mice were used as “normal lung” controls. After 14 days, 3 mice bearing tumors received 6Gy to the left lung with 6MV photons and the other three were treated as “unirradiated tumor” controls. At a 24-hour time point, lungs were excised and the specimens were sectioned using a cryostat; alternating sections were either stained with hematoxylin and eosin (H and E) for evaluation by a pathologist or unstained for Raman measurements. 240 total Raman spectra were collected; 84 from normal lung controls; 63 from unirradiated tumors and 64 from tumors irradiated with 6Gy in a single fraction. Raman spectra were also collected from normal lung tissues of mice with unirradiated tumors. Principal component analysis (PCA) and discriminant function analysis (DFA) were performed to analyze the data. Results: Raman bands assignable to DNA/RNA showed prominent contributions in tumor tissues while Raman bands associated with hemoglobin showed strong contributions in normal lung tissue. PCA/DFA analysis identified normal lung tissue and tumor with 100% and 98.4% accuracy, respectively, relative to pathologic scoring. Additionally, normal lung tissues from unirradiated mice bearing tumors were classified as normal with 100% accuracy. In a model consisting of unirradiated and irradiated tumors identification accuracy was 79.4% and 93.8% respectively, relative to pathologic assessment. Conclusion: Initial results demonstrate the promise for Raman spectroscopy in the diagnosis normal vs. lung metastases as well as the assessment of

  3. Development of doxorubicin-induced chronic cardiotoxicity in the B6C3F{sub 1} mouse model

    SciTech Connect (OSTI)

    Desai, Varsha G.; Herman, Eugene H.; Moland, Carrie L.; Branham, William S.; Lewis, Sherry M.; Davis, Kelly J.; George, Nysia I.; Lee, Taewon; Kerr, Susan; Fuscoe, James C.

    2013-01-01

    Serum levels of cardiac troponins serve as biomarkers of myocardial injury. However, troponins are released into the serum only after damage to cardiac tissue has occurred. Here, we report development of a mouse model of doxorubicin (DOX)-induced chronic cardiotoxicity to aid in the identification of predictive biomarkers of early events of cardiac tissue injury. Male B6C3F{sub 1} mice were administered intravenous DOX at 3 mg/kg body weight, or an equivalent volume of saline, once a week for 4, 6, 8, 10, 12, and 14 weeks, resulting in cumulative DOX doses of 12, 18, 24, 30, 36, and 42 mg/kg, respectively. Mice were sacrificed a week following the last dose. A significant reduction in body weight gain was observed in mice following exposure to a weekly DOX dose for 1 week and longer compared to saline-treated controls. DOX treatment also resulted in declines in red blood cell count, hemoglobin level, and hematocrit compared to saline-treated controls after the 2nd weekly dose until the 8th and 9th doses, followed by a modest recovery. All DOX-treated mice had significant elevations in cardiac troponin T concentrations in plasma compared to saline-treated controls, indicating cardiac tissue injury. Also, a dose-related increase in the severity of cardiac lesions was seen in mice exposed to 24 mg/kg DOX and higher cumulative doses. Mice treated with cumulative DOX doses of 30 mg/kg and higher showed a significant decline in heart rate, suggesting drug-induced cardiac dysfunction. Altogether, these findings demonstrate the development of DOX-induced chronic cardiotoxicity in B6C3F{sub 1} mice. -- Highlights: ? 24 mg/kg was a cumulative cardiotoxic dose of doxorubicin in male B6C3F{sub 1} mice. ? Doxorubicin-induced hematological toxicity was in association with splenomegaly. ? Doxorubicin induced severe testicular toxicity in B6C3F{sub 1} male mice.

  4. Mono-hydroxy methoxychlor alters levels of key sex steroids and steroidogenic enzymes in cultured mouse antral follicles

    SciTech Connect (OSTI)

    Craig, Zelieann R.; Leslie, Traci C.; Hatfield, Kimberly P.; Gupta, Rupesh K.; Flaws, Jodi A.

    2010-12-01

    Methoxychlor (MXC) is an organochlorine pesticide that reduces fertility in female rodents by decreasing antral follicle numbers and increasing follicular death. MXC is metabolized in the body to mono-hydroxy MXC (mono-OH). Little is known about the effects of mono-OH on the ovary. Thus, this work tested the hypothesis that mono-OH exposure decreases production of 17{beta}-estradiol (E{sub 2}) by cultured mouse antral follicles. Antral follicles were isolated from CD-1 mice (age 35-39 days) and exposed to dimethylsulfoxide (DMSO), or mono-OH (0.1-10 {mu}g/mL) for 96 h. Media and follicles were collected for analysis of sex steroid levels and mRNA expression, respectively. Mono-OH treatment (10 {mu}g/mL) decreased E{sub 2} (DMSO: 3009.72 {+-} 744.99 ng/mL; mono-OH 0.1 {mu}g/mL: 1679.66 {+-} 461.99 ng/mL; 1 {mu}g/mL: 1752.72 {+-} 532.41 ng/mL; 10 {mu}g/mL: 45.89 {+-} 33.83 ng/mL), testosterone (DMSO: 15.43 {+-} 2.86 ng/mL; mono-OH 0.1 {mu}g/mL: 17.17 {+-} 4.71 ng/mL; 1 {mu}g/mL: 13.64 {+-} 3.53 ng/mL; 10 {mu}g/mL: 1.29 {+-} 0.23 ng/mL), androstenedione (DMSO: 1.92 {+-} 0.34 ng/mL; mono-OH 0.1 {mu}g/mL: 1.49 {+-} 0.43 ng/mL; 1 {mu}g/mL: 0.64 {+-} 0.31 ng/mL; 10 {mu}g/mL: 0.12 {+-} 0.06 ng/mL) and progesterone (DMSO: 24.11 {+-} 4.21 ng/mL; mono-OH 0.1 {mu}g/mL: 26.77 {+-} 4.41 ng/mL; 1 {mu}g/mL: 20.90 {+-} 3.75 ng/mL; 10 {mu}g/mL: 9.44 {+-} 2.97 ng/mL) levels. Mono-OH did not alter expression of Star, Hsd3b1, Hsd17b1 and Cyp1b1, but it did reduce levels of Cyp11a1, Cyp17a1 and Cyp19a1 mRNA. Collectively, these data suggest that mono-OH significantly decreases levels of key sex steroid hormones and the expression of enzymes required for steroidogenesis.

  5. Linkage mapping of the aldo-2, Pax-5, Ambp, and D4H9S3E loci on mouse chromosome 4 in the region of homology with human chromosome 9

    SciTech Connect (OSTI)

    Pilz, A.; Abbott, C. ); Fountain, J. ); Peters, J. )

    1993-12-01

    The genes for aldolase-B (ALDOB), the [alpha]-microglobulin/bikunin precursor (AMBP), the paired box gene PAX5, and the anonymous DNA marker D9S3 map to human chromosome 9 (HSA9). The authors have set out to map the mouse homologues of each of these genes. The mouse genes for Pax-5 and Ambp previously been shown to map to MMU4. They have used an interspecific backcross to confirm these localizations and to map the mouse homologues of ALDOB (Aldo-2) and D9S3 (D4H9S3E) to the same chromosome. These genes were mapped with respect to the four anchor loci for MMU4. In addition, the panel of backcross DNAs had previously been typed for [delta]-amino levulinate dehydratase (Lv), orosomucoid-1 (Orm-1), and hexabranchion (Hxb), the human homologues of which map to HSA9q. The recombination distances [+-] the standard error between each pair of loci are D4Nds4-1.6[+-]1.1-D4H9S3E-4.0[+-]1.7 (Galt) 0.8[+-]0.8-Pax-5-4.8[+-]1.9-Aldo-2-6.3[+-]2.2-(Lv, Orm-1, Ambp)-1.6[+-]1.1-Hxb-4.0[+-]1.7-Tyrp-1-4.8[+-]1.9-Ifa. The data from this study have extended the known region of conserved synteny between human chromosome 9 and mouse chromosome 4. 17 refs., 2 figs.

  6. The inhibitory effect of ionizing radiation on Fc and C3 receptors on mouse and human leukocytes, and the protective potential of human albumin

    SciTech Connect (OSTI)

    Herrera, M.A.; Diaz-Perches, R.; Gutierrez, M.; Gamminio, E.; Liera, C.; Nieto, P.; Weiss-Steider, B. )

    1990-08-01

    The effect that ionizing radiation has in vitro on Fc and C3 receptors was evaluated at various doses and measured by means of erythrocytes coated with antibody (EA) and erythrocytes coated with antibody and complement (EAC) rosettes on human peripheral blood leukocytes (PBL) and on mouse bone marrow cells (BMC) and PBL. We found that the number of cells with either EA and EAC rosettes decreased as the radiation doses increased, and that they were almost absent when the highest doses were employed. We obtained evidence that albumin is a natural source of radio-protection for Fc and C3 receptors, and we showed that by increasing the amount of this molecule we could completely protect receptors for EA and EAC in vitro. Finally, the possible therapeutic value of the administration of human albumin to patients undergoing radiotherapy is discussed.

  7. CD45{sup low}c-Kit{sup high} cells have hematopoietic properties in the mouse aorta-gonad-mesonephros region

    SciTech Connect (OSTI)

    Nobuhisa, Ikuo; Department of Cell Fate Modulation, Institute of Molecular Embryology and Genetics Yamasaki, Shoutarou; Department of Cell Fate Modulation, Institute of Molecular Embryology and Genetics Taga, Tetsuya; Department of Cell Fate Modulation, Institute of Molecular Embryology and Genetics/Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, 860-0811

    2012-04-01

    Long-term reconstituting hematopoietic stem cells first arise from the aorta of the aorta-gonad-mesonephros (AGM) region in a mouse embryo. We have previously reported that in cultures of the dispersed AGM region, CD45{sup low}c-Kit{sup +} cells possess the ability to reconstitute multilineage hematopoietic cells, but investigations are needed to show that this is not a cultured artifact and to clarify when and how this population is present. Based on the expression profile of CD45 and c-Kit in freshly dissociated AGM cells from embryonic day 9.5 (E9.5) to E12.5 and aorta cells in the AGM from E13.5 to E15.5, we defined six cell populations (CD45{sup -}c-Kit{sup -}, CD45{sup -}c-Kit{sup low}, CD45{sup -}c-Kit{sup high}, CD45{sup low}c-Kit{sup high}, CD45{sup high}c-Kit{sup high}, and CD45{sup high}c-Kit{sup very} {sup low}). Among these six populations, CD45{sup low}c-Kit{sup high} cells were most able to form hematopoietic cell colonies, but their ability decreased after E11.5 and was undetectable at E13.5 and later. The CD45{sup low}c-Kit{sup high} cells showed multipotency in vitro. We demonstrated further enrichment of hematopoietic activity in the Hoechst dye-effluxing side population among the CD45{sup low}c-Kit{sup high} cells. Here, we determined that CD45{sup low}c-Kit{sup high} cells arise from the lateral plate mesoderm using embryonic stem cell-derived differentiation system. In conclusion, CD45{sup low}c-Kit{sup high} cells are the major hematopoietic cells of mouse AGM.

  8. Arsenic augments the uptake of oxidized LDL by upregulating the expression of lectin-like oxidized LDL receptor in mouse aortic endothelial cells

    SciTech Connect (OSTI)

    Hossain, Ekhtear; Ota, Akinobu; Karnan, Sivasundaram; Damdindorj, Lkhagvasuren; Takahashi, Miyuki; Konishi, Yuko; Konishi, Hiroyuki; Hosokawa, Yoshitaka

    2013-12-15

    Although chronic arsenic exposure is a well-known risk factor for cardiovascular diseases, including atherosclerosis, the molecular mechanism underlying arsenic-induced atherosclerosis remains obscure. Therefore, this study aimed to elucidate this molecular mechanism. We examined changes in the mRNA level of the lectin-like oxidized LDL (oxLDL) receptor (LOX-1) in a mouse aortic endothelial cell line, END-D, after sodium arsenite (SA) treatment. SA treatment significantly upregulated LOX-1 mRNA expression; this finding was also verified at the protein expression level. Flow cytometry and fluorescence microscopy analyses showed that the cellular uptake of fluorescence (Dil)-labeled oxLDL was significantly augmented with SA treatment. In addition, an anti-LOX-1 antibody completely abrogated the augmented uptake of Dil-oxLDL. We observed that SA increased the levels of the phosphorylated forms of nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-κB)/p65. SA-induced upregulation of LOX-1 protein expression was clearly prevented by treatment with an antioxidant, N-acetylcysteine (NAC), or an NF-κB inhibitor, caffeic acid phenethylester (CAPE). Furthermore, SA-augmented uptake of Dil-oxLDL was also prevented by treatment with NAC or CAPE. Taken together, our results indicate that arsenic upregulates LOX-1 expression through the reactive oxygen species-mediated NF-κB signaling pathway, followed by augmented cellular oxLDL uptake, thus highlighting a critical role of the aberrant LOX-1 signaling pathway in the pathogenesis of arsenic-induced atherosclerosis. - Highlights: • Sodium arsenite (SA) increases LOX-1 expression in mouse aortic endothelial cells. • SA enhances cellular uptake of oxidized LDL in dose-dependent manner. • SA-induced ROS generation enhances phosphorylation of NF-κB. • SA upregulates LOX-1 expression through ROS-activated NF-κB signaling pathway.

  9. Bisphenol A down-regulates rate-limiting Cyp11a1 to acutely inhibit steroidogenesis in cultured mouse antral follicles

    SciTech Connect (OSTI)

    Peretz, Jackye; Flaws, Jodi A.

    2013-09-01

    Bisphenol A (BPA) is the backbone of polycarbonate plastic products and the epoxy resin lining of aluminum cans. Previous studies have shown that exposure to BPA decreases sex steroid hormone production in mouse antral follicles. The current study tests the hypothesis that BPA first decreases the expression levels of the steroidogenic enzyme cytochrome P450 side-chain cleavage (Cyp11a1) and steroidogenic acute regulatory protein (StAR) in mouse antral follicles, leading to a decrease in sex steroid hormone production in vitro. Further, the current study tests the hypothesis that these effects are acute and reversible after removal of BPA. Exposure to BPA (10 μg/mL and 100 μg/mL) significantly decreased expression of Cyp11a1 and StAR beginning at 18 h and 72 h, respectively, compared to controls. Exposure to BPA (10 μg/mL and 100 μg/mL) significantly decreased progesterone levels beginning at 24 h and decreased androstenedione, testosterone, and estradiol levels at 72 h and 96 h compared to controls. Further, after removing BPA from the culture media at 20 h, expression of Cyp11a1 and progesterone levels were restored to control levels by 48 h and 72 h, respectively. Additionally, expression of StAR and levels of androstenedione, testosterone, and estradiol never decreased compared to controls. These data suggest that BPA acutely decreases expression of Cyp11a1 as early as 18 h and this reduction in Cyp11a1 may lead to a decrease in progesterone production by 24 h, followed by a decrease in androstenedione, testosterone, and estradiol production and expression of StAR at 72 h. Therefore, BPA exposure likely targets Cyp11a1 and steroidogenesis, but these effects are reversible with removal of BPA exposure. - Highlights: • BPA may target Cyp11a1 to inhibit steroidogenesis in antral follicles. • BPA may decrease the expression of Cyp11a1 prior to inhibiting steroidogenesis. • The adverse effects of BPA on steroidogenesis in antral follicles are reversible.

  10. Pregnenolone co-treatment partially restores steroidogenesis, but does not prevent growth inhibition and increased atresia in mouse ovarian antral follicles treated with mono-hydroxy methoxychlor

    SciTech Connect (OSTI)

    Craig, Zelieann R. Hannon, Patrick R. Flaws, Jodi A.

    2013-11-01

    Mono-hydroxy methoxychlor (mono-OH MXC) is a metabolite of the pesticide, methoxychlor (MXC). Although MXC is known to decrease antral follicle numbers, and increase follicle death in rodents, not much is known about the ovarian effects of mono-OH MXC. Previous studies indicate that mono-OH MXC inhibits mouse antral follicle growth, increases follicle death, and inhibits steroidogenesis in vitro. Further, previous studies indicate that CYP11A1 expression and production of progesterone (P{sub 4}) may be the early targets of mono-OH MXC in the steroidogenic pathway. Thus, this study tested whether supplementing pregnenolone, the precursor of progesterone and the substrate for HSD3B, would prevent decreased steroidogenesis, inhibited follicle growth, and increased follicle atresia in mono-OH MXC-treated follicles. Mouse antral follicles were exposed to vehicle (dimethylsulfoxide), mono-OH MXC (10 μg/mL), pregnenolone (1 μg/mL), or mono-OH MXC and pregnenolone together for 96 h. Levels of P{sub 4}, androstenedione (A), testosterone (T), estrone (E{sub 1}), and 17β-estradiol (E{sub 2}) in media were determined, and follicles were processed for histological evaluation of atresia. Pregnenolone treatment alone stimulated production of all steroid hormones except E{sub 2}. Mono-OH MXC-treated follicles had decreased sex steroids, but when given pregnenolone, produced levels of P{sub 4}, A, T, and E{sub 1} that were comparable to those in vehicle-treated follicles. Pregnenolone treatment did not prevent growth inhibition and increased atresia in mono-OH MXC-treated follicles. Collectively, these data support the idea that the most upstream effect of mono-OH MXC on steroidogenesis is by reducing the availability of pregnenolone, and that adding pregnenolone may not be sufficient to prevent inhibited follicle growth and survival. - Highlights: • Mono-OH MXC inhibited antral follicle steroidogenesis, growth, and survival. • Pregnenolone partially restored steroidogenesis

  11. BTG/Tob family members Tob1 and Tob2 inhibit proliferation of mouse embryonic stem cells via Id3 mRNA degradation

    SciTech Connect (OSTI)

    Chen, Yuanfan; Wang, Chenchen; Wu, Jenny; Li, Lingsong

    2015-07-03

    The mammalian BTG/Tob family is a group of proteins with anti-proliferative ability, and there are six members including BTG1, BTG2/PC3/Tis21, BTG3/ANA, BTG4/PC3B, Tob1/Tob and Tob2. Among them, Tob subfamily members, specifically Tob1/Tob and Tob2, have the most extensive C-terminal regions. As previously reported, overexpression of BTG/Tob proteins is associated with the inhibition of G1 to S-phase cell cycle progression and decreased cell proliferation in a variety of cell types. Tob subfamily proteins have similar anti-proliferative effects on cell cycle progression in cultured tumor cells. An important unresolved question is whether or not they have function in rapidly proliferating cells, such as embryonic stem cells (ESCs). Tob1 and Tob2 were expressed ubiquitously in mouse ESCs (mESCs), suggesting a possible role in early embryonic development and mESCs. To address the above question and explore the possible functions of the Tob subfamily in ESCs, we established ESCs from different genotypic knockout inner cell mass (ICM). We found that Tob1{sup −/−}, Tob2{sup −/−}, and Tob1/2 double knockout (DKO, Tob1{sup −/−} & Tob2{sup −/−}) ESCs grew faster than wild type (WT) ESCs without losing pluripotency, and we provide a possible mechanistic explanation for these observations: Tob1 and Tob2 inhibit the cell cycle via degradation of Id3 mRNA, which is a set of directly targeted genes of BMP4 signaling in mESCs that play critical roles in the maintenance of ESC properties. Together, our data suggest that BTG/Tob family protein Tob1 and Tob2 regulation cell proliferation does not compromise the basic properties of mESCs. - Highlights: • We established mouse Tob1/2 double knockout embryonic stem cells. • Tob1 and Tob2 inhibit the proliferation of ESCs without effect on pluripotency. • Tob1 and Tob2 involved in the degradation of Id3 in mESCs.

  12. Metabolite signatures in hydrophilic extracts of mouse lungs exposed to cigarette smoke revealed by 1H NMR metabolomics investigation

    SciTech Connect (OSTI)

    Hu, Jian Z.; Wang, Xuan; Feng, Ju; Webb-Robertson, Bobbie-Jo M.; Waters, Katrina M.; Tilton, Susan C.; Pounds, Joel G.; Corley, Richard A.; Liu, Maili; Hu, Mary Y.

    2015-05-12

    Herein, 1H-NMR metabolomics are carried out to evaluate the changes of metabolites in lungs of mice exposed to cigarette smoke. It is found that the concentrations of adenosine derivatives (i.e. ATP, ADP and AMP), inosine and uridine are significantly fluctuated in the lungs of mice exposed to cigarette smoke compared with those of controls regardless the mouse is obese or regular weight. The decreased ATP, ADP, AMP and elevated inosine predict that the deaminases in charge of adenosine derivatives to inosine derivatives conversion are altered in lungs of mice exposed to cigarette smoke. Transcriptional analysis reveals that the concentrations of adenosine monophosphate deaminase and adenosine deaminase are different in the lungs of mice exposed to cigarette smoke, confirming the prediction from metabolomics studies. We also found, for the first time, that the ratio of glycerophosphocholine (GPC) to phosphocholine (PC) is significantly increased in the lungs of obese mice compared with regular weight mice. The ratio of GPC/PC is further elevated in the lungs of obese group by cigarette smoke exposure. Since GPC/PC ratio is a known biomarker for cancer, these results may suggest that obese group is more susceptible to lung cancer when exposed to cigarette smoke.

  13. SU-E-CAMPUS-I-05: Internal Dosimetric Calculations for Several Imaging Radiopharmaceuticals in Preclinical Studies and Quantitative Assessment of the Mouse Size Impact On Them. Realistic Monte Carlo Simulations Based On the 4D-MOBY Model

    SciTech Connect (OSTI)

    Kostou, T; Papadimitroulas, P; Kagadis, GC; Loudos, G

    2014-06-15

    Purpose: Commonly used radiopharmaceuticals were tested to define the most important dosimetric factors in preclinical studies. Dosimetric calculations were applied in two different whole-body mouse models, with varying organ size, so as to determine their impact on absorbed doses and S-values. Organ mass influence was evaluated with computational models and Monte Carlo(MC) simulations. Methods: MC simulations were executed on GATE to determine dose distribution in the 4D digital MOBY mouse phantom. Two mouse models, 28 and 34 g respectively, were constructed based on realistic preclinical exams to calculate the absorbed doses and S-values of five commonly used radionuclides in SPECT/PET studies (18F, 68Ga, 177Lu, 111In and 99mTc).Radionuclide biodistributions were obtained from literature. Realistic statistics (uncertainty lower than 4.5%) were acquired using the standard physical model in Geant4. Comparisons of the dosimetric calculations on the two different phantoms for each radiopharmaceutical are presented. Results: Dose per organ in mGy was calculated for all radiopharmaceuticals. The two models introduced a difference of 0.69% in their brain masses, while the largest differences were observed in the marrow 18.98% and in the thyroid 18.65% masses.Furthermore, S-values of the most important target-organs were calculated for each isotope. Source-organ was selected to be the whole mouse body.Differences on the S-factors were observed in the 6.0–30.0% range. Tables with all the calculations as reference dosimetric data were developed. Conclusion: Accurate dose per organ and the most appropriate S-values are derived for specific preclinical studies. The impact of the mouse model size is rather high (up to 30% for a 17.65% difference in the total mass), and thus accurate definition of the organ mass is a crucial parameter for self-absorbed S values calculation.Our goal is to extent the study for accurate estimations in small animal imaging, whereas it is known

  14. In-111 chelate conjugates of human transferrin (HTr) and mouse monoclonal anti human transferrin receptor antibody (. cap alpha. HTrR MoAb) for tumor imaging

    SciTech Connect (OSTI)

    Goodwin, D.A.; Meares, C.F.; Diamanti, C.I.; McCall, M.; McTigue, M.; Torti, F.; Martin, B.

    1984-01-01

    At least one of the major pathways of uptake of the commonly used tumor scanning agent Ga-67 is via the transferrin receptor. This suggested the use of stably radio-labeled HTr, and ..cap alpha..HTrR MoAb for tumor imaging in humans. HTr and mouse ..cap alpha..HTrR MoAb were alkylated with 1-(parabromacetamidobenzyl)-EDTA. The mM Alkylproteins, approx. =1 chelate/molecule were labeled with 1-3 mCi In-111 citrate pH/sub 5/ (Sp Act approx. = 100-300 Ci/m mole). Images were made 24 hours after 1 mCi IV and in some patients blood levels, urine excretion and digitized whole body scans were obtained at 1, 24,48 and 96 hours post injection. Ten patients with biopsy proven prostate cancer were studied with In-111 HTr, and four with In-111 ..cap alpha.. HTrR MoAb; all had positive mets on bone scan. In-111 HTr persisted in the circulation with a T1/2 of approx. = four days, approx. = 5%/day being excreted in the urine, to a total of approx. = 60% in 21 days. Nine of ten scans were false negative due to the high blood background. In-111 ..cap alpha..HTrR disappeared rapidly from the blood; with most in the bone marrow at 24 hours. ROI analysis of three patients showed whole body 94% at 24 hours, 89% at 48 hours, and 82% at 96 hours (T1/2 = 10.7 days); liver 19% at 1 hour, 25% at 24 hours, and 21% at 96 hours; spleen 3% at 1 hour, 8% at 24 hours, 7.3% at 48 hours, and 3% at 96 hours. The high bone marrow background allowed only a few of the bone mets seen as bone scan to be visualized. Other tumor types not located in bone may be more easily seen.

  15. The combination of glutamate receptor antagonist MK-801 with tamoxifen and its active metabolites potentiates their antiproliferative activity in mouse melanoma K1735-M2 cells

    SciTech Connect (OSTI)

    Ribeiro, Mariana P.C.; Nunes-Correia, Isabel; Santos, Armanda E.; Custdio, Jos B.A.

    2014-02-15

    Recent reports suggest that N-methyl-D-aspartate receptor (NMDAR) blockade by MK-801 decreases tumor growth. Thus, we investigated whether other ionotropic glutamate receptor (iGluR) antagonists were also able to modulate the proliferation of melanoma cells. On the other hand, the antiestrogen tamoxifen (TAM) decreases the proliferation of melanoma cells, and is included in combined therapies for melanoma. As the efficacy of TAM is limited by its metabolism, we investigated the effects of the NMDAR antagonist MK-801 in combination with TAM and its active metabolites, 4-hydroxytamoxifen (OHTAM) and endoxifen (EDX). The NMDAR blockers MK-801 and memantine decreased mouse melanoma K1735-M2 cell proliferation. In contrast, the NMDAR competitive antagonist APV and the AMPA and kainate receptor antagonist NBQX did not affect cell proliferation, suggesting that among the iGluR antagonists only the NMDAR channel blockers inhibit melanoma cell proliferation. The combination of antiestrogens with MK-801 potentiated their individual effects on cell biomass due to diminished cell proliferation, since it decreased the cell number and DNA synthesis without increasing cell death. Importantly, TAM metabolites combined with MK-801 promoted cell cycle arrest in G1. Therefore, the data obtained suggest that the activity of MK-801 and antiestrogens in K1735-M2 cells is greatly enhanced when used in combination. - Highlights: MK-801 and memantine decrease melanoma cell proliferation. The combination of MK-801 with antiestrogens inhibits melanoma cell proliferation. These combinations greatly enhance the effects of the compounds individually. MK-801 combined with tamoxifen active metabolites induces cell cycle arrest in G1. The combination of MK-801 and antiestrogens is an innovative strategy for melanoma.

  16. CHIR99021 promotes self-renewal of mouse embryonic stem cells by modulation of protein-encoding gene and long intergenic non-coding RNA expression

    SciTech Connect (OSTI)

    Wu, Yongyan; Ai, Zhiying; Yao, Kezhen; Cao, Lixia; Du, Juan; Shi, Xiaoyan; Guo, Zekun; Zhang, Yong

    2013-10-15

    Embryonic stem cells (ESCs) can proliferate indefinitely in vitro and differentiate into cells of all three germ layers. These unique properties make them exceptionally valuable for drug discovery and regenerative medicine. However, the practical application of ESCs is limited because it is difficult to derive and culture ESCs. It has been demonstrated that CHIR99021 (CHIR) promotes self-renewal and enhances the derivation efficiency of mouse (m)ESCs. However, the downstream targets of CHIR are not fully understood. In this study, we identified CHIR-regulated genes in mESCs using microarray analysis. Our microarray data demonstrated that CHIR not only influenced the Wnt/β-catenin pathway by stabilizing β-catenin, but also modulated several other pluripotency-related signaling pathways such as TGF-β, Notch and MAPK signaling pathways. More detailed analysis demonstrated that CHIR inhibited Nodal signaling, while activating bone morphogenetic protein signaling in mESCs. In addition, we found that pluripotency-maintaining transcription factors were up-regulated by CHIR, while several developmental-related genes were down-regulated. Furthermore, we found that CHIR altered the expression of epigenetic regulatory genes and long intergenic non-coding RNAs. Quantitative real-time PCR results were consistent with microarray data, suggesting that CHIR alters the expression pattern of protein-encoding genes (especially transcription factors), epigenetic regulatory genes and non-coding RNAs to establish a relatively stable pluripotency-maintaining network. - Highlights: • Combined use of CHIR with LIF promotes self-renewal of J1 mESCs. • CHIR-regulated genes are involved in multiple pathways. • CHIR inhibits Nodal signaling and promotes Bmp4 expression to activate BMP signaling. • Expression of epigenetic regulatory genes and lincRNAs is altered by CHIR.

  17. Transplacental arsenic plus postnatal 12-O-teradecanoyl phorbol-13-acetate exposures associated with hepatocarcinogenesis induce similar aberrant gene expression patterns in male and female mouse liver

    SciTech Connect (OSTI)

    Liu Jie . E-mail: Liu6@niehs.nih.gov; Xie Yaxiong; Merrick, B. Alex; Shen Jun; Ducharme, Danica M.K.; Collins, Jennifer; Diwan, Bhalchandra A.; Logsdon, Daniel; Waalkes, Michael P.

    2006-06-15

    Our prior work shows that in utero arsenic exposure alone is a complete transplacental carcinogen, producing hepatocellular carcinoma in adult male offspring but not in females. In a follow-up study to potentially promote arsenic-initiated tumors, mice were exposed to arsenic (85 ppm) from gestation day 8 to 18 and then exposed to 12-O-teradecanoyl phorbol-13-acetate (TPA), a well-known tumor promoter after weaning. The dermal application of TPA (2 {mu}g/0.1 ml acetone, twice/week for 21 weeks) after transplacental arsenic did not further increase arsenic-induced liver tumor formation in adult males but significantly increased liver tumor formation in adult females. Thus, for comparison, liver tumors and normal liver samples taken from adult male and female mice at necropsy were analyzed for aberrant gene/protein expression by microarray, real-time RT-PCR and Western blot analysis. Arsenic/TPA treatment resulted in increased expression of {alpha}-fetoprotein, k-ras, c-myc, estrogen receptor-{alpha}, cyclin D1, cdk2na, plasminogen activator inhibitor-1, cytokeratin-8, cytokeratin-18, glutathione S-transferases and insulin-like growth factor binding proteins in liver and liver tumors from both male and female mice. Arsenic/TPA also decreased the expression of BRCA1, betaine-homocysteine methyltransferase, CYP7B1, CYP2F2 and insulin-like growth factor-1 in normal and cancerous livers. Alterations in these gene products were associated with arsenic/TPA-induced liver tumors, regardless of sex. Thus, transplacental arsenic plus postnatal TPA exposure induced similar aberrant gene expression patterns in male and female mouse liver, which are persistent and potentially important to the mechanism of arsenic initiation of hepatocarcinogenesis.

  18. Extracellular acidification synergizes with PDGF to stimulate migration of mouse embryo fibroblasts through activation of p38MAPK with a PTX-sensitive manner

    SciTech Connect (OSTI)

    An, Caiyan; Sato, Koichi; Wu, Taoya; Bao, Muqiri; Bao, Liang; Tobo, Masayuki; Damirin, Alatangaole

    2015-05-01

    The elucidation of the functional mechanisms of extracellular acidification stimulating intracellular signaling pathway is of great importance for developing new targets of treatment for solid tumors, and inflammatory disorders characterized by extracellular acidification. In the present study, we focus on the regulation of extracellular acidification on intracellular signaling pathways in mouse embryo fibroblasts (MEFs). We found extracellular acidification was at least partly involved in stimulating p38MAPK pathway through PTX-sensitive behavior to enhance cell migration in the presence or absence of platelet-derived growth factor (PDGF). Statistical analysis showed that the actions of extracellular acidic pH and PDGF on inducing enhancement of cell migration were not an additive effect. However, we also found extracellular acidic pH did inhibit the viability and proliferation of MEFs, suggesting that extracellular acidification stimulates cell migration probably through proton-sensing mechanisms within MEFs. Using OGR1-, GPR4-, and TDAG8-gene knock out technology, and real-time qPCR, we found known proton-sensing G protein-coupled receptors (GPCRs), transient receptor potential vanilloid subtype 1 (TRPV1), and acid-sensing ion channels (ASICs) were unlikely to be involved in the regulation of acidification on cell migration. In conclusion, our present study validates that extracellular acidification stimulates chemotactic migration of MEFs through activation of p38MAPK with a PTX-sensitive mechanism either by itself, or synergistically with PDGF, which was not regulated by the known proton-sensing GPCRs, TRPV1, or ASICs. Our results suggested that others proton-sensing GPCRs or ion channels might exist in MEFs, which mediates cell migration induced by extracellular acidification in the presence or absence of PDGF. - Highlights: • Acidic pH and PDGF synergize to stimulate MEFs migration via Gi/p38MAPK pathway. • Extracellular acidification inhibits the

  19. Evaluation of Aroclor 1260 exposure in a mouse model of diet-induced obesity and non-alcoholic fatty liver disease

    SciTech Connect (OSTI)

    Wahlang, Banrida; Song, Ming; Beier, Juliane I.; Cameron Falkner, K.; Al-Eryani, Laila; Clair, Heather B.; Prough, Russell A.; Osborne, Tanasa S.; Malarkey, David E.; Christopher States, J.; Cave, Matthew C.

    2014-09-15

    Polychlorinated biphenyls (PCBs) are persistent organic pollutants associated with non-alcoholic fatty liver disease (NAFLD) in epidemiologic studies. The purpose of this study was to evaluate the hepatic effects of a PCB mixture, Aroclor 1260, whose composition mimics human bioaccumulation patterns, in a mouse model of diet-induced obesity (DIO). Male C57Bl/6J mice were fed control diet or 42% high fat diet (HFD) and exposed to Aroclor 1260 (20 mg/kg or 200 mg/kg in corn oil) for 12 weeks. A glucose tolerance test was performed; plasma/tissues were obtained at necropsy for measurements of adipocytokine levels, histology, and gene expression. Aroclor 1260 exposure was associated with decreased body fat in HFD-fed mice but had no effect on blood glucose/lipid levels. Paradoxically, Aroclor 1260 + HFD co-exposed mice demonstrated increased hepatic inflammatory foci at both doses while the degree of steatosis did not change. Serum cytokines, ALT levels and hepatic expression of IL-6 and TNFα were increased only at 20 mg/kg, suggesting an inhibition of pro-inflammatory cytokine production at the 200 mg/kg exposure. Aroclor 1260 induced hepatic expression of cytochrome P450s including Cyp3a11 (Pregnane-Xenobiotic Receptor target) and Cyp2b10 (constitutive androstane receptor target) but Cyp2b10 inducibility was diminished with HFD-feeding. Cyp1a2 (aryl hydrocarbon Receptor target) was induced only at 200 mg/kg. In summary, Aroclor 1260 worsened hepatic and systemic inflammation in DIO. The results indicated a bimodal response of PCB-diet interactions in the context of inflammation which could potentially be explained by xenobiotic receptor activation. Thus, PCB exposure may be a relevant “second hit” in the transformation of steatosis to steatohepatitis. - Highlights: • Aroclor 1260 exposure decreased adiposity in mice fed with high fat diet • Aroclor 1260 exposure induced steatohepatitis in diet-induced obese mice • Aroclor 1260 (20 and 200 mg/kg) induced

  20. 2,3,7,8-Tetrachlorodibenzo-p-dioxin treatment alters eicosanoid levels in several organs of the mouse in an aryl hydrocarbon receptor-dependent fashion

    SciTech Connect (OSTI)

    Bui, Peter; Solaimani, Parrisa [Molecular Toxicology Program, University of California, Los Angeles, California 90095 (United States) [Molecular Toxicology Program, University of California, Los Angeles, California 90095 (United States); Dept of Pathology and Laboratory Medicine, University of California, Los Angeles, California 90095 (United States); Jonsson Comprehensive Cancer Center, University of California, Los Angeles, California 90095 (United States); Wu, Xiaomeng [Dept of Pathology and Laboratory Medicine, University of California, Los Angeles, California 90095 (United States) [Dept of Pathology and Laboratory Medicine, University of California, Los Angeles, California 90095 (United States); Jonsson Comprehensive Cancer Center, University of California, Los Angeles, California 90095 (United States); Hankinson, Oliver, E-mail: ohank@mednet.ucla.edu [Molecular Toxicology Program, University of California, Los Angeles, California 90095 (United States) [Molecular Toxicology Program, University of California, Los Angeles, California 90095 (United States); Dept of Pathology and Laboratory Medicine, University of California, Los Angeles, California 90095 (United States); Jonsson Comprehensive Cancer Center, University of California, Los Angeles, California 90095 (United States); Molecular Biology Institute, University of California, Los Angeles, California 90095 (United States)

    2012-03-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) adversely affects many mammalian organs and tissues. These effects are mediated by the aryl hydrocarbon receptor (AHR). CYP1A1, CYP1A2 and CYP1B1 are upregulated by the liganded AHR. These (and other) cytochromes P450 can metabolize arachidonic acid into a variety of bioactive eicosanoids. Towards investigating a potential role of eicosanoids in TCDD toxicity, arachidonic acid, two other unsaturated long-chain fatty acids, and up to twenty-five eicosanoids were measured in five organs/tissues of male and female wild-type and Ahr null mice treated or untreated with TCDD. TCDD generally increased the levels of the four dihydroxyeicosatrienoic acids (DHETs) and (where measured) 5,6-epoxyeicosatrienoic acid and 18-, 19- and 20-hydroxyeicosatrienoic acids (HETEs) in the serum, liver, spleen and lungs, but not the heart, of both sexes, and increased the levels in the serum, liver and spleen of several metabolites that are usually considered products of lipoxygenase activity, but which may also be generated by cytochromes P450. TCDD also increased the levels of the esterified forms of these eicosanoids in the liver in parallel with the corresponding free forms. The levels of prostanoids were generally not affected by TCDD. The above changes did not occur in Ahr null mice, and are therefore mediated by the AHR. TCDD increased the mRNA levels of Cyp1a1, Cyp1a2, Cyp1b1 and the Pla2g12a form of phospholipase A{sub 2} to varying degrees in the different organs, and these increases correlated with some but not all the changes in eicosanoids levels in the organs, suggesting that other enzymes may also be involved. -- Highlights: ? TCDD treatment increases the levels of many eicosanoids in several mouse organs. ? Products of both the cytochrome P450 and classical lipoxygenase pathways are increased. ? These increases are dependent on the aryl hydrocarbon receptor. ? Cyp1a1, Cyp1a2 and Cyp1b1 appear to be responsible for much but not all

  1. Sodium arsenite represses the expression of myogenin in C2C12 mouse myoblast cells through histone modifications and altered expression of Ezh2, Glp, and Igf-1

    SciTech Connect (OSTI)

    Hong, Gia-Ming; Present address: The University of Chicago, Section of Hematology Bain, Lisa J.

    2012-05-01

    Arsenic is a toxicant commonly found in water systems and chronic exposure can result in adverse developmental effects including increased neonatal death, stillbirths, and miscarriages, low birth weight, and altered locomotor activity. Previous studies indicate that 20 nM sodium arsenite exposure to C2C12 mouse myocyte cells delayed myoblast differentiation due to reduced myogenin expression, the transcription factor that differentiates myoblasts into myotubes. In this study, several mechanisms by which arsenic could alter myogenin expression were examined. Exposing differentiating C2C12 cells to 20 nM arsenic increased H3K9 dimethylation (H3K9me2) and H3K9 trimethylation (H3K9me3) by 3-fold near the transcription start site of myogenin, which is indicative of increased repressive marks, and reduced H3K9 acetylation (H3K9Ac) by 0.5-fold, indicative of reduced permissive marks. Protein expression of Glp or Ehmt1, a H3-K9 methyltransferase, was also increased by 1.6-fold in arsenic-exposed cells. In addition to the altered histone remodeling status on the myogenin promoter, protein and mRNA levels of Igf-1, a myogenic growth factor, were significantly repressed by arsenic exposure. Moreover, a 2-fold induction of Ezh2 expression, and an increased recruitment of Ezh2 (3.3-fold) and Dnmt3a (? 2-fold) to the myogenin promoter at the transcription start site (? 40 to + 42), were detected in the arsenic-treated cells. Together, we conclude that the repressed myogenin expression in arsenic-exposed C2C12 cells was likely due to a combination of reduced expression of Igf-1, enhanced nuclear expression and promoter recruitment of Ezh2, and altered histone remodeling status on myogenin promoter (? 40 to + 42). -- Highlights: ? Igf-1 expression is decreased in C2C12 cells after 20 nM arsenite exposure. ? Arsenic exposure alters histone remodeling on the myogenin promoter. ? Glp expression, a H3K9 methyltransferase, was increased in arsenic-exposed cells. ? Ezh2 and Dnmt3a

  2. 9. international mouse genome conference

    SciTech Connect (OSTI)

    1995-12-31

    This conference was held November 12--16, 1995 in Ann Arbor, Michigan. The purpose of this conference was to provide a multidisciplinary forum for exchange of state-of-the-art information on genetic mapping in mice. This report contains abstracts of presentations, focusing on the following areas: mutation identification; comparative mapping; informatics and complex traits; mutagenesis; gene identification and new technology; and genetic and physical mapping.

  3. 2,3,7,8-Tetrachlorodibenzo-p-dioxin activates the aryl hydrocarbon receptor and alters sex steroid hormone secretion without affecting growth of mouse antral follicles in vitro

    SciTech Connect (OSTI)

    Karman, Bethany N. Basavarajappa, Mallikarjuna S. Craig, Zelieann R. Flaws, Jodi A.

    2012-05-15

    The persistent environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an ovarian toxicant. These studies were designed to characterize the actions of TCDD on steroidogenesis and growth of intact mouse antral follicles in vitro. Specifically, these studies tested the hypothesis that TCDD exposure leads to decreased sex hormone production/secretion by antral follicles as well as decreased growth of antral follicles in vitro. Since TCDD acts through binding to the aryl hydrocarbon receptor (AHR), and the AHR has been identified as an important factor in ovarian function, we also conducted experiments to confirm the presence and activation of the AHR in our tissue culture system. To do so, we exposed mouse antral follicles for 96 h to a series of TCDD doses previously shown to have effects on ovarian tissues and cells in culture, which also encompass environmentally relevant and pharmacological exposures (0.1–100 nM), to determine a dose response for TCDD in our culture system for growth, hormone production, and expression of the Ahr and Cyp1b1. The results indicate that TCDD decreases progesterone, androstenedione, testosterone, and estradiol levels in a non-monotonic dose response manner without altering growth of antral follicles. The addition of pregnenolone substrate (10 μM) restores hormone levels to control levels. Additionally, Cyp1b1 levels were increased by 3–4 fold regardless of the dose of TCDD exposure, evidence of AHR activation. Overall, these data indicate that TCDD may act prior to pregnenolone formation and through AHR transcriptional control of Cyp1b1, leading to decreased hormone levels without affecting growth of antral follicles. -- Highlights: ►TCDD disrupts sex steroid hormone levels, but not growth of antral follicles. ►Pregnenolone co-treatment by-passes TCDD-induced steroid hormone disruption. ►TCDD affects steroid hormone levels through an AHR pathway in antral follicles.

  4. Absence of correlation between Sry polymorphisms and XY sex reversal caused by the M.m. domesticus Y chromosome

    SciTech Connect (OSTI)

    Carlisle, C.; Nagamine, C.M. [Vanderbilt Univ., School of Medicine, Nashville, TN (United States)] [Vanderbilt Univ., School of Medicine, Nashville, TN (United States); Winkinig, H.; Weichenhan, D. [Medizinische Universitaet Zu Luebeck (Germany)] [Medizinische Universitaet Zu Luebeck (Germany)

    1996-04-01

    Mus musculus domesticus Y chromosomes (Y{sup DOM} Chrs) vary in their ability to induce testes in the strain C57BL/6J. In severe cases, XY females develop (XY{sup DOM} sex reversal). To identify the molecular basis for the sex reversal, a 2.7-kb region of Sry, the testis-determining gene, was sequenced from Y{sup DOM} Chrs linked to normal testis determination, transient sex reversal, and severe sex reversal. Four mutations were identified. However, no correlation exists between these mutations and severity of XY{sup DOM} sex reversal. RT-PCR identified Sry transcripts in XY{sup DOM} sex-reversed fetal gonads at 11 d.p.c., the age when Sry is hypothesized to function. In addition, no correlation exists between XY{sup DOM} sex reversal and copy numbers of pSx1, a Y-repetitive sequence whose deletion is linked to XY sex reversal. We conclude that SRY protein variants, blockade of Sry transcription, and deletion of pSx1 sequences are not the underlying causes of XY{sup DOM} sex reversal. 63 refs., 6 figs., 6 tabs.

  5. Notch-modifying xylosyltransferase structures support an SNi-like retaining mechanism

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Yu, Hongjun; Li, Huilin; Takeuchi, Megumi; LeBarron, Jamie; Kantharia, Joshua; London, Erwin; Bakker, Hans; Haltiwanger, Robert S.; Takeuchi, Hideyuki

    2015-09-28

    A major question remaining in glycobiology is how a glycosyltransferase (GT) that retains the anomeric linkage of a sugar catalyzes the reaction. Xyloside α-1,3-xylosyltransferase (XXYLT1) is a retaining GT that regulates Notch receptor activation by adding xylose to the Notch extracellular domain. Here, using natural acceptor and donor substrates and active Mus musculus XXYLT1, we report a series of crystallographic snapshots along the reaction, including an unprecedented natural and competent Michaelis reaction complex for retaining enzymes. These structures strongly support the SNi-like reaction as the retaining mechanism for XXYLT1. Unexpectedly, the epidermal growth factor–like repeat acceptor substrate undergoes a largemore » conformational change upon binding to the active site, providing a structural basis for substrate specificity. As a result, our improved understanding of this retaining enzyme will accelerate the design of retaining GT inhibitors that can modulate Notch activity in pathological situations in which Notch dysregulation is known to cause cancer or developmental disorders.« less

  6. Notch-modifying xylosyltransferase structures support an SNi-like retaining mechanism

    SciTech Connect (OSTI)

    Yu, Hongjun; Li, Huilin; Takeuchi, Megumi; LeBarron, Jamie; Kantharia, Joshua; London, Erwin; Bakker, Hans; Haltiwanger, Robert S.; Takeuchi, Hideyuki

    2015-09-28

    A major question remaining in glycobiology is how a glycosyltransferase (GT) that retains the anomeric linkage of a sugar catalyzes the reaction. Xyloside α-1,3-xylosyltransferase (XXYLT1) is a retaining GT that regulates Notch receptor activation by adding xylose to the Notch extracellular domain. Here, using natural acceptor and donor substrates and active Mus musculus XXYLT1, we report a series of crystallographic snapshots along the reaction, including an unprecedented natural and competent Michaelis reaction complex for retaining enzymes. These structures strongly support the SNi-like reaction as the retaining mechanism for XXYLT1. Unexpectedly, the epidermal growth factor–like repeat acceptor substrate undergoes a large conformational change upon binding to the active site, providing a structural basis for substrate specificity. As a result, our improved understanding of this retaining enzyme will accelerate the design of retaining GT inhibitors that can modulate Notch activity in pathological situations in which Notch dysregulation is known to cause cancer or developmental disorders.

  7. Noggin and BMP4 co-modulate adult hippocampal neurogenesis in the APP{sub swe}/PS1{sub {Delta}E9} transgenic mouse model of Alzheimer's disease

    SciTech Connect (OSTI)

    Tang, Jun; Song, Min; Wang, Yanyan; Fan, Xiaotang; Xu, Haiwei; Bai, Yun

    2009-07-31

    In addition to the subventricular zone, the dentate gyrus of the hippocampus is one of the few brain regions in which neurogenesis continues into adulthood. Perturbation of neurogenesis can alter hippocampal function, and previous studies have shown that neurogenesis is dysregulated in Alzheimer disease (AD) brain. Bone morphogenetic protein-4 (BMP4) and its antagonist Noggin have been shown to play important roles both in embryonic development and in the adult nervous system, and may regulate hippocampal neurogenesis. Previous data indicated that increased expression of BMP4 mRNA within the dentate gyrus might contribute to decreased hippocampal cell proliferation in the APP{sub swe}/PS1{sub {Delta}E9} mouse AD model. However, it is not known whether the BMP antagonist Noggin contributes to the regulation of neurogenesis. We therefore studied the relative expression levels and localization of BMP4 and its antagonist Noggin in the dentate gyrus and whether these correlated with changes in neurogenesis in 6-12 mo old APP{sub swe}/PS1{sub {Delta}E9} transgenic mice. Bromodeoxyuridine (BrdU) was used to label proliferative cells. We report that decreased neurogenesis in the APP/PS1 transgenic mice was accompanied by increased expression of BMP4 and decreased expression of Noggin at both the mRNA and protein levels; statistical analysis showed that the number of proliferative cells at different ages correlated positively with Noggin expression and negatively with BMP4 expression. Intraventricular administration of a chimeric Noggin/Fc protein was used to block the action of endogenous BMP4; this resulted in a significant increase in the number of BrdU-labeled cells in dentate gyrus subgranular zone and hilus in APP/PS1 mice. These results suggest that BMP4 and Noggin co-modulate neurogenesis.

  8. Arsenic and chromium in drinking water promote tumorigenesis in a mouse colitis-associated colorectal cancer model and the potential mechanism is ROS-mediated Wnt/β-catenin signaling pathway

    SciTech Connect (OSTI)

    Wang, Xin; Mandal, Ardhendu K.; Saito, Hiroshi; Pulliam, Joseph F.; Lee, Eun Y.; Ke, Zun-Ji; Lu, Jian; Ding, Songze; Li, Li; Shelton, Brent J.; Tucker, Thomas; Evers, B. Mark; Zhang, Zhuo; Shi, Xianglin

    2012-07-01

    Exposure to carcinogenic metals, such as trivalent arsenic [As(III)] and hexavalent chromium [Cr(VI)], through drinking water is a major global public health problem and is associated with various cancers. However, the mechanism of their carcinogenicity remains unclear. In this study, we used azoxymethane/dextran sodium sulfate (AOM/DSS)-induced mouse colitis-associated colorectal cancer model to investigate their tumorigenesis. Our results demonstrate that exposure to As(III) or Cr(VI), alone or in combination, together with AOM/DSS pretreatment has a promotion effect, increasing the colorectal tumor incidence, multiplicity, size, and grade, as well as cell inflammatory response. Two-dimensional differential gel electrophoresis coupled with mass spectrometry revealed that As(III) or Cr(VI) treatment alone significantly changed the density of proteins. The expression of β-catenin and phospho-GSK was increased by treatment of carcinogenic metals alone. Concomitantly, the expression of NADPH oxidase1 (NOX1) and the level of 8-OHdG were also increased by treatment of carcinogenic metals alone. Antioxidant enzymes, such as superoxide dismutase (SOD) and catalase, were decreased. Similarly, in an in vitro system, exposure of CRL-1807 to carcinogenic metals increased reactive oxygen species (ROS) generation, the expression of β-catenin, phospho-GSK, and NOX1. Inhibition of ROS generation by addition of SOD or catalase inhibited β-catenin expression and activity. Our study provides a new animal model to study the carcinogenicity of As(III) and Cr(VI) and suggests that As(III) and Cr(VI) promote colorectal cancer tumorigenesis, at least partly, through ROS-mediated Wnt/β-catenin signaling pathway. -- Highlights: ► Carcinogenic metals in drinking water promote colorectal tumor formation in vivo. ► Carcinogenic metals induce β-catenin activation in vivo and in vitro. ► ROS generation induced by carcinogenic metals mediated β-catenin activation.

  9. Reduction of metastasis, cell invasion, and adhesion in mouse osteosarcoma by YM529/ONO-5920-induced blockade of the Ras/MEK/ERK and Ras/PI3K/Akt pathway

    SciTech Connect (OSTI)

    Tsubaki, Masanobu; Satou, Takao; Itoh, Tatsuki; Imano, Motohiro; Ogaki, Mitsuhiko; Yanae, Masashi; Depeartment of Pharmacy, Sakai Hospital, Kinki University School of Medicine, Sakai, Osaka 590-0132 ; Nishida, Shozo

    2012-03-15

    Osteosarcoma is one of the most common primary malignant bone tumors in children and adolescents. Some patients continue to have a poor prognosis, because of the metastatic disease. YM529/ONO-5920 is a nitrogen-containing bisphosphonate that has been used for the treatment of osteoporosis. YM529/ONO-5920 has recently been reported to induce apoptosis in various tumors including osteosarcoma. However, the mode of metastasis suppression in osteosarcoma by YM529/ONO-5920 is unclear. In the present study, we investigated whether YM529/ONO-5920 inhibited tumor cell migration, invasion, adhesion, or metastasis in the LM8 mouse osteosarcoma cell line. We found that YM529/ONO-5920 significantly inhibited metastasis, cell migration, invasion, and adhesion at concentrations that did not have antiproliferative effects on LM8 cells. YM529/ONO-5920 also inhibited the mRNA expression and protein activities of matrix metalloproteinases (MMPs). In addition, YM529/ONO-5920 suppressed phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) and the serine/threonine protein kinase B (Akt) by the inhibition of Ras prenylation. Moreover, U0126, a mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor, and LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor, also inhibited LM8 cell migration, invasion, adhesion, and metastasis, as well as the mRNA expression and protein activities of MMP-1, MMP-2, MMP-9, and MT1-MMP. The results indicated that YM529/ONO-5920 suppressed the Ras/MEK/ERK and Ras/PI3K/Akt pathways, thereby inhibiting LM8 cell migration, invasion, adhesion, and metastasis. These findings suggest that YM529/ONO-5920 has potential clinical applications for the treatment of tumor cell metastasis in osteosarcoma. -- Highlights: ? We investigated whether YM529/ONO-5920 inhibited tumor metastasis in osteosarcoma. ? YM529/ONO-5920 inhibited metastasis, cell migration, invasion, and adhesion. ? YM529/ONO-5920 suppressed Ras signalings. ? YM529/ONO-5920 has

  10. Sandia Energy - Sandia Maps Multiple Paths to Cleaner, Low-Temp...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Mark Musculus and his colleagues identified the sources of key pollutants from LTC engines. Understanding how LTC works as a combustion technique may lead to broader use of...

  11. TU-F-12A-01: Quantitative Non-Linear Compartment Modeling of 89Zr- and 124I- Labeled J591 Monoclonal Antibody Kinetics Using Serial Non-Invasive Positron Emission Tomography Imaging in a Pre-Clinical Human Prostate Cancer Mouse Model

    SciTech Connect (OSTI)

    Fung, EK; Cheal, SM; Chalasani, S; Fareedy, SB; Punzalan, B; Humm, JL; Osborne, JR; Larson, SM; Zanzonico, PB; Otto, B; Bander, NH

    2014-06-15

    Purpose: To examine the binding kinetics of human IgG monoclonal antibody J591 which targets prostate-specific membrane antigen (PSMA) in a pre-clinical mouse cancer model using quantitative PET compartmental analysis of two radiolabeled variants. Methods: PSMA is expressed in normal human prostate, and becomes highly upregulated in prostate cancer, making it a promising therapeutic target. Two forms of J591, radiolabeled with either {sup 89}Zr or {sup 124}I, were prepared. {sup 89}Zr is a radiometal that becomes trapped in the cell upon internalization by the antigen-antibody complex, while radioiodine leaves the cell. Mice with prostate cancer xenografts underwent non-invasive serial imaging on a Focus 120 microPET up to 144 hours post-injection of J591. A non-linear compartmental model describing the binding and internalization of antibody in tumor xenograft was developed and applied to the PET-derived time-activity curves. The antibody-antigen association rate constant (ka), total amount of antigen per gram tumor (Ag-total), internalization rate of antibody-antigen complex, and efflux rate of radioisotope from tumor were fitted using the model. The surface-bound and the internalized activity were also estimated. Results: Values for ka, Ag-total, and internalization rate were found to be similar regardless of radiolabel payload used. The efflux rate, however, was ∼ 9-fold higher for {sup 124}I-J591 than for {sup 89}Zr-J591. Time-dependent surface-bound and internalized radiotracer activity were similar for both radiolabels at early times post-injection, but clearly differed beyond 24 hours. Conclusion: Binding and internalization of J591 to PSMA-expressing tumor xenografts were similar when radiolabeled with either {sup 89}Zr or {sup 124}I payload. The difference in efflux of radioactivity from tumor may be attributable to differential biological fate intracellularly of the radioisotopes. This has great significance for radioimmunotherapy and antibody

  12. Saving Money and Fuel with a Click of a Mouse

    Broader source: Energy.gov [DOE]

    With so many options, it can be hard to decipher what car is right for you, or if there’s a clear economic benefit in trading up to a new vehicle. Fortunately, the Energy Department offers a number of tools that can help consumers save money and fuel, whether you’re in the market for a new vehicle or trying to make the most of your current one.

  13. RAPID/Best Practices/Memorandums of Understanding (MOUs) | Open...

    Open Energy Info (EERE)

    Agencies. If necessary, enable (through legislation or otherwise) state agencies to enter into agreements with the agencies of other states to establish consistent technical...

  14. Metabonomic Profiling of TASTPM Transgenic Alzheimer's Disease Mouse Model

    SciTech Connect (OSTI)

    Hu, Zeping; Browne, Edward R.; Liu, Tao; Angel, Thomas E.; Ho, Paul C.; Chun Yong Chan, Eric

    2012-12-07

    Identification of molecular mechanisms underlying early stage Alzheimer’s disease (AD) is important for the development of new therapies against and diagnosis of AD. In this study, non-targeted metabotyping of TASTPM transgenic AD mice was performed. The metabolic profiles of both brain and plasma of TASTPM mice were characterized using gas chromatography-mass spectrometry and compared to those of wild type C57BL/6J mice. TASTPM mice were metabolically distinct compared to wild type mice (Q28 Y = 0.587 and 0.766 for PLS-DA models derived from brain and plasma, respectively). A number of metabolites were found to be perturbed in TASTPM mice in both brain (D11 fructose, L-valine, L-serine, L-threonine, zymosterol) and plasma (D-glucose, D12 galactose, linoleic acid, arachidonic acid, palmitic acid and D-gluconic acid). In addition, enzyme immunoassay confirmed that selected endogenous steroids were significantly perturbed in brain (androstenedione and 17-OH-progesterone) and plasma (cortisol and testosterone) of TASTPM mice. Ingenuity pathway analysis revealed that perturbations related to amino acid metabolism (brain), steroid biosynthesis (brain), linoleic acid metabolism (plasma) and energy metabolism (plasma) accounted for the differentiation of TASTPM and wild-type

  15. The Crystal Structure of Mouse Exo70 Reveals Unique Features...

    Office of Scientific and Technical Information (OSTI)

    OSTI Identifier: 1186909 Resource Type: Journal Article Resource Relation: Journal Name: Journal of Molecular Biology; Journal Volume: 371; Journal Issue: (2) ; 08, 2007 Publisher: ...

  16. Cleaner, More Efficient Diesel Engines

    ScienceCinema (OSTI)

    Musculus, Mark

    2014-02-26

    Mark Musculus, an engine combustion scientist at Sandia National Laboratories, led a study that outlines the science base for auto and engine manufacturers to build the next generation of cleaner, more efficient engines using low-temperature combustion. Here, Musculus discusses the work at Sandia's Combustion Research Facility.

  17. Cleaner, More Efficient Diesel Engines

    SciTech Connect (OSTI)

    Musculus, Mark

    2013-08-13

    Mark Musculus, an engine combustion scientist at Sandia National Laboratories, led a study that outlines the science base for auto and engine manufacturers to build the next generation of cleaner, more efficient engines using low-temperature combustion. Here, Musculus discusses the work at Sandia's Combustion Research Facility.

  18. Heavy-Duty Low-Temperature and Diesel Combustion & Heavy-Duty...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Peer Evaluation PDF icon ace001musculus2011o.pdf More Documents & Publications Heavy-Duty Low-Temperature and Diesel Combustion & Heavy-Duty Combustion Modeling Heavy-Duty ...

  19. An Anisotropic Fluid-Solid Model of the Mouse Heart (Conference...

    Office of Scientific and Technical Information (OSTI)

    Resource Relation: Conference: Computers in Cardiology 2009, Park City, Utah September 13-16, 2009, 36:377-380 Publisher: Computers in Cardiology and IEEE, Piscataway, NJ, United ...

  20. Radioprotective effect of combinations of WR-2721 and mercaptopropionylglycine on mouse bone marrow chromosomes

    SciTech Connect (OSTI)

    Uma Devi, P.; Prasanna, P.G. )

    1990-11-01

    The radioprotective and toxic effects of low to moderate doses of S-2-(3-aminopropylamino)ethyl phosphorothioic acid (WR-2721) and its combination with mercaptopropionylglycine (MPG) on the chromosomes of the bone marrow cells of Swiss albino mice were studied at 24 h and 14 days postirradiation. Significant protection against radiation-induced chromosome aberrations was observed with 50 mg/kg WR-2721. The protection increased with the dose of the drug administered, and the degree of protection per unit dose increment was more pronounced at lower than at higher doses. A combination of WR-2721 and MPG given before exposure resulted in a significantly greater number of normal metaphases at 24 h postirradiation compared to the respective single-drug treatment groups. On Day 14 postirradiation, when the presence of WR-2721 resulted in an increase in the frequency of aberrant cells, combination with MPG helped to reduce this value markedly, especially at WR-2721 doses below 200 mg/kg. On the basis of these results it is suggested that 150 mg/kg WR-2721 may be considered an optimum dose for combination with MPG for protection of chromosomes of bone marrow cells when repeated drug administrations are not needed. Changes in the level of glutathione (GSH) in the blood were studied at different times following the administration of 150 mg/kg WR-2721 and its combination with MPG before sham irradiation or exposure to 4.5 Gy 60Co gamma rays. The results showed that WR-2721 elevated blood GSH levels significantly above normal values by the time radiation was delivered, while MPG did not. Glutathione appears to have an important role in the action of WR-2721, while protection by MPG may not be mediated through GSH. Injection of MPG after WR-2721 helps to maintain the higher GSH level for a longer duration compared to treatment with WR-2721 alone.

  1. Preliminary X-ray crystallographic studies of mouse UPR responsive protein P58(IPK) TPR fragment

    SciTech Connect (OSTI)

    Tao, Jiahui; Wu, Yunkun [Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Ron, David [Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016 (United States); Sha, Bingdong, E-mail: bdsha@uab.edu [Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States)

    2008-02-01

    To investigate the mechanism by which P58(IPK) functions to promote protein folding within the ER, a P58(IPK) TPR fragment without the C-terminal J-domain has been crystallized. Endoplasmic reticulum (ER) stress induces the unfolded protein response (UPR), which can promote protein folding and misfolded protein degradation and attenuate protein translation and protein translocation into the ER. P58(IPK) has been proposed to function as a molecular chaperone to maintain protein-folding homeostasis in the ER under normal and stressed conditions. P58(IPK) contains nine TPR motifs and a C-terminal J-domain within its primary sequence. To investigate the mechanism by which P58(IPK) functions to promote protein folding within the ER, a P58(IPK) TPR fragment without the C-terminal J-domain was crystallized. The crystals diffract to 2.5 resolution using a synchrotron X-ray source. The crystals belong to space group P2{sub 1}, with unit-cell parameters a = 83.53, b = 92.75, c = 84.32 , ? = 90.00, ? = 119.36, ? = 90.00. There are two P58(IPK) molecules in the asymmetric unit, which corresponds to a solvent content of approximately 60%. Structure determination by MAD methods is under way.

  2. Scanning Tranmission X-ray Microscopic Analysis of Purifed Melanosomes of the Mouse Iris

    SciTech Connect (OSTI)

    Anderson,M.; Haraszti, T.; Peterson, G.; Wirick, S.; Jacobsen, C.; John, S.; Grunze, M.

    2006-01-01

    Melanosomes are specialized intracellular membrane bound organelles that produce and store melanin pigment. The composition of melanin and distribution of melanosomes determine the color of many mammalian tissues, including the hair, skin, and iris. However, the presence of melanosomes within a tissue carries potentially detrimental risks related to the cytotoxic indole-quinone intermediates produced during melanin synthesis. In order to study melanosomal molecules, including melanin and melanin-related intermediates, we have refined methods allowing spectromicroscopic analysis of purified melanosomes using scanning transmission X-ray microscopy. Here, we present for the first time absorption data for melanosomes at the carbon absorption edge ranging from 284 to 290 eV. High-resolution images of melanosomes at discrete energies demonstrate that fully melanized mature melanosomes are internally non-homogeneous, suggesting the presence of an organized internal sub-structure. Spectra of purified melanosomes are complex, partially described by a predominating absorption band at 288.4 eV with additional contributions from several minor bands. Differences in these spectra were detectable between samples from two strains of inbred mice known to harbor genetically determined melanosomal differences, DBA/2J and C57BL/6J, and are likely to represent signatures arising from biologically relevant and tractable phenomena.

  3. Microsoft Word - FINAL 2010_SPFPA_CBA With MOUs.doc

    National Nuclear Security Administration (NNSA)

    ... prohibits or otherwise makes unlawful payment to a labor organization or membership in ... F. In cases where a deduction is made which duplicates a payment already made to the Local ...

  4. Carbamazepine suppresses calpain-mediated autophagy impairment after ischemia/reperfusion in mouse livers

    SciTech Connect (OSTI)

    Kim, Jae-Sung, E-mail: Jae.Kim@surgery.ufl.edu; Wang, Jin-Hee, E-mail: jin-hee.wang@surgery.ufl.edu; Biel, Thomas G., E-mail: Thomas.Biel@surgery.ufl.edu; Kim, Do-Sung, E-mail: do-sung.kim@surgery.med.ufl.edu; Flores-Toro, Joseph A., E-mail: Joseph.Flores-Toro@surgery.ufl.edu; Vijayvargiya, Richa, E-mail: rvijayvargiya@ufl.edu; Zendejas, Ivan, E-mail: ivan.zendejas@surgery.ufl.edu; Behrns, Kevin E., E-mail: Kevin.Behrns@surgery.ufl.edu

    2013-12-15

    Onset of the mitochondrial permeability transition (MPT) plays a causative role in ischemia/reperfusion (I/R) injury. Current therapeutic strategies for reducing reperfusion injury remain disappointing. Autophagy is a lysosome-mediated, catabolic process that timely eliminates abnormal or damaged cellular constituents and organelles such as dysfunctional mitochondria. I/R induces calcium overloading and calpain activation, leading to degradation of key autophagy-related proteins (Atg). Carbamazepine (CBZ), an FDA-approved anticonvulsant drug, has recently been reported to increase autophagy. We investigated the effects of CBZ on hepatic I/R injury. Hepatocytes and livers from male C57BL/6 mice were subjected to simulated in vitro, as well as in vivo I/R, respectively. Cell death, intracellular calcium, calpain activity, changes in autophagy-related proteins (Atg), autophagic flux, MPT and mitochondrial membrane potential after I/R were analyzed in the presence and absence of 20 ?M CBZ. CBZ significantly increased hepatocyte viability after reperfusion. Confocal microscopy revealed that CBZ prevented calcium overloading, the onset of the MPT and mitochondrial depolarization. Immunoblotting and fluorometric analysis showed that CBZ blocked calpain activation, depletion of Atg7 and Beclin-1 and loss of autophagic flux after reperfusion. Intravital multiphoton imaging of anesthetized mice demonstrated that CBZ substantially reversed autophagic defects and mitochondrial dysfunction after I/R in vivo. In conclusion, CBZ prevents calcium overloading and calpain activation, which, in turn, suppresses Atg7 and Beclin-1 depletion, defective autophagy, onset of the MPT and cell death after I/R. - Highlights: A mechanism of carbamazepine (CBZ)-induced cytoprotection in livers is proposed. Impaired autophagy is a key event contributing to lethal reperfusion injury. The importance of autophagy is extended and confirmed in an in vivo model. CBZ is a potential agent to improve liver function after liver surgery.

  5. SREL Reprint #3102

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Approximately 82% of all ESTs were identified using the BLASTX algorithm to Mus and Rattus, and 34 54% of all ESTs could be assigned to a biological process gene ontology ...

  6. Women @ Energy: Marie Rinkoski Spangler | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    preparation books for airplane mechanics. Marie earned her B.A. in physics from Oberlin College (as well as a B. Mus. in clarinet performance), followed by a M.S. in solid state ...

  7. Mauritius: Energy Resources | Open Energy Information

    Open Energy Info (EERE)

    "","visitedicon":"" Country Profile Name Mauritius Population 1,236,817 GDP 14 Energy Consumption 0.06 Quadrillion Btu 2-letter ISO code MU 3-letter ISO code MUS Numeric ISO...

  8. Properties of iron-doped multicrystalline silicon grown by the float-zone technique

    SciTech Connect (OSTI)

    Ciszek, T.F.; Wang, T.H.; Ahrenkiel, R.K.; Matson, R.

    1996-05-01

    Multicrystalline Fe-doped Si ingots were float-zoned from high-purity feed rods. Fe was introduced by pill-doping, which gives uniform impurity content for small segregation coefficients (k {approximately} 10{sup {minus}5} for Fe in Si). Fe concentrations were calculated from the initial weight of the Fe pill, the molten zone geomet and the growth parameters. Values in the range of 10{sup 12}-10{sup 16} atoms/cm{sup 3} were targeted. No additional electrically active dopants were introduced. Minority charge carrier lifetime (via YAG-laser-excited, 430-MHz ultra-high-frequency-coupled, photoconductive decay) was measured on the ingots, and wafers were cut to examine grain structure and electron-beam-induced current response of grain boundaries. Observed lifetimes decreased monotonically with increasing Fe content for similar grain sizes (from {approximately}10 {mu}s to 2 {mu}s for < 10{sup {minus}3} cm{sup 2} grains, from {approximately}30 {mu}s to 2 {mu}s for {approximately}5 x 10{sup {minus}3} cm{sup 2} grains, and from {approximately}300 {mu}s to 2 {mu}s for > 10{sup {minus}2} cm{sup 2} grains) as the Fe content increased to 1 {times} 10{sup 16} atoms/cm{sup 3}.

  9. Regulation Of Nf=kb And Mnsod In Low Dose Radiation Induced Adaptive Protection Of Mouse And Human Skin Cells

    SciTech Connect (OSTI)

    Jian Li

    2012-11-07

    A sampling of publications resulting from this grant is provided. One is on the subject of NF-κB-Mediated HER2 Overexpression in Radiation-Adaptive Resistance. Another is on NF-κB-mediated adaptive resistance to ionizing radiation.

  10. Ultraviolet germicidal irradiation and its effects on elemental distributions in mouse embryonic fibroblast cells in x-ray fluorescence microanalysis

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Jin, Qiaoling; Vogt, Stefan; Lai, Barry; Chen, Si; Finney, Lydia; Gleber, Sophie-Charlotte; Ward, Jesse; Deng, Junjing; Mak, Rachel; Moonier, Nena; et al

    2015-02-23

    Rapidly-frozen hydrated (cryopreserved) specimens combined with cryo-scanning x-ray fluorescence microscopy provide an ideal approach for investigating elemental distributions in biological cells and tissues. However, because cryopreservation does not deactivate potentially infectious agents associated with Risk Group 2 biological materials, one must be concerned with contamination of expensive and complicated cryogenic x-ray microscopes when working with such materials. We employed ultraviolet germicidal irradiation to decontaminate previously cryopreserved cells under liquid nitrogen, and then investigated its effects on elemental distributions under both frozen hydrated and freeze dried states with x-ray fluorescence microscopy. We show that the contents and distributions of most biologicallymore » important elements remain nearly unchanged when compared with non-ultraviolet-irradiated counterparts, even after multiple cycles of ultraviolet germicidal irradiation and cryogenic x-ray imaging. This provides a potential pathway for rendering Risk Group 2 biological materials safe for handling in multiuser cryogenic x-ray microscopes without affecting the fidelity of the results.« less

  11. Focused ultrasound treatment of abscesses induced by methicillin resistant Staphylococcus aureus: Feasibility study in a mouse model

    SciTech Connect (OSTI)

    Rieck, Birgit; Bates, David; Pichardo, Samuel E-mail: lcuriel@lakeheadu.ca; Curiel, Laura E-mail: lcuriel@lakeheadu.ca; Zhang, Kunyan; Escott, Nicholas; Mougenot, Charles

    2014-06-15

    Purpose: To study the therapeutic effect of focused ultrasound on abscesses induced by methicillin-resistantStaphylococcus aureus (MRSA). MRSA is a major nosocomial pathogen where immunocompromised patients are prone to develop infections that are less and less responsive to regular treatments. Because of its capability to induce a rise of temperature at a very precise location, the use of focused ultrasound represents a considerable opportunity for therapy of localized MRSA-related infections. Methods: 50μl of MRSA strain USA400 bacteria suspension at a concentration of 1.32 ± 0.5 × 10{sup 5} colony forming units (cfu)/μl was injected subcutaneously in the left flank of BALB/c mice. An abscess of 6 ± 2 mm in diameter formed after 48 h. A transducer operating at 3 MHz with a focal length of 50 mm and diameter of 32 mm was used to treat the abscess. The focal point was positioned 2 mm under the skin at the abscess center. Forty-eight hours after injection four ultrasound exposures of 9 s each were applied to each abscess under magnetic resonance imaging guidance. Each exposure was followed by a 1 min pause. These parameters were based on preliminary experiments to ensure repetitive accurate heating of the abscess. Real-time estimation of change of temperature was done using water-proton resonance frequency and a communication toolbox (matMRI) developed inhouse. Three experimental groups of animals each were tested: control, moderate temperature (MT), and high temperature (HT). MT and HT groups reached, respectively, 52.3 ± 5.1 and 63.8 ± 7.5 °C at the end of exposure. Effectiveness of the treatment was assessed by evaluating the bacteria amount of the treated abscess 1 and 4 days after treatment. Myeloperoxidase (MPO) assay evaluating the neutrophil amount was performed to assess the local neutrophil recruitment and the white blood cell count was used to evaluate the systemic inflammatory response after focused ultrasound treatment. Results: Macroscopic evaluation of treated abscess indicated a diminution of external size of abscess 1 day after treatment. Treatment did not cause open wounds. The median (lower to upper quartile) bacterial count 1 day after treatment was 6.18 × 10{sup 3} (0.76 × 10{sup 3}–11.18 × 10{sup 3}), 2.86 × 10{sup 3} (1.22 × 10{sup 3}–7.07 × 10{sup 3}), and 3.52 × 10{sup 3} (1.18 × 10{sup 3}–6.72 × 10{sup 3}) cfu/100 μl for control, MT and HT groups, respectively; for the 4-day end point, the count was 1.37 × 10{sup 3} (0.67 × 10{sup 3}–2.89 × 10{sup 3}), 1.35 × 10{sup 3} (0.09 × 10{sup 3}–2.96 × 10{sup 3}), and 0.07 × 10{sup 3} (0.03 × 10{sup 3}–0.36 × 10{sup 3}) cfu/100 μl for control, MT and HT, showing a significant reduction (p = 0.002) on the bacterial load four days after focused ultrasound treatment when treating at high temperature (HT). The MPO amount remained unchanged between groups and days, indicating no change on local neutrophil recruitment in the abscess caused by the treatment. The white blood cell count remained unchanged between groups and days indicating that no systemic inflammatory response was caused by the treatment. Conclusions: Focused ultrasound induces a therapeutic effect in abscesses induced by MRSA. This effect is observed as a reduction of the number bacteria without significantly altering the amount of MPO at the site of a MRSA-induced abscess. These initial results suggest that focused ultrasound is a viable option for the treatment of localized MRSA-related infections.

  12. Ultraviolet germicidal irradiation and its effects on elemental distributions in mouse embryonic fibroblast cells in x-ray fluorescence microanalysis

    SciTech Connect (OSTI)

    Jin, Qiaoling; Vogt, Stefan; Lai, Barry; Chen, Si; Finney, Lydia; Gleber, Sophie-Charlotte; Ward, Jesse; Deng, Junjing; Mak, Rachel; Moonier, Nena; Jacobsen, Chris; Brody, James P.

    2015-02-23

    Rapidly-frozen hydrated (cryopreserved) specimens combined with cryo-scanning x-ray fluorescence microscopy provide an ideal approach for investigating elemental distributions in biological cells and tissues. However, because cryopreservation does not deactivate potentially infectious agents associated with Risk Group 2 biological materials, one must be concerned with contamination of expensive and complicated cryogenic x-ray microscopes when working with such materials. We employed ultraviolet germicidal irradiation to decontaminate previously cryopreserved cells under liquid nitrogen, and then investigated its effects on elemental distributions under both frozen hydrated and freeze dried states with x-ray fluorescence microscopy. We show that the contents and distributions of most biologically important elements remain nearly unchanged when compared with non-ultraviolet-irradiated counterparts, even after multiple cycles of ultraviolet germicidal irradiation and cryogenic x-ray imaging. This provides a potential pathway for rendering Risk Group 2 biological materials safe for handling in multiuser cryogenic x-ray microscopes without affecting the fidelity of the results.

  13. Di(2-ethylhexyl) phthalate inhibits antral follicle growth, induces atresia, and inhibits steroid hormone production in cultured mouse antral follicles

    SciTech Connect (OSTI)

    Hannon, Patrick R. Brannick, Katherine E. Wang, Wei Gupta, Rupesh K. Flaws, Jodi A.

    2015-04-01

    Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental toxicant found in consumer products that causes ovarian toxicity. Antral follicles are the functional ovarian units and must undergo growth, survival from atresia, and proper regulation of steroidogenesis to ovulate and produce hormones. Previous studies have determined that DEHP inhibits antral follicle growth and decreases estradiol levels in vitro; however, the mechanism by which DEHP elicits these effects is unknown. The present study tested the hypothesis that DEHP directly alters regulators of the cell cycle, apoptosis, and steroidogenesis to inhibit antral follicle functionality. Antral follicles from adult CD-1 mice were cultured with vehicle control or DEHP (1–100 μg/ml) for 24–96 h to establish the temporal effects of DEHP on the follicle. Following 24–96 h of culture, antral follicles were subjected to gene expression analysis, and media were subjected to measurements of hormone levels. DEHP increased the mRNA levels of cyclin D2, cyclin dependent kinase 4, cyclin E1, cyclin A2, and cyclin B1 and decreased the levels of cyclin-dependent kinase inhibitor 1A prior to growth inhibition. Additionally, DEHP increased the mRNA levels of BCL2-associated agonist of cell death, BCL2-associated X protein, BCL2-related ovarian killer protein, B-cell leukemia/lymphoma 2, and Bcl2-like 10, leading to an increase in atresia. Further, DEHP decreased the levels of progesterone, androstenedione, and testosterone prior to the decrease in estradiol levels, with decreased mRNA levels of side-chain cleavage, 17α-hydroxylase-17,20-desmolase, 17β-hydroxysteroid dehydrogenase, and aromatase. Collectively, DEHP directly alters antral follicle functionality by inhibiting growth, inducing atresia, and inhibiting steroidogenesis. - Highlights: • DEHP inhibits antral follicle growth by dysregulating cell cycle regulators. • DEHP induces antral follicle atresia by dysregulating apoptosis regulators. • DEHP inhibits the production of antral follicle produced sex steroid hormones.

  14. Conditional inactivation of Brca1 in the mouse ovarian surface epithelium results in an increase in preneoplastic changes

    SciTech Connect (OSTI)

    Clark-Knowles, Katherine V. . E-mail: kclar075@uottawa.ca; Garson, Kenneth; Jonkers, Jos; Vanderhyden, Barbara C.

    2007-01-01

    Epithelial ovarian cancer (EOC) is thought to arise from the ovarian surface epithelium (OSE); however, the molecular events underlying this transformation are poorly understood. Germline mutations in the BRCA1 tumor suppressor gene result in a significantly increased risk of developing EOC and a large proportion of sporadic EOCs display some sort of BRCA1 dysfunction. Using mice with conditional expression of Brca1, we inactivated Brca1 in the murine OSE and demonstrate that this inactivation results in the development of preneoplastic changes, such as hyperplasia, epithelial invaginations, and inclusion cysts, which arise earlier and are more numerous than in control ovaries. These changes resemble the premalignant lesions that have been reported in human prophylactic oophorectomy specimens from women with BRCA1 germline mutation. We also report that inactivation of Brca1 in primary cultures of murine OSE cells leads to a suppression of proliferation due to increased apoptosis that can be rescued by concomitant inactivation of p53. These observations, along with our finding that these cells display an increased sensitivity to the DNA-damaging agent cisplatin, indicate that loss of function of Brca1 in OSE cells impacts both cellular growth control and DNA-damage repair which results in altered cell behavior manifested as morphological changes in vivo that arise earlier and are more numerous than what can be attributed to ageing.

  15. Biodiesel versus diesel exposure: Enhanced pulmonary inflammation, oxidative stress, and differential morphological changes in the mouse lung

    SciTech Connect (OSTI)

    Yanamala, Naveena; Birch, M. Eileen; Kisin, Elena; Bugarski, Aleksandar D.

    2013-10-15

    The use of biodiesel (BD) or its blends with petroleum diesel (D) is considered to be a viable approach to reduce occupational and environmental exposures to particulate matter (PM). Due to its lower particulate mass emissions compared to D, use of BD is thought to alleviate adverse health effects. Considering BD fuel is mainly composed of unsaturated fatty acids, we hypothesize that BD exhaust particles could induce pronounced adverse outcomes, due to their ability to readily oxidize. The main objective of this study was to compare the effects of particles generated by engine fueled with neat BD and neat petroleum-based D. Biomarkers of tissue damage and inflammation were significantly elevated in lungs of mice exposed to BD particulates. Additionally, BD particulates caused a significant accumulation of oxidatively modified proteins and an increase in 4-hydroxynonenal. The up-regulation of inflammatory cytokines/chemokines/growth factors was higher in lungs upon BD particulate exposure. Histological evaluation of lung sections indicated presence of lymphocytic infiltrate and impaired clearance with prolonged retention of BD particulate in pigment laden macrophages. Taken together, these results clearly indicate that BD exhaust particles could exert more toxic effects compared to D. - Highlights: • Exposure of mice to BDPM caused higher pulmonary toxicity compared to DPM. • Oxidative stress and inflammation were higher in BD vs to D exposed mice. • Inflammatory lymphocyte infiltrates were seen only in lungs of mice exposed to BD. • Ineffective clearance, prolonged PM retention was present only after BD exposure.

  16. The role of acetate in alcohol-induced alterations of uterine glucose metabolism in the mouse during pregnancy

    SciTech Connect (OSTI)

    Simm, B. ); Murdoch, R.N. )

    1990-01-01

    The acute exposure of mice to ethanol during post-implantation pregnancy has been reported to cause alterations in the levels of several glycolytic intermediates in the uterus, suggesting a possible indirect mechanism of alcohol embryo-toxicity. The present study was undertaken to assess whether the ethanol metabolite, acetate is implicated in this phenomenon. Blood and uterine alcohol concentrations in day 9 - pregnant Quackenbush Swiss mice were maximal 15 minutes after the intraperitoneal injection of ethanol, and fell to almost negligible levels 6 hours later. In response to this treatment, the levels of blood and uterine acetate increased, liver glycogen decreased, plasma glucose increased, and uterine glucose, glucose-6-phosphate (G-6-P), fructose-6-phosphate (F-6-P), and citrate increased. When acetate was administered to pregnant mice in amounts approximating those generated by exposure to alcohol, the levels of uterine F-6-P and citrate increased while other metabolic parameters remained unaffected. The administration of 4-methylpyrazole to mice subsequently treated with alcohol produced conditions of alcohol exposure in the absence of ethanol-derived acetate and depressed the ethanol-induced rise in uterine G-6-P and citrate.

  17. DNA repair efficiency in germ cells and early mouse embryos and consequences for radiation-induced transgenerational genomic damage

    SciTech Connect (OSTI)

    Marchetti, Francesco; Wyrobek, Andrew J.

    2009-01-18

    Exposure to ionizing radiation and other environmental agents can affect the genomic integrity of germ cells and induce adverse health effects in the progeny. Efficient DNA repair during gametogenesis and the early embryonic cycles after fertilization is critical for preventing transmission of DNA damage to the progeny and relies on maternal factors stored in the egg before fertilization. The ability of the maternal repair machinery to repair DNA damage in both parental genomes in the fertilizing egg is especially crucial for the fertilizing male genome that has not experienced a DNA repair-competent cellular environment for several weeks prior to fertilization. During the DNA repair-deficient period of spermatogenesis, DNA lesions may accumulate in sperm and be carried into the egg where, if not properly repaired, could result in the formation of heritable chromosomal aberrations or mutations and associated birth defects. Studies with female mice deficient in specific DNA repair genes have shown that: (i) cell cycle checkpoints are activated in the fertilized egg by DNA damage carried by the sperm; and (ii) the maternal genotype plays a major role in determining the efficiency of repairing genomic lesions in the fertilizing sperm and directly affect the risk for abnormal reproductive outcomes. There is also growing evidence that implicates DNA damage carried by the fertilizing gamete as a mediator of postfertilization processes that contribute to genomic instability in subsequent generations. Transgenerational genomic instability most likely involves epigenetic mechanisms or error-prone DNA repair processes in the early embryo. Maternal and embryonic DNA repair processes during the early phases of mammalian embryonic development can have far reaching consequences for the genomic integrity and health of subsequent generations.

  18. The systemic delivery of an oncolytic adenovirus expressing decorin inhibits bone metastasis in a mouse model of human prostate cancer

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Xu, Weidong; Neill, Thomas; Yang, Yuefeng; Hu, Zebin; Cleveland, Elyse; Wu, Ying; Hutten, Ryan; Xiao, Xianghui; Stock, Stuart R.; Shevrin, Daniel; et al

    2014-12-11

    In an effort to develop a new therapy for prostate cancer bone metastases, we have created Ad.dcn, a recombinant oncolytic adenovirus carrying the human decorin gene. Infection of PC-3 and DU-145, the human prostate tumor cells, with Ad.dcn or a non-replicating adenovirus Ad(E1-).dcn resulted in decorin expression; Ad.dcn produced high viral titers and cytotoxicity in human prostate tumor cells. Adenoviral-mediated decorin expression inhibited Met, the Wnt/β- catenin signaling axis, vascular endothelial growth factor A, reduced mitochondrial DNA levels, and inhibited tumor cell migration. To examine the anti-tumor response of Ad.dcn, PC-3-luc cells were inoculated in the left heart ventricle tomore » establish bone metastases in nude mice. Ad.dcn, in conjunction with control replicating and non-replicating vectors were injected via tail vein. The real-time monitoring of mice, once a week, by bioluminescence imaging and X-ray radiography showed that Ad.dcn produced significant inhibition of skeletal metastases. Analyses of the mice at the terminal time point indicated a significant reduction in the tumor burden, osteoclast number, serum TRACP 5b levels, osteocalcin levels, hypercalcemia, inhibition of cancer cachexia, and an increase in the animal survival. Finally, based on these studies, we believe that Ad.dcn can be developed as a potential new therapy for prostate cancer bone metastasis.« less

  19. S Synchrophasor

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    ieee power & energy magazine september/october 2015 U.S. Government work not protected by U.S Copyright. S Synchrophasor Technology and the DOE Digital Object Identifier 10.1109/MPE.2015.2431211 Date of publication: 18 August 2015 By Phil Overholt, David Ortiz, and Alison Silverstein synchrophasor technology has grown from a handful of phasor measurement units (pMUs) in the U.s. pacific northwest to a continental network of almost 2,000 pMUs in the past decade, which has helped to improve

  20. Process for recovery of hydrogen and

    DOE Patents [OSTI]

    James, Brian R.; Li-Lee, Chung; Lilga, Michael A.; Nelson, David A.

    1987-01-01

    on of sulfur Abstract A process of abstracting sulfur from H.sub.2 S and generating hydrogen is disclosed comprising dissolving Pd.sub.2 X.sub.2 (.mu.-dppm).sub.2 in a solvent and then introducing H.sub.2 S. The palladium complex abstracts sulfur, forming hydrogen and a (.mu.-S) complex. The (.mu.-S) complex is readily oxidizable to a (.mu.-SO.sub.2) adduct which spontaneously loses SO.sub.2 and regenerates the palladium complex.

  1. Engineering shallow spins in diamond with nitrogen delta-doping

    SciTech Connect (OSTI)

    Ohno, Kenichi; Joseph Heremans, F.; Bassett, Lee C.; Myers, Bryan A.; Toyli, David M.; Bleszynski Jayich, Ania C.; Palmstrom, Christopher J.; Awschalom, David D.

    2012-08-20

    We demonstrate nanometer-precision depth control of nitrogen-vacancy (NV) center creation near the surface of synthetic diamond using an in situ nitrogen delta-doping technique during plasma-enhanced chemical vapor deposition. Despite their proximity to the surface, doped NV centers with depths (d) ranging from 5 to 100 nm display long spin coherence times, T{sub 2} > 100 {mu}s at d = 5 nm and T{sub 2} > 600 {mu}s at d {>=} 50 nm. The consistently long spin coherence observed in such shallow NV centers enables applications such as atomic-scale external spin sensing and hybrid quantum architectures.

  2. Cytotoxic effects in 3T3-L1 mouse and WI-38 human fibroblasts following 72 hour and 7 day exposures to commercial silica nanoparticles

    SciTech Connect (OSTI)

    Stępnik, Maciej; Arkusz, Joanna; Smok-Pieniążek, Anna; Bratek-Skicki, Anna; Salvati, Anna; Lynch, Iseult; Dawson, Kenneth A.; Gromadzińska, Jolanta; De Jong, Wim H.; Rydzyński, Konrad

    2012-08-15

    The potential toxic effects in murine (3T3-L1) and human (WI-38) fibroblast cell lines of commercially available silica nanoparticles (NPs), Ludox CL (nominal size 21 nm) and CL-X (nominal size of 30 nm) were investigated with particular attention to the effect over long exposure times (the tests were run after 72 h exposure up to 7 days). These two formulations differed in physico-chemical properties and showed different stabilities in the cell culture medium used for the experiments. Ludox CL silica NPs were found to be cytotoxic only at the higher concentrations to the WI-38 cells (WST-1 and LDH assays) but not to the 3T3-L1 cells, whereas the Ludox CL-X silica NPs, which were less stable over the 72 h exposure, were cytotoxic to both cell lines in both assays. In the clonogenic assay both silica NPs induced a concentration dependent decrease in the surviving fraction of 3T3-L1 cells, with the Ludox CL-X silica NPs being more cytotoxic. Cell cycle analysis showed a trend indicating alterations in both cell lines at different phases with both silica NPs tested. Buthionine sulfoximine (γ-glutamylcysteine synthetase inhibitor) combined with Ludox CL-X was found to induce a strong decrease in 3T3-L1 cell viability which was not observed for the WI-38 cell line. This study clearly indicates that longer exposure studies may give important insights on the impact of nanomaterials on cells. However, and especially when investigating nanoparticle effects after such long exposure, it is fundamental to include a detailed physico-chemical characterization of the nanoparticles and their dispersions over the time scale of the experiment, in order to be able to interpret eventual impacts on cells. -- Highlights: ► Ludox CL silica NPs are cytotoxic to WI-38 fibroblasts but not to 3T3-L1 fibroblasts. ► Ludox CL-X silica NPs are cytotoxic to both cell lines. ► In clonogenic assay both silica NPs induce cytotoxicity, higher for CL-X silica. ► Cell cycle analysis shows alterations in both cell lines with both silica NP tested. ► Buthionine sulfoximine enhances cytotoxicity of Ludox CL-X in 3T3-L1 cells.

  3. Exposure to Ionizing Radiation Causes Long-Term Increase in Serum Estradiol and Activation of PI3K-Akt Signaling Pathway in Mouse Mammary Gland

    SciTech Connect (OSTI)

    Suman, Shubhankar; Johnson, Michael D.; Fornace, Albert J.; Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC ; Datta, Kamal

    2012-10-01

    Purpose: Exposure to ionizing radiation is an established risk factor for breast cancer. Radiation exposure during infancy, childhood, and adolescence confers the highest risk. Although radiation is a proven mammary carcinogen, it remains unclear where it acts in the complex multistage process of breast cancer development. In this study, we investigated the long-term pathophysiologic effects of ionizing radiation at a dose (2 Gy) relevant to fractionated radiotherapy. Methods and Materials: Adolescent (6-8 weeks old; n = 10) female C57BL/6J mice were exposed to 2 Gy total body {gamma}-radiation, the mammary glands were surgically removed, and serum and urine samples were collected 2 and 12 months after exposure. Molecular pathways involving estrogen receptor-{alpha} (ER{alpha}) and phosphatidylinositol-3-OH kinase (PI3K)-Akt signaling were investigated by immunohistochemistry and Western blot. Results: Serum estrogen and urinary levels of the oncogenic estrogen metabolite (16{alpha}OHE1) were significantly increased in irradiated animals. Immunostaining for the cellular proliferative marker Ki-67 and cyclin-D1 showed increased nuclear accumulation in sections of mammary glands from irradiated vs. control mice. Marked increase in p85{alpha}, a regulatory sub-unit of the PI3K was associated with increase in Akt, phospho-Akt, phospho-BAD, phospho-mTOR, and c-Myc in irradiated samples. Persistent increase in nuclear ER{alpha} in mammary tissues 2 and 12 months after radiation exposure was also observed. Conclusions: Taken together, our data not only support epidemiologic observations associating radiation and breast cancer but also, specify molecular events that could be involved in radiation-induced breast cancer.

  4. Effect of long-term culturing on the potential of mouse embryonic stem cells for in vitro and in vivo development

    SciTech Connect (OSTI)

    Mitalipov, Sh.M.; Mitalipova, M.M.; Ivanov, V.I.

    1994-11-01

    We performed comparative analysis of in vitro and in vivo pluripotency for two clones of ES-D3 cells subjected to different number of passages after the beginning of subcloning. Both clones of ES cells produced characteristically shaped colonies and embryoid bodies during culturing in suspension. High activity of alkaline phosphatase was demonstrated in ES cells by cytochemical staining. The proportion of aneuploid ES cells increased with the increase in the number of passages, as shown by karyotyping. Experiments on producing chimeric mice using ES cells have shown that clone D3W (passage 17) exceeds clone D3M (passage 42) both in terms of chimera proportion among the offspring and in terms of the extent of coat chimerism (proportion of agouti coat color (ES component) in the coat of chimeras). 26 refs., 4 figs., 3 tabs.

  5. Bisphenol A at a low concentration boosts mouse spermatogonial cell proliferation by inducing the G protein-coupled receptor 30 expression

    SciTech Connect (OSTI)

    Sheng, Zhi-Guo; Huang, Wei; Liu, Yu-Xiang; Zhu, Ben-Zhan

    2013-02-15

    Bisphenol A (BPA) is one of the most prevalent chemicals in daily-use materials, therefore, human exposure to BPA is ubiquitous. We found that low concentrations of BPA stimulate the spermatogonial GC-1 cells proliferation by G protein-coupled receptor 30 (GPR30)-mediated epidermal growth factor receptor (EGFR)-extracellular regulated kinase (ERK)-c-Fos pathway. However, through the same pathway GPR30 expression has been shown to be induced by EGF, an EGFR ligand. Thus, we want to know if low concentrations of BPA are able to induce the GPR30 expression and the possible mechanism(s) in GC-1 cells. By transient transfection with expression plasmids, 10{sup ?9} M BPA significantly transactivates the Gpr30-5?-flanking region through activating the GPR30, cGMP-dependent protein kinase (PKG), estrogen receptor-? (ER-?), and EFGR-ERK pathways. Furthermore, an activator protein-1 (AP-1) site located within this region is found to be responsible for the transactivation of BPA. Expectedly, through the same pathways, BPA significantly induces the gene and protein expression of GPR30. c-Fos is further observed to be strongly recruited to the AP-1 site in a chromatin immunoprecipitation assay and its dysfunction on the AP-1 site markedly suppresses the expression of GPR30, p-ERK1/2, p-Ser118-ER-? and cell proliferation by BPA. Our results demonstrate that a low-concentration BPA induces GPR30 expression through the GPR30-EFGR-ERK-c-Fos, ER-?, and PKG pathways, presumably boosting the cells proliferation via a regulatory loop. The present study provides a novel insight into the potential role of GPR30 in the initiation and progression of male germ cell cancer induced by environmentally relevant BPA. - Highlights: ? Low concentrations of BPA activate the PKG and GPR30-EFGR-ERK-ER-? pathways. ? Low concentrations of BPA activate the AP-1 site of Gpr30-5?-flanking region. ? Low concentrations of BPA induce the expression of GPR30 gene and protein. ? Low concentrations of BPA boost GC-1 cells proliferation via a regulatory loop.

  6. Application of a fuzzy neural network model in predicting polycyclic aromatic hydrocarbon-mediated perturbations of the Cyp1b1 transcriptional regulatory network in mouse skin

    SciTech Connect (OSTI)

    Larkin, Andrew; Siddens, Lisbeth K.; Krueger, Sharon K.; Tilton, Susan C.; Waters, Katrina M.; Williams, David E.; Baird, William M.

    2013-03-01

    Polycyclic aromatic hydrocarbons (PAHs) are present in the environment as complex mixtures with components that have diverse carcinogenic potencies and mostly unknown interactive effects. Non-additive PAH interactions have been observed in regulation of cytochrome P450 (CYP) gene expression in the CYP1 family. To better understand and predict biological effects of complex mixtures, such as environmental PAHs, an 11 gene input-1 gene output fuzzy neural network (FNN) was developed for predicting PAH-mediated perturbations of dermal Cyp1b1 transcription in mice. Input values were generalized using fuzzy logic into low, medium, and high fuzzy subsets, and sorted using k-means clustering to create Mamdani logic functions for predicting Cyp1b1 mRNA expression. Model testing was performed with data from microarray analysis of skin samples from FVB/N mice treated with toluene (vehicle control), dibenzo[def,p]chrysene (DBC), benzo[a]pyrene (BaP), or 1 of 3 combinations of diesel particulate extract (DPE), coal tar extract (CTE) and cigarette smoke condensate (CSC) using leave-one-out cross-validation. Predictions were within 1 log{sub 2} fold change unit of microarray data, with the exception of the DBC treatment group, where the unexpected down-regulation of Cyp1b1 expression was predicted but did not reach statistical significance on the microarrays. Adding CTE to DPE was predicted to increase Cyp1b1 expression, whereas adding CSC to CTE and DPE was predicted to have no effect, in agreement with microarray results. The aryl hydrocarbon receptor repressor (Ahrr) was determined to be the most significant input variable for model predictions using back-propagation and normalization of FNN weights. - Highlights: ? Tested a model to predict PAH mixture-mediated changes in Cyp1b1 expression ? Quantitative predictions in agreement with microarrays for Cyp1b1 induction ? Unexpected difference in expression between DBC and other treatments predicted ? Model predictions for combining PAH mixtures in agreement with microarrays ? Predictions highly dependent on aryl hydrocarbon receptor repressor expression.

  7. AAV-mediated delivery of the transcription factor XBP1s into the striatum reduces mutant Huntingtin aggregation in a mouse model of Huntington's disease

    SciTech Connect (OSTI)

    Zuleta, Amparo [Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago (Chile) [Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago (Chile); Center for Molecular Studies of the Cell, Institute of Biomedical Sciences, University of Chile, Santiago (Chile); Vidal, Rene L. [Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago (Chile) [Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago (Chile); Neurounion Biomedical Foundation, Santiago (Chile); Armentano, Donna; Parsons, Geoffrey [Department of Molecular Biology, Genzyme Corporation, 49 New York Avenue, Framingham, MA 01701 (United States)] [Department of Molecular Biology, Genzyme Corporation, 49 New York Avenue, Framingham, MA 01701 (United States); Hetz, Claudio, E-mail: chetz@med.uchile.cl [Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago (Chile) [Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago (Chile); Center for Molecular Studies of the Cell, Institute of Biomedical Sciences, University of Chile, Santiago (Chile); Department of Immunology and Infectious Diseases, Harvard School of Public Health, 651 Huntington Av., Boston, MA 02446 (United States); Neurounion Biomedical Foundation, Santiago (Chile)

    2012-04-13

    Highlights: Black-Right-Pointing-Pointer The contribution of ER stress to HD has not been directly addressed. Black-Right-Pointing-Pointer Expression of XBP1s using AAVs decreases Huntingtin aggregation in vivo. Black-Right-Pointing-Pointer We describe a new in vivo model of HD based on the expression of a large fragment of mHtt-RFP. -- Abstract: Huntington's disease (HD) is caused by mutations that expand a polyglutamine region in the amino-terminal domain of Huntingtin (Htt), leading to the accumulation of intracellular inclusions and progressive neurodegeneration. Recent reports indicate the engagement of endoplasmic reticulum (ER) stress responses in human HD post mortem samples and animal models of the disease. Adaptation to ER stress is mediated by the activation of the unfolded protein response (UPR), an integrated signal transduction pathway that attenuates protein folding stress by controlling the expression of distinct transcription factors including X-Box binding protein 1 (XBP1). Here we targeted the expression of XBP1 on a novel viral-based model of HD. We delivered an active form of XBP1 locally into the striatum of adult mice using adeno-associated vectors (AAVs) and co-expressed this factor with a large fragment of mutant Htt as a fusion protein with RFP (Htt588{sup Q95}-mRFP) to directly visualize the accumulation of Htt inclusions in the brain. Using this approach, we observed a significant reduction in the accumulation of Htt588{sup Q95}-mRFP intracellular inclusion when XBP1 was co-expressed in the striatum. These results contrast with recent findings indicating a protective effect of XBP1 deficiency in neurodegeneration using knockout mice, and suggest a potential use of gene therapy strategies to manipulate the UPR in the context of HD.

  8. Neurobehavioral impairments, generation of oxidative stress and release of pro-apoptotic factors after chronic exposure to sulphur mustard in mouse brain

    SciTech Connect (OSTI)

    Sharma, Deep Raj; Sunkaria, Aditya; Bal, Amanjit; Bhutia, Yangchen D.; Vijayaraghavan, R.; Flora, S.J.S.; Gill, Kiran Dip

    2009-10-15

    Recent global events have focused attention on the potential threat of international and domestic chemical terrorism, as well as the possibility of chemical warfare proliferation. Sulphur mustard (SM) is one of the potent chemical warfare agents (CWA), which initiates a cascade of events that converge on the redox mechanisms common to brain injury. The present study was designed to examine the effects of chronic SM exposure on neurobehavioral impairments, mitochondrial oxidative stress in male Swiss Albino mice and its role in inducing apoptotic neuronal cell death. The animals were divided into four groups (control, low, medium and high dose) of 5 animals each. Exposure to SM was given percutaneously daily for 12 weeks. The results demonstrated impairment in neurobehavioral indices viz. rota rod, passive avoidance and water maze tests in a dose dependent manner. There was a significant increase in lipid peroxidation and protein carbonyl content whereas, decrease in the activity of manganese superoxide dismutase (MnSOD), glutathione reductase and glutathione peroxidase suggesting impaired antioxidant defense system. Immunoblotting of cytochrome c, Bcl-2, Bax and activation of caspase-3 suggest induction of apoptosis in a dose dependent manner. Finally, increased p53 expression suggests that it may target the mitochondrial pathway for inducing apoptosis in response to DNA damage signals. In conclusion, chronic SM exposure may have the potential to generate oxidative stress which may trigger the release of cytochrome c as well as caspase-3 activation in neurons leading to cell death by apoptosis in a dose dependent manner which may in the end be responsible for the disruption of cognitive functions in mice.

  9. Lupeol induces p53 and cyclin-B-mediated G2/M arrest and targets apoptosis through activation of caspase in mouse skin

    SciTech Connect (OSTI)

    Nigam, Nidhi Prasad, Sahdeo; George, Jasmine; Shukla, Yogeshwer

    2009-04-03

    Lupeol, present in fruits and medicinal plants, is a biologically active compound that has been shown to have various pharmacological properties in experimental studies. In the present study, we demonstrated the modulatory effect of lupeol on 7,12-dimethylbenz[a]anthracene (DMBA)-induced alterations on cell proliferation in the skin of Swiss albino mice. Lupeol treatment showed significant (p < 0.05) preventive effects with marked inhibition at 48, 72, and 96 h against DMBA-mediated neoplastic events. Cell-cycle analysis showed that lupeol-induced G2/M-phase arrest (16-37%) until 72 h, and these inhibitory effects were mediated through inhibition of the cyclin-B-regulated signaling pathway involving p53, p21/WAF1, cdc25C, cdc2, and cyclin-B gene expression. Further lupeol-induced apoptosis was observed, as shown by an increased sub-G1 peak (28%) at 96 h, with upregulation of bax and caspase-3 genes and downregulation of anti-apoptotic bcl-2 and survivin genes. Thus, our results indicate that lupeol has novel anti-proliferative and apoptotic potential that may be helpful in designing strategies to fight skin cancer.

  10. Heavy-Duty Low-Temperature and Diesel Combustion & Heavy-Duty Combustion

    Broader source: Energy.gov (indexed) [DOE]

    Modeling | Department of Energy 1 DOE Hydrogen and Fuel Cells Program, and Vehicle Technologies Program Annual Merit Review and Peer Evaluation ace001_musculus_2011_o.pdf (1.84 MB) More Documents & Publications Heavy-Duty Low-Temperature and Diesel Combustion & Heavy-Duty Combustion Modeling Heavy-Duty Low-Temperature and Diesel Combustion & Heavy-Duty Combustion Modeling High Efficiency Fuel Reactivity Controlled Compression Ignition Combustion

  11. An In-Cylinder Imaging Survey of Low-Temperature, High-Efficiency

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Combustion Strategies | Department of Energy An In-Cylinder Imaging Survey of Low-Temperature, High-Efficiency Combustion Strategies An In-Cylinder Imaging Survey of Low-Temperature, High-Efficiency Combustion Strategies High speed imaging of in-cylinder spray and combustion luminosity of low temperature combustion strategies are contrasted to conventional gasoline and diesel engine combustion deer11_musculus.pdf (1.99 MB) More Documents & Publications Vehicle Technologies Office Merit

  12. In-Cylinder Imaging of Conventional and Advanced, Low-Temperature Diesel

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Combustion | Department of Energy In-Cylinder Imaging of Conventional and Advanced, Low-Temperature Diesel Combustion In-Cylinder Imaging of Conventional and Advanced, Low-Temperature Diesel Combustion 2005 Diesel Engine Emissions Reduction (DEER) Conference Presentations and Posters 2005_deer_musculus.pdf (379.48 KB) More Documents & Publications Heavy-Duty Low-Temperature and Diesel Combustion & Heavy-Duty Combustion Modeling Visualization of UHC Emissions for Low-Temperature

  13. A VME timing system for the tokamak ISTTOK

    SciTech Connect (OSTI)

    Varandas, C.A.F.; Carvalho, B.; Fernandes, H.; Sousa, J.; Cabral, J.A.C.

    1995-05-01

    This paper describes the ISTTOK timing system, which was built under a centralized philosophy based on a locally developed 16 channel, 1 {mu}s maximum resolution, VME unit. The trigger options for each channel are provided, following an innovatory approach, by a programmable pulse multiplexer. {copyright} {ital 1995} {ital American} {ital Institute} {ital of} {ital Physics}.

  14. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... and phosphatidylcholine in a cerebellum mouse brain thin tissue section were ... Distinguishing between features approximately 13 m apart in a cerebellum mouse brain thin ...

  15. Numerical investigation of pulse-modulated atmospheric radio frequency discharges in helium under different duty cycles

    SciTech Connect (OSTI)

    Sun Jizhong; Ding Zhengfen; Li Xuechun; Wang Dezhen [School of Physics and Optoelectronic Technology, Dalian University of Technology, Dalian 116023 (China); Wang Qi [Dalian Institute of Semiconductor Technology, School of Electronics Science and Technology, Dalian University of Technology, Dalian 116023 (China)

    2011-12-15

    Experiments observed that the pulse duty cycle has effects on the plasma homogeneity in pulse-modulated radio frequency (rf) discharges. In this paper, pulse-modulated rf (13.56 MHz) helium discharges are theoretically investigated using a two dimensional fluid model. With the pulse period being fixed to 15 {mu}s, it is found that when the pulse-on duration is over 4 {mu}s, i.e., the duty cycle is larger than approximately 27%, the discharge transits from an inhomogeneous to a homogeneous mode in every specific part of each pulse cycle under currently-used simulation parameters. More quantitative analysis shows that the discharge becomes more homogeneous as the duty cycle is increased but does not reach complete homogeneity. Possible reasons for the homogeneity improvement are discussed.

  16. Improved Measurement of the Positive-Muon Lifetime and Determination of the Fermi Constant

    SciTech Connect (OSTI)

    Chitwood, D. B.; Clayton, S. M.; Crnkovic, J.; Debevec, P. T.; Hertzog, D. W.; Kammel, P.; Kiburg, B.; Kunkle, J.; McNabb, R.; Mulhauser, F.; Oezben, C. S.; Polly, C. C.; Webber, D. M.; Winter, P.; Banks, T. I.; Crowe, K. M.; Lauss, B.; Barnes, M. J.; Wait, G. D.; Battu, S.

    2007-07-20

    The mean life of the positive muon has been measured to a precision of 11 ppm using a low-energy, pulsed muon beam stopped in a ferromagnetic target, which was surrounded by a scintillator detector array. The result, {tau}{sub {mu}}=2.197 013(24) {mu}s, is in excellent agreement with the previous world average. The new world average {tau}{sub {mu}}=2.197 019(21) {mu}s determines the Fermi constant G{sub F}=1.166 371(6)x10{sup -5} GeV{sup -2} (5 ppm). Additionally, the precision measurement of the positive-muon lifetime is needed to determine the nucleon pseudoscalar coupling g{sub P}.

  17. Development of high-voltage pulse-slicer unit with variable pulse duration for pulse radiolysis system

    SciTech Connect (OSTI)

    Upadhyay, J.; Sharma, M. L.; Navathe, C. P.; Toley, M. A.; Shinde, S. J.; Nadkarni, S. A.; Sarkar, S. K.

    2012-02-15

    A high-voltage pulse-slicer unit with variable pulse duration has been developed and integrated with a 7 MeV linear electron accelerator (LINAC) for pulse radiolysis investigation. The pulse-slicer unit provides switching voltage from 1 kV to 10 kV with rise time better than 5 ns. Two MOSFET based 10 kV switches were configured in differential mode to get variable duration pulses. The high-voltage pulse has been applied to the deflecting plates of the LINAC for slicing of electron beam of 2 {mu}s duration. The duration of the electron beam has been varied from 30 ns to 2 {mu}s with the optimized pulse amplitude of 7 kV to get corresponding radiation doses from 6 Gy to 167 Gy.

  18. Prompt-period measurement of the Annular Core Research Reactor prompt neutron generation time

    SciTech Connect (OSTI)

    Coats, R.L.; Talley, D.G.; Trowbridge, F.R.

    1994-07-01

    The prompt neutron generation time for the Annular Core Research Reactor was experimentally determined using a prompt-period technique. The resultant value of 25.5 {mu}s agreed well with the analytically determined value of 24 {mu}s. The three different methods of reactivity insertion determination yielded {+-}5% agreement in the experimental values of the prompt neutron generation time. Discrepancies observed in reactivity insertion values determined by the three methods used (transient rod position, relative delayed critical control rod positions, and relative transient rod and control rod positions) were investigated to a limited extent. Rod-shadowing and low power fuel/coolant heat-up were addressed as possible causes of the discrepancies.

  19. Laser synchronized high-speed shutter for spectroscopic application

    DOE Patents [OSTI]

    Miles, Paul C.; Porter, Eldon L.; Prast, Thomas L.; Sunnarborg, Duane A.

    2002-01-01

    A fast mechanical shutter, based on rotating chopper wheels, has been designed and implemented to shutter the entrance slit of a spectrograph. This device enables an exposure time of 9 .mu.s to be achieved for a 0.8 mm wide spectrograph entrance slit, achieves 100% transmission in the open state, and an essentially infinite extinction ratio. The device further incorporates chopper wheel position sensing electronics to permit the synchronous triggering of a laser source.

  20. Solid state switch

    DOE Patents [OSTI]

    Merritt, Bernard T.; Dreifuerst, Gary R.

    1994-01-01

    A solid state switch, with reverse conducting thyristors, is designed to operate at 20 kV hold-off voltage, 1500 A peak, 1.0 .mu.s pulsewidth, and 4500 pps, to replace thyratrons. The solid state switch is more reliable, more economical, and more easily repaired. The switch includes a stack of circuit card assemblies, a magnetic assist and a trigger chassis. Each circuit card assembly contains a reverse conducting thyristor, a resistor capacitor network, and triggering circuitry.

  1. The development of a one microsecond pulse length, repetitively pulsed, high power modulator and a long-pulse electron beam diode for the production of intense microwaves

    SciTech Connect (OSTI)

    Stringfield, R.M.; Faehl, R.J.; Fazio, M.V.; Hoeberling, R.F.; Kwan, T.J.T.; Rickel, D.G.; VanHaaften, F.; Wasierski, R.F.; Erickson, A.; Rust, K.

    1992-07-01

    This paper discusses the pulse power and explosive emission electron beam diode development effort we have undertaken to power a relativistic klystron amplifier (RKA) microwave source. The pulsed power and electron beam must enable the RKA to Produce one kilojoule of 13 GHz radiation per pulse at a 5 Hz repetition frequency. These efforts include tests and improvements of a 1 {mu}s pulse length thyratron switched modulator, and the computational and experimental design of a 1-{mu}s-pulse-length explosive emission electron gun. The one microsecond pulse length is almost an order of magnitude beyond what has been achieved heretofore with an RKA. Achieving a peak power approaching 1 GW for 1 {mu}s requires a well behaved electron beam on that time scale. An electron beam diode has been developed that delivers a peak current of 4 to 5 kA for a pulse duration exceeding 1 {mu}s, at a beam kinetic energy above 600 keV. BANSHEE is the high voltage modulator designed for use as an electron beam driver for high power microwave tube development. The BANSHEE output pulse design parameters are 1 MV and 10 kA, with a 1 {mu}s pulse width at a repetition rate of 3--5 Hz, driving a load of impedance of 100 ohms. BANSHEE is a thyratron-switched line-type modular with a pulse transformer output stage. The modulator design is pushing the state of the art in thyratron technology and capacitor lifetime. The results of the BANSHEE modulator testing are described.

  2. Method and apparatus for improved high power impulse magnetron sputtering

    DOE Patents [OSTI]

    Anders, Andre

    2013-11-05

    A high power impulse magnetron sputtering apparatus and method using a vacuum chamber with a magnetron target and a substrate positioned in the vacuum chamber. A field coil being positioned between the magnetron target and substrate, and a pulsed power supply and/or a coil bias power supply connected to the field coil. The pulsed power supply connected to the field coil, and the pulsed power supply outputting power pulse widths of greater that 100 .mu.s.

  3. A 120kV IGBT modulator for driving a pierce electron gun

    SciTech Connect (OSTI)

    Earley, L. M.; Brown, R. W.; Carlson, R. L.; Ferguson, P.; Haynes, W. B.; Kirbie, H. C.; Russell, S. J.; Sigler, F. E.; Smirnova, E. I.; Wheat, R. M.

    2004-01-01

    An IGBT modulator has been developed to drive a 120 kV, 23 A Pierce electron gun. The modulator is capable of producing pulses up to 10 {mu}s in width at repetition rates up to 10Hz with no active reset. The pulse rise time on the electron gun will be approximately 2 {mu}s and the remaining 8 {mu}s of flattop is tuned to have a ripple of less than 1 percent rms. The modulator technology was developed from a previous 50 kV prototype. The modulator consists of six boards, each with one EUPEC IGBT that drives a single common step-up transformer wound on METGLAS 2605SC cores. The six transformer cores share a common bi-filar output secondary winding. The modulator uses a fiber optic trigger system and has a high voltage cable output with an epoxy receptacle on the oil end and a ceramic receptacle on the vacuum end. The 120 kV electron gun was manufactured by MDS Co. and will be used to generate sheet electron beams from the standard pencil beam produced by the Pierce electron gun.

  4. Experimental Investigation of Axial and Beam-Riding Propulsive Physics with TEA CO{sub 2} laser

    SciTech Connect (OSTI)

    Kenoyer, D. A.; Salvador, I.; Myrabo, L. N.; Notaro, S. N.; Bragulla, P. W.

    2010-10-08

    A twin Lumonics K922M pulsed TEA CO{sub 2} laser system (pulse duration of approximately 100 ns FWHM spike, with optional 1 {mu}s tail, depending upon laser gas mix) was employed to experimentally measure both axial thrust and beam-riding behavior of Type no. 200 lightcraft engines, using a ballistic pendulum and Angular Impulse Measurement Device (AIMD, respectively. Beam-riding forces and moments were examined along with engine thrust-vectoring behavior, as a function of: a) laser beam lateral offset from the vehicle axis of symmetry; b) laser pulse energy ({approx}12 to 40 joules); c) pulse duration (100 ns, and 1 {mu}s); and d) engine size (97.7 mm to 161.2 mm). Maximum lateral momentum coupling coefficients (C{sub M}) of 75 N-s/MJ were achieved with the K922M laser whereas previous PLVTS laser (420 J, 18 {mu}s duration) results reached only 15 N-s/MJ--an improvement of 5x. Maximum axial C{sub M} performance with the K922M reached 225 N-s/MJ, or about {approx}3x larger than the lateral C{sub M} values. These axial C{sub M} results are sharply higher than the 120 N/MW previously reported for long pulse (e.g., 10-18 {mu}s)CO{sub 2} electric discharge lasers.

  5. Feasibility study of volumetric modulated arc therapy with constant dose rate for endometrial cancer

    SciTech Connect (OSTI)

    Yang, Ruijie; Wang, Junjie; Xu, Feng; Li, Hua; Zhang, Xile

    2013-10-01

    To investigate the feasibility, efficiency, and delivery accuracy of volumetric modulated arc therapy with constant dose rate (VMAT-CDR) for whole-pelvic radiotherapy (WPRT) of endometrial cancer. The nine-field intensity-modulated radiotherapy (IMRT), VMAT with variable dose-rate (VMAT-VDR), and VMAT-CDR plans were created for 9 patients with endometrial cancer undergoing WPRT. The dose distribution of planning target volume (PTV), organs at risk (OARs), and normal tissue (NT) were compared. The monitor units (MUs) and treatment delivery time were also evaluated. For each VMAT-CDR plan, a dry run was performed to assess the dosimetric accuracy with MatriXX from IBA. Compared with IMRT, the VMAT-CDR plans delivered a slightly greater V{sub 20} of the bowel, bladder, pelvis bone, and NT, but significantly decreased the dose to the high-dose region of the rectum and pelvis bone. The MUs decreased from 1105 with IMRT to 628 with VMAT-CDR. The delivery time also decreased from 9.5 to 3.2 minutes. The average gamma pass rate was 95.6% at the 3%/3 mm criteria with MatriXX pretreatment verification for 9 patients. VMAT-CDR can achieve comparable plan quality with significant shorter delivery time and smaller number of MUs compared with IMRT for patients with endometrial cancer undergoing WPRT. It can be accurately delivered and be an alternative to IMRT on the linear accelerator without VDR capability.

  6. Heavy-Duty Low-Temperature and Diesel Combustion & Heavy-Duty Combustion

    Broader source: Energy.gov (indexed) [DOE]

    Modeling | Department of Energy 09 DOE Hydrogen Program and Vehicle Technologies Program Annual Merit Review and Peer Evaluation Meeting, May 18-22, 2009 -- Washington D.C. ace_01_musculus.pdf (2.77 MB) More Documents & Publications Heavy-Duty Low-Temperature and Diesel Combustion & Heavy-Duty Combustion Modeling Vehicle Technologies Office Merit Review 2014: Heavy-Duty Low-Temperature and Diesel Combustion & Heavy-Duty Combustion Modeling Heavy-Duty Low-Temperature and Diesel

  7. Volvo SuperTruck - Powertrain Technologies for Efficiency Improvement |

    Broader source: Energy.gov (indexed) [DOE]

    | Department of Energy Presentation given at DEER 2006, August 20-24, 2006, Detroit, Michigan. Sponsored by the U.S. DOE's EERE FreedomCar and Fuel Partnership and 21st Century Truck Programs. 2006_deer_musculus.pdf (9.8 MB) More Documents & Publications In-Cylinder Processes of EGR-Diluted Low-Load, Low-Temperature Diesel Combustion A Conceptual Model for Partially PremixedLow-Temperature Diesel Combustion Based onIn-Cylinder Laser Diagnostics and Chemical Kinetics Modeling Heavy-Duty

  8. Visualization of UHC Emissions for Low-Temperature Diesel Engine Combustion

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    | Department of Energy Visualization of UHC Emissions for Low-Temperature Diesel Engine Combustion Visualization of UHC Emissions for Low-Temperature Diesel Engine Combustion Presentation given at DEER 2006, August 20-24, 2006, Detroit, Michigan. Sponsored by the U.S. DOE's EERE FreedomCar and Fuel Partnership and 21st Century Truck Programs. 2006_deer_musculus.pdf (9.8 MB) More Documents & Publications In-Cylinder Processes of EGR-Diluted Low-Load, Low-Temperature Diesel Combustion A

  9. In-Cylinder Processes of EGR-Diluted Low-Load, Low-Temperature Diesel

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Combustion | Department of Energy Processes of EGR-Diluted Low-Load, Low-Temperature Diesel Combustion In-Cylinder Processes of EGR-Diluted Low-Load, Low-Temperature Diesel Combustion In-Cylinder Processes of EGR-Diluted Low-Load, Low-Temperature Diesel Combustion deer09_musculus.pdf (2.35 MB) More Documents & Publications A Conceptual Model for Partially PremixedLow-Temperature Diesel Combustion Based onIn-Cylinder Laser Diagnostics and Chemical Kinetics Modeling Heavy-Duty

  10. Co-Optimization of Fuels and Engines (Co-Optima) -- Thrust II Engine Projects, Sprays, and Emissions Control Research

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    FT039 - Part 1 Co-Optimization of Fuels and Engines Advanced Engine Development Team Paul Miles, 4 Magnus Sjöberg, 4 John Dec, 4 Steve Ciatti, 1 Chris Kolodziej, 1 Scott Curran, 3 Mark Musculus, 4 Charles Mueller 4 1. Argonne National Laboratory 2. National Renewable Energy Laboratory 3. Oak Ridge National Laboratory 4. Sandia National Laboratories Co-Optima DOE VTO Management Team: Kevin Stork, Gurpreet Singh, & Leo Breton Thrust II engine projects June 9 th , 2016 Overview: Thrust II

  11. Quantitation of repaglinide and metabolites in mouse whole-body thin tissue sections using droplet-based liquid microjunction surface sampling-high-performance liquid chromatography-electrospray ionization tandem mass spectrometry

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Chen, Weiqi; Wang, Lifei; Van Berkel, Gary J.; Gan, Jinping; Kertesz, Vilmos

    2015-11-03

    Herein, quantitation aspects of a fully automated autosampler/HPLC-MS/MS system applied for unattended droplet-based surface sampling of repaglinide dosed thin tissue sections with subsequent HPLC separation and mass spectrometric analysis of parent drug and various drug metabolites was studied. Major organs (brain, lung, liver, kidney, muscle) from whole-body thin tissue sections and corresponding organ homogenates prepared from repaglinide dosed mice were sampled by surface sampling and by bulk extraction, respectively, and analyzed by HPLC-MS/MS. A semi-quantitative agreement between data obtained by surface sampling and that by employing organ homogenate extraction was observed. Drug concentrations obtained by the two methods followed themore » same patterns for post-dose time points (0.25, 0.5, 1 and 2 h). Drug amounts determined in the specific tissues was typically higher when analyzing extracts from the organ homogenates. Furthermore, relative comparison of the levels of individual metabolites between the two analytical methods also revealed good semi-quantitative agreement.« less

  12. NOSH-aspirin (NBS-1120), a novel nitric oxide- and hydrogen sulfide-releasing hybrid is a potent inhibitor of colon cancer cell growth in vitro and in a xenograft mouse model

    SciTech Connect (OSTI)

    Chattopadhyay, Mitali; Kodela, Ravinder; Olson, Kenneth R.; Kashfi, Khosrow

    2012-03-16

    Highlights: Black-Right-Pointing-Pointer NOSH-aspirin is the first dual acting NO and H{sub 2}S releasing hybrid. Black-Right-Pointing-Pointer Its IC{sub 50} for cell growth inhibition is in the low nano-molar range. Black-Right-Pointing-Pointer Structure-activity studies show that the sum of the parts does not equal the whole. Black-Right-Pointing-Pointer NOSH-aspirin reduced tumor growth by 85% in mice bearing a colon cancer xenograft. -- Abstract: Nonsteroidal anti-inflammatory drugs (NSAIDs) are prototypical anti-cancer agents. However, their long-term use is associated with adverse gastrointestinal effects. Recognition that endogenous gaseous mediators, nitric oxide (NO) and hydrogen sulfide (H{sub 2}S) can increase mucosal defense mechanisms has led to the development of NO- and H{sub 2}S-releasing NSAIDs with increased safety profiles. Here we report on a new hybrid, NOSH-aspirin, which is an NO- and H{sub 2}S-releasing agent. NOSH-aspirin inhibited HT-29 colon cancer growth with IC{sub 50}s of 45.5 {+-} 2.5, 19.7 {+-} 3.3, and 7.7 {+-} 2.2 nM at 24, 48, and 72 h, respectively. This is the first NSAID based agent with such high degree of potency. NOSH-aspirin inhibited cell proliferation, induced apoptosis, and caused G{sub 0}/G{sub 1} cell cycle block. Reconstitution and structure-activity studies representing a fairly close approximation to the intact molecule showed that NOSH-aspirin was 9000-fold more potent than the sum of its parts towards growth inhibition. NOSH-aspirin inhibited ovine COX-1 more than ovine COX-2. NOSH-ASA treatment of mice bearing a human colon cancer xenograft caused a reduction in volume of 85%. Taken together, these results demonstrate that NOSH-aspirin has strong anti-cancer potential and merits further evaluation.

  13. Quantitation of repaglinide and metabolites in mouse whole-body thin tissue sections using droplet-based liquid microjunction surface sampling-high-performance liquid chromatography-electrospray ionization tandem mass spectrometry

    SciTech Connect (OSTI)

    Chen, Weiqi; Wang, Lifei; Van Berkel, Gary J.; Gan, Jinping; Kertesz, Vilmos

    2015-11-03

    Herein, quantitation aspects of a fully automated autosampler/HPLC-MS/MS system applied for unattended droplet-based surface sampling of repaglinide dosed thin tissue sections with subsequent HPLC separation and mass spectrometric analysis of parent drug and various drug metabolites was studied. Major organs (brain, lung, liver, kidney, muscle) from whole-body thin tissue sections and corresponding organ homogenates prepared from repaglinide dosed mice were sampled by surface sampling and by bulk extraction, respectively, and analyzed by HPLC-MS/MS. A semi-quantitative agreement between data obtained by surface sampling and that by employing organ homogenate extraction was observed. Drug concentrations obtained by the two methods followed the same patterns for post-dose time points (0.25, 0.5, 1 and 2 h). Drug amounts determined in the specific tissues was typically higher when analyzing extracts from the organ homogenates. Furthermore, relative comparison of the levels of individual metabolites between the two analytical methods also revealed good semi-quantitative agreement.

  14. Mapping of the receptor protein-tyrosine kinase 10 to human chromosome 1q21-q23 and mouse chromosome 1H1-5 by fluorescence in situ hybridization

    SciTech Connect (OSTI)

    Edelhoff, S.; Disteche, C.M.; Lai, C.

    1995-01-01

    Receptor protein-tyrosine kinases (PTKs) play a critical role in the transduction of signals important to cell growth, differentiation, and survival. Mutations affecting the expression of receptor PTK genes have been associated with a number of vertebrate and invertebrate developmental abnormalities, and the aberrant regulation of tyrosine phosphorylation is implicated in a variety of neoplasias. One estimate suggests that approximately 100 receptor PTK genes exist in the mammalian genome, about half of which have been identified. The tyro-10 receptor protein-tyrosine kinase, first identified in a PCR-based survey for novel tyrosine kinases in the rat nervous system, defines a new subfamily of PTKs. It exhibits a catalytic domain most closely related to those found in the trk PTK receptor subfamily, which transduces signals for nerve growth factor and the related molecules brain-derived neurotrophic factor (BDNF), neurotrophin-3, and neurotrophin-4 (NT-3 and NT-4). Trk and the related PTK receptors trkB and trkC play a critical role in the neurotrophin-dependent survival of subsets of sensory and motor neurons. The predicted tyro-10 extracellular region is, however, distinct from that of the trk subfamily and is unique except for a domain shared with the blood coagulation factors V and VIII, thought to be involved in phospholipid binding. Although tyro-10 RNA is most abundant in heart and skeletal muscle in the adult rat, it is expressed in a wide variety of tissues, including the developing and mature brain. Tyro-10 appears identical to the murine TKT sequence reported by Karn et al. and exhibits a high degree of similarity with the CaK, DDR, and Nep PTKs. A ligand for tyro-10 has not yet been identified. 10 refs., 1 fig.

  15. Evaluation of delivered monitor unit accuracy of gated step-and-shoot IMRT using a two-dimensional detector array

    SciTech Connect (OSTI)

    Cheong, Kwang-Ho; Kang, Sei-Kwon; Lee, MeYeon; Kim, Su SSan; Park, SoAh; Hwang, Tae-Jin; Kim, Kyoung Ju; Oh, Do Hoon; Bae, Hoonsik; Suh, Tae-Suk

    2010-03-15

    Purpose: To overcome the problem of organ motion in intensity-modulated radiation therapy (IMRT), gated IMRT is often used for the treatment of lung cancer. In this study, the authors investigated the accuracy of the delivered monitor units (MUs) from each segment during gated IMRT using a two-dimensional detector array for user-specific verification purpose. Methods: The authors planned a 6 MV photon, seven-port step-and-shoot lung IMRT delivery. The respiration signals for gated IMRT delivery were obtained from the one-dimensional moving phantom using the real-time position management (RPM) system (Varian Medical Systems, Palo Alto, CA). The beams were delivered using a Clinac iX (Varian Medical Systems, Palo Alto, CA) with the Millennium 120 MLC. The MatriXX (IBA Dosimetry GmbH, Germany) was validated through consistency and reproducibility tests as well as comparison with measurements from a Farmer-type ion chamber. The authors delivered beams with varying dose rates and duty cycles and analyzed the MatriXX data to evaluate MU delivery accuracy. Results: There was quite good agreement between the planned segment MUs and the MUs computed from the MatriXX within {+-}2% error. The beam-on times computed from the MatriXX data were almost identical for all cases, and they matched well with the RPM beam-on and beam-off signals. A slight difference was observed between them, but it was less than 40 ms. The gated IMRT delivery demonstrated an MU delivery accuracy that was equivalent to ungated IMRT, and the delivered MUs with a gating signal agreed with the planned MUs within {+-}0.5 MU regardless of dose rate and duty cycle. Conclusions: The authors can conclude that gated IMRT is able to deliver an accurate dose to a patient during a procedure. The authors believe that the methodology and results can be transferred to other vendors' devices, particularly those that do not provide MLC log data for a verification purpose.

  16. Post World War II missions emerge for Y-12

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    of Sciences." "Under Hollaender, Bill and Liane Russell started a large-scale mouse-genetics project in 1947. They began to build up special mouse strains for study of the...

  17. Adaptive Generation of Multimaterial Grids from imaging data...

    Office of Scientific and Technical Information (OSTI)

    We outline a method for solving this problem, and illustrate the approach with a 3D fluid-solid mesh of the mouse heart. An MRI perfusion-fixed dataset of a mouse heart with 50m ...

  18. Fermilab | Director's Policy Manual | Home

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Financial Management Freedom of Information Act Requests Inclement Weather and Snow Policy Interactions with Legislators Issues Management Maintenance MOUs Between...

  19. On Target May 2013 | Jefferson Lab

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    May 2013 May 2013 The U.S. Department of Energy's Thomas Jefferson National Accelerator Facility Mouse Medicine: System Gets Clear, 3D Brain Scans of Moving Mice Mouse Medicine: System Gets Clear, 3D Brain Scans of Moving Mice Three markers attached to the head of a mouse enable the AwakeSPECT system to obtain detailed, functional images of the brain of a conscious mouse as it moves. Setting a mouse free to roam might alarm most people, but not researchers who have developed a new imaging system

  20. SU-E-T-100: Designing a QA Tool for Enhance Dynamic Wedges Based On Dynalog Files

    SciTech Connect (OSTI)

    Yousuf, A; Hussain, A

    2014-06-01

    Purpose: A robust quality assurance (QA) program for computer controlled enhanced dynamic wedge (EDW) has been designed and tested. Calculations to perform such QA test is based upon the EDW dynamic log files generated during dose delivery. Methods: Varian record and verify system generates dynamic log (dynalog) files during dynamic dose delivery. The system generated dynalog files contain information such as date and time of treatment, energy, monitor units, wedge orientation, and type of treatment. It also contains the expected calculated segmented treatment tables (STT) and the actual delivered STT for the treatment delivery as a verification record. These files can be used to assess the integrity and precision of the treatment plan delivery. The plans were delivered with a 6 MV beam from a Varian linear accelerator. For available EDW angles (10°, 15°, 20°, 25°, 30°, 45°, and 60°) Varian STT values were used to manually calculate monitor units for each segment. It can also be used to calculate the EDW factors. Independent verification of fractional MUs per segment was performed against those generated from dynalog files. The EDW factors used to calculate MUs in TPS were dosimetrically verified in solid water phantom with semiflex chamber on central axis. Results: EDW factors were generated from the STT provided by Varian and verified against practical measurements. The measurements were in agreement of the order of 1 % to the calculated EDW data. Variation between the MUs per segment obtained from dynalog files and those manually calculated was found to be less than 2%. Conclusion: An efficient and easy tool to perform routine QA procedure of EDW is suggested. The method can be easily implemented in any institution without a need for expensive QA equipment. An error of the order of ≥2% can be easily detected.

  1. SU-E-T-421: Feasibility Study of Volumetric Modulated Arc Therapy with Constant Dose Rate for Endometrial Cancer

    SciTech Connect (OSTI)

    Yang, R; Wang, J

    2014-06-01

    Purpose: To investigate the feasibility, efficiency, and delivery accuracy of volumetric modulated arc therapy with constant dose rate (VMAT-CDR) for whole-pelvic radiotherapy (WPRT) of endometrial cancer. Methods: The nine-Field intensity-modulated radiotherapy (IMRT), VMAT with variable dose-rate (VMAT-VDR), and VMAT-CDR plans were created for 9 patients with endometrial cancer undergoing WPRT. The dose distribution of planning target volume (PTV), organs at risk (OARs), and normal tissue (NT) were compared. The monitor units (MUs) and treatment delivery time were also evaluated. For each VMAT-CDR plan, a dry Run was performed to assess the dosimetric accuracy with MatriXX from IBA. Results: Compared with IMRT, the VMAT-CDR plans delivered a slightly greater V20 of the bowel, bladder, pelvis bone, and NT, but significantly decreased the dose to the high-dose region of the rectum and pelvis bone. The MUs Decreased from 1105 with IMRT to 628 with VMAT-CDR. The delivery time also decreased from 9.5 to 3.2 minutes. The average gamma pass rate was 95.6% at the 3%/3 mm criteria with MatriXX pretreatment verification for 9 patients. Conclusion: VMAT-CDR can achieve comparable plan quality with significant shorter delivery time and smaller number of MUs compared with IMRT for patients with endometrial cancer undergoing WPRT. It can be accurately delivered and be an alternative to IMRT on the linear accelerator without VDR capability. This work is supported by the grant project, National Natural; Science Foundation of China (No. 81071237)

  2. Cosmic ray neutron background reduction using localized coincidence veto neutron counting

    DOE Patents [OSTI]

    Menlove, Howard O.; Bourret, Steven C.; Krick, Merlyn S.

    2002-01-01

    This invention relates to both the apparatus and method for increasing the sensitivity of measuring the amount of radioactive material in waste by reducing the interference caused by cosmic ray generated neutrons. The apparatus includes: (a) a plurality of neutron detectors, each of the detectors including means for generating a pulse in response to the detection of a neutron; and (b) means, coupled to each of the neutrons detectors, for counting only some of the pulses from each of the detectors, whether cosmic ray or fission generated. The means for counting includes a means that, after counting one of the pulses, vetos the counting of additional pulses for a prescribed period of time. The prescribed period of time is between 50 and 200 .mu.s. In the preferred embodiment the prescribed period of time is 128 .mu.s. The veto means can be an electronic circuit which includes a leading edge pulse generator which passes a pulse but blocks any subsequent pulse for a period of between 50 and 200 .mu.s. Alternately, the veto means is a software program which includes means for tagging each of the pulses from each of the detectors for both time and position, means for counting one of the pulses from a particular position, and means for rejecting those of the pulses which originate from the particular position and in a time interval on the order of the neutron die-away time in polyethylene or other shield material. The neutron detectors are grouped in pods, preferably at least 10. The apparatus also includes means for vetoing the counting of coincidence pulses from all of the detectors included in each of the pods which are adjacent to the pod which includes the detector which produced the pulse which was counted.

  3. Recent experimental results from a long-pulse J-band relativistic klystron amplifier developmental effort

    SciTech Connect (OSTI)

    Kato, K.G.; Crouch, D.D.; Sar, D.R.; Speciale, R.A.; Carlsten, B.E.; Fazio, M.V.; Haynes, W.B.; Stringfield, R.M.

    1994-12-31

    Recent experimental results, supporting simulations, and design modeling are presented from a developmental effort to a produce a long pulse ({approximately}1{mu}s) J-band (5.85-8.2 GHz) relativistic klystron amplifier (RKA) of the high current NRL genealogy. This RKA is designed to operate at approximately 6.6 GHz, with a desired RF output {approximately}700 MW. Conversion of electron beam energy to microwave energy is obtained by a mock magnetically insulated coaxial converter which, in various incarnations, can be made to be either a cavity gap extractor or an inverse cathode.

  4. Passive Electrostatic Recycling Spectrometer of Desk-Top Size for Charged Particles of Low Kinetic Energy

    SciTech Connect (OSTI)

    Tessier, D. R.; Niu, Y.; Seccombe, D. P.; Reddish, T. J.; Alderman, A. J.; Birdsey, B. G.; Hammond, P.; Read, F. H.

    2007-12-21

    A passive electrostatic recycling spectrometer for charged particles is described and demonstrated to store electrons with typical kinetic energies of tens of eV. The design of the charged particle optics and the basic operating characteristics of the storage ring are discussed. The storage lifetime achieved is {approx}50 {mu}s, which is target gas pressure limited and corresponds to {approx}200 orbits of the 0.65 m orbital circumference. The storage ring also has controllable energy dispersive elements enabling it to operate as a spectroscopic device.

  5. Measurements of prompt radiation induced conductivity of Kapton.

    SciTech Connect (OSTI)

    Preston, Eric F.; Zarick, Thomas Andrew; Sheridan, Timothy J.; Hartman, E. Frederick; Stringer, Thomas Arthur

    2010-10-01

    We performed measurements of the prompt radiation induced conductivity in thin samples of Kapton (polyimide) at the Little Mountain Medusa LINAC facility in Ogden, UT. Three mil samples were irradiated with a 0.5 {mu}s pulse of 20 MeV electrons, yielding dose rates of 1E9 to 1E10 rad/s. We applied variable potentials up to 2 kV across the samples and measured the prompt conduction current. Analysis rendered prompt conductivity coefficients between 6E-17 and 2E-16 mhos/m per rad/s, depending on the dose rate and the pulse width.

  6. Departure Roger Anthoine

    ScienceCinema (OSTI)

    None

    2011-04-25

    Remerciements et discours du D.G. H.Schopper à l'occasion du départ de Roger Anthoine (attaché de presse), qui travaillait dans la communication et quitte le Cern après 27 ans de service. Il gardait des relations avec des médias internationaux et la presse locale; remise des cadeaux: album photo avec images des musés de Genève et un radio aviation; R.A. fait un résumé de ses activités et souvenirs et remercie ses collaborateurs

  7. Measurement of characteristics of an infrared free-electron laser with the L-band at Osaka University

    SciTech Connect (OSTI)

    Okuda, S.; Ishida, S.; Honda, Y.

    1995-12-31

    Free-electron laser (FEL) experiments have been conducted with the 38-MeV L-band electron linac at the Institute of Scientific and Industrial Research, Osaka University. It is a 1.3 GHz RF linac with a thermoionic gun, and equipped with two 12th and one 6th sub-harmonic prebunchers for producing the high-intensity single-bunch beam with a charge up to 67 nC/bunch. For oscillation experiments of FEL, the gun is replaced with that with a smaller cathode area in order to reduce the emittance of the beam. The normalized emittance has been measured to be 200 {pi} mm-mrad. The linac is operated in the long-pulse mode and one of the 12th sub-harmonic bunchers and the 6th sub-harmonic buncher are operated, so that the time duration of the macropulse is 4 {mu}s and the spacing between micropulses is 9.2 ns. The length of the micropulse is 30-40 ps and the charge in each micropulse is 2 nC. The electron beam from the linac is transported to a wiggler which has the period length of 6 cm and the number of periods of 32. The first half of the macropulse is lost in the transport line because the energy of electrons in that part gradually changes and there is a momentum slit in the transport line. An optical resonator is 5.53 m long and the round-trip time of light in it is 37 ns, which is precisely four times as long as the spacing of micropulses. Since the time duration of the macropulse passing through the wiggler is 1.8 {mu}s, the number of amplifications of light in the cavity is 49. The first lasing was achieved in 1994 at wavelengths between 32 and 40 {mu}m and preliminary results were reported at the l6th FEL Conference last year. The laser light was detected with a Ge:Be detector which has the time resolution of 3 {mu}s. Since the time duration of the macropulse of the laser fight is estimated to be less than 2 {mu}s, we could measure only the total energy in a macropulse of the output light.

  8. Hi-speed versatile serial crate controller for CAMAC

    SciTech Connect (OSTI)

    Horelick, D.

    1984-10-01

    A serial crate controller, primarily for use in the SLC CAMAC control system, has been designed, and has been in use for about 2 years. The design supports a party line approach, with up to 16 crates on a single twisted pair for data transfers, plus another pair for prompt L response. The bit rate is 5 megabits/s, and complete transaction times of about 10 ..mu..s are achieved for 16-bit data transfers over cables up to 1000 feet long. One of the primary objects of the design was simplicity - there are approximately 60 chips in the two-board unit.

  9. Strangelet search in Pb-Pb interactions at 158 GeV/{ital c} per nucleon

    SciTech Connect (OSTI)

    Appelquist, G.; Baglin, C.; Beringer, J.; Bohm, C.; Borer, K.; Bussiere, A.; Dittus, F.; Elsener, K.; Frei, D.; Gorodetzky, P.; Guillaud, J.P.; Hugentobler, E.; Klingenberg, R.; Linden, T.; Lohmann, K.D.; Moser, U.; Pal, T.; Pretzl, K.; Schacher, J.; Sellden, B.; Stoffel, F.; Tuominiemi, J.; Zhang, Q.P.

    1996-05-01

    The NA52 experiment searches for long-lived massive strange quark matter particles, so-called {ital strangelets}, produced in Pb-Pb collisions at a beam momentum of {ital p}{sub lab}=158 AGeV/{ital c}. Upper limits for the production of strangelets at zero degree production angle covering a mass to charge ratio up to 120 GeV/{ital c}{sup 2} and lifetimes {ital t}{sub lab}{approx_gt}1.2 {mu}s are given. The data presented here were taken during the 1994 lead beam running period at CERN. {copyright} {ital 1996 The American Physical Society.}

  10. SlISANA MARTINEZ Governor JOHN A. SANCHEZ Lieutenant Governor

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    SlISANA MARTINEZ Governor JOHN A. SANCHEZ Lieutenant Governor March 13, 2013 Jose Franco, Manager Carlsbad Field Office Department of Energy P.O. Box 3090 NEW MEXICO ENVIRONMENT DEPARTMENT Resource Protection Division Harold Runnels Building 1190 Saint Francis Drive (87505) P.O. Box 5469, Santa Fe, NM 87502-5469 Phone (505) 827-0419 Fax (505) 827-0310 www.nrnenv.state.l1m.us CERTIFIED MAIL - RETURN RECEIPT REQUESTED M. Farok Sharif, Project Manager Nuclear Waste Partnership LLC P.O. Box 2078

  11. Optical data recording by laser pulses in liquid-crystal cells with an azo-modified surface

    SciTech Connect (OSTI)

    Serak, S V; Agashkov, A V; Reshetnyak, V Yu

    2001-03-31

    The effect of trans-cis photoisomerisation of azofragments of a polymer film on the molecular reorientation of a liquid crystal is studied. It is shown that, using nanosecond laser pulses, one can perform both the reversible and static data recording in liquid-crystal cells with an azo-modified surface. The rise time of the reorientation is measured by the methods of dynamic holography to be about {approx} 30 {mu}s, and the grating efficiency achieves 15 %. (laser applications and other topics in quantum electronics)

  12. Solid state switch

    DOE Patents [OSTI]

    Merritt, B.T.; Dreifuerst, G.R.

    1994-07-19

    A solid state switch, with reverse conducting thyristors, is designed to operate at 20 kV hold-off voltage, 1,500 A peak, 1.0 [mu]s pulsewidth, and 4,500 pps, to replace thyratrons. The solid state switch is more reliable, more economical, and more easily repaired. The switch includes a stack of circuit card assemblies, a magnetic assist and a trigger chassis. Each circuit card assembly contains a reverse conducting thyristor, a resistor capacitor network, and triggering circuitry. 6 figs.

  13. Multiple protocol fluorometer and method

    DOE Patents [OSTI]

    Kolber, Zbigniew S.; Falkowski, Paul G.

    2000-09-19

    A multiple protocol fluorometer measures photosynthetic parameters of phytoplankton and higher plants using actively stimulated fluorescence protocols. The measured parameters include spectrally-resolved functional and optical absorption cross sections of PSII, extent of energy transfer between reaction centers of PSII, F.sub.0 (minimal), F.sub.m (maximal) and F.sub.v (variable) components of PSII fluorescence, photochemical and non-photochemical quenching, size of the plastoquinone (PQ) pool, and the kinetics of electron transport between Q.sub.a and PQ pool and between PQ pool and PSI. The multiple protocol fluorometer, in one embodiment, is equipped with an excitation source having a controlled spectral output range between 420 nm and 555 nm and capable of generating flashlets having a duration of 0.125-32 .mu.s, an interval between 0.5 .mu.s and 2 seconds, and peak optical power of up to 2 W/cm.sup.2. The excitation source is also capable of generating, simultaneous with the flashlets, a controlled continuous, background illumination.

  14. Understanding composite explosive energetics: 3, Reactive flow modeling of aluminum reaction kinetics in PETN and TNT

    SciTech Connect (OSTI)

    Tao, W.C.; Tarver, C.M.; Ornellas, D.L.

    1991-12-06

    Using Fabry-Perot interferometry techniques, we have determined that early time rate of energy release from detonating PETN and TNT explosives filled with 5 and 10 wt % of either 5 {mu}m of 18 {mu}m spherical aluminum (Al) particles. From the measured particle velocity data, we are able to infer the reaction rate of aluminum with the detonation products, and calculate the extent of reaction 1--3 {mu}s after the detonation. We observed that a substantional portion of the aluminum metal in all of the PETN and TNE formulations reacted within the timeframe of the one-dimensional experiment. In the PETN formulation filed with 5 wt % of 5 {mu}m aluminum, all of the metal reacted within 1.5 {mu}s, resulting in an increase of 22% in energy compared to pure PETN. A reactive-flow hydrodynamic model based on the Zeldovich-von Neumann-Doring (ZND) description of the reaction zone and subsequent reaction produce expansion (Taylor wave) is used to interpret the reaction rate of the aluminum particles with detonation product gases. The diffusion-controlled reaction mechanism for aluminum and the global kinetic parameters used in the model have been found to be consistent for all the PETN and TNT formulations.

  15. Understanding composite explosive energetics: 4. Reactive flow modeling of aluminum reaction kinetics in PETN and TNT using normalized product equation of state

    SciTech Connect (OSTI)

    Tao, W.C.; Tarver, C.M.; Kury, J.W.; Lee, C.G.; Ornellas, D.L.

    1993-07-01

    Using Fabry-Perot interferometry techniques, we have determined the early time rate of energy release from detonating PETN and TNT explosives filled with 5 to 20 wt % of either 5 {mu}m or 18 {mu}m spherical aluminum with the detonation products, and calculate the extent of reaction at 1--3 {mu}s after the detonation. All of the metal in PETN formulations filled with 5 wt % and 10 wt % of either 5 {mu}m or 18 {mu}m aluminum reacted within 1.5 {mu}s, resulting in an increase of 18--22% in energy compared to pure PETN. For TNT formulations, between 5 to 10 wt % aluminum reacts completely with the same timeframe. A reactive flow hydrodynamic code model based on the Zeldovich-von Neumann-Doring (ZND) description of the reaction zone and subsequent reaction product expansion (Taylor wave) is used to address the reaction rate of the aluminum particles with detonation product gases. The detonation product JWL equation of state is derived from that of pure PETN using a parametric normalization methodology.

  16. Population dynamics in epitaxial Er{sub 2}O{sub 3} thin films grown on Si(111)

    SciTech Connect (OSTI)

    Tawara, T.; Omi, H.; Hozumi, T.; Kaji, R.; Adachi, S.; Gotoh, H.; Sogawa, T.

    2013-06-17

    We grow single crystal erbium-oxide (Er{sub 2}O{sub 3}) epitaxially on a Si (111) substrate by using molecular beam epitaxy and investigate the population dynamics in Er{sup 3+} ions for the coherent manipulation of the population in Er{sub 2}O{sub 3}. Sharp and discrete Stark energy levels of the {sup 4}I{sub 13/2} manifold as small as 200 {mu}eV are observed with inhomogeneous broadening caused by the uniform crystal field of the epitaxial Er{sub 2}O{sub 3}. We also experimentally determine the time constant of the resonant population transfer between spatially distant Er{sup 3+}-ion sites, which is limited to the manipulation time of the population in the Er{sub 2}O{sub 3} crystals. Using selective excitation of the Stark level in the {sup 4}I{sub 13/2} manifold, we obtain the energy transfer times between spatially distant Er{sup 3+} ions, and they are about 2 {mu}s between sites whose crystallographic symmetry is different and 10 {mu}s between sites whose symmetry is the same.

  17. Shock initiation sensitivity of hexanitrostilbene (HNS)

    SciTech Connect (OSTI)

    Schwarz, A C

    1981-01-01

    Experiments were conducted to study the influence of powder morphology, sample density, diameter of the impacting flyer and duration of the stimulus on the shock initiation sensitivity of the high explosive, hexanitrostilbene. The shock stimulus was provided by a polyimide flyer accelerated by an electrically-exploded, metallic foil. Impact pressure (P) was controlled between 3.8 and 9.8 GPa and pulse duration (tau) was nominally 0.035 ..mu..s except for the last experiment where pulse duration varied. Powder morphology significantly influenced the shock amplitude required for initiation with the finest-particle HNS requiring the least pressure, 6.3 GPa, and exhibiting the sharpest threshold. Both a reduction in density of HNS, from 1.60 to 1.30 Mg/m/sup 3/, and an increase in flyer diameter affected a reduction in impact velocity (or pressure) needed to induce detonation. The line which separates detontion from non-detonation is expressed by P/sup 2/ /sup 4/ tau = constant for tau between 0.01 and 0.10 ..mu..s; for longer pulses the initiation criterion becomes one of constant pressure.

  18. The LEB to MEB transfer kicker system prototype

    SciTech Connect (OSTI)

    Pappas, C.; Wilson, M.; Anderson, D.

    1994-08-01

    The design requirements for the Low Energy Booster (LEB) extraction kicker system at the Superconducting Super Collider Laboratory (SSCL) were to deflect a 12 GeV/c beam through an angle of 1.5 mrad. The circumference of the LEB was 540 M. This resulted in a 0.06 T-m integrated field, of 1.8 {mu}s width with a 1% to 99% rise time of less than 80 ns and allowable pulse ripple of less than {plus_minus}1%. The repetition frequency was 10 Hz and the allowable timing jitter was 2 ns. The field was required to be uniform over a 2{times}4 cm area to {plus_minus}2.5%. The requirements for the Medium Energy Booster (MEB) injection kicker were similar except that a 99% to 1% pulse fall time of less than 2 {mu}s was needed. Prototypes of the pulsed power system and magnet to meet these requirements were built and tested at the SSCL. This paper describes the results of that testing.

  19. Wide-range voltage modulation

    SciTech Connect (OSTI)

    Rust, K.R.; Wilson, J.M.

    1992-06-01

    The Superconducting Super Collider`s Medium Energy Booster Abort (MEBA) kicker modulator will supply a current pulse to the abort magnets which deflect the proton beam from the MEB ring into a designated beam stop. The abort kicker will be used extensively during testing of the Low Energy Booster (LEB) and the MEB rings. When the Collider is in full operation, the MEBA kicker modulator will abort the MEB beam in the event of a malfunction during the filling process. The modulator must generate a 14-{mu}s wide pulse with a rise time of less than 1 {mu}s, including the delay and jitter times. It must also be able to deliver a current pulse to the magnet proportional to the beam energy at any time during ramp-up of the accelerator. Tracking the beam energy, which increases from 12 GeV at injection to 200 GeV at extraction, requires the modulator to operate over a wide range of voltages (4 kV to 80 kV). A vacuum spark gap and a thyratron have been chosen for test and evaluation as candidate switches for the abort modulator. Modulator design, switching time delay, jitter and pre-fire data are presented.

  20. Photoionization in the Precursor of Laser Supported Detonation by Ultraviolet Radiation

    SciTech Connect (OSTI)

    Shimamura, Kohei; Michigami, Keisuke; Wang, Bin; Komurasaki, Kimiya; Arakawa, Yoshihiro

    2011-11-10

    The propagation mechanism of laser-supported detonation (LSD) is important for designing laser propulsion for a detonation type thruster. The purpose of this work to was to confirm that photo-ionization in precursor is the predominant LSD sustainment mechanism. First of all, we tried to investigate the dependency of LSD duration on ambient gas species, air and argon. We took a series of high-speed images using the laser shadow-graphy. Besides, to estimate the UV photons emitted from the plasma, we used plasma emission spectroscopy and determined the electron temperature and density. As a result, the LSD duration of argon plasma and air plasma are 0.7 {mu}s and 0.3 {mu}s, resp. Besides, argon plasma emitted 10{sup 10} to 10{sup 14} photons/seconds, which was higher than air plasma. These results reveal that LSD propagation depends on the photon-contributing photoionization. The threshold photon-emission rate of LSD termination gives the elucidation of the LSD termination condition.

  1. Laser-induced temperature jump/time-resolved infrared study of the fast events in protein folding

    SciTech Connect (OSTI)

    Woodruff, W.H.; Dyer, R.B.; Williams, S. [Los Alamos National Laboratory, NM (United States); Callender, H.; Gilmanshin, R. [CUNY, NY (United States)

    1996-10-01

    Laser-induced temperature jump followed by time-resolved infrared probe of reaction dynamics are used to study the temporal evolution of polypeptide structure during protein folding and unfolding. Reactions are initiated in times of 50 ps or longer by T-jumps of 10`s of degrees, obtained by laser excitation of water overtone absorbances. Observation of the Amide I transient absorbances reveal melting lifetimes of helices unconstrained by tertiary structure to be ca. 160 ns in a model 21-peptide and ca. 30 ns in {open_quotes}molten globule{close_quotes} apomyoglobin. No other processes are observed in these systems over the timescale 50 ps to 2 ms. Equilibrium data suggest the corresponding helix formation lifetimes to be ca. 16 and 1 ns, respectively. In {open_quotes}native{close_quotes} apomyoglobin two helix melting lifetimes are observed and we infer that a third occurs on a timescale inaccessible to our experiment (> 1 ms). The shorter observed lifetime, as in the molten globule, is ca. 30 ns. The longer lifetime is ca. 70 {mu}s. We suggest that the slower process is helix melting that is rate-limited by the unfolding of tertiary structure. Equilibrium data suggest a lifetime of ca. 1 {mu}s for the development of these tertiary folds.

  2. Commissioning the FELI linac and UV-FEL facility

    SciTech Connect (OSTI)

    Tomimasu, T.; Saeki, K.; Miyauchi, Y.

    1995-12-31

    The FELI 165-MeV linac and UV-FEL facility are in the commissioning, stage. A thermionic triode gun of the 6-MeV injector emits 500-ps pulses of 2.3A at 22.3125MHz. These pulses are compressed to 60AX 7ps by a 714-MHz prebuncher and a 2856-MHz buncher and seven ETL type accelerating waveguides with a length of 2.93m. The length of the linac including bending sections of two S-type BT systems for two undulators used for IR-FEL oscillations is 46m. The buncher and these accelerating waveguides are powered by two klystrons (E3729, 2856MHz, total 48MW, 24-{mu}s flat top long pulses). The flatness of our klystron modulator pulses is 0.067% at 24-{mu}s duration. An rf-ageing for new four accelerating waveguides will be started in May. An S-type BT line for 165-MeV beam from the linac will be installed in the end of April. A 2.68-m undulator ({lambda}u=4.0cm, N=67, Kmax gap length {ge}16mm) and an optical cavity (Lc=6.72m) will be installed early in July. The beam conditionings for UV-FEL experiments will be started in July.

  3. Plasma rotation, dynamo, and nonlinear coupling in the reversed field pinch

    SciTech Connect (OSTI)

    Prager, S.C.; Almagri, A.F.; Cekic, M.

    1995-07-01

    Two important effects of MHD fluctuations in the RFP and tokamak are current generation (the dynamo effect) and mode locking. In the T1 and MST RFP experiments new results reveal the mode dynamics underlying these phenomena. In T1 the effect of specific magnetic Fourier modes on the current density profile is evident. In MST, the MHD dynamo term ({delta}v x {delta}B) is measured in the plasma edge, and found to account for the time dependence of the edge current throughout a sawtooth cycle. As edge resistivity is increased in T1 the fluctuation amplitude increases to maintain the dynamo-driven current, as expected from MHD computation. The modes responsible for the dynamo often lock to the local magnetic field error at the vertical cut in MST. The plasma rotation velocity has been measured with a fast Doppler spectrometer to a time resolution of 1 {mu}s. The plasma rotation and mode phase velocity are remarkably well-correlated, with both slowing, in the presence of an impulsive field error, in a 100 {mu}s timescale.

  4. Recent Upgrade of the Klystron Modulator at SLAC

    SciTech Connect (OSTI)

    Nguyen, M.N.; Burkhart, C.P.; Lam, B.K.; Morris, B.; /SLAC

    2011-11-04

    The SLAC National Accelerator Laboratory employs 244 klystron modulators on its two-mile-long linear accelerator that has been operational since the early days of the SLAC establishment in the sixties. Each of these original modulators was designed to provide 250 kV, 262 A and 3.5 {mu}S at up to 360 pps using an inductance-capacitance resonant charging system, a modified type-E pulse-forming network (PFN), and a pulse transformer. The modulator internal control comprised of large step-start resistor-contactors, vacuum-tube amplifiers, and 120 Vac relays for logical signals. A major, power-component-only upgrade, which began in 1983 to accommodate the required beam energy of the SLAC Linear Collider (SLC) project, raised the modulator peak output capacity to 360 kV, 420 A and 5.0 {mu}S at a reduced pulse repetition rate of 120 pps. In an effort to improve safety, performance, reliability and maintainability of the modulator, this recent upgrade focuses on the remaining three-phase AC power input and modulator controls. The upgrade includes the utilization of primary SCR phase control rectifiers, integrated fault protection and voltage regulation circuitries, and programmable logic controllers (PLC) -- with an emphasis on component physical layouts for safety and maintainability concerns. In this paper, we will describe the design and implementation of each upgraded component in the modulator control system. We will also report the testing and present status of the modified modulators.

  5. Independent calculation of monitor units for VMAT and SPORT

    SciTech Connect (OSTI)

    Chen, Xin; Bush, Karl; Ding, Aiping; Xing, Lei

    2015-02-15

    Purpose: Dose and monitor units (MUs) represent two important facets of a radiation therapy treatment. In current practice, verification of a treatment plan is commonly done in dose domain, in which a phantom measurement or forward dose calculation is performed to examine the dosimetric accuracy and the MU settings of a given treatment plan. While it is desirable to verify directly the MU settings, a computational framework for obtaining the MU values from a known dose distribution has yet to be developed. This work presents a strategy to calculate independently the MUs from a given dose distribution of volumetric modulated arc therapy (VMAT) and station parameter optimized radiation therapy (SPORT). Methods: The dose at a point can be expressed as a sum of contributions from all the station points (or control points). This relationship forms the basis of the proposed MU verification technique. To proceed, the authors first obtain the matrix elements which characterize the dosimetric contribution of the involved station points by computing the doses at a series of voxels, typically on the prescription surface of the VMAT/SPORT treatment plan, with unit MU setting for all the station points. An in-house Monte Carlo (MC) software is used for the dose matrix calculation. The MUs of the station points are then derived by minimizing the least-squares difference between doses computed by the treatment planning system (TPS) and that of the MC for the selected set of voxels on the prescription surface. The technique is applied to 16 clinical cases with a variety of energies, disease sites, and TPS dose calculation algorithms. Results: For all plans except the lung cases with large tissue density inhomogeneity, the independently computed MUs agree with that of TPS to within 2.7% for all the station points. In the dose domain, no significant difference between the MC and Eclipse Anisotropic Analytical Algorithm (AAA) dose distribution is found in terms of isodose contours

  6. Solar Innovation Timeline | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Solar Achievements Timeline INSTRUCTIONS Instructional graphic for mouse use. Click and ... to navigate through timeline. 2011 INDUSTRY Graphic of the U.S. Department of Energy logo. ...

  7. Sandia National Laboratories: Research: High Consequence, Automation, &

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Robotics: Mighty Mouse (M2) Mighty Mouse (M2) Mighty Mouse Mighty Mouse, or M2, earned its heroic name by saving the day at the White Sands Missile Range in southern New Mexico when a radioactive cylinder became jammed inside a metal sleeve. Its radiation field was far too dangerous for a human, even in a protective suit, to get near enough to free it. The White Sands team knew they needed a robot for the job and called Sandia's High Consequence, Automation, & Robotics (HCAR) team.

  8. Paul B. Selby, 1981 | U.S. DOE Office of Science (SC)

    Office of Science (SC) Website

    of a series of radiation-induced dominant skeletal mutations in the mouse that have important applications for the determination of risk estimates of low-level radiation ...

  9. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    Here we show that stimulation of the entorhinal cortex in mouse brain slices paradoxically generates spiking of mature neurons in the absence of immature neuron spiking. Immature ...

  10. Low excitatory innervation balances high intrinsic excitability...

    Office of Scientific and Technical Information (OSTI)

    Here we show that stimulation of the entorhinal cortex in mouse brain slices paradoxically generates spiking of mature neurons in the absence of immature neuron spiking. Immature ...

  11. Category:RAPID Best Practices | Open Energy Information

    Open Energy Info (EERE)

    Practices RAPIDBest PracticesCoordinating Permit Offices RAPIDBest PracticesLandscape-Scale Mitigation R cont. RAPIDBest PracticesMemorandums of Understanding (MOUs)...

  12. 1980s Forging Partnerships on the Information Front | OSTI, US...

    Office of Scientific and Technical Information (OSTI)

    Back to history 1980 Memorandum of Understanding (MOU) with the Nuclear Energy Agency (NEA) Databank signed for the exchange of computer codes 1981 Bilateral MOUs began with other ...

  13. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    The Crystal Structure of Mouse Exo70 Reveals Unique Features of the Mammalian Exocyst Moore, Brian A. ; Robinson, Howard H. ; Xu, Zhaohui ; Michigan-Med) August 2015 , Elsevier ...

  14. Transmission/Resource Library/NEPA | Open Energy Information

    Open Energy Info (EERE)

    Library Jump to: navigation, search ResourceLibraryHeader.png Planning Public Involvement GIS Tools and Maps Environmental Resources and Mitigation NEPA MOUs General...

  15. Research Portfolio Report Ultra-Deepwater: Drilling and Completion...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    ... experiments where possible. "Dynamic 3D" display with mouse-rotatable perspective views. ... any significant shear viscosity sensitivity to fiber concentration at ambient temperature. ...

  16. LANL: AOT & LANSCE The Pulse December 2009

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    ... Hillary Smith, Michael Jablin, and Jaroslaw Majewski (LANSCE- LC); and Joseph Hickey, Antoinette Trujillo, and James Freyer (B-9) used NR to examine living mouse fbroblast cells ...

  17. Finishing in the Future

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    for the Mouse and Human Genome Resources and Trace Archive, National Center for Biotechnology Information (NCBI) Genome Sequencing: Draft sequencing, assembly and quality ...

  18. l

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Human Genome 10 Years Later Super-strange Superconductors Good News from Glaciers About ... positive results when sorting mixtures of human and mouse blood cells of different sizes, ...

  19. Web-enabled Milestones Chart | OSTI, US Dept of Energy Office...

    Office of Scientific and Technical Information (OSTI)

    Web-enabled Milestones Chart Over the last decade, numerous milestones have been achieved, including many "firsts" in government web search technology. Mouse over the year to view ...

  20. Final Technical Report

    SciTech Connect (OSTI)

    Bult Carol J.

    2003-11-24

    The results of the DOE-funded Mouse Genome Sequence (MGS) project include a significant enhancement in the capacity of the community to connect biological knowledge with the mouse genome sequence in a comparative context. The resources developed as the result of the activities of the MGS project staff are used extensively by both individual researchers and other informatics groups.

  1. Spatiotemporal temperature and density characterization of high-power atmospheric flashover discharges over inert poly(methyl methacrylate) and energetic pentaerythritol tetranitrate dielectric surfaces

    SciTech Connect (OSTI)

    Tang, V.; Grant, C. D.; McCarrick, J. F.; Zaug, J. M.; Glascoe, E. A.; Wang, H.

    2012-03-01

    A flashover arc source that delivered up to 200 mJ on the 100s-of-ns time-scale to the arc and a user-selected dielectric surface was characterized for studying high-explosive kinetics under plasma conditions. The flashover was driven over thin pentaerythritol tetranitrate (PETN) and poly(methyl methacrylate) (PMMA) dielectric films and the resultant plasma was characterized in detail. Time- and space-resolved temperatures and electron densities of the plasma were obtained using atomic emission spectroscopy. The hydrodynamics of the plasma was captured through fast, visible imaging. Fourier transform infrared spectroscopy (FTIR) was used to characterize the films pre- and post-shot for any chemical alterations. Time-resolved infrared spectroscopy (TRIR) provided PETN depletion data during the plasma discharge. For both types of films, temperatures of 1.6-1.7 eV and electron densities of {approx}7-8 x 10{sup 17}/cm{sup 3}{approx}570 ns after the start of the discharge were observed with temperatures of 0.6-0.7 eV persisting out to 15 {mu}s. At 1.2 {mu}s, spatial characterization showed flat temperature and density profiles of 1.1-1.3 eV and 2-2.8 x 10{sup 17}/cm{sup 3} for PETN and PMMA films, respectively. Images of the plasma showed an expanding hot kernel starting from radii of {approx}0.2 mm at {approx}50 ns and reaching {approx}1.1 mm at {approx}600 ns. The thin films ablated or reacted several hundred nm of material in response to the discharge. First TRIR data showing the in situ reaction or depletion of PETN in response to the flashover arc were successfully obtained, and a 2-{mu}s, 1/e decay constant was measured. Preliminary 1 D simulations compared reasonably well with the experimentally determined plasma radii and temperatures. These results complete the first steps to resolving arc-driven PETN reaction pathways and their associated kinetic rates using in situ spectroscopy techniques.

  2. SU-E-T-11: A Dosimetric Comparison of Robotic Prostatic Radiosugery Using Multi- Leaf Collimation Vs Circular Collimators

    SciTech Connect (OSTI)

    Feng, J; Yang, J; Lamond, J; Lavere, N; Laciano, R; Ding, W; Arrigo, S; Brady, L

    2014-06-01

    Purpose: The study compared the dosimetry plans of Stereotatic Body Radiotherapy (SBRT) prostate cancer patients using the M6 Cyberknife with Multi-leaf Collimation (MLC) compared with the plans using G4 Cyberknife with circular collimators. Methods: Eight previously treated prostate cancer patients' SBRT plans using circular collimators, designed with Multiplan v3.5.3, were used as a benchmark. The CT, contours and the optimization scripts were imported into Multiplan v5.0 system and replanned with MLC. The same planning objectives were used: more than 95% of PTV received 36.25Gy, 90% of prostate received 40Gy and maximum dose <45Gy, in five fractions. For organs at risk, less than 1cc of rectum received 36Gy and less than 10cc of bladder received 37Gy. Plans were evaluated on parameters derived from dose volume. The beam number, MU and delivery time were recorded to compare the treatment efficiency. Results: The mean CTV volume was 41.3cc (27.5?57.6cc) and mean PTV volume was 76.77cc (59.1?99.7cc). The mean PTV coverage was comparable between MLC (98.87%) and cone (98.74%). MLC plans had a slightly more favorable homogeneity index (1.22) and conformity index (1.17), than the cone (1.24 and 1.15). The mean rectum volume of 36 Gy (0.52cc) of MLC plans was slightly larger than cone (0.38cc) and the mean bladder volume of 37 Gy was smaller in MLC (1.82cc) than in cone plans (3.09cc). The mean number of nodes and beams were 65.9 and 80.5 in MLC vs 65.9 and 203.6 in cone. The mean MUs were significantly less for MLC plans (24,228MUs) than cone (32,347MUs). The total delivery time (which included 5 minutes for setup) was less, 29.6min (26?32min) for MLC vs 45min (35?55min) for cone. Conclusion: While the differences in the dosimetry between the MLC and circular collimator plans were rather minor, the MLC plans were much more efficient and required significantly less treatment time.

  3. Volumetric-modulated arc radiotherapy for pancreatic malignancies: Dosimetric comparison with sliding-window intensity-modulated radiotherapy and 3-dimensional conformal radiotherapy

    SciTech Connect (OSTI)

    Nabavizadeh, Nima Simeonova, Anna O.; Waller, Joseph G.; Romer, Jeanna L.; Monaco, Debra L.; Elliott, David A.; Tanyi, James A.; Fuss, Martin; Thomas, Charles R.; Holland, John M.

    2014-10-01

    Volumetric-modulated arc radiotherapy (VMAT) is an iteration of intensity-modulated radiotherapy (IMRT), both of which deliver highly conformal dose distributions. Studies have shown the superiority of VMAT and IMRT in comparison with 3-dimensional conformal radiotherapy (3D-CRT) in planning target volume (PTV) coverage and organs-at-risk (OARs) sparing. This is the first study examining the benefits of VMAT in pancreatic cancer for doses more than 55.8 Gy. A planning study comparing 3D-CRT, IMRT, and VMAT was performed in 20 patients with pancreatic cancer. Treatments were planned for a 25-fraction delivery of 45 Gy to a large field followed by a reduced-volume 8-fraction external beam boost to 59.4 Gy in total. OARs and PTV doses, conformality index (CI) deviations from 1.0, monitor units (MUs) delivered, and isodose volumes were compared. IMRT and VMAT CI deviations from 1.0 for the large-field and the boost plans were equivalent (large field: 0.032 and 0.046, respectively; boost: 0.042 and 0.037, respectively; p > 0.05 for all comparisons). Both IMRT and VMAT CI deviations from 1.0 were statistically superior to 3D-CRT (large field: 0.217, boost: 0.177; p < 0.05 for all comparisons). VMAT showed reduction of the mean dose to the boost PTV (VMAT: 61.4 Gy, IMRT: 62.4 Gy, and 3D-CRT: 62.3 Gy; p < 0.05). The mean number of MUs per fraction was significantly lower for VMAT for both the large-field and the boost plans. VMAT delivery time was less than 3 minutes compared with 8 minutes for IMRT. Although no statistically significant dose reduction to the OARs was identified when comparing VMAT with IMRT, VMAT showed a reduction in the volumes of the 100% isodose line for the large-field plans. Dose escalation to 59.4 Gy in pancreatic cancer is dosimetrically feasible with shorter treatment times, fewer MUs delivered, and comparable CIs for VMAT when compared with IMRT.

  4. Dosimetric comparison of different multileaf collimator leaves in treatment planning of intensity-modulated radiotherapy for cervical cancer

    SciTech Connect (OSTI)

    Wang, Shichao; Ai, Ping; Xie, Li; Xu, Qingfeng; Bai, Sen; Lu, You; Li, Ping; Chen, Nianyong

    2013-01-01

    To study the effect of multileaf collimator (MLC) leaf widths (standard MLC [sMLC] width of 10 mm and micro-MLC [mMLC] width of 4 mm) on intensity-modulated radiotherapy (IMRT) for cervical cancer. Between January 2010 and August 2010, a retrospective analysis was conducted on 12 patients with cervical cancer. The treatment plans for all patients were generated with the same machine setup parameters and optimization methods in a treatment planning system (TPS) based on 2 commercial Elekta MLC devices. The dose distribution for the planning tumor volume (PTV), the dose sparing for organs at risk (OARs), the monitor units (MUs), and the number of IMRT segments were evaluated. For the delivery efficiency, the MUs were significantly higher in the sMLC-IMRT plan than in the mMLC-IMRT plan (802 ± 56.9 vs 702 ± 56.7; p < 0.05). The number of segments in the plans were 58.75 ± 1.8 and 59 ± 1.04 (p > 0.05). For the planning quality, the conformity index (CI) between the 2 paired IMRT plans with the mMLC and the sMLC did not differ significantly (average: 0.817 ± 0.024 vs 0.810 ± 0.028; p > 0.05). The differences of the homogeneity index (HI) between the 2 paired plans were statistically significant (average: 1.122 ± 0.010 vs 1.132 ± 0.014; p < 0.01). For OARs, the rectum, bladder, small intestine, and bony pelvis were evaluated in terms of V{sub 10}, V{sub 20}, V{sub 30}, and V{sub 40}, percentage of contoured OAR volumes receiving 10, 20, 30, and 40 Gy, respectively, and the mean dose (D{sub mean}) received. The IMRT plans with the mMLC protected the OARs better than the plans with the sMLC. There were significant differences (p < 0.05) in evaluated parameters between the 2 paired IMRT plans, except for V{sub 30} and V{sub 40} of the rectum and V{sub 10}, V{sub 20}, V{sub 40}, and D{sub mean} of the bladder. IMRT plans with the mMLC showed advantages over the plans with the sMLC in dose homogeneity for targets, dose sparing of OARs, and fewer MUs in cervical cancer.

  5. SU-E-T-606: A Novel Integrated VMAT/IMRT Technique For the Treatment of Non-Small Cell Lung Cancer

    SciTech Connect (OSTI)

    Zhao, N; Yang, R; Wang, J

    2014-06-01

    Purpose: To investigate a novel Integrated VMAT/IMRT technique which combines volumetric modulated arc therapy (VMAT) and intensity modulated radiation therapy (IMRT) for non-small cell lung cancer (NSCLC). Methods: 2 partial arcs VMAT, 5-field IMRT and Integrated VMAT/IMRT plans were created for 17 patients with NSCLC. The Integrated VMAT/IMRT technique consisted of 2 partial VMAT arcs and 5 IMRT fields. The dose distribution of planning target volume (PTV) and organs at risk (OARs) for Integrated VMAT/IMRT was compared with IMRT and VMAT. The monitor units (MUs) and treatment delivery time were also evaluated. For each plan, a dry run was performed to assess the dosimetric accuracy with MatriXX from IBA. Results: Integrated VMAT/IMRT significantly improved the target conformity and homogeneity. The V30 of normal lung for Integrated plans was significantly lower than IMRT plans (8.4% vs 9.2%; p<0.05). The V5 and mean lung dose (MLD) of normal lung for Integrated plans were 9.8% and 4.6% lower than VMAT plans (p<0.05). The maximum dose of spinal cord for Integrated plans was 4.9 Gy lower than IMRT plans (p<0.05). The mean delivery time of IMRT, VMAT and Integrated plans was 280 s, 114 s, and 327 s, respectively. The mean MUs needed for IMRT, VMAT and Integrated plans were 933, 512, and 737, respectively. The gamma pass rates were beyond 90% at the 3%/3 mm criteria when the gantry angles were set to 0 for pretreatment verification. Conclusion: Integrated VMAT/IMRT technique significantly reduced V5, V10 and MLD of normal lung compared with VMAT, and the irradiated volume of the OARs receiving medium to high dose with fewer MUs compared with IMRT. Integrated VMAT/IMRT technique can be a feasible radiotherapy technique with better plan quality and accurately delivered on the linear accelerator. Ruijie Yang was funded by the grant project: National Natural Science Foundation of China (No. 81071237). Other authors have no competing interest for this work.

  6. ABSOLUTE TIMING OF THE CRAB PULSAR WITH THE INTEGRAL/SPI TELESCOPE

    SciTech Connect (OSTI)

    Molkov, S.; Jourdain, E.; Roques, J. P.

    2010-01-01

    We have investigated the pulse shape evolution of the Crab pulsar emission in the hard X-ray domain of the electromagnetic spectrum. In particular, we have studied the alignment of the Crab pulsar phase profiles measured in the hard X-rays and in other wavebands. To obtain the hard X-ray pulse profiles, we have used six years (2003-2009, with a total exposure of about 4 Ms) of publicly available data of the SPI telescope on-board the International Gamma-Ray Astrophysics Laboratory observatory, folded with the pulsar time solution derived from the Jodrell Bank Crab Pulsar Monthly Ephemeris. We found that the main pulse in the hard X-ray 20-100 keV energy band leads the radio one by 8.18 +- 0.46 milliperiods in phase, or 275 +- 15 mus in time. Quoted errors represent only statistical uncertainties. Our systematic error is estimated to be approx40 mus and is mainly caused by the radio measurement uncertainties. In hard X-rays, the average distance between the main pulse and interpulse on the phase plane is 0.3989 +- 0.0009. To compare our findings in hard X-rays with the soft 2-20 keV X-ray band, we have used data of quasi-simultaneous Crab observations with the proportional counter array monitor on-board the Rossi X-Ray Timing Explorer mission. The time lag and the pulses separation values measured in the 3-20 keV band are 0.00933 +- 0.00016 (corresponding to 310 +- 6 mus) and 0.40016 +- 0.00028 parts of the cycle, respectively. While the pulse separation values measured in soft X-rays and hard X-rays agree, the time lags are statistically different. Additional analysis show that the delay between the radio and X-ray signals varies with energy in the 2-300 keV energy range. We explain such a behavior as due to the superposition of two independent components responsible for the Crab pulsed emission in this energy band.

  7. Recent progress in PNC`s MLIS Project

    SciTech Connect (OSTI)

    Yamaguchi, Hiromi; Suto, Osamu; Tashiro, Kiyoshi; Kawakami, Shigeaki; Shimazaki, Yoshihiro

    1994-12-31

    Research on the molecular laser isotope separation (MLIS) processing of uranium in Japan was initiated by the Institute of Physical and Chemical Research (RIKEN), who achieved a head separation factor as high as 4.7 in a single step using their original process. The Power Reactor and Nuclear Fuel Development Corporation (PNC) has continued the MLIS project in cooperation with RIKEN since 1988. The Japan Atomic Energy Committee will make a decision by about the year 2000 concerning whether or not to carry research and development efforts with respect to the laser enrichment technologies of uranium forward to the next stage. Our MUS development program was previously described in detail. In this paper we briefly discuss the fundamentals of the MLIS process and present some new information about our project.

  8. Observation of Stueckelberg oscillations in dipole-dipole interactions

    SciTech Connect (OSTI)

    Ditzhuijzen, C. S. E. van; Tauschinsky, Atreju; Van Linden van den Heuvell, H. B.

    2009-12-15

    We have observed Stueckelberg oscillations in the dipole-dipole interaction between Rydberg atoms with an externally applied radio-frequency field. The oscillating rf field brings the interaction between cold Rydberg atoms in two separated volumes into resonance. We observe multiphoton transitions when varying the amplitude of the rf field and the static electric field offset. The angular momentum states we use show a quadratic Stark shift, which leads to a fundamentally different behavior than linearly shifting states. Both cases are studied theoretically using the Floquet approach and are compared. The amplitude of the sidebands, related to the interaction strength, is given by the Bessel function in the linearly shifting case and by the generalized Bessel function in the quadratically shifting case. The oscillatory behavior of both functions corresponds to Stueckelberg oscillations, an interference effect described by the semiclassical Landau-Zener-Stueckelberg model. The measurements prove coherent dipole-dipole interaction during at least 0.6 mus.

  9. Ionization of Rb Rydberg atoms in the attractive nsnp dipole-dipole potential

    SciTech Connect (OSTI)

    Park, Hyunwook; Shuman, E. S.; Gallagher, T. F.

    2011-11-15

    We have observed the ionization of a cold gas of Rb Rydberg atoms which occurs when nsns van der Waals pairs of ns atoms of n{approx_equal} 40 on a weakly repulsive potential are transferred to an attractive dipole-dipole nsnp potential by a microwave transition. Comparing the measurements to a simple model shows that the initial 300-{mu}K thermal velocity of the atoms plays an important role. Excitation to a repulsive dipole-dipole potential does not lead to more ionization on a 15-{mu}s time scale than leaving the atoms in the weakly repulsive nsns state. This observation is slightly surprising since a radiative transition must occur to allow ionization in the latter case. Finally, by power broadening of the microwave transition, to allow transitions from the initial nsns state to the nsnp state over a broad range of internuclear spacings, it is possible to accelerate markedly the evolution to a plasma.

  10. Direct Observation of the Phenomenology of a Solid Thermal Explosion Using Time-Resolved Proton Radiography

    SciTech Connect (OSTI)

    Smilowitz, L.; Henson, B. F.; Romero, J. J.; Asay, B. W.; Schwartz, C. L.; Saunders, A.; Merrill, F. E.; Morris, C. L.; Kwiatkowski, K.; Hogan, G.; Nedrow, P.; Murray, M. M.; Thompson, T. N.; McNeil, W.; Rightley, P.; Marr-Lyon, M.

    2008-06-06

    We present a new phenomenology for burn propagation inside a thermal explosion based on dynamic radiography. Radiographic images were obtained of an aluminum cased solid cylindrical sample of a plastic bonded formulation of octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine. The phenomenology observed is ignition followed by cracking in the solid accompanied by the propagation of a radially symmetric front of increasing proton transmission. This is followed by a further increase in transmission through the sample, ending after approximately 100 {mu}s. We show that these processes are consistent with the propagation of a convective burn front followed by consumption of the remaining solid by conductive particle burning.

  11. Ion funnel ion trap and process

    DOE Patents [OSTI]

    Belov, Mikhail E [Richland, WA; Ibrahim, Yehia M [Richland, WA; Clowers, Biran H [West Richland, WA; Prior, David C [Hermiston, OR; Smith, Richard D [Richland, WA

    2011-02-15

    An ion funnel trap is described that includes a inlet portion, a trapping portion, and a outlet portion that couples, in normal operation, with an ion funnel. The ion trap operates efficiently at a pressure of .about.1 Torr and provides for: 1) removal of low mass-to-charge (m/z) ion species, 2) ion accumulation efficiency of up to 80%, 3) charge capacity of .about.10,000,000 elementary charges, 4) ion ejection time of 40 to 200 .mu.s, and 5) optimized variable ion accumulation times. Ion accumulation with low concentration peptide mixtures has shown an increase in analyte signal-to-noise ratios (SNR) of a factor of 30, and a greater than 10-fold improvement in SNR for multiply charged analytes.

  12. Aggregation behavior of hexaoxyethyleneglycol myristate and hexaoxyethyleneglycol mono (1-methyltridecane) ether and dynamics of their micelles in aqueous solution

    SciTech Connect (OSTI)

    Alami, E.; Zana, R. ); Van Os, N.M.; Jong, B. de; Kerkhof, F.J.M. ); Rupert, L.A.M. )

    1993-10-01

    The title surfactants have similar critical micelle concentrations and cloud temperatures. Their micellar solutions have been investigated by time resolved fluorescence quenching in the range 2--25 c. The micelle aggregation numbers of both surfactants do not differ much, and increase with temperature. Aggregation numbers are large, suggesting anisotropic micelles, and the results show that the micelles are polydisperse. Fast intermicellar exchange of material becomes detectable on the fluorescence timescale ([approximately]1 [mu]s) above T [approx] 10 C, i.e., some 35--40 C below the cloud temperature of the solution. This exchange probably occurs via micelle collisions with temporary merging. Overall the behavior of these two surfactants is very similar to that of the other ethoxylated nonionic surfactants previously examined.

  13. A digital optical phase-locked loop for diode lasers based on field programmable gate array

    SciTech Connect (OSTI)

    Xu Zhouxiang; Zhang Xian; Huang Kaikai; Lu Xuanhui

    2012-09-15

    We have designed and implemented a highly digital optical phase-locked loop (OPLL) for diode lasers in atom interferometry. The three parts of controlling circuit in this OPLL, including phase and frequency detector (PFD), loop filter and proportional integral derivative (PID) controller, are implemented in a single field programmable gate array chip. A structure type compatible with the model MAX9382/MCH12140 is chosen for PFD and pipeline and parallelism technology have been adapted in PID controller. Especially, high speed clock and twisted ring counter have been integrated in the most crucial part, the loop filter. This OPLL has the narrow beat note line width below 1 Hz, residual mean-square phase error of 0.14 rad{sup 2} and transition time of 100 {mu}s under 10 MHz frequency step. A main innovation of this design is the completely digitalization of the whole controlling circuit in OPLL for diode lasers.

  14. Deployment at the Savannah River Site of a standardized, modular transportable and connectable hazard category 2 nuclear system for repackaging TRU waste

    SciTech Connect (OSTI)

    Lussiez, G.; Hickman, S.; Anast, K. R.; Oliver, W. B.

    2004-01-01

    This paper describes the conception, design, fabrication and deployment of a modular, transportable, connectable Category 2 nuclear system deployed at the Savannah River site to be used for characterizing and repackaging Transuranic Waste destined for the Waste Isolation Pilot Plant (WIPP). A standardized Nuclear Category 2 and Performance Category 2 envelope called a 'Nuclear Transportainer' was conceived and designed that provides a safety envelope for nuclear operations. The Nuclear Transportainer can be outfitted with equipment that performs functions necessary to meet mission objectives, in this case repackaging waste for shipment to WIPP. Once outfitted with process and ventilation systems the Nuclear Transportainer is a Modular Unit (MU). Each MU is connectable to other MUS - nuclear or non-nuclear - allowing for multiple functions, command & control, or increasing capacity. The design took advantage of work already in-progress at Los Alamos National Laboratory (LANL) for a similar system to be deployed at LANL's Technical Area 54.

  15. Atom detection in a two-mode optical cavity with intermediate coupling: Autocorrelation studies

    SciTech Connect (OSTI)

    Norris, D. G.; Cahoon, E. J.; Orozco, L. A.

    2009-10-15

    We use an optical cavity in the regime of intermediate coupling between atom and cavity mode to detect single moving atoms. Degenerate polarization modes allow excitation of the atoms in one mode and collection of spontaneous emission in the other while keeping separate the two sources of light; we obtain a higher confidence and efficiency of detection by adding cavity-enhanced Faraday rotation. Both methods greatly benefit from coincidence detection of photons, attaining fidelities in excess of 99% in less than 1 {mu}s. Detailed studies of the second-order intensity autocorrelation function of light from the signal mode reveal evidence of antibunched photon emissions and the dynamics of single-atom transits.

  16. Critical Magnetic Field Determination of Superconducting Materials

    SciTech Connect (OSTI)

    Canabal, A.; Tajima, T.; Dolgashev, V.A.; Tantawi, S.G.; Yamamoto, T.; /Tsukuba, Natl. Res. Lab. Metrol.

    2011-11-04

    Superconducting RF technology is becoming more and more important. With some recent cavity test results showing close to or even higher than the critical magnetic field of 170-180 mT that had been considered a limit, it is very important to develop a way to correctly measure the critical magnetic field (H{sup RF}{sub c}) of superconductors in the RF regime. Using a 11.4 GHz, 50-MW, <1 {mu}s, pulsed power source and a TE013-like mode copper cavity, we have been measuring critical magnetic fields of superconductors for accelerator cavity applications. This device can eliminate both thermal and field emission effects due to a short pulse and no electric field at the sample surface. A model of the system is presented in this paper along with a discussion of preliminary experimental data.

  17. Phosphorescent organic light emitting diodes with high efficiency and brightness

    DOE Patents [OSTI]

    Forrest, Stephen R; Zhang, Yifan

    2015-11-12

    An organic light emitting device including a) an anode; b) a cathode; and c) an emissive layer disposed between the anode and the cathode, the emissive layer comprising an organic host compound and a phosphorescent compound exhibiting a Stokes Shift overlap greater than 0.3 eV. The organic light emitting device may further include a hole transport layer disposed between the emissive layer and the anode; and an electron transport layer disposed between the emissive layer and the cathode. In some embodiments, the phosphorescent compound exhibits a phosphorescent lifetime of less than 10 .mu.s. In some embodiments, the concentration of the phosphorescent compound ranges from 0.5 wt. % to 10 wt. %.

  18. Modulator considerations for beam chopping in the low energy beam transport at the SSC Laboratory

    SciTech Connect (OSTI)

    Anderson, D.; Pappas, G.

    1991-06-01

    Beam chopping in the low energy transport line at the Superconducting Super Collider Laboratory is accomplished using an electrostatic deflection system. LINAC requirements dictate the design of two modulators operating at 10 Hz with rise and fall times (as measured from approximately 10--99%) of {approximately}100 ns. Design of the first pulser, normally at 10 kV and pulsed to ground potential, utilizes a transformer-coupled diode-clamped solid state circuit to achieve the 2--35 {mu}s pulse width range required. The second pulser, which pulses from ground to approximately 7 kV, relies on a series vacuum tube circuit. The current designs, as well as recent test results and other circuit topologies considered, will be presented. 6 refs.

  19. Regulation of Meiotic Recombination

    SciTech Connect (OSTI)

    Gregory p. Copenhaver

    2011-11-09

    Meiotic recombination results in the heritable rearrangement of DNA, primarily through reciprocal exchange between homologous chromosome or gene conversion. In plants these events are critical for ensuring proper chromosome segregation, facilitating DNA repair and providing a basis for genetic diversity. Understanding this fundamental biological mechanism will directly facilitate trait mapping, conventional plant breeding, and development of genetic engineering techniques that will help support the responsible production and conversion of renewable resources for fuels, chemicals, and the conservation of energy (1-3). Substantial progress has been made in understanding the basal recombination machinery, much of which is conserved in organisms as diverse as yeast, plants and mammals (4, 5). Significantly less is known about the factors that regulate how often and where that basal machinery acts on higher eukaryotic chromosomes. One important mechanism for regulating the frequency and distribution of meiotic recombination is crossover interference - or the ability of one recombination event to influence nearby events. The MUS81 gene is thought to play an important role in regulating the influence of interference on crossing over. The immediate goals of this project are to use reverse genetics to identify mutants in two putative MUS81 homologs in the model plant Arabidopsis thaliana, characterize those mutants and initiate a novel forward genetic screen for additional regulators of meiotic recombination. The long-term goal of the project is to understand how meiotic recombination is regulated in higher eukaryotes with an emphasis on the molecular basis of crossover interference. The ability to monitor recombination in all four meiotic products (tetrad analysis) has been a powerful tool in the arsenal of yeast geneticists. Previously, the qrt mutant of Arabidopsis, which causes the four pollen products of male meiosis to remain attached, was developed as a facile system

  20. Study of the fast photoswitching of spin crossover nanoparticles outside and inside their thermal hysteresis loop

    SciTech Connect (OSTI)

    Galle, G.; Degert, J.; Freysz, E.; Etrillard, C.; Letard, J.-F.; Guillaume, F.

    2013-02-11

    We have studied the low spin to high spin phase transition induced by nanosecond laser pulses outside and within the thermal hysteresis loop of the [Fe(Htrz){sub 2} trz](BF{sub 4}){sub 2}-H{sub 2}O spin crossover nanoparticles. We demonstrate that, whatever the temperature of the compound, the photo-switching is achieved in less than 12.5 ns. Outside the hysteresis loop, the photo-induced high spin state remains up to 100 {mu}s and then relaxes. Within the thermal hysteresis loop, the photo-induced high spin state remains as long as the temperature of the sample is kept within the thermal loop. A Raman study indicates that the photo-switching can be completed using single laser pulse excitation.

  1. Suitability of epitaxial GaAs for x-ray imaging

    SciTech Connect (OSTI)

    Sun, G.C.; Talbi, N.; Verdeil, C.; Bourgoin, J.C.

    2004-09-20

    Because the rate of indirect photon-electron conversion for scintillator materials coupled with arrays of photodiodes is at least 25 times smaller than the rate of direct conversion, we examine the conditions to be fulfilled by semiconductors undergoing such direct conversion to be applied to x-ray imaging. Bulk grown materials are not well suited to this application, because large defect concentrations give rise to strongly nonuniform electronic properties. We argue that only epitaxial layers are suitable for use as imaging devices and we illustrate our argument using the case of thick epitaxial GaAs layers. Detectors made with such layers exhibit a good energy resolution, a charge collection efficiency which approaches 1, linearity over more than three orders of amplitude, no afterglow (a response time shorter than 20 {mu}s), and no charge-induced polarization effects.

  2. Emittance Studies of the BNL/SLAC/UCLA 1.6 Cell Photocathode RF Gun

    SciTech Connect (OSTI)

    Palmer, D.T.; Wang, X.J.; Miller, R.H.; Babzien, M.; Ben-Zvi, I.; Pellegrini, C.; Sheehan, J.; Skaritka, J.; Winick, H.; Woodle, M.; Yakimenko, V.; /Brookhaven

    2011-09-09

    The symmetrized 1.6 cell S-band photocathode gun developed by the BNL/SLAC/UCLA collaboration is in operation at the Brookhaven Accelerator Test Facility (ATF). A novel emittance compensation solenoid magnet has also been designed, built and is in operation at the ATF. These two subsystems form an emittance compensated photoinjector used for beam dynamics, advanced acceleration and free electron laser experiments at the ATF. The highest acceleration field achieved on the copper cathode is 150 MV/m, and the guns normal operating field is 130 MV/m. The maximum rf pulse length is 3 {mu}s. The transverse emittance of the photoelectron beam were measured for various injection parameters. The 1 nC emittance results are presented along with electron bunch length measurements that indicated that at above the 400 pC, space charge bunch lengthening is occurring. The thermal emittance, {epsilon}{sub o}, of the copper cathode has been measured.

  3. Luminescent and lasing characteristics of heavily doped Yb{sup 3+}:KY(WO{sub 4}){sub 2} crystals

    SciTech Connect (OSTI)

    Kisel', V E; Troshin, A E; Shcherbitskii, V G; Kuleshov, N V; Pavlyuk, A A; Brunner, F; Paschotta, R; Morier-Genoud, F; Keller, U

    2006-04-30

    The luminescence decay times are measured taking into account reabsorption for KY(WO{sub 4}){sub 2}:Yb(KYW:Yb) crystals with atomic concentrations of active ions from 0.2% to 30%. The radiative lifetime of Yb{sup 3+} ions was measured to be 233 {mu}s. The cw output power of 1.46 and 1.62 W was achieved with the slope efficiency 52% and 47% for Yb:KYW lasers with the atomic concentration of Yb{sup 3+} ions equal to 10% and 30%, respectively. Using a semiconductor mirror with a saturable absorber (SESAM) in the passive mode-locking regime, pulses of duration 194 and 180 fs were obtained at wavelengths of 1042 and 1039 nm for crystals with Yb{sup 3+} concentrations equal to 10% and 30%, respectively, the average output power being 0.63 and 0.75 W. (lasers and amplifiers)

  4. Suppression of beam induced pulse shortening modes in high power RF generator TW output structures

    SciTech Connect (OSTI)

    Haimson, J.; Mecklenburg, B.

    1992-12-31

    Several different style 11.4 GHz relativistic klystrons, operating with beam pulse widths of 50 ns and using large aperture, tapered phase-velocity TW structures,` have recently demonstrated output RF power levels in the range of 100 to 300 MW without breakdown or pulse shortening. To extend this performance into the long pulse regime (1 {mu}s) or to demonstrate a threefold increase in output power by using higher currents, the existing TW circuit designs must be modified (a) to reduce the cavity maximum surface E-fields by a factor of 2 to 3, and (b) to elevate the current threshold values of the beam induced higher order modes (HOM) to ensure avoidance of RF pulse shortening and associated instabilities. A technique for substantially elevating this threshold current is described, and microwave data and photographs are presented showing the degree of HOM damping achieved in a recently constructed 11.4 GHz TW structure.

  5. Ultra-short ion and neutron pulse production

    DOE Patents [OSTI]

    Leung, Ka-Ngo; Barletta, William A.; Kwan, Joe W.

    2006-01-10

    An ion source has an extraction system configured to produce ultra-short ion pulses, i.e. pulses with pulse width of about 1 .mu.s or less, and a neutron source based on the ion source produces correspondingly ultra-short neutron pulses. To form a neutron source, a neutron generating target is positioned to receive an accelerated extracted ion beam from the ion source. To produce the ultra-short ion or neutron pulses, the apertures in the extraction system of the ion source are suitably sized to prevent ion leakage, the electrodes are suitably spaced, and the extraction voltage is controlled. The ion beam current leaving the source is regulated by applying ultra-short voltage pulses of a suitable voltage on the extraction electrode.

  6. Aerodynamic force measurement on a large-scale model in a short duration test facility

    SciTech Connect (OSTI)

    Tanno, H.; Kodera, M.; Komuro, T.; Sato, K.; Takahasi, M.; Itoh, K.

    2005-03-01

    A force measurement technique has been developed for large-scale aerodynamic models with a short test time. The technique is based on direct acceleration measurements, with miniature accelerometers mounted on a test model suspended by wires. Measuring acceleration at two different locations, the technique can eliminate oscillations from natural vibration of the model. The technique was used for drag force measurements on a 3 m long supersonic combustor model in the HIEST free-piston driven shock tunnel. A time resolution of 350 {mu}s is guaranteed during measurements, whose resolution is enough for ms order test time in HIEST. To evaluate measurement reliability and accuracy, measured values were compared with results from a three-dimensional Navier-Stokes numerical simulation. The difference between measured values and numerical simulation values was less than 5%. We conclude that this measurement technique is sufficiently reliable for measuring aerodynamic force within test durations of 1 ms.

  7. Possible high power limitations from RF pulsed heating

    SciTech Connect (OSTI)

    Pritzkau, D.P.; Bowden, G.B.; Menegat, A.; Siemann, R.H. [Stanford Linear Accelerator Center, Stanford University, California 94309 (United States)

    1999-05-01

    One of the possible limitations to achieving high power in RF structures is damage to metal surfaces due to RF pulsed heating. Such damage may lead to degradation of RF performance. An experiment to study RF pulsed heating on copper has been developed at SLAC. The experiment consists of operating two pillbox cavities in the TE{sub 011} mode using a 50 MW X-Band klystron. The estimated temperature rise of the surface of copper is 350&hthinsp;{degree}C for a power input of 20 MW to each cavity with a pulse length of 1.5 {mu}s. Preliminary results from an experiment performed earlier are presented. A revised design for continued experiments is also presented along with relevant theory and calculations. {copyright} {ital 1999 American Institute of Physics.}

  8. SU-E-T-480: Radiobiological Dose Comparison of Single Fraction SRS, Multi-Fraction SRT and Multi-Stage SRS of Large Target Volumes Using the Linear-Quadratic Formula

    SciTech Connect (OSTI)

    Ding, C; Hrycushko, B; Jiang, S; Meyer, J; Timmerman, R

    2014-06-01

    Purpose: To compare the radiobiological effect on large tumors and surrounding normal tissues from single fraction SRS, multi-fractionated SRT, and multi-staged SRS treatment. Methods: An anthropomorphic head phantom with a centrally located large volume target (18.2 cm{sup 3}) was scanned using a 16 slice large bore CT simulator. Scans were imported to the Multiplan treatment planning system where a total prescription dose of 20Gy was used for a single, three staged and three fractionated treatment. Cyber Knife treatment plans were inversely optimized for the target volume to achieve at least 95% coverage of the prescription dose. For the multistage plan, the target was segmented into three subtargets having similar volume and shape. Staged plans for individual subtargets were generated based on a planning technique where the beam MUs of the original plan on the total target volume are changed by weighting the MUs based on projected beam lengths within each subtarget. Dose matrices for each plan were export in DICOM format and used to calculate equivalent dose distributions in 2Gy fractions using an alpha beta ratio of 10 for the target and 3 for normal tissue. Results: Singe fraction SRS, multi-stage plan and multi-fractionated SRT plans had an average 2Gy dose equivalent to the target of 62.89Gy, 37.91Gy and 33.68Gy, respectively. The normal tissue within 12Gy physical dose region had an average 2Gy dose equivalent of 29.55Gy, 16.08Gy and 13.93Gy, respectively. Conclusion: The single fraction SRS plan had the largest predicted biological effect for the target and the surrounding normal tissue. The multi-stage treatment provided for a more potent biologically effect on target compared to the multi-fraction SRT treatments with less biological normal tissue than single-fraction SRS treatment.

  9. TH-E-BRE-05: Analysis of Dosimetric Characteristics in Two Leaf Motion Calculator Algorithms for Sliding Window IMRT

    SciTech Connect (OSTI)

    Wu, L; Huang, B; Rowedder, B; Ma, B; Kuang, Y

    2014-06-15

    Purpose: The Smart leaf motion calculator (SLMC) in Eclipse treatment planning system is an advanced fluence delivery modeling algorithm as it takes into account fine MLC features including inter-leaf leakage, rounded leaf tips, non-uniform leaf thickness, and the spindle cavity etc. In this study, SLMC and traditional Varian LMC (VLMC) algorithms were investigated, for the first time, in dosimetric characteristics and delivery accuracy of sliding window (SW) IMRT. Methods: The SW IMRT plans of 51 cancer cases were included to evaluate dosimetric characteristics and dose delivery accuracy from leaf motion calculated by SLMC and VLMC, respectively. All plans were delivered using a Varian TrueBeam Linac. The DVH and MUs of the plans were analyzed. Three patient specific QA tools - independent dose calculation software IMSure, Delta4 phantom, and EPID portal dosimetry were also used to measure the delivered dose distribution. Results: Significant differences in the MUs were observed between the two LMCs (p≤0.001).Gamma analysis shows an excellent agreement between the planned dose distribution calculated by both LMC algorithms and delivered dose distribution measured by three QA tools in all plans at 3%/3 mm, leading to a mean pass rate exceeding 97%. The mean fraction of pixels with gamma < 1 of SLMC is slightly lower than that of VLMC in the IMSure and Delta4 results, but higher in portal dosimetry (the highest spatial resolution), especially in complex cases such as nasopharynx. Conclusion: The study suggests that the two LMCs generates the similar target coverage and sparing patterns of critical structures. However, SLMC is modestly more accurate than VLMC in modeling advanced MLC features, which may lead to a more accurate dose delivery in SW IMRT. Current clinical QA tools might not be specific enough to differentiate the dosimetric discrepancies at the millimeter level calculated by these two LMC algorithms. NIH/NIGMS grant U54 GM104944, Lincy Endowed

  10. Confinement analyses of the high-density field-reversed configuration plasma in the field-reversed configuration experiment with a liner

    SciTech Connect (OSTI)

    Zhang Shouyin; Intrator, T.P.; Wurden, G.A.; Waganaar, W.J.; Taccetti, J.M.; Renneke, R.; Grabowski, C.; Ruden, E.L.

    2005-05-15

    The focus of the field-reversed configuration (FRC) experiment with a liner (FRX-L) is the formation of a target FRC plasma for magnetized target fusion experiments. An FRC plasma with density of 10{sup 23} m{sup -3}, total temperature in the range of 150-300 eV, and a lifetime of {approx_equal}20 {mu}s is desired. Field-reversed {theta}-pinch technology is used with programed cusp fields at {theta}-coil ends to achieve non-tearing field line reconnections during FRC formation. Well-formed FRCs with density between (2-4)x10{sup 22} m{sup -3}, lifetime in the range of 15-20 {mu}s, and total temperature between 300-500 eV are reproducibly created. Key FRC parameters have standard deviation in the mean of 10% during consecutive shots. The FRCs are formed at 50 mTorr deuterium static fill using 2 kG net reversed bias field inside the {theta}-coil confinement region, with external main field unexpectedly ranging between 15-30 kG. The high-density FRCs confinement properties are approximately in agreement with empirical scaling laws obtained from previous experiments with fill pressure mostly less than 20 mTorr. Analyses in this paper reveal that reducing the external main field modulation and/or extending the {theta}-coil length in the FRX-L device are critical in achieving higher FRC parameters for application in magnetized target fusion.

  11. SU-E-T-580: Comparison of Cervical Carcinoma IMRT Plans From Four Commercial Treatment Planning Systems (TPS)

    SciTech Connect (OSTI)

    Cao, Y; Li, R; Chi, Z; Zhu, S

    2014-06-01

    Purpose: Different treatment planning systems (TPS) use different treatment optimization and leaf sequencing algorithms. This work compares cervical carcinoma IMRT plans optimized with four commercial TPSs to investigate the plan quality in terms of target conformity and delivery efficiency. Methods: Five cervical carcinoma cases were planned with the Corvus, Monaco, Pinnacle and Xio TPSs by experienced planners using appropriate optimization parameters and dose constraints to meet the clinical acceptance criteria. Plans were normalized for at least 95% of PTV to receive the prescription dose (Dp). Dose-volume histograms and isodose distributions were compared. Other quantities such as Dmin(the minimum dose received by 99% of GTV/PTV), Dmax(the maximum dose received by 1% of GTV/PTV), D100, D95, D90, V110%, V105%, V100% (the volume of GTV/PTV receiving 110%, 105%, 100% of Dp), conformity index(CI), homogeneity index (HI), the volume of receiving 40Gy and 50 Gy to rectum (V40,V50) ; the volume of receiving 30Gy and 50 Gy to bladder (V30,V50) were evaluated. Total segments and MUs were also compared. Results: While all plans meet target dose specifications and normal tissue constraints, the maximum GTVCI of Pinnacle plans was up to 0.74 and the minimum of Corvus plans was only 0.21, these four TPSs PTVCI had significant difference. The GTVHI and PTVHI of Pinnacle plans are all very low and show a very good dose distribution. Corvus plans received the higer dose of normal tissue. The Monaco plans require significantly less segments and MUs to deliver than the other plans. Conclusion: To deliver on a Varian linear-accelerator, the Pinnacle plans show a very good dose distribution. Corvus plans received the higer dose of normal tissue. The Monaco plans have faster beam delivery.

  12. SciSat AM: Stereo 03: Dosmetric evaluation of single versus multi-arc VMAT for lung SBRT

    SciTech Connect (OSTI)

    Karan, T; Taremi, M; Comsa, D; Allibhai, Z; Ryan, M; Le, K

    2014-08-15

    Five non-small cell lung cancer patients previously treated with stereotactic body radiation therapy using the VMAT (volumetric modulated arc therapy) technique were selected for this retrospective study. Plans were re-optimized using Pinnacle treatment planning system (v9.0, Philips Medical), with the basis for comparison a two-arc plan involving a 360 arc in addition to a 90 arc with a couch kick. Additionally a single 360 arc was optimized for comparison, as well as a partial arc covering ?230, avoiding the contralateral lung. All plans met target coverage criteria as dictated by RTOG0236. Plans were evaluated based on conformity, sparing of organs at risk and practical considerations of delivery. Conformity was best in the two-arc plan; however the decrease seen in one- and partial arc plans was not statistically significant as tested by the Wilcoxon rank sum test. The partial-arc plan resulted in the lowest esophagus and trachea dose and the highest heart dose, however none of the plans exceeded organ at risk tolerances for lung SBRT. Partial arcs resulted in plans with slightly cooler dose distributions, a decrease in low dose spillage and an overall lower mean lung dose. The decrease in treatment time was on average 36 and 40 seconds for single and partial arcs, respectively, with partial arcs requiring the lowest number of MUs. The slight decrease in conformity seen in one-arc plans is offset by an increase in efficiency (optimization and treatment time, MUs) making the implementation of a single or partial-arc treatment technique clinically desirable.

  13. SU-E-T-131: Dosimetric Impact and Evaluation of Different Heterogenity Algorithm in Volumetric Modulated Arc Therapy Plan for Stereotactic Ablative Radiotherapy Lung Treatment with the Flattening Filter Free Beam

    SciTech Connect (OSTI)

    Chung, J; Kim, J; Lee, J; Kim, Y

    2014-06-01

    Purpose: The present study aimed to investigate the dosimetric impacts of the anisotropic analytic algorithm (AAA) and the Acuros XB (AXB) plan for lung stereotactic ablative radiation therapy using flattening filter-free (FFF) beam. We retrospectively analyzed 10 patients. Methods: We retrospectively analyzed 10 patients. The dosimetric parameters for the target and organs at risk (OARs) from the treatment plans calculated with these dose calculation algorithms were compared. The technical parameters, such as the computation times and the total monitor units (MUs), were also evaluated. Results: A comparison of DVHs from AXB and AAA showed that the AXB plan produced a high maximum PTV dose by average 4.40% with a statistical significance but slightly lower mean PTV dose by average 5.20% compared to the AAA plans. The maximum dose to the lung was slightly higher in the AXB compared to the AAA. For both algorithms, the values of V5, V10 and V20 for ipsilateral lung were higher in the AXB plan more than those of AAA. However, these parameters for contralateral lung were comparable. The differences of maximum dose for the spinal cord and heart were also small. The computation time of AXB was found fast with the relative difference of 13.7% than those of AAA. The average of monitor units (MUs) for all patients was higher in AXB plans than in the AAA plans. These results indicated that the difference between AXB and AAA are large in heterogeneous region with low density. Conclusion: The AXB provided the advantages such as the accuracy of calculations and the reduction of the computation time in lung stereotactic ablative radiotherapy (SABR) with using FFF beam, especially for VMAT planning. In dose calculation with the media of different density, therefore, the careful attention should be taken regarding the impacts of different heterogeneity correction algorithms. The authors report no conflicts of interest.

  14. The earliest events in protein folding: Helix dynamics in proteins and model peptides

    SciTech Connect (OSTI)

    Dyer, R.B.; Williams, S.; Woodruff, W.H. [Los Alamos National Lab., NM (United States)] [and others

    1996-12-31

    The earliest events in protein folding are critically important in determining the folding pathway, but have proved difficult to study by conventional approaches. We have developed new rapid initiation methods and structure-specific probes to interrogate the earliest events of protein folding. Our focus is the pathways. Folding or unfolding reactions are initiated on a fast timescale (10 ns) using a laser induced temperature jump (15 C) and probed with time-resolved infrared spectroscopy. We obtained the kinetics of the helix-coil transition for a model 21-residue peptide. The observed rate constant k{sub obs} = k{sub f} + k{sub u} for reversible kinetics; from the observed rate (6 x 10{sup 6} s{sup -1}) and the equilibrium constant favoring folding of 7.5 at 27 C, we calculate a folding lifetime of 180 ns and an unfolding lifetime of 1.4 {mu}s. The {open_quotes}molten globule{close_quotes} form of apomyoglobin (horse, pH*3, 0.15M NaCl) shows similar kinetics for helix that is unconstrained by tertiary structure (helix with an unusually low Amide I frequency, near 1633 cm{sup -1}). In {open_quotes}native{close_quotes} apomyoglobin (horse, pH*5.3, 10 mM NaCl) two very different rates (45 ns and 70 {mu}s) are observed and we infer that a third occurs on a timescales inaccessible to our experiment (> 1 ms). We suggest that the slower processes are due to helix formation that is rate-limited by the formation of tertiary structure.

  15. SU-E-T-495: Neutron Induced Electronics Failure Rate Analysis for a Single Room Proton Accelerator

    SciTech Connect (OSTI)

    Knutson, N; DeWees, T; Klein, E

    2014-06-01

    Purpose: To determine the failure rate as a function of neutron dose of the range modulator's servo motor controller system (SMCS) while shielded with Borated Polyethylene (BPE) and unshielded in a single room proton accelerator. Methods: Two experimental setups were constructed using two servo motor controllers and two motors. Each SMCS was then placed 30 cm from the end of the plugged proton accelerator applicator. The motor was then turned on and observed from outside of the vault while being irradiated to known neutron doses determined from bubble detector measurements. Anytime the motor deviated from the programmed motion a failure was recorded along with the delivered dose. The experiment was repeated using 9 cm of BPE shielding surrounding the SMCS. Results: Ten SMCS failures were recorded in each experiment. The dose per monitor unit for the unshielded SMCS was 0.0211 mSv/MU and 0.0144 mSv/MU for the shielded SMCS. The mean dose to produce a failure for the unshielded SMCS was 63.5 58.3 mSv versus 17.0 12.2 mSv for the shielded. The mean number of MUs between failures were 2297 1891 MU for the unshielded SMCS and 2122 1523 MU for the shielded. A Wilcoxon Signed Ranked test showed the dose between failures were significantly different (P value = 0.044) while the number of MUs between failures were not (P value = 1.000). Statistical analysis determined a SMCS neutron dose of 5.3 mSv produces a 5% chance of failure. Depending on the workload and location of the SMCS, this failure rate could impede clinical workflow. Conclusion: BPE shielding was shown to not reduce the average failure of the SMCS and relocation of the system outside of the accelerator vault was required to lower the failure rate enough to avoid impeding clinical work flow.

  16. Elctronic current transducer for ehv circuits. Final report

    SciTech Connect (OSTI)

    Berkebile, L.E.

    1980-11-01

    As ehv and uhv grow a need arises for better current measuring methods. Conventional live tank current transformers become much larger and more costly as voltage withstand requirements become higher. Better accuracy is desirable as larger power flow occurs on interties between power systems. Improved high frequency response is required for advanced high speed relaying techniques and for current limiter operation. Previous current transducers have fulfilled some, but not all, of these requirements. The objective of this project is to provide an electronic current transducer that meets present and projected requirements. The specific objective of this project was to develop an electric current transducer with (1) amplitude error less than 0.3%; (2) dynamic range of twenty times rated current; (3) 10 kHz frequency response; (4) less than 100 ..mu..s turn on time; (5) digital output; and (6) utilizing fiber optic data transmission for EMI free operation. The project objectives have been met except that turn-on-time is 200 ..mu..s. The transducer developed utilizes a conventional current transformer and shunt to provide a reference signal to the electronic encoding system. The encoder power supply is obtained from a current transformer on the transmission line. No auxiliary power supply is required. The encoded data signal is transmitted serially over a single conductor optical fiber cable to the station control room, a distance of up to 300 m. The signal is decoded and converted to parallel digital output and an analog output signal is reconstructed too. This analog signal provides +-10V output to represent full scale peak line current.

  17. JLab, College of W&M researchers study radiation blockers while conducting

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    nuclear imaging of Iodine uptake in mouse tissues | Jefferson Lab JLab, College of W&amp;M researchers study radiation blockers while conducting nuclear imaging of Iodine uptake in mouse tissues JLab, College of W&M researchers study radiation blockers while conducting nuclear imaging of Iodine uptake in mouse tissues April 20, 2005 Scientists have found that a dose five times higher than the FDA-recommended dosage of potassium iodide in the event of a nuclear accident is needed to

  18. System Provides Clear Brain Scans of Awake, Unrestrained Mice | Jefferson

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Lab System Provides Clear Brain Scans of Awake, Unrestrained Mice System Provides Clear Brain Scans of Awake, Unrestrained Mice dynamic imaging of mice Three markers attached to the head of a mouse enable the AwakeSPECT system to obtain detailed, functional images of the brain of a conscious mouse as it moves around. NEWPORT NEWS, Va., April 9 - Setting a mouse free to roam might alarm most people, but not so for nuclear imaging researchers from the U.S. Department of Energy's Thomas

  19. Regional Dialogue Public Comments & Proposals (contracts/rd)

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    drive, click on the link with your right mouse button and select "Save Target As". Ken Canon, Executive Director, ICNU, June 13, 2005 (PDF, 4 pages, 73 kb, posted June 21, 2005)...

  20. Structure of Actin Cross-linked with alpha-Actinin: A Network...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    under in vitro conditions. We show in Fig. 1 (left) laser scanning confocal microscope images of the actin cytoskeleton in mouse fibroblast cells. (The image is showing only the...

  1. U.S. Energy Information Administration (EIA)

    Annual Energy Outlook [U.S. Energy Information Administration (EIA)]

    the chart data. Note that in some cases data cannot be provided due to its proprietary nature or licensing restrictions. Zooming On some charts dragging your mouse over a section...

  2. Monoclonal antibodies to human glycophorin A and cell lines for the production thereof

    DOE Patents [OSTI]

    Vanderlaan, Martin; Bigbee, William L.; Jensen, Ronald H.; Fong, Stella S. N.; Langlois, Richard G.

    1988-01-01

    Cloned mouse hybridoma cell lines have been established which continuously produce antibodies that are highly specific to and exhibit high affinity for glycophorin A.sup.N and differentiate between the M and N forms of human glycophorin A.

  3. Volume Visualization

    Office of Scientific and Technical Information (OSTI)

    ... and the similarity plot for the two fish species, which is mapped to the blue channel. ... are conserved regions in the human-mouse-chicken plot that are absent in the fish plot. ...

  4. ORNL-5904 DE82 C19734 ORNL-5904 Cootr»* No. W 7405-eng-2o

    Office of Scientific and Technical Information (OSTI)

    ... R.; Mitra, S. "Restriction Map of the Single-Stranded DNA Genome of Kilham Rat Virus ... of the Restriction of the Endogenous Virus of the RFMUn Mouse," p 255. Abstracts of ...

  5. Our Hidden Past: Biology, part 2 | Y-12 National Security Complex

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Time: 7:11 min. In their new home at "The Mouse House" at Y-12, researchers from ORNL's Biology Division conducted studies that led to standards such as dose rate effects that form ...

  6. Inhibiting Individual Notch Receptors Improves Treatment

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    in large tumors (approximately 2000 mm3). Bottom: Anti-NRR1 inhibits proper growth of blood vessels, resulting in a "hyper-vascularized" network of blood vessels in mouse neonate...

  7. Los Alamos National Laboratory announces Express Licensing program

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    of the software packages are freely available as either executable downloads or open-source software and may be accessed online with the click of a mouse." "By making access to...

  8. Translating Discoveries to Market Deployment

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    ... Storage (SMES) c) First combined MRI-PET imaging (on mouse liver) done with 52 Fe nanoparticles developed by BNL's radioisotope group a) BNL- patented RCMS pulse-to-pulse ...

  9. Jefferson Lab Detector Technology Aids Development of Cystic...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    the radiotracer, which is trapped in cells containing the transferred gene in the lungs and liver of the mouse. Click image for high-resolution file (7.8MB) Photo credit: Dr....

  10. Section 508 of the Rehabilitation Act | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    New and redesigned sites should be compliant when submitted to the Web Governance Team for ... Making PDFs accessible Developing web applications so they can be used without a mouse. ...

  11. History | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    History History This timeline features the key innovations that have advanced the solar industry in the United States. Learn more about these key events from 1955 to present. To see more details, either drag the timeline to the left or right or click the (+) icons. Solar Achievements Timeline INSTRUCTIONS Instructional graphic for mouse use. Click and drag screen or scroll mouse wheel to navigate through timeline. 2011 INDUSTRY Graphic of the U.S. Department of Energy logo. A yellow,

  12. Confidential balls minimizing in mean convex functional

    SciTech Connect (OSTI)

    Kaminsky, V.

    1994-12-31

    Let H be a Hilbert space, H{sub 0} {contained_in} H be a subspace in it; {Sigma}i{sigma}-algebra of Borel subsets from H{sub 0}, s = s(x, r) is the bal of radius r with the center at the point x {element_of} H and t = t(x, r) is its boundary, a sphere. Let measure {mu} defined on {Sigma} be finite nonnegative and satisfy the following condition: {mu}(H{sub 0}) = 1. By fixing two nonnegative numbers {mu}{sub 0}, where 0 < {mu}{sub 0} < 1, and R > 0, we indicate from {sigma}-algebra {Sigma} the class S = {l_brace}s,(x, r) {element_of} {Sigma}: {mu}(s) {>=} {mu}{sub o}, r {<=} R{r_brace}. Let {var_phi}(x) be a convex eigen functional on H such that it is bounded on each ball s {element_of} S{sub 0}. It is possible to introduce an averaging functional for each ball s {element_of} S {Phi}(s) = {sub {mu}(s)}{sup 1} {integral}{sub s(x, r)} {var_phi}(y){mu}(dy) = {sub {mu}(s(x, r))}{sup 1} {integral}{sub s({theta}, r)} {var_phi}(x + {xi}){mu}(d{xi}) = F(x, r) and to consider the following extremal problem {Phi}(s) {yields} inf{sub s{epsilon}S}. We can interpret such a formulation of the problem as an extremal problem with confidential condition ({mu}s) {>=} {mu}{sub 0}. It is possible to consider the formulations of problem of such type in order to generalize the classical problems in mathematical programming in which now we find an extremal subset of an extremal element. The following results are obtained: theorems about existence of an extremal ball, necessary condition for a ball to be extremal in problems of such types, sufficient conditions of extremality of the ball by stronger restrictions on functional and measure in the problem.

  13. Adaptation of existing facilities to isentropic compression experiments

    SciTech Connect (OSTI)

    Tasker, Douglas G; Mielke, Charles H; Rodriguez, George; Rickel, Dwight G

    2011-01-07

    We demonstrate that the established pulsed power infrastructure at the National High Magnetic Field Laboratory - Pulsed Field Facility (NHMFL-PFF) at the Los Alamos National Laboratory can be adapted to obtain high quality isentropic compression experiment (ICE) data on materials in extreme conditions of dynamic high pressure. Experiments utilized a single-turn magnet pulsed power system at the NHMFL-PFF that was originally designed to measure actinide samples in extremes of high magnetic field (to 300 Tesla). A simple modification to the single-turn magnet has converted it to a fast turnaround dynamic high pressure measurement system. This paper details the work done including important background details that indicate that much more can be accomplished with optimization of the load characteristics in terms of ultimate peak pressures. To match the rise time of the NHMFL capacitor bank ({approx}2 {mu}s versus {approx}0.5 {mu}s for the Sandia Z-machine) the sample dimensions can be relatively large, i.e., up to 5 mm thickness. The maximum stresses are {approx}50GPa (0.5 Mbar) at the maximum bank voltage (60 kV) and higher pressures may be possible if the sample is tamped. For the design and predictions of performance of the NHMFL-ICE experiment it is important to have good predictive models. A SPICE code simulation was chosen to model all aspects of the experiment, electrical and physical. To this end, accurate dynamic load models were developed to simulate the compression and expansion of the dynamic load at high pressures using shock physics principles. A series experiments have been performed which demonstrated the feasibility of the NHMFL-ICE technique. The results will be shown and discussed. The NHMFL-ICE technique is an excellent method for measuring equations of state (EOS) at megabar pressures. Because a complete EOS can be obtained in one experiment from zero to the peak pressure, and because many shots can be fired in one day, the technique promises to

  14. Human chromosome 17 comparative anchor loci are conserved on bovine chromosome 19

    SciTech Connect (OSTI)

    Yang, Y.P.; Womack, J.E.

    1995-05-20

    Eight comparative anchor loci on human chromosome 17, TP53, CHRNB1, THRA1, CRYB1, NF1, MPO, MYL4, and P4HB, were mapped to bovine chromosome 19 using bovine x hamster and bovine x mouse hybrid somatic cell lines. This completes the synteny mapping of human chromosome 17 comparative anchor loci in cattle, all of which have been mapped to bovine chromosome 19 and mouse chromosome 11, with the exception of CSH1. It is likely that the suggested homologue of human CSH1, PL1 on cattle chromosome 23, is a not true homologue of the human gene. This study reveals the largest conserved synteny segment among human, cattle, and mouse autosomes described to date. While all of the genes mapped to cattle chromosome 19 are on human chromosome 17, genes on mouse chromosome 11 are distributed on 7 human chromosomes, supporting the hypothesis that there is greater conservation of synteny between human and bovine chromosomes than between human and mouse. 37 refs., 2 figs., 2 tabs.

  15. Chromosomal localization, genomic structure, and allelic polymorphism of the human CD79a (lg-{alpha}/mb-1) gene

    SciTech Connect (OSTI)

    Hashimoto, S.; Gregersen, P.K.; Chiorazzi, N. |; Mohrenweiser, H.W.

    1994-12-31

    The germline DNA sequence of the human CD79a (Ig-{alpha}/mb-1) gene was determined by polymerase chain reaction sequencing of a cosmid clone derived from an arrayed human chromosome 19 library. The CD79a gene was localized to chromosome 19q13.2; this localization places the gene within the CEA-like gene cluster with the following gene order: -CEA-CGM1-CD79a-RPS11-ATP1A3-BGP-CGM9-. The genomic organization of the human CD79a gene resembles the mouse counterpart with five exons interrupted by four introns. Computer analyses suggest the presence of transcription regulatory elements known to be important in the regulation of mouse CD79a (AP-1, EBF, AP-2, MUF2, and SP-1 sites), as well as elements not found in the mouse gene (an NK-kB binding site and a series of E-box motifs). Similar to the mouse gene, the 5{prime} flanking region of human CD79a lacks a TATA box; however, unlike mouse CD79a, a classical octamer motif could not be identified in the human gene. Finally, a new Rsa I restriction fragment length polymorphism was defined in the non-coding regions of the human gene. 64 refs., 4 figs., 2 tabs.

  16. Carcinogenic effects in A/J mice of particulate of a coal-tar paint used in potable water systems

    SciTech Connect (OSTI)

    Robinson, M.; Laurie, R.D.; Bull, R.J.; Stober, J.A.

    1987-01-01

    Coal-tar paints are among the products used as inside coatings for water pipes and storage tanks to retard corrosion in potable water-supply systems. Four different formulations of these paints were tested in earlier work by this laboratory in the Ames mutagenesis and the mouse skin carcinogenesis bioassays(6). The paint most active in these assays was then tested in a particulate form in the lung adenoma assay with A/J mice. The paint was applied to clean glass plates, cured, collected and homogenized in 2% Emulphor. Doses of this coal-tar suspension were administered by gavage at 1.0, 10.0, and 55.0 mg in 0.2 ml per mouse 3 x weekly for 8 weeks. The total doses of coal-tar paint were 24, 240, and 1320 mg/mouse. Benzo(a)pyrene, administered in a parallel schedule to a total dose of 6 mg/mouse, served as positive control. A negative control group received an equivalent volume of 2% Emulphor. Animals were sacrificed at 9 months of age (8 months after first dose) and lung adenomas counted. A dose-related response, in the average number of lung tumors per mouse, was observed with the coal-tar particulate. There were also squamous-cell tumors of the forestomach in 42% of the mice receiving 55.0 mg coal tar paint per application.

  17. Knockdown of p53 suppresses Nanog expression in embryonic stem cells

    SciTech Connect (OSTI)

    Abdelalim, Essam Mohamed; Tooyama, Ikuo

    2014-01-10

    Highlights: We investigate the role of p53 in ESCs in the absence of DNA damage. p53 knockdown suppresses ESC proliferation. p53 knockdown downregulates Nanog expression. p53 is essential for mouse ESC self-renewal. -- Abstract: Mouse embryonic stem cells (ESCs) express high levels of cytoplasmic p53. Exposure of mouse ESCs to DNA damage leads to activation of p53, inducing Nanog suppression. In contrast to earlier studies, we recently reported that chemical inhibition of p53 suppresses ESC proliferation. Here, we confirm that p53 signaling is involved in the maintenance of mouse ESC self-renewal. RNA interference-mediated knockdown of p53 induced downregulation of p21 and defects in ESC proliferation. Furthermore, p53 knockdown resulted in a significant downregulation in Nanog expression at 24 and 48 h post-transfection. p53 knockdown also caused a reduction in Oct4 expression at 48 h post-transfection. Conversely, exposure of ESCs to DNA damage caused a higher reduction of Nanog expression in control siRNA-treated cells than in p53 siRNA-treated cells. These data show that in the absence of DNA damage, p53 is required for the maintenance of mouse ESC self-renewal by regulating Nanog expression.

  18. Strategies and tools for whole genome alignments

    SciTech Connect (OSTI)

    Couronne, Olivier; Poliakov, Alexander; Bray, Nicolas; Ishkhanov,Tigran; Ryaboy, Dmitriy; Rubin, Edward; Pachter, Lior; Dubchak, Inna

    2002-11-25

    The availability of the assembled mouse genome makespossible, for the first time, an alignment and comparison of two largevertebrate genomes. We have investigated different strategies ofalignment for the subsequent analysis of conservation of genomes that areeffective for different quality assemblies. These strategies were appliedto the comparison of the working draft of the human genome with the MouseGenome Sequencing Consortium assembly, as well as other intermediatemouse assemblies. Our methods are fast and the resulting alignmentsexhibit a high degree of sensitivity, covering more than 90 percent ofknown coding exons in the human genome. We have obtained such coveragewhile preserving specificity. With a view towards the end user, we havedeveloped a suite of tools and websites for automatically aligning, andsubsequently browsing and working with whole genome comparisons. Wedescribe the use of these tools to identify conserved non-coding regionsbetween the human and mouse genomes, some of which have not beenidentified by other methods.

  19. Alkylation damage repair in mammalian genomes

    SciTech Connect (OSTI)

    Mitra, S.; Roy, R.; Kim, N.K. |; Tano, K. |; Ibeanu, G.C. |; Dunn, W.C.; Natarajan, A.T.; Hartenstein, B.; Kaina, B.

    1992-11-01

    The repair of O{sup 6} -alkylguanine in DNA involves only O{sup 6} -methyltransferase (MGMT) while the repair of N-alkylpurines requires multiple proteins including N-methylpurine-DNA glycosylase (MPG). While the biochemical properties human and mouse MGMTs are very similar, the mouse MPG removes 7-methylguanine more efficiently than the human protein. An increased level of MGMT, without a change in the level of MPG associated with gene amplification, was observed in a mouse cell line resistant to 2-chloroethyl-N-nitrosourea. In contrast, no correlation was observed between MPG level and resistance to methyl methanesulfonate in Chinese hamster ovary (CHO) cells. This result suggests a protein other than MPG limits the repair rate of N-alkylpurine in CHO cells.

  20. Alkylation damage repair in mammalian genomes

    SciTech Connect (OSTI)

    Mitra, S.; Roy, R.; Kim, N.K. . Sealy Center for Molecular Science Oak Ridge National Lab., TN ); Tano, K. Oak Ridge National Lab., TN ); Ibeanu, G.C. Oak Ridge National Lab., TN ); Dunn, W.C. (

    1992-01-01

    The repair of O{sup 6} -alkylguanine in DNA involves only O{sup 6} -methyltransferase (MGMT) while the repair of N-alkylpurines requires multiple proteins including N-methylpurine-DNA glycosylase (MPG). While the biochemical properties human and mouse MGMTs are very similar, the mouse MPG removes 7-methylguanine more efficiently than the human protein. An increased level of MGMT, without a change in the level of MPG associated with gene amplification, was observed in a mouse cell line resistant to 2-chloroethyl-N-nitrosourea. In contrast, no correlation was observed between MPG level and resistance to methyl methanesulfonate in Chinese hamster ovary (CHO) cells. This result suggests a protein other than MPG limits the repair rate of N-alkylpurine in CHO cells.

  1. Sources and levels of ambient ocean sound near the antarctic peninsula

    SciTech Connect (OSTI)

    Dziak, Robert P.; Stafford, Kathleen M.; Matsumoto, Haruyoshi; Lee, Won Sang; Fowler, Matt J.

    2015-04-14

    Arrays of hydrophones were deployed within the Bransfield Strait and Scotia Sea (Antarctic Peninsula region) from 2005 to 2009 to record ambient ocean sound at frequencies of up to 125 and 500 Hz. Icequakes, which are broadband, short duration signals derived from fracturing of large free-floating icebergs, are a prominent feature of the ocean soundscape. Icequake activity peaks during austral summer and is minimum during winter, likely following freeze-thaw cycles. Iceberg grounding and rapid disintegration also releases significant acoustic energy, equivalent to large-scale geophysical events. Overall ambient sound levels can be as much as ~10–20 dB higher in the open, deep ocean of the Scotia Sea compared to the relatively shallow Bransfield Strait. Noise levels become lowest during the austral winter, as sea-ice cover suppresses wind and wave noise. Ambient noise levels are highest during austral spring and summer, as surface noise, ice cracking and biological activity intensifies. Vocalizations of blue (Balaenoptera musculus) and fin (B. physalus) whales also dominate the long-term spectra records in the 15–28 and 89 Hz bands. Blue whale call energy is a maximum during austral summer-fall in the Drake Passage and Bransfield Strait when ambient noise levels are a maximum and sea-ice cover is a minimum. Fin whale vocalizations were also most common during austral summer-early fall months in both the Bransfield Strait and Scotia Sea. The hydrophone data overall do not show sustained anthropogenic sources (ships and airguns), likely due to low coastal traffic and the typically rough weather and sea conditions of the Southern Ocean.

  2. Sources and levels of ambient ocean sound near the antarctic peninsula

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Dziak, Robert P.; Bohnenstiehl, DelWayne R.; Stafford, Kathleen M.; Matsumoto, Haruyoshi; Park, Minkyu; Lee, Won Sang; Fowler, Matt J.; Lau, Tai-Kwan; Haxel, Joseph H.; Mellinger, David K.; et al

    2015-04-14

    Arrays of hydrophones were deployed within the Bransfield Strait and Scotia Sea (Antarctic Peninsula region) from 2005 to 2009 to record ambient ocean sound at frequencies of up to 125 and 500 Hz. Icequakes, which are broadband, short duration signals derived from fracturing of large free-floating icebergs, are a prominent feature of the ocean soundscape. Icequake activity peaks during austral summer and is minimum during winter, likely following freeze-thaw cycles. Iceberg grounding and rapid disintegration also releases significant acoustic energy, equivalent to large-scale geophysical events. Overall ambient sound levels can be as much as ~10–20 dB higher in the open,more » deep ocean of the Scotia Sea compared to the relatively shallow Bransfield Strait. Noise levels become lowest during the austral winter, as sea-ice cover suppresses wind and wave noise. Ambient noise levels are highest during austral spring and summer, as surface noise, ice cracking and biological activity intensifies. Vocalizations of blue (Balaenoptera musculus) and fin (B. physalus) whales also dominate the long-term spectra records in the 15–28 and 89 Hz bands. Blue whale call energy is a maximum during austral summer-fall in the Drake Passage and Bransfield Strait when ambient noise levels are a maximum and sea-ice cover is a minimum. Fin whale vocalizations were also most common during austral summer-early fall months in both the Bransfield Strait and Scotia Sea. The hydrophone data overall do not show sustained anthropogenic sources (ships and airguns), likely due to low coastal traffic and the typically rough weather and sea conditions of the Southern Ocean.« less

  3. Design of an ultra low power CMOS pixel sensor for a future neutron personal dosimeter

    SciTech Connect (OSTI)

    Zhang, Y.; Hu-Guo, C.; Husson, D.; Hu, Y.

    2011-07-01

    Despite a continuously increasing demand, neutron electronic personal dosimeters (EPDs) are still far from being completely established because their development is a very difficult task. A low-noise, ultra low power consumption CMOS pixel sensor for a future neutron personal dosimeter has been implemented in a 0.35 {mu}m CMOS technology. The prototype is composed of a pixel array for detection of charged particles, and the readout electronics is integrated on the same substrate for signal processing. The excess electrons generated by an impinging particle are collected by the pixel array. The charge collection time and the efficiency are the crucial points of a CMOS detector. The 3-D device simulations using the commercially available Synopsys-SENTAURUS package address the detailed charge collection process. Within a time of 1.9 {mu}s, about 59% electrons created by the impact particle are collected in a cluster of 4 x 4 pixels with the pixel pitch of 80 {mu}m. A charge sensitive preamplifier (CSA) and a shaper are employed in the frond-end readout. The tests with electrical signals indicate that our prototype with a total active area of 2.56 x 2.56 mm{sup 2} performs an equivalent noise charge (ENC) of less than 400 e - and 314 {mu}W power consumption, leading to a promising prototype. (authors)

  4. Is the resilience of C{sub 60}{sup +} towards decomposition a question of time?

    SciTech Connect (OSTI)

    Lifshitz, C.; Sandler, P.; Gotkis, I.; Laskin, J.

    1993-12-31

    The authors have measured kinetic energy release distributions (KERDs) for the evaporation of C{sub 2} from C{sub 60}{sup +} and other fullerene cations. Through analysis of the KERDs by Klot`s theory the authors determined binding energies -- the C{sub 2} binding energy in C{sub 60}{sup +} is 5.23 eV. A thermochemical cycle gave 5.77 eV as the C{sub 2} binding energy in C{sub 60} neutral. Once these binding energies were known, it enabled calculations of time resolved breakdown curves for parent and daughter ions. These calculations included the option of energy relaxation through emission in the infra-red. It was found that C{sub 60}{sup +} is almost completely undissociated at t = 1 {mu}s at an internal energy of 30 eV. However, at t = 1s, it is completely dissociated. An intrinsic shift (IS) of 16.2 eV is predicted. These results explain SID (Surface Induced Decomposition) data by Whetten and coworkers. The applicability of Trouton`s Rule and evaporation to fullerene decompositions will be discussed. Alternative mechanisms, including the Rice {open_quotes}shrink wrap{close_quotes} mechanism, will be discussed in view of the apparent universality of the Gspann parameter, {gamma}=23.5.

  5. Spectrographic temperature measurement of a high power breakdown arc in a high pressure gas switch

    SciTech Connect (OSTI)

    Yeckel, Christopher; Curry, Randy

    2011-09-15

    A procedure for obtaining an approximate temperature value of conducting plasma generated during self-break closure of a RIMFIRE gas switch is described. The plasma is in the form of a breakdown arc which conducts approximately 12 kJ of energy in 1 {mu}s. A spectrographic analysis of the trigger-section of the 6-MV RIMFIRE laser triggered gas switch used in Sandia National Laboratory's ''Z-Machine'' has been made. It is assumed that the breakdown plasma has sufficiently approached local thermodynamic equilibrium allowing a black-body temperature model to be applied. This model allows the plasma temperature and radiated power to be approximated. The gas dielectric used in these tests was pressurized SF{sub 6}. The electrode gap is set at 4.59 cm for each test. The electrode material is stainless steel and insulator material is poly(methyl methacrylate). A spectrum range from 220 to 550 nanometers has been observed and calibrated using two spectral irradiance lamps and three spectrograph gratings. The approximate plasma temperature is reported.

  6. An innovative high-power constant-current pulsed-arc power-supply for a high-density pulsed-arc-plasma ion-source using a LaB{sub 6}-filament

    SciTech Connect (OSTI)

    Ueno, A.; Oguri, H.; Ikegami, K.; Namekawa, Y.; Ohkoshi, K.; Tokuchi, A.

    2010-02-15

    An innovative high-power constant-current (CC) pulsed-arc (PA) power-supply (PS) indispensable for a high-density PA plasma ion-source using a lanthanum hexaboride (LaB{sub 6}) filament was devised by combining a constant-voltage (CV) PA-PS, which is composed of an insulated gate bipolar transistor (IGBT) switch, a CV direct-current (dc) PS and a 270 mF capacitor with a CC-PA-PS, which is composed of an IGBT-switch, a CC-dc-PS and a 400 {mu}H inductor, through the inductor. The hybrid-CC-PA-PS succeeded in producing a flat arc-pulse with a peak power of 56 kW (400 Ax140 V) and a duty factor of more than 1.5%(600 {mu}sx25 Hz) for Japan Proton Accelerator Research Complex (J-PARC) H{sup -} ion-source stably. It also succeeded in shortening the 99% rising-time of the arc-pulse-current to about 20 {mu}s and tilting up or down the arc-pulse-current arbitrarily and almost linearly by changing the setting voltage of its CV-dc-PS.

  7. Generation of high charge state metal ion beams by electron cyclotron resonance heating of vacuum arc plasma in cusp trap

    SciTech Connect (OSTI)

    Nikolaev, A. G.; Savkin, K. P.; Oks, E. M.; Vizir, A. V.; Yushkov, G. Yu.; Vodopyanov, A. V.; Izotov, I. V.; Mansfeld, D. A.

    2012-02-15

    A method for generating high charge state heavy metal ion beams based on high power microwave heating of vacuum arc plasma confined in a magnetic trap under electron cyclotron resonance conditions has been developed. A feature of the work described here is the use of a cusp magnetic field with inherent ''minimum-B'' structure as the confinement geometry, as opposed to a simple mirror device as we have reported on previously. The cusp configuration has been successfully used for microwave heating of gas discharge plasma and extraction from the plasma of highly charged, high current, gaseous ion beams. Now we use the trap for heavy metal ion beam generation. Two different approaches were used for injecting the vacuum arc metal plasma into the trap - axial injection from a miniature arc source located on-axis near the microwave window, and radial injection from sources mounted radially at the midplane of the trap. Here, we describe preliminary results of heating vacuum arc plasma in a cusp magnetic trap by pulsed (400 {mu}s) high power (up to 100 kW) microwave radiation at 37.5 GHz for the generation of highly charged heavy metal ion beams.

  8. Charge-state-resolved ion energy distribution functions of cathodic vacuum arcs: A study involving the plasma potential and biased plasmas

    SciTech Connect (OSTI)

    Anders, Andre; Oks, Efim

    2007-02-15

    Charge-state-resolved ion energy distribution functions were measured for pulsed cathodic arcs taking the sheath into account that formed between the plasma and the entrance of a combined energy and mass spectrometer. An electron emitting probe was employed to independently determine the plasma potential. All results were obtained by averaging over several individual measurements because the instantaneous energy distributions and the plasma potential show large amplitude fluctuations due to the explosive nature of the arc plasma generation. It was found that the ion energy distribution functions in the plasma were independent of the ion charge state. This is in contrast to findings with continuously operating, direct-current arcs that employ a magnetic field at the cathode to steer the cathode spot motion. The different findings indicate the important role of the magnetic steering field for the plasma properties of direct-current arcs. The results are further supported by experiments with 'biased plasmas' obtained by shifting the potential of the anode. Finally, it was shown that the ion energy distributions were broader and shifted to higher energy at the beginning of each arc pulse. The characteristic time for relaxation to steady state distributions is about 100 {mu}s.

  9. High current multicharged metal ion source using high power gyrotron heating of vacuum arc plasma

    SciTech Connect (OSTI)

    Vodopyanov, A. V.; Golubev, S. V.; Khizhnyak, V. I.; Mansfeld, D. A.; Nikolaev, A. G.; Oks, E. M.; Savkin, K. P.; Vizir, A. V.; Yushkov, G. Yu.

    2008-02-15

    A high current, multi charged, metal ion source using electron heating of vacuum arc plasma by high power gyrotron radiation has been developed. The plasma is confined in a simple mirror trap with peak magnetic field in the plug up to 2.5 T, mirror ratio of 3-5, and length variable from 15 to 20 cm. Plasma formed by a cathodic vacuum arc is injected into the trap either (i) axially using a compact vacuum arc plasma gun located on axis outside the mirror trap region or (ii) radially using four plasma guns surrounding the trap at midplane. Microwave heating of the mirror-confined, vacuum arc plasma is accomplished by gyrotron microwave radiation of frequency 75 GHz, power up to 200 kW, and pulse duration up to 150 {mu}s, leading to additional stripping of metal ions by electron impact. Pulsed beams of platinum ions with charge state up to 10+, a mean charge state over 6+, and total (all charge states) beam current of a few hundred milliamperes have been formed.

  10. Characterization of Arc Generated Plasma Interactions with a Liquid Metal Medium

    SciTech Connect (OSTI)

    Hahn, Gregory C.; Martin, Elijah H.; Bourham, Mohamed A.

    2005-05-15

    Plasma interaction with first wall and interior reactor chamber components is an influencing factor in the design of inertial fusion facilities. The concept of a liquid metal wall, in which a circulating lithium curtain would be used, has been considered in many studies. The interaction of plasmas with moving liquid metals is a complex subject due to the influence of hydrodynamics, evaporation and droplet formation, nucleation and agglomeration of condensed particulates. To gain an understanding of some of the specific details of this interaction an experimental setup of an arc-generated plasma interacting with a liquid lead pool has been designed, constructed and operated. This simulation of the plasma-liquid interaction focuses on the particle condensation of the liquid metal after plasma interaction. The experiment generates transient high-density plasma over 50 {mu}s pulse duration. Plasma characteristics are determined by various diagnostics. A set of collection substrates are arranged to collect nucleated particulates condensing from the evolving plume. Particulate size and distribution are analyzed numerically using digital images.

  11. Nature of high-energy ions in the cathode plasma jet of a vacuum arc with high rate of current rise

    SciTech Connect (OSTI)

    Beilis, I.I.

    2004-10-04

    The production mechanism of extremely high-energy (up to 10 keV) ions observed in vacuum arcs having only a few tens of volts of arc voltage was considered. A model was developed for the plasma acceleration in a high-current ({>=}1 kA) short pulsed (<1 {mu}s) vacuum arc, taking into account the high rate of rise of the spot current (dI/dt>100 MA/s). A system of equations, including equations for the cathode spot and the plasma jet, was solved self-consistently with dI/dt in the range of 0.1-10 GA/s. It was shown that the plasma could be accelerated to the measured energy in the near spot region due to a gas dynamic mechanism and that the ion energy depends on the ratio of the ion flux to the electron flux. This ratio is determined by the cathode erosion rate. The calculated cathode erosion rate varies from 200 to 10 {mu}g/C when the ion energy increases from 0.1 to 10 keV and well agrees with measurements.

  12. GTA Beamloss-Monitor System

    SciTech Connect (OSTI)

    Rose, C.R.; Fortgang, C.M.; Power, J.P.

    1992-01-01

    The GTA Beamless-Monitor System at Los Alamos National Laboratory has been designed to detect high-energy particle loss in the accelerator beamline and shut down the accelerator before any damage can occur. To do this, the Beamless-Monitor System measures the induced gamma radiation, from (p, {gamma}) reactions, at 15 selected points along the beamline, converts this measured radiation to electrical signals integrates and compares them to preset limits, and, in the event of an over-limit condition causes the Fast-Protect System to shut down the entire accelerator. The system dynamic range exceeds 70 dB which will enable experimenters to use the Beamless-Monitor System to help steer the beam as well as provide signals for a Fast-Protect System. The system response time is less than 7 {mu}s assuming a step-function, worst-case beam spill of 50 mA. The system resolution, based on the noise floor of the electronics is about 1.3 mRads/s. Production units have been built and meet the above specifications. The remainder of the system will be installed and tested later in 1992/1993 with the GTA accelerator. The ionization chamber sensitivity and response time are described in the paper.

  13. GTA Beamloss-Monitor System

    SciTech Connect (OSTI)

    Rose, C.R.; Fortgang, C.M.; Power, J.P.

    1992-09-01

    The GTA Beamless-Monitor System at Los Alamos National Laboratory has been designed to detect high-energy particle loss in the accelerator beamline and shut down the accelerator before any damage can occur. To do this, the Beamless-Monitor System measures the induced gamma radiation, from (p, {gamma}) reactions, at 15 selected points along the beamline, converts this measured radiation to electrical signals integrates and compares them to preset limits, and, in the event of an over-limit condition causes the Fast-Protect System to shut down the entire accelerator. The system dynamic range exceeds 70 dB which will enable experimenters to use the Beamless-Monitor System to help steer the beam as well as provide signals for a Fast-Protect System. The system response time is less than 7 {mu}s assuming a step-function, worst-case beam spill of 50 mA. The system resolution, based on the noise floor of the electronics is about 1.3 mRads/s. Production units have been built and meet the above specifications. The remainder of the system will be installed and tested later in 1992/1993 with the GTA accelerator. The ionization chamber sensitivity and response time are described in the paper.

  14. Optical absorption and stimulated emission of neodymium in yttrium lithium fluoride

    SciTech Connect (OSTI)

    Ryan, J.R.; Beach, R. )

    1992-10-01

    A spectroscopic investigation of Nd{sup 3+} in yttrium lithium fluoride was performed. Spectrally and orientationally resolved cross sections for the {sup 4}{ital F}{sub 3/2}--{sup 4}{ital I}{sub 11/2} and {sup 4}{ital F}{sub 3/2}--{sup 4}{ital I}{sub 9/2} transitions are presented. We applied the Judd--Ofelt theory to measured absorption spectra to determine the orientation-averaged intensity parameters {Omega}{sub 2}=0.362{times}10{sup {minus}20} cm{sup 2}, {Omega}{sub 4}=4.02{times}10{sup {minus}20} cm{sup 2}, and {Omega}{sub 6}=4.84{times}10{sup {minus}20} cm{sup 2}. Using these intensity parameters, we predicted the radiative lifetime of the metastable {sup 4}{ital F}{sub 3/2} state to be 525 {mu}s, in excellent agreement with measured {sup 4}{ital F}{sub 3/2} decay signatures. Finally, absorption cross-section data are presented that will be of interest to the laser designer.

  15. Half-life measurements of isomeric states populated in projectile fragmentation

    SciTech Connect (OSTI)

    Bowry, M.; Podolay, Zs.

    2012-10-20

    The half-lives of excited isomeric states observed in {sup 195}Au, {sup 201}Tl and {sup 215}Rn are reported for the first time. Delayed {gamma}-rays were correlated with nuclei produced in the projectile fragmentation of relativistic {sup 238}U ions, unambiguously identified in terms of their atomic number (Z) and mass-to-charge ratio (A/Q) after traversing an in-flight separator. The observation of a long-lived isomeric state in {sup 195}Au with t{sub 1/2} = 16{sub -4}{sup +8}{mu}s is presented. Two shorter-lived isomeric states were detected in {sup 201}Tl and {sup 215}Rn with t{sub 1/2} = 95{sub -21}{sup +39} and 57{sub -12}{sup +21} ns respectively. In total 24 isomeric states were identified in different nuclei from Pt to Rn (A {approx} 200) during the current study, the majority of which were previously reported. The wealth of spectroscopic data provides the opportunity to determine the isomeric ratios over a wide range of Z, A and angular momentum (I h) of the reaction products. In particular, high-spin states with I Greater-Than-Or-Equivalent-To 18 h provide a robust test of theoretical models of fragmentation.

  16. Analysis methods for fast impurity ion dynamics data

    SciTech Connect (OSTI)

    Den Hartog, D.J.; Almagri, A.F.; Prager, S.C.; Fonck, R.J.

    1994-08-01

    A high resolution spectrometer has been developed and used on the MST reversed-field pinch (RFP) to measure passively impurity ion temperatures and flow velocities with 10 {mu}s temporal resolution. Such measurements of MHD-scale fluctuations are particularly relevant in the RFP because the flow velocity fluctuation induced transport of current (the ``MHD dynamo``) may produce the magnetic field reversal characteristic of an RFP. This instrument will also be used to measure rapid changes in the equilibrium flow velocity, such as occur during locking and H-mode transition. The precision of measurements made to date is <0.6 km/s. The authors are developing accurate analysis techniques appropriate to the reduction of this fast ion dynamics data. Moment analysis and curve-fitting routines have been evaluated for noise sensitivity and robustness. Also presented is an analysis method which correctly separates the flux-surface average of the correlated fluctuations in u and B from the fluctuations due to rigid shifts of the plasma column.

  17. High speed curved position sensitive detector

    DOE Patents [OSTI]

    Hendricks, Robert W.; Wilson, Jack W.

    1989-01-01

    A high speed curved position sensitive porportional counter detector for use in x-ray diffraction, the detection of 5-20 keV photons and the like. The detector employs a planar anode assembly of a plurality of parallel metallic wires. This anode assembly is supported between two cathode planes, with at least one of these cathode planes having a serpentine resistive path in the form of a meander having legs generally perpendicular to the anode wires. This meander is produced by special microelectronic fabrication techniques whereby the meander "wire" fans outwardly at the cathode ends to produce the curved aspect of the detector, and the legs of the meander are small in cross-section and very closely spaced whereby a spatial resolution of about 50 .mu.m can be achieved. All of the other performance characteristics are about as good or better than conventional position sensitive proportional counter type detectors. Count rates of up to 40,000 counts per second with 0.5 .mu.s shaping time constants are achieved.

  18. Conducting targets for /sup -/p production of ACOL past experience and prospects

    SciTech Connect (OSTI)

    Eaton, T.W.; Hancock, S.; Johnson, C.D.; Jones, E.; Maury, S.; Milner, S.; Schnuriger, J.C.; Sherwood, T.R.

    1985-10-01

    The Antiproton Collector (ACOL) project at CERN calls for a production target providing at least twice as many antiprotons into a given acceptance as the present passive target. The pulsed target under study must be able to withstand large current pulses of a hundred kiloamperes or more for 10 to 20 ..mu..s whilst at the same time it is hit by the proton beam of up to 2 X 10/sup 13/ ppp. Because of the very high radioactivity of the target region this new device should show a sufficient reliability before it hS put into operation. Previous experimental work with an active target, both in the laboratory and in the AA proton beam line, has shown that such a target gives a measured gain of 50% in the /sup -/p production yield, although the problem of making an assembly to withstand many weeks of pulsing has not been solved. A comparison of the main features of the four tests made in the AA is given. The mechanical and thermal behavior of a conducting metallic, solid or liquid target is studied, with particular emphasis on the shock wave, the thermal expansion and the magnetic unstable pinch effects, by means of computer calculations. A preliminary design of a metal conducting target is reported.

  19. Development of lithium beam emission spectroscopy as an edge fluctuation diagnostic for DIII-D

    SciTech Connect (OSTI)

    Thomas, D.M.

    1994-05-01

    As part of the DIII-D diagnostic complement designed to address L-H transition physics issues, we have developed and commissioned a diagnostic neutral lithium beam and multichannel fluorescence detection system to investigate the edge plasma density and its associated fluctuations. The use of lithium offers several advantages for tokamak edge beam emission spectroscopy (BES) studies, including large excitation cross sections which are relatively insensitive to temperature variation, the availability of the 670.8 nm resonance line well separated from most plasma line emission, and the suitability of modest beam energies and currents to probe even dense H-mode plasmas. These features permit measurements of collisionally induced fluctuations to be obtained with good spatial (<1 cm) and temporal (<10 {mu}s) resolution. The improvements over previous lithium beam diagnostics which were required to successfully make these measurements in a large, remotely controlled machine environment will be discussed, a long with the present state of the diagnostic system and our plans for future improvements of this technique.

  20. Dynamic processes in field-reversed-configuration compact toroids

    SciTech Connect (OSTI)

    Rej, D.J.

    1987-01-01

    In this lecture, the dynamic processes involved in field-reversed configuration (FRC) formation, translation, and compression will be reviewed. Though the FRC is related to the field-reversed mirror concept, the formation method used in most experiments is a variant of the field-reversed THETA-pinch. Formation of the FRC eqilibrium occurs rapidly, usually in less than 20 ..mu..s. The formation sequence consists of several coupled processes: preionization; radial implosion and compression; magnetic field line closure; axial contraction; equilibrium formation. Recent experiments and theory have led to a significantly improved understanding of these processes; however, the experimental method still relies on a somewhat empirical approach which involves the optimization of initial preionization plasma parameters and symmetry. New improvements in FRC formation methods include the use of lower voltages which extrapolate better to larger devices. The axial translation of compact toroid plasmas offers an attractive engineering convenience in a fusion reactor. FRC translation has been demonstrated in several experiments worldwide, and these plasmas are found to be robust, moving at speeds up to the Alfven velocity over distances of up to 16 m, with no degradation in the confinement. Compact toroids are ideal for magnetic compression. Translated FRCs have been compressed and heated by imploding liners. Upcoming experiments will rely on external flux compression to heat a translater FRC at 1-GW power levels. 39 refs.

  1. X-ray diffraction in the pulsed laser heated diamond anvil cell

    SciTech Connect (OSTI)

    Goncharov, Alexander F.; Struzhkin, Viktor V.; Dalton, D. Allen; Prakapenka, Vitali B.; Kantor, Innokenty; Rivers, Mark L.

    2010-11-15

    We have developed in situ x-ray synchrotron diffraction measurements of samples heated by a pulsed laser in the diamond anvil cell at pressure up to 60 GPa. We used an electronically modulated 2-10 kHz repetition rate, 1064-1075 nm fiber laser with 1-100 {mu}s pulse width synchronized with a gated x-ray detector (Pilatus) and time-resolved radiometric temperature measurements. This enables the time domain measurements as a function of temperature in a microsecond time scale (averaged over many events, typically more than 10 000). X-ray diffraction data, temperature measurements, and finite element calculations with realistic geometric and thermochemical parameters show that in the present experimental configuration, samples 4 {mu}m thick can be continuously temperature monitored (up to 3000 K in our experiments) with the same level of axial and radial temperature uniformities as with continuous heating. We find that this novel technique offers a new and convenient way of fine tuning the maximum sample temperature by changing the pulse width of the laser. This delicate control, which may also prevent chemical reactivity and diffusion, enables accurate measurement of melting curves, phase changes, and thermal equations of state.

  2. Studies on a VUV free electron laser at the TESLA Test Facility at DESY

    SciTech Connect (OSTI)

    Rossbach, J.

    1995-12-31

    The TESLA Test Facility (TTF) currently under construction at DESY is a test-bed for acceleration sections of a high-gradient, high efficiency superconducting linear collider. Due to ist unrivaled ability to sustain high beam quality during acceleration, a superconducting rf linac is considered the optimum choice to drive a Free Electron Laser (FEL). We aim at a photon wavelength of {lambda} = 6 manometer utilizing the TTF after is has been extended to 1 GeV beam energy. Due to lack of mirrors and seed-lasers in this wavelength regime, a single pass FEL and Self-Amplified-Spontaneous-Emission (SASE) is considered. A first test is foreseen at a larger photon wavelength. The overall design as well as both electron and photon beam properties will be discussed. To reach the desired photon wavelength, the main components that have to be added to the TTF are: (a) a low emittance rf gun including space charge compensation (b) a two stage bunch compressor increasing the peak bunch current from 100 A up to 2500 A (c) four more accelerating modules to achieve 1 GeV beam energy (d) a 25 m long undulator (period length 27 mm, peak field 0.5 T) The average brillance will be larger than 1-10{sup 22}photons/s/mm{sup 2}/mrad{sup 2}/0.1%. Each 800 {mu}s long pulse will contain up to 7200 equidistant bunches. The repetition frequency of the linac is 10 Hz.

  3. Binding Preferences, Surface Attachment, Diffusivity, and Orientation of a Family 1 Carbohydrate-Binding Module on Cellulose

    SciTech Connect (OSTI)

    Nimlos, M. R.; Beckham, G. T.; Matthews, J. F.; Bu, L.; Himmel, M. E.; Crowley, M. F.

    2012-06-08

    Cellulase enzymes often contain carbohydrate-binding modules (CBMs) for binding to cellulose. The mechanisms by which CBMs recognize specific surfaces of cellulose and aid in deconstruction are essential to understand cellulase action. The Family 1 CBM from the Trichoderma reesei Family 7 cellobiohydrolase, Cel7A, is known to selectively bind to hydrophobic surfaces of native cellulose. It is most commonly suggested that three aromatic residues identify the planar binding face of this CBM, but several recent studies have challenged this hypothesis. Here, we use molecular simulation to study the CBM binding orientation and affinity on hydrophilic and hydrophobic cellulose surfaces. Roughly 43 {mu}s of molecular dynamics simulations were conducted, which enables statistically significant observations. We quantify the fractions of the CBMs that detach from crystal surfaces or diffuse to other surfaces, the diffusivity along the hydrophobic surface, and the overall orientation of the CBM on both hydrophobic and hydrophilic faces. The simulations demonstrate that there is a thermodynamic driving force for the Cel7A CBM to bind preferentially to the hydrophobic surface of cellulose relative to hydrophilic surfaces. In addition, the simulations demonstrate that the CBM can diffuse from hydrophilic surfaces to the hydrophobic surface, whereas the reverse transition is not observed. Lastly, our simulations suggest that the flat faces of Family 1 CBMs are the preferred binding surfaces. These results enhance our understanding of how Family 1 CBMs interact with and recognize specific cellulose surfaces and provide insights into the initial events of cellulase adsorption and diffusion on cellulose.

  4. A fast spectroscopic diagnostic for the measurement of plasma impurity ion dynamics

    SciTech Connect (OSTI)

    Den Hartog, D.J.; Fonck, R.J.

    1994-04-01

    A high-resolution spectrometer has been developed and used to measure simultaneously impurity ion temperature and flow velocities in high temperature plasmas with 10 {mu}s temporal resolution (limited by digitization rate). This device is actually a duo-spectrometer: measurements from two different chordal views of the plasma can be made simultaneously via two separate quartz input fiber optic bundles coupled to the entrance slits which are tilted to compensate for line curvature. The dispersed spectra on the exit plane of the duo-spectrometer are coupled via quartz fiber optics to two arrays of 16 photomultiplier tubes each. Measurement made by recording the Doppler broadened and shifted 227.091 nm emission from the CV impurity ions in the MST reversed-field pinch (RFP) plasma have achieved precisions of <6 eV for temperatures of 150 Ev and <0.7 km/s for flow velocities of 6 km/s. Representative results from the MsT RFP indicate that the toroidal flow velocity drops and ion temperature increases during saw tooth events in MST.

  5. Characteristics of high-rate energy spectroscopy systems using HPGe coaxial detectors and time-variant filters

    SciTech Connect (OSTI)

    Britton, C.L.; Becker, T.H.; Paulus, T.J.; Trammell, R.C.

    1984-02-01

    A high-rate, high-resolution gamma spectrometer system is described. The system consists of a reverse electrode HPGe coaxial detector, a transistor reset preamplifier, an active, semi-Gaussian prefilter, a gated integrator, and a unique data acquisition system consisting of a 10 ..mu..s, 13 bit ADC, fast FIFO memory, 8k by 23 bit data memory, and computer interface circuitry under the control of a Z-80A ..mu..P. The effects of the various components on the throughput are described and throughput data is presented. The resolution and peak shift for various shaping times are presented for count rates up to 1 Mcps input rate using a mixed /sup 22/Na and /sup 60/Co source. The low rate resolutions of /sup 57/Co and /sup 60/Co for various shaping times using either the semi-Gaussian or gated integrator output are discussed as well as the low energy resolution and peak shifts in the presence of high energy events.

  6. Intensity-modulated radiosurgery with rapidarc for multiple brain metastases and comparison with static approach

    SciTech Connect (OSTI)

    Wang Jiazhu; Pawlicki, Todd; Rice, Roger; Mundt, Arno J.; Sandhu, Ajay; Lawson, Joshua; Murphy, Kevin T.

    2012-04-01

    Rotational RapidArc (RA) and static intensity-modulated radiosurgery (IMRS) have been used for brain radiosurgery. This study compares the 2 techniques from beam delivery parameters and dosimetry aspects for multiple brain metastases. Twelve patients with 2-12 brain lesions treated with IMRS were replanned using RA. For each patient, an optimal 2-arc RA plan from several trials was chosen for comparison with IMRS. Homogeneity, conformity, and gradient indexes have been calculated. The mean dose to normal brain and maximal dose to other critical organs were evaluated. It was found that monitor unit (MU) reduction by RA is more pronounced for cases with larger number of brain lesions. The MU-ratio of RA and IMRS is reduced from 104% to 39% when lesions increase from 2 to 12. The dose homogeneities are comparable in both techniques and the conformity and gradient indexes and critical organ doses are higher in RA. Treatment time is greatly reduced by RA in intracranial radiosurgery, because RA uses fewer MUs, fewer beams, and fewer couch angles.

  7. Propagation of gamma rays and production of free electrons in air

    SciTech Connect (OSTI)

    Dimant, Y. S.; Nusinovich, G. S.; Romero-Talamas, C. A.; Granatstein, V. L.; Sprangle, P.; Penano, J.

    2012-10-15

    This paper is devoted to the analysis of production of free electrons in air by gamma-rays leaking from radioactive materials. A model based on the Klein-Nishina scattering theory is used to calculate scattering cross sections and approximate the electron production rate. The model includes the effects of primary gamma-quanta radiated by the source as well as that scattered in air. Comparison of the model with the mcnpx kinetic code (http://mcnpx.lanl.gov/) in a sample problem shows excellent agreement. The motivation for this research comes from the recently proposed concept of remote detection of concealed radioactive materials [V. L. Granatstein and G. S. Nusinovich, J. Appl. Phys. 108, 063304 (2010)]. The concept is based on the breakdown in air at the focal point of a high-power beam of electromagnetic waves produced by a THz gyrotron with a 10-20 {mu}s pulse. The presence of a radioactive material can greatly exceed the production rate of free electrons over the natural background rate. Additional electrons act as seeds to initiate the breakdown and create sufficiently dense plasma at the focal region. The dense plasma can then be remotely detected as an unambiguous effect of the concealed radioactive material.

  8. Experimental study of a simple method to chop Penning SPS H{sup {minus}} beams

    SciTech Connect (OSTI)

    Smith, H.V. Jr.; Allison, P.; Schneider, J.D.; Stelzer, J.E.

    1994-08-01

    Accumulator rings proposed for use in high-intensity spallation-neutron sources require a chopped beam with particle-free gaps {approx}100 ns wide at 1--2 MHz rates with rise and fall times {le} 20 ns. Chopping the beam directly in the ion source may be an attractive way to provide the desired beam structure. A grounded collar placed in the drift region next to the emission aperture lowers the e{sup {minus}}/H{sup {minus}} ratio in the 8X source H{sup {minus}} beam. We electrically isolated the collar and biased it to modulate the extracted H{sup {minus}} current. Positive collar bias decreases the H{sup {minus}} beam by up to 90%. The fastest H{sup {minus}} current fall and rise times achieved to date are 400 ns and 2 {mu}s, respectively. The fall time is close to the pulser rise time ({approx}300 ns). The rise time is considerably longer than the pulser fall time ({approx}500 ns). Negative collar bias lowers the H{sup {minus}} beam by up to 50%.

  9. Deflagration-to-detonation transition project: quarterly report for the period September through November 1979

    SciTech Connect (OSTI)

    Lieberman, M. L.

    1980-07-01

    The activities of the Sandia Laboratories project on deflagration-to-detonation transition (DDT) pertain primarily to the development of small, safe, low-voltage, hot-wire detonators. Its major goals are: the formulation of a modeling capability for DDT of the explosive 2-(5-cyanotetrazolato)pentaamminecobalt(III) perchlorate (CP); the development of improved DDT materials; the establishment of a data base for corrosion, compatibility, and reliability of CP-loaded detonators; and the design and development of advanced DDT components. Progress in this research is reported. The planned development of the MC3423 detonator has been completed and the final design review meeting has been held. Additional work must be performed to establish satisfactory output function. Ignition sensitivity data have also been obtained. Ignition and shock testing experiments for development of the MC3533 detonator have been planned. An initial version of the component will utilize available MC3423 headers, while the final design will incorporate a new header that has been designed and ordered. Detonator performance studies have been planned to optimize CP density-length factors. Feasibility studies on the MC3196A detonator have continued in an effort to obtain a reliable 50-200 ..mu..s function time.

  10. Neutron measurements in search of cold fusion

    SciTech Connect (OSTI)

    Anderson, R.E.; Goulding, C.A.; Johnson, M.W.; Butterfield, K.B.; Gottesfeld, S.; Baker, D.A.; Springer, T.E.; Garzon, F.H.; Bolton, R.D.; Leonard, E.M.; Chancellor, T. )

    1991-05-10

    We have conducted a search for neutron emission from cold fusion systems of the electrochemical type and, to a lesser extent, the high-pressure gas cell type. Using a high-efficiency well counter and an NE 213 scintillator, the experiments were conducted on the earth's surface and in a shielded cave approximately 50 ft underground. After approximately 6500 h of counting time, we have obtained no evidence for cold fusion processes leading to neutron production. However, we have observed all three types of neutron data that have been presented as evidence for cold fusion: large positive fluctuations in the neutron counting rate, weak peaks near 2.5 MeV in the neutron energy spectrum, and bursts of up to 140 neutrons in 500-{mu}s intervals. The data were obtained under circumstances that clearly show our results to be data encountered as a part of the naturally occurring neutron background, which is due primarily to cosmic rays. Thus, observing these types of data does not, of itself, provide evidence for the existence of cold fusion processes. Artifacts in the data that were due to counter misbehavior were also observed to lead to long-term neutron bursts'' whose time duration varied from several hours to several days. We conclude that any experiments which attempt to observed neutron emission must include strong steps to ensure that the experiments deal adequately with both cosmic-ray processes and counter misbehavior.

  11. Progress on the Los Alamos heavy-ion injector

    SciTech Connect (OSTI)

    Wilson, D.C.; Riepe, K.B.; Ballard, E.O.; Meyer, E.A.; Shurter, R.P.; Van Haaften, F.W.; Humphries, S. Jr.

    1986-01-01

    Heavy-ion fusion using an induction linac requires injection of multiple high-current beams from a pulsed electrostatic accelerator at as high a voltage as practical. Los Alamos National Laboratory is developing a 16-beam, 2-MeV, pulsed electrostatic accelerator for Al/sup +/ ions. The ion source will use a pulsed metal vapor arc plasma. A biased grid will control plasma flux into the ion extraction region. This source has achieved a normalized emittance of epsilon/sub n/ < 3.10/sup -7/..pi..-m-rad with Al/sup +/ ions. An 800 kV Marx prototype with a laser fired diverter is being assembled. The ceramic accelerating column sections have been brazed and leak tested. Voltage hold off on a brazed sample was more than doubled by selective removal of the Ticusil braze fillet extending along the ceramic. A scaled test module held 250 kV for 50 ..mu..s, giving confidence that the full module can hold 175 kV per section. The pressure vessel should be received in June 1986. High-voltage testing of a 1 MV column will begin by early 1987.

  12. Ultrafast studies of solution dynamics

    SciTech Connect (OSTI)

    Woodruff, W.H.; Dyer, R.B.; Callender, R.H.

    1997-10-01

    This is the final report of a one-year, Laboratory Directed Research and Development (LDRD) project at Los Alamos National Laboratory (LANL). Fast chemical dynamics generally must be initiated photochemically. This limits the applicability of modern laser methods for following the structural changes that occur during chemical and biological reactions to those systems that have an electronic chromophore that has a significant yield of photoproduct when excited. This project has developed a new and entirely general approach to ultrafast initiation of reactions in solution: laser-induced temperature jump (T-jump). The results open entire new fields of study of ultrafast molecular dynamics in solution. The authors have demonstrated the T-jump technique on time scales of 50 ps and longer, and have applied it to study of the fast events in protein folding. They find that a general lifetime of alpha-helix formation is ca 100 ns, and that tertiary folds (in apomyoglobin) form in ca 100 {mu}s.

  13. Dedicated Laboratory Setup for CO{sub 2} TEA Laser Propulsion Experiments at Rensselaer Polytechnic Institute

    SciTech Connect (OSTI)

    Salvador, Israel I.; Kenoyer, David; Myrabo, Leik N.; Notaro, Samuel

    2010-10-08

    Laser propulsion research progress has traditionally been hindered by the scarcity of photon sources with desirable characteristics, as well as integrated specialized flow facilities in a dedicated laboratory environment. For TEA CO{sub 2} lasers, the minimal requirements are time-average powers of >100 W), and pulse energies of >10 J pulses with short duration (e.g., 0.1 to 1 {mu}s); furthermore, for the advanced pulsejet engines of interest here, the laser system must simulate pulse repetition frequencies of 1-10 kilohertz or more, at least for two (carefully sequenced) pulses. A well-equipped laser propulsion laboratory should have an arsenal of sensor and diagnostics tools (such as load cells, thrust stands, moment balances, pressure and heat transfer gages), Tesla-level electromagnet and permanent magnets, flow simulation facilities, and high-speed visualization systems, in addition to other related equipment, such as optics and gas supply systems. In this paper we introduce a cutting-edge Laser Propulsion Laboratory created at Rensselaer Polytechnic Institute, one of the very few in the world to be uniquely set up for beamed energy propulsion (BEP) experiments. The present BEP research program is described, along with the envisioned research strategy that will exploit current and expanded facilities in the near future.

  14. Electric field induced needle-pulsed arc discharge carbon nanotube production apparatus: Circuitry and mechanical design

    SciTech Connect (OSTI)

    Kia, Kaveh Kazemi; Bonabi, Fahimeh

    2012-12-15

    A simple and low cost apparatus is reported to produce multiwall carbon nanotubes and carbon nano-onions by a low power short pulsed arc discharge reactor. The electric circuitry and the mechanical design details and a micro-filtering assembly are described. The pulsed-plasma is generated and applied between two graphite electrodes. The pulse width is 0.3 {mu}s. A strong dc electric field is established along side the electrodes. The repetitive discharges occur in less than 1 mm distance between a sharp tip graphite rod as anode, and a tubular graphite as cathode. A hydrocarbon vapor, as carbon source, is introduced through the graphite nozzle in the cathode assembly. The pressure of the chamber is controlled by a vacuum pump. A magnetic field, perpendicular to the plasma path, is provided. The results show that the synergetic use of a pulsed-current and a dc power supply enables us to synthesize carbon nanoparticles with short pulsed plasma. The simplicity and inexpensiveness of this plan is noticeable. Pulsed nature of plasma provides some extra degrees of freedom that make the production more controllable. Effects of some design parameters such as electric field, pulse frequency, and cathode shape are discussed. The products are examined using scanning probe microscopy techniques.

  15. Periodic permanent magnet development for linear collider X-band klystrons

    SciTech Connect (OSTI)

    Sprehn, D.; Caryotakis, G.; Jongewaard, E.; Phillips, R. [Stanford Linear Accelerator Center, Stanford University, Stanford, California 94309 (United States)

    1999-05-07

    The Stanford Linear Accelerator Center (SLAC) klystron group is currently designing, fabricating and testing 11.424 GHz klystrons with peak output powers from 50 to 75 MW at 1 to 2 {mu}s rf pulsewidths as part of an effort to realize components necessary for the construction of the Next Linear Collider (NLC). In order to eliminate the projected operational-year energy bill for klystron solenoids, Periodic Permanent Magnet (PPM) focusing has been employed on our latest X-band klystron designs. A PPM beam tester has operated at the same repetition rate, voltage and average beam power required for a 75-MW NLC klystron. Prototype 50 and 75-MW PPM klystrons were built and tested during 1996 and 1997 which operate from 50 to 70 MW at efficiencies greater than 55%. Construction and testing of 75-MW research klystrons will continue while the design and reliability is perfected. This paper will discuss the design of these PPM klystrons and the results of testing to date along with future plans for the development of a low-cost Design for Manufacture (DFM) 75-MW klystron and invitation for industry participation.

  16. Periodic permanent magnet development for linear collider X-band klystrons

    SciTech Connect (OSTI)

    Sprehn, D.; Caryotakis, G.; Jongewaard, E.; Phillips, R. [Stanford Linear Accelerator Center, Stanford University, Stanford, California 94309 (United States)

    1999-05-01

    The Stanford Linear Accelerator Center (SLAC) klystron group is currently designing, fabricating and testing 11.424 GHz klystrons with peak output powers from 50 to 75 MW at 1 to 2 {mu}s rf pulsewidths as part of an effort to realize components necessary for the construction of the Next Linear Collider (NLC). In order to eliminate the projected operational-year energy bill for klystron solenoids, Periodic Permanent Magnet (PPM) focusing has been employed on our latest X-band klystron designs. A PPM beam tester has operated at the same repetition rate, voltage and average beam power required for a 75-MW NLC klystron. Prototype 50 and 75-MW PPM klystrons were built and tested during 1996 and 1997 which operate from 50 to 70 MW at efficiencies greater than 55{percent}. Construction and testing of 75-MW research klystrons will continue while the design and reliability is perfected. This paper will discuss the design of these PPM klystrons and the results of testing to date along with future plans for the development of a low-cost Design for Manufacture (DFM) 75-MW klystron and invitation for industry participation. {copyright} {ital 1999 American Institute of Physics.}

  17. Chemopreventive activity of compounds extracted from Casearia sylvestris (Salicaceae) Sw against DNA damage induced by particulate matter emitted by sugarcane burning near Araraquara, Brazil

    SciTech Connect (OSTI)

    Prieto, A.M.; Santos, A.G.; Csipak, A.R.; Caliri, C.M.; Silva, I.C.; Arbex, M.A.; Silva, F.S.; Marchi, M.R.R.

    2012-12-15

    Ethanolic extract of Casearia sylvestris is thought to be antimutagenic. In this study, we attempted to determine whether this extract and casearin X (a clerodane diterpene from C. sylvestris) are protective against the harmful effects of airborne pollutants from sugarcane burning. To that end, we used the Tradescantia micronucleus test in meiotic pollen cells of Tradescantia pallida, the micronucleus test in mouse bone marrow cells, and the comet assay in mouse blood cells. The mutagenic compound was total suspended particulate (TSP) from air. For the Tradescantia micronucleus test, T. pallida cuttings were treated with the extract at 0.13, 0.25, or 0.50 mg/ml. Subsequently, TSP was added at 0.3 mg/ml, and tetrads from the inflorescences were examined for micronuclei. For the micronucleus test in mouse bone marrow cells and the comet assay in mouse blood cells, Balb/c mice were treated for 15 days with the extract3.9, 7.5, or 15.0 mg/kg body weight (BW)or with casearin X0.3, 0.25, or 1.2 mg/kg BWafter which they received TSP (3.75 mg/kg BW). In T. pallida and mouse bone marrow cells, the extract was antimutagenic at all concentrations tested. In mouse blood cells, the extract was antigenotoxic at all concentrations, whereas casearin X was not antimutagenic but was antigenotoxic at all concentrations. We conclude that C. sylvestris ethanolic extract and casearin X protect DNA from damage induced by airborne pollutants from sugarcane burning. -- Highlights: ? We assessed DNA protection of C. sylvestris ethanolic extract. ? We assessed DNA protection of casearin X. ? We used Tradescantia pallida micronucleus test as screening. ? We used comet assay and micronucleus test in mice. ? The compounds protected DNA against sugar cane burning pollutants.

  18. Networked alpha and gamma spectral acquisition and analysis system

    SciTech Connect (OSTI)

    Wilcox, C.M.; Gross, J.M.

    1993-10-01

    This manual assumes a knowledge of (terminology used and a working familiarity with) the windowing system and mouse of the Sun computer workstation. See the appropriate Sun manuals for additional information. ALDO, the alpha detector control program, is used to control, monitor, and edit log information associated with the collection of alpha spectra. Actual data collection and control functions are performed by Mizar Real-Time computers for which ALDO acts as a friendly user command interface and status display. It is normally started as part of your login procedure, but may also be started from the ``NETSPEC Utilities`` submenu of the root menu. The root menu is obtained by pushing the right mouse button when the cursor is over the root window (background picture). To become a user of ALDO and the other programs in the NETSPEC system, contact the person who performs systems administration tasks for the Sun computers. Most user interaction with ALDO is by means of mouse manipulation of screen items such as buttons, checkboxes, and sliders. The action of pushing the left mouse button when the cursor is over an item is called selecting that item. The left mouse button is therefore called the select button. The right mouse button is the menu button because a limited number of options may be displayed when that button is pressed when the cursor is over an item with a triangle (inverted delta). In this document, names of selectable items are printed in bold when they are first mentioned or when emphasis is helpful. In general, items which do not apply to the current context are either disabled or made invisible in order to prevent selection.

  19. SU-E-T-376: 3-D Commissioning for An Image-Guided Small Animal Micro- Irradiation Platform

    SciTech Connect (OSTI)

    Qian, X; Wuu, C; Admovics, J

    2014-06-01

    Purpose: A 3-D radiochromic plastic dosimeter has been used to cross-test the isocentricity of a high resolution image-guided small animal microirradiation platform. In this platform, the mouse stage rotating for cone beam CT imaging is perpendicular to the gantry rotation for sub-millimeter radiation delivery. A 3-D dosimeter can be used to verify both imaging and irradiation coordinates. Methods: A 3-D dosimeter and optical CT scanner were used in this study. In the platform, both mouse stage and gantry can rotate 360 with rotation axis perpendicular to each other. Isocentricity and coincidence of mouse stage and gantry rotations were evaluated using star patterns. A 3-D dosimeter was placed on mouse stage with center at platform isocenter approximately. For CBCT isocentricity, with gantry moved to 90, the mouse stage rotated horizontally while the x-ray was delivered to the dosimeter at certain angles. For irradiation isocentricity, the gantry rotated 360 to deliver beams to the dosimeter at certain angles for star patterns. The uncertainties and agreement of both CBCT and irradiation isocenters can be determined from the star patterns. Both procedures were repeated 3 times using 3 dosimeters to determine short-term reproducibility. Finally, dosimeters were scanned using optical CT scanner to obtain the results. Results: The gantry isocentricity is 0.9 0.1 mm and mouse stage rotation isocentricity is about 0.91 0.11 mm. Agreement between the measured isocenters of irradiation and imaging coordinates was determined. The short-term reproducibility test yielded 0.5 0.1 mm between the imaging isocenter and the irradiation isocenter, with a maximum displacement of 0.7 0.1 mm. Conclusion: The 3-D dosimeter can be very useful in precise verification of targeting for a small animal irradiation research. In addition, a single 3-D dosimeter can provide information in both geometric and dosimetric uncertainty, which is crucial for translational studies.

  20. Mechanism for Clastogenic Activity of Naphthalene

    SciTech Connect (OSTI)

    Buchholz, Bruce A.

    2015-09-29

    Naphthalene incubations form DNA adducts in vitro in a dose dependent manner in both mouse and rat tissues. Rodent tissue incubations with naphthalene indicate that naphthalene forms as many DNA adducts as Benzo(a)pyrene, a known DNA binding carcinogen. The mouse airway has the greatest number of DNA adducts, corresponding to the higher metabolic activation of naphthalene in this location. Both rat tissues, the rat olfactory (tumor target) and the airways (non-tumor target), have similar levels of NA-DNA adducts, indicating that short term measures of initial adduct formation do not directly correlate with sites of tumor formation in the NTP bioassays.

  1. Introduction to High Performance Computers Richard Gerber NERSC User Services

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    What are the main parts of a computer? Merit Badge Requirements ... 4. Explain the following to your counselor: a. The five major parts of a computer. ... Boy Scouts of America Offer a Computers Merit Badge 5 What are the "5 major parts"? 6 Five Major Parts eHow.com Answers.com Fluther.com Yahoo! Wikipedia CPU CPU CPU CPU Motherboard RAM Monitor RAM RAM Power Supply Hard Drive Printer Storage Power Supply Removable Media Video Card Mouse Keyboard/ Mouse Video Card Secondary Storage

  2. Section CC

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    30 J-12-1 ATTACHMENT J-12 GOVERNMENT FURNISHED SERVICES AND INFORMATION TABLE J-12.1 GFS/I LIST FROM SECTION C (SOW) ID GFS/I GFS/I Due Contract Section GF0001 DOE will administer MOUs with other law enforcement agencies or other Federal agencies (e.g., U.S. Department of Defense [Yakima Training Center]). DOE will provide copies of MOUs and/or contracts to the MSC. As required C.2.1.1.1 GF0002 DOE will provide Federal Commissions for Hanford Patrol personnel. As required C.2.1.1.1 GF0003 DOE

  3. Transcriptional Regulation of Apolipoprotein A5 Gene Expression by the Nuclear Receptor ROR alpha

    SciTech Connect (OSTI)

    Genoux, Annelise; Dehondt, Helene; Helleboid-Chapman, Audrey; Duhem, Christian; Hum, Dean W.; Martin, Genevieve; Pennacchio, Len; Staels, Bart; Fruchart-Najib, Jamila; Fruchart, Jean-Charles

    2004-10-01

    Apolipoprotein A5 has recently been identified as a crucial determinant of plasma triglyceride levels. Our results showed that RORa up-regulates human APOA5 but has no effect on mouse apoa5 promoter. These data suggest an additional important physiological role for RORa in the regulation of genes involved in plasma triglyceride homeostasis in human and probably in the development of atherosclerosis

  4. Ballistic transfection of mammalian cells in vivo

    SciTech Connect (OSTI)

    Kolesnikov, V.A.; Zelenin, A.V.; Zelenina, I.A.

    1995-11-01

    The method of ballistic transfection initially proposed for genetic transformation of plants was used for animal cells in vitro and in situ. The method consists in bombarding the transfected cells with microparticles of heavy metals carrying foreign DNA. Penetrating the cell nucleus, the microparticles transport the introduced gene. Successful genetic transformation of the cultured mouse cells and fish embryos was realized, and this allowed the study of mammalian cells in situ. The performed studies allowed us to demonstrate expression of the reporter genes of chloramphenicol acetyltransferase, galactosidase, and neomycin phosphotransferase in the mouse liver, mammary gland and kidney explants, in the liver and cross-striated muscle of mouse and rat in situ, and in developing mouse embryos at the stages of two-cell embryo, morula, and blastocyst. All these genes were introduced by ballistic transfection. In the liver and cross-striated muscle the transgene activity was detected within two to three months after transfection. Thus, the ballistic introduction of the foreign genes in the cells in situ was demonstrated, and this opens possibilities for the use of this method in gene therapy. Methodical aspects of the bombarding and transfection are considered in detail, and the published data on transfection and genetic transformation of mammalian cells are discussed. 41 refs., 13 figs., 1 tab.

  5. Method and cell lines for the production of monoclonal antibodies to human glycophorin A

    DOE Patents [OSTI]

    Bigbee, W.L.; Fong, S.S.N.; Jensen, R.H.; Vanderlaan, M.

    Cloned mouse hybridoma cell lines have been established which continuously produce antibodies that differentiate between the M and N forms of human glycophorin A. These antibodies have potential application as human blood group reagents, as markers for terminally differentiated erythroid cells and as immunofluorescent labels of somatically variant human erythrocytes.

  6. Secure video communications system

    DOE Patents [OSTI]

    Smith, Robert L.

    1991-01-01

    A secure video communications system having at least one command network formed by a combination of subsystems. The combination of subsystems to include a video subsystem, an audio subsystem, a communications subsystem, and a control subsystem. The video communications system to be window driven and mouse operated, and having the ability to allow for secure point-to-point real-time teleconferencing.

  7. Cell lines for the production of monoclonal antibodies to human glycophorin A

    DOE Patents [OSTI]

    Bigbee, William L.; Fong, Stella S. N.; Jensen, Ronald H.; Vanderlaan, Martin; Langlois, Richard G.

    1988-01-01

    Cloned mouse hybridoma cell lines have been established which continuously produce antibodies that differentiate between the M and N forms of human glycophorin A. These antibodies have potential application as human blood group reagents, as markers for terminally differentiated erythroid cells and as immunofluorescent labels of somatically variant human erythrocytes.

  8. 360° Inside a Wind Tunnel | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    360° Inside a Wind Tunnel 360° Inside a Wind Tunnel Addthis Experience what it's like inside a wind tunnel with with this video! (make sure to use your mouse or move your mobile phone around to get the full effect). Learn more about the U.S. Department of Energy Collegiate Wind Competition

  9. Sandia National Laboratories: Research: High Consequence, Automation, &

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Robotics: Advanced Manipulation Manipulation Robotics Homepage About Robotics Research & Development Advanced Controls Advanced Manipulation Mighty Mouse (M2) Sandia Hand Cybernetics High-Consequence Automation Perception and Decision Tools Unique Mobility Facilities Publications and Factsheets Robotics Image Gallery Robotics Videos Contact Robotics Research Advanced Manipulation Addressing robotics challenges The Sandia Hand has overcome issues that have prevented widespread adoption of

  10. MicroRNA-130b targets Fmr1 and regulates embryonic neural progenitor cell proliferation and differentiation

    SciTech Connect (OSTI)

    Gong, Xi; Zhang, Kunshan; Wang, Yanlu; Wang, Junbang; Cui, Yaru; Li, Siguang; Luo, Yuping

    2013-10-04

    Highlights: We found that the 3? UTR of the Fmr1 mRNA is a target of miR-130b. MiR-130b suppresses the expression of Fmr1 in mouse embryonic stem cell. MiR-130b alters the proliferation of mouse embryonic stem cell. MiR-130b alters fate specification of mouse embryonic stem cell. -- Abstract: Fragile X syndrome, one of the most common forms of inherited mental retardation, is caused by expansion of the CGG repeat in the 5?-untranslated region of the X-linked Fmr1 gene, which results in transcriptional silencing and loss of expression of its encoded protein FMRP. The loss of FMRP increases proliferation and alters fate specification in adult neural progenitor cells (aNPCs). However, little is known about Fmr1 mRNA regulation at the transcriptional and post-transcriptional levels. In the present study, we report that miR-130b regulated Fmr1 expression by directly targeting its 3?-untranslated region (3? UTR). Up-regulation of miR-130b in mouse embryonic neural progenitor cells (eNPCs) decreased Fmr1 expression, markedly increased eNPC proliferation and altered the differentiation tendency of eNPCs, suggesting that antagonizing miR-130b may be a new therapeutic entry point for treating Fragile X syndrome.

  11. Conformationally constrained farnesoid X receptor (FXR) agonists: Heteroaryl replacements of the naphthalene

    SciTech Connect (OSTI)

    Bass, Jonathan Y.; Caravella, Justin A.; Chen, Lihong; Creech, Katrina L.; Deaton, David N.; Madauss, Kevin P.; Marr, Harry B.; McFadyen, Robert B.; Miller, Aaron B.; Mills, Wendy Y.; Navas, III, Frank; Parks, Derek J.; Smalley, Jr., Terrence L.; Spearing, Paul K.; Todd, Dan; Williams, Shawn P.; Wisely, G. Bruce

    2014-08-13

    To improve on the drug properties of GSK8062 1b, a series of heteroaryl bicyclic naphthalene replacements were prepared. The quinoline 1c was an equipotent FXR agonist with improved drug developability parameters relative to 1b. In addition, analog 1c lowered body weight gain and serum glucose in a DIO mouse model of diabetes.

  12. 2001 - 11 | Jefferson Lab

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    1 Nov 2001 Sat, 2001-11-17 00:00 Jefferson Lab Gets New Chief: Leemann takes top post (Times-Dispatch) Sat, 2001-11-17 00:00 Leemann Officially Takes Over Peninsula's Jefferson Lab (The Virginian-Pilot) Mon, 2001-11-05 00:00 Lab is Working to Build a Better Mouse Camera

  13. T-547: Microsoft Windows Human Interface Device (HID) Vulnerability

    Broader source: Energy.gov [DOE]

    Microsoft Windows does not properly warn the user before enabling additional Human Interface Device (HID) functionality over USB, which allows user-assisted attackers to execute arbitrary programs via crafted USB data, as demonstrated by keyboard and mouse data sent by malware on a Smartphone that the user connected to the computer.

  14. Planar velocity and scalar concentration measurements in shock-accelerated,unstable fluid interfaces.

    SciTech Connect (OSTI)

    Goodenough, C.; Kumar, S.; Marr-Lyon, M.; Boyts, A.; Prestridge, K. P.; Rightley, P. M.; Tomkins, C. D.; Cannon, M. T.; Kamm, J. R.; Rider, William; Zoldi, C. A.; Orlicz, G.; Vorobieff, P. V.

    2004-01-01

    We report applications of several high-speed photographic techniques to diagnose fluid instability and the onset of turbulence in an ongoing experimental study of the evolution of shock-accelerated, heavy-gas cylinders. Results are at Reynolds numbers well above that associated with the turbulent and mixing transitions. Recent developments in diagnostics enable high-resolution, planar (2D) measurements of velocity fields (using particle image velocimetry, or PIV) and scalar concentration (using planar laser-induced fluorescence, or PLIF). The purpose of this work is to understand the basic science of complex, shock-driven flows and to provide high-quality data for code validation and development. The combination of these high-speed optical methods, PIV and PLIF, is setting a new standard in validating large codes for fluid simulations. The PIV velocity measurements provide quantitative evidence of transition to turbulence. In the PIV technique, a frame transfer camera with a 1 ms separation is used to image flows illuminated by two 10 ns laser pulses. Individual particles in a seeded flow are tracked from frame to frame to produce a velocity field. Dynamic PLIF measurements of the concentration field are high-resolution, quantitative dynamic data that reveal finely detailed structure at several instances after shock passage. These structures include those associated with the incipient secondary instability and late-time transition. Multiple instances of the flow are captured using a single frame Apogee camera and laser pulses with 140 {mu}s spacing. We describe tradeoffs of diagnostic instrumentation to provide PLIF images.

  15. Clinical Utility of the Modified Segmental Boost Technique for Treatment of the Pelvis and Inguinal Nodes

    SciTech Connect (OSTI)

    Moran, M.S.; Castrucci, W.A.; Ahmad, M.; Song, H.; Lund, M.W.; Mani, S.; Chamberlain, Daniel; Higgins, S.A.

    2010-03-15

    Purpose: Low-lying pelvic malignancies often require simultaneous radiation to pelvis and inguinal nodes. We previously reported improved homogeneity with the modified segmental boost technique (MSBT) compared to that with traditional methods, using phantom models. Here we report our institutional clinical experience with MSBT. Methods and Materials: MSBT patients from May 2001 to March 2007 were evaluated. Parameters analyzed included isocenter/multileaf collimation shifts, time per fraction (four fields), monitor units (MU)/fraction, femoral doses, maximal dose relative to body mass index, and inguinal node depth. In addition, a dosimetric comparison of the MSBT versus intensity modulated radiation therapy (IMRT) was conducted. Results: Of the 37 MSBT patients identified, 32 were evaluable. Port film adjustments were required in 6% of films. Median values for each analyzed parameter were as follows: MU/fraction, 298 (range, 226-348); delivery time, 4 minutes; inguinal depth, 4.5 cm; volume receiving 45 Gy (V45), 7%; V27.5, 87%; body mass index, 25 (range, 16.0-33.8). Inguinal dose was 100% in all cases; in-field inhomogeneity ranged from 111% to 118%. IMRT resulted in significantly decreased dose to normal tissue but required more time for treatment planning and a higher number of MUs (1,184 vs. 313 MU). Conclusions: In our clinical experience, the mono-isocentric MSBT provides a high degree of accuracy, improved homogeneity compared with traditional techniques, ease of simulation, treatment planning, treatment delivery, and acceptable femoral doses for pelvic/inguinal radiation fields requiring 45 to 50.4 Gy. In addition, the MSBT delivers a relatively uniform dose distribution throughout the treatment volume, despite varying body habitus. Clinical scenarios for the use of MSBT vs. intensity-modulated radiation therapy are discussed. To our knowledge, this is the first study reporting the utility of MSBT in the clinical setting.

  16. SU-E-T-578: MCEBRT, A Monte Carlo Code for External Beam Treatment Plan Verifications

    SciTech Connect (OSTI)

    Chibani, O; Ma, C; Eldib, A

    2014-06-01

    Purpose: Present a new Monte Carlo code (MCEBRT) for patient-specific dose calculations in external beam radiotherapy. The code MLC model is benchmarked and real patient plans are re-calculated using MCEBRT and compared with commercial TPS. Methods: MCEBRT is based on the GEPTS system (Med. Phys. 29 (2002) 835846). Phase space data generated for Varian linac photon beams (6 15 MV) are used as source term. MCEBRT uses a realistic MLC model (tongue and groove, rounded ends). Patient CT and DICOM RT files are used to generate a 3D patient phantom and simulate the treatment configuration (gantry, collimator and couch angles; jaw positions; MLC sequences; MUs). MCEBRT dose distributions and DVHs are compared with those from TPS in absolute way (Gy). Results: Calculations based on the developed MLC model closely matches transmission measurements (pin-point ionization chamber at selected positions and film for lateral dose profile). See Fig.1. Dose calculations for two clinical cases (whole brain irradiation with opposed beams and lung case with eight fields) are carried out and outcomes are compared with the Eclipse AAA algorithm. Good agreement is observed for the brain case (Figs 2-3) except at the surface where MCEBRT dose can be higher by 20%. This is due to better modeling of electron contamination by MCEBRT. For the lung case an overall good agreement (91% gamma index passing rate with 3%/3mm DTA criterion) is observed (Fig.4) but dose in lung can be over-estimated by up to 10% by AAA (Fig.5). CTV and PTV DVHs from TPS and MCEBRT are nevertheless close (Fig.6). Conclusion: A new Monte Carlo code is developed for plan verification. Contrary to phantombased QA measurements, MCEBRT simulate the exact patient geometry and tissue composition. MCEBRT can be used as extra verification layer for plans where surface dose and tissue heterogeneity are an issue.

  17. SU-E-T-378: Limits and Possibilities of a Simplistic Approach to Whole Breast Radiation Therapy Planning

    SciTech Connect (OSTI)

    Hipp, E; Osa, E; No, H; Jozsef, G; Rosman, M; Formenti, S

    2014-06-01

    Purpose: Challenges for radiation therapy in developing countries include unreliable infrastructure and high patient load. We propose a system to treat whole breast in the prone position without computed tomography and/or planning software. Methods: Six parameters are measured using calipers and levels with the patient prone in the treatment position. (1) The largest separation; (2) the angle that separation makes with the horizontal; (3) the separation 2 cm posterior to the nipple; (4) the vertical distance between these two separations; (5) the sup/inf length and (6) angle of the desired posterior field edge. The data in (5) (6) and (2) provide field length, collimator and gantry angles. Isocenter is set to the midpoint of (1), anterior jaw setting is 20cm (half-beam setup), and the dose is prescribed to a point 1.5 cm anterior to isocenter. MUs and wedge angles are calculated using an MU calculator and by requiring 100% dose at that point and 100-105% at the midpoint of (3). Measurements on 30 CT scans were taken to obtain the data 1-6. To test the resulting MU/wedge combinations, they were entered into Eclipse (Varian) and dose distributions were calculated. The MU/wedge combinations were recorded and tabulated. Results: Performing a dose volume histogram analysis, the contoured breast V95 was 90.5%, and the average V90 was 94.1%. The maximum dose never exceeded 114.5%, (average 108%). The lung V20 was <5% for 96.7%, and the heart V5 was <10% for 93.3% of our sample. Conclusion: A method to provide prone whole breast treatment without CT-planning was developed. The method provides reasonable coverage and normal tissue sparing. This approach is not recommended if imaging and planning capabilities are available; it was designed to specifically avoid the need for CT planning and should be reserved to clinics that need to avoid that step.

  18. Gas-phase photodissociation of CH{sub 3}COCN at 308 nm by time-resolved Fourier-transform infrared emission spectroscopy

    SciTech Connect (OSTI)

    Yeh, Yu-Ying; Chao, Meng-Hsuan; Tsai, Po-Yu; Chang, Yuan-Bin; Tsai, Ming-Tsang; Lin, King-Chuen

    2012-01-28

    By using time-resolved Fourier-transform infrared emission spectroscopy, the fragments of HCN(v= 1, 2) and CO(v= 1-3) are detected in one-photon dissociation of acetyl cyanide (CH{sub 3}COCN) at 308 nm. The S{sub 1}(A'), {sup 1}(n{sub O}, {pi}*{sub CO}) state at 308 nm has a radiative lifetime of 0.46 {+-} 0.01 {mu}s, long enough to allow for Ar collisions that induce internal conversion and enhance the fragment yields. The rate constant of Ar collision-induced internal conversion is estimated to be (1-7) x 10{sup -12} cm{sup 3} molecule{sup -1} s{sup -1}. The measurements of O{sub 2} dependence exclude the production possibility of these fragments via intersystem crossing. The high-resolution spectra of HCN and CO are analyzed to determine the ro-vibrational energy deposition of 81 {+-} 7 and 32 {+-} 3 kJ/mol, respectively. With the aid of ab initio calculations, a two-body dissociation on the energetic ground state is favored leading to HCN + CH{sub 2}CO, in which the CH{sub 2}CO moiety may further undergo secondary dissociation to release CO. The production of CO{sub 2} in the reaction with O{sub 2} confirms existence of CH{sub 2} and a secondary reaction product of CO. The HNC fragment is identified but cannot be assigned, as restricted to a poor signal-to-noise ratio. Because of insufficient excitation energy at 308 nm, the CN and CH{sub 3} fragments that dominate the dissociation products at 193 nm are not detected.

  19. Generalizable Class Solutions for Treatment Planning of Spinal Stereotactic Body Radiation Therapy

    SciTech Connect (OSTI)

    Weksberg, David C.; Palmer, Matthew B.; Vu, Khoi N.; Rebueno, Neal C.; Sharp, Hadley J.; Luo, Dershan; Yang, James N.; Shiu, Almon S.; Rhines, Laurence D.; McAleer, Mary Frances; Brown, Paul D.; Chang, Eric L.

    2012-11-01

    Purpose: Spinal stereotactic body radiation therapy (SBRT) continues to emerge as an effective therapeutic approach to spinal metastases; however, treatment planning and delivery remain resource intensive at many centers, which may hamper efficient implementation in clinical practice. We sought to develop a generalizable class solution approach for spinal SBRT treatment planning that would allow confidence that a given plan provides optimal target coverage, reduce integral dose, and maximize planning efficiency. Methods and Materials: We examined 91 patients treated with spinal SBRT at our institution. Treatment plans were categorized by lesion location, clinical target volume (CTV) configuration, and dose fractionation scheme, and then analyzed to determine the technically achievable dose gradient. A radial cord expansion was subtracted from the CTV to yield a planning CTV (pCTV) construct for plan evaluation. We reviewed the treatment plans with respect to target coverage, dose gradient, integral dose, conformality, and maximum cord dose to select the best plans and develop a set of class solutions. Results: The class solution technique generated plans that maintained target coverage and improved conformality (1.2-fold increase in the 95% van't Riet Conformation Number describing the conformality of a reference dose to the target) while reducing normal tissue integral dose (1.3-fold decrease in the volume receiving 4 Gy (V{sub 4Gy}) and machine output (19% monitor unit (MU) reduction). In trials of planning efficiency, the class solution technique reduced treatment planning time by 30% to 60% and MUs required by {approx}20%: an effect independent of prior planning experience. Conclusions: We have developed a set of class solutions for spinal SBRT that incorporate a pCTV metric for plan evaluation while yielding dosimetrically superior treatment plans with increased planning efficiency. Our technique thus allows for efficient, reproducible, and high-quality spinal

  20. The effect of diluent gases on ignition delay times in the shock tube and in the rapid compression machine

    SciTech Connect (OSTI)

    Wuermel, J.; Silke, E.J.; Curran, H.J.; O Conaire, M.S.; Simmie, J.M.

    2007-10-15

    The diluent gas used in the preparation of test fuel/oxygen mixtures is inert and does not take part in the chemical reaction. However, it does have an effect on the measured ignition delay time both in rapid compression machines and in shock tubes - argon decelerates ignition in the RCM, but accelerates it in the shock tube under some conditions. This opposite effect is due to the times scales involved in these experimental devices. Typical ignition delay times in the RCM are in the region of 1-200 ms, while those in the shock tube are much shorter (10-1000 {mu}s). Comparative RCM experiments and simulations for helium, argon, xenon, and nitrogen have shown extreme heat loss in the postcompression period, particularly for helium. Autoignition measurements of 2,3-dimethylpentane have highlighted a direct dependency of ignition delay time on the type of diluent used, where longer ignition delay time were recorded with argon. This increased ignition delay time is due to the extreme cooling of argon in the postcompression period. This observation was strengthened by comparative experiments with helium and argon, where the diluent effect was even stronger for helium, caused by its higher thermal conductivity. In the shock tube, the diluent effect is opposite to that in the RCM. For dilute mixtures of isooctane, calculations have predicted that mixtures with argon will ignite faster than those with nitrogen, based on the relative heat capacities of the two diluent gases. Overall, we conclude that the choice of diluent gases in experimental devices must be made with care, as ignition delay times can depend strongly on the type of diluent gas used. (author)

  1. Optimized design for PIGMI

    SciTech Connect (OSTI)

    Hansborough, L.; Hamm, R.; Stovall, J.; Swenson, D.

    1980-01-01

    PIGMI (Pion Generator for Medical Irradiations) is a compact linear proton accelerator design, optimized for pion production and cancer treatment use in a hospital environment. Technology developed during a four-year PIGMI Prototype experimental program allows the design of smaller, less expensive, and more reliable proton linacs. A new type of low-energy accelerating structure, the radio-frequency quadrupole (RFQ) has been tested; it produces an exceptionally good-quality beam and allows the use of a simple 30-kV injector. Average axial electric-field gradients of over 9 MV/m have been demonstrated in a drift-tube linac (DTL) structure. Experimental work is underway to test the disk-and-washer (DAW) structure, another new type of accelerating structure for use in the high-energy coupled-cavity linac (CCL). Sufficient experimental and developmental progress has been made to closely define an actual PIGMI. It will consist of a 30-kV injector, and RFQ linac to a proton energy of 2.5 MeV, a DTL linac to 125 MeV, and a CCL linac to the final energy of 650 MeV. The total length of the accelerator is 133 meters. The RFQ and DTL will be driven by a single 440-MHz klystron; the CCL will be driven by six 1320-MHz klystrons. The peak beam current is 28 mA. The beam pulse length is 60 ..mu..s at a 60-Hz repetition rate, resulting in a 100-..mu..A average beam current. The total cost of the accelerator is estimated to be approx. $10 million.

  2. A LIGHT CURVE ANALYSIS OF CLASSICAL NOVAE: FREE-FREE EMISSION VERSUS PHOTOSPHERIC EMISSION

    SciTech Connect (OSTI)

    Hachisu, Izumi; Kato, Mariko E-mail: mariko@educ.cc.keio.ac.jp

    2015-01-10

    We analyzed light curves of seven relatively slower novae, PW Vul, V705 Cas, GQ Mus, RR Pic, V5558 Sgr, HR Del, and V723 Cas, based on an optically thick wind theory of nova outbursts. For fast novae, free-free emission dominates the spectrum in optical bands rather than photospheric emission, and nova optical light curves follow the universal decline law. Faster novae blow stronger winds with larger mass-loss rates. Because the brightness of free-free emission depends directly on the wind mass-loss rate, faster novae show brighter optical maxima. In slower novae, however, we must take into account photospheric emission because of their lower wind mass-loss rates. We calculated three model light curves of free-free emission, photospheric emission, and their sum for various white dwarf (WD) masses with various chemical compositions of their envelopes and fitted reasonably with observational data of optical, near-IR (NIR), and UV bands. From light curve fittings of the seven novae, we estimated their absolute magnitudes, distances, and WD masses. In PW Vul and V705 Cas, free-free emission still dominates the spectrum in the optical and NIR bands. In the very slow novae, RR Pic, V5558 Sgr, HR Del, and V723 Cas, photospheric emission dominates the spectrum rather than free-free emission, which makes a deviation from the universal decline law. We have confirmed that the absolute brightnesses of our model light curves are consistent with the distance moduli of four classical novae with known distances (GK Per, V603 Aql, RR Pic, and DQ Her). We also discussed the reason why the very slow novae are about ∼1 mag brighter than the proposed maximum magnitude versus rate of decline relation.

  3. A retrospective analysis for patient-specific quality assurance of volumetric-modulated arc therapy plans

    SciTech Connect (OSTI)

    Li, Guangjun; Wu, Kui; Peng, Guang; Zhang, Yingjie; Bai, Sen

    2014-01-01

    Volumetric-modulated arc therapy (VMAT) is now widely used clinically, as it is capable of delivering a highly conformal dose distribution in a short time interval. We retrospectively analyzed patient-specific quality assurance (QA) of VMAT and examined the relationships between the planning parameters and the QA results. A total of 118 clinical VMAT cases underwent pretreatment QA. All plans had 3-dimensional diode array measurements, and 69 also had ion chamber measurements. Dose distribution and isocenter point dose were evaluated by comparing the measurements and the treatment planning system (TPS) calculations. In addition, the relationship between QA results and several planning parameters, such as dose level, control points (CPs), monitor units (MUs), average field width, and average leaf travel, were also analyzed. For delivered dose distribution, a gamma analysis passing rate greater than 90% was obtained for all plans and greater than 95% for 100 of 118 plans with the 3%/3-mm criteria. The difference (mean ± standard deviation) between the point doses measured by the ion chamber and those calculated by TPS was 0.9% ± 2.0% for all plans. For all cancer sites, nasopharyngeal carcinoma and gastric cancer have the lowest and highest average passing rates, respectively. From multivariate linear regression analysis, the dose level (p = 0.001) and the average leaf travel (p < 0.001) showed negative correlations with the passing rate, and the average field width (p = 0.003) showed a positive correlation with the passing rate, all indicating a correlation between the passing rate and the plan complexity. No statistically significant correlation was found between MU or CP and the passing rate. Analysis of the results of dosimetric pretreatment measurements as a function of VMAT plan parameters can provide important information to guide the plan parameter setting and optimization in TPS.

  4. EFFECTS OF INTERMITTENT EMISSION: NOISE INVENTORY FOR THE SCINTILLATING PULSAR B0834+06

    SciTech Connect (OSTI)

    Gwinn, C. R.; Johnson, M. D.; Smirnova, T. V.; Stinebring, D. R. E-mail: michaeltdh@physics.ucsb.edu E-mail: dan.stinebring@oberlin.edu

    2011-05-20

    We compare signal and noise for observations of the scintillating pulsar B0834+06, using very long baseline interferometry and a single-dish spectrometer. Comparisons between instruments and with models suggest that amplitude variations of the pulsar strongly affect the amount and distribution of self-noise. We show that noise follows a quadratic polynomial with flux density, in spectral observations. Constant coefficients, indicative of background noise, agree well with expectation; whereas second-order coefficients, indicative of self-noise, are {approx}3 times values expected for a pulsar with constant on-pulse flux density. We show that variations in flux density during the 10 s integration accounts for the discrepancy. In the secondary spectrum, {approx}97% of spectral power lies within the pulsar's typical scintillation bandwidth and timescale; an extended scintillation arc contains {approx}3%. For a pulsar with constant on-pulse flux density, noise in the dynamic spectrum will appear as a uniformly distributed background in the secondary spectrum. We find that this uniform noise background contains 95% of noise in the dynamic spectrum for interferometric observations; but only 35% of noise in the dynamic spectrum for single-dish observations. Receiver and sky dominate noise for our interferometric observations, whereas self-noise dominates for single-dish. We suggest that intermittent emission by the pulsar, on timescales <300 {mu}s, concentrates self-noise near the origin in the secondary spectrum, by correlating noise over the dynamic spectrum. We suggest that intermittency sets fundamental limits on pulsar astrometry or timing. Accounting of noise may provide means for detection of intermittent sources, when effects of propagation are unknown or impractical to invert.

  5. Study of TFTR D-T neutron spectra using natural diamond detectors

    SciTech Connect (OSTI)

    Roquemore, A.L.; Krasilnikov, A.V., Gorelenkov, N.N.

    1996-12-31

    Three Natural Diamond Detector (NDD) based spectrometers have been used for neutron spectra measurement during Deuterium-Tritium (D-T) experiments using high power Neutral Beam Injection (NBI) and Ton Cyclotron Resonance Heating (ICRH) on the Tokamak Fusion Test Reactor (TFTR) in 1996. A 2-3 % energy resolution coupled with the high radiation resistance of NDDs (5 x 10{sup 14}n/cm{sup 2}) makes them ideal for measuring the D-T neutron spectra in the high radiation environment of TFTR tritium experiments. The compact size of the NDD made it possible to insert one of the detectors into one of the center channels of the TFTR multichannel neutron collimator to provide a vertical view perpendicular to the vessel midplane, Two other detectors were placed inside shields in TFTR test cell and provide measurements of the neutrons having angles of emission of 110- 180{degrees} and 60-12-{degrees} with respect to the direction of the plasma current. By using a 0.25 {mu}s shaping time of the Ortec 673 spectroscopy amplifier we were able to accumulate useful spectrometry data at count rates up to 1.5 x 10{sup 3} counts/sec. To model the D- T neutron spectra measured by each of three NDD`s the Neutron Source post TRANSP (NST) code and semi-analytical model were developed. A set of D-T and D-D plasmas is analyzed for the dynamics of D-T neutron spectral broadening for each of three NDD cones of view. The application of three NDD based D-T neutron -spectrometer array demonstrated the anisotropy of the ion distribution function. and provided a mature of the dynamics of the effective ion temperatures for each detector view, and determined the tangential velocity of resonant tritons during ICRH.

  6. MO-G-BRE-01: A Real-Time Virtual Delivery System for Photon Radiotherapy Delivery Monitoring

    SciTech Connect (OSTI)

    Shi, F; Gu, X; Jiang, S; Jia, X; Graves, Y

    2014-06-15

    Purpose: Treatment delivery monitoring is important for radiotherapy, which enables catching dosimetric error at the earliest possible opportunity. This project develops a virtual delivery system to monitor the dose delivery process of photon radiotherapy in real-time using GPU-based Monte Carlo (MC) method. Methods: The simulation process consists of 3 parallel CPU threads. A thread T1 is responsible for communication with a linac, which acquires a set of linac status parameters, e.g. gantry angles, MLC configurations, and beam MUs every 20 ms. Since linac vendors currently do not offer interface to acquire data in real time, we mimic this process by fetching information from a linac dynalog file at the set frequency. Instantaneous beam fluence map (FM) is calculated. A FM buffer is also created in T1 and the instantaneous FM is accumulated to it. This process continues, until a ready signal is received from thread T2 on which an inhouse developed MC dose engine executes on GPU. At that moment, the accumulated FM is transferred to T2 for dose calculations, and the FM buffer in T1 is cleared. Once the calculation finishes, the resulting 3D dose distribution is directed to thread T3, which displays it in three orthogonal planes overlaid on the CT image for treatment monitoring. This process continues to monitor the 3D dose distribution in real-time. Results: An IMRT and a VMAT cases used in our patient-specific QA are studied. Maximum dose differences between our system and treatment planning system are 0.98% and 1.58% for the two cases, respectively. The average time per MC calculation is 0.1sec with <2% relative uncertainty. The update frequency of ∼10Hz is considered as real time. Conclusion: By embedding a GPU-based MC code in a novel data/work flow, it is possible to achieve real-time MC dose calculations to monitor delivery process.

  7. PROSPECTS FOR PROBING THE SPACETIME OF Sgr A* WITH PULSARS

    SciTech Connect (OSTI)

    Liu, K.; Wex, N.; Kramer, M.; Cordes, J. M.; Lazio, T. J. W.

    2012-03-01

    The discovery of radio pulsars in compact orbits around Sgr A* would allow an unprecedented and detailed investigation of the spacetime of this supermassive black hole. This paper shows that pulsar timing, including that of a single pulsar, has the potential to provide novel tests of general relativity, in particular its cosmic censorship conjecture and no-hair theorem for rotating black holes. These experiments can be performed by timing observations with 100 {mu}s precision, achievable with the Square Kilometre Array for a normal pulsar at frequency above 15 GHz. Based on the standard pulsar timing technique, we develop a method that allows the determination of the mass, spin, and quadrupole moment of Sgr A*, and provides a consistent covariance analysis of the measurement errors. Furthermore, we test this method in detailed mock data simulations. It seems likely that only for orbital periods below {approx}0.3 yr is there the possibility of having negligible external perturbations. For such orbits, we expect a {approx}10{sup -3} test of the frame dragging and a {approx}10{sup -2} test of the no-hair theorem within five years, if Sgr A* is spinning rapidly. Our method is also capable of identifying perturbations caused by distributed mass around Sgr A*, thus providing high confidence in these gravity tests. Our analysis is not affected by uncertainties in our knowledge of the distance to the Galactic center, R{sub 0}. A combination of pulsar timing with the astrometric results of stellar orbits would greatly improve the measurement precision of R{sub 0}.

  8. Time-resolved imaging of millimeter waves using visible continuum from the positive column of a Cs-Xe dc discharge

    SciTech Connect (OSTI)

    Gitlin, M. S.; Golovanov, V. V.; Spivakov, A. G.; Tsvetkov, A. I.; Zelenogorskiy, V. V.

    2010-03-15

    We present a high-sensitivity technique for time-resolved imaging of millimeter waves (MMWs) using the visible continuum (VC) from the positive column (PC) of a medium-pressure Cs-Xe dc discharge. For the MMW imaging application, a uniform plasma slab of the PC of a Cs-Xe discharge with 10x8 cm{sup 2} aperture and 2 cm in thickness was generated for 45 Torr xenon. The imaging technique is based on the fact that the intensity of the e-Xe bremsstrahlung continuum from the PC increases in the visible region when the electrons in the plasma are heated by MMWs. It is shown that in the MMW intensity range from zero to the threshold of the microwave-induced plasma breakdown, the intensity of the VC from the PC of a Cs-Xe discharge increases approximately as a second-order polynomial function of the MMW intensity. The obtained experimental data agree well with our calculations of the dependence of the VC intensity on electron temperature. The Ka-band MMW field patterns at the output of conical horn antennas and in the quasioptical beam were imaged using the discharge technique. It is shown that the technique can be used for time-resolved measurement of the profiles of watt- and subwatt-level MMWs. An energy flux sensitivity of the technique of about 10 {mu}J/cm{sup 2} in the Ka-band was demonstrated. The temporal resolution of the technique is about 0.8 {mu}s. Our modeling of the transient behavior of the electron temperature in the PC shows that the time history of the electron temperature variation coincides well with the measured time history of the VC intensity variation.

  9. Measurements of charge state breeding efficiency at BNL test EBIS

    SciTech Connect (OSTI)

    Kondrashev, S.; Alessi, J.; Beebe, E.N.; Dickerson, C.; Ostroumov, P.N.; Pikin, A.; Savard, G.

    2011-04-02

    Charge breeding of singly charged ions is required to efficiently accelerate rare isotope ion beams for nuclear and astrophysics experiments, and to enhance the accuracy of low-energy Penning trap-assisted spectroscopy. An efficient charge breeder for the Californium Rare Isotope Breeder Upgrade (CARIBU) to the ANL Tandem Linear Accelerator System (ATLAS) facility is being developed using the BNL Test Electron Beam Ion Source (Test EBIS) as a prototype. Parameters of the CARIBU EBIS charge breeder are similar to those of the BNL Test EBIS except the electron beam current will be adjustable in the range from 1 to 2 {angstrom}. The electron beam current density in the CARIBU EBIS trap will be significantly higher than in existing operational charge state breeders based on the EBIS concept. The charge state breeding efficiency is expected to be about 25% for the isotope ions extracted from the CARIBU. For the success of our EBIS project, it is essential to demonstrate high breeding efficiency at the BNL Test EBIS tuned to the regime close to the parameters of the CARIBU EBIS at ANL. The breeding efficiency optimization and measurements have been successfully carried out using a Cs{sup +} surface ionization ion source for externally pulsed injection into the BNL Test EBIS. A Cs{sup +} ion beam with a total number of ions of 5 x 10{sup 8} and optimized pulse length of 70 {mu}s has been injected into the Test EBIS and charge-bred for 5.3 ms for two different electron beam currents 1 and 1.5 {angstrom}. In these experiments we have achieved 70% injection/extraction efficiency and breeding efficiency into the most abundant charge state 17%.

  10. SU-E-J-100: The Combination of Deformable Image Registration and Regions-Of-Interest Mapping Technique to Accomplish Accurate Dose Calculation On Cone Beam Computed Tomography for Esophageal Cancer

    SciTech Connect (OSTI)

    Huang, B-T; Lu, J-Y

    2015-06-15

    Purpose: We introduce a new method combined with the deformable image registration (DIR) and regions-of-interest mapping (ROIM) technique to accurately calculate dose on daily CBCT for esophageal cancer. Methods: Patients suffered from esophageal cancer were enrolled in the study. Prescription was set to 66 Gy/30 F and 54 Gy/30 F to the primary tumor (PTV66) and subclinical disease (PTV54) . Planning CT (pCT) were segmented into 8 substructures in terms of their differences in physical density, such as gross target volume (GTV), venae cava superior (SVC), aorta, heart, spinal cord, lung, muscle and bones. The pCT and its substructures were transferred to the MIM software to readout their mean HU values. Afterwards, a deformable planning CT to daily KV-CBCT image registration method was then utilized to acquire a new structure set on CBCT. The newly generated structures on CBCT were then transferred back to the treatment planning system (TPS) and its HU information were overridden manually with mean HU values obtained from pCT. Finally, the treatment plan was projected onto the CBCT images with the same beam arrangements and monitor units (MUs) to accomplish dose calculation. Planning target volume (PTV) and organs at risk (OARs) from both of the pCT and CBCT were compared to evaluate the dose calculation accuracy. Results: It was found that the dose distribution in the CBCT showed little differences compared to the pCT, regardless of whether PTV or OARs were concerned. Specifically, dose variation in GTV, PTV54, PTV66, SVC, lung and heart were within 0.1%. The maximum dose variation was presented in the spinal cord, which was up to 2.7% dose difference. Conclusion: The proposed method combined with DIR and ROIM technique to accurately calculate dose distribution on CBCT for esophageal cancer is feasible.

  11. SU-E-T-291: Sensitivity of a Simple 2D EPID in Vivo Dosimetry

    SciTech Connect (OSTI)

    Peca, S; Brown, D

    2014-06-01

    Purpose: As radiotherapy (RT) increases in complexity, so does motivation for in vivo dosimetry (IVD), which may detect errors such as: setup, beam shaping and dose delivered. We have recently developed an easy-toimplement method for two-dimensional IVD based on images taken with the electronic portal imaging device (EPID) in cine mode during treatment. The purpose of this work is to characterize its sensitivity to possible RT delivery errors. Methods: We introduced a series of modifications to a simple RT field (1010, 100MU, 300RR, 20cm homogeneous phantom) to simulate errors. These modifications included multi-leaf collimator (MLC) position, number of MUs, and collimator angle. We quantified the sensitivity to inhomogeneities by inserting variable amounts of solid lung and bone. Finally we delivered realistic fields to an anthropomorphic phantom to estimate sensitivity to gantry angle and setup errors. Results: Our EPIDIVD is sensitive to MLC positioning errors of 1mm and 3mm in the closed and open directions respectively, and to 3% MU variations. Sensitivity to collimator angle depends on field shape irregularity; in the case of a 10x10 field, we are sensitive to errors of 0.8. The sensitivity to inhomogeneities is limited by the nature of MV imaging: approximately 1% signal change is noted when switching 5cm of water to equal amounts of bone or lung. This suggests that the EPID-IVD is likely not sensitive to small setup or gantry angle errors, as confirmed by anthropomorphic tests. Conclusion: We have characterized a simple method of 2D dose reconstruction at isocenter depth inside the patient, which is sensitive to possible RT delivery errors. This method may be useful as a secondary safety check, to prevent large errors from being carried on to following fractions, and to record delivered dose. By using readily available hardware, it is easily implemented and may prove especially useful in centers with limited resources.

  12. Substation voltage upgrading. Volume 2, Substation insulation tests and design for fast front lightning impulses: Final report

    SciTech Connect (OSTI)

    Panek, J.; Elahi, H.; Lux, A.; Imece, A.F.; LaPanse, R.A.; Stewart, J.R.

    1992-04-01

    This report addresses specific issues to support sound yet not unduly conservative uprating practices for substations. The main parts of the report cover the insulation withstand and overvoltage protection aspects, environmental measurements, reliability criteria, and industry experience. First the insulation design concerns are addressed. Substation stress by a backflashover of the line insulation due to lightning in the vicinity of the substation is recognized as a critical stress. A representative part of a 550 kV BIL substation was erected at the EPRI High Voltage Transmission Research Center, where also a special test circuit was assembled to produce a fast front, slow tail (0.2/200 {mu}s) wave. The substation as well as some special configurations were tested for line-to-ground and line-to-line withstand. Computer studies were performed to complement the test results. A number of important conclusions was reached. The most prominent result in that the high frequency oscillations, as caused by reflections within the substation, do not effect the Critical Flashover Voltage (CFO). The present practice, based on the highest peak is therefore very conservative. The slow tail of the wave appears to dictate the CFO. An arrester model for computer studies to represent very fast as well as slow phenomena was derived. It is based on full scale arrester test data, made available in this project. The computer program to calculate arrester model parameters is also a part of the report. The electric environmental measurements are reported for the tested substation at the HVTRC and for the uprated substation of Public Service Company of Colorado, both before and after the uprating. The performance is satisfactory when corona free hardware is used. Insulation design criteria are analyzed based on substation reliability, the system viewpoint and consequences of the failure. Utility experience with uprated substations is reviewed.

  13. SU-E-T-584: Commissioning of the MC2 Monte Carlo Dose Computation Engine

    SciTech Connect (OSTI)

    Titt, U; Mirkovic, D; Liu, A; Ciangaru, G; Mohan, R; Anand, A; Perles, L

    2014-06-01

    Purpose: An automated system, MC2, was developed to convert DICOM proton therapy treatment plans into a sequence MCNPX input files, and submit these to a computing cluster. MC2 converts the results into DICOM format, and any treatment planning system can import the data for comparison vs. conventional dose predictions. This work describes the data and the efforts made to validate the MC2 system against measured dose profiles and how the system was calibrated to predict the correct number of monitor units (MUs) to deliver the prescribed dose. Methods: A set of simulated lateral and longitudinal profiles was compared to data measured for commissioning purposes and during annual quality assurance efforts. Acceptance criteria were relative dose differences smaller than 3% and differences in range (in water) of less than 2 mm. For two out of three double scattering beam lines validation results were already published. Spot checks were performed to assure proper performance. For the small snout, all available measurements were used for validation vs. simulated data. To calibrate the dose per MU, the energy deposition per source proton at the center of the spread out Bragg peaks (SOBPs) was recorded for a set of SOBPs from each option. Subsequently these were then scaled to the results of dose per MU determination based on published methods. The simulations of the doses in the magnetically scanned beam line were also validated vs. measured longitudinal and lateral profiles. The source parameters were fine tuned to achieve maximum agreement with measured data. The dosimetric calibration was performed by scoring energy deposition per proton, and scaling the results to a standard dose measurement of a 10 x 10 x 10 cm3 volume irradiation using 100 MU. Results: All simulated data passed the acceptance criteria. Conclusion: MC2 is fully validated and ready for clinical application.

  14. DNA–PKcs–SIN1 complexation mediates low-dose X-ray irradiation (LDI)-induced Akt activation and osteoblast differentiation

    SciTech Connect (OSTI)

    Xu, Yong; Fang, Shi-ji; Zhu, Li-juan; Zhu, Lun-qing; Zhou, Xiao-zhong

    2014-10-24

    Highlights: • LDI increases ALP activity, promotes type I collagen (Col I)/Runx2 mRNA expression. • LDI induces DNA–PKcs activation, which is required for osteoblast differentiation. • Akt activation mediates LDI-induced ALP activity and Col I/Runx2 mRNA increase. • DNA–PKcs–SIN1 complexation mediates LDI-induced Akt Ser-473 phosphorylation. • DNA–PKcs–SIN1 complexation is important for osteoblast differentiation. - Abstract: Low-dose irradiation (LDI) induces osteoblast differentiation, however the underlying mechanisms are not fully understood. In this study, we explored the potential role of DNA-dependent protein kinase catalytic subunit (DNA–PKcs)–Akt signaling in LDI-induced osteoblast differentiation. We confirmed that LDI promoted mouse calvarial osteoblast differentiation, which was detected by increased alkaline phosphatase (ALP) activity as well as mRNA expression of type I collagen (Col I) and runt-related transcription factor 2 (Runx2). In mouse osteoblasts, LDI (1 Gy) induced phosphorylation of DNA–PKcs and Akt (mainly at Ser-473). The kinase inhibitors against DNA–PKcs (NU-7026 and NU-7441) or Akt (LY294002, perifosine and MK-2206), as well as partial depletion of DNA–PKcs or Akt1 by targeted-shRNA, dramatically inhibited LDI-induced Akt activation and mouse osteoblast differentiation. Further, siRNA-knockdown of SIN1, a key component of mTOR complex 2 (mTORC2), also inhibited LDI-induced Akt Ser-473 phosphorylation as well as ALP activity increase and Col I/Runx2 expression in mouse osteoblasts. Co-immunoprecipitation (Co-IP) assay results demonstrated that LDI-induced DNA–PKcs–SIN1 complexation, which was inhibited by NU-7441 or SIN1 siRNA-knockdown in mouse osteoblasts. In summary, our data suggest that DNA–PKcs–SIN1 complexation-mediated Akt activation (Ser-473 phosphorylation) is required for mouse osteoblast differentiation.

  15. Improved mutagen testing systems in mice. Final report

    SciTech Connect (OSTI)

    Roderick, T.H.

    1992-12-31

    Our laboratory was the first to induce and ascertain a mammalian chromosomal inversion; we did this by searching for a high frequency of first meiotic anaphase bridges in testes of males whose fathers received post-spermatogonial radiation or mutagenesis from chromosomal breaking chemical mutagens. One test in was examined in each mouse, and those showing a high frequency were then mated to determine if the high frequency were passed on as a dominant and whether linkage analysis suggested the presence of an inversion. A very high incidence (exceeding 20% bridges in first meiotic anaphase bridges) was found in about 1 in 150 males examined and this frequency was generally found to be passed on to the offspring an predicted. Later cytological banding techniques were developed elsewhere and we used them to show visually the inverted orders of the inverted chromosomal segments. Since that time we have induced inversions covering most of the mouse genome.

  16. Improved mutagen testing systems in mice

    SciTech Connect (OSTI)

    Roderick, T.H.

    1992-01-01

    Our laboratory was the first to induce and ascertain a mammalian chromosomal inversion; we did this by searching for a high frequency of first meiotic anaphase bridges in testes of males whose fathers received post-spermatogonial radiation or mutagenesis from chromosomal breaking chemical mutagens. One test in was examined in each mouse, and those showing a high frequency were then mated to determine if the high frequency were passed on as a dominant and whether linkage analysis suggested the presence of an inversion. A very high incidence (exceeding 20% bridges in first meiotic anaphase bridges) was found in about 1 in 150 males examined and this frequency was generally found to be passed on to the offspring an predicted. Later cytological banding techniques were developed elsewhere and we used them to show visually the inverted orders of the inverted chromosomal segments. Since that time we have induced inversions covering most of the mouse genome.

  17. A review of MRI evaluation of demyelination in cuprizone murine model

    SciTech Connect (OSTI)

    Krutenkova, E. Pan, E.; Khodanovich, M.

    2015-11-17

    The cuprizone mouse model of non-autoimmune demyelination reproduces some phenomena of multiple sclerosis and is appropriate for validation and specification of a new method of non-invasive diagnostics. In the review new data which are collected using the new MRI method are compared with one or more conventional MRI tools. Also the paper reviewed the validation of MRI approaches using histological or immunohistochemical methods. Luxol fast blue histological staining and myelin basic protein immunostaining is widespread. To improve the accuracy of non-invasive conventional MRI, multimodal scanning could be applied. The new quantitative MRI method of fast mapping of the macromolecular proton fraction is a reliable biomarker of myelin in the brain and can be used for research of demyelination in animals. To date, a validation of MPF method on the CPZ mouse model of demyelination is not performed, although this method is probably the best way to evaluate demyelination using MRI.

  18. Establishing a process of irradiating small animal brain using a CyberKnife and a microCT scanner

    SciTech Connect (OSTI)

    Kim, Haksoo; Welford, Scott; Fabien, Jeffrey; Zheng, Yiran; Yuan, Jake; Brindle, James; Yao, Min; Lo, Simon; Wessels, Barry; Machtay, Mitchell; Sohn, Jason W.; Sloan, Andrew

    2014-02-15

    Purpose: Establish and validate a process of accurately irradiating small animals using the CyberKnife G4 System (version 8.5) with treatment plans designed to irradiate a hemisphere of a mouse brain based on microCT scanner images. Methods: These experiments consisted of four parts: (1) building a mouse phantom for intensity modulated radiotherapy (IMRT) quality assurance (QA), (2) proving usability of a microCT for treatment planning, (3) fabricating a small animal positioning system for use with the CyberKnife's image guided radiotherapy (IGRT) system, and (4)in vivo verification of targeting accuracy. A set of solid water mouse phantoms was designed and fabricated, with radiochromic films (RCF) positioned in selected planes to measure delivered doses. After down-sampling for treatment planning compatibility, a CT image set of a phantom was imported into the CyberKnife treatment planning system—MultiPlan (ver. 3.5.2). A 0.5 cm diameter sphere was contoured within the phantom to represent a hemispherical section of a mouse brain. A nude mouse was scanned in an alpha cradle using a microCT scanner (cone-beam, 157 × 149 pixels slices, 0.2 mm longitudinal slice thickness). Based on the results of our positional accuracy study, a planning treatment volume (PTV) was created. A stereotactic body mold of the mouse was “printed” using a 3D printer laying UV curable acrylic plastic. Printer instructions were based on exported contours of the mouse's skin. Positional reproducibility in the mold was checked by measuring ten CT scans. To verify accurate dose delivery in vivo, six mice were irradiated in the mold with a 4 mm target contour and a 2 mm PTV margin to 3 Gy and sacrificed within 20 min to avoid DNA repair. The brain was sliced and stained for analysis. Results: For the IMRT QA using a set of phantoms, the planned dose (6 Gy to the calculation point) was compared to the delivered dose measured via film and analyzed using Gamma analysis (3% and 3 mm). A

  19. Glucose cycling is markedly enhanced in pancreatic islets of obese hyperglycemic mice

    SciTech Connect (OSTI)

    Khan, A.; Chandramouli, V.; Ostenson, C.G.; Berggren, P.O.; Loew, H.L.; Landau, B.R.; Efendic, S. )

    1990-05-01

    Pancreatic islets from fed 7-month old lean and obese hyperglycemic mice (ob/ob) were incubated with 3H2O and 5.5 mM or 16.7 mM glucose. Incorporation of 3H into the medium glucose was taken as the measure of glucose-6-P hydrolysis to glucose. Glucose utilization was measured from the yield of 3H2O from (5-3H)glucose. Only 3-4% of the glucose phosphorylated was dephosphorylated by the lean mouse islets irrespective of the glucose concentration. In contrast, the ob/ob mouse islets at 5.5 mM glucose dephosphorylated 18% of the glucose phosphorylated and 30% at 16.7 mM. Thus, the islets of hyperglycemic mice demonstrate increased glucose cycling as compared to the islets of normoglycemic lean mice.

  20. Construction of highly extensive polymorphic DNA libraries by in-gel competitive reassociation procedure

    SciTech Connect (OSTI)

    Inoue, Shinichi; Kiyama, Ryoiti; Oishi, Michio

    1996-02-01

    Differential genomic DNA libraries between two mouse strains and from two human individuals were constructed by means of the in-gel competitive reassociation (IGCR) procedure, a procedure developed for cloning altered anonymous restriction fragments. The libraries were highly enriched fragments, approximately 60 and 40% for the mouse and human libraries, respectively, and, more importantly, maintained most of the original complexities of the RFLP fragments. Therefore, differential genomic DNA libraries constructed by the IGCR procedure, particularly for human genomic DNA, should offer highly extensive sources for polymorphic DNA sequences necessary for a variety of genome analyses, including studies on the origin and mechanism of biological diversity among the same species. 19 refs., 4 figs.

  1. Library Resources for Bac End Sequencing. Final Technical Report

    SciTech Connect (OSTI)

    Pieter J. de Jong

    2000-10-01

    Studies directed towards the specific aims outlined for this research award are summarized. The RPCI II Human Bac Library has been expanded by the addition of 6.9-fold genomic coverage. This segment has been generated from a MBOI partial digest of the same anonymous donor DNA used for the rest of the library. A new cloning vector, pTARBAC1, has been constructed and used in the construction of RPCI-II segment 5. This new cloning vector provides a new strategy in identifying targeted genomic regions and will greatly facilitate a large-scale analysis for positional cloning. A new maleCS7BC/6J mouse BAC library has been constructed. RPCI-23 contain 576 plates (approx 210,000 clones) and represents approximately 11-fold coverage of the mouse genome.

  2. Hybrid radiosity-SP{sub 3} equation based bioluminescence tomography reconstruction for turbid medium with low- and non-scattering regions

    SciTech Connect (OSTI)

    Chen, Xueli E-mail: jimleung@mail.xidian.edu.cn; Zhang, Qitan; Yang, Defu; Liang, Jimin E-mail: jimleung@mail.xidian.edu.cn

    2014-01-14

    To provide an ideal solution for a specific problem of gastric cancer detection in which low-scattering regions simultaneously existed with both the non- and high-scattering regions, a novel hybrid radiosity-SP{sub 3} equation based reconstruction algorithm for bioluminescence tomography was proposed in this paper. In the algorithm, the third-order simplified spherical harmonics approximation (SP{sub 3}) was combined with the radiosity equation to describe the bioluminescent light propagation in tissues, which provided acceptable accuracy for the turbid medium with both low- and non-scattering regions. The performance of the algorithm was evaluated with digital mouse based simulations and a gastric cancer-bearing mouse based in situ experiment. Primary results demonstrated the feasibility and superiority of the proposed algorithm for the turbid medium with low- and non-scattering regions.

  3. ChIP-seq Mapping of Distant-Acting Enhancers and Their In Vivo Activities

    SciTech Connect (OSTI)

    Visel, Axel; Pennacchio, Len A.

    2011-06-01

    The genomic location and function of most distant-acting transcriptional enhancers in the human genome remains unknown We performed ChIP-seq for various transcriptional coactivator proteins (such as p300) directly from different embryonic mouse tissues, identifying thousands of binding sitesTransgenic mouse experiments show that p300 and other co-activator peaks are highly predictive of genomic location AND tissue-specific activity patterns of distant-acting enhancersMost enhancers are active only in one or very few tissues Genomic location of tissue-specific p300 peaks correlates with tissue-specific expression of nearby genes Most binding sites are conserved, but the global degree of conservation varies between tissues

  4. Establishing a process of irradiating small animal brain using a CyberKnife and a microCT scanner

    SciTech Connect (OSTI)

    Kim, Haksoo; Welford, Scott; Fabien, Jeffrey; Zheng, Yiran; Yuan, Jake; Brindle, James; Yao, Min; Lo, Simon; Wessels, Barry; Machtay, Mitchell; Sohn, Jason W.; Sloan, Andrew

    2014-02-15

    Purpose: Establish and validate a process of accurately irradiating small animals using the CyberKnife G4 System (version 8.5) with treatment plans designed to irradiate a hemisphere of a mouse brain based on microCT scanner images. Methods: These experiments consisted of four parts: (1) building a mouse phantom for intensity modulated radiotherapy (IMRT) quality assurance (QA), (2) proving usability of a microCT for treatment planning, (3) fabricating a small animal positioning system for use with the CyberKnife's image guided radiotherapy (IGRT) system, and (4)in vivo verification of targeting accuracy. A set of solid water mouse phantoms was designed and fabricated, with radiochromic films (RCF) positioned in selected planes to measure delivered doses. After down-sampling for treatment planning compatibility, a CT image set of a phantom was imported into the CyberKnife treatment planning systemMultiPlan (ver. 3.5.2). A 0.5 cm diameter sphere was contoured within the phantom to represent a hemispherical section of a mouse brain. A nude mouse was scanned in an alpha cradle using a microCT scanner (cone-beam, 157 149 pixels slices, 0.2 mm longitudinal slice thickness). Based on the results of our positional accuracy study, a planning treatment volume (PTV) was created. A stereotactic body mold of the mouse was printed using a 3D printer laying UV curable acrylic plastic. Printer instructions were based on exported contours of the mouse's skin. Positional reproducibility in the mold was checked by measuring ten CT scans. To verify accurate dose delivery in vivo, six mice were irradiated in the mold with a 4 mm target contour and a 2 mm PTV margin to 3 Gy and sacrificed within 20 min to avoid DNA repair. The brain was sliced and stained for analysis. Results: For the IMRT QA using a set of phantoms, the planned dose (6 Gy to the calculation point) was compared to the delivered dose measured via film and analyzed using Gamma analysis (3% and 3 mm). A passing rate

  5. NETLMemorandum of Understanding or Agreement

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Memorandum of Understanding or Agreement Memorandums of Understanding (MOUs) OR Memorandums of Agreement (MOAs) are written agreements between NETL and other entities that state of scope of work for a specific project or state the terms of a partnering relationship. Parties to these agreements may include other federal agencies, local, state, international, or other government entities; the private sector; and educational institutions. An MOU or MOA is not considered a binding contract. It

  6. Supercomputing: Eye-Opening Possibilities in Imaging | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Supercomputing: Eye-Opening Possibilities in Imaging Supercomputing: Eye-Opening Possibilities in Imaging September 20, 2013 - 5:00pm Addthis This overlay of mass spectrometry images shows the spatial distribution of three different kind of lipids across a whole mouse cross-section. Lipids act as the structural components of cell membranes and are responsible for energy storage, among other things. | Photo courtesy of Wolfgang Reindl (Berkeley Lab). This overlay of mass spectrometry images shows

  7. Memorandum of Understanding (MOU) | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    of Understanding (MOU) Memorandum of Understanding (MOU) The following document is a sample Memorandum of Understanding for DOE laboratories to use as guidance in drafting lab MOUs. Sample_lab_MOU.pdf (200.89 KB) More Documents & Publications Memorandum of Understanding (MOU) Between the State of Nevada and the U.S. Department of Energy Memorandum of understanding between DOE and NGLIA Electric Power Research Institute Cooperation to Increase Energy Efficiency, March 6, 2008

  8. Finite Element Results Visualization for Unstructured Grids

    Energy Science and Technology Software Center (OSTI)

    1996-07-15

    GRIZ is a general-purpose post-processing application supporting interactive visualization of finite element analysis results on unstructured grids. In addition to basic pseudocolor renderings of state variables over the mesh surface, GRIZ provides modern visualization techniques such as isocontours and isosurfaces, cutting planes, vector field display, and particle traces. GRIZ accepts both command-line and mouse-driven input, and is portable to virtually any UNIX platform which provides Motif and OpenGl libraries.

  9. Microsoft Word - S08568_CY2011 Annual Rpt

    Office of Legacy Management (LM)

    2 Spatial ecology data for the Site are available for several data types and are stored in the GIS on the servers in Grand Junction, Colorado. The types of ecological spatial data that are available include annual weed distribution data (for selected species), annual weed control locations, biocontrol release locations, vegetation and wildlife monitoring locations (transect endpoints and sample points), vegetation community classifications, Preble's mouse habitat, wetland locations,

  10. 'Data Deluge' Pushes Mass Spec Imaging to New Heights

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    'Data Deluge' Pushes Mass Spec Imaging to New Heights 'Data Deluge' Pushes Mass Spec Imaging to New Heights MANTISSA Team Takes Novel Approach to Improve Experimental Data Analysis July 15, 2015 Contact: Kathy Kincade, +1 510 495 2124, kkincade@lbl.gov MANTISSA Ion-intensity visualization of the 20 most important ions in a mouse brain segment selected by the CX/CUR algorithm. Of the 20 ions, little redundancy is present, pointing to the effectiveness of the CX approach for information

  11. Radiolabelling and positron emission tomography of PT70, a time-dependent inhibitor of InhA, the Mycobacterium tuberculosis enoyl-ACP reductase

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Wang, Hui; Liu, Li; Lu, Yang; Pan, Pan; Hooker, Jacob M.; Fowler, Joanna S.; Tonge, Peter J.

    2015-07-14

    PT70 is a diaryl ether inhibitor of InhA, the enoyl-ACP reductase in the Mycobacterium tuberculosis fatty acid biosynthesis pathway. It has a residence time of 24 min on the target, and also shows antibacterial activity in a mouse model of tuberculosis infection. Due to the interest in studying target tissue pharmacokinetics of PT70, we developed a method to radiolabel PT70 with carbon-11 and have studied its pharmacokinetics in mice and baboons using positron emission tomography.

  12. 1980s Forging Partnerships on the Information Front | OSTI, US Dept of

    Office of Scientific and Technical Information (OSTI)

    Energy Office of Scientific and Technical Information 80s Forging Partnerships on the Information Front 1980s Forging Partnerships on the Information Front Back to history 1980 Memorandum of Understanding (MOU) with the Nuclear Energy Agency (NEA) Databank signed for the exchange of computer codes 1981 Bilateral MOUs began with other countries to exchange non-nuclear information 1981 Department of Energy Panel on International Scientific and Technical Information (STI) concluded that foreign

  13. Bone marrow-derived osteoblast progenitor cells in circulating blood contribute to ectopic bone formation in mice

    SciTech Connect (OSTI)

    Otsuru, Satoru; Tamai, Katsuto . E-mail: tamai@gts.med.osaka-u.ac.jp; Yamazaki, Takehiko; Yoshikawa, Hideki; Kaneda, Yasufumi

    2007-03-09

    Recent studies have suggested the existence of osteoblastic cells in the circulation, but the origin and role of these cells in vivo are not clear. Here, we examined how these cells contribute to osteogenesis in a bone morphogenetic protein (BMP)-induced model of ectopic bone formation. Following lethal dose-irradiation and subsequent green fluorescent protein-transgenic bone marrow cell-transplantation (GFP-BMT) in mice, a BMP-2-containing collagen pellet was implanted into muscle. Three weeks later, a significant number of GFP-positive osteoblastic cells were present in the newly generated ectopic bone. Moreover, peripheral blood mononuclear cells (PBMNCs) from the BMP-2-implanted mouse were then shown to include osteoblast progenitor cells (OPCs) in culture. Passive transfer of the PBMNCs isolated from the BMP-2-implanted GFP-mouse to the BMP-2-implanted nude mouse led to GFP-positive osteoblast accumulation in the ectopic bone. These data provide new insight into the mechanism of ectopic bone formation involving bone marrow-derived OPCs in circulating blood.

  14. Genetic maps of polymorphic DNA loci on rat chromosome 1

    SciTech Connect (OSTI)

    Ding, Yan-Ping; Remmers, E.F.; Longman, R.E.

    1996-09-01

    Genetic linkage maps of loci defined by polymorphic DNA markers on rat chromosome 1 were constructed by genotyping F2 progeny of F344/N x LEW/N, BN/SsN x LEW/N, and DA/Bkl x F344/Hsd inbred rat strains. In total, 43 markers were mapped, of which 3 were restriction fragment length polymorphisms and the others were simple sequence length polymorphisms. Nineteen of these markers were associated with genes. Six markers for five genes, {gamma}-aminobutyric acid receptor {beta}3 (Gabrb3), syntaxin 2 (Stx2), adrenergic receptor {beta}3 (Gabrb3), syntaxin 2 (Stx2), adrenergic receptor {beta}1 (Adrb1), carcinoembryonic antigen gene family member 1 (Cgm1), and lipogenic protein S14 (Lpgp), and 20 anonymous loci were not previously reported. Thirteen gene loci (Myl2, Aldoa, Tnt, Igf2, Prkcg, Cgm4, Calm3, Cgm3, Psbp1, Sa, Hbb, Ins1, and Tcp1) were previously mapped. Comparative mapping analysis indicated that the large portion of rat chromosome 1 is homologous to mouse chromosome 7, although the homologous to mouse chromosome 7, although the homologs of two rat genes are located on mouse chromosomes 17 and 19. Homologs of the rat chromosome 1 genes that we mapped are located on human chromosomes 6, 10, 11, 12, 15, 16, and 19. 38 refs., 1 fig., 3 tabs.

  15. Targeted disruption of Ataxia-telangiectasia mutated gene in miniature pigs by somatic cell nuclear transfer

    SciTech Connect (OSTI)

    Kim, Young June; Ahn, Kwang Sung; Kim, Minjeong; Kim, Min Ju; Park, Sang-Min; Ryu, Junghyun; Ahn, Jin Seop; Heo, Soon Young; Kang, Jee Hyun; Choi, You Jung; Choi, Seong-Jun; Shim, Hosup

    2014-10-03

    Highlights: • ATM gene-targeted pigs were produced by somatic cell nuclear transfer. • A novel large animal model for ataxia telangiectasia was developed. • The new model may provide an alternative to the mouse model. - Abstract: Ataxia telangiectasia (A-T) is a recessive autosomal disorder associated with pleiotropic phenotypes, including progressive cerebellar degeneration, gonad atrophy, and growth retardation. Even though A-T is known to be caused by the mutations in the Ataxia telangiectasia mutated (ATM) gene, the correlation between abnormal cellular physiology caused by ATM mutations and the multiple symptoms of A-T disease has not been clearly determined. None of the existing ATM mouse models properly reflects the extent to which neurological degeneration occurs in human. In an attempt to provide a large animal model for A-T, we produced gene-targeted pigs with mutations in the ATM gene by somatic cell nuclear transfer. The disrupted allele in the ATM gene of cloned piglets was confirmed via PCR and Southern blot analysis. The ATM gene-targeted pigs generated in the present study may provide an alternative to the current mouse model for the study of mechanisms underlying A-T disorder and for the development of new therapies.

  16. Assessment of dedicated low-dose cardiac micro-CT reconstruction algorithms using the left ventricular volume of small rodents as a performance measure

    SciTech Connect (OSTI)

    Maier, Joscha; Sawall, Stefan; Kachelrie, Marc

    2014-05-15

    Purpose: Phase-correlated microcomputed tomography (micro-CT) imaging plays an important role in the assessment of mouse models of cardiovascular diseases and the determination of functional parameters as the left ventricular volume. As the current gold standard, the phase-correlated Feldkamp reconstruction (PCF), shows poor performance in case of low dose scans, more sophisticated reconstruction algorithms have been proposed to enable low-dose imaging. In this study, the authors focus on the McKinnon-Bates (MKB) algorithm, the low dose phase-correlated (LDPC) reconstruction, and the high-dimensional total variation minimization reconstruction (HDTV) and investigate their potential to accurately determine the left ventricular volume at different dose levels from 50 to 500 mGy. The results were verified in phantom studies of a five-dimensional (5D) mathematical mouse phantom. Methods: Micro-CT data of eight mice, each administered with an x-ray dose of 500 mGy, were acquired, retrospectively gated for cardiac and respiratory motion and reconstructed using PCF, MKB, LDPC, and HDTV. Dose levels down to 50 mGy were simulated by using only a fraction of the projections. Contrast-to-noise ratio (CNR) was evaluated as a measure of image quality. Left ventricular volume was determined using different segmentation algorithms (Otsu, level sets, region growing). Forward projections of the 5D mouse phantom were performed to simulate a micro-CT scan. The simulated data were processed the same way as the real mouse data sets. Results: Compared to the conventional PCF reconstruction, the MKB, LDPC, and HDTV algorithm yield images of increased quality in terms of CNR. While the MKB reconstruction only provides small improvements, a significant increase of the CNR is observed in LDPC and HDTV reconstructions. The phantom studies demonstrate that left ventricular volumes can be determined accurately at 500 mGy. For lower dose levels which were simulated for real mouse data sets, the

  17. Classified computer configuration control system (C{sup 4}S), revision 3, user`s information

    SciTech Connect (OSTI)

    O`Callaghan, P.B.; Nelson, R.A.; Grambihler, A.J.

    1994-04-01

    The Classified Computer Configuration Control System (C{sup 4}S) allows security management to track pertinent information concerning classified computer systems in the scope of their control. Information is entered by the level security manager that is closest to the classified computer system. Managers that are further removed from systems can have consolidated information made available to them. C{sup 4}S can be used to generate reports that are as current as the last information that was entered into the database. C{sup 4}S offers data entry, data display, and data reporting. The user interface uses menus, entry forms, the mouse, and Hot Keys. C{sup 4}S provides help windows that are available at any time by pressing the F1 key. C{sup 4}S has help for each menu, data entry form, and general program information. You can browse a help window by pressing the arrows, page up, or page down keys. You control C{sup 4}S with program options selected from pull-down menus. You {open_quotes}select{close_quotes} by moving a highlight bar up and down or across the menu and pressing enter on one of the options. The highlight bar is moved using the arrow keys, mouse, or selection letters. Notice that a letter of each menu option is a different color from the other letters. This is the selection letter for that option. If you press the selection letter, the highlight bar will move to that option. You can also use a mouse to move the highlight bar to the option by moving the mouse pointer to the option and pressing the mouse button. Explanation of menu options or entry fields appear at the bottom of the screen. These explanations should help you use C{sup 4}S. If you need more help, it is available by pressing F1. C{sup 4}S will bring up a help window for the particular option you are working with. The authors of the program are P.B. O`Callaghan, A. J. Grambihler, and R.A. Nelson.

  18. SU-E-T-361: Clinical Benefit of Automatic Beam Gating Mixed with Breath Hold in Radiation Therapy of Left Breast

    SciTech Connect (OSTI)

    Wu, J; Hill, G; Spiegel, J; Ye, J; Mehta, V

    2014-06-01

    Purpose: To investigate the clinical and dosimetric benefits of automatic gating of left breast mixed with breath-hold technique. Methods: Two Active Breathing Control systems, ABC2.0 and ABC3.0, were used during simulation and treatment delivery. The two systems are different such that ABC2.0 is a breath-hold system without beam control capability, while ABC3.0 has capability in both breath-hold and beam gating. At simulation, each patient was scanned twice: one with free breathing (FB) and one with breath hold through ABC. Treatment plan was generated on the CT with ABC. The same plan was also recalculated on the CT with FB. These two plans were compared to assess plan quality. For treatments with ABC2.0, beams with MU > 55 were manually split into multiple subfields. All subfields were identical and shared the total MU. For treatment with ABC3.0, beam splitting was unnecessary. Instead, treatment was delivered in gating mode mixed with breath-hold technique. Treatment delivery efficiency using the two systems was compared. Results: The prescribed dose was 50.4Gy at 1.8Gy/fraction. The maximum heart dose averaged over 10 patients was 46.02.5Gy and 24.512.2Gy for treatments with FB and with ABC respectively. The corresponding heart V10 was 13.23.6% and 1.01.6% respectively. The averaged MUs were 99.87.5 for LMT, 99.29.4 for LLT. For treatment with ABC2.0, normally the original beam was split into 2 subfields. The averaged total time to delivery all beams was 4.30.4min for treatments with ABC2.0 and 3.30.6min for treatments with ABC3.0 in gating mode. Conclusion: Treatment with ABC tremendously reduced heart dose. Compared to treatments with ABC2.0, gating with ABC3.0 reduced the total treatment time by 23%. Use of ABC3.0 improved the delivery efficiency, and eliminated the possibility of mistreatments. The latter may happen with ABC2.0 where beam is not terminated when breath signal falls outside of the treatment window.

  19. SU-E-T-224: Is Monte Carlo Dose Calculation Method Necessary for Cyberknife Brain Treatment Planning?

    SciTech Connect (OSTI)

    Wang, L; Fourkal, E; Hayes, S; Jin, L; Ma, C

    2014-06-01

    Purpose: To study the dosimetric difference resulted in using the pencil beam algorithm instead of Monte Carlo (MC) methods for tumors adjacent to the skull. Methods: We retrospectively calculated the dosimetric differences between RT and MC algorithms for brain tumors treated with CyberKnife located adjacent to the skull for 18 patients (total of 27 tumors). The median tumor sizes was 0.53-cc (range 0.018-cc to 26.2-cc). The absolute mean distance from the tumor to the skull was 2.11 mm (range - 17.0 mm to 9.2 mm). The dosimetric variables examined include the mean, maximum, and minimum doses to the target, the target coverage (TC) and conformality index. The MC calculation used the same MUs as the RT dose calculation without further normalization and 1% statistical uncertainty. The differences were analyzed by tumor size and distance from the skull. Results: The TC was generally reduced with the MC calculation (24 out of 27 cases). The average difference in TC between RT and MC was 3.3% (range 0.0% to 23.5%). When the TC was deemed unacceptable, the plans were re-normalized in order to increase the TC to 99%. This resulted in a 6.9% maximum change in the prescription isodose line. The maximum changes in the mean, maximum, and minimum doses were 5.4 %, 7.7%, and 8.4%, respectively, before re-normalization. When the TC was analyzed with regards to target size, it was found that the worst coverage occurred with the smaller targets (0.018-cc). When the TC was analyzed with regards to the distance to the skull, there was no correlation between proximity to the skull and TC between the RT and MC plans. Conclusions: For smaller targets (< 4.0-cc), MC should be used to re-evaluate the dose coverage after RT is used for the initial dose calculation in order to ensure target coverage.

  20. Probing for exoplanets hiding in dusty debris disks: Disk imaging, characterization, and exploration with HST/STIS multi-roll coronagraphy

    SciTech Connect (OSTI)

    Schneider, Glenn; Hinz, Phillip M.; Grady, Carol A.; Hines, Dean C.; Debes, John H.; Perrin, Marshall D.; Moro-Martin, Amaya; Stark, Christopher C.; Kuchner, Marc J.; Woodgate, Bruce E.; Weinberger, Alycia J.; Rodigas, Timothy J.; Wisniewski, John P.; Silverstone, Murray D.; Jang-Condell, Hannah; Henning, Thomas; Serabyn, Eugene; Tamura, Motohide

    2014-10-01

    Spatially resolved scattered-light images of circumstellar debris in exoplanetary systems constrain the physical properties and orbits of the dust particles in these systems. They also inform on co-orbiting (but unseen) planets, the systemic architectures, and forces perturbing the starlight-scattering circumstellar material. Using Hubble Space Telescope (HST)/Space Telescope Imaging Spectrograph (STIS) broadband optical coronagraphy, we have completed the observational phase of a program to study the spatial distribution of dust in a sample of 10 circumstellar debris systems and 1 'mature' protoplanetrary disk, all with HST pedigree, using point-spread-function-subtracted multi-roll coronagraphy. These observations probe stellocentric distances ?5 AU for the nearest systems, and simultaneously resolve disk substructures well beyond corresponding to the giant planet and Kuiper Belt regions within our own solar system. They also disclose diffuse very low-surface-brightness dust at larger stellocentric distances. Herein we present new results inclusive of fainter disks such as HD 92945 (F {sub disk}/F {sub star} = 5 10{sup 5}), confirming, and better revealing, the existence of a narrow inner debris ring within a larger diffuse dust disk. Other disks with ring-like substructures and significant asymmetries and complex morphologies include HD 181327, for which we posit a spray of ejecta from a recent massive collision in an exo-Kuiper Belt; HD 61005, suggested to be interacting with the local interstellar medium; and HD 15115 and HD 32297, also discussed in the context of putative environmental interactions. These disks and HD 15745 suggest that debris system evolution cannot be treated in isolation. For AU Mic's edge-on disk, we find out-of-plane surface brightness asymmetries at ?5 AU that may implicate the existence of one or more planetary perturbers. Time-resolved images of the MP Mus protoplanetary disk provide spatially resolved temporal variability in the

  1. Dosimetric comparison of 3D conformal, IMRT, and V-MAT techniques for accelerated partial-breast irradiation (APBI)

    SciTech Connect (OSTI)

    Qiu, Jian-Jian; Chang, Zheng; Horton, Janet K.; Wu, Qing-Rong Jackie; Yoo, Sua; Yin, Fang-Fang

    2014-07-01

    The purpose is to dosimetrically compare the following 3 delivery techniques: 3-dimensional conformal radiation therapy (3D-CRT), intensity-modulated arc therapy (IMRT), and volumetric-modulated arc therapy (V-MAT) in the treatment of accelerated partial-breast irradiation (APBI). Overall, 16 patients with T1/2N0 breast cancer were treated with 3D-CRT (multiple, noncoplanar photon fields) on the RTOG 0413 partial-breast trial. These cases were subsequently replanned using static gantry IMRT and V-MAT technology to understand dosimetric differences among these 3 techniques. Several dosimetric parameters were used in plan quality evaluation, including dose conformity index (CI) and dose-volume histogram analysis of normal tissue coverage. Quality assurance studies including gamma analysis were performed to compare the measured and calculated dose distributions. The IMRT and V-MAT plans gave more conformal target dose distributions than the 3D-CRT plans (p < 0.05 in CI). The volume of ipsilateral breast receiving 5 and 10 Gy was significantly less using the V-MAT technique than with either 3D-CRT or IMRT (p < 0.05). The maximum lung dose and the ipsilateral lung volume receiving 10 (V{sub 10}) or 20 Gy (V{sub 20}) were significantly less with both V-MAT and IMRT (p < 0.05). The IMRT technique was superior to 3D-CRT and V-MAT of low dose distributions in ipsilateral lung (p < 0.05 in V{sub 5} and D{sub 5}). The total mean monitor units (MUs) for V-MAT (621.0 111.9) were 12.2% less than those for 3D-CRT (707.3 130.9) and 46.5% less than those for IMRT (1161.4 315.6) (p < 0.05). The average machine delivery time was 1.5 0.2 minutes for the V-MAT plans, 7.0 1.6 minutes for the 3D-CRT plans, and 11.5 1.9 minutes for the IMRT plans, demonstrating much less delivery time for V-MAT. Based on this preliminary study, V-MAT and IMRT techniques offer improved dose conformity as compared with 3D-CRT techniques without increasing dose to the ipsilateral lung. In terms

  2. Groundwaters of Florence (Italy): Trace element distribution and vulnerability of the aquifers

    SciTech Connect (OSTI)

    Bencini, A.; Ercolanelli, R.; Sbaragli, A.

    1993-11-01

    Geochemical and hydrogeological research has been carried out in Florence, to evaluate conductivity and main chemistry of groundwaters, the pattern of some possible pollutant chemical species (Fe, Mn, Cr, Cu, Pb, Zn, NO{sub 2}, NO{sub 3}), and the vulnerability of the aquifers. The plain is made up of Plio-Quaternary alluvial and lacustrine sediments for a maximum thickness of 600 m. Silts and clays, sometimes with lenses of sandy gravels, are dominant, while considerable deposits of sands, pebbles, and gravels occur along the course of the Arno river and its tributary streams, and represent the most important aquifer of the plain. Most waters show conductivity values around 1000-1200 {mu}S, and almost all of them have an alkaline-earth-bicarbonate chemical character. In western areas higher salt content of the groundwaters is evident. Heavy metal and NO{sub 2}, NO{sub 3} analyses point out that no important pollution phenomena affect the groundwaters; all mean values are below the maximum admissible concentration (MAC) for drinkable waters. Some anomalies of NO{sub 2}, NO{sub 3}, Fe, Mn, and Zn are present. The most plausible causes can be recognized in losses of the sewage system; use of nitrate compounds in agriculture; oxidation of well pipes. All the observations of Cr, Cu, and Pb are below the MAC; the median values of <3, 3.9, and 1.1 {mu}g/l, respectively, could be considered reference concentrations for groundwaters in calcareous lithotypes, under undisturbed natural conditions. Finally, a map of vulnerability shows that the areas near the Arno river are highly vulnerable, for the minimum thickness (or lacking) of sediments covering the aquifer. On the other hand, in the case of pollution, several factors not considered could significantly increase the self-purification capacity of the aquifer, such asdilution of groundwaters, bacteria oxidation of nitrogenous species, and sorption capacity of clay minerals and organic matter. 31 refs., 6 figs., 5 tabs.

  3. Induction Linac Pulsers

    SciTech Connect (OSTI)

    Faltens, Andris

    2011-01-07

    The pulsers used in most of the induction linacs evolved from the very large body of work that was done in the U.S. and Great Britain during the development of the pulsed magnetron for radar. The radar modulators started at {approx}100 kW and reached >10 MW by 1945. A typical pulse length was 1 {mu}s at a repetition rate of 1,000 pps. A very comprehensive account of the modulator development is Pulse Generators by Lebacqz and Glasoe, one of the Radiation Laboratory Series. There are many permutations of possible modulators, two of the choices being tube type and line type. In earlier notes I wrote that technically the vacuum tube pulser met all of our induction linac needs, in the sense that a number of tubes, in series and parallel if required, could produce our pulses, regulate their voltage, be useable in feed-forward correctors, and provide a low source impedance. At a lower speed, an FET array is similar, and we have obtained and tested a large array capable of >10 MW switching. A modulator with an electronically controlled output only needs a capacitor for energy storage and in a switched mode can transfer the energy from the capacitor to the load at high efficiency. Driving a full size Astron induction core and a simulated resistive 'beam load' we achieved >50% efficiency. These electronically controlled output pulses can produce the pulses we desire but are not used because of their high cost. The second choice, the line type pulser, visually comprises a closing switch and a distributed or a lumped element transmission line. The typical switch cannot open or stop conducting after the desired pulse has been produced, and consequently all of the initially stored energy is dissipated. This approximately halves the efficiency, and the original cost estimating program LIACEP used this factor of two, even though our circuits are usually worse, and even though our inveterate optimists often omit it. The 'missing' energy is that which is reflected back into the

  4. Differential metabolism of 4-hydroxynonenal in liver, lung and brain of mice and rats

    SciTech Connect (OSTI)

    Zheng, Ruijin; Dragomir, Ana-Cristina; Mishin, Vladimir; Richardson, Jason R.; Heck, Diane E.; Laskin, Debra L.; Laskin, Jeffrey D.

    2014-08-15

    The lipid peroxidation end-product 4-hydroxynonenal (4-HNE) is generated in tissues during oxidative stress. As a reactive aldehyde, it forms Michael adducts with nucleophiles, a process that disrupts cellular functioning. Liver, lung and brain are highly sensitive to xenobiotic-induced oxidative stress and readily generate 4-HNE. In the present studies, we compared 4-HNE metabolism in these tissues, a process that protects against tissue injury. 4-HNE was degraded slowly in total homogenates and S9 fractions of mouse liver, lung and brain. In liver, but not lung or brain, NAD(P)+ and NAD(P)H markedly stimulated 4-HNE metabolism. Similar results were observed in rat S9 fractions from these tissues. In liver, lung and brain S9 fractions, 4-HNE formed protein adducts. When NADH was used to stimulate 4-HNE metabolism, the formation of protein adducts was suppressed in liver, but not lung or brain. In both mouse and rat tissues, 4-HNE was also metabolized by glutathione S-transferases. The greatest activity was noted in livers of mice and in lungs of rats; relatively low glutathione S-transferase activity was detected in brain. In mouse hepatocytes, 4-HNE was rapidly taken up and metabolized. Simultaneously, 4-HNE-protein adducts were formed, suggesting that 4-HNE metabolism in intact cells does not prevent protein modifications. These data demonstrate that, in contrast to liver, lung and brain have a limited capacity to metabolize 4-HNE. The persistence of 4-HNE in these tissues may increase the likelihood of tissue injury during oxidative stress. - Highlights: • Lipid peroxidation generates 4-hydroxynonenal, a highly reactive aldehyde. • Rodent liver, but not lung or brain, is efficient in degrading 4-hydroxynonenal. • 4-hydroxynonenal persists in tissues with low metabolism, causing tissue damage.

  5. Gata4 expression in lateral mesoderm is downstream of BMP4 and isactivated directly by Forkhead and GATA transcription factors through adistal enhancer element

    SciTech Connect (OSTI)

    Rojas, Anabel; De Val, Sarah; Heidt, Analeah B.; Xu, Shan-Mei; Bristow, James; Black, Brian L.

    2005-05-20

    The GATA family of zinc-finger transcription factors plays key roles in the specification and differentiation of multiple cell types during development. GATA4 is an early regulator of gene expression during the development of endoderm and mesoderm, and genetic studies in mice have demonstrated that GATA4 is required for embryonic development.Despite the importance of GATA4 in tissue specification and differentiation, the mechanisms by which Gata4 expression is activated and the transcription factor pathways upstream of GATA4 remain largely undefined. To identify transcriptional regulators of Gata4 in the mouse,we screened conserved noncoding sequences from the mouse Gata4 gene for enhancer activity in transgenic embryos. Here, we define the regulation of a distal enhancer element from Gata4 that is sufficient to direct expression throughout the lateral mesoderm, beginning at 7.5 days of mouse embryonic development. The activity of this enhancer is initially broad but eventually becomes restricted to the mesenchyme surrounding the liver. We demonstrate that the function of this enhancer in transgenic embryos is dependent upon highly conserved Forkhead and GATA transcription factor binding sites, which are bound by FOXF1 and GATA4,respectively. Furthermore, the activity of the Gata4 lateral mesoderm enhancer is attenuated by the BMP antagonist Noggin, and the enhancer is not activated in Bmp4-null embryos. Thus, these studies establish that Gata4 is a direct transcriptional target of Forkhead and GATA transcription factors in the lateral mesoderm, and demonstrate that Gata4lateral mesoderm enhancer activation requires BMP4, supporting a model in which GATA4 serves as a downstream effector of BMP signaling in the lateral mesoderm.

  6. OSHA's approach to risk assessment for setting a revised occupational exposure standard for 1,3-butadiene

    SciTech Connect (OSTI)

    Grossman, E.A.; Martonik, J. )

    1990-06-01

    In its 1980 benzene decision (Industrial Union Department, ALF-CIO v. American Petroleum Institute, 448 U.S. 607 (1980)), the Supreme Court ruled that before he can promulgate any permanent health or safety standard, the Secretary (of Labor) is required to make a threshold finding that a place of employment is unsafe--in the sense that significant risks are present and can be lessened by a change in practices (448 U.S. at 642). The Occupational Safety and Health Administration (OSHA) has interpreted this to mean that whenever possible, it must quantify the risk associated with occupational exposure to a toxic substance at the current permissible exposure limit (PEL). If OSHA determines that there is significant risk to workers' health at its current standard, then it must quantify the risk associated with a variety of alternative standards to determine at what level, if any, occupational exposure to a substance no longer poses a significant risk. For rulemaking on occupational exposure to 1,3-butadiene, there are two studies that are suitable for quantitative risk assessment. One is a mouse inhalation bioassay conducted by the National Toxicology Program (NTP), and the other is a rat inhalation bioassay conducted by Hazelton Laboratories Europe. Of the four risk assessments that have been submitted to OSHA, all four have used the mouse and/or rat data with a variety of models to quantify the risk associated with occupational exposure to 1,3-butadiene. In addition, OSHA has performed its own risk assessment using the female mouse and female rat data and the one-hit and multistage models.

  7. Structure-based discovery of NANOG variant with enhanced properties to promote self-renewal and reprogramming of pluripotent stem cells

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Hayashi, Yohei; Caboni, Laura; Das, Debanu; Yumoto, Fumiaki; Clayton, Thomas; Deller, Marc C.; Nguyen, Phuong; Farr, Carol L.; Chiu, Hsiu -Ju; Miller, Mitchell D.; et al

    2015-03-30

    NANOG (from Irish mythology Tír na nÓg) transcription factor plays a central role in maintaining pluripotency, cooperating with OCT4 (also known as POU5F1 or OCT3/4), SOX2, and other pluripotency factors. Although the physiological roles of the NANOG protein have been extensively explored, biochemical and biophysical properties in relation to its structural analysis are poorly understood. Here we determined the crystal structure of the human NANOG homeodomain (hNANOG HD) bound to an OCT4 promoter DNA, which revealed amino acid residues involved in DNA recognition that are likely to be functionally important. We generated a series of hNANOG HD alanine substitution mutantsmore » based on the protein–DNA interaction and evolutionary conservation and determined their biological activities. Some mutant proteins were less stable, resulting in loss or decreased affinity for DNA binding. Overexpression of the orthologous mouse NANOG (mNANOG) mutants failed to maintain self-renewal of mouse embryonic stem cells without leukemia inhibitory factor. These results suggest that these residues are critical for NANOG transcriptional activity. Interestingly, one mutant, hNANOG L122A, conversely enhanced protein stability and DNA-binding affinity. The mNANOG L122A, when overexpressed in mouse embryonic stem cells, maintained their expression of self-renewal markers even when retinoic acid was added to forcibly drive differentiation. When overexpressed in epiblast stem cells or human induced pluripotent stem cells, the L122A mutants enhanced reprogramming into ground-state pluripotency. These findings indicate that structural and biophysical information on key transcriptional factors provides insights into the manipulation of stem cell behaviors and a framework for rational protein engineering.« less

  8. Structure-based discovery of NANOG variant with enhanced properties to promote self-renewal and reprogramming of pluripotent stem cells

    SciTech Connect (OSTI)

    Hayashi, Yohei; Caboni, Laura; Das, Debanu; Yumoto, Fumiaki; Clayton, Thomas; Deller, Marc C.; Nguyen, Phuong; Farr, Carol L.; Chiu, Hsiu -Ju; Miller, Mitchell D.; Elsliger, Marc -André; Deacon, Ashley M.; Godzik, Adam; Lesley, Scott A.; Tomoda, Kiichiro; Conklin, Bruce R.; Wilson, Ian A.; Yamanaka, Shinya; Fletterick, Robert J.

    2015-03-30

    NANOG (from Irish mythology Tír na nÓg) transcription factor plays a central role in maintaining pluripotency, cooperating with OCT4 (also known as POU5F1 or OCT3/4), SOX2, and other pluripotency factors. Although the physiological roles of the NANOG protein have been extensively explored, biochemical and biophysical properties in relation to its structural analysis are poorly understood. Here we determined the crystal structure of the human NANOG homeodomain (hNANOG HD) bound to an OCT4 promoter DNA, which revealed amino acid residues involved in DNA recognition that are likely to be functionally important. We generated a series of hNANOG HD alanine substitution mutants based on the protein–DNA interaction and evolutionary conservation and determined their biological activities. Some mutant proteins were less stable, resulting in loss or decreased affinity for DNA binding. Overexpression of the orthologous mouse NANOG (mNANOG) mutants failed to maintain self-renewal of mouse embryonic stem cells without leukemia inhibitory factor. These results suggest that these residues are critical for NANOG transcriptional activity. Interestingly, one mutant, hNANOG L122A, conversely enhanced protein stability and DNA-binding affinity. The mNANOG L122A, when overexpressed in mouse embryonic stem cells, maintained their expression of self-renewal markers even when retinoic acid was added to forcibly drive differentiation. When overexpressed in epiblast stem cells or human induced pluripotent stem cells, the L122A mutants enhanced reprogramming into ground-state pluripotency. These findings indicate that structural and biophysical information on key transcriptional factors provides insights into the manipulation of stem cell behaviors and a framework for rational protein engineering.

  9. Analysis of lung tumor initiation and progression in transgenic mice for Cre-inducible overexpression of Cul4A gene

    SciTech Connect (OSTI)

    Wang, Yang; Xu, Zhidong; Mao, Jian -Hua; Hung, Ming -Szu; Hsieh, David; Au, Alfred; Jablons, David M.; You, Liang

    2015-06-08

    Background: Lung cancer is the leading cause of morbidity and death worldwide. Although the available lung cancer animal models have been informative and further propel our understanding of human lung cancer, they still do not fully recapitulate the complexities of human lung cancer. The pathogenesis of lung cancer remains highly elusive because of its aggressive biologic nature and considerable heterogeneity, compared to other cancers. The association of Cul4A amplification with aggressive tumor growth and poor prognosis has been suggested. Our previous study suggested that Cul4A is oncogenic in vitro, but its oncogenic role in vivo has not been studied. Methods: Viral delivery approaches have been used extensively to model cancer in mouse models. In our experiments, we used Cre-recombinase induced overexpression of the Cul4A gene in transgenic mice to study the role of Cul4A on lung tumor initiation and progression and have developed a new model of lung tumor development in mice harboring a conditionally expressed allele of Cul4A. Results: Here we show that the use of a recombinant adenovirus expressing Cre-recombinase (“AdenoCre”) to induce Cul4A overexpression in the lungs of mice allows controls of the timing and multiplicity of tumor initiation. Following our mouse models, we are able to study the potential role of Cul4A in the development and progression in pulmonary adenocarcinoma as well. Conclusion: Our findings indicate that Cul4A is oncogenic in vivo, and this mouse model is a tool in understanding the mechanisms of Cul4A in human cancers and for testing experimental therapies targeting Cul4A.

  10. A preliminary regional PBPK model of lung metabolism for improving species dependent descriptions of 1,3-butadiene and its metabolites

    SciTech Connect (OSTI)

    Campbell, Jerry; Van Landingham, Cynthia; Crowell, Susan; Gentry, Robinan; Kaden, Debra; Fiebelkorn, Stacy; Loccisano, Anne; Clewell, Harvey

    2015-06-12

    1,3-Butadiene (BD), a volatile organic chemical (VOC), is used in synthetic rubber production and other industrial processes. It is detectable at low levels in ambient air as well as in tobacco smoke and gasoline vapors. Inhalation exposures to high concentrations of BD have been associated with lung cancer in both humans and experimental animals, although differences in species sensitivity have been observed. Metabolically active lung cells such as Pulmonary Type I and Type II epithelial cells and club cells (Clara cells)1 are potential targets of BD metabolite-induced toxicity. Metabolic capacities of these cells, their regional densities, and distributions vary throughout the respiratory tract as well as between species and cell types. Here we present a physiologically based pharmacokinetic (PBPK) model for BD that includes a regional model of lung metabolism, based on a previous model for styrene, to provide species-dependent descriptions of BD metabolism in the mouse, rat, and human. Since there are no in vivo data on BD pharmacokinetics in the human, the rat and mouse models were parameterized to the extent possible on the basis of in vitro metabolic data. Where it was necessary to use in vivo data, extrapolation from rat to mouse was performed to evaluate the level of uncertainty in the human model. A kidney compartment and description of downstream metabolism were also included in the model to allow for eventual use of available urinary and blood biomarker data in animals and humans to calibrate the model for estimation of BD exposures and internal metabolite levels. Results from simulated inhalation exposures to BD indicate that incorporation of differential lung region metabolism is important in describing species differences in pulmonary response and that these differences may have implications for risk assessments of human exposures to BD.

  11. A new anti-tumor strategy based on in vivo tumstatin overexpression after plasmid electrotransfer in muscle

    SciTech Connect (OSTI)

    Thevenard, Jessica; Mir, Lluis M.; Dupont-Deshorgue, Aurélie; Monboisse, Jean-Claude; Brassart-Pasco, Sylvie

    2013-03-22

    Highlights: ► A new therapeutic strategy based on tumstatin in vivo overexpression is proposed. ► pVAX1©–tumstatin electrotransfer in muscle mediates protein expression in muscle. ► A substantial expression of tumstatin is detected in the serum of electrotransfected mice. ► Tumstatin overexpression decreases tumor growth and increases mouse survival. -- Abstract: The NC1 domains from the different α(IV) collagen chains were found to exert anti-tumorigenic and/or anti-angiogenic activities. A limitation to the therapeutic use of these matrikines is the large amount of purified recombinant proteins, in the milligram range in mice that should be administered daily throughout the experimental procedures. In the current study, we developed a new therapeutic approach based on tumstatin (NC1α3(IV)) overexpression in vivo in a mouse melanoma model. Gene electrotransfer of naked plasmid DNA (pDNA) is particularly attractive because of its simplicity, its lack of immune responsiveness and its safety. The pDNA electrotransfer in muscle mediates a substantial gene expression that lasts several months. A pVAX1© vector containing the tumstatin cDNA was injected into the legs of C57BL/6 mice and submitted to electrotranfer. Sera were collected at different times and tumstatin was quantified by ELISA. Tumstatin secretion reached a plateau at day 21 with an expression level of 12 μg/mL. For testing the effects of tumstatin expression on tumor growth in vivo, B16F1 melanoma cells were subcutaneously injected in mice 7 days after empty pVAX1© (Mock) or pVAX1©–tumstatin electrotransfer. Tumstatin expression triggered a large decrease in tumor growth and an increase in mouse survival. This new therapeutic approach seems promising to inhibit tumor progression in vivo.

  12. Mechanisms of G1 cell cycle arrest and apoptosis in myeloma cells induced by hybrid-compound histone deacetylase inhibitor

    SciTech Connect (OSTI)

    Fujii, Seiko; Division of Maxillofacial Surgery, Kyushu Dental University ; Okinaga, Toshinori; Ariyoshi, Wataru; Oral Biology Research Center, Kyushu Dental University ; Takahashi, Osamu; Iwanaga, Kenjiro; Nishino, Norikazu; Tominaga, Kazuhiro; Nishihara, Tatsuji; Oral Biology Research Center, Kyushu Dental University

    2013-05-10

    Highlights: •Novel histone deacetylase inhibitor Ky-2, remarkably inhibits myeloma cell growth. •Ky-2 demonstrates no cytotoxicity against normal lymphocytic cells. •Ky-2 induces cell cycle arrest through the cell cycle-associated proteins. •Ky-2 induces Bcl-2-inhibitable apoptosis through a caspase-dependent cascade. -- Abstract: Objectives: Histone deacetylase (HDAC) inhibitors are new therapeutic agents, used to treat various types of malignant cancers. In the present study, we investigated the effects of Ky-2, a hybrid-compound HDAC inhibitor, on the growth of mouse myeloma cells. Materials and methods: Myeloma cells, HS-72, P3U1, and mouse normal cells were used in this study. Effect of HDAC inhibitors on cell viability was determined by WST-assay and trypan blue assay. Cell cycle was analyzed using flow cytometer. The expression of cell cycle regulatory and the apoptosis associated proteins were examined by Western blot analysis. Hoechst’s staining was used to detect apoptotic cells. Results: Our findings showed that Ky-2 decreased the levels of HDACs, while it enhanced acetylation of histone H3. Myeloma cell proliferation was inhibited by Ky-2 treatment. Interestingly, Ky-2 had no cytotoxic effects on mouse normal cells. Ky-2 treatment induced G1-phase cell cycle arrest and accumulation of a sub-G1 phase population, while Western blotting analysis revealed that expressions of the cell cycle-associated proteins were up-regulated. Also, Ky-2 enhanced the cleavage of caspase-9 and -3 in myeloma cells, followed by DNA fragmentation. In addition, Ky-2 was not found to induce apoptosis in bcl-2 overexpressing myeloma cells. Conclusion: These findings suggest that Ky-2 induces apoptosis via a caspase-dependent cascade and Bcl-2-inhibitable mechanism in myeloma cells.

  13. The PDZ-binding motif of Yes-associated protein is required for its co-activation of TEAD-mediated CTGF transcription and oncogenic cell transforming activity

    SciTech Connect (OSTI)

    Shimomura, Tadanori; Miyamura, Norio; Hata, Shoji; Miura, Ryota; Hirayama, Jun Nishina, Hiroshi

    2014-01-17

    Highlights: Loss of the PDZ-binding motif inhibits constitutively active YAP (5SA)-induced oncogenic cell transformation. The PDZ-binding motif of YAP promotes its nuclear localization in cultured cells and mouse liver. Loss of the PDZ-binding motif inhibits YAP (5SA)-induced CTGF transcription in cultured cells and mouse liver. -- Abstract: YAP is a transcriptional co-activator that acts downstream of the Hippo signaling pathway and regulates multiple cellular processes, including proliferation. Hippo pathway-dependent phosphorylation of YAP negatively regulates its function. Conversely, attenuation of Hippo-mediated phosphorylation of YAP increases its ability to stimulate proliferation and eventually induces oncogenic transformation. The C-terminus of YAP contains a highly conserved PDZ-binding motif that regulates YAPs functions in multiple ways. However, to date, the importance of the PDZ-binding motif to the oncogenic cell transforming activity of YAP has not been determined. In this study, we disrupted the PDZ-binding motif in the YAP (5SA) protein, in which the sites normally targeted by Hippo pathway-dependent phosphorylation are mutated. We found that loss of the PDZ-binding motif significantly inhibited the oncogenic transformation of cultured cells induced by YAP (5SA). In addition, the increased nuclear localization of YAP (5SA) and its enhanced activation of TEAD-dependent transcription of the cell proliferation gene CTGF were strongly reduced when the PDZ-binding motif was deleted. Similarly, in mouse liver, deletion of the PDZ-binding motif suppressed nuclear localization of YAP (5SA) and YAP (5SA)-induced CTGF expression. Taken together, our results indicate that the PDZ-binding motif of YAP is critical for YAP-mediated oncogenesis, and that this effect is mediated by YAPs co-activation of TEAD-mediated CTGF transcription.

  14. Implausibility of the vibrational theory of olfaction

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Block, Eric; Ertem, Mehmed Z.; Jang, Seogjoo; Matsunami, Hiroaki; Sekharan, Sivakumar; Dethier, Berenice; Gundala, Sivaji; Pan, Yi; Li, Shengju; Li, Zhen; et al

    2015-04-21

    The vibrational theory of olfaction assumes that electron transfer occurs across odorants at the active sites of odorant receptors (ORs), serving as a sensitive measure of odorant vibrational frequencies, ultimately leading to olfactory perception. A previous study reported that human subjects differentiated hydrogen/deuterium isotopomers (isomers with isotopic atoms) of the musk compound cyclopentadecanone as evidence supporting the theory. Here, we find no evidence for such differentiation at the molecular level. In fact, we find that the human musk-recognizing receptor, OR5AN1, identified using a heterologous OR expression system and robustly responding to cyclopentadecanone and muscone, fails to distinguish isotopomers of thesemore » compounds in vitro. Furthermore, the mouse (methylthio)methanethiol (MTMT)-recognizing receptor, MOR244-3, and other selected human and mouse ORs, responded similarly to normal, deuterated, and ¹³C isotopomers of their respective ligands, paralleling our results with the musk receptor OR5AN1. These findings suggest that the proposed vibration theory does not apply to the human musk receptor OR5AN1, mouse thiol receptor MOR244-3, or other ORs examined. Also, contrary to the vibration theory predictions, muscone-d₃₀ lacks the 1,380-1,550 cm⁻¹ IR bands claimed to be essential for musk odor. Furthermore, our theoretical analysis shows that the proposed electron transfer mechanism of the vibrational frequencies of odorants could be easily suppressed by quantum effects of non-odorant molecular vibrational modes. As a result, these and other concerns about electron transfer at ORs, together with our extensive experimental data, argue against the plausibility of the vibration theory.« less

  15. Implausibility of the vibrational theory of olfaction

    SciTech Connect (OSTI)

    Block, Eric; Ertem, Mehmed Z.; Jang, Seogjoo; Matsunami, Hiroaki; Sekharan, Sivakumar; Dethier, Berenice; Gundala, Sivaji; Pan, Yi; Li, Shengju; Li, Zhen; Lodge, Stephene N.; Ozbil, Mehmet; Jiang, Huihong; Penalba, Sonia Flores; Batista, Victor S.; Zhuang, Hanyi

    2015-04-21

    The vibrational theory of olfaction assumes that electron transfer occurs across odorants at the active sites of odorant receptors (ORs), serving as a sensitive measure of odorant vibrational frequencies, ultimately leading to olfactory perception. A previous study reported that human subjects differentiated hydrogen/deuterium isotopomers (isomers with isotopic atoms) of the musk compound cyclopentadecanone as evidence supporting the theory. Here, we find no evidence for such differentiation at the molecular level. In fact, we find that the human musk-recognizing receptor, OR5AN1, identified using a heterologous OR expression system and robustly responding to cyclopentadecanone and muscone, fails to distinguish isotopomers of these compounds in vitro. Furthermore, the mouse (methylthio)methanethiol (MTMT)-recognizing receptor, MOR244-3, and other selected human and mouse ORs, responded similarly to normal, deuterated, and ¹³C isotopomers of their respective ligands, paralleling our results with the musk receptor OR5AN1. These findings suggest that the proposed vibration theory does not apply to the human musk receptor OR5AN1, mouse thiol receptor MOR244-3, or other ORs examined. Also, contrary to the vibration theory predictions, muscone-d₃₀ lacks the 1,380-1,550 cm⁻¹ IR bands claimed to be essential for musk odor. Furthermore, our theoretical analysis shows that the proposed electron transfer mechanism of the vibrational frequencies of odorants could be easily suppressed by quantum effects of non-odorant molecular vibrational modes. As a result, these and other concerns about electron transfer at ORs, together with our extensive experimental data, argue against the plausibility of the vibration theory.

  16. Analysis of lung tumor initiation and progression in transgenic mice for Cre-inducible overexpression of Cul4A gene

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Wang, Yang; Xu, Zhidong; Mao, Jian -Hua; Hung, Ming -Szu; Hsieh, David; Au, Alfred; Jablons, David M.; You, Liang

    2015-06-08

    Background: Lung cancer is the leading cause of morbidity and death worldwide. Although the available lung cancer animal models have been informative and further propel our understanding of human lung cancer, they still do not fully recapitulate the complexities of human lung cancer. The pathogenesis of lung cancer remains highly elusive because of its aggressive biologic nature and considerable heterogeneity, compared to other cancers. The association of Cul4A amplification with aggressive tumor growth and poor prognosis has been suggested. Our previous study suggested that Cul4A is oncogenic in vitro, but its oncogenic role in vivo has not been studied. Methods:more » Viral delivery approaches have been used extensively to model cancer in mouse models. In our experiments, we used Cre-recombinase induced overexpression of the Cul4A gene in transgenic mice to study the role of Cul4A on lung tumor initiation and progression and have developed a new model of lung tumor development in mice harboring a conditionally expressed allele of Cul4A. Results: Here we show that the use of a recombinant adenovirus expressing Cre-recombinase (“AdenoCre”) to induce Cul4A overexpression in the lungs of mice allows controls of the timing and multiplicity of tumor initiation. Following our mouse models, we are able to study the potential role of Cul4A in the development and progression in pulmonary adenocarcinoma as well. Conclusion: Our findings indicate that Cul4A is oncogenic in vivo, and this mouse model is a tool in understanding the mechanisms of Cul4A in human cancers and for testing experimental therapies targeting Cul4A.« less

  17. A preliminary regional PBPK model of lung metabolism for improving species dependent descriptions of 1,3-butadiene and its metabolites

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Campbell, Jerry; Van Landingham, Cynthia; Crowell, Susan; Gentry, Robinan; Kaden, Debra; Fiebelkorn, Stacy; Loccisano, Anne; Clewell, Harvey

    2015-06-12

    1,3-Butadiene (BD), a volatile organic chemical (VOC), is used in synthetic rubber production and other industrial processes. It is detectable at low levels in ambient air as well as in tobacco smoke and gasoline vapors. Inhalation exposures to high concentrations of BD have been associated with lung cancer in both humans and experimental animals, although differences in species sensitivity have been observed. Metabolically active lung cells such as Pulmonary Type I and Type II epithelial cells and club cells (Clara cells)1 are potential targets of BD metabolite-induced toxicity. Metabolic capacities of these cells, their regional densities, and distributions vary throughoutmore » the respiratory tract as well as between species and cell types. Here we present a physiologically based pharmacokinetic (PBPK) model for BD that includes a regional model of lung metabolism, based on a previous model for styrene, to provide species-dependent descriptions of BD metabolism in the mouse, rat, and human. Since there are no in vivo data on BD pharmacokinetics in the human, the rat and mouse models were parameterized to the extent possible on the basis of in vitro metabolic data. Where it was necessary to use in vivo data, extrapolation from rat to mouse was performed to evaluate the level of uncertainty in the human model. A kidney compartment and description of downstream metabolism were also included in the model to allow for eventual use of available urinary and blood biomarker data in animals and humans to calibrate the model for estimation of BD exposures and internal metabolite levels. Results from simulated inhalation exposures to BD indicate that incorporation of differential lung region metabolism is important in describing species differences in pulmonary response and that these differences may have implications for risk assessments of human exposures to BD.« less

  18. News Archive | Princeton Plasma Physics Lab

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    September 30, 2011 Bottling Magnetic Reconnection: PPPL Scientists bring mysterious process down to earth By John Greenwald With the click of a computer mouse, a scientist at the U.S. Department of Energy's Princeton Plasma Physics Laboratory (PPPL) sends 10,000 volts of electricity into a chamber filled with hydrogen gas. The charge heats the gas to 100,000 degrees Centigrade. Read more... September 13, 2011 Lee Honored for Work in Plasma Simulations By Patti Wieser Wei-li Lee Wei-li Lee, a

  19. Alterations of urinary metabolite profile in model diabetic nephropathy

    SciTech Connect (OSTI)

    Stec, Donald F.; Wang, Suwan; Stothers, Cody; Avance, Josh; Denson, Deon; Harris, Raymond; Voziyan, Paul

    2015-01-09

    Highlights: • {sup 1}H NMR spectroscopy was employed to study urinary metabolite profile in diabetic mouse models. • Mouse urinary metabolome showed major changes that are also found in human diabetic nephropathy. • These models can be new tools to study urinary biomarkers that are relevant to human disease. - Abstract: Countering the diabetes pandemic and consequent complications, such as nephropathy, will require better understanding of disease mechanisms and development of new diagnostic methods. Animal models can be versatile tools in studies of diabetic renal disease when model pathology is relevant to human diabetic nephropathy (DN). Diabetic models using endothelial nitric oxide synthase (eNOS) knock-out mice develop major renal lesions characteristic of human disease. However, it is unknown whether they can also reproduce changes in urinary metabolites found in human DN. We employed Type 1 and Type 2 diabetic mouse models of DN, i.e. STZ-eNOS{sup −/−} C57BLKS and eNOS{sup −/−} C57BLKS db/db, with the goal of determining changes in urinary metabolite profile using proton nuclear magnetic resonance (NMR). Six urinary metabolites with significantly lower levels in diabetic compared to control mice have been identified. Specifically, major changes were found in metabolites from tricarboxylic acid (TCA) cycle and aromatic amino acid catabolism including 3-indoxyl sulfate, cis-aconitate, 2-oxoisocaproate, N-phenyl-acetylglycine, 4-hydroxyphenyl acetate, and hippurate. Levels of 4-hydroxyphenyl acetic acid and hippuric acid showed the strongest reverse correlation to albumin-to-creatinine ratio (ACR), which is an indicator of renal damage. Importantly, similar changes in urinary hydroxyphenyl acetate and hippurate were previously reported in human renal disease. We demonstrated that STZ-eNOS{sup −/−} C57BLKS and eNOS{sup −/−} C57BLKS db/db mouse models can recapitulate changes in urinary metabolome found in human DN and therefore can be

  20. High Frequency Active Auroral Research Program (HAARP) imager. Final report, 29 August 1991-29 August 1993

    SciTech Connect (OSTI)

    Lance, C.; Eather, R.

    1993-09-30

    A low-light-level monochromatic imaging system was designed and fabricated which was optimized to detect and record optical emissions associated with high-power rf heating of the ionosphere. The instrument is capable of detecting very low intensities, of the order of 1 Rayleigh, from typical ionospheric atomic and molecular emissions. This is achieved through co-adding of ON images during heater pulses and subtraction of OFF (background) images between pulses. Images can be displayed and analyzed in real time and stored in optical disc for later analysis. Full image processing software is provided which was customized for this application and uses menu or mouse user interaction.

  1. Creating a Tiny Human Body on a Chip

    ScienceCinema (OSTI)

    Hunsberger, Maren; Soscia, Dave; Moya, Monica

    2016-03-16

    LLNL science communicator Maren Hunsberger takes us "Inside the Lab" to learn about the iChip (In-vitro Chip-based Human Investigational Platform) project at Lawrence Livermore National Laboratory. "One application of the iChip system would be to develop new pharmaceutical drugs," explains Dave Soscia, LLNL postdoc. "When you test in a mouse for example, it's not as close to the human system as you can get. If we can take human cells and put them on devices and actually mimic the structure and function of the organ systems in the human, we can actually replace animal testing and even make a better system for testing pharmaceutical drugs."

  2. PPPL Scientists bring mysterious process down to earth | Princeton Plasma

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Physics Lab Bottling Magnetic Reconnection: PPPL Scientists bring mysterious process down to earth By John Greenwald September 30, 2011 Tweet Widget Google Plus One Share on Facebook With the click of a computer mouse, a scientist at the U.S. Department of Energy's Princeton Plasma Physics Laboratory (PPPL) sends 10,000 volts of electricity into a chamber filled with hydrogen gas. The charge heats the gas to 100,000 degrees Centigrade. In an instant -- one-thousandth of a second, to be

  3. OpenMSI: A Science Gateway to Sort Through Bio-Imaging's Big Datasets

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    OpenMSI: A Science Gateway to Sort Through Bio-Imaging's Big Datasets OpenMSI: A Science Gateway to Sort Through Bio-Imaging's Big Datasets August 27, 2013 Contact: Linda Vu, +1 510 495 2402, lvu@lbl.gov OpenMSINERSC.jpg This overlay of mass spectrometry images shows the spatial distribution of three different kind of lipids across a whole mouse cross-section. Lipids act as the structural components of cell membranes and are responsible for energy storage, among other things. Image credit:

  4. Ensemble Data Analysis ENvironment (EDEN)

    SciTech Connect (OSTI)

    Steed, Chad Allen

    2012-08-01

    The EDEN toolkit facilitates exploratory data analysis and visualization of global climate model simulation datasets. EDEN provides an interactive graphical user interface (GUI) that helps the user visually construct dynamic queries of the characteristically large climate datasets using temporal ranges, variable selections, and geographic areas of interest. EDEN reads the selected data into a multivariate visualization panel which features an extended implementation of parallel coordinates plots as well as interactive scatterplots. The user can query data in the visualization panel using mouse gestures to analyze different ranges of data. The visualization panel provides coordinated multiple views whereby selections made in one plot are propagated to the other plots.

  5. Development of BAC libraries and integrated physical mapping of human chromosome 22 using BACs. Annual report, July 1994--June 1995

    SciTech Connect (OSTI)

    Kim, U.J.; Shizuya, Hiroaki; Simon, M.I.

    1995-12-31

    BACs and fosmids are stable, nonchimeric, and highly representative cloning systems. BACs maintain large-fragment genomic inserts (100 to 300 kb) that are easily prepared for most types of experiments, including DNA sequencing. The authors have improved the methods for generating BACs and developed extensive BAC libraries. They have constructed human BAC libraries with more than 175,000 clones from male fibroblast and sperm, and a mouse BAC library with more than 200,000 clones. The authors are currently expanding human library with the aim of achieving total 50X coverage human genomic library using sperm samples from anonymous donors.

  6. 3D Charge Order Found in Superconductor

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    360° Inside a Wind Tunnel 360° Inside a Wind Tunnel Addthis Experience what it's like inside a wind tunnel with with this video! (make sure to use your mouse or move your mobile phone around to get the full effect). Learn more about the U.S. Department of Energy Collegiate Wind Competition

    :2:1 Crack Spread Figure 1 Source: U.S. Energy Information Administration, based on Thomson Reuters. A crack spread measures the difference between the purchase price of crude oil and the selling price of

  7. Gateways to the FANTOM5 promoter level mammalian expression atlas

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Lizio, Marina; Harshbarger, Jayson; Shimoji, Hisashi; Severin, Jessica; Kasukawa, Takeya; Sahin, Serkan; Abugessaisa, Imad; Fukuda, Shiro; Hori, Fumi; Ishikawa-Kato, Sachi; et al

    2015-01-05

    The FANTOM5 project investigates transcription initiation activities in more than 1,000 human and mouse primary cells, cell lines and tissues using CAGE. Based on manual curation of sample information and development of an ontology for sample classification, we assemble the resulting data into a centralized data resource (http://fantom.gsc.riken.jp/5/). In conclusion, this resource contains web-based tools and data-access points for the research community to search and extract data related to samples, genes, promoter activities, transcription factors and enhancers across the FANTOM5 atlas.

  8. Extraction and analysis of neuron firing signals from deep cortical video microscopy

    SciTech Connect (OSTI)

    Kerekes, Ryan A; Blundon, Jay

    2014-01-01

    We introduce a method for extracting and analyzing neuronal activity time signals from video of the cortex of a live animal. The signals correspond to the firing activity of individual cortical neurons. Activity signals are based on the changing fluorescence of calcium indicators in the cells over time. We propose a cell segmentation method that relies on a user-specified center point, from which the signal extraction method proceeds. A stabilization approach is used to reduce tissue motion in the video. The extracted signal is then processed to flatten the baseline and detect action potentials. We show results from applying the method to a cortical video of a live mouse.

  9. CHPRC1104-16_Rev06A

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Deep Vadose Zone Deep Vadose Zone Deep Vadose Zone Addressing contamination deep in the vadose zone Enter Please use your mouse to navigate CHPRC1104-16_Rev05_5-18-11 Contents • Where is the Hanford deep vadose zone? • What is the vadose zone? • How was it contaminated? • What are the risks? • Why is it so tough to clean up? • What is being done? • What’s next? • For more information Exit Contents Home Deep Vadose Zone Where is the Hanford deep vadose zone? At the Hanford Site in

  10. 2005 - 04 | Jefferson Lab

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    4 Apr 2005 Mon, 2005-04-25 14:00 Jefferson Lab's Detector Group builds small-animal imaging device for the German Cancer Research Center Wed, 2005-04-20 14:00 JLab, College of W&amp;M researchers study radiation blockers while conducting nuclear imaging of Iodine uptake in mouse tissues Wed, 2005-04-20 14:00 HAPPEx Results Hint at Strangely Magnetic Proton Wed, 2005-04-20 14:00 Is It or Isn't It? Pentaquark Debate Heats Up Mon, 2005-04-11 14:00 JLab, Hampton U. celebrate Einstein's love of

  11. Field Deployable Tritium Assay System Host Graphical User Interface Software

    Energy Science and Technology Software Center (OSTI)

    1998-05-12

    The FDTASHOST software is a Graphical User Interface for the Field Deployable Tritium Assay System (FDTAS - Invention Disclosure SRS-96-09-091 has been submitted). The program runs on the Host computer which is located in the Laboratory and connected to the FDTAS remote field system via a modem over a phone line. The operator receives status information and messages from the Remote system. The operator can enter in commands to be executed by the remote systemmore » using the mouse and a pull down menu.« less

  12. 2001 | Jefferson Lab

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Dec 2001 Tue, 2001-12-18 00:00 Husband, Wife Receive Ph.Ds in Physics From ODU (The Virginian-Pilot) Nov 2001 Sat, 2001-11-17 00:00 Jefferson Lab Gets New Chief: Leemann takes top post (Times-Dispatch) Sat, 2001-11-17 00:00 Leemann Officially Takes Over Peninsula's Jefferson Lab (The Virginian-Pilot) Mon, 2001-11-05 00:00 Lab is Working to Build a Better Mouse Camera (Daily Press) Oct 2001 Tue, 2001-10-30 00:00 NN Germ-Killing Research May Soon Target Anthrax: (Daily Press) Fri, 2001-10-26

  13. 2005 - 04 | Jefferson Lab

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    4 Apr 2005 Fri, 2005-04-22 00:00 Latest Data Deal 'Pentaquark' Sightings a Fresh Blow (Science Magazine) Thu, 2005-04-21 00:00 Nuclear imaging of iodine uptake in mouse tissues (Medical News Today) Wed, 2005-04-20 00:00 Pentaquark hunt draws a blank (NewScientist.com) Wed, 2005-04-20 00:00 Boffins five quarks short of a sub-atomic particle (The Register) Tue, 2005-04-19 00:00 Einstein and the violin (Symmetry) Tue, 2005-04-19 00:00 Deconstruction: Control Room (Symmetry) Mon, 2005-04-18 00:00

  14. GenoGraphics for OpenWindows trademark

    SciTech Connect (OSTI)

    Hagstrom, R.; Overbeek, R.; Price, M.; Zawada, D. ); Michaels, G.S.; Taylor, R. . Div. of Computer Research and Technology); Yoshida, Kaoru )

    1992-04-01

    GenoGraphics is a generic utility for constructing and querying one-dimensional linear plots. The outgrowth of a request from Dr. Cassandra Smith for a tool to facilitate her genome mapping research. GenoGraphics development has benefited from a continued collaboration with her. Written in Sun Microsystem's OpenWindows environment and the BTOL toolkit developed at Argonne National Laboratory. GenoGraphics provides an interactive, intuitive, graphical interface. Its features include: viewing multiple maps simultaneously, zooming, and querying by mouse clicking. By expediting plot generation, GenoGraphics gives the scientist more time to analyze data and a novel means for deducing conclusions.

  15. GenoGraphics for OpenWindows{trademark}

    SciTech Connect (OSTI)

    Hagstrom, R.; Overbeek, R.; Price, M.; Zawada, D.; Michaels, G.S.; Taylor, R.; Yoshida, Kaoru

    1992-04-01

    GenoGraphics is a generic utility for constructing and querying one-dimensional linear plots. The outgrowth of a request from Dr. Cassandra Smith for a tool to facilitate her genome mapping research. GenoGraphics development has benefited from a continued collaboration with her. Written in Sun Microsystem`s OpenWindows environment and the BTOL toolkit developed at Argonne National Laboratory. GenoGraphics provides an interactive, intuitive, graphical interface. Its features include: viewing multiple maps simultaneously, zooming, and querying by mouse clicking. By expediting plot generation, GenoGraphics gives the scientist more time to analyze data and a novel means for deducing conclusions.

  16. Clock-controlled output gene Dbp is a regulator of Arnt/Hif-1β gene expression in pancreatic islet β-cells

    SciTech Connect (OSTI)

    Nakabayashi, Hiroko; Ohta, Yasuharu Yamamoto, Masayoshi; Susuki, Yosuke; Taguchi, Akihiko; Tanabe, Katsuya; Kondo, Manabu; Hatanaka, Masayuki; Nagao, Yuko; Tanizawa, Yukio

    2013-05-03

    Highlights: •Arnt mRNA expressed in a circadian manner in mouse pancreatic islets. •Expressions of Dbp and Arnt damped in the islets of a diabetic model mouse. •DBP and E4BP4 regulate Arnt promoter activity by direct binding. •Arnt may have a role in connecting circadian rhythm and metabolism. -- Abstract: Aryl hydrocarbon receptor nuclear translocator (ARNT)/hypoxia inducible factor-1β (HIF-1β) has emerged as a potential determinant of pancreatic β-cell dysfunction and type 2 diabetes in humans. An 82% reduction in Arnt expression was observed in islets from type 2 diabetic donors as compared to non-diabetic donors. However, few regulators of Arnt expression have been identified. Meanwhile, disruption of the clock components CLOCK and BMAL1 is known to result in hypoinsulinemia and diabetes, but the molecular details remain unclear. In this study, we identified a novel molecular connection between Arnt and two clock-controlled output genes, albumin D-element binding protein (Dbp) and E4 binding protein 4 (E4bp4). By conducting gene expression studies using the islets of Wfs1{sup −/−} A{sup y}/a mice that develop severe diabetes due to β-cell apoptosis, we demonstrated clock-related gene expressions to be altered in the diabetic mice. Dbp mRNA decreased by 50%, E4bp4 mRNA increased by 50%, and Arnt mRNA decreased by 30% at Zeitgever Time (ZT) 12. Mouse pancreatic islets exhibited oscillations of clock gene expressions. E4BP4, a D-box negative regulator, oscillated anti-phase to DBP, a D-box positive regulator. We also found low-amplitude circadian expression of Arnt mRNA, which peaked at ZT4. Over-expression of DBP raised both mRNA and protein levels of ARNT in HEK293 and MIN6 cell lines. Arnt promoter-driven luciferase reporter assay in MIN6 cells revealed that DBP increased Arnt promoter activity by 2.5-fold and that E4BP4 competitively inhibited its activation. In addition, on ChIP assay, DBP and E4BP4 directly bound to D-box elements within the

  17. ECRbase: Database of Evolutionary Conserved Regions, Promoters, and Transcription Factor Binding Sites in Vertebrate Genomes

    DOE Data Explorer [Office of Scientific and Technical Information (OSTI)]

    Loots, Gabriela G. [LLNL; Ovcharenko, I. [LLNL

    Evolutionary conservation of DNA sequences provides a tool for the identification of functional elements in genomes. This database of evolutionary conserved regions (ECRs) in vertebrate genomes features a database of syntenic blocks that recapitulate the evolution of rearrangements in vertebrates and a comprehensive collection of promoters in all vertebrate genomes generated using multiple sources of gene annotation. The database also contains a collection of annotated transcription factor binding sites (TFBSs) in evolutionary conserved and promoter elements. ECRbase currently includes human, rhesus macaque, dog, opossum, rat, mouse, chicken, frog, zebrafish, and fugu genomes. (taken from paper in Journal: Bioinformatics, November 7, 2006, pp. 122-124

  18. The influence of TRP53 in the dose response of radiation-induced apoptosis, DNA repair and genomic stability in murine haematopoietic cells

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Lemon, Jennifer A.; Taylor, Kristina; Verdecchia, Kyle; Phan, Nghi; Boreham, Douglas R.

    2014-01-01

    Apoptotic and DNA damage endpoints are frequently used as surrogate markers of cancer risk, and have been well-studied in the Trp53+/- mouse model. We report the effect of differing Trp53 gene status on the dose response of ionizing radiation exposures (0.01-2 Gy), with the unique perspective of determining if effects of gene status remain at extended time points. Here we report no difference in the dose response for radiation-induced DNA double-strand breaks in bone marrow and genomic instability (MN-RET levels) in peripheral blood, between wild-type (Trp53+/+) and heterozygous (Trp53+/-) mice. The dose response for Trp53+/+ mice showed higher initial levelsmore » of radiation-induced lymphocyte apoptosis relative to Trp53+/- between 0 and 1 Gy. Although this trend was observed up to 12 hours post-irradiation, both genotypes ultimately reached the same level of apoptosis at 14 hours, suggesting the importance of late-onset p53-independent apoptotic responses in this mouse model. Expected radiation-induced G1 cell cycle delay was observed in Trp53+/+ but not Trp53+/-. Although p53 has an important role in cancer risk, we have shown its influence on radiation dose response can be temporally variable. This research highlights the importance of caution when using haematopoietic endpoints as surrogates to extrapolate radiation-induced cancer risk estimation.« less

  19. Roles of miRNAs in microcystin-LR-induced Sertoli cell toxicity

    SciTech Connect (OSTI)

    Zhou, Yuan; Wang, Hui; Wang, Cong; Qiu, Xuefeng; Benson, Mikael; Yin, Xiaoqin; Xiang, Zou; Li, Dongmei; and others

    2015-08-15

    Microcystin (MC)-LR, a cyclic heptapeptide, is a potent reproductive system toxin. To understand the molecular mechanisms of MC-induced reproductive system cytotoxicity, we evaluated global changes of miRNA and mRNA expression in mouse Sertoli cells following MC-LR treatment. Our results revealed that the exposure to MC-LR resulted in an altered miRNA expression profile that might be responsible for the modulation of mRNA expression. Bio-functional analysis indicated that the altered genes were involved in specific cellular processes, including cell death and proliferation. Target gene analysis suggested that junction injury in Sertoli cells exposed to MC-LR might be mediated by miRNAs through the regulation of the Sertoli cell-Sertoli cell pathway. Collectively, these findings may enhance our understanding on the modes of action of MC-LR on mouse Sertoli cells as well as the molecular mechanisms underlying the toxicity of MC-LR on the male reproductive system. - Highlights: • miRNAs were altered in Sertoli cells exposed to MC-LR. • Alerted genes were involved in different cell functions including the cell morphology. • MC-LR adversely affected Sertoli cell junction formation through the regulating miRNAs.

  20. A PAUF-neutralizing antibody targets both carcinoma and endothelial cells to impede pancreatic tumor progression and metastasis

    SciTech Connect (OSTI)

    Kim, Su Jin; Chang, Suhwan; Lee, Yangsoon; Kim, Na Young; Hwang, Yeonsil; Min, Hye Jin; Yoo, Kyung-Sook; Park, Eun Hye; Kim, Seokho; Chung, Young-Hwa; Park, Young Woo; Koh, Sang Seok

    2014-11-07

    Highlights: • PMAb83, a human monoclonal antibody against PAUF, impaired tumor progression in vivo. • PMAb83 attenuated aggressiveness of tumor cells and suppressed angiogenesis. • PMAb83 in combination with gemcitabine conferred improved survival of mouse model. - Abstract: Pancreatic adenocarcinoma up-regulated factor (PAUF) is expressed in pancreatic ductal adenocarcinoma (PDAC) and plays an important role in tumor progression and metastasis. Here we evaluate the anti-tumor efficacy of a human monoclonal antibody against PAUF, PMAb83, to provide a therapeutic intervention to treat the disease. PMAb83 reduced tumor growth and distant metastasis in orthotopically xenografted mice of human PDAC cells. PMAb83 treatment retarded proliferation along with weakened aggressiveness traits of the carcinoma cells. AKT/β-catenin signaling played a role in the carcinoma cell proliferation and the treated xenograft tumors exhibited reduced levels of β-catenin and cyclin D1. Moreover PMAb83 abrogated the PAUF-induced angiogenic responses of endothelial cells, reducing the density of CD31{sup +} vessels in the treated tumors. In combination with gemcitabine, PMAb83 conferred enhanced survival of xenografted mice by about twofold compared to gemcitabine alone. Taken together, our findings show that PMAb83 treatment decreases the aggressiveness of carcinoma cells and suppresses tumor vascularization, which culminates in mitigated tumor growth and metastasis with improved survival in PDAC mouse models.

  1. Matrix Effects in Biological Mass Spectrometry Imaging: Identification and Compensation

    SciTech Connect (OSTI)

    Lanekoff, Ingela T.; Stevens, Susan; Stenzel-Poore, Mary; Laskin, Julia

    2014-07-21

    Matrix effects in mass spectrometry imaging (MSI) may affect the observed molecular distribution in chemical and biological systems. In this study, we introduce an experimental approach that efficiently compensates for matrix effects in nanospray desorption electrospray ionization (nano-DESI) MSI without introducing any complexity into the experimental protocol. We demonstrate compensation for matrix effects in nano-DESI MSI of phosphatidylcholine (PC) in normal and ischemic mouse brain tissue by doping the nano-DESI solvent with PC standards. Specifically, we use mouse brain tissue of a middle cerebral artery occlusion (MCAO) stroke model with an ischemic region localized to one hemisphere of the brain. Due to similar suppression in ionization of endogenous PC molecules extracted from the tissue and PC standards added to the solvent, matrix effects are eliminated by normalizing the intensity of the sodium and potassium adducts of endogenous PC to the intensity of the corresponding adduct of the PC standard. This approach efficiently compensates for signal variations resulting from differences in the local concentrations of sodium and potassium in tissue sections and from the complexity of the extracted analyte mixture derived from local variations in molecular composition.

  2. Tenascin-W inhibits proliferation and differentiation of preosteoblasts during endochondral bone formation

    SciTech Connect (OSTI)

    Kimura, Hiroaki; Akiyama, Haruhiko . E-mail: hakiyama@kuhp.kyoto-u.ac.jp; Nakamura, Takashi; Crombrugghe, Benoit de

    2007-05-18

    We identified a cDNA encoding mouse Tenascin-W (TN-W) upregulated by bone morphogenetic protein (Bmp)2 in ATDC5 osteo-chondroprogenitors. In adult mice, TN-W was markedly expressed in bone. In mouse embryos, during endochondral bone formation TN-W was localized in perichondrium/periosteum, but not in trabecular and cortical bones. During bone fracture repair, cells in the newly formed perichondrium/periosteum surrounding the cartilaginous callus expressed TN-W. Furthermore, TN-W was detectable in perichondrium/periosteum of Runx2-null and Osterix-null embryos, indicating that TN-W is expressed in preosteoblasts. In CFU-F and -O cells, TN-W had no effect on initiation of osteogenesis of bone marrow cells, and in MC3T3-E1 osteoblastic cells TN-W inhibited cell proliferation and Col1a1 expression. In addition, TN-W suppressed canonical Wnt signaling which stimulates osteoblastic differentiation. Our results indicate that TN-W is a novel marker of preosteoblasts in early stage of osteogenesis, and that TN-W inhibits cell proliferation and differentiation of preosteoblasts mediated by canonical Wnt signaling.

  3. Immunoglobulin λ Gene Rearrangement Can Precede κ Gene Rearrangement

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Berg, Jörg; Mcdowell, Mindy; Jäck, Hans-Martin; Wabl, Matthias

    1990-01-01

    Imore » mmunoglobulin genes are generated during differentiation of B lymphocytes by joining gene segments. A mouse pre-B cell contains a functional immunoglobulin heavy-chain gene, but no light-chain gene. Although there is only one heavy-chain locus, there are two lightchain loci: κ and λ .It has been reported that κ loci in the germ-line configuration are never (in man) or very rarely (in the mouse) present in cells with functionally rearranged λ -chain genes. Two explanations have been proposed to explain this: (a) the ordered rearrangement theory, which postulates that light-chain gene rearrangement in the pre-B cell is first attempted at the κ locus, and that only upon failure to produce a functional κ chain is there an attempt to rearrange the λ locus; and (b) the stochastic theory, which postulates that rearrangement at the λ locus proceeds at a rate that is intrinsically much slower than that at the κ locus. We show here that λ -chain genes are generated whether or not the κ locus has lost its germ-line arrangement, a result that is compatible only with the stochastic theory.« less

  4. Characterization of evolutionary rates and constraints in three mammalian genomes

    SciTech Connect (OSTI)

    Cooper, Gregory M.; Brudno, Michael; Stone, Eric A.; Dubchak, Inna; Batzoglou, Serafim; Sidow, Arend

    2004-02-15

    We present an analysis of rates and patterns of microevolutionary phenomena that have shaped the human, mouse, and rat genomes since their last common ancestor. We find evidence for a shift in the mutational spectrum between the mouse and rat lineages, with the net effect being a relative increase in GC content in the rat genome. Our estimate for the neutral point substitution rate separating the two rodents is 0.196 substitutions per site, and 0.65 substitutions per site for the tree relating all three mammals. Small insertions and deletions of 1-10 bp in length (''microindels'') occur at approximately 5 percent of the point substitution rate. Inferred regional correlations in evolutionary rates between lineages and between types of sites support the idea that rates of evolution are influenced by local genomic or cell biological context. No substantial correlations between rates of point substitutions and rates of microindels are found, however, implying that the influences that affect these processes are distinct. Finally, we have identified those regions in the human genome that are evolving slowly, which are likely to include functional elements important to human biology. At least 5 percent of the human genome is under substantial constraint, most of which is noncoding.

  5. ChIP-seq Accurately Predicts Tissue-Specific Activity of Enhancers

    SciTech Connect (OSTI)

    Visel, Axel; Blow, Matthew J.; Li, Zirong; Zhang, Tao; Akiyama, Jennifer A.; Holt, Amy; Plajzer-Frick, Ingrid; Shoukry, Malak; Wright, Crystal; Chen, Feng; Afzal, Veena; Ren, Bing; Rubin, Edward M.; Pennacchio, Len A.

    2009-02-01

    A major yet unresolved quest in decoding the human genome is the identification of the regulatory sequences that control the spatial and temporal expression of genes. Distant-acting transcriptional enhancers are particularly challenging to uncover since they are scattered amongst the vast non-coding portion of the genome. Evolutionary sequence constraint can facilitate the discovery of enhancers, but fails to predict when and where they are active in vivo. Here, we performed chromatin immunoprecipitation with the enhancer-associated protein p300, followed by massively-parallel sequencing, to map several thousand in vivo binding sites of p300 in mouse embryonic forebrain, midbrain, and limb tissue. We tested 86 of these sequences in a transgenic mouse assay, which in nearly all cases revealed reproducible enhancer activity in those tissues predicted by p300 binding. Our results indicate that in vivo mapping of p300 binding is a highly accurate means for identifying enhancers and their associated activities and suggest that such datasets will be useful to study the role of tissue-specific enhancers in human biology and disease on a genome-wide scale.

  6. Construction of genome-wide physical BAC contigs using mapped cDNA as probes: Toward an integrated BAC library resource for genome sequencing and analysis. Annual report, July 1995--January 1997

    SciTech Connect (OSTI)

    Mitchell, S.C.; Bocskai, D.; Cao, Y.

    1997-12-31

    The goal of human genome project is to characterize and sequence entire genomes of human and several model organisms, thus providing complete sets of information on the entire structure of transcribed, regulatory and other functional regions for these organisms. In the past years, a number of useful genetic and physical markers on human and mouse genomes have been made available along with the advent of BAC library resources for these organisms. The advances in technology and resource development made it feasible to efficiently construct genome-wide physical BAC contigs for human and other genomes. Currently, over 30,000 mapped STSs and 27,000 mapped Unigenes are available for human genome mapping. ESTs and cDNAs are excellent resources for building contig maps for two reasons. Firstly, they exist in two alternative forms--as both sequence information for PCR primer pairs, and cDoreen genomic libraries efficiently for large number of DNA probes by combining over 100 cDNA probes in each hybridization. Second, the linkage and order of genes are rather conserved among human, mouse and other model organisms. Therefore, gene markers have advantages over random anonymous STSs in building maps for comparative genomic studies.

  7. Critical role of iodination for T cell recognition of thyroglobulin in experimental murine thyroid autoimmunity

    SciTech Connect (OSTI)

    Champion, B.R.; Rayner, D.C.; Byfield, P.G.H.; Page, K.R.; Chan, C.T.J.; Roitt, I.M.

    1987-12-01

    The authors have used two clonotypically distinct thyroglobulin (Tg)-specific, I-A/sup k/-restricted monoclonal T cell populations to investigate the role of thyroid peroxidase-catalyzed iodination in Tg recognition by autorreactive T cells. The results showed that these T cells could recognize Tg only it was sufficiently iodinated. Unlike normal mouse Tg, noniodinated mouse Tg was unable to induce significant thyroid lesions but could trigger the production of Tg autoantibodies. In these experiments, the importance of T cell recognition of iodination-related epitopes was emphasized by the inability of serum antibodies to distinguish Tg on the basis of iodine content, whether they were induced with normal or noniodinated Tg. Therefore, thyroid peroxidase-dependent modification of Tg would appear to be central to its recognition by autoreactive T cells and hence its capacity to induce autoimmune thyroid lesions. Proliferative responses of the Tg-specific T cell clone was assessed by the incorporation of (/sup 125/I) deoxyuridine. Anti-Tg antibody activity was determined by radioimmunoassay.

  8. Norathyriol Suppresses Skin Cancers Induced by Solar Ultraviolet Radiation by Targeting ERK Kinases

    SciTech Connect (OSTI)

    Li, Jixia; Malakhova, Margarita; Mottamal, Madhusoodanan; Reddy, Kanamata; Kurinov, Igor; Carper, Andria; Langfald, Alyssa; Oi, Naomi; Kim, Myoung Ok; Zhu, Feng; Sosa, Carlos P.; Zhou, Keyuan; Bode, Ann M.; Dong, Zigang

    2012-06-27

    Ultraviolet (UV) irradiation is the leading factor in the development of skin cancer, prompting great interest in chemopreventive agents for this disease. In this study, we report the discovery of norathyriol, a plant-derived chemopreventive compound identified through an in silico virtual screening of the Chinese Medicine Library. Norathyriol is a metabolite of mangiferin found in mango, Hypericum elegans, and Tripterospermum lanceolatum and is known to have anticancer activity. Mechanistic investigations determined that norathyriol acted as an inhibitor of extracellular signal-regulated kinase (ERK)1/2 activity to attenuate UVB-induced phosphorylation in mitogen-activated protein kinases signaling cascades. We confirmed the direct and specific binding of norathyriol with ERK2 through a cocrystal structural analysis. The xanthone moiety in norathyriol acted as an adenine mimetic to anchor the compound by hydrogen bonds to the hinge region of the protein ATP-binding site on ERK2. Norathyriol inhibited in vitro cell growth in mouse skin epidermal JB6 P+ cells at the level of G{sub 2}-M phase arrest. In mouse skin tumorigenesis assays, norathyriol significantly suppressed solar UV-induced skin carcinogenesis. Further analysis indicated that norathyriol mediates its chemopreventive activity by inhibiting the ERK-dependent activity of transcriptional factors AP-1 and NF-{kappa}B during UV-induced skin carcinogenesis. Taken together, our results identify norathyriol as a safe new chemopreventive agent that is highly effective against development of UV-induced skin cancer.

  9. Heavy metal transfers between trophic compartments in different ecosystems in Galicia (Northwest Spain): Essential elements

    SciTech Connect (OSTI)

    Gonzalez, X.I.; Aboal, J.R.; Fernandez, J.A.; Carballeira, A.

    2008-11-15

    In the present study, we determined the concentrations of Cu, Fe, Mn, and Zn in soil and several trophic compartments at a total of 16 sampling stations. The trophic compartments studied were primary producers, represented by two species of terrestrial mosses (Pseudoescleropodium purum and Hypnum cupressiforme) and oak trees (Quercus robur or Q. pyrenaica); primary consumers, represented by the wood mouse (Apodemus sylvaticus) and the yellow necked mouse (A. flavicollis); secondary consumers, represented by the shrew (Sorex granarius); and finally, detritivores, represented by slugs (Arion ater). Thirteen of the sampling stations were located in mature oak woodlands (Quercus sp.); two of the sampling stations were located in the area surrounding a restored lignite mine dump, and the other in an ultrabasic area. The analytical determinations revealed a lack of significant correlations among trophic compartments, possibly caused by effective regulation of metals by organisms and/or spatial variation in availability of metals from soil or food. Furthermore, the only element that showed a clear pattern of biomagnification was Cu; as for the other elements, there was always some divergence from such a pattern. Finally, the patterns of bioaccumulation in contaminated and woodland sampling stations were very similar, although there was enrichment of the concentrations of Cu, Mn, and Zn in the mice viscera, which, except for Mn, were related to higher edaphic concentrations.

  10. Radiosynthesis and biological evaluation of a novel enoyl-ACP reductase inhibitor for Staphylococcus aureus

    SciTech Connect (OSTI)

    Wang, Hui; Lu, Yang; Liu, Li; Kim, Sung Won; Hooker, Jacob M.; Fowler, Joanna S.; Tonge, Peter J.

    2014-09-06

    Here we evaluated the pharmacokinetics (PK) and pharmacodynamics (PD) of PT119, a potent Staphylococcus aureus enoyl-ACP reductase (saFabI) inhibitor with a Ki value of 0.01 nM and a residence time of 750 min on the enzyme target in mice. PT119 was found to have promising antibacterial activity in two different S. aureus infection models: it caused a 3 log reduction in the CFU’s in a mouse thigh muscle infection model and increased the survival rate from 0% to 50% in a mouse systemic infection model. PT119 was then radiolabeled with carbon-11 to evaluate its biodistribution and PK in both healthy and S. aureus infected mice using positron emission tomography (PET). The biodistribution of [11C]PT119 and/or its labeled metabolites did not differ significantly between the healthy group and the infected group, and PT119 was found to distribute equally between serum and tissue during the ~1 h of analysis permitted by the carbon-11 half life. This approach provides important data for PK/PD modeling and is the first step in identifying radiotracers that can non-invasively image bacterial infection in vivo.

  11. Poly(dimethylsiloxane) microchip-based immunoassay with multiple reaction zones: Toward on-chip multiplex detection platform

    SciTech Connect (OSTI)

    Shao, Guocheng; Wang, Jun; Li, Zhaohui; Saraf, Laxmikant V.; Wang, Wanjun; Lin, Yuehe

    2011-09-20

    In this work, a poly(dimethylsiloxane) (PDMS) microchip-based immuno-sensing platform with integrated pneumatic micro valves is described. The microchip was fabricated with multiple layer soft lithography technology. By controlling the activation status of corresponding valves, reagent flows in the microchannel network can be well manipulated so that immuno-reactions only take place at designated reaction zones (DRZs). Four DRZs are included in the prototype microchip. Since these DRZs are all isolated from each other by micro valves, cross contamination is prevented. Using the inner surface of the all-PDMS microchannel as immunoassay substrate, on-chip sandwich format solid phase immunoassay was performed to demonstrate the feasibility of this immuno-sensing platform. Mouse IgG and fluorescein isothiocyanate (FITC) were used as the model analyte and the signal reporter respectively. Only 10 ul sample is needed for the assay and low detection limit of 5 ng/ml (?33 pM) was achieved though low-cost polyclonal antibodies were used in our experiment for feasibility study only. The encouraging results from mouse IgG immunoassay proved the feasibility of our microchip design. With slight modification of the assay protocol, the same chip design can be used for multi-target detection and can provide a simple, cost-effective and integrated microchip solution for multiplex immunoassay applications.

  12. Using CAD software to simulate PV energy yield - The case of product integrated photovoltaic operated under indoor solar irradiation

    SciTech Connect (OSTI)

    Reich, N.H.; van Sark, W.G.J.H.M.; Turkenburg, W.C.; Sinke, W.C.

    2010-08-15

    In this paper, we show that photovoltaic (PV) energy yields can be simulated using standard rendering and ray-tracing features of Computer Aided Design (CAD) software. To this end, three-dimensional (3-D) sceneries are ray-traced in CAD. The PV power output is then modeled by translating irradiance intensity data of rendered images back into numerical data. To ensure accurate results, the solar irradiation data used as input is compared to numerical data obtained from rendered images, showing excellent agreement. As expected, also ray-tracing precision in the CAD software proves to be very high. To demonstrate PV energy yield simulations using this innovative concept, solar radiation time course data of a few days was modeled in 3-D to simulate distributions of irradiance incident on flat, single- and double-bend shapes and a PV powered computer mouse located on a window sill. Comparisons of measured to simulated PV output of the mouse show that also in practice, simulation accuracies can be very high. Theoretically, this concept has great potential, as it can be adapted to suit a wide range of solar energy applications, such as sun-tracking and concentrator systems, Building Integrated PV (BIPV) or Product Integrated PV (PIPV). However, graphical user interfaces of 'CAD-PV' software tools are not yet available. (author)

  13. Advanced slow-magic angle spinning probe for magnetic resonance imaging and spectroscopy

    DOE Patents [OSTI]

    Wind, Robert A.; Hu, Jian Zhi; Minard, Kevin R.; Rommereim, Donald N.

    2006-01-24

    The present invention relates to a probe and processes useful for magnetic resonance imaging and spectroscopy instruments. More particularly, the invention relates to a MR probe and processes for obtaining resolution enhancements of fluid objects, including live specimens, using an ultra-slow (magic angle) spinning (MAS) of the specimen combined with a modified phase-corrected magic angle turning (PHORMAT) pulse sequence. Proton NMR spectra were measured of the torso and the top part of the belly of a female BALBc mouse in a 2T field, while spinning the animal at a speed of 1.5 Hz. Results show that even in this relatively low field with PHORMAT, an isotropic spectrum is obtained with line widths that are a factor 4.6 smaller than those obtained in a stationary mouse. Resolution of 1H NMR metabolite spectra are thus significantly enhanced. Results indicate that PHORMAT has the potential to significantly increase the utility of 1H NMR spectroscopy for in vivo biochemical, biomedical and/or medical applications involving large-sized biological objects such as mice, rats and even humans within a hospital setting. For small-sized objects, including biological objects, such as excised tissues, organs, live bacterial cells, and biofilms, use of PASS at a spinning rate of 30 Hz and above is preferred.

  14. H2-M polymorphism in mice susceptible to collagen-induced arthritis involves the peptide binding groove

    SciTech Connect (OSTI)

    Walter, W.; Loos, M.; Maeurer, M.J.

    1996-12-31

    The ability to develop type II collagen (CII)-induced arthritis (CIA) in mice is associated with the major histocompatibility I-A gene and with as yet poorly defined regulatory molecules of the major histocompatibility complex (MHC) class II antigen processing and presentation pathway. H2-M molecules are thought to be involved in the loading of antigenic peptides into the MHC class II binding cleft. We sequenced H2-Ma, H2-Mb1, and H2-Mb2 genes from CIA-susceptible and -resistant mouse strains and identified four different Ma and Mb2 alleles, and three different Mb1 alleles defined by polymorphic residues within the predicted peptide binding groove. Most CIA-resistant mouse strains share common Ma, Mb1, and Mb2 alleles. In contrast, H2-M alleles designated Ma-III, Ma-IV, Mb1-III, and Mb2-IV could be exclusively identified in the CIA-susceptible H2{sup r} and H2{sup q} haplotypes, suggesting that allelic H2-M molecules may modulate the composition of different CII peptides loaded onto MHC class II molecules, presumably presenting {open_quotes}arthritogenic{close_quotes} epitopes to T lymphocytes. 42 refs., 4 figs., 3 tabs.

  15. Radiosynthesis and biological evaluation of a novel enoyl-ACP reductase inhibitor for Staphylococcus aureus

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Wang, Hui; Lu, Yang; Liu, Li; Kim, Sung Won; Hooker, Jacob M.; Fowler, Joanna S.; Tonge, Peter J.

    2014-09-06

    Here we evaluated the pharmacokinetics (PK) and pharmacodynamics (PD) of PT119, a potent Staphylococcus aureus enoyl-ACP reductase (saFabI) inhibitor with a Ki value of 0.01 nM and a residence time of 750 min on the enzyme target in mice. PT119 was found to have promising antibacterial activity in two different S. aureus infection models: it caused a 3 log reduction in the CFU’s in a mouse thigh muscle infection model and increased the survival rate from 0% to 50% in a mouse systemic infection model. PT119 was then radiolabeled with carbon-11 to evaluate its biodistribution and PK in both healthymore » and S. aureus infected mice using positron emission tomography (PET). The biodistribution of [11C]PT119 and/or its labeled metabolites did not differ significantly between the healthy group and the infected group, and PT119 was found to distribute equally between serum and tissue during the ~1 h of analysis permitted by the carbon-11 half life. This approach provides important data for PK/PD modeling and is the first step in identifying radiotracers that can non-invasively image bacterial infection in vivo.« less

  16. Controlled-Resonant Surface Tapping-Mode Scanning Probe Electrospray Ionization Mass Spectrometry Imaging

    SciTech Connect (OSTI)

    Lorenz, Matthias; Ovchinnikova, Olga S; Kertesz, Vilmos; Van Berkel, Gary J

    2014-01-01

    This paper reports on the advancement of a controlled-resonance surface tapping-mode single capillary liquid junction extraction/ESI emitter for mass spectrometry imaging. The basic instrumental setup and the general operation of the system were discussed and optimized performance metrics were presented. The ability to spot sample, lane scan and chemically image in an automated and controlled fashion were demonstrated. Rapid, automated spot sampling was demonstrated for a variety of compound types including the cationic dye basic blue 7, the oligosaccharide cellopentaose, and the protein equine heart cytochrome c. The system was used for lane scanning and chemical imaging of the cationic dye crystal violet in inked lines on glass and for lipid distributions in mouse brain thin tissue sections. Imaging of the lipids in mouse brain tissue under optimized conditions provided a spatial resolution of approximately 35 m based on the ability to distinguish between features observed both in the optical and mass spectral chemical images. The sampling spatial resolution of this system was comparable to the best resolution that has been reported for other types of atmospheric pressure liquid extraction-based surface sampling/ionization techniques used for mass spectrometry imaging.

  17. Mapping cis-Regulatory Domains in the Human Genome UsingMulti-Species Conservation of Synteny

    SciTech Connect (OSTI)

    Ahituv, Nadav; Prabhakar, Shyam; Poulin, Francis; Rubin, EdwardM.; Couronne, Olivier

    2005-06-13

    Our inability to associate distant regulatory elements with the genes that they regulate has largely precluded their examination for sequence alterations contributing to human disease. One major obstacle is the large genomic space surrounding targeted genes in which such elements could potentially reside. In order to delineate gene regulatory boundaries we used whole-genome human-mouse-chicken (HMC) and human-mouse-frog (HMF) multiple alignments to compile conserved blocks of synteny (CBS), under the hypothesis that these blocks have been kept intact throughout evolution at least in part by the requirement of regulatory elements to stay linked to the genes that they regulate. A total of 2,116 and 1,942 CBS>200 kb were assembled for HMC and HMF respectively, encompassing 1.53 and 0.86 Gb of human sequence. To support the existence of complex long-range regulatory domains within these CBS we analyzed the prevalence and distribution of chromosomal aberrations leading to position effects (disruption of a genes regulatory environment), observing a clear bias not only for mapping onto CBS but also for longer CBS size. Our results provide a genome wide data set characterizing the regulatory domains of genes and the conserved regulatory elements within them.

  18. Differentiation of C2C12 myoblasts expressing lamin A mutated at a site responsible for Emery-Dreifuss muscular dystrophy is improved by inhibition of the MEK-ERK pathway and stimulation of the PI3-kinase pathway

    SciTech Connect (OSTI)

    Favreau, Catherine; Delbarre, Erwan; Courvalin, Jean-Claude; Buendia, Brigitte

    2008-04-01

    Mutation R453W in A-type lamins, that are major nuclear envelope proteins, generates Emery-Dreifuss muscular dystrophy. We previously showed that mouse myoblasts expressing R453W-lamin A incompletely exit the cell cycle and differentiate into myocytes with a low level of multinucleation. Here we attempted to improve differentiation by treating these cells with a mixture of PD98059, an extracellular-regulated kinase (ERK) kinase (also known as mitogen-activated kinase, MEK) inhibitor, and insulin-like growth factor-II, an activator of phosphoinositide 3-kinase. We show that mouse myoblasts expressing R453W-lamin A were sensitive to the drug treatment as shown by (i) an increase in multinucleation, (ii) downregulation of proliferation markers (cyclin D1, hyperphosphorylated Rb), (iii) upregulation of myogenin, and (iv) sustained activation of p21 and cyclin D3. However, nuclear matrix anchorage of p21 and cyclin D3 in a complex with hypophosphorylated Rb that is critical to trigger cell cycle arrest and myogenin induction was deficient and incompletely restored by drug treatment. As the turn-over of R453W-lamin A at the nuclear envelope was greatly enhanced, we propose that R453W-lamin A impairs the capacity of the nuclear lamina to serve as scaffold for substrates of the MEK-ERK pathway and for MyoD-induced proteins that play a role in the differentiation process.

  19. Tuning the DARHT Axis-II linear induction accelerator focusing

    SciTech Connect (OSTI)

    Ekdahl, Carl A.

    2012-04-24

    Flash radiography of large hydrodynamic experiments driven by high explosives is a well-known diagnostic technique in use at many laboratories, and the Dual-Axis Radiography for Hydrodynamic Testing (DARHT) facility at Los Alamos produces flash radiographs of large hydrodynamic experiments. Two linear induction accelerators (LIAs) make the bremsstrahlung radiographic source spots for orthogonal views of each test. The 2-kA, 20-MeV Axis-I LIA creates a single 60-ns radiography pulse. The 1.7-kA, 16.5-MeV Axis-II LIA creates up to four radiography pulses by kicking them out of a longer pulse that has a 1.6-{mu}s flattop. The Axis-II injector, LIA, kicker, and downstream transport (DST) to the bremsstrahlung converter are described. Adjusting the magnetic focusing and steering elements to optimize the electron-beam transport through an LIA is often called 'tuning.' As in all high-current LIAs, the focusing field is designed to be as close to that of the ideal continuous solenoid as physically possible. In ideal continuous solenoidal transport a smoothly varying beam size can easily be found for which radial forces balance, and the beam is said to be 'matched' to the focusing field. A 'mismatched' beam exhibits unwanted oscillations in size, which are a source of free energy that contributes to emittance growth. This is undesirable, because in the absence of beam-target effects, the radiographic spot size is proportional to the emittance. Tuning the Axis-II LIA is done in two steps. First, the solenoidal focusing elements are set to values designed to provide a matched beam with little or no envelope oscillations, and little or no beam-breakup (BBU) instability growth. Then, steering elements are adjusted to minimize the motion of the centroid of a well-centered beam at the LIA exit. This article only describes the design of the tune for the focusing solenoids. The DARHT Axis-II LIA was required to be re-tuned after installing an accelerator cell to replace a failed

  20. Organic light emitting diodes (OLEDS) and OLED-based structurally integrated optical sensors

    SciTech Connect (OSTI)

    Cai, Yuankun

    2010-05-16

    microheterogeneity. Effect of TiO{sub 2} doping was also discussed. Stretched exponential analysis also generates calibration curves with higher sensitivity, which is preferred from the operational point of view. The work of enhanced integration was shown in chapter 7 with a polymer photodetector, which enables the preferred operation mode, decay time measurement, due to fast reponse (<20 {mu}s). Device thickness was enlarged for maximum absorption of the PL, which was realized by slow spincoating rate and shorter spincoating time. Film prepared this way shows more crystalline order by Raman spectra, probably due to slow evaporation. This also ensures charge transport is not affected even with a thick film as indicated in the response time. Combination of OLEDs and polymer photodetectors present opportunities for solution processed all-organic sensors, which enables cheap processing at large scale. Future development can focus on monolithically integration of OLEDs and organic photodetectors (OPD) on the same substrate at a small scale, which could be enabled by inkjet printing. As OLED and OPD technologies continue to advance, small-sized, flexible and all-organic structurally integrated sensor platforms will become true in the near future.

  1. Quality assurance for online adapted treatment plans: Benchmarking and delivery monitoring simulation

    SciTech Connect (OSTI)

    Li, Taoran Wu, Qiuwen; Yang, Yun; Rodrigues, Anna; Yin, Fang-Fang; Jackie Wu, Q.

    2015-01-15

    Purpose: An important challenge facing online adaptive radiation therapy is the development of feasible and efficient quality assurance (QA). This project aimed to validate the deliverability of online adapted plans and develop a proof-of-concept online delivery monitoring system for online adaptive radiation therapy QA. Methods: The first part of this project benchmarked automatically online adapted prostate treatment plans using traditional portal dosimetry IMRT QA. The portal dosimetry QA results of online adapted plans were compared to original (unadapted) plans as well as randomly selected prostate IMRT plans from our clinic. In the second part, an online delivery monitoring system was designed and validated via a simulated treatment with intentional multileaf collimator (MLC) errors. This system was based on inputs from the dynamic machine information (DMI), which continuously reports actual MLC positions and machine monitor units (MUs) at intervals of 50 ms or less during delivery. Based on the DMI, the system performed two levels of monitoring/verification during the delivery: (1) dynamic monitoring of cumulative fluence errors resulting from leaf position deviations and visualization using fluence error maps (FEMs); and (2) verification of MLC positions against the treatment plan for potential errors in MLC motion and data transfer at each control point. Validation of the online delivery monitoring system was performed by introducing intentional systematic MLC errors (ranging from 0.5 to 2 mm) to the DMI files for both leaf banks. These DMI files were analyzed by the proposed system to evaluate the systems performance in quantifying errors and revealing the source of errors, as well as to understand patterns in the FEMs. In addition, FEMs from 210 actual prostate IMRT beams were analyzed using the proposed system to further validate its ability to catch and identify errors, as well as establish error magnitude baselines for prostate IMRT delivery. Results

  2. Toward Designed Singlet Fission: Electronic States and Photophysics of 1,3-Diphenylisobenzofuran

    SciTech Connect (OSTI)

    Schwerin, A.F.; Miller, J.; Johnson, J.C.; Smith, M.B.; Sreearunothai, P.; Popovic, D.; Cerny, J.; Havlas, Z.; Paci, I.; Akdag, A.; MacLeod, M.K.; Chen, X.; David, D.E.; Ratner, M.A.; Nozik, A.J.; Mich, J.

    2009-12-21

    Single crystal molecular structure and solution photophysical properties are reported for 1,3-diphenylisobenzofuran (1), of interest as a model compound in studies of singlet fission. For the ground state of 1 and of its radical cation (1{sup +{sm_bullet}}) and anion (1{sup -{sm_bullet}}), we report the UV-visible absorption spectra, and for neutral 1, also the magnetic circular dichroism (MCD) and the decomposition of the absorption spectrum into purely polarized components, deduced from fluorescence polarization. These results were used to identify a series of singlet excited states. For the first excited singlet and triplet states of 1, the transient visible absorption spectra, S{sub 1} {yields} S{sub x} and sensitized T{sub 1} {yields} T{sub x}, and single exponential lifetimes, {tau}{sub F} = {approx} 5.3 ns and {tau}{sub T} = {approx}200 {mu}s, are reported. The spectra and lifetimes of S{sub 1} {yields} S{sub 0} fluorescence and sensitized T{sub 1} {yields} T{sub x} absorption of 1 were obtained in a series of solvents, as was the fluorescence quantum yield, {Phi}{sub F} = 0.95-0.99. No phosphorescence has been detected. The first triplet excitation energy of solid 1 (11,400 cm{sup -1}) was obtained by electron energy loss spectroscopy, in agreement with previously reported solution values. The fluorescence excitation spectrum suggests an onset of a nonradiative channel at {approx} 37,000 cm{sup -1}. Excitation energies and relative transition intensities are in agreement with those of ab initio (CC2) calculations after an empirical 3000 cm{sup -1} adjustment of the initial state energy to correct differentially for a better quality description of the initial relative to the terminal state of an absorption transition. The interpretation of the MCD spectrum used the semiempirical PPP method, whose results for the S{sub 0} {yields} S{sub x} spectrum require no empirical adjustment and are otherwise nearly identical with the CC2 results in all respects

  3. Online adaptation and verification of VMAT

    SciTech Connect (OSTI)

    Crijns, Wouter; Defraene, Gilles; Depuydt, Tom; Haustermans, Karin; Van Herck, Hans; Maes, Frederik; Van den Heuvel, Frank

    2015-07-15

    Purpose: This work presents a method for fast volumetric modulated arc therapy (VMAT) adaptation in response to interfraction anatomical variations. Additionally, plan parameters extracted from the adapted plans are used to verify the quality of these plans. The methods were tested as a prostate class solution and compared to replanning and to their current clinical practice. Methods: The proposed VMAT adaptation is an extension of their previous intensity modulated radiotherapy (IMRT) adaptation. It follows a direct (forward) planning approach: the multileaf collimator (MLC) apertures are corrected in the beam’s eye view (BEV) and the monitor units (MUs) are corrected using point dose calculations. All MLC and MU corrections are driven by the positions of four fiducial points only, without need for a full contour set. Quality assurance (QA) of the adapted plans is performed using plan parameters that can be calculated online and that have a relation to the delivered dose or the plan quality. Five potential parameters are studied for this purpose: the number of MU, the equivalent field size (EqFS), the modulation complexity score (MCS), and the components of the MCS: the aperture area variability (AAV) and the leaf sequence variability (LSV). The full adaptation and its separate steps were evaluated in simulation experiments involving a prostate phantom subjected to various interfraction transformations. The efficacy of the current VMAT adaptation was scored by target mean dose (CTV{sub mean}), conformity (CI{sub 95%}), tumor control probability (TCP), and normal tissue complication probability (NTCP). The impact of the adaptation on the plan parameters (QA) was assessed by comparison with prediction intervals (PI) derived from a statistical model of the typical variation of these parameters in a population of VMAT prostate plans (n = 63). These prediction intervals are the adaptation equivalent of the tolerance tables for couch shifts in the current clinical

  4. Detection of genotoxic and non-genotoxic carcinogens in Xpc{sup −/−}p53{sup +/−} mice

    SciTech Connect (OSTI)

    Melis, Joost P.M.; Leiden University Medical Center, Department of Toxicogenetics, Leiden ; Speksnijder, Ewoud N.; Kuiper, Raoul V.; Dutch Molecular Pathology Center, Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, Utrecht ; Salvatori, Daniela C.F.; Schaap, Mirjam M.; Leiden University Medical Center, Department of Toxicogenetics, Leiden ; Maas, Saskia; Robinson, Joke; Verhoef, Aart; Benthem, Jan van; Luijten, Mirjam; Steeg, Harry van

    2013-01-15

    An accurate assessment of the carcinogenic potential of chemicals and pharmaceutical drugs is essential to protect humans and the environment. Therefore, substances are extensively tested before they are marketed to the public. Currently, the rodent two-year bioassay is still routinely used to assess the carcinogenic potential of substances. However, over time it has become clear that this assay yields false positive results and also has several economic and ethical drawbacks including the use of large numbers of animals, the long duration, and the high cost. The need for a suitable alternative assay is therefore high. Previously, we have proposed the Xpa*p53 mouse model as a very suitable alternative to the two-year bioassay. We now show that the Xpc*p53 mouse model preserves all the beneficial traits of the Xpa*p53 model for sub-chronic carcinogen identification and can identify both genotoxic and non-genotoxic carcinogens. Moreover, Xpc*p53 mice appear to be more responsive than Xpa*p53 mice towards several genotoxic and non-genotoxic carcinogens. Furthermore, Xpc*p53 mice are far less sensitive than Xpa*p53 mice for the toxic activity of DNA damaging agents and as such clearly respond in a similar way as wild type mice do. These advantageous traits of the Xpc*p53 model make it a better alternative for in vivo carcinogen testing than Xpa*p53. This pilot study suggests that Xpc*p53 mice are suited for routine sub-chronic testing of both genotoxic and non-genotoxic carcinogens and as such represent a suitable alternative to possibly replace the murine life time cancer bioassay. Highlights: ► The Xpc*p53 mouse model is able to identify genotoxic and non-genotoxic carcinogens. ► Time, animals and cost can be significantly reduced compared to the 2-year bioassay. ► Xpc*p53 mice are more advantageous for carcinogen identification than Xpa*p53 mice. ► Xpc*p53 mice exhibit a wild type response upon exposure to genotoxicants.

  5. Sulforaphane is not an effective antagonist of the human pregnane X-receptor in vivo

    SciTech Connect (OSTI)

    Poulton, Emma Jane; Levy, Lisa; Lampe, Johanna W.; Shen, Danny D.; Tracy, Julia; Shuhart, Margaret C.; Thummel, Kenneth E.; Eaton, David L.

    2013-01-01

    Sulforaphane (SFN), is an effective in vitro antagonist of ligand activation of the human pregnane and xenobiotic receptor (PXR). PXR mediated CYP3A4 up-regulation is implicated in adverse drug-drug interactions making identification of small molecule antagonists a desirable therapeutic goal. SFN is not an antagonist to mouse or rat PXR in vitro; thus, normal rodent species are not suitable as in vivo models for human response. To evaluate whether SFN can effectively antagonize ligand activation of human PXR in vivo, a three-armed, randomized, crossover trial was conducted with 24 healthy adults. The potent PXR ligand — rifampicin (300 mg/d) was given alone for 7 days in arm 1, or in daily combination with 450 μmol SFN (Broccoli Sprout extract) in arm 2; SFN was given alone in arm 3. Midazolam as an in vivo phenotype marker of CYP3A was administered before and after each treatment arm. Rifampicin alone decreased midazolam AUC by 70%, indicative of the expected increase in CYP3A4 activity. Co-treatment with SFN did not reduce CYP3A4 induction. Treatment with SFN alone also did not affect CYP3A4 activity in the cohort as a whole, although in the subset with the highest basal CYP3A4 activity there was a statistically significant increase in midazolam AUC (i.e., decrease in CYP3A4 activity). A parallel study in humanized PXR mice yielded similar results. The parallel effects of SFN between humanized PXR mice and human subjects demonstrate the predictive value of humanized mouse models in situations where species differences in ligand-receptor interactions preclude the use of a native mouse model for studying human ligand-receptor pharmacology. -- Highlights: ► The effects of SFN on PXR mediated CYP3A4 induction in humanized PXR mice and humans were examined. ► SFN had no effect on rifampicin mediated CYP3A4 induction in humans or humanized mice. ► SFN had a modest effect on basal CYP3A4 activity among subjects with higher baseline activity. ► Humanized PXR

  6. Development of Biomarkers for Chronic Beryllium Disease in Mice

    SciTech Connect (OSTI)

    Gordon, Terry

    2013-01-25

    Beryllium is a strategic metal, indispensable for national defense programs in aerospace, telecommunications, electronics, and weaponry. Exposure to beryllium is an extensively documented occupational hazard that causes irreversible, debilitating granulomatous lung disease in as much as 3 - 5% of exposed workers. Mechanistic research on beryllium exposure-disease relationships has been severely limited by a general lack of a sufficient CBD animal model. We have now developed and tested an animal model which can be used for dissecting dose-response relationships and pathogenic mechanisms and for testing new diagnostic and treatment paradigms. We have created 3 strains of transgenic mice in which the human antigen-presenting moiety, HLA-DP, was inserted into the mouse genome. Each mouse strain contains HLA-DPB1 alleles that confer different magnitude of risk for chronic beryllium disease (CBD): HLA-DPB1*0401 (odds ratio = 0.2), HLA-DPB1*0201 (odds ratio = 15), HLA-DPB1*1701 (odds ratio = 240). Our preliminary work has demonstrated that the *1701 allele, as predicted by human studies, results in the greatest degree of sensitization in a mouse ear swelling test. We have also completed dose-response experiments examining beryllium-induced lung granulomas and identified susceptible and resistant inbred strains of mice (without the human transgenes) as well as quantitative trait loci that may contain gene(s) that modify the immune response to beryllium. In this grant application, we propose to use the transgenic and normal inbred strains of mice to identify biomarkers for the progression of beryllium sensitization and CBD. To achieve this goal, we propose to compare the sensitivity and accuracy of the lymphocyte proliferation test (blood and bronchoalveolar lavage fluid) with the ELISPOT test in the three HLA-DP transgenic mice strains throughout a 6 month treatment with beryllium particles. Because of the availability of high-throughput proteomics, we will also identify

  7. MO-G-BRF-09: Investigating Magnetic Field Dose Effects in Mice: A Monte Carlo Study

    SciTech Connect (OSTI)

    Rubinstein, A; Guindani, M; Followill, D; Melancon, A; Hazle, J; Court, L

    2014-06-15

    Purpose: In MRI-linac treatments, radiation dose distributions are affected by magnetic fields, especially at high-density/low-density interfaces. Radiobiological consequences of magnetic field dose effects are presently unknown; therefore, preclinical studies are needed to ensure the safe clinical use of MRI-linacs. This study investigates the optimal combination of beam energy and magnetic field strength needed for preclinical murine studies. Methods: The Monte Carlo code MCNP6 was used to simulate the effects of a magnetic field when irradiating a mouse-sized lung phantom with a 1.0cmx1.0cm photon beam. Magnetic field effects were examined using various beam energies (225kVp, 662keV[Cs-137], and 1.25MeV[Co-60]) and magnetic field strengths (0.75T, 1.5T, and 3T). The resulting dose distributions were compared to Monte Carlo results for humans with various field sizes and patient geometries using a 6MV/1.5T MRI-linac. Results: In human simulations, the addition of a 1.5T magnetic field caused an average dose increase of 49% (range:36%60%) to lung at the soft tissue-to-lung interface and an average dose decrease of 30% (range:25%36%) at the lung-to-soft tissue interface. In mouse simulations, the magnetic fields had no effect on the 225kVp dose distribution. The dose increases for the Cs-137 beam were 12%, 33%, and 49% for 0.75T, 1.5T, and 3.0T magnetic fields, respectively while the dose decreases were 7%, 23%, and 33%. For the Co-60 beam, the dose increases were 14%, 45%, and 41%, and the dose decreases were 18%, 35%, and 35%. Conclusion: The magnetic field dose effects observed in mouse phantoms using a Co-60 beam with 1.5T or 3T fields and a Cs-137 beam with a 3T field compare well with those seen in simulated human treatments with an MRI-linac. These irradiator/magnet combinations are suitable for preclinical studies investigating potential biological effects of delivering radiation therapy in the presence of a magnetic field. Partially funded by Elekta.

  8. Modulation of keratinocyte expression of antioxidants by 4-hydroxynonenal, a lipid peroxidation end product

    SciTech Connect (OSTI)

    Zheng, Ruijin; Heck, Diane E.; Mishin, Vladimir; Black, Adrienne T.; Shakarjian, Michael P.; Kong, Ah-Ng Tony; Laskin, Debra L.; Laskin, Jeffrey D.

    2014-03-01

    4-Hydroxynonenal (4-HNE) is a lipid peroxidation end product generated in response to oxidative stress in the skin. Keratinocytes contain an array of antioxidant enzymes which protect against oxidative stress. In these studies, we characterized 4-HNE-induced changes in antioxidant expression in mouse keratinocytes. Treatment of primary mouse keratinocytes and PAM 212 keratinocytes with 4-HNE increased mRNA expression for heme oxygenase-1 (HO-1), catalase, NADPH:quinone oxidoreductase (NQO1) and glutathione S-transferase (GST) A1-2, GSTA3 and GSTA4. In both cell types, HO-1 was the most sensitive, increasing 8698 fold within 6 h. Further characterization of the effects of 4-HNE on HO-1 demonstrated concentration- and time-dependent increases in mRNA and protein expression which were maximum after 6 h with 30 ?M. 4-HNE stimulated keratinocyte Erk1/2, JNK and p38 MAP kinases, as well as PI3 kinase. Inhibition of these enzymes suppressed 4-HNE-induced HO-1 mRNA and protein expression. 4-HNE also activated Nrf2 by inducing its translocation to the nucleus. 4-HNE was markedly less effective in inducing HO-1 mRNA and protein in keratinocytes from Nrf2 ?/? mice, when compared to wild type mice, indicating that Nrf2 also regulates 4-HNE-induced signaling. Western blot analysis of caveolar membrane fractions isolated by sucrose density centrifugation demonstrated that 4-HNE-induced HO-1 is localized in keratinocyte caveolae. Treatment of the cells with methyl-?-cyclodextrin, which disrupts caveolar structure, suppressed 4-HNE-induced HO-1. These findings indicate that 4-HNE modulates expression of antioxidant enzymes in keratinocytes, and that this can occur by different mechanisms. Changes in expression of keratinocyte antioxidants may be important in protecting the skin from oxidative stress. - Highlights: Lipid peroxidation generates 4-hydroxynonenal, a reactive aldehyde. 4-HNE induces antioxidant proteins in mouse keratinocytes. Induction of antioxidant proteins

  9. Predicting carcinogenicity of diverse chemicals using probabilistic neural network modeling approaches

    SciTech Connect (OSTI)

    Singh, Kunwar P.; Gupta, Shikha; Rai, Premanjali

    2013-10-15

    Robust global models capable of discriminating positive and non-positive carcinogens; and predicting carcinogenic potency of chemicals in rodents were developed. The dataset of 834 structurally diverse chemicals extracted from Carcinogenic Potency Database (CPDB) was used which contained 466 positive and 368 non-positive carcinogens. Twelve non-quantum mechanical molecular descriptors were derived. Structural diversity of the chemicals and nonlinearity in the data were evaluated using Tanimoto similarity index and BrockDechertScheinkman statistics. Probabilistic neural network (PNN) and generalized regression neural network (GRNN) models were constructed for classification and function optimization problems using the carcinogenicity end point in rat. Validation of the models was performed using the internal and external procedures employing a wide series of statistical checks. PNN constructed using five descriptors rendered classification accuracy of 92.09% in complete rat data. The PNN model rendered classification accuracies of 91.77%, 80.70% and 92.08% in mouse, hamster and pesticide data, respectively. The GRNN constructed with nine descriptors yielded correlation coefficient of 0.896 between the measured and predicted carcinogenic potency with mean squared error (MSE) of 0.44 in complete rat data. The rat carcinogenicity model (GRNN) applied to the mouse and hamster data yielded correlation coefficient and MSE of 0.758, 0.71 and 0.760, 0.46, respectively. The results suggest for wide applicability of the inter-species models in predicting carcinogenic potency of chemicals. Both the PNN and GRNN (inter-species) models constructed here can be useful tools in predicting the carcinogenicity of new chemicals for regulatory purposes. - Graphical abstract: Figure (a) shows classification accuracies (positive and non-positive carcinogens) in rat, mouse, hamster, and pesticide data yielded by optimal PNN model. Figure (b) shows generalization and predictive abilities

  10. Environmental Survey Report for ORNL: Small Mammal Abundance and Distribution Survey Oak Ridge National Environmental Research Park 2009 - 2010

    SciTech Connect (OSTI)

    Giffen, Neil R; Reasor, R. Scott; Campbell, Claire L.

    2009-12-01

    Sherman and pitfall traps. In total 227 small mammals representing nine species were captured during the course of the study. The most common species found in the study was the white-footed mouse (Peromyscus leucopus). The least common species found were the deer mouse (Peromyscus maniculatus), meadow jumping mouse (Zapus hudsonius), woodland vole (Microtus pinetorum), and northern short-tailed shrew (Blarina brevicauda).

  11. DEVELOPMENT OF AN EMAT IN-LINE INSPECTION SYSTEM FOR DETECTION, DISCRIMINATION, AND GRADING OF STRESS CORROSION CRACKING IN PIPELINES

    SciTech Connect (OSTI)

    Jeff Aron; Jeff Jia; Bruce Vance; Wen Chang; Raymond Pohler; Jon Gore; Stuart Eaton; Adrian Bowles; Tim Jarman

    2005-02-01

    This report describes prototypes, measurements, and results for a project to develop a prototype pipeline in-line inspection (ILI) tool that uses electromagnetic acoustic transducers (EMATs) to detect and grade stress corrosion cracking (SCC). The introduction briefly provides motivation and describes SCC, gives some background on EMATs and guided ultrasonic waves, and reviews promising results of a previous project using EMATs for SCC. The experimental section then describes lab measurement techniques and equipment, the lab mouse and prototypes for a mule, and scan measurements made on SCC. The mouse was a moveable and compact EMAT setup. The prototypes were even more compact circuits intended to be pulled or used in an ILI tool. The purpose of the measurements was to determine the best modes, transduction, and processing to use, to characterize the transducers, and to prove EMATs and mule components could produce useful results. Next, the results section summarizes the measurements and describes the mouse scans, processing, prototype circuit operating parameters, and performance for SH0 scans. Results are given in terms of specifications--like SNR, power, insertion loss--and parametric curves--such as signal amplitude versus magnetic bias or standoff, reflection or transmission coefficients versus crack depth. Initially, lab results indicated magnetostrictive transducers using both SH0 and SV1 modes would be worthwhile to pursue in a practical ILI system. However, work with mule components showed that SV1 would be too dispersive, so SV1 was abandoned. The results showed that reflection measurements, when normalized by the direct arrival are sensitive to and correlated with SCC. This was not true for transmission measurements. Processing yields a high data reduction, almost 60 to 1, and permits A and C scan display techniques and software already in use for pipeline inspection. An analysis of actual SH0 scan results for SCC of known dimensions showed that length

  12. A novel synthetic derivative of melatonin, 5-hydroxy-2’-isobutyl-streptochlorin (HIS), inhibits inflammatory responses via regulation of TRIF-dependent signaling and inflammasome activation

    SciTech Connect (OSTI)

    Shim, Do-Wan; Shin, Hee Jae; Han, Ji-Won; Ji, Young-Eun; Jang, Cheol-Hun; Koppula, Sushruta; Kang, Tae-Bong; Lee, Kwang-Ho

    2015-04-15

    Melatonin is substantially reported to possess anti-inflammatory properties. In the present study, we synthesized a novel melatonin derivative, 5-hydroxy-2′-isobutyl-streptochlorin (HIS), which displayed superior anti-inflammatory properties to its parent compound. Further, we explored its underlying mechanisms in cellular and experimental animal models. Lipopolysaccharide was used to induce in vitro inflammatory responses in RAW 264.7 macrophages. LPS-primed macrophages were pulsed with biologically unrelated toxic molecules to evaluate the role of HIS on inflammasome activation. In vivo verifications were carried out using acute lung injury (ALI) and Escherichia coli-induced septic shock mouse models. HIS inhibited the production of proinflammatory mediators and cytokines such as nitric oxide, cyclooxygenase 2, IL-1β, IL-6 and TNF-α in LPS-stimulated RAW 264.7 macrophages. HIS suppressed the infiltration of immune cells into the lung and the production of pro-inflammatory cytokines such as IL-6 and TNF-α in broncho-alveolar lavage fluid in the ALI mouse model. Mechanistic studies revealed that the inhibitory effects of HIS were mediated through the regulation of the TIR domain-containing, adaptor-inducing, interferon-β (TRIF)-dependent signaling pathway from toll-like receptors. Further, HIS attenuated IL-1β secretion via the inhibition of NLRP3 inflammasome activation independent of mitochondrial ROS production. Furthermore, HIS suppressed IL-1β, IL-6 and interferon-β production in peritoneal lavage in the Escherichia coli-induced sepsis mouse model. In conclusion, HIS exerted potent anti-inflammatory effects via the regulation of TRIF-dependent signaling and inflammasome activation. Notably, the superior anti-inflammatory properties of this derivative compared with its parent compound could be a promising lead for treating various inflammatory-mediated diseases. - Highlights: • Νovel compound, 5-hydroxy-2′-isobutyl-streptochlorin (HIS) was

  13. An integrated distributed processing interface for supercomputers and workstations

    SciTech Connect (OSTI)

    Campbell, J.; McGavran, L.

    1989-01-01

    Access to documentation, communication between multiple processes running on heterogeneous computers, and animation of simulations of engineering problems are typically weak in most supercomputer environments. This presentation will describe how we are improving this situation in the Computer Research and Applications group at Los Alamos National Laboratory. We have developed a tool using UNIX filters and a SunView interface that allows users simple access to documentation via mouse driven menus. We have also developed a distributed application that integrated a two point boundary value problem on one of our Cray Supercomputers. It is controlled and displayed graphically by a window interface running on a workstation screen. Our motivation for this research has been to improve the usual typewriter/static interface using language independent controls to show capabilities of the workstation/supercomputer combination. 8 refs.

  14. Applications in Data-Intensive Computing

    SciTech Connect (OSTI)

    Shah, Anuj R.; Adkins, Joshua N.; Baxter, Douglas J.; Cannon, William R.; Chavarría-Miranda, Daniel; Choudhury, Sutanay; Gorton, Ian; Gracio, Deborah K.; Halter, Todd D.; Jaitly, Navdeep; Johnson, John R.; Kouzes, Richard T.; Macduff, Matt C.; Marquez, Andres; Monroe, Matthew E.; Oehmen, Christopher S.; Pike, William A.; Scherrer, Chad; Villa, Oreste; Webb-Robertson, Bobbie-Jo M.; Whitney, Paul D.; Zuljevic, Nino

    2010-04-01

    This book chapter, to be published in Advances in Computers, Volume 78, in 2010 describes applications of data intensive computing (DIC). This is an invited chapter resulting from a previous publication on DIC. This work summarizes efforts coming out of the PNNL's Data Intensive Computing Initiative. Advances in technology have empowered individuals with the ability to generate digital content with mouse clicks and voice commands. Digital pictures, emails, text messages, home videos, audio, and webpages are common examples of digital content that are generated on a regular basis. Data intensive computing facilitates human understanding of complex problems. Data-intensive applications provide timely and meaningful analytical results in response to exponentially growing data complexity and associated analysis requirements through the development of new classes of software, algorithms, and hardware.

  15. Development of Oral Fomulation of SCV-07 for Use in Tuberculosis

    SciTech Connect (OSTI)

    2007-11-16

    An evaluation of the immunomodulatory peptide SCV-07 was conducted as a possible therapeutic treatment for tuberculosis. This evaluation included mouse models, clinical trials and various forms of the drug such as liquid injection and development of an oral pill. It was found that SCV-07 significantly increased the survival rate of animals infected with lethal doses of Mycobacterium bovis. It enhanced the functional activity of macrophages in a dose-dependent fashion. The combination of SCV-07 with bacteriostatic drugs, such as izoniazid, was particularly effective. Phase II clinical trials in a TB clinic demonstrated that the usage of the injection form of SCV-07 for lung TB treatment in combination with standard chemotherapy decreased the quantity of patients with positive sputum assays for Mycobacteria, promoted healing of cavities in lungs, stabilized parameters of cell immunity, and resulted in a significant improvement in the general condition of patients. Clinical trials results of the oral drug form are still being evaluated.

  16. Phase contrast portal imaging using synchrotron radiation

    SciTech Connect (OSTI)

    Umetani, K.; Kondoh, T.

    2014-07-15

    Microbeam radiation therapy is an experimental form of radiation treatment with great potential to improve the treatment of many types of cancer. We applied a synchrotron radiation phase contrast technique to portal imaging to improve targeting accuracy for microbeam radiation therapy in experiments using small animals. An X-ray imaging detector was installed 6.0 m downstream from an object to produce a high-contrast edge enhancement effect in propagation-based phase contrast imaging. Images of a mouse head sample were obtained using therapeutic white synchrotron radiation with a mean beam energy of 130 keV. Compared to conventional portal images, remarkably clear images of bones surrounding the cerebrum were acquired in an air environment for positioning brain lesions with respect to the skull structure without confusion with overlapping surface structures.

  17. Using the Gene Ontology to Enrich Biological Pathways

    SciTech Connect (OSTI)

    Sanfilippo, Antonio P.; Baddeley, Robert L.; Beagley, Nathaniel; McDermott, Jason E.; Riensche, Roderick M.; Taylor, Ronald C.; Gopalan, Banu

    2009-12-10

    Most current approaches to automatic pathway generation are based on a reverse engineering approach in which pathway plausibility is solely derived from microarray gene expression data. These approaches tend to lack in generality and offer no independent validation as they are too reliant on the pathway observables that guide pathway generation. By contrast, alternative approaches that use prior biological knowledge to validate pathways inferred from gene expression data may err in the opposite direction as the prior knowledge is usually not sufficiently tuned to the pathology of focus. In this paper, we present a novel pathway generation approach that combines insights from the reverse engineering and knowledge-based approaches to increase the biological plausibility of automatically generated regulatory networks and describe an application of this approach to transcriptional data from a mouse model of neuroprotection during stroke.

  18. Reconstructing cerebrovascular networks under local physiological constraints by integer programming

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Rempfler, Markus; Schneider, Matthias; Ielacqua, Giovanna D.; Xiao, Xianghui; Stock, Stuart R.; Klohs, Jan; Szekely, Gabor; Andres, Bjoern; Menze, Bjoern H.

    2015-04-23

    We introduce a probabilistic approach to vessel network extraction that enforces physiological constraints on the vessel structure. The method accounts for both image evidence and geometric relationships between vessels by solving an integer program, which is shown to yield the maximum a posteriori (MAP) estimate to the probabilistic model. Starting from an over-connected network, it is pruning vessel stumps and spurious connections by evaluating the local geometry and the global connectivity of the graph. We utilize a high-resolution micro computed tomography (µCT) dataset of a cerebrovascular corrosion cast to obtain a reference network and learn the prior distributions of ourmore » probabilistic model. As a result, we perform experiments on micro magnetic resonance angiography (µMRA) images of mouse brains and discuss properties of the networks obtained under different tracking and pruning approaches.« less

  19. Low excitatory innervation balances high intrinsic excitability of immature dentate neurons

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Dieni, Cristina V.; Panichi, Roberto; Aimone, James B.; Kuo, Chay T.; Wadiche, Jacques I.; Overstreet-Wadiche, Linda

    2016-04-20

    Persistent neurogenesis in the dentate gyrus produces immature neurons with high intrinsic excitability and low levels of inhibition that are predicted to be more broadly responsive to afferent activity than mature neurons. Mounting evidence suggests that these immature neurons are necessary for generating distinct neural representations of similar contexts, but it is unclear how broadly responsive neurons help distinguish between similar patterns of afferent activity. Here we show that stimulation of the entorhinal cortex in mouse brain slices paradoxically generates spiking of mature neurons in the absence of immature neuron spiking. Immature neurons with high intrinsic excitability fail to spikemore » due to insufficient excitatory drive that results from low innervation rather than silent synapses or low release probability. Here, our results suggest that low synaptic connectivity prevents immature neurons from responding broadly to cortical activity, potentially enabling excitable immature neurons to contribute to sparse and orthogonal dentate representations.« less

  20. Properties of zirconia thin films deposited by laser ablation

    SciTech Connect (OSTI)

    Cancea, V. N.; Filipescu, M.; Colceag, D.; Dinescu, M.; Mustaciosu, C.

    2013-11-13

    Zirconia thin films have been deposited by laser ablation of a ceramic ZrO{sub 2} target in vacuum or in oxygen background at 0.01 mbar. The laser beam generated by an ArF laser (λ=193 nm, ν=40 Hz) has been focalized on the target through a spherical lens at an incident angle of 45°. The laser fluence has been established to a value from 2.0 to 3.4 Jcm{sup −2}. A silicon (100) substrate has been placed parallel to the target, at a distance of 4 cm, and subsequently has been heated to temperatures ranging between 300 °C and 600 °C. Thin films morphology has been characterized by atomic force microscopy and secondary ion mass spectrometry. Biocompatibility of these thin films has been assessed by studying the cell attachment of L929 mouse fibroblasts.

  1. Protein A suppresses immune responses during Staphylococcus aureus bloodstream infection in guinea pigs

    SciTech Connect (OSTI)

    Kim, Hwan Keun; Falugi, Fabiana; Thomer, Lena; Missiakas, Dominique M.; Schneewind, Olaf

    2015-01-06

    Staphylococcus aureus infection is not associated with the development of protective immunity, and disease relapses occur frequently. We hypothesize that protein A, a factor that binds immunoglobulin Fcγ and cross-links VH3 clan B cell receptors (IgM), is the staphylococcal determinant for host immune suppression. To test this, vertebrate IgM was examined for protein A cross-linking. High VH3 binding activity occurred with human and guinea immunoglobulin, whereas mouse and rabbit immunoglobulins displayed little and no binding, respectively. Establishing a guinea pig model of S. aureus bloodstream infection, we show that protein A functions as a virulence determinant and suppresses host B cell responses. Immunization with SpAKKAA, which cannot bind immunoglobulin, elicits neutralizing antibodies that enable guinea pigs to develop protective immunity.

  2. Protein A suppresses immune responses during Staphylococcus aureus bloodstream infection in guinea pigs

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Kim, Hwan Keun; Falugi, Fabiana; Thomer, Lena; Missiakas, Dominique M.; Schneewind, Olaf

    2015-01-06

    Staphylococcus aureus infection is not associated with the development of protective immunity, and disease relapses occur frequently. We hypothesize that protein A, a factor that binds immunoglobulin Fcγ and cross-links VH3 clan B cell receptors (IgM), is the staphylococcal determinant for host immune suppression. To test this, vertebrate IgM was examined for protein A cross-linking. High VH3 binding activity occurred with human and guinea immunoglobulin, whereas mouse and rabbit immunoglobulins displayed little and no binding, respectively. Establishing a guinea pig model of S. aureus bloodstream infection, we show that protein A functions as a virulence determinant and suppresses host Bmore » cell responses. Immunization with SpAKKAA, which cannot bind immunoglobulin, elicits neutralizing antibodies that enable guinea pigs to develop protective immunity.« less

  3. Laboratory evaluation of the hazard to wood mice, Apodemus sylvaticus, from the agricultural use of methiocarb molluscicide pellets

    SciTech Connect (OSTI)

    Tarrant, K.A.; Westlake, G.E.

    1988-01-01

    Laboratory studies have been carried out to determine the toxicity of methiocarb pellets to wild trapped wood mice in order to provide some background data prior to any further evaluation of hazard in the field. In this study, wood mice were exposed to dry and to dampened methiocarb pellets in order to reproduce field trial application conditions. Field observations of methiocarb pellets indicate that the physical character changes under dry and wet weather conditions. This may affect their relative attractiveness and potential toxicity to wood mice. The laboratory assessment of exposed wood mice included measurement of brain esterase activities, methiocarb residues in selected mouse tissue, carcasses, and histological evaluation of kidney, liver and lungs.

  4. Institute for Molecular Medicine Research Program

    SciTech Connect (OSTI)

    Phelps, Michael E

    2012-12-14

    The objectives of the project are the development of new Positron Emission Tomography (PET) imaging instrumentation, chemistry technology platforms and new molecular imaging probes to examine the transformations from normal cellular and biological processes to those of disease in pre-clinical animal models. These technology platforms and imaging probes provide the means to: 1. Study the biology of disease using pre-clinical mouse models and cells. 2. Develop molecular imaging probes for imaging assays of proteins in pre-clinical models. 3. Develop imaging assays in pre-clinical models to provide to other scientists the means to guide and improve the processes for discovering new drugs. 4. Develop imaging assays in pre-clinical models for others to use in judging the impact of drugs on the biology of disease.

  5. Enhanced-locality fiber-optic two-photon-fluorescence live-brain interrogation

    SciTech Connect (OSTI)

    Fedotov, I. V.; Doronina-Amitonova, L. V.; Sidorov-Biryukov, D. A.; Fedotov, A. B.; Anokhin, K. V.; Kilin, S. Ya.; Sakoda, K.; Zheltikov, A. M.

    2014-02-24

    Two-photon excitation is shown to substantially enhance the locality of fiber-based optical interrogation of strongly scattering biotissues. In our experiments, a high-numerical-aperture, large-core-are fiber probe is used to deliver the 200-fs output of a 100-MHz mode-locked ytterbium fiber laser to samples of live mouse brain, induce two-photon fluorescence of nitrogen–vacancy centers in diamond markers in brain sample. Fiber probes with a high numerical aperture and a large core area are shown to enable locality enhancement in fiber-laser–fiber-probe two-photon brain excitation and interrogation without sacrificing the efficiency of fluorescence response collection.

  6. DEVELOPMENT OF AN INSPECTION PLATFORM AND A SUITE OF SENSORS FOR ASSESSING CORROSION AND MECHANICAL DAMAGE ON UNPIGGABLE TRANSMISSION MAINS

    SciTech Connect (OSTI)

    George C. Vradis; William Leary

    2004-03-01

    The National Energy Technology Laboratory of the US Department of Energy (under Award DE-FC26-02NT41645) and the NYSEARCH Committee of the Northeast Gas Association (previous the New York Gas Group), have sponsored research to develop a robotic pipeline inspection system capable of navigation through the typical physical and operational obstacles that make transmission and distribution pipelines unpiggable. The research contractors, Foster-Miller and GE Oil & Gas (PII North America) have performed an engineering study and developed a conceptual design that meets all the requirements for navigating and inspecting unpiggable transmission pipelines. Based on Foster-Miller's previous efforts developing the Pipe Mouse robot, the RoboScan inspection robot (Figure ES-1) meets the navigational and physical challenges of unpiggable pipelines through an innovative modular platform design, segmented MFL inspection modules and improvements to the inter-module coupling design.

  7. Structural Genomics of Protein Phosphatases

    SciTech Connect (OSTI)

    Almo,S.; Bonanno, J.; Sauder, J.; Emtage, S.; Dilorenzo, T.; Malashkevich, V.; Wasserman, S.; Swaminathan, S.; Eswaramoorthy, S.; et al

    2007-01-01

    The New York SGX Research Center for Structural Genomics (NYSGXRC) of the NIGMS Protein Structure Initiative (PSI) has applied its high-throughput X-ray crystallographic structure determination platform to systematic studies of all human protein phosphatases and protein phosphatases from biomedically-relevant pathogens. To date, the NYSGXRC has determined structures of 21 distinct protein phosphatases: 14 from human, 2 from mouse, 2 from the pathogen Toxoplasma gondii, 1 from Trypanosoma brucei, the parasite responsible for African sleeping sickness, and 2 from the principal mosquito vector of malaria in Africa, Anopheles gambiae. These structures provide insights into both normal and pathophysiologic processes, including transcriptional regulation, regulation of major signaling pathways, neural development, and type 1 diabetes. In conjunction with the contributions of other international structural genomics consortia, these efforts promise to provide an unprecedented database and materials repository for structure-guided experimental and computational discovery of inhibitors for all classes of protein phosphatases.

  8. Threatened and Endangered Species Habitat Management Plan for Los Alamos National Laboratory

    SciTech Connect (OSTI)

    Keller, David Charles; Hathcock, Charles Dean

    2015-11-17

    Los Alamos National Laboratory’s (LANL) Threatened and Endangered Species Habitat Management Plan (HMP) fulfills a commitment made to the U.S. Department of Energy (DOE) in the “Final Environmental Impact Statement for the Dual-Axis Radiographic Hydrodynamic Test Facility Mitigation Action Plan” (DOE 1996). The HMP received concurrence from the U.S. Fish and Wildlife Service (USFWS) in 1999 (USFWS consultation numbers 2-22-98-I-336 and 2-22-95-I-108). This 2015 update retains the management guidelines from the 1999 HMP for listed species, updates some descriptive information, and adds the New Mexico Meadow Jumping Mouse (Zapus hudsonius luteus) and Yellow-billed Cuckoo (Coccyzus americanus) which were federally listed in 2014 (Keller 2015: USFWS consultation number 02ENNM00- 2015-I-0538).

  9. Modification of the effects of continuous low dose rate irradiation by concurrent chemotherapy infusion

    SciTech Connect (OSTI)

    Fu, K.K.; Rayner, P.A.; Lam, K.N.

    1984-08-01

    The combined effects of continuous low dose rate irradiation (CLDRI) and concurrent infusion of bleomycin, cyclophosphamide, cis-platinum, 5-fluorouracil, actinomycin D, and mitomycin C were studied in the SCC VII/SF tumor, a squamous cell carcinoma and the jejunal crypt cells in the mouse. For the SCC VII/SF tumor, enhanced cell killing was seen with each of the six drugs when infused concurrently with CLDRI; the greatest enhancement was seen with mitomycin C and cis-platinum. For the jejunal crypt cells, enhanced cell killing was seen primarily with bleomycin. The authors results suggest a therapeutic gain with concurrent CLDRI and chemotherapy infusion for five of the six chemotherapeutic drugs studied with the exception of bleomycin.

  10. Structural and Functional Profiling of the Human Histone Methyltransferase SMYD3

    SciTech Connect (OSTI)

    Foreman, Kenneth W.; Brown, Mark; Park, Frances; Emtage, Spencer; Harriss, June; Das, Chhaya; Zhu, Li; Crew, Andy; Arnold, Lee; Shaaban, Salam; Tucker, Philip

    2012-10-23

    The SET and MYND Domain (SMYD) proteins comprise a unique family of multi-domain SET histone methyltransferases that are implicated in human cancer progression. Here we report an analysis of the crystal structure of the full length human SMYD3 in a complex with an analog of the S-adenosyl methionine (SAM) methyl donor cofactor. The structure revealed an overall compact architecture in which the 'split-SET' domain adopts a canonical SET domain fold and closely assembles with a Zn-binding MYND domain and a C-terminal superhelical 9 ?-helical bundle similar to that observed for the mouse SMYD1 structure. Together, these structurally interlocked domains impose a highly confined binding pocket for histone substrates, suggesting a regulated mechanism for its enzymatic activity. Our mutational and biochemical analyses confirm regulatory roles of the unique structural elements both inside and outside the core SET domain and establish a previously undetected preference for trimethylation of H4K20.

  11. Cloning of fragments of novel homeobox genes expressed during regeneration in planarians

    SciTech Connect (OSTI)

    Lukyanov, K.A.; Tarabykin, V.S.; Potapov, V.K.

    1994-11-01

    The polymerase chain reaction with degenerate primers corresponding to the most conservative amino acids 16-21 (ELEKEF) and 49-54 (WPQNRR) of the Antennapedia class homeodomains was used for the amplification of cDNA from regenerating planarians (asexual race of Dugesia tigrina). A total of six new Antennapedia-like homeobox sequences, designated Dutarh-1-Dutarh-6 (Dugesia tigrina asexual race homeobox gene), have been identified. Their comparison with other homeobox genes using a Genebee software (the EMBL Data Library) showed that all sequences except Dutarh-6 belong to the Antennapedia class. Dutarh-6 is closely related to a recently described novel homeobox gene subfamily which includes mouse mesodermal homeobox genes Max-1 and Max-2 and rat homeobox gene Gax. 17 refs., 2 figs.

  12. rVISTA for Comparative Sequence-Based Discovery of Functional Transcription Factor Binding Sites

    SciTech Connect (OSTI)

    Loots, Gabriela G.; Ovcharenko, Ivan; Pachter, Lior; Dubchak, Inna; Rubin, Edward M.

    2002-03-08

    Identifying transcriptional regulatory elements represents a significant challenge in annotating the genomes of higher vertebrates. We have developed a computational tool, rVISTA, for high-throughput discovery of cis-regulatory elements that combines transcription factor binding site prediction and the analysis of inter-species sequence conservation. Here, we illustrate the ability of rVISTA to identify true transcription factor binding sites through the analysis of AP-1 and NFAT binding sites in the 1 Mb well-annotated cytokine gene cluster1 (Hs5q31; Mm11). The exploitation of orthologous human-mouse data set resulted in the elimination of 95 percent of the 38,000 binding sites predicted upon analysis of the human sequence alone, while it identified 87 percent of the experimentally verified binding sites in this region.

  13. {open_quotes}The effects of diabetes on the activity of the enzyme glutamine: fructose-6-phosphate amindotransferase{close_quotes}

    SciTech Connect (OSTI)

    Nelson, S.P.

    1994-12-31

    Hexsoamine synthetic pathway (HexNSP) controls the supply of essential substrates for glycoprotein synthesis. In vitro studies suggest that increased flux of glucose via the hexsoamine synthetic pathway may play a role in glucose induced insulin resistance of glucose transport. Glutamine: fructose-6-phosphate amindotransferase (GFAT) controls flux into the hexsoamine synthetic pathway; the major products are UDPN-acetylhexosamines (UDP.HexNac=UDP.GlcNAc= UDP.GalNac). I examined whether diabetes ({approximately} 7 days post intravenous streptozotocin, and genetically linked) affects the activity of glutamine: fructose-6-phosphate in rat and mouse skeletal muscle in vivo. Nucleotide linked HexNAc were analyzed by high pressure liquid chromatography(HPLC) in deproteinized hind limb muscle extracts.

  14. Six degree of freedom sensor

    DOE Patents [OSTI]

    Vann, C.S.

    1999-03-16

    This small, non-contact optical sensor increases the capability and flexibility of computer controlled machines by detecting its relative position to a workpiece in all six degrees of freedom (DOF). At a fraction of the cost, it is over 200 times faster and up to 25 times more accurate than competing 3-DOF sensors. Applications range from flexible manufacturing to a 6-DOF mouse for computers. Until now, highly agile and accurate machines have been limited by their inability to adjust to changes in their tasks. By enabling them to sense all six degrees of position, these machines can now adapt to new and complicated tasks without human intervention or delay--simplifying production, reducing costs, and enhancing the value and capability of flexible manufacturing. 3 figs.

  15. Apolipoprotein gene involved in lipid metabolism

    DOE Patents [OSTI]

    Rubin, Edward; Pennacchio, Len A.

    2007-07-03

    Methods and materials for studying the effects of a newly identified human gene, APOAV, and the corresponding mouse gene apoAV. The sequences of the genes are given, and transgenic animals which either contain the gene or have the endogenous gene knocked out are described. In addition, single nucleotide polymorphisms (SNPs) in the gene are described and characterized. It is demonstrated that certain SNPs are associated with diseases involving lipids and triglycerides and other metabolic diseases. These SNPs may be used alone or with SNPs from other genes to study individual risk factors. Methods for intervention in lipid diseases, including the screening of drugs to treat lipid-related or diabetic diseases are also disclosed.

  16. Six degree of freedom sensor

    DOE Patents [OSTI]

    Vann, Charles S.

    1999-01-01

    This small, non-contact optical sensor increases the capability and flexibility of computer controlled machines by detecting its relative position to a workpiece in all six degrees of freedom (DOF). At a fraction of the cost, it is over 200 times faster and up to 25 times more accurate than competing 3-DOF sensors. Applications range from flexible manufacturing to a 6-DOF mouse for computers. Until now, highly agile and accurate machines have been limited by their inability to adjust to changes in their tasks. By enabling them to sense all six degrees of position, these machines can now adapt to new and complicated tasks without human intervention or delay--simplifying production, reducing costs, and enhancing the value and capability of flexible manufacturing.

  17. Palmitoylation of SARS-CoV S protein is necessary for partitioning into detergent-resistant membranes and cell-cell fusion but not interaction with M protein

    SciTech Connect (OSTI)

    McBride, Corrin E.; Machamer, Carolyn E.

    2010-09-15

    Coronaviruses are enveloped RNA viruses that generally cause mild disease in humans. However, the recently emerged coronavirus that caused severe acute respiratory syndrome (SARS-CoV) is the most pathogenic human coronavirus discovered to date. The SARS-CoV spike (S) protein mediates virus entry by binding cellular receptors and inducing fusion between the viral envelope and the host cell membrane. Coronavirus S proteins are palmitoylated, which may affect function. Here, we created a non-palmitoylated SARS-CoV S protein by mutating all nine cytoplasmic cysteine residues. Palmitoylation of SARS-CoV S was required for partitioning into detergent-resistant membranes and for cell-cell fusion. Surprisingly, however, palmitoylation of S was not required for interaction with SARS-CoV M protein. This contrasts with the requirement for palmitoylation of mouse hepatitis virus S protein for interaction with M protein and may point to important differences in assembly and infectivity of these two coronaviruses.

  18. Reconstructing cerebrovascular networks under local physiological constraints by integer programming

    SciTech Connect (OSTI)

    Rempfler, Markus; Schneider, Matthias; Ielacqua, Giovanna D.; Xiao, Xianghui; Stock, Stuart R.; Klohs, Jan; Szekely, Gabor; Andres, Bjoern; Menze, Bjoern H.

    2015-04-23

    We introduce a probabilistic approach to vessel network extraction that enforces physiological constraints on the vessel structure. The method accounts for both image evidence and geometric relationships between vessels by solving an integer program, which is shown to yield the maximum a posteriori (MAP) estimate to the probabilistic model. Starting from an over-connected network, it is pruning vessel stumps and spurious connections by evaluating the local geometry and the global connectivity of the graph. We utilize a high-resolution micro computed tomography (µCT) dataset of a cerebrovascular corrosion cast to obtain a reference network and learn the prior distributions of our probabilistic model. As a result, we perform experiments on micro magnetic resonance angiography (µMRA) images of mouse brains and discuss properties of the networks obtained under different tracking and pruning approaches.

  19. Systematic identification of genes and transduction pathways involved in radio-adaptive response

    SciTech Connect (OSTI)

    Wu, Honglu

    2015-05-22

    Low doses of radiation have been shown to protect against the biological effects of later exposure to toxic levels of radiation. In this study, we propose to identify the molecular mechanisms of this adaptive response by systematically identifying the genes that play a role in radio-protection. In the original proposal, a human cell line that is well-documented to exhibit the radio-adaptive effect was to be used. In this revised study plan, we will use a mouse model, C57BL/6, which has also been well investigated for radio-adaptation. The goal of the proposed study is to enhance our understanding of cellular responses to low doses of radiation exposure at the molecular level.

  20. Augmenting drug–carrier compatibility improves tumour nanotherapy efficacy

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Zhao, Yiming; Fay, Francois; Hak, Sjoerd; Manuel Perez-Aguilar, Jose; Sanchez-Gaytan, Brenda L.; Goode, Brandon; Duivenvoorden, Raphael; de Lange Davies, Catharina; Bjorkoy, Astrid; Weinstein, Harel; et al

    2016-04-13

    A major goal of cancer nanotherapy is to use nanoparticles as carriers for targeted delivery of anti-tumour agents. The drug–carrier association after intravenous administration is essential for efficient drug delivery to the tumour. However, a large number of currently available nanocarriers are self-assembled nanoparticles whose drug-loading stability is critically affected by the in vivo environment. Here we used in vivo FRET imaging to systematically investigate how drug–carrier compatibility affects drug release in a tumour mouse model. We found the drug’s hydrophobicity and miscibility with the nanoparticles are two independent key parameters that determine its accumulation in the tumour. Next, wemore » applied these findings to improve chemotherapeutic delivery by augmenting the parent drug’s compatibility; as a result, we achieved better antitumour efficacy. Lastly, our results help elucidate nanomedicines’ in vivo fate and provide guidelines for efficient drug delivery.« less