National Library of Energy BETA

Sample records for human skin model

  1. The Effects of Low Dose Irradiation on Inflammatory Response Proteins in a 3D Reconstituted Human Skin Tissue Model

    SciTech Connect (OSTI)

    Varnum, Susan M.; Springer, David L.; Chaffee, Mary E.; Lien, Katie A.; Webb-Robertson, Bobbie-Jo M.; Waters, Katrina M.; Sacksteder, Colette A.


    Skin responses to moderate and high doses of ionizing radiation include the induction of DNA repair, apoptosis, and stress response pathways. Additionally, numerous studies indicate that radiation exposure leads to inflammatory responses in skin cells and tissue. However, the inflammatory response of skin tissue to low dose radiation (<10 cGy) is poorly understood. In order to address this, we have utilized a reconstituted human skin tissue model (MatTek EpiDerm FT) and assessed changes in 23 cytokines twenty-four and forty eight hours following treatment of skin with either 3 or 10 cGy low-dose of radiation. Three cytokines, IFN-?, IL-2, MIP-1?, were significantly altered in response to low dose radiation. In contrast, seven cytokines were significantly altered in response to a high radiation dose of 200 cGy (IL-2, IL-10, IL-13, IFN-?, MIP-1?, TNF ?, and VEGF) or the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (G-CSF, GM-CSF, IL-1?, IL-8, MIP-1?, MIP-1?, RANTES). Additionally, radiation induced inflammation appears to have a distinct cytokine response relative to the non-radiation induced stressor, TPA. Overall, these results indicate that there are subtle changes in the inflammatory protein levels following exposure to low dose radiation and this response is a sub-set of what is seen following a high dose in a human skin tissue model.

  2. Quantitative Proteomic Profiling of Low Dose Ionizing Radiation Effects in a Human Skin Model

    SciTech Connect (OSTI)

    Hengel, Shawna; Aldrich, Joshua T.; Waters, Katrina M.; Pasa-Tolic, Ljiljana; Stenoien, David L.


    To assess molecular responses to low doses of radiation that may be encountered during medical diagnostic procedures, nuclear accidents, or terrorist acts, a quantitative global proteomic approach was used to identify protein alterations in a reconstituted human skin tissue treated with 10 cGy of ionizing radiation. Subcellular fractionation was employed to remove highly abundant structural proteins and provide insight on radiation induced alterations in protein abundance and localization. In addition, peptides were post-fractionated using high resolution 2-dimensional liquid chromatography to increase the dynamic range of detection of protein abundance and translocation changes. Quantitative data was obtained by labeling peptides with 8-plex isobaric iTRAQ tags. A total of 207 proteins were detected with statistically significant alterations in abundance and/or subcellular localization compared to sham irradiated tissues. Bioinformatics analysis of the data indicated that the top canonical pathways affected by low dose radiation are related to cellular metabolism. Among the proteins showing alterations in abundance, localization and proteolytic processing was the skin barrier protein filaggrin which is consistent with our previous observation that ionizing radiation alters profilaggrin processing with potential effects on skin barrier functions. In addition, a large number of proteases and protease regulators were affected by low dose radiation exposure indicating that altered proteolytic activity may be a hallmark of low dose radiation exposure. While several studies have demonstrated altered transcriptional regulation occurs following low dose radiation exposures, the data presented here indicates post-transcriptional regulation of protein abundance, localization, and proteolytic processing play an important role in regulating radiation responses in complex human tissues.

  3. 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.


    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.

  4. High and Low Doses of Ionizing Radiation Induce Different Secretome Profiles in a Human Skin Model

    SciTech Connect (OSTI)

    Zhang, Qibin; Matzke, Melissa M.; Schepmoes, Athena A.; Moore, Ronald J.; Webb-Robertson, Bobbie-Jo M.; Hu, Zeping; Monroe, Matthew E.; Qian, Weijun; Smith, Richard D.; Morgan, William F.


    It is postulated that secreted soluble factors are important contributors of bystander effect and adaptive responses observed in low dose ionizing radiation. Using multidimensional liquid chromatography-mass spectrometry based proteomics, we quantified the changes of skin tissue secretome the proteins secreted from a full thickness, reconstituted 3-dimensional skin tissue model 48 hr after exposure to 3, 10 and 200 cGy of X-rays. Overall, 135 proteins showed statistical significant difference between the sham (0 cGy) and any of the irradiated groups (3, 10 or 200 cGy) on the basis of Dunnett adjusted t-test; among these, 97 proteins showed a trend of downregulation and 9 proteins showed a trend of upregulation with increasing radiation dose. In addition, there were 21 and 8 proteins observed to have irregular trends with the 10 cGy irradiated group either having the highest or the lowest level among all three radiated doses. Moreover, two proteins, carboxypeptidase E and ubiquitin carboxyl-terminal hydrolase isozyme L1 were sensitive to ionizing radiation, but relatively independent of radiation dose. Conversely, proteasome activator complex subunit 2 protein appeared to be sensitive to the dose of radiation, as rapid upregulation of this protein was observed when radiation doses were increased from 3, to 10 or 200 cGy. These results suggest that different mechanisms of action exist at the secretome level for low and high doses of ionizing radiation.

  5. Absorption of ethanol, acetone, benzene and 1,2-dichloroethane through human skin in vitro: a test of diffusion model predictions

    SciTech Connect (OSTI)

    Gajjar, Rachna M.; Kasting, Gerald B.


    The overall goal of this research was to further develop and improve an existing skin diffusion model by experimentally confirming the predicted absorption rates of topically-applied volatile organic compounds (VOCs) based on their physicochemical properties, the skin surface temperature, and the wind velocity. In vitro human skin permeation of two hydrophilic solvents (acetone and ethanol) and two lipophilic solvents (benzene and 1,2-dichloroethane) was studied in Franz cells placed in a fume hood. Four doses of each {sup 14}C-radiolabed compound were tested — 5, 10, 20, and 40 μL cm{sup −2}, corresponding to specific doses ranging in mass from 5.0 to 63 mg cm{sup −2}. The maximum percentage of radiolabel absorbed into the receptor solutions for all test conditions was 0.3%. Although the absolute absorption of each solvent increased with dose, percentage absorption decreased. This decrease was consistent with the concept of a stratum corneum deposition region, which traps small amounts of solvent in the upper skin layers, decreasing the evaporation rate. The diffusion model satisfactorily described the cumulative absorption of ethanol; however, values for the other VOCs were underpredicted in a manner related to their ability to disrupt or solubilize skin lipids. In order to more closely describe the permeation data, significant increases in the stratum corneum/water partition coefficients, K{sub sc}, and modest changes to the diffusion coefficients, D{sub sc}, were required. The analysis provided strong evidence for both skin swelling and barrier disruption by VOCs, even by the minute amounts absorbed under these in vitro test conditions. - Highlights: • Human skin absorption of small doses of VOCs was measured in vitro in a fume hood. • The VOCs tested were ethanol, acetone, benzene and 1,2-dichloroethane. • Fraction of dose absorbed for all compounds at all doses tested was less than 0.3%. • The more aggressive VOCs absorbed at higher levels than

  6. Athletic equipment microbiota are shaped by interactions with human skin

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

    Wood, Mariah; Gibbons, Sean M.; Lax, Simon; Eshoo-Anton, Tifani W.; Owens, Sarah M.; Kennedy, Suzanne; Gilbert, Jack A.; Hampton-Marcell, Jarrad T.


    Background: Americans spend the vast majority of their lives in built environments. Even traditionally outdoor pursuits, such as exercising, are often now performed indoors. Bacteria that colonize these indoor ecosystems are primarily derived from the human microbiome. The modes of human interaction with indoor surfaces and the physical conditions associated with each surface type determine the steady-state ecology of the microbial community. Results: Bacterial assemblages associated with different surfaces in three athletic facilities, including floors, mats, benches, free weights, and elliptical handles, were sampled every other hour (8 am to 6 pm) for 2 days. Surface and equipment type hadmore » a stronger influence on bacterial community composition than the facility in which they were housed. Surfaces that were primarily in contact with human skin exhibited highly dynamic bacterial community composition and non-random co-occurrence patterns, suggesting that different host microbiomes—shaped by selective forces—were being deposited on these surfaces through time. Bacterial assemblages found on the floors and mats changed less over time, and species co-occurrence patterns appeared random, suggesting more neutral community assembly. Conclusions: These longitudinal patterns highlight the dramatic turnover of microbial communities on surfaces in regular contact with human skin. By uncovering these longitudinal patterns, this study promotes a better understanding of microbe-human interactions within the built environment.« less

  7. In vitro dermal absorption of pyrethroid pesticides in human and rat skin

    SciTech Connect (OSTI)

    Hughes, Michael F.; Edwards, Brenda C.


    Dermal exposure to pyrethroid pesticides can occur during manufacture and application. This study examined the in vitro dermal absorption of pyrethroids using rat and human skin. Dermatomed skin from adult male Long Evans rats or human cadavers was mounted in flow-through diffusion cells, and radiolabeled bifenthrin, deltamethrin or cis-permethrin was applied in acetone to the skin. Fractions of receptor fluid were collected every 4 h. At 24 h, the skins were washed with soap and water to remove unabsorbed chemical. The skin was then solubilized. Two additional experiments were performed after washing the skin; the first was tape-stripping the skin and the second was the collection of receptor fluid for an additional 24 h. Receptor fluid, skin washes, tape strips and skin were analyzed for radioactivity. For rat skin, the wash removed 53-71% of the dose and 26-43% remained in the skin. The cumulative percentage of the dose at 24 h in the receptor fluid ranged from 1 to 5%. For human skin, the wash removed 71-83% of the dose and 14-25% remained in the skin. The cumulative percentage of the dose at 24 h in the receptor fluid was 1-2%. Tape-stripping removed 50-56% and 79-95% of the dose in rat and human skin, respectively, after the wash. From 24-48 h, 1-3% and about 1% of the dose diffused into the receptor fluid of rat and human skin, respectively. The pyrethroids bifenthrin, deltamethrin and cis-permethrin penetrated rat and human skin following dermal application in vitro. However, a skin wash removed 50% or more of the dose from rat and human skin. Rat skin was more permeable to the pyrethroids than human skin. Of the dose in skin, 50% or more was removed by tape-stripping, suggesting that permeation of pyrethroids into viable tissue could be impeded. The percentage of the dose absorbed into the receptor fluid was considerably less than the dose in rat and human skin. Therefore, consideration of the skin type used and fractions analyzed are important when using

  8. MUTZ-3 derived Langerhans cells in human skin equivalents show differential migration and phenotypic plasticity after allergen or irritant exposure

    SciTech Connect (OSTI)

    Kosten, Ilona J.; Spiekstra, Sander W.; Gruijl, Tanja D. de; Gibbs, Susan


    After allergen or irritant exposure, Langerhans cells (LC) undergo phenotypic changes and exit the epidermis. In this study we describe the unique ability of MUTZ-3 derived Langerhans cells (MUTZ-LC) to display similar phenotypic plasticity as their primary counterparts when incorporated into a physiologically relevant full-thickness skin equivalent model (SE-LC). We describe differences and similarities in the mechanisms regulating LC migration and plasticity upon allergen or irritant exposure. The skin equivalent consisted of a reconstructed epidermis containing primary differentiated keratinocytes and CD1a{sup +} MUTZ-LC on a primary fibroblast-populated dermis. Skin equivalents were exposed to a panel of allergens and irritants. Topical exposure to sub-toxic concentrations of allergens (nickel sulfate, resorcinol, cinnamaldehyde) and irritants (Triton X-100, SDS, Tween 80) resulted in LC migration out of the epidermis and into the dermis. Neutralizing antibody to CXCL12 blocked allergen-induced migration, whereas anti-CCL5 blocked irritant-induced migration. In contrast to allergen exposure, irritant exposure resulted in cells within the dermis becoming CD1a{sup −}/CD14{sup +}/CD68{sup +} which is characteristic of a phenotypic switch of MUTZ-LC to a macrophage-like cell in the dermis. This phenotypic switch was blocked with anti-IL-10. Mechanisms previously identified as being involved in LC activation and migration in native human skin could thus be reproduced in the in vitro constructed skin equivalent model containing functional LC. This model therefore provides a unique and relevant research tool to study human LC biology in situ under controlled in vitro conditions, and will provide a powerful tool for hazard identification, testing novel therapeutics and identifying new drug targets. - Highlights: • MUTZ-3 derived Langerhans cells integrated into skin equivalents are fully functional. • Anti-CXCL12 blocks allergen-induced MUTZ-LC migration.

  9. Enhanced human papillomavirus type 8 oncogene expression levels are crucial for skin tumorigenesis in transgenic mice

    SciTech Connect (OSTI)

    Hufbauer, M.; Lazic, D.; Akguel, B.; Brandsma, J.L.; Pfister, H.; Weissenborn, S.J.


    Human papillomavirus 8 (HPV8) is involved in skin cancer development in epidermodysplasia verruciformis patients. Transgenic mice expressing HPV8 early genes (HPV8-CER) developed papillomas, dysplasias and squamous cell carcinomas. UVA/B-irradiation and mechanical wounding of HPV8-CER mouse skin led to prompt papilloma induction in about 3 weeks. The aim of this study was to analyze the kinetics and level of transgene expression in response to skin irritations. Transgene expression was already enhanced 1 to 2 days after UVA/B-irradiation or tape-stripping and maintained during papilloma development. The enhanced transgene expression could be assigned to UVB and not to UVA. Papilloma development was thus always paralleled by an increased transgene expression irrespective of the type of skin irritation. A knock-down of E6 mRNA by tattooing HPV8-E6-specific siRNA led to a delay and a lower incidence of papilloma development. This indicates that the early increase of viral oncogene expression is crucial for induction of papillomatosis.

  10. Green tea polyphenol, (?)-epigallocatechin-3-gallate, induces toxicity in human skin cancer cells by targeting ?-catenin signaling

    SciTech Connect (OSTI)

    Singh, Tripti; Katiyar, Santosh K.


    The green tea polyphenol, (?)-epigallocatechin-3-gallate (EGCG), has been shown to have anti-carcinogenic effects in several skin tumor models, and efforts are continued to investigate the molecular targets responsible for its cytotoxic effects to cancer cells. Our recent observation that ?-catenin is upregulated in skin tumors suggested the possibility that the anti-skin carcinogenic effects of EGCG are mediated, at least in part, through its effects on ?-catenin signaling. We have found that treatment of the A431 and SCC13 human skin cancer cell lines with EGCG resulted in reduced cell viability and increased cell death and that these cytotoxic effects were associated with inactivation of ?-catenin signaling. Evidence of EGCG-induced inactivation of ?-catenin included: (i) reduced accumulation of nuclear ?-catenin; (ii) enhanced levels of casein kinase1?, reduced phosphorylation of glycogen synthase kinase-3?, and increased phosphorylation of ?-catenin on critical serine{sup 45,33/37} residues; and (iii) reduced levels of matrix metalloproteinase (MMP)-2 and MMP-9, which are down-stream targets of ?-catenin. Treatment of cells with prostaglandin E2 (PGE{sub 2}) enhanced the accumulation of ?-catenin and enhanced ?-catenin signaling. Treatment with either EGCG or an EP2 antagonist (AH6809) reduced the PGE{sub 2}-enhanced levels of cAMP, an upstream regulator of ?-catenin. Inactivation of ?-catenin by EGCG resulted in suppression of cell survival signaling proteins. siRNA knockdown of ?-catenin in A431 and SCC13 cells reduced cell viability. Collectively, these data suggest that induction of cytotoxicity in skin cancer cells by EGCG is mediated by targeting of ?-catenin signaling and that the ?-catenin signaling is upregulated by inflammatory mediators. - Highlights: EGCG inhibits cancer cell viability through inactivation of ?-catenin signaling. Inactivation of ?-catenin involves the downregulation of inflammatory mediators. EGCG inactivates ?-catenin in

  11. Predicting chemically-induced skin reactions. Part I: QSAR models of skin sensitization and their application to identify potentially hazardous compounds

    SciTech Connect (OSTI)

    Alves, Vinicius M.; Muratov, Eugene; Fourches, Denis; Strickland, Judy; Kleinstreuer, Nicole; Tropsha, Alexander


    Repetitive exposure to a chemical agent can induce an immune reaction in inherently susceptible individuals that leads to skin sensitization. Although many chemicals have been reported as skin sensitizers, there have been very few rigorously validated QSAR models with defined applicability domains (AD) that were developed using a large group of chemically diverse compounds. In this study, we have aimed to compile, curate, and integrate the largest publicly available dataset related to chemically-induced skin sensitization, use this data to generate rigorously validated and QSAR models for skin sensitization, and employ these models as a virtual screening tool for identifying putative sensitizers among environmental chemicals. We followed best practices for model building and validation implemented with our predictive QSAR workflow using Random Forest modeling technique in combination with SiRMS and Dragon descriptors. The Correct Classification Rate (CCR) for QSAR models discriminating sensitizers from non-sensitizers was 71–88% when evaluated on several external validation sets, within a broad AD, with positive (for sensitizers) and negative (for non-sensitizers) predicted rates of 85% and 79% respectively. When compared to the skin sensitization module included in the OECD QSAR Toolbox as well as to the skin sensitization model in publicly available VEGA software, our models showed a significantly higher prediction accuracy for the same sets of external compounds as evaluated by Positive Predicted Rate, Negative Predicted Rate, and CCR. These models were applied to identify putative chemical hazards in the Scorecard database of possible skin or sense organ toxicants as primary candidates for experimental validation. - Highlights: • It was compiled the largest publicly-available skin sensitization dataset. • Predictive QSAR models were developed for skin sensitization. • Developed models have higher prediction accuracy than OECD QSAR Toolbox. • Putative

  12. Human papillomavirus types detected in skin warts and cancer differ in their transforming properties but commonly counteract UVB induced protective responses in human keratinocytes

    SciTech Connect (OSTI)

    Shterzer, Naama; Heyman, Dariya; Shapiro, Beny; Yaniv, Abraham; Jackman, Anna; Serour, Francis; Chaouat, Malka; Gonen, Pinhas; Tommasino, Massimo; Sherman, Levana


    In the present study, E6E7 and E6 proteins of human papillomaviruses (HPVs) associated with skin warts and cancer were compared for their transforming and carcinogenic abilities in primary human keratinocytes (PHKs). We show that E6E7 of cancer associated beta HPV types, notably 49 and 24, were able to extend the life span and enhance the clonogenic efficiency of PHKs when maintained in serum free/low calcium medium. Activities of the beta HPV E6E7 were lower than those of HPV16 E6E7. In contrast, E6 proteins from HPV types detected in skin warts or cancer, notably 10, 49 and 38, attenuated UVB induced protective responses in PHKs including cell death, proliferation arrest and accumulation of the proapoptotic proteins, p53, bax or bak. Together, this investigation revealed functional differences and commonalities between HPVs associated with skin warts and cancer, and allowed the identification of specific properties of beta HPVs supporting their involvement in skin carcinogenesis. - Highlights: • Primary keratinocytes were used to evaluate transforming and carcinogenic abilities of cutaneous HPVs. • E6E7 of cancer associated β HPV types transform primary human keratinocytes. • E6 proteins of cancer and wart associated HPVs inhibit UVB induced cell death. • E6s of cancer and wart associated HPVs attenuate UVB induced proliferation arrest. • E6s of cancer and wart associated HPVs attenuate UVB induced apoptosis signaling.

  13. Human Performance Modeling for Dynamic Human Reliability Analysis

    SciTech Connect (OSTI)

    Boring, Ronald Laurids; Joe, Jeffrey Clark; Mandelli, Diego


    Part of the U.S. Department of Energy’s (DOE’s) Light Water Reac- tor Sustainability (LWRS) Program, the Risk-Informed Safety Margin Charac- terization (RISMC) Pathway develops approaches to estimating and managing safety margins. RISMC simulations pair deterministic plant physics models with probabilistic risk models. As human interactions are an essential element of plant risk, it is necessary to integrate human actions into the RISMC risk framework. In this paper, we review simulation based and non simulation based human reliability analysis (HRA) methods. This paper summarizes the founda- tional information needed to develop a feasible approach to modeling human in- teractions in RISMC simulations.

  14. Response-surface models for deterministic effects of localized irradiation of the skin by discrete {beta}/{gamma} -emitting sources

    SciTech Connect (OSTI)

    Scott, B.R.


    Individuals who work at nuclear reactor facilities can be at risk for deterministic effects in the skin from exposure to discrete {Beta}- and {gamma}-emitting ({Beta}{gamma}E) sources (e.g., {Beta}{gamma}E hot particles) on the skin or clothing. Deterministic effects are non-cancer effects that have a threshold and increase in severity as dose increases (e.g., ulcer in skin). Hot {Beta}{gamma}E particles are {sup 60}Co- or nuclear fuel-derived particles with diameters > 10 {mu}m and < 3 mm and contain at least 3.7 kBq (0.1 {mu}Ci) of radioactivity. For such {Beta}{gamma}E sources on the skin, it is the beta component of the dose that is most important. To develop exposure limitation systems that adequately control exposure of workers to discrete {Beta}{gamma}E sources, models are needed for systems that adequately control exposure of workers to discrete {Beta}{gamma}E sources, models are needed for evaluating the risk of deterministic effects of localized {Beta} irradiation of the skin. The purpose of this study was to develop dose-rate and irradiated-area dependent, response-surface models for evaluating risks of significant deterministic effects of localized irradiation of the skin by discrete {Beta}{gamma}E sources and to use modeling results to recommend approaches to limiting occupational exposure to such sources. The significance of the research results as follows: (1) response-surface models are now available for evaluating the risk of specific deterministic effects of localized irradiation of the skin; (2) modeling results have been used to recommend approaches to limiting occupational exposure of workers to {Beta} radiation from {Beta}{gamma}E sources on the skin or on clothing; and (3) the generic irradiated-volume, weighting-factor approach to limiting exposure can be applied to other organs including the eye, the ear, and organs of the respiratory or gastrointestinal tract and can be used for both deterministic and stochastic effects.

  15. Arsenic transformation predisposes human skin keratinocytes to UV-induced DNA damage yet enhances their survival apparently by diminishing oxidant response

    SciTech Connect (OSTI)

    Sun Yang; Kojima, Chikara; Chignell, Colin; Mason, Ronald; Waalkes, Michael P.


    Inorganic arsenic and UV, both human skin carcinogens, may act together as skin co-carcinogens. We find human skin keratinocytes (HaCaT cells) are malignantly transformed by low-level arsenite (100 nM, 30 weeks; termed As-TM cells) and with transformation concurrently undergo full adaptation to arsenic toxicity involving reduced apoptosis and oxidative stress response to high arsenite concentrations. Oxidative DNA damage (ODD) is a possible mechanism in arsenic carcinogenesis and a hallmark of UV-induced skin cancer. In the current work, inorganic arsenite exposure (100 nM) did not induce ODD during the 30 weeks required for malignant transformation. Although acute UV-treatment (UVA, 25 J/cm{sup 2}) increased ODD in passage-matched control cells, once transformed by arsenic to As-TM cells, acute UV actually further increased ODD (> 50%). Despite enhanced ODD, As-TM cells were resistant to UV-induced apoptosis. The response of apoptotic factors and oxidative stress genes was strongly mitigated in As-TM cells after UV exposure including increased Bcl2/Bax ratio and reduced Caspase-3, Nrf2, and Keap1 expression. Several Nrf2-related genes (HO-1, GCLs, SOD) showed diminished responses in As-TM cells after UV exposure consistent with reduced oxidant stress response. UV-exposed As-TM cells showed increased expression of cyclin D1 (proliferation gene) and decreased p16 (tumor suppressor). UV exposure enhanced the malignant phenotype of As-TM cells. Thus, the co-carcinogenicity between UV and arsenic in skin cancer might involve adaptation to chronic arsenic exposure generally mitigating the oxidative stress response, allowing apoptotic by-pass after UV and enhanced cell survival even in the face of increased UV-induced oxidative stress and increased ODD. - Highlights: > Arsenic transformation adapted to UV-induced apoptosis. > Arsenic transformation diminished oxidant response. > Arsenic transformation enhanced UV-induced DNA damage.

  16. PCB153 reduces telomerase activity and telomere length in immortalized human skin keratinocytes (HaCaT) but not in human foreskin keratinocytes (NFK)

    SciTech Connect (OSTI)

    Senthilkumar, P.K.; Robertson, L.W.; Department of Occupational and Environmental Health, The University of Iowa, Iowa City, IA ; Ludewig, G.


    Polychlorinated biphenyls (PCBs), ubiquitous environmental pollutants, are characterized by long term-persistence in the environment, bioaccumulation, and biomagnification in the food chain. Exposure to PCBs may cause various diseases, affecting many cellular processes. Deregulation of the telomerase and the telomere complex leads to several biological disorders. We investigated the hypothesis that PCB153 modulates telomerase activity, telomeres and reactive oxygen species resulting in the deregulation of cell growth. Exponentially growing immortal human skin keratinocytes (HaCaT) and normal human foreskin keratinocytes (NFK) were incubated with PCB153 for 48 and 24 days, respectively, and telomerase activity, telomere length, superoxide level, cell growth, and cell cycle distribution were determined. In HaCaT cells exposure to PCB153 significantly reduced telomerase activity, telomere length, cell growth and increased intracellular superoxide levels from day 6 to day 48, suggesting that superoxide may be one of the factors regulating telomerase activity, telomere length and cell growth compared to untreated control cells. Results with NFK cells showed no shortening of telomere length but reduced cell growth and increased superoxide levels in PCB153-treated cells compared to untreated controls. As expected, basal levels of telomerase activity were almost undetectable, which made a quantitative comparison of treated and control groups impossible. The significant down regulation of telomerase activity and reduction of telomere length by PCB153 in HaCaT cells suggest that any cell type with significant telomerase activity, like stem cells, may be at risk of premature telomere shortening with potential adverse health effects for the affected organism. -- Highlights: ► Human immortal (HaCaT) and primary (NFK) keratinocytes were exposed to PCB153. ► PCB153 significantly reduced telomerase activity and telomere length in HaCaT. ► No effect on telomere length and

  17. Modeling and Simulation of Human Behavior in Buildings

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

    Laboratory Modeling and Simulation of Human Behavior in Buildings 2015 Building ... to IEA EBC Annex 66 4 Complexity of Human Behavior * Inherent uncertainty * ...


    SciTech Connect (OSTI)

    Ronald L. Boring; Donald D. Dudenhoeffer; Bruce P. Hallbert; Brian F. Gore


    This paper summarizes an emerging collaboration between Idaho National Laboratory and NASA Ames Research Center regarding the utilization of high-fidelity MIDAS simulations for modeling control room crew performance at nuclear power plants. The key envisioned uses for MIDAS-based control room simulations are: (i) the estimation of human error with novel control room equipment and configurations, (ii) the investigative determination of risk significance in recreating past event scenarios involving control room operating crews, and (iii) the certification of novel staffing levels in control rooms. It is proposed that MIDAS serves as a key component for the effective modeling of risk in next generation control rooms.

  19. Integrated Human Futures Modeling in Egypt

    SciTech Connect (OSTI)

    Passell, Howard D.; Aamir, Munaf Syed; Bernard, Michael Lewis; Beyeler, Walter E.; Fellner, Karen Marie; Hayden, Nancy Kay; Jeffers, Robert Fredric; Keller, Elizabeth James Kistin; Malczynski, Leonard A.; Mitchell, Michael David; Silver, Emily; Tidwell, Vincent C.; Villa, Daniel; Vugrin, Eric D.; Engelke, Peter; Burrow, Mat; Keith, Bruce


    The Integrated Human Futures Project provides a set of analytical and quantitative modeling and simulation tools that help explore the links among human social, economic, and ecological conditions, human resilience, conflict, and peace, and allows users to simulate tradeoffs and consequences associated with different future development and mitigation scenarios. In the current study, we integrate five distinct modeling platforms to simulate the potential risk of social unrest in Egypt resulting from the Grand Ethiopian Renaissance Dam (GERD) on the Blue Nile in Ethiopia. The five platforms simulate hydrology, agriculture, economy, human ecology, and human psychology/behavior, and show how impacts derived from development initiatives in one sector (e.g., hydrology) might ripple through to affect other sectors and how development and security concerns may be triggered across the region. This approach evaluates potential consequences, intended and unintended, associated with strategic policy actions that span the development-security nexus at the national, regional, and international levels. Model results are not intended to provide explicit predictions, but rather to provide system-level insight for policy makers into the dynamics among these interacting sectors, and to demonstrate an approach to evaluating short- and long-term policy trade-offs across different policy domains and stakeholders. The GERD project is critical to government-planned development efforts in Ethiopia but is expected to reduce downstream freshwater availability in the Nile Basin, fueling fears of negative social and economic impacts that could threaten stability and security in Egypt. We tested these hypotheses and came to the following preliminary conclusions. First, the GERD will have an important short-term impact on water availability, food production, and hydropower production in Egypt, depending on the short- term reservoir fill rate. Second, the GERD will have a very small impact on

  20. Sandia Energy - Results from the Human Resilience Index and Modeling...

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

    Results from the Human Resilience Index and Modeling project were reported recently in the National Intelligence Council's Global Trends 2030 Report Home Infrastructure Security...

  1. Massively Parallel Models of the Human Circulatory System (Conference...

    Office of Scientific and Technical Information (OSTI)

    Massively Parallel Models of the Human Circulatory System Citation Details In-Document ... Sponsoring Org: USDOE Country of Publication: United States Language: English Subject: 59 ...

  2. Transgenic rats overexpressing the human MrgX3 gene show cataracts and an abnormal skin phenotype

    SciTech Connect (OSTI)

    Kaisho, Yoshihiko . E-mail:; Watanabe, Takuya; Nakata, Mitsugu; Yano, Takashi; Yasuhara, Yoshitaka; Shimakawa, Kozo; Mori, Ikuo; Sakura, Yasufumi; Terao, Yasuko; Matsui, Hideki; Taketomi, Shigehisa


    The human MrgX3 gene, belonging to the mrgs/SNSRs (mass related genes/sensory neuron specific receptors) family, was overexpressed in transgenic rats using the actin promoter. Two animal lines showed cataracts with liquification/degeneration and swelling of the lens fiber cells. The transient epidermal desquamation was observed in line with higher gene expression. Histopathology of the transgenic rats showed acanthosis and focal parakeratosis. In the epidermis, there was an increase in cellular keratin 14, keratin 10, and loricrin, as well as PGP 9.5 in innervating nerve fibers. These phenotypes accompanied an increase in the number of proliferating cells. These results suggest that overexpression of the human MrgX3 gene causes a disturbance of the normal cell-differentiation process.

  3. Some aspects of statistical modeling of human-error probability

    SciTech Connect (OSTI)

    Prairie, R. R.


    Human reliability analyses (HRA) are often performed as part of risk assessment and reliability projects. Recent events in nuclear power have shown the potential importance of the human element. There are several on-going efforts in the US and elsewhere with the purpose of modeling human error such that the human contribution can be incorporated into an overall risk assessment associated with one or more aspects of nuclear power. An effort that is described here uses the HRA (event tree) to quantify and model the human contribution to risk. As an example, risk analyses are being prepared on several nuclear power plants as part of the Interim Reliability Assessment Program (IREP). In this process the risk analyst selects the elements of his fault tree that could be contributed to by human error. He then solicits the HF analyst to do a HRA on this element.

  4. Neutron skins and neutron stars

    SciTech Connect (OSTI)

    Piekarewicz, J.


    The neutron-skin thickness of heavy nuclei provides a fundamental link to the equation of state of neutron-rich matter, and hence to the properties of neutron stars. The Lead Radius Experiment ('PREX') at Jefferson Laboratory has recently provided the first model-independence evidence on the existence of a neutron-rich skin in {sup 208}Pb. In this contribution we examine how the increased accuracy in the determination of neutron skins expected from the commissioning of intense polarized electron beams may impact the physics of neutron stars.

  5. Modeling aspects of human memory for scientific study.

    SciTech Connect (OSTI)

    Caudell, Thomas P.; Watson, Patrick; McDaniel, Mark A.; Eichenbaum, Howard B.; Cohen, Neal J.; Vineyard, Craig Michael; Taylor, Shawn Ellis; Bernard, Michael Lewis; Morrow, James Dan; Verzi, Stephen J.


    Working with leading experts in the field of cognitive neuroscience and computational intelligence, SNL has developed a computational architecture that represents neurocognitive mechanisms associated with how humans remember experiences in their past. The architecture represents how knowledge is organized and updated through information from individual experiences (episodes) via the cortical-hippocampal declarative memory system. We compared the simulated behavioral characteristics with those of humans measured under well established experimental standards, controlling for unmodeled aspects of human processing, such as perception. We used this knowledge to create robust simulations of & human memory behaviors that should help move the scientific community closer to understanding how humans remember information. These behaviors were experimentally validated against actual human subjects, which was published. An important outcome of the validation process will be the joining of specific experimental testing procedures from the field of neuroscience with computational representations from the field of cognitive modeling and simulation.

  6. Modeling Human Behavior to Anticipate Insider Attacks

    SciTech Connect (OSTI)

    Greitzer, Frank L.; Hohimer, Ryan E.


    The insider threat ranks among the most pressing cybersecurity challenges that threaten government and industry information infrastructures. To date, no systematic methods have been developed that provide a complete and effective approach to prevent data leakage, espionage and sabotage. Current practice is forensic in nature, relegating to the analyst the bulk of the responsibility to monitor, analyze, and correlate an overwhelming amount of data. We describe a predictive modeling framework that integrates a diverse set of data sources from the cyber domain as well as inferred psychological/motivational factors that may underlie malicious insider exploits. This comprehensive threat assessment approach provides automated support for the detection of high-risk behavioral triggers to help focus the analysts attention and inform the analysis. Designed to be domain independent, the system may be applied to many different threat and warning analysis/sensemaking problems.

  7. Human performance modeling for system of systems analytics :soldier fatigue.

    SciTech Connect (OSTI)

    Lawton, Craig R.; Campbell, James E.; Miller, Dwight Peter


    The military has identified Human Performance Modeling (HPM) as a significant requirement and challenge of future systems modeling and analysis initiatives as can be seen in the Department of Defense's (DoD) Defense Modeling and Simulation Office's (DMSO) Master Plan (DoD 5000.59-P 1995). To this goal, the military is currently spending millions of dollars on programs devoted to HPM in various military contexts. Examples include the Human Performance Modeling Integration (HPMI) program within the Air Force Research Laboratory, which focuses on integrating HPMs with constructive models of systems (e.g. cockpit simulations) and the Navy's Human Performance Center (HPC) established in September 2003. Nearly all of these initiatives focus on the interface between humans and a single system. This is insufficient in the era of highly complex network centric SoS. This report presents research and development in the area of HPM in a system-of-systems (SoS). Specifically, this report addresses modeling soldier fatigue and the potential impacts soldier fatigue can have on SoS performance.

  8. Science-Based Simulation Model of Human Performance for Human Reliability Analysis

    SciTech Connect (OSTI)

    Dana L. Kelly; Ronald L. Boring; Ali Mosleh; Carol Smidts


    Human reliability analysis (HRA), a component of an integrated probabilistic risk assessment (PRA), is the means by which the human contribution to risk is assessed, both qualitatively and quantitatively. However, among the literally dozens of HRA methods that have been developed, most cannot fully model and quantify the types of errors that occurred at Three Mile Island. Furthermore, all of the methods lack a solid empirical basis, relying heavily on expert judgment or empirical results derived in non-reactor domains. Finally, all of the methods are essentially static, and are thus unable to capture the dynamics of an accident in progress. The objective of this work is to begin exploring a dynamic simulation approach to HRA, one whose models have a basis in psychological theories of human performance, and whose quantitative estimates have an empirical basis. This paper highlights a plan to formalize collaboration among the Idaho National Laboratory (INL), the University of Maryland, and The Ohio State University (OSU) to continue development of a simulation model initially formulated at the University of Maryland. Initial work will focus on enhancing the underlying human performance models with the most recent psychological research, and on planning follow-on studies to establish an empirical basis for the model, based on simulator experiments to be carried out at the INL and at the OSU.

  9. Age and gender specific biokinetic model for strontium in humans

    SciTech Connect (OSTI)

    Shagina, N. B.; Tolstykh, E. I.; Degteva, M. O.; Anspaugh, L. R.; Napier, Bruce A.


    A biokinetic model for strontium in humans is necessary for quantification of internal doses due to strontium radioisotopes. The ICRP-recommended biokinetic model for strontium has limitation for use in a population study, because it is not gender specific and does not cover all age ranges. The extensive Techa River data set on 90Sr in humans (tens of thousands of measurements) is a unique source of data on long-term strontium retention for men and women of all ages at intake. These, as well as published data, were used for evaluation of age- and gender-specific parameters for a new compartment biokinetic model for strontium (Sr-AGe model). The Sr-AGe model has similar structure as the ICRP model for the alkaline earth elements. The following parameters were mainly reevaluated: gastro-intestinal absorption and parameters related to the processes of bone formation and resorption defining calcium and strontium transfers in skeletal compartments. The Sr-AGe model satisfactorily describes available data sets on strontium retention for different kinds of intake (dietary and intravenous) at different ages (080 years old) and demonstrates good agreement with data sets for different ethnic groups. The Sr-AGe model can be used for dose assessment in epidemiological studies of general population exposed to ingested strontium radioisotopes.

  10. Tumors of the skin and soft tissues

    SciTech Connect (OSTI)

    Weller, R.E.


    The majority of the body surface is covered by the skin. Many internal disorders are reflected in the condition of the skin. One of the major functions of the skin is protection of the other organ systems from a variety of environmental insults. In this role, the skin itself is exposed to factors that can ultimately cause chronic diseases and cancer. Since it is relatively easy to recognize skin abnormalities, most skin cancers are brought to professional attention sooner than other types of cancer. However, due to the close resemblance between many skin neoplasms and noncancerous dermatologic disorders, these neoplasms may be mistreated for months or even years. In veterinary oncology, as in human medicine, most cancers can be effectively treated or cured following an accurate diagnosis. Once diagnosed, skin neoplasms should be aggressively treated. If causal factors are known, exposure to these factors should be limited through removal of the agent (for chemical carcinogens) or limiting exposure to the agent (for other carcinogens such as sunlight). 10 tabs. (MHB)

  11. A Revised Model for Dosimetry in the Human Small Intestine

    SciTech Connect (OSTI)

    John Poston; Nasir U. Bhuiyan; R. Alex Redd; Neil Parham; Jennifer Watson


    A new model for an adult human gastrointestinal tract (GIT) has been developed for use in internal dose estimations to the wall of the GIT and to the other organs and tissues of the body from radionuclides deposited in the lumenal contents of the five sections of the GIT. These sections were the esophasgus, stomach, small intestine, upper large intestine, and the lower large intestine. The wall of each section was separated from its lumenal contents.

  12. microRNA Alterations Driving Acute and Late Stages of Radiation-Induced Fibrosis in a Murine Skin Model

    SciTech Connect (OSTI)

    Simone, Brittany A.; Ly, David; Savage, Jason E.; Hewitt, Stephen M.; Dan, Tu D.; Ylaya, Kris; Shankavaram, Uma; Lim, Meng; Jin, Lianjin; Camphausen, Kevin; Mitchell, James B.; Simone, Nicole L.


    Purpose: Although ionizing radiation is critical in treating cancer, radiation-induced fibrosis (RIF) can have a devastating impact on patients' quality of life. The molecular changes leading to radiation-induced fibrosis must be elucidated so that novel treatments can be designed. Methods and Materials: To determine whether microRNAs (miRs) could be responsible for RIF, the fibrotic process was induced in the right hind legs of 9-week old CH3 mice by a single-fraction dose of irradiation to 35Gy, and the left leg served as an unirradiated control. Fibrosis was quantified by measurements of leg length compared with control leg length. By 120days after irradiation, the irradiated legs were 20% (P=.013) shorter on average than were the control legs. Results: Tissue analysis was done on muscle, skin, and subcutaneous tissue from irradiated and control legs. Fibrosis was noted on both gross and histologic examination by use of a pentachrome stain. Microarrays were performed at various times after irradiation, including 7days, 14days, 50days, 90days, and 120days after irradiation. miR-15a, miR-21, miR-30a, and miR-34a were the miRs with the most significant alteration by array with miR-34a, proving most significant on confirmation by reverse transcriptase polymerase chain reaction, c-Met, a known effector of fibrosis and downstream molecule of miR-34a, was evaluated by use of 2cell lines: HCT116 and 1522. The cell lines were exposed to various stressors to induce miR changes, specifically ionizing radiation. Additionally, invitro transfections with pre-miRs and anti-miRs confirmed the relationship of miR-34a and c-Met. Conclusions: Our data demonstrate an inverse relationship with miR-34a and c-Met; the upregulation of miR-34a in RIF causes inhibition of c-Met production. miRs may play a role in RIF; in particular, miR-34a should be investigated as a potential target to prevent or treat this devastating side effect of irradiation.

  13. A biokinetic model for systemic technetium in adult humans

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

    Leggett, Richard Wayne; Giussani, Augusto


    The International Commission on Radiological Protection (ICRP) currently is updating its biokinetic and dosimetric models for internally deposited radionuclides. Technetium (Tc), the lightest element that exists only in radioactive form, has two important isotopes from the standpoint of potential risk to humans: the long-lived isotope 99Tm(T1/2=2.1x105 y) is present in high concentration in nuclear waste, and the short-lived isotope 99mTc (T1/2=6.02 h) is the most commonly used radionuclide in diagnostic nuclear medicine. This paper reviews data on the biological behavior of technetium and proposes a biokinetic model for systemic technetium in the adult human body for use in radiation protection.more » Compared with the ICRP s current occupational model for systemic technetium, the proposed model provides a more realistic description of the paths of movement of technetium in the body; provides greater consistency with experimental and medical data; and, for most radiosensitive organs, yields substantially different estimates of cumulative activity (total radioactive decays within the organ) following uptake of 99Tm or 99mTc to blood.« less

  14. A biokinetic model for systemic technetium in adult humans

    SciTech Connect (OSTI)

    Leggett, Richard Wayne; Giussani, Augusto


    The International Commission on Radiological Protection (ICRP) currently is updating its biokinetic and dosimetric models for internally deposited radionuclides. Technetium (Tc), the lightest element that exists only in radioactive form, has two important isotopes from the standpoint of potential risk to humans: the long-lived isotope 99Tm(T1/2=2.1x105 y) is present in high concentration in nuclear waste, and the short-lived isotope 99mTc (T1/2=6.02 h) is the most commonly used radionuclide in diagnostic nuclear medicine. This paper reviews data on the biological behavior of technetium and proposes a biokinetic model for systemic technetium in the adult human body for use in radiation protection. Compared with the ICRP s current occupational model for systemic technetium, the proposed model provides a more realistic description of the paths of movement of technetium in the body; provides greater consistency with experimental and medical data; and, for most radiosensitive organs, yields substantially different estimates of cumulative activity (total radioactive decays within the organ) following uptake of 99Tm or 99mTc to blood.

  15. A biokinetic model for systemic technetium in adult humans

    SciTech Connect (OSTI)

    Leggett, Richard Wayne; Giussani, Augusto


    The International Commission on Radiological Protection (ICRP) currently is updating its biokinetic and dosimetric models for internally deposited radionuclides. Technetium (Tc), the lightest element that exists only in radioactive form, has two important isotopes from the standpoint of potential risk to humans: the long-lived isotope 99Tm (T1/2=2.1x105 y) is present in high concentration in nuclear waste, and the short-lived isotope 99mTc (T1/2=6.02 h) is the most commonly used radionuclide in diagnostic nuclear medicine. This paper reviews data on the biological behavior of technetium and proposes a biokinetic model for systemic technetium in the adult human body for use in radiation protection. Compared with the ICRP s current occupational model for systemic technetium, the proposed model provides a more realistic description of the paths of movement of technetium in the body; provides greater consistency with experimental and medical data; and, for most radiosensitive organs, yields substantially different estimates of cumulative activity (total radioactive decays within the organ) following uptake of 99Tm or 99mTc to blood.

  16. Computational Human Performance Modeling For Alarm System Design

    SciTech Connect (OSTI)

    Jacques Hugo


    The introduction of new technologies like adaptive automation systems and advanced alarms processing and presentation techniques in nuclear power plants is already having an impact on the safety and effectiveness of plant operations and also the role of the control room operator. This impact is expected to escalate dramatically as more and more nuclear power utilities embark on upgrade projects in order to extend the lifetime of their plants. One of the most visible impacts in control rooms will be the need to replace aging alarm systems. Because most of these alarm systems use obsolete technologies, the methods, techniques and tools that were used to design the previous generation of alarm system designs are no longer effective and need to be updated. The same applies to the need to analyze and redefine operators alarm handling tasks. In the past, methods for analyzing human tasks and workload have relied on crude, paper-based methods that often lacked traceability. New approaches are needed to allow analysts to model and represent the new concepts of alarm operation and human-system interaction. State-of-the-art task simulation tools are now available that offer a cost-effective and efficient method for examining the effect of operator performance in different conditions and operational scenarios. A discrete event simulation system was used by human factors researchers at the Idaho National Laboratory to develop a generic alarm handling model to examine the effect of operator performance with simulated modern alarm system. It allowed analysts to evaluate alarm generation patterns as well as critical task times and human workload predicted by the system.

  17. A Dynamic Approach to Modeling Dependence Between Human Failure Events

    SciTech Connect (OSTI)

    Boring, Ronald Laurids


    In practice, most HRA methods use direct dependence from THERP—the notion that error be- gets error, and one human failure event (HFE) may increase the likelihood of subsequent HFEs. In this paper, we approach dependence from a simulation perspective in which the effects of human errors are dynamically modeled. There are three key concepts that play into this modeling: (1) Errors are driven by performance shaping factors (PSFs). In this context, the error propagation is not a result of the presence of an HFE yielding overall increases in subsequent HFEs. Rather, it is shared PSFs that cause dependence. (2) PSFs have qualities of lag and latency. These two qualities are not currently considered in HRA methods that use PSFs. Yet, to model the effects of PSFs, it is not simply a matter of identifying the discrete effects of a particular PSF on performance. The effects of PSFs must be considered temporally, as the PSFs will have a range of effects across the event sequence. (3) Finally, there is the concept of error spilling. When PSFs are activated, they not only have temporal effects but also lateral effects on other PSFs, leading to emergent errors. This paper presents the framework for tying together these dynamic dependence concepts.

  18. Modeling of laser ablation and fragmentation of human calculi

    SciTech Connect (OSTI)

    Gitomer, S.; Jones, R.D.; Howsare, C.


    The large-scale radiation-hydrodynamics computer code LASNEX, has been used to model experimental results in the laser ablation and fragmentation of renal and biliary calculi. Recent experiments have demonstrated laser ablation and fragmentation of human calculi in vitro and in vivo. In the interaction, laser light incident upon the calculus is of sufficient intensity to produce a plasma (a hot ionized gas). The physical picture which emerges is as follows. The plasma couples to acoustic and shear waves which then propagate through the dense stone material, causing spall and fracture by reflection from material discontinuities or boundaries. Experiments have thus far yielded data on the interaction against which models can be tested. Data on the following have been published: (1) light emission, (2) absorption and emission spectra, (3) fragmentation efficiency, (4) cavitation bubble dynamics and (5) mass removal. We have performed one dimensional simulations of the laser-matter interaction to elucidate the important physical mechanisms. We find that good quantitative fits between simulation and experiment are obtained for visible light emission, electron temperature, electron density, plasma pressure and cavitation bubble growth. With regard to mass removal, experiment and simulation are consistent with each other and give an excellent estimate of the ablation threshold. The modeling indicates that a very small ablation layer at the surface of the calculus is responsible for significant mass loss by fragmentation within the bulk of the calculus. With such quantitative fits in hand, we believe this type of modeling can now be applied to the study of other procedures involving plasma formation of interest to the medical community. 25 refs., 7 figs.

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

    SciTech Connect (OSTI)

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


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

  20. On the tear resistance of skin

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

    Yang, Wen; Sherman, Vincent R.; Gludovatz, Bernd; Schaible, Eric; Stewart, Polite; Ritchie, Robert O.; Meyers, Marc A.


    Tear resistance is vitally important for the various functions of skin, especially protection from predatorial attack. Here, we mechanistically quantify the extreme tear resistance of skin and identify the underlying structural features, which lead to its sophisticated failure mechanisms. Here we explain why it is virtually impossible to propagate a tear in rabbit skin, chosen as a model material for the dermis of vertebrates. Finally, we express the deformation in terms of four mechanisms of collagen fibril activity in skin under tensile loading that virtually eliminate the possibility of tearing in pre-notched samples: fibril straightening, fibril reorientation towards the tensilemore » direction, elastic stretching and interfibrillar sliding, all of which contribute to the redistribution of the stresses at the notch tip.« less

  1. Modeling human risk: Cell & molecular biology in context

    SciTech Connect (OSTI)


    It is anticipated that early in the next century manned missions into outer space will occur, with a mission to Mars scheduled between 2015 and 2020. However, before such missions can be undertaken, a realistic estimation of the potential risks to the flight crews is required. One of the uncertainties remaining in this risk estimation is that posed by the effects of exposure to the radiation environment of outer space. Although the composition of this environment is fairly well understood, the biological effects arising from exposure to it are not. The reasons for this are three-fold: (1) A small but highly significant component of the radiation spectrum in outer space consists of highly charged, high energy (HZE) particles which are not routinely experienced on earth, and for which there are insufficient data on biological effects; (2) Most studies on the biological effects of radiation to date have been high-dose, high dose-rate, whereas in space, with the exception of solar particle events, radiation exposures will be low-dose, low dose-rate; (3) Although it has been established that the virtual absence of gravity in space has a profound effect on human physiology, it is not clear whether these effects will act synergistically with those of radiation exposure. A select panel will evaluate the utilizing experiments and models to accurately predict the risks associated with exposure to HZE particles. Topics of research include cellular and tissue response, health effects associated with radiation damage, model animal systems, and critical markers of Radiation response.

  2. Sprayed skin turbine component

    DOE Patents [OSTI]

    Allen, David B


    Fabricating a turbine component (50) by casting a core structure (30), forming an array of pits (24) in an outer surface (32) of the core structure, depositing a transient liquid phase (TLP) material (40) on the outer surface of the core structure, the TLP containing a melting-point depressant, depositing a skin (42) on the outer surface of the core structure over the TLP material, and heating the assembly, thus forming both a diffusion bond and a mechanical interlock between the skin and the core structure. The heating diffuses the melting-point depressant away from the interface. Subsurface cooling channels (35) may be formed by forming grooves (34) in the outer surface of the core structure, filling the grooves with a fugitive filler (36), depositing and bonding the skin (42), then removing the fugitive material.

  3. Hypoxia perturbs aryl hydrocarbon receptor signaling and CYP1A1 expression induced by PCB 126 in human skin and liver-derived cell lines

    SciTech Connect (OSTI)

    Vorrink, Sabine U.; Severson, Paul L.; Kulak, Mikhail V.; Futscher, Bernard W.; Domann, Frederick E.


    The aryl hydrocarbon receptor (AhR) is an important mediator of toxic responses after exposure to xenobiotics including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and dioxin-like polychlorinated biphenyls (PCBs). Activation of AhR responsive genes requires AhR dimerization with the aryl hydrocarbon receptor nuclear translocator (ARNT), a heterodimeric partner also shared by the hypoxia-inducible factor-1α (HIF-1α) protein. TCDD-stimulated AhR transcriptional activity can be influenced by hypoxia; however, it less well known whether hypoxia interferes with AhR transcriptional transactivation in the context of PCB-mediated AhR activation in human cells. Elucidation of this interaction is important in liver hepatocytes which extensively metabolize ingested PCBs and experience varying degrees of oxygen tension during normal physiologic function. This study was designed to assess the effect of hypoxia on AhR transcriptional responses after exposure to 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126). Exposure to 1% O{sub 2} prior to PCB 126 treatment significantly inhibited CYP1A1 mRNA and protein expression in human HepG2 and HaCaT cells. CYP1A1 transcriptional activation was significantly decreased upon PCB 126 stimulation under conditions of hypoxia. Additionally, hypoxia pre-treatment reduced PCB 126 induced AhR binding to CYP1 target gene promoters. Importantly, ARNT overexpression rescued cells from the inhibitory effect of hypoxia on XRE-luciferase reporter activity. Therefore, the mechanism of interference of the signaling crosstalk between the AhR and hypoxia pathways appears to be at least in part dependent on ARNT availability. Our results show that AhR activation and CYP1A1 expression induced by PCB 126 were significantly inhibited by hypoxia and hypoxia might therefore play an important role in PCB metabolism and toxicity. - Highlights: • Significant crosstalk exists between AhR and HIF-1α signaling. • Hypoxia perturbs PCB 126 induced AhR function and

  4. Neutron skin thickness and neutron star equations of state: a strong relationship

    SciTech Connect (OSTI)

    Menezes, D. P.; Avancini, S. S.; Marinelli, J. R.; Watanabe de Moraes, M. M.; Providencia, C.


    A density dependent hadronic model and a common parametrization of the non-linear Walecka model are used to obtain the lead neutron skin thickness through its proton and neutron density profiles. The neutron skin thickness is known to reflect the equation of state properties. A direct correlation between the neutron skin thickness and the slope of the symmetry energy is found.

  5. Skin contamination dosimeter

    DOE Patents [OSTI]

    Hamby, David M.; Farsoni, Abdollah T.; Cazalas, Edward


    A technique and device provides absolute skin dosimetry in real time at multiple tissue depths simultaneously. The device uses a phoswich detector which has multiple scintillators embedded at different depths within a non-scintillating material. A digital pulse processor connected to the phoswich detector measures a differential distribution (dN/dH) of count rate N as function of pulse height H for signals from each of the multiple scintillators. A digital processor computes in real time from the differential count-rate distribution for each of multiple scintillators an estimate of an ionizing radiation dose delivered to each of multiple depths of skin tissue corresponding to the multiple scintillators embedded at multiple corresponding depths within the non-scintillating material.

  6. A mid-layer model for human reliability analysis : understanding the cognitive causes of human failure events.

    SciTech Connect (OSTI)

    Shen, Song-Hua; Chang, James Y. H.; Boring,Ronald L.; Whaley, April M.; Lois, Erasmia; Hendrickson, Stacey M. Langfitt; Oxstrand, Johanna H.; Forester, John Alan; Kelly, Dana L.; Mosleh, Ali


    The Office of Nuclear Regulatory Research (RES) at the US Nuclear Regulatory Commission (USNRC) is sponsoring work in response to a Staff Requirements Memorandum (SRM) directing an effort to establish a single human reliability analysis (HRA) method for the agency or guidance for the use of multiple methods. As part of this effort an attempt to develop a comprehensive HRA qualitative approach is being pursued. This paper presents a draft of the method's middle layer, a part of the qualitative analysis phase that links failure mechanisms to performance shaping factors. Starting with a Crew Response Tree (CRT) that has identified human failure events, analysts identify potential failure mechanisms using the mid-layer model. The mid-layer model presented in this paper traces the identification of the failure mechanisms using the Information-Diagnosis/Decision-Action (IDA) model and cognitive models from the psychological literature. Each failure mechanism is grouped according to a phase of IDA. Under each phase of IDA, the cognitive models help identify the relevant performance shaping factors for the failure mechanism. The use of IDA and cognitive models can be traced through fault trees, which provide a detailed complement to the CRT.

  7. Toward Real-time Modeling of Human Heart Ventricles at Cellular...

    Office of Scientific and Technical Information (OSTI)

    Simulation of Drug-induced Arrhythmias Citation Details In-Document Search Title: Toward Real-time Modeling of Human Heart Ventricles at Cellular Resolution: Multi-hour Simulation ...

  8. A naturalistic decision making model for simulated human combatants

    SciTech Connect (OSTI)



    The authors describe a naturalistic behavioral model for the simulation of small unit combat. This model, Klein's recognition-primed decision making (RPD) model, is driven by situational awareness rather than a rational process of selecting from a set of action options. They argue that simulated combatants modeled with RPD will have more flexible and realistic responses to a broad range of small-scale combat scenarios. Furthermore, they note that the predictability of a simulation using an RPD framework can be easily controlled to provide multiple evaluations of a given combat scenario. Finally, they discuss computational issues for building an RPD-based behavior engine for fully automated combatants in small conflict scenarios, which are being investigated within Sandia's Next Generation Site Security project.

  9. ARM - Measurement - Surface skin temperature

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

    skin temperature ARM Data Discovery Browse Data Comments? We would love to hear from you! Send us a note below or call us at 1-888-ARM-DATA. Send Measurement : Surface skin temperature The radiative surface skin temperature, from an IR thermometer measuring the narrowband radiating temperature of the ground surface in its field of view. Categories Surface Properties, Radiometric Instruments The above measurement is considered scientifically relevant for the following instruments. Refer to the

  10. Correlation between human observer performance and model observer performance in differential phase contrast CT

    SciTech Connect (OSTI)

    Li, Ke; Garrett, John; Chen, Guang-Hong


    Purpose: With the recently expanding interest and developments in x-ray differential phase contrast CT (DPC-CT), the evaluation of its task-specific detection performance and comparison with the corresponding absorption CT under a given radiation dose constraint become increasingly important. Mathematical model observers are often used to quantify the performance of imaging systems, but their correlations with actual human observers need to be confirmed for each new imaging method. This work is an investigation of the effects of stochastic DPC-CT noise on the correlation of detection performance between model and human observers with signal-known-exactly (SKE) detection tasks.Methods: The detectabilities of different objects (five disks with different diameters and two breast lesion masses) embedded in an experimental DPC-CT noise background were assessed using both model and human observers. The detectability of the disk and lesion signals was then measured using five types of model observers including the prewhitening ideal observer, the nonprewhitening (NPW) observer, the nonprewhitening observer with eye filter and internal noise (NPWEi), the prewhitening observer with eye filter and internal noise (PWEi), and the channelized Hotelling observer (CHO). The same objects were also evaluated by four human observers using the two-alternative forced choice method. The results from the model observer experiment were quantitatively compared to the human observer results to assess the correlation between the two techniques.Results: The contrast-to-detail (CD) curve generated by the human observers for the disk-detection experiments shows that the required contrast to detect a disk is inversely proportional to the square root of the disk size. Based on the CD curves, the ideal and NPW observers tend to systematically overestimate the performance of the human observers. The NPWEi and PWEi observers did not predict human performance well either, as the slopes of their CD

  11. Scale and the representation of human agency in the modeling of agroecosystems

    SciTech Connect (OSTI)

    Preston, Benjamin L.; King, Anthony W.; Ernst, Kathleen M.; Absar, Syeda Mariya; Nair, Sujithkumar Surendran; Parish, Esther S.


    Human agency is an essential determinant of the dynamics of agroecosystems. However, the manner in which agency is represented within different approaches to agroecosystem modeling is largely contingent on the scales of analysis and the conceptualization of the system of interest. While appropriate at times, narrow conceptualizations of agroecosystems can preclude consideration for how agency manifests at different scales, thereby marginalizing processes, feedbacks, and constraints that would otherwise affect model results. Modifications to the existing modeling toolkit may therefore enable more holistic representations of human agency. Model integration can assist with the development of multi-scale agroecosystem modeling frameworks that capture different aspects of agency. In addition, expanding the use of socioeconomic scenarios and stakeholder participation can assist in explicitly defining context-dependent elements of scale and agency. Finally, such approaches, however, should be accompanied by greater recognition of the meta agency of model users and the need for more critical evaluation of model selection and application.

  12. Extrapolation of systemic bioavailability assessing skin absorption and epidermal and hepatic metabolism of aromatic amine hair dyes in vitro

    SciTech Connect (OSTI)

    Manwaring, John; Rothe, Helga; Obringer, Cindy; Foltz, David J.; Baker, Timothy R.; Troutman, John A.; Hewitt, Nicola J.; Goebel, Carsten


    Approaches to assess the role of absorption, metabolism and excretion of cosmetic ingredients that are based on the integration of different in vitro data are important for their safety assessment, specifically as it offers an opportunity to refine that safety assessment. In order to estimate systemic exposure (AUC) to aromatic amine hair dyes following typical product application conditions, skin penetration and epidermal and systemic metabolic conversion of the parent compound was assessed in human skin explants and human keratinocyte (HaCaT) and hepatocyte cultures. To estimate the amount of the aromatic amine that can reach the general circulation unchanged after passage through the skin the following toxicokinetically relevant parameters were applied: a) Michaelis–Menten kinetics to quantify the epidermal metabolism; b) the estimated keratinocyte cell abundance in the viable epidermis; c) the skin penetration rate; d) the calculated Mean Residence Time in the viable epidermis; e) the viable epidermis thickness and f) the skin permeability coefficient. In a next step, in vitro hepatocyte K{sub m} and V{sub max} values and whole liver mass and cell abundance were used to calculate the scaled intrinsic clearance, which was combined with liver blood flow and fraction of compound unbound in the blood to give hepatic clearance. The systemic exposure in the general circulation (AUC) was extrapolated using internal dose and hepatic clearance, and C{sub max} was extrapolated (conservative overestimation) using internal dose and volume of distribution, indicating that appropriate toxicokinetic information can be generated based solely on in vitro data. For the hair dye, p-phenylenediamine, these data were found to be in the same order of magnitude as those published for human volunteers. - Highlights: • An entirely in silico/in vitro approach to predict in vivo exposure to dermally applied hair dyes • Skin penetration and epidermal conversion assessed in human

  13. Surety of human elements of high consequence systems: An organic model

    SciTech Connect (OSTI)



    Despite extensive safety analysis and application of safety measures, there is a frequent lament, ``Why do we continue to have accidents?'' Two breakdowns are prevalent in risk management and prevention. First, accidents result from human actions that engineers, analysts and management never envisioned and second, controls, intended to preclude/mitigate accident sequences, prove inadequate. This paper addresses the first breakdown, the inability to anticipate scenarios involving human action/inaction. The failure of controls has been addressed in a previous publication (Forsythe and Grose, 1998). Specifically, this paper presents an approach referred to as surety. The objective of this approach is to provide high levels of assurance in situations where potential system failure paths cannot be fully characterized. With regard to human elements of complex systems, traditional approaches to human reliability are not sufficient to attain surety. Consequently, an Organic Model has been developed to account for the organic properties exhibited by engineered systems that result from human involvement in those systems.

  14. Help:Skins | Open Energy Information

    Open Energy Info (EERE)

    on the my preferences link in the upper right while logged in then click on the Skin button to change your skin. You can also preview the skin by clicking the (preview)...

  15. Breakthrough antibacterial approach could resolve serious skin...

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

    ... by >16-fold into the deep tissue layers of the skin without inducing skin irritation. ... by the Materials Research Science and Engineering Centers Program of the National Science ...

  16. Predictivity of dog co-culture model, primary human hepatocytes and HepG2 cells for the detection of hepatotoxic drugs in humans

    SciTech Connect (OSTI)

    Atienzar, Franck A.; Novik, Eric I.; Gerets, Helga H.; Parekh, Amit; Delatour, Claude; Cardenas, Alvaro; MacDonald, James; Yarmush, Martin L.; Dhalluin, Stphane


    Drug Induced Liver Injury (DILI) is a major cause of attrition during early and late stage drug development. Consequently, there is a need to develop better in vitro primary hepatocyte models from different species for predicting hepatotoxicity in both animals and humans early in drug development. Dog is often chosen as the non-rodent species for toxicology studies. Unfortunately, dog in vitro models allowing long term cultures are not available. The objective of the present manuscript is to describe the development of a co-culture dog model for predicting hepatotoxic drugs in humans and to compare the predictivity of the canine model along with primary human hepatocytes and HepG2 cells. After rigorous optimization, the dog co-culture model displayed metabolic capacities that were maintained up to 2 weeks which indicates that such model could be also used for long term metabolism studies. Most of the human hepatotoxic drugs were detected with a sensitivity of approximately 80% (n = 40) for the three cellular models. Nevertheless, the specificity was low approximately 40% for the HepG2 cells and hepatocytes compared to 72.7% for the canine model (n = 11). Furthermore, the dog co-culture model showed a higher superiority for the classification of 5 pairs of close structural analogs with different DILI concerns in comparison to both human cellular models. Finally, the reproducibility of the canine system was also satisfactory with a coefficient of correlation of 75.2% (n = 14). Overall, the present manuscript indicates that the dog co-culture model may represent a relevant tool to perform chronic hepatotoxicity and metabolism studies. - Highlights: Importance of species differences in drug development. Relevance of dog co-culture model for metabolism and toxicology studies. Hepatotoxicity: higher predictivity of dog co-culture vs HepG2 and human hepatocytes.

  17. The Use Of Computational Human Performance Modeling As Task Analysis Tool

    SciTech Connect (OSTI)

    Jacuqes Hugo; David Gertman


    During a review of the Advanced Test Reactor safety basis at the Idaho National Laboratory, human factors engineers identified ergonomic and human reliability risks involving the inadvertent exposure of a fuel element to the air during manual fuel movement and inspection in the canal. There were clear indications that these risks increased the probability of human error and possible severe physical outcomes to the operator. In response to this concern, a detailed study was conducted to determine the probability of the inadvertent exposure of a fuel element. Due to practical and safety constraints, the task network analysis technique was employed to study the work procedures at the canal. Discrete-event simulation software was used to model the entire procedure as well as the salient physical attributes of the task environment, such as distances walked, the effect of dropped tools, the effect of hazardous body postures, and physical exertion due to strenuous tool handling. The model also allowed analysis of the effect of cognitive processes such as visual perception demands, auditory information and verbal communication. The model made it possible to obtain reliable predictions of operator performance and workload estimates. It was also found that operator workload as well as the probability of human error in the fuel inspection and transfer task were influenced by the concurrent nature of certain phases of the task and the associated demand on cognitive and physical resources. More importantly, it was possible to determine with reasonable accuracy the stages as well as physical locations in the fuel handling task where operators would be most at risk of losing their balance and falling into the canal. The model also provided sufficient information for a human reliability analysis that indicated that the postulated fuel exposure accident was less than credible.

  18. Scale and the representation of human agency in the modeling of agroecosystems

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

    Preston, Benjamin L.; King, Anthony W.; Ernst, Kathleen M.; Absar, Syeda Mariya; Nair, Sujithkumar Surendran; Parish, Esther S.


    Human agency is an essential determinant of the dynamics of agroecosystems. However, the manner in which agency is represented within different approaches to agroecosystem modeling is largely contingent on the scales of analysis and the conceptualization of the system of interest. While appropriate at times, narrow conceptualizations of agroecosystems can preclude consideration for how agency manifests at different scales, thereby marginalizing processes, feedbacks, and constraints that would otherwise affect model results. Modifications to the existing modeling toolkit may therefore enable more holistic representations of human agency. Model integration can assist with the development of multi-scale agroecosystem modeling frameworks that capturemore » different aspects of agency. In addition, expanding the use of socioeconomic scenarios and stakeholder participation can assist in explicitly defining context-dependent elements of scale and agency. Finally, such approaches, however, should be accompanied by greater recognition of the meta agency of model users and the need for more critical evaluation of model selection and application.« less

  19. Effects of phenylpropanolamine (PPA) on in vitro human erythrocyte membranes and molecular models

    SciTech Connect (OSTI)

    Suwalsky, Mario; Zambrano, Pablo; Mennickent, Sigrid; Villena, Fernando; Sotomayor, Carlos P.; Aguilar, Luis F.; Bolognin, Silvia


    Research highlights: {yields} PPA is a common ingredient in cough-cold medication and appetite suppressants. {yields} Reports on its effects on human erythrocytes are very scarce. {yields} We found that PPA induced in vitro morphological changes to human erythrocytes. {yields} PPA interacted with isolated unsealed human erythrocyte membranes. {yields} PPA interacted with class of lipid present in the erythrocyte membrane outer monolayer. -- Abstract: Norephedrine, also called phenylpropanolamine (PPA), is a synthetic form of the ephedrine alkaloid. After reports of the occurrence of intracranial hemorrhage and other adverse effects, including several deaths, PPA is no longer sold in USA and Canada. Despite the extensive information about PPA toxicity, reports on its effects on cell membranes are scarce. With the aim to better understand the molecular mechanisms of the interaction of PPA with cell membranes, ranges of concentrations were incubated with intact human erythrocytes, isolated unsealed human erythrocyte membranes (IUM), and molecular models of cell membranes. The latter consisted in bilayers built-up of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), phospholipid classes present in the outer and inner monolayers of most plasmatic cell membranes, respectively. The capacity of PPA to perturb the bilayer structures of DMPC and DMPE was assessed by X-ray diffraction, DMPC large unilamellar vesicles (LUV) and IUM were studied by fluorescence spectroscopy, and intact human erythrocytes were observed by scanning electron microscopy (SEM). This study presents evidence that PPA affects human red cell membranes as follows: (a) in SEM studies on human erythrocytes it was observed that 0.5 mM PPA induced shape changes; (b) in IUM PPA induced a sharp decrease in the fluorescence anisotropy in the lipid bilayer acyl chains in a concentration range lower than 100 {mu}M; (c) X-ray diffraction studies showed that PPA in the 0.1-0.5 m

  20. A Human Life-Stage Physiologically Based Pharmacokinetic and Pharmacodynamic Model for Chlorpyrifos: Development and Validation

    SciTech Connect (OSTI)

    Smith, Jordan N.; Hinderliter, Paul M.; Timchalk, Charles; Bartels, M. J.; Poet, Torka S.


    Sensitivity to chemicals in animals and humans are known to vary with age. Age-related changes in sensitivity to chlorpyrifos have been reported in animal models. A life-stage physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model was developed to computationally predict disposition of CPF and its metabolites, chlorpyrifos-oxon (the ultimate toxicant) and 3,5,6-trichloro-2-pyridinol (TCPy), as well as B-esterase inhibition by chlorpyrifos-oxon in humans. In this model, age-dependent body weight was calculated from a generalized Gompertz function, and compartments (liver, brain, fat, blood, diaphragm, rapid, and slow) were scaled based on body weight from polynomial functions on a fractional body weight basis. Blood flows among compartments were calculated as a constant flow per compartment volume. The life-stage PBPK/PD model was calibrated and tested against controlled adult human exposure studies. Model simulations suggest age-dependent pharmacokinetics and response may exist. At oral doses ? 0.55 mg/kg of chlorpyrifos (significantly higher than environmental exposure levels), 6 mo old children are predicted to have higher levels of chlorpyrifos-oxon in blood and higher levels of red blood cell cholinesterase inhibition compared to adults from equivalent oral doses of chlorpyrifos. At lower doses that are more relevant to environmental exposures, the model predicts that adults will have slightly higher levels of chlorpyrifos-oxon in blood and greater cholinesterase inhibition. This model provides a computational framework for age-comparative simulations that can be utilized to predict CPF disposition and biological response over various postnatal life-stages.

  1. Modeling and Simulation for Exploring Human-Robot Team Interaction Requirements

    SciTech Connect (OSTI)

    Dudenhoeffer, Donald Dean; Bruemmer, David Jonathon; Davis, Midge Lee


    Small-sized and micro-robots will soon be available for deployment in large-scale forces. Consequently, the ability of a human operator to coordinate and interact with largescale robotic forces is of great interest. This paper describes the ways in which modeling and simulation have been used to explore new possibilities for human-robot interaction. The paper also discusses how these explorations have fed implementation of a unified set of command and control concepts for robotic force deployment. Modeling and simulation can play a major role in fielding robot teams in actual missions. While live testing is preferred, limitations in terms of technology, cost, and time often prohibit extensive experimentation with physical multi-robot systems. Simulation provides insight, focuses efforts, eliminates large areas of the possible solution space, and increases the quality of actual testing.

  2. Turbine vane with high temperature capable skins

    DOE Patents [OSTI]

    Morrison, Jay A.


    A turbine vane assembly includes an airfoil extending between an inner shroud and an outer shroud. The airfoil can include a substructure having an outer peripheral surface. At least a portion of the outer peripheral surface is covered by an external skin. The external skin can be made of a high temperature capable material, such as oxide dispersion strengthened alloys, intermetallic alloys, ceramic matrix composites or refractory alloys. The external skin can be formed, and the airfoil can be subsequently bi-cast around or onto the skin. The skin and the substructure can be attached by a plurality of attachment members extending between the skin and the substructure. The skin can be spaced from the outer peripheral surface of the substructure such that a cavity is formed therebetween. Coolant can be supplied to the cavity. Skins can also be applied to the gas path faces of the inner and outer shrouds.

  3. Models of human operators: Their need and usefulness for improvement of advanced control systems and control rooms

    SciTech Connect (OSTI)

    Knee, H.E.; Schryver, J.C.


    Models of human behavior and cognition (HB C) are necessary for understanding the total response of complex systems. Many such model have come available over the past thirty years for various applications. Many potential model users remain skeptical about their practically, acceptability, and usefulness. Such hesitancy stems in part from disbelief in the ability to model complex cognitive processes, and a belief that relevant human behavior can be adequately accounted for through the use of common-sense heuristics. This paper will highlight several models of HB C and identify existing and potential applications in attempt to dispel such notions. 26 refs.

  4. Dose-rate models for human survival after exposure to ionizing radiation

    SciTech Connect (OSTI)

    Jones, T.D.; Morris, M.D.; Young, R.W.


    This paper reviews new estimates of the L/sub 50/ in man by Mole and by Rotblat, the biological processes contributing to hematologic death, the collection of animal experiments dealing with hematologic death, and the use of regression analysis to make new estimates of human mortality based on all relevant animal studies. Regression analysis of animal mortality data has shown that mortality is dependent strongly on dose rate, species, body weight, and time interval over which the exposure is delivered. The model has predicted human LD/sub 50/s of 194, 250, 310, and 360 rad to marrow when the exposure time is a minute, an hour, a day, and a week, respectively.

  5. Modeling and Quantification of Team Performance in Human Reliability Analysis for Probabilistic Risk Assessment

    SciTech Connect (OSTI)

    Jeffrey C. JOe; Ronald L. Boring


    Probabilistic Risk Assessment (PRA) and Human Reliability Assessment (HRA) are important technical contributors to the United States (U.S.) Nuclear Regulatory Commission’s (NRC) risk-informed and performance based approach to regulating U.S. commercial nuclear activities. Furthermore, all currently operating commercial NPPs in the U.S. are required by federal regulation to be staffed with crews of operators. Yet, aspects of team performance are underspecified in most HRA methods that are widely used in the nuclear industry. There are a variety of "emergent" team cognition and teamwork errors (e.g., communication errors) that are 1) distinct from individual human errors, and 2) important to understand from a PRA perspective. The lack of robust models or quantification of team performance is an issue that affects the accuracy and validity of HRA methods and models, leading to significant uncertainty in estimating HEPs. This paper describes research that has the objective to model and quantify team dynamics and teamwork within NPP control room crews for risk informed applications, thereby improving the technical basis of HRA, which improves the risk-informed approach the NRC uses to regulate the U.S. commercial nuclear industry.

  6. Pharmacokinetic modeling: Prediction and evaluation of route dependent dosimetry of bisphenol A in monkeys with extrapolation to humans

    SciTech Connect (OSTI)

    Fisher, Jeffrey W. Twaddle, Nathan C.; Vanlandingham, Michelle; Doerge, Daniel R.


    A physiologically based pharmacokinetic (PBPK) model was developed for bisphenol A (BPA) in adult rhesus monkeys using intravenous (iv) and oral bolus doses of 100 {mu}g d6-BPA/kg (). This calibrated PBPK adult monkey model for BPA was then evaluated against published monkey kinetic studies with BPA. Using two versions of the adult monkey model based on monkey BPA kinetic data from and , the aglycone BPA pharmacokinetics were simulated for human oral ingestion of 5 mg d16-BPA per person (Voelkel et al., 2002). Voelkel et al. were unable to detect the aglycone BPA in plasma, but were able to detect BPA metabolites. These human model predictions of the aglycone BPA in plasma were then compared to previously published PBPK model predictions obtained by simulating the Voelkel et al. kinetic study. Our BPA human model, using two parameter sets reflecting two adult monkey studies, both predicted lower aglycone levels in human serum than the previous human BPA PBPK model predictions. BPA was metabolized at all ages of monkey (PND 5 to adult) by the gut wall and liver. However, the hepatic metabolism of BPA and systemic clearance of its phase II metabolites appear to be slower in younger monkeys than adults. The use of the current non-human primate BPA model parameters provides more confidence in predicting the aglycone BPA in serum levels in humans after oral ingestion of BPA. -- Highlights: Black-Right-Pointing-Pointer A bisphenol A (BPA) PBPK model for the infant and adult monkey was constructed. Black-Right-Pointing-Pointer The hepatic metabolic rate of BPA increased with age of the monkey. Black-Right-Pointing-Pointer The systemic clearance rate of metabolites increased with age of the monkey. Black-Right-Pointing-Pointer Gut wall metabolism of orally administered BPA was substantial across all ages of monkeys. Black-Right-Pointing-Pointer Aglycone BPA plasma concentrations were predicted in humans orally given oral doses of deuterated BPA.

  7. 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.


    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.

  8. Human Factors Engineering Program Review Model (NUREG-0711)Revision 3: Update Methodology and Key Revisions

    SciTech Connect (OSTI)

    OHara J. M.; Higgins, J.; Fleger, S.


    The U.S. Nuclear Regulatory Commission (NRC) reviews the human factors engineering (HFE) programs of applicants for nuclear power plant construction permits, operating licenses, standard design certifications, and combined operating licenses. The purpose of these safety reviews is to help ensure that personnel performance and reliability are appropriately supported. Detailed design review procedures and guidance for the evaluations is provided in three key documents: the Standard Review Plan (NUREG-0800), the HFE Program Review Model (NUREG-0711), and the Human-System Interface Design Review Guidelines (NUREG-0700). These documents were last revised in 2007, 2004 and 2002, respectively. The NRC is committed to the periodic update and improvement of the guidance to ensure that it remains a state-of-the-art design evaluation tool. To this end, the NRC is updating its guidance to stay current with recent research on human performance, advances in HFE methods and tools, and new technology being employed in plant and control room design. NUREG-0711 is the first document to be addressed. We present the methodology used to update NUREG-0711 and summarize the main changes made. Finally, we discuss the current status of the update program and the future plans.


    SciTech Connect (OSTI)

    Corley, Richard A.; Kabilan, Senthil; Kuprat, Andrew P.; Carson, James P.; Minard, Kevin R.; Jacob, Rick E.; Timchalk, Charles; Glenny, Robb W.; Pipavath, Sudhaker; Cox, Timothy C.; Wallis, Chris; Larson, Richard; Fanucchi, M.; Postlewait, Ed; Einstein, Daniel R.


    Coupling computational fluid dynamics (CFD) with physiologically based pharmacokinetic (PBPK) models is useful for predicting site-specific dosimetry of airborne materials in the respiratory tract and elucidating the importance of species differences in anatomy, physiology, and breathing patterns. Historically, these models were limited to discrete regions of the respiratory system. CFD/PBPK models have now been developed for the rat, monkey, and human that encompass airways from the nose or mouth to the lung. A PBPK model previously developed to describe acrolein uptake in nasal tissues was adapted to the extended airway models as an example application. Model parameters for each anatomic region were obtained from the literature, measured directly, or estimated from published data. Airflow and site-specific acrolein uptake patterns were determined under steadystate inhalation conditions to provide direct comparisons with prior data and nasalonly simulations. Results confirmed that regional uptake was dependent upon airflow rates and acrolein concentrations with nasal extraction efficiencies predicted to be greatest in the rat, followed by the monkey, then the human. For human oral-breathing simulations, acrolein uptake rates in oropharyngeal and laryngeal tissues were comparable to nasal tissues following nasal breathing under the same exposure conditions. For both breathing modes, higher uptake rates were predicted for lower tracheo-bronchial tissues of humans than either the rat or monkey. These extended airway models provide a unique foundation for comparing dosimetry across a significantly more extensive range of conducting airways in the rat, monkey, and human than prior CFD models.

  10. Modelling of micromachining of human tooth enamel by erbium laser radiation

    SciTech Connect (OSTI)

    Belikov, A V; Skrypnik, A V; Shatilova, K V


    We consider a 3D cellular model of human tooth enamel and a photomechanical cellular model of enamel ablation by erbium laser radiation, taking into account the structural peculiarities of enamel, energy distribution in the laser beam cross section and attenuation of laser energy in biological tissue. The surface area of the texture in enamel is calculated after its micromachining by erbium laser radiation. The influence of the surface area on the bond strength of enamel with dental filling materials is discussed. A good correlation between the computer simulation of the total work of adhesion and experimentally measured bond strength between the dental filling material and the tooth enamel after its micromachining by means of YAG : Er laser radiation is attained. (laser biophotonics)

  11. Investigation of in-vivo skin autofluorescence lifetimes under long-term cw optical excitation

    SciTech Connect (OSTI)

    Lihachev, A; Ferulova, I; Vasiljeva, K; Spigulis, J


    The main results obtained during the last five years in the field of laser-excited in-vivo human skin photobleaching effects are presented. The main achievements and results obtained, as well as methods and experimental devices are briefly described. In addition, the impact of long-term 405-nm cw low-power laser excitation on the skin autofluorescence lifetime is experimentally investigated. (laser biophotonics)

  12. An international comparison of models and approaches for the estimation of the radiological exposure of non-human biota.

    SciTech Connect (OSTI)

    Beresford, N. A.; Balonov, M.; Beaugelin-Seiller, K.; Brown, J.; Copperstone, D.; Hingston, J. L.; Horyna, J.; Hosseini, A.; Howard, B. J.; Kamboj, S.; Nedveckaite, T.; Olyslaegers, G.; Sazykina, T.; Vives i Batlle, J.; Yankovich , T. L.; Yu, C.; Environmental Science Division; Centre for Ecology and Hydrology; Inter. Atomic Energy Agency; Inst. de Radioprotection et de Surete Nucleaire; Norwegian Radiatioin Protection Authority; England & Wales Environment Agency; SUJB; Inst. of Physics; SCK CEN; SPA-Typhoon; Westlakes Scientific Consulting Limited; Atomic Energy Canada Limited


    Over the last decade a number of models and approaches have been developed for the estimation of the exposure of non-human biota to ionizing radiations. In some countries these are now being used in regulatory assessments. However, to date there has been no attempt to compare the outputs of the different models used. This paper presents the work of the International Atomic Energy Agency's EMRAS Biota Working Group which compares the predictions of a number of such models in model-model and model-data inter-comparisons.

  13. Human performance modeling for system of systems analytics: combat performance-shaping factors.

    SciTech Connect (OSTI)

    Lawton, Craig R.; Miller, Dwight Peter


    The US military has identified Human Performance Modeling (HPM) as a significant requirement and challenge of future systems modeling and analysis initiatives. To support this goal, Sandia National Laboratories (SNL) has undertaken a program of HPM as an integral augmentation to its system-of-system (SoS) analytics capabilities. The previous effort, reported in SAND2005-6569, evaluated the effects of soldier cognitive fatigue on SoS performance. The current effort began with a very broad survey of any performance-shaping factors (PSFs) that also might affect soldiers performance in combat situations. The work included consideration of three different approaches to cognition modeling and how appropriate they would be for application to SoS analytics. This bulk of this report categorizes 47 PSFs into three groups (internal, external, and task-related) and provides brief descriptions of how each affects combat performance, according to the literature. The PSFs were then assembled into a matrix with 22 representative military tasks and assigned one of four levels of estimated negative impact on task performance, based on the literature. Blank versions of the matrix were then sent to two ex-military subject-matter experts to be filled out based on their personal experiences. Data analysis was performed to identify the consensus most influential PSFs. Results indicate that combat-related injury, cognitive fatigue, inadequate training, physical fatigue, thirst, stress, poor perceptual processing, and presence of chemical agents are among the PSFs with the most negative impact on combat performance.

  14. Neural and Synaptic Defects in slytherin a Zebrafish Model for Human Congenital Disorders of Glycosylation

    SciTech Connect (OSTI)

    Y Song; J Willer; P Scherer; J Panzer; A Kugath; E Skordalakes; R Gregg; G Willer; R Balice-Gordon


    Congenital disorder of glycosylation type IIc (CDG IIc) is characterized by mental retardation, slowed growth and severe immunodeficiency, attributed to the lack of fucosylated glycoproteins. While impaired Notch signaling has been implicated in some aspects of CDG IIc pathogenesis, the molecular and cellular mechanisms remain poorly understood. We have identified a zebrafish mutant slytherin (srn), which harbors a missense point mutation in GDP-mannose 4,6 dehydratase (GMDS), the rate-limiting enzyme in protein fucosylation, including that of Notch. Here we report that some of the mechanisms underlying the neural phenotypes in srn and in CGD IIc are Notch-dependent, while others are Notch-independent. We show, for the first time in a vertebrate in vivo, that defects in protein fucosylation leads to defects in neuronal differentiation, maintenance, axon branching, and synapse formation. Srn is thus a useful and important vertebrate model for human CDG IIc that has provided new insights into the neural phenotypes that are hallmarks of the human disorder and has also highlighted the role of protein fucosylation in neural development.

  15. Stationary turbine component with laminated skin

    DOE Patents [OSTI]

    James, Allister W.


    A stationary turbine engine component, such as a turbine vane, includes a internal spar and an external skin. The internal spar is made of a plurality of spar laminates, and the external skin is made of a plurality of skin laminates. The plurality of skin laminates interlockingly engage the plurality of spar laminates such that the external skin is located and held in place. This arrangement allows alternative high temperature materials to be used on turbine engine components in areas where their properties are needed without having to make the entire component out of such material. Thus, the manufacturing difficulties associated with making an entire component of such a material and the attendant high costs are avoided. The skin laminates can be made of advanced generation single crystal superalloys, intermetallics and refractory alloys.

  16. Psychosocial and Cultural Modeling in Human Computation Systems: A Gamification Approach

    SciTech Connect (OSTI)

    Sanfilippo, Antonio P.; Riensche, Roderick M.; Haack, Jereme N.; Butner, R. Scott


    “Gamification”, the application of gameplay to real-world problems, enables the development of human computation systems that support decision-making through the integration of social and machine intelligence. One of gamification’s major benefits includes the creation of a problem solving environment where the influence of cognitive and cultural biases on human judgment can be curtailed through collaborative and competitive reasoning. By reducing biases on human judgment, gamification allows human computation systems to exploit human creativity relatively unhindered by human error. Operationally, gamification uses simulation to harvest human behavioral data that provide valuable insights for the solution of real-world problems.

  17. Development of a Rhesus Monkey Lung Geometry Model and Application to Particle Deposition in Comparison to Humans

    SciTech Connect (OSTI)

    Asgharian, Bahman; Price, Owen; McClellan, Gene; Corley, Richard A.; Einstein, Daniel R.; Jacob, Rick E.; Harkema, Jack R.; Carey, Stephen A.; Schelegle, Edward; Hyde, D.; Kimbell, Julia; Miller, Frederick J.


    The exposure-dose-response characterization of an inhalation hazard established in an animal species needs to be translated to an equivalent characterization in humans relative to comparable doses or exposure scenarios. Here, the first geometry model of the conducting airways for rhesus monkeys is developed based upon CT images of the conducting airways of a 6-month-old male, rhesus monkey. An algorithm was developed for adding the alveolar region airways using published rhesus morphometric data. The resultant lung geometry model can be used in mechanistic particle or gaseous dosimetry models. Such dosimetry models require estimates of the upper respiratory tract volume of the animal and the functional residual capacity, as well as of the tidal volume and breathing frequency of the animal. The relationship of these variables to rhesus monkeys of differing body weights was established by synthesizing and modeling published data as well as modeling pulmonary function measurements on 121 rhesus control animals. Deposition patterns of particles up to 10 ?m in size were examined for endotracheal and and up to 5 ?m for spontaneous breathing in infant and young adult monkeys and compared to those for humans. Deposition fraction of respirable size particles was found to be higher in the conducting airways of infant and young adult rhesus monkeys compared to humans. Due to the filtering effect of the conducting airways, pulmonary deposition in rhesus monkeys was lower than that in humans. Future research areas are identified that would either allow replacing assumptions or improving the newly developed lung model.

  18. Comparison of microenvironmental CO concentrations in two cities for human exposure modeling

    SciTech Connect (OSTI)

    Ott, W.R.; Mage, D.T.; Thomas, J. )


    The microenvironmental components of the CO concentration in two cities are compared by subtracting the ambient background concentration from personal exposures measured in Denver, Colorado, and Washington, DC. Two surrogate measures for the ambient background concentration are tested. Both improve the similarity of the means in the two cities, but the Denver standard deviations are higher than those in Washington, DC. Microenvironments containing the internal combustion engine have both higher means and standard deviations in Denver compared with Washington, DC. The Washington, DC, mean concentration for automobiles, for example, was 59% of the Denver mean (2.0 ppm versus 4.9 ppm). Washington, DC, had approximately 57% of the Denver emissions, and the difference in mean CO concentrations is roughly consistent with the lower emissions in Washington, DC, due to lower elevation. A surprising finding is that mean CO exposure levels caused by cooking with gas stoves in Washington, DC, were only 58% of the levels in Denver (1.9 ppm and 3.3 ppm, respectively). This result suggests that elevation may exert an influence on gas stove emissions that is similar to its influence on internal combustion engines. Using an averaging time model, analysis of the autocorrelation of sleeping and office microenvironments suggests that considerable serial dependency exists. The microenvironmental data and findings in this paper have important implications for constructing human exposure-activity pattern models. For future human exposure field studies, the findings emphasize the importance of measuring background values in a location that is extremely close to each microenvironment studied.

  19. Review and analysis of the literature in the area of human performance modeling

    SciTech Connect (OSTI)

    Burton, H.D.; Butler, J.; Banks, W.W.; Berghage, T.E.


    The following review of the literature in the area of human performance modeling was compiled in conjunction with work sponsored by the US Naval Health Research Center, San Diego, California, on the application of human performance data in wargaming models and simulation. The results were obtained by searching a number of on-line retrieval systems, downloading the data, and processing it using software developed by the Technology Information Systems Program. Databases which were searched included PsycINFO (American Psychological Association), Compendex (Engineering Index), Inspec (Institute of Electrical Engineers), NTIS (National Technical Information Service), DROLS (Department of Defense), NASA-Recon (National Aeronautics and Space Administration), Science Citation Index (Institute for Scientific Information), Conference Papers Index (Cambridge Scientific Abstracts), and a number of other databases which produced no retrieval results. Those citations identified as part of the PsycINFO databases are reprinted with permission of the American Psychological Association, publisher of Psychological abstracts and the PsycINFO database (Copyright c 1967--1988 by the American Psychological Association), and may not be reproduced without its prior permission. The retrieval citations were then converted to a common format, duplicates were eliminated, and the resulting master set was sorted and formatted for printing. Indexes and various analyses were produced as the final step in creating this publication. The major listing is alphabetical by author and includes abstracts where they were available. An index to authors follows as well as several frequency lists to provide an overview of the coverage. Additional information concerning either the bibliography or the software used to create it may be obtained form Hilary Burton, TIS Program, Lawrence Livermore National Laboratory.

  20. Physiologically based kinetic modeling of bioactivation and detoxification of the alkenylbenzene methyleugenol in human as compared with rat

    SciTech Connect (OSTI)

    Al-Subeihi, Ala' A.A.; Spenkelink, Bert; Punt, Ans; Boersma, Marelle G.; Bladeren, Peter J. van; Rietjens, Ivonne M.C.M.


    This study defines a physiologically based kinetic (PBK) model for methyleugenol (ME) in human based on in vitro and in silico derived parameters. With the model obtained, bioactivation and detoxification of methyleugenol (ME) at different doses levels could be investigated. The outcomes of the current model were compared with those of a previously developed PBK model for methyleugenol (ME) in male rat. The results obtained reveal that formation of 1′-hydroxymethyleugenol glucuronide (1′HMEG), a major metabolic pathway in male rat liver, appears to represent a minor metabolic pathway in human liver whereas in human liver a significantly higher formation of 1′-oxomethyleugenol (1′OME) compared with male rat liver is observed. Furthermore, formation of 1′-sulfooxymethyleugenol (1′HMES), which readily undergoes desulfonation to a reactive carbonium ion (CA) that can form DNA or protein adducts (DA), is predicted to be the same in the liver of both human and male rat at oral doses of 0.0034 and 300 mg/kg bw. Altogether despite a significant difference in especially the metabolic pathways of the proximate carcinogenic metabolite 1′-hydroxymethyleugenol (1′HME) between human and male rat, the influence of species differences on the ultimate overall bioactivation of methyleugenol (ME) to 1′-sulfooxymethyleugenol (1′HMES) appears to be negligible. Moreover, the PBK model predicted the formation of 1′-sulfooxymethyleugenol (1′HMES) in the liver of human and rat to be linear from doses as high as the benchmark dose (BMD{sub 10}) down to as low as the virtual safe dose (VSD). This study shows that kinetic data do not provide a reason to argue against linear extrapolation from the rat tumor data to the human situation. -- Highlights: ► A PBK model is made for bioactivation and detoxification of methyleugenol in human. ► Comparison to the PBK model in male rat revealed species differences. ► PBK results support linear extrapolation from high to low

  1. Cognitive models applied to human effectiveness in national security environments (ergonomics of augmented cognition system design and application).

    SciTech Connect (OSTI)

    Ntuen, Celestine; Winchester, Woodrow III


    In complex simulation systems where humans interact with computer-generated agents, information display and the interplay of virtual agents have become dominant media and modalities of interface design. This design strategy is reflected in augmented reality (AR), an environment where humans interact with computer-generated agents in real-time. AR systems can generate large amount of information, multiple solutions in less time, and perform far better in time-constrained problem solving. The capabilities of AR have been leveraged to augment cognition in human information processing. In this sort of augmented cognition (AC) work system, while technology has become the main source for information acquisition from the environment, the human sensory and memory capacities have failed to cope with the magnitude and scale of information they encounter. This situation generates opportunity for excessive cognitive workloads, a major factor in degraded human performance. From the human effectiveness point of view, research is needed to develop, model, and validate simulation tools that can measure the effectiveness of an AR technology used to support the amplification of human cognition. These tools will allow us to predict human performance for tasks executed under an AC tool construct. This paper presents an exploration of ergonomics issues relevant to AR and AC systems design. Additionally, proposed research to investigate those ergonomic issues is discussed.

  2. A Multi-Methods Approach to HRA and Human Performance Modeling: A Field Assessment

    SciTech Connect (OSTI)

    Jacques Hugo; David I Gertman


    The Advanced Test Reactor (ATR) is a research reactor at the Idaho National Laboratory is primarily designed and used to test materials to be used in other, larger-scale and prototype reactors. The reactor offers various specialized systems and allows certain experiments to be run at their own temperature and pressure. The ATR Canal temporarily stores completed experiments and used fuel. It also has facilities to conduct underwater operations such as experiment examination or removal. In reviewing the ATR safety basis, a number of concerns were identified involving the ATR canal. A brief study identified ergonomic issues involving the manual handling of fuel elements in the canal that may increase the probability of human error and possible unwanted acute physical outcomes to the operator. In response to this concern, that refined the previous HRA scoping analysis by determining the probability of the inadvertent exposure of a fuel element to the air during fuel movement and inspection was conducted. The HRA analysis employed the SPAR-H method and was supplemented by information gained from a detailed analysis of the fuel inspection and transfer tasks. This latter analysis included ergonomics, work cycles, task duration, and workload imposed by tool and workplace characteristics, personal protective clothing, and operational practices that have the potential to increase physical and mental workload. Part of this analysis consisted of NASA-TLX analyses, combined with operational sequence analysis, computational human performance analysis (CHPA), and 3D graphical modeling to determine task failures and precursors to such failures that have safety implications. Experience in applying multiple analysis techniques in support of HRA methods is discussed.

  3. Modeling and Simulation Approaches to Developing Human Performance Measures in Nuclear Industry

    SciTech Connect (OSTI)

    Bruce P. Hallbert; Jeffrey C. Joe; Molly J. Keefe; Julius J. Persensky


    Human performance is a key component to the safe operation of nuclear power plants. Further, human performance is quite variable, and while some variability may be random, much of it may be attributed to factors that are difficult to assess. There is a need to identify and assess aspects of human performance that relate to plant safety and to develop measures that can be used to successfully assess human performance for purposes of research that can lead to technical basis for developing human factors review criteria.

  4. Laser speckle contrast imaging of skin blood perfusion responses...

    Office of Scientific and Technical Information (OSTI)

    Laser speckle contrast imaging of skin blood perfusion responses induced by laser coagulation Citation Details In-Document Search Title: Laser speckle contrast imaging of skin ...

  5. Skin thickness effects on in vivo LXRF

    SciTech Connect (OSTI)

    Preiss, I.L.; Washington, W. II


    The analysis of lead concentration in bone utilizing LXRF can be adversely effected by overlying issue. A quantitative measure of the attenuation of the 10.5 keV Pb L a x-ray signal by skin and skin equivalent plastic has been conducted. Concentration ranges in plaster of Paris and goat bone from 7 to 90 ppm with attenuators of Lucite{reg_sign} and pig skin were examined. It is concluded that no quantitative or semi quantitative analysis can be achieved if overlying sue thickness exceeds 3 mm for Ph concentrations of less than 30 porn Ph in bone.

  6. Proof-of-Concept Demonstrations for Computation-Based Human Reliability Analysis. Modeling Operator Performance During Flooding Scenarios

    SciTech Connect (OSTI)

    Joe, Jeffrey Clark; Boring, Ronald Laurids; Herberger, Sarah Elizabeth Marie; Mandelli, Diego; Smith, Curtis Lee


    The United States (U.S.) Department of Energy (DOE) Light Water Reactor Sustainability (LWRS) program has the overall objective to help sustain the existing commercial nuclear power plants (NPPs). To accomplish this program objective, there are multiple LWRS “pathways,” or research and development (R&D) focus areas. One LWRS focus area is called the Risk-Informed Safety Margin and Characterization (RISMC) pathway. Initial efforts under this pathway to combine probabilistic and plant multi-physics models to quantify safety margins and support business decisions also included HRA, but in a somewhat simplified manner. HRA experts at Idaho National Laboratory (INL) have been collaborating with other experts to develop a computational HRA approach, called the Human Unimodel for Nuclear Technology to Enhance Reliability (HUNTER), for inclusion into the RISMC framework. The basic premise of this research is to leverage applicable computational techniques, namely simulation and modeling, to develop and then, using RAVEN as a controller, seamlessly integrate virtual operator models (HUNTER) with 1) the dynamic computational MOOSE runtime environment that includes a full-scope plant model, and 2) the RISMC framework PRA models already in use. The HUNTER computational HRA approach is a hybrid approach that leverages past work from cognitive psychology, human performance modeling, and HRA, but it is also a significant departure from existing static and even dynamic HRA methods. This report is divided into five chapters that cover the development of an external flooding event test case and associated statistical modeling considerations.

  7. A Multi-Route Model of Nicotine-Cotinine Pharmacokinetics, Pharmacodynamics and Brain Nicotinic Acetylcholine Receptor Binding in Humans

    SciTech Connect (OSTI)

    Teeguarden, Justin G.; Housand, Conrad; Smith, Jordan N.; Hinderliter, Paul M.; Gunawan, Rudy; Timchalk, Charles


    The pharmacokinetics of nicotine, the pharmacologically active alkaloid in tobacco responsible for addiction, are well characterized in humans. We developed a physiologically based pharmacokinetic/pharmacodynamic model of nicotine pharmacokinetics, brain dosimetry and brain nicotinic acetylcholine receptor (nAChRs) occupancy. A Bayesian framework was applied to optimize model parameters against multiple human data sets. The resulting model was consistent with both calibration and test data sets, but in general underestimated variability. A pharmacodynamic model relating nicotine levels to increases in heart rate as a proxy for the pharmacological effects of nicotine accurately described the nicotine related changes in heart rate and the development and decay of tolerance to nicotine. The PBPK model was utilized to quantitatively capture the combined impact of variation in physiological and metabolic parameters, nicotine availability and smoking compensation on the change in number of cigarettes smoked and toxicant exposure in a population of 10,000 people presented with a reduced toxicant (50%), reduced nicotine (50%) cigarette Across the population, toxicant exposure is reduced in some but not all smokers. Reductions are not in proportion to reductions in toxicant yields, largely due to partial compensation in response to reduced nicotine yields. This framework can be used as a key element of a dosimetry-driven risk assessment strategy for cigarette smoke constituents.

  8. A revised model of ex-vivo reduction of hexavalent chromium in human and rodent gastric juices

    SciTech Connect (OSTI)

    Schlosser, Paul M. Sasso, Alan F.


    Chronic oral exposure to hexavalent chromium (Cr-VI) in drinking water has been shown to induce tumors in the mouse gastrointestinal (GI) tract and rat oral cavity. The same is not true for trivalent chromium (Cr-III). Thus reduction of Cr-VI to Cr-III in gastric juices is considered a protective mechanism, and it has been suggested that the difference between the rate of reduction among mice, rats, and humans could explain or predict differences in sensitivity to Cr-VI. We evaluated previously published models of gastric reduction and believe that they do not fully describe the data on reduction as a function of Cr-VI concentration, time, and (in humans) pH. The previous models are parsimonious in assuming only a single reducing agent in rodents and describing pH-dependence using a simple function. We present a revised model that assumes three pools of reducing agents in rats and mice with pH-dependence based on known speciation chemistry. While the revised model uses more fitted parameters than the original model, they are adequately identifiable given the available data, and the fit of the revised model to the full range of data is shown to be significantly improved. Hence the revised model should provide better predictions of Cr-VI reduction when integrated into a corresponding PBPK model. - Highlights: • Hexavalent chromium (Cr-VI) reduction in gastric juices is a key detoxifying step. • pH-dependent Cr-VI reduction rates are explained using known chemical speciation. • Reduction in rodents appears to involve multiple pools of electron donors. • Reduction appears to continue after 60 min, although more slowly than initial rates.

  9. Evaluation of the interindividual human variation in bioactivation of methyleugenol using physiologically based kinetic modeling and Monte Carlo simulations

    SciTech Connect (OSTI)

    Al-Subeihi, Ala' A.A.; Alhusainy, Wasma; Kiwamoto, Reiko; Spenkelink, Bert; Bladeren, Peter J. van; Rietjens, Ivonne M.C.M.; Punt, Ans


    The present study aims at predicting the level of formation of the ultimate carcinogenic metabolite of methyleugenol, 1′-sulfooxymethyleugenol, in the human population by taking variability in key bioactivation and detoxification reactions into account using Monte Carlo simulations. Depending on the metabolic route, variation was simulated based on kinetic constants obtained from incubations with a range of individual human liver fractions or by combining kinetic constants obtained for specific isoenzymes with literature reported human variation in the activity of these enzymes. The results of the study indicate that formation of 1′-sulfooxymethyleugenol is predominantly affected by variation in i) P450 1A2-catalyzed bioactivation of methyleugenol to 1′-hydroxymethyleugenol, ii) P450 2B6-catalyzed epoxidation of methyleugenol, iii) the apparent kinetic constants for oxidation of 1′-hydroxymethyleugenol, and iv) the apparent kinetic constants for sulfation of 1′-hydroxymethyleugenol. Based on the Monte Carlo simulations a so-called chemical-specific adjustment factor (CSAF) for intraspecies variation could be derived by dividing different percentiles by the 50th percentile of the predicted population distribution for 1′-sulfooxymethyleugenol formation. The obtained CSAF value at the 90th percentile was 3.2, indicating that the default uncertainty factor of 3.16 for human variability in kinetics may adequately cover the variation within 90% of the population. Covering 99% of the population requires a larger uncertainty factor of 6.4. In conclusion, the results showed that adequate predictions on interindividual human variation can be made with Monte Carlo-based PBK modeling. For methyleugenol this variation was observed to be in line with the default variation generally assumed in risk assessment. - Highlights: • Interindividual human differences in methyleugenol bioactivation were simulated. • This was done using in vitro incubations, PBK modeling

  10. Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33 secreted from impaired vessels in the skin compared to fractionated irradiation

    SciTech Connect (OSTI)

    Lee, Eun-Jung; Kim, Jun Won; Yoo, Hyun; Kwak, Woori; Choi, Won Hoon; Cho, Seoae; Choi, Yu Jeong; Lee, Yoon-Jin; Cho, Jaeho


    We have revealed in a porcine skin injury model that eosinophil recruitment was dose-dependently enhanced by a single high-dose irradiation. In this study, we investigated the underlying mechanism of eosinophil-associated skin fibrosis and the effect of high-dose-per-fraction radiation. The dorsal skin of a mini-pig was divided into two sections containing 4-cm{sup 2} fields that were irradiated with 30 Gy in a single fraction or 5 fractions and biopsied regularly over 14 weeks. Eosinophil-related Th2 cytokines such as interleukin (IL)-4, IL-5, and C–C motif chemokine-11 (CCL11/eotaxin) were evaluated by quantitative real-time PCR. RNA-sequencing using 30 Gy-irradiated mouse skin and functional assays in a co-culture system of THP-1 and irradiated-human umbilical vein endothelial cells (HUVECs) were performed to investigate the mechanism of eosinophil-mediated radiation fibrosis. Single high-dose-per-fraction irradiation caused pronounced eosinophil accumulation, increased profibrotic factors collagen and transforming growth factor-β, enhanced production of eosinophil-related cytokines including IL-4, IL-5, CCL11, IL-13, and IL-33, and reduced vessels compared with 5-fraction irradiation. IL-33 notably increased in pig and mouse skin vessels after single high-dose irradiation of 30 Gy, as well as in irradiated HUVECs following 12 Gy. Blocking IL-33 suppressed the migration ability of THP-1 cells and cytokine secretion in a co-culture system of THP-1 cells and irradiated HUVECs. Hence, high-dose-per-fraction irradiation appears to enhance eosinophil-mediated fibrotic responses, and IL-33 may be a key molecule operating in eosinophil-mediated fibrosis in high-dose-per fraction irradiated skin. - Highlights: • Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33. • Vascular endothelial cells damaged by high-dose radiation secrete IL-33. • Blocking IL-33 suppressed migration of inflammatory cells and cytokine secretion. • IL

  11. Applying Human-performance Models to Designing and Evaluating Nuclear Power Plants: Review Guidance and Technical Basis

    SciTech Connect (OSTI)

    O'Hara, J.M.


    Human performance models (HPMs) are simulations of human behavior with which we can predict human performance. Designers use them to support their human factors engineering (HFE) programs for a wide range of complex systems, including commercial nuclear power plants. Applicants to U.S. Nuclear Regulatory Commission (NRC) can use HPMs for design certifications, operating licenses, and license amendments. In the context of nuclear-plant safety, it is important to assure that HPMs are verified and validated, and their usage is consistent with their intended purpose. Using HPMs improperly may generate misleading or incorrect information, entailing safety concerns. The objective of this research was to develop guidance to support the NRC staff's reviews of an applicant's use of HPMs in an HFE program. The guidance is divided into three topical areas: (1) HPM Verification, (2) HPM Validation, and (3) User Interface Verification. Following this guidance will help ensure the benefits of HPMs are achieved in a technically sound, defensible manner. During the course of developing this guidance, I identified several issues that could not be addressed; they also are discussed.

  12. Dynamic modeling of injection-induced fault reactivation and ground motion and impact on surface structures and human perception

    SciTech Connect (OSTI)

    Rutqvist, Jonny; Cappa, Frederic; Rinaldi, Antonio P.; Godano, Maxime


    We summarize recent modeling studies of injection-induced fault reactivation, seismicity, and its potential impact on surface structures and nuisance to the local human population. We used coupled multiphase fluid flow and geomechanical numerical modeling, dynamic wave propagation modeling, seismology theories, and empirical vibration criteria from mining and construction industries. We first simulated injection-induced fault reactivation, including dynamic fault slip, seismic source, wave propagation, and ground vibrations. From co-seismic average shear displacement and rupture area, we determined the moment magnitude to about Mw = 3 for an injection-induced fault reactivation at a depth of about 1000 m. We then analyzed the ground vibration results in terms of peak ground acceleration (PGA), peak ground velocity (PGV), and frequency content, with comparison to the U.S. Bureau of Mines vibration criteria for cosmetic damage to buildings, as well as human-perception vibration limits. For the considered synthetic Mw = 3 event, our analysis showed that the short duration, high frequency ground motion may not cause any significant damage to surface structures, and would not cause, in this particular case, upward CO2 leakage, but would certainly be felt by the local population.

  13. Dynamic modeling of injection-induced fault reactivation and ground motion and impact on surface structures and human perception

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

    Rutqvist, Jonny; Cappa, Frederic; Rinaldi, Antonio P.; Godano, Maxime


    We summarize recent modeling studies of injection-induced fault reactivation, seismicity, and its potential impact on surface structures and nuisance to the local human population. We used coupled multiphase fluid flow and geomechanical numerical modeling, dynamic wave propagation modeling, seismology theories, and empirical vibration criteria from mining and construction industries. We first simulated injection-induced fault reactivation, including dynamic fault slip, seismic source, wave propagation, and ground vibrations. From co-seismic average shear displacement and rupture area, we determined the moment magnitude to about Mw = 3 for an injection-induced fault reactivation at a depth of about 1000 m. We then analyzed themore » ground vibration results in terms of peak ground acceleration (PGA), peak ground velocity (PGV), and frequency content, with comparison to the U.S. Bureau of Mines’ vibration criteria for cosmetic damage to buildings, as well as human-perception vibration limits. For the considered synthetic Mw = 3 event, our analysis showed that the short duration, high frequency ground motion may not cause any significant damage to surface structures, and would not cause, in this particular case, upward CO2 leakage, but would certainly be felt by the local population.« less

  14. Prediction of rodent carcinogenic potential of naturally occurring chemicals in the human diet using high-throughput QSAR predictive modeling

    SciTech Connect (OSTI)

    Valerio, Luis G. . E-mail:; Arvidson, Kirk B.; Chanderbhan, Ronald F.; Contrera, Joseph F.


    Consistent with the U.S. Food and Drug Administration (FDA) Critical Path Initiative, predictive toxicology software programs employing quantitative structure-activity relationship (QSAR) models are currently under evaluation for regulatory risk assessment and scientific decision support for highly sensitive endpoints such as carcinogenicity, mutagenicity and reproductive toxicity. At the FDA's Center for Food Safety and Applied Nutrition's Office of Food Additive Safety and the Center for Drug Evaluation and Research's Informatics and Computational Safety Analysis Staff (ICSAS), the use of computational SAR tools for both qualitative and quantitative risk assessment applications are being developed and evaluated. One tool of current interest is MDL-QSAR predictive discriminant analysis modeling of rodent carcinogenicity, which has been previously evaluated for pharmaceutical applications by the FDA ICSAS. The study described in this paper aims to evaluate the utility of this software to estimate the carcinogenic potential of small, organic, naturally occurring chemicals found in the human diet. In addition, a group of 19 known synthetic dietary constituents that were positive in rodent carcinogenicity studies served as a control group. In the test group of naturally occurring chemicals, 101 were found to be suitable for predictive modeling using this software's discriminant analysis modeling approach. Predictions performed on these compounds were compared to published experimental evidence of each compound's carcinogenic potential. Experimental evidence included relevant toxicological studies such as rodent cancer bioassays, rodent anti-carcinogenicity studies, genotoxic studies, and the presence of chemical structural alerts. Statistical indices of predictive performance were calculated to assess the utility of the predictive modeling method. Results revealed good predictive performance using this software's rodent carcinogenicity module of over 1200 chemicals

  15. Dietary chromium and nickel enhance UV-carcinogenesis in skin...

    Office of Scientific and Technical Information (OSTI)

    chromium and nickel enhance UV-carcinogenesis in skin of hairless mice The skin cancer enhancing effect of chromium (in male mice) and nickel in UVR-irradiated female Skh1...

  16. Self-cleaning skin-like prosthetic polymer surfaces

    DOE Patents [OSTI]

    Simpson, John T.; Ivanov, Ilia N.; Shibata, Jason


    An external covering and method of making an external covering for hiding the internal endoskeleton of a mechanical (e.g., prosthetic) device that exhibits skin-like qualities is provided. The external covering generally comprises an internal bulk layer in contact with the endoskeleton of the prosthetic device and an external skin layer disposed about the internal bulk layer. The external skin layer is comprised of a polymer composite with carbon nanotubes embedded therein. The outer surface of the skin layer has multiple cone-shaped projections that provide the external skin layer with superhydrophobicity. The carbon nanotubes are preferably vertically aligned between the inner surface and outer surface of the external skin layer in order to provide the skin layer with the ability to transmit heat. Superhydrophobic powders may optionally be used as part of the polymer composite or applied as a coating to the surface of the skin layer to enhance superhydrophobicity.

  17. Encapsulated human hepatocellular carcinoma cells by alginate gel beads as an in vitro metastasis model

    SciTech Connect (OSTI)

    Xu, Xiao-xi; Liu, Chang [Laboratory of Biomedical Material Engineering, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023 (China); University of Chinese Academy of Sciences, 19A Yuquanlu, Beijing 100049 (China); Liu, Yang [Laboratory of Biomedical Material Engineering, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023 (China); Li, Nan [Laboratory of Biomedical Material Engineering, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023 (China); University of Chinese Academy of Sciences, 19A Yuquanlu, Beijing 100049 (China); Guo, Xin [Laboratory of Biomedical Material Engineering, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023 (China); Wang, Shu-jun [Laboratory of Biomedical Material Engineering, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023 (China); School of Life Science and Biotechnology, Dalian University of Technology, 2 Linggong Road, Dalian 116024 (China); Sun, Guang-wei, E-mail: [Laboratory of Biomedical Material Engineering, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023 (China); Wang, Wei [Laboratory of Biomedical Material Engineering, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023 (China); Ma, Xiao-jun, E-mail: [Laboratory of Biomedical Material Engineering, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023 (China)


    Hepatocellular carcinoma (HCC) is the most common primary liver cancer and often forms metastases, which are the most important prognostic factors. For further elucidation of the mechanism underlying the progression and metastasis of HCC, a culture system mimicking the in vivo tumor microenvironment is needed. In this study, we investigated the metastatic ability of HCC cells cultured within alginate gel (ALG) beads. In the culture system, HCC cells formed spheroids by proliferation and maintained in nuclear abnormalities. The gene and protein expression of metastasis-related molecules was increased in ALG beads, compared with the traditional adhesion culture. Furthermore, several gene expression levels in ALG bead culture system were even closer to liver cancer tissues. More importantly, in vitro invasion assay showed that the invasion cells derived from ALG beads was 7.8-fold higher than adhesion cells. Our results indicated that the in vitro three-dimensional (3D) model based on ALG beads increased metastatic ability compared with adhesion culture, even partly mimicked the in vivo tumor tissues. Moreover, due to the controllable preparation conditions, steady characteristics and production at large-scale, the 3D ALG bead model would become an important tool used in the high-throughput screening of anti-metastasis drugs and the metastatic mechanism research. -- Highlights: We established a 3D metastasis model mimicking the metastatic ability in vivo. The invasion ability of cells derived from our model was increased significantly. The model is easy to reproduce, convenient to handle, and amenable for large-scale.

  18. A bacterial model for expression of mutations in the human ornithine transcarbamylase (OTC) gene

    SciTech Connect (OSTI)

    Tuchman, M.; McCann, M.T.; Qureshi, A.A.


    OTC is a mitochondrial enzyme catalyzing the formation of citrulline from carbamyl phosphate and ornithine. X-linked deficiency of OTC is the most prevalent genetic defect of ureagenesis. Mutations and polymorphisms in the OTC gene identified in deficient patients have indicated the occurrence of many family-specific, unique alleles. Due to the low frequency of recurrent mutations, distinguishing between deleterious mutations and polymorphisms is difficult. Using a human OTC gene containing plasmid driven by a tac promoter, we have devised a simple and efficient method for expressing mutations in the mature human OTC enzyme. To demonstrate this method, PCR engineered site-directed mutagenesis was employed to generated cDNA fragments which contained either the R151Q or R277W known mutations found in patients with neonatal and late-onset OTC deficiency, respectively. The normal allele for each mutation was also generated by an identical PCR procedure. Digestion with Bgl II- and Sty I-generated mutant and normal replacement cassettes containing the respective mutant and wild type sequences. Upon transformation of JM109 E.coli cells, OTC enzymatic activity was measured at log and stationary phases of growth using a radiochromatographic method. The R141Q mutation abolished enzymatic activity (<0.02% of normal), whereas the R277W mutation expressed partial activity (2.3% of normal). In addition, a PCR-generated mutation, A280V, resulted in 73% loss of catalytic activity. This OTC expression system is clinically applicable for distinguishing between mutations and polymorphisms, and it can be used to investigate the effects of mutations on various domains of the OTC gene.

  19. Using Models to Provide Predicted Ranges for Building-Human Interfaces: Preprint

    SciTech Connect (OSTI)

    Long, N.; Scheib, J.; Pless, S.; Schott, M.


    Most building energy consumption dashboards provide only a snapshot of building performance; whereas some provide more detailed historic data with which to compare current usage. This paper will discuss the Building Agent(tm) platform, which has been developed and deployed in a campus setting at the National Renewable Energy Laboratory as part of an effort to maintain the aggressive energyperformance achieved in newly constructed office buildings and laboratories. The Building Agent(tm) provides aggregated and coherent access to building data, including electric energy, thermal energy, temperatures, humidity, and lighting levels, and occupant feedback, which are displayed in various manners for visitors, building occupants, facility managers, and researchers. This paper focuseson the development of visualizations for facility managers, or an energy performance assurance role, where metered data are used to generate models that provide live predicted ranges of building performance by end use. These predicted ranges provide simple, visual context for displayed performance data without requiring users to also assess historical information or trends. Several energymodelling techniques were explored including static lookup-based performance targets, reduced-order models derived from historical data using main effect variables such as solar radiance for lighting performance, and integrated energy models using a whole-building energy simulation program.

  20. Human-machine interactions

    DOE Patents [OSTI]

    Forsythe, J. Chris; Xavier, Patrick G.; Abbott, Robert G.; Brannon, Nathan G.; Bernard, Michael L.; Speed, Ann E.


    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.

  1. 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


    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.

  2. Therapeutic potential of a non-steroidal bifunctional anti-inflammatory and anti-cholinergic agent against skin injury induced by sulfur mustard

    SciTech Connect (OSTI)

    Chang, Yoke-Chen; Wang, James D.; Hahn, Rita A.; Gordon, Marion K.; Joseph, Laurie B.; Heck, Diane E.; Heindel, Ned D.; Young, Sherri C.; Sinko, Patrick J.; Casillas, Robert P.; Laskin, Jeffrey D.; Laskin, Debra L.; Gerecke, Donald R.


    Sulfur mustard (bis(2-chloroethyl) sulfide, SM) is a highly reactive bifunctional alkylating agent inducing edema, inflammation, and the formation of fluid-filled blisters in the skin. Medical countermeasures against SM-induced cutaneous injury have yet to be established. In the present studies, we tested a novel, bifunctional anti-inflammatory prodrug (NDH 4338) designed to target cyclooxygenase 2 (COX2), an enzyme that generates inflammatory eicosanoids, and acetylcholinesterase, an enzyme mediating activation of cholinergic inflammatory pathways in a model of SM-induced skin injury. Adult SKH-1 hairless male mice were exposed to SM using a dorsal skin vapor cup model. NDH 4338 was applied topically to the skin 24, 48, and 72 h post-SM exposure. After 96 h, SM was found to induce skin injury characterized by edema, epidermal hyperplasia, loss of the differentiation marker, keratin 10 (K10), upregulation of the skin wound marker keratin 6 (K6), disruption of the basement membrane anchoring protein laminin 322, and increased expression of epidermal COX2. NDH 4338 post-treatment reduced SM-induced dermal edema and enhanced skin re-epithelialization. This was associated with a reduction in COX2 expression, increased K10 expression in the suprabasal epidermis, and reduced expression of K6. NDH 4338 also restored basement membrane integrity, as evidenced by continuous expression of laminin 332 at the dermal–epidermal junction. Taken together, these data indicate that a bifunctional anti-inflammatory prodrug stimulates repair of SM induced skin injury and may be useful as a medical countermeasure. - Highlights: • Bifunctional anti-inflammatory prodrug (NDH4338) tested on SM exposed mouse skin • The prodrug NDH4338 was designed to target COX2 and acetylcholinesterase. • The application of NDH4338 improved cutaneous wound repair after SM induced injury. • NDH4338 treatment demonstrated a reduction in COX2 expression on SM injured skin. • Changes of skin repair

  3. Modeled microgravity suppressed invasion and migration of human glioblastoma U87 cells through downregulating store-operated calcium entry

    SciTech Connect (OSTI)

    Shi, Zi-xuan; Rao, Wei; Wang, Huan; Wang, Nan-ding; Si, Jing-Wen; Zhao, Jiao; Li, Jun-chang; Wang, Zong-ren


    Glioblastoma is the most common brain tumor and is characterized with robust invasion and migration potential resulting in poor prognosis. Previous investigations have demonstrated that modeled microgravity (MMG) could decline the cell proliferation and attenuate the metastasis potential in several cell lines. In this study, we studied the effects of MMG on the invasion and migration potentials of glioblastoma in human glioblastoma U87 cells. We found that MMG stimulation significantly attenuated the invasion and migration potentials, decreased thapsigargin (TG) induced store-operated calcium entry (SOCE) and downregulated the expression of Orai1 in U87 cells. Inhibition of SOCE by 2-APB or stromal interaction molecule 1 (STIM1) downregulation both mimicked the effects of MMG on the invasion and migration potentials in U87 cells. Furthermore, upregulation of Orai1 significantly weakened the effects of MMG on the invasion and migration potentials in U87 cells. Therefore, these findings indicated that MMG stimulation inhibited the invasion and migration potentials of U87 cells by downregulating the expression of Orai1 and sequentially decreasing the SOCE, suggesting that MMG might be a new potential therapeutic strategy in glioblastoma treatment in the future. - Highlights: • Modeled microgravity (MMG) suppressed migration and invasion in U87 cells. • MMG downregulated the SOCE and the expression of Orai1. • SOCE inhibition mimicked the effects of MMG on migration and invasion potentials. • Restoration of SOCE diminished the effects of MMG on migration and invasion.

  4. Ultrasonic technique for characterizing skin burns

    DOE Patents [OSTI]

    Goans, Ronald E.; Cantrell, Jr., John H.; Meyers, F. Bradford; Stambaugh, Harry D.


    This invention, a method for ultrasonically determining the depth of a skin burn, is based on the finding that the acoustical impedance of burned tissue differs sufficiently from that of live tissue to permit ultrasonic detection of the interface between the burn and the underlying unburned tissue. The method is simple, rapid, and accurate. As compared with conventional practice, it provides the important advantage of permitting much earlier determination of whether a burn is of the first, second, or third degree. In the case of severe burns, the usual two - to three-week delay before surgery may be reduced to about 3 days or less.

  5. SU-E-J-93: Development of Pre-Contoured Human Model Library in DICOM-RT Format for the Epidemiological Study of the Radiotherapy Patients

    SciTech Connect (OSTI)

    Pyakuryal, A; Lee, C; Lee, C; Pelletier, C; Jung, J


    Purpose: Prior to 3D conformal radiation therapy planning, patient anatomy information was mostly limited to 2D beams-eye-view from the conventional simulator. To analyze the outcomes of such treatments for radiation late effects, 3D computational human models are often used in commercial treatment planning systems (TPSs). However, several underlying difficulties such as time-consuming manual delineation procedures of a large number of structures in the model have always limited its applications. Primary objective of this work was to develop a human model library for the epidemiological study by converting 3D-surface model organs to DICOM-RT format (DICOM-RT structure) using an in-house built software. We converted the ICRP reference human models to DICOM-RT models, which can be readily adopted for various dose calculations. Methods: MATLAB based code were utilized to convert the contour drawings extracted in text-format from the 3D graphic-tool, Rhinoceros into DICOM-RT structure format for 50 different organs of each model using a 16GB dual-core processor. The conversion periods were measured for each DICOM-RT models, and the reconstructed structure volumes were validated against the original 3D-surface models in the TPS. Ten reference hybrid whole-body models (8-pediatric and 2-adults) were automatically processed to create DICOM-RT computational human model library. Results: Mean contour conversion period was found to be 580 (N=2) and 394.5 (N=8) seconds for 50 organs in the adult and pediatric models respectively. A good agreement for large organs (NRMSD <1.0%) and small organs (NRMSD <7.7%) was also observed between the original volumes and corresponding DICOM-RT structure volumes of the organs. Conclusion: The ICRP reference human models were converted into DICOM-RT format to support the epidemiological study using a large cohort of conventional radiotherapy patients. Due to its DICOM-compatibility, the library may be implemented to many other different

  6. Metasurface skin invisibility cloak makes 3D objects disappear

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

    Metasurface skin invisibility cloak makes 3D objects disappear Click to share on Facebook (Opens in new window) Click to share on Twitter (Opens in new window) Click to share on Reddit (Opens in new window) Click to share on Pinterest (Opens in new window) Invisibility skin cloaks on the microscopic scale might prove valuable for hiding the detailed layout of microelectronic components or for security encryption purposes. This image is a A 3-D illustration of a metasurface skin cloak made from

  7. Turbine blade having a constant thickness airfoil skin

    DOE Patents [OSTI]

    Marra, John J


    A turbine blade is provided for a gas turbine comprising: a support structure comprising a base defining a root of the blade and a framework extending radially outwardly from the base, and an outer skin coupled to the support structure framework. The skin has a generally constant thickness along substantially the entire radial extent thereof. The framework and the skin define an airfoil of the blade.

  8. Mathematical model for predicting the probability of acute mortality in a human population exposed to accidentally released airborne radionuclides. Final report for Phase I

    SciTech Connect (OSTI)

    Filipy, R.E.; Borst, F.J.; Cross, F.T.; Park, J.F.; Moss, O.R.; Roswell, R.L.; Stevens, D.L.


    A mathematical model was constructed for the purpose of predicting the fraction of human population which would die within 1 year of an accidental exposure to airborne radionuclides. The model is based on data from laboratory experiments with rats, dogs and baboons, and from human epidemiological data. Doses from external, whole-body irradiation and from inhaled, alpha- and beta-emitting radionuclides are calculated for several organs. The probabilities of death from radiation pneumonitis and from bone marrow irradiation are predicted from doses accumulated within 30 days of exposure to the radioactive aerosol. The model is compared with existing similar models under hypothetical exposure conditions. Suggestions for further experiments with inhaled radionuclides are included. 25 refs., 16 figs., 13 tabs.

  9. Quercitrin protects skin from UVB-induced oxidative damage

    SciTech Connect (OSTI)

    Yin, Yuanqin; Li, Wenqi; Son, Young-Ok; Sun, Lijuan; Lu, Jian; Kim, Donghern; Wang, Xin; Yao, Hua; Wang, Lei; Pratheeshkumar, Poyil; Hitron, Andrew J.; Luo, Jia; Gao, Ning; Shi, Xianglin; Zhang, Zhuo


    Exposure of the skin to ultraviolet B (UVB) radiation causes oxidative damage to skin, resulting in sunburn, photoaging, and skin cancer. It is generally believed that the skin damage induced by UV irradiation is a consequence of generation of reactive oxygen species (ROS). Recently, there is an increased interest in the use of natural products as chemopreventive agents for non-melanoma skin cancer (NMSC) due to their antioxidants and anti-inflammatory properties. Quercitrin, glycosylated form of quercetin, is the most common flavonoid in nature with antioxidant properties. The present study investigated the possible beneficial effects of quercitrin to inhibit UVB irradiation-induced oxidative damage in vitro and in vivo. Our results showed that quercitrin decreased ROS generation induced by UVB irradiation in JB6 cells. Quercitrin restored catalase expression and GSH/GSSG ratio reduced by UVB exposure, two major antioxidant enzymes, leading to reductions of oxidative DNA damage and apoptosis and protection of the skin from inflammation caused by UVB exposure. The present study demonstrated that quercitrin functions as an antioxidant against UVB irradiation-induced oxidative damage to skin. - Highlights: • Oxidative stress plays a key role in UV-induced cell and tissue injuries. • Quercitrin decreases ROS generation and restores antioxidants irradiated by UVB. • Quercitrin reduces UVB-irradiated oxidative DNA damage, apoptosis, and inflammation. • Quercitrin functions as an antioxidant against UVB-induced skin injuries.

  10. Method and apparatus to measure the depth of skin burns

    DOE Patents [OSTI]

    Dickey, Fred M.; Holswade, Scott C.


    A new device for measuring the depth of surface tissue burns based on the rate at which the skin temperature responds to a sudden differential temperature stimulus. This technique can be performed without physical contact with the burned tissue. In one implementation, time-dependent surface temperature data is taken from subsequent frames of a video signal from an infrared-sensitive video camera. When a thermal transient is created, e.g., by turning off a heat lamp directed at the skin surface, the following time-dependent surface temperature data can be used to determine the skin burn depth. Imaging and non-imaging versions of this device can be implemented, thereby enabling laboratory-quality skin burn depth imagers for hospitals as well as hand-held skin burn depth sensors the size of a small pocket flashlight for field use and triage.

  11. U.S. Department of Energy Human Subjects Research Database (HSRD) A model for internal oversight and external transparency

    SciTech Connect (OSTI)

    Oak Ridge Institute for Science and Education


    This poster introduces the Department of Energy (DOE) Human Subjects Research Database (HSRD), which contains information on all Department of Energy research projects involving human subjects that: are funded by DOE; are conducted in DOE facilities; are performed by DOE personnel; include current or former DOE or contract personnel.

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

    SciTech Connect (OSTI)

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


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

  13. Pulse testing in the presence of wellbore storage and skin effects

    SciTech Connect (OSTI)

    Ogbe, D.O.; Brigham, W.E.


    A pulse test is conducted by creating a series of short-time pressure transients in an active (pulsing) well and recording the observed pressure response at an observation (responding) well. Using the pressure response and flow rate data, the transmissivity and storativity of the tested formation can be determined. Like any other pressure transient data, the pulse-test response is significantly influenced by wellbore storage and skin effects. The purpose of this research is to examine the influence of wellbore storage and skin effects on interference testing in general and on pulse-testing in particular, and to present the type curves and procedures for designing and analyzing pulse-test data when wellbore storage and skin effects are active at either the responding well or the pulsing well. A mathematical model for interference testing was developed by solving the diffusivity equation for radial flow of a single-phase, slightly compressible fluid in an infinitely large, homogeneous reservoir. When wellbore storage and skin effects are present in a pulse test, the observed response amplitude is attenuated and the time lag is inflated. Consequently, neglecting wellbore storage and skin effects in a pulse test causes the calculated storativity to be over-estimated and the transmissivity to be under-estimated. The error can be as high as 30%. New correlations and procedures are developed for correcting the pulse response amplitude and time lag for wellbore storage effects. Using these correlations, it is possible to correct the wellbore storage-dominated response amplitude and time lag to within 3% of their expected values without wellbore storage, and in turn to calculate the corresponding transmissivity and storativity. Worked examples are presented to illustrate how to use the new correction techniques. 45 references.

  14. Skin-sparing Helical Tomotherapy vs 3D-conformal Radiotherapy for Adjuvant Breast Radiotherapy: In Vivo Skin Dosimetry Study

    SciTech Connect (OSTI)

    Capelle, Lisa; Warkentin, Heather; MacKenzie, Marc; Joseph, Kurian; Gabos, Zsolt; Pervez, Nadeem; Tankel, Keith; Chafe, Susan; Amanie, John; Ghosh, Sunita; Parliament, Matthew; Abdulkarim, Bassam


    Purpose: We investigated whether treatment-planning system (TPS)-calculated dose accurately reflects skin dose received for patients receiving adjuvant breast radiotherapy (RT) with standard three-dimensional conformal RT (3D-CRT) or skin-sparing helical tomotherapy (HT). Methods and Materials: Fifty patients enrolled in a randomized controlled trial investigating acute skin toxicity from adjuvant breast RT with 3D-CRT compared to skin-sparing HT, where a 5-mm strip of ipsilateral breast skin was spared. Thermoluminescent dosimetry or optically stimulated luminescence measurements were made in multiple locations and were compared to TPS-calculated doses. Skin dosimetric parameters and acute skin toxicity were recorded in these patients. Results: With HT there was a significant correlation between calculated and measured dose in the medial and lateral ipsilateral breast (r = 0.67, P<.001; r = 0.44, P=.03, respectively) and the medial and central contralateral breast (r = 0.73, P<.001; r = 0.88, P<.001, respectively). With 3D-CRT there was a significant correlation in the medial and lateral ipsilateral breast (r = 0.45, P=.03; r = 0.68, P<.001, respectively); the medial and central contralateral breast (r = 0.62, P=.001; r = 0.86, P<.001, respectively); and the mid neck (r = 0.42, P=.04, respectively). On average, HT-calculated dose overestimated the measured dose by 14%; 3D-CRT underestimated the dose by 0.4%. There was a borderline association between highest measured skin dose and moist desquamation (P=.05). Skin-sparing HT had greater skin homogeneity (homogeneity index of 1.39 vs 1.65, respectively; P=.005) than 3D-CRT plans. HT plans had a lower skin{sub V50} (1.4% vs 5.9%, respectively; P=.001) but higher skin{sub V40} and skin{sub V30} (71.7% vs 64.0%, P=.02; and 99.0% vs 93.8%, P=.001, respectively) than 3D-CRT plans. Conclusion: The 3D-CRT TPS more accurately reflected skin dose than the HT TPS, which tended to overestimate dose received by 14% in patients

  15. Comparison of fixation and processing methods for hairless guinea pig skin following sulfur mustard exposure. (Reannouncement with new availability information)

    SciTech Connect (OSTI)

    Bryant, M.A.; Braue Jr, E.H.


    Ten anesthetized hairless guinea pigs Crl:IAF(HA)BR were exposed to 10 pi of neat sulfur mustard (HD) in a vapor cup on their skin for 7 min. At 24 h postexposure, the guinea pigs were euthanatized and skin sections taken for histologic evaluation. The skin was fixed using either 10% neutral buffered formalin (NBF), McDowell Trump fixative (4CF-IG), Zenker`s formol-saline (Helly`s fluid), or Zenker`s fluid. Fixed skin sections were cut in half: one half was embedded in paraffin and the other half in plastic (glycol methacrylate). Paraffin-embedded tissue was stained with hematoxylin and eosin; plastic-embedded tissue was stained with Lee`s methylene blue basic fuchsin. Skin was also frozen unfixed, sectioned by cryostat, and stained with pinacyanole. HD-exposed skin was evaluated histologically for the presence of epidermal and follicular necrosis, microblister formation, epidermitis, and intracellular edema to determine the optimal fixation and embedding method for lesion preservation. The percentage of histologic sections with lesions varied little between fixatives and was similar for both paraffin and plastic embedding material. Plastic-embedded sections were thinner, allowing better histologic evaluation, but were more difficult to stain. Plastic embedding material did not infiltrate tissue fixed in Zenker`s fluid or Zenker`s formol-saline. Frozen tissue sections were prepared in the least processing time and lesion preservation was comparable to fixed tissue. It was concluded that standard histologic processing using formalin fixation and paraffin embedding is adequate for routine histopathological evaluation of HD skin lesions in the hairless guinea pig.... Sulfur mustard, Vesicating agents, Pathology, Hairless guinea pig model, Fixation.

  16. Human bronchial epithelial BEAS-2B cells, an appropriate in vitro model to study heavy metals induced carcinogenesis

    SciTech Connect (OSTI)

    Park, Youn-hee; Kim, Donghern; Dai, Jin; Zhang, Zhuo


    Occupational and environmental exposure to arsenic (III) and chromium VI (Cr(VI)) have been confirmed to cause lung cancer. Mechanisms of these metals carcinogenesis are still under investigation. Selection of cell lines to be used is essential for the studies. Human bronchial epithelial BEAS-2B cells are the cells to be utilized by most of scientists. However, due to p53 missense mutation (CCG → TCG) at codon 47 and the codon 72 polymorphism (CGC → CCC) in BEAS-2B cells, its usage has frequently been questioned. The present study has examined activity and expression of 53 and its downstream target protein p21 upon acute or chronic exposure of BEAS-2B cells to arsenic and Cr(VI). The results show that short-term exposure of BEAS-2B cells to arsenic or Cr(VI) was able to activate both p53 and p21. Chronic exposure of BEAS-2B cells to these two metals caused malignant cell transformation and tumorigenesis. In arsenic-transformed BEAS-2B cells reductions in p53 promoter activity, mRNA expression, and phosphorylation of p53 at Ser392 were observed, while the total p53 protein level remained the same compared to those in passage-matched parent ones. p21 promoter activity and expression were decreased in arsenic-transformed cells. Cr(VI)-transformed cells exhibit elevated p53 promoter activity, mRNA expression, and phosphorylation at Ser15, but reduced phosphorylation at Ser392 and total p53 protein level compared to passage-matched parent ones. p21 promoter activity and expression were elevated in Cr(VI)-transformed cells. These results demonstrate that p53 is able to respond to exposure of arsenic or Cr(VI), suggesting that BEAS-2B cells are an appropriate in vitro model to investigate arsenic or Cr(VI) induced lung cancer. - Highlights: • Short-term exposure of BEAS-2B cells to arsenic or Cr(VI) activates p53 and p21. • Chronic exposure of BEAS-2B cells to arsenic or Cr(VI) causes cell transformation and tumorigenesis. • Arsenic-transformed cells exhibit

  17. The Kauai Skin Cancer Study--1983 to 1992

    SciTech Connect (OSTI)

    Reizner, G.T. )


    The Kauai Skin Cancer Study began as a modest effort in 1983 to look at this island's skin cancer incidence. David Elpern MD, Kauai's only dermatologist at the time, was interested in the large number of these tumors in his practice. He first enlisted his office staff to help keep track of the numbers and type of these skin cancers. Along with this information, the basic demographic data on each patient was collected. These records became the first entries into what has become a decade-long project.

  18. Metasurface skin invisibility cloak makes 3D objects disappear

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

    Metasurface skin invisibility cloak makes 3D objects disappear Click to share on Facebook (Opens in new window) Click to share on Twitter (Opens in new window) Click to share on ...

  19. Synopsis: Getting Under the Neutron Skin (Physics) | Jefferson Lab

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

    Synopsis: Getting Under the Neutron Skin (Physics) External Link: By jlab_admin on Thu, 2012-03-15

  20. Skin-Like Prosthetic Polymer Surfaces - Energy Innovation Portal

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

    Startup America Startup America Industrial Technologies Industrial Technologies Advanced Materials Advanced Materials Find More Like This Return to Search Skin-Like Prosthetic Polymer Surfaces Oak Ridge National Laboratory Contact ORNL About This Technology Technology Marketing Summary Artificial limbs help to restore normal function to amputees. Surface materials for prostheses need to look realistic, hold up to exposure, and mimic skin. ORNL scientists combined superhydrophobic polymer

  1. Total human exposure: Basic concepts, EPA field studies, and future research needs

    SciTech Connect (OSTI)

    Ott, W.R. )


    Historically, environmental regulatory programs designed to protect public health have monitored pollutants only in geophysical carrier media (for example, outdoor air, streams, soil). Field studies have identified a gap between the levels observed in geophysical carrier media and the concentrations with which people actually come into contact: their daily exposures. A new approach--Total Human Exposure (THE)--has evolved to fill this gap and provide the critical data needed for accurately assessing public health risk. The THE approach considers a three-dimensional bubble around each person and measures the concentrations of all pollutants contacting that bubble, either through the air, food, water, or skin. Two basic THE approaches have emerged: (1) the direct approach using probability samples of populations and measuring pollutant concentrations in the food eaten, air breathed, water drunk, and skin contacted; and (2) the indirect approach using human activity pattern-exposure models to predict population exposure distributions. Using the direct approach, EPA has conducted over 20 field studies for pollutants representing four groups--volatile organic compounds, carbon monoxide, pesticides, and particles--in 15 cities in 12 states. The indirect modeling approach has been applied to several of these pollutants. Additional research is needed in a great variety of areas. Even from the few projects completed thus far, the THE approach has yielded a rich new data base for risk assessments and has provided many surprises about the relative contribution of various pollutant sources to public health risk. 74 references.

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

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

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


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

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

    SciTech Connect (OSTI)

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


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

  4. Bimetallic alloy electrocatalysts with multilayered platinum-skin surfaces

    DOE Patents [OSTI]

    Stamenkovic, Vojislav R.; Wang, Chao; Markovic, Nenad M.


    Compositions and methods of preparing a bimetallic alloy having enhanced electrocatalytic properties are provided. The composition comprises a PtNi substrate having a surface layer, a near-surface layer, and an inner layer, where the surface layer comprises a nickel-depleted composition, such that the surface layer comprises a platinum skin having at least one atomic layer of platinum.

  5. JLab Physicists Measure the Skin of a Nucleus (Science) | Jefferson Lab

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

    Physicists Measure the Skin of a Nucleus (Science) External Link: By jlab_admin on Fri, 2012-03-02

  6. Human Resources | Argonne National Laboratory

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

    Human Resources

  7. The human genome project

    SciTech Connect (OSTI)

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


    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.

  8. Modeling

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

    Modeling & Analysis, News, News & Events, Photovoltaic, Renewable Energy, Research & Capabilities, Solar, Solar Newsletter, SunShot, Systems Analysis Sandia Develops Stochastic ...

  9. Modeling

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

    Monte Carlo modeling it was found that for noisy signals with a significant background component, accuracy is improved by fitting the total emission data which includes the...

  10. Modeling

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

    Solar Sandia Labs Releases New Version of PVLib Toolbox Sandia has released version 1.3 of PVLib, its widely used Matlab toolbox for modeling photovoltaic (PV) power ...

  11. Modeling

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

    ... Sandia Will Host PV Bankability Workshop at Solar Power International (SPI) 2013 Computational Modeling & Simulation, Distribution Grid Integration, Energy, Facilities, Grid ...

  12. Modeling

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

    Science and Actuarial Practice" Read More Permalink New Project Is the ACME of Computer Science to Address Climate Change Analysis, Climate, Global Climate & Energy, Modeling, ...

  13. Modeling

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

    Though adequate for modeling mean transport, this approach does not address ... Microphysics such as diffusive transport and chemical kinetics are represented by ...

  14. Lithium Ion Battery Performance of Silicon Nanowires With Carbon Skin

    SciTech Connect (OSTI)

    Bogart, Timothy D.; Oka, Daichi; Lu, Xiaotang; Gu, Meng; Wang, Chong M.; Korgel, Brian A.


    Silicon (Si) nanomaterials have emerged as a leading candidate for next generation lithium-ion battery anodes. However, the low electrical conductivity of Si requires the use of conductive additives in the anode film. Here we report a solution-based synthesis of Si nanowires with a conductive carbon skin. Without any conductive additive, the Si nanowire electrodes exhibited capacities of over 2000 mA h g-1 for 100 cycles when cycled at C/10 and over 1200 mA h g-1 when cycled more rapidly at 1C against Li metal.. In situ transmission electron microscopy (TEM) observation reveals that the carbon skin performs dual roles: it speeds lithiation of the Si nanowires significantly, while also constraining the final volume expansion. The present work sheds light on ways to optimize lithium battery performance by smartly tailoring the nanostructure of composition of materials based on silicon and carbon.

  15. Modeling

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

    with application in modeling NDCX-II experiments Wangyi Liu 1 , John Barnard 2 , Alex Friedman 2 , Nathan Masters 2 , Aaron Fisher 2 , Alice Koniges 2 , David Eder 2 1 LBNL, USA, 2...

  16. Modeling

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

    NASA Earth at Night Video EC, Energy, Energy Efficiency, Global, Modeling, News & Events, Solid-State Lighting, Videos NASA Earth at Night Video Have you ever wondered what the ...

  17. Microbial Metabolism Shifts Towards an Adverse Profile with Supplementary Iron in the TIM-2 In vitro Model of the Human Colon

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

    Kortman, Guus A. M.; Dutilh, Bas E.; Maathuis, Annet J. H.; Engelke, Udo F.; Boekhorst, Jos; Keegan, Kevin P.; Nielsen, Fiona G. G.; Betley, Jason; Weir, Jacqueline C.; Kingsbury, Zoya; et al


    Oral iron administration in African children can increase the risk for infections. However, it remains unclear to what extent supplementary iron affects the intestinal microbiome. We here explored the impact of iron preparations on microbial growth and metabolism in the well-controlled TNO's in vitro model of the large intestine (TIM-2). The model was inoculated with a human microbiota, without supplementary iron, or with 50 or 250 μmol/L ferrous sulfate, 50 or 250 μmol/L ferric citrate, or 50 μmol/L hemin. High resolution responses of the microbiota were examined by 16S rDNA pyrosequencing, microarray analysis, and metagenomic sequencing. The metabolome was assessedmore » by fatty acid quantification, gas chromatography-mass spectrometry (GC-MS), and 1H-NMR spectroscopy. Cultured intestinal epithelial Caco-2 cells were used to assess fecal water toxicity. Microbiome analysis showed, among others, that supplementary iron induced decreased levels of Bifidobacteriaceae and Lactobacillaceae, while it caused higher levels of Roseburia and Prevotella. Metagenomic analyses showed an enrichment of microbial motility-chemotaxis systems, while the metabolome markedly changed from a saccharolytic to a proteolytic profile in response to iron. Branched chain fatty acids and ammonia levels increased significantly, in particular with ferrous sulfate. Importantly, the metabolite-containing effluent from iron-rich conditions showed increased cytotoxicity to Caco-2 cells. In conclusion, our explorations indicate that in the absence of host influences, iron induces a more hostile environment characterized by a reduction of microbes that are generally beneficial, and increased levels of bacterial metabolites that can impair the barrier function of a cultured intestinal epithelial monolayer.« less

  18. Apparatus for testing skin samples or the like

    DOE Patents [OSTI]

    Holland, J.M.


    An apparatus for testing the permeability of living skin samples has a flat base with a plurality of sample-holding cavities formed in its upper surface, the samples being placed in counterbores in the cavities with the epidermis uppermost. O-rings of Teflon washers are respectively placed on the samples and a flat cover is connected to the base to press the rings against the upper surfaces of the samples. Media to maintain tissue viability and recovery of metabolites is introduced into the lower portion of the sample-holding cavities through passages in the base. Test materials are introduced through holes in the cover plate after assembly of the chamber.

  19. Emergence of pygmy dipole resonances: Magic numbers and neutron skins

    SciTech Connect (OSTI)

    Inakura, Tsunenori; Nakatsukasa, Takashi; Yabana, Kazuhiro


    The pygmy dipole resonances (PDR) for even-even nuclei in 8{<=}Z{<=}40 are studied performing a systematic calculation of the random-phase approximation with the Skyrme functional of SkM*. The calculation is fully self-consistent and does not assume any symmetry in the nuclear shape of the ground state. In every isotopic chain, the PDR emerges by showing a peak of the E1 strength at energies less than 10 MeV. The E1 strength of the PDR strongly depends on the position of the Fermi level and shows a clear correlation with the occupation of the orbits with the orbital angular momenta less than 3({h_bar}/2{pi}) (l{<=}2). We also found a strong correlation between the isotopic dependence of the neutron skin thickness and the pygmy dipole strength. The fraction of the energy-weighted strength exhausted by the PDR and the neutron skin thickness show a linear correlation with the universal rate of about 0.2 fm{sup -1}.

  20. Modeling

    SciTech Connect (OSTI)

    Loth, E.; Tryggvason, G.; Tsuji, Y.; Elghobashi, S. E.; Crowe, Clayton T.; Berlemont, A.; Reeks, M.; Simonin, O.; Frank, Th; Onishi, Yasuo; Van Wachem, B.


    Slurry flows occur in many circumstances, including chemical manufacturing processes, pipeline transfer of coal, sand, and minerals; mud flows; and disposal of dredged materials. In this section we discuss slurry flow applications related to radioactive waste management. The Hanford tank waste solids and interstitial liquids will be mixed to form a slurry so it can be pumped out for retrieval and treatment. The waste is very complex chemically and physically. The ARIEL code is used to model the chemical interactions and fluid dynamics of the waste.

  1. Fibre Diffraction Analysis of Skin Offers a Very Early and Extremely...

    Office of Scientific and Technical Information (OSTI)

    Test for Prostate Cancer Citation Details In-Document Search Title: Fibre Diffraction Analysis of Skin Offers a Very Early and Extremely Accurate Diagnostic Test for ...

  2. Fibre Diffraction Analysis of Skin Offers a Very Early and Extremely...

    Office of Scientific and Technical Information (OSTI)

    Accurate Diagnostic Test for Prostate Cancer Title: Fibre Diffraction Analysis of Skin Offers a Very Early and Extremely Accurate Diagnostic Test for Prostate Cancer Double ...

  3. Inhibitory effect of cucurbitacin B on imiquimod-induced skin inflammation

    SciTech Connect (OSTI)

    Li, Zheng Jun; Shin, Jung-Min; Choi, Dae-Kyoung; Lim, Seul Ki; Yoon, Tae-Jin; Lee, Young Ho; Sohn, Kyung-Cheol; Im, Myung; Lee, Young; Seo, Young-Joon; Kim, Chang Deok; Lee, Jeung-Hoon


    Psoriasis is a common skin disease, of which pathogenesis involves the increase of inflammatory reaction in epidermal cells. In an attempt to find therapeutics for psoriasis, we found that cucurbitacin B has an inhibitory potential on imiquimod-induced inflammation of keratinocytes. Cucurbitacin B significantly inhibited imiquimod-induced expression of crucial psoriatic cytokines, such as IL-8 and CCL20, via down-regulation of NF-κB and STAT3 signaling pathway in human keratinocytes. In addition, keratinocyte proliferation was markedly inhibited by cucurbitacin B. The potential beneficial effect of cucurbitacin B on psoriasis was further validated in imiquimod-induced psoriasiform dermatitis of experimental animal. Topical application of cucurbitacin B resulted in significant reduction of epidermal hyperplasia and inflammatory cytokines production, and ameliorated the psoriatic symptom. Taken together, these results suggest that cucurbitacin B may be a potential candidate for the treatment of psoriasis. - Highlights: • Cucurbitacin B has a potential for inhibiting the growth of keratinocytes. • Cucurbitacin B inhibits imiquimod-induced inflammatory reaction in keratinocytes. • Cucurbitacin B inhibits imiquimod-induced psoriasiform dermatitis in experimental animal.

  4. 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


    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.

  5. Effects of radioactive hot particles on pig skin

    SciTech Connect (OSTI)

    Kaurin, D.G.; Baum, J.W.; Schaefer, C.W.


    The purpose of these studies was to determine the incidence and severity of lesions resulting from very localized deposition of dose to skin from small (< 0.5 mm) discrete radioactive particles as produced in the work environments of nuclear reactors. Hanford mini-pigs were exposed, both on a slightly off the skin, to localized replicate doses from 0.31 to 64 Gy (averaged over 1 cm{sup 2} at 70 {mu}m depth unless noted otherwise) using Sc-46, Yb-175, Tm-170, and fissioned UC{sub 2} isotopes having maximum beta-particle energies from about 0.3 to 3 MeV. Erythema and scabs (indicating ulceration) were scored for up to 71 days post-irradiation. The responses followed normal cumulative probability distributions, and therefore, no true threshold could be defined. Hence, 10 and 50% scab incidence rates were deduced using probit analyses. The lowest dose which produced 10% incidence was about 1 Gy for Yb-175 (0.5 MeV maximum energy) beta particle exposures, and about 3 to 9 Gy for other isotopes. The histopathology of lesions was determined at several doses. Single exposures to doses as large as 1,790 Gy were also given, and results were observed for up to 144 days post-exposure. Severity of detriment was estimated by analyzing the results in terms of lesion diameter, persistence, and infection. Over 1,100 sites were exposed. Only two exposed sites became infected after doses near 5000 Gy; the lesions healed quickly on treatment. 105 refs., 145 figs., 47 tabs.

  6. Protecting the radiation-damaged skin from friction: a mini review

    SciTech Connect (OSTI)

    Herst, Patries M


    Radiation-induced skin reactions are an unavoidable side effect of external beam radiation therapy, particularly in areas prone to friction and excess moisture such as the axilla, head and neck region, perineum and skin folds. Clinical studies investigating interventions for preventing or managing these reactions have largely focussed on formulations with moisturising, anti-inflammatory, anti-microbial and wound healing properties. However, none of these interventions has emerged as a consistent candidate for best practice. Much less emphasis has been placed on evaluating ways to protect the radiation-damaged skin from friction and excess moisture. This mini review analyses the clinical evidence for barrier products that form a protective layer by adhering very closely to the skin folds and do not cause further trauma to the radiation-damaged skin upon removal. A database search identified only two types of barrier products that fitted these criteria and these were tested in two case series and six controlled clinical trials. Friction protection was most effective when the interventions were used from the start of treatment and continued for several weeks after completion of treatment. Soft silicone dressings (Mepilex Lite and Mepitel Film) and Cavilon No Sting Barrier Film, but not Cavilon Moisturizing Barrier Cream, decreased skin reaction severity, most likely due to differences in formulation and skin build-up properties. It seems that prophylactic use of friction protection of areas at risk could be a worthwhile addition to routine care of radiation-damaged skin.

  7. Density dependence of the symmetry energy from neutron skin thickness in finite nuclei

    SciTech Connect (OSTI)

    Vinas, X.; Centelles, M.; Roca-Maza, X.; Warda, M.


    The density dependence of the symmetry energy, characterized by the parameter L, is studied using information provided by the neutron skin thickness in finite nuclei. An estimate of L is obtained from experimental data of antiprotonic atoms. We also discuss the ability of parity violating electron scatering to obtain information about the neutron skin thickness in {sup 208}Pb.

  8. Temporal and spatial features of the formation of DNA adducts in sulfur mustard-exposed skin

    SciTech Connect (OSTI)

    Batal, Mohamed; Boudry, Isabelle; Mouret, Stéphane; Wartelle, Julien; Emorine, Sandy; Bertoni, Marine; Bérard, Izabel; and others


    Sulfur mustard (SM) is a chemical warfare agent that targets skin where it induces large blisters. DNA alkylation is a critical step to explain SM-induced cutaneous symptoms. We determined the kinetics of formation of main SM–DNA adducts and compare it with the development of the SM-induced pathogenesis in skin. SKH-1 mice were exposed to 2, 6 and 60 mg/kg of SM and treated skin was biopsied between 6 h and 21 days. Formation of SM DNA adducts was dose-dependent with a maximum immediately after exposure. However, adducts were persistent and still detectable 21 days post-exposure. The time-dependent formation of DNA adducts was also found to be correlated with the appearance of apoptotic cells. This temporal correlation suggests that these two early events are responsible for the severity of the damage to the skin. Besides, SM–DNA adducts were also detected in areas located next to contaminated zone, thus suggesting that SM diffuses in skin. Altogether, this work provides for the first time a clear picture of SM-induced genotoxicity using DNA adducts as a marker. - Highlights: • Sulfur mustard adducts are formed in DNA after skin exposure. • DNA damage formation is an early event in the pathological process of skin burn. • The amount of SM–DNA adducts is maximal at the earliest time point investigated. • Adducts are still detected 3 weeks after exposure. • Sulfur mustard diffuses in skin especially when large doses are applied.

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

    SciTech Connect (OSTI)

    Ronald Laurids Boring


    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.

  10. Cyanidin-3-glucoside inhibits UVB-induced oxidative damage and inflammation by regulating MAP kinase and NF-κB signaling pathways in SKH-1 hairless mice skin

    SciTech Connect (OSTI)

    Pratheeshkumar, Poyil; Son, Young-Ok; Wang, Xin; Divya, Sasidharan Padmaja; Joseph, Binoy; Hitron, John Andrew; Wang, Lei; Kim, Donghern; Yin, Yuanqin; Roy, Ram Vinod; Lu, Jian; Zhang, Zhuo; Wang, Yitao; and others


    Skin cancer is one of the most commonly diagnosed cancers in the United States. Exposure to ultraviolet-B (UVB) radiation induces inflammation and photocarcinogenesis in mammalian skin. Cyanidin-3-glucoside (C3G), a member of the anthocyanin family, is present in various vegetables and fruits especially in edible berries, and displays potent antioxidant and anticarcinogenic properties. In this study, we have assessed the in vivo effects of C3G on UVB irradiation induced chronic inflammatory responses in SKH-1 hairless mice, a well-established model for UVB-induced skin carcinogenesis. Here, we show that C3G inhibited UVB-induced skin damage and inflammation in SKH-1 hairless mice. Our results indicate that C3G inhibited glutathione depletion, lipid peroxidation and myeloperoxidation in mouse skin by chronic UVB exposure. C3G significantly decreased the production of UVB-induced pro-inflammatory cytokines, such as IL-6 and TNF-α, associated with cutaneous inflammation. Likewise, UVB-induced inflammatory responses were diminished by C3G as observed by a remarkable reduction in the levels of phosphorylated MAP kinases, Erk1/2, p38, JNK1/2 and MKK4. Furthermore, C3G also decreased UVB-induced cyclooxygenase-2 (COX-2), PGE{sub 2} and iNOS levels, which are well-known key mediators of inflammation and cancer. Treatment with C3G inhibited UVB-induced nuclear translocation of NF-κB and degradation of IκBα in mice skin. Immunofluorescence assay revealed that topical application of C3G inhibited the expression of 8-hydroxy-2′-deoxyguanosine, proliferating cell nuclear antigen, and cyclin D1 in chronic UVB exposed mouse skin. Collectively, these data indicates that C3G can provide substantial protection against the adverse effects of UVB radiation by modulating UVB-induced MAP kinase and NF-κB signaling pathways. - Highlights: • C3G inhibited UVB-induced oxidative damage and inflammation. • C3G inhibited UVB-induced COX-2, iNOS and PGE{sub 2} production. • C3G

  11. 2,6-Dithiopurine, a nucleophilic scavenger, protects against mutagenesis in mouse skin treated in vivo with 2-(chloroethyl) ethyl sulfide, a mustard gas analog

    SciTech Connect (OSTI)

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


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

  12. Dosimeter for measuring skin dose and more deeply penetrating radiation

    DOE Patents [OSTI]

    Jones, Donald E.; Parker, DeRay; Boren, Paul R.


    A personnel dosimeter includes a plurality of compartments containing thermoluminescent dosimeter phosphors for registering radiation dose absorbed in the wearer's sensitive skin layer and for registering more deeply penetrating radiation. Two of the phosphor compartments communicate with thin windows of different thicknesses to obtain a ratio of shallowly penetrating radiation, e.g. beta. A third phosphor is disposed within a compartment communicating with a window of substantially greater thickness than the windows of the first two compartments for estimating the more deeply penetrating radiation dose. By selecting certain phosphors that are insensitive to neutrons and by loading the holder material with netruon-absorbing elements, energetic neutron dose can be estimated separately from other radiation dose. This invention also involves a method of injection molding of dosimeter holders with thin windows of consistent thickness at the corresponding compartments of different holders. This is achieved through use of a die insert having the thin window of precision thickness in place prior to the injection molding step.

  13. Predicting the Occurrence of Cosmetic Defects in Automotive Skin Panels

    SciTech Connect (OSTI)

    Hazra, S.; Williams, D.; Roy, R.; Aylmore, R.; Allen, M.; Hollingdale, D.


    The appearance of defects such as 'hollows' and 'shock lines' can affect the perceived quality and attractiveness of automotive skin panels. These defects are the result of the stamping process and appear as small, localized deviations from the intended styling of the panels. Despite their size, they become visually apparent after the application of paint and the perceived quality of a panel may become unacceptable. Considerable time is then dedicated to minimizing their occurrence through tool modifications. This paper will investigate the use of the wavelet transform as a tool to analyze physically measured panels. The transform has two key aspects. The first is its ability to distinguish small scale local defects from large scale styling curvature. The second is its ability to characterize the shape of a defect in terms of its wavelength and a 'correlation value'. The two features of the transform enable it to be used as a tool for locating and predicting the severity of defects. The paper will describe the transform and illustrate its application on test cases.

  14. Method for preparing dosimeter for measuring skin dose

    DOE Patents [OSTI]

    Jones, Donald E.; Parker, DeRay; Boren, Paul R.


    A personnel dosimeter includes a plurality of compartments containing thermoluminescent dosimeter phosphors for registering radiation dose absorbed in the wearer's sensitive skin layer and for registering more deeply penetrating radiation. Two of the phosphor compartments communicate with thin windows of different thicknesses to obtain a ratio of shallowly penetrating radiation, e.g. beta. A third phosphor is disposed within a compartment communicating with a window of substantially greater thickness than the windows of the first two compartments for estimating the more deeply penetrating radiation dose. By selecting certain phosphors that are insensitive to neutrons and by loading the holder material with neutron-absorbing elements, energetic neutron dose can be estimated separately from other radiation dose. This invention also involves a method of injection molding of dosimeter holders with thin windows of consistent thickness at the corresponding compartments of different holders. This is achieved through use of a die insert having the thin window of precision thickness in place prior to the injection molding step.

  15. Sensitivity of the electric dipole polarizability to the neutron skin thickness in {sup 208}Pb

    SciTech Connect (OSTI)

    Roca-Maza, X.; Agrawal, B. K.; Colo, G.; Nazarewicz, W.; Paar, N.; Piekarewicz, J.; Reinhard, P.-G.; Vretenar, D.


    The static dipole polarizability, {alpha}{sub D}, in {sup 208}Pb has been recently measured with highresolution via proton inelastic scattering at the Research Center for Nuclear Physics (RCNP) [1]. This observable is thought to be intimately connected with the neutron skin thickness, r{sub skin}, of the same nucleus and, more fundamentally, it is believed to be associated with the density dependence of the nuclear symmetry energy. The impact of r{sub skin} on {alpha}{sub D} in {sup 208}Pb is investigated and discussed on the basis of a large and representative set of relativistic and non-relativistic nuclear energy density functionals (EDF) [2].

  16. Estimation of neutrophil infiltration into hairless guinea pig skin treated with 2,2' -dichlorodiethyl sulfide

    SciTech Connect (OSTI)

    Bongiovanni, R.; Millard, C.B.; Schulz, S.M.; Romano, J.M.


    Despite growing acceptance of the hairless guinea pig (HPG) for evaluating sulfur mustard (2,2'dichlorodiethylsulfide, HD) skin injury, there are presently few antivesicant drug assessment endpoints validated in vivo for this model. We measured the activity of myeloperoxidase (MPO) to characterize the dose- and time-dependence of polymorphonuclear leukocyte (PMN) infiltration during development of the HD lesion. Biopsies were obtained from the dorsal thoracic-lumbar area of HGPs at successive 3 hr time intervals for up to 24 hrs following controlled exposure to either 5, 7, 8 or 10 min HD vapor. The presence of PMNs, as judged by MPO levels, peaked at 9 hrs irrespective of total HD vapor dose. The maximum response was a 20-fold increase compared to unexposed control sites at 9 hrs following 10 min HD vapor. This time period coincides with epidermal detachment characterized previously by electron microscopy in the HGP. By 24 hrs post-exposure, the MPO levels subsided markedly (2-fold compared to controls). These results suggest that PMNs participate in the HGP cutaneous inflammatory response following exposure to HD and that MPO may be a useful biological marker for evaluating putative antivesicants.

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

    SciTech Connect (OSTI)

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


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

  18. Norathyriol Suppresses Skin Cancers Induced by Solar Ultraviolet Radiation by Targeting ERK Kinases

    SciTech Connect (OSTI)

    Li, Jixia; Malakhova, Margarita; Mottamal, Madhusoodanan; Reddy, Kanamata; Kurinov, Igor; Carper, Andria; Langfald, Alyssa; Oi, Naomi; Kim, Myoung Ok; Zhu, Feng; Sosa, Carlos P.; Zhou, Keyuan; Bode, Ann M.; Dong, Zigang


    Ultraviolet (UV) irradiation is the leading factor in the development of skin cancer, prompting great interest in chemopreventive agents for this disease. In this study, we report the discovery of norathyriol, a plant-derived chemopreventive compound identified through an in silico virtual screening of the Chinese Medicine Library. Norathyriol is a metabolite of mangiferin found in mango, Hypericum elegans, and Tripterospermum lanceolatum and is known to have anticancer activity. Mechanistic investigations determined that norathyriol acted as an inhibitor of extracellular signal-regulated kinase (ERK)1/2 activity to attenuate UVB-induced phosphorylation in mitogen-activated protein kinases signaling cascades. We confirmed the direct and specific binding of norathyriol with ERK2 through a cocrystal structural analysis. The xanthone moiety in norathyriol acted as an adenine mimetic to anchor the compound by hydrogen bonds to the hinge region of the protein ATP-binding site on ERK2. Norathyriol inhibited in vitro cell growth in mouse skin epidermal JB6 P+ cells at the level of G{sub 2}-M phase arrest. In mouse skin tumorigenesis assays, norathyriol significantly suppressed solar UV-induced skin carcinogenesis. Further analysis indicated that norathyriol mediates its chemopreventive activity by inhibiting the ERK-dependent activity of transcriptional factors AP-1 and NF-{kappa}B during UV-induced skin carcinogenesis. Taken together, our results identify norathyriol as a safe new chemopreventive agent that is highly effective against development of UV-induced skin cancer.

  19. SU-E-CAMPUS-I-04: Automatic Skin-Dose Mapping for An Angiographic System with a Region-Of-Interest, High-Resolution Detector

    SciTech Connect (OSTI)

    Vijayan, S; Rana, V; Setlur Nagesh, S; Ionita, C; Rudin, S; Bednarek, D


    Purpose: Our real-time skin dose tracking system (DTS) has been upgraded to monitor dose for the micro-angiographic fluoroscope (MAF), a high-resolution, small field-of-view x-ray detector. Methods: The MAF has been mounted on a changer on a clinical C-Arm gantry so it can be used interchangeably with the standard flat-panel detector (FPD) during neuro-interventional procedures when high resolution is needed in a region-of-interest. To monitor patient skin dose when using the MAF, our DTS has been modified to automatically account for the change in scatter for the very small MAF FOV and to provide separated dose distributions for each detector. The DTS is able to provide a color-coded mapping of the cumulative skin dose on a 3D graphic model of the patient. To determine the correct entrance skin exposure to be applied by the DTS, a correction factor was determined by measuring the exposure at the entrance surface of a skull phantom with an ionization chamber as a function of entrance beam size for various beam filters and kVps. Entrance exposure measurements included primary radiation, patient backscatter and table forward scatter. To allow separation of the dose from each detector, a parameter log is kept that allows a replay of the procedure exposure events and recalculation of the dose components.The graphic display can then be constructed showing the dose distribution from the MAF and FPD separately or together. Results: The DTS is able to provide separate displays of dose for the MAF and FPD with field-size specific scatter corrections. These measured corrections change from about 49% down to 10% when changing from the FPD to the MAF. Conclusion: The upgraded DTS allows identification of the patient skin dose delivered when using each detector in order to achieve improved dose management as well as to facilitate peak skin-dose reduction through dose spreading. Research supported in part by Toshiba Medical Systems Corporation and NIH Grants R43FD0158401, R44FD


    SciTech Connect (OSTI)

    Roger Lew; Brian P. Dyre; Steffen Werner; Jeffrey C. Joe; Brian Wotring; Tuan Tran


    The development of real-time predictors of mental workload is critical for the practical application of augmented cognition to human-machine systems. This paper explores a novel method based on a short-time Fourier transform (STFT) for analyzing galvanic skin conductance (SC) and pupillometry time-series data to extract estimates of mental workload with temporal bandwidth high-enough to be useful for augmented cognition applications. We tested the method in the context of a process control task based on the DURESS simulation developed by Vincente and Pawlak (1994; ported to Java by Cosentino,& Ross, 1999). SC, pupil dilation, blink rate, and visual scanning patterns were measured for four participants actively engaged in controlling the simulation. Fault events were introduced that required participants to diagnose errors and make control adjustments to keep the simulator operating within a target range. We were interested in whether the STFT of these measures would produce visible effects of the increase in mental workload and stress associated with these events. Graphical exploratory data analysis of the STFT showed visible increases in the power spectrum across a range of frequencies directly following fault events. We believe this approach shows potential as a relatively unobtrusive, low-cost, high bandwidth measure of mental workload that could be particularly useful for the application of augmented cognition to human-machine systems.

  1. SU-E-I-53: Variation in Measurements of Breast Skin Thickness Obtained Using Different Imaging Modalities

    SciTech Connect (OSTI)

    Nguyen, U; Kumaraswamy, N; Markey, M


    Purpose: To investigate variation in measurements of breast skin thickness obtained using different imaging modalities, including mammography, computed tomography (CT), ultrasound, and magnetic resonance imaging (MRI). Methods: Breast skin thicknesses as measured by mammography, CT, ultrasound, and MRI were compared. Mammographic measurements of skin thickness were obtained from published studies that utilized standard positioning (upright) and compression. CT measurements of skin thickness were obtained from a published study of a prototype breast CT scanner in which the women were in the prone position and the breast was uncompressed. Dermatological ultrasound exams of the breast skin were conducted at our institution, with the subjects in the upright position and the breast uncompressed. Breast skin thickness was calculated from breast MRI exams at our institution, with the patient in the prone position and the breast uncompressed. Results: T tests for independent samples demonstrated significant differences in the mean breast skin thickness as measured by different imaging modalities. Repeated measures ANOVA revealed significant differences in breast skin thickness across different quadrants of the breast for some modalities. Conclusion: The measurement of breast skin thickness is significantly different across different imaging modalities. Differences in the amount of compression and differences in patient positioning are possible reasons why measurements of breast skin thickness vary by modality.

  2. Effects of Diet on Resource Utilization by a Model Human Gut Microbiota Containing Bacteroides cellulosilyticus WH2, a Symbiont with an Extensive Glycobiome

    SciTech Connect (OSTI)

    McNulty, Nathan; Wu, Meng; Erickson, Alison L; Pan, Chongle; Erickson, Brian K; Martens, Eric C; Pudlo, Nicholas A; Muegge, Brian; Henrissat, Bernard; Hettich, Robert {Bob} L; Gordon, Jeffrey


    The human gut microbiota is an important metabolic organ, yet little is known about how its individual species interact, establish dominant positions, and respond to changes in environmental factors such as diet. In this study, gnotobiotic mice were colonized with an artificial microbiota comprising 12 sequenced human gut bacterial species and fed oscillating diets of disparate composition. Rapid, reproducible, and reversible changes in the structure of this assemblage were observed. Time-series microbial RNA-Seq analyses revealed staggered functional responses to diet shifts throughout the assemblage that were heavily focused on carbohydrate and amino acid metabolism. High-resolution shotgun metaproteomics confirmed many of these responses at a protein level. One member, Bacteroides cellulosilyticus WH2, proved exceptionally fit regardless of diet. Its genome encoded more carbohydrate active enzymes than any previously sequenced member of the Bacteroidetes. Transcriptional profiling indicated that B. cellulosilyticus WH2 is an adaptive forager that tailors its versatile carbohydrate utilization strategy to available dietary polysaccharides, with a strong emphasis on plant-derived xylans abundant in dietary staples like cereal grains. Two highly expressed, diet-specific polysaccharide utilization loci (PULs) in B. cellulosilyticus WH2 were identified, one with characteristics of xylan utilization systems. Introduction of a B. cellulosilyticus WH2 library comprising .90,000 isogenic transposon mutants into gnotobiotic mice, along with the other artificial community members, confirmed that these loci represent critical diet-specific fitness determinants. Carbohydrates that trigger dramatic increases in expression of these two loci and many of the organism s 111 other predicted PULs were identified by RNA-Seq during in vitro growth on 31 distinct carbohydrate substrates, allowing us to better interpret in vivo RNA-Seq and proteomics data. These results offer insight

  3. ORISE: Protecting Human Subjects

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

    Protecting Human Subjects Protecting Human Subjects The U.S. Department of Energy (DOE) Human Subjects Research Program exists to ensure that all research conducted at DOE ...

  4. Human Resources Specialist (Human Resources Development)

    Broader source: [DOE]

    This position is located in the Leadership and Organizational Development group of Learning and Development (NHT), Human Capital Management (NH), Chief Administrative Officer (N). Human Capital...

  5. The Effect of the iBEAM Evo Carbon Fiber Tabletop on Skin Sparing

    SciTech Connect (OSTI)

    Simpson, John B. Godwin, Guy A.


    Replicating the attenuation properties of the treatment tabletop are of primary importance for accurate treatment planning; however, the effect of the tabletop on the skin-sparing properties of x-rays can be overlooked. Under some conditions, the reaction of skin to the radiation can be so serious as to be the dose-limiting organ for radiotherapy treatment. Hence, an understanding of the magnitude of the reduction in skin sparing is important. Because of the development of image-guided radiotherapy, modern tabletops have been developed without the use of metal supports that otherwise provided the necessary level of rigidity. Rigidity is instead provided by compressed foam within a carbon-fiber shell, which, although it provides artefact-free imaging and high levels of rigidity, has an adverse affect on the dose in the build-up region. Representative of this type is the iBEAM evo tabletop, whose effect on the skin dose was determined at 6-MV, 10-MV, and 18-MV x-rays. Skin dose was found to increase by 60-70% owing to the tabletop, with the effect increasing with field size and decreasing with energy. By considering an endpoint of erythema, a radiobiological advantage of selecting 10 MV over 6 MV for applicable treatments was demonstrated.

  6. Total skin electron beam therapy using an inclinable couch on motorized table and a compensating filter

    SciTech Connect (OSTI)

    Fuse, H.; Suzuki, K.; Shida, K.; Takahashi, H.; Kobayashi, D.; Seki, M.; Mori, Y.; Sakae, T.; Isobe, T.; Okumura, T.; Sakurai, H.


    Total skin electron beam is a specialized technique that involves irradiating the entire skin from the skin surface to only a few millimetres in depth. In the Stanford technique, the patient is in a standing position and six different directional positions are used during treatment. Our technique uses large electron beams in six directions with an inclinable couch on motorized table and a compensating filter was also used to spread the electron beam and move its intensity peak. Dose uniformity measurements were performed using Gafchromic films which indicated that the surface dose was 2.04 0.05 Gy. This technique can ensure the dose reproducibility because the patient is fixed in place using an inclinable couch on a motorized table.

  7. Uncertainty analysis of 208Pb neutron skin predictions with chiral interactions

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

    Sammarruca, Francesca


    Here, we report predictions for the neutron skin in 208Pb using chiral two- and three-body interactions at increasing orders of chiral effective field theory and varying resolution scales. Closely related quantities, such as the slope of the symmetry energy, are also discussed. As a result, the sensitivity of the skin to just pure neutron matter pressure when going from order 2 to order 4 of chiral effective theory is singled out in a set of calculations that employ an empirical equation of state for symmetric nuclear matter.


    SciTech Connect (OSTI)

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


    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

  9. Cancer Associated Fibroblasts express pro-inflammatory factors in human breast and ovarian tumors

    SciTech Connect (OSTI)

    Erez, Neta; Glanz, Sarah; Raz, Yael; Avivi, Camilla; Barshack, Iris


    Highlights: •CAFs in human breast and ovarian tumors express pro-inflammatory factors. •Expression of pro-inflammatory factors correlates with tumor invasiveness. •Expression of pro-inflammatory factors is associated with NF-κb activation in CAFs. -- Abstract: Inflammation has been established in recent years as a hallmark of cancer. Cancer Associated Fibroblasts (CAFs) support tumorigenesis by stimulating angiogenesis, cancer cell proliferation and invasion. We previously demonstrated that CAFs also mediate tumor-enhancing inflammation in a mouse model of skin carcinoma. Breast and ovarian carcinomas are amongst the leading causes of cancer-related mortality in women and cancer-related inflammation is linked with both these tumor types. However, the role of CAFs in mediating inflammation in these malignancies remains obscure. Here we show that CAFs in human breast and ovarian tumors express high levels of the pro-inflammatory factors IL-6, COX-2 and CXCL1, previously identified to be part of a CAF pro-inflammatory gene signature. Moreover, we show that both pro-inflammatory signaling by CAFs and leukocyte infiltration of tumors are enhanced in invasive ductal carcinoma as compared with ductal carcinoma in situ. The pro-inflammatory genes expressed by CAFs are known NF-κB targets and we show that NF-κB is up-regulated in breast and ovarian CAFs. Our data imply that CAFs mediate tumor-promoting inflammation in human breast and ovarian tumors and thus may be an attractive target for stromal-directed therapeutics.

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

    SciTech Connect (OSTI)

    Jian Li


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

  11. Generation of insulin-producing cells from gnotobiotic porcine skin-derived stem cells

    SciTech Connect (OSTI)

    Yang, Ji Hoon; Lee, Sung Ho; Heo, Young Tae; Uhm, Sang Jun; Lee, Hoon Taek


    A major problem in the treatment of type 1 diabetes mellitus is the limited availability of alternative sources of insulin-producing cells for islet transplantation. In this study, we investigated the effect of bone morphogenetic protein 4 (BMP-4) treatments of gnotobiotic porcine skin-derived stem cells (gSDSCs) on their reprogramming and subsequent differentiation into insulin-producing cells (IPCs). We isolated SDSCs from the ear skin of a gnotobiotic pig. During the proliferation period, the cells expressed stem-cell markers Oct-4, Sox-2, and CD90; nestin expression also increased significantly. The cells could differentiate into IPCs after treatments with activin-A, glucagon-like peptide-1 (GLP-1), and nicotinamide. After 15 days in the differentiation medium, controlled gSDSCs began expressing endocrine progenitor genes and proteins (Ngn3, Neuro-D, PDX-1, NKX2.2, NKX6.1, and insulin). The IPCs showed increased insulin synthesis after glucose stimulation. The results indicate that stem cells derived from the skin of gnotobiotic pigs can differentiate into IPCs under the appropriate conditions in vitro. Our three-stage induction protocol could be applied without genetic modification to source IPCs from stem cells in the skin of patients with diabetes for autologous transplantation.

  12. Human factors in software development

    SciTech Connect (OSTI)

    Curtis, B.


    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.

  13. 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) ... U.S. Department of Energy (DOE) laboratories involved in human subjects research projects. ...

  14. 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 ...

  15. Human Reliability Assessment

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

    ... Signup SlideShare Human Reliability Assessment HomeStationary PowerNuclear EnergyNuclear Energy Safety TechnologiesRisk and Safety AssessmentHuman Reliability Assessment ...

  16. Bleomycin-induced epithelial–mesenchymal transition in sclerotic skin of mice: Possible role of oxidative stress in the pathogenesis

    SciTech Connect (OSTI)

    Zhou, Cheng-Fan; Zhou, Deng-Chuan; Zhang, Jia-Xiang; Wang, Feng; Cha, Wan-Sheng; Wu, Chang-Hao; Zhu, Qi-Xing


    Epithelial–mesenchymal transition (EMT) derived myofibroblasts are partly responsible for the increased collagen synthesis and deposition that occur in tissue fibrosis; however EMT occurrence in skin fibrosis and its mechanism remain unknown. The aim of this study was to investigate whether epithelial cells undergo EMT and determine the role of oxidative stress in this process. BALB/c mice were subcutaneously injected with bleomycin (BLM) or phosphate buffer saline (PBS) into the shaved back daily for 2, 3, and 4 weeks. Skin collagen deposition was evaluated by histopathology and Western blotting. EMT characteristics in the skin were determined by histopathology and immunofluorescent staining for E-cadherin and vimentin, which were further evaluated by Western blotting and reverse transcriptase polymerase chain reaction (RT-PCR). To investigate the role of oxidative stress in EMT, the antioxidant N-acetylcysteine (NAC) was intraperitoneally (100 mg/kg body weight/day) injected daily for 3 weeks. The epithelial suprabasal cells were detached from the basement membrane zone (BMZ) in the sclerotic skin treated with BLM. Immunofluorescent staining indicated vimentin-positive epithelial cells frequently occurring in the thickened epidermis of BLM-treated mice. Western blotting and RT-PCR showed that the expression of E-cadherin was significantly decreased but that of vimentin significantly increased in the skin treated with BLM. NAC attenuated BLM induced oxidative damage, changes in E-cadherin and vimentin expressions and collagen deposition in the sclerotic skin of mice. This study provides the first evidence that BLM induces the EMT of the epithelial cells superficial to the basement membrane zone in the skin fibrosis. Oxidative stress may contribute, at least in part, to BLM induced EMT and skin fibrosis in mice. - Highlights: • We provided the first evidence that EMT occurred in BLM-induced skin fibrosis. • Epithelial cells superficial to the BMZ underwent

  17. Effect of Ion Skin Depth on Relaxation of Merging Spheromaks to a Field-Reversed Configuration

    SciTech Connect (OSTI)

    Kawamori, Eiichirou; Ono, Yasushi


    The effect of ion skin depth on the relaxation of merging spheromaks to a field-reversed configuration (FRC) is studied experimentally for a wide range of size parameter S* (ratio of minor radius to ion skin depth) from 1 to 7. The two merging spheromaks are observed to relax to an FRC or a new spheromak depending on whether the initial poloidal eigenvalue is smaller or larger than a threshold value. The bifurcation value is found to increase with decreasing size parameter S{sup *}, indicating that the low-S* condition provides a wide bifurcated range of relaxation to an FRC. The FRC-style relaxation under the low-S* conditions was accompanied by the suppression of the low-n modes (n is the toroidal mode number) activity. The fast rotations of the modes were followed by suppression of the low-n modes.

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

    SciTech Connect (OSTI)

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


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

  19. Technical Note: Skin thickness measurements using high-resolution flat-panel cone-beam dedicated breast CT

    SciTech Connect (OSTI)

    Shi Linxi; Vedantham, Srinivasan; Karellas, Andrew; O'Connell, Avice M.


    Purpose: To determine the mean and range of location-averaged breast skin thickness using high-resolution dedicated breast CT for use in Monte Carlo-based estimation of normalized glandular dose coefficients. Methods: This study retrospectively analyzed image data from a clinical study investigating dedicated breast CT. An algorithm similar to that described by Huang et al.['The effect of skin thickness determined using breast CT on mammographic dosimetry,' Med. Phys. 35(4), 1199-1206 (2008)] was used to determine the skin thickness in 137 dedicated breast CT volumes from 136 women. The location-averaged mean breast skin thickness for each breast was estimated and the study population mean and range were determined. Pathology results were available for 132 women, and were used to investigate if the distribution of location-averaged mean breast skin thickness varied with pathology. The effect of surface fitting to account for breast curvature was also studied. Results: The study mean ({+-} interbreast SD) for breast skin thickness was 1.44 {+-} 0.25 mm (range: 0.87-2.34 mm), which was in excellent agreement with Huang et al. Based on pathology, pair-wise statistical analysis (Mann-Whitney test) indicated that at the 0.05 significance level, there were no significant difference in the location-averaged mean breast skin thickness distributions between the groups: benign vs malignant (p= 0.223), benign vs hyperplasia (p= 0.651), hyperplasia vs malignant (p= 0.229), and malignant vs nonmalignant (p= 0.172). Conclusions: Considering this study used a different clinical prototype system, and the study participants were from a different geographical location, the observed agreement between the two studies suggests that the choice of 1.45 mm thick skin layer comprising the epidermis and the dermis for breast dosimetry is appropriate. While some benign and malignant conditions could cause skin thickening, in this study cohort the location-averaged mean breast skin thickness

  20. Topical efficacy of dimercapto-chelating agents against lewisite-induced skin lesions in SKH-1 hairless mice

    SciTech Connect (OSTI)

    Mouret, Stéphane; Wartelle, Julien; Emorine, Sandy; Bertoni, Marine; Nguon, Nina; Cléry-Barraud, Cécile; Dorandeu, Frédéric; Boudry, Isabelle


    Lewisite is a potent chemical warfare arsenical vesicant that can cause severe skin lesions. Today, lewisite exposure remains possible during demilitarization of old ammunitions and as a result of deliberate use. Although its cutaneous toxicity is not fully elucidated, a specific antidote exists, the British anti-lewisite (BAL, dimercaprol) but it is not without untoward effects. Analogs of BAL, less toxic, have been developed such as meso-2,3-dimercaptosuccinic acid (DMSA) and have been employed for the treatment of heavy metal poisoning. However, efficacy of DMSA against lewisite-induced skin lesions remains to be determined in comparison with BAL. We have thus evaluated in this study the therapeutic efficacy of BAL and DMSA in two administration modes against skin lesions induced by lewisite vapor on SKH-1 hairless mice. Our data demonstrate a strong protective efficacy of topical application of dimercapto-chelating agents in contrast to a subcutaneous administration 1 h after lewisite exposure, with attenuation of wound size, necrosis and impairment of skin barrier function. The histological evaluation also confirms the efficacy of topical application by showing that treatments were effective in reversing lewisite-induced neutrophil infiltration. This protective effect was associated with an epidermal hyperplasia. However, for all the parameters studied, BAL was more effective than DMSA in reducing lewisite-induced skin injury. Together, these findings support the use of a topical form of dimercaprol-chelating agent against lewisite-induced skin lesion within the first hour after exposure to increase the therapeutic management and that BAL, despite its side-effects, should not be abandoned. - Highlights: • Topically applied dimercapto-chelating agents reduce lewisite-induced skin damage. • One topical application of BAL or DMSA is sufficient to reverse lewisite effects. • Topical BAL is more effective than DMSA to counteract lewisite-induced skin damage.

  1. Understanding the origins of human cancer

    SciTech Connect (OSTI)

    Alexandrov, L. B.


    All cancers originate from a single cell that starts to behave abnormally, to divide uncontrollably, and, eventually, to invade adjacent tissues (1). The aberrant behavior of this single cell is due to somatic mutations—changes in the genomic DNA produced by the activity of different mutational processes (1). These various mutational processes include exposure to exogenous or endogenous mutagens, abnormal DNA editing, the incomplete fidelity of DNA polymerases, and failure of DNA repair mechanisms (2). Early studies that sequenced TP53, the most commonly mutated gene in human cancer, provided evidence that mutational processes leave distinct imprints of somatic mutations on the genome of a cancer cell (3). For example, C:G>A:T transversions predominate in smoking-associated lung cancer, whereas C:G>T:A transitions occurring mainly at dipyrimidines and CC:GG>TT:AA double-nucleotide substitutions are common in ultraviolet light–associated skin cancers. Moreover, these patterns of mutations matched the ones induced experimentally by tobacco mutagens and ultraviolet light, respectively, the major, known, exogenous carcinogenic influences in these cancer types, and demonstrated that examining patterns of mutations in cancer genomes can yield information about the mutational processes that cause human cancer (4).

  2. Understanding the origins of human cancer

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

    Alexandrov, L. B.


    All cancers originate from a single cell that starts to behave abnormally, to divide uncontrollably, and, eventually, to invade adjacent tissues (1). The aberrant behavior of this single cell is due to somatic mutations—changes in the genomic DNA produced by the activity of different mutational processes (1). These various mutational processes include exposure to exogenous or endogenous mutagens, abnormal DNA editing, the incomplete fidelity of DNA polymerases, and failure of DNA repair mechanisms (2). Early studies that sequenced TP53, the most commonly mutated gene in human cancer, provided evidence that mutational processes leave distinct imprints of somatic mutations on themore » genome of a cancer cell (3). For example, C:G>A:T transversions predominate in smoking-associated lung cancer, whereas C:G>T:A transitions occurring mainly at dipyrimidines and CC:GG>TT:AA double-nucleotide substitutions are common in ultraviolet light–associated skin cancers. Moreover, these patterns of mutations matched the ones induced experimentally by tobacco mutagens and ultraviolet light, respectively, the major, known, exogenous carcinogenic influences in these cancer types, and demonstrated that examining patterns of mutations in cancer genomes can yield information about the mutational processes that cause human cancer (4).« less

  3. Trichloroethylene toxicity in a human hepatoma cell line

    SciTech Connect (OSTI)

    Thevenin, E.; McMillian, J.


    The experiments conducted in this study were designed to determine the usefullness of hepatocyte cultures and a human hepatoma cell line as model systems for assessing human susceptibility to hepatocellular carcinoma due to exposure to trichloroethylene. The results from these studies will then be analyzed to determine if human cell lines can be used to conduct future experiments of this nature.

  4. 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


    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.

  5. Ontology-enriched Visualization of Human Anatomy

    SciTech Connect (OSTI)

    Pouchard, LC


    The project focuses on the problem of presenting a human anatomical 3D model associated with other types of human systemic information ranging from physiological to anatomical information while navigating the 3D model. We propose a solution that integrates a visual 3D interface and navigation features with the display of structured information contained in an ontology of anatomy where the structures of the human body are formally and semantically linked. The displayed and annotated anatomy serves as a visual entry point into a patient's anatomy, medical indicators and other information. The ontology of medical information provides labeling to the highlighted anatomical parts in the 3D display. Because of the logical organization and links between anatomical objects found in the ontology and associated 3D model, the analysis of a structure by a physician is greatly enhanced. Navigation within the 3D visualization and between this visualization and objects representing anatomical concepts within the model is also featured.

  6. ARM - Human Causes

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

    Study Hall About ARM Global Warming FAQ Just for Fun Meet our Friends Cool Sites Teachers Teachers' Toolbox Lesson Plans Human Causes Some of the human activities which can cause ...

  7. Human Genome: DOE Origins

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

    Human Genome Research: DOE Origins Resources with Additional Information Charles DeLisi Charles DeLisi The genesis of the Department of Energy (DOE) human genome project took place ...

  8. Characterization of a MOSkin detector for in vivo skin dose measurements during interventional radiology procedures

    SciTech Connect (OSTI)

    Safari, M. J.; Wong, J. H. D.; Ng, K. H.; Jong, W. L.; Cutajar, D. L.; Rosenfeld, A. B.


    Purpose: The MOSkin is a MOSFET detector designed especially for skin dose measurements. This detector has been characterized for various factors affecting its response for megavoltage photon beams and has been used for patient dose measurements during radiotherapy procedures. However, the characteristics of this detector in kilovoltage photon beams and low dose ranges have not been studied. The purpose of this study was to characterize the MOSkin detector to determine its suitability for in vivo entrance skin dose measurements during interventional radiology procedures. Methods: The calibration and reproducibility of the MOSkin detector and its dependency on different radiation beam qualities were carried out using RQR standard radiation qualities in free-in-air geometry. Studies of the other characterization parameters, such as the dose linearity and dependency on exposure angle, field size, frame rate, depth-dose, and source-to-surface distance (SSD), were carried out using a solid water phantom under a clinical x-ray unit. Results: The MOSkin detector showed good reproducibility (94%) and dose linearity (99%) for the dose range of 2 to 213 cGy. The sensitivity did not significantly change with the variation of SSD (±1%), field size (±1%), frame rate (±3%), or beam energy (±5%). The detector angular dependence was within ±5% over 360° and the dose recorded by the MOSkin detector in different depths of a solid water phantom was in good agreement with the Markus parallel plate ionization chamber to within ±3%. Conclusions: The MOSkin detector proved to be reliable when exposed to different field sizes, SSDs, depths in solid water, dose rates, frame rates, and radiation incident angles within a clinical x-ray beam. The MOSkin detector with water equivalent depth equal to 0.07 mm is a suitable detector for in vivo skin dosimetry during interventional radiology procedures.

  9. Human Behavior, Standards and Tools to Improve Design & Operation |

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

    Department of Energy Human Behavior, Standards and Tools to Improve Design & Operation Human Behavior, Standards and Tools to Improve Design & Operation Three steps of the technical approach to the human energy behavior loop: (1) Investigate the operations of building energy and services systems through behavior-related data collection, (2) Understand the human behavior through data analytics, data mining, and modeling, and (3) Improve the building performance by applying behavioral

  10. Ultrastructural Study on Ultra-Low Frequency Electromagnetic Fields and Transfer Factor Effects on Skin Ulcers

    SciTech Connect (OSTI)

    Cadena, M. S. Reyes; Chapul, L. Sanchez; Perez, Javier; Garcia, M. N. Jimenez; Lopez, M. A. Jimenez; Espindola, M. E. Sanchez; Perez, R. Paniagua; Hernandez, N. A.; Paniagua, G.; Uribe, F.; Nava, J. J. Godina; Segura, M. A. Rodriguez


    We determined the effect of 120Hz ultra low frequency electromagnetic field (ELF) on the healing process of skin in 20 Wistar rats distributed in four groups in which chronic dermal ulcers had been produced. The first two groups received a dose of the transfer factor and interferon-beta (IFN-{beta}) every 24 h during 12 days. The third group (positive control) received only electromagnetic field (ELF) sessions, and in the fourth group (negative control), no treatment was applied. The electromagnetic field was applied through a Helmholtz coils; 30 Gauss of intensity. Results shown histological changes that improve the healing process in animals subjected to ELF together with the transfer factor.

  11. Analysis of Human Genetic Linkage

    SciTech Connect (OSTI)

    Boehnke, M.


    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.

  12. Report: EM Human Capital Initiatives

    Office of Environmental Management (EM)

    HUMAN CAPITAL September 25, 2008 Submitted by the EMAB Human Capital Subcommittee Background: The enhancement of the Office of Environmental Management's (EM) human capital has ...

  13. An exposure chamber for studies on human perception of DC electric fields and ions

    SciTech Connect (OSTI)

    Nguyen, D.H.; Maruvada, P.S. )


    Direct current (DC) transmission lines are often used, for technical and economic reasons, as interconnections in modern high voltage power systems, which are essentially of the alternating current (AC) type. Significant differences exist, however, between the field effects produced in the vicinity of AC and DC transmission lines. DC electric fields induce charges, on the surface of a conducting body such as a human being and may therefore be ''perceived'' by humans due to hair stimulation and other sensations experienced by the skin. A human being exposed to the ionized field of a DC transmission line experiences not only surface charges but also the conducted ion currents. A systematic laboratory study has been undertaken by Hydro Quebec to investigate human perception, using well established psycho physical techniques, of DC electric fields and ions. The design, construction and operation of an exposure chamber for this purpose, in the high voltage laboratory of IREQ, are described in this paper.

  14. Corporate Human Resources Information Services (CHIRS) PIA, Office of Human

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

    Capitol Management | Department of Energy Corporate Human Resources Information Services (CHIRS) PIA, Office of Human Capitol Management Corporate Human Resources Information Services (CHIRS) PIA, Office of Human Capitol Management Corporate Human Resources Information Services (CHIRS) PIA, Office of Human Capitol Management Corporate Human Resources Information Services (CHIRS) PIA, Office of Human Capitol Management (80.67 KB) More Documents & Publications MOX Services Unclassified

  15. Human Genome: DOE Origins

    Office of Scientific and Technical Information (OSTI)

    of the Department of Energy; DOE Technical Report; 1988 Mapping and Sequencing the Human Genome; DOE Technical Report; 1988 Understanding our Genetic Inheritance: The U.S....

  16. Jefferson Lab Human Resources

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

    ... Sponsor click on this link to nominate a student: SPONSOR NOMINATION FORM If you have any questions please contact: Human Resources Jefferson Science Associates 628 Hofstadter Rd., ...

  17. 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 ...

  18. Jefferson Lab Human Resources

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

    Human Resources Consultants Cassandra Andrews, HR Consultant, Employee Relations & Recruitment (757) 269-7068, Kelly Allmon, HR Consultant, Recruitment & ...

  19. Red emission phosphor for real-time skin dosimeter for fluoroscopy and interventional radiology

    SciTech Connect (OSTI)

    Nakamura, Masaaki Chida, Koichi; Zuguchi, Masayuki


    Purpose: There are no effective real-time direct skin dosimeters for interventional radiology. Such a scintillation dosimeter would be available if there was a suitable red emission phosphor in the medical x-ray range, since the silicon photodiode is a highly efficient device for red light. However, it is unknown whether there is a suitable red emission phosphor. The purpose of this study is to find a suitable red emission phosphor that can be used in x-ray dosimeters. Methods: Five kinds of phosphors which emit red light when irradiated with electron beams or ultraviolet rays in practical devices were chosen. For the brightness measurement, phosphor was put into transparent plastic cells or coated onto plastic sheets. The phosphors were irradiated with medical range x-rays [60–120 kV(peak), maximum dose rate of 160 mGy min{sup −1}], and the emission was measured by a luminance meter. Several characteristics, such as brightness, dose rate dependence, tube voltage dependence, and brightness stability, were investigated. Results: The luminescence of Y V O{sub 4}:Eu, (Y,Gd,Eu) BO{sub 3}, and Y{sub 2}O{sub 3}:Eu significantly deteriorated by 5%–10% when irradiated with continuous 2 Gy x-rays. The 0.5MgF{sub 2}⋅3.5MgO⋅GeO{sub 2}:Mn phosphor did not emit enough. Only the Y{sub 2}O{sub 2}S:Eu,Sm phosphor had hardly any brightness deterioration, and it had a linear relationship so that the x-ray dose rate could be determined from the brightness with sufficient accuracy. For the tube voltage dependence of the Y{sub 2}O{sub 2}S:Eu,Sm phosphor, the brightness per unit dose rate with 120 kV(peak) x-rays was 30% higher than that with 60 kV(peak) x-rays. Conclusions: Five kinds of phosphors were chosen as an x-ray scintillator for a real-time direct skin dosimeter. The Y V O{sub 4}:Eu, (Y,Gd,Eu)BO{sub 3}, and Y{sub 2}O{sub 3}:Eu phosphors had brightness deterioration caused by the x-rays. Only the Y{sub 2}O{sub 2}S:Eu,Sm phosphor had hardly any brightness deterioration

  20. Neutron-skin thickness from the study of the anti-analog giant dipole resonance

    SciTech Connect (OSTI)

    Krasznahorkay, A.; Stuhl, L.; Csatlos, M.; Algora, A.; and others


    The {gamma}-decay of the anti-analog of the giant dipole resonance (AGDR) to the isobaric analog state has been measured following the p({sup 124}Sn,n) reaction at a beam energy of 600 MeV/nucleon. The energy of the transition was also calculated with state-of-the-art self-consistent relativistic random-phase approximation (RPA) and turned out to be very sensitive to the neutronskin thickness ({Delta}R{sub pn}). By comparing the theoretical results with the measured one, the {Delta}R{sub pn} value for {sup 124}Sn was deduced to be 0.21 {+-} 0.07 fm, which agrees well with the previous results. The present method offers new possibilities for measuring the neutron-skin thicknesses of very exotic isotopes.

  1. Experimental study of the nonlinear diffusion of a magnetic field and skin explosion of cylindrical conductors

    SciTech Connect (OSTI)

    Chaikovsky, S. A.; Datsko, I. M.; Labetskaya, N. A.; Rybka, D. V.; Ratakhin, N. A.; Oreshkin, V. I.


    The paper presents the results of an experimental study of the skin explosion of cylindrical conductors of diameter 1–3 mm (copper, aluminum, titanium, steel 3, and stainless steel) at a peak magnetic field of 200–600 T. The experiments were carried out on the MIG pulsed power generator at a current of up to 2.5 MA and a current rise time of 100 ns. The surface explosion of a conductor was identified by the appearance of a flash of extreme ultraviolet radiation. A minimum magnetic induction has been determined below which no plasma is generated at the conductor surface. For copper, aluminum, steel 3, titanium, and stainless steel, the minimum magnetic induction has been estimated to be (to within 10%) 375, 270, 280, 220, and 245 T, respectively.

  2. Method of forming a continuous polymeric skin on a cellular foam material

    DOE Patents [OSTI]

    Duchane, David V.; Barthell, Barry L.


    Hydrophobic cellular material is coated with a thin hydrophilic polymer skin which stretches tightly over the outer surface of the foam but which does not fill the cells of the foam, thus resulting in a polymer-coated foam structure having a smoothness which was not possible in the prior art. In particular, when the hydrophobic cellular material is a specially chosen hydrophobic polymer foam and is formed into arbitrarily chosen shapes prior to the coating with hydrophilic polymer, inertial confinement fusion (ICF) targets of arbitrary shapes can be produced by subsequently coating the shapes with metal or with any other suitable material. New articles of manufacture are produced, including improved ICF targets, improved integrated circuits, and improved solar reflectors and solar collectors. In the coating method, the cell size of the hydrophobic cellular material, the viscosity of the polymer solution used to coat, and the surface tensin of the polymer solution used to coat are all very important to the coating.

  3. The neutron skin in neutron-rich nuclei at Jefferson Lab

    SciTech Connect (OSTI)

    Dalton, Mark M.


    The Jefferson Lab program to measure the symmetry energy of neutron-rich nuclear matter, using precision electroweak methods, is progressing well. The initial measurement by the PREX experiment, leading to a 2-sigma determination of the "neutron skin" in {sup 208}Pb , has been published. Design and preparation for a further, more-precise measurement on {sup 208}Pb is progressing well and there is general acceptance of the great advantage to a further measurement on {sup 48}Ca . The surprising ancillary result that the beam-normal single-spin asymmetry for {sup 208}Pb is consistent with zero is also now in the literature. This paper will discuss the current experimental situation of the program.

  4. Protection of Human Subjects

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


    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.

  5. Protection of Human Subjects

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


    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.

  6. Double trisomy mosaic (47,XXX/48,XXX,+13) confirmed by FISH and skin fibroblast culture

    SciTech Connect (OSTI)

    Lieber, E.; Grady, V.; Dosik, H.


    A 4 lb 8 oz female was born to a 49-year-old woman (P1200G12) at 40 weeks. The baby had tetralogy of Fallot, polydactyly, microcephaly, low set simple ears, posterior cleft of the soft palate and overlapping flexion deformities of both hands. The eyes were deep set. The clinical impression was trisomy 13. The baby is not doing well and needs a gastrotomy tube for feeding. Sucking is allright but swallowing is impeded. An MRI showed an anomaly of the corpus callosum. The ophthalmological examination showed no abnormalities. A chromosome study on a 2-day peripheral blood sample resulted in poor growth and poor morphology; however, 20 Giemsa-banded cells revealed a 47,XXX karyotype. A second specimen was obtained to search for mosaicism and a blood smear revealed nuclear projections on the neutrophils. FISH analysis using whole chromosome painting probe (Life Technologies) first identified the extra chromosome number 13, the final results showing five of sixty metaphase cells (8.3%) with trisomy 13. Cytogenetic analysis using Giemsa-banding technique revealed four cells in fifty examined (8.0%) with a 48,XXX,+13 karyotype. In order to further evaluate the mosaicism, cytogenetic analysis of a skin fibroblast culture was performed. Twenty one of twenty three cells examined (91.3%) showed the 48,XXX,+13 karyotype. FISH analysis of the skin biopsy revealed eighteen of twenty cells (90.9%) with the trisomy 13. The FISH technique is an important enhancement to routine cytogenetic studies when they do not immediately correlate with clinical impressions.

  7. Modeling & Analysis

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

    Facilities, Modeling, Modeling, Modeling & Analysis, Modeling & Analysis, Renewable Energy, Research & Capabilities, Wind Energy, Wind News Virtual LIDAR Model Helps Researchers ...

  8. Validation of in vitro cell models used in drug metabolism and transport studies; genotyping of cytochrome P450, phase II enzymes and drug transporter polymorphisms in the human hepatoma (HepG2), ovarian carcinoma (IGROV-1) and colon carcinoma (CaCo-2, LS180) cell lines

    SciTech Connect (OSTI)

    Brandon, Esther F.A.; Bosch, Tessa M.; Deenen, Maarten J.; Levink, Rianne; Wal, Everdina van der; Meerveld, Joyce B.M. van; Bijl, Monique; Beijnen, Jos H. |; Schellens, Jan H.M. |; Meijerman, Irma . E-mail:


    Human cell lines are often used for in vitro biotransformation and transport studies of drugs. In vivo, genetic polymorphisms have been identified in drug-metabolizing enzymes and ABC-drug transporters leading to altered enzyme activity, or a change in the inducibility of these enzymes. These genetic polymorphisms could also influence the outcome of studies using human cell lines. Therefore, the aim of our study was to pharmacogenotype four cell lines frequently used in drug metabolism and transport studies, HepG2, IGROV-1, CaCo-2 and LS180, for genetic polymorphisms in biotransformation enzymes and drug transporters. The results indicate that, despite the presence of some genetic polymorphisms, no real effects influencing the activity of metabolizing enzymes or drug transporters in the investigated cell lines are expected. However, this characterization will be an aid in the interpretation of the results of biotransformation and transport studies using these in vitro cell models.

  9. SU-E-T-68: Clinical Implementation of Total Skin Electron Beam Therapy: A New- York Presbyterian Hospital Experience

    SciTech Connect (OSTI)

    Afghan, M; Shih, R; Chen, H


    Purpose: Total skin electron beam therapy (TSET) is used in the treatment of rare skin diseases such as mycosis fungoides, the most common type of cutaneous T-cell lymphoma. We report our experience with clinical implementation of TSET. Methods: A modified six-dual-field irradiation technique was chosen to deliver TSET. A Varian Trilogy linear accelerator with a nominal 6 MeV beam using high dose rate total skin electron mode (HDTSe) was employed. The recommendations of AAPM task group report 23 were followed for the commissioning. An acrylic plate (energy degrader) of 3.2 mm depth was mounted on the HDTSe applicator. The nominal source to skin distance was set at 450 cm. The optimum tilt angle of the gantry was determined using NACP-02 ionization chamber embedded in certified therapy grade solid water. Percent depth dose measurements were performed using ionization chamber and radiochromic films embedded in solid water and anthropomorphic phantom. For absolute dose measurements, TG-51 formalism was employed. The dose distribution on the entire skin was measured by irradiating the anthropomorphic phantom, with TLDs attached, mimicking the real treatment. Results: The 3.2 mm acrylic plate mounted on the HDTSe applicator degraded the energy of the electron beam to 4.1 MeV in the treatment plane, located at an SSD of 450 cm. The optimum tilt angle was found to be 20. A single-dual field had a longitudinal uniformity, measured at a depth of dose maximum, of 7% over a length of about 200 cm. For the entire treatment the multiplication factor was found to be 2.86. On the surface of the phantom, the dose varied from 108% to 93% of the prescription dose. Conclusion: We have successfully commissioned TSET meeting the guidelines of the TG report 23, and treated our first patient on February 25, 2014.

  10. Human Genome Project

    SciTech Connect (OSTI)

    Block, S.; Cornwall, J.; Dally, W.; Dyson, F.; Fortson, N.; Joyce, G.; Kimble, H. J.; Lewis, N.; Max, C.; Prince, T.; Schwitters, R.; Weinberger, P.; Woodin, W. H.


    The study reviews Department of Energy supported aspects of the United States Human Genome Project, the joint National Institutes of Health/Department of Energy program to characterize all human genetic material, to discover the set of human genes, and to render them accessible for further biological study. The study concentrates on issues of technology, quality assurance/control, and informatics relevant to current effort on the genome project and needs beyond it. Recommendations are presented on areas of the genome program that are of particular interest to and supported by the Department of Energy.

  11. Human body impedance for electromagnetic hazard analysis in the VLF to MF band

    SciTech Connect (OSTI)

    Kanai, H.; Chatterjee, I.; Gandhi, O.P.


    A knowledge of the average electrical impedance of the human body is essential for the analysis of electromagnetic hazards in the VLF to MF band. The purpose of the measurements was to determine the average body impedance of several human subjects as a function of frequency. Measurements were carried out with the subjects standing barefoot on a ground plane and touching various metal electrodes with the hand or index finger. The measured impedance includes the electrode polarization and skin impedances, spread impedance near the electrode, body impedance, stray capacitance between the body surface and ground, and inductance due to the body and grounding strap. These components are separated and simplified equivalent circuits are presented for body impedance of humans exposed to free-space electromagnetic waves as well as in contact with large ungrounded metallic objects therein.

  12. A New Type of Pilus from the Human Microbiome | Stanford Synchrotron...

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

    A New Type of Pilus from the Human Microbiome Friday, July 29, 2016 Figure legend: Models ... 20 structures of P. gingivalis pilins or their homologs from the human gut microbiome. ...

  13. Human Reliability Program Overview

    SciTech Connect (OSTI)

    Bodin, Michael


    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.

  14. Protection of Human Subjects

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


    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

  15. Protection of Human Subjects

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


    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.

  16. Human Resource Management Delegation

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


    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.

  17. Biosphere Process Model Report

    SciTech Connect (OSTI)

    J. Schmitt


    To evaluate the postclosure performance of a potential monitored geologic repository at Yucca Mountain, a Total System Performance Assessment (TSPA) will be conducted. Nine Process Model Reports (PMRs), including this document, are being developed to summarize the technical basis for each of the process models supporting the TSPA model. These reports cover the following areas: (1) Integrated Site Model; (2) Unsaturated Zone Flow and Transport; (3) Near Field Environment; (4) Engineered Barrier System Degradation, Flow, and Transport; (5) Waste Package Degradation; (6) Waste Form Degradation; (7) Saturated Zone Flow and Transport; (8) Biosphere; and (9) Disruptive Events. Analysis/Model Reports (AMRs) contain the more detailed technical information used to support TSPA and the PMRs. The AMRs consists of data, analyses, models, software, and supporting documentation that will be used to defend the applicability of each process model for evaluating the postclosure performance of the potential Yucca Mountain repository system. This documentation will ensure the traceability of information from its source through its ultimate use in the TSPA-Site Recommendation (SR) and in the National Environmental Policy Act (NEPA) analysis processes. The objective of the Biosphere PMR is to summarize (1) the development of the biosphere model, and (2) the Biosphere Dose Conversion Factors (BDCFs) developed for use in TSPA. The Biosphere PMR does not present or summarize estimates of potential radiation doses to human receptors. Dose calculations are performed as part of TSPA and will be presented in the TSPA documentation. The biosphere model is a component of the process to evaluate postclosure repository performance and regulatory compliance for a potential monitored geologic repository at Yucca Mountain, Nevada. The biosphere model describes those exposure pathways in the biosphere by which radionuclides released from a potential repository could reach a human receptor

  18. Simulation and Non-Simulation Based Human Reliability Analysis Approaches

    SciTech Connect (OSTI)

    Boring, Ronald Laurids; Shirley, Rachel Elizabeth; Joe, Jeffrey Clark; Mandelli, Diego


    Part of the U.S. Department of Energy’s Light Water Reactor Sustainability (LWRS) Program, the Risk-Informed Safety Margin Characterization (RISMC) Pathway develops approaches to estimating and managing safety margins. RISMC simulations pair deterministic plant physics models with probabilistic risk models. As human interactions are an essential element of plant risk, it is necessary to integrate human actions into the RISMC risk model. In this report, we review simulation-based and non-simulation-based human reliability assessment (HRA) methods. Chapter 2 surveys non-simulation-based HRA methods. Conventional HRA methods target static Probabilistic Risk Assessments for Level 1 events. These methods would require significant modification for use in dynamic simulation of Level 2 and Level 3 events. Chapter 3 is a review of human performance models. A variety of methods and models simulate dynamic human performance; however, most of these human performance models were developed outside the risk domain and have not been used for HRA. The exception is the ADS-IDAC model, which can be thought of as a virtual operator program. This model is resource-intensive but provides a detailed model of every operator action in a given scenario, along with models of numerous factors that can influence operator performance. Finally, Chapter 4 reviews the treatment of timing of operator actions in HRA methods. This chapter is an example of one of the critical gaps between existing HRA methods and the needs of dynamic HRA. This report summarizes the foundational information needed to develop a feasible approach to modeling human interactions in the RISMC simulations.

  19. Estimating pediatric entrance skin dose from digital radiography examination using DICOM metadata: A quality assurance tool

    SciTech Connect (OSTI)

    Brady, S. L. Kaufman, R. A.


    Purpose: To develop an automated methodology to estimate patient examination dose in digital radiography (DR) imaging using DICOM metadata as a quality assurance (QA) tool. Methods: Patient examination and demographical information were gathered from metadata analysis of DICOM header data. The x-ray system radiation output (i.e., air KERMA) was characterized for all filter combinations used for patient examinations. Average patient thicknesses were measured for head, chest, abdomen, knees, and hands using volumetric images from CT. Backscatter factors (BSFs) were calculated from examination kVp. Patient entrance skin air KERMA (ESAK) was calculated by (1) looking up examination technique factors taken from DICOM header metadata (i.e., kVp and mA s) to derive an air KERMA (k{sub air}) value based on an x-ray characteristic radiation output curve; (2) scaling k{sub air} with a BSF value; and (3) correcting k{sub air} for patient thickness. Finally, patient entrance skin dose (ESD) was calculated by multiplying a massenergy attenuation coefficient ratio by ESAK. Patient ESD calculations were computed for common DR examinations at our institution: dual view chest, anteroposterior (AP) abdomen, lateral (LAT) skull, dual view knee, and bone age (left hand only) examinations. Results: ESD was calculated for a total of 3794 patients; mean age was 11 8 yr (range: 2 months to 55 yr). The mean ESD range was 0.190.42 mGy for dual view chest, 0.281.2 mGy for AP abdomen, 0.180.65 mGy for LAT view skull, 0.150.63 mGy for dual view knee, and 0.100.12 mGy for bone age (left hand) examinations. Conclusions: A methodology combining DICOM header metadata and basic x-ray tube characterization curves was demonstrated. In a regulatory era where patient dose reporting has become increasingly in demand, this methodology will allow a knowledgeable user the means to establish an automatable dose reporting program for DR and perform patient dose related QA testing for digital x

  20. 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 ...

  1. Human Resources | The Ames Laboratory

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

    Human Resources The mission of the Human Resource Department is to support the goals of The Ames Laboratory by providing support services which promote a work environmnent ...

  2. Human Genome Research: Decoding DNA

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

    Human Genome Research: Decoding DNA Resources with Additional Information Charles DeLisi ... role in proposing and initiating the Human Genome Program in 1986. The U.S. ...

  3. ORISE: Human Subjects Research Database

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

    Human Subjects Research Database Section 10, Part 745 of the Code of Federal Regulations ... on all research projects that involve human subjects and that are funded by DOE, ...

  4. New light on human evolution

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

    light on human evolution New light on human evolution Scientists recently unearthed 8 million-year-old gorilla fossils from the Chorora Formation in Ethiopia, which indicate the ...

  5. Search Method for Real-time Knowledge Discovery Modeled on the...

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

    Search Method for Real-time Knowledge Discovery Modeled on the Human Brain Oak Ridge ... information processing properties of the human brain to computational knowledge discovery. ...

  6. Reactivity enhancement of oxide skins in reversible Ti-doped NaAlH{sub 4}

    SciTech Connect (OSTI)

    Delmelle, Renaud; Borgschulte, Andreas; Gehrig, Jeffrey C.; Züttel, Andreas


    The reversibility of hydrogen sorption in complex hydrides has only been shown unambiguously for NaAlH{sub 4} doped with transition metal compounds. Despite a multitude of investigations of the effect of the added catalyst on the hydrogen sorption kinetics of NaAlH{sub 4}, the mechanism of catalysis remains elusive so far. Following the decomposition of TiCl{sub 3}-doped NaAlH{sub 4} by in-situ X-ray photoelectron spectroscopy (XPS), we link the chemical state of the dopant with those of the hydride and decomposition products. Titanium and aluminium change their oxidation states during cycling. The change of the formal oxidation state of Al from III to zero is partly due to the chemical reaction from NaAlH{sub 4} to Al. Furthermore, aluminium oxide is formed (Al{sub 2}O{sub 3}), which coexists with titanium oxide (Ti{sub 2}O{sub 3}). The interplay of metallic and oxidized Ti with the oxide skin might explain the effectiveness of Ti and similar dopants (Ce, Zr…)

  7. Reduction of skin effect losses in double-level-T-gate structure

    SciTech Connect (OSTI)

    Mikulics, M. Hardtdegen, H.; Arango, Y. C.; Adam, R.; Fox, A.; Grützmacher, D.; Gregušová, D.; Novák, J.; Stanček, S.; Kordoš, P.; Sofer, Z.; Juul, L.; Marso, M.


    We developed a T-gate technology based on selective wet etching yielding 200 nm wide T-gate structures used for fabrication of High Electron Mobility Transistors (HEMT). Major advantages of our process are the use of only standard photolithographic process and the ability to generate T-gate stacks. A HEMT fabricated on AlGaN/GaN/sapphire with gate length L{sub g} = 200 nm and double-stacked T-gates exhibits 60 GHz cutoff frequency showing ten-fold improvement compared to 6 GHz for the same device with 2 μm gate length. HEMTs with a double-level-T-gate (DLTG) structure exhibit up to 35% improvement of f{sub max} value compared to a single T-gate device. This indicates a significant reduction of skin effect losses in DLTG structure compared to its standard T-gate counterpart. These results agree with the theoretical predictions.

  8. Skin explosion of double-layer conductors in fast-rising high magnetic fields

    SciTech Connect (OSTI)

    Chaikovsky, S. A. Datsko, I. M.; Labetskaya, N. A.; Ratakhin, N. A.


    An experiment has been performed to study the electrical explosion of thick cylindrical conductors using the MIG pulsed power generator capable of producing a peak current of 2.5 MA within 100?ns rise time. The experimental goal was to compare the skin explosion of a solid conductor with that of a double-layer conductor whose outer layer had a lower conductivity than the inner one. It has been shown that in magnetic fields of peak induction up to 300?T and average induction rise rate 3??10{sup 9}?T/s, the double-layer structure of a conductor makes it possible to achieve higher magnetic induction at the conductor surface before it explodes. This can be accounted for, in particular, by the reduction of the ratio of the Joule heat density to the energy density of the magnetic field at the surface of a double-layer conductor due to redistribution of the current density over the conductor cross section.

  9. Human Capital - DOE Directives, Delegations, and Requirements

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

    Human Capital by Website Administrator Back

  10. Fibre Diffraction Analysis of Skin Offers a Very Early and Extremely Accurate Diagnostic Test for Prostate Cancer

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

    James, Veronica J.; O’Malley Ford


    Double blind analysis of a batch of thirty skin tissue samples from potential prostate cancer sufferers correctly identified all “control” patients, patients with high and low grade prostate cancers, the presence of benign prostate hyperplasia (BPH), perineural invasions, and the one lymphatic invasion. Identification was by analysis of fibre diffraction patterns interpreted using a schema developed from observations in nine previous studies. The method, schema, and specific experiment results are reported in this paper, with some implications then drawn.

  11. Human MSH2 protein

    DOE Patents [OSTI]

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


    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.

  12. Human MSH2 protein

    DOE Patents [OSTI]

    de la Chapelle, Albert; Vogelstein, Bert; Kinzler, Kenneth W.


    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.

  13. Oral administration of drugs with hypersensitivity potential induces germinal center hyperplasia in secondary lymphoid organ/tissue in Brown Norway rats, and this histological lesion is a promising candidate as a predictive biomarker for drug hypersensitivity occurrence in humans

    SciTech Connect (OSTI)

    Tamura, Akitoshi Miyawaki, Izuru; Yamada, Toru; Kimura, Juki; Funabashi, Hitoshi


    It is important to evaluate the potential of drug hypersensitivity as well as other adverse effects during the preclinical stage of the drug development process, but validated methods are not available yet. In the present study we examined whether it would be possible to develop a new predictive model of drug hypersensitivity using Brown Norway (BN) rats. As representative drugs with hypersensitivity potential in humans, phenytoin (PHT), carbamazepine (CBZ), amoxicillin (AMX), and sulfamethoxazole (SMX) were orally administered to BN rats for 28 days to investigate their effects on these animals by examinations including observation of clinical signs, hematology, determination of serum IgE levels, histology, and flow cytometric analysis. Skin rashes were not observed in any animals treated with these drugs. Increases in the number of circulating inflammatory cells and serum IgE level did not necessarily occur in the animals treated with these drugs. However, histological examination revealed that germinal center hyperplasia was commonly induced in secondary lymphoid organs/tissues in the animals treated with these drugs. In cytometric analysis, changes in proportions of lymphocyte subsets were noted in the spleen of the animals treated with PHT or CBZ during the early period of administration. The results indicated that the potential of drug hypersensitivity was identified in BN rat by performing histological examination of secondary lymphoid organs/tissues. Data obtained herein suggested that drugs with hypersensitivity potential in humans gained immune reactivity in BN rat, and the germinal center hyperplasia induced by administration of these drugs may serve as a predictive biomarker for drug hypersensitivity occurrence. - Highlights: We tested Brown Norway rats as a candidate model for predicting drug hypersensitivity. The allergic drugs did not induce skin rash, whereas D-penicillamine did so in the rats. Some of allergic drugs increased inflammatory

  14. Approximate Model for Turbulent Stagnation Point Flow.

    SciTech Connect (OSTI)

    Dechant, Lawrence


    Here we derive an approximate turbulent self-similar model for a class of favorable pressure gradient wedge-like flows, focusing on the stagnation point limit. While the self-similar model provides a useful gross flow field estimate this approach must be combined with a near wall model is to determine skin friction and by Reynolds analogy the heat transfer coefficient. The combined approach is developed in detail for the stagnation point flow problem where turbulent skin friction and Nusselt number results are obtained. Comparison to the classical Van Driest (1958) result suggests overall reasonable agreement. Though the model is only valid near the stagnation region of cylinders and spheres it nonetheless provides a reasonable model for overall cylinder and sphere heat transfer. The enhancement effect of free stream turbulence upon the laminar flow is used to derive a similar expression which is valid for turbulent flow. Examination of free stream enhanced laminar flow suggests that the rather than enhancement of a laminar flow behavior free stream disturbance results in early transition to turbulent stagnation point behavior. Excellent agreement is shown between enhanced laminar flow and turbulent flow behavior for high levels, e.g. 5% of free stream turbulence. Finally the blunt body turbulent stagnation results are shown to provide realistic heat transfer results for turbulent jet impingement problems.

  15. Metabolome of human gut microbiome is predictive of host dysbiosis

    SciTech Connect (OSTI)

    Larsen, Peter E.; Dai, Yang


    Background: Humans live in constant and vital symbiosis with a closely linked bacterial ecosystem called the microbiome, which influences many aspects of human health. When this microbial ecosystem becomes disrupted, the health of the human host can suffer; a condition called dysbiosis. The community compositions of human microbiomes also vary dramatically from individual to individual, and over time, making it difficult to uncover the underlying mechanisms linking the microbiome to human health. We propose that a microbiome’s interaction with its human host is not necessarily dependent upon the presence or absence of particular bacterial species, but instead is dependent on its community metabolome; an emergent property of the microbiome. Results: Using data from a previously published, longitudinal study of microbiome populations of the human gut, we extrapolated information about microbiome community enzyme profiles and metabolome models. Using machine learning techniques, we demonstrated that the aggregate predicted community enzyme function profiles and modeled metabolomes of a microbiome are more predictive of dysbiosis than either observed microbiome community composition or predicted enzyme function profiles. Conclusions: Specific enzyme functions and metabolites predictive of dysbiosis provide insights into the molecular mechanisms of microbiome–host interactions. The ability to use machine learning to predict dysbiosis from microbiome community interaction data provides a potentially powerful tool for understanding the links between the human microbiome and human health, pointing to potential microbiome-based diagnostics and therapeutic interventions.

  16. Metabolome of human gut microbiome is predictive of host dysbiosis

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

    Larsen, Peter E.; Dai, Yang


    Background: Humans live in constant and vital symbiosis with a closely linked bacterial ecosystem called the microbiome, which influences many aspects of human health. When this microbial ecosystem becomes disrupted, the health of the human host can suffer; a condition called dysbiosis. The community compositions of human microbiomes also vary dramatically from individual to individual, and over time, making it difficult to uncover the underlying mechanisms linking the microbiome to human health. We propose that a microbiome’s interaction with its human host is not necessarily dependent upon the presence or absence of particular bacterial species, but instead is dependent onmore » its community metabolome; an emergent property of the microbiome. Results: Using data from a previously published, longitudinal study of microbiome populations of the human gut, we extrapolated information about microbiome community enzyme profiles and metabolome models. Using machine learning techniques, we demonstrated that the aggregate predicted community enzyme function profiles and modeled metabolomes of a microbiome are more predictive of dysbiosis than either observed microbiome community composition or predicted enzyme function profiles. Conclusions: Specific enzyme functions and metabolites predictive of dysbiosis provide insights into the molecular mechanisms of microbiome–host interactions. The ability to use machine learning to predict dysbiosis from microbiome community interaction data provides a potentially powerful tool for understanding the links between the human microbiome and human health, pointing to potential microbiome-based diagnostics and therapeutic interventions.« less

  17. Human Resources | The Ames Laboratory

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

    Budget Human Resources The Human Resources function in NNSA is a vital partnership between all levels of NNSA management. It requires effective collaboration with the Service Center's Office of Human Capital Management Services. The Headquarters' Office of Human Capital Management Programs is organized into the following five divisions. Policy and Planning The Policy and Planning Division will be responsible for the development, implementation, and oversight of, human resources management

  18. Human Reliability Program Handbook

    Broader source: [DOE]

    The Human Reliability Program is a security and safety reliability program designed to ensure that individuals who occupy positions affording access to certain materials, nuclear explosive devices, facilities, and programs meet the highest standards of reliability and physical and mental suitability.

  19. SU-E-T-560: Commissioning An HDR Freiburg Flap Applicator for Skin Lesion Treatment

    SciTech Connect (OSTI)

    Dou, K; Li, B; Lerma, F; Aroumougame, V; Sarfaraz, M; Laser, B; Jacobs, M


    Purpose: Flexible Freiburg flap used with high dose rate afterloaders is easy to cut into any size for any body site and to dwell with a precise source position, conforms to curved skin surface and then to the planned target. However, unlike intracavity or interstitial situations, incomplete scatter environment due to flap applicators exposed to air might lead to dose difference between the delivered and planned. This research is focused on the dose deviation of incomplete scatter versus full scatter. Methods: A 12x12 cm of Freiburg flap applicator was used for the validation. A Nucletron Oncentra Brachy Ver. 4.3 treatment planning system (TPS) was used for treatment planning. However, no heterogeneity correction incorporated into the brachytherap TPS needs to be considered. A Philips Brilliance CT Big Bore was employed for CT scan. Radiation was delivered using a Nucletron HDR remote afterloader system. A 10cm bolus was used to cover the flap for obtaining a full scatter. An OSL, ion chamber, and Gafchromic EBT2 film were used for commissioning the flap applicator. Results: The applicator calibration at 5mm depth was performed using an OSL dosimeter. Applicator source dwelling positions with 1D and 2D array exposed to and recorded by Gafchromic EBT2 film showed an agreement within 1mm. 1D array of Freiburg flap exhibited 4.2% cooler in dose with incomplete scatter than full scatter. 2D array showed 7.1% lower in dose for incomplete scatter than full scatter. The deviation was found more than 10% beyond 8cm in depth. Conclusion: Significant dose deviation caused by the incomplete scatter environment was found to be 7.1% at 1cm depth. This deviation was increased with increasing depth. The inaccuracy resulted from the incomplete scatter can be fixed by either placing a bolus on the top of the flap or making the plan at least 7% hotter.

  20. A parametric study of the drift-tearing mode using an extended-magnetohydrodynamic model

    SciTech Connect (OSTI)

    King, Jacob R.; Kruger, S. E.


    The linear, collisional, constant-ψ drift-tearing mode is analyzed for different regimes of the plasma-β, ion-skin-depth parameter space with an unreduced, extended-magnetohydrodynamic model. Here, new dispersion relations are found at moderate plasma β and previous drift-tearing results are classified as applicable at small plasma β.

  1. A parametric study of the drift-tearing mode using an extended-magnetohydrodynamic model

    SciTech Connect (OSTI)

    King, J. R.; Kruger, S. E.


    The linear, collisional, constant-ψ drift-tearing mode is analyzed for different regimes of the plasma-β, ion-skin-depth parameter space with an unreduced, extended-magnetohydrodynamic model. New dispersion relations are found at moderate plasma β and previous drift-tearing results are classified as applicable at small plasma β.

  2. Hyaluronan in human malignancies

    SciTech Connect (OSTI)

    Sironen, R.K.; Department of Pathology, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio ; Tammi, M.; Tammi, R.; Auvinen, P.K.; Anttila, M.; Department of Gynecology and Obstetrics, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio ; Kosma, V-M.


    Hyaluronan, a major macropolysaccharide in the extracellular matrix of connective tissues, is intimately involved in the biology of cancer. Hyaluronan accumulates into the stroma of various human tumors and modulates intracellular signaling pathways, cell proliferation, motility and invasive properties of malignant cells. Experimental and clinicopathological evidence highlights the importance of hyaluronan in tumor growth and metastasis. A high stromal hyaluronan content is associated with poorly differentiated tumors and aggressive clinical behavior in human adenocarcinomas. Instead, the squamous cell carcinomas and malignant melanomas tend to have a reduced hyaluronan content. In addition to the stroma-cancer cell interaction, hyaluronan can influence stromal cell recruitment, tumor angiogenesis and epithelial-mesenchymal transition. Hyaluronan receptors, hyaluronan synthases and hyaluronan degrading enzymes, hyaluronidases, are involved in the modulation of cancer progression, depending on the tumor type. Furthermore, intracellular signaling and angiogenesis are affected by the degradation products of hyaluronan. Hyaluronan has also therapeutic implications since it is involved in multidrug resistance.

  3. Human Factors Engineering Analysis Tool

    Energy Science and Technology Software Center (OSTI)


    HFE-AT is a human factors engineering (HFE) software analysis tool (AT) for human-system interface design of process control systems, and is based primarily on NUREG-0700 guidance.

  4. Global Warming and Human Health

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

    American Geophysical Union Global Warming and Human Health WHEN: Jul 27, 2015 5:30 PM - ... Event Description The main reason we are concerned about human-induced climate change is ...

  5. 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 risks to human subjects in research are minimal and to provide protection with respect to the rights and welfare of research subjects. The Oak Ridge Institute for Science and Education (ORISE) administers the Oak Ridge Sitewide Institutional Review Board (ORSIRB) and manages the ORISE Human Subjects website. The

  6. Scientists model brain structure to help computers recognize...

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

    The team tried developing a computer model based on human neural structure and function, ... Introspectively, we know that the human brain solves this problem very well. We only have ...

  7. Protection against 2-chloroethyl ethyl sulfide (CEES) - induced cytotoxicity in human keratinocytes by an inducer of the glutathione detoxification pathway

    SciTech Connect (OSTI)

    Abel, Erika L.; Bubel, Jennifer D.; Simper, Melissa S.; Powell, Leslie; McClellan, S. Alex; Andreeff, Michael; MacLeod, Michael C.; DiGiovanni, John


    Sulfur mustard (SM or mustard gas) was first used as a chemical warfare agent almost 100 years ago. Due to its toxic effects on the eyes, lungs, and skin, and the relative ease with which it may be synthesized, mustard gas remains a potential chemical threat to the present day. SM exposed skin develops fluid filled bullae resulting from potent cytotoxicity of cells lining the basement membrane of the epidermis. Currently, there are no antidotes for SM exposure; therefore, chemopreventive measures for first responders following an SM attack are needed. Glutathione (GSH) is known to have a protective effect against SM toxicity, and detoxification of SM is believed to occur, in part, via GSH conjugation. Therefore, we screened 6 potential chemopreventive agents for ability to induce GSH synthesis and protect cultured human keratinocytes against the SM analog, 2-chloroethyl ethyl sulfide (CEES). Using NCTC2544 human keratinocytes, we found that both sulforaphane and methyl-2-cyano-3,12-dioxooleana-1,9-dien-28-oate (CDDO-Me) stimulated nuclear localization of Nrf2 and induced expression of the GSH synthesis gene, GCLM. Additionally, we found that treatment with CDDO-Me elevated reduced GSH content of NCTC2544 cells and preserved their viability by {approx} 3-fold following exposure to CEES. Our data also suggested that CDDO-Me may act additively with 2,6-dithiopurine (DTP), a nucleophilic scavenging agent, to increase the viability of keratinocytes exposed to CEES. These results suggest that CDDO-Me is a promising chemopreventive agent for SM toxicity in the skin. - Highlights: > CDDO-Me treatment increased intracellular GSH in human keratinocytes. > CDDO-Me increased cell viability following exposure to the half-mustard, CEES. > The cytoprotective effect of CDDO-Me was likely due to scavenging with endogenous GSH.

  8. Protection of Human Research Subjects

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


    The Order establishes DOE-specific policy and principles for the protection of human subjects involved in DOE research, and DOE procedures and responsibilities for implementing the policy and requirements set forth in Title 45 Code of Federal Regulations (CFR) Part 46, Protection of Human Subjects, and 10 CFR Part 745, Protection of Human Subjects. Supersedes DOE O 443.1B.

  9. Human Capital Management Accountability Program

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


    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.

  10. Ecological succession and viability of human-associated microbiota on restroom surfaces

    SciTech Connect (OSTI)

    Gibbons, Sean M.; Schwartz, Tara; Fouquier, Jennifer; Mitchell, Michelle; Sangwan, Naseer; Gilbert, Jack A.; Kelley, Scott T.; Elkins, C. A.


    Human-associated bacteria dominate the built environment (BE). Following decontamination of floors, toilet seats, and soap dispensers in four public restrooms, in situ bacterial communities were characterized hourly, daily, and weekly to determine their successional ecology. The viability of cultivable bacteria, following the removal of dispersal agents (humans), was also assessed hourly. A late-successional community developed within 5 to 8 h on restroom floors and showed remarkable stability over weeks to months. Despite late-successional dominance by skin- and outdoor-associated bacteria, the most ubiquitous organisms were predominantly gut-associated taxa, which persisted following exclusion of humans. Staphylococcus represented the majority of the cultivable community, even after several hours of human exclusion. Methicillin-resistant Staphylococcus aureus (MRSA)-associated virulence genes were found on floors but were not present in assembled Staphylococcus pan-genomes. Viral abundances, which were predominantly enterophages, human papilloma virus, and herpesviruses, were significantly correlated with bacterial abundances and showed an unexpectedly low virus-to-bacterium ratio in surface-associated samples, suggesting that bacterial hosts are mostly dormant on BE surfaces.