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Sample records for human mammary epithelial

  1. Enhanced growth medium and method for culturing human mammary epithelial cells

    DOE Patents [OSTI]

    Stampfer, Martha R. (7290 Sayre Dr., Oakland, CA 94611); Smith, Helene S. (5693 Cabot Dr., Oakland, CA 94611); Hackett, Adeline J. (82 Evergreen Dr., Orinda, CA 94563)

    1983-01-01

    Methods are disclosed for isolating and culturing human mammary epithelial cells of both normal and malignant origin. Tissue samples are digested with a mixture including the enzymes collagenase and hyaluronidase to produce clumps of cells substantially free from stroma and other undesired cellular material. Growing the clumps of cells in mass culture in an enriched medium containing particular growth factors allows for active cell proliferation and subculture. Clonal culture having plating efficiencies of up to 40% or greater may be obtained using individual cells derived from the mass culture by plating the cells on appropriate substrates in the enriched media. The clonal growth of cells so obtained is suitable for a quantitative assessment of the cytotoxicity of particular treatment. An exemplary assay for assessing the cytotoxicity of the drug adriamycin is presented.

  2. Loss of p53 protein during radiation transformation of primary human mammary epithelial cells

    SciTech Connect (OSTI)

    Wazer, D.E.; Chu, Qiuming; Liu, Xiao Long; Gao, Qingshen; Safaii, H.; Band, V. (Tufts Univ. School of Medicine, Boston, MA (United States))

    1994-04-01

    The causative factors leading to breast cancer are largely unknown. Increased incidence of breast cancer following diagnostic or therapeutic radiation suggests that radiation may contribute to mammary oncogenesis. This report describes the in vitro neoplastic transformation of a normal human mammary epithelial cell strain, 76N, by fractionated [gamma]-irradiation at a clinically used dose (30 Gy). The transformed cells (76R-30) were immortal, had reduced growth factor requirements, and produced tumors in nude mice. Remarkably, the 76R-30 cells completely lacked the p53 tumor suppressor protein. Loss of p53 was due to deletion of the gene on one allele and a 26-bp deletion within the third intron on the second allele which resulted in abnormal splicing out of either the third or fourth exon from the mRNA. PCR with a mutation-specific primer showed that intron 3 mutation was present in irradiated cells before selection for immortal phenotype. 76R-30 cells did not exhibit G[sub 1] arrest in response to radiation, indicating a loss of p53-mediated function. Expression of the wild-type p53 gene in 76R-30 cells led to their growth inhibition. Thus, loss of p53 protein appears to have contributed to neoplastic transformation of these cells. This unique model should facilitate analyses of molecular mechanisms of radiation-induced breast cancer and allow identification of p53-regulated cellular genes in breast cells. 44 refs., 8 figs., 1 tab.

  3. HER/ErbB Receptor Interactions and Signaling Patterns in Human Mammary Epithelial Cells

    SciTech Connect (OSTI)

    Zhang, Yi; Opresko, Lee K.; Shankaran, Harish; Chrisler, William B.; Wiley, H. S.; Resat, Haluk

    2009-10-31

    Knowledge about signaling pathways is typically compiled based on data gathered using different cell lines. This approach implicitly assumes that cell line dependence is not important, which can be misleading because different cell lines do not always respond to a particular stimulus in the same way. The lack of coherent data collected from closely related cellular systems can be detrimental to the efforts to understand the regulation of biological processes. In this study, we report the development of a library of human mammary epithelial (HME) cell lines which express endogenous levels of the cell surface receptor EGFR/HER1, and different levels of HER2 and HER3. Using our clone library, we have quantified the interactions among the HER1-3 receptors and systematically investigated the existing hypotheses about their interaction patterns. Contrary to earlier suggestions, we find that lateral interactions with HER2 do not lead to strong transactivation between EGFR and HER3. Our study identified HER2 as the dominant dimerization partner for both EGFR and HER3, and revealed that EGFR and HER3 activations are only weakly linked in HME cells. We have also quantified the time-dependent activation patterns of the downstream effectors Erk and Akt. We found that HER3 signaling makes the strongest contribution to Akt activation and that, stimulation of either EGFR or HER3 pathways activate Erk at significant levels. Our study shows that cell libraries formed from closely related clones can be a powerful resource for pursuing the quantitative investigations that are necessary for developing a systems level understanding of cell signaling.

  4. Ionizing radiation predisposes non-malignant human mammary epithelial cells to undergo TGF beta-induced epithelial to mesenchymal transition

    E-Print Network [OSTI]

    2007-01-01

    Health Effects; the Low Dose Radiation Program of the DOElong-term, low-dose ionizing radiation exposure in humans.

  5. Immortalization of normal human mammary epithelial cells in two steps by direct targeting of senescence barriers does not require gross genomic alterations

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

    Garbe, James C.; Vrba, Lukas; Sputova, Klara; Fuchs, Laura; Novak, Petr; Brothman, Arthur R.; Jackson, Mark; Chin, Koei; LaBarge, Mark A.; Watts, George; et al

    2014-10-29

    Telomerase reactivation and immortalization are critical for human carcinoma progression. However, little is known about the mechanisms controlling this crucial step, due in part to the paucity of experimentally tractable model systems that can examine human epithelial cell immortalization as it might occur in vivo. We achieved efficient non-clonal immortalization of normal human mammary epithelial cells (HMEC) by directly targeting the 2 main senescence barriers encountered by cultured HMEC. The stress-associated stasis barrier was bypassed using shRNA to p16INK4; replicative senescence due to critically shortened telomeres was bypassed in post-stasis HMEC by c-MYC transduction. Thus, 2 pathologically relevant oncogenic agentsmore »are sufficient to immortally transform normal HMEC. The resultant non-clonal immortalized lines exhibited normal karyotypes. Most human carcinomas contain genomically unstable cells, with widespread instability first observed in vivo in pre-malignant stages; in vitro, instability is seen as finite cells with critically shortened telomeres approach replicative senescence. Our results support our hypotheses that: (1) telomere-dysfunction induced genomic instability in pre-malignant finite cells may generate the errors required for telomerase reactivation and immortalization, as well as many additional “passenger” errors carried forward into resulting carcinomas; (2) genomic instability during cancer progression is needed to generate errors that overcome tumor suppressive barriers, but not required per se; bypassing the senescence barriers by direct targeting eliminated a need for genomic errors to generate immortalization. Achieving efficient HMEC immortalization, in the absence of “passenger” genomic errors, should facilitate examination of telomerase regulation during human carcinoma progression, and exploration of agents that could prevent immortalization.« less

  6. Immortalization of normal human mammary epithelial cells in two steps by direct targeting of senescence barriers does not require gross genomic alterations

    SciTech Connect (OSTI)

    Garbe, James C.; Vrba, Lukas; Sputova, Klara; Fuchs, Laura; Novak, Petr; Brothman, Arthur R.; Jackson, Mark; Chin, Koei; LaBarge, Mark A.; Watts, George; Futscher, Bernard W.; Stampfer, Martha R.

    2014-10-29

    Telomerase reactivation and immortalization are critical for human carcinoma progression. However, little is known about the mechanisms controlling this crucial step, due in part to the paucity of experimentally tractable model systems that can examine human epithelial cell immortalization as it might occur in vivo. We achieved efficient non-clonal immortalization of normal human mammary epithelial cells (HMEC) by directly targeting the 2 main senescence barriers encountered by cultured HMEC. The stress-associated stasis barrier was bypassed using shRNA to p16INK4; replicative senescence due to critically shortened telomeres was bypassed in post-stasis HMEC by c-MYC transduction. Thus, 2 pathologically relevant oncogenic agents are sufficient to immortally transform normal HMEC. The resultant non-clonal immortalized lines exhibited normal karyotypes. Most human carcinomas contain genomically unstable cells, with widespread instability first observed in vivo in pre-malignant stages; in vitro, instability is seen as finite cells with critically shortened telomeres approach replicative senescence. Our results support our hypotheses that: (1) telomere-dysfunction induced genomic instability in pre-malignant finite cells may generate the errors required for telomerase reactivation and immortalization, as well as many additional “passenger” errors carried forward into resulting carcinomas; (2) genomic instability during cancer progression is needed to generate errors that overcome tumor suppressive barriers, but not required per se; bypassing the senescence barriers by direct targeting eliminated a need for genomic errors to generate immortalization. Achieving efficient HMEC immortalization, in the absence of “passenger” genomic errors, should facilitate examination of telomerase regulation during human carcinoma progression, and exploration of agents that could prevent immortalization.

  7. Integrated analysis reveals that STAT3 is central to the crosstalk between HER/ErbB receptor signaling pathways in human mammary epithelial cells

    SciTech Connect (OSTI)

    Gong, Chunhong; Zhang, Yi; Shankaran, Harish; Resat, Haluk

    2015-01-01

    Human epidermal growth factor receptors (HER, also known as ErbB) drive cellular proliferation, pro-survival and stress responses by activating several downstream kinases, in particular ERK, p38, JNK (SAPK), the PI3K/AKT, as well as various transcriptional regulators such as STAT3. When co-expressed, first three members of HER family (HER1-3) can form homo- and hetero-dimers. Based on the considerable evidence which suggest that every receptor dimer activates intracellular signaling pathways differentially, we hypothesized that the HER dimerization pattern is a better predictor of downstream signaling than the total receptor activation levels. We validated our hypothesis using a combination of model-based analysis to quantify the HER dimerization patterns and multi-factorial experiments where HER dimerization patterns and signaling crosstalk were rationally perturbed. We have measured the activation of HER1-3 receptors and of the sentinel signaling proteins ERK, AKT, p38, JNK, STAT3 as a function of time in a panel of human mammary epithelial (HME) cells expressing different levels of HER1-3 stimulated with various ligand combinations. Our analysis using multiple ways of clustering the activation data has confirmed that the HER receptor dimer is a better predictor of the signaling through p38, ERK and AKT pathways than the total HER receptor expression and activation levels. Targeted inhibition studies to identify the causal effects allowed us to obtain a consensus regulatory interaction model, which revealed that STAT3 occupies a central role in the crosstalk between the studied pathways.

  8. 4-Hydroxyestradiol induces oxidative stress and apoptosis in human mammary epithelial cells: possible protection by NF-{kappa}B and ERK/MAPK

    SciTech Connect (OSTI)

    Chen Zhihua [National Research Laboratory of Molecular Carcinogenesis and Chemoprevention, College of Pharmacy, Seoul National University, Shinlim-dong, Kwanak-ku, Seoul 151-742 (Korea, Republic of); Na, Hye-Kyung [National Research Laboratory of Molecular Carcinogenesis and Chemoprevention, College of Pharmacy, Seoul National University, Shinlim-dong, Kwanak-ku, Seoul 151-742 (Korea, Republic of); Hurh, Yeon-Jin [National Research Laboratory of Molecular Carcinogenesis and Chemoprevention, College of Pharmacy, Seoul National University, Shinlim-dong, Kwanak-ku, Seoul 151-742 (Korea, Republic of); Surh, Young-Joon [National Research Laboratory of Molecular Carcinogenesis and Chemoprevention, College of Pharmacy, Seoul National University, Shinlim-dong, Kwanak-ku, Seoul 151-742 (Korea, Republic of)]. E-mail: surh@plaza.snu.ac.kr

    2005-10-01

    Catechol estrogens, the hydroxylated metabolites of 17{beta}-estradiol (E{sub 2}), have been considered to be implicated in estrogen-induced carcinogenesis. 4-Hydroxyestradiol (4-OHE{sub 2}), an oxidized metabolite of E{sub 2} formed preferentially by cytochrome P450 1B1, reacts with DNA to form depurinating adducts thereby exerting genotoxicity and carcinogenicity. 4-OHE{sub 2} undergoes 2-electron oxidation to quinone via semiquinone, and during this process, reactive oxygen species (ROS) can be generated to cause DNA damage and cell death. In the present study, 4-OHE{sub 2} was found to elicit cytotoxicity in cultured human mammary epithelial (MCF-10A) cells, which was blocked by the antioxidant trolox. MCF-10A cells treated with 4-OHE{sub 2} exhibited increased intracellular ROS accumulation and 8-oxo-7,8-dihydroxy-2'-deoxyguanosine formation, and underwent apoptosis as determined by poly(ADP-ribose)polymerase cleavage and disruption of mitochondrial transmembrane potential. The redox-sensitive transcription factor nuclear factor {kappa}B (NF-{kappa}B) was transiently activated by 4-OHE{sub 2} treatment. Cotreatment of MCF-10A cells with the NF-{kappa}B inhibitor, L-1-tosylamido-2-phenylethyl chloromethyl ketone, exacerbated 4-OHE{sub 2}-induced cell death. 4-OHE{sub 2} also caused transient activation of extracellular signal-regulated protein kinases (ERK) involved in transmitting cell survival or death signals. A pharmacological inhibitor of ERK aggravated the 4-OHE{sub 2}-induced cytotoxicity, supporting the pivotal role of ERK in protecting against catechol estrogen-induced oxidative cell death.

  9. Proliferation of Estrogen Receptor alpha Positive Mammary Epithelial Cells is Restrained by TGFbeta1 in Adult Mice

    SciTech Connect (OSTI)

    Ewan, Kenneth B.R.; Oketch-Rabah, Hellen A.; Ravani, Shraddha A.; Shyamala, G.; Moses, Harold L.; Barcellos-Hoff, Mary Helen

    2005-03-03

    Transforming growth factor {beta}1 (TGF{beta}1) is a potent inhibitor of mammary epithelial proliferation. In human breast, estrogen receptor {alpha} (ER{alpha}) cells rarely co-localize with markers of proliferation, but their increased frequency correlates with breast cancer risk. To determine whether TGF{beta}1 is necessary for the quiescence of ER{alpha}-positive population, we examined mouse mammary epithelial gland at estrus. Approximately 35% of cells showed TGF{beta}1 activation, which co-localized with nuclear receptor-phosphorylated Smad 2/3, indicating that TGF{beta} signaling is autocrine. Furthermore, nuclear Smad co-localized with nuclear ER{alpha}. To test whether TGF{beta} was functional, we examined genetically engineered mice with different levels of TGF{beta}1. ER{alpha} co-localization with markers of proliferation (i.e. Ki-67 or BrdU) at estrus was significantly increased in the mammary glands of Tgf{beta}1 C57/bl/129SV heterozygote mice. This relationship was maintained following pregnancy, but was absent at puberty. Conversely, mammary epithelial expression of constitutively active TGF{beta}1 via the MMTV promoter suppressed proliferation of ER{alpha} positive cells. Thus, TGF{beta}1 activation functionally restrains ER{alpha} positive cells from proliferating in adult mammary gland. Accordingly, we propose that TGF{beta}1 dysregulation may promote proliferation of ER{alpha} positive cells associated with breast cancer risk in humans.

  10. Multiple Mechanisms are Responsible for Transactivation of the Epidermal Growth Factor Receptor in Mammary Epithelial Cells

    SciTech Connect (OSTI)

    Rodland, Karin D.; Bollinger, Nikki; Ippolito, Danielle L.; Opresko, Lee; Coffey, Robert J.; Zangar, Richard C.; Wiley, H. S.

    2008-11-14

    REVIEW ENTIRE DOCUMENT AT: https://pnlweb.pnl.gov/projects/bsd/ERICA%20Manuscripts%20for%20Review/KD%20Rodland%20D7E80/HMEC_transactivation_ms01_15+Figs.pdf ABSTRACT: Using a single nontransformed strain of human mammary epithelial cells, we found that the ability of multiple growth factors and cytokines to induce ERK phosphorylation was dependent on EGFR activity. These included lysophosphatidic acid (LPA), uridine triphosphate, growth hormone, vascular endothelial growth factor, insulin-like growth factor-1 (IGF-1), and tumor necrosis factoralpha. In contrast, hepatocyte growth factor could stimulate ERK phosphorylation independent of EGFR activity...

  11. Persistence of gamma-H2AX and 53BP1 foci in proliferating and nonproliferating human mammary epithelial cells after exposure to gamma-rays or iron ions

    SciTech Connect (OSTI)

    Groesser, Torsten; Chang, Hang; Fontenay, Gerald; Chen, James; Costes, Sylvain V.; Barcellos-Hoff, Mary Helen; Parvin, Bahram; Rydberg, Bjorn

    2010-12-22

    To investigate {gamma}-H2AX (phosphorylated histone H2AX) and 53BP1 (tumour protein 53 binding protein No. 1) foci formation and removal in proliferating and non-proliferating human mammary epithelial cells (HMEC) after exposure to sparsely and densely ionizing radiation under different cell culture conditions. HMEC cells were grown either as monolayers (2D) or in extracellular matrix to allow the formation of acinar structures in vitro (3D). Foci numbers were quantified by image analysis at various time points after exposure. Our results reveal that in non-proliferating cells under 2D and 3D cell culture conditions, iron-ion induced {gamma}-H2AX foci were still present at 72 h after exposure, although 53BP1 foci returned to control levels at 48 h. In contrast in proliferating HMEC, both {gamma}-H2AX and 53BP1 foci decreased to control levels during the 24-48 h time interval after irradiation under 2D conditions. Foci numbers decreased faster after {gamma}-ray irradiation and returned to control levels by 12 h regardless of marker, cell proliferation status, and cell culture condition. Conclusions: The disappearance of radiation induced {gamma}-H2AX and 53BP1 foci in HMEC have different dynamics that depend on radiation quality and proliferation status. Notably, the general patterns do not depend on the cell culture condition (2D versus 3D). We speculate that the persistent {gamma}-H2AX foci in iron-ion irradiated non-proliferating cells could be due to limited availability of double strand break (DSB) repair pathways in G0/G1-phase, or that repair of complex DSB requires replication or chromatin remodeling.

  12. EGF-receptor phosphorylation and downstream signaling are activated by benzo[a]pyrene 3,6-quinone and benzo[a]pyrene 1,6-quinone in human mammary epithelial cells

    SciTech Connect (OSTI)

    Rodriguez-Fragoso, Lourdes [Facultad de Farmacia, Universidad Autonoma del Estado de Morelos, Avenida Universidad 1001 Col. Chamilpa, Cuernavaca 62210, Morelos (Mexico); Melendez, Karla; Hudson, Laurie G.; Lauer, Fredine T. [University of New Mexico, College of Pharmacy Toxicology Program, Albuquerque, New Mexico (United States); Burchiel, Scott W. [University of New Mexico, College of Pharmacy Toxicology Program, Albuquerque, New Mexico (United States)], E-mail: sburchiel@salud.unm.edu

    2009-03-15

    Benzo[a]pyrene (BaP) is activated by xenobiotic-metabolizing enzymes to highly mutagenic and carcinogenic metabolites. Previous studies in this laboratory have shown that benzo[a]pyrene quinones (BPQs), 1,6-BPQ and 3,6-BPQ, are able to induce epidermal growth factor receptor (EGFR) cell signaling through the production of reactive oxygen species. Recently, we have reported that BPQs have the potential to induce the expression of genes involved in numerous pathways associated with cell proliferation and survival in human mammary epithelial cells. In the present study we demonstrated that BPQs not only induced EGFR tyrosine autophosphorylation, but also induced EGFR-dependent tyrosine phosphorylation of phospholipase C-{gamma}1 and several signal transducers and activators of transcription (STATs). The effects of BPQs were evaluated in a model of EGF withdrawal in MCF10-A cells. We found that BPQs (1 {mu}M), induced EGFR tyrosine phosphorylation at positions Y845, Y992, Y1068, and Y1086. PLC-{gamma}1 phosphorylation correlated with the phosphorylation of tyrosine-Y992, a proposed docking site for PLC-{gamma}1 on the EGFR. Additionally, we found that BPQs induced the activation of STAT-1, STAT-3, STAT-5a and STAT-5b. STAT5 was shown to translocate to the nucleus following 3,6-BPQ and 1,6-BPQ exposures. Although the patterns of phosphorylation at EGFR, PLC-{gamma}1 and STATs were quite similar to those induced by EGF, an important difference between BPQ-mediated signaling of the EGFR was observed. Signaling produced by EGF ligand produced a rapid disappearance of EGFR from the cell surface, whereas BPQ signaling maintained EGFR receptors on the cell membrane. Thus, the results of these studies show that 1,6-BPQ and 3,6-BPQ can produce early events as evidenced by EGFR expression, and a prolonged transactivation of EGFR leading to downstream cell signaling pathways.

  13. ERK and PI3K regulate different aspects of the epithelial to mesenchymal transition of mammary tumor cells induced by truncated MUC1

    SciTech Connect (OSTI)

    Horn, Galit; Gaziel, Avital [Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978 (Israel) [Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978 (Israel); The Alec and Myra Marmot Hybridoma Unit, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978 (Israel); Wreschner, Daniel H. [Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978 (Israel) [Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978 (Israel); Biomodifying LLC, San Diego, CA 92122 (United States); Smorodinsky, Nechama I., E-mail: nechama@post.tau.ac.il [Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978 (Israel); The Alec and Myra Marmot Hybridoma Unit, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978 (Israel); Ehrlich, Marcelo [Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978 (Israel)] [Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978 (Israel)

    2009-05-01

    Epithelial to mesenchymal transition (EMT) integrates changes to cell morphology and signaling pathways resulting from modifications to the cell's transcriptional response. Different combinations of stimuli ignite this process in the contexts of development or tumor progression. The human MUC1 gene encodes multiple alternatively spliced forms of a polymorphic oncoprotein that is aberrantly expressed in epithelial malignancies. MUC1 is endowed with various signaling modules and has the potential to mediate proliferative and morphological changes characteristic of the progression of epithelial tumors. The tyrosine-rich cytoplasmic domain and the heavily glycosylated extracellular domain both play a role in MUC1-mediated signal transduction. However, the attribution of function to specific domains of MUC1 is difficult due to the concomitant presence of multiple forms of the protein, which stem from alternative splicing and proteolytic cleavage. Here we show that DA3 mouse mammary tumor cells stably transfected with a truncated genomic fragment of human MUC1 undergo EMT. In their EMT, these cells demonstrate altered [i] morphology, [ii] signaling pathways and [iii] expression of epithelial and mesenchymal markers. Similarly to well characterized human breast cancer cell lines, cells transfected with truncated MUC1 show an ERK-dependent increased spreading on fibronectin, and a PI3K-dependent enhancement of their proliferative rate.

  14. EGF-Receptor-Mediated Mammary Epithelial Cell Migration is Driven by Sustained ERK Signaling from Autocrine Stimulation

    SciTech Connect (OSTI)

    Joslin, Elizabeth J.; Opresko, Lee; Wells, Alan; Wiley, H. S.; Lauffenburger, Douglas A.

    2007-10-15

    Aberrant expression of epidermal growth factor (EGF) receptor family ligands, as well as the receptors themselves, has been implicated in various types of cancers. EGF family ligands are synthesized as membrane-anchored proteins requiring proteolytic release to form the mature soluble factor. Despite the pathophysiological importance of autocrine systems, how the rate of protease-mediated ligand release quantitatively influences receptor-mediated signaling and consequent cell behavior is poorly understood. Therefore, we explored the relationship between autocrine EGF release rates and receptor-mediated ERK activation and migration in human mammary epithelial cells. A quantitative spectrum of EGF release rates was achieved using a set of chimeric transmembrane EGF ligand precursors modulated by the addition of the metalloprotease inhibitor batimastat. We found that ERK activation increased with increasing ligand release rates despite concomitant EGF receptor downregulation. Cell migration speed depended linearly on the steady-state phospho-ERK level obtained from either autocrine or exogenous ligand, but was much greater at any given phospho-ERK level for autocrine compared to exogenous stimulation. In contrast, cell proliferation rates were relatively constant across the various treatment conditions. Thus, in these cells, ERK-mediated migration stimulated by EGF receptor signaling is most sensitively regulated by autocrine ligand control mechanisms.

  15. Chromosomal changes in cultured human epithelial cells transformed by low- and high-LET radiation

    SciTech Connect (OSTI)

    Yang, Tracy Chui-hsu; Craise, L.M; Prioleau, J.C.; Stampfer, M.R.; Rhim, J.S.

    1990-11-01

    For a better assessment of radiation risk in space, an understanding of the responses of human cells, especially the epithelial cells, to low- and high-LET radiation is essential. In our laboratory, we have successfully developed techniques to study the neoplastic transformation of two human epithelial cell systems by ionizing radiation. These cell systems are human mammary epithelial cells (H184B5) and human epidermal keratinocytes (HEK). Both cell lines are immortal, anchorage dependent for growth, and nontumorigenic in athymic nude nice. Neoplastic transformation was achieved by irradiation cells successively. Our results showed that radiogenic cell transformation is a multistep process and that a single exposure of ionizing radiation can cause only one step of transformation. It requires, therefore, multihits to make human epithelial cells fully tumorigenic. Using a simple karyotyping method, we did chromosome analysis with cells cloned at various stages of transformation. We found no consistent large terminal deletion of chromosomes in radiation-induced transformants. Some changes of total number of chromosomes, however, were observed in the transformed cells. These transformants provide an unique opportunity for further genetic studies at a molecular level. 15 refs., 9 figs., 2 tabs.

  16. Homology with vesicle fusion mediator syntaxin-1a predicts determinants ofepimorphin/syntaxin-2 function in mammary epithelial morphogenesis

    SciTech Connect (OSTI)

    Chen, Connie S.; Nelson, Celeste M.; Khauv, Davitte; Bennett, Simone; Radisky, Evette S.; Hirai, Yohei; Bissell, Mina J.; Radisky, Derek C.

    2009-06-03

    We have shown that branching morphogenesis of mammary ductal structures requires the action of the morphogen epimorphin/syntaxin-2. Epimorphin, originally identified as an extracellular molecule, is identical to syntaxin-2, an intracellular molecule that is a member of the extensively investigated syntaxin family of proteins that mediate vesicle trafficking. We show here that although epimorphin/syntaxin-2 is highly homologous to syntaxin-1a, only epimorphin/syntaxin-2 can stimulate mammary branching morphogenesis. We construct a homology model of epimorphin/syntaxin-2 based on the published structure of syntaxin-1a, and we use this model to identify the structural motif responsible for the morphogenic activity. We identify four residues located within the cleft between helices B and C that differ between syntaxin-1a and epimorphin/syntaxin-2; through site-directed mutagenesis of these four amino acids, we confer the properties of epimorphin for cell adhesion, gene activation, and branching morphogenesis onto the inactive syntaxin-1a template. These results provide a dramatic demonstration of the use of structural information about one molecule to define a functional motif of a second molecule that is related at the sequence level but highly divergent functionally.

  17. Heterocellular interaction enhances recruitment of {alpha} and {beta}-catenins and ZO-2 into functional gap-junction complexes and induces gap junction-dependant differentiation of mammary epithelial cells

    SciTech Connect (OSTI)

    Talhouk, Rabih S. [Department of Biology, Faculty of Arts and Sciences, American University of Beirut, Beirut (Lebanon)], E-mail: rtalhouk@aub.edu.lb; Mroue, Rana; Mokalled, Mayssa; Abi-Mosleh, Lina; Nehme, Ralda; Ismail, Ayman; Khalil, Antoine [Department of Biology, Faculty of Arts and Sciences, American University of Beirut, Beirut (Lebanon); Zaatari, Mira [Department of Human Morphology, Faculty of Medicine, American University of Beirut, Beirut (Lebanon); El-Sabban, Marwan E. [Department of Human Morphology, Faculty of Medicine, American University of Beirut, Beirut (Lebanon)], E-mail: me00@aub.edu.lb

    2008-11-01

    Gap junctions (GJ) are required for mammary epithelial differentiation. Using epithelial (SCp2) and myoepithelial-like (SCg6) mouse-derived mammary cells, the role of heterocellular interaction in assembly of GJ complexes and functional differentiation ({beta}-casein expression) was evaluated. Heterocellular interaction is critical for {beta}-casein expression, independent of exogenous basement membrane or cell anchoring substrata. Functional differentiation of SCp2, co-cultured with SCg6, is more sensitive to GJ inhibition relative to homocellular SCp2 cultures differentiated by exogenous basement membrane. Connexin (Cx)32 and Cx43 levels were not regulated across culture conditions; however, GJ functionality was enhanced under differentiation-permissive conditions. Immunoprecipitation studies demonstrated association of junctional complex components ({alpha}-catenin, {beta}-catenin and ZO-2) with Cx32 and Cx43, in differentiation conditions, and additionally with Cx30 in heterocellular cultures. Although {beta}-catenin did not shuttle between cadherin and GJ complexes, increased association between connexins and {beta}-catenin in heterocellular cultures was observed. This was concomitant with reduced nuclear {beta}-catenin, suggesting that differentiation in heterocellular cultures involves sequestration of {beta}-catenin in GJ complexes.

  18. Stromal-epithelial interactions in aging and cancer: Senescent fibroblasts alter epithelial cell differentiation

    SciTech Connect (OSTI)

    Parrinello, Simona; Coppe, Jean-Philippe; Krtolica, Ana; Campisi, Judith

    2004-07-14

    Cellular senescence suppresses cancer by arresting cells at risk for malignant tumorigenesis. However, senescent cells also secrete molecules that can stimulate premalignant cells to proliferate and form tumors, suggesting the senescence response is antagonistically pleiotropic. We show that premalignant mammary epithelial cells exposed to senescent human fibroblasts in mice irreversibly lose differentiated properties, become invasive and undergo full malignant transformation. Moreover, using cultured mouse or human fibroblasts and non-malignant breast epithelial cells, we show that senescent fibroblasts disrupt epithelial alveolar morphogenesis, functional differentiation, and branching morphogenesis. Further, we identify MMP-3 as the major factor responsible for the effects of senescent fibroblasts on branching morphogenesis. Our findings support the idea that senescent cells contribute to age-related pathology, including cancer, and describe a new property of senescent fibroblasts--the ability to alter epithelial differentiation--that might also explain the loss of tissue function and organization that is a hallmark of aging.

  19. Characterisation of epithelial progenitor cells for human and mouse thymus 

    E-Print Network [OSTI]

    Farley, Alison

    2009-01-01

    The thymus is a complex cellular structure made up of several interdependent cell types and is the primary site for T cell development. A population of fetal thymic epithelial cells (TEC), marked by MTS20 and MTS24, when ...

  20. Lumican induces human corneal epithelial cell migration and integrin expression via ERK 1/2 signaling

    SciTech Connect (OSTI)

    Seomun, Young [Laboratory of Ophthalmology and Visual Science, Korean Eye Tissue and Gene Bank related to Blindness, College of Medicine, Catholic University of Korea, 505 Banpo-dong, Seocho-ku, Seoul 137-040 (Korea, Republic of); Joo, Choun-Ki [Laboratory of Ophthalmology and Visual Science, Korean Eye Tissue and Gene Bank related to Blindness, College of Medicine, Catholic University of Korea, 505 Banpo-dong, Seocho-ku, Seoul 137-040 (Korea, Republic of)], E-mail: ckjoo@catholic.ac.kr

    2008-07-18

    Lumican is a major proteoglycans of the human cornea. Lumican knock-out mice have been shown to lose corneal transparency and to display delayed wound healing. The purpose of this study was to define the role of lumican in corneal epithelial cell migration. Over-expression of lumican in human corneal epithelial (HCE-T) cells increased both cell migration and proliferation, and increased levels of integrins {alpha}2 and {beta}1. ERK 1/2 was also activated in lumican over-expressed cells. When we treated HCE-T cells with the ERK-specific inhibitor U0126, cell migration and the expression of integrin {beta}1 were completely blocked. These data provide evidence that lumican stimulates cell migration in the corneal epithelium by activating ERK 1/2, and point to a novel signaling pathway implicated in corneal epithelial cell migration.

  1. IL-8 Production in Human Lung Fibroblasts and Epithelial Cells Activated by the Pseudomonas Autoinducer

    E-Print Network [OSTI]

    Springer, Timothy A.

    IL-8 Production in Human Lung Fibroblasts and Epithelial Cells Activated by the Pseudomonas is caused, in part, by the produc- tion of the chemokine IL-8, which recruits neutrophils into the lung. These findings support the concept that the severe lung damage that accompanies P. aeruginosa infections

  2. Establishment of three-dimensional cultures of human pancreatic duct epithelial cells

    SciTech Connect (OSTI)

    Gutierrez-Barrera, Angelica M. [Department of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Unit 426, 1515 Holcombe Boulevard, Houston, TX 77030 (United States); Menter, David G. [Department of Thoracic Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX (United States); Abbruzzese, James L. [Department of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Unit 426, 1515 Holcombe Boulevard, Houston, TX 77030 (United States); Reddy, Shrikanth A.G. [Department of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Unit 426, 1515 Holcombe Boulevard, Houston, TX 77030 (United States)]. E-mail: sa08366@wotan.mdacc.tmc.edu

    2007-07-06

    Three-dimensional (3D) cultures of epithelial cells offer singular advantages for studies of morphogenesis or the role of cancer genes in oncogenesis. In this study, as part of establishing a 3D culture system of pancreatic duct epithelial cells, we compared human pancreatic duct epithelial cells (HPDE-E6E7) with pancreatic cancer cell lines. Our results show, that in contrast to cancer cells, HPDE-E6E7 organized into spheroids with what appeared to be apical and basal membranes and a luminal space. Immunostaining experiments indicated that protein kinase Akt was phosphorylated (Ser473) and CTMP, a negative Akt regulator, was expressed in both HPDE-E6E7 and cancer cells. However, a nuclear pool of CTMP was detectable in HPDE-E6E7 cells that showed a dynamic concentrated expression pattern, a feature that further distinguished HPDE-E637 cells from cancer cells. Collectively, these data suggest that 3D cultures of HPDE-E6E7 cells are useful for investigating signaling and morphological abnormalities in pancreatic cancer cells.

  3. Parsing ERK Activation Reveals Quantitatively Equivalent Contributions From Epidermal Growth Factor Receptor and HER2 In Human Mammary Epithelial Cells

    SciTech Connect (OSTI)

    Hendriks, Bart S.; Orr, Galya; Wells, Alan H.; Wiley, H. S.; Lauffenburger, Douglas A.

    2005-02-18

    HER2, a member of the EGFR tyrosine kinase family, functions as an accessory EGFR signaling component and alters EGFR trafficking by heterodimerization. HER2 overexpression leads to aberrant cell behavior including enhanced proliferation and motility. Here we apply a combination of computational modeling and quantitative experimental studies of the dynamic interactions between EGFR and HER2, and their downstream activation of extracellular signal-related kinase (ERK) to understand this complex signaling system. Using cells expressing different levels of HER2 relative to the EGFR, we can separate relative contributions of EGFR and HER2 to signaling amplitude and duration. Based on our model calculations, we demonstrate that, in contrast with previous suggestions in the literature, the intrinsic capabilities of EGFR and HER2 to activated ERK are quantitatively equivalent . We find that HER2-mediated effects on EGFR dimerization and trafficking are sufficient to explain the detected HER2-mediated amplification of EGF-induced ERK signaling. Our model suggests that transient amplification of ERK activity by HER2 arises predominantly from the 2-to-1 stoichiometry of receptor kinase to bound ligand in EGFR/HER2 heterodimers compared to the 1-to-1 stoichiometry of the EGFR homodimer, but alterations in receptor trafficking, with resultant EGFR sparing, cause the sustained HER2-mediated enhancement of ERK signaling.

  4. Theophylline prevents NAD{sup +} depletion via PARP-1 inhibition in human pulmonary epithelial cells

    SciTech Connect (OSTI)

    Moonen, Harald J.J. . E-mail: h.moonen@grat.unimaas.nl; Geraets, Liesbeth; Vaarhorst, Anika; Bast, Aalt; Wouters, Emiel F.M.; Hageman, Geja J.

    2005-12-30

    Oxidative DNA damage, as occurs during exacerbations in chronic obstructive pulmonary disease (COPD), highly activates the nuclear enzyme poly(ADP-ribose)polymerase-1 (PARP-1). This can lead to cellular depletion of its substrate NAD{sup +}, resulting in an energy crisis and ultimately in cell death. Inhibition of PARP-1 results in preservation of the intracellular NAD{sup +} pool, and of NAD{sup +}-dependent cellular processes. In this study, PARP-1 activation by hydrogen peroxide decreased intracellular NAD{sup +} levels in human pulmonary epithelial cells, which was found to be prevented in a dose-dependent manner by theophylline, a widely used compound in the treatment of COPD. This enzyme inhibition by theophylline was confirmed in an ELISA using purified human PARP-1 and was found to be competitive by nature. These findings provide new mechanistic insights into the therapeutic effect of theophylline in oxidative stress-induced lung pathologies.

  5. Group B Streptococcal b-Hemolysin/Cytolysin Promotes Invasion of Human Lung Epithelial Cells and the Release of Interleukin-8

    E-Print Network [OSTI]

    Nizet, Victor

    Group B Streptococcal b-Hemolysin/Cytolysin Promotes Invasion of Human Lung Epithelial Cells and lung injury are hallmarks of early-onset neonatal group B streptococcal (GBS) infections. Production. To elucidate the contribution of the b-h/c toxin to lung injury, the interactions of GBS wild-type strains

  6. Involvement of HIF-2?-mediated inflammation in arsenite-induced transformation of human bronchial epithelial cells

    SciTech Connect (OSTI)

    Xu, Yuan; Zhao, Yue; Xu, Wenchao; Luo, Fei; Wang, Bairu; Li, Yuan; Pang, Ying; Liu, Qizhan, E-mail: drqzliu@hotmail.com

    2013-10-15

    Arsenic is a well established human carcinogen that causes diseases of the lung. Some studies have suggested a link between inflammation and lung cancer; however, it is unknown if arsenite-induced inflammation causally contributes to arsenite-caused malignant transformation of cells. In this study, we investigated the molecular mechanisms underlying inflammation during neoplastic transformation induced in human bronchial epithelial (HBE) cells by chronic exposure to arsenite. The results showed that, on acute or chronic exposure to arsenite, HBE cells over-expressed the pro-inflammatory cytokines, interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-1? (IL-1?). The data also indicated that HIF-2? was involved in arsenite-induced inflammation. Moreover, IL-6 and IL-8 were essential for the malignant progression of arsenite-transformed HBE cells. Thus, these experiments show that HIF-2? mediates arsenite-induced inflammation and that such inflammation is involved in arsenite-induced malignant transformation of HBE cells. The results provide a link between the inflammatory response and the acquisition of a malignant transformed phenotype by cells chronically exposed to arsenite and thus establish a previously unknown mechanism for arsenite-induced carcinogenesis. - Highlights: • Arsenite induces inflammation. • Arsenite-induced the increases of IL-6 and IL-8 via HIF-2?. • Inflammation is involved in arsenite-induced carcinogenesis.

  7. Study of inflammatory signalling in epithelial ovarian cancer and the normal human mesothelium 

    E-Print Network [OSTI]

    Fegan, Kenneth Scott

    2010-01-01

    Epithelial Ovarian Cancer (EOC) kills more women annually in the United Kingdom than any other gynaecological cancer. Survival rates for women diagnosed with EOC have not improved over the past 30 years, due to the often ...

  8. Continuous human cell lines and method of making same

    DOE Patents [OSTI]

    Stampfer, M.R.

    1985-07-01

    Substantially genetically stable continuous human cell lines derived from normal human mammary epithelial cells (HMEC) and processes for making and using the same. In a preferred embodiment, the cell lines are derived by treating normal human mammary epithelial tissue with a chemical carcinogen such as benzo(a)pyrene. The novel cell lines serve as useful substrates for elucidating the potential effects of a number of toxins, carcinogens and mutagens as well as of the addition of exogenous genetic material. The autogenic parent cells from which the cell lines are derived serve as convenient control samples for testing. The cell lines are not neoplastically transformed, although they have acquired several properties which distinguish them from their normal progenitors. 2 tabs.

  9. Unraveling the microenvironmental influences on the normal mammary gland and induction and progression of breast cancer

    SciTech Connect (OSTI)

    Weigelt, Britta; Bissell, Mina J.

    2008-06-26

    The normal mammary gland and invasive breast cancer are both complex 'organs' composed of multiple cell types as well as extracellular matrix (ECM) in three-dimensional (3D) space. Conventionally, both normal and malignant breast cells are studied in vitro as two-dimensional (2D) monolayers of epithelial cells, which results in the loss of structure and tissue function. Many laboratories are now investigating regulation of signaling function in normal mammary gland using 3D cultures. However, it is important also to assay malignant breast cells ex vivo in a physiologically relevant environment to more closely mimic tumor architecture, signal transduction regulation and tumor behavior in vivo. Here we present the potential of these 3D models for drug testing, target validation and guidance of patient selection for clinical trials. We argue also that in order to get full insight into the biology of the normal and malignant breast, and to create in vivo-like models for therapeutic approaches in humans, we need to continue to create more complex heterotypic models to approach the full context the cells encounter in the human body.

  10. Hypo-responsiveness of interleukin-8 production in human embryonic epithelial intestine 407 cells independent of NF-{kappa}B pathway: New lessons from endotoxin and ribotoxic deoxynivalenol

    SciTech Connect (OSTI)

    Moon, Yuseok [Department of Microbiology and Immunology, Medical Research Institute, Pusan National University School of Medicine, Busan, 602-739 (Korea, Republic of)], E-mail: moon@pusan.ac.kr; Yang, Hyun; Park, Seung-Hwan [Department of Microbiology and Immunology, Medical Research Institute, Pusan National University School of Medicine, Busan, 602-739 (Korea, Republic of)

    2008-08-15

    Mucosal epithelium senses external toxic insults and transmits the danger signals into the epithelial cells in order to activate a broad range of inflammatory responses. However, pre-exposure to the commensal endotoxins can induce inflammatory tolerance and maintain the homeostasis without excessive immune responses. We recently reported that ribotoxin deoxynivalenol (DON) and its derivatives elicited the pro-inflammatory response as the mucosal insults in human epithelial cells. Taking the knowledge into consideration, we tested the hypothesis that endotoxin pre-exposure can attenuate ribotoxin-induced epithelial interleukin-8 (IL-8) production via a tolerance mechanism. Pre-exposure to endotoxin repressed IL-8 release and its gene expression. However, inflammatory tolerance was not mediated by the attenuated NF-{kappa}B activation which has been generally recognized as the major mediator of LPS-mediated toll-like receptor (TLR) signaling pathway. Instead, pre-exposure to endotoxin was observed to trigger the delayed induction of peroxisome proliferator-activated receptor gamma (PPAR-{gamma}) which contributed to the diminished IL-8 production in the human epithelial cells. Moreover, endogenous PPAR-{gamma} agonist suppressed toxicant-mediated interleukin-8 production and IL-8 mRNA stability. Taken together, endotoxin induced hypo-production of pro-inflammatory cytokine IL-8 in the human epithelial cells, which was associated with the delayed activation of PPAR-{gamma} expression by pre-existing endotoxin.

  11. SU-E-J-105: Stromal-Epithelial Responses to Fractionated Radiotherapy

    SciTech Connect (OSTI)

    Qayyum, M

    2014-06-01

    Purpose: The stromal-epithelial-cell interactions that are responsible for directing normal breast-tissue development and maintenance play a central role in the progression of breast cancer. In the present study, we developed three-dimensional (3-D) cell co-cultures used to study cancerous mammary cell responses to fractionated radiotherapy. In particular, we focused on the role of the reactive stroma in determining the therapeutic ratio for postsurgical treatment. Methods: Cancerous human mammary epithelial cells were cultured in a 3-D collagen matrix with human fibroblasts stimulated by various concentrations of transforming growth factor beta 1 (TGF-?1). These culture samples were designed to model the post-lumpectomy mammary stroma in the presence of residual cancer cells. We tracked over time the changes in medium stiffness, fibroblast-cell activation (conversion to cancer activated fibroblasts (CAF)), and proliferation of both cell types under a variety of fractionated radiotherapy protocols. Samples were exposed to 6 MV X-rays from a linear accelerator in daily fraction sizes of 90, 180 and 360 cGy over five days in a manner consistent with irradiation exposure during radiotherapy. Results: We found in fractionation studies with fibroblasts and CAF that higher doses per fraction may be more effective early on in deactivating cancer-harboring cellular environments. Higher-dose fraction schemes inhibit contractility in CAF and prevent differentiation of fibroblasts, thereby metabolically uncoupling tumor cells from their surrounding stroma. Yet, over a longer time period, the higher dose fractions may slow wound healing and increase ECM stiffening that could stimulate proliferation of surviving cancer cells. Conclusion: The findings suggest that dose escalation to the region with residual disease can deactivate the reactive stroma, thus minimizing the cancer promoting features of the cellular environment. Large-fraction irradiation may be used to sterilize residual tumor cells and inhibit activation of intracellular transduction pathways that are promoted during the post-surgical woundhealing period. NIH award R01CA138882.

  12. Transport in the Mammary Glands

    E-Print Network [OSTI]

    Quezada, Ana

    2015-01-01

    the blood stream into the ducts of the mammary glands isof toxins present in the breast ducts. The multi-layer modelparticles into the breast ducts. Our model predicts the

  13. 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.

  14. Macrophage-stimulating protein attenuates gentamicin-induced inflammation and apoptosis in human renal proximal tubular epithelial cells

    SciTech Connect (OSTI)

    Lee, Ko Eun [Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of)] [Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Kim, Eun Young [Department of Physiology, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of)] [Department of Physiology, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Kim, Chang Seong; Choi, Joon Seok; Bae, Eun Hui; Ma, Seong Kwon [Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of)] [Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Kim, Kyung Keun [Department of Pharmacology, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of)] [Department of Pharmacology, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Lee, Jong Un [Department of Physiology, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of)] [Department of Physiology, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Kim, Soo Wan, E-mail: skimw@chonnam.ac.kr [Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of)

    2013-05-10

    Highlights: •MSP/RON system is activated in rat kidney damaged by gentamicin. •MSP inhibits GM-induced cellular apoptosis and inflammation in HK-2 cells. •MSP attenuates GM-induced activation of MAPKs and NF-?B pathways in HK-2 cells. -- Abstract: The present study aimed to investigate whether macrophage-stimulating protein (MSP) treatment attenuates renal apoptosis and inflammation in gentamicin (GM)-induced tubule injury and its underlying molecular mechanisms. To examine changes in MSP and its receptor, recepteur d’origine nantais (RON) in GM-induced nephropathy, rats were injected with GM for 7 days. Human renal proximal tubular epithelial (HK-2) cells were incubated with GM for 24 h in the presence of different concentrations of MSP and cell viability was measured by MTT assay. Apoptosis was determined by flow cytometry of cells stained with fluorescein isothiocyanate-conjugated annexin V protein and propidium iodide. Expression of Bcl-2, Bax, caspase-3, cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-?B), I?B-?, and mitogen-activated protein kinases (MAPKs) was analyzed by semiquantitative immunoblotting. MSP and RON expression was significantly greater in GM-treated rats, than in untreated controls. GM-treatment reduced HK-2 cell viability, an effect that was counteracted by MSP. Flow cytometry and DAPI staining revealed GM-induced apoptosis was prevented by MSP. GM reduced expression of anti-apoptotic protein Bcl-2 and induced expression of Bax and cleaved caspase 3; these effects and GM-induced expression of COX-2 and iNOS were also attenuated by MSP. GM caused MSP-reversible induction of phospho-ERK, phospho-JNK, and phospho-p38. GM induced NF-?B activation and degradation of I?B-?; the increase in nuclear NF-?B was blocked by inhibitors of ERK, JNK, p-38, or MSP pretreatment. These findings suggest that MSP attenuates GM-induced inflammation and apoptosis by inhibition of the MAPKs/NF-?B signaling pathways.

  15. Laminin and biomimetic extracellular elasticity enhance functional differentiation in mammary epithelia

    SciTech Connect (OSTI)

    Alcaraz, Jordi; Xu, Ren; Mori, Hidetoshi; Nelson, Celeste M.; Mroue, Rana; Spencer, Virginia A.; Brownfield, Doug; Radisky, Derek C.; Bustamante, Carlos; Bissell, Mina J.

    2008-10-20

    In the mammary gland, epithelial cells are embedded in a 'soft' environment and become functionally differentiated in culture when exposed to a laminin-rich extracellular matrix gel. Here, we define the processes by which mammary epithelial cells integrate biochemical and mechanical extracellular cues to maintain their differentiated phenotype. We used single cells cultured on top of gels in conditions permissive for {beta}-casein expression using atomic force microscopy to measure the elasticity of the cells and their underlying substrata. We found that maintenance of {beta}-casein expression required both laminin signalling and a 'soft' extracellular matrix, as is the case in normal tissues in vivo, and biomimetic intracellular elasticity, as is the case in primary mammary epithelial organoids. Conversely, two hallmarks of breast cancer development, stiffening of the extracellular matrix and loss of laminin signalling, led to the loss of {beta}-casein expression and non-biomimetic intracellular elasticity. Our data indicate that tissue-specific gene expression is controlled by both the tissues unique biochemical milieu and mechanical properties, processes involved in maintenance of tissue integrity and protection against tumorigenesis.

  16. TBX3 over-expression causes mammary gland hyperplasia and increases mammary stem-like cells in an inducible transgenic mouse model

    E-Print Network [OSTI]

    Liu, Jing; Esmailpour, Taraneh; Shang, Xiying; Gulsen, Gultekin; Liu, Andy; Huang, Taosheng

    2011-01-01

    al. : TBX3 over-expression causes mammary gland hyperplasiaAccess TBX3 over-expression causes mammary gland hyperplasiahaploinsufficiency of TBX3 causes Ulnar Mammary Syndrome (

  17. Nickel compounds induce apoptosis in human bronchial epithelial Beas-2B cells by activation of c-Myc through ERK pathway

    SciTech Connect (OSTI)

    Li Qin; Suen, T.-C.; Sun Hong; Arita, Adriana [New York University School of Medicine, Nelson Institute of Environmental Medicine, 57 Old Forge Road, NY 10987 (United States); Costa, Max [New York University School of Medicine, Nelson Institute of Environmental Medicine, 57 Old Forge Road, NY 10987 (United States)], E-mail: max.costa@nyumc.org

    2009-03-01

    Nickel compounds are carcinogenic to humans and have been shown to alter epigenetic homeostasis. The c-Myc protein controls 15% of human genes and it has been shown that fluctuations of c-Myc protein alter global epigenetic marks. Therefore, the regulation of c-Myc by nickel ions in immortalized but not tumorigenic human bronchial epithelial Beas-2B cells was examined in this study. It was found that c-Myc protein expression was increased by nickel ions in non-tumorigenic Beas-2B and human keratinocyte HaCaT cells. The results also indicated that nickel ions induced apoptosis in Beas-2B cells. Knockout of c-Myc and its restoration in a rat cell system confirmed the essential role of c-Myc in nickel ion-induced apoptosis. Further studies in Beas-2B cells showed that nickel ion increased the c-Myc mRNA level and c-Myc promoter activity, but did not increase c-Myc mRNA and protein stability. Moreover, nickel ion upregulated c-Myc in Beas-2B cells through the MEK/ERK pathway. Collectively, the results demonstrate that c-Myc induction by nickel ions occurs via an ERK-dependent pathway and plays a crucial role in nickel-induced apoptosis in Beas-2B cells.

  18. Expression of Autoactivated Stromelysin-1 in Mammary Glands of Transgenic Mice Leads to a Reactive Stroma During Early Development

    SciTech Connect (OSTI)

    Thomasset, N.; Lochter, A.; Sympson, C.J.; Lund, L.R.; Williams, D.R.; Behrendtsen, O.; Werb, Z.; Bissell, M.J.

    1998-04-24

    Extracellular matrix and extracellular matrix-degrading matrix metalloproteinases play a key role in interactions between the epithelium and the mesenchyme during mammary gland development and disease. In patients with breast cancer, the mammary mesenchyme undergoes a stromal reaction, the etiology of which is unknown. We previously showed that targeting of an autoactivating mutant of the matrix metalloproteinase stromelysin-1 to mammary epithelia of transgenic mice resulted in reduced mammary function during pregnancy and development of preneoplastic and neoplastic lesions. Here we examine the cascade of alterations before breast tumor formation in the mammary gland stroma once the expression of the stromelysin-1 transgene commences. Beginning in postpubertal virgin animals, low levels of transgene expression in mammary epithelia led to increased expression of endogenous stromelysin-1 in stromal fibroblasts and up-regulation of other matrix metalloproteinases, without basement membrane disruption. These changes were accompanied by the progressive development of a compensatory reactive stroma, characterized by increased collagen content and vascularization in glands from virgin mice. This remodeling of the gland affected epithelial-mesenchymal communication as indicated by inappropriate expression of tenascin-C starting by day 6 of pregnancy. This, together with increased transgene expression, led to basement membrane disruption starting by day 15 of pregnancy. We propose that the highly reactive stroma provides a prelude to breast epithelial tumors observed in these animals. Epithelial development depends on an exquisite series of inductive and instructive interactions between the differentiating epithelium and the mesenchymal (stromal) compartment. The epithelium, which consists of luminal and myoepithelial cells, is separated from the stroma by a basement membrane (BM), which plays a central role in mammary gland homeostasis and gene expression. In vivo, stromal cells produce fibronectin, collagens, proteoglycans, and some components of the BM, as well as a number of proteinases that can effectively degrade BM constituents. Stromal and epithelial cells of the mammary gland interact to regulate BM synthesis and degradation and, thus, mammary function. Matrix metalloproteinases (MMPs) are extracellular matrix (ECM)-degrading enzymes involved in mammary gland morphogenesis and involution. During late pregnancy and lactation, when the gland becomes fully functional, the expression of MMPs is low however, during involution, when the gland loses function and is remodeled, synthesis of ECM-degrading proteinases increases dramatically.11 Disturbance of the balance between MMPs and MMP inhibitors leads to either unscheduled involution or prolonged lactation. Mammary glands of virgin mice expressing an autoactivating stromelysin-1 (SL-1) transgene display supernumerary branches and precocious alveolar development, accompanied by the synthesis of {beta}-casein at levels found normally only during early pregnancy. During late pregnancy, increased expression of the SL-1 transgene leads to a reduction in expression of pregnancy-specific genes. Later in life, some SL-1 transgenic mice develop hyperplastic, dysplastic, and ductal carcinoma in situ-like lesions, as well as malignant tumors. Little is known about the sequence of changes that occurs before formation of an overt reactive stroma in breast cancer. In the present study, we address the question of whether and how the stromal compartment is altered as a consequence of inappropriate SL-1 transgene expression in the epithelium.

  19. Adhesion gene regulation in mammary cell proliferation

    E-Print Network [OSTI]

    Lau, Eric HonYui

    2011-01-01

    A. , et al. , Nectin: an adhesion molecule involved in OF CALIFORNIA, MERCED Adhesion Gene Regulation in Mammary1 1.2 Role of Adhesion Molecules in Development and

  20. STORM: A General Model to Determine the Number and Adaptive Changes of Epithelial Stem Cells in Teleost, Murine and Human Intestinal Tracts

    E-Print Network [OSTI]

    Wang, Zhengyuan

    Intestinal stem cells play a pivotal role in the epithelial tissue renewal, homeostasis and cancer development. The lack of a general marker for intestinal stem cells across species has hampered analysis of stem cell number ...

  1. YY1 modulates taxane response in epithelial ovarian cancer

    E-Print Network [OSTI]

    Matsumura, Noriomi

    2009-01-01

    A), but not to cisplatin (B) in ovarian cancer cell lines.al. Human epithelial ovarian cancer allelotype. Cancer Resallelotyping of human ovarian cancer. Br J Cancer 1994;69(

  2. The accumulations of HIF-1? and HIF-2? by JNK and ERK are involved in biphasic effects induced by different levels of arsenite in human bronchial epithelial cells

    SciTech Connect (OSTI)

    Xu, Yuan; Li, Yuan [Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu (China) [Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu (China); The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu (China); Li, Huiqiao [Qujing Center for Disease Control and Prevention, Qujing 655000, Yunnan (China)] [Qujing Center for Disease Control and Prevention, Qujing 655000, Yunnan (China); Pang, Ying; Zhao, Yue; Jiang, Rongrong; Shen, Lu [Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu (China) [Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu (China); The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu (China); Zhou, Jianwei; Wang, Xinru [The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu (China)] [The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu (China); Liu, Qizhan, E-mail: drqzliu@hotmail.com [Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu (China) [Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu (China); The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu (China)

    2013-01-15

    The biphasic effects of arsenite, in which low levels of arsenite induce cell proliferation and high levels of arsenite induce DNA damage and apoptosis, apparently contribute to arsenite-induced carcinogenesis. However, the mechanisms underlying this phenomenon are not well understood. In this study, we investigated the effects of different levels of arsenite on cell proliferation, DNA damage and apoptosis as well as on signal transduction pathways in human bronchial epithelial (HBE) cells. Our results show that a low level of arsenite activates extracellular signal-regulated kinases (ERK), which probably mediate arsenite-inhibited degradation of ubiquitinated hypoxia-inducible factor-2? (HIF-2?) in HBE cells. ERK inhibition blocks cell proliferation induced by a low level of arsenite, in part via HIF-2?. In contrast, a high level of arsenite activates c-Jun N-terminal kinases (JNK), which provoke a response to suppress ubiquitinated HIF-1? degradation. Down-regulation of HIF-1? by inhibiting JNK, however, increases the DNA damage but decreases the apoptosis induced by a high level of arsenite. Thus, data in the present study suggest that the accumulations of HIF-1? and HIF-2? by JNK and ERK are involved in different levels of arsenite-induced biphasic effects, with low levels of arsenite inducing cell proliferation and high levels of arsenite inducing DNA damage and apoptosis in HBE cells. -- Highlights: ? Biphasic effects induced by different concentrations of arsenite. ? Different regulation of ERK or JNK signal pathway by arsenite. ? Different regulation of HIF1? or HIF 2? by arsenite.

  3. Secretory pathway Ca2+/Mn2+-ATPase isoform 2 and lactation: specific localization of plasmalemmal and secretory pathway Ca2+ pump isoforms in the mammary gland

    SciTech Connect (OSTI)

    Faddy, Helen M.; Smart, Chanel E.; Xu, Ren; Lee, Genee Y.; Kenny, Paraic A.; Feng, Mingye; Rao, Rajini; Brown, Melissa A.; Bissell, Mina J.; Roberts-Thomson, Sarah J.; Monteith, Gregory R.

    2008-04-09

    The supply of calcium to the developing neonate via milk is an important physiological process. Until recently the mechanism for the enrichment of milk with calcium was thought to be almost entirely mediated via the secretory pathway. However, recent studies suggest that a specific isoform of the plasma membrane calcium ATPase, PMCA2, is the primary mechanism for calcium transport into milk, highlighting a major role for apical calcium transport. We compared the expression of the recently identified secretory calcium ATPase, SPCA2, and SPCA1, in the mouse mammary gland during different stages of development. SPCA2 levels increased over 35 fold during lactation, while SPCA1 increased only a modest two fold. The potential importance of SPCA2 in lactation was also highlighted by its localization to luminal secretory cells of the mammary gland during lactation, while SPCA1 was expressed throughout the cells of the mammary gland. We also observed major differences in the localization of PMCA2 and PMCA1 during lactation. Using the SCp2 mouse mammary epithelial cell 3D culture model, differences in the sub-cellular distribution of PMCA2 and PMCA1 were clear. These studies highlight the likely specific roles of PMCA2 and SPCA2 in lactation, and link the recently characterized SPCA2 calcium pump to the supply of calcium into milk and the regulation of Golgi resident enzymes important in lactation. They also indicate that calcium transport into milk is a complex interplay between apical and secretory pathways.

  4. Arsenite evokes IL-6 secretion, autocrine regulation of STAT3 signaling, and miR-21 expression, processes involved in the EMT and malignant transformation of human bronchial epithelial cells

    SciTech Connect (OSTI)

    Luo, Fei; Xu, Yuan; Ling, Min; Zhao, Yue; Xu, Wenchao; Liang, Xiao; Jiang, Rongrong; Wang, Bairu; Bian, Qian; Liu, Qizhan

    2013-11-15

    Arsenite is an established human carcinogen, and arsenite-induced inflammation contributes to malignant transformation of cells, but the molecular mechanisms by which cancers are produced remain to be established. The present results showed that, evoked by arsenite, secretion of interleukin-6 (IL-6), a pro-inflammatory cytokine, led to the activation of STAT3, a transcription activator, and to increased levels of a microRNA, miR-21. Blocking IL-6 with anti-IL-6 antibody and inhibiting STAT3 activation reduced miR-21 expression. For human bronchial epithelial cells, cultured in the presence of anti-IL-6 antibody for 3 days, the arsenite-induced EMT and malignant transformation were reversed. Thus, IL-6, acting on STAT3 signaling, which up-regulates miR-21in an autocrine manner, contributes to the EMT induced by arsenite. These data define a link from inflammation to EMT in the arsenite-induced malignant transformation of HBE cells. This link, mediated through miRNAs, establishes a mechanism for arsenite-induced lung carcinogenesis. - Highlights: • Arsenite evokes IL-6 secretion. • IL-6 autocrine mediates STAT3 signaling and up-regulates miR-21expression. • Inflammation is involved in arsenite-induced EMT.

  5. ErbB2, but not ErbB1, reinitiates proliferation and induces luminal repopulation in epithelial acini

    SciTech Connect (OSTI)

    Muthuswamy, Senthil K; Li, Dongmei; Lelievre, Sophie; Bissell, Mina J; Brugge, Joan S

    2001-08-08

    Both ErbB1 and ErbB2 are overexpressed or amplified in breast tumors. To examine the effects of activating ErbB receptors in a context that mimics polarized epithelial cells in vivo, we activated ErbB1 and ErbB2 homodimers in preformed, growth-arrested mammary acini cultured in three-dimensional basement membrane gels. Activation of ErbB2, but not that of ErbB1, led to a reinitiation of cell proliferation and altered the properties of mammary acinar structures. These altered structures share several properties with early-stage tumors, including a loss of proliferative suppression, an absence of lumen, retention of the basement membrane and a lack of invasive properties. ErbB2 activation also disrupted tight junctions and the cell polarity of polarized epithelia, whereas ErbB1 activation did not have any effect. Our results indicate that ErbB receptors differ in their ability to induce early stages of mammary carcinogenesis in vitro and this three-dimensional model system can reveal biological activities of oncogenes that cannot be examined in vitro in standard transformation assays.

  6. Original article Sensitization of the bovine mammary gland to

    E-Print Network [OSTI]

    Boyer, Edmond

    (ReceivedI October I )96; accepted 4 February 1997) Summary ― The effect of repeated infusions intramammary infusions of E cnli endotoxin (33 pg) 24 h apart in the same mammary quarter. Along with the second infusion, the cows received one dose of endotoxin in the contralateral quarter. Milk was collected

  7. Epithelial–mesenchymal transition during oncogenic transformation induced by hexavalent chromium involves reactive oxygen species-dependent mechanism in lung epithelial cells

    SciTech Connect (OSTI)

    Ding, Song-Ze; Yang, Yu-Xiu; Li, Xiu-Ling; Michelli-Rivera, Audrey; Han, Shuang-Yin; Wang, Lei; Pratheeshkumar, Poyil; Wang, Xin; Lu, Jian; Yin, Yuan-Qin; Budhraja, Amit; Hitron, Andrew J.

    2013-05-15

    Hexavalent chromium [Cr(VI)] is an important human carcinogen associated with pulmonary diseases and lung cancer. Exposure to Cr(VI) induces DNA damage, cell morphological change and malignant transformation in human lung epithelial cells. Despite extensive studies, the molecular mechanisms remain elusive, it is also not known if Cr(VI)-induced transformation might accompany with invasive properties to facilitate metastasis. We aimed to study Cr(VI)-induced epithelial–mesenchymal transition (EMT) and invasion during oncogenic transformation in lung epithelial cells. The results showed that Cr(VI) at low doses represses E-cadherin mRNA and protein expression, enhances mesenchymal marker vimentin expression and transforms the epithelial cell into fibroblastoid morphology. Cr(VI) also increases cell invasion and promotes colony formation. Further studies indicated that Cr(VI) uses multiple mechanisms to repress E-cadherin expression, including activation of E-cadherin repressors such as Slug, ZEB1, KLF8 and enhancement the binding of HDAC1 in E-cadherin gene promoter, but DNA methylation is not responsible for the loss of E-cadherin. Catalase reduces Cr(VI)-induced E-cadherin and vimentin protein expression, attenuates cell invasion in matrigel and colony formation on soft agar. These results demonstrate that exposure to a common human carcinogen, Cr(VI), induces EMT and invasion during oncogenic transformation in lung epithelial cells and implicate in cancer metastasis and prevention. - Graphical abstract: Epithelial–mesenchymal transition during oncogenic transformation induced by hexavalent chromium involves reactive oxygen species-dependent mechanisms in lung epithelial cells. - Highlights: • We study if Cr(VI) might induce EMT and invasion in epithelial cells. • Cr(VI) induces EMT by altering E-cadherin and vimentin expression. • It also increases cell invasion and promotes oncogenic transformation. • Catalase reduces Cr(VI)-induced EMT, invasion and transformation.

  8. Effect of Intravenous Amino Acid Infusion on Leucine Oxidation Across the Mammary Gland

    E-Print Network [OSTI]

    Bequette, Brian J.

    Effect of Intravenous Amino Acid Infusion on Leucine Oxidation Across the Mammary Gland) and the AA infusion periods. Although blood flow to the mammary gland and the arterial concen- tration of most AA other than leucine were increased by the AA infusion, milk and protein yields did not change

  9. The interplay of matrix metalloproteinases, morphogens and growth factors is necessary for branching of mammary epithelial cells

    E-Print Network [OSTI]

    Simian, M.

    2010-01-01

    processed for casein and gelatin substrate gels as described1 mg/ml of a-casein or gelatin (both from Sigma). AfterB, as shown by casein and gelatin zymography respectively (

  10. Alveolocapillary model system to study alveolar re-epithelialization

    SciTech Connect (OSTI)

    Willems, Coen H.M.P.; Zimmermann, Luc J.I.; Sanders, Patricia J.L.T.; Wagendorp, Margot; Kloosterboer, Nico; Cohen Tervaert, Jan Willem; Duimel, Hans J.Q.; Verheyen, Fons K.C.P.; Iwaarden, J. Freek van

    2013-01-01

    In the present study an in vitro bilayer model system of the pulmonary alveolocapillary barrier was established to investigate the role of the microvascular endothelium on re-epithelialization. The model system, confluent monolayer cultures on opposing sides of a porous membrane, consisted of a human microvascular endothelial cell line (HPMEC-ST1.6R) and an alveolar type II like cell line (A549), stably expressing EGFP and mCherry, respectively. These fluorescent proteins allowed the real time assessment of the integrity of the monolayers and the automated analysis of the wound healing process after a scratch injury. The HPMECs significantly attenuated the speed of re-epithelialization, which was associated with the proximity to the A549 layer. Examination of cross-sectional transmission electron micrographs of the model system revealed protrusions through the membrane pores and close contact between the A549 cells and the HPMECs. Immunohistochemical analysis showed that these close contacts consisted of heterocellular gap-, tight- and adherens-junctions. Additional analysis, using a fluorescent probe to assess gap-junctional communication, revealed that the HPMECs and A549 cells were able to exchange the fluorophore, which could be abrogated by disrupting the gap junctions using connexin mimetic peptides. These data suggest that the pulmonary microvascular endothelium may impact the re-epithelialization process. -- Highlights: ? Model system for vital imaging and high throughput screening. ? Microvascular endothelium influences re-epithelialization. ? A549 cells form protrusions through membrane to contact HPMEC. ? A549 cells and HPMECs form heterocellular tight-, gap- and adherens-junctions.

  11. Nesfatin-1 inhibits ovarian epithelial carcinoma cell proliferation in vitro

    SciTech Connect (OSTI)

    Xu, Yang; Pang, Xiaoyan; Dong, Mei; Wen, Fang Zhang, Yi

    2013-11-01

    Highlights: •Nesfatin-1 inhibits the proliferation and growth of HO-8910 cells by G1 phase arrest. •Nesfatin-1 enhances HO-8910 cell apoptosis. •Nesfatin-1 inhibits HO-8910 cell proliferation via mTOR and RhoA/ROCK signaling pathway. •The first report of nesfatin-1-mediated proliferation in ovarian epithelial carcinoma. -- Abstract: Nesfatin-1, an 82-amino-acid peptide derived from a 396-amino-acid precursor protein nucleobindin 2 (NUCB2), was originally identified in hypothalamic nuclei involved in the regulation of food intake. It was recently reported that nesfatin-1 is a novel depot specific adipokine preferentially produced by subcutaneous tissue, with obesity- and food deprivation-regulated expression. Although a relation between ovarian cancer mortality and obesity has been previously established, a role of nesfatin-1 in ovarian epithelial carcinoma remains unknown. The aim of the present study is to examine the effect of nesfatin-1 on ovary carcinoma cells proliferation. We found that nesfatin-1 inhibits the proliferation and growth of HO-8910 cells by G1 phase arrest, this inhibition could be abolished by nesfatin-1 neutralizing antibody. Nesfatin-1 enhances HO-8910 cell apoptosis, activation of mammalian target of rapamycin (mTOR) and RhoA/ROCK signaling pathway block the effects of nesfatin-1-induced apoptosis, therefore reverses the inhibition of HO-8910 cell proliferation by nesfatin-1. In conclusion, the present study demonstrated that nesfatin-1 can inhibit the proliferation in human ovarian epithelial carcinoma cell line HO-8910 cells through inducing apoptosis via mTOR and RhoA/ROCK signaling pathway. This study provides a novel regulatory signaling pathway of nesfatin-1-regulated ovarian epithelial carcinoma growth and may contribute to ovarian cancer prevention and therapy, especially in obese patients.

  12. Retinal Pigment Epithelial (RPE) Verification of melanin function as a light activated ROS scavenger

    E-Print Network [OSTI]

    role in protecting our skin from the damaging effects of UV radiation and in preventing skin cancer officinalis, a species of cuttlefish, were added to cultured human retinal pigment epithelial (RPE) cells only native melanin. These experiments conclusively demonstrate that melanin serves as a light

  13. Annexin A9 (ANXA9) biomarker and therapeutic target in epithelial cancer

    DOE Patents [OSTI]

    Hu, Zhi (El Cerrito, CA); Kuo, Wen-Lin (San Ramon, CA); Neve, Richard M. (San Mateo, CA); Gray, Joe W. (San Francisco, CA)

    2012-06-12

    Amplification of the ANXA9 gene in human chromosomal region 1q21 in epithelial cancers indicates a likelihood of both in vivo drug resistance and metastasis, and serves as a biomarker indicating these aspects of the disease. ANXA9 can also serve as a therapeutic target. Interfering RNAs (iRNAs) (such as siRNA and miRNA) and shRNA adapted to inhibit ANXA9 expression, when formulated in a therapeutic composition, and delivered to cells of the tumor, function to treat the epithelial cancer.

  14. Enhancement of cancer stem-like and epithelial?mesenchymal transdifferentiation property in oral epithelial cells with long-term nicotine exposure: Reversal by targeting SNAIL

    SciTech Connect (OSTI)

    Yu, Cheng-Chia; School of Dentistry, Chung Shan Medical University, Taichung, Taiwan; Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan ; Chang, Yu-Chao; Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan

    2013-02-01

    Cigarette smoking is one of the major risk factors in the development and further progression of tumorigenesis, including oral squamous cell carcinoma (OSCC). Recent studies suggest that interplay cancer stem-like cells (CSCs) and epithelial?mesenchymal transdifferentiation (EMT) properties are responsible for the tumor maintenance and metastasis in OSCC. The aim of the present study was to investigate the effects of long-term exposure with nicotine, a major component in cigarette, on CSCs and EMT characteristics. The possible reversal regulators were further explored in nicotine-induced CSCs and EMT properties in human oral epithelial (OE) cells. Long-term exposure with nicotine was demonstrated to up-regulate ALDH1 population in normal gingival and primary OSCC OE cells dose-dependently. Moreover, long-term nicotine treatment was found to enhance the self-renewal sphere-forming ability and stemness gene signatures expression and EMT regulators in OE cells. The migration/cell invasiveness/anchorage independent growth and in vivo tumor growth by nude mice xenotransplantation assay was enhanced in long-term nicotine-stimulated OE cells. Knockdown of Snail in long-term nicotine-treated OE cells was found to reduce their CSCs properties. Therapeutic delivery of Si-Snail significantly blocked the xenograft tumorigenesis of long-term nicotine-treated OSCC cells and largely significantly improved the recipient survival. The present study demonstrated that the enrichment of CSCs coupled EMT property in oral epithelial cells induced by nicotine is critical for the development of OSCC tumorigenesis. Targeting Snail might offer a new strategy for the treatment of OSCC patients with smoking habit. -- Highlights: ? Sustained nicotine treatment induced CSCs properties of oral epithelial cells. ? Long-term nicotine treatment enhance EMT properties of oral epithelial cells. ? Long-term nicotine exposure increased tumorigenicity of oral epithelial cells. ? Si-Snail blocked xenograft tumorigenesis of long-term nicotine-treated OSCC cells.

  15. NF-kappa B- and AP-1-mediated induction of human beta defensin-2 in intestinal epithelial cells by Escherichia coli Nissle 1917: A novel effect of a probiotic bacterium

    E-Print Network [OSTI]

    2004-01-01

    and E. Isolauri. 2002. Probiotics: an overview of bene?cial17. Isolauri, E. 2001. Probiotics in human disease. Am. J.and S. Salminen. 2002. Probiotics: a role in the treatment

  16. Tissue architecture: the ultimate regulator of breast epithelial function

    SciTech Connect (OSTI)

    Bissell, Mina J; Rizki, Aylin; Mian, Saira

    2003-10-20

    A problem in developmental biology that continues to take center stage is how higher organisms generate diverse tissues and organs given the same cellular genotype. In cell and tumor biology, the key question is not the production of form, but its preservation: how do tissues and organs maintain homeostasis, and how do cells within tissues lose or overcome these controls in cancer? Undoubtedly, mechanisms that maintain tissue specificity should share features with those employed to drive formation of the tissues. However, they are unlikely to be identical. At a simplistic level, developmental pathways may be thought of as a series of extremely rapid short-term events. Each new step depends on what came before, and the outcome is the organism itself at birth. All organs, with a few notable exceptions, such as the mammary gland and the brain, 'arrive' together and are complete when the organism is born. In mice and humans, these events occur in a mere 21 days and 9 months respectively. The stability of the differentiated state and the homeostasis of the organism, on the other hand, will last 40-110 times longer. How does the organism achieve this feat? How are tissues maintained? These questions also relate fundamentally to how tissues become malignant and, although not discussed here, to aging. While there is much literature on differentiation - loosely defined as the gain of a single or a series of functions - we know much less about the forces and the pathways that maintain organ morphology and function as a unit. This may be partly because it is difficult to study a tissue as a unit in vivo and there are few techniques that allow maintenance of organs in vitro long enough and in such a way as to make cell and molecular biology experiments possible. Techniques for culturing cells in three-dimensional gels (3D) as a surrogate for tissues, however, have been steadily improving and the method is now used by several laboratories. In this commentary we discuss the following: first, how our laboratory came to develop a model of the mammary gland acinus; second, what this model has told us about mechanisms that govern tissue specificity and malignancy; and third, possible directions for future studies. We summarize the evidence for the central role of ECM signaling in the maintenance of mammary function in culture and (more briefly) its role in tumorigenesis. This is followed by a discussion of the role that tissue architecture and tissue polarity (as opposed to cell polarity) may play in these processes. In an elegantly written and reasoned essay, Kirschner et al. coined the new science of developmental biology 'molecular vitalism'. They framed new concepts for self-organization as well as schemes for information flow in biological organization. Rao et al. reviewed and elaborated on differential-equation-based models of biochemical reaction networks and intracellular noise, with emphasis on bacteria and phage. Similarly, Hartwell et al. discussed the synergy between experiment and theory in elucidating 'modules' - collections of interacting molecules - and in unraveling how these modules collaborate to perform cellular functions such as signal transduction. We believe that many of these ideas will also be applicable to the maintenance of tissue specificity. As much as we agree with Kirschner et al. regarding the limitations of the machine analogy to biological systems, we conclude with thoughts on how we may proceed to model the complex tissue networks that govern breast tissue architecture. We suggest that our understanding of the structure and function of breast tissue would benefit from examining recent techniques for modeling large complex networks such as the World Wide Web and the Internet backbone among others.

  17. Identification of genetic loci that control mammary tumor susceptibility through the host microenvironment

    SciTech Connect (OSTI)

    Zhang, Pengju; Lo, Alvin; Huang, Yurong; Huang, Ge; Liang, Guozhou; Mott, Joni; Karpen, Gary H.; Blakely, Eleanor A.; Bissell, Mina J.; Barcellos-Hoff, Mary Helen; Snijders, Antoine M.; Mao, Jian-Hua

    2015-03-09

    The interplay between host genetics, tumor microenvironment and environmental exposure in cancer susceptibility remains poorly understood. Here we assessed the genetic control of stromal mediation of mammary tumor susceptibility to low dose ionizing radiation (LDIR) using backcrossed F1 into BALB/c (F1Bx) between cancer susceptible (BALB/c) and resistant (SPRET/EiJ) mouse strains. Tumor formation was evaluated after transplantation of non-irradiated Trp53-/- BALB/c mammary gland fragments into cleared fat pads of F1Bx hosts. Genome-wide linkage analysis revealed 2 genetic loci that constitute the baseline susceptibility via host microenvironment. However, once challenged with LDIR, we discovered 13 additional loci that were enriched for genes involved in cytokines, including TGF?1 signaling. Surprisingly, LDIR-treated F1Bx cohort significantly reduced incidence of mammary tumors from Trp53-/- fragments as well as prolonged tumor latency, compared to sham-treated controls. We demonstrated further that plasma levels of specific cytokines were significantly correlated with tumor latency. Using an ex vivo 3-D assay, we confirmed TGF?1 as a strong candidate for reduced mammary invasion in SPRET/EiJ, which could explain resistance of this strain to mammary cancer risk following LDIR. Our results open possible new avenues to understand mechanisms of genes operating via the stroma that affect cancer risk from external environmental exposures.

  18. Identification of genetic loci that control mammary tumor susceptibility through the host microenvironment

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

    Zhang, Pengju; Lo, Alvin; Huang, Yurong; Huang, Ge; Liang, Guozhou; Mott, Joni; Karpen, Gary H.; Blakely, Eleanor A.; Bissell, Mina J.; Barcellos-Hoff, Mary Helen; et al

    2015-03-09

    The interplay between host genetics, tumor microenvironment and environmental exposure in cancer susceptibility remains poorly understood. Here we assessed the genetic control of stromal mediation of mammary tumor susceptibility to low dose ionizing radiation (LDIR) using backcrossed F1 into BALB/c (F1Bx) between cancer susceptible (BALB/c) and resistant (SPRET/EiJ) mouse strains. Tumor formation was evaluated after transplantation of non-irradiated Trp53-/- BALB/c mammary gland fragments into cleared fat pads of F1Bx hosts. Genome-wide linkage analysis revealed 2 genetic loci that constitute the baseline susceptibility via host microenvironment. However, once challenged with LDIR, we discovered 13 additional loci that were enriched for genesmore »involved in cytokines, including TGF?1 signaling. Surprisingly, LDIR-treated F1Bx cohort significantly reduced incidence of mammary tumors from Trp53-/- fragments as well as prolonged tumor latency, compared to sham-treated controls. We demonstrated further that plasma levels of specific cytokines were significantly correlated with tumor latency. Using an ex vivo 3-D assay, we confirmed TGF?1 as a strong candidate for reduced mammary invasion in SPRET/EiJ, which could explain resistance of this strain to mammary cancer risk following LDIR. Our results open possible new avenues to understand mechanisms of genes operating via the stroma that affect cancer risk from external environmental exposures.« less

  19. Dietary linoleate-enhanced metastasis of 4526 murine mammary tumors

    SciTech Connect (OSTI)

    Hubbard, N.E.

    1987-01-01

    The influence of quantitative differences in dietary linoleic acid (18:2) and of the cyclooxygenase inhibitor, indomethacin (IM), on the metastasis of line 4526 mammary tumors was investigated. All mice were fed high fat (20%, w/w), semipurified diets that were prepared using different mixtures of coconut (primarily saturated) and safflower (mostly 18:2) oil and thus contained either 1, 2, 4, 8, or 12% 18:2 (w/w). The spontaneous metastasis of 4526 tumor cells from primary sites, was increased 2-4 fold in mice that were fed diets containing higher levels of 18:2 (8 and 12%). Chronic treatment of mice with a relatively low dosage of IM reduced the growth rate of primary 4526 tumors, slightly reduced metastasis in mice fed 1 and 4% 18:2, and completely inhibited the increased metastasis observed in mice fed 12% 18:2. Treatment with a higher dosage of IM reduced metastasis even further compared to controls, but did not decrease growth rate compared to the low dosage of IM. The level of 18:2 in the diet did not appear to affect the incorporation of {sup 3}H-thymidine into tumor cells of metastatic lung nodules. The effect of 18:2 may be through a modulation of arachidonic acid metabolism. This modulation, in turn, may affect particular steps in the metastatic cascade such as lodgement and survival of tumor cells.

  20. Mechanical compression attenuates normal human bronchial epithelial wound healing

    E-Print Network [OSTI]

    Arold, Stephen P.; Malavia, Nikita; George, Steven C.

    2009-01-01

    Open Access Research Mechanical compression attenuatesto the application of mechanical compression in the presenceResults: We found that mechanical compression and scrape

  1. Human Papillomaviruses; Epithelial Tropisms, and the Development of Neoplasia

    E-Print Network [OSTI]

    Egawa, Nagayasu; Egawa, Kiyofumi; Griffin, Heather; Doorbar, John

    2015-01-01

    adaptations are thought to have created new ecological niches for papillomavirus to colonise, which in 94 turn drove viral radiation followed by co-speciation with their hosts [16]. Through this route, papillo-95 maviruses have developed their remarkable... , E5 also contributes to viral genome amplification as a result of its ability to stabilize epidermal 298 growth factor (EGF) receptor and to enhance mitogen-activated protein (MAP) kinase activity. E5 also 299 modulates both extracellular...

  2. Biomolecular interactions and responses of human epithelial and...

    Office of Scientific and Technical Information (OSTI)

    the toxicology of ENMs (e.g., the ability of inhaled nanoparticles to cross the blood-brain barrier; Kwon et al., 2008, J. Occup. Health 50, 1) has spurred a recent realization...

  3. Biomolecular interactions and responses of human epithelial and macrophage

    Office of Scientific and Technical Information (OSTI)

    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 WebQuantity of NaturalDukeWakefieldSulfate Reducing Bacteria (Technical Report) | SciTechReport)(Technical Report)cells to engineered

  4. Biomolecular interactions and responses of human epithelial and macrophage

    Office of Scientific and Technical Information (OSTI)

    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 WebQuantity of NaturalDukeWakefieldSulfate Reducing Bacteria (Technical Report) | SciTechReport)(Technical Report)cells to engineeredcells

  5. Response of Human Lung Epithelial Cells to Engineered Nanoparticles.

    Office of Scientific and Technical Information (OSTI)

    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 WebQuantity of NaturalDukeWakefieldSulfateSciTech ConnectSpeedingConnect(Conference)Factory: Linearcuprate|(Conference) | SciTech

  6. The stimulus-dependent co-localization of serum- and glucocorticoid-regulated protein kinase (Sgk) and Erk/MAPK in mammary tumor cells involves the mutual interaction with the importin-alpha nuclear import protein

    SciTech Connect (OSTI)

    Buse, Patricia; Maiyar, Anita C.; Failor, Kim L.; Tran, Susan; Leong, Meredith L.L. [Department of Molecular and Cell Biology and The Cancer Research Laboratory, University of California at Berkeley, Berkeley, CA 94720-3200 (United States); Firestone, Gary L. [Department of Molecular and Cell Biology and The Cancer Research Laboratory, University of California at Berkeley, Berkeley, CA 94720-3200 (United States)], E-mail: glfire@berkeley.edu

    2007-09-10

    In Con8 rat mammary epithelial tumor cells, indirect immunofluorescence revealed that Sgk (serum- and glucocorticoid-regulated kinase) and Erk/MAPK (extracellular signal-regulated protein kinase/mitogen activated protein kinase) co-localized to the nucleus in serum-treated cells and to the cytoplasmic compartment in cells treated with the synthetic glucocorticoid dexamethasone. Moreover, the subcellular distribution of the importin-alpha nuclear transport protein was similarly regulated in a signal-dependent manner. In vitro GST-pull down assays revealed the direct interaction of importin-alpha with either Sgk or Erk/MAPK, while RNA interference knockdown of importin-alpha expression disrupted the localization of both Sgk and Erk into the nucleus of serum-treated cells. Wild type or kinase dead forms of Sgk co-immunoprecipitated with Erk/MAPK from either serum- or dexamethasone-treated mammary tumor cells, suggesting the existence of a protein complex containing both kinases. In serum-treated cells, nucleus residing Sgk and Erk/MAPK were both hyperphosphorylated, indicative of their active states, whereas, in dexamethasone-treated cells Erk/MAPK, but not Sgk, was in its inactive hypophosphorylated state. Treatment with a MEK inhibitor, which inactivates Erk/MAPK, caused the relocalization of both Sgk and ERK to the cytoplasm. We therefore propose that the signal-dependent co-localization of Sgk and Erk/MAPK mediated by importin-alpha represents a new pathway of signal integration between steroid and serum/growth factor-regulated pathways.

  7. Research Article Epithelial Phenotype Confers Resistance of Ovarian Cancer

    E-Print Network [OSTI]

    Hemminki, Akseli

    Research Article Epithelial Phenotype Confers Resistance of Ovarian Cancer Cells to Oncolytic, Helsinki, Finland Abstract We studied the susceptibility of primary ovarian cancer cells to oncolytic oncolysis, we discovered that the epithelial phenotype of ovarian cancer represents a barrier to infection

  8. Identification of Genomic Predictors of Response to the CDK4/6 Inhibitor Palbociclib using the UCLATORL Panel of Human Cancer Cell Lines

    E-Print Network [OSTI]

    Conklin, Dylan Francis

    2013-01-01

    invasive epithelial ovarian cancer. Cancer treatment reviewsto breast and ovarian cancer. European journal of cancer 42,locus in advanced human ovarian-cancer. Int J Oncol 6, 129-

  9. Structural studies of the human polymeric immunoglobulin receptor

    E-Print Network [OSTI]

    Hamburger, Agnes Eva, 1976-

    2005-01-01

    The human polymeric immunoglobulin receptor, pIgR, is a glycosylated type I transmembrane protein expressed on the basolateral surface of secretory epithelial cells. pIgR plays a key role in mucosal immunity and, together ...

  10. MicroRNA expression in canine mammary cancer 

    E-Print Network [OSTI]

    Boggs, Rene' Michelle

    2008-10-10

    to act as both tumor suppressors and oncogenes in several different cancers, expression patterns of ten miRNAs (miR-15a, miR-16, miR-17-5p, miR-21, miR-29b, miR-125b, miR-145, miR-155, miR-181b, let-7f) known to be associated with human breast cancer were...

  11. CX3CR1 Is Expressed by Prostate Epithelial Cells and Androgens Regulate the Levels of CX3CL1/Fractalkine in the Bone Marrow

    E-Print Network [OSTI]

    Fatatis, Alessandro

    CX3CR1 Is Expressed by Prostate Epithelial Cells and Androgens Regulate the Levels of CX3CL1 human osteoblasts in vitro. Thus, the interaction of fractalkine with its receptor CX3CR1 could play a crucial role in vivo by directing circulating prostate cancer cells to the bone. We found that although CX

  12. Oestrogen metabolism and action in epithelial ovarian cancer 

    E-Print Network [OSTI]

    Ren, Xia

    2011-11-25

    Ovarian cancer is the most fatal of all gynecological malignancies. Epithelial ovarian cancer (EOC) accounts for about 90% of malignant ovarian tumours and is thought to originate mostly from ovarian surface epithelium ...

  13. Quantifying stretching and rearrangement in epithelial sheet migration

    E-Print Network [OSTI]

    Lee, Rachel M.

    Although understanding the collective migration of cells, such as that seen in epithelial sheets, is essential for understanding diseases such as metastatic cancer, this motion is not yet as well characterized as individual ...

  14. IL1{beta}-mediated Stromal COX-2 signaling mediates proliferation and invasiveness of colonic epithelial cancer cells

    SciTech Connect (OSTI)

    Zhu, Yingting; Tissue Tech Inc, Miami, FL 33173 ; Zhu, Min; Lance, Peter

    2012-11-15

    COX-2 is a major inflammatory mediator implicated in colorectal inflammation and cancer. However, the exact origin and role of COX-2 on colorectal inflammation and carcinogenesis are still not well defined. Recently, we reported that COX-2 and iNOS signalings interact in colonic CCD18Co fibroblasts. In this article, we investigated whether activation of COX-2 signaling by IL1{beta} in primary colonic fibroblasts obtained from normal and cancer patients play a critical role in regulation of proliferation and invasiveness of human colonic epithelial cancer cells. Our results demonstrated that COX-2 level was significantly higher in cancer associated fibroblasts than that in normal fibroblasts with or without stimulation of IL-1{beta}, a powerful stimulator of COX-2. Using in vitro assays for estimating proliferative and invasive potential, we discovered that the proliferation and invasiveness of the epithelial cancer cells were much greater when the cells were co-cultured with cancer associated fibroblasts than with normal fibroblasts, with or without stimulation of IL1{beta}. Further analysis indicated that the major COX-2 product, prostaglandin E{sub 2}, directly enhanced proliferation and invasiveness of the epithelial cancer cells in the absence of fibroblasts. Moreover, a selective COX-2 inhibitor, NS-398, blocked the proliferative and invasive effect of both normal and cancer associate fibroblasts on the epithelial cancer cells, with or without stimulation of IL-1{beta}. Those results indicate that activation of COX-2 signaling in the fibroblasts plays a major role in promoting proliferation and invasiveness of the epithelial cancer cells. In this process, PKC is involved in the activation of COX-2 signaling induced by IL-1{beta} in the fibroblasts.

  15. Extracellular matrix control of mammary gland morphogenesis and tumorigenesis: insights from imaging

    SciTech Connect (OSTI)

    Ghajar, Cyrus M; Bissell, Mina J

    2008-10-23

    The extracellular matrix (ECM), once thought to solely provide physical support to a tissue, is a key component of a cell's microenvironment responsible for directing cell fate and maintaining tissue specificity. It stands to reason, then, that changes in the ECM itself or in how signals from the ECM are presented to or interpreted by cells can disrupt tissue organization; the latter is a necessary step for malignant progression. In this review, we elaborate on this concept using the mammary gland as an example. We describe how the ECM directs mammary gland formation and function, and discuss how a cell's inability to interpret these signals - whether as a result of genetic insults or physicochemical alterations in the ECM - disorganizes the gland and promotes malignancy. By restoring context and forcing cells to properly interpret these native signals, aberrant behavior can be quelled and organization re-established. Traditional imaging approaches have been a key complement to the standard biochemical, molecular, and cell biology approaches used in these studies. Utilizing imaging modalities with enhanced spatial resolution in live tissues may uncover additional means by which the ECM regulates tissue structure, on different length scales, through its pericellular organization (short-scale) and by biasing morphogenic and morphostatic gradients (long-scale).

  16. Tumor CellDerived and Macrophage-Derived Cathepsin B Promotes Progression and Lung Metastasis of Mammary Cancer

    E-Print Network [OSTI]

    Bogyo, Matthew

    Tumor Cell­Derived and Macrophage-Derived Cathepsin B Promotes Progression and Lung Metastasis of mammary cancers compared with wild-type PyMT mice. Lung metastasis volumes were significantly reduced in PyMT;ctsb+/À , an effect that was not further enhanced in PyMT;ctsbÀ/À mice. Furthermore, lung

  17. Confocal Microscopy and Nuclear Segmentation Algorithm for Quantitative Imaging of Epithelial Tissue 

    E-Print Network [OSTI]

    Harris, Meagan Alyssa

    2015-07-08

    for imaging epithelial tissues and an image processing algorithm for segmentation of epithelial nuclei. A rapid beam and stage scanning combination was used to acquire fluorescence confocal images of cellular and tissue features along the length of excised...

  18. Secretory pathway Ca2+/Mn2+-ATPase isoform 2 and lactation: specific localization of plasmalemmal and secretory pathway Ca2+ pump isoforms in the mammary gland

    E-Print Network [OSTI]

    Faddy, Helen M.

    2008-01-01

    and secretory pathway Ca 2+ pump isoforms in the mammaryMD, USA. Running head: Calcium pump isoforms in the mammaryof the plasma membrane Ca2+ pump. A study using specific

  19. Role for oestrogen in dynamic interactions between cell types within the human endometrium 

    E-Print Network [OSTI]

    Gibson, Douglas Alistair

    2012-11-30

    The human endometrium is a complex multicellular tissue, located within the cavity of the uterus. Its luminal surface is defined by a layer of epithelial cells supported on a multicellular stroma containing fibroblasts, ...

  20. Vitamin D Enhances Corneal Epithelial Barrier Function Zhaohong Yin,1

    E-Print Network [OSTI]

    Hammock, Bruce D.

    Vitamin D Enhances Corneal Epithelial Barrier Function Zhaohong Yin,1 Victorina Pintea,1 Yanping contain mRNA for the vitamin D receptor (VDR) and 1 -hydroxylase, the enzyme required to convert 25(OH)D3 to 1,25(OH)2D3, and measured vitamin D metabolite concentra- tions in aqueous and vitreous humor

  1. Stromal COX-2 signaling activated by deoxycholic acid mediates proliferation and invasiveness of colorectal epithelial cancer cells

    SciTech Connect (OSTI)

    Zhu, Yingting; Tissue Tech Inc., Miami, FL 33173 ; Zhu, Min; Lance, Peter

    2012-08-31

    Highlights: Black-Right-Pointing-Pointer Human colonic cancer associated fibroblasts are major sources of COX-2 and PGE{sub 2}. Black-Right-Pointing-Pointer The fibroblasts interact with human colonic epithelial cancer cells. Black-Right-Pointing-Pointer Activation of COX-2 signaling in the fibroblasts affects behavior of the epithelia. Black-Right-Pointing-Pointer Protein Kinase C controls the activation of COX-2 signaling. -- Abstract: COX-2 is a major regulator implicated in colonic cancer. However, how COX-2 signaling affects colonic carcinogenesis at cellular level is not clear. In this article, we investigated whether activation of COX-2 signaling by deoxycholic acid (DCA) in primary human normal and cancer associated fibroblasts play a significant role in regulation of proliferation and invasiveness of colonic epithelial cancer cells. Our results demonstrated while COX-2 signaling can be activated by DCA in both normal and cancer associated fibroblasts, the level of activation of COX-2 signaling is significantly greater in cancer associated fibroblasts than that in normal fibroblasts. In addition, we discovered that the proliferative and invasive potential of colonic epithelial cancer cells were much greater when the cells were co-cultured with cancer associated fibroblasts pre-treated with DCA than with normal fibroblasts pre-treated with DCA. Moreover, COX-2 siRNA attenuated the proliferative and invasive effect of both normal and cancer associate fibroblasts pre-treated with DCA on the colonic cancer cells. Further studies indicated that the activation of COX-2 signaling by DCA is through protein kinase C signaling. We speculate that activation of COX-2 signaling especially in cancer associated fibroblasts promotes progression of colonic cancer.

  2. Sensitive Targeted Quantification of ERK Phosphorylation Dynamics and Stoichiometry in Human Cells without Affinity Enrichment

    SciTech Connect (OSTI)

    Shi, Tujin; Gao, Yuqian; Gaffrey, Matthew J.; Nicora, Carrie D.; Fillmore, Thomas L.; Chrisler, William B.; Gritsenko, Marina A.; Wu, Chaochao; He, Jintang; Bloodsworth, Kent J.; Zhao, Rui; Camp, David G.; Liu, Tao; Rodland, Karin D.; Smith, Richard D.; Wiley, H. S.; Qian, Weijun

    2014-12-17

    Mass spectrometry-based targeted quantification is a promising technology for site-specific quantification of posttranslational modifications (PTMs). However, a major constraint of most targeted MS approaches is the limited sensitivity for quantifying low-abundance PTMs, requiring the use of affinity reagents to enrich specific PTMs. Herein, we demonstrate the direct site-specific quantification of ERK phosphorylation isoforms (pT, pY, pTpY) and their relative stoichiometries using a highly sensitive targeted MS approach termed high-pressure, high-resolution separations with intelligent selection and multiplexing (PRISM). PRISM provides effective enrichment of target peptides within a given fraction from complex biological matrix with minimal sample losses, followed by selected reaction monitoring (SRM) quantification. The PRISM-SRM approach enabled direct quantification of ERK phosphorylation in human mammary epithelial cells (HMEC) from as little as 25 µg tryptic peptides from whole cell lysates. Compared to immobilized metal-ion affinity chromatography, PRISM provided >10-fold improvement in signal intensities, presumably due to the better peptide recovery of PRISM for handling small size samples. This approach was applied to quantify ERK phosphorylation dynamics in HMEC treated by different doses of EGF at both the peak activation (10 min) and steady state (2 h). At 10 min, the maximal ERK activation was observed with 0.3 ng/mL dose, whereas the maximal steady state level of ERK activation at 2 h was at 3 ng/ml dose, corresponding to 1200 and 9000 occupied receptors, respectively. At 10 min, the maximally activated pTpY isoform represented ~40% of total ERK, falling to less than 10% at 2 h. The time course and dose-response profiles of individual phosphorylated ERK isoforms indicated that singly phosphorylated pT-ERK never increases significantly, while the increase of pY-ERK paralleled that of pTpY-ERK. This data supports for a processive, rather than distributed, model of ERK phosphorylation. The PRISM-SRM quantification of protein phosphorylation illustrates the potential for simultaneous quantification of multiple PTMs.

  3. Stat3 controls cell death during mammary gland involution by regulating uptake of milk fat globules and lysosomal membrane permeabilization

    E-Print Network [OSTI]

    Sargeant, Timothy J.; Lloyd-Lewis, Bethan; Resemann, Henrike K.; Ramos-Montoya, Antonio; Skepper, Jeremy; Watson, Christine J.

    2014-10-05

    of vacuoles has previously been described in some forms of caspase- independent cell death in a variety of organisms. One of the earliest descriptions is of cells dying during metamorphosis of insect intersegmental muscle cells 46 . The role of vacuoles... ) background strain female mice that were between 4-6 months old. The mice were bred in regular IVC cages with food and water ad libitum and environmental enrichment. For mammary gland studies, virgin female mice between the ages of 7-10 weeks old were mated...

  4. Analysis of Epithelial and Mesenchymal Markers in Ovarian Cancer Reveals Phenotypic Heterogeneity and

    E-Print Network [OSTI]

    Hemminki, Akseli

    Analysis of Epithelial and Mesenchymal Markers in Ovarian Cancer Reveals Phenotypic Heterogeneity and Translational Medicine, Palacky University, Olomouc, Czech Republic Abstract In our studies of ovarian cancer growth is driven by E/M-MP cells, which give rise to epithelial ovarian cancer cells. In contrast

  5. Supplemental Materials and Methods TGF bioassay. To quantify the levels of active and total TGF, we used mink lung epithelial

    E-Print Network [OSTI]

    Nelson, Celeste M.

    used mink lung epithelial cells (MLEC) that produce luciferase under the control of the PAI-1 promoter

  6. Ionizing Radiation Promotes Migration and Invasion of Cancer Cells Through Transforming Growth Factor-Beta-Mediated Epithelial-Mesenchymal Transition

    SciTech Connect (OSTI)

    Zhou Yongchun [Department of Radiation Oncology, Xijing Hospital Fourth Military Medical University, Xi'an (China); Department of Radiation Medicine, College of Preventive Medicine, Xijing Hospital Fourth Military Medical University, Xi'an (China); Liu Junye; Li Jing; Zhang Jie [Department of Radiation Medicine, College of Preventive Medicine, Xijing Hospital Fourth Military Medical University, Xi'an (China); Xu Yuqiao [Department of Pathology, Xijing Hospital Fourth Military Medical University, Xi'an (China); Zhang Huawei; Qiu Lianbo; Ding Guirong [Department of Radiation Medicine, College of Preventive Medicine, Xijing Hospital Fourth Military Medical University, Xi'an (China); Su Xiaoming [Department of Radiation Oncology, 306th Hospital of PLA, Beijing (China); Mei Shi [Department of Radiation Oncology, Xijing Hospital Fourth Military Medical University, Xi'an (China); Guo Guozhen, E-mail: guozhenguo@hotmail.com [Department of Radiation Medicine, College of Preventive Medicine, Xijing Hospital Fourth Military Medical University, Xi'an (China)

    2011-12-01

    Purpose: To examine whether ionizing radiation enhances the migratory and invasive abilities of cancer cells through transforming growth factor (TGF-{beta})-mediated epithelial-mesenchymal transition (EMT). Methods and Materials: Six cancer cell lines originating from different human organs were irradiated by {sup 60}Co {gamma}-ray at a total dose of 2 Gy, and the changes associated with EMT, including morphology, EMT markers, migration and invasion, were observed by microscope, Western blot, immunofluorescence, scratch assay, and transwell chamber assay, respectively. Then the protein levels of TGF-{beta} in these cancer cells were detected by enzyme-linked immunosorbent assay, and the role of TGF-{beta} signaling pathway in the effect of ionizing radiation on EMT was investigate by using the specific inhibitor SB431542. Results: After irradiation with {gamma}-ray at a total dose of 2 Gy, cancer cells presented the mesenchymal phenotype, and compared with the sham-irradiation group the expression of epithelial markers was decreased and of mesenchymal markers was increased, the migratory and invasive capabilities were strengthened, and the protein levels of TGF-{beta} were enhanced. Furthermore, events associated with EMT induced by IR in A549 could be reversed through inhibition of TGF-{beta} signaling. Conclusions: These results suggest that EMT mediated by TGF-{beta} plays a critical role in IR-induced enhancing of migratory and invasive capabilities in cancer cells.

  7. Suppression of renal fibrosis by galectin-1 in high glucose-treated renal epithelial cells

    SciTech Connect (OSTI)

    Okano, Kazuhiro, E-mail: kaokano@kc.twmu.ac.jp; Tsuruta, Yuki; Yamashita, Tetsuri; Takano, Mari; Echida, Yoshihisa; Nitta, Kosaku

    2010-11-15

    Diabetic nephropathy is the most common cause of chronic kidney disease. We investigated the ability of intracellular galectin-1 (Gal-1), a prototype of endogenous lectin, to prevent renal fibrosis by regulating cell signaling under a high glucose (HG) condition. We demonstrated that overexpression of Gal-1 reduces type I collagen (COL1) expression and transcription in human renal epithelial cells under HG conditions and transforming growth factor-{beta}1 (TGF-{beta}1) stimulation. Matrix metalloproteinase 1 (MMP1) is stimulated by Gal-1. HG conditions and TGF-{beta}1 treatment augment expression and nuclear translocation of Gal-1. In contrast, targeted inhibition of Gal-1 expression reduces COL1 expression and increases MMP1 expression. The Smad3 signaling pathway is inhibited, whereas two mitogen-activated protein kinase (MAPK) pathways, p38 and extracellular signal-regulated kinase (ERK), are activated by Gal-1, indicating that Gal-1 regulates these signaling pathways in COL1 production. Using specific inhibitors of Smad3, ERK, and p38 MAPK, we showed that ERK MAPK activated by Gal-1 plays an inhibitory role in COL1 transcription and that activation of the p38 MAPK pathway by Gal-1 plays a negative role in MMP1 production. Taken together, two MAPK pathways are stimulated by increasing levels of Gal-1 in the HG condition, leading to suppression of COL1 expression and increase of MMP1 expression.

  8. Autophagy protects type II alveolar epithelial cells from Mycobacterium tuberculosis infection

    SciTech Connect (OSTI)

    Guo, Xu-Guang [Center for Clinical Laboratory Medicine of PLA, Xijing Hospital, Fourth Military Medical University, Xi'an (China) [Center for Clinical Laboratory Medicine of PLA, Xijing Hospital, Fourth Military Medical University, Xi'an (China); Department of Laboratory Medicine, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou (China); Ji, Tian-Xing [Department of Laboratory Medicine, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou (China)] [Department of Laboratory Medicine, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou (China); Xia, Yong, E-mail: gysyxy@gmail.com [Center for Clinical Laboratory Medicine of PLA, Xijing Hospital, Fourth Military Medical University, Xi'an (China)] [Center for Clinical Laboratory Medicine of PLA, Xijing Hospital, Fourth Military Medical University, Xi'an (China); Ma, Yue-Yun, E-mail: cmbmayy@fmmu.edu.cn [Center for Clinical Laboratory Medicine of PLA, Xijing Hospital, Fourth Military Medical University, Xi'an (China)] [Center for Clinical Laboratory Medicine of PLA, Xijing Hospital, Fourth Military Medical University, Xi'an (China)

    2013-03-08

    Highlights: ? We investigated the protective effect of autophagy pathway against MTB infection. ? MTB-infected A549 cells had higher LDH release. ? Inhibition of autophagy signaling significantly enhanced the MTB-induced necrosis. ? Autophagy prevents apoptosis and promotes cell survival in infected cells. -- Abstract: This study was designed to investigate the protective effect of the autophagy signaling pathway against Mycobacterium tuberculosis infection in type II alveolar epithelial cells. An in vitro M. tuberculosis system was established using human A549 cells. Infection-induced changes in the expression of the autophagic marker LC3 were assessed by reverse transcription-PCR and Western blotting. Morphological changes in autophagosomes were detected by transmission electron microscopy (TEM). The function of the autophagy signaling pathway during infection was assessed by measuring the level of cell death and the amount of lactate dehydrogenase (LDH) released in the presence or absence of the inhibitor 3-methyladenine (3-MA). In addition, effects on LDH release were assessed after the siRNA-mediated knockdown of the essential autophagosomal structural membrane protein Atg5. LC3 mRNA expression was significantly reduced in M.tuberculosis-infected A549 cells (16888.76 ± 1576.34 vs. uninfected: 12744.29 ± 1089.37; P < 0.05). TEM revealed M.tuberculosis bacilli-containing compartments that were surrounded by double membranes characteristic of the autophagic process. M.tuberculosis-infected A549 cells released more LDH (1.45 ± 0.12 vs. uninfected: 0.45 ± 0.04; P < 0.05). The inhibition of autophagy signaling significantly enhanced M.tuberculosis-induced necrosis (3-MA: 75 ± 5% vs. untreated: 15 ± 1%; P < 0.05) and LDH release (3-MA: 2.50 ± 0.24 vs. untreated: 0.45 ± 0.04; Atg5 knockdown: 3.19 ± 0.29 vs. untreated: 1.28 ± 0.11; P < 0.05). Our results indicate that autophagy signaling pathway prevents apoptosis in type II alveolar epithelial cells infected with M.tuberculosis and may represent a molecular target for promoting cell survival during infection by respiratory pathogens.

  9. Aire unleashes stalled RNA polymerase to induce ectopic gene expression in thymic epithelial cells

    E-Print Network [OSTI]

    Giraud, Matthieu

    Aire is a transcriptional regulator that induces expression of peripheral tissue antigens (PTA) in thymic medullary epithelial cells (MECs), driving immunological self-tolerance in differentiating T cells. To elucidate its ...

  10. ZEB1 is a central mediator of the Epithelial-Mesenchymal Transition

    E-Print Network [OSTI]

    Kah, Kong Jie

    2012-01-01

    Carcinomas are solid tumors arising from epithelial tissue, and account for the majority of cancer deaths in the United States. In most occurrences of carcinoma, it is the metastases that kill, not the primary tumor. The ...

  11. Gap junction intercellular communication: a microinjection investigation of fibroblast and epithelial cell lines 

    E-Print Network [OSTI]

    Pahlka, Raymond Benton

    2002-01-01

    The objectives of this research were threefold. The first objective was to develop a protocol for unbiased microinjection of the fluorescent dye Lucifer Yellow to normal fibroblast and epithelial cell lines. I determined the optimal equipment...

  12. NON-INVASIVE OPTICAL DETECTION OF EPITHELIAL CANCER USING OBLIQUE INCIDENCE DIFFUSE REFLECTANCE SPECTROSCOPY 

    E-Print Network [OSTI]

    Garcia-Uribe, Alejandro

    2010-01-16

    DETECTION OF EPITHELIAL CANCER USING OBLIQUE INCIDENCE DIFFUSE REFLECTANCE SPECTROSCOPY A Dissertation by ALEJANDRO GARCIA URIBE Submitted to the Office of Graduate Studies of Texas A&M University in partial fulfillment of the requirements... for the degree of DOCTOR OF PHILOSOPHY May 2009 Major Subject: Electrical Engineering NON-INVASIVE OPTICAL DETECTION OF EPITHELIAL CANCER USING OBLIQUE INCIDENCE DIFFUSE REFLECTANCE SPECTROSCOPY A Dissertation by ALEJANDRO GARCIA URIBE...

  13. YY1 modulates taxane response in epithelial ovarian cancer

    SciTech Connect (OSTI)

    Matsumura, Noriomi; Huang, Zhiqing; Baba, Tsukasa; Lee, Paula S.; Barnett, Jason C.; Mori, Seiichi; Chang, Jeffrey T.; Kuo, Wen-Lin; Gusberg, Alison H.; Whitaker, Regina S.; Gray, JoeW.; Fujii, Shingo; Berchuck, Andrew; Murphy, Susan K.

    2008-10-10

    The results of this study show that a high YY1 gene signature (characterized by coordinate elevated expression of transcription factor YY1 and putative YY1 target genes) within serous epithelial ovarian cancers is associated with enhanced response to taxane-based chemotherapy and improved survival. If confirmed in a prospective study, these results have important implications for the potential future use of individualized therapy in treating patients with ovarian cancer. Identification of the YY1 gene signature profile within a tumor prior to initiation of chemotherapy may provide valuable information about the anticipated response of these tumors to taxane-based drugs, leading to better informed decisions regarding chemotherapeutic choice. Survival of ovarian cancer patients is largely dictated by their response to chemotherapy, which depends on underlying molecular features of the malignancy. We previously identified YIN YANG 1 (YY1) as a gene whose expression is positively correlated with ovarian cancer survival. Herein we investigated the mechanistic basis of this association. Epigenetic and genetic characteristics of YY1 in serous epithelial ovarian cancer (SEOC) were analyzed along with YY1 mRNA and protein. Patterns of gene expression in primary SEOC and in the NCI60 database were investigated using computational methods. YY1 function and modulation of chemotherapeutic response in vitro was studied using siRNA knockdown. Microarray analysis showed strong positive correlation between expression of YY1 and genes with YY1 and transcription factor E2F binding motifs in SEOC and in the NCI60 cancer cell lines. Clustering of microarray data for these genes revealed that high YY1/E2F3 activity positively correlates with survival of patients treated with the microtubule stabilizing drug paclitaxel. Increased sensitivity to taxanes, but not to DNA crosslinking platinum agents, was also characteristic of NCI60 cancer cell lines with a high YY1/E2F signature. YY1 knockdown in ovarian cancer cell lines results in inhibition of anchorage-independent growth, motility and proliferation, but also increases resistance to taxanes, with no effect on cisplatin sensitivity. These results, together with the prior demonstration of augmentation of microtubule-related genes by E2F3, suggest that enhanced taxane sensitivity in tumors with high YY1/E2F activity may be mediated by modulation of putative target genes with microtubule function.

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

    SciTech Connect (OSTI)

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

    2012-10-01

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

  15. URG11 mediates hypoxia-induced epithelial-to-mesenchymal transition by modulation of E-cadherin and {beta}-catenin

    SciTech Connect (OSTI)

    Du, Rui; Huang, Chen [Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi'an (China)] [Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi'an (China); Bi, Qian [State Key Laboratory of Cancer Biology and Xijing Digestive Hospital, Fourth Military Medical University, Xi'an (China)] [State Key Laboratory of Cancer Biology and Xijing Digestive Hospital, Fourth Military Medical University, Xi'an (China); Zhai, Ying [Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi'an (China)] [Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi'an (China); Xia, Lin; Liu, Jie [State Key Laboratory of Cancer Biology and Xijing Digestive Hospital, Fourth Military Medical University, Xi'an (China)] [State Key Laboratory of Cancer Biology and Xijing Digestive Hospital, Fourth Military Medical University, Xi'an (China); Sun, Shiren, E-mail: ningsun@fmmu.edu.cn [Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi'an (China)] [Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi'an (China); Fan, Daiming [State Key Laboratory of Cancer Biology and Xijing Digestive Hospital, Fourth Military Medical University, Xi'an (China)] [State Key Laboratory of Cancer Biology and Xijing Digestive Hospital, Fourth Military Medical University, Xi'an (China)

    2010-01-01

    Upregulated gene 11 (URG11), recently identified as a new HBx-upregulated gene that may activate {beta}-catenin and Wnt signaling, was found to be upregulated in a human tubule cell line under low oxygen. Here, we investigated the potential role of URG11 in hypoxia-induced renal tubular epithelial-to-mesenchymal (EMT). Overexpression of URG11 in a human proximal tubule cell line (HK2) promoted a mesenchymal phenotype accompanied by reduced expression of the epithelial marker E-cadherin and increased expression of the mesenchymal markers vimentin and {alpha}-SMA, while URG11 knockdown by siRNA effectively reversed hypoxia-induced EMT. URG11 promoted the expression of {beta}-catenin and increased its nuclear accumulation under normoxic conditions through transactivation of the {beta}-catenin promoter. This in turn upregulated {beta}-catenin/T-cell factor (TCF) and its downstream effector genes, vimentin, and {alpha}-SMA. In vivo, strong expression of URG11 was observed in the tubular epithelia of 5/6-nephrectomized rats, and a Western blot analysis demonstrated a close correlation between HIF-1{alpha} and URG11 protein levels. Altogether, our results indicate that URG11 mediates hypoxia-induced EMT through the suppression of E-cadherin and the activation of the {beta}-catenin/TCF pathway.

  16. In vitro models for airway epithelial cell culture

    E-Print Network [OSTI]

    Sivathanu, Vivek

    2013-01-01

    This work is about the development of a physiologically relevant model of the human airway. Various factors such as the cell model, physiochemical factors such as the cell substrate properties including its stiffness, shear ...

  17. Mechanisms of lead transport in two intestinal epithelial cell lines 

    E-Print Network [OSTI]

    Dekaney, Christopher Matthew

    1996-01-01

    Toxic effects of lead (Pb) have been recognized for as long as the heavy metal has been used in society; however, Pb toxicity is still a problem today in humans and animals. The primary targets of Pb toxicity are the ...

  18. Alpha1 and Alpha2 Integrins Mediate Invasive Activity of Mouse Mammary Carcinoma Cells through Regulation of Stromelysin-1 Expression

    SciTech Connect (OSTI)

    Lochter, Andre; Navre, Marc; Werb, Zena; Bissell, Mina J

    1998-06-29

    Tumor cell invasion relies on cell migration and extracellular matrix proteolysis. We investigated the contribution of different integrins to the invasive activity of mouse mammary carcinoma cells. Antibodies against integrin subunits {alpha}6 and {beta}1, but not against {alpha}1 and {alpha}2, inhibited cell locomotion on a reconstituted basement membrane in two-dimensional cell migration assays, whereas antibodies against {beta}1, but not against a6 or {alpha}2, interfered with cell adhesion to basement membrane constituents. Blocking antibodies against {alpha}1 integrins impaired only cell adhesion to type IV collagen. Antibodies against {alpha}1, {alpha}2, {alpha}6, and {beta}1, but not {alpha}5, integrin subunits reduced invasion of a reconstituted basement membrane. Integrins {alpha}1 and {alpha}2, which contributed only marginally to motility and adhesion, regulated proteinase production. Antibodies against {alpha}1 and {alpha}2, but not {alpha}6 and {beta}1, integrin subunits inhibited both transcription and protein expression of the matrix metalloproteinase stromelysin-1. Inhibition of tumor cell invasion by antibodies against {alpha}1 and {alpha}2 was reversed by addition of recombinant stromelysin-1. In contrast, stromelysin-1 could not rescue invasion inhibited by anti-{alpha}6 antibodies. Our data indicate that {alpha}1 and {alpha}2 integrins confer invasive behavior by regulating stromelysin-1 expression, whereas {alpha}6 integrins regulate cell motility. These results provide new insights into the specific functions of integrins during tumor cell invasion.

  19. Dietary fat modulation of mammary tumor growth and metabolism demonstrated by /sup 31/P-nuclear magnetic resonance

    SciTech Connect (OSTI)

    Erickson, K.L.; Buckman, D.K.; Hubbard, N.E.; Ross, B.

    1986-03-05

    The relationship of dietary fat concentration and saturation on the growth and metabolic activity of line 168 was studied using syngeneic mice fed 6 experimental diets before and during tumor growth. Tumor latency was significantly greater for mice fed a diet containing the minimum of essential fatty acids (EFA, 0.5% corn oil) or 8% coconut oil (SF) than for mice fed 8 or 20% safflower oil (PUF) or 20% SF. Changes in dietary fat resulted in alterations of tumor cell and serum fatty acid composition but not the number of inflammatory cells infiltrating the tumor. /sup 31/P-surface coil NMR was used to measure possible changes in tumor metabolism in vivo. Although pH decreased from 7.2 to 6.6 as the tumor volume increased, there was no difference in pH among dietary groups. There was an inverse relationship between both sugar phosphate (SP)/Pi and ATP/Pi ratios and tumor volume; those ratios for mice fed an EFA deficient or minimal EFA diet decreased at a different rate than ratios for mice fed diets with additional fat. Tumors of mice fed diets containing no or a low level (0.3%) of 18:2 had higher SP/ATP ratios than mice fed diets containing a moderate level (approx. 4%) of 18:2. Thus, high levels of dietary fat had a significant effect on promotion of mammary tumors during early stages of tumor growth. Differences in tumor volume associated with dietary fat may be related to changes in the levels of high energy phosphate metabolites.

  20. Airway epithelial gene expression in the diagnostic evaluation of smokers with suspect lung cancer

    E-Print Network [OSTI]

    Cai, Long

    Airway epithelial gene expression in the diagnostic evaluation of smokers with suspect lung cancer, Timothy Anderson6, Norman Gerry7, Joseph Keane4, Marc E Lenburg7 & Jerome S Brody1 Lung cancer smokers with suspicion of lung cancer could be used as a lung cancer biomarker. Using a training set (n

  1. Polymorphisms in Stromal Genes and Susceptibility to Serous Epithelial Ovarian Cancer: A Report from the Ovarian Cancer Association Consortium

    E-Print Network [OSTI]

    2011-01-01

    and serous epithelial ovarian cancer stratified by case PLoSLumican SNPs and Serous Ovarian Cancer References 1. JemalEpidemiology and etiology of ovarian cancer. Semin Oncol 18:

  2. Flow induces epithelial-mesenchymal transition, cellular heterogeneity and biomarker modulation in 3D ovarian cancer nodules

    E-Print Network [OSTI]

    Demirci, Utkan

    Seventy-five percent of patients with epithelial ovarian cancer present with advanced-stage disease that is extensively disseminated intraperitoneally and prognosticates the poorest outcomes. Primarily metastatic within ...

  3. Antioxidant and Anti-Inflamatory Effects and Mechanisms of Green Tea in Vitro in Vascular Epithelial Cells 

    E-Print Network [OSTI]

    Hasan, Abida

    2011-08-04

    -1 ANTIOXIDANT AND ANTI-INFLAMATORY EFFECTS AND MECHANISMS OF GREEN TEA IN VITRO IN VASCULAR EPITHELIAL CELLS Major: Nutritional Sciences April 2009 Submitted to the Office of Undergraduate Research Texas A&M University in partial... fulfillment of the requirements for the designation as UNDERGRADUATE RESEARCH SCHOLAR A Senior Scholars Thesis by ABIDA HASAN ANTIOXIDANT AND ANTI-INFLAMATORY EFFECTS AND MECHANISMS OF GREEN AND YAUPON TEA IN VITRO IN VASCULAR EPITHELIAL...

  4. Mechanisms of disease: epithelial-mesenchymal transition and back again: does cellular plasticity fuel neoplastic progression?

    SciTech Connect (OSTI)

    Bissell, Mina J; Turley, Eva A.; Veiseh, Mandana; Radisky, Derek C.; Bissell, Mina J.

    2008-02-13

    Epithelial-mesenchymal transition (EMT) is a conversion that facilitates organ morphogenesis and tissue remodeling in physiological processes such as embryonic development and wound healing. A similar phenotypic conversion is also detected in fibrotic diseases and neoplasia, which is associated with disease progression. EMT in cancer epithelial cells often seems to be an incomplete and bi-directional process. In this Review, we discuss the phenomenon of EMT as it pertains to tumor development, focusing on exceptions to the commonly held rule that EMT promotes invasion and metastasis. We also highlight the role of the RAS-controlled signaling mediators, ERK1, ERK2 and PI3-kinase, as microenvironmental responsive regulators of EMT.

  5. Human energy

    E-Print Network [OSTI]

    Sawyer, Suzana

    2010-01-01

    This is the power of human energy that Chevron neverExperience the power of ‘‘Human Energy’’: S. Sawyer (&)s voice returns: ‘‘This is the power of human energy. ’’ In

  6. Id-1 is induced in MDCK epithelial cells by activated Erk/MAPK pathway in response to expression of the Snail and E47 transcription factors

    SciTech Connect (OSTI)

    Jorda, Mireia [IDIBELL-Institut de Recerca Oncologica, Centre d'Oncologia Molecular, Barcelona (Spain); Vinyals, Antonia [IDIBELL-Institut de Recerca Oncologica, Centre d'Oncologia Molecular, Barcelona (Spain); Marazuela, Anna [IDIBELL-Institut de Recerca Oncologica, Centre d'Oncologia Molecular, Barcelona (Spain); Cubillo, Eva [Instituto de Investigaciones Biomedicas 'Alberto Sols' (CSIC-UAM) and Departamento de Bioquimica (UAM), Madrid (Spain); Olmeda, David [Instituto de Investigaciones Biomedicas 'Alberto Sols' (CSIC-UAM) and Departamento de Bioquimica (UAM), Madrid (Spain); Valero, Eva [IDIBELL-Institut de Recerca Oncologica, Centre d'Oncologia Molecular, Barcelona (Spain); Cano, Amparo [Instituto de Investigaciones Biomedicas 'Alberto Sols' (CSIC-UAM) and Departamento de Bioquimica (UAM), Madrid (Spain); Fabra, Angels [IDIBELL-Institut de Recerca Oncologica, Centre d'Oncologia Molecular, Barcelona (Spain)]. E-mail: afabra@idibell.org

    2007-07-01

    Id-1, a member of the helix-loop-helix transcription factor family has been shown to be involved in cell proliferation, angiogenesis and invasion of many types of human cancers. We have previously shown that stable expression of E47 and Snail repressors of the E-cadherin promoter in MDCK epithelial cell line triggers epithelial mesenchymal transition (EMT) concomitantly with changes in gene expression. We show here that both factors activate the Id-1 gene promoter and induce Id-1 mRNA and protein. The upregulation of the Id-1 gene occurs through the transactivation of the promoter by the Erk/MAPK signaling pathway. Moreover, oncogenic Ras is also able to activate Id-1 promoter in MDCK cells in the absence of both E47 and Snail transcription factors. Several transcriptionally active regulatory elements have been identified in the proximal promoter, including AP-1, Sp1 and four putative E-boxes. By EMSA, we only detected an increased binding to Sp1 and AP-1 elements in E47- and Snail-expressing cells. Binding is affected by the treatment of cells with PD 98059 MEK inhibitor, suggesting that MAPK/Erk contributes to the recruitment or assembly of proteins to Id-1 promoter. Small interfering RNA directed against Sp1 reduced Id-1 expression and the upregulation of the promoter, indicating that Sp1 is required for Id-1 induction in E47- and Snail-expressing cells. Our results provide new insights into how some target genes are activated during and/or as a consequence of the EMT triggered by both E47 and Snail transcription factors.

  7. Normal and tumor-derived myoepithelial cells differ in their ability to interact with luminal breast epithelial cells for polarity and basement membrane deposition

    E-Print Network [OSTI]

    Gudjonsson, Thorarinn

    2010-01-01

    myoepithelial cell line derived from a neonatal rat mammaryhuman breast carcinoma derived epithelial cells. Cancer Res.a serpin myoepithelium-derived serine proteinase inhibitor

  8. Effect of taurine on advanced glycation end products-induced hypertrophy in renal tubular epithelial cells

    SciTech Connect (OSTI)

    Huang, J.-S. [Department of Biological Science and Technology, Chung Hwa University of Medical Technology, Tainan 717, Taiwan (China)], E-mail: jaushyang12@hotmail.com; Chuang, L.-Y. [Department of Biochemistry, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Guh, J.-Y. [Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Yang, Y.-L.; Hsu, M.-S. [Department of Biological Science and Technology, Chung Hwa University of Medical Technology, Tainan 717, Taiwan (China)

    2008-12-01

    Mounting evidence indicates that advanced glycation end products (AGE) play a major role in the development of diabetic nephropathy (DN). Taurine is a well documented antioxidant agent. To explore whether taurine was linked to altered AGE-mediated renal tubulointerstitial fibrosis in DN, we examined the molecular mechanisms of taurine responsible for inhibition of AGE-induced hypertrophy in renal tubular epithelial cells. We found that AGE (but not non-glycated BSA) caused inhibition of cellular mitogenesis rather than cell death by either necrosis or apoptosis. There were no changes in caspase 3 activity, bcl-2 protein expression, and mitochondrial cytochrome c release in BSA, AGE, or the antioxidant taurine treatments in these cells. AGE-induced the Raf-1/extracellular signal-regulated kinase (ERK) activation was markedly blocked by taurine. Furthermore, taurine, the Raf-1 kinase inhibitor GW5074, and the ERK kinase inhibitor PD98059 may have the ability to induce cellular proliferation and cell cycle progression from AGE-treated cells. The ability of taurine, GW5074, or PD98059 to inhibit AGE-induced hypertrophy was verified by the observation that it significantly decreased cell size, cellular hypertrophy index, and protein levels of RAGE, p27{sup Kip1}, collagen IV, and fibronectin. The results obtained in this study suggest that taurine may serve as the potential anti-fibrotic activity in DN through mechanism dependent of its Raf-1/ERK inactivation in AGE-induced hypertrophy in renal tubular epithelial cells.

  9. Estrogen inhibits cell cycle progression and retinoblastoma phosphorylation in rhesus ovarian surface epithelial cell culture

    SciTech Connect (OSTI)

    Wright, Jay W.; Stouffer, Richard L.; Rodland, Karin D.

    2003-10-31

    Estrogen promotes the growth of some ovarian cancer cells at nanomolar concentrations, but has been shown to inhibit growth of normal ovarian surface epithelial (OSE) cells at micromolar concentrations (1?g/ml). OSE cells express the estrogen receptor (ER)-?, and are the source of 90% of various cancers. The potential sensitivity of OSE cells to estrogen stresses the importance of understanding the estrogen-dependent mechanisms at play in OSE proliferation and transformation, as well as in anticancer treatment. We investigated the effects of estradiol on cell proliferation in vitro, and demonstrate an intracellular locus of action of estradiol in cultured rhesus ovarian surface epithelial (RhOSE) cells. We show that ovarian and breast cells are growth-inhibited by micromolar concentration of estradiol and that this inhibition correlates with estrogen receptor expression. We further show that normal rhesus OSE cells do not activate ERK or Akt in response to estradiol nor does estradiol block the ability of serum to stimulate ERK or induce cyclin D expression. Contrarily, estradiol inhibits serum-dependent retinoblastoma protein (Rb) phosphorylation and blocks DNA synthesis. This inhibition does not formally arrest cells and is reversible within hours of estrogen withdrawal. Our data are consistent with growth inhibition by activation of Rb and indicate that sensitivity to hormone therapy in anticancer treatment can be modulated by cell cycle regulators downstream of the estrogen receptor.

  10. Copyright @ 200 by the Shock Society. Unauthorized reproduction of this article is prohibited.8 TRANSCRIPTIONAL PROFILES OF HUMAN EPITHELIAL CELLS

    E-Print Network [OSTI]

    Stormo, Gary

    into the regulatory pathways that control gene expression in response to stress and potentially identify novel heat involved during the stress response. KEYWORDS--Heat shock, heat shock proteins, stress response, hep2, gene The heat shock, or stress, response was discovered in 1962 with the description of a set of genes whose

  11. The chitinase-like protein YKL-40 increases mucin5AC production in human bronchial epithelial cells

    SciTech Connect (OSTI)

    Liu, Chunyi; Li, Qi [Division of Respiratory Medicine, Second Affiliated Hospital, Chongqing Medical University, No. 74, Linjiang Road, Yuzhong District, Chongqing 400010 (China); Zhou, Xiangdong, E-mail: zxd999@263.net [Division of Respiratory Medicine, Second Affiliated Hospital, Chongqing Medical University, No. 74, Linjiang Road, Yuzhong District, Chongqing 400010 (China); Kolosov, Victor P.; Perelman, Juliy M. [Far Eastern Scientific Center of Physiology and Pathology of Respiration, Siberian Branch, Russian Academy of Medical Sciences, Blagoveshchensk (Russian Federation)

    2013-11-01

    Mucus overproduction is an important feature in patients with chronic inflammatory airway diseases. However, the regulatory mechanisms that mediate excessive mucin production remain elusive. Recently, the level of YKL-40, a chitinase-like protein, has been found to be significantly increased in chronic inflammatory airway diseases and has been shown to be associated with the severity of these diseases. In this study, we sought to explore the effect of YKL-40 on mucin5AC (MUC5AC) production in chronic inflammatory airway diseases and the potential signaling pathways involved in this process. We found that elevated YKL-40 levels increased the mRNA and protein expression of MUC5AC in a dose- and time-dependent manner, in association with the phosphorylation of extracellular signal-regulated kinase (ERK) and nuclear factor ?B (NF-?B), reflecting their activation. These responses were significantly suppressed by the knockdown of protease-activating receptor 2 (PAR2) with specific small interfering RNA or the inhibitors of ERK and NF-?B. YKL-40-induced MUC5AC overproduction was also effectively attenuated by the inhibitor of focal adhesion kinase (FAK). Taken together, these results imply that YKL-40 can stimulate excessive MUC5AC production through PAR2- and FAK-mediated mechanisms. - Highlights: • MUC5AC is the major secreted mucin in chronic inflammatory airway diseases. • YKL-40 is a prototype of the chitinase-like protein in mammals. • YKL-40 is an active player in chronic inflammatory airway diseases. • YKL-40 can increase MUC5AC production via PAR2-mediated pathway. • FAK is another candidate to mediate YKL-40-induced MUC5AC overexpression.

  12. 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

  13. Chromosomal mapping of the human and mouse homologues of two new members of the AP-2 family of transcription factors

    SciTech Connect (OSTI)

    Williamson, J.A.; Sheer, D. [ICRF, London (United Kingdom)] [ICRF, London (United Kingdom); Bosher, J.M. [Hammersmith Hospital, Longon (United Kingdom)] [and others] [Hammersmith Hospital, Longon (United Kingdom); and others

    1996-07-01

    The AP-2 transcription factor has been shown to play an important role in the development of tissues of ectodermal origin and has also been implicated in mammary oncogenesis. It has recently been found that AP-2 is encoded by a family of related genes, AP-2{alpha}, AP-2{beta}, and AP-2{gamma}. As a further step in understanding the role of each of these genes has in development, we have used fluorescence in situ hybridization to map the chromosomal locations of the mouse and human homologues of the newly isolated AP-2{beta} and AP-2{gamma} genes. Tcfap2b and Tcfap2c map to mouse chromosomes 1A2-4 and 2H3-4, respectively, while TFAP2B and TFAP2C map to human chromosomes 6p12 and 20q13.2, the later being a region that is frequently amplified in breast carcinoma. 20 refs., 1 fig., 1 tab.

  14. PI3K, Erk Signaling in BMP7-Induced Epithelial-Mesenchymal Transition (EMT) of PC-3 Prostate Cancer

    E-Print Network [OSTI]

    Chuong, Cheng-Ming

    PI3K, Erk Signaling in BMP7-Induced Epithelial- Mesenchymal Transition (EMT) of PC-3 Prostate kinase and Erk were found to suppress BMP-induced morphological changes both in 2D and 3D conditions. These results suggest that, besides the Smad signaling pathways, BMP-induced activation of PI3K and Erk

  15. Low doses ionizing radiation enhances the invasiveness of breast cancer cells by inducing epithelial-mesenchymal transition

    SciTech Connect (OSTI)

    Zhang, Xin; Li, Xiaoyan; Zhang, Ning; Yang, Qifeng; Moran, Meena S.

    2011-08-19

    Highlights: {yields} Low doses ionizing irradiation would enhance the invasiveness of breast cancer cells by inducing EMT. {yields} Low doses ionizing radiation induced morphologic changes in breast cancer cells. {yields} Low doses ionizing radiation led to upregulation of mesenchymal markers and down-regulation of epithelial markers. {yields} Low doses ionizing radiation increased migration and invasion of breast cancer cells. -- Abstract: Epithelial-mesenchymal transition (EMT) is a process cellular morphologic and molecular alterations facilitate cell invasion. We hypothesized that low dose ionizing irradiation (LDIR) enhances the invasiveness of breast cancer cells by inducing EMT. The effects of LDIR on cellular morphology and the EMT markers of MCF-7 breast cancer cells were analyzed by western blot/RT-PCR and migration/invasion was examined using the transwell assay. We found that LDIR led to the phenotypic changes of EMT in MCF-7 cells and down-regulation of epithelial differentiation markers and transcriptional induction of mesenchymal markers. Furthermore, the radiated cells demonstrated enhanced migration/invasion MCF-7 cells compared with non-radiated cells. In summary, LDIR promotes the invasiveness of breast cancer cells through epithelial to mesenchymal transition. These findings may ultimately provide a new targeted approach for improving the therapeutic effectiveness of radiation in breast cancer.

  16. Pinkbar is an epithelial-specific BAR domain protein that generates planar membrane structures

    SciTech Connect (OSTI)

    Pykäläinen, Anette; Boczkowska, Malgorzata; Zhao, Hongxia; Saarikangas, Juha; Rebowski, Grzegorz; Jansen, Maurice; Hakanen, Janne; Koskela, Essi V.; Peränen, Johan; Vihinen, Helena; Jokitalo, Eija; Salminen, Marjo; Ikonen, Elina; Dominguez, Roberto; Lappalainen, Pekka

    2013-05-29

    Bin/amphipysin/Rvs (BAR)-domain proteins sculpt cellular membranes and have key roles in processes such as endocytosis, cell motility and morphogenesis. BAR domains are divided into three subfamilies: BAR- and F-BAR-domain proteins generate positive membrane curvature and stabilize cellular invaginations, whereas I-BAR-domain proteins induce negative curvature and stabilize protrusions. We show that a previously uncharacterized member of the I-BAR subfamily, Pinkbar, is specifically expressed in intestinal epithelial cells, where it localizes to Rab13-positive vesicles and to the plasma membrane at intercellular junctions. Notably, the BAR domain of Pinkbar does not induce membrane tubulation but promotes the formation of planar membrane sheets. Structural and mutagenesis analyses reveal that the BAR domain of Pinkbar has a relatively flat lipid-binding interface and that it assembles into sheet-like oligomers in crystals and in solution, which may explain its unique membrane-deforming activity.

  17. Long-term Survival Outcomes Following Internal Mammary Node Irradiation in Stage II-III Breast Cancer: Results of a Large Retrospective Study With 12-Year Follow-up

    SciTech Connect (OSTI)

    Chang, Jee Suk; Park, Won; Kim, Yong Bae; Lee, Ik Jae; Keum, Ki Chang; Lee, Chang Geol; Choi, Doo Ho; Suh, Chang-Ok; Huh, Seung Jae

    2013-08-01

    Purpose: To examine the effect of internal mammary node irradiation (IMNI) on disease-free survival (DFS) and overall survival (OS) in breast cancer patients treated with modified radical mastectomy and postoperative radiation therapy. Methods and Materials: Between 1994 and 2002, 396 patients with stage II-III breast cancer were treated with postmastectomy radiation therapy with (n=197) or without (n=199) IMNI. Patients who received neoadjuvant chemotherapy were excluded. IMNI was administered at the clinical discretion of the treating physician. Median RT dose was 50.4 Gy (range, 45.0-59.4 Gy) in 28 fractions, with inclusion of the supraclavicular fossa in 96% of patients. Adjuvant chemotherapy was administered to 99.7% of the patients and endocrine therapy to 53%. Results: The median follow-up was 149 months (range, 124-202). IMNI patients had more advanced nodal stage and non-high grade tumors than those without IMNI (P<.001). Otherwise, disease and treatment characteristics were well balanced. The 10-year DFS with and without IMNI was 65% and 57%, respectively (P=.05). Multivariate analysis demonstrated that IMNI was an independent, positive predictor of DFS (hazard ratio [HR], 0.70; P=.02). Benefits of IMNI in DFS were seen most apparently in N2 patients (HR, 0.44; 95% confidence interval [CI], 0.26-0.74) and inner/central tumors (HR, 0.55; 95% CI, 0.34-0.90). The 10-year OS with and without IMNI was 72% and 66%, respectively (P=.62). The 10-year DFS and OS were 61%, and 69%, respectively. Conclusions: Internal mammary node irradiation significantly improved DFS in postmastectomy breast cancer patients. Pending long-term results from randomized trials, treatment of internal mammary nodes should be considered in postmastectomy radiation therapy.

  18. Rab11 Is Required for Epithelial Cell Viability, Terminal Differentiation, and Suppression of Tumor-Like Growth in the Drosophila Egg Chamber

    E-Print Network [OSTI]

    Xu, Jiang; Lan, Lan; Bogard, Nicholas; Mattione, Cristin; Cohen, Robert S.

    2011-05-23

    Background: The Drosophila egg chamber provides an excellent system in which to study the specification and differentiation of epithelial cell fates because all of the steps, starting with the division of the corresponding stem cells, called...

  19. Core epithelial-to-mesenchymal transition interactome gene-expression signature is associated with claudin-low and metaplastic breast cancer subtypes

    E-Print Network [OSTI]

    Zhou, Alicia Y.

    The epithelial-to-mesenchymal transition (EMT) produces cancer cells that are invasive, migratory, and exhibit stem cell characteristics, hallmarks of cells that have the potential to generate metastases. Inducers of the ...

  20. Tumor hypomethylation at 6p21.3 associates with longer time to recurrence of high-grade serous epithelial ovarian cancer

    E-Print Network [OSTI]

    2014-01-01

    Mayo Clinic SPORE in Ovarian Cancer to E.L. Goode, and R25Grade Serous Epithelial Ovarian Cancer Chen Wang 1 , Mine S.et al. Epigenome-wide ovarian cancer analysis identi?es a

  1. Aberrant, ectopic expression of VEGF and VEGF receptors 1 and 2 in malignant colonic epithelial cells. Implications for these cells growth via an autocrine mechanism

    SciTech Connect (OSTI)

    Ahluwalia, Amrita [Veterans Affairs Long Beach Healthcare System, Long Beach, CA (United States)] [Veterans Affairs Long Beach Healthcare System, Long Beach, CA (United States); Jones, Michael K. [Veterans Affairs Long Beach Healthcare System, Long Beach, CA (United States) [Veterans Affairs Long Beach Healthcare System, Long Beach, CA (United States); Department of Medicine, University of California, Irvine, CA (United States); Szabo, Sandor [Veterans Affairs Long Beach Healthcare System, Long Beach, CA (United States) [Veterans Affairs Long Beach Healthcare System, Long Beach, CA (United States); Department of Pathology, University of California, Irvine, CA (United States); Tarnawski, Andrzej S., E-mail: amrita.ahluwalia@va.gov [Veterans Affairs Long Beach Healthcare System, Long Beach, CA (United States); Department of Medicine, University of California, Irvine, CA (United States)

    2013-08-09

    Highlights: •Malignant colonic epithelial cells express VEGF and its receptors. •Cultured colon cancer cells secrete VEGF into the medium. •Inhibition of VEGF receptor significantly decreases colon cancer cell proliferation. •VEGF is critical for colon cancer cell growth. -- Abstract: Vascular endothelial growth factor A (referred to as VEGF) is implicated in colon cancer growth. Currently, the main accepted mechanism by which VEGF promotes colon cancer growth is via the stimulation of angiogenesis, which was originally postulated by late Judah Folkman. However, the cellular source of VEGF in colon cancer tissue; and, the expression of VEGF and its receptors VEGF-R1 and VEGF-R2 in colon cancer cells are not fully known and are subjects of controversy. Material and methods: We examined and quantified expression of VEGF, VEGF-R1 and VEGF-R2 in three different human colonic tissue arrays containing sections of adenocarcinoma (n = 43) and normal mucosa (n = 41). In human colon cancer cell lines HCT116 and HT29 and normal colon cell lines NCM356 and NCM460, we examined expression of VEGF, VEGF-R1 and VEGF-R2 mRNA and protein, VEGF production and secretion into the culture medium; and, the effect of a potent, selective inhibitor of VEGF receptors, AL-993, on cell proliferation. Results: Human colorectal cancer specimens had strong expression of VEGF in cancer cells and also expressed VEGF-R1 and VEGF-R2.In vitro studies showed that human colon cancer cell lines, HCT116 and HT29, but not normal colonic cell lines, express VEGF, VEGF-R1 and VEGF-R2 and secrete VEGF into the medium up to a concentration 2000 pg/ml within 48 h. Furthermore, we showed that inhibition of VEGF receptors using a specific VEGF-R inhibitor significantly reduced proliferation (by >50%) of cultured colon cancer cell lines. Conclusions: Our findings support the contention that VEGF generated by colon cancer cells stimulates their growth directly through an autocrine mechanism that is independent of its primary function in the induction of angiogenesis.

  2. 3,5,4?-Trimethoxystilbene, a natural methoxylated analog of resveratrol, inhibits breast cancer cell invasiveness by downregulation of PI3K/Akt and Wnt/?-catenin signaling cascades and reversal of epithelial–mesenchymal transition

    SciTech Connect (OSTI)

    Tsai, Jie-Heng; Hsu, Li-Sung; Lin, Chih-Li; Hong, Hui-Mei; Pan, Min-Hsiung; Way, Tzong-Der; Chen, Wei-Jen

    2013-11-01

    The molecular basis of epithelial–mesenchymal transition (EMT) functions as a potential therapeutic target for breast cancer because EMT may endow breast tumor-initiating cells with stem-like characteristics and enable the dissemination of breast cancer cells. We have recently verified the antitumor activity of 3,5,4?-trimethoxystilbene (MR-3), a naturally methoxylated derivative of resveratrol, in colorectal cancer xenografts via an induction of apoptosis. The effect of MR-3 on EMT and the invasiveness of human MCF-7 breast adenocarcinoma cell line were also explored. We found that MR-3 significantly increased epithelial marker E-cadherin expression and triggered a cobblestone-like morphology of MCF-7 cells, while reciprocally decreasing the expression of mesenchymal markers, such as snail, slug, and vimentin. In parallel with EMT reversal, MR-3 downregulated the invasion and migration of MCF-7 cells. Exploring the action mechanism of MR-3 on the suppression of EMT and invasion indicates that MR-3 markedly reduced the expression and nuclear translocation of ?-catenin, accompanied with the downregulation of ?-catenin target genes and the increment of membrane-bound ?-catenin. These results suggest the involvement of Wnt/?-catenin signaling in the MR-3-induced EMT reversion of MCF-7 cells. Notably, MR-3 restored glycogen synthase kinase-3? activity by inhibiting the phosphorylation of Akt, the event required for ?-catenin destruction via a proteasome-mediated system. Overall, these findings indicate that the anti-invasive activity of MR-3 on MCF-7 cells may result from the suppression of EMT via down-regulating phosphatidylinositol 3-kinase (PI3K)/AKT signaling, and consequently, ?-catenin nuclear translocation. These occurrences ultimately lead to the blockage of EMT and the invasion of breast cancer cells. - Highlights: • MR-3 blocked MCF-7 cell invasion by inducing a reversal of EMT. • Wnt/?-catenin signaling is involved in MR-3-induced EMT reversion of MCF-7 cells. • Knockdown of ?-catenin was sufficient to restore epithelial marker E-cadherin levels. • MR-3 recovered the function of GSK-3? that inhibits ?-catenin nuclear translocation.

  3. Spleen tyrosine kinase mediates high glucose-induced transforming growth factor-{beta}1 up-regulation in proximal tubular epithelial cells

    SciTech Connect (OSTI)

    Yang, Won Seok; Chang, Jai Won [Division of Nephrology, Department of Internal Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul (Korea, Republic of)] [Division of Nephrology, Department of Internal Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul (Korea, Republic of); Han, Nam Jeong [Department of Cell Biology, Asan Institute for Life Sciences, Seoul (Korea, Republic of)] [Department of Cell Biology, Asan Institute for Life Sciences, Seoul (Korea, Republic of); Lee, Sang Koo [Division of Nephrology, Department of Internal Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul (Korea, Republic of)] [Division of Nephrology, Department of Internal Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul (Korea, Republic of); Park, Su-Kil, E-mail: skpark@amc.seoul.kr [Division of Nephrology, Department of Internal Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul (Korea, Republic of)] [Division of Nephrology, Department of Internal Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul (Korea, Republic of)

    2012-09-10

    The role of spleen tyrosine kinase (Syk) in high glucose-induced intracellular signal transduction has yet to be elucidated. We investigated whether Syk is implicated in high glucose-induced transforming growth factor-{beta}1 (TGF-{beta}1) up-regulation in cultured human proximal tubular epithelial cells (HK-2 cell). High glucose increased TGF-{beta}1 gene expression through Syk, extracellular signal-regulated kinase (ERK), AP-1 and NF-{kappa}B. High glucose-induced AP-1 DNA binding activity was decreased by Syk inhibitors and U0126 (an ERK inhibitor). Syk inhibitors suppressed high glucose-induced ERK activation, whereas U0126 had no effect on Syk activation. High glucose-induced NF-{kappa}B DNA binding activity was also decreased by Syk inhibitors. High glucose increased nuclear translocation of p65 without serine phosphorylation of I{kappa}B{alpha} and without degradation of I{kappa}B{alpha}, but with an increase in tyrosine phosphorylation of I{kappa}B{alpha} that may account for the activation of NF-{kappa}B. Both Syk inhibitors and Syk-siRNA attenuated high glucose-induced I{kappa}B{alpha} tyrosine phosphorylation and p65 nuclear translocation. Depletion of p21-activated kinase 2 (Pak2) by transfection of Pak2-siRNA abolished high glucose-induced Syk activation. In summary, high glucose-induced TGF-{beta}1 gene transcription occurred through Pak2, Syk and subsequent ERK/AP-1 and NF-{kappa}B pathways. This suggests that Syk might be implicated in the diabetic kidney disease.

  4. TGF-{beta}-stimulated aberrant expression of class III {beta}-tubulin via the ERK signaling pathway in cultured retinal pigment epithelial cells

    SciTech Connect (OSTI)

    Chung, Eun Jee [Department of Ophthalmology, National Health Insurance Corporation Ilsan Hospital, Gyeonggi-do (Korea, Republic of)] [Department of Ophthalmology, National Health Insurance Corporation Ilsan Hospital, Gyeonggi-do (Korea, Republic of); Chun, Ji Na; Jung, Sun-Ah [Konyang University Myunggok Medical Research Institute, Kim's Eye Hospital, Konyang University College of Medicine, Seoul (Korea, Republic of)] [Konyang University Myunggok Medical Research Institute, Kim's Eye Hospital, Konyang University College of Medicine, Seoul (Korea, Republic of); Cho, Jin Won [Department of Biology, Yonsei University, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-749 (Korea, Republic of)] [Department of Biology, Yonsei University, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-749 (Korea, Republic of); Lee, Joon H., E-mail: joonhlee@konyang.ac.kr [Konyang University Myunggok Medical Research Institute, Kim's Eye Hospital, Konyang University College of Medicine, Seoul (Korea, Republic of)

    2011-11-18

    Highlights: Black-Right-Pointing-Pointer TGF-{beta} induces aberrant expression of {beta}III in RPE cells via the ERK pathway. Black-Right-Pointing-Pointer TGF-{beta} increases O-GlcNAc modification of {beta}III in RPE cells. Black-Right-Pointing-Pointer Mature RPE cells have the capacity to express a neuron-associated gene by TGF-{beta}. -- Abstract: The class III {beta}-tubulin isotype ({beta}{sub III}) is expressed exclusively by neurons within the normal human retina and is not present in normal retinal pigment epithelial (RPE) cells in situ or in the early phase of primary cultures. However, aberrant expression of class III {beta}-tubulin has been observed in passaged RPE cells and RPE cells with dedifferentiated morphology in pathologic epiretinal membranes from idiopathic macular pucker, proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR). Transforming growth factor-{beta} (TGF-{beta}) has been implicated in dedifferentiation of RPE cells and has a critical role in the development of proliferative vitreoretinal diseases. Here, we investigated the potential effects of TGF-{beta} on the aberrant expression of class III {beta}-tubulin and the intracellular signaling pathway mediating these changes. TGF-{beta}-induced aberrant expression and O-linked-{beta}-N-acetylglucosamine (O-GlcNac) modification of class III {beta}-tubulin in cultured RPE cells as determined using Western blotting, RT-PCR and immunocytochemistry. TGF-{beta} also stimulated phosphorylation of ERK. TGF-{beta}-induced aberrant expression of class III {beta}-tubulin was significantly reduced by pretreatment with U0126, an inhibitor of ERK phosphorylation. Our findings indicate that TGF-{beta} stimulated aberrant expression of class III {beta}-tubulin via activation of the ERK signaling pathway. These data demonstrate that mature RPE cells have the capacity to express a neuron-associated gene in response to TGF-{beta} stimulation and provide useful information towards understanding the pathogenesis of proliferative vitreoretinal diseases.

  5. The bacterial signal indole increases epithelial-cell tight-junction resistance and attenuates indicators

    E-Print Network [OSTI]

    Wood, Thomas K.

    results are similar to those observed with probiotic strains and suggest that indole could be important | interkingdom signaling | probiotics The human gastrointestinal (GI) tract is rich in a diverse range

  6. Human Subjects Section 6. Protection of Human

    E-Print Network [OSTI]

    Heller, Barbara

    Human Subjects Section 6. Protection of Human Subjects This section is required for applicants answering "yes" to the question "Are human subjects involved?" on the R&R Other Project Information form subjects applicants must provide a justification in this section for the claim that no human subjects

  7. Transcriptional regulation of human RANK ligand gene expression by E2F1

    SciTech Connect (OSTI)

    Hu Yan [Department of Stress Biology, Roswell Park Cancer Institute, Buffalo, NY 14263 (United States); Sun Meng [Department of Urology and Cancer Center, University of California at Davis, School of Medicine, 4860 Y Street, Suite 3500, Sacramento, CA 95817 (United States); Graduate Program of Pharmacology and Toxicology, University of California at Davis, Sacramento, CA 95817 (United States); Nadiminty, Nagalakshmi; Lou Wei [Department of Urology and Cancer Center, University of California at Davis, School of Medicine, 4860 Y Street, Suite 3500, Sacramento, CA 95817 (United States); Pinder, Elaine [Department of Urology and Cancer Center, University of California at Davis, School of Medicine, 4860 Y Street, Suite 3500, Sacramento, CA 95817 (United States); Graduate Program of Pharmacology and Toxicology, University of California at Davis, Sacramento, CA 95817 (United States); Gao, Allen C. [Department of Urology and Cancer Center, University of California at Davis, School of Medicine, 4860 Y Street, Suite 3500, Sacramento, CA 95817 (United States); Graduate Program of Pharmacology and Toxicology, University of California at Davis, Sacramento, CA 95817 (United States)], E-mail: acgao@ucdavis.edu

    2008-06-06

    Receptor activator of nuclear factor kappa B ligand (RANKL) is a critical osteoclastogenic factor involved in the regulation of bone resorption, immune function, the development of mammary gland and cardiovascular system. To understand the transcriptional regulation of RANKL, we amplified and characterized a 1890 bp 5'-flanking sequence of human RANKL gene (-1782 bp to +108 bp relative to the transcription start site). Using a series of deletion mutations of the 1890 bp RANKL promoter, we identified a 72 bp region (-172 to -100 bp) mediating RANKL basal transcriptional activity. Sequence analysis revealed a putative E2F binding site within this 72 bp region in the human RANKL promoter. Overexpression of E2F1 increased RANKL promoter activity, while down-regulation of E2F1 expression by small interfering RNA decreased RANKL promoter activity. RT-PCR and enzyme linked immunosorbent assays (ELISA) further demonstrated that E2F1 induced the expression of RANKL. Electrophoretic gel mobility shift assays (EMSA) and antibody competition assays confirmed that E2F1 proteins bind to the consensus E2F binding site in the RANKL promoter. Mutation of the E2F consensus binding site in the RANKL promoter profoundly reduced the basal promoter activity and abolished the transcriptional modulation of RANKL by E2F1. These results suggest that E2F1 plays an important role in regulating RANKL transcription through binding to the E2F consensus binding site.

  8. Open Access Week Planning Materials 

    E-Print Network [OSTI]

    2012-01-01

    mammary epithelium (Seagroves et al. 2000). 16 The previous sections have described the importance of mesenchymal- or stromal-epithelial interactions in the specification, patterning, and growth of the mouse mammary gland, and these interactions.... Recently, Dr. Seagroves and colleagues evaluated the effect of C/ebpb loss on mammary development (Seagroves et al. 2000). In that study, they showed that in the absence of 21 C/ebpb, the distribution of Pgr positive cells resembles that found...

  9. KRFTWRK – Global Human Electricity

    E-Print Network [OSTI]

    Prohaska, Rainer

    2009-01-01

    in the generation of human power, where energy is gained byparticipant runs a virtual human power plant. Per every "by muscle-power and chemical processes of human bodies. For

  10. Human-machine interactions

    DOE Patents [OSTI]

    Forsythe, J. Chris (Sandia Park, NM); Xavier, Patrick G. (Albuquerque, NM); Abbott, Robert G. (Albuquerque, NM); Brannon, Nathan G. (Albuquerque, NM); Bernard, Michael L. (Tijeras, NM); Speed, Ann E. (Albuquerque, NM)

    2009-04-28

    Digital technology utilizing a cognitive model based on human naturalistic decision-making processes, including pattern recognition and episodic memory, can reduce the dependency of human-machine interactions on the abilities of a human user and can enable a machine to more closely emulate human-like responses. Such a cognitive model can enable digital technology to use cognitive capacities fundamental to human-like communication and cooperation to interact with humans.

  11. Jefferson Lab Human Resources

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

    Human Resources The Human Resources team is fully integrated with Jefferson Lab's mission, committed to providing quality customer service based on expertise, innovation and...

  12. Protective effects of pulmonary epithelial lining fluid on oxidative stress and DNA single-strand breaks caused by ultrafine carbon black, ferrous sulphate and organic extract of diesel exhaust particles

    SciTech Connect (OSTI)

    Chuang, Hsiao-Chi [School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan (China) [School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan (China); Cheng, Yi-Ling; Lei, Yu-Chen [Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan (China)] [Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan (China); Chang, Hui-Hsien [Institute of Environmental Health, College of Public Health, National Taiwan University, Taipei, Taiwan (China)] [Institute of Environmental Health, College of Public Health, National Taiwan University, Taipei, Taiwan (China); Cheng, Tsun-Jen, E-mail: tcheng@ntu.edu.tw [Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan (China) [Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan (China); Department of Public Health, College of Public Health, National Taiwan University, Taipei, Taiwan (China)

    2013-02-01

    Pulmonary epithelial lining fluid (ELF) is the first substance to make contact with inhaled particulate matter (PM) and interacts chemically with PM components. The objective of this study was to determine the role of ELF in oxidative stress, DNA damage and the production of proinflammatory cytokines following physicochemical exposure to PM. Ultrafine carbon black (ufCB, 15 nm; a model carbonaceous core), ferrous sulphate (FeSO{sub 4}; a model transition metal) and a diesel exhaust particle (DEP) extract (a model organic compound) were used to examine the acellular oxidative potential of synthetic ELF and non-ELF systems. We compared the effects of exposure to ufCB, FeSO{sub 4} and DEP extract on human alveolar epithelial Type II (A549) cells to determine the levels of oxidative stress, DNA single-strand breaks and interleukin-8 (IL-8) production in ELF and non-ELF systems. The effects of ufCB and FeSO{sub 4} on the acellular oxidative potential, cellular oxidative stress and DNA single-strand breakage were mitigated significantly by the addition of ELF, whereas there was no decrease following treatment with the DEP extract. There was no significant effect on IL-8 production following exposure to samples that were suspended in ELF/non-ELF systems. The results of the present study indicate that ELF plays an important role in the initial defence against PM in the pulmonary environment. Experimental components, such as ufCB and FeSO{sub 4}, induced the production of oxidative stress and led to DNA single-strand breaks, which were moderately prevented by the addition of ELF. These findings suggest that ELF plays a protective role against PM-driven oxidative stress and DNA damage. -- Highlights: ? To determine the role of ELF in ROS, DNA damage and IL-8 after exposure to PM. ? ufCB, FeSO{sub 4} and DEP extract were used to examine the protective effects of ELF. ? PM-driven oxidative stress and DNA single-strand breakage were mitigated by ELF. ? The findings suggest that ELF has a protective role against PM. ? The synthetic ELF system could reduce the use of animals in PM-driven ROS testing.

  13. human spaceflight and operations

    E-Print Network [OSTI]

    Anand, Mahesh

    1 human spaceflight and operations Lunar Lander human spaceflight and operations #12;2 human cooperation in exploration prim ary objective opportunity for investigations #12;3 human spaceflight No RHUs LANDING SITE South Polar Reliant on Solar Power generation + conventional thermal control LAUNCHER

  14. Programming with human computation

    E-Print Network [OSTI]

    Little, Greg (Danny Greg)

    2011-01-01

    Amazon's Mechanical Turk provides a programmatically accessible micro-task market, allowing a program to hire human workers. This has opened the door to a rich field of research in human computation where programs orchestrate ...

  15. Patenting Human Evolution

    E-Print Network [OSTI]

    Torrance, Andrew W.

    2008-06-01

    to thorough analysis and debate prior to the imminent arrival of human genetic enhancement technologies. Otherwise, patent law may drive human evolution in directions either unplanned - or worse - undesired....

  16. Cellular interactions via conditioned media induce in vivo nephron generation from tubular epithelial cells or mesenchymal stem cells

    SciTech Connect (OSTI)

    Machiguchi, Toshihiko Nakamura, Tatsuo

    2013-06-07

    Highlights: •We have attempted in vivo nephron generation using conditioned media. •Vascular and tubular cells do cross-talks on cell proliferation and tubular changes. •Tubular cells suppress these changes in mesenchymal stem cells. •Tubular cells differentiate mesenchymal stem cells into tubular cells. •Nephrons can be created from implanted tubular cells or mesenchymal stem cells. -- Abstract: There are some successful reports of kidney generation by utilizing the natural course of kidney development, namely, the use of an artificially treated metanephros, blastocyst or ureteric bud. Under a novel concept of cellular interactions via conditioned media (CMs), we have attempted in vivo nephron generation from tubular epithelial cells (TECs) or mesenchymal stem cells (MSCs). Here we used 10× CMs of vascular endothelial cells (VECs) and TECs, which is the first to introduce a CM into the field of organ regeneration. We first present stimulative cross-talks induced by these CMs between VECs and TECs on cell proliferation and morphological changes. In MSCs, TEC-CM suppressed these changes, however, induced cytokeratin expression, indicating the differentiation of MSCs into TECs. As a result, glomerular and tubular structures were created following the implantation of TECs or MSCs with both CMs. Our findings suggest that the cellular interactions via CMs might induce in vivo nephron generation from TECs or MSCs. As a promoting factor, CMs could also be applied to the regeneration of other organs and tissues.

  17. Mangiferin exerts antitumor activity in breast cancer cells by regulating matrix metalloproteinases, epithelial to mesenchymal transition, and ?-catenin signaling pathway

    SciTech Connect (OSTI)

    Li, Hongzhong; Huang, Jing; Yang, Bing; Xiang, Tingxiu; Yin, Xuedong; Peng, Weiyan; Cheng, Wei; Wan, Jingyuan; Luo, Fuling; Li, Hongyuan; Ren, Guosheng

    2013-10-01

    Although mangiferin which is a naturally occurring glucosylxanthone has exhibited promising anticancer activities, the detailed molecular mechanism of mangiferin on cancers still remains enigmatic. In this study, the anticancer activity of mangiferin was evaluated in breast cancer cell line-based in vitro and in vivo models. We showed that mangiferin treatment resulted in decreased cell viability and suppression of metastatic potential in breast cancer cells. Further mechanistic investigation revealed that mangiferin induced decreased matrix metalloproteinase (MMP)-7 and -9, and reversal of epithelial–mesenchymal transition (EMT). Moreover, it was demonstrated that mangiferin significantly inhibited the activation of ?-catenin pathway. Subsequent experiments showed that inhibiting ?-catenin pathway might play a central role in mangiferin-induced anticancer activity through modulation of MMP-7 and -9, and EMT. Consistent with these findings in vitro, the antitumor potential was also verified in mangiferin-treated MDA-MB-231 xenograft mice where significantly decreased tumor volume, weight and proliferation, and increased apoptosis were obtained, with lower expression of MMP-7 and -9, vimentin and active ?-catenin, and higher expression of E-cadherin. Taken together, our study suggests that mangiferin might be used as an effective chemopreventive agent against breast cancer. - Highlights: • Mangiferin inhibits growth and metastatic potential in breast cancer cells. • Mangiferin down-regulates MMP-7 and -9 in breast cancer cells. • Mangiferin induces the reversal of EMT in metastatic breast cancer cells. • Mangiferin inhibits the activation of ?-catenin pathway in breast cancer cells. • Inhibiting ?-catenin is responsible for the antitumor activity of mangiferin.

  18. Human Functional Brain Imaging

    E-Print Network [OSTI]

    Rambaut, Andrew

    Human Functional Brain Imaging 1990­2009 September 2011 Portfolio Review #12;2 | Portfolio Review: Human Functional Brain ImagingThe Wellcome Trust is a charity registered in England and Wales, no's role in supporting human functional brain imaging and have informed `our' speculations for the future

  19. Developments in Human Communication

    E-Print Network [OSTI]

    Thompson, Michael

    CMST 1B03 Developments in Human Communication: Part & Present Amanda Etches-Johnson Mills Research in Human Communication Session Outline 1. Finding Books Using MORRIS 2. Finding Journal Articles using: Developments in Human Communication What is MORRIS anyway? · MORRIS is McMaster's library catalogue · Shows

  20. Sandia Energy - Human Reliability Assessment

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

    Human Reliability Assessment Home Stationary Power Nuclear Fuel Cycle Nuclear Energy Safety Technologies Risk and Safety Assessment Human Reliability Assessment Human Reliability...

  1. Human Factors @ UB Fall 2010 Human Factors

    E-Print Network [OSTI]

    Krovi, Venkat

    . Outsourcing aviation maintenance: Hu- man factors implications, specifically for communications. C. Drury, K. Guy, C. Wenner. International Journal of Aviation Psychology, 2010, 20, 124 ­ 143. #12;2 Human Factors

  2. Apical polarity in three-dimensional culture systems: where to now?

    SciTech Connect (OSTI)

    Inman, J.L.; Bissell, Mina

    2010-01-21

    Delineation of the mechanisms that establish and maintain the polarity of epithelial tissues is essential to understanding morphogenesis, tissue specificity and cancer. Three-dimensional culture assays provide a useful platform for dissecting these processes but, as discussed in a recent study in BMC Biology on the culture of mammary gland epithelial cells, multiple parameters that influence the model must be taken into account.

  3. Jefferson Lab Human Resources

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

    JLab Diversity Policies 200 Human Resources 202 Equal Employment Opportunity and Affirmative Action 203 Employment 208 Employee Performance and Conduct 209 Staff Development 210...

  4. ORISE: Human Subjects Protection

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

    Human Subjects Protection The Oak Ridge Institute for Science and Education (ORISE) performs technical assessments to assist U.S. Department of Energy (DOE) laboratories involved...

  5. Structural studies of human Naked2: A biologically active intrinsically unstructured protein

    SciTech Connect (OSTI)

    Hu Tianhui; Krezel, Andrzej M.; Li Cunxi; Coffey, Robert J. . E-mail: robert.coffey@vanderbilt.edu

    2006-12-01

    Naked1 and 2 are two mammalian orthologs of Naked Cuticle, a canonical Wnt signaling antagonist in Drosophila. Naked2, but not Naked1, interacts with transforming growth factor-{alpha} (TGF{alpha}) and escorts TGF{alpha}-containing vesicles to the basolateral membrane of polarized epithelial cells. Full-length Naked2 is poorly soluble. Since most functional domains, including the Dishevelled binding region, EF-hand, vesicle recognition, and membrane targeting motifs, reside in the N-terminal half of the protein, we expressed and purified the first 217 residues of human Naked2 and performed a functional analysis of this fragment. Its circular dichroism (CD) and nuclear magnetic resonance (NMR) spectra showed no evidence of secondary and/or tertiary structure. The fragment did not bind calcium or zinc. These results indicate that the N-terminal half of Naked2 behaves as an intrinsically unstructured protein.

  6. The human genome project

    SciTech Connect (OSTI)

    Yager, T.D.; Zewert, T.E.; Hood, L.E. )

    1994-04-01

    The Human Genome Project (HGP) is a coordinated worldwide effort to precisely map the human genome and the genomes of selected model organisms. The first explicit proposal for this project dates from 1985 although its foundations (both conceptual and technological) can be traced back many years in genetics, molecular biology, and biotechnology. The HGP has matured rapidly and is producing results of great significance.

  7. HUMANITIES & SOCIAL SCIENCES

    E-Print Network [OSTI]

    Yang, Eui-Hyeok

    , The Role of Technology in Film, and even the History of Aeronautics-- in each case, at the request of the students. HUMANITIES & SOCIAL SCIENCES STEVENS INSTITUTE OF TECHNOLOGY www.stevens.edu MAJORS: + History in this ever- changing, fast-paced, technology-driven world. They also investigate how human in- novation

  8. Human Functional Brain Imaging

    E-Print Network [OSTI]

    Rambaut, Andrew

    Human Functional Brain Imaging 1990­2009 September 2011 Portfolio Review Summary Brain Imaging #12 Dale ­ one of our first Trustees. Understanding the brain remains one of our key strategic aims today three-fold: · to identify the key landmarks and influences on the human functional brain imaging

  9. Protection of Human Subjects

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

    2007-12-20

    The order establishes Department of Energy (DOE) procedures and responsibilities for implementing the policy and requirements set forth in 10 Code of Federal Regulations (CFR) Part 745, Protection of Human Subjects; and in DOE P 443.1A, Protection of Human Subjects, dated 12-20-07. Cancels DOE O 443.1. Canceled by DOE O 443.1B.

  10. Protection of Human Subjects

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

    2000-05-15

    To establish DOE procedures and responsibilities for implementing the policy and requirements set forth in 10 CFR Part 745, Protection of Human Subjects, ad in DOE P 443.1, Policy on the Protection of Human Subjects. Cancels DOE O 1300.3. Canceled by DOE O 443.1A.

  11. Department of Humanities Program in Technology and the Humanities

    E-Print Network [OSTI]

    ; ethics in the professions; history of art and architecture; humanizing technology; information seek- ingHumanities Department of Humanities Program in Technology and the Humanities Siegel Hall 218 3301 S' Graduate Program in Technology and Humanities prepares students for careers in emerging forms of technology

  12. Cell Motility and Deformability in the Pathogenesis of Lung Cancer

    E-Print Network [OSTI]

    Pagano, Paul Carmelo

    2015-01-01

    might prevent a cell from moving at full capacity because itfull malignant phenotype on human bronchial epithelial cells.full malignant phenotype on human bronchial epithelial cells.

  13. Special Issue on Human Computing

    E-Print Network [OSTI]

    Nijholt, Anton

    The seven articles in this special issue focus on human computing. Most focus on two challenging issues in human computing, namely, machine analysis of human behavior in group interactions and context-sensitive modeling.

  14. carleton.ca Human Rights

    E-Print Network [OSTI]

    Dawson, Jeff W.

    , including social movements, domestic legislation, international statutes, and human rights declarations the development of historical and contemporary social movements, and the effects of global capitalismcarleton.ca Human Rights #12;Human rights contribute, through theory and practice, to people

  15. Human Reliability Program Overview

    SciTech Connect (OSTI)

    Bodin, Michael

    2012-09-25

    This presentation covers the high points of the Human Reliability Program, including certification/decertification, critical positions, due process, organizational structure, program components, personnel security, an overview of the US DOE reliability program, retirees and academia, and security program integration.

  16. KRFTWRK – Global Human Electricity

    E-Print Network [OSTI]

    Prohaska, Rainer

    2009-01-01

    Power Network 2.1.1 Virtual Power Plants The Global Powernetwork, based on "Virtual Power Plants", called "VPP". A "participant runs a virtual human power plant. Per every "

  17. Protection of Human Subjects

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

    2007-12-20

    The Policy is to establish DOE-specific principles for the protection of human subjects involved in DOE research. Cancels DOE P 443.1. Canceled by DOE O 443.1B

  18. Human-spacesuit interaction :

    E-Print Network [OSTI]

    Hilbert, Alexandra Marie

    2015-01-01

    Extravehicular activities (EVA), or space walks, are a critical and complex aspect of human spaceflight missions. To prepare for safe and successful execution of the required tasks, astronauts undergo extensive training ...

  19. Protection of Human Subjects

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

    2000-05-15

    The purpose of this Policy is to establish DOE-specific policy for the protection of human subjects involved in DOE research. Canceled by DOE P 443.1A.

  20. Human Resource Management Delegation

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

    1996-06-28

    The notice is to clarifies and updates existing Human Resource Management Delegation Authorities and the levels to which they are delegated. Expired 6-28-97. Does not cancel any directives.

  1. The Evolution of Human Cooperation

    E-Print Network [OSTI]

    Gintis, Herbert; Doebeli, Michael; Flack, Jessica

    2012-01-01

    684 Gintis, H. 2011. The Evolution of Human Cooperation.misunderstandings about cultural evolution. Human Nat. 19,Feldman, M. , 1981. Cultural Evolution. Princeton University

  2. ORISE: Protecting Human Subjects Website

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

    Protecting Human Subjects Website Institutions that engage in human subjects research are required by federal policy to establish an institutional review board (IRB) to ensure that...

  3. The Human Genome From human genome to other

    E-Print Network [OSTI]

    Linial, Michal

    The Human Genome Project From human genome to other genomes and to gene function June 2000 From genome to health Structural Genomics initiative #12;What is the Human Genome Project? · U.S. govt that arise from genome research #12;The Human Genome Project Project began in 1990 as a $3 billion, 15-year

  4. Policy on Human Subjects Research Policy on Human Subjects

    E-Print Network [OSTI]

    Sridhar, Srinivas

    Policy on Human Subjects Research 10/15/2014 Policy on Human Subjects Research I. Purpose and Scope ethical standards for the protection of human subjects, consistent with the principles of the Nuremberg Code and the Belmont Report. Accordingly, the University has established the Office of Human Subject

  5. CONSTRUCTING VIRTUAL HUMAN LIFE SIMULATIONS

    E-Print Network [OSTI]

    Kallmann, Marcelo

    , Virtual Environments, Behavioral Animation, Object Interaction, Python. 1. INTRODUCTION Virtual humanCONSTRUCTING VIRTUAL HUMAN LIFE SIMULATIONS Marcelo Kallmann, Etienne de Sevin and Daniel Thalmann human life simulations. Our main goal is to have virtual human actors living and working autonomously

  6. Human MSH2 protein

    DOE Patents [OSTI]

    de la Chapelle, Albert (Helsingfors, FI); Vogelstein, Bert (Baltimore, MD); Kinzler, Kenneth W. (Baltimore, MD)

    1997-01-01

    The human MSH2 gene, responsible for hereditary non-polyposis colorectal cancer, was identified by virtue of its homology to the MutS class of genes, which are involved in DNA mismatch repair. The sequence of cDNA clones of the human gene are provided, and the sequence of the gene can be used to demonstrate the existence of germ line mutations in hereditary non-polyposis colorectal cancer (HNPCC) kindreds, as well as in replication error.sup.+ (RER.sup.+) tumor cells.

  7. Human MSH2 protein

    DOE Patents [OSTI]

    Chapelle, A. de la; Vogelstein, B.; Kinzler, K.W.

    1997-01-07

    The human MSH2 gene, responsible for hereditary non-polyposis colorectal cancer, was identified by virtue of its homology to the MutS class of genes, which are involved in DNA mismatch repair. The sequence of cDNA clones of the human gene are provided, and the sequence of the gene can be used to demonstrate the existence of germ line mutations in hereditary non-polyposis colorectal cancer (HNPCC) kindreds, as well as in replication error{sup +} (RER{sup +}) tumor cells. 19 figs.

  8. Human Genome: DOE Origins

    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 likeUniverse (JournalvivoHigh energyHighlandWorkshop-SummerHow is theHughHumanHuman Genome

  9. Adhesion gene regulation in mammary cell proliferation

    E-Print Network [OSTI]

    Lau, Eric HonYui

    2011-01-01

    Sciences, C.L.  Corning Ultra?Low Attachment Surface cells per well into ultra-low attachment 6 well plates (cells were grown in either ultra-low attachment plates or

  10. ENGINEERING AND HUMAN HEALTH

    E-Print Network [OSTI]

    Saskatchewan, University of

    ENGINEERING AND HUMAN HEALTH: FROM THE INSIDE OUT Engineering research on small scales could have huge health implications College of Engineering U N I V E R S I T Y O F S A S K ATC H E WA N CO L L E G 17 Alumni accolades College of Engineering THOROUGHUNIVERSITY OF SASKATCHEWAN COLLEGE OF ENGINEERING

  11. An EMT-Driven Alternative Splicing Program Occurs in Human Breast Cancer and Modulates Cellular Phenotype

    E-Print Network [OSTI]

    Shapiro, Irina M.

    Epithelial-mesenchymal transition (EMT), a mechanism important for embryonic development, plays a critical role during malignant transformation. While much is known about transcriptional regulation of EMT, alternative ...

  12. Texas Tech University Human Resources

    E-Print Network [OSTI]

    Rock, Chris

    to redevelop Texas Tech University's human resource functions into a high-performing human capital managementTexas Tech University Human Resources Strategic Plan January 1, 2014 - December 31, 2016 #12;2 Mission Texas Tech University is recognized as a premier institution and a workplace of choice. This work

  13. Understanding Human Experience Henry Kautz

    E-Print Network [OSTI]

    Kautz, Henry

    Understanding Human Experience Henry Kautz One of the earliest goals of research in artificial intelligence was to create systems that can interpret and understand day to day human experience. Early work on the goal of building systems that understand human experience. Each of the previous barriers is weakened

  14. Human Capital Management Accountability Program

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

    2008-08-01

    The Order establishes requirements, roles and responsibilities for the Human Capital Management Accountability Program (HCMAP) for human resources programs and personnel and ensures that human capital activities are regulatory and procedurally compliant with Federal statutes and Departmental policies. Does not cancel other directives.

  15. Sequential Causal Learning in Humans and Rats

    E-Print Network [OSTI]

    Lu, Hongjing; Rojas, Randall R.; Beckers, Tom; Yuille, Alan

    2008-01-01

    selection, to a human experiment that employed pretraining (group (white) in human experiment by Beckers et al. (2005).set used for the human experiments, we increased the

  16. Sequential Causal Learning in Humans and Rats

    E-Print Network [OSTI]

    Hongjing Lu; Randall R. Rojas; Tom Beckers; Alan Yuille

    2011-01-01

    selection, to a human experiment that employed pretraining (group (white) in human experiment by Beckers et al. (2005).set used for the human experiments, we increased the

  17. Allele-specific gene regulation in humans

    E-Print Network [OSTI]

    Maynard, Nathaniel David

    2008-01-01

    1 Introduction The Human Genome Project has provided thefrom clones and the human genome project have revealed thatVariation The Human Genome Project provided scientists with

  18. Project ATHENA creates surrogate human organ systems

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

    Project ATHENA creates surrogate human organ systems Project ATHENA creates surrogate human organ systems The development of miniature surrogate human organs, coupled with highly...

  19. Timescales of Massive Human Entrainment

    E-Print Network [OSTI]

    Fusaroli, Riccardo; Mislove, Alan; Paxton, Alexandra; Matlock, Teenie; Dale, Rick

    2014-01-01

    The past two decades have seen an upsurge of interest in the collective behaviors of complex systems composed of many agents. In this paper, we extend concepts of entrainment to the dynamics of human collective attention. We demonstrate that large scale human entrainment may hold across a number of distinct scales, in an exquisitely time locked fashion. Using a large scale database of human communication data, we analyze and describe three different time scales of human entrainment in electronic media. We sought a distinct shared experience that provided a test bed for quantifying large scale human entrainment. We conducted a detailed investigation of the real time unfolding of human entrainment, as expressed by the content and patterns of hundreds of thousands of messages on Twitter, during the 2012 US presidential debates. By time locking these data sources, we quantify the real time impact of the debate on human attention. We show that social behavior covaries second by second to the interactional dynamics...

  20. Human Genome Program

    SciTech Connect (OSTI)

    Not Available

    1993-01-01

    The DOE Human Genome program has grown tremendously, as shown by the marked increase in the number of genome-funded projects since the last workshop held in 1991. The abstracts in this book describe the genome research of DOE-funded grantees and contractors and invited guests, and all projects are represented at the workshop by posters. The 3-day meeting includes plenary sessions on ethical, legal, and social issues pertaining to the availability of genetic data; sequencing techniques, informatics support; and chromosome and cDNA mapping and sequencing.

  1. HUMAN MACHINE COOPERATIVE TELEROBOTICS

    SciTech Connect (OSTI)

    William R. Hamel; Spivey Douglass; Sewoong Kim; Pamela Murray; Yang Shou; Sriram Sridharan; Ge Zhang; Scott Thayer; Rajiv V. Dubey

    2003-06-30

    The remediation and deactivation and decommissioning (D&D) of nuclear waste storage tanks using telerobotics is one of the most challenging tasks faced in environmental cleanup. Since a number of tanks have reached the end of their design life and some of them have leaks, the unstructured, uncertain and radioactive environment makes the work inefficient and expensive. However, the execution time of teleoperation consumes ten to hundred times that of direct contact with an associated loss in quality. Thus, a considerable effort has been expended to improve the quality and efficiency of telerobotics by incorporating into teleoperation and robotic control functions such as planning, trajectory generation, vision, and 3-D modeling. One example is the Robot Task Space Analyzer (RTSA), which has been developed at the Robotics and Electromechanical Systems Laboratory (REMSL) at the University of Tennessee in support of the D&D robotic work at the Oak Ridge National Laboratory and the National Energy Technology Laboratory. This system builds 3-D models of the area of interest in task space through automatic image processing and/or human interactive manual modeling. The RTSA generates a task plan file, which describes the execution of a task including manipulator and tooling motions. The high level controller of the manipulator interprets the task plan file and executes the task automatically. Thus, if the environment is not highly unstructured, a tooling task, which interacts with environment, will be executed in the autonomous mode. Therefore, the RTSA not only increases the system efficiency, but also improves the system reliability because the operator will act as backstop for safe operation after the 3-D models and task plan files are generated. However, unstructured conditions of environment and tasks necessitate that the telerobot operates in the teleoperation mode for successful execution of task. The inefficiency in the teleoperation mode led to the research described as Human Machine Cooperative Telerobotics (HMCTR). The HMCTR combines the telerobot with robotic control techniques to improve the system efficiency and reliability in teleoperation mode. In this topical report, the control strategy, configuration and experimental results of Human Machines Cooperative Telerobotics (HMCTR), which modifies and limits the commands of human operator to follow the predefined constraints in the teleoperation mode, is described. The current implementation is a laboratory-scale system that will be incorporated into an engineering-scale system at the Oak Ridge National Laboratory in the future.

  2. Human portable preconcentrator system

    DOE Patents [OSTI]

    Linker, Kevin L. (Albuquerque, NM); Bouchier, Francis A. (Albuquerque, NM); Hannum, David W. (Albuquerque, NM); Rhykerd, Jr., Charles L. (Albuquerque, NM)

    2003-01-01

    A preconcentrator system and apparatus suited to human portable use wherein sample potentially containing a target chemical substance is drawn into a chamber and through a pervious screen. The screen is adapted to capture target chemicals and then, upon heating, to release those chemicals into the chamber. Chemicals captured and then released in this fashion are then carried to a portable chemical detection device such as a portable ion mobility spectrometer. In the preferred embodiment, the means for drawing sample into the chamber comprises a reversible fan which, when operated in reverse direction, creates a backpressure that facilitates evolution of captured target chemicals into the chamber when the screen is heated.

  3. ORISE: Protecting Human Subjects

    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 WebQuantity ofkandz-cm11 Outreach Home Room NewsInformationJesseworkSURVEY UNIVERSE TheForensicPerformanceProtecting Human Subjects

  4. Proliferation of rhesus ovarian surface epithelial cells in culture: Lack of mitogenic response to steroid or gonadotropic hormones

    SciTech Connect (OSTI)

    Wright, Jay W.; Toth-Fejel, Suellen; Stouffer, Richard L.; Rodland, Karin D.

    2002-06-30

    Ovarian cancer is the most lethal gynecological cancer and approximately 90% of ovarian cancers derive from the ovarian surface epithelium (OSE), yet the biology of the OSE is poorly understood. Factors associated with increased risk of non-hereditary ovarian cancer include the formation of inclusion cysts, effects of reproductive hormones cytokeratin, vimentin, N-cadherin, E-cadherin, estrogen receptor-a, and progesterone receptor. We show that these cells activate MAP Kinase and proliferate in response to extracellular calcium, as do human and rat OSE. In contrast, the gonadotropic hormones FSH (4-400 IU/L), LH (8.5-850 IU/l), and hCG (10-1000 IU/l) fail to stimulate proliferation. We find that concentrations of progesterone and estrogen normally present in follicles just prior to ovulation ( ~1000 ng/ml) significantly decrease the number of mitotically active RhOSE cells as determined by PCNA labelling, total cell count, and 3H-thymidine uptake, while lower steroid concentrations have no effect.

  5. PIA - Human Resources - Personal Information Change Request ...

    Energy Savers [EERE]

    Human Resources - Personal Information Change Request - Idaho National Engineering Laboratory PIA - Human Resources - Personal Information Change Request - Idaho National...

  6. Human subjects research handbook: Protecting human research subjects. Second edition

    SciTech Connect (OSTI)

    NONE

    1996-01-30

    This handbook serves as a guide to understanding and implementing the Federal regulations and US DOE Orders established to protect human research subjects. Material in this handbook is directed towards new and continuing institutional review board (IRB) members, researchers, institutional administrators, DOE officials, and others who may be involved or interested in human subjects research. It offers comprehensive overview of the various requirements, procedures, and issues relating to human subject research today.

  7. Human portable preconcentrator system

    DOE Patents [OSTI]

    Linker, Kevin L.; Brusseau, Charles A.; Hannum, David W.; Puissant, James G.; Varley, Nathan R.

    2003-08-12

    A preconcentrator system and apparatus suited to human portable use wherein sample potentially containing a target chemical substance is drawn into a chamber and through a pervious screen. The screen is adapted to capture target chemicals and then, upon heating, to release those chemicals into the chamber. Chemicals captured and then released in this fashion are then carried to a portable chemical detection device such as a portable ion mobility spectrometer. In the preferred embodiment, the means for drawing sample into the chamber comprises a reversible fan which, when operated in reverse direction, creates a backpressure that facilitates evolution of captured target chemicals into the chamber when the screen is heated. The screen can be positioned directly in front of the detector prior to heating to improve detection capability.

  8. Human-computer interface

    DOE Patents [OSTI]

    Anderson, Thomas G.

    2004-12-21

    The present invention provides a method of human-computer interfacing. Force feedback allows intuitive navigation and control near a boundary between regions in a computer-represented space. For example, the method allows a user to interact with a virtual craft, then push through the windshield of the craft to interact with the virtual world surrounding the craft. As another example, the method allows a user to feel transitions between different control domains of a computer representation of a space. The method can provide for force feedback that increases as a user's locus of interaction moves near a boundary, then perceptibly changes (e.g., abruptly drops or changes direction) when the boundary is traversed.

  9. Human Reliability Program Workshop

    SciTech Connect (OSTI)

    Landers, John; Rogers, Erin; Gerke, Gretchen

    2014-05-18

    A Human Reliability Program (HRP) is designed to protect national security as well as worker and public safety by continuously evaluating the reliability of those who have access to sensitive materials, facilities, and programs. Some elements of a site HRP include systematic (1) supervisory reviews, (2) medical and psychological assessments, (3) management evaluations, (4) personnel security reviews, and (4) training of HRP staff and critical positions. Over the years of implementing an HRP, the Department of Energy (DOE) has faced various challenges and overcome obstacles. During this 4-day activity, participants will examine programs that mitigate threats to nuclear security and the insider threat to include HRP, Nuclear Security Culture (NSC) Enhancement, and Employee Assistance Programs. The focus will be to develop an understanding of the need for a systematic HRP and to discuss challenges and best practices associated with mitigating the insider threat.

  10. Editorial: The Human Genome Project

    E-Print Network [OSTI]

    Crawford, Michael H.; Baer, A.S.; Hall, R.; Omenn, G.S.; Thomson, G.J.; Wilson, A.C.

    1990-08-01

    iv / Editorial: The Human Genome Project Dear readers, The last few decades have seen a number of exciting developments in genetics. First, Watson and Crick broke the genetic code; since then, tech-nologic and methodologic breakthroughs have... permitted the study and direct manipulation of our DNA. Now there is an international ground swell to map and sequence the human genome. The Bush administration had originally requested $128 million in last year's budget for the Human Genome Project. However...

  11. Protection of Human Research Subjects

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

    2015-07-20

    Changes are made to harmonize the definitions in this Order with those in the Federal regulations for the protection of human subjects (10 CFR Part 745), specifically, splitting the definition "human subject research" into "research" and "human subject," and adopting, verbatim, the definitions of "research" and "human subject" from 10 CFR Part 745 and adding the definition of "generalizable," since the determination of whether a project is "research" in 10 CFR Part 745 hinges on whether the work being conducted is generalizable. Small corrections and updates have been made to the references, links, and organization titles.

  12. Quantum physics and human values

    SciTech Connect (OSTI)

    Stapp, H.P.

    1989-09-01

    This report discusses the following concepts: the quantum conception of nature; the quantum conception of man; and the impact upon human values. (LSP).

  13. ORISE: Human Subjects Research Database

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

    in support of the HSRD database: Database maintenance Federal Internet server access Software development Quality assurancequality control Project assistance Human Subjects...

  14. mir-30d Regulates multiple genes in the autophagy pathway and impairs autophagy process in human cancer cells

    SciTech Connect (OSTI)

    Yang, Xiaojun; Department of General Surgery, Gansu Provincial Hospital, Lanzhou, Gansu 710000 ; Zhong, Xiaomin; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011 ; Tanyi, Janos L.; Shen, Jianfeng; Xu, Congjian; Gao, Peng; Zheng, Tim M.; DeMichele, Angela; Zhang, Lin

    2013-02-15

    Highlights: ? Gene set enrichment analysis indicated mir-30d might regulate the autophagy pathway. ? mir-30d represses the expression of BECN1, BNIP3L, ATG12, ATG5 and ATG2. ? BECN1, BNIP3L, ATG12, ATG5 and ATG2 are direct targets of mir-30d. ? mir-30d inhibits autophagosome formation and LC3B-I conversion to LC3B-II. ? mir-30d regulates the autophagy process. -- Abstract: In human epithelial cancers, the microRNA (miRNA) mir-30d is amplified with high frequency and serves as a critical oncomir by regulating metastasis, apoptosis, proliferation, and differentiation. Autophagy, a degradation pathway for long-lived protein and organelles, regulates the survival and death of many cell types. Increasing evidence suggests that autophagy plays an important function in epithelial tumor initiation and progression. Using a combined bioinformatics approach, gene set enrichment analysis, and miRNA target prediction, we found that mir-30d might regulate multiple genes in the autophagy pathway including BECN1, BNIP3L, ATG12, ATG5, and ATG2. Our further functional experiments demonstrated that the expression of these core proteins in the autophagy pathway was directly suppressed by mir-30d in cancer cells. Finally, we showed that mir-30d regulated the autophagy process by inhibiting autophagosome formation and LC3B-I conversion to LC3B-II. Taken together, our results provide evidence that the oncomir mir-30d impairs the autophagy process by targeting multiple genes in the autophagy pathway. This result will contribute to understanding the molecular mechanism of mir-30d in tumorigenesis and developing novel cancer therapy strategy.

  15. A human breast cell model of pre-invasive to invasive transition

    SciTech Connect (OSTI)

    Bissell, Mina J; Rizki, Aylin; Weaver, Valerie M.; Lee, Sun-Young; Rozenberg, Gabriela I.; Chin, Koei; Myers, Connie A.; Bascom, Jamie L.; Mott, Joni D.; Semeiks, Jeremy R.; Grate, Leslie R.; Mian, I. Saira; Borowsky, Alexander D.; Jensen, Roy A.; Idowu, Michael O.; Chen, Fanqing; Chen, David J.; Petersen, Ole W.; Gray, Joe W.; Bissell, Mina J.

    2008-03-10

    A crucial step in human breast cancer progression is the acquisition of invasiveness. There is a distinct lack of human cell culture models to study the transition from pre-invasive to invasive phenotype as it may occur 'spontaneously' in vivo. To delineate molecular alterations important for this transition, we isolated human breast epithelial cell lines that showed partial loss of tissue polarity in three-dimensional reconstituted-basement membrane cultures. These cells remained non-invasive; however, unlike their non-malignant counterparts, they exhibited a high propensity to acquire invasiveness through basement membrane in culture. The genomic aberrations and gene expression profiles of the cells in this model showed a high degree of similarity to primary breast tumor profiles. The xenograft tumors formed by the cell lines in three different microenvironments in nude mice displayed metaplastic phenotypes, including squamous and basal characteristics, with invasive cells exhibiting features of higher grade tumors. To find functionally significant changes in transition from pre-invasive to invasive phenotype, we performed attribute profile clustering analysis on the list of genes differentially expressed between pre-invasive and invasive cells. We found integral membrane proteins, transcription factors, kinases, transport molecules, and chemokines to be highly represented. In addition, expression of matrix metalloproteinases MMP-9,-13,-15,-17 was up regulated in the invasive cells. Using siRNA based approaches, we found these MMPs to be required for the invasive phenotype. This model provides a new tool for dissection of mechanisms by which pre-invasive breast cells could acquire invasiveness in a metaplastic context.

  16. Integrated design environment for human performance and human reliability analysis

    SciTech Connect (OSTI)

    Nelson, W.R.

    1997-05-01

    Work over the last few years at the Idaho National Engineering and Environmental Laboratory (INEEL) has included a major focus on applying human performance and human reliability knowledge and methods as an integral element of system design and development. This work has been pursued in programs in a wide variety of technical domains, beginning with nuclear power plant operations. Since the mid-1980`s the laboratory has transferred the methods and tools developed in the nuclear domain to military weapons systems and aircraft, offshore oil and shipping operations, and commercial aviation operations and aircraft design. Through these diverse applications the laboratory has developed an integrated approach and framework for application of human performance analysis, human reliability analysis (HRA), operational data analysis, and simulation studies of human performance to the design and development of complex systems. This approach was recently tested in the NASA Advanced Concepts Program {open_quotes}Structured Human Error Analysis for Aircraft Design.{close_quotes} This program resulted in the prototype software tool THEA (Tool for Human Error Analysis) for incorporating human error analysis in the design of commercial aircraft, focusing on airplane maintenance tasks. Current effort is directed toward applying this framework to the development of advanced Air Traffic Management (ATM) systems as part of NASA`s Advanced Air Transportation Technologies (AATT) program. This paper summarizes the approach, describes recent and current applications in commercial aviation, and provides perspectives on how the approach could be utilized in the nuclear power industry.

  17. Simulating human behavior for national security human interactions.

    SciTech Connect (OSTI)

    Bernard, Michael Lewis; Hart, Dereck H.; Verzi, Stephen J.; Glickman, Matthew R.; Wolfenbarger, Paul R.; Xavier, Patrick Gordon

    2007-01-01

    This 3-year research and development effort focused on what we believe is a significant technical gap in existing modeling and simulation capabilities: the representation of plausible human cognition and behaviors within a dynamic, simulated environment. Specifically, the intent of the ''Simulating Human Behavior for National Security Human Interactions'' project was to demonstrate initial simulated human modeling capability that realistically represents intra- and inter-group interaction behaviors between simulated humans and human-controlled avatars as they respond to their environment. Significant process was made towards simulating human behaviors through the development of a framework that produces realistic characteristics and movement. The simulated humans were created from models designed to be psychologically plausible by being based on robust psychological research and theory. Progress was also made towards enhancing Sandia National Laboratories existing cognitive models to support culturally plausible behaviors that are important in representing group interactions. These models were implemented in the modular, interoperable, and commercially supported Umbra{reg_sign} simulation framework.

  18. History of Humanities Associate Editors

    E-Print Network [OSTI]

    Mateo, Jill M.

    History of Humanities Associate Editors Rick Altman, Film Studies, University of Iowa Carolyn History of Science and Humanities, Utrecht University David Cram, History of Linguistics, University, Max Planck Institute for the History of Science Caroline van Eck, Art and Architecture, Leiden

  19. The human activity of visualization

    E-Print Network [OSTI]

    Wright, Dawn Jeannine

    Griffin et al 2006 #12;Human-Computer Interaction: Software of the Mind each user has a setThe human activity of visualization cultural and psychological factors in representation; Gibbon 1998; Marcus 2000) conventions and metaphors of Westerners may not hold worldwide colors

  20. The Human Genome Diversity Project

    SciTech Connect (OSTI)

    Cavalli-Sforza, L.

    1994-12-31

    The Human Genome Diversity Project (HGD Project) is an international anthropology project that seeks to study the genetic richness of the entire human species. This kind of genetic information can add a unique thread to the tapestry knowledge of humanity. Culture, environment, history, and other factors are often more important, but humanity`s genetic heritage, when analyzed with recent technology, brings another type of evidence for understanding species` past and present. The Project will deepen the understanding of this genetic richness and show both humanity`s diversity and its deep and underlying unity. The HGD Project is still largely in its planning stages, seeking the best ways to reach its goals. The continuing discussions of the Project, throughout the world, should improve the plans for the Project and their implementation. The Project is as global as humanity itself; its implementation will require the kinds of partnerships among different nations and cultures that make the involvement of UNESCO and other international organizations particularly appropriate. The author will briefly discuss the Project`s history, describe the Project, set out the core principles of the Project, and demonstrate how the Project will help combat the scourge of racism.

  1. Acquired tolerance in cadmium-adapted lung epithelial cells: Roles of the c-Jun N-terminal kinase signaling pathway and basal level of metallothionein

    SciTech Connect (OSTI)

    Lau, Andy T.Y. [Department of Anatomy, Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong (China); Zhang Jian [Department of Biochemistry, University of Vermont College of Medicine, Burlington, VT 05405 (United States); Chiu, J.-F. [Department of Anatomy, Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong (China) and Department of Biochemistry, University of Vermont College of Medicine, Burlington, VT 05405 (United States)]. E-mail: jfchiu@hkucc.hku.hk

    2006-08-15

    Cadmium-resistant cells were developed in our laboratory with rat lung epithelial cells (LECs) by stepwise exposure of LECs to cadmium chloride from 1 {mu}M to 20 {mu}M after 20 passages. To investigate the Cd-resistant phenotype in a long-term perspective, cadmium-resistant cells adapted to 20 {mu}M cadmium (Cd{sup R}) were then cultured in the absence of cadmium for various passages [Cd{sup R}(-n)]. All these adapted cells were significantly protected from cadmium toxicity as compared to parental cadmium-sensitive LECs (Cd{sup S}). The cadmium-resistant phenotype of adapted cells was relatively stable in the absence of cadmium for as long as 40 passages. Basal mRNA level of metallothionein-1 (MT-1) was dramatically higher in Cd{sup R} than in Cd{sup R}(-), which may account for the higher Cd-resistance of Cd{sup R} than Cd{sup R}(-). MT-1 mRNA level decreased drastically in Cd{sup R} after cadmium removal, suggesting that the high basal level of MT-1 in Cd{sup R} may be only partially responsible for cadmium-resistance. Treatment of cells with high levels of cadmium resulted in decreased phosphorylation of c-Jun N-terminal kinase (JNK1/2) in adapted cells than in sensitive cells and this cadmium-induced JNK activity was blocked by JNK inhibitor II, SP600125. Ro318220, a strong activator of JNK, reverted cadmium-sensitive phenotype in adapted cells. Taken together, our results suggest that during cadmium adaptation, cells develop tolerance to cell death, generally due to perturbation of the JNK signaling pathway and the nonresponsiveness of JNK phosphorylation is critical for the Cd-tolerance in these cells.

  2. Human retinoblastoma gene

    SciTech Connect (OSTI)

    Bookstein, R.; Lee, E.Y.H.P.; Peccei, A.; Lee, W.H. (Dept. of Pathology M-012 and Center for Molecular Genetics, Univ. of California, San Diego, La Jolla, CA (US))

    1989-04-01

    Mutational inactivation of the retinoblastoma (RB) gene is considered a fundamental event in the formation of several types of human cancer. A substantial proportion of RB gene mutations are partial or complete deletions that extend an unknown distance beyond one or both ends of the gene. To provide a framework for measuring the extent of these deletions, the authors have constructed a long-range restriction map of SfiI sites spanning 850 kilobases around the RB gene. This map was applied in a molecular analysis of RB gene deletion in breast cancer cell line MB468. A previous study of this cell line demonstrated deletion of the entire RB gene except for exons 1 and 2. Genomic clones containing the deletion junction were isolated from a library made from MB468 DNA. A probe obtained from the far side of the deletion junction was used to localize and clone the unknown 3' endpoint, demonstrating that the chromosomal mutation in this case was a simple deletion spanning 200 kilobases. Sequence analysis of the deletion junction indicated a conservative deletion with no loss or gain of nucleotides. The deletion endpoints had no sequence homology to each other or to any repetitive sequence family, such as Alu, so the recombination event was illegitimate. Structural analysis of this and other RB gene deletions is important for understanding molecular mechanisms of recessive oncogenesis.

  3. Human Reliability Analysis for Digital Human-Machine Interfaces

    SciTech Connect (OSTI)

    Ronald L. Boring

    2014-06-01

    This paper addresses the fact that existing human reliability analysis (HRA) methods do not provide guidance on digital human-machine interfaces (HMIs). Digital HMIs are becoming ubiquitous in nuclear power operations, whether through control room modernization or new-build control rooms. Legacy analog technologies like instrumentation and control (I&C) systems are costly to support, and vendors no longer develop or support analog technology, which is considered technologically obsolete. Yet, despite the inevitability of digital HMI, no current HRA method provides guidance on how to treat human reliability considerations for digital technologies.

  4. The effect of low dose ionizing radiation on homeostasis and functional integrity in an organotypic human skin model

    SciTech Connect (OSTI)

    von Neubeck, Claere; Geniza, Matthew; Kauer, Paula M.; Robinson, Joseph E.; Chrisler, William B.; Sowa, Marianne B.

    2015-05-01

    Outside the protection of earth’s atmosphere, astronauts are exposed to low doses of high linear energy transfer (LET) radiation. Future NASA plans for deep space missions or a permanent settlement on the moon are limited by the health risks associated with space radiation exposures. There is a paucity of direct epidemiological data for low dose exposures to space radiation-relevant high LET ions. Health risk models are used to estimate the risk for such exposures, though these models are based on high dose experiments. There is increasing evidence, however, that low and high dose exposures result in different signaling events at the molecular level, and may involve different response mechanisms. Further, despite their low abundance, high LET particles have been identified as the major contributor to health risk during manned space flight. The human skin is exposed in every external radiation scenario, making it an ideal epithelial tissue model in which to study radiation induced effects. Here, we exposed an in vitro three dimensional (3-D) human organotypic skin tissue model to low doses of high LET oxygen (O), silicon (Si) and iron (Fe) ions. We measured proliferation and differentiation profiles in the skin tissue and examined the integrity of the skin’s barrier function. We discuss the role of secondary particles in changing the proportion of cells receiving a radiation dose, emphasizing the possible impact on radiation-induced health issues in astronauts.

  5. Structural elucidation of the hormonal inhibition mechanism of the bile acid cholate on human carbonic anhydrase II

    SciTech Connect (OSTI)

    Boone, Christopher D. [University of Florida, PO Box 100267, Gainesville, FL 32610 (United States); Tu, Chingkuang [University of Florida, PO Box 100245, Gainesville, FL 32610 (United States); McKenna, Robert, E-mail: rmckenna@ufl.edu [University of Florida, PO Box 100267, Gainesville, FL 32610 (United States)

    2014-06-01

    The structure of human carbonic anhydrase II in complex with cholate has been determined to 1.54 Å resolution. Elucidation of the novel inhibition mechanism of cholate will aid in the development of a nonsulfur-containing, isoform-specific therapeutic agent. The carbonic anhydrases (CAs) are a family of mostly zinc metalloenzymes that catalyze the reversible hydration/dehydration of CO{sub 2} into bicarbonate and a proton. Human isoform CA II (HCA II) is abundant in the surface epithelial cells of the gastric mucosa, where it serves an important role in cytoprotection through bicarbonate secretion. Physiological inhibition of HCA II via the bile acids contributes to mucosal injury in ulcerogenic conditions. This study details the weak biophysical interactions associated with the binding of a primary bile acid, cholate, to HCA II. The X-ray crystallographic structure determined to 1.54 Å resolution revealed that cholate does not make any direct hydrogen-bond interactions with HCA II, but instead reconfigures the well ordered water network within the active site to promote indirect binding to the enzyme. Structural knowledge of the binding interactions of this nonsulfur-containing inhibitor with HCA II could provide the template design for high-affinity, isoform-specific therapeutic agents for a variety of diseases/pathological states, including cancer, glaucoma, epilepsy and osteoporosis.

  6. Human genome. 1993 Program report

    SciTech Connect (OSTI)

    Not Available

    1994-03-01

    The purpose of this report is to update the Human Genome 1991-92 Program Report and provide new information on the DOE genome program to researchers, program managers, other government agencies, and the interested public. This FY 1993 supplement includes abstracts of 60 new or renewed projects and listings of 112 continuing and 28 completed projects. These two reports, taken together, present the most complete published view of the DOE Human Genome Program through FY 1993. Research is progressing rapidly toward 15-year goals of mapping and sequencing the DNA of each of the 24 different human chromosomes.

  7. Personnel / Human Resource Management MGTK 302 Online

    E-Print Network [OSTI]

    Diestel, Geoff

    competencies: Strategic Human Resource Management: Knowledge of strategic management concepts (strategyPersonnel / Human Resource Management MGTK 302 Online Fall 2014 YOUR INSTRUCTOR Name: Ms. Amanda of human resource management; relationship between personnel management and organizations' emerging role

  8. Essays on Human Development and Public Policy

    E-Print Network [OSTI]

    Raykar, Neha

    2011-01-01

    Statistics released by the Ministry of Human Resource Development of IndiaStatistics released by the Ministry of Human Resource Development of India.India (1991), and National Human Development Report (2001). The descriptive statistics

  9. Engineering humanized mice for improved hematopoietic reconstitution

    E-Print Network [OSTI]

    Drake, Adam

    Humanized mice are immunodeficient animals engrafted with human hematopoietic stem cells that give rise to various lineages of human blood cells throughout the life of the mouse. This article reviews recent advances in the ...

  10. Human rights: in the real world 

    E-Print Network [OSTI]

    Brown, Abbe

    2006-01-01

    An analysis of the relevance of human rights to litigation and exploitation of intellectual property rights in the UK. The paper considers the impact of the Human Rights Act 1998, and other human rights instruments, ...

  11. Guest editorial: Special issue on human computing

    E-Print Network [OSTI]

    Pantic, Maja

    The seven articles in this special issue focus on human computing. Most focus on two challenging issues in human computing, namely, machine analysis of human behavior in group interactions and context-sensitive modeling.

  12. Rethinking optimal control of human movements

    E-Print Network [OSTI]

    Huh, Dongsung

    2012-01-01

    movements”. In: Human muscle power, pp. 131–150. Todorov,movements”. In: Human muscle power, pp. 131–150. Todorov,movements”. In: Human muscle power, pp. 131–150. Sutton, GG

  13. Human Genome Education Program

    SciTech Connect (OSTI)

    Richard Myers; Lane Conn

    2000-05-01

    The funds from the DOE Human Genome Program, for the project period 2/1/96 through 1/31/98, have provided major support for the curriculum development and field testing efforts for two high school level instructional units: Unit 1, ''Exploring Genetic Conditions: Genes, Culture and Choices''; and Unit 2, ''DNA Snapshots: Peaking at Your DNA''. In the original proposal, they requested DOE support for the partial salary and benefits of a Field Test Coordinator position to: (1) complete the field testing and revision of two high school curriculum units, and (2) initiate the education of teachers using these units. During the project period of this two-year DOE grant, a part-time Field-Test Coordinator was hired (Ms. Geraldine Horsma) and significant progress has been made in both of the original proposal objectives. Field testing for Unit 1 has occurred in over 12 schools (local and non-local sites with diverse student populations). Field testing for Unit 2 has occurred in over 15 schools (local and non-local sites) and will continue in 12-15 schools during the 96-97 school year. For both curricula, field-test sites and site teachers were selected for their interest in genetics education and in hands-on science education. Many of the site teachers had no previous experience with HGEP or the unit under development. Both of these first-year biology curriculum units, which contain genetics, biotechnology, societal, ethical and cultural issues related to HGP, are being implemented in many local and non-local schools (SF Bay Area, Southern California, Nebraska, Hawaii, and Texas) and in programs for teachers. These units will reach over 10,000 students in the SF Bay Area and continues to receive support from local corporate and private philanthropic organizations. Although HGEP unit development is nearing completion for both units, data is still being gathered and analyzed on unit effectiveness and student learning. The final field testing result from this analysis will contribute to the final revisions of each unit during the second-year of this grant.

  14. Biomechanics of the human chorioamnion

    E-Print Network [OSTI]

    Prévost, Thibault Philippe

    2006-01-01

    The human fetal membrane, namely the chorioamnion, is the structural soft tissue retaining the amniotic fluid and the fetus during pregnancy. Its biomechanical integrity is crucial for maintaining a healthy gestation and ...

  15. Robot Manipulation in Human Environments

    E-Print Network [OSTI]

    Edsinger, Aaron

    2007-01-16

    Human environments present special challenges for robot manipulation. They are often dynamic, difficult to predict, and beyond the control of a robot engineer. Fortunately, many characteristics of these settings can be ...

  16. Robot manipulation in human environments

    E-Print Network [OSTI]

    Edsinger, Aaron Ladd, 1972-

    2007-01-01

    Human environments present special challenges for robot manipulation. They are often dynamic, difficult to predict, and beyond the control of a robot engineer. Fortunately, many characteristics of these settings can be ...

  17. Contractor Human Resource Management Programs

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

    1996-09-30

    The purpose of this directive is to establish Department of Energy (DOE) responsibilities and requirements for the management and oversight of contractor Human Resource Management (HR) programs. Chg 1, 5-8-98; Chg 2, 11-22-09

  18. Contractor Human Resource Management Programs

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

    1996-09-30

    The purpose of this directive is to establish Department of Energy (DOE) responsibilities and requirements for the management and oversight of contractor Human Resource Management (HR) programs. Chg 1, 5-8-98; Chg 2, 11-22-09.

  19. Reservations to human rights treaties 

    E-Print Network [OSTI]

    McCall-Smith, Kasey Lowe

    2012-06-26

    This thesis examines the default application of the 1969 Vienna Convention on the Law of Treaties reservation rules to reservations to human rights treaties. The contemporary practice of formulating reservations allows ...

  20. Human Factors of Reporting Systems

    E-Print Network [OSTI]

    Johnson, C.W.

    Johnson,C.W. P. Carayon (ed.), A Handbook of Human Factors and Ergonomics in Healthcare and Patient Safety, Lawrence Erlbaum, London, UK. pp 715-750 Lawrence Erlbaum Associates

  1. Ideal Observers for Detecting Human Motion: Correspondence Noise

    E-Print Network [OSTI]

    HongJing Lo; Alan Yuille

    2011-01-01

    psychophysical experiments showed that human performance waspsychophysics experiments to determine how humans performedpsychophysical experiments which are consistent with humans

  2. Protection of Human Research Subjects

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

    2009-12-09

    The order establishes Department of Energy (DOE) procedures and responsibilities for implementing the policy and requirements set forth in Title 10 Code of Federal Regulations (CFR) Part 745, Protection of Human Subjects, 45 CFR Part 46, and the Secretarial Policy Memorandum on Military or Intelligence-Related Human Subject Research, December 9, 2009. Supersedes DOE O 443.1A and DOE P 443.1A.

  3. The Politics of Human Rights in Argentina

    E-Print Network [OSTI]

    Brysk, Alison

    2013-01-01

    Valente,  Marcela.  “Argentina’s  Biggest  Human  Rights  Motor  is  Linked  to  Argentina’s  ‘Dirty  War’”.   New  fortune  of  my  heart.   Argentina's  1985  human  rights  

  4. Cholesterol enhances amyloid {beta} deposition in mouse retina by modulating the activities of A{beta}-regulating enzymes in retinal pigment epithelial cells

    SciTech Connect (OSTI)

    Wang, Jiying [Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519 (Japan)] [Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519 (Japan); Ohno-Matsui, Kyoko, E-mail: k.ohno.oph@tmd.ac.jp [Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519 (Japan)] [Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519 (Japan); Morita, Ikuo [Section of Cellular Physiological Chemistry, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519 (Japan)] [Section of Cellular Physiological Chemistry, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519 (Japan)

    2012-08-10

    Highlights: Black-Right-Pointing-Pointer Cholesterol-treated RPE produces more A{beta} than non-treated RPE. Black-Right-Pointing-Pointer Neprilysin expression and activity decreased in cholesterol-treated RPE. Black-Right-Pointing-Pointer {alpha}-Secretase expression and activity decreased in cholesterol-treated RPE. Black-Right-Pointing-Pointer Cholesterol-enriched diet induced subRPE deposits in aged mice. Black-Right-Pointing-Pointer A{beta} were present in cholesterol-enriched-diet-induced subRPE deposits in aged mice. -- Abstract: Subretinally-deposited amyloid {beta} (A{beta}) is a main contributor of developing age-related macular degeneration (AMD). However, the mechanism causing A{beta} deposition in AMD eyes is unknown. Hypercholesterolemia is a significant risk for developing AMD. Thus, we investigated the effects of cholesterol on A{beta} production in retinal pigment epithelial (RPE) cells in vitro and in the mouse retina in vivo. RPE cells isolated from senescent (12-month-old) C57BL/6 mice were treated with 10 {mu}g/ml cholesterol for 48 h. A{beta} amounts in culture supernatants were measured by ELISA. Activity and expression of enzymes and proteins that regulate A{beta} production were examined by activity assay and real time PCR. The retina of mice fed cholesterol-enriched diet was examined by transmission electron microscopy. Cholesterol significantly increased A{beta} production in cultured RPE cells. Activities of A{beta} degradation enzyme; neprilysin (NEP) and anti-amyloidogenic secretase; {alpha}-secretase were significantly decreased in cell lysates of cholesterol-treated RPE cells compared to non-treated cells, but there was no change in the activities of {beta}- or {gamma}-secretase. mRNA levels of NEP and {alpha}-secretase (ADAM10 and ADAM17) were significantly lower in cholesterol-treated RPE cells than non-treated cells. Senescent (12-month-old) mice fed cholesterol-enriched chow developed subRPE deposits containing A{beta}, whereas age-matched mice fed standard rodent chow diet did not. Activities and mRNA levels of NEP and {alpha}-secretase were significantly lower in native RPE cells freshly isolated from cholesterol-enriched chow fed mice compared to standard rodent chow fed mice. These findings suggest that cholesterol enhances subretinal A{beta} accumulation by modulating the activities of enzymes degrading and processing A{beta} in RPE cells in senescent subjects.

  5. Genomics and the human genome project: implications for psychiatry

    E-Print Network [OSTI]

    Kelsoe, J R

    2004-01-01

    300 Genomics and the Human Genome Project: implications forpast decade the Human Genome Project has made extraordinaryto each other. The Human Genome Project has approached human

  6. China and the Humanities: At the Crossroads of the Human and the Humane

    E-Print Network [OSTI]

    Tchou, W. Kang

    2013-01-01

    Genius, xx feudalism, in China, 16 fields of coeval copresence, 68 fields of copresence called configurations, 63 fifth generation directors, 117 Fifth International Confer- ence on New Directions in the Humanities, xviii film scholarship, in contem...

  7. Epithelial topology Radhika Nagpal,1

    E-Print Network [OSTI]

    Gibson, Matt

    to metallurgy, spawning an interest in mathematical properties of biological pattern that has persisted

  8. Collective migration of epithelial sheets

    E-Print Network [OSTI]

    Murrell, Michael Peter

    2009-01-01

    The varied movements of the epithelium play vital roles in the development and renewal of complex tissues, from the separation of tissues in the early embryo, to homeostasis in the adult. Their movement is intricately ...

  9. The SACADA database for human reliability and human performance

    SciTech Connect (OSTI)

    Y. James Chang; Dennis Bley; Lawrence Criscione; Barry Kirwan; Ali Mosleh; Todd Madary; Rodney Nowell; Robert Richards; Emilie M. Roth; Scott Sieben; Antonios Zoulis

    2014-05-01

    Lack of appropriate and sufficient human performance data has been identified as a key factor affecting human reliability analysis (HRA) quality especially in the estimation of human error probability (HEP). The Scenario Authoring, Characterization, and Debriefing Application (SACADA) database was developed by the U.S. Nuclear Regulatory Commission (NRC) to address this data need. An agreement between NRC and the South Texas Project Nuclear Operating Company (STPNOC) was established to support the SACADA development with aims to make the SACADA tool suitable for implementation in the nuclear power plants' operator training program to collect operator performance information. The collected data would support the STPNOC's operator training program and be shared with the NRC for improving HRA quality. This paper discusses the SACADA data taxonomy, the theoretical foundation, the prospective data to be generated from the SACADA raw data to inform human reliability and human performance, and the considerations on the use of simulator data for HRA. Each SACADA data point consists of two information segments: context and performance results. Context is a characterization of the performance challenges to task success. The performance results are the results of performing the task. The data taxonomy uses a macrocognitive functions model for the framework. At a high level, information is classified according to the macrocognitive functions of detecting the plant abnormality, understanding the abnormality, deciding the response plan, executing the response plan, and team related aspects (i.e., communication, teamwork, and supervision). The data are expected to be useful for analyzing the relations between context, error modes and error causes in human performance.

  10. ATHENA, the Desktop Human "Body"

    ScienceCinema (OSTI)

    Iyer, Rashi; Harris, Jennifer

    2015-01-05

    Creating surrogate human organs, coupled with insights from highly sensitive mass spectrometry technologies, a new project is on the brink of revolutionizing the way we screen new drugs and toxic agents. ATHENA, the Advanced Tissue-engineered Human Ectypal Network Analyzer project team, is developing four human organ constructs - liver, heart, lung and kidney - that are based on a significantly miniaturized platform. Each organ component will be about the size of a smartphone screen, and the whole ATHENA "body" of interconnected organs would fit neatly on a desk. "By developing this 'homo minutus,' we are stepping beyond the need for animal or Petri dish testing: There are huge benefits in developing drug and toxicity analysis systems that can mimic the response of actual human organs," said Rashi Iyer, a senior scientist at Los Alamos National Laboratory, the lead laboratory on the five-year, $19 million multi-institutional effort. The project is supported by the Defense Threat Reduction Agency (DTRA). Some 40 percent of pharmaceuticals fail their clinical trials, Iyer noted, and there are thousands of chemicals whose effects on humans are simply unknown. Providing a realistic, cost-effective and rapid screening system such as ATHENA with high-throughput capabilities could provide major benefits to the medical field, screening more accurately and offering a greater chance of clinical trial success.

  11. ATHENA, the Desktop Human "Body"

    SciTech Connect (OSTI)

    Iyer, Rashi; Harris, Jennifer

    2014-09-29

    Creating surrogate human organs, coupled with insights from highly sensitive mass spectrometry technologies, a new project is on the brink of revolutionizing the way we screen new drugs and toxic agents. ATHENA, the Advanced Tissue-engineered Human Ectypal Network Analyzer project team, is developing four human organ constructs - liver, heart, lung and kidney - that are based on a significantly miniaturized platform. Each organ component will be about the size of a smartphone screen, and the whole ATHENA "body" of interconnected organs would fit neatly on a desk. "By developing this 'homo minutus,' we are stepping beyond the need for animal or Petri dish testing: There are huge benefits in developing drug and toxicity analysis systems that can mimic the response of actual human organs," said Rashi Iyer, a senior scientist at Los Alamos National Laboratory, the lead laboratory on the five-year, $19 million multi-institutional effort. The project is supported by the Defense Threat Reduction Agency (DTRA). Some 40 percent of pharmaceuticals fail their clinical trials, Iyer noted, and there are thousands of chemicals whose effects on humans are simply unknown. Providing a realistic, cost-effective and rapid screening system such as ATHENA with high-throughput capabilities could provide major benefits to the medical field, screening more accurately and offering a greater chance of clinical trial success.

  12. Division of Human Resources EMERGENCY CLOSING INFORMATION

    E-Print Network [OSTI]

    Meyers, Steven D.

    Division of Human Resources EMERGENCY CLOSING INFORMATION Human Resources / Attendance and Leave of Human Resources EMERGENCY CLOSING INFORMATION Human Resources / Attendance and Leave Emergency Closing Information Form questions: (813) 974-5717 Rev. 04/2010 Disruption of Power or Water

  13. Low-Income Weatherization: The Human Dimension

    Broader source: Energy.gov [DOE]

    This presentation focuses on how the human dimension saves energy within low-income weatherization programs.

  14. Shotgun coverage of human genome computing

    E-Print Network [OSTI]

    Eddy, Sean

    take about 1.5 million pages. The Human Genome Project would not be possible if our revolution were-author collection of chapters on the various uses of computing in the Human Genome Project. Peculiarly absent fromShotgun coverage of human genome computing Human Genome Computing, Second Edition edited by Martin

  15. Doug Brutlag 2015 Sequencing the Human Genome

    E-Print Network [OSTI]

    Brutlag, Doug

    Project: Should we do it? · Service, R. F. (2001). The human genome: Objection #1: big biology is bad://www.elec-intro.com/m13-cloning #12;© Doug Brutlag 2015 Public Human Genome Project Strategy Published in Nature 15 The Human Genome Project: How should we do it? · Weber, J. L., & Myers, E. W. (1997). Human whole-genome

  16. Hominid/Human Evolution Geology 331

    E-Print Network [OSTI]

    Kammer, Thomas

    baby chimps more than adult chimps. Humans are said to be paedomorphic. #12;Neoteny in Human Evolution. Humans resemble baby apes more than adult apes. Humans are said to be paedomorphic. Chimp Gorilla #12 fossils #12;A Hominid Jawbone in Ethiopia #12;Sahelanthropus tchadensis, 6.5 MY old #12;Sahelanthropus

  17. WILD PIG ATTACKS ON HUMANS

    SciTech Connect (OSTI)

    Mayer, J.

    2013-04-12

    Attacks on humans by wild pigs (Sus scrofa) have been documented since ancient times. However, studies characterizing these incidents are lacking. In an effort to better understand this phenomenon, information was collected from 412 wild pig attacks on humans. Similar to studies of large predator attacks on humans, data came from a variety of sources. The various attacks compiled occurred in seven zoogeographic realms. Most attacks occurred within the species native range, and specifically in rural areas. The occurrence was highest during the winter months and daylight hours. Most happened under non-hunting circumstances and appeared to be unprovoked. Wounded animals were the chief cause of these attacks in hunting situations. The animals involved were typically solitary, male and large in size. The fate of the wild pigs involved in these attacks varied depending upon the circumstances, however, most escaped uninjured. Most human victims were adult males traveling on foot and alone. The most frequent outcome for these victims was physical contact/mauling. The severity of resulting injuries ranged from minor to fatal. Most of the mauled victims had injuries to only one part of their bodies, with legs/feet being the most frequent body part injured. Injuries were primarily in the form of lacerations and punctures. Fatalities were typically due to blood loss. In some cases, serious infections or toxemia resulted from the injuries. Other species (i.e., pets and livestock) were also accompanying some of the humans during these attacks. The fates of these animals varied from escaping uninjured to being killed. Frequency data on both non-hunting and hunting incidents of wild pig attacks on humans at the Savannah River Site, South Carolina, showed quantitatively that such incidents are rare.

  18. Intelligent Escort Robot Moving together with Human Methods for Human Position Recognition

    E-Print Network [OSTI]

    Ohya, Akihisa

    : Light-emitting device used in the experiments. robot is able to know the distance to the human thanksIntelligent Escort Robot Moving together with Human ­ Methods for Human Position Recognition in everyday life by interacting with humans. In order to escort a human, the robot needs to know the position

  19. Identifying the Addressee in Human-Human-Robot Interactions based on Head Pose and Speech

    E-Print Network [OSTI]

    Schultz, Tanja

    Identifying the Addressee in Human-Human-Robot Interactions based on Head Pose and Speech Michael In this work we investigate the power of acoustic and visual cues, and their combination, to identify the addressee in a human-human-robot interaction. Based on eighteen audio- visual recordings of two human beings

  20. Human MutationSPECIAL ARTICLE Planning the Human Variome Project: The Spain Report

    E-Print Network [OSTI]

    : The remarkable progress in characterizing the human genome sequence, exemplified by the Human Genome ProjectHuman MutationSPECIAL ARTICLE Planning the Human Variome Project: The Spain Reportà Jim Kaput,1yz-Sook Yoo,93 on behalf of contributors to the Human Variome Project Planning Meeting 1 Division

  1. Human factors in software development

    SciTech Connect (OSTI)

    Curtis, B.

    1986-01-01

    This book presents an overview of ergonomics/human factors in software development, recent research, and classic papers. Articles are drawn from the following areas of psychological research on programming: cognitive ergonomics, cognitive psychology, and psycholinguistics. Topics examined include: theoretical models of how programmers solve technical problems, the characteristics of programming languages, specification formats in behavioral research and psychological aspects of fault diagnosis.

  2. Human retroviruses and AIDS 1994

    SciTech Connect (OSTI)

    Myers, G.; Korber, B.; Wain-Hobson, S.; Jeang, Kuan-Teh; Henderson, L.E.; Pavlakis, G.N.

    1995-01-01

    This compendium, including accompanying floppy diskettes, is the result of an effort to compile and rapidly publish all relevant molecular data concerning the human immunodeficiency viruses (HIV) and related retroviruses. The scope of the compendium and database is best summarized by the five parts it comprises: (I) Nucleic Acid Alignments and Sequences; (II) Amino Acid Alignments; (III) Analysis; (IV) Related Sequences; (V) Database communications.

  3. Human Resources, Safety & Risk Management

    E-Print Network [OSTI]

    1 Human Resources, Safety & Risk Management 1600 Holloway Avenue, ADM 252 San Francisco, California OF RISK AND AGREEMENT TO PAY CLAIMS Activity: San Francisco State University Campus Recreation Department participating in this Activity. I am aware of the risks associated with traveling to/from and participating

  4. Analysis of Human Genetic Linkage

    SciTech Connect (OSTI)

    Boehnke, M.

    1991-01-01

    Linkage analysis continues in its golden age. The convergence of several factors - advances in molecular biology, advances in statistical models and algorithms, and advances in computing technology - have made possible remarkable successes in the mapping of human genetic diseases and in the construction of human genetic maps. The goals of mapping all the most important simple Mendelian disorders and constructing fine-structure genetic maps for each of the human chromosomes soon will be reached, and linkage methods promise to help us understand the etiologies of many common and complex familial diseases. With the continuing rapid advance of the field, the appearance of the revised edition of Dr. Ott's book is particularly welcome. As with the first edition, the goal of the revised edition is to provide a concise, easy-to-read introduction to human linkage analysis. The revised edition includes chapters on basic genetics and cytogenetics, genes and genetic polymorphisms, aspects of statistical inference, methods of linkage analysis, the informativeness of family data, multipoint linkage analysis, penetrance, numerical and computerized methods, the variability of the recombination fraction, inconsistencies, and linkage analysis with disease loci. The results is not an encyclopedia providing everything one could ever want to know about linkage analysis but, rather, a guide to the important methods, topics, and problems of linkage analysis today. Overall, the book achieves an excellent compromise between presenting important conclusions and working out the details.

  5. POSITION DESCRIPTIONS GUIDELINE HUMAN RESOURCES

    E-Print Network [OSTI]

    Su, Xiao

    and activities related to successful human resources operations such as: recruitment and selection, job may also help you develop recruiting materials, and ensure consistency and equity among positions of Labor (O*Net), or the Bureau of Labor Statistics (Occupational Outlook Handbook) may be excellent

  6. SALARY ADVANCE REQUEST HUMAN RESOURCES

    E-Print Network [OSTI]

    Su, Xiao

    SALARY ADVANCE REQUEST HUMAN RESOURCES Employee Support Services | One Washington Square | San José, CA 95192-0046 | 408-924-2250 408-924-1701 (fax) Instructions: A request for a salary advance should: Department: Division/College: Campus Phone #: Employee Status: (check one) Faculty Staff REASON FOR SALARY

  7. EMERGENCY HIRE GUIDELINES HUMAN RESOURCES

    E-Print Network [OSTI]

    Su, Xiao

    EMERGENCY HIRE GUIDELINES HUMAN RESOURCES Workforce Planning · One Washington Square · San José, Ca 95192-0046 · Phone 408-924-2250 · Fax 408-924-1784 SUBJECT: EMERGENCY HIRES RESPONSIBLE UNIT & CONTACT: Workforce Planning; Sr. Workforce Planning Analyst DATE: May 2, 2008 I. PURPOSE / DESCRIPTION The Emergency

  8. A Literary Human Exinction Scenario

    SciTech Connect (OSTI)

    Tonn, Bruce Edward

    2009-11-01

    Mary Wollstonecraft Shelly's (MWS) novel, The Last Man, published in 1826, is an epic narrative about the destruction of the human race. This paper provides a synopsis of this book and assesses its relationships to contemporary future studies. The paper also delves into the history of apocalyptic writing and thinking, using this book an entry point to past literature.

  9. COLLEGE OF ENGINEERING Human Health

    E-Print Network [OSTI]

    COLLEGE OF ENGINEERING Human Health #12;Welcome to our Health issue ­ Please take the time to read the exciting stories about how our faculty, students, and alumni are engineering solutions to health care to tackle large worldwide health problems. A few years ago, the College of Engineering made a strategic

  10. Spatio-temporal Neuroimaging of Visual Processing of Human and Robot Actions in Humans

    E-Print Network [OSTI]

    Urgen, Burcu Aysen

    2015-01-01

    H. (2006). Human-inspired robots. IEEE Intelligent Sys. 21,K. (2007). Socially intelligent robots: dimensionsof human-robot interaction. Philos. Trans. R. Soc. Lond. B

  11. Calcitriol inhibits Ether-a go-go potassium channel expression and cell proliferation in human breast cancer cells

    SciTech Connect (OSTI)

    Garcia-Becerra, Rocio [Department of Reproductive Biology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga No. 15, Tlalpan 14000 Mexico, D.F. (Mexico)] [Department of Reproductive Biology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga No. 15, Tlalpan 14000 Mexico, D.F. (Mexico); Diaz, Lorenza, E-mail: lorenzadiaz@gmail.com [Department of Reproductive Biology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga No. 15, Tlalpan 14000 Mexico, D.F. (Mexico)] [Department of Reproductive Biology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga No. 15, Tlalpan 14000 Mexico, D.F. (Mexico); Camacho, Javier [Department of Pharmacology, Centro de Investigacion y de Estudios Avanzados, Instituto Politecnico Nacional, Av. Instituto Politecnico Nacional 2508, San Pedro Zacatenco 07360, Mexico, D.F. (Mexico)] [Department of Pharmacology, Centro de Investigacion y de Estudios Avanzados, Instituto Politecnico Nacional, Av. Instituto Politecnico Nacional 2508, San Pedro Zacatenco 07360, Mexico, D.F. (Mexico); Barrera, David; Ordaz-Rosado, David; Morales, Angelica [Department of Reproductive Biology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga No. 15, Tlalpan 14000 Mexico, D.F. (Mexico)] [Department of Reproductive Biology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga No. 15, Tlalpan 14000 Mexico, D.F. (Mexico); Ortiz, Cindy Sharon [Department of Pathology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga No. 15, Tlalpan 14000 Mexico, D.F. (Mexico)] [Department of Pathology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga No. 15, Tlalpan 14000 Mexico, D.F. (Mexico); Avila, Euclides [Department of Reproductive Biology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga No. 15, Tlalpan 14000 Mexico, D.F. (Mexico)] [Department of Reproductive Biology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga No. 15, Tlalpan 14000 Mexico, D.F. (Mexico); Bargallo, Enrique [Department of Breast Tumors, Instituto Nacional de Cancerologia, Av. San Fernando No. 22, Tlalpan 14080, Mexico, D.F. (Mexico)] [Department of Breast Tumors, Instituto Nacional de Cancerologia, Av. San Fernando No. 22, Tlalpan 14080, Mexico, D.F. (Mexico); Arrecillas, Myrna [Department of Pathology, Instituto Nacional de Cancerologia, Av. San Fernando No. 22, Tlalpan 14080, Mexico, D.F. (Mexico)] [Department of Pathology, Instituto Nacional de Cancerologia, Av. San Fernando No. 22, Tlalpan 14080, Mexico, D.F. (Mexico); Halhali, Ali; Larrea, Fernando [Department of Reproductive Biology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga No. 15, Tlalpan 14000 Mexico, D.F. (Mexico)] [Department of Reproductive Biology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga No. 15, Tlalpan 14000 Mexico, D.F. (Mexico)

    2010-02-01

    Antiproliferative actions of calcitriol have been shown to occur in many cell types; however, little is known regarding the molecular basis of this process in breast carcinoma. Ether-a-go-go (Eag1) potassium channels promote oncogenesis and are implicated in breast cancer cell proliferation. Since calcitriol displays antineoplastic effects while Eag1 promotes tumorigenesis, and both factors antagonically regulate cell cycle progression, we investigated a possible regulatory effect of calcitriol upon Eag1 as a mean to uncover new molecular events involved in the antiproliferative activity of this hormone in human breast tumor-derived cells. RT real-time PCR and immunocytochemistry showed that calcitriol suppressed Eag1 expression by a vitamin D receptor (VDR)-dependent mechanism. This effect was accompanied by inhibition of cell proliferation, which was potentiated by astemizole, a nonspecific Eag1 inhibitor. Immunohistochemistry and Western blot demonstrated that Eag1 and VDR abundance was higher in invasive-ductal carcinoma than in fibroadenoma, and immunoreactivity of both proteins was located in ductal epithelial cells. Our results provide evidence of a novel mechanism involved in the antiproliferative effects of calcitriol and highlight VDR as a cancer therapeutic target for breast cancer treatment and prevention.

  12. Crystal structure of human dynein light chain Dnlc2A: Structural insights into the interaction with IC74

    SciTech Connect (OSTI)

    Liu Junfeng; Wang Zhanxin; Wang Xinquan; Tang Qun; An Xiaomin; Gui Lulu; Liang Dongcai . E-mail: dcliang@sun5.ibp.ac.cn

    2006-10-27

    The human light chain of the motor protein dynein, Dnlc2A, is also a novel TGF-{beta}-signaling component, which is altered with high frequency in epithelial ovarian cancer. It is an important mediator of dynein and the development of cancer, owing to its ability to bind to the dynein intermediate light chain (DIC) IC74 and to regulate TGF-{beta}-dependent transcriptional events. Here we report the 2.1-A crystal structure of Dnlc2A using single anomalous diffraction. The proteins form a homodimer in solution and interact mainly through the helix {alpha}{sub 2}, strand {beta}{sub 3}, and the loop following this strand in each protein to generate a 10-stranded {beta}-sheet core. The surface of the {beta}-sheet core is mainly positively charged and predicted (by software PPI-Pred) to be the site that interacts with other partners. At the same time, the residues 79-82, 88, and 90 of each molecule formed two holes in the core. Residue 89 of each molecule, which is crucial for the DIC binding function of Dnlc2A, is within the holes. On the basis of these observations, we propose that the homodimer is the structural and functional unit maintained by hydrogen bonding interactions and hydrophobic packing, and that the patch of the surface of the {beta}-sheet core is the main area of interaction with other partners. Furthermore, the two holes would be the key sites to interact with IC74.

  13. Human Fertilisation and Embryology Bill A briefing for MPs on the need for research involving human and human admixed embryos.

    E-Print Network [OSTI]

    Rambaut, Andrew

    cells for research. The Bill allows research, under license, on four types of HAEs, which contain bothHuman Fertilisation and Embryology Bill A briefing for MPs on the need for research involving human and human admixed embryos. Prepared by the Academy of Medical Sciences, the Medical Research Council

  14. Human-Centered Sustainable Product Design

    E-Print Network [OSTI]

    Agogino, Alice M.

    Inquiry ­! Green Building Design !! Week 2 ­! Brainstorming and Creative Design ­! Life Cycle Analysis / Sustainability Needs Human- centered design Uneconomical green design Unadopted green systems Sustainable systemsHuman-Centered Sustainable Product Design !!Module Overview !!Need Finding Methods 1 ME Module

  15. Human Dimensions of Wildlife Research Norman Dandy

    E-Print Network [OSTI]

    Human Dimensions of Wildlife Research Norman Dandy Social & Economic Research Group #12;Wildlife) · Human-dimensions of species management (HDSM) Research Projects #12;Collaborative Frameworks for Land of woodland landscapes ­ discussion groups, · Choice experiments, · Fellowships / Placements, · Newsletters

  16. Bioinformatics for the human microbiome project

    E-Print Network [OSTI]

    Gevers, Dirk

    Microbes inhabit virtually all sites of the human body, yet we know very little about the role they play in our health. In recent years, there has been increasing interest in studying human-associated microbial communities, ...

  17. Epidemiology, classification and evolution of human rhinoviruses 

    E-Print Network [OSTI]

    McIntyre, Chloe Leanne

    2013-07-06

    Human rhinoviruses (HRV) are extremely common human respiratory pathogens, most commonly associated with mild upper respiratory tract infections. The three known species of HRV (HRV-A, -B and –C) are members of the family ...

  18. Propeller based human powered swimming device

    E-Print Network [OSTI]

    Bunker, Kristine (Kristine Alina)

    2014-01-01

    Currently the only human powered swimming device widely sold on the market are swim flippers. However, flippers are not efficient for the human body, and there is a potential to increase the speed while swimming with a ...

  19. Original Paper Human sensorimotor learning for

    E-Print Network [OSTI]

    Babic, Jan

    . The concept is to consider the target robot platform as a tool to be controlled intuitively by a human to drive a car. After human learning, the skilled control of the robot is used to build an autonomous

  20. NIST Update NIST Human Identity Project Team

    E-Print Network [OSTI]

    NIST Update NIST Human Identity Project Team National Institute of Standards and Technology Standard Set (ESS) STRs using the CEPH human genome diversity panel, Forensic Sci. Int. Genet. (2010), doi

  1. Oceans and Human Health (and climate change)

    E-Print Network [OSTI]

    Zhou, Xianghong Jasmine

    Oceans and Human Health (and climate change) Tracy K. Collier Science Dimensions and Ocean Health in a Changing Climate, USC March 12, 2013 1 #12 use Climate change Closes the loop in understanding connections between ocean health and human health

  2. Cost estimation of human systems integration

    E-Print Network [OSTI]

    Liu, Kevin K. (Kevin Kaitan), 1986-

    2010-01-01

    Human Systems Integration (HSI) is the interdisciplinary technical and management processes for integrating human considerations within and across all system elements. The goal of this research is to develop a better ...

  3. Human adaptation of avian influenza viruses

    E-Print Network [OSTI]

    Srinivasan, Karunya

    2012-01-01

    Human adaptation of avian influenza viruses pose an enormous public health challenge as the human population is predominantly naive to avian influenza antigens. As such, constant surveillance is needed to monitor the ...

  4. Human factors in waste management

    SciTech Connect (OSTI)

    Moray, N.

    1994-10-01

    This article examines the role of human factors in radioactive waste management. Although few problems and ergonomics are special to radioactive waste management, some problems are unique especially with long term storage. The entire sociotechnical system must be looked at in order to see where improvement can take place because operator errors, as seen in Chernobyl and Bhopal, are ultimately the result of management errors.

  5. Contractor Human Resource Management Programs

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

    1996-09-29

    This directive establishes DOE responsibilities and requirements for the management and oversight of contractor Human Resource Management (HR) programs. Chg 1, 5-8-98; Chg 2, 11-22-09; Chg 3, 2-23-10; Chg 4, 4-29-13. DOE O 350.1 Chg 5, dated 9-30-2014, cancels Chapters I-III of DOE O 350.1 Chg 4

  6. Contractor Human Resource Management Programs

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

    1996-09-30

    The purpose of this directive is to establish Department of Energy (DOE) responsibilities and requirements for the management and oversight of contractor Human Resource Management (HR) programs. Chg 1, 5-8-98; Chg 2, 11-22-09; Chg 3, 2-23-10; Chg 4, 4-29-13. This order cancels DOE O 3220.1A, DOE O 3220.4A, DOE O 3220.6A, and DOE O 3309.1A.

  7. Integrating Human Performance and Technology

    SciTech Connect (OSTI)

    Ronald K. Farris; Heather Medema

    2012-05-01

    Human error is a significant factor in the cause and/or complication of events that occur in the commercial nuclear industry. In recent years, great gains have been made using Human Performance (HU) tools focused on targeting individual behaviors. However, the cost of improving HU is growing and resistance to add yet another HU tool certainly exists, particularly for those tools that increase the paperwork for operations. Improvements in HU that are the result of leveraging existing technology, such as hand-held mobile technologies, have the potential to reduce human error in controlling system configurations, safety tag-outs, and other verifications. Operator rounds, valve line-up verifications, containment closure verifications, safety & equipment protection, and system tagging can be supported by field-deployable wireless technologies. These devices can also support the availability of critical component data in the main control room and other locations. This research pilot project reviewing wireless hand-held technology is part of the Light Water Reactor Sustainability Program (LWRSP), a research and development (R&D) program sponsored by the U. S. Department of Energy (DOE). The project is being performed in close collaboration with industry R&D programs to provide the technical foundations for licensing, and managing the long-term, safe, and economical operation of current nuclear power plants. The LWRSP vision is to develop technologies and other solutions that can improve the reliability, sustain the safety, and extend the life of the current nuclear reactor fleet.

  8. PIA - Human Resources - Personal Information Change Request ...

    Energy Savers [EERE]

    - Personal Information Change Request - Idaho National Engineering Laboratory PIA - Human Resources - Personal Information Change Request - Idaho National Engineering Laboratory...

  9. "Mill’s Conception of Human Rights"

    E-Print Network [OSTI]

    Harrar, Souad Chaherli

    2008-01-01

    his article Bentham (7) Mill reproaches two main points toof human nature. Mill reproaches Bentham for his inability

  10. GDB - Human Genome Database final report

    SciTech Connect (OSTI)

    Talbot, C. Conover, Jr.

    2002-01-08

    This is the DOE final report for the GDB, Human Genome Database, project at the Johns Hopkins University.

  11. Induction of human breast cell carcinogenesis by triclocarban and intervention by curcumin

    SciTech Connect (OSTI)

    Sood, Shilpa; Choudhary, Shambhunath; Wang, Hwa-Chain Robert

    2013-09-06

    Highlights: •Triclocarban exposure induces breast epithelial cell carcinogenesis. •Triclocarban induces the Erk–Nox pathway, ROS elevation, and DNA damage. •Physiological doses of triclocarban induce cellular carcinogenesis. •Non-cytotoxic curcumin blocks triclocarban-induced carcinogenesis and pathways. -- Abstract: More than 85% of breast cancers are sporadic and attributable to long-term exposure to environmental carcinogens and co-carcinogens. To identify co-carcinogens with abilities to induce cellular pre-malignancy, we studied the activity of triclocarban (TCC), an antimicrobial agent commonly used in household and personal care products. Here, we demonstrated, for the first time, that chronic exposure to TCC at physiologically-achievable nanomolar concentrations resulted in progressive carcinogenesis of human breast cells from non-cancerous to pre-malignant. Pre-malignant carcinogenesis was measured by increasingly-acquired cancer-associated properties of reduced dependence on growth factors, anchorage-independent growth and increased cell proliferation, without acquisition of cellular tumorigenicity. Long-term TCC exposure also induced constitutive activation of the Erk–Nox pathway and increases of reactive oxygen species (ROS) in cells. A single TCC exposure induced transient induction of the Erk–Nox pathway, ROS elevation, increased cell proliferation, and DNA damage in not only non-cancerous breast cells but also breast cancer cells. Using these constitutively- and transiently-induced changes as endpoints, we revealed that non-cytotoxic curcumin was effective in intervention of TCC-induced cellular pre-malignancy. Our results lead us to suggest that the co-carcinogenic potential of TCC should be seriously considered in epidemiological studies to reveal the significance of TCC in the development of sporadic breast cancer. Using TCC-induced transient and constitutive endpoints as targets will likely help identify non-cytotoxic preventive agents, such as curcumin, effective in suppressing TCC-induced cellular pre-malignancy.

  12. Division of Human Resources Assessing Education and

    E-Print Network [OSTI]

    Meyers, Steven D.

    Division of Human Resources Assessing Education and Past Work Experience Questions (813) 974 of Human Resources Assessing Education and Past Work Experience Questions (813) 974-2970 Recruitment the applicant's education for United States educational equivalency. Human Resources will use the review

  13. Human factors: a necessary tool for industry

    SciTech Connect (OSTI)

    Starcher, K.O.

    1984-03-09

    The need for human factors (ergonomics) input in the layout of a ferroelectric ceramics laboratory is presented as an example of the overall need for human factors professionals in industry. However, even in the absence of one trained in human factors, knowledge of a few principles in ergonomics will provide many possibilities for improving performance in the industrial environment.

  14. Human Computation Must Be Reproducible Praveen Paritosh

    E-Print Network [OSTI]

    Tomkins, Andrew

    and evaluation of experiments. We argue that human computation has similar properties, and that the resultsHuman Computation Must Be Reproducible Praveen Paritosh Google 345 Spear St, San Francisco, CA 94105. pkp@google.com ABSTRACT Human computation is the technique of performing a com- putational

  15. Rita LaCivita Chief Human

    E-Print Network [OSTI]

    Rita LaCivita Chief Human Resources Officer Patricia Fantin Secretary to the Chief Human Resources Assistant Rosalyn Power Pension, Benefits & Records Administrator Monika Burgess Receptionist/ Benefits-Chancellor Alina Jaworska- Sobiesiak Laboratory Safety Coordinator UNIVERSITY OF WINDSOR DEPARTMENT OF HUMAN

  16. Mathematics of Planet Earth: Sustainable Human Environments

    E-Print Network [OSTI]

    .htm #12;3 Sustainable Human Environments · Rapidly growing urban environments present new and evolving1 Mathematics of Planet Earth: Sustainable Human Environments Fred Roberts Rutgers University #12;2 Sustainable Human Environments · In 1900, only 13% of the world's population lived in cities. · By 2050

  17. Mathematics of Planet Earth: Sustainable Human Environments

    E-Print Network [OSTI]

    ;11 Sustainable Human Environments · Rapidly growing urban environments present new and evolving challenges1 Mathematics of Planet Earth: Sustainable Human Environments Fred Roberts Rutgers University #12 with workshops: Sustainable Human Environments (Rutgers U.), April 23-25, 2014 Global Change (UC Berkeley), May

  18. Modeling, Animation, and Rendering of Human Figures

    E-Print Network [OSTI]

    Güdükbay, Ugur

    7 Modeling, Animation, and Rendering of Human Figures Ugur G¨ud¨ukbay, B¨ulent ¨Ozg¨u¸c, Aydemir, Ankara, Turkey Human body modeling and animation has long been an important and challenging area virtual humans in action: video games, films, television, virtual reality, ergonomics, medicine

  19. Humans, Robots and Market Crashes: A Laboratory Study ?

    E-Print Network [OSTI]

    Feldman, Todd; Friedman, Daniel

    2008-01-01

    Based Models and Human Subject Experiments. Handbook of Com-data from our experiments combining humans and robots, usingbetween laboratory experiment with human subjects and agent

  20. The Human Genome Project and its Social Implications

    E-Print Network [OSTI]

    Meyer, Paul B

    1990-01-01

    The Human Genome Project and its Social Implications By Paulit is about the Human Genome Project. In a sense this isheredity. The Human Genome Project is concerned essentially

  1. On the Levy-walk Nature of Human Mobility: Do Humans Walk like Monkeys?

    E-Print Network [OSTI]

    Young, R. Michael

    such as the power-law distributions of human inter-contact times and that the simulation performance of mobileOn the Levy-walk Nature of Human Mobility: Do Humans Walk like Monkeys? Injong Rhee, Minsu Shin, Seongik Hong, Kyunghan Lee and Song Chong Abstract--We report that human walk patterns closely follow Levy

  2. Tracking Human Body Parts Using Particle Filters Constrained by Human Biomechanics

    E-Print Network [OSTI]

    Nebel, Jean-Christophe

    Tracking Human Body Parts Using Particle Filters Constrained by Human Biomechanics J. Mart´inez1, J articulated model. It is constrained only by biomechanical knowledge about human bipedal motion, instead. It relies on a generative approach based on a 2D model constrained only by human biomechanics. The inclusion

  3. Policies and Procedures for Human Subject Research Procedures for the Review of Human Subjects Research

    E-Print Network [OSTI]

    Policies and Procedures for Human Subject Research June 1997 #12;Procedures for the Review of Human Subjects Research I. General Description of the System of Review of Research Involving Human Subjects involving human subjects must be reviewed prior to conducting any research. Research studies which involve

  4. College of Health and Human Sciences College of Health and Human

    E-Print Network [OSTI]

    College of Health and Human Sciences College of Health and Human Sciences Office in L.L. Gibbons Sciences Fermentation Science and Technology Health and Exercise Science Human Development and Family Merchandising Nutrition COLLEGE PROGRAMS The College of Health and Human Sciences comprises six academic

  5. Human Reliability Analysis for Design: Using Reliability Methods for Human Factors Issues

    SciTech Connect (OSTI)

    Ronald Laurids Boring

    2010-11-01

    This paper reviews the application of human reliability analysis methods to human factors design issues. An application framework is sketched in which aspects of modeling typically found in human reliability analysis are used in a complementary fashion to the existing human factors phases of design and testing. The paper provides best achievable practices for design, testing, and modeling. Such best achievable practices may be used to evaluate and human system interface in the context of design safety certifications.

  6. Report: EM Human Capital Initiatives

    Office of Environmental Management (EM)

    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 WebQuantity of Natural GasAdjustments (BillionProvedTravelInformationCollectionGridReno Roundtable SummaryEM Communications August 24,HUMAN

  7. Contractor Human Resource Management Programs

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

    1996-09-30

    This directive establishes DOE responsibilities and requirements for the management and oversight of contractor Human Resource Management (HR) programs. Chg 1, 5-8-98; Chg 2, 11-22-09; Chg 3, 2-23-10; Chg 4, 4-29-13. DOE O 350.1 Chg 5, dated 9-30-2014, supersedes DOE O 350.1 Chg 4. The Order is revised to reflect the cancellation of Chapters 1-3 due to the incorporation of these chapters into DOE Order 350.3; reflect organizational changes; delete reference to the DOE Retrospective Rating Insurance Plan, which is no longer available; remove the CRD from Chapter VII.

  8. Simulation of human decision making

    DOE Patents [OSTI]

    Forsythe, J. Chris (Sandia Park, NM); Speed, Ann E. (Albuquerque, NM); Jordan, Sabina E. (Albuquerque, NM); Xavier, Patrick G. (Albuquerque, NM)

    2008-05-06

    A method for computer emulation of human decision making defines a plurality of concepts related to a domain and a plurality of situations related to the domain, where each situation is a combination of at least two of the concepts. Each concept and situation is represented in the computer as an oscillator output, and each situation and concept oscillator output is distinguishable from all other oscillator outputs. Information is input to the computer representative of detected concepts, and the computer compares the detected concepts with the stored situations to determine if a situation has occurred.

  9. Human Genome Research: Decoding 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 WebQuantity ofkandz-cm11 Outreach Home Room NewsInformation CurrentHenry Bellamy, Ph.D.Food Drive HolidayHoursaUS Dept ofHui-YuanHuman

  10. Human Resources | The Ames Laboratory

    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 WebQuantity ofkandz-cm11 Outreach Home Room NewsInformation CurrentHenry Bellamy, Ph.D.Food Drive HolidayHoursaUS DeptInstituteHuman

  11. Human Resources | Argonne National Laboratory

    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 likeUniverse (JournalvivoHigh energyHighlandWorkshop-SummerHow isColoradoHuman Resources

  12. ORISE: Protecting Human Subjects Website

    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 WebQuantity ofkandz-cm11 Outreach Home Room NewsInformationJesseworkSURVEY UNIVERSE TheForensicPerformanceProtecting Human

  13. Linking Humans and Systems in Nuclear Power

    SciTech Connect (OSTI)

    Jacques Hugo

    2013-02-01

    Traditional engineering methods do not make provision for the integration of human considerations, while traditional human factors methods do not scale well to the complexity of large-scale nuclear power plant projects. Although the need for up-to-date human factors engineering processes and tools is recognised widely in industry, so far no formal guidance has been developed. This article proposes such a framework.

  14. Stochastic Image Grammars for Human Pose Estimation

    E-Print Network [OSTI]

    Rothrock, Brandon

    2013-01-01

    relations over relative posi- tion and orientation. TheTrained Using 3D Human Pose Annotations. ” In InternationalDetecting Actions, Poses, and Objects with Relational

  15. Global Environmental Change and Human Security

    E-Print Network [OSTI]

    Kunnas, Jan

    2011-01-01

    impacts and responses to environmental change making it anhuman security or environmental change if the lecturer isReview: Global Environmental Change and Human Security By

  16. Human factors challenges for advanced process control

    SciTech Connect (OSTI)

    Stubler, W.F.; O`Hara, J..M.

    1996-08-01

    New human-system interface technologies provide opportunities for improving operator and plant performance. However, if these technologies are not properly implemented, they may introduce new challenges to performance and safety. This paper reports the results from a survey of human factors considerations that arise in the implementation of advanced human-system interface technologies in process control and other complex systems. General trends were identified for several areas based on a review of technical literature and a combination of interviews and site visits with process control organizations. Human factors considerations are discussed for two of these areas, automation and controls.

  17. Apparatus and methods for a human extender

    DOE Patents [OSTI]

    Jansen, John F. (Knoxville, TN)

    2001-01-01

    A human extender controller for interface between a human operator and a physical object through a physical plant. The human extender controller uses an inner-feedback loop to increase the equivalent damping of the operating system to stabilize the system when it contacts with the environment and reduces the impact of the environment variation by utilizing a high feedback gain, determined by a root locus sketch. Because the stability of the human extender controller of the present invention is greatly enhanced over that of the prior art, the present invention is able to achieve a force reflection ratio 500 to 1 and capable of handling loads above the two (2) ton range.

  18. Human Driver Model for SmartAHS

    E-Print Network [OSTI]

    Delorme, Delphine; Song, Bongsob

    2001-01-01

    the Human Factors field (Rockwell 1988, Bhises et al.1986,Amsterdam, pp. 91-100. Rockwell, T. H. , (1988) Spare visual

  19. Supplement: Thousands of human mobile element

    E-Print Network [OSTI]

    Pratt, Vaughan

    Supplement: Thousands of human mobile element fragments undergo strong purifying selection near Supplemental material Supplemental text, tables, and figures. S1 pan-boreoeutherian mobile elements Mobile

  20. Prenatal programming of human neurological function.

    E-Print Network [OSTI]

    Sandman, Curt A; Davis, Elysia P; Buss, Claudia; Glynn, Laura M

    2011-01-01

    exposure: fetal programming and later life vulnerability toet al. , “Epigenetic programming by maternal behavior,”Review Article Prenatal Programming of Human Neurological

  1. Genomic mosaicism in the human brain

    E-Print Network [OSTI]

    Westra, Jurjen Willem

    2008-01-01

    Zlokovic BV (2008) The blood-brain barrier in health andmosaicism in the human brain ………………………………………. Chapter Threethe Alzheimer’s disease brain ………………………………. Chapter Five DNA

  2. Immunogenic compositions comprising human immunodeficiency virus...

    Office of Scientific and Technical Information (OSTI)

    Patent: Immunogenic compositions comprising human immunodeficiency virus (HIV) mosaic Nef proteins Citation Details In-Document Search Title: Immunogenic compositions comprising...

  3. Solar Energy Education. Humanities: activities and teacher's...

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

    and teacher's guide. Field test edition Citation Details In-Document Search Title: Solar Energy Education. Humanities: activities and teacher's guide. Field test edition ...

  4. Vorinostat, an HDAC inhibitor attenuates epidermoid squamous cell carcinoma growth by dampening mTOR signaling pathway in a human xenograft murine model

    SciTech Connect (OSTI)

    Kurundkar, Deepali; Srivastava, Ritesh K.; Chaudhary, Sandeep C. [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, 1530 3rd Avenue South, VH 509, Birmingham, AL 35294-0019 (United States)] [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, 1530 3rd Avenue South, VH 509, Birmingham, AL 35294-0019 (United States); Ballestas, Mary E. [Department of Pediatrics Infectious Disease, Children's of Alabama, School of Medicine, University of Alabama at Birmingham, AL (United States)] [Department of Pediatrics Infectious Disease, Children's of Alabama, School of Medicine, University of Alabama at Birmingham, AL (United States); Kopelovich, Levy [Division of Cancer Prevention, National Cancer Institute, 6130 Executive Blvd., Suite 2114, Bethesda, MD 20892 (United States)] [Division of Cancer Prevention, National Cancer Institute, 6130 Executive Blvd., Suite 2114, Bethesda, MD 20892 (United States); Elmets, Craig A. [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, 1530 3rd Avenue South, VH 509, Birmingham, AL 35294-0019 (United States)] [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, 1530 3rd Avenue South, VH 509, Birmingham, AL 35294-0019 (United States); Athar, Mohammad, E-mail: mathar@uab.edu [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, 1530 3rd Avenue South, VH 509, Birmingham, AL 35294-0019 (United States)] [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, 1530 3rd Avenue South, VH 509, Birmingham, AL 35294-0019 (United States)

    2013-01-15

    Histone deacetylase (HDAC) inhibitors are potent anticancer agents and show efficacy against various human neoplasms. Vorinostat is a potent HDAC inhibitor and has shown potential to inhibit growth of human xenograft tumors. However, its effect on the growth of skin neoplasm remains undefined. In this study, we show that vorinostat (2 ?M) reduced expression of HDAC1, 2, 3, and 7 in epidermoid carcinoma A431 cells. Consistently, it increased acetylation of histone H3 and p53. Vorinostat (100 mg/kg body weight, IP) treatment reduced human xenograft tumor growth in highly immunosuppressed nu/nu mice. Histologically, the vorinostat-treated tumor showed features of well-differentiation with large necrotic areas. Based on proliferating cell nuclear antigen (PCNA) staining and expression of cyclins D1, D2, E, and A, vorinostat seems to impair proliferation by down-regulating the expression of these proteins. However, it also induced apoptosis. The mechanism by which vorinostat blocks proliferation and makes tumor cells prone to apoptosis, involved inhibition of mTOR signaling which was accompanied by reduction in cell survival AKT and extracellular-signal regulated kinase (ERK) signaling pathways. Our data provide a novel mechanism-based therapeutic intervention for cutaneous squamous cell carcinoma (SCC). Vorinostat may be utilized to cure skin neoplasms in organ transplant recipient (OTR). These patients have high morbidity and surgical removal of these lesions which frequently develop in these patients, is difficult. -- Highlights: ? Vorinostat reduces SCC growth in a xenograft murine model. ? Vorinostat dampens proliferation and induces apoptosis in tumor cells. ? Diminution in mTOR, Akt and ERK signaling underlies inhibition in proliferation. ? Vorinostat by inhibiting HDACs inhibits epithelial–mesenchymal transition.

  5. Compressive stress enhances coordinated migration of mammary carcinoma cells

    E-Print Network [OSTI]

    Tse, Janet M. (Janet Man-Yu)

    2010-01-01

    Cancer research has traditionally focused on genetic and biochemical changes during tumor progression. Uncontrolled cell proliferation of a solid tumor in a confined space not only creates well-studied oxidative stress ...

  6. Mfge8 is critical for mammary gland remodeling during involution

    E-Print Network [OSTI]

    2005-01-01

    Rockford, IL) in 5 mM potassium ferrocyanide crystalline, 5mM potassium ferrocyanide trihydrate, and 2 mM magnesium

  7. An Agenda for Human-Computer Interaction Research: Science and Technology Serving Human Needs

    E-Print Network [OSTI]

    Shneiderman, Ben

    An Agenda for Human-Computer Interaction Research: Science and Technology Serving Human Needs and technology planners respond to the growing activity in human-computer interaction, a broad perspective may and challenges for the continued growth of HCI. Partnerships among universities, corporations, government

  8. Human-Driven Spatial Language for Human-Robot Interaction Marjorie Skubic and Zhiyu Huo

    E-Print Network [OSTI]

    He, Zhihai "Henry"

    to comprehend spatial descriptions. As a first step, a series of human subject experiments is being conducted adults. Based on the results of these human subject experiments, algorithms will be developed for robot will ultimately be tested in future human subject experiments using both virtual and physical robots. Thus

  9. The Human Microbiome Project: A Community Resource for the Healthy Human Microbiome

    E-Print Network [OSTI]

    Gevers, Dirk

    The Human Microbiome Project (HMP) [1],[2] is a concept that was long in the making. After the Human Genome Project, interest grew in sequencing the “other genome" of microbes carried in and on the human body [3],[4]. ...

  10. More Human than Human? A Visual Processing Approach to Exploring Believability of Android Faces

    E-Print Network [OSTI]

    More Human than Human? A Visual Processing Approach to Exploring Believability of Android Faces is core to android science, the challenge of creating a robot that can pass as a near human. While researchers are making great strides in improving the quality of androids and their likeness to people

  11. Conduct of Human Subjects Research -1 -Approved: 02/05/2015 Conduct of Human Subjects Research

    E-Print Network [OSTI]

    Hammack, Richard

    Conduct of Human Subjects Research - 1 - Approved: 02/05/2015 Conduct of Human Subjects Research Policy Type: Administrative Responsible Office: Office of Research Subjects Protection Initial Policy Approved: 02/05/2015 Current Revision Approved: 02/05/2015 Policy Statement and Purpose Human subjects

  12. Inclusion of Human Subjects in Research Human Subjects Involvement and Characteristics

    E-Print Network [OSTI]

    Firestone, Jeremy

    Inclusion of Human Subjects in Research Human Subjects Involvement and Characteristics: · Describe the proposed involvement of human subjects in the work outlined in the Research Design and Methods section. · Describe the characteristics of the subject population, including their anticipated number, age range

  13. SCHOOL OF HEALTH & APPLIED HUMAN SCIENCES College of Health & Human Services

    E-Print Network [OSTI]

    Olszewski Jr., Edward A.

    SCHOOL OF HEALTH & APPLIED HUMAN SCIENCES College of Health & Human Services University of North Carolina Wilmington FACT SHEET 2011-2012 About the School of Health and Applied Human Sciences · Founded and Recreation in 1977, and subsequently the Department of Health, Physical Education and Recreation (HPER

  14. Chronic OVA allergen challenged Siglec-F deficient mice have increased mucus, remodeling, and epithelial Siglec-F ligands which are up-regulated by IL-4 and IL-13.

    E-Print Network [OSTI]

    2010-01-01

    human eosinophil apoptosis. Blood 12. Vitale C, Romagnani C,Falco M, Ponte M, Vitale M, Moretta A, Bacigalupo A, Moretta

  15. Psychology 4330, Spring 2011. Human Factors Engineering

    E-Print Network [OSTI]

    Sanders, Matthew

    with an interest in design should remember that it is not really possible to teach ergonomic design per se without: Guastello, S. J. (2006). Human factors engineering and ergonomics: A systems approach. Mahwah, NJ: Lawrence/19 Introduction to human factors (T1) 1/24 Usability evaluation methods (T2) 1/31 Systems that change over time (T

  16. Computational Approaches Towards Human Genome Annotation

    E-Print Network [OSTI]

    Singh, Jaswinder Pal

    Computational Approaches Towards Human Genome Annotation Mark Gerstein Molecular Biophysics of the human genome. My talk will be concerned with topics within this area, in particular annotating pseudogenes (protein fossils) in the genome. I will discuss a comprehensive pseudogene identification pipeline

  17. Lecture 25: Evolution & Human-caused evolution

    E-Print Network [OSTI]

    Lecture 25: Evolution & Humans · Human-caused evolution · Global climate change · Exploitation:1786 Final, 14 Dec, 8-10 Review session, 13 Dec, Wednesday, 11am, 201 Abelson Evolution ­ relevance? A better populations ­ Conservation of biodiversity ­ Pests ­ Diseases Global warming and evolution · Moderation

  18. Contemporary Climate Change: Human Causes and Responses

    E-Print Network [OSTI]

    California at Davis, University of

    39 Contemporary Climate Change: Human Causes and Responses Dr. Ralph J. Cicerone, President is "Climate Change: Human Causes and Responses." I am aware of what the Chancellor's Colloquium series chemistry and climate change has involved him in shaping science and environmental policy at the highest

  19. West Virginia University Division of Human Resources

    E-Print Network [OSTI]

    Mohaghegh, Shahab

    Division of Human Resources Web page hr.wvu.edu. In the event of a conflict between the current posted version and this printed copy, the posted version on the Web page is controlling. Page 1 of 2 Employment been posted on the WVU Division of Human Resources Web page hr.wvu.edu. In the event of a conflict

  20. West Virginia University Division of Human Resources

    E-Print Network [OSTI]

    Mohaghegh, Shahab

    on the WVU Division of Human Resources Web page hr.wvu.edu. In the event of a conflict between the current posted version and this printed copy, the posted version on the Web page is controlling. Page 1 of 3 Division of Human Resources Web page hr.wvu.edu. In the event of a conflict between the current posted

  1. West Virginia University Division of Human Resources

    E-Print Network [OSTI]

    Mohaghegh, Shahab

    on the WVU Division of Human Resources Web page hr.wvu.edu. In the event of a conflict between the current posted version and this printed copy, the posted version on the Web page is controlling. Page 1 of 2 been posted on the WVU Division of Human Resources Web page hr.wvu.edu. In the event of a conflict

  2. West Virginia University Division of Human Resources

    E-Print Network [OSTI]

    Mohaghegh, Shahab

    Division of Human Resources Web page hr.wvu.edu. In the event of a conflict between the current posted version and this printed copy, the posted version on the Web page is controlling. Page 1 of 2 Access been posted on the WVU Division of Human Resources Web page hr.wvu.edu. In the event of a conflict

  3. West Virginia University Division of Human Resources

    E-Print Network [OSTI]

    Mohaghegh, Shahab

    on the WVU Division of Human Resources Web page hr.wvu.edu. In the event of a conflict between the current posted version and this printed copy, the posted version on the Web page is controlling. Page 1 of 2 of this administrative procedure has been posted on the WVU Division of Human Resources Web page hr.wvu.edu. In the event

  4. HumanResources Summary of Results

    E-Print Network [OSTI]

    36 scored questions in each survey Assess commitment and dedication plus effective environment How% participation rate) #12;HumanResources Office of STAFF 3 Engagement Process and Timeline Survey (October) Review #12;HumanResources Office of STAFF Benchmarks · 2013 Same Unit Results: Results from this same unit

  5. Mathematics of Planet Earth: Sustainable Human Environments

    E-Print Network [OSTI]

    : · Sustainable Human Environments cluster: Pre-workshop: Urban Planning for Climate Events Sept. 2013 Post. Dust storm in Malihttp://citadel.sjfc.edu/students/rnr00577/e-port/msti260/urban.htm #12;11 Sustainable1 Mathematics of Planet Earth: Sustainable Human Environments Fred Roberts Rutgers University #12

  6. Personnel / Human Resource Management MGTK 302 Online

    E-Print Network [OSTI]

    Diestel, Geoff

    LEARNING OBJECTIVES Upon successful completion of the Personnel & Human Resource Management (P/HRM) course environment that influence human resource management. Explain the influence on HRM functions an understanding of HRM's integrated role in an organization. Workforce Planning and Employment: Knowledge

  7. Biofuel Plant, Clearfield County, PA Human Dimensions

    E-Print Network [OSTI]

    Omiecinski, Curtis

    to communicate effectively with stakeholders affected by natural resource and envi ronmental change issuesBiofuel Plant, Clearfield County, PA Human Dimensions of Natural Resources and the Environment Intercollege DualTitle Program For more information, please contact: Human Dimensions of Natural Resources

  8. Atomic magnetometer for human magnetoencephalograpy.

    SciTech Connect (OSTI)

    Schwindt, Peter; Johnson, Cort N.

    2010-12-01

    We have developed a high sensitivity (<5 fTesla/{radical}Hz), fiber-optically coupled magnetometer to detect magnetic fields produced by the human brain. This is the first demonstration of a noncryogenic sensor that could replace cryogenic superconducting quantum interference device (SQUID) magnetometers in magnetoencephalography (MEG) and is an important advance in realizing cost-effective MEG. Within the sensor, a rubidium vapor is optically pumped with 795 laser light while field-induced optical rotations are measured with 780 nm laser light. Both beams share a single optical axis to maximize simplicity and compactness. In collaboration with neuroscientists at The Mind Research Network in Albuquerque, NM, the evoked responses resulting from median nerve and auditory stimulation were recorded with the atomic magnetometer and a commercial SQUID-based MEG system with signals comparing favorably. Multi-sensor operation has been demonstrated with two AMs placed on opposite sides of the head. Straightforward miniaturization would enable high-density sensor arrays for whole-head magnetoencephalography.

  9. Depth-resolved monitoring of diffusion of hyperosmotic agents in normal and malignant human esophagus tissues using optical coherence tomography in-vitro

    SciTech Connect (OSTI)

    Zhao Qingliang; Guo Zhouyi; Wei Huajiang; Yang Hongqin; Xie Shusen

    2011-10-31

    Depth-resolved monitoring with differentiation and quantification of glucose diffusion in healthy and abnormal esophagus tissues has been studied in vitro. Experiments have been performed using human normal esophagus and esophageal squamous cell carcinoma (ESCC) tissues by the optical coherence tomography (OCT). The images have been continuously acquired for 120 min in the experiments, and the depth-resolved and average permeability coefficients of the 40 % glucose solution have been calculated by the OCT amplitude (OCTA) method. We demonstrate the capability of the OCT technique for depth-resolved monitoring, differentiation, and quantifying of glucose diffusion in normal esophagus and ESCC tissues. It is found that the permeability coefficients of the 40 % glucose solution are not uniform throughout the normal esophagus and ESCC tissues and increase from (3.30 {+-} 0.09) Multiplication-Sign 10{sup -6} and (1.57 {+-} 0.05) Multiplication-Sign 10{sup -5} cm s{sup -1} at the mucous membrane of normal esophagus and ESCC tissues to (1.82 {+-} 0.04) Multiplication-Sign 10{sup -5} and (3.53 {+-} 0.09) Multiplication-Sign 10{sup -5} cm s{sup -1} at the submucous layer approximately 742 {mu}m away from the epithelial surface of normal esophagus and ESCC tissues, respectively. (optical coherence tomography)

  10. PASSIVE CONTROL OF FLUID POWERED HUMAN POWER AMPLIFIERS

    E-Print Network [OSTI]

    Li, Perry Y.

    PASSIVE CONTROL OF FLUID POWERED HUMAN POWER AMPLIFIERS Perry Y. Li and Venkat Durbha Center is proposed for the control of fluid powered human power amplifiers. Human power amplifiers are mechanical human power amplifier interacts with the human opeartor and other environments passively

  11. Initial sequencing and analysis of the human genome

    E-Print Network [OSTI]

    Boetticher, Gary D.

    Initial sequencing and analysis of the human genome International Human Genome Sequencing. ............................................................................................................................................................................................................................................................................ The human genome holds an extraordinary trove of information about human development, physiology, medicine a draft sequence of the human genome. We also present an initial analysis of the data, describing some

  12. Human retroviruses and AIDS 1997

    SciTech Connect (OSTI)

    Korber, B.; Foley, B.; Leitner, T.

    1997-12-01

    This compendium is the result of an effort to compile, organize, and rapidly publish as much relevant molecular data concerning the human immunodeficiency viruses (HIV) and related retroviruses as possible. The scope of the compendium and database is best summarized by the four parts that it comprises: (1) Nucleic Acid Alignments, (2) Amino Acid Alignments, (3) Reviews and Analyses, and (4) Related Sequences. Information within all the parts is updated throughout the year on the Web site, http://hiv-web.lanl.gov. This year we are not including floppy diskettes as the entire compendium is available both at our Web site and at our ftp site. If you need floppy diskettes please contact either Bette Korber (btk@t10.lanl.gov) or Kersti Rock (karm@t10.lanl.gov) by email or fax ((505) 665-4453). While this publication could take the form of a review or sequence monograph, it is not so conceived. Instead, the literature from which the database is derived has simply been summarized and some elementary computational analyses have been performed upon the data. Interpretation and commentary have been avoided insofar as possible so that the reader can form his or her own judgments concerning the complex information. The exception to this are reviews submitted by experts in areas deemed of particular and basic importance to research involving AIDS viral sequence information. These are included in Part III, and are contributed by scientists with particular expertise in the area of interest. In addition to the general descriptions below of the parts of the compendium, the user should read the individual introductions for each part.

  13. Human Reliability Considerations for Small Modular Reactors

    SciTech Connect (OSTI)

    OHara J. M.; Higgins, H.; DAgostino, A.; Erasmia, L.

    2012-01-27

    Small modular reactors (SMRs) are a promising approach to meeting future energy needs. Although the electrical output of an individual SMR is relatively small compared to that of typical commercial nuclear plants, they can be grouped to produce as much energy as a utility demands. Furthermore, SMRs can be used for other purposes, such as producing hydrogen and generating process heat. The design characteristics of many SMRs differ from those of current conventional plants and may require a distinct concept of operations. The U.S. Nuclear Regulatory Commission (NRC) conducted research to examine the human factors engineering and the operational aspects of SMRs. The research identified thirty potential human-performance issues that should be considered in the NRC's reviews of SMR designs and in future research activities. The purpose of this report is to illustrate how the issues can support SMR probabilistic risk analyses and their review by identifying potential human failure events for a subset of the issues. As part of addressing the human contribution to plant risk, human reliability analysis practitioners identify and quantify the human failure events that can negatively impact normal or emergency plant operations. The results illustrated here can be generalized to identify additional human failure events for the issues discussed and can be applied to those issues not discussed in this report.

  14. Too much ‘digital’, too little ‘humanities’? An attempt to explain why many humanities scholars are reluctant converts to Digital Humanities

    E-Print Network [OSTI]

    Porsdam, Helle

    2011-01-01

    6 Ibid. 7 Brett Bobley, quoted in Patricia Cohen, “Digital Keys for Unlocking the Humanities’ Riches.” See also Tony Hey, Stewart Tansley, and Kristin Tolle (eds.), The Fourth Paradigm: Data-Intensive Scientific Discovery (Microsoft Research, 2009...

  15. Human dopamine receptor and its uses

    DOE Patents [OSTI]

    Civelli, Olivier (Portland, OR); Van Tol, Hubert Henri-Marie (Toronto, CA)

    1999-01-01

    The present invention is directed toward the isolation, characterization and pharmacological use of the human D4 dopamine receptor. The nucleotide sequence of the gene corresponding to this receptor and alleleic variant thereof are provided by the invention. The invention also includes recombinant eukaryotic expression constructs capable of expressing the human D4 dopamine receptor in cultures of transformed eukaryotic cells. The invention provides cultures of transformed eukaryotic cells which synthesize the human D4 dopamine receptor, and methods for characterizing novel psychotropic compounds using such cultures.

  16. Human epididymis protein 4 (HE4) plays a key role in ovarian cancer cell adhesion and motility

    SciTech Connect (OSTI)

    Lu, Renquan; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032 ; Sun, Xinghui; Department of Medicine, Harvard Medical School, MA 02115 ; Xiao, Ran; Zhou, Lei; Gao, Xiang; Guo, Lin; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer We generated stable transduced HE4 overexpression and knockdown cells. Black-Right-Pointing-Pointer HE4 was associated with EOC cell adhesion and motility. Black-Right-Pointing-Pointer HE4 might have some effects on activation of EGFR-MAPK signaling pathway. Black-Right-Pointing-Pointer HE4 play an important role in EOC tumorigenicity. -- Abstract: Human epididymis protein 4 (HE4) is a novel and specific biomarker for epithelial ovarian cancer (EOC). We previously demonstrated that serum HE4 levels were significantly elevated in the majority of EOC patients but not in subjects with benign disease or healthy controls. However, the precise mechanism of HE4 protein function is unknown. In this study, we generated HE4-overexpressing SKOV3 cells and found that stably transduced cells promoted cell adhesion and migration. Knockdown of HE4 expression was achieved by stable transfection of SKOV3 cells with a construct encoding a short hairpin DNA directed against the HE4 gene. Correspondingly, the proliferation and spreading ability of HE4-expressed cells were inhibited by HE4 suppression. Mechanistically, impaired EGFR and Erk1/2 phosphorylation were observed in cells with HE4 knockdown. The phosphorylation was restored when the knockdown cells were cultured in conditioned medium containing HE4. Moreover, in vivo tumorigenicity showed that HE4 suppression markedly inhibited the growth of tumors. This suggests that expression of HE4 is associated with cancer cell adhesion, migration and tumor growth, which can be related to its effects on the EGFR-MAPK signaling pathway. Our results provide evidence of the cellular and molecular mechanisms that may underlie the motility-promoting role of HE4 in EOC progression. The role of HE4 as a target for gene-based therapy might be considered in future studies.

  17. Ensuring Safety in Human Robot Collaboration in Assembly

    E-Print Network [OSTI]

    Gupta, Satyandra K.

    into anthropic environments High inertia High power actuation Electrical threats Human errors · TraditionalEnsuring Safety in Human Robot Collaboration in Assembly Applications Satyandra K. Gupta, Krishnanand Kaipa, Carlos Morato, and Boxuan Zhao #12;Human Robot Collaboration · Robots welding, bolting

  18. Scientific Bibliography on Human Powered Submarines, through 1997

    E-Print Network [OSTI]

    Brueggeman, Peter

    1997-01-01

    delivery to the water, human power plant, overall vehicleBenetti-Longhini, L et al Human Power: the Technical Journalprocess DeRoos, B et al Human Power: the Technical Journal

  19. Models and evaluation of human-machine systems

    E-Print Network [OSTI]

    Bayout Alvarenga, Marco Antonio

    1993-01-01

    The field of human-machine systems and human-machine interfaces is very multidisciplinary. We have to navigate between the knowledge waves brought by several areas of the human learning: cognitive psychology, artificial ...

  20. HUMAN FACTORS GUIDANCE FOR CONTROL ROOM EVALUATION

    SciTech Connect (OSTI)

    OHARA,J.; BROWN,W.; STUBLER,W.; HIGGINS,J.; WACHTEL,J.; PERSENSKY,J.J.

    2000-07-30

    The Human-System Interface Design Review Guideline (NUREG-0700, Revision 1) was developed by the US Nuclear Regulatory Commission (NRC) to provide human factors guidance as a basis for the review of advanced human-system interface technologies. The guidance consists of three components: design review procedures, human factors engineering guidelines, and a software application to provide design review support called the ``Design Review Guideline.'' Since it was published in June 1996, Rev. 1 to NUREG-0700 has been used successfully by NRC staff, contractors and nuclear industry organizations, as well as by interested organizations outside the nuclear industry. The NRC has committed to the periodic update and improvement of the guidance to ensure that it remains a state-of-the-art design evaluation tool in the face of emerging and rapidly changing technology. This paper addresses the current research to update of NUREG-0700 based on the substantial work that has taken place since the publication of Revision 1.

  1. Achieving a Fieldable, Acquisition Process for Human-

    E-Print Network [OSTI]

    Cummings, Mary "Missy"

    Centered Design Environment or Complex Systems. Czaja, Sara J., 1997. "Systems Design and Evaluation," in Handbook of Human Factors and Ergonomics, 2nd Edition. John Wiley and Sons, Inc. Deal, S. (moderator

  2. Pantomimic Gestures for Human-Robot Interaction

    E-Print Network [OSTI]

    Burke, Michael; Lasenby, Joan

    2015-09-23

    This work introduces a pantomimic gesture interface, which classifies human hand gestures using unmanned aerial vehicle (UAV) behaviour recordings as training data. We argue that pantomimic gestures are more intuitive than iconic gestures and show...

  3. Implications of the Human Genome Project

    SciTech Connect (OSTI)

    Kitcher, P.

    1998-11-01

    The Human Genome Project (HGP), launched in 1991, aims to map and sequence the human genome by 2006. During the fifteen-year life of the project, it is projected that $3 billion in federal funds will be allocated to it. The ultimate aims of spending this money are to analyze the structure of human DNA, to identify all human genes, to recognize the functions of those genes, and to prepare for the biology and medicine of the twenty-first century. The following summary examines some of the implications of the program, concentrating on its scientific import and on the ethical and social problems that it raises. Its aim is to expose principles that might be used in applying the information which the HGP will generate. There is no attempt here to translate the principles into detailed proposals for legislation. Arguments and discussion can be found in the full report, but, like this summary, that report does not contain any legislative proposals.

  4. 2011-2015 Human Capital Management Plan

    Office of Energy Efficiency and Renewable Energy (EERE)

    The Office of Legacy Management (LM) needs skilled and engaged staff to accomplish our mission and carry out our responsibilities to the American people. This Human Capital Management Plan (HCMP or...

  5. Identifying the structural discontinuities of human interactions

    E-Print Network [OSTI]

    Grauwin, Sebastian; Sobolevsky, Stanislav; Hövel, Philipp; Simini, Filippo; Vanhoof, Maarten; Smoreda, Zbigniew; Barabasi, Albert-Laszlo; Ratti, Carlo

    2015-01-01

    The idea of a hierarchical spatial organization of society lies at the core of seminal theories in human geography that have strongly influenced our understanding of social organization. In the same line, the recent availability of large-scale human mobility and communication data has offered novel quantitative insights hinting at a strong geographical confinement of human interactions within neighboring regions, extending to local levels within countries. However, models of human interaction largely ignore this effect. Here, we analyze several country-wide networks of telephone calls and uncover a systematic decrease of communication induced by borders which we identify as the missing variable in state-of-the-art models. Using this empirical evidence, we propose an alternative modeling framework that naturally stylize the damping effect of borders. We show that this new notion substantially improves the predictive power of widely used interaction models, thus increasing our ability to predict social activiti...

  6. Analysis of biomarkers for complex human diseases 

    E-Print Network [OSTI]

    Ansari, Morad

    2009-01-01

    The aims of this study were to analyse known and potential biomarkers of common and genetically complex human disorders and to identify genetic and environmental variation associated with plasma biomarker concentrations. ...

  7. History of Human Biology (1929–2009)

    E-Print Network [OSTI]

    Crawford, Michael H.

    2010-01-01

    The journal Human Biology was founded 80 years ago by Raymond Pearl, an eminent biologist and professor of biometry and vital statistics at Johns Hopkins University. In celebration of the 80th anniversary of the founding of this journal, I...

  8. HST.071 Human Reproductive Biology, Fall 2002

    E-Print Network [OSTI]

    Klapholz, Henry

    Lectures and clinical case discussions designed to provide the student with a clear understanding of the physiology, endocrinology, and pathology of human reproduction. Emphasis is on the role of technology in reproductive ...

  9. A Computational Framework Incorporating Human and Social

    E-Print Network [OSTI]

    Stanford University

    A Computational Framework Incorporating Human and Social Behaviors for Occupant-centric Egress BEHAVIORS FOR OCCUPANT- CENTRIC EGRESS SIMULATION A DISSERTATION SUBMITTED TO THE DEPARTMENT OF CIVIL. Studies of catastrophic incidents have highlighted the need to consider occupants' behaviors

  10. 1 2/19/2014 Human Resources

    E-Print Network [OSTI]

    1 2/19/2014 Human Resources Consulting Services Dave Lett, Manager (Acting) Energy, Team Lead Nuclear Science and Engineering Michelle Mazerolle, Team Lead Physical Sciences Michele Lusk Manager* Facilities and Operations Katie Waldrop, Team Lead Business Services; Environment, Safety

  11. Personnel / Human Resource Management MGTK 302 Online

    E-Print Network [OSTI]

    Diestel, Geoff

    of the Personnel & Human Resource Management (P/HRM) course, the student will be able to: each student will be able, ethics, scorecard metrics, global HRM, etc.) related to designing and implementing effective

  12. Personnel / Human Resource Management MGTK 302 ONLINE

    E-Print Network [OSTI]

    Diestel, Geoff

    of the Personnel & Human Resource Management (P/HRM) course, the student will be able to: each student will be able, ethics, scorecard metrics, global HRM, etc.) related to designing and implementing effective

  13. Human Factors of Healthcare Reporting Systems

    E-Print Network [OSTI]

    Johnson, C.W.

    Johnson,C.W. P. Carayon (ed), A Handbook of Human Factors and Ergonomics in Healthcare and Patient Safety, Lawrence Erlbaum, London, UK pp 525-560 Lawrence Erlbaum Associates

  14. Enhancing Human and Planetary Health Through Innovation

    SciTech Connect (OSTI)

    Brown, Ben

    2014-10-17

    Ben Brown mesmerizes the audience on how to enhance human and planetary health through innovation at our '8 Big Ideas' Science at the Theater event on October 8th, 2014, in Oakland, California.

  15. Human Capital Accountability Program--Withdrawn

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

    2012-11-15

    Withdrawn 3-26-14. The purpose of maintaining and updating this directive is to (1) Ensure compliance with applicable laws, regulations, and other directives. (2) Reduce the risk of DOE losing any of its personnel authorities. (3) Incorporate functional accountability to ensure that Human Resource Directors' position descriptions and classifications are appropriate, selections result in quality leadership with skills needed, and performance plans and evaluations are consistent with Department and Administration human resources priorities and audit findings.

  16. Balanced Virtual Humans Interacting with their Environment

    E-Print Network [OSTI]

    Rennuit, Antoine; Merlhiot, Xavier; Andriot, Claude; Guillaume, François; Chevassus, Nicolas; Chablat, Damien; Chedmail, Patrick

    2007-01-01

    The animation of human avatars seems very successful; the computer graphics industry shows outstanding results in films everyday, the game industry achieves exploits... Nevertheless, the animation and control processes of such manikins are very painful. It takes days to a specialist to build such animated sequences, and it is not adaptive to any type of modifications. Our main purpose is the virtual human for engineering, especially virtual prototyping. As for this domain of activity, such amounts of time are prohibitive.

  17. Human immunodeficiency virus type 1 clade M mosaic gag polypeptides...

    Office of Scientific and Technical Information (OSTI)

    Patent: Human immunodeficiency virus type 1 clade M mosaic gag polypeptides Citation Details In-Document Search Title: Human immunodeficiency virus type 1 clade M mosaic gag...

  18. High-Performance Affordable Housing with Habitat for Humanity...

    Office of Environmental Management (EM)

    High-Performance Affordable Housing with Habitat for Humanity - Building America Top Innovation High-Performance Affordable Housing with Habitat for Humanity - Building America Top...

  19. PIA - Savannah River Nuclear Solutions (SRNS) Human Resource...

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

    (SRNS) Human Resource Management System (HRMS) PIA - Savannah River Nuclear Solutions (SRNS) Human Resource Management System (HRMS) PIA - Savannah River Nuclear Solutions (SRNS)...

  20. DOE Jobs Online (Hiring Manager), Office of Human Capitol Management...

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

    Jobs Online (Hiring Manager), Office of Human Capitol Management Innovation and Solutions DOE Jobs Online (Hiring Manager), Office of Human Capitol Management Innovation and...

  1. Human Health Risk & Environmental Analysis | Clean Energy | ORNL

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

    Human Health Risk and Environmental Analysis SHARE Human Health Risk and Environmental Analysis Help decision makers assess emerging technologies and methods for identifying and...

  2. Miliary Tuberculosis Coinfection with the Human Immunodeficiency Virus

    E-Print Network [OSTI]

    Esteve, Erika; Supervía, August; Pallàs, Oriol; Martínez, María T; Montero, María M; del Baño, Francisco

    2010-01-01

    human immunodeficiency virus, and foreign birth in Northwith Human Immunodeficiency Virus Erika Esteve, MD* Augusthuman immunodeficiency virus (HIV). 1 In the United States,

  3. Annual Mandatory Training for Managers, Supervisors and Human...

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

    Annual Mandatory Training for Managers, Supervisors and Human Resource Professionals on Veteran Employment and USERRA Annual Mandatory Training for Managers, Supervisors and Human...

  4. Irradiation Effects on Human Cortical Bone Fracture Behavior

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

    Irradiation Effects on Human Cortical Bone Fracture Behavior Print Human bone is strong but still fallible. To better predict fracturing in bone, researchers need a mechanistic...

  5. Creating LTS&M Efficiencies While Protecting Human Health and...

    Office of Environmental Management (EM)

    Creating LTS&M Efficiencies While Protecting Human Health and the Environment Creating LTS&M Efficiencies While Protecting Human Health and the Environment October 13, 2015 -...

  6. Endothelial influences enhance human pluripotent stem cell -derived cardiomyocyte maturation

    E-Print Network [OSTI]

    Wei, Karen A.

    2011-01-01

    Human embryonic stem cell-derived cardiomyocytes survive andet al. , Cardiomyocytes derived from human embryonic stemcardiac function by hESC-derived cardiomyocytes correlates

  7. Human-robot cross-training: Computational formulation, modeling and evaluation of a human team training strategy

    E-Print Network [OSTI]

    Nikolaidis, Stefanos

    We design and evaluate human-robot cross-training, a strategy widely used and validated for effective human team training. Cross-training is an interactive planning method in which a human and a robot iteratively switch ...

  8. Impact of the [delta]F508 Mutation in First Nucleotide-binding Domain of Human Cystic Fibrosis Transmembrane Conductance Regulator on Domain Folding and Structure

    SciTech Connect (OSTI)

    Lewis, Hal A.; Zhao, Xun; Wang, Chi; Sauder, J. Michael; Rooney, Isabelle; Noland, Brian W.; Lorimer, Don; Kearins, Margaret C.; Conners, Kris; Condon, Brad; Maloney, Peter C.; Guggino, William B.; Hunt, John F.; Emtage, Spencer (SG); (Columbia); (JHU)

    2010-07-19

    Cystic fibrosis is caused by defects in the cystic fibrosis transmembrane conductance regulator (CFTR), commonly the deletion of residue Phe-508 (DeltaF508) in the first nucleotide-binding domain (NBD1), which results in a severe reduction in the population of functional channels at the epithelial cell surface. Previous studies employing incomplete NBD1 domains have attributed this to aberrant folding of DeltaF508 NBD1. We report structural and biophysical studies on complete human NBD1 domains, which fail to demonstrate significant changes of in vitro stability or folding kinetics in the presence or absence of the DeltaF508 mutation. Crystal structures show minimal changes in protein conformation but substantial changes in local surface topography at the site of the mutation, which is located in the region of NBD1 believed to interact with the first membrane spanning domain of CFTR. These results raise the possibility that the primary effect of DeltaF508 is a disruption of proper interdomain interactions at this site in CFTR rather than interference with the folding of NBD1. Interestingly, increases in the stability of NBD1 constructs are observed upon introduction of second-site mutations that suppress the trafficking defect caused by the DeltaF508 mutation, suggesting that these suppressors might function indirectly by improving the folding efficiency of NBD1 in the context of the full-length protein. The human NBD1 structures also solidify the understanding of CFTR regulation by showing that its two protein segments that can be phosphorylated both adopt multiple conformations that modulate access to the ATPase active site and functional interdomain interfaces.

  9. Three Human Cell Types Respond to Multi-Walled Carbon Nanotubes and Titanium Dioxide Nanobelts with Cell-Specific Transcriptomic and Proteomic Expression Patterns.

    SciTech Connect (OSTI)

    Tilton, Susan C.; Karin, Norman J.; Tolic, Ana; Xie, Yumei; Lai, Xianyin; Hamilton, Raymond F.; Waters, Katrina M.; Holian, Andrij; Witzmann, Frank A.; Orr, Galya

    2014-08-01

    The growing use of engineered nanoparticles (NPs) in commercial and medical applications raises the urgent need for tools that can predict NP toxicity. Global transcriptome and proteome analyses were conducted on three human cell types, exposed to two high aspect ratio NP types, to identify patterns of expression that might indicate high versus low NP toxicity. Three cell types representing the most common routes of human exposure to NPs, including macrophage-like (THP-1), small airway epithelial and intestinal (Caco-2/HT29-MTX) cells, were exposed to TiO2 nanobelts (TiO2-NB; high toxicity) and multi-walled carbon nanotubes (MWCNT; low toxicity) at low (10 µg/mL) and high (100 µg/mL) concentrations for 1 and 24 h. Unique patterns of gene and protein expressions were identified for each cell type, with no differentially expressed (p < 0.05, 1.5-fold change) genes or proteins overlapping across all three cell types. While unique to each cell type, the early response was primarily independent of NP type, showing similar expression patterns in response to both TiO2-NB and MWCNT. The early response might, therefore, indicate a general response to insult. In contrast, the 24 h response was unique to each NP type. The most significantly (p < 0.05) enriched biological processes in THP-1 cells indicated TiO2-NB regulation of pathways associated with inflammation, apoptosis, cell cycle arrest, DNA replication stress and genomic instability, while MWCNT-regulated pathways indicated increased cell proliferation, DNA repair and anti-apoptosis. These two distinct sets of biological pathways might, therefore, underlie cellular responses to high and low NP toxicity, respectively.

  10. A technique for human error analysis (ATHEANA)

    SciTech Connect (OSTI)

    Cooper, S.E.; Ramey-Smith, A.M.; Wreathall, J.; Parry, G.W. [and others

    1996-05-01

    Probabilistic risk assessment (PRA) has become an important tool in the nuclear power industry, both for the Nuclear Regulatory Commission (NRC) and the operating utilities. Human reliability analysis (HRA) is a critical element of PRA; however, limitations in the analysis of human actions in PRAs have long been recognized as a constraint when using PRA. A multidisciplinary HRA framework has been developed with the objective of providing a structured approach for analyzing operating experience and understanding nuclear plant safety, human error, and the underlying factors that affect them. The concepts of the framework have matured into a rudimentary working HRA method. A trial application of the method has demonstrated that it is possible to identify potentially significant human failure events from actual operating experience which are not generally included in current PRAs, as well as to identify associated performance shaping factors and plant conditions that have an observable impact on the frequency of core damage. A general process was developed, albeit in preliminary form, that addresses the iterative steps of defining human failure events and estimating their probabilities using search schemes. Additionally, a knowledge- base was developed which describes the links between performance shaping factors and resulting unsafe actions.

  11. Entrainment and Turn-Taking in Human-Human Dialogue Rivka Levitan 1,2

    E-Print Network [OSTI]

    Benus, Stefan

    Entrainment and Turn-Taking in Human-Human Dialogue Rivka Levitan 1,2 , Stefan Benus 3 , Agust@cs.columbia.edu Abstract Interlocutors in spoken conversations have been shown to entrain, or become similar to each other, in multi- ple dimensions. We investigate the relationship between entrainment and turn-taking. We show

  12. Study questions: Energy & Environment: Humans & Nature 18 May 2012 Two `Laws' of human nature

    E-Print Network [OSTI]

    Study questions: Energy & Environment: Humans & Nature 18 May 2012 Two `Laws' of human nature 1. Jevons' Law, or the law of diminishing marginal utility One of the class (sorry, can't remember who) posted an interesting note on `Jevons' Law'. This would seem to be a danger signal for the hopeful

  13. Learned Human-in-the-Loop Decision Making

    E-Print Network [OSTI]

    Basso, Brandon

    2012-01-01

    that it was human. - Alan Turing Introduction Learning is agreat frequency. - Alan Turing Introduction The Generalized

  14. Reviewing the human dimensions of wildlife management and recreation

    E-Print Network [OSTI]

    to wildlife management? Who opposes wildlife management and why? Change in the human dimensions of wildlifeReviewing the human dimensions of wildlife management and recreation Mariella Marzano Norman Dandy Centre for Human & Ecological Sciences Forest Research #12;Human Dimensions of Species Management http

  15. Assembly and Analysis of Extended Human Genomic Contig Regions

    E-Print Network [OSTI]

    Rouchka, Eric

    @ibc.wustl.edu; states@ibc.wustl.edu Abstract The Human Genome Project (HGP) has led to the deposit of human genomic The U.S. Human Genome Project, coordinated by the United States Department of Energy (DOEAssembly and Analysis of Extended Human Genomic Contig Regions Eric C. Rouchka and David J. States

  16. METHOD Open Access A standard variation file format for human

    E-Print Network [OSTI]

    Yandell, Mark

    was originally developed during the human genome project to compare human genome annotations [17]. ImportantlyMETHOD Open Access A standard variation file format for human genome sequences Martin G Reese1 data. The 10Gen dataset, ten human genomes in GVF format, is freely available for com- munity analysis

  17. Inducing Self-Selected Human Engagement in Robotic Locomotion Training

    E-Print Network [OSTI]

    Collins, Steven H.

    to a human therapist, such as electromyographic activity; they can endure longer, more intense, and more

  18. Skeletal Adaptations in Humans How are we anatomically different?

    E-Print Network [OSTI]

    posteriorly #12;Skeletal Adaptations in Humans · Vertebral Column ­ lumbar + cervical curvatures ­ more

  19. Virtual Humans for Animation, Ergonomics, and Simulation Norman Badler

    E-Print Network [OSTI]

    Badler, Norman I.

    Virtual Humans for Animation, Ergonomics, and Simulation Norman Badler Center for Human Modeling speed and control methods needed to portray 3D virtual humans suitable for real interactive applications of Pennsylvania with the Jack system. Various aspects of real­time virtual humans are considered

  20. Learning expressive human-like head motion sequences from speech

    E-Print Network [OSTI]

    Busso, Carlos

    With the development of new trends in human-machine interfaces, animated feature films and video games, better avatars and virtual agents are required that more accurately mimic how humans communicate and interact. Gestures the emotional perception of facial animations [6]. Given the importance of head motion in human-human

  1. Production and Playback of Human Figure Motion for Visual Simulation

    E-Print Network [OSTI]

    Badler, Norman I.

    -line production and real-time playback of motion for articulated human gures in 3D virtual environments, for later playback. We present our system in the context of a simple problem: Animating human gures in virtual worlds containing simulated humans. Whether these human gures rep- resent the users' virtual

  2. Protection of Human Subjects in Last Updated July, 2014

    E-Print Network [OSTI]

    ................................................................................................................................1 History of the Human Subjects Protection System .....................................................................28 Informed Consent for Internet Research

  3. Do myoepithelial cells hold the key for breast tumorprogression?

    SciTech Connect (OSTI)

    Polyak, Kornelia; Hu, Min

    2005-11-18

    Mammary myoepithelial cells have been the foster child of breast cancer biology and have been largely ignored since they were considered to be less important for tumorigenesis than luminal epithelial cells from which most of breast carcinomas are thought to arise. In recent years as our knowledge in stem cell biology and the cellular microenvironment has been increasing myoepithelial cells are slowly starting to gain more attention. Emerging data raise the hypothesis if myoepithelial cells play a key role in breast tumor progression by regulating the in situ to invasive carcinoma transition and if myoepithelial cells are part of the mammary stem cell niche. Paracrine interactions between myoepithelial and luminal epithelial cells are known to be important for cell cycle arrest, establishing epithelial cell polarity, and inhibiting migration and invasion. Based on these functions normal mammary myoepithelial cells have been called ''natural tumor suppressors''. However, during tumor progression myoepithelial cells seem to loose these properties and eventually they themselves diminish as tumors become invasive. Better understanding of myoepithelial cell function and their role in tumor progression may lead to their exploitation for cancer therapeutic and preventative measures.

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

    SciTech Connect (OSTI)

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

    2003-05-15

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

  5. Advancing Usability Evaluation through Human Reliability Analysis

    SciTech Connect (OSTI)

    Ronald L. Boring; David I. Gertman

    2005-07-01

    This paper introduces a novel augmentation to the current heuristic usability evaluation methodology. The SPAR-H human reliability analysis method was developed for categorizing human performance in nuclear power plants. Despite the specialized use of SPAR-H for safety critical scenarios, the method also holds promise for use in commercial off-the-shelf software usability evaluations. The SPAR-H method shares task analysis underpinnings with human-computer interaction, and it can be easily adapted to incorporate usability heuristics as performance shaping factors. By assigning probabilistic modifiers to heuristics, it is possible to arrive at the usability error probability (UEP). This UEP is not a literal probability of error but nonetheless provides a quantitative basis to heuristic evaluation. When combined with a consequence matrix for usability errors, this method affords ready prioritization of usability issues.

  6. Human factors in nuclear technology - a history

    SciTech Connect (OSTI)

    Jones, D.B. )

    1992-01-01

    Human factors, human factors engineering (HFE), or ergonomics did not receive much formal attention in nuclear technology prior to the Three Mile Island Unit 2 (TMI-2) incident. Three principal reasons exist for this lack of concern. First, emerging technologies show little concern with how people will use a new system. Making the new technology work is considered more important than the people who will use it. Second, the culture of the users of nuclear power did not recognize a need for human factors. Traditional utilities had well established and effective engineering designs for control of electric power generation, while medicine considered the use of nuclear isotopes another useful tool, not requiring special ergonomics. Finally, the nuclear industry owed much to Admiral Rickover. He was definitely opposed.

  7. United Nations Human Space Technology Initiative (HSTI)

    E-Print Network [OSTI]

    Ochiai, M; Steffens, H; Balogh, W; Haubold, H J; Othman, M; Doi, T

    2015-01-01

    The Human Space Technology Initiative was launched in 2010 within the framework of the United Nations Programme on Space Applications implemented by the Office for Outer Space Affairs of the United Nations. It aims to involve more countries in activities related to human spaceflight and space exploration and to increase the benefits from the outcome of such activities through international cooperation, to make space exploration a truly international effort. The role of the Initiative in these efforts is to provide a platform to exchange information, foster collaboration between partners from spacefaring and non-spacefaring countries, and encourage emerging and developing countries to take part in space research and benefit from space applications. The Initiative organizes expert meetings and workshops annually to raise awareness of the current status of space exploration activities as well as of the benefits of utilizing human space technology and its applications. The Initiative is also carrying out primary ...

  8. Planet-scale Human Mobility Measurement

    E-Print Network [OSTI]

    Pan Hui; Richard Mortier; Tristan Henderson; Jon Crowcroft

    2009-09-18

    Research into, and design and construction of mobile systems and algorithms requires access to large-scale mobility data. Unfortunately, the wireless and mobile research community lacks such data. For instance, the largest available human contact traces contain only 100 nodes with very sparse connectivity, limited by experimental logistics. In this paper we pose a challenge to the community: how can we collect mobility data from billions of human participants? We re-assert the importance of large-scale datasets in communication network design, and claim that this could impact fundamental studies in other academic disciplines. In effect, we argue that planet-scale mobility measurements can help to save the world. For example, through understanding large-scale human mobility, we can track and model and contain the spread of epidemics of various kinds.

  9. An Agent-Based System Assisting Humans in Complex Tasks by Analysis of a Human's State and Performance

    E-Print Network [OSTI]

    Treur, Jan

    becomes too high, the agent can assist the human in a number of ways. Experiments show that the supportAn Agent-Based System Assisting Humans in Complex Tasks by Analysis of a Human's State, michael}@forcevisionlab.nl Abstract Human task performance varies depending on the task, environment

  10. Annotated bibliography of human factors applications literature

    SciTech Connect (OSTI)

    McCafferty, D.B.

    1984-09-30

    This bibliography was prepared as part of the Human Factors Technology Project, FY 1984, sponsored by the Office of Nuclear Safety, US Department of Energy. The project was conducted by Lawrence Livermore National Laboratory, with Essex Corporation as a subcontractor. The material presented here is a revision and expansion of the bibliographic material developed in FY 1982 as part of a previous Human Factors Technology Project. The previous bibliography was published September 30, 1982, as Attachment 1 to the FY 1982 Project Status Report.

  11. Model-based Analysis of HER Activation in Cells Co-Expressing EGFR, HER2 and HER3.

    SciTech Connect (OSTI)

    Shankaran, Harish; Zhang, Yi; Tan, Yunbing; Resat, Haluk

    2013-08-22

    The HER/ErbB family of receptor tyrosine kinases drive critical responses in normal physiology and cancer, and the expression levels of the various HER receptors are critical determinants of clinical outcomes. HER activation is driven by the formation of various dimer complexes between members of this receptor family. The HER dimer types can have differential effects on downstream signaling and phenotypic outcomes. We constructed an integrated mathematical model of HER activation and trafficking to quantitatively link receptor expression levels to dimerization and activation. We parameterized the model with a comprehensive set of HER phosphorylation and abundance data collected in a panel of human mammary epithelial cells expressing varying levels of EGFR, HER2 and HER3. Although parameter estimation yielded multiple solutions, predictions for dimer phosphorylation were in agreement with each other. We validated the model using experiments where pertuzumab was used to block HER2 dimerization. We used the model to predict HER dimerization and activation patterns in a panel of epithelial cells lines with known HER expression levels. Simulations over the range of expression levels seen in various cell lines indicate that: i) EGFR phosphorylation is driven by HER1/1 and HER1/2 dimers, and not HER1/3 dimers, ii) HER1/2 and HER2/3 dimers both contribute significantly to HER2 activation with the EGFR expression level determining the relative importance of these species, and iii) the HER2/3 dimer is largely responsible for HER3 activation. The model can be used to predict phosphorylated dimer levels for any given HER expression profile. This information in turn can be used to quantify the potencies of the various HER dimers, and can potentially inform personalized therapeutic approaches.

  12. Top-down and bottom-up definitions of human failure events in human reliability analysis

    SciTech Connect (OSTI)

    Boring, Ronald Laurids

    2014-10-01

    In the probabilistic risk assessments (PRAs) used in the nuclear industry, human failure events (HFEs) are determined as a subset of hardware failures, namely those hardware failures that could be triggered by human action or inaction. This approach is top-down, starting with hardware faults and deducing human contributions to those faults. Elsewhere, more traditionally human factors driven approaches would tend to look at opportunities for human errors first in a task analysis and then identify which of those errors is risk significant. The intersection of top-down and bottom-up approaches to defining HFEs has not been carefully studied. Ideally, both approaches should arrive at the same set of HFEs. This question is crucial, however, as human reliability analysis (HRA) methods are generalized to new domains like oil and gas. The HFEs used in nuclear PRAs tend to be top-down—defined as a subset of the PRA—whereas the HFEs used in petroleum quantitative risk assessments (QRAs) often tend to be bottom-up—derived from a task analysis conducted by human factors experts. The marriage of these approaches is necessary in order to ensure that HRA methods developed for top-down HFEs are also sufficient for bottom-up applications.

  13. Division of Human Resources Criminal History

    E-Print Network [OSTI]

    Meyers, Steven D.

    include a local criminal records check through local law enforcement agencies. The typical turnaround timeDivision of Human Resources Criminal History Background Check Procedures Questions (813) 9742970 HR Services/Background Checks Rev. 12/2012 Criminal History Background Check The University of South Florida

  14. Integrating Human Factors with Software Engineering Practices

    E-Print Network [OSTI]

    of the 38th Annual Meeting of the Human Factors and Ergonomics Society, Nashville, TN, October, 1994. Also to the design, development, and evaluation of usable and useful interactive systems, and presents a rationale Ergonomics and Safety Technology, Inc. Pittsburgh, PA 15213 USA jtr001@delphi.com 1. Introduction The design

  15. CHEMISTRY 1010 CHEMISTRY, HUMANITY AND ENVIRONMENT

    E-Print Network [OSTI]

    Simons, Jack

    : Chemistry 1010 aims to promote understanding of the basic environmental ingredients, energy, atomsCHEMISTRY 1010 CHEMISTRY, HUMANITY AND ENVIRONMENT Spring 2006 Instructor: Dr. Laya Kesner, HEB - 002 H ST 205 11:50 a.m.-12:40 p.m. Teaching Assistant: Chem 1010-002 Michelle Taliaferro, michelle@chemistry

  16. Human Health Science Building Geothermal Heat Pumps

    Broader source: Energy.gov [DOE]

    Project objectives: Construct a ground sourced heat pump, heating, ventilation, and air conditioning system for the new Oakland University Human Health Sciences Building utilizing variable refrigerant flow (VRF) heat pumps. A pair of dedicated outdoor air supply units will utilize a thermally regenerated desiccant dehumidification section. A large solar thermal system along with a natural gas backup boiler will provide the thermal regeneration energy.

  17. Modeling Human Foraging Brian D. Glass

    E-Print Network [OSTI]

    Maddox, W. Todd

    Modeling Human Foraging Brian D. Glass Department of Psychology University of Texas at Austin Thanks to W. Todd Maddox Arthur B. Markman Scott Lauritzen Cognition & Perception Group #12;Foraging What from group experiments like these? You learn about group behavior, with little to say about behavior

  18. Social transmission of face preferences among humans

    E-Print Network [OSTI]

    Indiana University

    Social transmission of face preferences among humans Benedict C. Jones1,*, Lisa M. DeBruine1 researchers to propose that social transmission of mate preferences may influence sexual selection for male traits. Although it has been suggested that social transmission may also influence mate preferences

  19. Human-Centered Sustainable Product !!Environmental impact

    E-Print Network [OSTI]

    Agogino, Alice M.

    Human-Centered Sustainable Product Design !!Environmental impact of buildings !!Green Building million tons annually) ·! 12% of potable water in the U.S. Environmental Impact of Buildings Environmental-ND: Neighborhood development (pilot program) Leadership in Energy & Environmental Design www.usgbc.org Gail Brager

  20. What Do Walking Humans Want From Mechatronics?

    E-Print Network [OSTI]

    Collins, Steven H.

    What Do Walking Humans Want From Mechatronics? (Invited Presentation) Steven H. Collins Department for millions of individuals. One branch of the emerging field of bio-mechatronics seeks to meet the mobility in mechatronics. II. SIMULATIONS, ROBOTS, AND OTHER MODELS Many assistive robotic devices are designed based

  1. Research Article Human Brain Activity Time-

    E-Print Network [OSTI]

    Zacks, Jeffrey M.

    Research Article Human Brain Activity Time- Locked to Narrative Event Boundaries Nicole K. Speer to or reading descriptions of everyday activities (e.g., reading about a person making cookies; Speer & Zacks, 2005; Speer, Zacks, & Reynolds, 2006). These findings are not altogether surprising given theories

  2. Risk Management Department of Human Resource Services

    E-Print Network [OSTI]

    de Lijser, Peter

    Risk Management Department of Human Resource Services Workers' Compensation Update INJURY to identify and address potential safety hazards. It also assists Risk Management staff determine in a timely manager or supervisor will contact Risk Management to arrange transportation. An employee who needs

  3. Risk Management Department of Human Resource Services

    E-Print Network [OSTI]

    de Lijser, Peter

    Risk Management Department of Human Resource Services Workers' Compensation Update WORKERS and are available by contacting the Risk Management department. Please do not add this form to any packets kept' COMPENSATION PHARMACY BENEFIT MANAGEMENT PROGRAM The California State University system has partnered

  4. Risk Management Department of Human Resource Services

    E-Print Network [OSTI]

    de Lijser, Peter

    Risk Management Department of Human Resource Services Workers' Compensation Update RETURN TO WORK or supervisor upon returning to work. The manager or supervisor should fax a copy of the release to Risk, the University's Workers' Compensation Program Manager, at extension 2824 or visit the Risk Management Website

  5. THE UNIVERSITY OF WESTERN ONTARIO Human Resources

    E-Print Network [OSTI]

    Cunningham, Ian

    Radiation Safety Coordinator on matters of all radiation safety including nuclear substances and radiationTHE UNIVERSITY OF WESTERN ONTARIO Human Resources Occupational Health and Safety SAFETY MANUAL FOR NON-MEDICAL X-RAY EQUIPMENT Prepared by Mr. H. Ly Radiation Safety Coordinator Approved

  6. IIT Lewis College of Human Sciences COMMUNICATION

    E-Print Network [OSTI]

    Heller, Barbara

    IIT Lewis College of Human Sciences COMMUNICATION As a student in the Communication program at IIT and Business, or Professional and Technical Communication. We live in a world where the modes of communication to focusing on one medium such as TV, radio, or print, as many communication programs do. We are one

  7. The role of human Web assistants in

    E-Print Network [OSTI]

    Aberg, Johan

    The role of human Web assistants in e-commerce: an analysis and a usability study Johan AÊberg and Nahid Shahmehri Introduction Web-based electronic commerce is just in its youth. Still, the amount of shopping on the Web in the USA has been estimated to be US$7 billion US dollars for Christmas 1999

  8. Human Resources Behaviour and Conduct Handbook

    E-Print Network [OSTI]

    Balasuriya, Sanjeeva

    Human Resources Behaviour and Conduct Handbook Fair Treatment Procedure Information Sheet: Fair Handbook Fair Treatment Procedure Effective Date: 16 October 2014 Version 1.0 Authorised by Manager, HR and Conduct Handbook Behaviour and Conduct Handbook Fair Treatment Procedure Effective Date: 16 October 2014

  9. Employee Handbook DEPARTMENT OF HUMAN RESOURCES

    E-Print Network [OSTI]

    Gopalakrishnan, K.

    SPA/CSS Employee Handbook June 2014 DEPARTMENT OF HUMAN RESOURCES WelcomeWelcomeWelcome #12;2 This handbook contains brief summarized statements of policies, procedures, and programs that are applicable Handbook. The information included in this handbook supersedes any information put forth in any previous

  10. Understanding complexity in the human brain

    E-Print Network [OSTI]

    Gazzaniga, Michael

    Understanding complexity in the human brain Danielle S. Bassett1 and Michael S. Gazzaniga2 1 the ultimate aim of neuroscientific enquiry is to gain an understanding of the brain and how its work- ings of mind­brain mechanisms if the cumulative findings from these neu- roscientific studies are coupled

  11. West Virginia University Division of Human Resources

    E-Print Network [OSTI]

    Mohaghegh, Shahab

    Resources Web page hr.wvu.edu. In the event of a conflict between the current posted version and this printed copy, the posted version on the Web page is controlling. Page 1 of 9 Family Medical Leave Act Division of Human Resources Web page hr.wvu.edu. In the event of a conflict between the current posted

  12. Human Resources Organizational Readiness Project: An Overview

    E-Print Network [OSTI]

    Finzi, Adrien

    and easily interface with SAP software Managed by a special Human Resources project team Will be undertaken in close coordination with the BUworks program team HR Organizational Readiness Project BUworks / SAP of SAP Enhanced data security within the new system Current job "system" is 30 years old ­ it must

  13. COURSE SYLLABUS MGMT 3313 HUMAN RESOURCE MANAGEMENT

    E-Print Network [OSTI]

    COURSE SYLLABUS MGMT 3313 ­ HUMAN RESOURCE MANAGEMENT Spring 2015 INSTRUCTOR: R. Evan Davis, Ph.D. OFFICE: 010 Classroom Building TELEPHONE: (405) 744-3011 E-MAIL: robert.evan.davis@okstate.edu OFFICE via skype or other technology if it is more convenient) COURSE SITE: D2L (Online Classroom): http

  14. CUNY EXPORT CONTROL PROCEDURES 7. Human Resources

    E-Print Network [OSTI]

    Rosen, Jay

    CUNY EXPORT CONTROL PROCEDURES 7. Human Resources This section addresses the I-129 certification process for visa applicants4 who may have access to export controlled items. It also addresses the process) will require an export license to access export controlled technology or technical data during the course

  15. HUMAN RESOURCES SALARY PACKAGING PAYMENT OPTIONS

    E-Print Network [OSTI]

    Tobar, Michael

    HUMAN RESOURCES SALARY PACKAGING PAYMENT OPTIONS This form is for staff employed by The University of Western Australia for salary packaging fitness memberships and renewals offered by UWA Sport member to access salary packaging arrangements. SECTION 1 ­ MEMBERSHIP MEMBERSHIP Start Date (dd

  16. Division of Human Resources Termination Of

    E-Print Network [OSTI]

    Meyers, Steven D.

    Division of Human Resources Termination Of Domestic Partnership Health Stipend Questions (813) 974 Insurance Stipend will terminate as of the Effective Date on this Termination of Domestic Partnership Health. ______ The Domestic Partnership Declaration attested to and filed by me with USF shall be and is terminated

  17. Human Resources Security Access Matrix Function Training

    E-Print Network [OSTI]

    Wu, Shin-Tson

    June 2013 Human Resources Security Access Matrix Function Training Course Required Class Mode Training Course Prerequisite Security Access Form Required Contact for Additional Information Complete Electronic I-9 Forms REC001: I-9 /E-Verify Web Training OR Online OR None Electronic I-9 Security Access Form

  18. ANTHROPOMETRY FOR COMPUTER GRAPHICS HUMAN FIGURES

    E-Print Network [OSTI]

    Badler, Norman I.

    ANTHROPOMETRY FOR COMPUTER GRAPHICS HUMAN FIGURES Marc R. Grosso1 Richard D. Quach2 Ernest Otani3, Warren, Michigan 48090-9040. i #12;Contents 1 Introduction 1 2 Anthropometry Issues 1 3 Implementation : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : 21 11.4 Spreadsheet Anthropometry Scaling System (SASS

  19. Workshop Reports Understanding Paleoclimate and Human Evolution

    E-Print Network [OSTI]

    Reiners, Peter W.

    (DSDP) drill cores collected in the Gulf of Aden. This paper, as well as subsequent ones (de and Paleolakes Drilling Project byAndrewCohen,RamonArrowsmith,AnnaK.Behrensmeyer,ChristopherCampisano, Craig.10.2009 60 Scientific Drilling, No. 8, September 2009 Workshop Reports Understanding the evolution of humans

  20. The University of Oklahoma HUMAN RESOURCES

    E-Print Network [OSTI]

    Oklahoma, University of

    The University of Oklahoma HUMAN RESOURCES MEMORANDUM TO: All OU employees FROM completed such a process, and the Staff Handbook was amended by the University of Oklahoma Board of Regents.11.2 FAMILY AND MEDICAL LEAVE ACT (FMLA) The University of Oklahoma Staff Handbook ­ Amended July 1, 2011

  1. Stimulus exposure effects in human associative learning

    E-Print Network [OSTI]

    Gluck, Mark

    Stimulus exposure effects in human associative learning Catherine E. Myers Rutgers University, Newark, NJ, U.S.A. Lindsay M. Oliver Glasgow Caledonian University, Glasgow, U.K. Stacey G. Warren should be sent to Catherine E. Myers, Department of Psychology, Rutgers University, Newark, NJ 07102, U

  2. Human-Centered Parametric Bicycle Timothy Dietz

    E-Print Network [OSTI]

    1 Human-Centered Parametric Bicycle Interface Timothy Dietz Markus Rippel Chenjie Wang Sen Yang ME.............................................................................. 16 3.5.3 Bicycle Parameter Part................................................................................ 17 3.5.4 The link between body measurement and bicycle dimension in automatic version 18 3.5.5 Output

  3. Division of Human Resources Nonresident Alien Federal

    E-Print Network [OSTI]

    Meyers, Steven D.

    Division of Human Resources Nonresident Alien Federal Withholding Requirements Questions (813) 974 classified as nonresident aliens for tax purposes with regard to their federal withholding taxes.gov. In brief, the Form W-4 requirements for individuals who are nonresident aliens (NRA) for tax purposes

  4. Exploring Paradigms of Human Resource Development 

    E-Print Network [OSTI]

    Hurt, Andrew Christopher

    2011-10-21

    This study focused on the issue of paradigms in Human Resource Development (HRD). Its purpose was to validate the HRD Cube as a synthesized model of HRD and to explicate some of the extant paradigms of HRD. The study was carried out by examining...

  5. Genomic Comparisons of Humans and Chimpanzees

    E-Print Network [OSTI]

    Genomic Comparisons of Humans and Chimpanzees Ajit Varki1 and David L. Nelson2 1 Glycobiology, anthropogeny, genetics, evolution, hominid Abstract The genome consists of the entire DNA present of the chimpanzee genome is now available, providing opportunities to better understand genetic contributions

  6. Virginia Commonwealth University Human Resources | Contacts

    E-Print Network [OSTI]

    Hammack, Richard

    Jobs Click "More search options" to access advanced search options Enter terms in the search box to search eJobs notes and tips 4 Searching 4 About user groups 5 About modules 6 The message bar 6 Your watchGuide to eJobs Virginia Commonwealth University | Human Resources 4 eJobs notes and tips Searching in e

  7. Wild-type human p53 transactivates the human proliferating cell nuclear antigen promoter

    SciTech Connect (OSTI)

    Shivakumar, C.V.; Brown, D.R.; Deb, S.; Deb, S.P. [Univ. of Texas Health Science Center, San Antonio, TX (United States)

    1995-12-01

    The p53 tumor suppressor protein negatively regulates cell growth and somatic mutations in the p53 gene lead to uncontrolled cell growth and oncogenesis. This report describes research which demonstrates, using a number of different cell lines, that at low levels, wild-type p53 transactivates the human proliferating cell nuclear antigen (PCNA) promoter. When expressed at similar levels, tumor-derived p53 mutants did not transactivate the PCNA promoter. It also reports the identification of a wild-type human p53-binding site on the human PCNA promote. 84 refs., 5 figs, 3 tabs.

  8. Structure of the EGF receptor transactivation circuit integrates multiple signals with cell context

    SciTech Connect (OSTI)

    Joslin, Elizabeth J.; Shankaran, Harish; Opresko, Lee K.; Bollinger, Nikki; Lauffenburger, Douglas A.; Wiley, H. S.

    2010-05-10

    Transactivation of the epidermal growth factor receptor (EGFR) has been proposed to be a mechanism by which a variety of cellular inputs can be integrated into a single signaling pathway, but the regulatory topology of this important system is unclear. To understand the transactivation circuit, we first created a “non-binding” reporter for ligand shedding. We then quantitatively defined how signals from multiple agonists were integrated both upstream and downstream of the EGFR into the extracellular signal regulated kinase (ERK) cascade in human mammary epithelial cells. We found that transactivation is mediated by a recursive autocrine circuit where ligand shedding drives EGFR-stimulated ERK that in turn drives further ligand shedding. The time from shedding to ERK activation is fast (<5 min) whereas the recursive feedback is slow (>15 min). Simulations showed that this delay in positive feedback greatly enhanced system stability and robustness. Our results indicate that the transactivation circuit is constructed so that the magnitude of ERK signaling is governed by the sum of multiple direct inputs, while recursive, autocrine ligand shedding controls signal duration.

  9. AZU-1: A Candidate Breast Tumor Suppressor and Biomarker for Tumor Progression

    SciTech Connect (OSTI)

    Chen, Huei-Mei; Schmeichel, Karen L; Mian, I. Saira; Lelie`vre, Sophie; Petersen, Ole W; Bissell, Mina J

    2000-02-04

    To identify genes misregulated in the final stages of breast carcinogenesis, we performed differential display to compare the gene expression patterns of the human tumorigenic mammary epithelial cells, HMT-3522-T4-2, with those of their immediate premalignant progenitors, HMT-3522-S2. We identified a novel gene, called anti-zuai-1 (AZU-1), that was abundantly expressed in non- and premalignant cells and tissues but was appreciably reduced in breast tumor cell types and in primary tumors. The AZU-1 gene encodes an acidic 571-amino-acid protein containing at least two structurally distinct domains with potential protein-binding functions: an N-terminal serine and proline-rich domain with a predicted immunoglobulin-like fold and a C-terminal coiled-coil domain. In HMT-3522 cells, the bulk of AZU-1 protein resided in a detergent-extractable cytoplasmic pool and was present at much lower levels in tumorigenic T4-2 cells than in their nonmalignant counterparts. Reversion of the tumorigenic phenotype of T4-2 cells, by means described previously, was accompanied by the up-regulation of AZU-1. In addition, reexpression of AZU-1 in T4-2 cells, using viral vectors, was sufficient to reduce their malignant phenotype substantially, both in culture and in vivo. These results indicate that AZU-1 is a candidate breast tumor suppressor that may exert its effects by promoting correct tissue morphogenesis.

  10. Restriction of Receptor Movement Alters Cellular Response: Physical Force Sensing by EphA2

    SciTech Connect (OSTI)

    Salaita, Khalid; Nair, Pradeep M; Petit, Rebecca S; Neve, Richard M; Das, Debopriya; Gray, Joe W; Groves, Jay T

    2009-09-09

    Activation of the EphA2 receptor tyrosine kinase by ephrin-A1 ligands presented on apposed cell surfaces plays important roles in development and exhibits poorly understood functional alterations in cancer. We reconstituted this intermembrane signaling geometry between live EphA2-expressing human breast cancer cells and supported membranes displaying laterally mobile ephrin-A1. Receptor-ligand binding, clustering, and subsequent lateral transport within this junction were observed. EphA2 transport can be blocked by physical barriers nanofabricated onto the underlying substrate. This physical reorganization of EphA2 alters the cellular response to ephrin-A1, as observed by changes in cytoskeleton morphology and recruitment of a disintegrin and metalloprotease 10. Quantitative analysis of receptor-ligand spatial organization across a library of 26 mammary epithelial cell lines reveals characteristic differences that strongly correlate with invasion potential. These observations reveal a mechanism for spatio-mechanical regulation of EphA2 signaling pathways.

  11. Network Analysis of Epidermal Growth Factor Signaling using Integrated Genomic, Proteomic and Phosphorylation Data

    SciTech Connect (OSTI)

    Waters, Katrina M.; Liu, Tao; Quesenberry, Ryan D.; Willse, Alan R.; Bandyopadhyay, Somnath; Kathmann, Loel E.; Weber, Thomas J.; Smith, Richard D.; Wiley, H. S.; Thrall, Brian D.

    2012-03-29

    To understand how integration of multiple data types can help decipher cellular responses at the systems level, we analyzed the mitogenic response of human mammary epithelial cells to epidermal growth factor (EGF) using whole genome microarrays, mass spectrometry-based proteomics and large-scale western blots with over 1000 antibodies. A time course analysis revealed significant differences in the expression of 3172 genes and 596 proteins, including protein phosphorylation changes measured by western blot. Integration of these disparate data types showed that each contributed qualitatively different components to the observed cell response to EGF and that varying degrees of concordance in gene expression and protein abundance measurements could be linked to specific biological processes. Networks inferred from individual data types were relatively limited, whereas networks derived from the integrated data recapitulated the known major cellular responses to EGF and exhibited more highly connected signaling nodes than networks derived from any individual dataset. While cell cycle regulatory pathways were altered as anticipated, we found the most robust response to mitogenic concentrations of EGF was induction of matrix metalloprotease cascades, highlighting the importance of the EGFR system as a regulator of the extracellular environment. These results demonstrate the value of integrating multiple levels of biological information to more accurately reconstruct networks of cellular response.

  12. Human Age Estimation From Skeletal and Dental Human Age Estimation From Skeletal and Dental

    E-Print Network [OSTI]

    Lucy, David

    and Section for Forensic Odontology, Oslo, Norway, for willingly providing what must be the world's most, likelihood, senescence, ageing, hard-tissue. Anthropologists and forensic scientists have found adult human

  13. Exuberant innovation: The Human Genome Project

    E-Print Network [OSTI]

    Gisler, Monika; Woodard, Ryan

    2010-01-01

    We present a detailed synthesis of the development of the Human Genome Project (HGP) from 1986 to 2003 in order to test the "social bubble" hypothesis that strong social interactions between enthusiastic supporters of the HGP weaved a network of reinforcing feedbacks that led to a widespread endorsement and extraordinary commitment by those involved in the project, beyond what would be rationalized by a standard cost-benefit analysis in the presence of extraordinary uncertainties and risks. The vigorous competition and race between the initially public project and several private initiatives is argued to support the social bubble hypothesis. We also present quantitative analyses of the concomitant financial bubble concentrated on the biotech sector. Confirmation of this hypothesis is offered by the present consensus that it will take decades to exploit the fruits of the HGP, via a slow and arduous process aiming at disentangling the extraordinary complexity of the human complex body. The HGP has ushered other...

  14. Justice and the human genome project

    SciTech Connect (OSTI)

    Murphy, T.F.; Lappe, M.A.

    1995-04-01

    This book is a collection of nine essays originally presented at a conference entitled {open_quotes}Justice and the Human Genome{close_quotes} held in Chicago in late 1991. The goal of the articles in this collection is to explore questions of justice raised by developments in genomic research and by applications of genetic knowledge and technology. The Human Genome Project (HGP) is used as a starting point for exploring these questions, but, as Marc Lappe recognizes, the database generated by HGP research will have implications far beyond the medical applications frequently used to justify this research effort. Thus, the book`s contributors consider questions of justice in relation to screening and testing for various predispositions, conditions, and diseases and gene therapy but also examine testing for other characteristics, forensic uses of genetic information, issues associated with DNA banks, and (hypothetical) genetic enhancement possibilities.

  15. Justice and the Human Genome Project

    SciTech Connect (OSTI)

    Murphy, T.F.; Lappe, M.

    1992-12-31

    Most of the essays gathered in this volume were first presented at a conference, Justice and the Human Genome, in Chicago in early November, 1991. The goal of the, conference was to consider questions of justice as they are and will be raised by the Human Genome Project. To achieve its goal of identifying and elucidating the challenges of justice inherent in genomic research and its social applications the conference drew together in one forum members from academia, medicine, and industry with interests divergent as rate-setting for insurance, the care of newborns, and the history of ethics. The essays in this volume address a number of theoretical and practical concerns relative to the meaning of genomic research.

  16. Justice and the Human Genome Project

    SciTech Connect (OSTI)

    Murphy, T.F.; Lappe, M.

    1992-01-01

    Most of the essays gathered in this volume were first presented at a conference, Justice and the Human Genome, in Chicago in early November, 1991. The goal of the, conference was to consider questions of justice as they are and will be raised by the Human Genome Project. To achieve its goal of identifying and elucidating the challenges of justice inherent in genomic research and its social applications the conference drew together in one forum members from academia, medicine, and industry with interests divergent as rate-setting for insurance, the care of newborns, and the history of ethics. The essays in this volume address a number of theoretical and practical concerns relative to the meaning of genomic research.

  17. From HumanFrom Human--Subject Experiments ToSubject Experiments To ComputationalComputational--Agent ExperimentsAgent Experiments

    E-Print Network [OSTI]

    Tesfatsion, Leigh

    1 From HumanFrom Human--Subject Experiments ToSubject Experiments To Computational Experiments - 100% human 100% computational agents What is Agent-based Comp Econ (ACE)? - 100% computational://www.econ.iastate.edu/tesfatsi/aexper.htm #12;3 Spectrum of Possible Experiments 100% human Humans with computer access Human

  18. The Emergence of ActualThe Emergence of Actual Human Disease as a Model forHuman Disease as a Model for

    E-Print Network [OSTI]

    Boguski, Mark S.

    + Chromosomome +e + ""icsics"" == GenomicsGenomics 1990 Human Genome Project launched1990 Human Genome Project launched 1998 Human Genome Project1998 Human Genome Project acceleratedaccelerated 20002000 ""DraftThe Emergence of ActualThe Emergence of Actual Human Disease as a Model forHuman Disease as a Model

  19. Trust-based design of human-guided algorithms

    E-Print Network [OSTI]

    Thomer, Joseph L. (Joseph Louis)

    2007-01-01

    By combining the strengths of human and computers, Human Machine Collaborative Decision Making has been shown to generate higher quality solutions in less time than conventional computerized methods. In many cases, it is ...

  20. Differentiated human stem cells resemble fetal, not adult, ? cells

    E-Print Network [OSTI]

    Hrvatin, Sinisa

    Human pluripotent stem cells (hPSCs) have the potential to generate any human cell type, and one widely recognized goal is to make pancreatic ? cells. To this end, comparisons between differentiated cell types produced in ...

  1. TurKit: Human Computation Algorithms on Mechanical Turk

    E-Print Network [OSTI]

    Little, Danny Greg

    Mechanical Turk (MTurk) provides an on-demand source of human computation. This provides a tremendous opportunity to explore algorithms which incorporate human computation as a function call. However, various systems ...

  2. Human-automation interaction for lunar landing aimpoint redesignation

    E-Print Network [OSTI]

    Needham, Jennifer M

    2008-01-01

    Human-automation interactions are a critical area of research in systems with modem automation. The decision-making portion of tasks presents a special challenge for human-automation interactions because of the many factors ...

  3. Reasons vs. Causes: Emergence as experienced by the human agent

    E-Print Network [OSTI]

    Jorion, Paul J

    2007-01-01

    Marriage, Authority, and Final Causes. New York: Free Press.Causes and reasons When talking of human beings, it is oftenwith explanations in terms of “causes” of collective human

  4. BigNeuron: Unlocking the Secrets of the Human Brain

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

    BigNeuron: Unlocking the Secrets of the Human Brain BigNeuron: Unlocking the Secrets of the Human Brain Berkeley Researchers and Supercomputers to Help Create a Standard 3D Neuron...

  5. Human rights enforcement: a fundamental duty of the sovereign state 

    E-Print Network [OSTI]

    Englehart, Ellen Marie

    1997-01-01

    Human rights enforcement is an important issue within international law. Unfortunately, the status quo of human rights within international law is unsatisfactory. Men, women and children suffer daily violations of their ...

  6. Ecological niche and geographic distribution of human monkeypox in Africa

    E-Print Network [OSTI]

    Levine, Rebecca S.; Peterson, A. Townsend; Yorita, Krista L.; Carroll, Darin S.; Damon, Inger K.; Reynolds, Mary G.

    2007-01-31

    Monkeypox virus, a zoonotic member of the genus Orthopoxviridae, can cause a severe, smallpox-like illness in humans. Monkeypox virus is thought to be endemic to forested areas of western and Central Africa. Considerably more is known about human...

  7. Essays on human capital and financial economics by Jialan Wang.

    E-Print Network [OSTI]

    Wang, Jialan, Ph.D. Massachusetts Institute of Technology

    2010-01-01

    This thesis consists of three essays examining issues related to human capital, careers, and financial economics. In the first chapter, I examine how the process of corporate bankruptcy varies by human capital intensity ...

  8. Food Science and Human Nutrition Graduate Program Handbook

    E-Print Network [OSTI]

    Food Science and Human Nutrition Graduate Program Handbook Department of Food Science and Human........................................................................... 12 2.10. Use of Hazardous Materials.............................................................. 14 3.4. Selection of the Major Professor

  9. Human walking model predicts joint mechanics, electromyography and mechanical economy

    E-Print Network [OSTI]

    Endo, Ken

    In this paper, we present an under-actuated model of human walking, comprising only a soleus muscle and flexion/extension monoarticular hip muscles. The remaining muscle groups of the human leg are modeled using quasi-passive, ...

  10. Assessing the performance of human-automation collaborative planning systems

    E-Print Network [OSTI]

    Ryan, Jason C. (Jason Christopher)

    2011-01-01

    Planning and Resource Allocation (P/RA) Human Supervisory Control (HSC) systems utilize the capabilities of both human operators and automated planning algorithms to schedule tasks for complex systems. In these systems, ...

  11. A model of muscle-tendon function in human walking

    E-Print Network [OSTI]

    Endo, Ken, Ph. D. Massachusetts Institute of Technology

    2012-01-01

    In order to motivate the design of legged machines that walk as humans do, this thesis investigates how leg muscles and tendons work mechanically during level-ground human walking at self-selected speeds. I hypothesize ...

  12. Groundwater Resources Assessment under the Pressures of Humanity

    E-Print Network [OSTI]

    1 GRAPHIC GRAPHIC Groundwater Resources Assessment under the Pressures of Humanity and Climate Changes Aframeworkdocument GRAPHICSeriesN°2 .................. #12;2 Groundwater Resources Assessment groundwater management considering projected climate change and linked human effects. GRAPHIC provides

  13. Texas Center for Digital Humanities and New Media 

    E-Print Network [OSTI]

    Earhart, Amy; Ives, Maura; Burkart, Patrick; Ezell, Margaret; Harner, James; Ramasubramanian, Srividya; Vieira de Castro, Filipe; Morris, Jeff; Dox, Donnalee; Urbina, Eduardo; Burlbaw, Lynn M.; Carpenter, B. Stephen II; Davis, Trina J.; Yadav, Manjit; Herbert, Bruce; Akleman, Ergun; Furuta, Richard; Shipman, Frank; Vedlitz, Arnold

    2009-01-01

    We propose the creation of a Center for Digital Humanities, Media and Culture (formerly titled Texas Center for Digital Humanities and New Media). The Center will address two related grand challenges: the need to investigate ...

  14. Human error contribution to nuclear materials-handling events

    E-Print Network [OSTI]

    Sutton, Bradley (Bradley Jordan)

    2007-01-01

    This thesis analyzes a sample of 15 fuel-handling events from the past ten years at commercial nuclear reactors with significant human error contributions in order to detail the contribution of human error to fuel-handling ...

  15. Human Reliability Analysis for Small Modular Reactors

    SciTech Connect (OSTI)

    Ronald L. Boring; David I. Gertman

    2012-06-01

    Because no human reliability analysis (HRA) method was specifically developed for small modular reactors (SMRs), the application of any current HRA method to SMRs represents tradeoffs. A first- generation HRA method like THERP provides clearly defined activity types, but these activity types do not map to the human-system interface or concept of operations confronting SMR operators. A second- generation HRA method like ATHEANA is flexible enough to be used for SMR applications, but there is currently insufficient guidance for the analyst, requiring considerably more first-of-a-kind analyses and extensive SMR expertise in order to complete a quality HRA. Although no current HRA method is optimized to SMRs, it is possible to use existing HRA methods to identify errors, incorporate them as human failure events in the probabilistic risk assessment (PRA), and quantify them. In this paper, we provided preliminary guidance to assist the human reliability analyst and reviewer in understanding how to apply current HRA methods to the domain of SMRs. While it is possible to perform a satisfactory HRA using existing HRA methods, ultimately it is desirable to formally incorporate SMR considerations into the methods. This may require the development of new HRA methods. More practicably, existing methods need to be adapted to incorporate SMRs. Such adaptations may take the form of guidance on the complex mapping between conventional light water reactors and small modular reactors. While many behaviors and activities are shared between current plants and SMRs, the methods must adapt if they are to perform a valid and accurate analysis of plant personnel performance in SMRs.

  16. Human Resource Directors (HRD) | Department of Energy

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

    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 Delicious Rank EERE: Alternative Fuelsof Energy ServicesContractingManagement » Human Resource Directors (HRD)

  17. Human Resources Reports | Department of Energy

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

    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 Delicious Rank EERE: Alternative Fuelsof Energy ServicesContractingManagement » Human Resource Directors

  18. Human factors engineering program review model

    SciTech Connect (OSTI)

    Not Available

    1994-07-01

    The staff of the Nuclear Regulatory Commission is performing nuclear power plant design certification reviews based on a design process plan that describes the human factors engineering (HFE) program elements that are necessary and sufficient to develop an acceptable detailed design specification and an acceptable implemented design. There are two principal reasons for this approach. First, the initial design certification applications submitted for staff review did not include detailed design information. Second, since human performance literature and industry experiences have shown that many significant human factors issues arise early in the design process, review of the design process activities and results is important to the evaluation of an overall design. However, current regulations and guidance documents do not address the criteria for design process review. Therefore, the HFE Program Review Model (HFE PRM) was developed as a basis for performing design certification reviews that include design process evaluations as well as review of the final design. A central tenet of the HFE PRM is that the HFE aspects of the plant should be developed, designed, and evaluated on the basis of a structured top-down system analysis using accepted HFE principles. The HFE PRM consists of ten component elements. Each element in divided into four sections: Background, Objective, Applicant Submittals, and Review Criteria. This report describes the development of the HFE PRM and gives a detailed description of each HFE review element.

  19. Current trends in mapping human genes

    SciTech Connect (OSTI)

    Mckusick, V.A. )

    1991-01-01

    The human is estimated to have at least 50,000 expressed genes (gene loci). Some information is available concerning about 5,000 of these gene loci and about 1,900 have been mapped, i.e., assigned to specific chromosomes (and in most instances particular chromosome regions). Progress has been achieved by a combination of physical mapping (e.g., study of somatic cell hybrids and chromosomal in situ hybridization) and genetic mapping (e.g., genetic linkage studies). New methods for both physical and genetic mapping are expanding the armamentarium. The usefulness of the mapping information is already evident; the spin-off from the Human Genome Project (HGP) begins immediately. the complete nucleotide sequence is the ultimate map of the human genome. Sequencing, although already under way for limited segments of the genome, will await further progress in gene mapping, and in particular creation of contig maps for each chromosome. Meanwhile the technology of sequencing and sequence information handling will be developed.

  20. Monoamine oxidase: Radiotracer chemistry and human studies

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

    Fowler, Joanna S.; Logan, Jean; Shumay, Elena; Alia-Klein, Nelly; Wang, Gene-Jack; Volkow, Nora D.

    2015-03-01

    Monoamine oxidase (MAO) oxidizes amines from both endogenous and exogenous sources thereby regulating the concentration of neurotransmitter amines such as serot onin, norepinephrine and dopamine as well as many xenobiotics. MAO inhibitor drugs are used in the treatment of Parkinson’s disease and in depression stimulating the development of radiotracer tools to probe the role of MAO in normal human biology and in disease. Over the past 30 since the first radiotracers were developed and the first PET images of MAO in humans were carried out, PET studies of brain MAO in healthy volunteers and in patients have identified different variablesmore »which have contributed to different MAO levels in brain and in peripheral organs. MAO radiotracers and PET have also been used to study the current and developing MAO inhibitor drugs including the selection of doses for clinical trials. In this article, we describe (1) the development of MAO radiotracers; (2) human studies including the relationship of brain MAO levels to genotype, personality, neurological and psychiatric disorders; (3) examples of the use of MAO radiotracers in drug research and development. We will conclude with outstanding needs to improve the radiotracers which are currently used and possible new applications.« less

  1. Individual Differences in Human Reliability Analysis

    SciTech Connect (OSTI)

    Jeffrey C. Joe; Ronald L. Boring

    2014-06-01

    While human reliability analysis (HRA) methods include uncertainty in quantification, the nominal model of human error in HRA typically assumes that operator performance does not vary significantly when they are given the same initiating event, indicators, procedures, and training, and that any differences in operator performance are simply aleatory (i.e., random). While this assumption generally holds true when performing routine actions, variability in operator response has been observed in multiple studies, especially in complex situations that go beyond training and procedures. As such, complexity can lead to differences in operator performance (e.g., operator understanding and decision-making). Furthermore, psychological research has shown that there are a number of known antecedents (i.e., attributable causes) that consistently contribute to observable and systematically measurable (i.e., not random) differences in behavior. This paper reviews examples of individual differences taken from operational experience and the psychological literature. The impact of these differences in human behavior and their implications for HRA are then discussed. We propose that individual differences should not be treated as aleatory, but rather as epistemic. Ultimately, by understanding the sources of individual differences, it is possible to remove some epistemic uncertainty from analyses.

  2. Human-system Interfaces for Automatic Systems

    SciTech Connect (OSTI)

    OHara, J.M.; Higgins,J.; Fleger, S.; Barnes V.

    2010-11-07

    Automation is ubiquitous in modern complex systems, and commercial nuclear- power plants are no exception. Automation is applied to a wide range of functions including monitoring and detection, situation assessment, response planning, and response implementation. Automation has become a 'team player' supporting personnel in nearly all aspects of system operation. In light of its increasing use and importance in new- and future-plants, guidance is needed to conduct safety reviews of the operator's interface with automation. The objective of this research was to develop such guidance. We first characterized the important HFE aspects of automation, including six dimensions: levels, functions, processes, modes, flexibility, and reliability. Next, we reviewed literature on the effects of all of these aspects of automation on human performance, and on the design of human-system interfaces (HSIs). Then, we used this technical basis established from the literature to identify general principles for human-automation interaction and to develop review guidelines. The guidelines consist of the following seven topics: automation displays, interaction and control, automation modes, automation levels, adaptive automation, error tolerance and failure management, and HSI integration. In addition, our study identified several topics for additional research.

  3. Intrinsic radiation resistance in human chondrosarcoma cells

    SciTech Connect (OSTI)

    Moussavi-Harami, Farid [Departments of Orthopaedics and Rehabilitation, University of Iowa, Iowa City, IA 52242 (United States); Mollano, Anthony [Departments of Orthopaedics and Rehabilitation, University of Iowa, Iowa City, IA 52242 (United States); Martin, James A. [Departments of Orthopaedics and Rehabilitation, University of Iowa, Iowa City, IA 52242 (United States); Ayoob, Andrew [Departments of Orthopaedics and Rehabilitation, University of Iowa, Iowa City, IA 52242 (United States); Domann, Frederick E. [Department of Radiation Oncology, Iowa City, IA 52245 (United States); Gitelis, Steven [Department of Internal Medicine, Section of Medical Oncology, Chicago, IL 60612 (United States); Department of Orthopaedics Rush-Presbyterian St. Luke's Medical Center, Chicago, IL 60612 (United States); Buckwalter, Joseph A. [Departments of Orthopaedics and Rehabilitation, University of Iowa, Iowa City, IA 52242 (United States)]. E-mail: joseph-buckwalter@uiowa.edu

    2006-07-28

    Human chondrosarcomas rarely respond to radiation treatment, limiting the options for eradication of these tumors. The basis of radiation resistance in chondrosarcomas remains obscure. In normal cells radiation induces DNA damage that leads to growth arrest or death. However, cells that lack cell cycle control mechanisms needed for these responses show intrinsic radiation resistance. In previous work, we identified immortalized human chondrosarcoma cell lines that lacked p16{sup ink4a}, one of the major tumor suppressor proteins that regulate the cell cycle. We hypothesized that the absence of p16{sup ink4a} contributes to the intrinsic radiation resistance of chondrosarcomas and that restoring p16{sup ink4a} expression would increase their radiation sensitivity. To test this we determined the effects of ectopic p16{sup ink4a} expression on chondrosarcoma cell resistance to low-dose {gamma}-irradiation (1-5 Gy). p16{sup ink4a} expression significantly increased radiation sensitivity in clonogenic assays. Apoptosis did not increase significantly with radiation and was unaffected by p16{sup ink4a} transduction of chondrosarcoma cells, indicating that mitotic catastrophe, rather than programmed cell death, was the predominant radiation effect. These results support the hypothesis that p16{sup ink4a} plays a role in the radiation resistance of chondrosarcoma cell lines and suggests that restoring p16 expression will improve the radiation sensitivity of human chondrosarcomas.

  4. Monoamine oxidase: Radiotracer chemistry and human studies

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

    Fowler, Joanna S. [Brookhaven National Lab. (BNL), Upton, NY (United States); Logan, Jean [New York Univ., Langone Medical Center, New York, NY (United States); Shumay, Elena [National Inst. on Alcohol Abuse and Alcoholism, National Inst. of Health, Betheseda, MD (United States); Alia-Klein, Nelly [Mount Sinai School of Medicine, New York, NY (United States); Wang, Gene-Jack [National Inst. on Alcohol Abuse and Alcoholism, National Inst. of Health, Betheseda, MD (United States); Volkow, Nora D. [National Inst. on Alcohol Abuse and Alcoholism, National Inst. of Health, Betheseda, MD (United States); National Inst. on Drug Abuse, National Inst. of Health, Bethesda, MD (United States)

    2015-03-01

    Monoamine oxidase (MAO) oxidizes amines from both endogenous and exogenous sources thereby regulating the concentration of neurotransmitter amines such as serot onin, norepinephrine and dopamine as well as many xenobiotics. MAO inhibitor drugs are used in the treatment of Parkinson’s disease and in depression stimulating the development of radiotracer tools to probe the role of MAO in normal human biology and in disease. Over the past 30 since the first radiotracers were developed and the first PET images of MAO in humans were carried out, PET studies of brain MAO in healthy volunteers and in patients have identified different variables which have contributed to different MAO levels in brain and in peripheral organs. MAO radiotracers and PET have also been used to study the current and developing MAO inhibitor drugs including the selection of doses for clinical trials. In this article, we describe (1) the development of MAO radiotracers; (2) human studies including the relationship of brain MAO levels to genotype, personality, neurological and psychiatric disorders; (3) examples of the use of MAO radiotracers in drug research and development. We will conclude with outstanding needs to improve the radiotracers which are currently used and possible new applications.

  5. SU-E-J-107: Supervised Learning Model of Aligned Collagen for Human Breast Carcinoma Prognosis

    SciTech Connect (OSTI)

    Bredfeldt, J; Liu, Y; Conklin, M; Keely, P; Eliceiri, K; Mackie, T

    2014-06-01

    Purpose: Our goal is to develop and apply a set of optical and computational tools to enable large-scale investigations of the interaction between collagen and tumor cells. Methods: We have built a novel imaging system for automating the capture of whole-slide second harmonic generation (SHG) images of collagen in registry with bright field (BF) images of hematoxylin and eosin stained tissue. To analyze our images, we have integrated a suite of supervised learning tools that semi-automatically model and score collagen interactions with tumor cells via a variety of metrics, a method we call Electronic Tumor Associated Collagen Signatures (eTACS). This group of tools first segments regions of epithelial cells and collagen fibers from BF and SHG images respectively. We then associate fibers with groups of epithelial cells and finally compute features based on the angle of interaction and density of the collagen surrounding the epithelial cell clusters. These features are then processed with a support vector machine to separate cancer patients into high and low risk groups. Results: We validated our model by showing that eTACS produces classifications that have statistically significant correlation with manual classifications. In addition, our system generated classification scores that accurately predicted breast cancer patient survival in a cohort of 196 patients. Feature rank analysis revealed that TACS positive fibers are more well aligned with each other, generally lower density, and terminate within or near groups of epithelial cells. Conclusion: We are working to apply our model to predict survival in larger cohorts of breast cancer patients with a diversity of breast cancer types, predict response to treatments such as COX2 inhibitors, and to study collagen architecture changes in other cancer types. In the future, our system may be used to provide metastatic potential information to cancer patients to augment existing clinical assays.

  6. Digital Human Modeling for Palpatory Medical Training with Haptic Feedback

    E-Print Network [OSTI]

    Williams II, Robert L.

    Modeling for Applied Ergonomics and Human Factors Engineering, Chapter 48, ISBN 978- 0-8058-5646. #12 Evaluation Results

  7. Global environmental change: Modifying human contributions through education

    SciTech Connect (OSTI)

    Carter, L.M.

    1997-12-31

    The 1995 Intergovernmental Panel on Climate Change (IPCC) Science report concludes that evidence now available {open_quotes}points toward a discernible human influence on global climate{close_quotes}. Reductions in emissions will require changes in human behavior. Knowledge, often through education, is an important moderator of human environmental behavior. This study assessed whether gains in global environmental change knowledge would lead to changes in human behaviors that could be deemed environmentally responsible.

  8. Human Reliability Program (HRP) - HPMC Occupational Health Services

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

    EpidemiologyHealth Data Analysis Human Reliability Program (HRP) Industrial Rehabilitation & Ergonomics Infection Control & Immunizations Influenza Immunization Program...

  9. Ultraviolet-light-induced transformation of human primary cells

    SciTech Connect (OSTI)

    Sutherland, B.M.

    1981-01-01

    The development of model systems for probing the ultraviolet radiation induced oncogenic transformation of human skin cells is described. (ACR)

  10. Human Portable Radiation Detection System Communications Package Evaluation

    SciTech Connect (OSTI)

    Morgen, Gerald P.; Peterson, William W.

    2009-06-11

    Testing and valuation of the Human Portable Radiation Detection System Communications Package for the US Coast Guard.

  11. Human System Simulation in Support of Human Performance Technical Basis at NPPs

    SciTech Connect (OSTI)

    David Gertman; Katya Le Blanc; alan mecham; william phoenix; Magdy Tawfik; Jeffrey Joe

    2010-06-01

    This paper focuses on strategies and progress toward establishing the Idaho National Laboratory’s (INL’s) Human Systems Simulator Laboratory at the Center for Advanced Energy Studies (CAES), a consortium of Idaho State Universities. The INL is one of the National Laboratories of the US Department of Energy. One of the first planned applications for the Human Systems Simulator Laboratory is implementation of a dynamic nuclear power plant simulation (NPP) where studies of operator workload, situation awareness, performance and preference will be carried out in simulated control rooms including nuclear power plant control rooms. Simulation offers a means by which to review operational concepts, improve design practices and provide a technical basis for licensing decisions. In preparation for the next generation power plant and current government and industry efforts in support of light water reactor sustainability, human operators will be attached to a suite of physiological measurement instruments and, in combination with traditional Human Factors Measurement techniques, carry out control room tasks in simulated advanced digital and hybrid analog/digital control rooms. The current focus of the Human Systems Simulator Laboratory is building core competence in quantitative and qualitative measurements of situation awareness and workload. Of particular interest is whether introduction of digital systems including automated procedures has the potential to reduce workload and enhance safety while improving situation awareness or whether workload is merely shifted and situation awareness is modified in yet to be determined ways. Data analysis is carried out by engineers and scientists and includes measures of the physical and neurological correlates of human performance. The current approach supports a user-centered design philosophy (see ISO 13407 “Human Centered Design Process for Interactive Systems, 1999) wherein the context for task performance along with the requirements of the end-user are taken into account during the design process and the validity of design is determined through testing of real end users

  12. Comparative Analysis of Korean Human Gut Microbiota by Barcoded Pyrosequencing

    E-Print Network [OSTI]

    Bae, Jin-Woo

    @khu.ac.kr Introduction After the completion of the Human Genome Project (HGP), many scientists were disappointed of human health and disease. Therefore, after the HGP, Human Microbiome Project (HMP) was initiated to fill a gap between our current understanding derived from HGP and actual physiological phenomenon

  13. Symposium on Human Performance Modeling Wayne D. Gray (Organizer)

    E-Print Network [OSTI]

    Gray, Wayne

    -TG) of the Human Factors & Ergonomics Society. Three Research Talks and a Panel Discussion were presented. Each The Human Performance Modeling Technical Group (HPM-TG) of the Human Factors and Ergonomics Society (HFES by Pew (2007, 2008). Technical Talks An Accessible Cognitive Modeling Tool for Evaluation of Pilot

  14. SHORT REPORT Micropatterning of human embryonic stem cells

    E-Print Network [OSTI]

    Zandstra, Peter W.

    SHORT REPORT Micropatterning of human embryonic stem cells dissects the mesoderm and endoderm in revised form 10 November 2008; accepted 13 November 2008 Abstract Human pluripotent cells such as human embryonic stem cells (hESC) are a great potential source of cells for cell-based therapies; however

  15. Dynamics of a bouncing ball in human performance Dagmar Sternad

    E-Print Network [OSTI]

    Sternad, Dagmar

    of a dynamically stable period-one regime. In a series of experiments, human subjects bounced a ball rhythmically human movement and physical experi- mental systems is that while the variables and parameters of physical experiments are under the experimenter's control, human subjects when bouncing a ball have

  16. Bayesian optimization explains human active search Department of Computer Science

    E-Print Network [OSTI]

    Itti, Laurent

    , predicts human per- formance and searched locations better. In 6 follow-up controlled experiments over 76 literature, we design and conduct a series of experiments to understand human search and active learning;2 Experiments and Results We seek to study human search behavior directly on 1D function optimization

  17. A Brief History of Human Computer Interaction Technology

    E-Print Network [OSTI]

    A Brief History of Human Computer Interaction Technology Brad A. Myers December, 1996 CMU­CS­96 development of major advances in human­ computer interaction technology, emphasizing the pivotal role, of NCCOSC or the U.S. Government. #12; Keywords: Human Computer Interaction, History, User Interfaces

  18. Systems for Human-Powered Mobile Computing Joseph A. Paradiso

    E-Print Network [OSTI]

    Systems for Human-Powered Mobile Computing Joseph A. Paradiso Responsive Environments Group MIT and obtrusive. On the other hand, having humans actively drive generators used to power electronics (e of human body sources and activities. After summarizing different energy harvesting modalities

  19. Human Motion Capture Data Compression by Model-Based Indexing

    E-Print Network [OSTI]

    Bhandarkar, Suchendra "Suchi" M.

    Human Motion Capture Data Compression by Model-Based Indexing: A Power Aware Approach Siddhartha Chattopadhyay, Suchendra M. Bhandarkar, Member, IEEE, and Kang Li Abstract--Human Motion Capture (MoCap) data can be used for animation of virtual human-like characters in distributed virtual reality applications

  20. A Survey of Human Computation Systems Man-Ching Yuen

    E-Print Network [OSTI]

    Chen, Ling-Jyh

    arti- ficial intelligence (AI) problems through human power. There exists some AI problems gives a discussion and conclusion of our work. II. INITIATORY HUMAN COMPUTATION As computation powerA Survey of Human Computation Systems Man-Ching Yuen Dept. of Computer Science & Engineering

  1. Human Factors Aspects of Power System Flow Animation

    E-Print Network [OSTI]

    Human Factors Aspects of Power System Flow Animation Douglas A. Wiegmann, Gavin R. Essenberg experimental results associated with human factors aspects of using animation to display electric power system. Index Terms--Power System Operations and Planning, Power System Visualization, Animation, Human Factors

  2. school of education, health, and human performance Boundless

    E-Print Network [OSTI]

    Kunkle, Tom

    school of education, health, and human performance #12;Boundless: The Campaign for the College the next era of the School of Education, Health, and Human Performance. The magnitude of our goal reflects for meaningful research, service and learning. The School of Education, Health, and Human Performance

  3. Evaluation Criteria for Human-Automation Performance Birsen Donmez

    E-Print Network [OSTI]

    Cummings, Mary "Missy"

    Evaluation Criteria for Human-Automation Performance Metrics Birsen Donmez MIT Dept. of Aero(617)252-1512 missyc@mit.edu ABSTRACT Previous research has identified broad metric classes for human- automation. INTRODUCTION Human-automation teams are common in many domains, such as military operations, process control

  4. International Compilation of Human Research Standards 2015 Edition

    E-Print Network [OSTI]

    Kay, Mark A.

    1 International Compilation of Human Research Standards 2015 Edition Compiled By: Office for Human Research Protections U.S. Department of Health and Human Services PURPOSE The International Compilation organizations. This Compilation was developed for use by researchers, IRBs/Research Ethics Committees, sponsors

  5. RESEARCH INVOLVING HUMANS University Policy No.: RH8105

    E-Print Network [OSTI]

    Victoria, University of

    1 RESEARCH INVOLVING HUMANS University Policy No.: RH8105 Classification: Research Approving: Mandated Review: September, 2017 Associated Procedures Procedures for Conducting Human Research PURPOSE 1.00 The purpose of this policy is to: a) set out provisions to ensure Research Involving Human Participants

  6. Humans to Mars Fifty Years of Mission Planning,

    E-Print Network [OSTI]

    Rathbun, Julie A.

    Humans to Mars Fifty Years of Mission Planning, 1950--2000 David S. F. Portree Monographs in Aerospace History #21 NASA SP-2001-4521 Humans to Mars Fifty Years of Mission Planning, 1950--2000 David S. F. Portree #12;Humans to Mars Fifty Years of Mission Planning, 1950­2000 by David S. F. Portree NASA

  7. The Human Plutonium Injection Experiments William Moss and Roger Eckhardt

    E-Print Network [OSTI]

    Massey, Thomas N.

    that was pertinent to those and LouisHempelmann #12;similar radiation experi- ments with humans. This article177 The Human Plutonium Injection Experiments William Moss and Roger Eckhardt T he human plutonium injection experiments carried out during and after the Manhattan Project have received tremendous noto

  8. Optimizing the BACEnd Strategy for Sequencing the Human Genome

    E-Print Network [OSTI]

    Shamir, Ron

    University, Tel Aviv, 69978, Israel. 1 #12; 1 Introduction With the Human Genome Project moving from the map sequencing has become central. The classical strategy set forth by the founders of the Human Genome ProjectOptimizing the BAC­End Strategy for Sequencing the Human Genome Richard M. Karp \\Lambda Ron Shamir

  9. Identification of Human Gene Core Promoters Michael Q. Zhang1

    E-Print Network [OSTI]

    supplement at http://www.genome.org.] As the Human Genome Project enters its large-scale sequencing phaseIdentification of Human Gene Core Promoters in Silico Michael Q. Zhang1 Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724 USA Identification of the 5 -end of human genes requires

  10. Classifying Human-Robot Interaction: An Updated Taxonomy*

    E-Print Network [OSTI]

    Yanco, Holly A.

    Classifying Human-Robot Interaction: An Updated Taxonomy* Holly A. Yanco Computer Science-7803-8566-7/04/$20.00 2004 IEEE. Abstract - This paper extends a taxonomy of human- robot interaction (HRI) introduced taxonomy. New classifications include measures of the social nature of the task (human interaction roles

  11. West Virginia University 1 College of Education and Human Services

    E-Print Network [OSTI]

    Mohaghegh, Shahab

    West Virginia University 1 College of Education and Human Services Degrees Offered · Doctor of Education and Human Services, located in Allen Hall on the Evansdale campus, offers graduate-level programs Services in the Office of Student Advising and Records of the College of Education and Human Services, P

  12. West Virginia University 1 College of Education and Human Services

    E-Print Network [OSTI]

    Mohaghegh, Shahab

    West Virginia University 1 College of Education and Human Services Degrees Offered · Bachelor The College of Education and Human Services is divided into five academic departments: Counseling experiences in a professional development school. The College of Education and Human Services cooperates

  13. West Virginia University 1 College of Education and Human Services

    E-Print Network [OSTI]

    Mohaghegh, Shahab

    West Virginia University 1 College of Education and Human Services Degrees Offered · Bachelor Nature of Programs The College of Education and Human Services (CEHS) is divided into five academic programs In the College of Education and Human Services (CEHS) focus on preparing professionals whose

  14. West Virginia University 1 College of Education and Human Services

    E-Print Network [OSTI]

    Mohaghegh, Shahab

    West Virginia University 1 College of Education and Human Services Degrees Offered · Doctor The College of Education and Human Services, located in Allen Hall on the Evansdale campus, offers graduate like additional information about the graduate programs in the College of Education and Human Services

  15. Human Trajectory Forecasting In Indoor Environments Using Geometric Context

    E-Print Network [OSTI]

    . In addressing this problem, we have built a model to estimate the occupancy behavior of humans based enhancement in the accuracy of trajectory forecasting by incorporating the occupancy behavior model. Keywords Trajectory forecasting, human occupancy behavior, 3D ge- ometric context 1. INTRODUCTION Given a human

  16. Human Robot Interaction in Mobile Robot Applications Akihisa Ohya

    E-Print Network [OSTI]

    Ohya, Akihisa

    Human Robot Interaction in Mobile Robot Applications Akihisa Ohya PRESTO, JST / University the usefulness of mobile robots by showing concrete applications in human daily life through this study Robot moving together with human is presented first. A teleoperated book browsing robot is described

  17. Assay for mutagenesis in heterozygous diploid human lymphoblasts

    DOE Patents [OSTI]

    Skopek, Thomas R. (Somerville, MA); Liber, Howard L. (Brookline, MA); Penman, Bruce W. (Cambridge, MA); Thilly, William G. (Cambridge, MA); Hoppe, IV, Henry (Arlington, MA)

    1981-01-01

    An assay is disclosed for determining mutagenic damage caused by the administration of a known or suspected mutagen to diploid human lymphoblastoid cell lines. The gene locus employed for this assay is the gene for thymidine kinase, uridine kinase, or cytidine deaminase. Since human lymphoblastoid cells contain two genes for these enzymes, heterozygotes of human lymphoblastoid cells are used in this assay.

  18. UNLV DIVISION OF RESEARCH POLICY ON RESEARCH INVOLVING HUMAN SUBJECTS

    E-Print Network [OSTI]

    Walker, Lawrence R.

    UNLV DIVISION OF RESEARCH POLICY ON RESEARCH INVOLVING HUMAN SUBJECTS RESPONsmLE ADMINISTRATOR: VICE PRESIDENT FOR RESEARCH RESPONSmLE OFFICE(S): OFFICE OF RESEARCH INTEGRITY - HUMAN SUBJECTS rules and procedures, when conducting research involving human subjects. ENTITIES AFFECTED BY Tms POLICY

  19. Protection of Human Subjects in Research at NIST

    E-Print Network [OSTI]

    Protection of Human Subjects in Research at NIST Alan H. Cookson, NIST IRB Chair Melissa J. Lieberman, Office of NIST Counsel May 2006 #12;Outline · Definition of research involving human subjects · Procedures ­ non-use of human subjects, exemptions, IRB review, NIST institutional review · Role of IRB · IRB

  20. World Data Center for Human Interactions in the Environment

    E-Print Network [OSTI]

    Columbia University

    on Climate Change and Official Statistics Oslo, Norway, 14-16 April 2008 #12;World Data Center for Human processes of climate change, exposure, sensitivity and adaptation #12;World Data Center for Human;World Data Center for Human Interactions in the Environment Impacts of Climate Change, Examples 8