National Library of Energy BETA

Sample records for dna damage response

  1. Ubiquitylation, neddylation and the DNA damage response

    E-Print Network [OSTI]

    Brown, Jessica S.; Jackson, Stephen P.

    2015-04-01

    , collectively termed the DNA damage response (DDR), requires the recruitment and subsequent post-translational modification (PTM) of a complex network of proteins. Ubiquitin and the ubiquitin-like protein (UBL) SUMO have established roles in regulating...

  2. Functional role of p53 N-terminal phosphorylation in regulating the p53 response to DNA damage

    E-Print Network [OSTI]

    Chao, Connie

    2006-01-01

    the p53 Responses to DNA Damage. Proc. Natl. Acad. Sci. USAapoptosis following DNA damage. EMBO J. 19, 4967-4975. Chao,Herrlich, P. (1999). DNA damage induced p53 stabilization:

  3. Reconstitution of the cellular response to DNA damage in vitro using damage-activated extracts from mammalian cells

    SciTech Connect (OSTI)

    Roper, Katherine; Coverley, Dawn

    2012-03-10

    In proliferating mammalian cells, DNA damage is detected by sensors that elicit a cellular response which arrests the cell cycle and repairs the damage. As part of the DNA damage response, DNA replication is inhibited and, within seconds, histone H2AX is phosphorylated. Here we describe a cell-free system that reconstitutes the cellular response to DNA double strand breaks using damage-activated cell extracts and naieve nuclei. Using this system the effect of damage signalling on nuclei that do not contain DNA lesions can be studied, thereby uncoupling signalling and repair. Soluble extracts from G1/S phase cells that were treated with etoposide before isolation, or pre-incubated with nuclei from etoposide-treated cells during an in vitro activation reaction, restrain both initiation and elongation of DNA replication in naieve nuclei. At the same time, H2AX is phosphorylated in naieve nuclei in a manner that is dependent upon the phosphatidylinositol 3-kinase-like protein kinases. Notably, phosphorylated H2AX is not focal in naieve nuclei, but is evident throughout the nucleus suggesting that in the absence of DNA lesions the signal is not amplified such that discrete foci can be detected. This system offers a novel screening approach for inhibitors of DNA damage response kinases, which we demonstrate using the inhibitors wortmannin and LY294002. -- Highlights: Black-Right-Pointing-Pointer A cell free system that reconstitutes the response to DNA damage in the absence of DNA lesions. Black-Right-Pointing-Pointer Damage-activated extracts impose the cellular response to DNA damage on naieve nuclei. Black-Right-Pointing-Pointer PIKK-dependent response impacts positively and negatively on two separate fluorescent outputs. Black-Right-Pointing-Pointer Can be used to screen for inhibitors that impact on the response to damage but not on DNA repair. Black-Right-Pointing-Pointer LY294002 and wortmannin demonstrate the system's potential as a pathway focused screening approach.

  4. ATM Phosphorylates and Activates the Transcription Factor MEF2D for Neuronal Survival in Response to DNA Damage

    E-Print Network [OSTI]

    Chan, Shing Fai

    2009-01-01

    by ATM in response to DNA damage. Science, 281, 1674-1677.J. and Kastan M. B. (2003). DNA damage activates ATM throughgene product causes oxidative damage in target organs. Proc.

  5. Cellular responses against DNA damaged by platinum anticancer drugs

    E-Print Network [OSTI]

    Jung, Yongwon, 1977-

    2005-01-01

    The anticancer activity of platinum-based drugs such as cisplatin, carboplatin, and oxaliplatin is mediated by their ability to attack DNA such that generated adducts trigger numerous cellular responses. A better understanding ...

  6. A CRTC2 Repressor Role Regulates DNA Damage Response Genes in Germinal Center B-cells

    E-Print Network [OSTI]

    Schontzler, Olivia Tersa

    2012-01-01

    as DNA damage response (DDR) genes throughout this proposal.binding to and repression of DDR genes. Secondly, repressorcontextual repressor role on DDR genes as part of an ATM

  7. Functional analysis of p53 N-terminal phosphorylation and C-terminal multiple posttranslational modifications in regulating p53 responses to DNA damage

    E-Print Network [OSTI]

    Feng, Lijin

    2006-01-01

    C. W. , and Appella, E. DNA damage activates p53 through aby ATM in Response to DNA Damage. Science 133.Shieh, S. Y. ,Y. , and Prives, C. DNA damage-induced phosphorylation of

  8. Conserved and Unconventional Responses to DNA Damage in Tetrahymena 

    E-Print Network [OSTI]

    Sandoval Oporto, Pamela

    2012-07-16

    ). B-type cyclins (Clb1-6) are necessary for S phase and mitotic progression. Cdk1- Clb5 and Cdk-Clb6, promote DNA replication and are the most active complex in regulating DNA synthesis, their levels are highly maintained until the end of the cell..., the presence of specifics CDK-inhibitors, such Sic1 and Far1 during G1 phase, promote the accumulation of high levels of inactive CDK prior to triggering a cellular transition and offers an aditionalregulation of CDK (Alberghina et al., 2004; Schwob et al...

  9. Nucleolar exit of RNF8 and BRCA1 in response to DNA damage

    SciTech Connect (OSTI)

    Guerra-Rebollo, Marta; Mateo, Francesca; Franke, Kristin; Huen, Michael S.Y.; Lopitz-Otsoa, Fernando; Rodriguez, Manuel S.; Plans, Vanessa; Thomson, Timothy M.

    2012-11-01

    The induction of DNA double-strand breaks (DSBs) elicits a plethora of responses that redirect many cellular functions to the vital task of repairing the injury, collectively known as the DNA damage response (DDR). We have found that, in the absence of DNA damage, the DSB repair factors RNF8 and BRCA1 are associated with the nucleolus. Shortly after exposure of cells to {gamma}-radiation, RNF8 and BRCA1 translocated from the nucleolus to damage foci, a traffic that was reverted several hours after the damage. RNF8 interacted through its FHA domain with the ribosomal protein RPSA, and knockdown of RPSA caused a depletion of nucleolar RNF8 and BRCA1, suggesting that the interaction of RNF8 with RPSA is critical for the nucleolar localization of these DDR factors. Knockdown of RPSA or RNF8 impaired bulk protein translation, as did {gamma}-irradiation, the latter being partially countered by overexpression of exogenous RNF8. Our results suggest that RNF8 and BRCA1 are anchored to the nucleolus through reversible interactions with RPSA and that, in addition to its known functions in DDR, RNF8 may play a role in protein synthesis, possibly linking the nucleolar exit of this factor to the attenuation of protein synthesis in response to DNA damage. -- Highlights: Black-Right-Pointing-Pointer RNF8 and BRCA1 are associated with the nucleolus of undamaged cells. Black-Right-Pointing-Pointer Upon {gamma}-radiation, RNF8 and BRCA1 are translocated from the nucleolus to damage foci. Black-Right-Pointing-Pointer The ribosomal protein RPSA anchors RNF8 to the nucleolus. Black-Right-Pointing-Pointer RNF8 may play previously unsuspected roles in protein synthesis.

  10. Telomere Regulation in Arabidopsis thaliana by the CST Capping Complex and DNA Damage Response Proteins 

    E-Print Network [OSTI]

    Boltz, Kara A.

    2013-09-11

    The ends of chormosomes are capped by telomeres, which distinguish the termini from damaged DNA. Paradoxically, DNA repair proteins are also required for telomere maintenance. How DNA repair pathways are regulated to ...

  11. Persistent activation of DNA damage signaling in response to complex mixtures of PAHs in air particulate matter

    SciTech Connect (OSTI)

    Jarvis, Ian W.H.; Bergvall, Christoffer; Bottai, Matteo; Westerholm, Roger; Stenius, Ulla; Dreij, Kristian

    2013-02-01

    Complex mixtures of polycyclic aromatic hydrocarbons (PAHs) are present in air particulate matter (PM) and have been associated with many adverse human health effects including cancer and respiratory disease. However, due to their complexity, the risk of exposure to mixtures is difficult to estimate. In the present study the effects of binary mixtures of benzo[a]pyrene (BP) and dibenzo[a,l]pyrene (DBP) and complex mixtures of PAHs in urban air PM extracts on DNA damage signaling was investigated. Applying a statistical model to the data we observed a more than additive response for binary mixtures of BP and DBP on activation of DNA damage signaling. Persistent activation of checkpoint kinase 1 (Chk1) was observed at significantly lower BP equivalent concentrations in air PM extracts than BP alone. Activation of DNA damage signaling was also more persistent in air PM fractions containing PAHs with more than four aromatic rings suggesting larger PAHs contribute a greater risk to human health. Altogether our data suggests that human health risk assessment based on additivity such as toxicity equivalency factor scales may significantly underestimate the risk of exposure to complex mixtures of PAHs. The data confirms our previous findings with PAH-contaminated soil (Niziolek-Kierecka et al., 2012) and suggests a possible role for Chk1 Ser317 phosphorylation as a biological marker for future analyses of complex mixtures of PAHs. -- Highlights: ? Benzo[a]pyrene (BP), dibenzo[a,l]pyrene (DBP) and air PM PAH extracts were compared. ? Binary mixture of BP and DBP induced a more than additive DNA damage response. ? Air PM PAH extracts were more potent than toxicity equivalency factor estimates. ? Larger PAHs (> 4 rings) contribute more to the genotoxicity of PAHs in air PM. ? Chk1 is a sensitive marker for persistent activation of DNA damage signaling from PAH mixtures.

  12. RhoJ Regulates Melanoma Chemoresistance by Suppressing Pathways that Sense DNA Damage

    E-Print Network [OSTI]

    Ho, Hsiang; Aruri, Jayavani; Kapadia, Rubina; Mehr, Hootan; White, Michael A.; Ganesan, Anand K.

    2012-01-01

    Pathways that Sense DNA Damage $watermark-text Hsiang Ho 1 ,16. Roos WP, Kaina B. DNA damage-induced apoptosis: FromDNA lesions to the DNA damage response and apoptosis. Cancer

  13. The role of mismatch repair and recombination in cellular responses to the DNA damaging anticancer drug Cisplatin

    E-Print Network [OSTI]

    Zdraveski, Zoran Z. (Zoran Zare), 1969-

    2002-01-01

    Cisplatin (cis-diamminedichloroplatinum(ll)) is a successful DNA-damaging anticancer drug used in the treatment of testicular, ovarian and other tumors. In the past decade, several mutually non-exclusive hypotheses have ...

  14. Anc1 : a new player in the cellular response to DNA damage

    E-Print Network [OSTI]

    Erlich, Rachel L

    2007-01-01

    The continuity of living organisms depends on their ability to protect their genomes from a constant assault by internal and external sources of damage. To this end, cells have developed a variety of mechanisms to avoid ...

  15. Response of DNA repair and replication systems to exocyclic nucleic acid base damage

    E-Print Network [OSTI]

    ?r?v?stava, Nidhi

    2012-01-01

    Genomes experience an often hostile environment that creates a vast array of damages that can give rise to myriad biological outcomes. Fortunately, cells are equipped with networks such as direct reversal, base excision ...

  16. DNA damage responses in the context of the cell division cycle

    E-Print Network [OSTI]

    Giunta, Simona

    2010-11-16

    cycle describes the process whereby a cell replicates its DNA and divides to produce two genetically identical daughter cells. Essentially, two types of cell cycle control mechanisms exist: a cascade of protein phosphorylations that act as an “engine... and inducing displacement of base pairing (Patel and Picha, 2000). (3) In the ‘rotatory pump model’, similarly to the torsional model, MCM acts as rotary motor but the rotatory movement along the DNA helical axis occurs at a distance from the replication...

  17. Method for assaying clustered DNA damages

    DOE Patents [OSTI]

    Sutherland, Betsy M.

    2004-09-07

    Disclosed is a method for detecting and quantifying clustered damages in DNA. In this method, a first aliquot of the DNA to be tested for clustered damages with one or more lesion-specific cleaving reagents under conditions appropriate for cleavage of the DNA to produce single-strand nicks in the DNA at sites of damage lesions. The number average molecular length (Ln) of double stranded DNA is then quantitatively determined for the treated DNA. The number average molecular length (Ln) of double stranded DNA is also quantitatively determined for a second, untreated aliquot of the DNA. The frequency of clustered damages (.PHI..sub.c) in the DNA is then calculated.

  18. Chk2 regulates transcription-independent p53-mediated apoptosis in response to DNA damage

    SciTech Connect (OSTI)

    Chen Chen [Department of Geriatric Research, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8522 (Japan); Shimizu, Shigeomi [Department of Post-Genomics Diseases, Osaka University Medical School, Suita, Osaka 565-0871 (Japan); Tsujimoto, Yoshihide [Department of Post-Genomics Diseases, Osaka University Medical School, Suita, Osaka 565-0871 (Japan); Motoyama, Noboru [Department of Geriatric Research, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8522 (Japan)]. E-mail: motoyama@nils.go.jp

    2005-07-29

    The tumor suppressor protein p53 plays a central role in the induction of apoptosis in response to genotoxic stress. The protein kinase Chk2 is an important regulator of p53 function in mammalian cells exposed to ionizing radiation (IR). Cells derived from Chk2-deficient mice are resistant to the induction of apoptosis by IR, and this resistance has been thought to be a result of the defective transcriptional activation of p53 target genes. It was recently shown, however, that p53 itself and histone H1.2 translocate to mitochondria and thereby induces apoptosis in a transcription-independent manner in response to IR. We have now examined whether Chk2 also regulates the transcription-independent induction of apoptosis by p53 and histone H1.2. The reduced ability of IR to induce p53 stabilization in Chk2-deficient thymocytes was associated with a marked impairment of p53 and histone H1 translocation to mitochondria. These results suggest that Chk2 regulates the transcription-independent mechanism of p53-mediated apoptosis by inducing stabilization of p53 in response to IR.

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

    E-Print Network [OSTI]

    Marchetti, Francesco

    2009-01-01

    Kastan, M. B. (1997). DNA damage induces phosphorylation ofby ATM in response to DNA damage. Science 281, Barber, R. ,Nussenzweig, A. (2002). DNA damage-induced G2-M checkpoint

  20. Systems Biology Model of Interactions Between Tissue Growth Factors and DNA Damage Pathways: Low Dose Response and Cross-Talk in TGFbeta and ATM Signaling

    SciTech Connect (OSTI)

    O'Neill, Peter; Anderson, Jennifer

    2014-10-02

    The etiology of radiation carcinogenesis has been described in terms of aberrant changes that span several levels of biological organization. Growth factors regulate many important cellular and tissue functions including apoptosis, differentiation and proliferation. A variety of genetic and epigenetic changes of growth factors have been shown to contribute to cancer initiation and progression. It is known that cellular and tissue damage to ionizing radiation is in part initiated by the production of reactive oxygen species, which can activate cytokine signaling, and the DNA damage response pathways, most notably the ATM signaling pathway. Recently the transforming growth factor ? (TGF?) pathway has been shown to regulate or directly interact with the ATM pathway in the response to radiation. The relevance of this interaction with the ATM pathway is not known although p53 becomes phosphorylated and DNA damage responses are involved. However, growth factor interactions with DNA damage responses have not been elucidated particularly at low doses and further characterization of their relationship to cancer processes is warranted. Our goal will be to use a systems biology approach to mathematically and experimentally describe the low dose responses and cross-talk between the ATM and TGF? pathways initiated by low and high LET radiation. We will characterize ATM and TGF? signaling in epithelial and fibroblast cells using 2D models and ultimately extending to 3D organotypic cell culture models to begin to elucidate possible differences that may occur for different cell types and/or inter-cellular communication. We will investigate the roles of the Smad and Activating transcription factor 2 (ATF2) proteins as the potential major contributors to cross- talk between the TGF? and ATM pathways, and links to cell cycle control and/or the DNA damage response, and potential differences in their responses at low and high doses. We have developed various experimental approaches to apply to these problems using confocal microscopy and flow cytometry to detail changes at low dose/dose-rate in order to understand individual cell responses, and will establish our mathematical models based on the experimental findings resulting from changes in DNA repair, apoptosis and proliferation.

  1. Micropatterned cell arrays for detecting DNA damage

    E-Print Network [OSTI]

    Mittal, Sukant

    2008-01-01

    Numerous agents are capable of interacting with DNA and damaging it. Permanent changes in the DNA structure can be both mutagenic and cytotoxic; therefore, methods to measure the susceptibility of cells to mutations are ...

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

    E-Print Network [OSTI]

    Marchetti, Francesco

    2008-01-01

    male germ cells handle DNA damage? Toxicol. Appl. Pharmacol.strand breaks and DNA base damage at different cellularrelationship to genetic damage, Mutat. Res. 216 (1989) 221-

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

    E-Print Network [OSTI]

    Marchetti, Francesco

    2008-01-01

    male germ cells handle DNA damage? Toxicol. Appl. Pharmacol.strand breaks and DNA base damage at different cellularrelationship to genetic damage, Mutat. Res. 216 (1989) 221-

  4. Recognition of Platinum?DNA Damage by Poly(ADP-ribose) Polymerase-1

    E-Print Network [OSTI]

    Zhu, Guangyu

    Poly(ADP-ribose) polymerase-1 (PARP-1) was recently identified as a platinum?DNA damage response protein. To investigate the properties of binding of PARP-1 to different platinum?DNA adducts in greater detail, biotinylated ...

  5. Characterizing the DNA damage response by cell tracking algorithms and cell features classification using high-content time-lapse analysis

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

    Georgescu, Walter; Osseiran, Alma; Rojec, Maria; Liu, Yueyong; Bombrun, Maxime; Tang, Jonathan; Costes, Sylvain V.; Huen, Michael Shing-Yan

    2015-06-24

    Traditionally, the kinetics of DNA repair have been estimated using immunocytochemistry by labeling proteins involved in the DNA damage response (DDR) with fluorescent markers in a fixed cell assay. However, detailed knowledge of DDR dynamics across multiple cell generations cannot be obtained using a limited number of fixed cell time-points. Here we report on the dynamics of 53BP1 radiation induced foci (RIF) across multiple cell generations using live cell imaging of non-malignant human mammary epithelial cells (MCF10A) expressing histone H2B-GFP and the DNA repair protein 53BP1-mCherry. Using automatic extraction of RIF imaging features and linear programming techniques, we were ablemore »to characterize detailed RIF kinetics for 24 hours before and 24 hours after exposure to low and high doses of ionizing radiation. High-content-analysis at the single cell level over hundreds of cells allows us to quantify precisely the dose dependence of 53BP1 protein production, RIF nuclear localization and RIF movement after exposure to X-ray. Using elastic registration techniques based on the nuclear pattern of individual cells, we could describe the motion of individual RIF precisely within the nucleus. We show that DNA repair occurs in a limited number of large domains, within which multiple small RIFs form, merge and/or resolve with random motion following normal diffusion law. Large foci formation is shown to be mainly happening through the merging of smaller RIF rather than through growth of an individual focus. We estimate repair domain sizes of 7.5 to 11 µm2 with a maximum number of ~15 domains per MCF10A cell. This work also highlights DDR which are specific to doses larger than 1 Gy such as rapid 53BP1 protein increase in the nucleus and foci diffusion rates that are significantly faster than for spontaneous foci movement. We hypothesize that RIF merging reflects a "stressed" DNA repair process that has been taken outside physiological conditions when too many DSB occur at once. High doses of ionizing radiation lead to RIF merging into repair domains which in turn increases DSB proximity and misrepair. Such finding may therefore be critical to explain the supralinear dose dependence for chromosomal rearrangement and cell death measured after exposure to ionizing radiation.« less

  6. Characterizing the DNA damage response by cell tracking algorithms and cell features classification using high-content time-lapse analysis

    SciTech Connect (OSTI)

    Georgescu, Walter; Osseiran, Alma; Rojec, Maria; Liu, Yueyong; Bombrun, Maxime; Tang, Jonathan; Costes, Sylvain V.; Huen, Michael Shing-Yan

    2015-06-24

    Traditionally, the kinetics of DNA repair have been estimated using immunocytochemistry by labeling proteins involved in the DNA damage response (DDR) with fluorescent markers in a fixed cell assay. However, detailed knowledge of DDR dynamics across multiple cell generations cannot be obtained using a limited number of fixed cell time-points. Here we report on the dynamics of 53BP1 radiation induced foci (RIF) across multiple cell generations using live cell imaging of non-malignant human mammary epithelial cells (MCF10A) expressing histone H2B-GFP and the DNA repair protein 53BP1-mCherry. Using automatic extraction of RIF imaging features and linear programming techniques, we were able to characterize detailed RIF kinetics for 24 hours before and 24 hours after exposure to low and high doses of ionizing radiation. High-content-analysis at the single cell level over hundreds of cells allows us to quantify precisely the dose dependence of 53BP1 protein production, RIF nuclear localization and RIF movement after exposure to X-ray. Using elastic registration techniques based on the nuclear pattern of individual cells, we could describe the motion of individual RIF precisely within the nucleus. We show that DNA repair occurs in a limited number of large domains, within which multiple small RIFs form, merge and/or resolve with random motion following normal diffusion law. Large foci formation is shown to be mainly happening through the merging of smaller RIF rather than through growth of an individual focus. We estimate repair domain sizes of 7.5 to 11 µm2 with a maximum number of ~15 domains per MCF10A cell. This work also highlights DDR which are specific to doses larger than 1 Gy such as rapid 53BP1 protein increase in the nucleus and foci diffusion rates that are significantly faster than for spontaneous foci movement. We hypothesize that RIF merging reflects a "stressed" DNA repair process that has been taken outside physiological conditions when too many DSB occur at once. High doses of ionizing radiation lead to RIF merging into repair domains which in turn increases DSB proximity and misrepair. Such finding may therefore be critical to explain the supralinear dose dependence for chromosomal rearrangement and cell death measured after exposure to ionizing radiation.

  7. IN VITRO MUTAGENIC AND DNA AND CHROMOSOMAL DAMAGE ACTIVITY BY...

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

    IN VITRO MUTAGENIC AND DNA AND CHROMOSOMAL DAMAGE ACTIVITY BY SURFACTANT DISPERSION OR SOLVENT EXTRACT OF A REFERENCE DIESEL EXHAUST PARTICULATE MATERIAL IN VITRO MUTAGENIC AND DNA...

  8. Single cell trapping and DNA damage analysis using microwell arrays

    E-Print Network [OSTI]

    Wood, David

    With a direct link to cancer, aging, and heritable diseases as well as a critical role in cancer treatment, the importance of DNA damage is well-established. The intense interest in DNA damage in applications ranging from ...

  9. Regulation of DNA damage tolerance : studies of the translesion synthesis DNA ploymerase eta in Saccharomyces cerevisiae

    E-Print Network [OSTI]

    Woodruff, Rachel Van Etten

    2008-01-01

    All organisms must control the effects of DNA damage to protect the integrity of their genomes. In addition to DNA repair, this requires DNA damage tolerance pathways, which allow the continuation of essential processes ...

  10. 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.

  11. 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.

  12. DNA Damage Causes p27^(Kip1) Accumulation Through COP1 Signaling 

    E-Print Network [OSTI]

    Choi, Hyun Ho

    2014-05-06

    p27 is a critical CDK inhibitor involved in cell cycle regulation, but its response to DNA damage remains unclear. Constitutive photomorphogenesis 1 (COP1), a p53- targeting E3 ubiquitin ligase, is downregulated by DNA damage, but the biological...

  13. The dynamic interplay between DNA damage and metabolism : the metabolic fate and transport of DNA lesions and novel DNA damage derived from intermediary metabolism

    E-Print Network [OSTI]

    Jumpathong, Watthanachai

    2014-01-01

    The work presented in this thesis explores two novel and complementary facets of endogenous DNA damage: the development of biomarkers of inflammation based on metabolites of DNA damage products and the formation of DNA ...

  14. DNA-damage-mediated remodeling of normal and tumor microenvironments modulates cell survival

    E-Print Network [OSTI]

    Gilbert, Luke A. (Luke Andrew)

    2012-01-01

    Chemotherapeutic regimens involve the systemic administration of genotoxic compounds that induce cancer cell death via well-established DNA damage response signaling networks. While modern chemotherapeutic regimens can be ...

  15. Chimeric proteins for detection and quantitation of DNA mutations, DNA sequence variations, DNA damage and DNA mismatches

    DOE Patents [OSTI]

    McCutchen-Maloney, Sandra L. (Pleasanton, CA)

    2002-01-01

    Chimeric proteins having both DNA mutation binding activity and nuclease activity are synthesized by recombinant technology. The proteins are of the general formula A-L-B and B-L-A where A is a peptide having DNA mutation binding activity, L is a linker and B is a peptide having nuclease activity. The chimeric proteins are useful for detection and identification of DNA sequence variations including DNA mutations (including DNA damage and mismatches) by binding to the DNA mutation and cutting the DNA once the DNA mutation is detected.

  16. DNA damage in cells exhibiting radiation-induced genomic instability

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

    Keszenman, Deborah J.; Kolodiuk, Lucia; Baulch, Janet E.

    2015-02-22

    Cells exhibiting radiation induced genomic instability exhibit varied spectra of genetic and chromosomal aberrations. Even so, oxidative stress remains a common theme in the initiation and/or perpetuation of this phenomenon. Isolated oxidatively modified bases, abasic sites, DNA single strand breaks and clustered DNA damage are induced in normal mammalian cultured cells and tissues due to endogenous reactive oxygen species generated during normal cellular metabolism in an aerobic environment. While sparse DNA damage may be easily repaired, clustered DNA damage may lead to persistent cytotoxic or mutagenic events that can lead to genomic instability. In this study, we tested the hypothesismore »that DNA damage signatures characterised by altered levels of endogenous, potentially mutagenic, types of DNA damage and chromosomal breakage are related to radiation-induced genomic instability and persistent oxidative stress phenotypes observed in the chromosomally unstable progeny of irradiated cells. The measurement of oxypurine, oxypyrimidine and abasic site endogenous DNA damage showed differences in non-double-strand breaks (DSB) clusters among the three of the four unstable clones evaluated as compared to genomically stable clones and the parental cell line. These three unstable clones also had increased levels of DSB clusters. The results of this study demonstrate that each unstable cell line has a unique spectrum of persistent damage and lead us to speculate that alterations in DNA damage signaling and repair may be related to the perpetuation of genomic instability.« less

  17. Yeast Rad17 Mec3 Ddc1: A sliding clamp for the DNA damage checkpoint

    E-Print Network [OSTI]

    Burgers, Peter M.

    lead to inhibition of the cdk kinases that drive the cell cycle are relatively well understood to cell cycle arrest. Rad24 interacts with the four small subunits of replication factor C (RFC) to form of cellular responses which includes DNA repair, apoptosis, and cell- cycle arrest. The DNA damage checkpoint

  18. Calculation of complex DNA damage induced by ions

    E-Print Network [OSTI]

    Eugene Surdutovich; David C. Gallagher; Andrey V. Solov'yov

    2012-01-27

    This paper is devoted to the analysis of the complex damage of DNA irradiated by ions. The analysis and assessment of complex damage is important because cells in which it occurs are less likely to survive because the DNA repair mechanisms may not be sufficiently effective. We studied the flux of secondary electrons through the surface of nucleosomes and calculated the radial dose and the distribution of clustered damage around the ion's track. The calculated radial dose distribution is compared to simulations. The radial distribution of the complex damage is found to be different from that of the dose. Comparison with experiments may solve the question of what is more lethal for the cell, damage complexity or absorbed energy. We suggest a way to calculate the probability of cell death based on the complexity of the damage. This work is done within the framework of the phenomenon-based multiscale approach to radiation damage by ions.

  19. DNA Damage by Fasicularin Sanjay Dutta, Hideki Abe, Sakae Aoyagi, Chihiro Kibayashi, and Kent S. Gates*,

    E-Print Network [OSTI]

    Gates, Kent. S.

    DNA Damage by Fasicularin Sanjay Dutta, Hideki Abe, Sakae Aoyagi, Chihiro Kibayashi, and Kent S that a DNA repair- deficient cell line is hypersensitive to fasicularin suggest that an ability to damage DNA of DNA damage. For example, oxidatiVe damage at guanine residues can also generate base-labile lesions.13

  20. Nanofoams Response to Radiation Damage

    SciTech Connect (OSTI)

    Fu, Engang [Los Alamos National Laboratory; Serrano De Caro, Magdalena [Los Alamos National Laboratory; Wang, Yongqiang [Los Alamos National Laboratory; Nastasi, Michael [Nebraska Center for Energy Sciences Research, University of Nebraska-Lincoln, NE 68508; Zepeda-Ruiz, Luis [PLS, Lawrence Livermore National Laboratory, Livermore, CA 94551; Bringa, Eduardo M. [CONICET and Inst. Ciencias Basicas, Universidad Nacional de Cuyo, Mendoza, 5500 Argentina; Baldwin, Jon K. [Los Alamos National Laboratory; Caro, Jose A. [Los Alamos National Laboratory

    2012-07-30

    Conclusions of this presentation are: (1) np-Au foams were successfully synthesized by de-alloying process; (2) np-Au foams remain porous structure after Ne ion irradiation to 1 dpa; (3) SFTs were observed in irradiated np-Au foams with highest and intermediate flux, while no SFTs were observed with lowest flux; (4) SFTs were observed in irradiated np-Au foams at RT, whereas no SFTs were observed at LNT irradiation; (5) The diffusivity of vacancies in Au at RT is high enough so that the vacancies have enough time to agglomerate and thus collapse. As a result, SFTs were formed; (6) The high flux created much more damage/time, vacancies don't have enough time to diffuse or recombine. As a result, SFTs were formed.

  1. Engineering a single cell microarray platform for high throughput DNA damage and repair analysis

    E-Print Network [OSTI]

    Weingeist, David McGregor

    2012-01-01

    DNA damage contributes to cancer, aging, and heritable diseases. Ironically, DNA damaging agents are also commonly used in current cancer treatment. We therefore need robust, high throughput, and inexpensive tools for ...

  2. DNA Strand Damage Product Analysis Provides Evidence That the Tumor Cell-Specific Cytotoxin Tirapazamine

    E-Print Network [OSTI]

    Gates, Kent. S.

    DNA Strand Damage Product Analysis Provides Evidence That the Tumor Cell-Specific Cytotoxin DNA strand damage that is initiated by the abstraction of hydrogen atoms from the deoxyribose damage. We find that the action of TPZ on duplex DNA under hypoxic conditions generates 5-methylene-2

  3. A novel role for the transcriptional modulator NusA in DNA repair/damage tolerance pathways in Escherichia coli

    E-Print Network [OSTI]

    Cohen, Susan E., Ph. D. Massachusetts Institute of Technology

    2009-01-01

    All organisms must contend with the consequences of DNA damage, induced by a variety of both endogenous and exogenous sources. Mechanisms of DNA repair and DNA damage tolerance are crucial for cellular survival after DNA ...

  4. Endogenous DNA Damage and Risk of Testicular Germ Cell Tumors

    SciTech Connect (OSTI)

    Cook, M B; Sigurdson, A J; Jones, I M; Thomas, C B; Graubard, B I; Korde, L; Greene, M H; McGlynn, K A

    2008-01-18

    Testicular germ cell tumors (TGCT) are comprised of two histologic groups, seminomas and nonseminomas. We postulated that the possible divergent pathogeneses of these histologies may be partially explained by variable endogenous DNA damage. To assess our hypothesis, we conducted a case-case analysis of seminomas and nonseminomas using the alkaline comet assay to quantify single-strand DNA breaks and alkali-labile sites. The Familial Testicular Cancer study and the U.S. Radiologic Technologists cohort provided 112 TGCT cases (51 seminomas & 61 nonseminomas). A lymphoblastoid cell line was cultured for each patient and the alkaline comet assay was used to determine four parameters: tail DNA, tail length, comet distributed moment (CDM) and Olive tail moment (OTM). Odds ratios (OR) and 95% confidence intervals (95%CI) were estimated using logistic regression. Values for tail length, tail DNA, CDM and OTM were modeled as categorical variables using the 50th and 75th percentiles of the seminoma group. Tail DNA was significantly associated with nonseminoma compared to seminoma (OR{sub 50th percentile} = 3.31, 95%CI: 1.00, 10.98; OR{sub 75th percentile} = 3.71, 95%CI: 1.04, 13.20; p for trend=0.039). OTM exhibited similar, albeit statistically non-significant, risk estimates (OR{sub 50th percentile} = 2.27, 95%CI: 0.75, 6.87; OR{sub 75th percentile} = 2.40, 95%CI: 0.75, 7.71; p for trend=0.12) whereas tail length and CDM showed no association. In conclusion, the results for tail DNA and OTM indicate that endogenous DNA damage levels are higher in patients who develop nonseminoma compared with seminoma. This may partly explain the more aggressive biology and younger age-of-onset of this histologic subgroup compared with the relatively less aggressive, later-onset seminoma.

  5. Inhibition of HAS2 induction enhances the radiosensitivity of cancer cells via persistent DNA damage

    SciTech Connect (OSTI)

    Shen, Yan Nan; Shin, Hyun-Jin; Joo, Hyun-Yoo; Park, Eun-Ran; Kim, Su-Hyeon; Hwang, Sang-Gu; Park, Sang Jun; Kim, Chun-Ho; Lee, Kee-Ho

    2014-01-17

    Highlights: •HAS2 may be a promising target for the radiosensitization of human cancer. •HAS2 is elevated (up to ?10-fold) in irradiated radioresistant and -sensitive cancer cells. •HAS2 knockdown sensitizes cancer cells to radiation. •HAS2 knockdown potentiates irradiation-induced DNA damage and apoptotic death. •Thus, the irradiation-induced up-regulation of HAS2 contributes to the radioresistance of cancer cells. -- Abstract: Hyaluronan synthase 2 (HAS2), a synthetic enzyme for hyaluronan, regulates various aspects of cancer progression, including migration, invasion and angiogenesis. However, the possible association of HAS2 with the response of cancer cells to anticancer radiotherapy, has not yet been elucidated. Here, we show that HAS2 knockdown potentiates irradiation-induced DNA damage and apoptosis in cancer cells. Upon exposure to radiation, all of the tested human cancer cell lines exhibited marked (up to 10-fold) up-regulation of HAS2 within 24 h. Inhibition of HAS2 induction significantly reduced the survival of irradiated radioresistant and -sensitive cells. Interestingly, HAS2 depletion rendered the cells to sustain irradiation-induced DNA damage, thereby leading to an increase of apoptotic death. These findings indicate that HAS2 knockdown sensitizes cancer cells to radiation via persistent DNA damage, further suggesting that the irradiation-induced up-regulation of HAS2 contributes to the radioresistance of cancer cells. Thus, HAS2 could potentially be targeted for therapeutic interventions aimed at radiosensitizing cancer cells.

  6. Balancing repair and tolerance of DNA damage caused by alkylating agents

    E-Print Network [OSTI]

    Fu, Dragony

    Alkylating agents constitute a major class of frontline chemotherapeutic drugs that inflict cytotoxic DNA damage as their main mode of action, in addition to collateral mutagenic damage. Numerous cellular pathways, including ...

  7. Tensile damage response from discrete element virtual testing

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    Tensile damage response from discrete element virtual testing A. DELAPLACE LMT-Cachan, ENS Cachan conditions on brittle materials, damage can generally not be re- duced to a simple scalar. Microcrack into account the damage anisotropy in phenomenological models is a possible option, but the identification

  8. Detection and quantitation of single nucleotide polymorphisms, DNA sequence variations, DNA mutations, DNA damage and DNA mismatches

    DOE Patents [OSTI]

    McCutchen-Maloney, Sandra L. (Pleasanton, CA)

    2002-01-01

    DNA mutation binding proteins alone and as chimeric proteins with nucleases are used with solid supports to detect DNA sequence variations, DNA mutations and single nucleotide polymorphisms. The solid supports may be flow cytometry beads, DNA chips, glass slides or DNA dips sticks. DNA molecules are coupled to solid supports to form DNA-support complexes. Labeled DNA is used with unlabeled DNA mutation binding proteins such at TthMutS to detect DNA sequence variations, DNA mutations and single nucleotide length polymorphisms by binding which gives an increase in signal. Unlabeled DNA is utilized with labeled chimeras to detect DNA sequence variations, DNA mutations and single nucleotide length polymorphisms by nuclease activity of the chimera which gives a decrease in signal.

  9. Damage to Model DNA Fragments from Very Low-Energy (Electrons

    E-Print Network [OSTI]

    Simons, Jack

    Damage to Model DNA Fragments from Very Low-Energy (Electrons Joanna Berdys,, Iwona-mail: simons@chemistry.utah.edu Abstract: Although electrons having enough energy to ionize or electronically suggested that even lower- energy electrons (most recently 1 eV and below) can also damage DNA. The findings

  10. DNA Base Damage by the Antitumor Agent 3-Amino-1,2,4-benzotriazine 1,4-Dioxide (Tirapazamine)

    E-Print Network [OSTI]

    Gates, Kent. S.

    DNA Base Damage by the Antitumor Agent 3-Amino-1,2,4-benzotriazine 1,4-Dioxide (Tirapazamine: Tirapazamine is a bioreductively activated DNA-damaging agent that selectively kills the hypoxic cells found cellular target for tirapazamine; however, the structural nature of the DNA damage inflicted by this drug

  11. Mechanistic investigation of anticancer agents that damage DNA and interact with the estrogen receptor

    E-Print Network [OSTI]

    Gopal, Sreeja

    2009-01-01

    One of the primary goals of cancer chemotherapy is the design of antitumor agents that achieve selective targeting of tumor cells while minimizing toxicity to normal tissues. We have synthesized a series of DNA damaging ...

  12. ALS-associated mutation FUS-R521C causes DNA damage and RNA splicing defects

    E-Print Network [OSTI]

    2014-01-01

    ALS-associated mutation FUS-R521C causes DNA damage and RNAof human wild- type FUS causes progressive motor neuronof human wild- type FUS causes progressive motor neuron

  13. Mechanistic investigation of an anticancer agent that damages DNA and interacts with the androgen receptor

    E-Print Network [OSTI]

    Proffitt, Kyle David

    2009-01-01

    The 11[beta] molecule comprises a ligand for the androgen receptor (AR), which is crucial to progression and survival of many prostate cancers, tethered to a DNA-damaging aniline mustard. The compound was designed to exhibit ...

  14. To be submitted to Continuum Mechanics and Thermodynamics From the onset of damage to rupture: construction of responses with damage

    E-Print Network [OSTI]

    Boyer, Edmond

    To be submitted to Continuum Mechanics and Thermodynamics From the onset of damage to rupture: construction of responses with damage localization for a general class of gradient damage models Kim Pham solutions for the traction problem of an elastic damaging bar. This bar has a softening behavior which obeys

  15. Controlled degradation by ClpXP protease tunes the levels of the excision repair protein UvrA to the extent of DNA damage

    E-Print Network [OSTI]

    Pruteanu, Mihaela

    UV irradiation damages DNA and activates expression of genes encoding proteins helpful for survival under DNA stress. These proteins are often deleterious in the absence of DNA damage. Here, we investigate mechanisms used ...

  16. Cytogenetic status and oxidative DNA-damage induced by atorvastatin in human peripheral blood lymphocytes: Standard and Fpg-modified comet assay

    SciTech Connect (OSTI)

    Gajski, Goran Garaj-Vrhovac, Vera; Orescanin, Visnja

    2008-08-15

    To investigate the genotoxic potential of atorvastatin on human lymphocytes in vitro standard comet assay was used in the evaluation of basal DNA damage and to investigate possible oxidative DNA damage produced by reactive oxygen species (ROS) Fpg-modified version of comet assay was also conducted. In addition to these techniques the new criteria for scoring micronucleus test were applied for more complete detection of baseline damage in binuclear lymphocytes exposed to atorvastatin 80 mg/day in different time periods by virtue of measuring the frequency of micronuclei, nucleoplasmic bridges and nuclear buds. All parameters obtained with the standard comet assay and Fpg-modified comet assay were significantly higher in the treated than in control lymphocytes. The Fpg-modified comet assay showed a significantly greater tail length, tail intensity, and tail moment in all treated lymphocytes than did the standard comet assay, which suggests that oxidative stress is likely to be responsible for DNA damage. DNA damage detected by the standard comet assay indicates that some other mechanism is also involved. In addition to the comet assay, a total number of micronuclei, nucleoplasmic bridges and nuclear buds were significantly higher in the exposed than in controlled lymphocytes. Regression analyses showed a positive correlation between the results obtained by the comet (Fpg-modified and standard) and micronucleus assay. Overall, the study demonstrated that atorvastatin in its highest dose is capable of producing damage on the level of DNA molecule and cell.

  17. Reactive Molecular Dynamics study on the first steps of DNA-damage by free hydroxyl radicals

    E-Print Network [OSTI]

    Abolfath, Ramin M; Brabec, Thomas

    2011-01-01

    We employ a large scale molecular simulation based on bond-order ReaxFF to simulate the chemical reaction and study the damage to a large fragment of DNA-molecule in the solution by ionizing radiation. We illustrate that the randomly distributed clusters of diatomic OH-radicals that are primary products of megavoltage ionizing radiation in water-based systems are the main source of hydrogen-abstraction as well as formation of carbonyl- and hydroxyl-groups in the sugar-moiety that create holes in the sugar-rings. These holes grow up slowly between DNA-bases and DNA-backbone and the damage collectively propagate to DNA single and double strand break.

  18. Nitrative DNA damage induced by multi-walled carbon nanotube via endocytosis in human lung epithelial cells

    SciTech Connect (OSTI)

    Guo, Feiye; Ma, Ning; Horibe, Yoshiteru; Kawanishi, Shosuke; Murata, Mariko; Hiraku, Yusuke

    2012-04-15

    Carbon nanotube (CNT) has a promising usage in the field of material science for industrial purposes because of its unique physicochemical property. However, intraperitoneal administration of CNT was reported to cause mesothelioma in experimental animals. Chronic inflammation may contribute to carcinogenesis induced by fibrous materials. 8-Nitroguanine is a mutagenic DNA lesion formed during inflammation and may play a role in CNT-induced carcinogenesis. In this study, we examined 8-nitroguanine formation in A549 human lung alveolar epithelial cells treated with multi-walled CNT (MWCNT) by fluorescent immunocytochemistry. Both MWCNTs with diameter of 20–30 nm (CNT20) and 40–70 nm (CNT40) significantly induced 8-nitroguanine formation at 5 and 10 ?g/ml (p < 0.05), which persisted for 24 h, although there was no significant difference in DNA-damaging abilities of these MWCNTs. MWCNTs significantly induced the expression of inducible nitric oxide synthase (iNOS) for 24 h (p < 0.05). MWCNTs also significantly increased the level of nitrite, a hydrolysis product of oxidized NO, in the culture supernatant at 4 and 8 h (p < 0.05). MWCNT-induced 8-nitroguanine formation and iNOS expression were largely suppressed by inhibitors of iNOS (1400 W), nuclear factor-?B (Bay11-7082), actin polymerization (cytochalasin D), caveolae-mediated endocytosis (methyl-?-cyclodextrin, MBCD) and clathrin-mediated endocytosis (monodansylcadaverine, MDC). Electron microscopy revealed that MWCNT was mainly located in vesicular structures in the cytoplasm, and its cellular internalization was reduced by MBCD and MDC. These results suggest that MWCNT is internalized into cells via clathrin- and caveolae-mediated endocytosis, leading to inflammatory reactions including iNOS expression and resulting nitrative DNA damage, which may contribute to carcinogenesis. Highlights: ?Multi-walled carbon nanotube (MWCNT) caused DNA damage in A549 cells. ?MWCNT formed 8-nitroguanine, a DNA lesion associated with inflammatory response. ?MWCNT was internalized into cells via caveolin- and clathrin-mediated endocytosis. ?8-Nitroguanine formation and iNOS expression involved these types of endocytosis. ?Internalized MWCNT plays a key role in inflammatory response and DNA damage.

  19. Understanding cell fate decisions in response to 0?-Methylguanine DNA lesions

    E-Print Network [OSTI]

    Noonan, Ericka Marie

    2011-01-01

    The stability of the genome is constantly challenged by both endogenous and exogenous DNA damaging agents. DNA damage, if left unrepaired, can give rise to permanent genetic alterations that ultimately increase our risk ...

  20. Rat colonic reactive oxygen species production and DNA damage are mediated by diet and age 

    E-Print Network [OSTI]

    Henderson, Cara Aletha Everett

    2001-01-01

    increase with age, and it is possible that ROS and/or DNA damage accumulate in aged animals and lead to carcinogenic mutations. Dietary factors, particularly fat and fiber, are important risk modifiers of colon cancer. Differences in the production of ROS...

  1. Genome-Wide Identification and 3D Modeling of Proteins involved in DNA Damage Recognition and Repair (Final Report)

    SciTech Connect (OSTI)

    Ruben A. Abagyan, PhD

    2004-04-15

    OAK-B135 DNA Damage Recognition and Repair (DDR and R) proteins play a critical role in cellular responses to low-dose radiation and are associated with cancer. the authors have performed a systematic, genome-wide computational analysis of genomic data for human genes involved in the DDR and R process. The significant achievements of this project include: (1) Construction of the computational pipeline for searching DDR and R genes, building and validation of 3D models of proteins involved in DDR and R; (2) Functional and structural annotation of the 3D models and generation of comprehensive lists of suggested knock-out mutations; (3) Important improvement of macromolecular docking technology and its application to predict the DNA-Protein complex conformation; (4) Development of a new algorithm for improved analysis of high-density oligonucleotide arrays for gene expression profiling; (5) Construction and maintenance of the DNA Damage Recognition and Repair Database; and (6) Producing 14 research papers (10 published and 4 in preparation).

  2. Protection of cisplatin-induced spermatotoxicity, DNA damage and chromatin abnormality by selenium nano-particles

    SciTech Connect (OSTI)

    Rezvanfar, Mohammad Amin; Rezvanfar, Mohammad Ali; Shahverdi, Ahmad Reza; Ahmadi, Abbas; Baeeri, Maryam; Mohammadirad, Azadeh; Abdollahi, Mohammad

    2013-02-01

    Cisplatin (CIS), an anticancer alkylating agent, induces DNA adducts and effectively cross links the DNA strands and so affects spermatozoa as a male reproductive toxicant. The present study investigated the cellular/biochemical mechanisms underlying possible protective effect of selenium nano-particles (Nano-Se) as an established strong antioxidant with more bioavailability and less toxicity, on reproductive toxicity of CIS by assessment of sperm characteristics, sperm DNA integrity, chromatin quality and spermatogenic disorders. To determine the role of oxidative stress (OS) in the pathogenesis of CIS gonadotoxicity, the level of lipid peroxidation (LPO), antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) and peroxynitrite (ONOO) as a marker of nitrosative stress (NS) and testosterone (T) concentration as a biomarker of testicular function were measured in the blood and testes. Thirty-two male Wistar rats were equally divided into four groups. A single IP dose of CIS (7 mg/kg) and protective dose of Nano-Se (2 mg/kg/day) were administered alone or in combination. The CIS-exposed rats showed a significant increase in testicular and serum LPO and ONOO level, along with a significant decrease in enzymatic antioxidants levels, diminished serum T concentration and abnormal histologic findings with impaired sperm quality associated with increased DNA damage and decreased chromatin quality. Coadministration of Nano-Se significantly improved the serum T, sperm quality, and spermatogenesis and reduced CIS-induced free radical toxic stress and spermatic DNA damage. In conclusion, the current study demonstrated that Nano-Se may be useful to prevent CIS-induced gonadotoxicity through its antioxidant potential. Highlights: ? Cisplatin (CIS) affects spermatozoa as a male reproductive toxicant. ? Effect of Nano-Se on CIS-induced spermatotoxicity was investigated. ? CIS-exposure induces oxidative sperm DNA damage and impairs steroidogenesis. ? Nano-Se retained sperm quality against CIS-induced free radicals toxic stress.

  3. Kinetic gating mechanism of DNA damage recognition by Rad4/XPC

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

    Chen, Xuejing; Velmurugu, Yogambigai; Zheng, Guanqun; Park, Beomseok; Shim, Yoonjung; Kim, Youngchang; Liu, Lili; Van Houten, Bennett; He, Chuan; Ansari, Anjum; et al

    2015-01-06

    The xeroderma pigmentosum C (XPC) complex initiates nucleotide excision repair by recognizing DNA lesions before recruiting downstream factors. How XPC detects structurally diverse lesions embedded within normal DNA is unknown. Here we present a crystal structure that captures the yeast XPC orthologue (Rad4) on a single register of undamaged DNA. The structure shows that a disulphide-tethered Rad4 flips out normal nucleotides and adopts a conformations similar to that seen with damaged DNA. Contrary to many DNA repair enzymes that can directly reject non-target sites as structural misfits, our results suggest that Rad4/XPC uses a kinetic gating mechanism whereby lesion selectivitymore »arises from the kinetic competition between DNA opening and the residence time of Rad4/XPC per site. This mechanism is further supported by measurements of Rad4-induced lesion-opening times using temperature-jump pertubation spectroscopy. Kinetic gating may be a general mechanism used by site-specific DNA-binding proteins to minimize time-consuming interrogations of non-target sites.« less

  4. Plasma induced DNA damage: Comparison with the effects of ionizing radiation

    SciTech Connect (OSTI)

    Lazovi?, S.; Maleti?, D.; Pua?, N.; Malovi?, G.; Petrovi?, Z. Lj.; Leskovac, A.; Filipovi?, J.; Joksi?, G.

    2014-09-22

    We use human primary fibroblasts for comparing plasma and gamma rays induced DNA damage. In both cases, DNA strand breaks occur, but of fundamentally different nature. Unlike gamma exposure, contact with plasma predominantly leads to single strand breaks and base-damages, while double strand breaks are mainly consequence of the cell repair mechanisms. Different cell signaling mechanisms are detected confirming this (ataxia telangiectasia mutated - ATM and ataxia telangiectasia and Rad3 related - ATR, respectively). The effective plasma doses can be tuned to match the typical therapeutic doses of 2?Gy. Tailoring the effective dose through plasma power and duration of the treatment enables safety precautions mainly by inducing apoptosis and consequently reduced frequency of micronuclei.

  5. Quantitative Analysis of Clustered DNA Damages Induced by Silicon Beams of Different Kinetic Energy

    SciTech Connect (OSTI)

    Keszenman D. J.; Keszenman, D.J.; Bennett, P.V.; Sutherland, B.M.; Wilson, P.F.

    2013-05-14

    Humans may b exposed to highly energetic charged particle radiation as a result of medical treatments, occupational activitie or accidental events. In recent years, our increasing presence and burgeoning interest in space exploration beyond low Earth orbit has led to a large increase in the research of the biological effects ofcharged particle radiation typical of that encountered in the space radiation environment. The study of the effects of these types of radiation qualities in terms ofDNA damage induction and repair is fundamental to understand mechanisms both underlying their greater biological effectiveness as we)) as the short and long term risks of health effects such as carcinogenesis, degen rative diseases and premature aging. Charged particle radiation induces a variety of DNA alterations, notably bistranded clustered damages, defined as two or more closely-opposed strand break , oxidized bases or abasic sites within a few helical turns. The induction of such highly complex DNA damage enhances the probability of incorrect or incomplete repair and thus constitutes greater potential for genomic instability, cell death and transformation.

  6. DAMAGE DETECTION BASED ON STRUCTURAL RESPONSE TO TEMPERATURE CHANGES AND MODEL UPDATING

    E-Print Network [OSTI]

    Boyer, Edmond

    DAMAGE DETECTION BASED ON STRUCTURAL RESPONSE TO TEMPERATURE CHANGES AND MODEL UPDATING Marian The paper proposes use of measured structural response to temperature loads for purposes of damage identification. As opposed to the most common approaches, which rely on suppressing temperature effects in damage

  7. Investigations of DNA damage induction and repair resulting from cellular exposure to high dose-rate pulsed proton beams

    SciTech Connect (OSTI)

    Renis, M.; Malfa, G.; Tomasello, B.; Borghesi, M.; Schettino, G.; Favetta, M.; Romano, F.; Cirrone, G. A. P.; Manti, L.

    2013-07-26

    Studies regarding the radiobiological effects of low dose radiation, microbeam irradiation services have been developed in the world and today laser acceleration of protons and heavy ions may be used in radiation therapy. The application of different facilities is essential for studying bystander effects and relating signalling phenomena in different cells or tissues. In particular the use of ion beams results advantageous in cancer radiotherapy compared to more commonly used X-rays, since the ability of ions in delivering lethal amount of doses into the target tumour avoiding or limiting damage to the contiguous healthy tissues. At the INFN-LNS in Catania, a multidisciplinary radiobiology group is strategically structured aimed to develop radiobiological research, finalised to therapeutic applications, compatible with the use of high dose laser-driven ion beams. The characteristic non-continuous dose rates with several orders of magnitude of laser-driven ion beams makes this facility very interesting in the cellular systems' response to ultra-high dose rates with non-conventional pulse time intervals cellular studies. Our group have projected to examine the effect of high dose laser-driven ion beams on two cellular types: foetal fibroblasts (normal control cells) and DU145 (prostate cancer cells), studying the modulation of some different bio-molecular parameters, in particular cell proliferation and viability, DNA damage, redox cellular status, morphological alterations of both the cytoskeleton components and some cell organelles and the possible presence of apoptotic or necrotic cell death. Our group performed preliminary experiments with high energy (60 MeV), dose rate of 10 Gy/min, doses of 1, 2, 3 Gy and LET 1 keV/?m on human foetal fibroblasts (control cells). We observed that cell viability was not influenced by the characteristics of the beam, the irradiation conditions or the analysis time. Conversely, DNA damage was present at time 0, immediately following irradiation in a dose-dependent manner. The analysis of repair capability showed that the cells irradiated with 1 and 2 Gy almost completely recovered from the damage, but not, however, 3 Gy treated cells in which DNA damage was not recovered. In addition, the results indicate the importance of the use of an appropriate control in radiobiological in vitro analysis.

  8. Genome-Wide Identification and 3D Modeling of Proteins involved in DNA Damage Recognition and Repair (Final Report)

    SciTech Connect (OSTI)

    Abagyan, Ruben; An, Jianghong

    2005-08-12

    DNA Damage Recognition and Repair (DDR&R) proteins play a critical role in cellular responses to low-dose radiation and are associated with cancer. We have performed a systematic, genome-wide computational analysis of genomic data for human genes involved in the DDR&R process. The significant achievements of this project include: 1) Construction of the computational pipeline for searching DDR&R genes, building and validation of 3D models of proteins involved in DDR&R; 2) Functional and structural annotation of the 3D models and generation of comprehensive lists of suggested knock-out mutations; and the development of a method to predict the effects of mutations. Large scale testing of technology to identify novel small binding pockets in protein structures leading to new DDRR inhibitor strategies 3) Improvements of macromolecular docking technology (see the CAPRI 1-3 and 4-5 results) 4) Development of a new algorithm for improved analysis of high-density oligonucleotide arrays for gene expression profiling; 5) Construction and maintenance of the DNA Damage Recognition and Repair Database; 6) Producing 15 research papers (12 published and 3 in preparation).

  9. Mechanism for Damage to DNA by Low-Energy Electrons Robyn Barrios, Piotr Skurski, and Jack Simons*

    E-Print Network [OSTI]

    Simons, Jack

    Mechanism for Damage to DNA by Low-Energy Electrons Robyn Barrios, Piotr Skurski, and Jack Simons electronic structure calculations on a portion of DNA, the results of which provide support for a mechanism that produces single-strand breaks (SSBs) with low-energy electrons. This mechanism involves attaching a low

  10. Generation of DNA-Damaging Reactive Oxygen Species via the Autoxidation of Hydrogen Sulfide under Physiologically Relevant

    E-Print Network [OSTI]

    Gates, Kent. S.

    Generation of DNA-Damaging Reactive Oxygen Species via the Autoxidation of Hydrogen Sulfide under found that micromolar concentrations of H2S generated single-strand DNA cleavage. Mechanistic studies indicate that this process involved autoxidation of H2S to generate superoxide, hydrogen peroxide, and

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

    E-Print Network [OSTI]

    Marchetti, Francesco

    2008-01-01

    toxicity studies of 1,3-butadiene in rodents, Environ.developmental toxicity of 1,3-butadiene, Toxicology 113 (response study for 1,3- butadiene-induced dominant lethal

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

    E-Print Network [OSTI]

    Marchetti, Francesco

    2008-01-01

    toxicity studies of 1,3-butadiene in rodents, Environ.developmental toxicity of 1,3-butadiene, Toxicology 113 (response study for 1,3- butadiene-induced dominant lethal

  13. Damage detection for applications undergoing axial (membrane) response

    SciTech Connect (OSTI)

    Duffey, T.A. [Duffey (T.A.), Tijeras, NM (United States); Farrar, C.R.; Doebling, S.W. [Los Alamos National Lab., NM (United States)

    1997-12-01

    This paper extends and applies recently reported damage identification methods, previously utilized for flexural vibrations only, to axial-type vibrations. The methods are applied to an 8-DOF linear spring-mass system, which models a multi-degree-of-freedom axial or membrane system. The goal of the work is to detect damage (as indicated by reduction in stiffness of one or more of the elements) as well as to locate the damage elements. Two damage detection methods were investigated--the change-in-flexibility method and the damage-index method. Both were found to successfully locate the damaged element(s) for 10% reduction in element stiffness. The change-in-flexibility method indicated damage location even when only a limited number of lower modes were included.

  14. Robust damage assessment of multiple cracks based on the Frequency Response Function and the Constitutive Relation

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    Robust damage assessment of multiple cracks based on the Frequency Response Function a damage assessment technique for the non destructive detection and sizing of multiple open cracks in beams, many researchers have performed extensive investigations and damage assess- ment techniques based

  15. Spatiotemporal characterization of ionizing radiation induced DNA damage foci and their relation to chromatin organization

    SciTech Connect (OSTI)

    Costes, Sylvain V; Chiolo, Irene; Pluth, Janice M.; Barcellos-Hoff, Mary Helen; Jakob, Burkhard

    2009-09-15

    DNA damage sensing proteins have been shown to localize to the sites of DSB within seconds to minutes following ionizing radiation (IR) exposure, resulting in the formation of microscopically visible nuclear domains referred to as radiation-induced foci (RIF). This review characterizes the spatio-temporal properties of RIF at physiological doses, minutes to hours following exposure to ionizing radiation, and it proposes a model describing RIF formation and resolution as a function of radiation quality and nuclear densities. Discussion is limited to RIF formed by three interrelated proteins ATM (Ataxia telangiectasia mutated), 53BP1 (p53 binding protein 1) and ?H2AX (phosphorylated variant histone H2AX). Early post-IR, we propose that RIF mark chromatin reorganization, leading to a local nuclear scaffold rigid enough to keep broken DNA from diffusing away, but open enough to allow the repair machinery. We review data indicating clear kinetic and physical differences between RIF emerging from dense and uncondensed regions of the nucleus. At later time post-IR, we propose that persistent RIF observed days following exposure to ionizing radiation are nuclear ?scars? marking permanent disruption of the chromatin architecture. When DNA damage is resolved, such chromatin modifications should not necessarily lead to growth arrest and it has been shown that persistent RIF can replicate during mitosis. Thus, heritable persistent RIF spanning over tens of Mbp may affect the transcriptome of a large progeny of cells. This opens the door for a non DNA mutation-based mechanism of radiation-induced phenotypes.

  16. 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.

  17. Structural health monitoring (SHM) entails the use of structural response data to identify the existence, location, and severity of structural damage. However, damage

    E-Print Network [OSTI]

    Lynch, Jerome P.

    the existence, location, and severity of structural damage. However, damage detection is a challenging problem because damage is a local phenomenon difficult to observe using global measures of structural response. With the existence and location of damage unknown a priori, sensor strategies monitoring the structure

  18. A Mitotic Phosphorylation Feedback Network Connects Cdk1, Plk1, 53BP1, and Chk2 to Inactivate the G2/M DNA Damage Checkpoint

    E-Print Network [OSTI]

    Yaffe, Michael B.

    DNA damage checkpoints arrest cell cycle progression to facilitate DNA repair. The ability to survive genotoxic insults depends not only on the initiation of cell cycle checkpoints but also on checkpoint maintenance. While ...

  19. Damage Threats and Response of Final Optics for Laser-Fusion Power Plants

    E-Print Network [OSTI]

    Tillack, Mark

    Damage Threats and Response of Final Optics for Laser-Fusion Power Plants M. S. Tillack1 , S. A-1597 The final optics for laser-IFE (inertial fusion energy) power plants will be exposed to a variety of damage to be the most serious concerns for a power plant. 1. Introduction Survival of the final optic is one of the most

  20. Silencing of poly(ADP-ribose) glycohydrolase sensitizes lung cancer cells to radiation through the abrogation of DNA damage checkpoint

    SciTech Connect (OSTI)

    Nakadate, Yusuke; Department of Bioengineering, Graduate School of Engineering, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585 ; Kodera, Yasuo; Kitamura, Yuka; Tachibana, Taro; Tamura, Tomohide; Koizumi, Fumiaki

    2013-11-29

    Highlights: •Radiosensitization by PARG silencing was observed in multiple lung cancer cells. •PAR accumulation was enhanced by PARG silencing after DNA damage. •Radiation-induced G2/M arrest and checkpoint activation were impaired by PARG siRNA. -- Abstract: Poly(ADP-ribose) glycohydrolase (PARG) is a major enzyme that plays a role in the degradation of poly(ADP-ribose) (PAR). PARG deficiency reportedly sensitizes cells to the effects of radiation. In lung cancer, however, it has not been fully elucidated. Here, we investigated whether PARG siRNA contributes to an increased radiosensitivity using 8 lung cancer cell lines. Among them, the silencing of PARG induced a radiosensitizing effect in 5 cell lines. Radiation-induced G2/M arrest was largely suppressed by PARG siRNA in PC-14 and A427 cells, which exhibited significantly enhanced radiosensitivity in response to PARG knockdown. On the other hand, a similar effect was not observed in H520 cells, which did not exhibit a radiosensitizing effect. Consistent with a cell cycle analysis, radiation-induced checkpoint signals were not well activated in the PC-14 and A427 cells when treated with PARG siRNA. These results suggest that the increased sensitivity to radiation induced by PARG knockdown occurs through the abrogation of radiation-induced G2/M arrest and checkpoint activation in lung cancer cells. Our findings indicate that PARG could be a potential target for lung cancer treatments when used in combination with radiotherapy.

  1. Removal of N-Alkyl Modifications from N[superscript 2]-Alkylguanine and N[superscript 4]-Alkylcytosine in DNA by the Adaptive Response Protein AlkB

    E-Print Network [OSTI]

    Li, Deyu

    The AlkB enzyme is an Fe(II)- and ?-ketoglutarate-dependent dioxygenase that repairs DNA alkyl lesions by a direct reversal of damage mechanism as part of the adaptive response in E. coli. The reported substrate scope of ...

  2. Predictive storm damage modeling and optimizing crew response to improve storm response operations

    E-Print Network [OSTI]

    Whipple, Sean David

    2014-01-01

    Utility infrastructures are constantly damaged by naturally occurring weather. Such damage results in customer service interruption and repairs are necessary to return the system to normal operation. In most cases these ...

  3. Spin-blockade effect and coherent control of DNA-damage by free radicals: a proposal on bio-spintronics

    E-Print Network [OSTI]

    Abolfath, Ramin M

    2011-01-01

    Coherent control of OH-free radicals interacting with the spin-triplet state of a DNA molecule is investigated. A model Hamiltonian for molecular spin singlet-triplet resonance is developed. We illustrate that the spin-triplet state in DNA molecules can be efficiently populated, as the spin-injection rate can be tuned to be orders of magnitudes greater than the decay rate due to small spin-orbit coupling in organic molecules. Owing to the nano-second life-time of OH free radicals, a non-equilibrium free energy barrier induced by the injected spin triplet state that lasts approximately longer than one-micro second in room temperature can efficiently block the initial Hydrogen abstraction and DNA damage. For a direct demonstration of the spin-blockade effect, a molecular simulation based on an {\\em ab-initio} Car-Parrinello molecular dynamics is deployed.

  4. P450 aromatase alterations and DNA damage as avian pollution biomarkers in cliff and cave swallow breeding near the Rio Grande region, Texas 

    E-Print Network [OSTI]

    Sitzlar, Megan Annette

    2006-04-12

    populations lacking proper water and sewage infrastructure. Cliff (Petrochelidon pyrrhonota) and cave (P. fulva) swallows breeding near the Rio Grande were selected to monitor aromatase activity alterations and DNA damage. Swallows were sampled at six sites...

  5. Earthquake Damage Detection in the Imperial County Services Building III: Analysis of Wave Travel Times via Impulse Response Functions

    E-Print Network [OSTI]

    Southern California, University of

    1 Earthquake Damage Detection in the Imperial County Services Building III: Analysis of Wave Travel characteristics of the structure, and are not sensitive to local damage. Wave travel times between selected changes in such characteristics of response are potentially more sensitive to local damage. In this paper

  6. Combined experimental and computational analysis of DNA damage signaling reveals context-dependent roles for Erk in apoptosis and G1/S arrest after genotoxic stress

    E-Print Network [OSTI]

    Tentner, Andrea R

    Following DNA damage, cells display complex multi-pathway signaling dynamics that connect cell-cycle arrest and DNA repair in G1, S, or G2/M phase with phenotypic fate decisions made between survival, cell-cycle re-entry ...

  7. Manipulation of cellular DNA repair by early adenovirus proteins

    E-Print Network [OSTI]

    Orazio, Nicole Ise

    2010-01-01

    The function of BLM in the DDR and in processing of DNA endscellular DNA damage response (DDR) functions to inhibit thespecific components of the DDR, and provides insight into

  8. 1934 Research Paper C. elegans RAD-5/CLK-2 defines a new DNA damage

    E-Print Network [OSTI]

    Gartner, Anton

    ,pathways that lead to a transient cell cycle arrest that allows for DNA United Kingdom. Institute for Molecular Department of Biology, Coker Hall, University of and life span. However, clk-2(qm37) is the only C. elegans

  9. DNA Damage Induced by Low-Energy Electrons: Electron Transfer and Diffraction

    SciTech Connect (OSTI)

    Zheng Yi; Wagner, J. Richard; Sanche, Leon [Groupe de Recherche en Sciences des Radiations, Faculte de Medecine, Universite de Sherbrooke, Sherbrooke, QC J1H 5N4 (Canada)

    2006-05-26

    Thin films of the short single strand of DNA, GCAT, in which guanine (G) or adenine (A) have been removed, were bombarded under vacuum by 4 to 15 eV electrons. The fragments corresponding to base release and strand breaks (SB) were analyzed by high performance liquid chromatography and their yields compared with those obtained from unmodified GCAT. From such a comparison, it is shown that, using GCAT as a model system (1) most SB result from electron capture by DNA bases followed by electron transfer to the phosphate group and (2) the initial capture probability depends on the coherence of the electron wave within the tetramer.

  10. Neddylation promotes ubiquitylation and release of Ku from DNA damage sites

    E-Print Network [OSTI]

    Brown, Jessica S.; Lukashchuk, Natalia; Sczaniecka-Clift, Matylda; Britton, Sébastien; le Sage, Carlos; Calsou, Patrick; Beli, Petra; Galanty, Yaron; Jackson, Stephen P.

    2015-04-23

    -Universite´ Paul Sabatier, .ac.uk (Y.G.), s.jackson@gurdon.cam.ac.uk (S.P.J.) commons.org/licenses/by/4.0/). DNA-PKcs, PAXX, and end-processing factors leading to repair by the DNA ligase IV/XRCC4/XLF complex (Davis and Chen, 2013; Grundy et al., 2014; Wang... , T., Chou, Y.C., Willems, A.R., Meyer-Schaller, N., Hecht, M.L., Tyers, M., Peter, M., and Sicheri, F. (2008). Dcn1 functions as a scaffold-type E3 ligase for cullin neddylation. Mol. Cell 29, 23–35. Li, T., Guan, J., Huang, Z., Hu, X., and Zheng, X...

  11. DNA-PKcs-Mediated Transcriptional Regulation Drives Prostate Cancer Progression and Metastasis

    E-Print Network [OSTI]

    2015-01-01

    the DNA damage response (DDR) and mainte- nance of genomicet al. , 2008), suggesting a DDR-inde- pendent role for DNA-pathways associated with DDR were also enriched (Table S1).

  12. Melatonin Protects Human Cells from Clustered DNA Damages, Killing and Acquisition of Soft Agar Growth Induced by X-rays or 970 MeV/n Fe ions

    SciTech Connect (OSTI)

    Das, B.; Sutherland, B.; Bennett, P. V.; Cutter, N. C.; Sutherland, J. C.

    2011-06-01

    We tested the ability of melatonin (N-acetyl-5 methoxytryptamine), a highly effective radical scavenger and human hormone, to protect DNA in solution and in human cells against induction of complex DNA clusters and biological damage induced by low or high linear energy transfer radiation (100 kVp X-rays, 970 MeV/nucleon Fe ions). Plasmid DNA in solution was treated with increasing concentrations of melatonin (0.0-3.5 mM) and were irradiated with X-rays. Human cells (28SC monocytes) were also irradiated with X-rays and Fe ions with and without 2 mM melatonin. Agarose plugs containing genomic DNA were subjected to Contour Clamped Homogeneous Electrophoretic Field (CHEF) followed by imaging and clustered DNA damages were measured by using Number Average length analysis. Transformation experiments on human primary fibroblast cells using soft agar colony assay were carried out which were irradiated with Fe ions with or without 2 mM melatonin. In plasmid DNA in solution, melatonin reduced the induction of single- and double-strand breaks. Pretreatment of human 28SC cells for 24 h before irradiation with 2 mM melatonin reduced the level of X-ray induced double-strand breaks by {approx}50%, of abasic clustered damages about 40%, and of Fe ion-induced double-strand breaks (41% reduction) and abasic clusters (34% reduction). It decreased transformation to soft agar growth of human primary cells by a factor of 10, but reduced killing by Fe ions only by 20-40%. Melatonin's effective reduction of radiation-induced critical DNA damages, cell killing, and striking decrease of transformation suggest that it is an excellent candidate as a countermeasure against radiation exposure, including radiation exposure to astronaut crews in space travel.

  13. (CANCER RESEARCH 53. I02.VI026. March I. 1993] Benzene and Its Phenolic Metabolites Produce Oxidative DNA Damage in HL60

    E-Print Network [OSTI]

    California at Berkeley, University of

    (CANCER RESEARCH 53. I02.VI026. March I. 1993] Benzene and Its Phenolic Metabolites Produce ABSTRACT Benzene, an important industrial chemical, is myelotoxic and leuke- mogenic in humans effects. Here we report the induction of oxida- tive DNA damage by benzene and its phenolic metabolites

  14. DNA Self-Assembly of Targeted Near-Infrared-Responsive Gold Nanoparticles for Cancer Thermo-Chemotherapy

    E-Print Network [OSTI]

    Xiao, Zeyu

    Targeted cancer therapy: Inspired by the ability of DNA hybridization, a targeted near-infrared (NIR) light-responsive delivery system has been developed through simple DNA self-assembly (see picture; PEG=polyethylene ...

  15. Imaging the early material response associated with exit surface damage in fused silica

    SciTech Connect (OSTI)

    Demos, S G; Raman, R N; Negres, R A

    2010-11-05

    The processes involved at the onset of damage initiation on the surface of fused silica have been a topic of extensive discussion and thought for more than four decades. Limited experimental results have helped develop models covering specific aspects of the process. In this work we present the results of an experimental study aiming at imaging the material response from the onset of the observation of material modification during exposure to the laser pulse through the time point at which material ejection begins. The system involves damage initiation using a 355 nm pulse, 7.8 ns FWHM in duration and imaging of the affected material volume with spatial resolution on the order of 1 {micro}m using as strobe light a 150 ps laser pulse that is appropriately timed with respect to the pump pulse. The observations reveal that the onset of material modification is associated with regions of increased absorption, i.e., formation of an electronic excitation, leading to a reduction in the probe transmission to only a few percent within a time interval of about 1 ns. This area is subsequently rapidly expanding with a speed of about 1.2 {micro}m/ns and is accompanied by the formation and propagation of radial cracks. These cracks appear to initiate about 2 ns after the start of the expansion of the modified region. The damage sites continue to grow for about 25 ns but the mechanism of expansion after the termination of the laser pulse is via formation and propagation of lateral cracks. During this time, the affected area of the surface appears to expand forming a bulge of about 40 {micro}m in height. The first clear observation of material cluster ejection is noted at about 50 ns delay.

  16. The BWR lower head response during a large-break LOCA with core damage

    SciTech Connect (OSTI)

    Alammar, M.A. [GPU Nuclear Corp., Parsippany, NJ (United States)

    1996-12-31

    Some of the important issues in severe accident management guidelines development deal with estimating the time to lower head vessel failure after core damage and the time window available for water injection that would prevent vessel failure. These issues are obviously scenario dependent, but bounding estimates are needed. The scenario chosen for this purpose was a design-basis accident (DBA) loss-of-coolant accident (LOCA) because it was one of the contributors to the Oyster Creek containment failure frequency. Oyster Creek is a 1930-MW(thermal) boiling water reactor (BWR)-2. The lower head response models have improved since the Three Mile Island unit 2 (TMI-2) vessel investigation project (VIP) results became known, specifically the addition of rapid- and slow-cooling models. These mechanisms were found to have taken place in the TMI-2 lower head during debris cooldown and were important contributors in preventing vessel failure.

  17. Persistent Inhibition of ABL Tyrosine Kinase Causes Enhanced Apoptotic Response to TRAIL and Disrupts the Pro-Apoptotic Effect of Chloroquine

    E-Print Network [OSTI]

    Sridevi, P; Nhiayi, MK; Setten, RL; Wang, JYJ

    2013-01-01

    the DNA damage response (DDR) as a result of caspase-DNA fragmentation, and this DDR response contributes to23,24]. This caspase-induced DDR may explain the Tumor

  18. Regulation of epithelial-mesenchymal transition and DNA damage responses by singleminded-2s 

    E-Print Network [OSTI]

    Laffin, Brian Edward

    2009-05-15

    Virtually all signaling pathways that play key roles in development such as the transfroming growth factor (TGF)-beta, notch, and wnt pathways also influence tumor formation, implying that cancer is in a sense development ...

  19. Characterization of Biological Effects of Computed Tomography by Assessing the DNA Damage Response

    E-Print Network [OSTI]

    Elgart, Shona Robin

    2014-01-01

    Between Low- and High-Dose Effects. Radiation Research 2012;low doses of ionizing radiation to inform risk assessment for diagnostic radiographic procedures. 1.1 Specific Research

  20. 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

  1. DNA-based Self-Assembly of Chiral Plasmonic Nanostructures with Tailored Optical Response

    E-Print Network [OSTI]

    Kuzyk, Anton; Fan, Zhiyuan; Pardatscher, Günther; Roller, Eva-Maria; Högele, Alexander; Simmel, Friedrich C; Govorov, Alexander O; Liedl, Tim

    2011-01-01

    Surface plasmon resonances generated in metallic nanostructures can be utilized to tailor electromagnetic fields. The precise spatial arrangement of such structures can result in surprising optical properties that are not found in any naturally occurring material. Here, the designed activity emerges from collective effects of singular components equipped with limited individual functionality. Top-down fabrication of plasmonic materials with a predesigned optical response in the visible range by conventional lithographic methods has remained challenging due to their limited resolution, the complexity of scaling, and the difficulty to extend these techniques to three-dimensional architectures. Molecular self-assembly provides an alternative route to create such materials which is not bound by the above limitations. We demonstrate how the DNA origami method can be used to produce plasmonic materials with a tailored optical response at visible wavelengths. Harnessing the assembly power of 3D DNA origami, we arran...

  2. IH Report #04-010 April 2004 Water Damage Response (Mold Prevention)

    E-Print Network [OSTI]

    , discard books and papers Photocopy important/valuable items, discard originals or Freeze in frost-free freezer or meat locker and consult with a restoration/water damage professional. Carpet and backing ­ dry

  3. Insulin signaling, dietary restriction and DNA damage : multiple roles for smk-1 in the mediation of C. elegans life span

    E-Print Network [OSTI]

    Wolff, Suzanne Christine

    2008-01-01

    involved in resistance to heat stress, a common correlatedamage, UV damage, and heat stress are tightly coupled to2003), and induced by heat stress (mtl-1 and hsp-12.6) (

  4. Modeling of Damage, Permeability Changes and Pressure Responses during Excavation of the TSX Tunnel in Granitic Rock at URL, Canada

    E-Print Network [OSTI]

    Rutqvist, Jonny

    2009-01-01

    Modeling of Damage, Permeability Changes and Pressureof excavation-induced damage, permeability changes, andrange of approaches to model damage and permeability changes

  5. DNA-based Self-Assembly of Chiral Plasmonic Nanostructures with Tailored Optical Response

    E-Print Network [OSTI]

    Anton Kuzyk; Robert Schreiber; Zhiyuan Fan; Günther Pardatscher; Eva-Maria Roller; Alexander Högele; Friedrich C. Simmel; Alexander O. Govorov; Tim Liedl

    2011-08-18

    Surface plasmon resonances generated in metallic nanostructures can be utilized to tailor electromagnetic fields. The precise spatial arrangement of such structures can result in surprising optical properties that are not found in any naturally occurring material. Here, the designed activity emerges from collective effects of singular components equipped with limited individual functionality. Top-down fabrication of plasmonic materials with a predesigned optical response in the visible range by conventional lithographic methods has remained challenging due to their limited resolution, the complexity of scaling, and the difficulty to extend these techniques to three-dimensional architectures. Molecular self-assembly provides an alternative route to create such materials which is not bound by the above limitations. We demonstrate how the DNA origami method can be used to produce plasmonic materials with a tailored optical response at visible wavelengths. Harnessing the assembly power of 3D DNA origami, we arranged metal nanoparticles with a spatial accuracy of 2 nm into nanoscale helices. The helical structures assemble in solution in a massively parallel fashion and with near quantitative yields. As a designed optical response, we generated giant circular dichroism and optical rotary dispersion in the visible range that originates from the collective plasmon-plasmon interactions within the nanohelices. We also show that the optical response can be tuned through the visible spectrum by changing the composition of the metal nanoparticles. The observed effects are independent of the direction of the incident light and can be switched by design between left- and right-handed orientation. Our work demonstrates the production of complex bulk materials from precisely designed nanoscopic assemblies and highlights the potential of DNA self-assembly for the fabrication of plasmonic nanostructures.

  6. A model of interactions between radiation-induced oxidative stress, protein and DNA damage in Deinococcus radiodurans

    E-Print Network [OSTI]

    Brenner, David Jonathan

    . For example, oxidative stress triggered by even quite low doses of radiation can produce an alteration repair may function more efficiently. These processes probably occur to some extent even at low doses of radiation/oxidative stress, but they are easiest to investigate at high doses, where both DNA and protein

  7. 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 extract—3.9, 7.5, or 15.0 mg/kg body weight (BW)—or with casearin X—0.3, 0.25, or 1.2 mg/kg BW—after 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.

  8. The influence of TRP53 in the dose response of radiation-induced apoptosis, DNA repair and genomic stability in murine haematopoietic cells

    SciTech Connect (OSTI)

    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 levels 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.

  9. A variable DNA recognition site organization establishes the LiaR-mediated cell envelope stress response of enterococci to daptomycin

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

    Davlieva, Milya; Shi, Yiwen; Leonard, Paul G.; Johnson, Troy A.; Zianni, Michael R.; Arias, Cesar A.; Ladbury, John E.; Shamoo, Yousif

    2015-04-19

    LiaR is a ‘master regulator’ of the cell envelope stress response in enterococci and many other Gram-positive organisms. Mutations to liaR can lead to antibiotic resistance to a variety of antibiotics including the cyclic lipopeptide daptomycin. LiaR is phosphorylated in response to membrane stress to regulate downstream target operons. Using DNA footprinting of the regions upstream of the liaXYZ and liaFSR operons we show that LiaR binds an extended stretch of DNA that extends beyond the proposed canonical consensus sequence suggesting a more complex level of regulatory control of target operons. We go on to determine the biochemical and structuralmore »basis for increased resistance to daptomycin by the adaptive mutation to LiaR (D191N) first identified from the pathogen Enterococcus faecalis S613. LiaRD191N increases oligomerization of LiaR to form a constitutively activated tetramer that has high affinity for DNA even in the absence of phosphorylation leading to increased resistance. The crystal structures of the LiaR DNA binding domain complexed to the putative consensus sequence as well as an adjoining secondary sequence show that upon binding, LiaR induces DNA bending that is consistent with increased recruitment of RNA polymerase to the transcription start site and upregulation of target operons.« less

  10. Reduced repair capacity of a DNA clustered damage site comprised of 8-oxo-7,8-dihydro-2'-deoxyguanosine and 2-deoxyribonolactone results in an increased mutagenic potential of these lesions

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

    Cunniffe, Siobhan; O’Neill, Peter; Greenberg, Marc M.; Lomax, Martine E.

    2014-04-01

    A signature of ionizing radiation is the induction of DNA clustered damaged sites. Non-double strand break (DSB) clustered damage has been shown to compromise the base excision repair pathway, extending the lifetimes of the lesions within the cluster, compared to isolated lesions. This increases the likelihood the lesions persist to replication and thus increasing the mutagenic potential of the lesions within the cluster. Lesions formed by ionizing radiation include 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) and 2-deoxyribonolactone (dL). dL poses an additional challenge to the cell as it is not repaired by the short-patch base excision repair pathway. Here we show recalcitrant dL repairmore »is reflected in mutations observed when DNA containing it and a proximal 8-oxodGuo is replicated in Escherichia coli. 8-oxodGuo in close proximity to dL on the opposing DNA strand results in an enhanced frequency of mutation of the lesions within the cluster and a 20 base sequence flanking the clustered damage site in an E. coli based plasmid assay. In vitro repair of a dL lesion is reduced when compared to the repair of an abasic (AP) site and a tetrahydrofuran (THF), and this is due mainly to a reduction in the activity of polymerase ?, leading to retarded FEN1 and ligase 1 activities. This study has given insights in to the biological effects of clusters containing dL.« less

  11. Analysis of Flow Cytometry DNA Damage Response Protein Activation Kinetics Following X-rays and High Energy Iron Nuclei Exposure

    E-Print Network [OSTI]

    Chappell, Lori J.

    2011-01-01

    various qualities of low dose radiation in normal humanto various qualities of low dose radiation. INTRODUCTION AnCellular mechanisms for low-dose ionizing radiation-induced

  12. Analysis of Flow Cytometry DNA Damage Response Protein Activation Kinetics Following X-rays and High Energy Iron Nuclei Exposure

    SciTech Connect (OSTI)

    Universities Space Research Association; Chappell, Lori J.; Whalen, Mary K.; Gurai, Sheena; Ponomarev, Artem; Cucinotta, Francis A.; Pluth, Janice M.

    2010-12-15

    We developed a mathematical method to analyze flow cytometry data to describe the kinetics of {gamma}H2AX and pATF2 phosphorylations ensuing various qualities of low dose radiation in normal human fibroblast cells. Previously reported flow cytometry kinetic results for these DSB repair phospho-proteins revealed that distributions of intensity were highly skewed, severely limiting the detection of differences in the very low dose range. Distributional analysis reveals significant differences between control and low dose samples when distributions are compared using the Kolmogorov-Smirnov test. Radiation quality differences are found in the distribution shapes and when a nonlinear model is used to relate dose and time to the decay of the mean ratio of phosphoprotein intensities of irradiated samples to controls. We analyzed cell cycle phase and radiation quality dependent characteristic repair times and residual phospho-protein levels with these methods. Characteristic repair times for {gamma}H2AX were higher following Fe nuclei as compared to X-rays in G1 cells (4.5 {+-} 0.46 h vs 3.26 {+-} 0.76 h, respectively), and in S/G2 cells (5.51 {+-} 2.94 h vs 2.87 {+-} 0.45 h, respectively). The RBE in G1 cells for Fe nuclei relative to X-rays for {gamma}H2AX was 2.05 {+-} 0.61 and 5.02 {+-} 3.47, at 2 h and 24-h postirradiation, respectively. For pATF2, a saturation effect is observed with reduced expression at high doses, especially for Fe nuclei, with much slower characteristic repair times (>7 h) compared to X-rays. RBEs for pATF2 were 0.66 {+-} 0.13 and 1.66 {+-} 0.46 at 2 h and 24 h, respectively. Significant differences in {gamma}H2AX and pATF2 levels comparing irradiated samples to control were noted even at the lowest dose analyzed (0.05 Gy) using these methods of analysis. These results reveal that mathematical models can be applied to flow cytometry data to uncover important and subtle differences following exposure to various qualities of low dose radiation.

  13. Cell cycle and DNA damage response regulation by Spy1, and the intersection of FGFR and NFkappaB pathways

    E-Print Network [OSTI]

    McAndrew, Christopher William

    2010-01-01

    switching in mammary oncogenesis. Mol Cancer Res Li, Y. &of Growth Regulation and Oncogenesis. Chapter 1, in full, iswhich is significant for oncogenesis. A recent report found

  14. Cell cycle and DNA damage response regulation by Spy1, and the intersection of FGFR and NFkappaB pathways

    E-Print Network [OSTI]

    McAndrew, Christopher William

    2010-01-01

    Silva LF, Duncker BP. ORC function in late G1: maintaining128-30. DePamphilis ML. The 'ORC cycle': a novel pathway forOrigin Recognition Complex (ORC), cdc6/18, cdc45, cdt1, the

  15. Cell cycle and DNA damage response regulation by Spy1, and the intersection of FGFR and NFkappaB pathways

    E-Print Network [OSTI]

    McAndrew, Christopher William

    2010-01-01

    Cycle. Wiley Encyclopedia of Chemical Biology (In Press)in The Wiley Encyclopedia of Chemical Biology, McAndrew, CW;in The Wiley Encyclopedia of Chemical Biology, McAndrew, CW;

  16. DNA repair: Dynamic defenders against cancer and aging

    SciTech Connect (OSTI)

    Fuss, Jill O.; Cooper, Priscilla K.

    2006-04-01

    You probably weren't thinking about your body's cellular DNA repair systems the last time you sat on the beach in the bright sunshine. Fortunately, however, while you were subjecting your DNA to the harmful effects of ultraviolet light, your cells were busy repairing the damage. The idea that our genetic material could be damaged by the sun was not appreciated in the early days of molecular biology. When Watson and Crick discovered the structure of DNA in 1953 [1], it was assumed that DNA is fundamentally stable since it carries the blueprint of life. However, over 50 years of research have revealed that our DNA is under constant assault by sunlight, oxygen, radiation, various chemicals, and even our own cellular processes. Cleverly, evolution has provided our cells with a diverse set of tools to repair the damage that Mother Nature causes. DNA repair processes restore the normal nucleotide sequence and DNA structure of the genome after damage [2]. These responses are highly varied and exquisitely regulated. DNA repair mechanisms are traditionally characterized by the type of damage repaired. A large variety of chemical modifications can alter normal DNA bases and either lead to mutations or block transcription if not repaired, and three distinct pathways exist to remove base damage. Base excision repair (BER) corrects DNA base alterations that do not distort the overall structure of the DNA helix such as bases damaged by oxidation resulting from normal cellular metabolism. While BER removes single damaged bases, nucleotide excision repair (NER) removes short segments of nucleotides (called oligonucleotides) containing damaged bases. NER responds to any alteration that distorts the DNA helix and is the mechanism responsible for repairing bulky base damage caused by carcinogenic chemicals such as benzo [a]pyrene (found in cigarette smoke and automobile exhaust) as well as covalent linkages between adjacent pyrimidine bases resulting from the ultraviolet (UV) component of sunlight. NER can be divided into two classes based on where the repair occurs. NER occurring in DNA that is not undergoing transcription (i.e., most of the genome) is called global genome repair (GGR or GGNER), while NER taking place in the transcribed strand of active genes is called transcription-coupled repair (TCR or TC-NER). We will explore NER in more detail below. Mismatch repair (MMR) is another type of excision repair that specifically removes mispaired bases resulting from replication errors. DNA damage can also result in breaks in the DNA backbone, in one or both strands. Single-strand breaks (SSBs) are efficiently repaired by a mechanism that shares common features with the later steps in BER. Double-strand breaks (DSBs) are especially devastating since by definition there is no intact complementary strand to serve as a template for repair, and even one unrepaired DSB can be lethal [3]. In cells that have replicated their DNA prior to cell division, the missing information can be supplied by the duplicate copy, or sister chromatid, and DSBs in these cells are faithfully repaired by homologous recombination involving the exchange of strands of DNA between the two copies. However, most cells in the body are non-dividing, and in these cells the major mechanism for repairing DSBs is by non-homologous end joining (NHEJ), which as the name implies involves joining two broken DNA ends together without a requirement for homologous sequence and which therefore has a high potential for loss of genetic information.

  17. Protein Bridges DNA Base and Nucleotide Excision Repair Pathways

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

    Bridges DNA Base and Nucleotide Excision Repair Pathways Print Alkyltransferase proteins (AGT) protect cells from the biological effects of DNA damage caused by the addition...

  18. Atypical Response Regulator ChxR from Chlamydia trachomatis Is Structurally Poised for DNA Binding

    E-Print Network [OSTI]

    Barta, Michael L.; Hickey, John Michael; Anbanandam, Asokan; Dyer, Kevin; Hammel, Michal; Hefty, P. Scott

    2014-03-19

    ] and are as follows: PhoB (1QQI); YycF (2D1V); HP1043 (2HQR); OmpR (2JPB); PhoP (2PMU); KdpE (3ZQ7) for effector domains and DrrD (1KGS); DrrB (1P2F); PrrA (1YS6); MtrA (2GWR); HP1043 (2HQR); RegX3 (2OQR); PhoP (3R0J) for full-length structures. Representations of all... in the chxR promoter with a dissociation constant (Kd) of approximately 44 nM [17]. To determine if ChxREff (residues 115–227) alone can to bind to DNA, an electrophoretic mobility Table 2. SAXS Parameters for Data Validation and Interpretation. SAXS...

  19. How the DNA sequence affects the Hill curve of transcriptional response

    E-Print Network [OSTI]

    M. Sheinman; Y. Kafri

    2011-11-16

    The Hill coefficient is often used as a direct measure of the cooperativity of binding processes. It is an essential tool for probing properties of reactions in many biochemical systems. Here we analyze existing experimental data and demonstrate that the Hill coefficient characterizing the binding of transcription factors to their cognate sites can in fact be larger than one -- the standard indication of cooperativity -- even in the absence of any standard cooperative binding mechanism. By studying the problem analytically, we demonstrate that this effect occurs due to the disordered binding energy of the transcription factor to the DNA molecule and the steric interactions between the different copies of the transcription factor. We show that the enhanced Hill coefficient implies a significant reduction in the number of copies of the transcription factors which is needed to occupy a cognate site and, in many cases, can explain existing estimates for numbers of the transcription factors in cells. The mechanism is general and should be applicable to other biological recognition processes.

  20. IMPULSE RESPONSE ANALYSIS OF THE VAN NUYS 7-STORY HOTEL DURING 11 EARTHQUAKES AND EARTHQUAKE DAMAGE DETECTION

    E-Print Network [OSTI]

    Southern California, University of

    propagating waves are measured in the Van Nuys 7- story hotel, located in the Los Angeles metropolitan area response data from 11 earthquakes over a period of 24 years are analyzed. Changes in wave travel times). Also, wave travel times are used to estimate the fundamental fixed-base frequency of the building, 1f

  1. High-resolution sequencing of DNA G-quadruplex secondary structures in the human genome

    E-Print Network [OSTI]

    Chambers, Vicki S.; Marsico, Giovanni; Boutell, Jonathan M.; Antonio, Marco Di; Smith, Geoffrey P.; Balasubramanian, Shankar

    2015-07-20

    . A novel small molecule that alters shelterin integrity and triggers a 215 DNA-damage response at telomeres. J. Am. Chem. Soc. 130, 15758-15759, (2008). 216 22 Hud, N. V., Smith, F. W., Anet, F. A. L. & Feigon, J. The selectivity for K+ versus Na...

  2. Nonenzymatic Role for WRN in Preserving Nascent DNA Strands after Replication Stress

    SciTech Connect (OSTI)

    Su, Fengtao [Univ. of Texas Southwestern Medical Center, Dallas, TX (United States); Mukherjee, Shibani [Univ. of Texas Southwestern Medical Center, Dallas, TX (United States); Yang, Yanyong [Univ. of Texas Southwestern Medical Center, Dallas, TX (United States); Mori, Eiichiro [Univ. of Texas Southwestern Medical Center, Dallas, TX (United States); Bhattacharya, Souparno [Univ. of Texas Southwestern Medical Center, Dallas, TX (United States); Kobayashi, Junya [Kyoto Univ. (Japan); Yannone, Steven  M. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Chen, David  J. [Univ. of Texas Southwestern Medical Center, Dallas, TX (United States); Asaithamby, Aroumougame [Univ. of Texas Southwestern Medical Center, Dallas, TX (United States)

    2014-11-20

    WRN, the protein defective in Werner syndrome (WS), is a multifunctional nuclease involved in DNA damage repair, replication, and genome stability maintenance. It was assumed that the nuclease activities of WRN were critical for these functions. Here, we report a nonenzymatic role for WRN in preserving nascent DNA strands following replication stress. We found that lack of WRN led to shortening of nascent DNA strands after replication stress. Furthermore, we discovered that the exonuclease activity of MRE11 was responsible for the shortening of newly replicated DNA in the absence of WRN. Mechanistically, the N-terminal FHA domain of NBS1 recruits WRN to replication-associated DNA double-stranded breaks to stabilize Rad51 and to limit the nuclease activity of its C-terminal binding partner MRE11. Thus, this previously unrecognized nonenzymatic function of WRN in the stabilization of nascent DNA strands sheds light on the molecular reason for the origin of genome instability in WS individuals.

  3. Nonlocal Damage Models 8.1 Basic Types of Nonlocal Damage Formulations

    E-Print Network [OSTI]

    Jirasek, Milan

    Chapter 8 Nonlocal Damage Models 8.1 Basic Types of Nonlocal Damage Formulations 8.1.1 Formulations Motivated by Isotropic Damage A number of nonlocal concepts giving local response in the linear elastic damage model from Section 5.2. Certain models use a formulation in which the role of the equivalent

  4. Searching for the nik Operon: How a Ligand-Responsive Transcription Factor Hunts for Its DNA Binding Site

    E-Print Network [OSTI]

    Phillips, Christine M.

    Transcription factors regulate a wide variety of genes in the cell and play a crucial role in maintaining cellular homeostasis. A major unresolved issue is how transcription factors find their specific DNA binding sequence ...

  5. Property Loss / Damage Report Damage Loss Details

    E-Print Network [OSTI]

    Ponce, V. Miguel

    Property Loss / Damage Report Damage Loss Details Date & Time of Damage / Loss: Type of damage / loss: Location - specific address / room: Project / Grant associated with damage / loss - grant Police: When was damage / loss first discovered - BY WHOM: Pictures available or attached? Was personal

  6. The Escherichia coli RhaS Transcriptional Activator: Transcriptional Activation by the DNA-Binding Domain, The Interdomain Effector Response, and Negative Autoregulation

    E-Print Network [OSTI]

    Skredenske, Jeffrey M.

    2012-05-31

    : The AraC/XylS family activator RhaS negatively 78 autoregulates rhaSR expression by preventing cyclic AMP receptor protein activation 1 CHAPTER 1 Transcription Activation by the DNA-Binding Domain of the AraC Family Protein Rha... encodes a second L-rhamnose responsive transcription activator, RhaR (37). RhaR activates transcription of the operon that encodes the two activator proteins, rhaSR (37, 38). All three operons in the L-rhamnose regulon also require a second activator...

  7. Local chromatin structure of heterochromatin regulates repeatedDNA stability, nucleolus structure, and genome integrity

    SciTech Connect (OSTI)

    Peng, Jamy C.

    2007-05-05

    Heterochromatin constitutes a significant portion of the genome in higher eukaryotes; approximately 30% in Drosophila and human. Heterochromatin contains a high repeat DNA content and a low density of protein-encoding genes. In contrast, euchromatin is composed mostly of unique sequences and contains the majority of single-copy genes. Genetic and cytological studies demonstrated that heterochromatin exhibits regulatory roles in chromosome organization, centromere function and telomere protection. As an epigenetically regulated structure, heterochromatin formation is not defined by any DNA sequence consensus. Heterochromatin is characterized by its association with nucleosomes containing methylated-lysine 9 of histone H3 (H3K9me), heterochromatin protein 1 (HP1) that binds H3K9me, and Su(var)3-9, which methylates H3K9 and binds HP1. Heterochromatin formation and functions are influenced by HP1, Su(var)3-9, and the RNA interference (RNAi) pathway. My thesis project investigates how heterochromatin formation and function impact nuclear architecture, repeated DNA organization, and genome stability in Drosophila melanogaster. H3K9me-based chromatin reduces extrachromosomal DNA formation; most likely by restricting the access of repair machineries to repeated DNAs. Reducing extrachromosomal ribosomal DNA stabilizes rDNA repeats and the nucleolus structure. H3K9me-based chromatin also inhibits DNA damage in heterochromatin. Cells with compromised heterochromatin structure, due to Su(var)3-9 or dcr-2 (a component of the RNAi pathway) mutations, display severe DNA damage in heterochromatin compared to wild type. In these mutant cells, accumulated DNA damage leads to chromosomal defects such as translocations, defective DNA repair response, and activation of the G2-M DNA repair and mitotic checkpoints that ensure cellular and animal viability. My thesis research suggests that DNA replication, repair, and recombination mechanisms in heterochromatin differ from those in euchromatin. Remarkably, human euchromatin and fly heterochromatin share similar features; such as repeated DNA content, intron lengths and open reading frame sizes. Human cells likely stabilize their DNA content via mechanisms and factors similar to those in Drosophila heterochromatin. Furthermore, my thesis work raises implications for H3K9me and chromatin functions in complex-DNA genome stability, repeated DNA homogenization by molecular drive, and in genome reorganization through evolution.

  8. Nanotechnology with DNA DNA Nanodevices

    E-Print Network [OSTI]

    Ludwig-Maximilians-Universität, München

    Nanotechnology with DNA DNA Nanodevices Friedrich C. Simmel* and Wendy U. Dittmer A DNA actuator. Introduction.............285 2. Overview: DNA Nanotechnology.......285 3. Prototypes of Nanomechanical DNA overview of DNA nanotechnology as a whole is given. The most important properties of DNA molecules

  9. Identification and characterization of tac5, a telomerase activation mutant, characterization of DNA damage responses and assessment of interactions between telomere-related proteins in Arabidopsis thaliana 

    E-Print Network [OSTI]

    Jasti, Madhuri

    2009-05-15

    species were water, winter, and cultivated fields. Information regarding probability of infectious agent survival and transfer will be used in the future to advance current epidemiological models, including geographicautomata (Ward et al. 2007: In Press...

  10. Infection-induced colitis in mice causes dynamic and tissue-specific changes in stress response and DNA damage leading to colon cancer

    E-Print Network [OSTI]

    Mangerich, Aswin

    Helicobacter hepaticus-infected Rag2-/- mice emulate many aspects of human inflammatory bowel disease, including the development of colitis and colon cancer. To elucidate mechanisms of inflammation-induced carcinogenesis, ...

  11. DNA Mixture DNA Mixture

    E-Print Network [OSTI]

    ;Introductions J.M. Butler ­ Wisconsin DNA Mixture Training May 12, 2009 http://www.cstl.nist.gov/biotech.M. Butler ­ Wisconsin DNA Mixture Training May 12, 2009 http://www.cstl.nist.gov/biotech textbook (now in its 2nd Edition) · STRBase website: http://www.cstl.nist.gov/biotech/strbase/ · Family

  12. Quantifying a bystander response following microbeam irradiation using single-cell RT-PCR analyses

    E-Print Network [OSTI]

    studies of radiation-induced bystander responses reported that exposure to very low doses of a for Radiological Research, Columbia University, New York, NY, USA Objective. There is growing recognition that the effects of ionizing radiation may extend to more than those cells that directly suffer damage to DNA

  13. Role of DNA repair protein ERCC1 in skin cancer 

    E-Print Network [OSTI]

    Song, Liang

    2009-01-01

    Nucleotide excision repair (NER) is one of the major repair systems for removal of DNA lesions. The NER pathway has evolved mainly to repair UV-induced DNA damage and is also active against a broad range of endogenously ...

  14. Alkbh8 Regulates Selenocysteine-Protein Expression to Protect against Reactive Oxygen Species Damage

    E-Print Network [OSTI]

    Endres, Lauren

    Environmental and metabolic sources of reactive oxygen species (ROS) can damage DNA, proteins and lipids to promote disease. Regulation of gene expression can prevent this damage and can include increased transcription, ...

  15. DAMAGE ESTIMATION USING MULTI-OBJECTIVE GENETIC ALGORITHMS Faisal Shabbir

    E-Print Network [OSTI]

    Boyer, Edmond

    DAMAGE ESTIMATION USING MULTI-OBJECTIVE GENETIC ALGORITHMS Faisal Shabbir 1 , Piotr Omenzetter 2 1.omenzetter@abdn.ac.uk ABSTRACT It is common to estimate structural damage severity by updating a structural model against experimental responses at different damage states. When experimental results from the healthy and damaged

  16. Euler buckling and nonlinear kinking of double-stranded DNA

    E-Print Network [OSTI]

    Cohen, Adam E.

    physiological conditions: at high curvature, does the DNA bend smoothly, or does it kink like a drinking straw and damage). These aspects of DNA mechanics are likely to influence protein binding and DNA packaging, yet the effect of single-nucleotide mismatches on DNA bending. Our data support a model of linear elastic bending

  17. Nowcasting Disaster Damage

    E-Print Network [OSTI]

    Kryvasheyeu, Yury; Obradovich, Nick; Moro, Esteban; Van Hentenryck, Pascal; Fowler, James; Cebrian, Manuel

    2015-01-01

    Could social media data aid in disaster response and damage assessment? Countries face both an increasing frequency and intensity of natural disasters due to climate change. And during such events, citizens are turning to social media platforms for disaster-related communication and information. Social media improves situational awareness, facilitates dissemination of emergency information, enables early warning systems, and helps coordinate relief efforts. Additionally, spatiotemporal distribution of disaster-related messages helps with real-time monitoring and assessment of the disaster itself. Here we present a multiscale analysis of Twitter activity before, during, and after Hurricane Sandy. We examine the online response of 50 metropolitan areas of the United States and find a strong relationship between proximity to Sandy's path and hurricane-related social media activity. We show that real and perceived threats -- together with the physical disaster effects -- are directly observable through the intens...

  18. Genomic response to Wnt signalling is highly context-dependent - Evidence from DNA microarray and chromatin immunoprecipitation screens of Wnt/TCF targets

    SciTech Connect (OSTI)

    Railo, Antti [Oulu Centre for Cell Matrix Research, Biocenter Oulu, Laboratory of Developmental Biology and Department of Medical Biochemistry and Molecular Biology, FIN-90014, University of Oulu, P. O. Box 5000 (Finland)] [Oulu Centre for Cell Matrix Research, Biocenter Oulu, Laboratory of Developmental Biology and Department of Medical Biochemistry and Molecular Biology, FIN-90014, University of Oulu, P. O. Box 5000 (Finland); Pajunen, Antti [Department of Biochemistry, University of Oulu (Finland)] [Department of Biochemistry, University of Oulu (Finland); Itaeranta, Petri; Naillat, Florence; Vuoristo, Jussi; Kilpelaeinen, Pekka [Oulu Centre for Cell Matrix Research, Biocenter Oulu, Laboratory of Developmental Biology and Department of Medical Biochemistry and Molecular Biology, FIN-90014, University of Oulu, P. O. Box 5000 (Finland)] [Oulu Centre for Cell Matrix Research, Biocenter Oulu, Laboratory of Developmental Biology and Department of Medical Biochemistry and Molecular Biology, FIN-90014, University of Oulu, P. O. Box 5000 (Finland); Vainio, Seppo, E-mail: Seppo.Vainio@oulu.fi [Oulu Centre for Cell Matrix Research, Biocenter Oulu, Laboratory of Developmental Biology and Department of Medical Biochemistry and Molecular Biology, FIN-90014, University of Oulu, P. O. Box 5000 (Finland)] [Oulu Centre for Cell Matrix Research, Biocenter Oulu, Laboratory of Developmental Biology and Department of Medical Biochemistry and Molecular Biology, FIN-90014, University of Oulu, P. O. Box 5000 (Finland)

    2009-10-01

    Wnt proteins are important regulators of embryonic development, and dysregulated Wnt signalling is involved in the oncogenesis of several human cancers. Our knowledge of the downstream target genes is limited, however. We used a chromatin immunoprecipitation-based assay to isolate and characterize the actual gene segments through which Wnt-activatable transcription factors, TCFs, regulate transcription and an Affymetrix microarray analysis to study the global transcriptional response to the Wnt3a ligand. The anti-{beta}-catenin immunoprecipitation of DNA-protein complexes from mouse NIH3T3 fibroblasts expressing a fusion protein of {beta}-catenin and TCF7 resulted in the identification of 92 genes as putative TCF targets. GeneChip assays of gene expression performed on NIH3T3 cells and the rat pheochromocytoma cell line PC12 revealed 355 genes in NIH3T3 and 129 genes in the PC12 cells with marked changes in expression after Wnt3a stimulus. Only 2 Wnt-regulated genes were shared by both cell lines. Surprisingly, Disabled-2 was the only gene identified by the chromatin immunoprecipitation approach that displayed a marked change in expression in the GeneChip assay. Taken together, our approaches give an insight into the complex context-dependent nature of Wnt pathway transcriptional responses and identify Disabled-2 as a potential new direct target for Wnt signalling.

  19. SUBSPACE-BASED DETECTION OF FATIGUE DAMAGE ON JACKET SUPPORT STRUCTURES OF OFFSHORE WIND TURBINES

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    SUBSPACE-BASED DETECTION OF FATIGUE DAMAGE ON JACKET SUPPORT STRUCTURES OF OFFSHORE WIND TURBINES damage in real size structural components of offshore wind turbines. KEYWORDS : Damage detection, Offshore wind turbines, Numerical response simulation. INTRODUCTION Offshore wind turbines are exposed

  20. Response

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

    Response SEAB Recommendations Related to the Evaluation of New Funding Constructs for Energy R&D in the Department of Energy Introduction Over the past seven years, the Department...

  1. Convention on Supplementary Compensation for Nuclear Damage Contingent...

    Energy Savers [EERE]

    Section 934 Convention on Supplementary Compensation for Nuclear Damage Contingent Cost Allocation, Section 934 LES comments in response to Notice of Inquiry on Convention on...

  2. Structural basis for the inhibition of human alkyladenine DNA by 3,N4-ethenocytosine containing DNA

    E-Print Network [OSTI]

    Lingaraju, Gondichatnahalli M.

    Reactive oxygen and nitrogen species, generated by neutrophils and macrophages in chronically inflamed tissues, readily damage DNA, producing a variety of potentially genotoxic etheno base lesions; such inflammation-related ...

  3. Response

    Energy Savers [EERE]

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative Fuels Data Center Home Page on Google Bookmark EERE: Alternative Fuels Data Center Home Page on DeliciousMathematicsEnergyInterestedReplacement-2-A Wholesale PowerNatural GasBreakoutResponse SEAB Recommendations

  4. Responsibility

    Energy Savers [EERE]

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative Fuels Data Center Home Page on Google Bookmark EERE: Alternative Fuels Data Center Home Page on DeliciousMathematicsEnergyInterestedReplacement-2-A Wholesale PowerNaturalEnergy Response

  5. Inter-individual variation in DNA repair capacity: A need for multi-pathway functional assays to promote translational DNA repair research

    E-Print Network [OSTI]

    Nagel, Zachary D.

    Why does a constant barrage of DNA damage lead to disease in some individuals, while others remain healthy? This article surveys current work addressing the implications of inter-individual variation in DNA repair capacity ...

  6. Liver Kinase B1 Controls T Follicular Helper Cell Differentiation and Germinal Center Formation through Regulation of Nuclear Factor kappa-light-chain-enhancer of Activated B cells

    E-Print Network [OSTI]

    Walsh, Nicole Corinne

    2015-01-01

    class switch recombination DDR: DNA damage response Deptor:activate a DNA damage response (DDR) program orchestrated byoutcomes are recognized for DDR signaling in response to DNA

  7. G2 Checkpoint Responses in Arabidopsis

    SciTech Connect (OSTI)

    Britt, Anne

    2013-03-18

    This project focused on the mechanism and biological significance of the G2 arrest response to replication stress in plants. We employed both forward and reverse genetic approaches to identify genes required for this response. A total of 3 different postdocs, 5 undergraduates, and 2 graduate students participated in the project. We identified several genes required for damage response in plants, including homologs of genes previously identified in animals (ATM and ATR), novel, a plant-specific genes (SOG1) and a gene known in animals but previously thought to be missing from the Arabidopsis genome (ATRIP). We characterized the transcriptome of gamma-irradiated plants, and found that plants, unlike animals, express a robust transcriptional response to damage, involving genes that regulate the cell cycle and DNA metabolism. This response requires both ATM and the transcription factor SOG1. We found that both ATM and ATR play a role in meiosis in plants. We also found that plants have a cell-type-specific programmed cell death response to ionizing radiation and UV light, and that this response requires ATR, ATM, and SOG1. These results were published in a series of 5 papers.

  8. System and damage identification of civil structures

    E-Print Network [OSTI]

    Moaveni, Babak

    2007-01-01

    12 Damage Index Methods. . . . . . . . . . . . . . . .Model Updating for Damage Identification . . . . . . . .298 x Damage Factors and Residual

  9. Photoaffinity Labeling Reveals Nuclear Proteins That Uniquely Recognize Cisplatin?DNA Interstrand Cross-Links

    E-Print Network [OSTI]

    Zhu, Guangyu

    The DNA-binding inorganic compound cisplatin is one of the most successful anticancer drugs. The detailed mechanism by which cells recognize and process cisplatin?DNA damage is of great interest. Although the family of ...

  10. Nonenzymatic Role for WRN in Preserving Nascent DNA Strands after Replication Stress

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

    Su, Fengtao; Mukherjee, Shibani; Yang, Yanyong; Mori, Eiichiro; Bhattacharya, Souparno; Kobayashi, Junya; Yannone, Steven  M.; Chen, David  J.; Asaithamby, Aroumougame

    2014-11-20

    WRN, the protein defective in Werner syndrome (WS), is a multifunctional nuclease involved in DNA damage repair, replication, and genome stability maintenance. It was assumed that the nuclease activities of WRN were critical for these functions. Here, we report a nonenzymatic role for WRN in preserving nascent DNA strands following replication stress. We found that lack of WRN led to shortening of nascent DNA strands after replication stress. Furthermore, we discovered that the exonuclease activity of MRE11 was responsible for the shortening of newly replicated DNA in the absence of WRN. Mechanistically, the N-terminal FHA domain of NBS1 recruits WRNmore »to replication-associated DNA double-stranded breaks to stabilize Rad51 and to limit the nuclease activity of its C-terminal binding partner MRE11. Thus, this previously unrecognized nonenzymatic function of WRN in the stabilization of nascent DNA strands sheds light on the molecular reason for the origin of genome instability in WS individuals.« less

  11. Identifying structural damage from images

    E-Print Network [OSTI]

    Chen, ZhiQiang

    2009-01-01

    feature extraction methods ( A). . . . . . . . . . . .damage feature extraction methods (B). . . . . . . . . . . .a damage feature extraction method and a multi-level

  12. DAMAGE DETECTION IN A WIND TURBINE BLADE BASED ON TIME SERIES Simon Hoell, Piotr Omenzetter

    E-Print Network [OSTI]

    Boyer, Edmond

    DAMAGE DETECTION IN A WIND TURBINE BLADE BASED ON TIME SERIES METHODS Simon Hoell, Piotr Omenzetter (SHM) systems. Different methods have been developed for detection of damages in WT blades. However a damage detection method based on autocorrelations of response accelerations. The damage sensitive feature

  13. Structural damage detection using frequency response functions 

    E-Print Network [OSTI]

    Dincal, Selcuk

    2006-04-12

    Model ............................................................................ 93 Figure 5.9 FRF for the 2 nd Floor – 1 st - 3 rd Story Braces Are Broken SIMO – 12 DOF Symmetric Model... ............................................................................ 93 Figure 5.10 FRF for the 3 rd Floor – 1 st - 3 rd Story Braces Are Broken SIMO – 12 DOF Symmetric Model ............................................................................ 94 Figure 5.11 FRF for the 4 th Floor – 1 st - 3 rd...

  14. Antaphid interactions on Asclepias syriaca are mediated by plant genotype and caterpillar damage

    E-Print Network [OSTI]

    Mooney, Kailen A.

    1 Ant­aphid interactions on Asclepias syriaca are mediated by plant genotype and caterpillar damage in induced responses to herbivory. Here we test whether induced responses to leaf damage and genotypic-way factorial field experiment manipulating plant genotype, leaf damage by specialist monarch caterpillars

  15. Comparative Analysis of Four Oxidized Guanine Lesions from Reactions of DNA with Peroxynitrite, Singlet Oxygen, and ?-Radiation

    E-Print Network [OSTI]

    Cui, Liang

    Oxidative damage to DNA has many origins, including irradiation, inflammation, and oxidative stress, but the chemistries are not the same. The most oxidizable base in DNA is 2-deoxyguanosine (dG), and the primary oxidation ...

  16. RADIATION DAMAGE OF GERMANIUM DETECTORS

    E-Print Network [OSTI]

    Pehl, Richard H.

    2011-01-01

    the high-energy proton damage than was the planar detector.as far as radiation damage is concerned. Unfortunately, some28-29, 1978 LBL-7967 RADIATION DAMAGE OF GERMANIUM DETECTORS

  17. Nondestructive Damage Detection in General Beams 

    E-Print Network [OSTI]

    Dincal, Selcuk

    2010-12-08

    is to provide NDE methodologies that simultaneously identify the location, the extent, and the severity of damage in general beams. By general beams, we mean beyond Euler-Bernoulli beams (i.e. slender beams) to deep beams and stubby beams whose response may...

  18. Controlling Beaver Damage 

    E-Print Network [OSTI]

    Texas Wildlife Services

    2007-03-13

    Beavers are important because their dams stabilize creek flow, slow runoff and create ponds. However, these same dams can negatively alter the flow of creeks. Damage prevention, control and various trapping methods are discussed in this publication....

  19. Controlling Feral Hog Damage 

    E-Print Network [OSTI]

    Texas Wildlife Services

    2008-04-15

    This publication discusses the distribution of feral hogs as well as their habitats, food habits and reproduction. Feral hogs can damage crops and kill lambs and kid goats. Methods of control are also explained....

  20. Investigating the Role of Vitamin D and DNA Repair in Influencing Cancer Presentation and Outcomes 

    E-Print Network [OSTI]

    Syed, Moinuddin Mohammed

    2014-09-26

    differences in DNA repair genes exist, which may in turn contribute to underlying differences in DNA repair capacity. These genes with high Fst value represent all six known common DNA repair pathways and DDR response. This supports our hypothesis...

  1. Plate damage identification using wave propagation and impedance methods.

    SciTech Connect (OSTI)

    Wait, J. R. (Jeannette R.); Park, G. H. (Gyu Hae); Sohn, H. (Hoon); Farrar, C. R. (Charles R.)

    2004-01-01

    This paper illustrates an integrated approach for identifying structural damage in an aluminum plate. Piezoelectric (PZT) materials are used to actuatehense the dynamic response of the structure. Two damage identification techniques are integrated in this study, including Lamb wave propagations and impedance methods. In Lamb wave propagations, one PZT launches an elastic wave through the structure, and responses are measured by an array of PZT sensors. The changes in both wave attenuation and reflection are used to detect and locate the damage. The impedance method monitors the variations in structural mechanical impedance, which is coupled with the electrical impedance of the PZT. Both methods operate in high frequency ranges at which there are measurable changes in structural responses even for incipient damage such as small cracks or loose connections. This paper summarizes two methods used for damage identification, experimental procedures, and additional issues that can be used as a guideline for future investigations.

  2. A UNIFIED FAILURE/DAMAGE APPROACH TO BATTLE DAMAGE REGENERATION

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    A UNIFIED FAILURE/DAMAGE APPROACH TO BATTLE DAMAGE REGENERATION : APPLICATION TO GROUND MILITARY-availability. Military weapon systems availability can be affected by system failures or by damage to the system damage into account in their more general dependability studies. This paper takes a look at the issues

  3. Cytokine secretion profiles in primary cultured cells and in mice stimulated with plasmid DNA

    E-Print Network [OSTI]

    Yoshida, Hiroyuki

    2006-10-27

    University Elimination of DNA by antigen presenting cells Gene therapy Infection Leakage Processing Macrophages and dendritic cells Apoptotic or necrotic cells Endogenous DNA DNA Virus Plasmid DNA Exogenous DNA CpG motif5?- Pur Pur CG Pyr Pyr -3? Danger... signal Naked CpG DNA DNA lipoplex Macrophages or dendritic cells ???? ???? Cytokine geneNF-?B AP-1 ???? ???? Endosome Nucleus ? TLR9 Interferon ?/? gene Inflammatory cytokines TNF-?, IL-6 etc. Type I interferon IFN-?, INF-? ? Mechanisms of immune response...

  4. Atomistic simulations of radiation damage in amorphous metal alloys

    E-Print Network [OSTI]

    Baumer, Richard E. (Richard Edward)

    2013-01-01

    While numerous fundamental studies have characterized the atomic-level radiation response mechanisms in irradiated crystalline alloys, comparatively little is known regarding the mechanisms of radiation damage in amorphous ...

  5. Uncertainty of silicon 1-MeV damage function

    SciTech Connect (OSTI)

    Danjaji, M.B.; Griffin, P.J.

    1997-02-01

    The electronics radiation hardness-testing community uses the ASTM E722-93 Standard Practice to define the energy dependence of the nonionizing neutron damage to silicon semiconductors. This neutron displacement damage response function is defined to be equal to the silicon displacement kerma as calculated from the ORNL Si cross-section evaluation. Experimental work has shown that observed damage ratios at various test facilities agree with the defined response function to within 5%. Here, a covariance matrix for the silicon 1-MeV neutron displacement damage function is developed. This uncertainty data will support the electronic radiation hardness-testing community and will permit silicon displacement damage sensors to be used in least squares spectrum adjustment codes.

  6. Structural damage detection using the holder exponent.

    SciTech Connect (OSTI)

    Farrar, C. R. (Charles R.); Do, N. B. (Nguyen B.); Green, S. R. (Scott R.); Schwartz, T. A. (Timothy A.)

    2002-01-01

    This paper implements a damage detection strategy that identifies damage sensitive features associated with nonlinearities. Some rion-linezlrities result from discontinuities introduced into the data by certain types of darnage. These discontinuities may also result from noise in the measured dynamic response data or can be caused by random excitation of the system. The Holder Exponent, which is a measure of the degree to which a signal is differentiable, is used to detect the discontinuities. By studying the Holder bponent as a function af time, a statistical model is developed that classifies changes in the Holder Exponent that are associated with clamage-induced discontinuities. The results show that for certain cases, the Holder Exponent is an effective technique to detect damage.

  7. Damage monitoring in sandwich beams by modal parameter shifts: A comparative study of burst random and sine dwell

    E-Print Network [OSTI]

    Mailhes, Corinne

    1 Damage monitoring in sandwich beams by modal parameter shifts: A comparative study of burst Abstract: This paper presents an experimental study on the effects of multi-site damage on the vibration response of honeycomb sandwich beams, damaged by two different ways i.e., impact damage and core

  8. Impact of DNA damage proteins on the adenoviral lifecycle

    E-Print Network [OSTI]

    Lakdawala, Seema Sailesh

    2009-01-01

    Mutations in members of the DDR pathway result in diseases (2002). Activation of the DDR requires viral replication (observation suggests that the DDR proteins may negatively

  9. Microfluidic DNA sample preparation method and device

    DOE Patents [OSTI]

    Krulevitch, Peter A. (Pleasanton, CA); Miles, Robin R. (Danville, CA); Wang, Xiao-Bo (San Diego, CA); Mariella, Raymond P. (Danville, CA); Gascoyne, Peter R. C. (Bellaire, TX); Balch, Joseph W. (Livermore, CA)

    2002-01-01

    Manipulation of DNA molecules in solution has become an essential aspect of genetic analyses used for biomedical assays, the identification of hazardous bacterial agents, and in decoding the human genome. Currently, most of the steps involved in preparing a DNA sample for analysis are performed manually and are time, labor, and equipment intensive. These steps include extraction of the DNA from spores or cells, separation of the DNA from other particles and molecules in the solution (e.g. dust, smoke, cell/spore debris, and proteins), and separation of the DNA itself into strands of specific lengths. Dielectrophoresis (DEP), a phenomenon whereby polarizable particles move in response to a gradient in electric field, can be used to manipulate and separate DNA in an automated fashion, considerably reducing the time and expense involved in DNA analyses, as well as allowing for the miniaturization of DNA analysis instruments. These applications include direct transport of DNA, trapping of DNA to allow for its separation from other particles or molecules in the solution, and the separation of DNA into strands of varying lengths.

  10. Ectopic ERK Expression Induces Phenotypic Conversion of C10 Cells and Alters DNA Methyltransferase Expression

    SciTech Connect (OSTI)

    Sontag, Ryan L.; Weber, Thomas J.

    2012-05-04

    In some model systems constitutive extracellular signal regulated kinase (ERK) activation is sufficient to promote an oncogenic phenotype. Here we investigate whether constitutive ERK expression influences phenotypic conversion in murine C10 type II alveolar epithelial cells. C10 cells were stably transduced with an ERK1-green fluorescent protein (ERK1-GFP) chimera or empty vector and ectopic ERK expression was associated with the acquisition of soft agar focus-forming potential in late passage, but not early passage cells. Late passage ERK1-GFP cells exhibited a significant increase in the expression of DNA methyl transferases (DNMT1 and 3b) and a marked increase in sensitivity to 5-azacytidine (5-azaC)-mediated toxicity, relative to early passage ERK1-GFP cells and vector controls. The expression of xeroderma pigmentosum complementation group A (XPA) and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) were significantly increased in late passage cells, suggesting enhanced DNA damage recognition and repair activity which we interpret as a reflection of genomic instability. Phospho-ERK levels were dramatically decreased in late passage ERK1-GFP cells, relative to early passage and vector controls, and phospho-ERK levels were restored by treatment with sodium orthovanadate, indicating a role for phosphatase activity in this response. Collectively these observations suggest that ectopic ERK expression promotes phenotypic conversion of C10 cells that is associated with latent effects on epigenetic programming and phosphatase activities.

  11. RADIATION DAMAGE OF GERMANIUM DETECTORS

    E-Print Network [OSTI]

    Pehl, Richard H.

    2011-01-01

    occurring within the detector, radiation may also change theLBL-7967 RADIATION DAMAGE OF GERMANIUM DETECTORS Richard H.LBL-7967 RADIATION DAMAGE OF GERMANIUM DETECTORS* Richard H.

  12. One-electron Oxidation of a Pyrenyl Photosensitizer Covalently Attached to DNA and Competition Between its Further Oxidation and DNA Hole Injection

    E-Print Network [OSTI]

    Yun, Byeong Hwa

    The photosensitized hole injection and guanine base damage phenomena have been investigated in the DNA sequence, 5?-d(CATG[subscript 1] [superscript Py]CG[subscript 2]TCCTAC) with a site-specifically positioned pyrene-like ...

  13. DNA repair of a single UV photoproduct in a designed nucleosome

    SciTech Connect (OSTI)

    Kosmoskil, Joseph V.; Ackerman, Eric J. ); Smerdon, Michael J.

    2001-08-28

    Eukaryotic DNA repair enzymes must interact with the architectural hierarchy of chromatin. The challenge of finding damaged DNA complexed with histone proteins in nucleosomes is complicated by the need to maintain local chromatin structures involved in regulating other DNA processing events. The heterogeneity of lesions induced by DNA-damaging agents has led us to design homogeneously damaged substrates to directly compare repair of naked DNA with that of nucleosomes. Here we report that nucleotide excision repair in Xenopus nuclear extracts can effectively repair a single UV radiation photoproduct located 5 bases from the dyad center of a positioned nucleosome, although the nucleosome is repaired at about half the rate at which the naked DNA fragment is. Extract repair within the nucleosome is > 50-fold more rapid than either enzymatic photoreversal or endonuclease cleavage of the lesion in vitro. Furthermore, nucleosome formation occurs (after repair) only on damaged naked DNA ( 165-bp fragments) during a 1-h incubation in these extracts, even in the presence of a large excess of undamaged DNA. This is an example of selective nucleosome assembly by Xenopus nuclear extracts on a short linear DNA fragment containing a DNA lesion.

  14. Advance the DNA computing 

    E-Print Network [OSTI]

    Qiu, Zhiquan Frank

    2004-09-30

    It has been previously shown that DNA computing can solve those problems currently intractable on even the fastest electronic computers. The algorithm design for DNA computing, however, is not straightforward. A strong background in both the DNA...

  15. Controlling Armadillo Damage 

    E-Print Network [OSTI]

    Texas Wildlife Services

    2007-03-13

    of overlapping rings. The under- parts are covered with soft skin and a few long hairs. The armadillo is about the size of an opos- sum. Its front feet are well adapted for digging. Tracks made by an armadillo appear to have been made by a three-toed animal... and other invertebrates, as well as on small amounts of fruit and vegetable matter such as berries and tender roots. Damage Although armadillos are beneficial because they eat insects and other invertebrates, they sometimes become a nuisance by digging...

  16. Synthesis of DNA

    DOE Patents [OSTI]

    Mariella, Jr., Raymond P. (Danville, CA)

    2008-11-18

    A method of synthesizing a desired double-stranded DNA of a predetermined length and of a predetermined sequence. Preselected sequence segments that will complete the desired double-stranded DNA are determined. Preselected segment sequences of DNA that will be used to complete the desired double-stranded DNA are provided. The preselected segment sequences of DNA are assembled to produce the desired double-stranded DNA.

  17. DNA Engine Thermal Cycler

    E-Print Network [OSTI]

    Raizada, Manish N.

    ® Peltier Thermal Cycler PTC-0200 DNA Engine Cycler Operations Manual Version 4.0 #12;ii Tech Support: 1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .vi The DNA Engine® Peltier Thermal Cycler Introduction

  18. Diphenylarsinic acid, a chemical warfare-related neurotoxicant, promotes liver carcinogenesis via activation of aryl hydrocarbon receptor signaling and consequent induction of oxidative DAN damage in rats

    SciTech Connect (OSTI)

    Wei, Min; Yamada, Takanori; Yamano, Shotaro; Kato, Minoru; Kakehashi, Anna; Fujioka, Masaki; Tago, Yoshiyuki; Kitano, Mistuaki; Wanibuchi, Hideki, E-mail: wani@med.osaka-cu.ac.jp

    2013-11-15

    Diphenylarsinic acid (DPAA), a chemical warfare-related neurotoxic organic arsenical, is present in the groundwater and soil in some regions of Japan due to illegal dumping after World War II. Inorganic arsenic is carcinogenic in humans and its organic arsenic metabolites are carcinogenic in animal studies, raising serious concerns about the carcinogenicity of DPAA. However, the carcinogenic potential of DPAA has not yet been evaluated. In the present study we found that DPAA significantly enhanced the development of diethylnitrosamine-induced preneoplastic lesions in the liver in a medium-term rat liver carcinogenesis assay. Evaluation of the expression of cytochrome P450 (CYP) enzymes in the liver revealed that DPAA induced the expression of CYP1B1, but not any other CYP1, CYP2, or CYP3 enzymes, suggesting that CYP1B1 might be the enzyme responsible for the metabolic activation of DPAA. We also found increased oxidative DNA damage, possibly due to elevated CYP1B1 expression. Induction of CYP1B1 has generally been linked with the activation of AhR, and we found that DPAA activates the aryl hydrocarbon receptor (AhR). Importantly, the promotion effect of DPAA was observed only at a dose that activated the AhR, suggesting that activation of AhR and consequent induction of AhR target genes and oxidative DNA damage plays a vital role in the promotion effects of DPAA. The present study provides, for the first time, evidence regarding the carcinogenicity of DPAA and indicates the necessity of comprehensive evaluation of its carcinogenic potential using long-term carcinogenicity studies. - Highlights: • DPAA, an environmental neurotoxicant, promotes liver carcinogenesis in rats. • DPAA is an activator of AhR signaling pathway. • DPAA promoted oxidative DNA damage in rat livers. • AhR target gene CYP 1B1 might be involved in the metabolism of DPAA.

  19. DAMAGE DIAGNOSIS CONSIDERING CHANGING EVNIRONMENTAL CONDITIONS

    SciTech Connect (OSTI)

    H. SOHN; K. WORDER; C. FARRAR

    2001-05-01

    The primary objective of novelty detection is to examine a system's dynamic response to determine if the system significantly deviates from an initial baseline condition. In reality, the system is often subject to changing environmental and operation conditions that affect its dynamic characteristics. Such variations include changes in loading, boundary conditions, temperature, and moisture. Most damage diagnosis techniques, however, generally neglect the effects of these changing ambient conditions. Here, a novelty detection technique is developed explicitly taking into account these natural variations of the system in order to minimize false positive indications of true system changes. Auto-associative neural networks are employed to discriminate system changes of interest such as structural deterioration and damage from the natural variations of the system.

  20. Radiation Damage/Materials Modification

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

    ion irradiation is an important tool for studying radiation damage effects Materials in a nuclear reactor are exposed to extreme temperature and radiation conditions that degrade...

  1. Shock Initiation of Damaged Explosives

    SciTech Connect (OSTI)

    Chidester, S K; Vandersall, K S; Tarver, C M

    2009-10-22

    Explosive and propellant charges are subjected to various mechanical and thermal insults that can increase their sensitivity over the course of their lifetimes. To quantify this effect, shock initiation experiments were performed on mechanically and thermally damaged LX-04 (85% HMX, 15% Viton by weight) and PBX 9502 (95% TATB, 5% Kel-F by weight) to obtain in-situ manganin pressure gauge data and run distances to detonation at various shock pressures. We report the behavior of the HMX-based explosive LX-04 that was damaged mechanically by applying a compressive load of 600 psi for 20,000 cycles, thus creating many small narrow cracks, or by cutting wedge shaped parts that were then loosely reassembled, thus creating a few large cracks. The thermally damaged LX-04 charges were heated to 190 C for long enough for the beta to delta solid - solid phase transition to occur, and then cooled to ambient temperature. Mechanically damaged LX-04 exhibited only slightly increased shock sensitivity, while thermally damaged LX-04 was much more shock sensitive. Similarly, the insensitive explosive PBX 9502 was mechanically damaged using the same two techniques. Since PBX 9502 does not undergo a solid - solid phase transition but does undergo irreversible or 'rachet' growth when thermally cycled, thermal damage to PBX 9502 was induced by this procedure. As for LX-04, the thermally damaged PBX 9502 demonstrated a greater shock sensitivity than mechanically damaged PBX 9502. The Ignition and Growth reactive flow model calculated the increased sensitivities by igniting more damaged LX-04 and PBX 9502 near the shock front based on the measured densities (porosities) of the damaged charges.

  2. XRCC1 & DNA MTases : direct and indirect modulation of inflammation-induced DNA damage

    E-Print Network [OSTI]

    Mutamba, James T. (James Tendai)

    2011-01-01

    Cancer causes 13% of all deaths worldwide. Inflammation-mediated cancer accounts for ~15% of all malignancies, strongly necessitating investigation of the molecular interactions at play. Inflammatory reactive oxygen and ...

  3. Radiation Damage: Accelerator Surprises

    E-Print Network [OSTI]

    McDonald, Kirk

    of this process. · Helium gas production adds, becoming increasingly important at high energies. · Graphite as material properties including its temperature. These dependencies ­ amplified by increased helium gas production for high-energy beams - are responsible for "surprises/unknowns" learned recently at accelerators

  4. Sensitivity of silicon 1-MeV damage function to cross-section evaluation

    SciTech Connect (OSTI)

    Griffin, P.J.; Danjaji, M.B.

    1995-12-31

    The electronics radiation hardness-testing community uses the American Society for Testing and Materials (ASTM) E722-93 Standard Practice to define the energy dependence of the nonionizing neutron damage to silicon semiconductors. This neutron displacement damage response function is defined to be equal to the silicon displacement kerma. An Oak Ridge National Laboratory (ORNL) {sup 28}Si cross-section evaluation and the NJOY code are used to define the standard response function to be used in reporting 1-MeV (silicon) neutron damage and in determining neutron damage equivalence between test facilities. This paper provides information for the precision and bias section of the E722 standard.

  5. Homologous recombination contributes to the repair of DNA double-strand breaks induced by high-energy iron ions

    SciTech Connect (OSTI)

    Zafar, Faria; Seidler, Sara B.; Kronenberg, Amy; Schild, David; Wiese, Claudia

    2010-06-29

    To test the contribution of homologous recombinational repair (HRR) in repairing DNA damaged sites induced by high-energy iron ions, we used: (1) HRR-deficient rodent cells carrying a deletion in the RAD51D gene and (2) syngeneic human cells impaired for HRR by RAD51D or RAD51 knockdown using RNA interference. We show that in response to iron ions, HRR contributes to cell survival in rodent cells, and that HRR-deficiency abrogates RAD51 foci formation. Complementation of the HRR defect by human RAD51D rescues both enhanced cytotoxicity and RAD51 foci formation. For human cells irradiated with iron ions, cell survival is decreased, and, in p53 mutant cells, the levels of mutagenesis are increased when HRR is impaired. Human cells synchronized in S phase exhibit more pronounced resistance to iron ions as compared with cells in G1 phase, and this increase in radioresistance is diminished by RAD51 knockdown. These results implicate a role for RAD51-mediated DNA repair (i.e. HRR) in removing a fraction of clustered lesions induced by charged particle irradiation. Our results are the first to directly show the requirement for an intact HRR pathway in human cells in ensuring DNA repair and cell survival in response to high-energy high LET radiation.

  6. Damage-prone regions in structural composite materials are difficult to detect and even harder to repair. Damage is preceded by complex spatial and temporal changes in stress state, and it is

    E-Print Network [OSTI]

    Wisconsin at Madison, University of

    Materials Seminar Damage-prone regions in structural composite materials are difficult to detect and even harder to repair. Damage is preceded by complex spatial and temporal changes in stress state about in response to damage or high-stress conditions include: (1) signal generation to warn of ensuing

  7. Liquid-crystalline ordering of antimicrobial peptide–DNA complexes controls TLR9 activation

    E-Print Network [OSTI]

    Schmidt, Nathan W.; Jin, Fan; Lande, Roberto; Curk, Tine; Xian, Wujing; Lee, Calvin; Frasca, Loredana; Frenkel, Daan; Dobnikar, Jure; Gilliet, Michel; Wong, Gerard C. L.

    2015-06-08

    binding and thereby the immune response. Our results suggest that it is possible to control TLR9 activation and modulate immune responses deterministically. Main Text TLR9 binding of DNA is complex and multi-factorial1-4. Microbial DNA is typically... to an isolated DNA chain. If there are ? available binding sites on DNA to which receptors can attach, the expected number of receptors, nB, that are actually bound to the DNA is less than ?: (1) where ? is the binding free energy of receptors to DNA, which...

  8. DNA and the 'magic rings' trick October 11, 2010

    E-Print Network [OSTI]

    Kowalczykowski, Stephen C.

    influences, such as radiation or chemicals, and also from normal cellular processes. Unrepaired, DNA damage in these patients. Holliday junctions were only definitively shown to exist in mitotically dividing cells in April Dorsey Griffith UC Davis Cancer Center dorsey.griffith@ucdmc.ucdavis.edu Phone: (916) 734-9118 Andy Fell

  9. DNA Topology: Fundamentals

    E-Print Network [OSTI]

    Mirkin, Sergei

    in Genome Functioning . Biological Role of Alternative DNA Structures Figure 1 A hypothetical circular DNA. 1ENCYCLOPEDIA OF LIFE SCIENCES / & 2001 Nature Publishing Group / www.els.net #12;topological

  10. Freezing Spring Temperatures Damage Knobcone Pine

    E-Print Network [OSTI]

    Freezing Spring Temperatures Damage Knobcone Pine Stanley L. Krugman U. S. FOREST SERVICE RESEARCH, Stanley L. 1966. Freezing spring temperatures damage knobcone pine conelets. Berkeley, Calif.. Pacific pine, conelets, freezing temperature) Krugman, Stanley L. 1966. Freezing spring temperatures damage

  11. Building Damage, Death and Downtime Risk Attenuation in Earthquakes 

    E-Print Network [OSTI]

    Huang, Yinghui

    2012-07-16

    Whether it is for pre-event prevention and preparedness or for post-event response and recovery of a catastrophic earthquake, estimates of damage, death and downtime (3d) losses are needed by engineers, owners, and policy makers. In this research, a...

  12. Applying nonlinear resonant ultrasound spectroscopy to improving thermal damage

    E-Print Network [OSTI]

    at interrogating the mechanical damage influence on the nonlinear response, applying bend- ing, or longitudinal in this paper. In addition, feasibility and sensitivity of applying shear modes for the NRUS method are explored modulus9 in the stress strain relationship in one dimension can be written M , = M0 1 - - 2 - ¯ - + sign

  13. Estimating Hurricane Outage and Damage Risk in Power Distribution System 

    E-Print Network [OSTI]

    Han, Seung Ryong

    2009-05-15

    Hurricanes have caused severe damage to the electric power system throughout the Gulf coast region of the U.S., and electric power is critical to post-hurricane disaster response as well as to long-term recovery for impacted areas. Managing...

  14. Engineering a comet-based platform for specific, sensitive, and high throughput assessment of multiple DNA repair pathways in humans

    E-Print Network [OSTI]

    Ge, Jing, Ph. D. Massachusetts Institute of Technology

    2015-01-01

    Human exposure to dangerous genotoxins is unavoidable, as DNA damaging agents are ubiquitous both in our environment and within our cells. The diversity in lesions induced by these agents led to the evolution of several ...

  15. DNA Sequencing apparatus

    DOE Patents [OSTI]

    Tabor, Stanley (Cambridge, MA); Richardson, Charles C. (Chestnut Hill, MA)

    1992-01-01

    An automated DNA sequencing apparatus having a reactor for providing at least two series of DNA products formed from a single primer and a DNA strand, each DNA product of a series differing in molecular weight and having a chain terminating agent at one end; separating means for separating the DNA products to form a series bands, the intensity of substantially all nearby bands in a different series being different, band reading means for determining the position an This invention was made with government support including a grant from the U.S. Public Health Service, contract number AI-06045. The U.S. government has certain rights in the invention.

  16. An integrated active sensing system for damage identifcation and prognosis

    SciTech Connect (OSTI)

    Wait, J. R. (Jeannette R.); Park, G. H. (Gyu Hae); Sohn, H. (Hoon); Farrar, C. R. (Charles R.)

    2004-01-01

    This paper illustrates an integrated approach for identifying structural damage. Two damage identification techniques, Lamb wave propagation and impedance-based methods, are investigated utilizing piezoelectric (PZT) actuators/sensors. The Lamb wave propagation and the impedance methods operate in high frequency ranges (typically > 30 kHz) at which there are measurable changes in structural responses even for incipient damage such as small cracks, debonding, delamination, and loose connections. In Lamb wave propagation, one PZT is used to launch an elastic wave through the structure, and responses are measured by an array of sensors. The technique used for the Lamb wave propagation method looks for the possibility of damage by tracking changes in transmission velocity and wave attenuation/reflections. Experimental results show that this method works well for surface anomalies. The impedance method monitors the variations in structural mechanical impedance, which is coupled with the electrical impedance of the PZT. Through monitoring the measured electrical impedance and comparing it to a baseline measurement, a decision can be made about whether or not structural damage has occurred or is imminent. In addition, significant advances have been made recently by incorporating advanced statistic-based signal processing techniques into the impedance methods. To date, several sets of experiments have been conducted on a cantilevered aluminum plate and composite plate to demonstrate the feasibility of this combined active sensing technology.

  17. Utility of geo-informatics for disaster risk management: linking structural damage

    E-Print Network [OSTI]

    Utility of geo-informatics for disaster risk management: linking structural damage assessment) Geoinformatics for disaster risk management (hazard/risk/vulnerability/damage) www.unu-drm.nl Training of disaster risk management (my focus is on post-disaster response/ recovery) Use of object-oriented image

  18. Damage in porous media due to salt crystallization

    E-Print Network [OSTI]

    Noushine Shahidzadeh-Bonn; Julie Desarnaud; François Bertrand; Xavier Chateau; Daniel Bonn

    2010-07-13

    We investigate the origins of salt damage in sandstones for the two most common salts: sodium chloride and sulfate. The results show that the observed difference in damage between the two salts is directly related to the kinetics of crystallization and the interfacial properties of the salt solutions and crystals with respect to the stone. We show that, for sodium sulfate, the existence of hydrated and anhydrous crystals and specifically their dissolution and crystallization kinetics are responsible for the damage. Using magnetic resonance imaging and optical microscopy we show that when water imbibes sodium sulfate contaminated sandstones, followed by drying at room temperature, large damage occurs in regions where pores are fully filled with salts. After partial dissolution, anhydrous sodium sulfate salt present in these regions gives rise to a very rapid growth of the hydrated phase of sulfate in the form of clusters that form on or close to the remaining anhydrous microcrystals. The rapid growth of these clusters generates stresses in excess of the tensile strength of the stone leading to the damage. Sodium chloride only forms anhydrous crystals that consequently do not cause damage in the experiments.

  19. Molecular dissection of the roles of the SOD genes in mammalian response to low dose irradiation

    SciTech Connect (OSTI)

    Eric Y. Chuang

    2006-08-31

    It has been long recognized that a significant fraction of the radiation-induced genetic damage to cells are caused by secondary oxidative species. Internal cellular defense systems against oxidative stress play significant roles in countering genetic damage induced by ionizing radiation. The role of the detoxifying enzymes may be even more prominent in the case of low-dose, low-LET irradiation, as the majority of genetic damage may be caused by secondary oxidative species. In this study we have attempted to decipher the roles of the superoxide dismutase (SOD) genes, which are responsible for detoxifying the superoxide anions. We used adenovirus vectors to deliver RNA interference (RNAi or siRNA) technology to down-regulate the expression levels of the SOD genes. We have also over-expressed the SOD genes by use of recombinant adenovirus vectors. Cells infected with the vectors were then subjected to low dose ?-irradiation. Total RNA were extracted from the exposed cells and the expression of 9000 genes were profiled by use of cDNA microarrays. The result showed that low dose radiation had clear effects on gene expression in HCT116 cells. Both over-expression and down-regulation of the SOD1 gene can change the expression profiles of sub-groups of genes. Close to 200 of the 9000 genes examined showed over two-fold difference in expression under various conditions. Genes with changed expression pattern belong to many categories that include: early growth response, DNA-repair, ion transport, apoptosis, and cytokine response.

  20. DAMAGE LOCALIZATION USING LOAD VECTORS Dionisio Bernal

    E-Print Network [OSTI]

    Bernal, Dionisio

    DAMAGE LOCALIZATION USING LOAD VECTORS Dionisio Bernal Associate Professor Department of Civil: A technique to localize damage in structures that can be treated as linear in the pre and post-damage state is presented. Central to the approach is the computation of a set of vectors, designated as Damage Locating

  1. Cellular response to low dose radiation: Role of phosphatidylinositol-3 kinase like kinases

    SciTech Connect (OSTI)

    Balajee, A.S.; Meador, J.A.; Su, Y.

    2011-03-24

    It is increasingly realized that human exposure either to an acute low dose or multiple chronic low doses of low LET radiation has the potential to cause different types of cancer. Therefore, the central theme of research for DOE and NASA is focused on understanding the molecular mechanisms and pathways responsible for the cellular response to low dose radiation which would not only improve the accuracy of estimating health risks but also help in the development of predictive assays for low dose radiation risks associated with tissue degeneration and cancer. The working hypothesis for this proposal is that the cellular mechanisms in terms of DNA damage signaling, repair and cell cycle checkpoint regulation are different for low and high doses of low LET radiation and that the mode of action of phosphatidylinositol-3 kinase like kinases (PIKK: ATM, ATR and DNA-PK) determines the dose dependent cellular responses. The hypothesis will be tested at two levels: (I) Evaluation of the role of ATM, ATR and DNA-PK in cellular response to low and high doses of low LET radiation in simple in vitro human cell systems and (II) Determination of radiation responses in complex cell microenvironments such as human EpiDerm tissue constructs. Cellular responses to low and high doses of low LET radiation will be assessed from the view points of DNA damage signaling, DNA double strand break repair and cell cycle checkpoint regulation by analyzing the activities (i.e. post-translational modifications and kinetics of protein-protein interactions) of the key target proteins for PI-3 kinase like kinases both at the intra-cellular and molecular levels. The proteins chosen for this proposal are placed under three categories: (I) sensors/initiators include ATM ser1981, ATR, 53BP1, gamma-H2AX, MDC1, MRE11, Rad50 and Nbs1; (II) signal transducers include Chk1, Chk2, FANCD2 and SMC1; and (III) effectors include p53, CDC25A and CDC25C. The primary goal of this proposal is to elucidate the differences in cellular defense mechanisms between low and high doses of low LET radiation and to define the radiation doses where the cellular DNA damage signaling and repair mechanisms tend to shift. This information is critically important to address and advance some of the low dose research program objectives of DOE. The results of this proposed study will lead to a better understanding of the mechanisms for the cellular responses to low and high doses of low LET radiation. Further, systematic analysis of the role of PIKK signaling pathways as a function of radiation dose in tissue microenvironment will provide useful mechanistic information for improving the accuracy of radiation risk assessment for low doses. Knowledge of radiation responses in tissue microenvironment is important for the accurate prediction of ionizing radiation risks associated with cancer and tissue degeneration in humans.

  2. Application of Nonlinear Elastic Resonance Spectroscopy For Damage Detection In Concrete: An Interesting Story

    SciTech Connect (OSTI)

    Byers, Loren W.; Ten Cate, James A.; Johnson, Paul A.

    2012-06-28

    Nonlinear resonance ultrasound spectroscopy experiments conducted on concrete cores, one chemically and mechanically damaged by alkali-silica reactivity, and one undamaged, show that this material displays highly nonlinear wave behavior, similar to many other damaged materials. They find that the damaged sample responds more nonlinearly, manifested by a larger resonant peak and modulus shift as a function of strain amplitude. The nonlinear response indicates that there is a hysteretic influence in the stress-strain equation of state. Further, as in some other materials, slow dynamics are present. The nonlinear response they observe in concrete is an extremely sensitive indicator of damage. Ultimately, nonlinear wave methods applied to concrete may be used to guide mixing, curing, or other production techniques, in order to develop materials with particular desired qualities such as enhanced strength or chemical resistance, and to be used for damage inspection.

  3. Introduction: DNA Electrophoresis Fralin Life Science

    E-Print Network [OSTI]

    Hopkins, William A.

    .................................... 12 Student Pre-Lab Activity: What is DNA? DNA extraction from strawberry ..... Teacher guide: DNA extraction from strawberry.................................. 14 Student guide: DNA extraction from strawberry.................................. 16

  4. Damage detection in initially nonlinear systems

    SciTech Connect (OSTI)

    Bornn, Luke [Los Alamos National Laboratory; Farrar, Charles [Los Alamos National Laboratory; Park, Gyuhae [Los Alamos National Laboratory

    2009-01-01

    The primary goal of Structural Health Monitoring (SHM) is to detect structural anomalies before they reach a critical level. Because of the potential life-safety and economic benefits, SHM has been widely studied over the past decade. In recent years there has been an effort to provide solid mathematical and physical underpinnings for these methods; however, most focus on systems that behave linearly in their undamaged state - a condition that often does not hold in complex 'real world' systems and systems for which monitoring begins mid-lifecycle. In this work, we highlight the inadequacy of linear-based methodology in handling initially nonlinear systems. We then show how the recently developed autoregressive support vector machine (AR-SVM) approach to time series modeling can be used for detecting damage in a system that exhibits initially nonlinear response. This process is applied to data acquired from a structure with induced nonlinearity tested in a laboratory environment.

  5. Electromagnetic Interrogation Techniques Damage Detection

    E-Print Network [OSTI]

    Electromagnetic Interrogation Techniques for Damage Detection H. T. Banks and M. L. Joyner Center.P. Winfree Nasa Langley Research Center Hampton, VA Plenary Lecture, Electromagnetic Nondestructive Evaluation 2001 (ENDE 2001), Kobe, Japan, May 18-19, 20001 #12;Electromagnetic Interrogation Techniques

  6. Electromagnetic Interrogation Techniques Damage Detection

    E-Print Network [OSTI]

    Electromagnetic Interrogation Techniques for Damage Detection H. T. Banks #3; and M. L. Joyner Wincheski and W.P. Winfree Nasa Langley Research Center Hampton, VA #3; Plenary Lecture, Electromagnetic Nondestructive Evaluation 2001 (ENDE 2001), Kobe, Japan, May 18­19, 20001 #12; Electromagnetic Interrogation

  7. Zinc chromate induces chromosome instability and DNA double strand breaks in human lung cells

    SciTech Connect (OSTI)

    Xie Hong; Holmes, Amie L.; Young, Jamie L.; Qin Qin; Joyce, Kellie; Pelsue, Stephen C.; Peng Cheng; Wise, Sandra S.; Jeevarajan, Antony S.; Wallace, William T.; Hammond, Dianne; Wise, John Pierce E-mail: John.Wise@usm.maine.edu

    2009-02-01

    Hexavalent chromium Cr(VI) is a respiratory toxicant and carcinogen, with solubility playing an important role in its carcinogenic potential. Zinc chromate, a water insoluble or 'particulate' Cr(VI) compound, has been shown to be carcinogenic in epidemiology studies and to induce tumors in experimental animals, but its genotoxicity is poorly understood. Our study shows that zinc chromate induced concentration-dependent increases in cytotoxicity, chromosome damage and DNA double strand breaks in human lung cells. In response to zinc chromate-induced breaks, MRE11 expression was increased and ATM and ATR were phosphorylated, indicating that the DNA double strand break repair system was initiated in the cells. In addition, our data show that zinc chromate-induced double strand breaks were only observed in the G2/M phase population, with no significant amount of double strand breaks observed in G1 and S phase cells. These data will aid in understanding the mechanisms of zinc chromate toxicity and carcinogenesis.

  8. Collateral damage: Evolution with displacement of fracture distribution and secondary fault strands in fault damage zones

    E-Print Network [OSTI]

    Savage, Heather M.; Brodsky, Emily E.

    2011-01-01

    E. McCallum (1999), Reservoir damage around faults: OutcropSkar (2005), Controls on damage zone asymmetry of a normal2007), The evolution of the damage zone with fault growth in

  9. Method for producing damage resistant optics

    DOE Patents [OSTI]

    Hackel, Lloyd A. (Livermore, CA); Burnham, Alan K. (Livermore, CA); Penetrante, Bernardino M. (San Ramon, CA); Brusasco, Raymond M. (Livermore, CA); Wegner, Paul J. (Livermore, CA); Hrubesh, Lawrence W. (Pleasanton, CA); Kozlowski, Mark R. (Windsor, CA); Feit, Michael D. (Livermore, CA)

    2003-01-01

    The present invention provides a system that mitigates the growth of surface damage in an optic. Damage to the optic is minimally initiated. In an embodiment of the invention, damage sites in the optic are initiated, located, and then treated to stop the growth of the damage sites. The step of initiating damage sites in the optic includes a scan of the optic using a laser to initiate defects. The exact positions of the initiated sites are identified. A mitigation process is performed that locally or globally removes the cause of subsequent growth of the damaged sites.

  10. Damage detection using frequency domain ARX models and extreme value statistics

    SciTech Connect (OSTI)

    Fasel, T. R. (Timothy R.); Sohn, H. (Hoon); Farrar, C. R. (Charles R.)

    2002-01-01

    Structural health monitoring (SHM) is fast becoming a field of great importance as engineers seek for new ways to ensure the safety of structures throughout their designed lifetime. Current methods for analyzing the dynamic response of structures often use standard frequency response functions to model linear system input/output relationships. However, these functions do not account for the nonlinear response of a system, which damage often introduces. In this study, an auto-regressive model with exogenous inputs (ARX) in the frequency domain is used to extract damage sensitive features, explicitly considering the nonlinear effect in the frequency domain. Furthermore, because of the non-Gaussian nature of the extracted features, extreme value statistics (EVS) is employed to develop a robust damage classifier. The applicability of the ARX model combined with EVS to nonlinear damage detection is demonstrated using vibration data obtained from a laboratory experiment of a three-story building model.

  11. Detection and Repair of Ionizing Radiation-Induced DNA Double Strand Breaks: New Developments in Nonhomologous End Joining

    SciTech Connect (OSTI)

    Wang, Chen [Departments of Biochemistry and Molecular Biology and Oncology, and Southern Alberta Cancer Research Institute, University of Calgary, Calgary (Canada)] [Departments of Biochemistry and Molecular Biology and Oncology, and Southern Alberta Cancer Research Institute, University of Calgary, Calgary (Canada); Lees-Miller, Susan P., E-mail: leesmill@ucalgary.ca [Departments of Biochemistry and Molecular Biology and Oncology, and Southern Alberta Cancer Research Institute, University of Calgary, Calgary (Canada)

    2013-07-01

    DNA damage can occur as a result of endogenous metabolic reactions and replication stress or from exogenous sources such as radiation therapy and chemotherapy. DNA double strand breaks are the most cytotoxic form of DNA damage, and defects in their repair can result in genome instability, a hallmark of cancer. The major pathway for the repair of ionizing radiation-induced DSBs in human cells is nonhomologous end joining. Here we review recent advances on the mechanism of nonhomologous end joining, as well as new findings on its component proteins and regulation.

  12. Detection of damage in axial (membrane) systems

    SciTech Connect (OSTI)

    Duffey, T.A. [Duffey (T.A.), Tijeras, NM (United States); Baker, W.E. [Univ. of New Mexico, Albuquerque, NM (United States). Dept. of Mechanical Engineering; Farrar, C.R. [Los Alamos National Lab., NM (United States); Rhee, W.H. [Texas Tech Univ., Lubbock, TX (United States). Dept. of Mechanical Engineering

    1998-12-31

    In a recent paper, two methods of damage identification (Modified Damage Index and Change-in-Flexibility) were applied to detection of damage in an 8-DOF vibrating system. The goal of the work was to detect damage (reduction in stiffness of one or more of the elements) as well as to locate the particular damaged elements (S). However, the investigation was limited to numerical simulations only. In this paper, a physical, spring-mass model of a similar, degenerate 8-DOF system (7 normal modes plus a rigid-body mode) was constructed. Experiments were then performed and the modal properties of the system were determined in undamaged and damaged states. Excitation was provided either by an impact hammer or by an electromechanical shaker. Damage was induced by replacing one of the springs with a spring of lower stiffness. The Modified Damage Index method clearly isolated the location of damage for a variety of damage locations and levels of damage. The Change-in-Flexibility method, however, was found to be less reliable. The ability of the method to locate damage depended strongly on location and the level of damage as well as the number of modes included.

  13. 2010 MICROBIAL STRESS RESPONSE GORDON RESEARCH CONFERENCE, JULY 18-23, 2010

    SciTech Connect (OSTI)

    Sarah Ades

    2011-07-23

    The 2010 Gordon Research Conference on Microbial Stress Responses provides an open and exciting forum for the exchange of scientific discoveries on the remarkable mechanisms used by microbes to survive in nearly every niche on the planet. Understanding these stress responses is critical for our ability to control microbial survival, whether in the context of biotechnology, ecology, or pathogenesis. From its inception in 1994, this conference has traditionally employed a very broad definition of stress in microbial systems. Sessions will cover the major steps of stress responses from signal sensing to transcriptional regulation to the effectors that mediate responses. A wide range of stresses will be represented. Some examples include (but are not limited to) oxidative stress, protein quality control, antibiotic-induced stress and survival, envelope stress, DNA damage, and nutritional stress. The 2010 meeting will also focus on the role of stress responses in microbial communities, applied and environmental microbiology, and microbial development. This conference brings together researchers from both the biological and physical sciences investigating stress responses in medically- and environmentally relevant microbes, as well as model organisms, using cutting-edge techniques. Computational, systems-level, and biophysical approaches to exploring stress responsive circuits will be integrated throughout the sessions alongside the more traditional molecular, physiological, and genetic approaches. The broad range of excellent speakers and topics, together with the intimate and pleasant setting at Mount Holyoke College, provide a fertile ground for the exchange of new ideas and approaches.

  14. A damage model for fracking

    E-Print Network [OSTI]

    Norris, J Quinn; Rundle, John B

    2015-01-01

    Injections of large volumes of water into tight shale reservoirs allows the extraction of oil and gas not previously accessible. This large volume "super" fracking induces damage that allows the oil and/or gas to flow to an extraction well. The purpose of this paper is to provide a model for understanding super fracking. We assume that water is injected from a small spherical cavity into a homogeneous elastic medium. The high pressure of the injected water generates hoop stresses that reactivate natural fractures in the tight shales. These fractures migrate outward as water is added creating a spherical shell of damaged rock. The porosity associated with these fractures is equal to the water volume injected. We obtain an analytic expression for this volume. We apply our model to a typical tight shale reservoir and show that the predicted water volumes are in good agreement with the volumes used in super fracking.

  15. KU Public Safety Office Criminal Damage

    E-Print Network [OSTI]

    KU Public Safety Office ! Criminal Damage The unidentified white male pictured below is a suspect in the damage of a Coca-Cola vending machine in the Parking Services lobby at 1501 Irving Hill Drive and damage to Coca-Cola vending machines across the campus. Suspect Description: W/M, 5 feet 10 inches, 150

  16. Multiscale Modeling of Radiation Damage in

    E-Print Network [OSTI]

    Multiscale Modeling of Radiation Damage in Fusion Reactor Materials Brian D. Wirth, R.J. Kurtz-7405-Eng-48. #12;Presentation overview · Introduction to fusion reactor materials and radiation damage. tailor He HFIR isotopic tailor He HFIR target/RB He appmHe displacement damage (dpa) ffuussiioonn

  17. Density Functional Theory Models for Radiation Damage

    E-Print Network [OSTI]

    Density Functional Theory Models for Radiation Damage S.L. Dudarev EURATOM/CCFE Fusion Association and informative as the most advanced experimental techniques developed for the observation of radiation damage investigation and assessment of radiation damage effects, offering new insight into the origin of temperature

  18. Structural Damage Detection and Localization Using NETSHM

    E-Print Network [OSTI]

    Gnawali, Omprakash

    Structural Damage Detection and Localization Using NETSHM Krishna Chintalapudi, Jeongyeup Paek and localize damage in large civil structures. Structural engineers often implement and test SHM algorithms the intricacies of wireless networking, or the details of sensor data acquisition. We have implemented a damage

  19. Histone H3K4me3 Binding Is Required for the DNA Repair and Apoptotic Activities of ING1 Tumor

    E-Print Network [OSTI]

    Verkhusha, Vladislav V.

    of growth 1 (ING1) is implicated in oncogenesis, DNA damage repair, and apoptosis. Mutations within the ING11) is a member of the recently discovered family of tumor suppressors implicated in oncogenesis

  20. Becky Hill Green Mountain DNA Conference LT-DNA Analysis

    E-Print Network [OSTI]

    Becky Hill ­ Green Mountain DNA Conference LT-DNA Analysis July 26, 2010 http of the Chief Medical Examiner, NYC Green Mountain DNA Conference Burlington, VT July 26, 2010 Low Template (LT generally aim for 0.5-2 ng 100 pg template 5 pg template #12;Becky Hill ­ Green Mountain DNA Conference LT

  1. Correlating cookoff violence with pre-ignition damage.

    SciTech Connect (OSTI)

    Wente, William Baker; Hobbs, Michael L.; Kaneshige, Michael Jiro

    2010-03-01

    Predicting the response of energetic materials during accidents, such as fire, is important for high consequence safety analysis. We hypothesize that responses of ener-getic materials before and after ignition depend on factors that cause thermal and chemi-cal damage. We have previously correlated violence from PETN to the extent of decom-position at ignition, determined as the time when the maximum Damkoehler number ex-ceeds a threshold value. We seek to understand if our method of violence correlation ap-plies universally to other explosive starting with RDX.

  2. Damage Detection in Plate Structures using Guided Ultrasonic Waves

    E-Print Network [OSTI]

    Jarmer, Gregory James Sylvester

    2009. “Evaluation of the Damage Detection Capability of alikelihood Estimation of Damage Location in Guided- waveStatistically-based Damage Detection in Geometrically-

  3. Micromechanical Damage Models for Continuous Fiber Reinforced Composite Materials

    E-Print Network [OSTI]

    Wu, Yi

    2013-01-01

    2008). Micromechanical modeling of damage and fracture ofmatrix viscoplasticity and evolving damage, Journal of theW.A. (1998). Stochastic damage evolution and failure in

  4. Blast damage mitigation of steel structures from near- contact charges

    E-Print Network [OSTI]

    Wolfson, Janet Crumrine

    2008-01-01

    OF CALIFORNIA, SAN DIEGO Blast Damage Mitigation of Steel35  Damage Levels Observed in LaboratoryFigure 3.34: Progression of damage for a Ballistic Loading

  5. Cognitive Empathy Following Orbitofrontal Cortex and Dorsolateral Prefrontal Cortex Damage

    E-Print Network [OSTI]

    Goodkind, Madeleine Shirley

    2010-01-01

    following bilateral damage to the human amygdala. Nature,as a measure of frontal lobe damage. Journal of Clinical andcaused by frontal damage fail to respond autonomically to

  6. RADIATION DAMAGE RESISTANCE OF REVERSE ELECTRODE GE COAXIAL DETECTORS

    E-Print Network [OSTI]

    Pehl, Richard H.

    2011-01-01

    Parker, "Radiation Damage of Germanium Detectors", Bull. Am.to radiation damage between the two detectors was clearlyRADIATION DAMAGE RESISTANCE OF REVERSE ELECTRODE GE COAXIAL DETECTORS

  7. Multiplex analysis of DNA

    DOE Patents [OSTI]

    Church, George M. (Boston, MA); Kieffer-Higgins, Stephen (Dorchester, MA)

    1992-01-01

    This invention features vectors and a method for sequencing DNA. The method includes the steps of: a) ligating the DNA into a vector comprising a tag sequence, the tag sequence includes at least 15 bases, wherein the tag sequence will not hybridize to the DNA under stringent hybridization conditions and is unique in the vector, to form a hybrid vector, b) treating the hybrid vector in a plurality of vessels to produce fragments comprising the tag sequence, wherein the fragments differ in length and terminate at a fixed known base or bases, wherein the fixed known base or bases differs in each vessel, c) separating the fragments from each vessel according to their size, d) hybridizing the fragments with an oligonucleotide able to hybridize specifically with the tag sequence, and e) detecting the pattern of hybridization of the tag sequence, wherein the pattern reflects the nucleotide sequence of the DNA.

  8. Shear Unzipping of DNA

    E-Print Network [OSTI]

    Buddhapriya Chakrabarti; David R. Nelson

    2009-04-09

    We study theoretically the mechanical failure of a simple model of double stranded DNA under an applied shear. Starting from a more microscopic Hamiltonian that describes a sheared DNA, we arrive at a nonlinear generalization of a ladder model of shear unzipping proposed earlier by deGennes [deGennes P. G. C. R. Acad. Sci., Ser. IV; Phys., Astrophys. 2001, 1505]. Using this model and a combination of analytical and numerical methods, we study the DNA "unzipping" transition when the shearing force exceeds a critical threshold at zero temperature. We also explore the effects of sequence heterogeneity and finite temperature and discuss possible applications to determine the strength of colloidal nanoparticle assemblies functionalized by DNA.

  9. Rapid Damage eXplorer (RDX): A Probabilistic Framework for Learning Changes From Bitemporal Images

    SciTech Connect (OSTI)

    Vatsavai, Raju

    2012-01-01

    Recent decade has witnessed major changes on the Earth, for example, deforestation, varying cropping and human settlement patterns, and crippling damages due to disasters. Accurate damage assessment caused by major natural and anthropogenic disasters is becoming critical due to increases in human and economic loss. This increase in loss of life and severe damages can be attributed to the growing population, as well as human migration to the disaster prone regions of the world. Rapid assessment of these changes and dissemination of accurate information is critical for creating an effective emergency response. Change detection using high-resolution satellite images is a primary tool in assessing damages, monitoring biomass and critical infrastructures, and identifying new settlements. In this demo, we present a novel supervised probabilistic framework for identifying changes using very high-resolution multispectral, and bitemporal remote sensing images. Our demo shows that the rapid damage explorer (RDX) system is resilient to registration errors and differing sensor characteristics.

  10. DNA microarray analyses reveal a post-irradiation differential time-dependent gene expression profile in yeast cells exposed to X-rays and {gamma}-rays

    SciTech Connect (OSTI)

    Kimura, Shinzo [Laboratory of Environmental Biology, Department of Preventive Medicine, Hokkaido University School of Medicine, Sapporo 060-8638 (Japan); Ishidou, Emi [Human Stress Signal Research Center (HSS), National Institute of Advanced Industrial Science and Technology (AIST) WEST, 16-1 Onogawa, Tsukuba, Ibaraki 305-8569 (Japan); Kurita, Sakiko [Human Stress Signal Research Center (HSS), National Institute of Advanced Industrial Science and Technology (AIST) WEST, 16-1 Onogawa, Tsukuba, Ibaraki 305-8569 (Japan); Suzuki, Yoshiteru [Human Stress Signal Research Center (HSS), National Institute of Advanced Industrial Science and Technology (AIST) WEST, 16-1 Onogawa, Tsukuba, Ibaraki 305-8569 (Japan); Shibato, Junko [Human Stress Signal Research Center (HSS), National Institute of Advanced Industrial Science and Technology (AIST) WEST, 16-1 Onogawa, Tsukuba, Ibaraki 305-8569 (Japan); Rakwal, Randeep [Human Stress Signal Research Center (HSS), National Institute of Advanced Industrial Science and Technology (AIST) WEST, 16-1 Onogawa, Tsukuba, Ibaraki 305-8569 (Japan)]. E-mail: rakwal-68@aist.go.jp; Iwahashi, Hitoshi [Human Stress Signal Research Center (HSS), National Institute of Advanced Industrial Science and Technology (AIST) WEST, 16-1 Onogawa, Tsukuba, Ibaraki 305-8569 (Japan)

    2006-07-21

    Ionizing radiation (IR) is the most enigmatic of genotoxic stress inducers in our environment that has been around from the eons of time. IR is generally considered harmful, and has been the subject of numerous studies, mostly looking at the DNA damaging effects in cells and the repair mechanisms therein. Moreover, few studies have focused on large-scale identification of cellular responses to IR, and to this end, we describe here an initial study on the transcriptional responses of the unicellular genome model, yeast (Saccharomyces cerevisiae strain S288C), by cDNA microarray. The effect of two different IR, X-rays, and gamma ({gamma})-rays, was investigated by irradiating the yeast cells cultured in YPD medium with 50 Gy doses of X- and {gamma}-rays, followed by resuspension of the cells in YPD for time-course experiments. The samples were collected for microarray analysis at 20, 40, and 80 min after irradiation. Microarray analysis revealed a time-course transcriptional profile of changed gene expressions. Up-regulated genes belonged to the functional categories mainly related to cell cycle and DNA processing, cell rescue defense and virulence, protein and cell fate, and metabolism (X- and {gamma}-rays). Similarly, for X- and {gamma}-rays, the down-regulated genes belonged to mostly transcription and protein synthesis, cell cycle and DNA processing, control of cellular organization, cell fate, and C-compound and carbohydrate metabolism categories, respectively. This study provides for the first time a snapshot of the genome-wide mRNA expression profiles in X- and {gamma}-ray post-irradiated yeast cells and comparatively interprets/discusses the changed gene functional categories as effects of these two radiations vis-a-vis their energy levels.

  11. Structural-Damage Detection by Distributed Piezoelectric Transducers and Tuned Electric Circuits

    E-Print Network [OSTI]

    F. dell'Isola; F. Vestroni; S. Vidoli

    2010-07-13

    A novel technique for damage detection of structures is introduced and discussed. It is based on purely electric measurements of the state variables of an electric network coupled to the main structure through a distributed set of piezoelectric patches. The constitutive parameters of this auxiliary network are optimized to increase the sensitivity of global measurements- as the frequency, response functions relative to selected electric degrees of freedom-with respect to a given class of variations in the structural-mechanical properties. Because the proposed method is based on purely electric input and output measurements, it allows for accurate results in the identification and localization of damages. Use of the electric frequency-response function to identify the mechanical damage leads to nonconvex optimization problems; therefore the proposed sensitivity-enhanced identification procedure becomes computationally efficient if an a priori knowledge about the damage is available.

  12. Impurity-doped optical shock, detonation and damage location sensor

    DOE Patents [OSTI]

    Weiss, J.D.

    1995-02-07

    A shock, detonation, and damage location sensor providing continuous fiber-optic means of measuring shock speed and damage location, and could be designed through proper cabling to have virtually any desired crush pressure. The sensor has one or a plurality of parallel multimode optical fibers, or a singlemode fiber core, surrounded by an elongated cladding, doped along their entire length with impurities to fluoresce in response to light at a different wavelength entering one end of the fiber(s). The length of a fiber would be continuously shorted as it is progressively destroyed by a shock wave traveling parallel to its axis. The resulting backscattered and shifted light would eventually enter a detector and be converted into a proportional electrical signals which would be evaluated to determine shock velocity and damage location. The corresponding reduction in output, because of the shortening of the optical fibers, is used as it is received to determine the velocity and position of the shock front as a function of time. As a damage location sensor the sensor fiber cracks along with the structure to which it is mounted. The size of the resulting drop in detector output is indicative of the location of the crack. 8 figs.

  13. Impurity-doped optical shock, detonation and damage location sensor

    DOE Patents [OSTI]

    Weiss, Jonathan D. (Albuquerque, NM)

    1995-01-01

    A shock, detonation, and damage location sensor providing continuous fiber-optic means of measuring shock speed and damage location, and could be designed through proper cabling to have virtually any desired crush pressure. The sensor has one or a plurality of parallel multimode optical fibers, or a singlemode fiber core, surrounded by an elongated cladding, doped along their entire length with impurities to fluoresce in response to light at a different wavelength entering one end of the fiber(s). The length of a fiber would be continuously shorted as it is progressively destroyed by a shock wave traveling parallel to its axis. The resulting backscattered and shifted light would eventually enter a detector and be converted into a proportional electrical signals which would be evaluated to determine shock velocity and damage location. The corresponding reduction in output, because of the shortening of the optical fibers, is used as it is received to determine the velocity and position of the shock front as a function of time. As a damage location sensor the sensor fiber cracks along with the structure to which it is mounted. The size of the resulting drop in detector output is indicative of the location of the crack.

  14. Crystal structure of a p53 core tetramer bound to DNA

    SciTech Connect (OSTI)

    Malecka, K.A.; Ho, W.C.; Marmorstein, R.; (Penn)

    2009-09-02

    The tumor suppressor p53 regulates downstream genes in response to many cellular stresses and is frequently mutated in human cancers. Here, we report the use of a crosslinking strategy to trap a tetrameric p53 DNA-binding domain (p53DBD) bound to DNA and the X-ray crystal structure of the protein/DNA complex. The structure reveals that two p53DBD dimers bind to B form DNA with no relative twist and that a p53 tetramer can bind to DNA without introducing significant DNA bending. The numerous dimer-dimer interactions involve several strictly conserved residues, thus suggesting a molecular basis for p53DBD-DNA binding cooperativity. Surface residue conservation of the p53DBD tetramer bound to DNA highlights possible regions of other p53 domain or p53 cofactor interactions.

  15. Hepatitis C virus NS3/4A protein interacts with ATM, impairs DNA repair and enhances sensitivity to ionizing radiation

    SciTech Connect (OSTI)

    Lai, Chao-Kuen; Jeng, King-Song [Institute of Molecular Biology, Academia Sinica, Taipei, 115, Taiwan (China); Machida, Keigo [Department of Molecular Microbiology and Immunology, University of Southern California, Keck School of Medicine, 2001 Zonal Avenue, Los Angeles, CA 90033 (United States); Cheng, Yi-Sheng [Institute of Molecular Biology, Academia Sinica, Taipei, 115, Taiwan (China); Lai, Michael M.C. [Institute of Molecular Biology, Academia Sinica, Taipei, 115, Taiwan (China); Department of Molecular Microbiology and Immunology, University of Southern California, Keck School of Medicine, 2001 Zonal Avenue, Los Angeles, CA 90033 (United States)], E-mail: michlai@gate.sinica.edu.tw

    2008-01-20

    Hepatitis C virus (HCV) infection is frequently associated with the development of hepatocellular carcinomas and non-Hodgkin's B-cell lymphomas. Nonstructural protein 3 (NS3) of HCV possesses serine protease, nucleoside triphosphatase, and helicase activities, while NS4A functions as a cofactor for the NS3 serine protease. Here, we show that HCV NS3/4A interacts with the ATM (ataxia-telangiectasia mutated), a cellular protein essential for cellular response to irradiation. The expression of NS3/4A caused cytoplasmic translocation of either endogenous or exogenous ATM and delayed dephosphorylation of the phosphorylated ATM and {gamma}-H2AX following ionizing irradiation. As a result, the irradiation-induced {gamma}-H2AX foci persisted longer in the NS3/4A-expressing cells. Furthermore, these cells showed increased comet tail moment in single-cell electrophoresis assay, indicating increased double-strand DNA breaks. The cells harboring an HCV replicon also exhibited cytoplasmic localization of ATM and increased sensitivity to irradiation. These results demonstrate that NS3/4A impairs the efficiency of DNA repair by interacting with ATM and renders the cells more sensitive to DNA damage. This effect may contribute to HCV oncogenesis.

  16. Structure of an aprataxin?DNA complex with insights into AOA1 neurodegenerative disease

    SciTech Connect (OSTI)

    Tumbale, Percy; Appel, C. Denise; Kraehenbuehl, Rolf; Robertson, Patrick D.; Williams, Jessica S.; Krahn, Joe; Ahel, Ivan; Williams, R. Scott (NIEHS); (Manchester)

    2012-09-17

    DNA ligases finalize DNA replication and repair through DNA nick-sealing reactions that can abort to generate cytotoxic 5'-adenylation DNA damage. Aprataxin (Aptx) catalyzes direct reversal of 5'-adenylate adducts to protect genome integrity. Here the structure of a Schizosaccharomyces pombe Aptx-DNA-AMP-Zn{sup 2+} complex reveals active site and DNA interaction clefts formed by fusing a histidine triad (HIT) nucleotide hydrolase with a DNA minor groove-binding C{sub 2}HE zinc finger (Znf). An Aptx helical 'wedge' interrogates the base stack for sensing DNA ends or DNA nicks. The HIT-Znf, the wedge and an '[F/Y]PK' pivot motif cooperate to distort terminal DNA base-pairing and direct 5'-adenylate into the active site pocket. Structural and mutational data support a wedge-pivot-cut HIT-Znf catalytic mechanism for 5'-adenylate adduct recognition and removal and suggest that mutations affecting protein folding, the active site pocket and the pivot motif underlie Aptx dysfunction in the neurodegenerative disorder ataxia with oculomotor apraxia 1 (AOA1).

  17. Continuum limits of bistable spring models of carbon nanotube arrays accounting for material damage

    E-Print Network [OSTI]

    T. Blesgen; F. Fraternali; J. R. Raney; A. Amendola; C. Daraio

    2011-12-10

    Using chains of bistable springs, a model is derived to investigate the plastic behavior of carbon nanotube arrays with damage. We study the preconditioning effect due to the loading history by computing analytically the stress-strain pattern corresponding to a fatigue-type damage of the structure. We identify the convergence of the discrete response to the limiting case of infinitely many springs, both analytically in the framework of Gamma-convergence, as well as numerically.

  18. Coarse-graining DNA for simulations of DNA nanotechnology

    E-Print Network [OSTI]

    Jonathan P. K. Doye; Thomas E. Ouldridge; Ard A. Louis; Flavio Romano; Petr Sulc; Christian Matek; Benedict E. K. Snodin; Lorenzo Rovigatti; John S. Schreck; Ryan M. Harrison; William P. J. Smith

    2013-08-18

    To simulate long time and length scale processes involving DNA it is necessary to use a coarse-grained description. Here we provide an overview of different approaches to such coarse graining, focussing on those at the nucleotide level that allow the self-assembly processes associated with DNA nanotechnology to be studied. OxDNA, our recently-developed coarse-grained DNA model, is particularly suited to this task, and has opened up this field to systematic study by simulations. We illustrate some of the range of DNA nanotechnology systems to which the model is being applied, as well as the insights it can provide into fundamental biophysical properties of DNA.

  19. Coarse-graining DNA for simulations of DNA nanotechnology

    E-Print Network [OSTI]

    Doye, Jonathan P K; Louis, Ard A; Romano, Flavio; Sulc, Petr; Matek, Christian; Snodin, Benedict E K; Rovigatti, Lorenzo; Schreck, John S; Harrison, Ryan M; Smith, William P J

    2013-01-01

    To simulate long time and length scale processes involving DNA it is necessary to use a coarse-grained description. Here we provide an overview of different approaches to such coarse graining, focussing on those at the nucleotide level that allow the self-assembly processes associated with DNA nanotechnology to be studied. OxDNA, our recently-developed coarse-grained DNA model, is particularly suited to this task, and has opened up this field to systematic study by simulations. We illustrate some of the range of DNA nanotechnology systems to which the model is being applied, as well as the insights it can provide into fundamental biophysical properties of DNA.

  20. Chondrocyte outgrowth into a gelatin scaffold in a single impact load model of damage/repair - effect of BMP-2

    E-Print Network [OSTI]

    Henson, Frances M D; Vincent, Thea A

    2007-12-05

    damage repair response in mature equine articular cartilage explants following single impact load and subsequent culture [3]. This response is characterised Published: 5 December 2007 BMC Musculoskeletal Disorders 2007, 8:120 doi:10... ) degenerative joint disease, specifically osteoarthritis (OA) [2]. by the appearance of chondrocyte repair cells on damaged cartilage. This apparent mobilisation of chondrocytes has BMC Musculoskeletal Disorders 2007, 8:120 http://www.biomedcentral.com/1471...

  1. Corrosion-induced damage raises serious implications

    SciTech Connect (OSTI)

    Kane, R.D.; Cayard, M.S. [CLI International, Inc., Houston, TX (United States)

    1997-06-01

    One of the most difficult and often underestimated aspects of pipeline rehabilitation is the assessment of corrosion-induced damage. This question involves evaluation of damage from prior service as well as consideration of conditions which may pose additional time-dependent degradation which could affect the future serviceability of the pipeline. The present study examines the assessment of pipeline damage and rehabilitation requirements through knowledge of materials of construction, operating conditions, field inspection and service records.

  2. Structural damage identification in wind turbine blades using piezoelectric active sensing with ultrasonic validation

    SciTech Connect (OSTI)

    Claytor, Thomas N [Los Alamos National Laboratory; Ammerman, Curtt N [Los Alamos National Laboratory; Park, Gyu Hae [Los Alamos National Laboratory; Farinholt, Kevin M [Los Alamos National Laboratory; Farrar, Charles R [Los Alamos National Laboratory; Atterbury, Marie K [Los Alamos National Laboratory

    2010-01-01

    This paper gives a brief overview of a new project at LANL in structural damage identification for wind turbines. This project makes use of modeling capabilities and sensing technology to understand realistic blade loading on large turbine blades, with the goal of developing the technology needed to automatically detect early damage. Several structural health monitoring (SHM) techniques using piezoelectric active materials are being investigated for the development of wireless, low power sensors that interrogate sections of the wind turbine blade using Lamb wave propagation data, frequency response functions (FRFs), and time-series analysis methods. The modeling and sensor research will be compared with extensive experimental testing, including wind tunnel experiments, load and fatigue tests, and ultrasonic scans - on small- to mid-scale turbine blades. Furthermore, this study will investigate the effect of local damage on the global response of the blade by monitoring low-frequency response changes.

  3. DNA polymerase having modified nucleotide binding site for DNA sequencing

    DOE Patents [OSTI]

    Tabor, S.; Richardson, C.

    1997-03-25

    A modified gene encoding a modified DNA polymerase is disclosed. The modified polymerase incorporates dideoxynucleotides at least 20-fold better compared to the corresponding deoxynucleotides as compared with the corresponding naturally-occurring DNA polymerase. 6 figs.

  4. Searching for DNA Lesions: Structural Evidence for Lower- and Higher-Affinity DNA Binding Conformations of Human Alkyladenine DNA Glycosylase

    E-Print Network [OSTI]

    Drennan, Catherine L.

    To efficiently repair DNA, human alkyladenine DNA glycosylase (AAG) must search the million-fold excess of unmodified DNA bases to find a handful of DNA lesions. Such a search can be facilitated by the ability of glycosylases, ...

  5. Prediction of Damage Zone Growth in Composites Using Continuum Damage Mechanics 

    E-Print Network [OSTI]

    McLendon, Wesley R.

    2010-07-14

    The continuum damage mechanics (CDM) approach is widely used to model damage in polymer matrix composite materials which are represented using the homogenized properties of the fiber and matrix constituents. CDM simplifies the problem of accounting...

  6. Final Report [The c-Abl signaling network in the radioadaptive response

    SciTech Connect (OSTI)

    Chi-Min, Yuan

    2014-01-28

    The radioadaptive response, or radiation hormesis, i.e. a low dose of radiation can protect cells and organisms from the effects of a subsequent higher dose, is a widely recognized phenomenon. Mechanisms underlying such radiation hormesis, however, remain largely unclear. Preliminary studies indicate an important role of c-Abl signaling in mediating the radioadaptive response. We propose to investigate how c-Abl regulates the crosstalk between p53 and NF?B in response to low doses irradiation. We found in our recent study that low dose IR induces a reciprocal p53 suppression and NF?B activation, which induces HIF-a and subsequently a metabolic reprogramming resulting in a transition from oxidative phosphorylation to glycolysis. Of importance is that this glycolytic switch is essential for the radioadaptive response. This low-dose radiationinduced HIF1? activation was in sharp contrast with the high-dose IR-induced p53 activation and HIF1? inhibition. HIF1? and p53 seem to play distinct roles in mediating the radiation dose-dependent metabolic response. The induction of HIF1?-mediated glycolysis is restricted to a low dose range of radiation, which may have important implications in assessing the level of radiation exposure and its potential health risk. Our results support a dose-dependent metabolic response to IR. When IR doses are below the threshold of causing detectable DNA damage (<0.2Gy) and thus little p53 activation, HIF1? is induced resulting in induction of glycolysis and increased radiation resistance. When the radiation dose reaches levels eliciting DNA damage, p53 is activated and diminishes the activity of HIF1? and glycolysis, leading to the induction of cell death. Our work challenges the LNT model of radiation exposure risk and provides a metabolic mechanism of radioadaptive response. The study supports a need for determining the p53 and HIF1? activity as a potential reliable biological readout of radiation exposure in humans. The exquisite sensitivity of cellular metabolism to low doses of radiation could also serve as a valuable biomarker for estimating the health effects of low-level radiation exposure.

  7. Ecosystem health at the texas coastal bend: a spatial analysis of exposure and response 

    E-Print Network [OSTI]

    Bissett, Wesley Thurlow, Jr.

    2009-05-15

    of aging or exposure to genotoxic substances (Bickham et al. 1998;Clark et al. 2000;Custer et al. 1997;Custer et al. 1994;Custer et al. 2000;Kalina et al. 1998;Lowcock et al. 1997;Wickliffe and Bickham 1998). These changes are induced through DNA strand... breaks, faulty replication associated with a damaged DNA template, and through inhibition of DNA synthesis (Albertini et al. 2000). Chromosomal aberrations are detectable when cells are in the mitotic phase of the cell cycle. This limits...

  8. Damage Identification with Linear Discriminant Operators

    SciTech Connect (OSTI)

    Farrar, C.R.; Nix, D.A.; Duffey, T.A.; Cornwell, P.J.; Pardoen, G.C.

    1999-02-08

    This paper explores the application of statistical pattern recognition and machine learning techniques to vibration-based damage detection. First, the damage detection process is described in terms of a problem in statistical pattern recognition. Next, a specific example of a statistical-pattern-recognition-based damage detection process using a linear discriminant operator, ''Fisher's Discriminant'', is applied to the problem of identifying structural damage in a physical system. Accelerometer time histories are recorded from sensors attached to the system as that system is excited using a measured input. Linear Prediction Coding (LPC) coefficients are utilized to convert the accelerometer time-series data into multi-dimensional samples representing the resonances of the system during a brief segment of the time series. Fisher's discriminant is then used to find the linear projection of the LPC data distributions that best separates data from undamaged and damaged systems. The method i s applied to data from concrete bridge columns as the columns are progressively damaged. For this case, the method captures a clear distinction between undamaged and damaged vibration profiles. Further, the method assigns a probability of damage that can be used to rank systems in order of priority for inspection.

  9. MODELING LONGITUDINAL DAMAGE IN SHIP COLLISIONS

    E-Print Network [OSTI]

    Brown, Alan

    . Performing Organization Name and Address Department of Aerospace and Ocean Engineering. 10. Work Unit No made excellent progress towards predicting damage penetration in ship collisions. This project focuses collision data for penetrating collisions. 17. Key Words ship collisions, longitudinal ship damage 18

  10. DNA Structural Nanotechnology Duke University

    E-Print Network [OSTI]

    Reif, John H.

    DNA Structural Nanotechnology John Reif Duke University Graduate Students: Harish Chandran&Caltech Tube Lattices #12;Ned Seeman New York University, USA Ned Seeman: Father of DNA Nanotechnology His Initial Ideas & Motivation for DNA Nanotechnology #12;Cube Chen & Seeman, Nature350:631 (1991) Truncated

  11. Enhancing tumor cell response to chemotherapy through nanoparticle-mediated codelivery of siRNA and cisplatin prodrug

    E-Print Network [OSTI]

    Xu, Xiaoyang

    Cisplatin and other DNA-damaging chemotherapeutics are widely used to treat a broad spectrum of malignancies. However, their application is limited by both intrinsic and acquired chemoresistance. Most mutations that result ...

  12. The probability of double-strand breaks in giant DNA decreases markedly as the DNA concentration increases

    E-Print Network [OSTI]

    Shimobayashi, Shunsuke F; Mori, Toshiaki; Yoshikawa, Kenichi

    2012-01-01

    DNA double-strand breaks (DSBs) represent a serious source of damage for all living things and thus there have been many quantitative studies of DSBs both in vivo and in vitro. Despite this fact, the processes that lead to their production have not yet been clearly understood, and there is no established theory that can account for the statistics of their production, in particular, the number of DSBs per base pair per unit Gy, here denoted by P1, which is the most important parameter for evaluating the degree of risk posed by DSBs. Here, using the single-molecule observation method with giant DNA molecules (166 kbp), we evaluate the number of DSBs caused by gamma-ray irradiation. We find that P1 is nearly inversely proportional to the DNA concentration above a certain threshold DNA concentration. A simple model that accounts for the marked decrease of P1 shows that it is necessary to consider the characteristics of giant DNA molecules as semiflexible polymers to interpret the intrinsic mechanism of DSBs.

  13. Identifying a transcriptional signature for cell sensitivity to the cancer chemotherapy agent, BCNU

    E-Print Network [OSTI]

    Valiathan, Chandni Rajan

    2011-01-01

    Many organisms have evolved DNA damage response mechanisms to deal with the constant damage to DNA caused by endogenous and exogenous agents. These mechanisms activate cell cycle checkpoints to allow time for DNA repair ...

  14. An overview of modal-based damage identification methods

    SciTech Connect (OSTI)

    Farrar, C.R.; Doebling, S.W. [Los Alamos National Lab., NM (United States). Engineering Analysis Group

    1997-09-01

    This paper provides an overview of methods that examine changes in measured vibration response to detect, locate, and characterize damage in structural and mechanical systems. The basic idea behind this technology is that modal parameters (notably frequencies, mode shapes, and modal damping) are functions of the physical properties of the structure (mass, damping, and stiffness). Therefore, changes in the physical properties will cause detectable changes in the modal properties. The motivation for the development of this technology is first provided. The methods are then categorized according to various criteria such as the level of damage detection provided, model-based vs. non-model-based methods and linear vs. nonlinear methods. This overview is limited to methods that can be adapted to a wide range of structures (i.e., are not dependent on a particular assumed model form for the system such as beam-bending behavior and methods and that are not based on updating finite element models). Next, the methods are described in general terms including difficulties associated with their implementation and their fidelity. Past, current and future-planned applications of this technology to actual engineering systems are summarized. The paper concludes with a discussion of critical issues for future research in the area of modal-based damage identification.

  15. [Localized fracture damage effects in toughened ceramics]. Final report

    SciTech Connect (OSTI)

    1997-12-31

    The primary research goal was to investigate localized fracture damage due to single point cutting of ceramic materials and then to compare this to multipoint cutting during precision grinding of the same materials. Two test systems were designed and constructed for the single-point cutting tests. The first system used a PZT actuator for closed-loop load control. An acoustic emission data acquisition system was used for crack initiation detection. The second test system employed a high-precision diamond-turning machine for closed-loop position (cutting depth) control. A high stiffness load cell and data acquisition system were used for crack initiation detection. Microcutting tests were carried out on silicon, borosilicate glass and CVD silicon carbide. The crack initiation thresholds and the fracture damage distribution were determined as a function of the loading conditions using a Vickers diamond as the cutting tool. The grinding tests were done using a plunge-grinding technique with metal-bonded diamond wheels. Optical microscopy, surface roughness and specific cutting energy were measured in order to characterize the fracture damage as a function of the grinding infeed rate. Simulation models were developed in order to estimate the average grain-depth of cut in grinding so that the response could be compared to the single-point microcutting tests.

  16. O[superscript 6]-Methylguanine DNA lesions induce an intra-S-phase arrest from which cells exit into apoptosis governed by early and late multi-pathway signaling network activation

    E-Print Network [OSTI]

    Noonan, Ericka M.

    The O[superscript 6]-methylguanine (O[superscript 6]MeG) DNA lesion is well known for its mutagenic, carcinogenic, and cytotoxic properties, and understanding how a cell processes such damage is of critical importance for ...

  17. Extreme bendability of DNA double helix due to bending asymmetry

    E-Print Network [OSTI]

    Hossein Salari; B. Eslami-Mossallam; M. S. Naderi; M. R. Ejtehadi

    2015-05-23

    Experimental data of the DNA cyclization (J-factor) at short length scales, as a way to study the elastic behavior of tightly bent DNA, exceed the theoretical expectation based on the wormlike chain (WLC) model by several orders of magnitude. Here, we propose that asymmetric bending rigidity of the double helix in the groove direction can be responsible for extreme bendability of DNA at short length scales and it also facilitates DNA loop formation at these lengths. To account for the bending asymmetry, we consider the asymmetric elastic rod (AER) model which has been introduced and parametrized in an earlier study (B. Eslami-Mossallam and M. Ejtehadi, Phys. Rev. E 80, 011919 (2009)). Exploiting a coarse grained representation of DNA molecule at base pair (bp) level, and using the Monte Carlo simulation method in combination with the umbrella sampling technique, we calculate the loop formation probability of DNA in the AER model. We show that, for DNA molecule has a larger J-factor compared to the WLC model which is in excellent agreement with recent experimental data.

  18. Extreme bendability of DNA double helix due to bending asymmetry

    E-Print Network [OSTI]

    Salari, Hossein; Naderi, M S; Ejtehadi, M R

    2015-01-01

    Experimental data of the DNA cyclization (J-factor) at short length scales, as a way to study the elastic behavior of tightly bent DNA, exceed the theoretical expectation based on the wormlike chain (WLC) model by several orders of magnitude. Here, we propose that asymmetric bending rigidity of the double helix in the groove direction can be responsible for extreme bendability of DNA at short length scales and it also facilitates DNA loop formation at these lengths. To account for the bending asymmetry, we consider the asymmetric elastic rod (AER) model which has been introduced and parametrized in an earlier study (B. Eslami-Mossallam and M. Ejtehadi, Phys. Rev. E 80, 011919 (2009)). Exploiting a coarse grained representation of DNA molecule at base pair (bp) level, and using the Monte Carlo simulation method in combination with the umbrella sampling technique, we calculate the loop formation probability of DNA in the AER model. We show that, for DNA molecule has a larger J-factor compared to the WLC model w...

  19. Seismic damage estimation for buried pipelines - challenges after three decades of progress

    SciTech Connect (OSTI)

    Pineda-porras, Omar Andrey; Najafi, Mohammand

    2009-01-01

    This paper analyzes the evolution over the past three decades of seismic damage estimation for buried pipelines and identifies some challenges for future research studies on the subject. The first section of this paper presents a chronological description of the evolution since the mid-1970s of pipeline fragility relations - the most common tool for pipeline damage estimation - and follows with a careful analysis of the use of several ground motion parameters as pipeline damage indicators. In the second section of the paper, four gaps on the subject are identified and proposed as challenges for future research studies. The main conclusion of this work is that enhanced fragility relations must be developed for improving pipeline damage estimation, which must consider relevant parameters that could influence the seismic response of pipelines.

  20. DNA Methylation as a Biomarker for Preeclampsia

    SciTech Connect (OSTI)

    Anderson, Cindy M.; Ralph, Jody L.; Wright, Michelle L.; Linggi, Bryan E.; Ohm, Joyce E.

    2014-10-01

    Background: Preeclampsia contributes significantly to pregnancy-associated morbidity and mortality as well as future risk of cardiovascular disease in mother and offspring, and preeclampsia in offspring. The lack of reliable methods for early detection limits the opportunities for prevention, diagnosis, and timely treatment. Purpose: The purpose of this study was to explore distinct DNA methylation patterns associated with preeclampsia in both maternal cells and fetal-derived tissue that represent potential biomarkers to predict future preeclampsia and inheritance in children. Method: A convenience sample of nulliparous women (N = 55) in the first trimester of pregnancy was recruited for this prospective study. Genome-wide DNA methylation was quantified in first-trimester maternal peripheral white blood cells and placental chorionic tissue from normotensive women and those with preeclampsia (n = 6/group). Results: Late-onset preeclampsia developed in 12.7% of women. Significant differences in DNA methylation were identified in 207 individual linked cytosine and guanine (CpG) sites in maternal white blood cells collected in the first trimester (132 sites with gain and 75 sites with loss of methylation), which were common to approximately 75% of the differentially methylated CpG sites identified in chorionic tissue of fetal origin. Conclusion: This study is the first to identify maternal epigenetic targets and common targets in fetal-derived tissue that represent putative biomarkers for early detection and heritable risk of preeclampsia. Findings may pave the way for diagnosis of preeclampsia prior to its clinical presentation and acute damaging effects, and the potential for prevention of the detrimental long-term sequelae.

  1. Underground infrastructure damage for a Chicago scenario

    SciTech Connect (OSTI)

    Dey, Thomas N; Bos, Rabdall J

    2011-01-25

    Estimating effects due to an urban IND (improvised nuclear device) on underground structures and underground utilities is a challenging task. Nuclear effects tests performed at the Nevada Test Site (NTS) during the era of nuclear weapons testing provides much information on how underground military structures respond. Transferring this knowledge to answer questions about the urban civilian environment is needed to help plan responses to IND scenarios. Explosions just above the ground surface can only couple a small fraction of the blast energy into an underground shock. The various forms of nuclear radiation have limited penetration into the ground. While the shock transmitted into the ground carries only a small fraction of the blast energy, peak stresses are generally higher and peak ground displacement is lower than in the air blast. While underground military structures are often designed to resist stresses substantially higher than due to the overlying rocks and soils (overburden), civilian structures such as subways and tunnels would generally only need to resist overburden conditions with a suitable safety factor. Just as we expect the buildings themselves to channel and shield air blast above ground, basements and other underground openings as well as changes of geology will channel and shield the underground shock wave. While a weaker shock is expected in an urban environment, small displacements on very close-by faults, and more likely, soils being displaced past building foundations where utility lines enter could readily damaged or disable these services. Immediately near an explosion, the blast can 'liquefy' a saturated soil creating a quicksand-like condition for a period of time. We extrapolate the nuclear effects experience to a Chicago-based scenario. We consider the TARP (Tunnel and Reservoir Project) and subway system and the underground lifeline (electric, gas, water, etc) system and provide guidance for planning this scenario.

  2. Fleet DNA (Presentation)

    SciTech Connect (OSTI)

    Walkokwicz, K.; Duran, A.

    2014-06-01

    The Fleet DNA project objectives include capturing and quantifying drive cycle and technology variation for the multitude of medium- and heavy-duty vocations; providing a common data storage warehouse for medium- and heavy-duty vehicle fleet data across DOE activities and laboratories; and integrating existing DOE tools, models, and analyses to provide data-driven decision making capabilities. Fleet DNA advantages include: for Government - providing in-use data for standard drive cycle development, R&D, tech targets, and rule making; for OEMs - real-world usage datasets provide concrete examples of customer use profiles; for fleets - vocational datasets help illustrate how to maximize return on technology investments; for Funding Agencies - ways are revealed to optimize the impact of financial incentive offers; and for researchers -a data source is provided for modeling and simulation.

  3. DNA waves and water

    E-Print Network [OSTI]

    L. Montagnier; J. Aissa; E. Del Giudice; C. Lavallee; A. Tedeschi; G. Vitiello

    2010-12-23

    Some bacterial and viral DNA sequences have been found to induce low frequency electromagnetic waves in high aqueous dilutions. This phenomenon appears to be triggered by the ambient electromagnetic background of very low frequency. We discuss this phenomenon in the framework of quantum field theory. A scheme able to account for the observations is proposed. The reported phenomenon could allow to develop highly sensitive detection systems for chronic bacterial and viral infections.

  4. War damages and reconstruction of Peruca dam

    SciTech Connect (OSTI)

    Nonveiller, E.; Rupcic, J.; Sever, Z.

    1999-04-01

    The paper describes the heavy damages caused by blasting in the Peruca rockfill dam in Croatia in January 1993. Complete collapse of the dam by overtopping was prevented through quick action of the dam owner by dumping clayey gravel on the lowest sections of the dam crest and opening the bottom outlet of the reservoir, thus efficiently lowering the water level. After the damages were sufficiently established and alternatives for restoration of the dam were evaluated, it was decided to construct a diaphragm wall through the damaged core in the central dam part as the impermeable dam element and to rebuild the central clay core at the dam abutments. Reconstruction works are described.

  5. Semantic Responsibility 

    E-Print Network [OSTI]

    Toribio, Josefa

    2002-01-01

    In this paper I attempt to develop a notion of responsibility (semantic responsibility) that is to the notion of belief what epistemic responsibility is to the notion of justification. 'Being semantically responsible' ...

  6. Kinetics of Mismatch Formation opposite Lesions by the Replicative DNA Polymerase from Bacteriophage RB69

    SciTech Connect (OSTI)

    Hogg, Matthew; Rudnicki, Jean; Midkiff, John; Reha-Krantz, Linda; Doubli, Sylvie; Wallace, Susan S. (Alberta); (Vermont)

    2010-04-12

    The fidelity of DNA replication is under constant threat from the formation of lesions within the genome. Oxidation of DNA bases leads to the formation of altered DNA bases such as 8-oxo-7,8-dihydroguanine, commonly called 8-oxoG, and 2-hydroxyadenenine, or 2-OHA. In this work we have examined the incorporation kinetics opposite these two oxidatively derived lesions as well as an abasic site analogue by the replicative DNA polymerase from bacteriophage RB69. We compared the kinetic parameters for both wild type and the low fidelity L561A variant. While nucleotide incorporation rates (k{sub pol}) were generally higher for the variant, the presence of a lesion in the templating position reduced the ability of both the wild-type and variant DNA polymerases to form ternary enzyme-DNA-dNTP complexes. Thus, the L561A substitution does not significantly affect the ability of the RB69 DNA polymerase to recognize damaged DNA; instead, the mutation increases the probability that nucleotide incorporation will occur. We have also solved the crystal structure of the L561A variant forming an 8-oxoG {center_dot} dATP mispair and show that the propensity for forming this mispair depends on an enlarged polymerase active site.

  7. DAMAGE ASSESSMENT OF COMPOSITE PLATE STRUCTURES WITH UNCERTAINTY

    E-Print Network [OSTI]

    Boyer, Edmond

    DAMAGE ASSESSMENT OF COMPOSITE PLATE STRUCTURES WITH UNCERTAINTY Chandrashekhar M.* , Ranjan Uncertainties associated with a structural model and measured vibration data may lead to unreliable damage that material uncertainties in composite structures cause considerable problem in damage assessment which can

  8. New navel orangeworm sanitation standards ?could reduce almond damage

    E-Print Network [OSTI]

    Higbee, Bradley S.; Siegel, Joel P

    2009-01-01

    disruption, dispersal and damage prediction. Proc 34thtype and amount of insect damage. J Ag Food Chem 49:4513–9.standards could reduce almond damage by Bradley S. Higbee

  9. RADIATION DAMAGE TO BSCCO-2223 FROM 50 MEV PROTONS

    E-Print Network [OSTI]

    Zeller, A.F.; Ronningen, R.M.; Godeke, A.; Heilbronn, L.H.; McMahan-Norris, P.; Gupta, R.

    2007-01-01

    RADIATION DAMAGE TO BSCCO-2223 FROM 50 MEV PROTONS A. F.BSCCO-2223. Radiation damage. INTRODUCTION The magnets incomponents be resistant to damage. One solution [1] is to

  10. A Damage-Revelation Rationale for Coupon Remedies

    E-Print Network [OSTI]

    Polinsky, A. Mitchell; Rubinfeld, Daniel L.

    2006-01-01

    Bargaining and the Design of Damage Awards,” 10 Journal ofpage 1 Revised: March 2006 A DAMAGE-REVELATION RATIONALE FORin a setting in which damages vary among plaintiffs and are

  11. INSTANTANEOUS DAMAGE IDENTIFICATION AND LOCALIZATION THROUGH SPARSE LASER ULTRASONIC SCANNING

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    INSTANTANEOUS DAMAGE IDENTIFICATION AND LOCALIZATION THROUGH SPARSE LASER ULTRASONIC SCANNING This study proposes an instantaneous damage identification and localization technique through sparse laser ultrasonic signals are obtained, a damage index (DI) representing the violation of the linear reciprocity

  12. A Damage-Revelation Rationale for Coupon Remedies

    E-Print Network [OSTI]

    Polinsky, A. Mitchell; Rubinfeld, Daniel L

    2007-01-01

    Bargaining and the Design of Damage Awards,’’ 10 Journal ofGramlich, Fred. 1986. ‘‘Scrip Damages in Antitrust Cases,’’in the Assessment of Damages,’’ 39 Journal of Law and

  13. Assessing United States hurricane damage under different environmental conditions

    E-Print Network [OSTI]

    Maheras, Anastasia Francis

    2012-01-01

    Hurricane activity between 1979 and 2011 was studied to determine damage statistics under different environmental conditions. Hurricanes cause billions of dollars of damage every year in the United States, but damage ...

  14. Unified Creep Plasticity Damage (UCPD) Model for Rigid Polyurethane Foams.

    SciTech Connect (OSTI)

    Neilsen, Michael K.; Lu, Wei-Yang; Scherzinger, William M.; Hinnerichs, Terry D.; Lo, Chi S.

    2015-06-01

    Numerous experiments were performed to characterize the mechanical response of several different rigid polyurethane foams (FR3712, PMDI10, PMDI20, and TufFoam35) to large deformation. In these experiments, the effects of load path, loading rate, and temperature were investigated. Results from these experiments indicated that rigid polyurethane foams exhibit significant volumetric and deviatoric plasticity when they are compressed. Rigid polyurethane foams were also found to be very strain-rate and temperature dependent. These foams are also rather brittle and crack when loaded to small strains in tension or to larger strains in compression. Thus, a new Unified Creep Plasticity Damage (UCPD) model was developed and implemented into SIERRA with the name Foam Damage to describe the mechanical response of these foams to large deformation at a variety of temperatures and strain rates. This report includes a description of recent experiments and experimental findings. Next, development of a UCPD model for rigid, polyurethane foams is described. Selection of material parameters for a variety of rigid polyurethane foams is then discussed and finite element simulations with the new UCPD model are compared with experimental results to show behavior that can be captured with this model.

  15. Thin Film Femtosecond Laser Damage Competition

    SciTech Connect (OSTI)

    Stolz, C J; Ristau, D; Turowski, M; Blaschke, H

    2009-11-14

    In order to determine the current status of thin film laser resistance within the private, academic, and government sectors, a damage competition was started at the 2008 Boulder Damage Symposium. This damage competition allows a direct comparison of the current state of the art of high laser resistance coatings since they are tested using the same damage test setup and the same protocol. In 2009 a high reflector coating was selected at a wavelength of 786 nm at normal incidence at a pulse length of 180 femtoseconds. A double blind test assured sample and submitter anonymity so only a summary of the results are presented here. In addition to the laser resistance results, details of deposition processes, coating materials and layer count, and spectral results will also be shared.

  16. Damage spreading and coupling in Markov chains

    E-Print Network [OSTI]

    Etienne P. Bernard; Cédric Chanal; Werner Krauth

    2011-06-23

    In this paper, we relate the coupling of Markov chains, at the basis of perfect sampling methods, with damage spreading, which captures the chaotic nature of stochastic dynamics. For two-dimensional spin glasses and hard spheres we point out that the obstacle to the application of perfect-sampling schemes is posed by damage spreading rather than by the survey problem of the entire configuration space. We find dynamical damage-spreading transitions deeply inside the paramagnetic and liquid phases, and show that critical values of the transition temperatures and densities depend on the coupling scheme. We discuss our findings in the light of a classic proof that for arbitrary Monte Carlo algorithms damage spreading can be avoided through non-Markovian coupling schemes.

  17. Formation damage in underbalanced drilling operations 

    E-Print Network [OSTI]

    Reyes Serpa, Carlos Alberto

    2003-01-01

    Formation damage has long been recognized as a potential source of reduced productivity and injectivity in both horizontal and vertical wells. From the moment that the pay zone is being drilled until the well is put on production, a formation...

  18. Dealing with Storm-Damaged Trees 

    E-Print Network [OSTI]

    Kirk, Melanie; Taylor, Eric; Foster, C. Darwin

    2005-10-25

    -Damaged Trees Melanie R. Kirk, Extension Program Specialist, Eric L. Taylor, Assistant Professor and Extension Specialist, and C. Darwin Foster, Associate Department Head and Extension Program Leader for Forestry, The Texas A&M University System Downed trees...

  19. In Situ Analysis of 8-Oxo-7,8-dihydro-2?-deoxyguanosine Oxidation Reveals Sequence- and Agent-Specific Damage Spectra

    E-Print Network [OSTI]

    Lim, Kok Seong

    Guanine is a major target for oxidation in DNA, with 8-oxo-7,8-dihydro-2?-deoxyguanosine (8-oxodG) as a major product. 8-oxodG is itself significantly more susceptible to oxidation than guanine, with the resulting damage ...

  20. Controlled ion implant damage profile for etching

    DOE Patents [OSTI]

    Arnold, Jr., George W. (Tijeras, NM); Ashby, Carol I. H. (Edgewood, NM); Brannon, Paul J. (Albuquerque, NM)

    1990-01-01

    A process for etching a material such as LiNbO.sub.3 by implanting ions having a plurality of different kinetic energies in an area to be etched, and then contacting the ion implanted area with an etchant. The various energies of the ions are selected to produce implant damage substantially uniformly throughout the entire depth of the zone to be etched, thus tailoring the vertical profile of the damaged zone.

  1. Cable Damage Detection System and Algorithms Using Time Domain Reflectometry

    SciTech Connect (OSTI)

    Clark, G A; Robbins, C L; Wade, K A; Souza, P R

    2009-03-24

    This report describes the hardware system and the set of algorithms we have developed for detecting damage in cables for the Advanced Development and Process Technologies (ADAPT) Program. This program is part of the W80 Life Extension Program (LEP). The system could be generalized for application to other systems in the future. Critical cables can undergo various types of damage (e.g. short circuits, open circuits, punctures, compression) that manifest as changes in the dielectric/impedance properties of the cables. For our specific problem, only one end of the cable is accessible, and no exemplars of actual damage are available. This work addresses the detection of dielectric/impedance anomalies in transient time domain reflectometry (TDR) measurements on the cables. The approach is to interrogate the cable using time domain reflectometry (TDR) techniques, in which a known pulse is inserted into the cable, and reflections from the cable are measured. The key operating principle is that any important cable damage will manifest itself as an electrical impedance discontinuity that can be measured in the TDR response signal. Machine learning classification algorithms are effectively eliminated from consideration, because only a small number of cables is available for testing; so a sufficient sample size is not attainable. Nonetheless, a key requirement is to achieve very high probability of detection and very low probability of false alarm. The approach is to compare TDR signals from possibly damaged cables to signals or an empirical model derived from reference cables that are known to be undamaged. This requires that the TDR signals are reasonably repeatable from test to test on the same cable, and from cable to cable. Empirical studies show that the repeatability issue is the 'long pole in the tent' for damage detection, because it is has been difficult to achieve reasonable repeatability. This one factor dominated the project. The two-step model-based approach is summarized as follows: Step 1, Cable Modeling: Given input-output TDR signals s(n) and x{sub U}(n) for a cable known to be free of damage, system identification algorithms are used to compute a dynamic prediction-error cable model that has output {cflx x}{sub U}(n). The model is declared valid when the innovations e{sub U}(n) = x{sub U}(n) {cflx x}{sub U}(n) satisfy a statistical zero-mean whiteness test. This validated model output is then used as a known reference to which other cables can be compared. Step 2, Cable Testing: The TDR output signal x{sub D}(n) from a cable under test is compared with the model output {cflx x}{sub U}(n) by computing the innovations e{sub D}(n) = x{sub D}(n) {cflx x}{sub U}(n). The innovations are tested using a short-term whiteness test statistic, which employs a statistical confidence interval. If the cable passes the test, this implies that the model is valid and the cable is declared undamaged. If the cable fails the test, this indicates a model mismatch, which means that the cable's dielectric properties have changed; and this implies that the cable is damaged. The test threshold is adjusted to maximize probability of detection and minimize probability of false alarm according to an empirically determined receiver operating characteristic (ROC) curve. An associated confidence interval on the probability of correct classification is also provided. The effectiveness of the algorithm is demonstrated using measured TDR signals for undamaged and damaged cables. Experimental and algorithmic methods for coping with repeatability issues are presented. The model-based damage detection algorithms have been shown to perform well for some representative examples of real TDR signals acquired using the two-dimensional (2D) mockup fixture. If the damage causes a short circuit, then damage detection performance is generally good to excellent. Examples include the cases demonstrated in this report for cuts and pinholes. If the damage does not cause a short circuit, then damage detection performance is generally poor to fair. Examples include

  2. Condition/damage monitoring methodologies.

    SciTech Connect (OSTI)

    Farrar, C. R. (Charles R.); Sohn, Hong Yong

    2001-01-01

    COSMOS, in cooperation with the Advanced National Seismic System (ANSS), is sponsoring an invited workshop entitled Strong-Motion Instrumentation of Buildings. The workshop is motivated by the need to obtain broad input from earthquake engineering professionals for the purpose of developing guidelines for strong motion instrumentation of buildings as part of the ANSS instrument installation effort. The ANSS has been authorized capital finding for 6,000 strong-motion instruments. It is expected that funding for purchase and installation of instruments will be appropriated over a period of several years. The instrument installations must meet multiple monitoring objectives including instrumentation of buildings of various types, urban reference stations, and emergency response and recovery actions. An important opportunity therefore, exists to comprehensively define strong-motion monitoring needs as an underpinning basis for developing guidelines for installation of this important monitoring system. This workshop will specifically address instrumentation of buildings.

  3. Analysis of substrate specificity of Schizosaccharomyces pombe Mag1 alkylpurine DNA glycosylase

    SciTech Connect (OSTI)

    Adhikary, Suraj; Eichman, Brandt F.

    2014-10-02

    DNA glycosylases specialized for the repair of alkylation damage must identify, with fine specificity, a diverse array of subtle modifications within DNA. The current mechanism involves damage sensing through interrogation of the DNA duplex, followed by more specific recognition of the target base inside the active site pocket. To better understand the physical basis for alkylpurine detection, we determined the crystal structure of Schizosaccharomyces pombe Mag1 (spMag1) in complex with DNA and performed a mutational analysis of spMag1 and the close homologue from Saccharomyces cerevisiae (scMag). Despite strong homology, spMag1 and scMag differ in substrate specificity and cellular alkylation sensitivity, although the enzymological basis for their functional differences is unknown. We show that Mag preference for 1,N{sup 6}-ethenoadenine ({var_epsilon}A) is influenced by a minor groove-interrogating residue more than the composition of the nucleobase-binding pocket. Exchanging this residue between Mag proteins swapped their {var_epsilon}A activities, providing evidence that residues outside the extrahelical base-binding pocket have a role in identification of a particular modification in addition to sensing damage.

  4. DNA | Open Energy Information

    Open Energy Info (EERE)

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative Fuels Data Center Home Page on Google Bookmark EERE: Alternative Fuels Data Center Home Page on QA:QA J-E-1 SECTION J APPENDIX E LISTStar EnergyLawler,CoalConcordiaConsumerLEDSEnergyDMS Company Ltd Jump to:DNA Jump

  5. A high-throughput in vivo micronucleus assay for genome instability screening in mice

    E-Print Network [OSTI]

    Balmus, Gabriel; Karp, Natasha A.; Ng, Bee Ling; Jackson, Stephen P.; Adams, David J.; McIntyre, Rebecca E.

    2014-12-31

    and detection of molecules involved in the response to exogenous DNA damaging agents DNA damage response (DDR) defects can be revealed by treating mice that show normal spontaneous micronucleus frequencies with genotoxic agents. Upon treatment, micronuclei... or for the identification of deficiencies that are only apparent, or amplified, in response to DDR challenge because they are only necessary for the response to exogenous DNA damaging 640 agents rather than endogenous DNA damaging agents. This procedure will enable...

  6. Spatiotemporal characterization of ionizing radiation induced DNA damage foci and their relation to chromatin organization

    E-Print Network [OSTI]

    Costes, Sylvain V

    2010-01-01

    germ cells and after low-dose gamma-radiation: relationshipsexposure to low doses of ionizing radiation. Mutat Res (after exposure to low doses of ionizing radiation. Mutat Res

  7. Recommendations for Standardized Description of and Nomenclature Concerning Oxidatively Damaged Nucleobases in DNA

    E-Print Network [OSTI]

    Cooke, Marcus S.

    Despite being a relatively young field, the study of oxidative stress has attracted huge interest. With the advent of simple and relatively inexpensive assays (sometimes from commercial suppliers), a growing number of ...

  8. Inflammation-Induced Cell Proliferation Potentiates DNA Damage-Induced Mutations In Vivo

    E-Print Network [OSTI]

    Kiraly, Orsolya

    Mutations are a critical driver of cancer initiation. While extensive studies have focused on exposure-induced mutations, few studies have explored the importance of tissue physiology as a modulator of mutation susceptibility ...

  9. A comparison of DNA damage probes in two HMEC lines with X-irradiation

    E-Print Network [OSTI]

    Wisnewski, Christy L.; Bjornstad, Kathleen A.; Rosen, Christoper J.; Chang, Polly Y.; Blakely, Eleanor A.

    2008-01-01

    IN TWO HMEC LINES WITH X-IRRADIATION CHRISTY L. WISNEWSKI,prior to the experiment. Irradiation Four well LabTek slidesVictoreen probe 154. Following irradiation, slides or dishes

  10. DOE contractors' workshop: Cellular and molecular aspects of radiation induced DNA damage and repair

    SciTech Connect (OSTI)

    Not Available

    1987-01-01

    For four decades the US Department of Energy and its predecessors have been the lead federal agency in supporting radiation biology research. Over the years emphasis in this program has gradually shifted from dose-effect studies on animals to research on the effects of radiations of various qualities on cells and molecules. Mechanistic studies on the action of radiation at the subcellular level are few in number and there is a need for more research in this area if we are to gain a better understanding of how radiation affects living cells. The intent of this workshop was to bring together DOE contractors and grantees who are investigating the effects of radiation at the cellular and molecular levels. The aims were to foster the exchange of information on research projects and experimental results, promote collaborative research efforts, and obtain an overview of research currently supported by the Health Effects Research Division of the Office of Health and Environmental Research. The latter is needed by the Office for program planning purposes. This report on the workshop which took place in Albuquerque, New Mexico on March 10-11, 1987, includes an overview with future research recommendations, extended abstracts of the plenary presentations, shorter abstracts of each poster presentation, a workshop agenda and the names and addresses of the attendees.

  11. Forensic DNA data banking by state crime labortaories

    SciTech Connect (OSTI)

    McEwen, J.E.

    1995-06-01

    This article reports the results of a survey of the responsible crime laboratories in the first 19 states with legislation establishing forensic DNA data banks. The survey inquired into the labs` policies and procedures regarding the collection, storage, and analysis of samples; the retention of samples and data; search protocols; access to samples and data by third parties; and related matters. The research suggests that (1) the number of samples collected from convicted offenders for DNA data banking has far surpassed the number that have been analyzed; (2) data banks have already been used in a small but growing number of cases, to locate suspects and to identify associations between unresolved cases; (3) crime labs currently plan to retain indefinitely the samples collected for their data banks; and (4) the nature and extent of security safeguards that crime labs have implemented for their data banks vary among states. The recently enacted DNA Identification Act (1994) will provide $40 million in federal matching grants to states for DNA analysis activities, so long as states comply with specified quality-assurance standards, submit to external proficiency testing, and limit access to DNA information. Although these additional funds should help to ease some sample backlogs, it remains unclear how labs will allocate the funds, as between analyzing samples for their data banks and testing evidence samples in cases without suspects. The DNA Identification Act provides penalties for the disclosure or obtaining of DNA data held by data banks that participate in CODIS, the FBI`s evolving national network of DNA data banks, but individual crime labs must also develop stringent internal safeguards to prevent breaches of data-bank security. 9 refs., 3 tabs.

  12. Subcellular Spatial Correlation of Particle Traversal and Biological Response in Clinical Ion Beams

    SciTech Connect (OSTI)

    Niklas, Martin; Abdollahi, Amir; Akselrod, Mark S.; Debus, Jürgen; Jäkel, Oliver; and others

    2013-12-01

    Purpose: To report on the spatial correlation of physical track information (fluorescent nuclear track detectors, FNTDs) and cellular DNA damage response by using a novel hybrid detector (Cell-Fit-HD). Methods and Materials: The FNTDs were coated with a monolayer of human non-small cell lung carcinoma (A549) cells and irradiated with carbon ions (270.55 MeV u{sup ?1}, rising flank of the Bragg peak). Phosphorylated histone variant H2AX accumulating at the irradiation-induced double-strand break site was labeled (RIF). The position and direction of ion tracks in the FNTD were registered with the location of the RIF sequence as an ion track surrogate in the cell layer. Results: All RIF sequences could be related to their corresponding ion tracks, with mean deviations of 1.09 ?m and ?1.72 ?m in position and of 2.38° in slope. The mean perpendicular between ion track and RIF sequence was 1.58 ?m. The mean spacing of neighboring RIFs exhibited a regular rather than random spacing. Conclusions: Cell-Fit-HD allows for unambiguous spatial correlation studies of cell damage with respect to the intracellular ion traversal under therapeutic beam conditions.

  13. Prevention of Salt Damage inPrevention of Salt Damage in LimestoneLimestone

    E-Print Network [OSTI]

    Petta, Jason

    Prevention of Salt Damage inPrevention of Salt Damage in LimestoneLimestone Kathy Whitaker.jpg #12;Introduction: Sodium Sulfate Thenardite: Na2SO4 Mirabilite: Na2SO4·10H2O Salt exposure for 5 weeks the stone by capillary uptake of water containing the dissolved salt. Degradation of mortar. #12

  14. Damage and Damage Prediction for Wood Shearwalls Subjected to Simulated Earthquake Loads

    E-Print Network [OSTI]

    Gupta, Rakesh

    -structure predictive damage model and its integration into the development of a performance-based seismic design and refinement of modern strength-based seismic design codes were in use. One result of this significant damage-based seismic design PBSD philosophy for woodframe structures. Such phi- losophies are currently being developed

  15. DAMAGE DETECTION IN COMPOSITES BY NONCONTACT LASER Byeongjin Park

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    DAMAGE DETECTION IN COMPOSITES BY NONCONTACT LASER ULTRASONIC Byeongjin Park 1 , Hoon Sohn 1 author: p.malinowski@imp.gda.pl ABSTRACT This study proposes an instantaneous damage localization, are obtained. Then possible damage locations are estimated through time-of-flight triangulation of damage

  16. RUPTURE BY DAMAGE ACCUMULATION IN ROCKS David Amitrano

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    RUPTURE BY DAMAGE ACCUMULATION IN ROCKS David Amitrano LIRIGM, Université J. Fourier, Grenoble of rocks is associated with microcracks nucleation and propagation, i.e. damage. The accumulation of damage as strength and modulus. The damage process can be studied both statically by direct observation of thin

  17. Ductile damage parameters identification for cold metal forming applications

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    Ductile damage parameters identification for cold metal forming applications Pierre damage mechanics is essential to predict failure during cold metal forming applications. Several damage models can be found in the literature. These damage models are coupled with the mechanical behavior so

  18. Flavin-Induced Oligomerization in Escherichia coli Adaptive Response Protein AidB

    SciTech Connect (OSTI)

    Hamill, Michael J.; Jost, Marco; Wong, Cintyu; Elliott, Sean J.; Drennan, Catherine L. (MIT); (BU)

    2011-11-21

    The process known as 'adaptive response' allows Escherichia coli to respond to small doses of DNA-methylating agents by upregulating the expression of four proteins. While the role of three of these proteins in mitigating DNA damage is well understood, the function of AidB is less clear. Although AidB is a flavoprotein, no catalytic role has been established for the bound cofactor. Here we investigate the possibility that flavin plays a structural role in the assembly of the AidB tetramer. We report the generation and biophysical characterization of deflavinated AidB and of an AidB mutant that has greatly reduced affinity for flavin adenine dinucleotide (FAD). Using fluorescence quenching and analytical ultracentrifugation, we find that apo AidB has a high affinity for FAD, as indicated by an apparent dissociation constant of 402.1 {+-} 35.1 nM, and that binding of substoichiometric amounts of FAD triggers a transition in the AidB oligomeric state. In particular, deflavinated AidB is dimeric, whereas the addition of FAD yields a tetramer. We further investigate the dimerization and tetramerization interfaces of AidB by determining a 2.8 {angstrom} resolution crystal structure in space group P3{sub 2} that contains three intact tetramers in the asymmetric unit. Taken together, our findings provide strong evidence that FAD plays a structural role in the formation of tetrameric AidB.

  19. Method to reduce damage to backing plate

    DOE Patents [OSTI]

    Perry, Michael D. (Livermore, CA); Banks, Paul S. (Livermore, CA); Stuart, Brent C. (Fremont, CA)

    2001-01-01

    The present invention is a method for penetrating a workpiece using an ultra-short pulse laser beam without causing damage to subsequent surfaces facing the laser. Several embodiments are shown which place holes in fuel injectors without damaging the back surface of the sack in which the fuel is ejected. In one embodiment, pulses from an ultra short pulse laser remove about 10 nm to 1000 nm of material per pulse. In one embodiment, a plasma source is attached to the fuel injector and initiated by common methods such as microwave energy. In another embodiment of the invention, the sack void is filled with a solid. In one other embodiment, a high viscosity liquid is placed within the sack. In general, high-viscosity liquids preferably used in this invention should have a high damage threshold and have a diffusing property.

  20. Thermal Damage Characterization of Energetic Materials

    SciTech Connect (OSTI)

    Hsu, P C; DeHaven, M R; Springer, H K; Maienschein, J L

    2009-08-14

    We conducted thermal damage experiments at 180?C on PBXN-9 and characterized its material properties. Volume expansion at high temperatures was very significant which led to a reduction in material density. 2.6% of weight loss was observed, which was higher than other HMX-based formulations. Porosity of PBXN-9 increased to 16% after thermal exposure. Small-scale safety tests (impact, friction, and spark) showed no significant sensitization when the damaged samples were tested at room temperature. Gas permeation measurements showed that gas permeability in damaged materials was several orders of magnitude higher than that in pristine materials. In-situ measurements of gas permeability and density were proved to be possible at higher temperatures.

  1. Seawater can damage Saudi sandstone oil reservoirs

    SciTech Connect (OSTI)

    Dahab, A.S. (King Saud Univ., Riyadh (SA))

    1990-12-10

    Experiments have shown that formation damage from waterflooding of the Aramco and Alkhafji sandstones of Saudi Arabia will not occur if the salinity of the injected brines is higher than 20% NaCl. Because the connate water in these reservoirs has a high salt content of up to 231,000 ppm, Saudi oil fields are almost always susceptible to formation damage when flooded with seawater (about 38,500 ppm). The productive behavior of a reservoir can be affected by clay crystals developed within rock pores.

  2. Resistance of cotton to pink bollworm damage 

    E-Print Network [OSTI]

    Brazzel, J. R.

    1956-01-01

    for resistance to pink bollworra damage, College Station, Texas, 1SAI . 12. Group comparisons analyses for a number of cottons with Deltapine TA based on number of larvae re? covered per gram of boll weight in greenhouse screening experiments for pink... screening experiment for resistance to pink bollworm damage, College Station, Texas, 195U- 1955: (A) Deltapine 15, (B) G^ thurberi, (C) Texas 389, (D) MW-298, (E) G^ stocksii, '(F) Stoneville 2-B x G. tomentosum, (G) Hexaploia Z-61j., (H) MW-1U7 . ? 5U...

  3. Gabriele Simi1 BaBar SVT: Radiation Damage and BaBar SVT: Radiation Damage and

    E-Print Network [OSTI]

    California at Santa Cruz, University of

    Gabriele Simi1 BaBar SVT: Radiation Damage and BaBar SVT: Radiation Damage and Other OperationalBar and SVTIntro to BaBar and SVT Radiation Environment Damage to Si Detectors Damage to Front End Electronics for Photon and KL detection DIRC for K/ separation DCH for charged particle tracking SVT for tracking

  4. Delay-active damage versus non-local enhancement for anisotropic damage dynamics computations with alternated loading

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    Delay-active damage versus non-local enhancement for anisotropic damage dynamics computations, Laboratoire d'´etudes dynamiques F-91191 GIF-SUR-YVETTE Abstract Anisotropic damage thermodynamics framework of anisotropic visco-damage, by introducing a material strain rate effect in the cases of positive hydro- static

  5. Damage mechanisms in the dynamic fracture of nominally brittle polymers

    E-Print Network [OSTI]

    Davy Dalmas; Claudia Guerra; Julien Scheibert; Daniel Bonamy

    2013-04-23

    Linear Elastic Fracture Mechanics (LEFM) provides a consistent framework to evaluate quantitatively the energy flux released to the tip of a growing crack. Still, the way in which the crack selects its velocity in response to this energy flux remains far from completely understood. To uncover the underlying mechanisms, we experimentally studied damage and dissipation processes that develop during the dynamic failure of polymethylmethacrylate (PMMA), classically considered as the archetype of brittle amorphous materials. We evidenced a well-defined critical velocity along which failure switches from nominally-brittle to quasi-brittle, where crack propagation goes hand in hand with the nucleation and growth of microcracks. Via post-mortem analysis of the fracture surfaces, we were able to reconstruct the complete spatiotemporal microcracking dynamics with micrometer/nanosecond resolution. We demonstrated that the true local propagation speed of individual crack fronts is limited to a fairly low value, which can be much smaller than the apparent speed measured at the continuum-level scale. By coalescing with the main front, microcracks boost the macroscale velocity through an acceleration factor of geometrical origin. We discuss the key role of damage-related internal variables in the selection of macroscale fracture dynamics.

  6. Development of a general purpose code to couple experimental modal analysis and damage identification algorithms

    SciTech Connect (OSTI)

    Doebling, S.W.; Farrar, C.R. [Los Alamos National Lab., NM (United States). Engineering Analysis Group; Cornwell, P.J. [Rose Hulman Inst. of Tech., Terre Haute, IN (United States). Dept. of Mechanical Engineering

    1998-03-01

    This paper introduces a new toolbox of graphical interface software algorithms for the numerical simulation of vibration tests, analysis of modal data, finite element model correlation, and the comparison of both linear and nonlinear damage identification techniques. This toolbox is unique because it contains several different vibration-based damage identification algorithms, categorized as those which use only measured response and sensor location information (non-model-based techniques) and those which use finite element model correlation (model-based techniques). Another unique feature of this toolbox is the wide range of algorithms for experimental modal analysis. The toolbox also contains a unique capability that utilizes the measured coherence functions and Monte Carlo analysis to perform statistical uncertainty analysis on the modal parameters and damage identification results.

  7. Damage detection technique by measuring laser-based mechanical impedance

    SciTech Connect (OSTI)

    Lee, Hyeonseok; Sohn, Hoon [Department of Civil and Environmental Engineering, Korea Advanced Institute of Science and Technology (Daehak-ro 291, Yuseong-gu, Daejeon 305-701) (Korea, Republic of)

    2014-02-18

    This study proposes a method for measurement of mechanical impedance using noncontact laser ultrasound. The measurement of mechanical impedance has been of great interest in nondestructive testing (NDT) or structural health monitoring (SHM) since mechanical impedance is sensitive even to small-sized structural defects. Conventional impedance measurements, however, have been based on electromechanical impedance (EMI) using contact-type piezoelectric transducers, which show deteriorated performances induced by the effects of a) Curie temperature limitations, b) electromagnetic interference (EMI), c) bonding layers and etc. This study aims to tackle the limitations of conventional EMI measurement by utilizing laser-based mechanical impedance (LMI) measurement. The LMI response, which is equivalent to a steady-state ultrasound response, is generated by shooting the pulse laser beam to the target structure, and is acquired by measuring the out-of-plane velocity using a laser vibrometer. The formation of the LMI response is observed through the thermo-mechanical finite element analysis. The feasibility of applying the LMI technique for damage detection is experimentally verified using a pipe specimen under high temperature environment.

  8. Severe fuel-damage scoping test performance. [PWR

    SciTech Connect (OSTI)

    Gruen, G.E.; Buescher, B.J.

    1983-01-01

    As a result of the Three Mile Island Unit-2 (TMI-2) accident, the Nuclear Regulatory Commission has initiated a severe fuel damage test program to evaluate fuel rod and core response during severe accidents similar to TMI-2. The first test of Phase I of this series has been successfully completed in the Power Burst Facility at the Idaho National Engineering Laboratory. Following the first test, calculations were performed using the TRAC-BD1 computer code with actual experimental boundary conditions. This paper discusses the test conduct and performance and presents the calculated and measured test bundle results. The test resulted in a slow heatup to 2000 K over about 4 h, with an accelerated reaction of the zirconium cladding at temperatures above 1600 K in the lower part or the bundle and 2000 K in the upper portion of the bundle.

  9. Undulator Radiation Damage Experience at LCLS

    SciTech Connect (OSTI)

    Nuhn, H. D.; Field, C.; Mao, S.; Levashov, Y.; Santana, M.; Welch, J. N.; Wolf, Z.

    2015-01-06

    The SLAC National Accelerator Laboratory has been running the Linac Coherent Light Source (LCLS), the first x-ray Free Electron Laser since 2009. Undulator magnet damage from radiation, produced by the electron beam traveling through the 133-m long straight vacuum tube, has been and is a concern. A damage measurement experiment has been performed in 2007 in order to obtain dose versus damage calibrations. Radiation reduction and detection devices have been integrated into the LCLS undulator system. The accumulated radiation dose rate was continuously monitored and recorded. In addition, undulator segments have been routinely removed from the beamline to be checked for magnetic (50 ppm, rms) and mechanic (about 0.25 µm, rms) changes. A reduction in strength of the undulator segments is being observed, at a level, which is now clearly above the noise. Recently, potential sources for the observed integrated radiation levels have been investigated. The paper discusses the results of these investigation as well as comparison between observed damage and measured dose accumulations and discusses, briefly, strategies for the new LCLS-II upgrade, which will be operating at more than 300 times larger beam rate.

  10. Gas condensate damage in hydraulically fractured wells 

    E-Print Network [OSTI]

    Adeyeye, Adedeji Ayoola

    2004-09-30

    This project is a research into the effect of gas condensate damage in hydraulically fractured wells. It is the result of a problem encountered in producing a low permeability formation from a well in South Texas owned by the El Paso Production...

  11. How do energetic ions damage metallic surfaces?

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

    Osetskiy, Yury N.; Calder, Andrew F.; Stoller, Roger E.

    2015-02-20

    Surface modification under bombardment by energetic ions observed under different conditions in structural and functional materials and can be either unavoidable effect of the conditions or targeted modification to enhance materials properties. Understanding basic mechanisms is necessary for predicting properties changes. The mechanisms activated during ion irradiation are of atomic scale and atomic scale modeling is the most suitable tool to study these processes. In this paper we present results of an extensive simulation program aimed at developing an understanding of primary surface damage in iron by energetic particles. We simulated 25 keV self-ion bombardment of Fe thin films withmore »(100) and (110) surfaces at room temperature. A large number of simulations, ~400, were carried out allow a statistically significant treatment of the results. The particular mechanism of surface damage depends on how the destructive supersonic shock wave generated by the displacement cascade interacts with the free surface. Three basic scenarios were observed, with the limiting cases being damage created far below the surface with little or no impact on the surface itself, and extensive direct surface damage on the timescale of a few picoseconds. In some instances, formation of large vacancy loops beneath the free surface was observed, which may explain some earlier experimental observations.« less

  12. 1 GENERAL DESCRIPTION OF BAOTOU EARTHQUAKE DAMAGES

    E-Print Network [OSTI]

    Spencer Jr., Billie F.

    frame gallery (west) of No. 5 coke oven system of BISC. It acted in the violation of the national, water towers, bridges, substations, gas holders, open-hearth furnaces and reservoirs etc, 50% of them and heat supplying pipe networks, as well as gas pipelines for the municipal utilities. Damages

  13. Normalized cDNA libraries

    DOE Patents [OSTI]

    Soares, M.B.; Efstratiadis, A.

    1997-06-10

    This invention provides a method to normalize a directional cDNA library constructed in a vector that allows propagation in single-stranded circle form comprising: (a) propagating the directional cDNA library in single-stranded circles; (b) generating fragments complementary to the 3{prime} noncoding sequence of the single-stranded circles in the library to produce partial duplexes; (c) purifying the partial duplexes; (d) melting and reassociating the purified partial duplexes to moderate Cot; and (e) purifying the unassociated single-stranded circles, thereby generating a normalized cDNA library. 4 figs.

  14. Normalized cDNA libraries

    DOE Patents [OSTI]

    Soares, Marcelo B. (New York, NY); Efstratiadis, Argiris (Englewood, NJ)

    1997-01-01

    This invention provides a method to normalize a directional cDNA library constructed in a vector that allows propagation in single-stranded circle form comprising: (a) propagating the directional cDNA library in single-stranded circles; (b) generating fragments complementary to the 3' noncoding sequence of the single-stranded circles in the library to produce partial duplexes; (c) purifying the partial duplexes; (d) melting and reassociating the purified partial duplexes to moderate Cot; and (e) purifying the unassociated single-stranded circles, thereby generating a normalized cDNA library.

  15. Sequence independent amplification of DNA

    DOE Patents [OSTI]

    Bohlander, S.K.

    1998-03-24

    The present invention is a rapid sequence-independent amplification procedure (SIA). Even minute amounts of DNA from various sources can be amplified independent of any sequence requirements of the DNA or any a priori knowledge of any sequence characteristics of the DNA to be amplified. This method allows, for example, the sequence independent amplification of microdissected chromosomal material and the reliable construction of high quality fluorescent in situ hybridization (FISH) probes from YACs or from other sources. These probes can be used to localize YACs on metaphase chromosomes but also--with high efficiency--in interphase nuclei. 25 figs.

  16. Multiscale QM/MM Molecular Dynamics Study on the First Steps of Guanine-Damage by Free Hydroxyl Radicals in Solution

    E-Print Network [OSTI]

    Abolfath, Ramin M; Rajnarayanam, R; Brabec, Thomas; Kodym, Reinhard; Papiez, Lech

    2012-01-01

    Understanding the damage of DNA bases from hydrogen abstraction by free OH radicals is of particular importance to reveal the effect of hydroxyl radicals produced by the secondary effect of radiation. Previous studies address the problem with truncated DNA bases as ab-initio quantum simulation required to study such electronic spin dependent processes are computationally expensive. Here, for the first time, we employ a multiscale and hybrid Quantum-Mechanical-Molecular-Mechanical simulation to study the interaction of OH radicals with guanine-deoxyribose-phosphate DNA molecular unit in the presence of water where all the water molecules and the deoxyribose-phosphate fragment are treated with the simplistic classical Molecular-Mechanical scheme. Our result illustrates that the presence of water strongly alters the hydrogen-abstraction reaction as the hydrogen bonding of OH radicals with water restricts the relative orientation of the OH-radicals with respective to the the DNA base (here guanine). This results ...

  17. Induction and Persistence of Large ?H2AX Foci by High Linear Energy Transfer Radiation in DNA-Dependent protein kinase–Deficient Cells

    SciTech Connect (OSTI)

    Bracalente, Candelaria; Ibañez, Irene L.; Molinari, Beatriz; Palmieri, Mónica; Kreiner, Andrés; Valda, Alejandro; and others

    2013-11-15

    Purpose: To evaluate the cell response to DNA double-strand breaks induced by low and high linear energy transfer (LET) radiations when the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs), an essential protein of the nonhomologous end-joining repair pathway, lacks kinase activity. Methods and Materials: CHO10B2, a Chinese hamster ovary cell line, and its derived radiosensitive mutant cell line, irs-20, lacking DNA-PKcs activity, were evaluated after 0 to 3 Gy of ?-rays, plateau and Bragg peak protons, and lithium beams by clonogenic assay, and as a measurement of double-strand breaks, phosphorylated H2AX (?H2AX) foci number and size were quantified by immunocytofluorescence. Results: Irs-20 exhibited greater radiosensitivity and a higher amount of ?H2AX foci than CHO10B2 at 6 hours after irradiation for all types of radiations. Remarkably, CHO10B2 and irs-20 maintained their difference in radiosensitivity after high-LET radiation. Six hours after low-LET radiations, irs-20 did not reach basal levels of ?H2AX at high doses, whereas CHO10B2 recovered basal levels for all doses. After high-LET radiation, only CHO10B2 exhibited a reduction in ?H2AX foci, but it never reached basal levels. Persistent foci in irs-20 confirmed a repair deficiency. Interestingly, after 30 minutes of high-LET radiation both cell lines exhibited large foci (size >0.9 ?m{sup 2}) related to the damage nature, whereas at 6 hours irs-20 showed a higher amount of large foci than CHO10B2, with a 7-fold increase at 3 Gy, that could also be associated to radiosensitivity. Conclusions: We demonstrated, for the first time, an association between deficient DNA-PKcs activity and not only high levels of H2AX phosphorylation but also persistence and size increase of ?H2AX foci after high-LET irradiation.

  18. Topics in Forensic DNA Analysis &

    E-Print Network [OSTI]

    chemistry from the University of Virginia. His dissertation research, which was conducted at the FBI Academy guest of the FBI's Scientific Working Group on DNA Analysis Methods (SWGDAM) and a member

  19. Most eukaryotic organisms modify their genomic DNA in certain regions of the genomes through the addition of

    E-Print Network [OSTI]

    Jacobsen, Steve

    -specific CHROMOMETHYLASE3 (CMT3) is responsible for DNA methylation at CNG sites (CNG methylation), as well as a subset in different combinations of sequence contexts suggested that CG, CNG, and CHH methylation act in a partially

  20. Autoregressive modeling with state-space embedding vectors for damage detection under operational and environmental variability

    SciTech Connect (OSTI)

    Farrar, Charles [Los Alamos National Laboratory; Figueiredo, Eloi [UNIV OF PORTO; Todd, Michael [UCSD; Flynn, Eric [UCSD

    2010-01-01

    A nonlinear time series approach is presented to detect damage in systems by using a state-space reconstruction to infer the geometrical structure of a deterministic dynamical system from observed time series response at multiple locations. The unique contribution of this approach is using a Multivariate Autoregressive (MAR) model of a baseline condition to predict the state space, where the model encodes the embedding vectors rather than scalar time series. A hypothesis test is established that the MAR model will fail to predict future response if damage is present in the test condition, and this test is investigated for robustness in the context of operational and environmental variability. The applicability of this approach is demonstrated using acceleration time series from a base-excited 3-story frame structure.

  1. Laser damage creates backdoors in quantum communications

    E-Print Network [OSTI]

    Vadim Makarov; Jean-Philippe Bourgoin; Poompong Chaiwongkhot; Mathieu Gagne; Thomas Jennewein; Sarah Kaiser; Raman Kashyap; Matthieu Legre; Carter Minshull; Shihan Sajeed

    2015-10-12

    Quantum communication protocols such as quantum cloud computing, digital signatures, coin-tossing, secret-sharing, and key distribution, using similar optical technologies, claim to provide unconditional security guaranteed by quantum mechanics. Among these protocols, the security of quantum key distribution (QKD) is most scrutinized and believed to be guaranteed as long as implemented devices are properly characterized and existing implementation loopholes are identified and patched. Here we show that this assumption is not true. We experimentally demonstrate a class of attacks based on laser damage, capable of creating new security loopholes on-demand. We perform it on two different implementations of QKD and coin-tossing protocols, and create new information leakage side-channels. Our results show that quantum communication protocols cannot guarantee security alone, but will always have to be supported by additional technical countermeasures against laser damage.

  2. Carbon Fiber Damage in Particle Beam

    E-Print Network [OSTI]

    Dehning, B; Kroyer, T; Meyer, M; Sapinski, M

    2011-01-01

    Carbon fibers are commonly used as moving targets in beam wire scanners. The heating of the fiber due to energy loss of the particles travelling through is simulated with Geant4. The heating induced by the beam electromagnetic field is estimated with ANSYS. The heat transfer and sublimation processes are modelled. Due to the model nonlinearity, a numerical approach based on discretization of the wire movement is used to solve it for particular beams. Radiation damage to the fiber is estimated with SRIM. The model is tested with available SPS and LEP data and a dedicated damage test on the SPS beam is performed followed by a post-mortem analysis of the wire remnants. Predictions for the LHC beams are made.

  3. Extraction of PCR-amplifiable genomic DNA from Bacillus anthracisspores

    SciTech Connect (OSTI)

    Torok, Tamas

    2003-05-19

    Bacterial endospore disruption and nucleic acid extractionresulting in DNA of PCR-amplifiable quality and quantity are not trivial.Responding to the needs of the Hazardous Materials Response Unit (HMRU),Laboratory Division, Federal Bureau of Investigation, protocols weredeveloped to close these gaps. Effectiveness and reproducibility of thetechniques were validated with laboratory grown pure spores of Bacillusanthracis and its close phylogenetic neighbors, and with spiked soils anddamaged samples.

  4. Department 8450 electrical overstress, EOS, and electrostatic discharge, ESD, damage control handbook

    SciTech Connect (OSTI)

    Tockey, R.J.

    1989-04-01

    This Handbook prescribes requirements and procedures to be used when electrical overstress/electrostatic discharge vulnerable product is being handled, packaged, and/or processed. All employees of department 8450 are required to: (1) observe the requirements and procedures when involved in pertinent, in-house activities, and (2) insure that vulnerable material, for which 8450 is responsible, is not exposed to possibly damaging environments when it is in the hands of others. 4 figs.

  5. Damage threshold of platinum coating used for optics for self...

    Office of Scientific and Technical Information (OSTI)

    Published Article: Damage threshold of platinum coating used for optics for self-seeding of soft x-ray free electron laser Title: Damage threshold of platinum coating used for...

  6. Conservation of Severely Damaged Paper Using Passivation Polymers 

    E-Print Network [OSTI]

    Eilert, Eloise

    2012-10-19

    This work examined the use of passivation polymers in the conservation of severely damaged paper. It specifically investigated the use of this functional polymer treatment to address the issues of damage to paper caused ...

  7. Damage analysis in asphalt concrete mixtures based on parameter relationships 

    E-Print Network [OSTI]

    Song, Injun

    2004-11-15

    Asphalt pavements experience damage due to traffic loading under various environmental conditions. Damage can be caused by viscopl microcracks, fracture due to fatigue cracking, or fracture due to thermal cracking. Asphalt pavements have...

  8. Radiation damage in cubic-stabilized zirconia

    SciTech Connect (OSTI)

    Costantini, Jean-Marc; Beuneu, Francois; Weber, William J

    2013-01-01

    Cubic yttria-stabilized zirconia (YSZ) can be used for nuclear applications as an inert matrix for actinide immobilization or transmutation. Indeed, the large amount of native oxygen vacancies leads to a high radiation tolerance of this material owing to defect recombination occurring in the atomic displacements cascades induced by fast neutron irradiation or ion implantations, as showed by Molecular dynamics (MD) simulations. Amorphization cannot be obtained in YSZ either by nuclear-collision or electronic-excitation damage, just like in urania. A kind of polygonization structure with slightly disoriented crystalline domains is obtained in both cases. In the first steps of damage, specific isolated point defects (like F+-type color centers) and point-defect clusters are produced by nuclear collisions with charged particles or neutrons. Further increase of damage leads to dislocation-loop formation, then to collapse of the dislocation network into a polygonization structure. For swift heavy ion irradiations, a similar polygonization structure is obtained above a threshold stopping power value of about 20-30 keV nm-1.

  9. Effective charge and free energy of DNA inside an ion channel

    E-Print Network [OSTI]

    Jingshan Zhang; B. I. Shklovskii

    2008-03-03

    Translocation of a single stranded DNA (ssDNA) through an alpha-hemolysin channel in a lipid membrane driven by applied transmembrane voltage V was extensively studied recently. While the bare charge of the ssDNA piece inside the channel is approximately 12 (in units of electron charge) measurements of different effective charges resulted in values between one and two. We explain these challenging observations by a large self-energy of a charge in the narrow water filled gap between ssDNA and channel walls, related to large difference between dielectric constants of water and lipid, and calculate effective charges of ssDNA. We start from the most fundamental stall charge $q_s$, which determines the force $F_s= q_s V/L$ stalling DNA against the voltage V (L is the length of the channel). We show that the stall charge $q_s$ is proportional to the ion current blocked by DNA, which is small due to the self-energy barrier. Large voltage V reduces the capture barrier which DNA molecule should overcome in order to enter the channel by $|q_c|V$, where $q_c$ is the effective capture charge. We expressed it through the stall charge $q_s$. We also relate the stall charge $q_s$ to two other effective charges measured for ssDNA with a hairpin in the back end: the charge $q_u$ responsible for reduction of the barrier for unzipping of the hairpin and the charge $q_e$ responsible for DNA escape in the direction of hairpin against the voltage. At small V we explain reduction of the capture barrier with the salt concentration.

  10. Salvaging Timber: What should I do with my damaged timber? 

    E-Print Network [OSTI]

    Taylor, Eric; Foster, C. Darwin

    2005-10-31

    preparation costs. Wind-damaged trees may not qualify as sawtimber because of the internal damage they suf- fered. Estimating in Damage Landowners should get help from professional foresters to determine the value of damaged tim- ber. However, if you... representative may be able to obtain this information for you. Determine the value of tim- ber lost as Timber value = acreage x timber value per acre Determining timber value per acre requires a tim- ber inventory. Wind storms tend to blow down trees...

  11. Characterization of nanoparticle-DNA conjugate and control of DNA conformation on particle surface

    E-Print Network [OSTI]

    Park, Sunho, 1976-

    2009-01-01

    Nano-science has exploited the hybridization and de-hybridization phenomena of DNA which are one of its fundamental functions. In particular, conjugates of gold nanoparticles and DNA (Au NP-DNA) have been extensively ...

  12. Genomic DNA methylation in various developmental stages of two plant pathogenic fungi 

    E-Print Network [OSTI]

    Schliesing, Laura Jo

    1990-01-01

    showing Southern hybridization of pRW614a to a blot of S. rolfsii mycelial DNA digested with HpaII and Mspl. Autoradiogram showing Southern hybridization of pRW614a to a blot of P. omnivorum mycelial and sclerotial DNA digested with Sau3AI and Mbo...I. Autoradiogram showing Southern hybridization of pRW614a to a blot of S. rolfsii mycelial and sclerotial DNA digested with Sau3AI and MboI. Page 27 28 29 31 34 I. INTRODUCTION To date, the molecular mechanisms responsible for the activity of genes...

  13. Ice Storm Damage Greater Along the Terrestrial-Aquatic Interface

    E-Print Network [OSTI]

    Kraft, Clifford E.

    Ice Storm Damage Greater Along the Terrestrial-Aquatic Interface in Forested Landscapes Andrew A- tems. In 1998, a severe ice storm damaged over ten million hectares of forest across northern New York investigated the spatial arrangement of forest damage at the terrestrial-aquatic interface, an ecological edge

  14. Probabilistic Damage Detection Based on Large Area Electronics Sensing Sheets

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    Probabilistic Damage Detection Based on Large Area Electronics Sensing Sheets Yao Yao and Branko-stage damage detection and characterization requires continuous sensing over large areas of structure are not sensitive to damage. In this research, a probabilistic approach based on Monte Carlo (MC) simulations

  15. Photogrammetry Assisted Rapid Measurement of Earthquake-Induced Building Damage

    E-Print Network [OSTI]

    Kamat, Vineet R.

    Photogrammetry Assisted Rapid Measurement of Earthquake-Induced Building Damage Fei Dai, PhD Hong for rapidly measuring structural damage induced in tall buildings by seismic events such as earthquakes) sustained at key floors along the edge of a damaged building. The measured drift can then be used to compute

  16. DAMAGE AND ROCKVOLATILE MIXTURE EFFECTS ON IMPACT CRATER FORMATION

    E-Print Network [OSTI]

    Stewart, Sarah T.

    DAMAGE AND ROCK­VOLATILE MIXTURE EFFECTS ON IMPACT CRATER FORMATION JOHN D. O'KEEFE, SARAH T models for material damage, dilatancy, and inhomogeneous materials (mixtures). We found that a strength degradation (damage) model was necessary to produce faulting in homogeneous materials. Both normal and thrust

  17. Damage Detection and Characterization in Smart Material Structures \\Lambda y

    E-Print Network [OSTI]

    Damage Detection and Characterization in Smart Material Structures \\Lambda y H.T. Banks and Y. Wang Nos. NAS1­ 18605 and NAS1­19480. #12; 1 Introduction It has been known for some time that damage­maps'' as done in the thermal based tomography techniques of [BK1, BK2, BKW] wherein the damaged physical domain

  18. DAMAGE LOCALIZATION IN PLATES USING DLVs Dionisio Bernal1

    E-Print Network [OSTI]

    Bernal, Dionisio

    DAMAGE LOCALIZATION IN PLATES USING DLVs Dionisio Bernal1 and Ariel Levy2 Department of Civil Associate Professor, 2 Graduate Student ABSTRACT The performance of a technique to localize damage based on the computation of load vectors that create stress fields that bypass the damaged region is investigated

  19. Saga of Glass Damage in Urban Environments Continues

    E-Print Network [OSTI]

    Kareem, Ahsan

    Saga of Glass Damage in Urban Environments Continues: Consequences of Aerodynamics and Debris Laboratory University of Notre Dame The Saga of Glass Damage in Urban Environments Continues: Consequences east of the city of Houston. Initial reconnaissance suggested that the observed glass/cladding damage

  20. Flagler County, Florida Hurricane and Storm Damage Reduction Project

    E-Print Network [OSTI]

    US Army Corps of Engineers

    Flagler County, Florida Hurricane and Storm Damage Reduction Project 26 August 2014 ABSTRACT: The proposed Flagler County hurricane and storm damage reduction project is located on the northeast coast miles of shoreline to assess the feasibility of providing Federal Hurricane and Storm Damage Reduction

  1. STOCHASTIC MODELING OF HURRICANE DAMAGE UNDER CLIMATE CHANGE

    E-Print Network [OSTI]

    Katz, Richard

    STOCHASTIC MODELING OF HURRICANE DAMAGE UNDER CLIMATE CHANGE Rick Katz Institute for Study from Hurricanes (2) Stochastic Model for Damage (3) Effects of El Niño (4) Trends in Extreme Hurricanes (5) Unresolved Issues #12;(1) Economic Damage from Hurricanes · Data -- Pielke and Landsea (1998) Web

  2. Magnetic tweezers to studyMagnetic tweezers to studyMagnetic tweezers to studyMagnetic tweezers to study DNA motorsDNA motorsDNA motorsDNA motors

    E-Print Network [OSTI]

    Ritort, Felix

    to study DNA motorsDNA motorsDNA motorsDNA motors MariaMariaMariaMaria MañosasMañosasMañosasMañosas Ritort) · Applications: 1. Tracking DNA motors: (i) Helicases (ii) Annealing motor 2. Studying a multiprotein system: DNA hexamers (Dong et al, JBC 1995) Tracking DNA motors: (i) Helicases #12;Passive: helicase behaves

  3. Climate change risk and response

    E-Print Network [OSTI]

    Kahrl, Fredrich; Roland-Holst, David

    2008-01-01

    electric power outages. Storm damage to transmission lineselectric power and transportation sectors. Storm damage to transmission lines

  4. The Structure of DNA within Cationic Lipid/DNA Complexes

    E-Print Network [OSTI]

    Braun, Chad S.; Jas, Gouri S.; Choosakoonriang, Sirirat; Koe, Gary S.; Smith, Janet G.; Middaugh, C. Russell

    2003-02-01

    hexagonal phase of cationic liposome-DNA complexes related to DNA release and delivery. Science. 281:78–81. Koppel, D. E. 1972. Analysis of macromolecular polydispersity in inten- sity correlation spectroscopy: the method of cumulants. J. Chem. Phys. 57:4814..., DOTAP, 1,2-dioleoyl-sn-glycero-3-phosphatidyletha- nolamine, and cholesterol were purchased from Avanti Polar Lipids (Alabaster, AL). Poly(dG) Æ poly(dC) (4 kbp), poly(dA) Æ poly(dT) (;229 bp), poly(dGdC) Æ poly(dGdC) (724 bp), and poly(dAdT) Æ poly(d...

  5. Identification of new functions for BRCT domains

    E-Print Network [OSTI]

    Mohammad, Duaa H

    2008-01-01

    Our lab identified the tandem BRCT domains of PTIP function as a DNA damage responsive phospho binding domain that recognizes proteins phosphorylated by ATM and ATR after DNA damage. The PTIP tandem BRCT domains are ...

  6. Identification of Intrinsic Order and Disorder in the DNA Repair Protein XPA

    SciTech Connect (OSTI)

    Iakoucheva, Lilia M.; Kimzey, Amy L.; Masselon, Christophe D.; Bruce, James E.; Garner, Ethan C.; Brown, Celeste J.; Dunker, A. K.; Smith, Richard D.; Ackerman, Eric J.

    2001-03-01

    The damage recognition protein XPA is required to recognize a wide variety of bulky lesions during nucleotide excision repair (NER). Independent NMR solution structures of a human XPA protein (hXPA) fragment comprising approximately one-third of the full-length protein, the minimal DNA-binding domain (MBD), revealed that ~30% of the molecule was structurally disordered. To better characterize structural features of XPA, we performed time-resolved trypsin proteolysis on active, full-length recombinant Xenopus XPA protein (xXPA). The resulting proteolytic fragments were analyzed by electrospray ionization interface coupled to a Fourier transform ion cyclotron resonance (ESI-FTICR) mass spectrometry, SDS-polyacrylamide gel electrophoresis (PAGE), and selected N-terminal sequence determinations. The mass spectrum of the full-length xXPA was consistent with the predicted sequence, 30922.02 vs. 30922.45 Da; respectively. Moreover, the mass spectrometric data allowed the assignment of multiple xXPA fragments not resolvable by SDS PAGE. Full-length xXPA exhibited aberrant mobility on SDS-PAGE with an apparent MW of ~40 kDa. To test predictions that a Glu-rich region (E70-E76) or other local regions of high charge were responsible for this ~40% aberrant SDS-PAGE mobility, the MW's of partial proteolytic fragments from ~5 to 25 kDa precisely determined by ESI-FTICR MS were correlated with their gel positions. Surprisingly, all tested partial tryptic fragments within this size-range exhibited 10-42% divergence between calculated MW and that estimated by SDS-PAGE, thus indicating the origin of anomalous migration of XPA is not localized. The computer program Predictor of Natural Disordered Regions (PONDR) correctly identified several regions of xXPA either sensitive or resistant to partial proteolysis, thereby indicating that disorder in XPA shares sequence features with other well-characterized intrinsically unstructured proteins.

  7. Evidence for a Role of Salicylic Acid in the Oxidative Damage Generated by NaCl and Osmotic Stress in

    E-Print Network [OSTI]

    Málaga, Universidad de

    Evidence for a Role of Salicylic Acid in the Oxidative Damage Generated by NaCl and Osmotic Stress plays a role in the plant response to adverse environmental conditions, such as salt and osmotic during salt and osmotic stresses. This hypothesis is supported by the following observations. First

  8. Mechanical Damage from Cavitation in High Intensity Focused Ultrasound Accelerated Thrombolysis

    E-Print Network [OSTI]

    Weiss, Hope

    2012-01-01

    for Mechanical Damage . . . . . . . . . . . . . . . .3.3.3 Connection to Mechanical Damage . . . . . . 3.41.2.5 Assessing mechanical damage . . 1.3 Bubble

  9. Abdominal damage control surgery and reconstruction: world society of emergency surgery position paper

    E-Print Network [OSTI]

    Godat, Laura; Kobayashi, Leslie; Costantini, Todd; Coimbra, Raul

    2013-01-01

    as: Godat et al. : Abdominal damage control surgery andAD, Feliciano DV: Trauma damage control. In Trauma. 6thpatient which indicate damage control and predict outcome.

  10. Mechanical Damage from Cavitation in High Intensity Focused Ultrasound Accelerated Thrombolysis

    E-Print Network [OSTI]

    Weiss, Hope

    2012-01-01

    Mechanical Damage . . . . . . . . . . . . . . . . . .iiiMethod for Estimation of Cavitation Damage for an EmbeddedMethod for Estimation of Cavitation Damage for an Embedded

  11. Damage, Fear, and Transformation: International Currency Systems and Postwar Japan's Currency Policies

    E-Print Network [OSTI]

    Lee, Sangbaik

    2012-01-01

    will suffer a serious damage. ” 291 Above, we have surveyedparticularly for alleviating the damage incurred by the yenDamage, Fear, and Transformation: International Currency

  12. Damage Identification of a Composite Beam Using Finite Element Model Updating

    E-Print Network [OSTI]

    Moaveni, Babak; He, Xianfei; Conte, Joel P; De Callafon, Raymond A.

    2008-01-01

    Shevitz, D. W. (1996), Damage identification in structuresreview of vibration-based damage identification methods, TheM. , & Samman, M. M. (1991), Damage detection from changes

  13. Natural Resource Damage Assessment Cooperation and Integration

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

    2012-06-19

    The Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA), 42 U.S.C. 9601, et seq., Executive Order 12580, and CERCLA's implementing regulations in the National Contingency Plan (NCP), 40 CFR Part 300, give the DOE three roles at DOE facilities undergoing environmental cleanup: lead response agency, natural resource trustee, and the party responsible for releases and threatened releases of hazardous substances. Does not cancel other directives.

  14. Surface state reconstruction in ion-damaged SmB?

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

    Wakeham, N.; Wang, Y. Q.; Fisk, Z.; Ronning, F.; Thompson, J. D.

    2015-02-01

    We have used ion-irradiation to damage the (001) surfaces of SmB? single crystals to varying depths, and have measured the resistivity as a function of temperature for each depth of damage. We observe a reduction in the residual resistivity with increasing depth of damage. Our data are consistent with a model in which the surface state is not destroyed by the ion-irradiation, but instead the damaged layer is poorly conducting and the initial surface state is reconstructed below the damage. This behavior is consistent with a surface state that is topologically protected.

  15. Vibration-Based Damage Detection in Rotating Machinery

    SciTech Connect (OSTI)

    Farrar, C.R.; Duffey, T.A.

    1999-06-28

    Damage detection as determined from changes in the vibration characteristics of a system has been a popular research topic for the last thirty years. Numerous damage identification algorithms have been proposed for detecting and locating damage in structural and mechanical systems. To date, these damage-detection methods have shown mixed results. A particular application of vibration-based damage detection that has perhaps enjoyed the greatest success is that of damage detection in rotating machinery. This paper summarizes the state of technology in vibration-based damage detection applied to rotating machinery. The review interprets the damage detection process in terms of a statistical pattern recognition paradigm that encompasses all vibration-based damage detection methods and applications. The motivation for the study reported herein is to identify the reasons that vibration-based damage detection has been successfully applied to rotating machinery, but has yet to show robust applications to civil engineering infrastructure. The paper concludes by comparing and contrasting the vibration-based damage detection applied to rotating machinery with large civil engineering infrastructure applications.

  16. Damage of MEMS thermal actuators heated by laser irradiation.

    SciTech Connect (OSTI)

    Walraven, Jeremy Allen; Klody, Kelly Anne; Sackos, John T.; Phinney, Leslie Mary

    2005-01-01

    Optical actuation of microelectromechanical systems (MEMS) is advantageous for applications for which electrical isolation is desired. Thirty-two polycrystalline silicon opto-thermal actuators, optically-powered MEMS thermal actuators, were designed, fabricated, and tested. The design of the opto-thermal actuators consists of a target for laser illumination suspended between angled legs that expand when heated, providing the displacement and force output. While the amount of displacement observed for the opto-thermal actuators was fairly uniform for the actuators, the amount of damage resulting from the laser heating ranged from essentially no damage to significant amounts of damage on the target. The likelihood of damage depended on the target design with two of the four target designs being more susceptible to damage. Failure analysis of damaged targets revealed the extent and depth of the damage.

  17. Damage of MEMS thermal actuators heated by laser irradiation.

    SciTech Connect (OSTI)

    Walraven, Jeremy Allen; Klody, Kelly Anne; Sackos, John T.; Phinney, Leslie Mary

    2004-11-01

    Optical actuation of microelectromechanical systems (MEMS) is advantageous for applications for which electrical isolation is desired. Thirty-two polycrystalline silicon opto-thermal actuators, optically-powered MEMS thermal actuators, were designed, fabricated, and tested. The design of the opto-thermal actuators consists of a target for laser illumination suspended between angled legs that expand when heated, providing the displacement and force output. While the amount of displacement observed for the opto-thermal actuators was fairly uniform for the actuators, the amount of damage resulting from the laser heating ranged from essentially no damage to significant amounts of damage on the target. The likelihood of damage depended on the target design with two of the four target designs being more susceptible to damage. Failure analysis of damaged targets revealed the extent and depth of the damage.

  18. Minimizing radiation damage in nonlinear optical crystals

    DOE Patents [OSTI]

    Cooke, D. Wayne (Santa Fe, NM); Bennett, Bryan L. (Los Alamos, NM); Cockroft, Nigel J. (Santa Fe, NM)

    1998-01-01

    Methods are disclosed for minimizing laser induced damage to nonlinear crystals, such as KTP crystals, involving various means for electrically grounding the crystals in order to diffuse electrical discharges within the crystals caused by the incident laser beam. In certain embodiments, electrically conductive material is deposited onto or into surfaces of the nonlinear crystals and the electrically conductive surfaces are connected to an electrical ground. To minimize electrical discharges on crystal surfaces that are not covered by the grounded electrically conductive material, a vacuum may be created around the nonlinear crystal.

  19. Minimizing radiation damage in nonlinear optical crystals

    DOE Patents [OSTI]

    Cooke, D.W.; Bennett, B.L.; Cockroft, N.J.

    1998-09-08

    Methods are disclosed for minimizing laser induced damage to nonlinear crystals, such as KTP crystals, involving various means for electrically grounding the crystals in order to diffuse electrical discharges within the crystals caused by the incident laser beam. In certain embodiments, electrically conductive material is deposited onto or into surfaces of the nonlinear crystals and the electrically conductive surfaces are connected to an electrical ground. To minimize electrical discharges on crystal surfaces that are not covered by the grounded electrically conductive material, a vacuum may be created around the nonlinear crystal. 5 figs.

  20. 1. (a) Why are DNA-targeted drugs largely used as anticancer agents and not as, say, antibacterial or antifungal agents?

    E-Print Network [OSTI]

    Gates, Kent. S.

    CHEM 4170 Homework 4 1. (a) Why are DNA-targeted drugs largely used as anticancer agents and not as, say, antibacterial or antifungal agents? (b) Provide an explanation for how anticancer drugs can-damaging drugs mentioned in Question 1). (b) However, some medicinal chemists believe that these compounds

  1. DIAMOND: A graphical interface toolbox for comparative modal analysis and damage identification

    SciTech Connect (OSTI)

    Doebling, S.W.; Farrar, C.R. [Los Alamos National Lab., NM (United States). Engineering Sciences and Applications Div.; Cornwell, P.J. [Rose Hulman Inst. of Tech., Terre Haute, IN (United States)

    1997-06-01

    This paper introduces a new toolbox of graphical-interface software algorithms for the numerical simulation of vibration tests, analysis of modal data, finite element model correlation, and the comparison of both linear and nonlinear damage identification techniques. This toolbox is unique because it contains several different vibration-based damage identification algorithms, categorized as those which use only measured response and sensor location information (non-model-based techniques) and those which use finite element model correlation (model-based techniques). Another unique feature of this toolbox is the wide range of algorithms for experimental modal analysis. The toolbox also contains a unique capability that utilizes the measured coherence functions and Monte Carlo analysis to perform statistical uncertainty analysis on the modal parameters and damage identification results. This paper contains a detailed description of the various modal analysis, damage identification, and model correlation capabilities of toolbox, and also shows a sample application which uses the toolbox to analyze the statistical uncertainties on the results of a series of modal tests performed on a highway bridge.

  2. The Initiation of Bacterial DNA Replication

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

    for this system. Instead, DnaA forms an open right-handed helix. In addition, the architecture indicates that this AAA+ superhelix will wrap coils of the DNA around its exterior,...

  3. Towards Privacy Preserving of Forensic DNA Databases 

    E-Print Network [OSTI]

    Liu, Sanmin

    2012-02-14

    Protecting privacy of individuals is critical for forensic genetics. In a kinship/identity testing, related DNA profiles between user's query and the DNA database need to be extracted. However, unrelated profiles cannot be revealed to each other...

  4. 7th International Workshop on Microbeam Probes of Cellular Radiation Response

    SciTech Connect (OSTI)

    Brenner, David J.

    2009-07-21

    The extended abstracts that follow present a summary of the Proceedings of the 7th International Workshop: Microbeam Probes of Cellular Radiation Response, held at Columbia University’s Kellogg Center in New York City on March 15–17, 2006. These International Workshops on Microbeam Probes of Cellular Radiation Response have been held regularly since 1993 (1–5). Since the first workshop, there has been a rapid growth (see Fig. 1) in the number of centers developing microbeams for radiobiological research, and worldwide there are currently about 30 microbeams in operation or under development. Single-cell/single-particle microbeam systems can deliver beams of different ionizing radiations with a spatial resolution of a few micrometers down to a few tenths of a micrometer. Microbeams can be used to addressquestions relating to the effects of low doses of radiation (a single radiation track traversing a cell or group of cells), to probe subcellular targets (e.g. nucleus or cytoplasm), and to address questions regarding the propagation of information about DNA damage (for example, the radiation-induced bystander effect). Much of the recent research using microbeams has been to study low-dose effects and ‘‘non-targeted’’ responses such as bystander effects, genomic instability and adaptive responses. This Workshop provided a forum to assess the current state of microbeam technology and current biological applications and to discuss future directions for development, both technological and biological. Over 100 participants reviewed the current state of microbeam research worldwide and reported on new technological developments in the fields of both physics and biology.

  5. Gene induction and adaptive responses in irradiated cells: Mechanisms and clinical implications

    SciTech Connect (OSTI)

    Lehnert, S. [McGill Univ., Quebec (Canada)

    1995-01-01

    A characteristic of living things, conserved throughout evolution, is their capacity to react to environmental insult. From bacteria to yeast to human cells, environmental inputs induce changes in the program of genes expressed. A subset of this response, of particular interest to the radiobiologists and radiation oncologists who gathered for this meeting, is the case of radiation-mediated gene induction. A large number of genes have been reported to be up/down-regulated by ionizing radiation; some of these have been identified, while others have so far preserved their anonymity as bands and blots on gels and membranes. It is safe to say that many more such genes will be discovered in the future as the scientific and clinical significance of these processes is better understood. Substantial evidence, extending back many years, suggests the existence of an adaptive response, apparent as cellular radioprotective mechanisms which can be up-regulated after a small dose of radiation. At the molecular level, the timing of the changes in expression of induced genes and of the changes in levels of nuclear and cytoplasmic proteins which they encode is such as to support involvement of these elements in induced radioresistance. The adaptive response is one component of the battery of intrinsic factors which influence the response of tumors to radiation. Radiation-induced gene products encompass a spectrum of activities including cell cycle control, DNA repair, signal transduction, apoptosis and oncogenesis, all of which can influence tumor radioresponse and contribute to the multifactorial radioresistant phenotype. Growth factors and cytokines are encoded by several early and late-responding genes whose expression is up-regulated by radiation. These must be assumed to affect the toxicity of radiation toward early- and late-responding normal tissues profoundly by promoting repair or conversely by acting synergistically to enhance radiation damage.

  6. Chromosome specific repetitive DNA sequences

    DOE Patents [OSTI]

    Moyzis, Robert K. (Los Alamos, NM); Meyne, Julianne (Los Alamos, NM)

    1991-01-01

    A method is provided for determining specific nucleotide sequences useful in forming a probe which can identify specific chromosomes, preferably through in situ hybridization within the cell itself. In one embodiment, chromosome preferential nucleotide sequences are first determined from a library of recombinant DNA clones having families of repetitive sequences. Library clones are identified with a low homology with a sequence of repetitive DNA families to which the first clones respectively belong and variant sequences are then identified by selecting clones having a pattern of hybridization with genomic DNA dissimilar to the hybridization pattern shown by the respective families. In another embodiment, variant sequences are selected from a sequence of a known repetitive DNA family. The selected variant sequence is classified as chromosome specific, chromosome preferential, or chromosome nonspecific. Sequences which are classified as chromosome preferential are further sequenced and regions are identified having a low homology with other regions of the chromosome preferential sequence or with known sequences of other family me This invention is the result of a contract with the Department of Energy (Contract No. W-7405-ENG-36).

  7. The Future of Forensic DNA

    E-Print Network [OSTI]

    History and Mission · National Institute of Standards and Technology (NIST) was created in 1901The Future of Forensic DNA John M. Butler, PhD National Institute of Standards and Technology.S. Department of Commerce with a mission to develop and promote measurement, standards, and technology

  8. Origami DNA model Mountain fold

    E-Print Network [OSTI]

    Csürös, Miklós

    Origami DNA model Mountain fold Solid lines are "mountains" and are to be folded away from you with the peak pointing towards you. 1. Fold all solid lines going lengthwise down the page into "mountain folds fold 2. Fold all dashed lines going lengthwise down the page into "valley folds". Mountain folds along

  9. The Future of Forensic DNA

    E-Print Network [OSTI]

    ;Checks and Controls on DNA Results Community FBI Quality Assurance Standards (and interlaboratory studies Washington D.C. Dulles Airport Reagan National Airport BWI Airport NIST FBI Lab Baltimore, MD Richmond, VA Materials (SRMs) Helps meet FBI QAS and ISO 17025 requirements Traceable standards to ensure accurate

  10. DNA Mixture Interpretation & Statistical Analysis

    E-Print Network [OSTI]

    of Standards and Technology Gaithersburg, Maryland John M. Butler CIB Forensic Science Center Training Seminar Mixture Workshop This workshop is for analysts, technical reviewers and technical leaders performing) National recommendations of the technical UK DNA working group on mixture interpretation for the NDNAD

  11. DNA sequencing protocols BN Danforth

    E-Print Network [OSTI]

    Danforth, Bryan Nicholas

    in the degradation of DNA. (7) Spin the tubes down at the end to remove condensation from tops of tubes. B. Extraction and RNA digestion. NOTE: We now skip the Rnase step. You will need: Phenol and gently invert several times. This step removes the phenol from the previous extraction. Spin

  12. Biological Physics of DNA Typeset by FoilTEX 1

    E-Print Network [OSTI]

    Potsdam, Universität

    fragments to ssDNA Labelling: eg radioact probe fragm & Xray film http;Packaging of DNA in bacteria 11 #12;DNA melting 12 #12;Polymerase chain reaction Heating dsDNA sample 2

  13. DNA extraction techniques for DNA barcoding of minute gall-inhabiting wasps

    E-Print Network [OSTI]

    extraction methods were compared to determine their efficacy in isolating DNA. Success of each methodDNA extraction techniques for DNA barcoding of minute gall-inhabiting wasps GUDRUN DITTRICH, South Africa Abstract DNA extraction from minute hymenopterans and their larvae is difficult

  14. DNA Word Design Strategy for Creating Sets of Non-interacting Oligonucleotides for DNA Microarrays

    E-Print Network [OSTI]

    DNA Word Design Strategy for Creating Sets of Non-interacting Oligonucleotides for DNA Microarrays mismatches with the complements of all the other members in the set. These "DNA word" sets are denoted as nbm. To achieve good discrimination between each DNA word in each set generated using the template-map strategy

  15. Probe and method for DNA detection

    DOE Patents [OSTI]

    Yeh, Hsin-Chih; Werner, James Henry; Sharma, Jaswinder Kumar; Martinez, Jennifer Suzanne

    2013-07-02

    A hybridization probe containing two linear strands of DNA lights up upon hybridization to a target DNA using silver nanoclusters that have been templated onto one of the DNA strands. Hybridization induces proximity between the nanoclusters on one strand and an overhang on the other strand, which results in enhanced fluorescence emission from the nanoclusters.

  16. MATERIALS AND METHODS 1) DNA extraction

    E-Print Network [OSTI]

    Collins, Gary S.

    MATERIALS AND METHODS 1) DNA extraction · DNA was extracted from the ileo-cecal nodes of 475 Holstein cows from two herds using the Qiagen DNA extraction kit (Valencia, CA). 2) Map detection · Map was extracted from ileo-cecal nodes using Ambion's MagMAX Total Nucleic Acid Isolation kit (Austin, TX

  17. Multicopy single-stranded DNA directs intestinal colonization of enteric pathogens

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

    Elfenbein, Johanna R.; Knodler, Leigh A.; Nakayasu, Ernesto S.; Ansong, Charles; Brewer, Heather M.; Bogomolnaya, Lydia; Adams, L. Garry; McClelland, Michael; Adkins, Joshua N.; Andrews-Polymenis, Helene L.; et al

    2015-09-14

    Multicopy single-stranded DNAs (msDNAs) are hybrid RNA-DNA molecules encoded on retroelements called retrons and produced by the action of retron reverse transcriptases. Retrons are widespread in bacteria but the natural function of msDNA has remained elusive despite 30 years of study. The major roadblock to elucidation of the function of these unique molecules has been the lack of any identifiable phenotypes for mutants unable to make msDNA. We report that msDNA of the zoonotic pathogen Salmonella Typhimurium is necessary for colonization of the intestine. Similarly, we observed a defect in intestinal persistence in an enteropathogenic E. coli mutant lacking itsmore »retron reverse transcriptase. Under anaerobic conditions in the absence of msDNA, proteins of central anaerobic metabolism needed for Salmonella colonization of the intestine are dysregulated. We show that the msDNA-deficient mutant can utilize nitrate, but not other alternate electron acceptors in anaerobic conditions. Consistent with the availability of nitrate in the inflamed gut, a neutrophilic inflammatory response partially rescued the ability of a mutant lacking msDNA to colonize the intestine. These findings together indicate that the mechanistic basis of msDNA function during Salmonella colonization of the intestine is proper production of proteins needed for anaerobic metabolism. We further conclude that a natural function of msDNA is to regulate protein abundance, the first attributable function for any msDNA. Our data provide novel insight into the function of this mysterious molecule that likely represents a new class of regulatory molecules.« less

  18. Binding of undamaged double stranded DNA to vaccinia virus uracil-DNA glycosylase

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

    Schormann, Norbert; Banerjee, Surajit; Ricciardi, Robert; Chattopadhyay, Debasish

    2015-06-02

    Background: Uracil-DNA glycosylases are evolutionarily conserved DNA repair enzymes. However, vaccinia virus uracil-DNA glycosylase (known as D4), also serves as an intrinsic and essential component of the processive DNA polymerase complex during DNA replication. In this complex D4 binds to a unique poxvirus specific protein A20 which tethers it to the DNA polymerase. At the replication fork the DNA scanning and repair function of D4 is coupled with DNA replication. So far, DNA-binding to D4 has not been structurally characterized. Results: This manuscript describes the first structure of a DNA-complex of a uracil-DNA glycosylase from the poxvirus family. This alsomore »represents the first structure of a uracil DNA glycosylase in complex with an undamaged DNA. In the asymmetric unit two D4 subunits bind simultaneously to complementary strands of the DNA double helix. Each D4 subunit interacts mainly with the central region of one strand. DNA binds to the opposite side of the A20-binding surface on D4. In comparison of the present structure with the structure of uracil-containing DNA-bound human uracil-DNA glycosylase suggests that for DNA binding and uracil removal D4 employs a unique set of residues and motifs that are highly conserved within the poxvirus family but different in other organisms. Conclusion: The first structure of D4 bound to a truly non-specific undamaged double-stranded DNA suggests that initial binding of DNA may involve multiple non-specific interactions between the protein and the phosphate backbone.« less

  19. Radiation Damage in Polarized Ammonia Solids

    E-Print Network [OSTI]

    K. Slifer

    2007-11-28

    Solid NH3 and ND3 provide a highly polarizable, radiation resistant source of polarized protons and deuterons and have been used extensively in high luminosity experiments investigating the spin structure of the nucleon. Over the past twenty years, the UVA polarized target group has been instrumental in producing and polarizing much of the material used in these studies, and many practical considerations have been learned in this time. In this discussion, we analyze the polarization performance of the solid ammonia targets used during the recent JLab Eg4 run. Topics include the rate of polarization decay with accumulated charge, the annealing procedure for radiation damaged targets to recover polarization, and the radiation induced change in optimum microwave frequency used to polarize the sample. We also discuss the success we have had in implementing frequency modulation of the polarizing microwave frequency.

  20. The application of ultrasonics to assess damage in composite materials 

    E-Print Network [OSTI]

    Eden, John Gregory

    1985-01-01

    of the plies in the laminate, the loading history, and the current state of damage in the laminate. Reifsnider [1] describes damage in terms of 'critical elements' and 'subcr itical elements'. Critical elements are defined as damage which results... in the final failure of a laminate (i. e, , 0 degree ply failure in tensile loading, unstable plies that have not buckled under compressive loading, etc. ). Subcritical elements include porosity, micr ovoid growth, matrix or ack- ing, matrix/fiber debonding...

  1. Continuum-based Multiscale Computational Damage Modeling of Cementitous Composites 

    E-Print Network [OSTI]

    Kim, Sun-Myung

    2011-08-08

    , aggregates, and interfacial transition zone (ITZ) and interaction among components at meso-scale, and the interaction between reinforcements, such as fiber and carbon nanotubes (CNTs) and mortar matrix or the ITZ at nano scale in order to predict more... of Advisory Committee: Dr. Rashid K. Abu Al-Rub Based on continuum damage mechanics (CDM), an isotropic and anisotropic damage model coupled with a novel plasticity model for plain concrete is proposed in this research. Two different damage evolution laws...

  2. A matrix damage accumulation model for laminated composites 

    E-Print Network [OSTI]

    Lo, David Chi Shing

    1990-01-01

    and the damage variable. A complementary scalar valued dairiage variable was proposed by Rabotnov [33] as an extension. This damage variable & quantif'ying the reduction in load carrying area due to void formation. , was defined as The influence of the current... The aforeurentioned damage growth laws are representative of those found in the current literature. the nxajority of winch are of the evolutions rv type and share 22 a phenomenological basis. Some of these have been extensively modified for specific applications...

  3. 01-07-2000 - Undergroud Cables Damaged during Excavation Work...

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

    0 - Undergroud Cables Damaged during Excavation Work Document Number: NA Effective Date: 012000 File (public): 01-07-2000bluealert(2)...

  4. Demonstration of damage with a wireless sensor network

    SciTech Connect (OSTI)

    Tanner, Neal A.; Farrar, C. R. (Charles R.)

    2001-01-01

    A damage detection system was developed with commercially available wireless sensors. Statistical process control methods were used to monitor the correlation of vibration data from two accelerometers mounted across a joint. Changes in correlation were used to detect damage to the joint. All data processing was done remotely on a microprocessor integrated with the wireless sensors to allow for the transmission of a simple damaged or undamaged status for each monitored joint. Additionally, a portable demonstration structure was developed to showcase the capabilities of the damage detection system to monitor joint failure in real time.

  5. Investigation of Microscale Damage Evolution in High-Strength...

    Office of Scientific and Technical Information (OSTI)

    Alloy. Citation Details In-Document Search Title: Investigation of Microscale Damage Evolution in High-Strength Al Alloy. Authors: Jin, Huiqing ; Lu, Wei-Yang ; Mota, Alejandro ;...

  6. Investigation of Microscale Damage Evolution in High Strength...

    Office of Scientific and Technical Information (OSTI)

    Alloy. Citation Details In-Document Search Title: Investigation of Microscale Damage Evolution in High Strength A1 Alloy. Authors: Jin, Huiqing ; Lu, Wei-Yang ; Mota, Alejandro ;...

  7. Convention on Supplementary Compensation for Nuclear Damage Contingent...

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

    is extended to October 27, 2010. Convention on Supplementary Compensation for Nuclear Damage Contingent Cost Allocation More Documents & Publications CSCExtension.PDF...

  8. Thermomechanics of damage and fatigue by a phase field model

    E-Print Network [OSTI]

    Giovambattista Amendola; Mauro Fabrizio

    2014-10-26

    In the paper we present an isothermal model for describing damage and fatigue by the use of the Ginzburg-Landau (G-L) equation. Fatigue produces progressive damage, which is related with a variation of the internal structure of the material. The G-L equation studies the evolution of the order parameter, which describes the constitutive arrangement of the system and, in this framework, the evolution of damage. The thermodynamic coherence of the model is proved. In the last part of the work, we extend the results of the paper to a non-isothermal system, where fatigue contains thermal effects, which increase the damage of materials.

  9. Soft x-ray free-electron laser induced damage to inorganic scintillators

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

    Burian, Tomáš; Hájková, V?ra; Chalupský, Jaromír; Vyšín, Lud?k; Bohá?ek, Pavel; P?e?ek, Martin; Wild, Jan; Özkan, Cigdem; Coppola, Nicola; Farahani, Shafagh Dastjani; et al

    2015-01-07

    An irreversible response of inorganic scintillators to intense soft x-ray laser radiation was investigated at the FLASH (Free-electron LASer in Hamburg) facility. Three ionic crystals, namely, Ce:YAG (cerium-doped yttrium aluminum garnet), PbWO4 (lead tungstate), and ZnO (zinc oxide), were exposed to single 4.6 nm ultra-short laser pulses of variable pulse energy (up to 12 ?J) under normal incidence conditions with tight focus. Damaged areas produced with various levels of pulse fluences, were analyzed on the surface of irradiated samples using differential interference contrast (DIC) and atomic force microscopy (AFM). The effective beam area of 22.2 ± 2.2 ?m2 was determinedmore »by means of the ablation imprints method with the use of poly(methyl methacrylate) - PMMA. Applied to the three inorganic materials, this procedure gave almost the same values of an effective area. The single-shot damage threshold fluence was determined for each of these inorganic materials. The Ce:YAG sample seems to be the most radiation resistant under the given irradiation conditions, its damage threshold was determined to be as high as 660.8 ± 71.2 mJ/cm2. Contrary to that, the PbWO4 sample exhibited the lowest radiation resistance with a threshold fluence of 62.6 ± 11.9 mJ/cm2. The threshold for ZnO was found to be 167.8 ± 30.8 mJ/cm2. Both interaction and material characteristics responsible for the damage threshold difference are discussed in the article.« less

  10. Electromagnetic Signals from Bacterial DNA

    E-Print Network [OSTI]

    A. Widom; J. Swain; Y. N. Srivastava; S. Sivasubramanian

    2012-02-09

    Chemical reactions can be induced at a distance due to the propagation of electromagnetic signals during intermediate chemical stages. Although is is well known at optical frequencies, e.g. photosynthetic reactions, electromagnetic signals hold true for muck lower frequencies. In E. coli bacteria such electromagnetic signals can be generated by electric transitions between energy levels describing electrons moving around DNA loops. The electromagnetic signals between different bacteria within a community is a "wireless" version of intercellular communication found in bacterial communities connected by "nanowires". The wireless broadcasts can in principle be of both the AM and FM variety due to the magnetic flux periodicity in electron energy spectra in bacterial DNA orbital motions.

  11. Fleet DNA Project (Fact Sheet)

    SciTech Connect (OSTI)

    Not Available

    2012-10-01

    The Fleet DNA Project - designed by the U.S. Department of Energy's National Renewable Energy Laboratory (NREL) in partnership with Oak Ridge National Laboratory - aims to accelerate the evolution of advanced vehicle development and support the strategic deployment of market-ready technologies that reduce costs, fuel consumption, and emissions. At the heart of the Fleet DNA Project is a clearinghouse of medium- and heavy-duty commercial fleet transportation data for optimizing the design of advanced vehicle technologies or for selecting a given technology to invest in. An easy-to-access online database will help vehicle manufacturers and fleets understand the broad operational range for many of today's commercial vehicle vocations.

  12. Channel plate for DNA sequencing

    DOE Patents [OSTI]

    Douthart, R.J.; Crowell, S.L.

    1998-01-13

    This invention is a channel plate that facilitates data compaction in DNA sequencing. The channel plate has a length, a width and a thickness, and further has a plurality of channels that are parallel. Each channel has a depth partially through the thickness of the channel plate. Additionally an interface edge permits electrical communication across an interface through a buffer to a deposition membrane surface. 15 figs.

  13. Revision of laser-induced damage threshold evaluation from damage probability data

    SciTech Connect (OSTI)

    Bataviciute, Gintare; Grigas, Povilas; Smalakys, Linas; Melninkaitis, Andrius [Laser Research Center, Vilnius University, Sauletekio al. 10, LT-10223 Vilnius (Lithuania)

    2013-04-15

    In this study, the applicability of commonly used Damage Frequency Method (DFM) is addressed in the context of Laser-Induced Damage Threshold (LIDT) testing with pulsed lasers. A simplified computer model representing the statistical interaction between laser irradiation and randomly distributed damage precursors is applied for Monte Carlo experiments. The reproducibility of LIDT predicted from DFM is examined under both idealized and realistic laser irradiation conditions by performing numerical 1-on-1 tests. A widely accepted linear fitting resulted in systematic errors when estimating LIDT and its error bars. For the same purpose, a Bayesian approach was proposed. A novel concept of parametric regression based on varying kernel and maximum likelihood fitting technique is introduced and studied. Such approach exhibited clear advantages over conventional linear fitting and led to more reproducible LIDT evaluation. Furthermore, LIDT error bars are obtained as a natural outcome of parametric fitting which exhibit realistic values. The proposed technique has been validated on two conventionally polished fused silica samples (355 nm, 5.7 ns).

  14. Unlimited Damage Accumulation in Metallic Materials Under Cascade-Damage Conditions

    SciTech Connect (OSTI)

    Barashev, Aleksandr [University of Liverpool; Golubov, Stanislav I [ORNL

    2008-09-01

    Most experiments on neutron or heavy-ion cascade-produced irradiation of pure metals and metallic alloys demonstrate unlimited void growth as well as development of the dislocation structure. In contrast, the theory of radiation damage predicts saturation of void swelling at sufficiently high irradiation doses and, accordingly, termination of accumulation of interstitial-type defects. It is shown in the present paper that, under conditions of steady production of one-dimensionally (1-D) mobile clusters of self-interstitial atoms (SIAs) in displacement cascades, any one of the following three conditions can result in indefinite damage accumulation. First, if the fraction of SIAs generated in the clustered form is smaller than some finite value of the order of the dislocation bias factor. Second, if solute, impurity or transmuted atoms form atmospheres around voids and repel the SIA clusters. Third, if spatial correlations between voids and other defects, such as second-phase precipitates and dislocations, exist that provide shadowing of voids from the SIA clusters. The driving force for the development of such correlations is the same as for void lattice formation and is argued to be always present under cascade-damage conditions. It is emphasised that the mean-free path of 1-D migrating SIA clusters is typically at least an order of magnitude longer than the average distance between microstructural defects; hence spatial correlations on the same scale should be taken into consideration. A way of developing a predictive theory is discussed. An interpretation

  15. Radiation damage to neutron and proton irradiated GaAs particle detectors

    E-Print Network [OSTI]

    M. Rogalla; Th. Eich; N. Evans; S. Joost; M. Kienzle; R. Geppert; R. Goeppert; R. Irsigler; J. Ludwig; K. Runge; Th. Schmid

    1997-04-04

    The radiation damage in 200 um thick Schottky diodes made on semi-insulating (SI) undoped GaAs Liquid Encapsulated Czochralski (LEC) bulk material with resistivities between 0.4 and 8.9*10E7 Ohm*cm were studied using alpha-spectroscopy, signal response to minimum ionising particles (MIP), I-V and CV-measurements. The results have been analysed to investigate the influence of the substrate resistivity on the detector performance after neutron and proton irradiation. The leakage current density, signal response to alpha-particles and MIPs show a strong dependence on the resistivity before and after irradiation. An observed decrease of the electron mean free drift length before and after irradiation with increasing substrate resistivity can be explained by a model involving the different ionisation ratios of defects, which are introduced by the irradiation. Comparison of the radiation damage due to neutrons and protons gives a hardness factor of 7+-0.9 for 24 GeV/c protons. The best detectors show a response to MIPs of 5250 e- at 200 V reverse bias after a irradiation level of 2*10E14 p/cm^2.

  16. EP 1165-2-1 FLOOD DAMAGE REDUCTION

    E-Print Network [OSTI]

    US Army Corps of Engineers

    EP 1165-2-1 30 Jul 99 13-1 CHAPTER 13 FLOOD DAMAGE REDUCTION 13-1. The Federal Interest. Congress, in the Flood Control Act of 1936, established as a nationwide policy that flood control (i.e., flood damage consideration of all alternatives in controlling flood waters, reducing the susceptibility of property to flood

  17. Damage detection in mechanical structures using extreme value statistic.

    SciTech Connect (OSTI)

    Worden, K.; Allen, D. W. (David W.); Sohn, H. (Hoon); Farrar, C. R. (Charles R.)

    2002-01-01

    The first and most important objective of any damage identification algorithms is to ascertain with confidence if damage is present or not. Many methods have been proposed for damage detection based on ideas of novelty detection founded in pattern recognition and multivariate statistics. The philosophy of novelty detection is simple. Features are first extracted from a baseline system to be monitored, and subsequent data are then compared to see if the new features are outliers, which significantly depart from the rest of population. In damage diagnosis problems, the assumption is that outliers are generated from a damaged condition of the monitored system. This damage classification necessitates the establishment of a decision boundary. Choosing this threshold value is often based on the assumption that the parent distribution of data is Gaussian in nature. While the problem of novelty detection focuses attention on the outlier or extreme values of the data i.e. those points in the tails of the distribution, the threshold selection using the normality assumption weighs the central population of data. Therefore, this normality assumption might impose potentially misleading behavior on damage classification, and is likely to lead the damage diagnosis astray. In this paper, extreme value statistics is integrated with the novelty detection to specifically model the tails of the distribution of interest. Finally, the proposed technique is demonstrated on simulated numerical data and time series data measured from an eight degree-of-freedom spring-mass system.

  18. Melt-band instabilities with two-phase damage

    E-Print Network [OSTI]

    Rudge, John F.; Bercovici, David

    2015-03-09

    phase. For the damage partitioning frac- tion we assume small values within the range 10?4 ? fI ? 10 ?2, which is comparable to that inferred by Rozel et al. (2011) and Austin & Evans (2007), although these studies were more rele- vant for damage...

  19. Proton Irradiation Damage Assessment of Carbon Reinforced Composites

    E-Print Network [OSTI]

    McDonald, Kirk

    Proton Irradiation Damage Assessment of Carbon Reinforced Composites: 2-D & 3-D Weaved Structures. of thermal expansion (CTE). #12;Positive news regarding 3D Carbon composite kept coming !! Irradiation damage-carbon under heavy irradiation (LHC Phase-I collimator material) Phase 2 Expose 2D & 3D carbon

  20. Walton County Coastal Storm Damage Reduction Project Walton County, FL

    E-Print Network [OSTI]

    US Army Corps of Engineers

    to reduce coastal storm damages by constructing berms and dunes along 18.8 miles of Walton County shoreline;vegetation and replacement of dune walkover structures as required. Material for the berm and duneWalton County Coastal Storm Damage Reduction Project Walton County, FL 13 December 2012 ABSTRACT

  1. Viscoelastic damage modeling of sinkhole formation Eyal Shalev*, Vladimir Lyakhovsky

    E-Print Network [OSTI]

    Lyakhovsky, Vladimir

    Viscoelastic damage modeling of sinkhole formation Eyal Shalev*, Vladimir Lyakhovsky Geological 2012 Keywords: Sinkholes Damage Viscoelasticity Modeling a b s t r a c t The sinkholes along the Dead Sea coast are observed in two main sedimentary environments: alluvial fan sinkholes, which usually

  2. INTERPOL Tsunami Evaluation Working The DVI Response to the South East Asian Tsunami between

    E-Print Network [OSTI]

    Spirtes, Peter

    1 INTERPOL Tsunami Evaluation Working Group The DVI Response to the South East Asian Tsunami The Geographic Event 25 Regional Impact of the Tsunami 28 Initial Thai response 36 International response 42 DVI Register DVI Disaster Victim Identification DNA Deoxyribonucleic acid TTVI Thai Tsunami Victim

  3. Solution found to chronic trim damage

    SciTech Connect (OSTI)

    Smirl, P.A. [Design Engineering Control Components Inc., Rancho Santa Margarita, CA (United States); Edwards, T.W. [Edwards (T.W.), Sun City, CA (United States)

    1997-09-01

    For some time, 2-inch single-stage gas-pressure letdown valve trim at a large Mideast oil and gas production facility suffered severe erosion damage, and experienced noise/vibration problems both within the valves themselves and the downstream piping. It was determined that the trim erosion which caused the problem was due to high oxide corrosion products from the upstream piping passing at high velocity (1,020 ft/sec) through the single-stage, drilled-hole-cage valve trim. This was also the source of the noise/vibration problems. Since it takes into account fluid density, it has been established that velocity head (V2/2) is a better criterion than just pure fluid velocity in judging design adequacy in pressure-reducing valves. It is very useful in eliminating the destructive effects of high fluid velocity and noise/vibration problems. In this case, the actual velocity head equaled 360 psi. For these reasons, it was decided to replace these single-stage pressure-reduction valves with multi-stage pressure-reduction valves capable of limiting this high velocity. These valves are described.

  4. How Damage Diversification Can Reduce Systemic Risk

    E-Print Network [OSTI]

    Burkholz, Rebekka; Schweitzer, Frank

    2015-01-01

    We consider the problem of risk diversification in complex networks. Nodes represent e.g. financial actors, whereas weighted links represent e.g. financial obligations (credits/debts). Each node has a risk to fail because of losses resulting from defaulting neighbors, which may lead to large failure cascades. Classical risk diversification strategies usually neglect network effects and therefore suggest that risk can be reduced if possible losses (i.e., exposures) are split among many neighbors (exposure diversification, ED). But from a complex networks perspective diversification implies higher connectivity of the system as a whole which can also lead to increasing failure risk of a node. To cope with this, we propose a different strategy (damage diversification, DD), i.e. the diversification of losses that are imposed on neighboring nodes as opposed to losses incurred by the node itself. Here, we quantify the potential of DD to reduce systemic risk in comparison to ED. For this, we develop a branching proce...

  5. Mesoscale polycrystal calculations of damage in spallation in metals

    SciTech Connect (OSTI)

    Tonks, Davis L [Los Alamos National Laboratory; Bingert, John F [Los Alamos National Laboratory; Livescu, Veronica [Los Alamos National Laboratory; Luo, Shengnian [Los Alamos National Laboratory; Bronkhorst, C A [Los Alamos National Laboratory

    2010-01-01

    The goal of this project is to produce a damage model for spallation in metals informed by the polycrystalline grain structure at the mesoscale. Earlier damage models addressed the continuwn macroscale in which these effects were averaged out. In this work we focus on cross sections from recovered samples examined with EBSD (electron backscattered diffraction), which reveal crystal grain orientations and voids. We seek to understand the loading histories of specific sample regions by meshing up the crystal grain structure of these regions and simulating the stress, strain, and damage histories in our hydro code, FLAG. The stresses and strain histories are the fundamental drivers of damage and must be calculated. The calculated final damage structures are compared with those from the recovered samples to validate the simulations.

  6. Photochemistry of psoralen-DNA adducts, biological effects of psoralen-DNA adducts, applications of psoralen-DNA photochemistry

    SciTech Connect (OSTI)

    Shi, Yun-bo

    1988-03-01

    This thesis consists of three main parts and totally eight chapters. In Part I, The author will present studies on the photochemistry of psoralen-DNA adducts, specifically, the wavelength dependencies for the photoreversals of thymidine-HMT (4'-hydroxymethyl-4, 5', 8-trimenthylpsoralen) monoadducts and diadduct and the same adducts incorporated in DNA helices and the wavelength dependecies for the photocrossslinking of thymidine-HMT monoadducts in double-stranded helices. In Part II, The author will report some biological effects of psoralen-DNA adducts, i.e., the effects on double-stranded DNA stability, DNA structure, and transcription by E. coli and T7 RNA polymerases. Finally, The author will focus on the applications of psoralen-DNA photochemistry to investigation of protein-DNA interaction during transcription, which includes the interaction of E. coli and T7 RNA polymerases with DNA in elongation complexes arrested at specific psoralen-DNA adduct sites as revealed by DNase I footprinting experiments. 123 refs., 52 figs., 12 tabs.

  7. Damage identification and health monitoring of structural and mechanical systems from changes in their vibration characteristics: A literature review

    SciTech Connect (OSTI)

    Doebling, S.W.; Farrar, C.R.; Prime, M.B.; Shevitz, D.W.

    1996-05-01

    This report contains a review of the technical literature concerning the detection, location, and characterization of structural damage via techniques that examine changes in measured structural vibration response. The report first categorizes the methods according to required measured data and analysis technique. The analysis categories include changes in modal frequencies, changes in measured mode shapes (and their derivatives), and changes in measured flexibility coefficients. Methods that use property (stiffness, mass, damping) matrix updating, detection of nonlinear response, and damage detection via neural networks are also summarized. The applications of the various methods to different types of engineering problems are categorized by type of structure and are summarized. The types of structures include beams, trusses, plates, shells, bridges, offshore platforms, other large civil structures, aerospace structures, and composite structures. The report describes the development of the damage-identification methods and applications and summarizes the current state-of-the-art of the technology. The critical issues for future research in the area of damage identification are also discussed.

  8. First Characterization of Avian Memory T Lymphocyte Responses to Avian Influenza Virus Proteins 

    E-Print Network [OSTI]

    Singh, Shailbala

    2011-02-22

    responses induced by intramuscular inoculation of chickens with AIV HA and NP expressing cDNA plasmids or a non-replicating human adenovirus vector were identified through ex vivo stimulation with virus infected, major histocompatibility complex (MHC...

  9. DNA Sequencing Using capillary Electrophoresis

    SciTech Connect (OSTI)

    Dr. Barry Karger

    2011-05-09

    The overall goal of this program was to develop capillary electrophoresis as the tool to be used to sequence for the first time the Human Genome. Our program was part of the Human Genome Project. In this work, we were highly successful and the replaceable polymer we developed, linear polyacrylamide, was used by the DOE sequencing lab in California to sequence a significant portion of the human genome using the MegaBase multiple capillary array electrophoresis instrument. In this final report, we summarize our efforts and success. We began our work by separating by capillary electrophoresis double strand oligonucleotides using cross-linked polyacrylamide gels in fused silica capillaries. This work showed the potential of the methodology. However, preparation of such cross-linked gel capillaries was difficult with poor reproducibility, and even more important, the columns were not very stable. We improved stability by using non-cross linked linear polyacrylamide. Here, the entangled linear chains could move when osmotic pressure (e.g. sample injection) was imposed on the polymer matrix. This relaxation of the polymer dissipated the stress in the column. Our next advance was to use significantly lower concentrations of the linear polyacrylamide that the polymer could be automatically blown out after each run and replaced with fresh linear polymer solution. In this way, a new column was available for each analytical run. Finally, while testing many linear polymers, we selected linear polyacrylamide as the best matrix as it was the most hydrophilic polymer available. Under our DOE program, we demonstrated initially the success of the linear polyacrylamide to separate double strand DNA. We note that the method is used even today to assay purity of double stranded DNA fragments. Our focus, of course, was on the separation of single stranded DNA for sequencing purposes. In one paper, we demonstrated the success of our approach in sequencing up to 500 bases. Other application papers of sequencing up to this level were also published in the mid 1990's. A major interest of the sequencing community has always been read length. The longer the sequence read per run the more efficient the process as well as the ability to read repeat sequences. We therefore devoted a great deal of time to studying the factors influencing read length in capillary electrophoresis, including polymer type and molecule weight, capillary column temperature, applied electric field, etc. In our initial optimization, we were able to demonstrate, for the first time, the sequencing of over 1000 bases with 90% accuracy. The run required 80 minutes for separation. Sequencing of 1000 bases per column was next demonstrated on a multiple capillary instrument. Our studies revealed that linear polyacrylamide produced the longest read lengths because the hydrophilic single strand DNA had minimal interaction with the very hydrophilic linear polyacrylamide. Any interaction of the DNA with the polymer would lead to broader peaks and lower read length. Another important parameter was the molecular weight of the linear chains. High molecular weight (> 1 MDA) was important to allow the long single strand DNA to reptate through the entangled polymer matrix. In an important paper, we showed an inverse emulsion method to prepare reproducibility linear polyacrylamide polymer with an average MWT of 9MDa. This approach was used in the polymer for sequencing the human genome. Another critical factor in the successful use of capillary electrophoresis for sequencing was the sample preparation method. In the Sanger sequencing reaction, high concentration of salts and dideoxynucleotide remained. Since the sample was introduced to the capillary column by electrokinetic injection, these salt ions would be favorably injected into the column over the sequencing fragments, thus reducing the signal for longer fragments and hence reading read length. In two papers, we examined the role of individual components from the sequencing reaction and then developed a protocol to reduce the deleterio

  10. An analysis of the kinetics of thermal damage and movement of damage front in laser irradiated egg white 

    E-Print Network [OSTI]

    Azeemi, Aamer Amjed

    1993-01-01

    the process of thermal coagulation. This study assumes tissue to be composed of two or more components, having different rates of damage. The results of this model are then used to find an effective rate of damage for a single rate model which would yield...

  11. Tsai, Hsiao, Bruneau: Overview of building damages in 921 Chi-Chi earthquake 93 Overview of Building Damages in

    E-Print Network [OSTI]

    Bruneau, Michel

    Tsai, Hsiao, Bruneau: Overview of building damages in 921 Chi-Chi earthquake 93 Overview of Building Damages in 921 Chi-Chi Earthquake K.C. Tsai 1) Chiang Pi Hsiao 2) Michel Bruneau 3) 1) Professor, Architecture and Building Research Institute, Ministry of Interior, Taipei, Taiwan, R.O.C. 3) Professor

  12. Assembling semiconductor nanocomposites using DNA replication technologies.

    SciTech Connect (OSTI)

    Heimer, Brandon W.; Crown, Kevin K.; Bachand, George David

    2005-11-01

    Deoxyribonucleic acid (DNA) molecules represent Nature's genetic database, encoding the information necessary for all cellular processes. From a materials engineering perspective, DNA represents a nanoscale scaffold with highly refined structure, stability across a wide range of environmental conditions, and the ability to interact with a range of biomolecules. The ability to mass-manufacture functionalized DNA strands with Angstrom-level resolution through DNA replication technology, however, has not been explored. The long-term goal of the work presented in this report is focused on exploiting DNA and in vitro DNA replication processes to mass-manufacture nanocomposite materials. The specific objectives of this project were to: (1) develop methods for replicating DNA strands that incorporate nucleotides with ''chemical handles'', and (2) demonstrate attachment of nanocrystal quantum dots (nQDs) to functionalized DNA strands. Polymerase chain reaction (PCR) and primer extension methodologies were used to successfully synthesize amine-, thiol-, and biotin-functionalized DNA molecules. Significant variability in the efficiency of modified nucleotide incorporation was observed, and attributed to the intrinsic properties of the modified nucleotides. Noncovalent attachment of streptavidin-coated nQDs to biotin-modified DNA synthesized using the primer extension method was observed by epifluorescence microscopy. Data regarding covalent attachment of nQDs to amine- and thiol-functionalized DNA was generally inconclusive; alternative characterization tools are necessary to fully evaluate these attachment methods. Full realization of this technology may facilitate new approaches to manufacturing materials at the nanoscale. In addition, composite nQD-DNA materials may serve as novel recognition elements in sensor devices, or be used as diagnostic tools for forensic analyses. This report summarizes the results obtained over the course of this 1-year project.

  13. Enhancing the DNA Patent Database

    SciTech Connect (OSTI)

    Walters, LeRoy B.

    2008-02-18

    Final Report on Award No. DE-FG0201ER63171 Principal Investigator: LeRoy B. Walters February 18, 2008 This project successfully completed its goal of surveying and reporting on the DNA patenting and licensing policies at 30 major U.S. academic institutions. The report of survey results was published in the January 2006 issue of Nature Biotechnology under the title “The Licensing of DNA Patents by US Academic Institutions: An Empirical Survey.” Lori Pressman was the lead author on this feature article. A PDF reprint of the article will be submitted to our Program Officer under separate cover. The project team has continued to update the DNA Patent Database on a weekly basis since the conclusion of the project. The database can be accessed at dnapatents.georgetown.edu. This database provides a valuable research tool for academic researchers, policymakers, and citizens. A report entitled Reaping the Benefits of Genomic and Proteomic Research: Intellectual Property Rights, Innovation, and Public Health was published in 2006 by the Committee on Intellectual Property Rights in Genomic and Protein Research and Innovation, Board on Science, Technology, and Economic Policy at the National Academies. The report was edited by Stephen A. Merrill and Anne-Marie Mazza. This report employed and then adapted the methodology developed by our research project and quoted our findings at several points. (The full report can be viewed online at the following URL: http://www.nap.edu/openbook.php?record_id=11487&page=R1). My colleagues and I are grateful for the research support of the ELSI program at the U.S. Department of Energy.

  14. DNA

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

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative Fuels Data Center Homesum_a_epg0_fpd_mmcf_m.xls" ,"Available from WebQuantityBonneville Power Administration would like submit theCovalent Bonding Low-Cost Ground8 GasDEVELOPMENTS E P I IT h it cdrives

  15. DNA

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

    blueprint of a bacterium's "molecular machinery," showing how bacterial immune systems fight off the viruses that infect them. By tracking down how bacterial defense systems work,...

  16. Base Excision by Thymine DNA Glycosylase Mediates DNA-Directed Cytotoxicity of 5-Fluorouracil 

    E-Print Network [OSTI]

    Selfridge J.; Schar P.; Lettieri T.; Schuermann D.; Saito Y.; Focke F.; Kunz C.

    2009-04-01

    5-Fluorouracil (5-FU), a chemotherapeutic drug commonly used in cancer treatment, imbalances nucleotide pools, thereby favoring misincorporation of uracil and 5-FU into genomic DNA. The processing of these bases by DNA repair activities was proposed...

  17. Protein-DNA Interactions Determine the Shapes of DNA Toroids Condensed in Virus Capsids

    E-Print Network [OSTI]

    Podgornik, Rudolf

    Protein-DNA Interactions Determine the Shapes of DNA Toroids Condensed in Virus Capsids Ame (13), or the virus capsid itself (14­16), either upon addition of spermine (Spm4þ ) or in a monovalent

  18. DNA binding specificity of the p73 DNA-binding domain

    E-Print Network [OSTI]

    Tse, Pui Wah

    2011-01-01

    of DNA recognition by p53 tetramers. Mol Cell 22, 741-753.site as a self-assembled tetramer. Structure 18, 246- Chene,structure of a p53 core tetramer bound to DNA. Oncogene 28,

  19. Microstructure in the extreme environment: understanding and predicting dynamic damage processes

    SciTech Connect (OSTI)

    Dennis-koller, Darcie L [Los Alamos National Laboratory; Cerreta, Ellen K [Los Alamos National Laboratory; Bronkhorst, Curt A [Los Alamos National Laboratory; Escobedo-diaz, Juan P [Los Alamos National Laboratory

    2010-12-21

    The future of materials science: strategic application for functionally controlled materials properties is emphasized by the need to control material performance in extreme environments. To this end, this study examines the separate effects of kinetics (in the form of dynamic loading rate and shock wave shape) from that of length-scale effects (in the form of microstructural defect distributions). Recently available mesoscale modeling techniques are being used to capture a physical link between kinetic and length-scale influences on dynamic loading. This work contributes innovative new tools in the form of shock-wave shaping techniques in dynamic experimentation, materials characterization, lending insight into 3D damage field analysis at micron resolution, and the physics necessary to provide predictive capabilities for dynamic damage evolution. Experimental results tailored for the discreet understanding of length-scale and kinetic effects during dynamic loading are obtained to provide the basis for the development of process-aware material performance models. The understanding of length-scale and kinetic effects in extreme environments of dynamic loading advances the understanding of current emerging issues relevant to phenomena such as inclusion related failure in metals, grain size dependence on ejecta, and benefits of interfaces in mitigating defect development specifically driven by the need to tailor material response. Finally, the coupling of experimental techniques with theory and simulation is aimed at advancing process-aware damage modeling as well as transitioning materials science from observation to property control.

  20. DNA-guided nanoparticle assemblies

    DOE Patents [OSTI]

    Gang, Oleg; Nykypanchuk, Dmytro; Maye, Mathew; van der Lelie, Daniel

    2013-07-16

    In some embodiments, DNA-capped nanoparticles are used to define a degree of crystalline order in assemblies thereof. In some embodiments, thermodynamically reversible and stable body-centered cubic (bcc) structures, with particles occupying <.about.10% of the unit cell, are formed. Designs and pathways amenable to the crystallization of particle assemblies are identified. In some embodiments, a plasmonic crystal is provided. In some aspects, a method for controlling the properties of particle assemblages is provided. In some embodiments a catalyst is formed from nanoparticles linked by nucleic acid sequences and forming an open crystal structure with catalytically active agents attached to the crystal on its surface or in interstices.

  1. DNA: The Strand that Connects Us All

    SciTech Connect (OSTI)

    Kaplan, Matt (University of Arizona Genetics Core) [University of Arizona Genetics Core

    2011-03-29

    Learn how the methods and discoveries of human population genetics are applied for personal genealogical reconstruction and anthropological testing. Dr. Kaplan starts with a short general review of human genetics and the biology behind this form of DNA testing. He looks at how DNA testing is performed and how samples are processed in the University of Arizona laboratory. He also examines examples of personal genealogical results from Family Tree DNA and personal anthropological results from the Genographic Project. Finally, he describes the newest project in the UA laboratory, the DNA Shoah Project.

  2. DNA sequencing using fluorescence background electroblotting membrane

    DOE Patents [OSTI]

    Caldwell, K.D.; Chu, T.J.; Pitt, W.G.

    1992-05-12

    A method for the multiplex sequencing on DNA is disclosed which comprises the electroblotting or specific base terminated DNA fragments, which have been resolved by gel electrophoresis, onto the surface of a neutral non-aromatic polymeric microporous membrane exhibiting low background fluorescence which has been surface modified to contain amino groups. Polypropylene membranes are preferably and the introduction of amino groups is accomplished by subjecting the membrane to radio or microwave frequency plasma discharge in the presence of an aminating agent, preferably ammonia. The membrane, containing physically adsorbed DNA fragments on its surface after the electroblotting, is then treated with crosslinking means such as UV radiation or a glutaraldehyde spray to chemically bind the DNA fragments to the membrane through amino groups contained on the surface. The DNA fragments chemically bound to the membrane are subjected to hybridization probing with a tagged probe specific to the sequence of the DNA fragments. The tagging may be by either fluorophores or radioisotopes. The tagged probes hybridized to the target DNA fragments are detected and read by laser induced fluorescence detection or autoradiograms. The use of aminated low fluorescent background membranes allows the use of fluorescent detection and reading even when the available amount of DNA to be sequenced is small. The DNA bound to the membranes may be reprobed numerous times. No Drawings

  3. SnapShot: DNA Polymerases II Mammals

    E-Print Network [OSTI]

    Foti, James J.

    DNA polymerases ensure the faithful duplication of genetic information inside the nuclease and mitochondria of eukaryotic cells and the nucleoid of prokaryotic cells. These remarkable enzymes synthesize polynucleotide ...

  4. Regulation of a senescence checkpoint response by the E2F1 transcription factor and p14ARF tumor suppressor

    SciTech Connect (OSTI)

    Dimri, Goberdhan P.; Itahana, Koji; Acosta, Meileen; Campisi, Judith

    1999-11-05

    Normal cells do not divide indefinitely due to a process known as replicative senescence. Human cells arrest growth with a senescent phenotype when they acquire one or more critically short telomere as a consequence of cell division. Recent evidence suggests that certain types of DNA damage, chromatin remodeling, or oncogenic forms of Rasor Raf can also elicit a senescence response. We show here that E2F1, a multifunctional transcription factor that binds the retinoblastoma (pRb) tumor suppressor and can either promote or suppress tumorigenesis, induces a senescent phenotype when overexpressed in normal human fibroblasts. Normal human cells stably arrested proliferation and expressed several markers of replicative senescence in response to E2F1. This activity of E2F1 was independent of its pRb binding activity, but dependent on its ability to stimulate gene expression. The E2F1 target gene critical for the senescence response appeared to be the p14ARF tumor suppressor. Replicatively senescent human fibroblasts overexpressed p14ARF, and ectopic expression of p14ARF in presenescent cells induced a phenotype similar to that induced by E2F1. Consistent with a critical role for p14ARF, cells with compromised p53 function were immune to senescence induction by E2F1, as were cells deficient in p14ARF. Our findings support the idea that the senescence response is a critical tumor suppressive mechanism, provide an explanation for the apparently paradoxical roles of E2F1 in oncogenesis, and identify p14ARF as a potentially important mediator of the senescent phenotype.

  5. Radiation Damage In Reactor Cavity Concrete

    SciTech Connect (OSTI)

    Field, Kevin G; Le Pape, Yann; Naus, Dan J; Remec, Igor; Busby, Jeremy T; Rosseel, Thomas M; Wall, Dr. James Joseph

    2015-01-01

    License renewal up to 60 years and the possibility of subsequent license renewal to 80 years has established a renewed focus on long-term aging of nuclear generating stations materials, and recently, on concrete. Large irreplaceable sections of most nuclear generating stations include concrete. The Expanded Materials Degradation Analysis (EMDA), jointly performed by the Department of Energy, the Nuclear Regulatory Commission and Industry, identified the urgent need to develop a consistent knowledge base on irradiation effects in concrete [1]. Much of the historical mechanical performance data of irradiated concrete [2] does not accurately reflect typical radiation conditions in NPPs or conditions out to 60 or 80 years of radiation exposure [3]. To address these potential gaps in the knowledge base, The Electric Power Research Institute and Oak Ridge National Laboratory are working to disposition radiation damage as a degradation mechanism. This paper outlines the research program within this pathway including: (i) defining the upper bound of the neutron and gamma dose levels expected in the biological shield concrete for extended operation (80 years of operation and beyond), (ii) determining the effects of neutron and gamma irradiation as well as extended time at temperature on concrete, (iii) evaluating opportunities to irradiate prototypical concrete under accelerated neutron and gamma dose levels to establish a conservative bound and share data obtained from different flux, temperature, and fluence levels, (iv) evaluating opportunities to harvest and test irradiated concrete from international NPPs, (v) developing cooperative test programs to improve confidence in the results from the various concretes and research reactors, (vi) furthering the understanding of the effects of radiation on concrete (see companion paper) and (vii) establishing an international collaborative research and information exchange effort to leverage capabilities and knowledge.

  6. Assessment of substrate-stabilizing factors for DnaK on the folding of aggregation-prone proteins

    SciTech Connect (OSTI)

    Ryu, Kisun; Kim, Chul Woo; Kim, Byung Hee [Department of Biotechnology, College of Engineering, Yonsei University, 134 Shinchon-Dong, Seodaemun-Gu, Seoul 120-749 (Korea, Republic of); Han, Kyoung Sim [Protheon Incorporated, Yonsei Engineering Research Center B120E, 134 Shinchon-Dong, Seodaemun-Gu, Seoul 120-749 (Korea, Republic of); Kim, Kyun-Hwan [Department of Pharmacology, School of Medicine, and Center for Diagnostic Medicine, Institute of Biomedical Science and Technology, Konkuk University, Seoul 143-701 (Korea, Republic of); Choi, Seong Il [Department of Biotechnology, College of Engineering, Yonsei University, 134 Shinchon-Dong, Seodaemun-Gu, Seoul 120-749 (Korea, Republic of); Institute of Life Science and Biotechnology, Yonsei University, 134 Shinchon-Dong, Seodaemun-Gu, Seoul 120-749 (Korea, Republic of)], E-mail: seongilchoi@daum.net; Seong, Baik L. [Department of Biotechnology, College of Engineering, Yonsei University, 134 Shinchon-Dong, Seodaemun-Gu, Seoul 120-749 (Korea, Republic of); Protheon Incorporated, Yonsei Engineering Research Center B120E, 134 Shinchon-Dong, Seodaemun-Gu, Seoul 120-749 (Korea, Republic of); Institute of Life Science and Biotechnology, Yonsei University, 134 Shinchon-Dong, Seodaemun-Gu, Seoul 120-749 (Korea, Republic of)], E-mail: blseong@yonsei.ac.kr

    2008-08-15

    Hydrophobic interactions between molecular chaperones and their nonnative substrates have been believed to be mainly responsible for both substrate recognition and stabilization against aggregation. However, the hydrophobic contact area between DnaK and its substrate proteins is very limited and other factors of DnaK for the substrate stabilization could not be excluded. Here, we covalently fused DnaK to the N-termini of aggregation-prone proteins in vivo. In the context of a fusion protein, DnaK has the ability to efficiently solubilize its linked proteins. The point mutation of the residue of DnaK critical for the substrate recognition and the deletion of the C-terminal substrate-binding domain did not have significant effect on the solubilizing ability of DnaK. The results imply that other factors of DnaK, distinct from the hydrophobic shielding of folding intermediates, also contributes to stabilization of its noncovalently bound substrates against aggregation. Elucidation of the nature of these factors would further enhance our understanding of the substrate stabilization of DnaK for expedited protein folding.

  7. Response Elements

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

    2007-07-11

    The Guide provides acceptable methods for meeting the requirement of DOE O 151.1C for response elements that respond or contribute to response as needed in an emergency. Supersedes DOE G 151.1-1, Volume 3-1, DOE G 151.1-1, Volume 3-2, DOE G 151.1-1, Volume 3-3, DOE G 151.1-1, Volume 3-4, DOE G 151.1-1, Volume 4-1, DOE G 151.1-1, Volume 4-2, DOE G 151.1-1, Volume 4-3, DOE G 151.1-1, Volume 4-4, DOE G 151.1-1, Volume 4-5, and DOE G 151.1-1, Volume 4-6.

  8. DNA Profiling Using Solid-State Nanopores: Detection of DNA-Binding

    E-Print Network [OSTI]

    Meller, Amit

    a 3.5 nm pore results from threading of a dye-intercalated DNA molecule, as compared to the typical for drug development, necessitating new in vitro methods for rapid and low-cost assessment of the binding molecules, which give the DNA/intercalator complex a bulkier structure than that of native DNA. Furthermore

  9. Ancient DNA Chronology within Sediment Deposits: Are Paleobiological Reconstructions Possible and Is DNA Leaching a Factor?

    E-Print Network [OSTI]

    Nielsen, Rasmus

    Ancient DNA Chronology within Sediment Deposits: Are Paleobiological Reconstructions Possible reported the successful extraction of ancient DNA (aDNA) from both frozen and nonfrozen sediments (even sediments up to 3300 years old at 2 cave sites in the North Island of New Zealand. These sites are ideal

  10. Dellaporta DNA Extraction Citation: Stephen L. Dellaporta,Jonathan Wood , James B. Hicks. A plant DNA

    E-Print Network [OSTI]

    Wurtele, Eve Syrkin

    1 Dellaporta DNA Extraction Citation: Stephen L. Dellaporta,Jonathan Wood , James B. Hicks. A plant supernatant and lightly dry DNA pellets by inverting the tubes on paper towels for 10 min. #12;4 12. Redissolve each DNA pellet with 0.7 mL EB2. May need to let sit overnight at 4°C if having trouble dissolving

  11. Calibration of damage parameters is an important issue for the use of damage laws, and particularly for industrial manufacturing processes. This paper deals with an

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    1 Abstract Calibration of damage parameters is an important issue for the use of damage laws Lemaitre damage parameters using tensile tests. An adapted objective function is built, and Efficient, ductile damage, global measurement. 1 Introduction An actual industrial issue is the study of material

  12. Characterization of Damage in Sandstones along the Mojave Section of the San Andreas Fault: Implications for the Shallow Extent of Damage

    E-Print Network [OSTI]

    Ben-Zion, Yehuda

    Characterization of Damage in Sandstones along the Mojave Section of the San Andreas Fault: Implications for the Shallow Extent of Damage Generation ORY DOR,1,5 JUDITH S. CHESTER,2 YEHUDA BEN-ZION,1 shallow generation of rock damage during an earthquake rupture, we measure the degree of fracture damage

  13. Observed damage during Argon gas cluster depth profiles of compound semiconductors

    SciTech Connect (OSTI)

    Barlow, Anders J. Portoles, Jose F.; Cumpson, Peter J.

    2014-08-07

    Argon Gas Cluster Ion Beam (GCIB) sources have become very popular in XPS and SIMS in recent years, due to the minimal chemical damage they introduce in the depth-profiling of polymer and other organic materials. These GCIB sources are therefore particularly useful for depth-profiling polymer and organic materials, but also (though more slowly) the surfaces of inorganic materials such as semiconductors, due to the lower roughness expected in cluster ion sputtering compared to that introduced by monatomic ions. We have examined experimentally a set of five compound semiconductors, cadmium telluride (CdTe), gallium arsenide (GaAs), gallium phosphide (GaP), indium arsenide (InAs), and zinc selenide (ZnSe) and a high-? dielectric material, hafnium oxide (HfO), in their response to argon cluster profiling. An experimentally determined HfO etch rate of 0.025?nm/min (3.95?×?10{sup ?2}?amu/atom in ion) for 6?keV Ar gas clusters is used in the depth scale conversion for the profiles of the semiconductor materials. The assumption has been that, since the damage introduced into polymer materials is low, even though sputter yields are high, then there is little likelihood of damaging inorganic materials at all with cluster ions. This seems true in most cases; however, in this work, we report for the first time that this damage can in fact be very significant in the case of InAs, causing the formation of metallic indium that is readily visible even to the naked eye.

  14. Mathematical analysis of fully coupled approach to creep damage

    E-Print Network [OSTI]

    A. V. Shutov; A. -M. Saendig

    2006-01-25

    We prove the existence and uniqueness of solution to a classical creep damage problem. We formulate a sufficient condition for the problem to have a unique smooth solution, locally in time. This condition is stated in terms of smoothness of given data, such as solid geometry, boundary conditions, applied loads, and initial conditions. Counterexamples with an arbitrary small lifetime of a structure are also given, showing the mechanical interpretation of imposed smoothness conditions. The proposed theory gives a rigorous framework for a strain localization analysis. The influence of the damage gradient on the strain localization process is characterized within this framework and a measure of the damage localization is proposed.

  15. Assessing Hail and Freeze Damage to Field Corn and Sorghum 

    E-Print Network [OSTI]

    Livingston, Stephen

    1995-11-30

    New Growth. Physical damage to young corn can be experienced from a freeze or heavy frost, from blowing sand and whipping in high winds, and from hail. Sometimes it may be a combination of several events. With each of these the growing point has... sunshine and temperatures above 55?F to support photosynthesis and to grow through any extended stress period once seed stores are depleted. Frost Damage (27 to 32?F). Tissue loss from frost damage is directly proportional to how low the temperature falls...

  16. Simulated Hail Damage Experiments in Cotton. 

    E-Print Network [OSTI]

    Lane, Harry C.

    1959-01-01

    shows that the main cause of variation in response to defoliation was the effect of 100 percent defolia- tion. Removal of two-thirds of the leaves caused some reduction in yield, but only 100 percent defoli- ation consistently reduced yield... and reflertetl largely the effect of removal ol fruicing limbs at the late stages ot growth. The interaction of added injury time5 tlf ation was not significant, but certain of the tr towards greater retluctions with' defoliation in the data have been...

  17. Allostery through protein-induced DNA bubbles

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

    Traverso, Joseph J.; Manoranjan, Valipuram S.; Bishop, A. R.; Rasmussen, Kim Ø.; Voulgarakis, Nikolaos K.

    2015-03-12

    Allostery through DNA is increasingly recognized as an important modulator of DNA functions. Here, we show that the coalescence of protein-induced DNA bubbles can mediate allosteric interactions that drive protein aggregation. We propose that such allostery may regulate DNA's flexibility and the assembly of the transcription machinery. Mitochondrial transcription factor A (TFAM), a dual-function protein involved in mitochondrial DNA (mtDNA) packaging and transcription initiation, is an ideal candidate to test such a hypothesis owing to its ability to locally unwind the double helix. Numerical simulations demonstrate that the coalescence of TFAM-induced bubbles can explain experimentally observed TFAM oligomerization. The resultingmore »melted DNA segment, approximately 10 base pairs long, around the joints of the oligomers act as flexible hinges, which explains the efficiency of TFAM in compacting DNA. Since mitochondrial polymerase (mitoRNAP) is involved in melting the transcription bubble, TFAM may use the same allosteric interaction to both recruit mitoRNAP and initiate transcription.« less

  18. DNA Nanomechanical Switches under Folding Kinetics Control

    E-Print Network [OSTI]

    Meller, Amit

    DNA Nanomechanical Switches under Folding Kinetics Control Virgile Viasnoff,, Amit Meller operate at equilibrium under changes in solution composition. We propose an alternative DNA switch design after heat denaturation drives the switch to its lowest energy conformation, while rapid cooling (>100

  19. Dynamics and control of DNA sequence amplification

    SciTech Connect (OSTI)

    Marimuthu, Karthikeyan [Department of Chemical Engineering and Center for Advanced Process Decision-Making, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213 (United States); Chakrabarti, Raj, E-mail: raj@pmc-group.com, E-mail: rajc@andrew.cmu.edu [Department of Chemical Engineering and Center for Advanced Process Decision-Making, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213 (United States); Division of Fundamental Research, PMC Advanced Technology, Mount Laurel, New Jersey 08054 (United States)

    2014-10-28

    DNA amplification is the process of replication of a specified DNA sequence in vitro through time-dependent manipulation of its external environment. A theoretical framework for determination of the optimal dynamic operating conditions of DNA amplification reactions, for any specified amplification objective, is presented based on first-principles biophysical modeling and control theory. Amplification of DNA is formulated as a problem in control theory with optimal solutions that can differ considerably from strategies typically used in practice. Using the Polymerase Chain Reaction as an example, sequence-dependent biophysical models for DNA amplification are cast as control systems, wherein the dynamics of the reaction are controlled by a manipulated input variable. Using these control systems, we demonstrate that there exists an optimal temperature cycling strategy for geometric amplification of any DNA sequence and formulate optimal control problems that can be used to derive the optimal temperature profile. Strategies for the optimal synthesis of the DNA amplification control trajectory are proposed. Analogous methods can be used to formulate control problems for more advanced amplification objectives corresponding to the design of new types of DNA amplification reactions.

  20. Recombinant DNA encoding a desulfurization biocatalyst

    DOE Patents [OSTI]

    Rambosek, J.; Piddington, C.S.; Kovacevich, B.R.; Young, K.D.; Denome, S.A.

    1994-10-18

    This invention relates to a recombinant DNA molecule containing a gene or genes which encode a biocatalyst capable of desulfurizing a fossil fuel which contains organic sulfur molecules. For example, the present invention encompasses a recombinant DNA molecule containing a gene or genes of a strain of Rhodococcus rhodochrous. 13 figs.

  1. Prospects & Overviews Integrating DNA barcode data and

    E-Print Network [OSTI]

    DeSalle, Rob

    , and description Paul Z. Goldstein and Rob DeSalleà DNA barcodes, like traditional sources of taxonomic information interpretation. The role of DNA barcoding in generating hypotheses of new taxa in need of formal taxonomic information but also for our comprehension of the magnitude of species diversity and its disappearance

  2. Deepwater Horizon Natural Resource Damage Assessment Deepwater Horizon Trustees Announce Agreement in Principle for

    E-Print Network [OSTI]

    ) ------- The Deepwater Horizon oil spill Natural Resource Damage Assessment Trustees (Trustees) today announced another Horizon oil spill Natural Resource Damage Assessment and restoration will continue until the publicDeepwater Horizon Natural Resource Damage Assessment Deepwater Horizon Trustees Announce Agreement

  3. Damage to HDPE geomembrane from interface shear over gravelly compacted clay liner

    E-Print Network [OSTI]

    Thielmann, Stuart

    2012-01-01

    R. S. (2011). “Geomembrane damage due to static and cyclic66 Figure 4.10. GM damage results after shearing for Testsshear displacement on shear strength and GM damage for test

  4. DAMAGE DETECTION METHODS ON WIND TURBINE BLADE TESTING WITH WIRED AND WIRELESS ACCELEROMETER SENSORS

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    DAMAGE DETECTION METHODS ON WIND TURBINE BLADE TESTING WITH WIRED AND WIRELESS ACCELEROMETER degrees of damage. Excitation was performed in two ways: near the delamination zone to demonstrate their performance. We explore methods for determining damage. We first explore results

  5. Effect of cumulative seismic damage and corrosion on life-cycle cost of reinforced concrete bridges 

    E-Print Network [OSTI]

    Kumar, Ramesh

    2009-05-15

    reinforced concrete (RC) bridges in earthquake prone regions. The approach is developed by combining cumulative seismic damage and damage associated to corrosion due to environmental conditions. Cumulative seismic damage is obtained from a low-cycle fatigue...

  6. The shape of the DNA minor groove directs binding by the DNA-bending protein Fis

    SciTech Connect (OSTI)

    Stella, Stefano; Cascio, Duilio; Johnson, Reid C.

    2010-06-21

    The bacterial nucleoid-associated protein Fis regulates diverse reactions by bending DNA and through DNA-dependent interactions with other control proteins and enzymes. In addition to dynamic nonspecific binding to DNA, Fis forms stable complexes with DNA segments that share little sequence conservation. Here we report the first crystal structures of Fis bound to high- and low-affinity 27-base-pair DNA sites. These 11 structures reveal that Fis selects targets primarily through indirect recognition mechanisms involving the shape of the minor groove and sequence-dependent induced fits over adjacent major groove interfaces. The DNA shows an overall curvature of {approx}65{sup o}, and the unprecedented close spacing between helix-turn-helix motifs present in the apodimer is accommodated by severe compression of the central minor groove. In silico DNA structure models show that only the roll, twist, and slide parameters are sufficient to reproduce the changes in minor groove widths and recreate the curved Fis-bound DNA structure. Models based on naked DNA structures suggest that Fis initially selects DNA targets with intrinsically narrow minor grooves using the separation between helix-turn-helix motifs in the Fis dimer as a ruler. Then Fis further compresses the minor groove and bends the DNA to generate the bound structure.

  7. Elastic and Proton Dynamics of the DNA

    E-Print Network [OSTI]

    V. L. Golo

    2008-03-28

    The subject of this report is the dynamics of elastic system in conjunction with hydrogen bonds of the DNA. We draw attention to the draw-back of the familiar rod model of the DNA, and make a case of constructing models that could accommodate the intrinsic structure of the DNA. In this respect studying the interplay among the elastic system and the protons of the DNA, is of interest, for it could accommodate the inter-strand as well as the tunneling modes of protons. Following this direction, we come to the conclusion that the elastic-proton dynamics may have a bearing on biophysics of the DNA. The phenomenon of point mutations is discussed within this framework.

  8. Programmable DNA-mediated multitasking processor

    E-Print Network [OSTI]

    Shu, Jian-Jun; Yong, Kian-Yan; Shao, Fangwei; Lee, Kee Jin

    2015-01-01

    Because of DNA appealing features as perfect material, including minuscule size, defined structural repeat and rigidity, programmable DNA-mediated processing is a promising computing paradigm, which employs DNAs as information storing and processing substrates to tackle the computational problems. The massive parallelism of DNA hybridization exhibits transcendent potential to improve multitasking capabilities and yield a tremendous speed-up over the conventional electronic processors with stepwise signal cascade. As an example of multitasking capability, we present an in vitro programmable DNA-mediated optimal route planning processor as a functional unit embedded in contemporary navigation systems. The novel programmable DNA-mediated processor has several advantages over the existing silicon-mediated methods, such as conducting massive data storage and simultaneous processing via much fewer materials than conventional silicon devices.

  9. Method for sequencing DNA base pairs

    DOE Patents [OSTI]

    Sessler, A.M.; Dawson, J.

    1993-12-14

    The base pairs of a DNA structure are sequenced with the use of a scanning tunneling microscope (STM). The DNA structure is scanned by the STM probe tip, and, as it is being scanned, the DNA structure is separately subjected to a sequence of infrared radiation from four different sources, each source being selected to preferentially excite one of the four different bases in the DNA structure. Each particular base being scanned is subjected to such sequence of infrared radiation from the four different sources as that particular base is being scanned. The DNA structure as a whole is separately imaged for each subjection thereof to radiation from one only of each source. 6 figures.

  10. Storing data encoded DNA in living organisms

    DOE Patents [OSTI]

    Wong; Pak C. (Richland, WA), Wong; Kwong K. (Sugar Land, TX), Foote; Harlan P. (Richland, WA)

    2006-06-06

    Current technologies allow the generation of artificial DNA molecules and/or the ability to alter the DNA sequences of existing DNA molecules. With a careful coding scheme and arrangement, it is possible to encode important information as an artificial DNA strand and store it in a living host safely and permanently. This inventive technology can be used to identify origins and protect R&D investments. It can also be used in environmental research to track generations of organisms and observe the ecological impact of pollutants. Today, there are microorganisms that can survive under extreme conditions. As well, it is advantageous to consider multicellular organisms as hosts for stored information. These living organisms can provide as memory housing and protection for stored data or information. The present invention provides well for data storage in a living organism wherein at least one DNA sequence is encoded to represent data and incorporated into a living organism.

  11. Probabilistic aspects of progressive damage in composite structures

    E-Print Network [OSTI]

    Reynante, Brandon M

    2011-01-01

    The effects and importance of incorporating probabilistic aspects of the progression of damage in the analysis of composite structures are assessed. Two specific cases of graphite/epoxy with centrally-located holes are ...

  12. Obstacles to Determining Punitive Damages in Class Actions

    E-Print Network [OSTI]

    Hines, Laura J.

    2001-01-01

    Courts and commentators have often embraced the class action device as an ideal means of assessing punitive damages fairly in mass tort cases. In this Article, Professor Hines sounds a cautionary note by identifying a number of procedural...

  13. Embedded Damage Detection in Water Pipelines Using Wireless Sensor Networks

    E-Print Network [OSTI]

    Shinozuka, Masanobu

    Embedded Damage Detection in Water Pipelines Using Wireless Sensor Networks Hadil Mustafa real-time detec- tion algorithm for detecting rupture events in water pipelines noninvasively reducing the total energy consumption significantly. Index Terms--Water pipeline monitoring, ruptures

  14. Neutron and gamma irradiation damage to organic materials.

    SciTech Connect (OSTI)

    White, Gregory Von, II; Bernstein, Robert

    2012-04-01

    This document discusses open literature reports which investigate the damage effects of neutron and gamma irradiation on polymers and/or epoxies - damage refers to reduced physical chemical, and electrical properties. Based on the literature, correlations are made for an SNL developed epoxy (Epon 828-1031/DDS) with an expected total fast-neutron fluence of {approx}10{sup 12} n/cm{sup 2} and a {gamma} dosage of {approx}500 Gy received over {approx}30 years at < 200 C. In short, there are no gamma and neutron irradiation concerns for Epon 828-1031/DDS. To enhance the fidelity of our hypotheses, in regards to radiation damage, we propose future work consisting of simultaneous thermal/irradiation (neutron and gamma) experiments that will help elucidate any damage concerns at these specified environmental conditions.

  15. Activation and radiation damage in the environment of hadron accelerators

    E-Print Network [OSTI]

    Kiselev, Daniela

    2013-01-01

    A component which suffers radiation damage usually also becomes radioactive, since the source of activation and radiation damage is the interaction of the material with particles from an accelerator or with reaction products. However, the underlying mechanisms of the two phenomena are different. These mechanisms are described here. Activation and radiation damage can have far-reaching consequences. Components such as targets, collimators, and beam dumps are the first candidates for failure as a result of radiation damage. This means that they have to be replaced or repaired. This takes time, during which personnel accumulate dose. If the dose to personnel at work would exceed permitted limits, remote handling becomes necessary. The remaining material has to be disposed of as radioactive waste, for which an elaborate procedure acceptable to the authorities is required. One of the requirements of the authorities is a complete nuclide inventory. The methods used for calculation of such inventories are presented,...

  16. Lengthscale effects in the damage and failure of composites

    E-Print Network [OSTI]

    Chambers, Jeffrey Thomas

    2014-01-01

    The primary objective of this work is to investigate and identify lengthscale effects associated with damage in composite materials and their structures, and to determine how these lengthscales vary across levels of ...

  17. Multiscale Computational Modeling of Multiphase Composites with Damage 

    E-Print Network [OSTI]

    Cheng, Feifei

    2013-11-01

    A multiscale computational framework for multiphase composites considering damage is developed in this research. In micro-scale, micromechanics based homogenization methods are used to estimate effective elastic moduli of graded Ti_(2)Al...

  18. Secondary sex ratios and male lifespan: Damaged or culled cohorts

    E-Print Network [OSTI]

    Catalano, Ralph; Bruckner, Tim

    2006-01-01

    9. Lazarus, J. (2002) in Sex Ratios: Concepts and ResearchSecondary sex ratios and male lifespan: Damaged or culledreduce the human secondary sex ratio (i.e. , the odds of a

  19. Viscoelastic{Viscoplastic Damage Model for Asphalt Concrete 

    E-Print Network [OSTI]

    Graham, Michael A.

    2010-10-12

    in experiments, and their model was limited to uniaxial loading. Chehab et al. (2003) developed a continuum viscoelastoplastic model for undamaged asphalt concrete, but its scope was also limited to uniaxial characterization. Uzan (2005) developed a damaged...

  20. Nondestrutive damage detection by simultaneous identification of stiffness and damping 

    E-Print Network [OSTI]

    Hyung, Sang Su

    2009-05-15

    The objective of this study is to develop a nondestructive damage evaluation methodology that can identify simultaneously both stiffness and damping changes in a structure. Two approaches are used to meet the stated objectives. First, a method...

  1. Evaluation of moisture damage within asphalt concrete mixes 

    E-Print Network [OSTI]

    Shah, Brij D.

    2004-09-30

    (Member) (Head of Department) August 2003 Major Subject: Civil Engineering iii ABSTRACT Evaluation of Moisture Damage within Asphalt Concrete Mixes. (August 2003) Brij D. Shah, B.E., Gujarat University Chair...

  2. 2-ethylpyridine, a cigarette smoke component, causes mitochondrial damage in human retinal pigment epithelial cells in vitro

    E-Print Network [OSTI]

    Kenney, MC; Mansoor, S; Gupta, N; Falatoonzadeh, P; Kuppermann, BD

    2014-01-01

    a cigarette smoke component, causes mitochondrial damage ina cigarette smoke component, causes mitochondrial damage ina cigarette smoke component, causes mitochondrial damage in

  3. Particulate Carrier Systems for Mucosal DNA Vaccine Delivery

    E-Print Network [OSTI]

    Borchard, Gerrit

    2006-10-26

    Streptomyces griseus Stop solution: 1M KOH In humans: degradation by lysozyme Incubation with chitosanase (1) GPEN 2006 Free DNA chitoplexes Incubation with chitosanase, 37?C Intact DNA ? Degraded chitosan Intact DNA ? Extraction with phenol: chloroform... Streptomyces griseus Stop solution: 1M KOH In humans: degradation by lysozyme Incubation with chitosanase (1) GPEN 2006 Free DNA chitoplexes Incubation with chitosanase, 37?C Intact DNA ? Degraded chitosan Intact DNA ? Extraction with phenol: chloroform...

  4. Development of a failure prediction method for damaged tubular members 

    E-Print Network [OSTI]

    Ritter, James Edward

    1992-01-01

    DEVELOPMENT OF A FAILURE PREDICTION METHOD FOR DAMAGED TUBULAR MEMBERS A Thesis by ZAMES EDWARD RITTER Submitted to the Office of Graduate Studies of Texas A&M University in partial fulfillment of the requirements for the degree of MASTER... OF SCIENCE May 1992 Major Subject: Civil Engineering DEVELOPMEMT OF A FAILURE PREDICTION METHOD FOR DAMAGED TUBULAR MEMBER8 A Thesis by JAMES EDWARD RITTER Approved as to style and content by: T ry L. Kohutek (Chair of Committee) Loren D. Lutes...

  5. Predicting threshold and location of laser damage on optical surfaces

    DOE Patents [OSTI]

    Siekhaus, Wigbert (Berkeley, CA)

    1987-01-01

    An apparatus useful in the prediction of the damage threshold of various optical devices, the location of weak spots on such devices and the location, identification, and elimination of optical surface impurities comprising, a focused and pulsed laser, an photo electric detector/imaging means, and a timer. The weak spots emit photoelectrons when subjected to laser intensities that are less than the intensity actually required to produce the damage. The weak spots may be eliminated by sustained exposure to the laser beam.

  6. An investigation of damage accumulation in graphite/epoxy laminates 

    E-Print Network [OSTI]

    Norvell, Robert Gerald

    1985-01-01

    AN INVESTIGATION OF DAMAGE ACCUMULATION IN GRAPHITE/EPOXY LAMINATES A Thesis by ROBERT GERALD NORVELL Submitted to the Graduate College of Texas A&M University in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE... August 1985 Major Subject: Aerospace Engineering AN INVESTIGATION OF DAMAGE ACCUMULATION IN GRAPHITE/EPOXY LAMINATES A Thesis by ROBERT GERALD NORVELL Approved as to style and content by: David H. Allen (Co-Chair of C mmitt. ) Richard A. Schap...

  7. Demand Response and Open Automated Demand Response

    E-Print Network [OSTI]

    LBNL-3047E Demand Response and Open Automated Demand Response Opportunities for Data Centers G described in this report was coordinated by the Demand Response Research Center and funded by the California. Demand Response and Open Automated Demand Response Opportunities for Data Centers. California Energy

  8. Microfluidics: Kinetics of Hybridized DNA With Fluid Flow Variations...

    Office of Scientific and Technical Information (OSTI)

    Conference: Microfluidics: Kinetics of Hybridized DNA With Fluid Flow Variations. Citation Details In-Document Search Title: Microfluidics: Kinetics of Hybridized DNA With Fluid...

  9. Topoisomerase II Structure Suggests Novel DNA Cleavage Mechanism

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

    Topoisomerase II Structure Suggests Novel DNA Cleavage Mechanism Print Type II topoisomerases are molecular machines that regulate DNA supercoiling and separate interlocked...

  10. Integrated Molecular Analysis Indicates Undetectable Change in DNA Damage in Mice after Continuous Irradiation at ~ 400-fold Natural Background Radiation

    E-Print Network [OSTI]

    Olipitz, Werner

    Background: In the event of a nuclear accident, people are exposed to elevated levels of continuous low dose-rate radiation. Nevertheless, most of the literature describes the biological effects of acute radiation.

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

    E-Print Network [OSTI]

    Marchetti, Francesco

    2009-01-01

    Development and the DOE Low Dose Radiation Research Program.in vivo by low doses of gamma radiation. Rad Res 156, 324-7.

  12. Accurate Prediction of BRCA1 and BRCA2 heterozygous genotype using expression profiling after induced DNA damage

    E-Print Network [OSTI]

    Kote-Jarai, Z.; Matthews, L.; Osorio, A.; Shanley, S.; Giddings, I.; Moseews, F.; Locke, I.; Evans, G.; Girolami, M.

    Kote-Jarai,Z. Matthews,L. Osorio,A. Shanley,S. Giddings,I. Moseews,F. Locke,I. Evans,G. Girolami,M. Williams,R. Campbell,C. Clinical Cancer Research, Vol. 12, No. 13, pp. 3896 - 3901

  13. Insulin signaling, dietary restriction and DNA damage : multiple roles for smk-1 in the mediation of C. elegans life span

    E-Print Network [OSTI]

    Wolff, Suzanne Christine

    2008-01-01

    America 96, 10152-10157. Simmer, F. , Moorman, C. , van der2 (pAD48; (Dillin et al. , 2002a)), smk-1 (Simmer et al. ,2003), or cyc-1 (Simmer et al. , 2003). A second smk-1 RNAi

  14. Insulin signaling, dietary restriction and DNA damage : multiple roles for smk-1 in the mediation of C. elegans life span

    E-Print Network [OSTI]

    Wolff, Suzanne Christine

    2008-01-01

    Insulin-regulated hepatic gluconeogenesis through FOXO1-PGC-an upregulation in gluconeogenesis in the efforts to keep

  15. Mechanism and Site of Attack for Direct Damage to DNA by Low-Energy Electrons X. Pan and L. Sanche

    E-Print Network [OSTI]

    Simons, Jack

    to the dissociation of temporary anions formed by the capture of the incident electron by the deoxyribose unit and substitution by sulfur of the oxygen doubly bonded to phosphorous. The following four differ- ent samples were of Calgary. A sulfur (1S) was substituted at one end of one backbone in the single (ss) and double (ds

  16. Structural Characterization of Clostridium acetobutylicum 8-Oxoguanine DNA Glycosylase in Its Apo Form and in Complex with 8-Oxodeoxyguanosine

    SciTech Connect (OSTI)

    Faucher, Frédérick; Robey-Bond, Susan M.; Wallace, Susan S.; Doublié, Sylvie; (Vermont)

    2009-06-30

    DNA is subject to a multitude of oxidative damages generated by oxidizing agents from metabolism and exogenous sources and by ionizing radiation. Guanine is particularly vulnerable to oxidation, and the most common oxidative product 8-oxoguanine (8-oxoG) is the most prevalent lesion observed in DNA molecules. 8-OxoG can form a normal Watson-Crick pair with cytosine (8-oxoG:C), but it can also form a stable Hoogsteen pair with adenine (8-oxoG:A), leading to a G:C {yields} T:A transversion after replication. Fortunately, 8-oxoG is recognized and excised by either of two DNA glycosylases of the base excision repair pathway: formamidopyrimidine-DNA glycosylase and 8-oxoguanine DNA glycosylase (Ogg). While Clostridium acetobutylicum Ogg (CacOgg) DNA glycosylase can specifically recognize and remove 8-oxoG, it displays little preference for the base opposite the lesion, which is unusual for a member of the Ogg1 family. This work describes the crystal structures of CacOgg in its apo form and in complex with 8-oxo-2'-deoxyguanosine. A structural comparison between the apo form and the liganded form of the enzyme reveals a structural reorganization of the C-terminal domain upon binding of 8-oxoG, similar to that reported for human OGG1. A structural comparison of CacOgg with human OGG1, in complex with 8-oxoG containing DNA, provides a structural rationale for the lack of opposite base specificity displayed by CacOgg.

  17. Gel Electrophoresis of Gold-DNA Nanoconjugates

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

    Pellegrino, T.; Sperling, R. A.; Alivisatos, A. P.; Parak, W. J.

    2007-01-01

    Gold-DNA conjugates were investigated in detail by a comprehensive gel electrophoresis study based on 1200 gels. A controlled number of single-stranded DNA of different length was attached specifically via thiol-Au bonds to phosphine-stabilized colloidal gold nanoparticles. Alternatively, the surface of the gold particles was saturated with single stranded DNA of different length either specifically via thiol-Au bonds or by nonspecific adsorption. From the experimentally determined electrophoretic mobilities, estimates for the effective diameters of the gold-DNA conjugates were derived by applying two different data treatment approaches. The first method is based on making a calibration curve for the relation between effectivemore »diameters and mobilities with gold nanoparticles of known diameter. The second method is based on Ferguson analysis which uses gold nanoparticles of known diameter as reference database. Our study shows that effective diameters derived from gel electrophoresis measurements are affected with a high error bar as the determined values strongly depend on the method of evaluation, though relative changes in size upon binding of molecules can be detected with high precision. Furthermore, in this study, the specific attachment of DNA via gold-thiol bonds to Au nanoparticles is compared to nonspecific adsorption of DNA. Also, the maximum number of DNA molecules that can be bound per particle was determined.« less

  18. Method of quantitating dsDNA

    DOE Patents [OSTI]

    Stark, Peter C. (Los Alamos, NM); Kuske, Cheryl R. (Los Alamos, NM); Mullen, Kenneth I. (Los Alamos, NM)

    2002-01-01

    A method for quantitating dsDNA in an aqueous sample solution containing an unknown amount of dsDNA. A first aqueous test solution containing a known amount of a fluorescent dye-dsDNA complex and at least one fluorescence-attenutating contaminant is prepared. The fluorescence intensity of the test solution is measured. The first test solution is diluted by a known amount to provide a second test solution having a known concentration of dsDNA. The fluorescence intensity of the second test solution is measured. Additional diluted test solutions are similarly prepared until a sufficiently dilute test solution having a known amount of dsDNA is prepared that has a fluorescence intensity that is not attenuated upon further dilution. The value of the maximum absorbance of this solution between 200-900 nanometers (nm), referred to herein as the threshold absorbance, is measured. A sample solution having an unknown amount of dsDNA and an absorbance identical to that of the sufficiently dilute test solution at the same chosen wavelength is prepared. Dye is then added to the sample solution to form the fluorescent dye-dsDNA-complex, after which the fluorescence intensity of the sample solution is measured and the quantity of dsDNA in the sample solution is determined. Once the threshold absorbance of a sample solution obtained from a particular environment has been determined, any similarly prepared sample solution taken from a similar environment and having the same value for the threshold absorbance can be quantified for dsDNA by adding a large excess of dye to the sample solution and measuring its fluorescence intensity.

  19. Structural Health Monitoring for Impact Damage in Composite Structures.

    SciTech Connect (OSTI)

    Roach, Dennis P.; Raymond Bond; Doug Adams

    2014-08-01

    Composite structures are increasing in prevalence throughout the aerospace, wind, defense, and transportation industries, but the many advantages of these materials come with unique challenges, particularly in inspecting and repairing these structures. Because composites of- ten undergo sub-surface damage mechanisms which compromise the structure without a clear visual indication, inspection of these components is critical to safely deploying composite re- placements to traditionally metallic structures. Impact damage to composites presents one of the most signi fi cant challenges because the area which is vulnerable to impact damage is generally large and sometimes very dif fi cult to access. This work seeks to further evolve iden- ti fi cation technology by developing a system which can detect the impact load location and magnitude in real time, while giving an assessment of the con fi dence in that estimate. Fur- thermore, we identify ways by which impact damage could be more effectively identi fi ed by leveraging impact load identi fi cation information to better characterize damage. The impact load identi fi cation algorithm was applied to a commercial scale wind turbine blade, and results show the capability to detect impact magnitude and location using a single accelerometer, re- gardless of sensor location. A technique for better evaluating the uncertainty of the impact estimates was developed by quantifying how well the impact force estimate meets the assump- tions underlying the force estimation technique. This uncertainty quanti fi cation technique was found to reduce the 95% con fi dence interval by more than a factor of two for impact force estimates showing the least uncertainty, and widening the 95% con fi dence interval by a fac- tor of two for the most uncertain force estimates, avoiding the possibility of understating the uncertainty associated with these estimates. Linear vibration based damage detection tech- niques were investigated in the context of structural stiffness reductions and impact damage. A method by which the sensitivity to damage could be increased for simple structures was presented, and the challenges of applying that technique to a more complex structure were identi fi ed. The structural dynamic changes in a weak adhesive bond were investigated, and the results showed promise for identifying weak bonds that show little or no static reduction in stiffness. To address these challenges in identifying highly localized impact damage, the possi- bility of detecting damage through nonlinear dynamic characteristics was also identi fi ed, with a proposed technique which would leverage impact location estimates to enable the detection of impact damage. This nonlinear damage identi fi cation concept was evaluated on a composite panel with a substructure disbond, and the results showed that the nonlinear dynamics at the damage site could be observed without a baseline healthy reference. By further developing impact load identi fi cation technology and combining load and damage estimation techniques into an integrated solution, the challenges associated with impact detection in composite struc- tures can be effectively solved, thereby reducing costs, improving safety, and enhancing the operational readiness and availability of high value assets.

  20. STATISTICAL DAMAGE CLASSIFICATION USING SEQUENTIAL PROBABILITY RATIO TESTS.

    SciTech Connect (OSTI)

    SOHN, HOON; ALLEN, DAVID W; WORDEN, KEITH; FARRAR, CHARLES R

    2002-02-16

    The primary objective of damage detection is to ascertain with confidence if damage is present or not within a structure of interest. In this study, a damage classification problem is cast in the context of the statistical pattern recognition paradigm. First, a time prediction model, called an autoregressive and autoregressive with exogenous inputs (AR-ARX) model, is fit to a vibration signal measured during a normal operating condition of the structure. When a new time signal is recorded from an unknown state of the system, the prediction errors are computed for the new data set using the time prediction model. When the structure undergoes structural degradation, it is expected that the prediction errors will increase for the damage case. Based on this premise, a damage classifier is constructed using a sequential hypothesis testing technique called the sequential probability ratio test (SPRT). The SPRT is one form of parametric statistical inference tests, and the adoption of the SPRT to damage detection problems can improve the early identification of conditions that could lead to performance degradation and safety concerns. The sequential test assumes a probability distribution of the sample data sets, and a Gaussian distribution of the sample data sets is often used. This assumption, however, might impose potentially misleading behavior on the extreme values of the data, i.e. those points in the tails of the distribution. As the problem of damage detection specifically focuses attention on the tails, the assumption of normality is likely to lead the analysis astray. To overcome this difficulty, the performance of the SPRT is improved by integrating extreme values statistics, which specifically models behavior in the tails of the distribution of interest into the SPRT.

  1. Nanopores formed by DNA origami: a review

    E-Print Network [OSTI]

    Bell, Nicholas A. W.; Keyser, Ulrich F.

    2014-06-10

    , coated with hydrophobic moieties, into a lipid bilayer. Recent work in these two branches is now discussed. Hybrid nanopores formed by trapping DNA origami onto a solid state nanopore The combination of DNA origami and solid state nanopores was first... (1982) Nucleic acid junctions and lattices. J. Theor. Biol. 99, 237–47. 28 Rothemund PWK (2006) Folding DNA to create nanoscale shapes and patterns. Nature 440, 297– 302. 29 Kuzyk A, Schreiber R, Fan Z, Pardatscher G, Roller E-M, Högele A, Simmel FC...

  2. Differential analysis of high-throughput quantitative genetic interaction data

    E-Print Network [OSTI]

    Bean, Gordon J; Ideker, Trey

    2012-01-01

    DNA damage response (DDR)). Other biological networks, suchespecially in context of the DDR. Thus, differentialThese gene pairs indicate DDR- relevant interactions that

  3. Characterization of a Y-Family DNA Polymerase eta from the Eukaryotic ThermophileAlvinella pompejana

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

    Kashiwagi, Sayo; Kuraoka, Isao; Fujiwara, Yoshie; Hitomi, Kenichi; Cheng, Quen J.; Fuss, Jill O.; Shin, David S.; Masutani, Chikahide; Tainer, John A.; Hanaoka, Fumio; et al

    2010-01-01

    Human DNA polymerase?(HsPol?) plays an important role in translesion synthesis (TLS), which allows for replication past DNA damage such as UV-inducedcis-syncyclobutane pyrimidine dimers (CPDs). Here, we characterized ApPol?from the thermophilic wormAlvinella pompejana, which inhabits deep-sea hydrothermal vent chimneys. ApPol?shares sequence homology with HsPol?and contains domains for binding ubiquitin and proliferating cell nuclear antigen. Sun-induced UV does not penetrateAlvinella'senvironment; however, this novel DNA polymerase catalyzed efficient and accurate TLS past CPD, as well as 7,8-dihydro-8-oxoguanine and isomers of thymine glycol induced by reactive oxygen species. In addition, we found that ApPol?is more thermostable than HsPol?, as expected from its habitat temperature.more »Moreover, the activity of this enzyme was retained in the presence of a higher concentration of organic solvents. Therefore, ApPol?provides a robust, human-like Pol?that is more active after exposure to high temperatures and organic solvents.« less

  4. Extremely low-frequency electromagnetic fields cause DNA strand breaks in normal Vero cells

    E-Print Network [OSTI]

    Cosmin Teodor Miha; Gabriela Vochita; Florin Brinza; Pincu Rotinberg

    2013-01-23

    Extremely low frequency electromagnetic fields aren't considered as a real carcinogenic agent despite the fact that some studies have showed impairment of the DNA integrity in different cells lines. The aim of this study was evaluation of the late effects of a 100 Hz and 5.6 mT electromagnetic field, applied continuously or discontinuously, on the DNA integrity of Vero cells assessed by alkaline Comet assay and by cell cycle analysis. Normal Vero cells were exposed to extremely low frequency electromagnetic fields (100 Hz, 5.6 mT) for 45 minutes. The Comet assay and cell cycle analysis were performed 48 hours after the treatment. Exposed samples presented an increase of the number of cells with high damaged DNA as compared with non-exposed cells. Quantitative evaluation of the comet assay showed a significantly ($cells. Cell cycle analysis showed an increase of the frequency of the cells in S phase, proving the occurrence of single strand breaks. The most probable mechanism of induction of the registered effects is the production of different types of reactive oxygen species.

  5. Characterization of a Y-Family DNA Polymerase eta from the Eukaryotic Thermophile Alvinella pompejana

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

    Kashiwagi, Sayo; Kuraoka, Isao; Fujiwara, Yoshie; Hitomi, Kenichi; Cheng, Quen J.; Fuss, Jill O.; Shin, David S.; Masutani, Chikahide; Tainer, John A.; Hanaoka, Fumio; et al

    2010-01-01

    Human DNA polymerase ? (HsPol ? ) plays an important role in translesion synthesis (TLS), which allows for replication past DNA damage such as UV-induced cis-syn cyclobutane pyrimidine dimers (CPDs). Here, we characterized ApPol ? from the thermophilic worm Alvinella pompejana , which inhabits deep-sea hydrothermal vent chimneys. ApPol ? shares sequence homology with HsPol ? and contains domains for binding ubiquitin and proliferating cell nuclear antigen. Sun-induced UV does not penetrate Alvinella's environment; however, this novel DNA polymerase catalyzed efficient and accurate TLS past CPD, as well asmore »7,8-dihydro-8-oxoguanine and isomers of thymine glycol induced by reactive oxygen species. In addition, we found that ApPol ? is more thermostable than HsPol ? , as expected from its habitat temperature. Moreover, the activity of this enzyme was retained in the presence of a higher concentration of organic solvents. Therefore, ApPol ? provides a robust, human-like Pol ? that is more active after exposure to high temperatures and organic solvents. « less

  6. DNA Assembly Line for Nano-Construction

    ScienceCinema (OSTI)

    Oleg Gang

    2010-01-08

    Building on the idea of using DNA to link up nanoparticles scientists at Brookhaven National Lab have designed a molecular assembly line for high-precision nano-construction. Nanofabrication is essential for exploiting the unique properties of nanoparticl

  7. Casting inorganic structures with DNA molds

    E-Print Network [OSTI]

    Sun, Wei

    We report a general strategy for designing and synthesizing inorganic nanostructures with arbitrarily prescribed three-dimensional shapes. Computationally designed DNA strands self-assemble into a stiff “nanomold” that ...

  8. Deoxyribose oxidation chemistry and endogenous DNA adducts

    E-Print Network [OSTI]

    Zhou, Xinfeng

    2006-01-01

    Endogenous and exogenous oxidants react with cellular macromolecules to generate a variety of electrophiles that react with DNA produce cytotoxic and mutagenic adducts. One source of such electrophiles is deoxyribose in ...

  9. NIJ-Funded Research in Forensic DNA

    E-Print Network [OSTI]

    Standards Funding from the FBI S&T Branch through NIST Information Access Division httpDNA) · Technology Evaluation and Development ­ Rapid multiplex PCR protocols* (PCR: 3 hr to FBI

  10. Intriguing DNA Editor Has a Structural Trigger

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

    "plug in" very specific snippets of DNA coding for a variety of reasons. For example, microbes could be re-engineered to consume specific environmental toxins or to produce better...

  11. Linear Thermodynamics of Rodlike DNA Filtration

    E-Print Network [OSTI]

    Li, Zirui

    Linear thermodynamics transportation theory is employed to study filtration of rodlike DNA molecules. Using the repeated nanoarray consisting of alternate deep and shallow regions, it is demonstrated that the complex ...

  12. Extracting biological knowledge from DNA sequences

    SciTech Connect (OSTI)

    De La Vega, F.M.; Thieffry, D.; Collado-Vides, J.

    1996-12-31

    This session describes the elucidation of information from dna sequences and what challenges computational biologists face in their task of summarizing and deciphering the human genome. Techniques discussed include methods from statistics, information theory, artificial intelligence and linguistics. 1 ref.

  13. Mitochondrial bioenergetics and drug-induced toxicity in a panel of mouse embryonic fibroblasts with mitochondrial DNA single nucleotide polymorphisms

    SciTech Connect (OSTI)

    Pereira, Claudia V.; Oliveira, Paulo J. [CNC—Center for Neuroscience and Cell Biology, University of Coimbra (Portugal)] [CNC—Center for Neuroscience and Cell Biology, University of Coimbra (Portugal); Will, Yvonne [Compound Safety Prediction, Pfizer Global Research and Development, Groton, CT (United States)] [Compound Safety Prediction, Pfizer Global Research and Development, Groton, CT (United States); Nadanaciva, Sashi, E-mail: sashi.nadanaciva@pfizer.com [Compound Safety Prediction, Pfizer Global Research and Development, Groton, CT (United States)] [Compound Safety Prediction, Pfizer Global Research and Development, Groton, CT (United States)

    2012-10-15

    Mitochondrial DNA (mtDNA) variations including single nucleotide polymorphisms (SNPs) have been proposed to be involved in idiosyncratic drug reactions. However, current in vitro and in vivo models lack the genetic diversity seen in the human population. Our hypothesis is that different cell strains with distinct mtDNA SNPs may have different mitochondrial bioenergetic profiles and may therefore vary in their response to drug-induced toxicity. Therefore, we used an in vitro system composed of four strains of mouse embryonic fibroblasts (MEFs) with mtDNA polymorphisms. We sequenced mtDNA from embryonic fibroblasts isolated from four mouse strains, C57BL/6J, MOLF/EiJ, CZECHII/EiJ and PERA/EiJ, with the latter two being sequenced for the first time. The bioenergetic profile of the four strains of MEFs was investigated at both passages 3 and 10. Our results showed that there were clear differences among the four strains of MEFs at both passages, with CZECHII/EiJ having a lower mitochondrial robustness when compared to C57BL/6J, followed by MOLF/EiJ and PERA/EiJ. Seven drugs known to impair mitochondrial function were tested for their effect on the ATP content of the four strains of MEFs in both glucose- and galactose-containing media. Our results showed that there were strain-dependent differences in the response to some of the drugs. We propose that this model is a useful starting point to study compounds that may cause mitochondrial off-target toxicity in early stages of drug development, thus decreasing the number of experimental animals used. -- Highlights: ? mtDNA SNPs may be linked to individual predisposition to drug-induced toxicity. ? CZECHII/EiJ and PERA/EiJ mtDNA was sequenced for the first time in this study. ? Strain-dependent mitochondrial capacity differences were measured. ? Strain-dependent differences in response to mitochondrial toxicants were observed.

  14. Advanced Demand Responsive Lighting

    E-Print Network [OSTI]

    Advanced Demand Responsive Lighting Host: Francis Rubinstein Demand Response Research Center demand responsive lighting systems ­ Importance of dimming ­ New wireless controls technologies · Advanced Demand Responsive Lighting (commenced March 2007) #12;Objectives · Provide up-to-date information

  15. The unholy trinity: taxonomy, species delimitation and DNA barcoding

    E-Print Network [OSTI]

    DeSalle, Rob

    The unholy trinity: taxonomy, species delimitation and DNA barcoding Rob DeSalle*, Mary G. Egan are clarified and resolved, before the use of DNA as a tool for taxonomy and species delimitation can framework for interweaving classical taxonomy with the goals of `DNA barcoding'. Keywords: DNA barcoding

  16. Synopsis: Repulsion Helps Virus Pack DNA APS/Joan Tycko

    E-Print Network [OSTI]

    Smith, Douglas E.

    Synopsis: Repulsion Helps Virus Pack DNA APS/Joan Tycko Repulsive DNA-DNA Interactions Accelerate, and Douglas E. Smith Phys. Rev. Lett. 112, 248101 (2014) Published June 17, 2014 Featured in Physics Editors reported in Physical Review Letters show that, surprisingly, switching the DNA self-interaction from

  17. ABBREVIATIONS: AHR, Ah receptor; RACE, rapid amplification of cDNA ends; TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin; DRE, dioxin-responsive element; ARNT, Ah receptor nuclear translocator; PAS, Per/Ah receptor nuclear translocator/Ah receptor/Sim; GAPDH, g

    E-Print Network [OSTI]

    Bradfield, Christopher A.

    ,3,7,8-tetrachlorodibenzo-p-dioxin; DRE, dioxin-responsive element; ARNT, Ah receptor nuclear translocator; PAS, Per/helix-loop-helix protein that mediates the toxic effects of 2,3,7,8-tetrachlorodibenzo-p- dioxin. A comparison the biological effects of TCDD (or "dioxin") and related planar aromatic compounds (1). Models to describe

  18. Damage and Mortality Assessment of Redwood and Mixed Conifer Forest Types

    E-Print Network [OSTI]

    Standiford, Richard B.

    347 Damage and Mortality Assessment of Redwood and Mixed Conifer Forest Types in Santa Cruz County left with tough decisions on how to treat tree damage and mortality compounded by the Pine Mountain a method for evaluating damage and mortality. Qualitative criteria for evaluating stand damage focused

  19. Damage In a Random Mlerstructure: Size Effects, Fractals, and Entropy Maximization

    E-Print Network [OSTI]

    Ostoja-Starzewski, Martin

    Damage In a Random Mler©structure: Size Effects, Fractals, and Entropy Maximization Martin Ostoja a micromechanical approach to damage growth in graph- representable microstructures is presented. Damage is denned in scatter of strength, and the fractal character of damage geometry, and thus provides a basis

  20. Radiation damage calculation in PHITS Y. Iwamoto1, K. Niita2, T. Sawai1,

    E-Print Network [OSTI]

    McDonald, Kirk

    Radiation damage calculation in PHITS 1 Y. Iwamoto1, K. Niita2, T. Sawai1, R.M. Ronningen3, T Feb. ­ 15 Feb. 2012 #12;2 Introduction Radiation damage model in PHITS Radiation damage calculation As the power of proton and heavy-ion accelerators is increasing, the prediction of the structural damage