National Library of Energy BETA

Sample records for human skin cells

  1. 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.

    2013-12-01

    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 skin cancer cells by inhibition of cAMP and PGE{sub 2}. siRNA knockdown of ?-catenin or COX-2 reduces the viability of cancer cells.

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

    SciTech Connect (OSTI)

    Hughes, Michael F.; Edwards, Brenda C.

    2010-07-15

    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 in vitro dermal absorption data for risk assessment.

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

    Office of Scientific and Technical Information (OSTI)

    (Journal Article) | DOE PAGES DOE PAGES Search Results Accepted Manuscript: Athletic equipment microbiota are shaped by interactions with human skin Title: Athletic equipment microbiota are shaped by interactions with human skin 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

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

    Office of Scientific and Technical Information (OSTI)

    (Journal Article) | SciTech Connect Athletic equipment microbiota are shaped by interactions with human skin Citation Details In-Document Search Title: Athletic equipment microbiota are shaped by interactions with human skin 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.

  5. 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.

    2010-08-01

    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.

  6. 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.

    2012-12-01

    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.

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

    SciTech Connect (OSTI)

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

    2015-05-01

    Outside the protection of earths 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 skins 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.

  8. 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.

    2011-09-15

    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.

  9. 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.

    2012-02-15

    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 telomerase activity was found in NFK. ? Increased intracellular superoxide levels and reduced cell growth was seen in both. ? PCB153 may damage telomerase expressing cells like stem cells.

  10. 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.

    2014-07-29

    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.

  11. 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.

    2014-11-15

    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 ?L 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 diffusion model predictions. We conclude that even small exposures to VOCs temporarily alter skin permeability.

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

    Office of Scientific and Technical Information (OSTI)

    Response of Human Lung Epithelial Cells to Engineered Nanoparticles. Citation Details In-Document Search Title: Response of Human Lung Epithelial Cells to Engineered Nanoparticles. ...

  13. Molecular clocks control mutation rate in human cells

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

    in human cells Mutational processes may be responsible for a large proportion of human cancer, contribute to human ageing December 1, 2015 Cancer and ageing could be predetermined...

  14. 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.

    2014-03-18

    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.

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

    SciTech Connect (OSTI)

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

    2005-05-13

    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.

  16. Molecular clocks control mutation rate in human cells

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

    and contribute to human ageing. November 20, 2015 In research reported in the journal Nature Genetics, two clock-like mutational processes have been found in human cells and the...

  17. Neutrons provide new insights into human cell behavior

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

    Neutrons provide new insights into human cell behavior Community Connections: Your link to news and opportunities from Los Alamos National Laboratory Latest Issue: Dec. 2015-Jan....

  18. Bio-inspired nanocomposite assemblies as smart skin components. (Technical

    Office of Scientific and Technical Information (OSTI)

    Report) | SciTech Connect Bio-inspired nanocomposite assemblies as smart skin components. Citation Details In-Document Search Title: Bio-inspired nanocomposite assemblies as smart skin components. There is national interest in the development of sophisticated materials that can automatically detect and respond to chemical and biological threats without the need for human intervention. In living systems, cell membranes perform such functions on a routine basis, detecting threats,

  19. Comparative mutagenesis of human cells in vivo and in vitro

    SciTech Connect (OSTI)

    Thilly, W.G.

    1992-05-01

    This report discusses measuring methods of point mutations; high density cell cultures for low dose studies; measurement and sequence determination of mutations in DNA; the mutational spectra of styrene oxide and ethlyene oxide in TK-6 cells; mutational spectrum of Cr in human lymphoblast cells; mutational spectra of radon in TK-6 cells; and the mutational spectra of smokeless tobacco. (CBS)

  20. Continuous human cell lines and method of making same

    DOE Patents [OSTI]

    Stampfer, Martha R. (Oakland, CA)

    1989-01-01

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

  1. Continuous human cell lines and method of making same

    DOE Patents [OSTI]

    Stampfer, M.R.

    1985-07-01

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

  2. Fluorescent tracking of nickel ions in human cultured cells (Journal

    Office of Scientific and Technical Information (OSTI)

    Article) | SciTech Connect Fluorescent tracking of nickel ions in human cultured cells Citation Details In-Document Search Title: Fluorescent tracking of nickel ions in human cultured cells The carcinogenic activity of various nickel (Ni) compounds is likely dependent upon their ability to enter cells and elevate intracellular levels of Ni ions. Water-insoluble Ni compounds such as NiS and Ni{sub 3}S{sub 2} were shown in vitro to enter cells by phagocytosis and potently induce tumors in

  3. Human Papillomavirus (HPV) Infection in Squamous Cell Carcinomas Arising

    Office of Scientific and Technical Information (OSTI)

    From the Oropharynx: Detection of HPV DNA and p16 Immunohistochemistry as Diagnostic and Prognostic Indicators-A Pilot Study (Journal Article) | SciTech Connect Human Papillomavirus (HPV) Infection in Squamous Cell Carcinomas Arising From the Oropharynx: Detection of HPV DNA and p16 Immunohistochemistry as Diagnostic and Prognostic Indicators-A Pilot Study Citation Details In-Document Search Title: Human Papillomavirus (HPV) Infection in Squamous Cell Carcinomas Arising From the Oropharynx:

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

    Office of Scientific and Technical Information (OSTI)

    (Conference) | SciTech Connect Response of Human Lung Epithelial Cells to Engineered Nanoparticles. Citation Details In-Document Search Title: Response of Human Lung Epithelial Cells to Engineered Nanoparticles. Abstract not provided. Authors: Bachand, George ; Bachand, Marlene ; Brozik, Susan Marie ; Achyuthan, Komandoor ; Allen, Amy Publication Date: 2011-10-01 OSTI Identifier: 1120230 Report Number(s): SAND2011-7265C 482189 DOE Contract Number: DE-AC04-94AL85000 Resource Type: Conference

  5. Increasing cell culture population doublings for long-term growth of finite life span human cell cultures

    DOE Patents [OSTI]

    Stampfer, Martha R; Garbe, James C

    2015-02-24

    Cell culture media formulations for culturing human epithelial cells are herein described. Also described are methods of increasing population doublings in a cell culture of finite life span human epithelial cells and prolonging the life span of human cell cultures. Using the cell culture media disclosed alone and in combination with addition to the cell culture of a compound associated with anti-stress activity achieves extended growth of pre-stasis cells and increased population doublings and life span in human epithelial cell cultures.

  6. Clock-like mutational processes in human somatic cells

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

    Alexandrov, Ludmil B.; Jones, Philip H.; Wedge, David C.; Sale, Julian E.; Campbell, Peter J.; Nik-Zainal, Serena; Stratton, Michael R.

    2015-11-09

    During the course of a lifetime, somatic cells acquire mutations. Different mutational processes may contribute to the mutations accumulated in a cell, with each imprinting a mutational signature on the cell's genome. Some processes generate mutations throughout life at a constant rate in all individuals, and the number of mutations in a cell attributable to these processes will be proportional to the chronological age of the person. Using mutations from 10,250 cancer genomes across 36 cancer types, we investigated clock-like mutational processes that have been operating in normal human cells. Two mutational signatures show clock-like properties. Both exhibit different mutationmore » rates in different tissues. However, their mutation rates are not correlated, indicating that the underlying processes are subject to different biological influences. For one signature, the rate of cell division may influence its mutation rate. This paper provides the first survey of clock-like mutational processes operating in human somatic cells.« less

  7. Trichodermin induces cell apoptosis through mitochondrial dysfunction and endoplasmic reticulum stress in human chondrosarcoma cells

    SciTech Connect (OSTI)

    Su, Chen-Ming; Wang, Shih-Wei; Lee, Tzong-Huei; Tzeng, Wen-Pei; Hsiao, Che-Jen; Liu, Shih-Chia; Tang, Chih-Hsin

    2013-10-15

    Chondrosarcoma is the second most common primary bone tumor, and it responds poorly to both chemotherapy and radiation treatment. Nalanthamala psidii was described originally as Myxosporium in 1926. This is the first study to investigate the anti-tumor activity of trichodermin (trichothec-9-en-4-ol, 12,13-epoxy-, acetate), an endophytic fungal metabolite from N. psidii against human chondrosarcoma cells. We demonstrated that trichodermin induced cell apoptosis in human chondrosarcoma cell lines (JJ012 and SW1353 cells) instead of primary chondrocytes. In addition, trichodermin triggered endoplasmic reticulum (ER) stress protein levels of IRE1, p-PERK, GRP78, and GRP94, which were characterized by changes in cytosolic calcium levels. Furthermore, trichodermin induced the upregulation of Bax and Bid, the downregulation of Bcl-2, and the dysfunction of mitochondria, which released cytochrome c and activated caspase-3 in human chondrosarcoma. In addition, animal experiments illustrated reduced tumor volume, which led to an increased number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells and an increased level of cleaved PARP protein following trichodermin treatment. Together, this study demonstrates that trichodermin is a novel anti-tumor agent against human chondrosarcoma cells both in vitro and in vivo via mitochondrial dysfunction and ER stress. - Highlights: Trichodermin induces chondrosarcoma apoptosis. ER stress is involved in trichodermin-induced cell death. Trichodermin induces chondrosarcoma death in vivo.

  8. Raman Spectroscopy of DNA Packaging in Individual Human Sperm Cells distinguishes Normal from Abnormal Cells

    SciTech Connect (OSTI)

    Huser, T; Orme, C; Hollars, C; Corzett, M; Balhorn, R

    2009-03-09

    Healthy human males produce sperm cells of which about 25-40% have abnormal head shapes. Increases in the percentage of sperm exhibiting aberrant sperm head morphologies have been correlated with male infertility, and biochemical studies of pooled sperm have suggested that sperm with abnormal shape may contain DNA that has not been properly repackaged by protamine during spermatid development. We have used micro-Raman spectroscopy to obtain Raman spectra from individual human sperm cells and examined how differences in the Raman spectra of sperm chromatin correlate with cell shape. We show that Raman spectra of individual sperm cells contain vibrational marker modes that can be used to assess the efficiency of DNA-packaging for each cell. Raman spectra obtained from sperm cells with normal shape provide evidence that DNA in these sperm is very efficiently packaged. We find, however, that the relative protein content per cell and DNA packaging efficiencies are distributed over a relatively wide range for sperm cells with both normal and abnormal shape. These findings indicate that single cell Raman spectroscopy should be a valuable tool in assessing the quality of sperm cells for in-vitro fertilization.

  9. Fulvestrant radiosensitizes human estrogen receptor-positive breast cancer cells

    SciTech Connect (OSTI)

    Wang, Jing; Department of Oncology, Affiliated Hospital of Qingdao University Medical College, Shandong Province ; Yang, Qifeng; Haffty, Bruce G.; Li, Xiaoyan; Moran, Meena S.

    2013-02-08

    Highlights: ? Fulvestrant radiosensitizes MCF-7 cells. ? Fulvestrant increases G1 arrest and decreases S phase in MCF-7 cells. ? Fulvestrant down-regulates DNA-PKcs and RAD51 in MCF-7 cells. -- Abstract: The optimal sequencing for hormonal therapy and radiation are yet to be determined. We utilized fulvestrant, which is showing promise as an alternative to other agents in the clinical setting of hormonal therapy, to assess the cellular effects of concomitant anti-estrogen therapy (fulvestrant) with radiation (F + RT). This study was conducted to assess the effects of fulvestrant alone vs. F + RT on hormone-receptor positive breast cancer to determine if any positive or negative combined effects exist. The effects of F + RT on human breast cancer cells were assessed using MCF-7 clonogenic and tetrazolium salt colorimetric (MTT) assays. The assays were irradiated with a dose of 0, 2, 4, 6 Gy fulvestrant. The effects of F + RT vs. single adjuvant treatment alone on cell-cycle distribution were assessed using flow cytometry; relative expression of repair proteins (Ku70, Ku80, DNA-PKcs, Rad51) was assessed using Western Blot analysis. Cell growth for radiation alone vs. F + RT was 0.885 0.013 vs. 0.622 0.029 @2 Gy, 0.599 0.045 vs. 0.475 0.054 @4 Gy, and 0.472 0.021 vs. 0.380 0.018 @6 Gy RT (p = 0.003). While irradiation alone induced G2/M cell cycle arrest, the combination of F + RT induced cell redistribution in the G1 phase and produced a significant decrease in the proportion of cells in G2 phase arrest and in the S phase in breast cancer cells (p < 0.01). Furthermore, levels of repair proteins DNA-PKcs and Rad51 were significantly decreased in the cells treated with F + RT compared with irradiation alone. F + RT leads to a decrease in the surviving fraction, increased cell cycle arrest, down regulating of nonhomologous repair protein DNA-PKcs and homologous recombination repair protein RAD51. Thus, our findings suggest that F + RT increases breast cancer cell radiosensitivity compared with radiation alone. These findings have salient implications for designing clinical trials using fulvestrant and radiation therapy.

  10. Selective destruction of cells infected with human immunodeficiency virus

    DOE Patents [OSTI]

    Keener, William K.; Ward, Thomas E.

    2003-09-30

    Compositions and methods for selectively killing a cell containing a viral protease are disclosed. The composition is a variant of a protein synthesis inactivating toxin wherein a viral protease cleavage site is interposed between the A and B chains. The variant of the type II ribosome-inactivating protein is activated by digestion of the viral protease cleavage site by the specific viral protease. The activated ribosome-inactivating protein then kills the cell by inactivating cellular ribosomes. A preferred embodiment of the invention is specific for human immunodeficiency virus (HIV) and uses ricin as the ribosome-inactivating protein. In another preferred embodiment of the invention, the variant of the ribosome-inactivating protein is modified by attachment of one or more hydrophobic agents. The hydrophobic agent facilitates entry of the variant of the ribosome-inactivating protein into cells and can lead to incorporation of the ribosome-inactivating protein into viral particles. Still another preferred embodiment of the invention includes a targeting moiety attached to the variants of the ribosome-inactivating protein to target the agent to HIV infectable cells.

  11. Selective Destruction Of Cells Infected With The Human Immunodeficiency Virus

    DOE Patents [OSTI]

    Keener, William K.; Ward, Thomas E.

    2006-03-28

    Compositions and methods for selectively killing a cell containing a viral protease are disclosed. The composition is a varient of a protein synthesis inactivating toxin wherein a viral protease cleavage site is interposed between the A and B chains. The variant of the type II ribosome-inactivating protein is activated by digestion of the viral protease cleavage site by the specific viral protease. The activated ribosome-inactivating protein then kills the cell by inactivating cellular ribosomes. A preferred embodiment of the invention is specific for human immunodeficiency virus (HIV) and uses ricin as the ribosome-inactivating protein. In another preferred embodiment of the invention, the variant of the ribosome-inactivating protein is modified by attachment of one or more hydrophobic agents. The hydrophobic agent facilitates entry of the variant of the ribosome-inactivating protein into cells and can lead to incorporation of the ribosome-inactivating protein into viral particles. Still another preferred embodiment of the invention includes a targeting moiety attached to the variants of the ribosome-inactivating protein to target the agent to HIV infectable cells.

  12. Cell lines for the production of monoclonal antibodies to human glycophorin A

    DOE Patents [OSTI]

    Bigbee, William L. (Livermore, CA); Fong, Stella S. N. (Del Mar, CA); Jensen, Ronald H. (Livermore, CA); Vanderlaan, Martin (San Ramon, CA); Langlois, Richard G. (Livermore, CA)

    1988-01-01

    Cloned mouse hybridoma cell lines have been established which continuously produce antibodies that differentiate between the M and N forms of human glycophorin A. These antibodies have potential application as human blood group reagents, as markers for terminally differentiated erythroid cells and as immunofluorescent labels of somatically variant human erythrocytes.

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

    SciTech Connect (OSTI)

    Jian Li

    2012-11-07

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

  14. Over-expression of human endosulfatase-1 exacerbates cadmium-induced injury to transformed human lung cells in vitro

    SciTech Connect (OSTI)

    Zhang, Huiying; Department of Environmental and Molecular Toxicology, College of Agriculture and Life Sciences, NC State University, Raleigh, NC 27695 ; Newman, Donna R.; Bonner, James C.; Sannes, Philip L.

    2012-11-15

    Environmental exposure to cadmium is known to cause damage to alveolar epithelial cells of the lung, impair their capacity to repair, and result in permanent structural alterations. Cell surface heparan sulfate proteoglycans (HSPGs) can modulate cell responses to injury through their interactions with soluble effector molecules. These interactions are often sulfate specific, and the removal of sulfate groups from HS side chains could be expected to influence cellular injury, such as that caused by exposure to cadmium. The goal of this study was to define the role 6-O-sulfate plays in cellular responses to cadmium exposure in two pulmonary epithelial cancer cell lines (H292 and A549) and in normal human primary alveolar type II (hAT2) cells. Sulfate levels were modified by transduced transient over-expression of 6-O-endosulfatase (HSulf-1), a membrane-bound enzyme which specifically removes 6-O-sulfate groups from HSPG side chains. Results showed that cadmium decreased cell viability and activated apoptosis pathways at low concentrations in hAT2 cells but not in the cancer cells. HSulf-1 over-expression, on the contrary, decreased cell viability and activated apoptosis pathways in H292 and A549 cells but not in hAT2 cells. When combined with cadmium, HSulf-1 over-expression further decreased cell viability and exacerbated the activation of apoptosis pathways in the transformed cells but did not add to the toxicity in hAT2 cells. The finding that HSulf-1 sensitizes these cancer cells and intensifies the injury induced by cadmium suggests that 6-O-sulfate groups on HSPGs may play important roles in protection against certain environmental toxicants, such as heavy metals. -- Highlights: ? Primary human lung alveolar type 2 (hAT2) cells and H292 and A549 cells were used. ? Cadmium induced apoptosis in hAT2 cells but not in H292 or A549 cells. ? HSulf-1exacerbates apoptosis induced by cadmium in H292 and A549 but not hAT2 cells.

  15. Mortalin antibody-conjugated quantum dot transfer from human mesenchymal stromal cells to breast cancer cells requires cellcell interaction

    SciTech Connect (OSTI)

    Pietil, Mika; Lehenkari, Petri; Kuvaja, Paula; Kaakinen, Mika; Kaul, Sunil C.; Wadhwa, Renu; Uemura, Toshimasa

    2013-11-01

    The role of tumor stroma in regulation of breast cancer growth has been widely studied. However, the details on the type of heterocellular cross-talk between stromal and breast cancer cells (BCCs) are still poorly known. In the present study, in order to investigate the intercellular communication between human mesenchymal stromal cells (hMSCs) and breast cancer cells (BCCs, MDA-MB-231), we recruited cell-internalizing quantum dots (i-QD) generated by conjugation of cell-internalizing anti-mortalin antibody and quantum dots (QD). Co-culture of illuminated and color-coded hMSCs (QD655) and BCCs (QD585) revealed the intercellular transfer of QD655 signal from hMSCs to BCCs. The amount of QD double positive BCCs increased gradually within 48 h of co-culture. We found prominent intercellular transfer of QD655 in hanging drop co-culture system and it was non-existent when hMSCs and BBCs cells were co-cultured in trans-well system lacking imminent cellcell contact. Fluorescent and electron microscope analyses also supported that the direct cell-to-cell interactions may be required for the intercellular transfer of QD655 from hMSCs to BCCs. To the best of our knowledge, the study provides a first demonstration of transcellular crosstalk between stromal cells and BCCs that involve direct contact and may also include a transfer of mortalin, an anti-apoptotic and growth-promoting factor enriched in cancer cells.

  16. Accelerated cellular senescence phenotype of GAPDH-depleted human lung carcinoma cells

    SciTech Connect (OSTI)

    Phadke, Manali; Krynetskaia, Natalia; Mishra, Anurag; Krynetskiy, Evgeny; Jayne Haines Center for Pharmacogenomics, Temple University School of Pharmacy, Philadelphia, PA 19140

    2011-07-29

    Highlights: {yields} We examined the effect of glyceraldehyde 3-phosphate (GAPDH) depletion on proliferation of human carcinoma A549 cells. {yields} GAPDH depletion induces accelerated senescence in tumor cells via AMPK network, in the absence of DNA damage. {yields} Metabolic and genetic rescue experiments indicate that GAPDH has regulatory functions linking energy metabolism and cell cycle. {yields} Induction of senescence in LKB1-deficient lung cancer cells via GAPDH depletion suggests a novel strategy to control tumor cell proliferation. -- Abstract: Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is a pivotal glycolytic enzyme, and a signaling molecule which acts at the interface between stress factors and the cellular apoptotic machinery. Earlier, we found that knockdown of GAPDH in human carcinoma cell lines resulted in cell proliferation arrest and chemoresistance to S phase-specific cytotoxic agents. To elucidate the mechanism by which GAPDH depletion arrests cell proliferation, we examined the effect of GAPDH knockdown on human carcinoma cells A549. Our results show that GAPDH-depleted cells establish senescence phenotype, as revealed by proliferation arrest, changes in morphology, SA-{beta}-galactosidase staining, and more than 2-fold up-regulation of senescence-associated genes DEC1 and GLB1. Accelerated senescence following GAPDH depletion results from compromised glycolysis and energy crisis leading to the sustained AMPK activation via phosphorylation of {alpha} subunit at Thr172. Our findings demonstrate that GAPDH depletion switches human tumor cells to senescent phenotype via AMPK network, in the absence of DNA damage. Rescue experiments using metabolic and genetic models confirmed that GAPDH has important regulatory functions linking the energy metabolism and the cell cycle networks. Induction of senescence in LKB1-deficient non-small cell lung cancer cells via GAPDH depletion suggests a novel strategy to control tumor cell proliferation.

  17. Analysis of differential protein expression in normal and neoplastic human breast epithelial cell lines

    SciTech Connect (OSTI)

    Williams, K.; Chubb, C.; Huberman, E.; Giometti, C.S.

    1997-07-01

    High resolution two dimensional get electrophoresis (2DE) and database analysis was used to establish protein expression patterns for cultured normal human mammary epithelial cells and thirteen breast cancer cell lines. The Human Breast Epithelial Cell database contains the 2DE protein patterns, including relative protein abundances, for each cell line, plus a composite pattern that contains all the common and specifically expressed proteins from all the cell lines. Significant differences in protein expression, both qualitative and quantitative, were observed not only between normal cells and tumor cells, but also among the tumor cell lines. Eight percent of the consistently detected proteins were found in significantly (P < 0.001) variable levels among the cell lines. Using a combination of immunostaining, comigration with purified protein, subcellular fractionation, and amino-terminal protein sequencing, we identified a subset of the differentially expressed proteins. These identified proteins include the cytoskeletal proteins actin, tubulin, vimentin, and cytokeratins. The cell lines can be classified into four distinct groups based on their intermediate filament protein profile. We also identified heat shock proteins; hsp27, hsp60, and hsp70 varied in abundance and in some cases in the relative phosphorylation levels among the cell lines. Finally, we identified IMP dehydrogenase in each of the cell lines, and found the levels of this enzyme in the tumor cell lines elevated 2- to 20-fold relative to the levels in normal cells.

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

    DOE Patents [OSTI]

    Vanderlaan, Martin (San Ramon, CA); Bigbee, William L. (Livermore, CA); Jensen, Ronald H. (Livermore, CA); Fong, Stella S. N. (San Diego, CA); Langlois, Richard G. (Livermore, CA)

    1988-01-01

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

  19. Comparison of direct exposure of human lung cells to modern engine exhaust

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

    partricles | Department of Energy direct exposure of human lung cells to modern engine exhaust partricles Comparison of direct exposure of human lung cells to modern engine exhaust partricles 2003 DEER Conference Presentation: Oak Ridge National Laboratory PDF icon 2003_deer_storey.pdf More Documents & Publications Pro-Inflammatory Cytokine Responses to Exposure to Diesel Soot Relationship Between Composition and Toxicity of Engine Emissions Comparative Toxicity of Combined Particle and

  20. Soluble interleukin 2 receptors are released from activated human lymphoid cells in vitro

    SciTech Connect (OSTI)

    Rubin, L.A.; Kurman, C.C.; Fritz, M.E.; Biddison, W.E.; Boutin, B.; Yarchoan, R.; Nelson, D.L.

    1985-11-01

    With the use of an enzyme-linked immunoabsorbent assay to measure soluble human interleukin 2 receptors (IL 2R), certain human T cell leukemia virus I (HTLV I)-positive T cell lines were found to spontaneously release large quantities of IL 2R into culture supernatants. This was not found with HTLV I-negative and IL 2 independent T cell lines, and only one of seven B cell-derived lines examined produced small amounts of IL 2R. In addition to this constitutive production of soluble IL 2R by certain cell lines, normal human peripheral blood mononuclear cells (PBMC) could be induced to release soluble IL 2R by plant lectins, the murine monoclonal antibody OKT3, tetanus toxoid, and allogeneic cells. Such activated cells also expressed cellular IL 2R measurable in detergent solubilized cell extracts. The generation of cellular and supernatant IL 2R was: dependent on cellular activation, rapid, radioresistant (3000 rad), and inhibited by cycloheximide treatment. NaDodSO4-polyacrylamide gel electrophoresis analysis of soluble IL 2R demonstrated molecules of apparent Mr = 35,000 to 40,000, and 45,000 to 50,000, respectively, somewhat smaller than the mature surface receptor on these cells. The release of soluble IL 2R appears to be a characteristic marker of T lymphocyte activation and might serve an immunoregulatory function during both normal and abnormal cell growth and differentiation.

  1. Transcriptome analysis of the human T lymphocyte cell line Jurkat and human peripheral blood mononuclear cells exposed to deoxynivalenol (DON): New mechanistic insights

    SciTech Connect (OSTI)

    Katika, Madhumohan R.; Department of Health Risk Analysis and Toxicology, Maastricht University; Netherlands Toxicogenomics Centre ; Hendriksen, Peter J.M.; Netherlands Toxicogenomics Centre ; Shao, Jia; Department of Health Risk Analysis and Toxicology, Maastricht University; Netherlands Toxicogenomics Centre ; Loveren, Henk van; National Institute for Public Health and the Environment , Bilthoven; Netherlands Toxicogenomics Centre ; Peijnenburg, Ad; Netherlands Toxicogenomics Centre

    2012-10-01

    Deoxynivalenol (DON) or vomitoxin is a commonly encountered type-B trichothecene mycotoxin, produced by Fusarium species predominantly found in cereals and grains. DON is known to exert toxic effects on the gastrointestinal, reproductive and neuroendocrine systems, and particularly on the immune system. Depending on dose and exposure time, it can either stimulate or suppress immune function. The main objective of this study was to obtain a deeper insight into DON-induced effects on lymphoid cells. For this, we exposed the human T-lymphocyte cell line Jurkat and human peripheral blood mononuclear cells (PBMCs) to various concentrations of DON for various times and examined gene expression changes by DNA microarray analysis. Jurkat cells were exposed to 0.25 and 0.5 ?M DON for 3, 6 and 24 h. Biological interpretation of the microarray data indicated that DON affects various processes in these cells: It upregulates genes involved in ribosome structure and function, RNA/protein synthesis and processing, endoplasmic reticulum (ER) stress, calcium-mediated signaling, mitochondrial function, oxidative stress, the NFAT and NF-?B/TNF-? pathways, T cell activation and apoptosis. The effects of DON on the expression of genes involved in ER stress, NFAT activation and apoptosis were confirmed by qRT-PCR. Other biochemical experiments confirmed that DON activates calcium-dependent proteins such as calcineurin and M-calpain that are known to be involved in T cell activation and apoptosis. Induction of T cell activation was also confirmed by demonstrating that DON activates NFATC1 and induces its translocation from the cytoplasm to the nucleus. For the gene expression profiling of PBMCs, cells were exposed to 2 and 4 ?M DON for 6 and 24 h. Comparison of the Jurkat microarray data with those obtained with PBMCs showed that most of the processes affected by DON in the Jurkat cell line were also affected in the PBMCs. -- Highlights: ? The human T cell line Jurkat and human PBMCs were exposed to DON. ? Whole-genome microarray experiments were performed. ? Microarray data indicates that DON affects ribosome and RNA/protein synthesis. ? DON treatment induces ER stress, calcium mediated signaling, NFAT and NF-?B. ? Exposure to DON induces T cell activation, oxidative stress and apoptosis.

  2. Generation of knock-in primary human T cells using Cas9 ribonucleoproteins

    SciTech Connect (OSTI)

    Schumann, Kathrin; Lin, Steven; Boyer, Eric; Simeonov, Dimitre R.; Subramaniam, Meena; Gate, Rachel E.; Haliburton, Genevieve E.; Ye, Chun J.; Bluestone, Jeffrey A.; Doudna, Jennifer A.; Marson, Alexander

    2015-07-27

    T-cell genome engineering holds great promise for cell-based therapies for cancer, HIV, primary immune deficiencies, and autoimmune diseases, but genetic manipulation of human T cells has been challenging. Improved tools are needed to efficiently knock out genes and knock in targeted genome modifications to modulate T-cell function and correct disease-associated mutations. CRISPR/Cas9 technology is facilitating genome engineering in many cell types, but in human T cells its efficiency has been limited and it has not yet proven useful for targeted nucleotide replacements. Here we report efficient genome engineering in human CD4+ T cells using Cas9:single-guide RNA ribonucleoproteins (Cas9 RNPs). Cas9 RNPs allowed ablation of CXCR4, a coreceptor for HIV entry. Cas9 RNP electroporation caused up to ~40% of cells to lose high-level cell-surface expression of CXCR4, and edited cells could be enriched by sorting based on low CXCR4 expression. Importantly, Cas9 RNPs paired with homology-directed repair template oligonucleotides generated a high frequency of targeted genome modifications in primary T cells. Targeted nucleotide replacement was achieved in CXCR4 and PD-1 (PDCD1), a regulator of T-cell exhaustion that is a validated target for tumor immunotherapy. Deep sequencing of a target site confirmed that Cas9 RNPs generated knock-in genome modifications with up to ~20% efficiency, which accounted for up to approximately one-third of total editing events. These results establish Cas9 RNP technology for diverse experimental and therapeutic genome engineering applications in primary human T cells.

  3. Generation of knock-in primary human T cells using Cas9 ribonucleoproteins

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

    Schumann, Kathrin; Lin, Steven; Boyer, Eric; Simeonov, Dimitre R.; Subramaniam, Meena; Gate, Rachel E.; Haliburton, Genevieve E.; Ye, Chun J.; Bluestone, Jeffrey A.; Doudna, Jennifer A.; et al

    2015-07-27

    T-cell genome engineering holds great promise for cell-based therapies for cancer, HIV, primary immune deficiencies, and autoimmune diseases, but genetic manipulation of human T cells has been challenging. Improved tools are needed to efficiently “knock out” genes and “knock in” targeted genome modifications to modulate T-cell function and correct disease-associated mutations. CRISPR/Cas9 technology is facilitating genome engineering in many cell types, but in human T cells its efficiency has been limited and it has not yet proven useful for targeted nucleotide replacements. Here we report efficient genome engineering in human CD4+ T cells using Cas9:single-guide RNA ribonucleoproteins (Cas9 RNPs). Cas9more » RNPs allowed ablation of CXCR4, a coreceptor for HIV entry. Cas9 RNP electroporation caused up to ~40% of cells to lose high-level cell-surface expression of CXCR4, and edited cells could be enriched by sorting based on low CXCR4 expression. Importantly, Cas9 RNPs paired with homology-directed repair template oligonucleotides generated a high frequency of targeted genome modifications in primary T cells. Targeted nucleotide replacement was achieved in CXCR4 and PD-1 (PDCD1), a regulator of T-cell exhaustion that is a validated target for tumor immunotherapy. Deep sequencing of a target site confirmed that Cas9 RNPs generated knock-in genome modifications with up to ~20% efficiency, which accounted for up to approximately one-third of total editing events. These results establish Cas9 RNP technology for diverse experimental and therapeutic genome engineering applications in primary human T cells.« less

  4. Human serum activates CIDEB-mediated lipid droplet enlargement in hepatoma cells

    SciTech Connect (OSTI)

    Singaravelu, Ragunath; National Research Council of Canada, Ottawa, Ontario K1A 0R6 ; Lyn, Rodney K.; National Research Council of Canada, Ottawa, Ontario K1A 0R6 ; Srinivasan, Prashanth; Delcorde, Julie; National Research Council of Canada, Ottawa, Ontario K1A 0R6 ; Steenbergen, Rineke H.; Tyrrell, D. Lorne; Li Ka Shing Institute of Virology, Katz Centre for Pharmacy and Health Research, Edmonton, Alberta T6G 2S2 ; Pezacki, John P.

    2013-11-15

    Highlights: Human serum induced differentiation of hepatoma cells increases cellular lipid droplet (LD) size. The observed increase in LD size correlates with increased PGC-1? and CIDEB expression. Induction of CIDEB expression correlates with rescue of VLDL secretion and loss of ADRP. siRNA knockdown of CIDEB impairs the human serum mediated increase in LD size. This system represents a cost-efficient model to study CIDEBs role in lipid biology. -- Abstract: Human hepatocytes constitutively express the lipid droplet (LD) associated protein cell death-inducing DFFA-like effector B (CIDEB). CIDEB mediates LD fusion, as well as very-low-density lipoprotein (VLDL) maturation. However, there are limited cell culture models readily available to study CIDEBs role in these biological processes, as hepatoma cell lines express negligible levels of CIDEB. Recent work has highlighted the ability of human serum to differentiate hepatoma cells. Herein, we demonstrate that culturing Huh7.5 cells in media supplemented with human serum activates CIDEB expression. This activation occurs through the induced expression of PGC-1?, a positive transcriptional regulator of CIDEB. Coherent anti-Stokes Raman scattering (CARS) microscopy revealed a correlation between CIDEB levels and LD size in human serum treated Huh7.5 cells. Human serum treatment also resulted in a rapid decrease in the levels of adipose differentiation-related protein (ADRP). Furthermore, individual overexpression of CIDEB was sufficient to down-regulate ADRP protein levels. siRNA knockdown of CIDEB revealed that the human serum mediated increase in LD size was CIDEB-dependent. Overall, our work highlights CIDEBs role in LD fusion, and presents a new model system to study the PGC-1?/CIDEB pathways role in LD dynamics and the VLDL pathway.

  5. Baicalein inhibits the migration and invasive properties of human hepatoma cells

    SciTech Connect (OSTI)

    Chiu, Yung-Wei; Lin, Tseng-Hsi; Huang, Wen-Shih; Teng, Chun-Yuh; Liou, Yi-Sheng; Kuo, Wu-Hsien; Lin, Wea-Lung; Huang, Hai-I; Tung, Jai-Nien; Huang, Chih-Yang; Liu, Jer-Yuh; Wang, Wen-Hung; Hwang, Jin-Ming

    2011-09-15

    Flavonoids have been demonstrated to exert health benefits in humans. We investigated whether the flavonoid baicalein would inhibit the adhesion, migration, invasion, and growth of human hepatoma cell lines, and we also investigated its mechanism of action. The separate effects of baicalein and baicalin on the viability of HA22T/VGH and SK-Hep1 cells were investigated for 24 h. To evaluate their invasive properties, cells were incubated on matrigel-coated transwell membranes in the presence or absence of baicalein. We examined the effect of baicalein on the adhesion of cells, on the activation of matrix metalloproteinases (MMPs), protein kinase C (PKC), and p38 mitogen-activated protein kinase (MAPK), and on tumor growth in vivo. We observed that baicalein suppresses hepatoma cell growth by 55%, baicalein-treated cells showed lower levels of migration than untreated cells, and cell invasion was significantly reduced to 28%. Incubation of hepatoma cells with baicalein also significantly inhibited cell adhesion to matrigel, collagen I, and gelatin-coated substrate. Baicalein also decreased the gelatinolytic activities of the matrix metalloproteinases MMP-2, MMP-9, and uPA, decreased p50 and p65 nuclear translocation, and decreased phosphorylated I-kappa-B (IKB)-{beta}. In addition, baicalein reduced the phosphorylation levels of PKC{alpha} and p38 proteins, which regulate invasion in poorly differentiated hepatoma cells. Finally, when SK-Hep1 cells were grown as xenografts in nude mice, intraperitoneal (i.p.) injection of baicalein induced a significant dose-dependent decrease in tumor growth. These results demonstrate the anticancer properties of baicalein, which include the inhibition of adhesion, invasion, migration, and proliferation of human hepatoma cells in vivo. - Highlight: > Baicalein inhibits several essential steps in the onset of metastasis.

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

    DOE Patents [OSTI]

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

    1983-01-01

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

  7. Distinct p53 genomic binding patterns in normal and cancer-derived human cells

    SciTech Connect (OSTI)

    Botcheva K.; McCorkle S. R.; McCombie W. R.; Dunn J. J.; Anderson C. W.

    2011-12-15

    We report here genome-wide analysis of the tumor suppressor p53 binding sites in normal human cells. 743 high-confidence ChIP-seq peaks representing putative genomic binding sites were identified in normal IMR90 fibroblasts using a reference chromatin sample. More than 40% were located within 2 kb of a transcription start site (TSS), a distribution similar to that documented for individually studied, functional p53 binding sites and, to date, not observed by previous p53 genome-wide studies. Nearly half of the high-confidence binding sites in the IMR90 cells reside in CpG islands, in marked contrast to sites reported in cancer-derived cells. The distinct genomic features of the IMR90 binding sites do not reflect a distinct preference for specific sequences, since the de novo developed p53 motif based on our study is similar to those reported by genome-wide studies of cancer cells. More likely, the different chromatin landscape in normal, compared with cancer-derived cells, influences p53 binding via modulating availability of the sites. We compared the IMR90 ChIPseq peaks to the recently published IMR90 methylome1 and demonstrated that they are enriched at hypomethylated DNA. Our study represents the first genome-wide, de novo mapping of p53 binding sites in normal human cells and reveals that p53 binding sites reside in distinct genomic landscapes in normal and cancer-derived human cells.

  8. Reconstitution activity of hypoxic cultured human cord blood CD34-positive cells in NOG mice

    SciTech Connect (OSTI)

    Shima, Haruko; Takubo, Keiyo; Iwasaki, Hiroko; Yoshihara, Hiroki; Gomei, Yumiko; Hosokawa, Kentaro; Arai, Fumio; Takahashi, Takao; Suda, Toshio

    2009-01-16

    Hematopoietic stem cells (HSCs) reside in hypoxic areas of the bone marrow. However, the role of hypoxia in the maintenance of HSCs has not been fully characterized. We performed xenotransplantation of human cord blood cells cultured in hypoxic or normoxic conditions into adult NOD/SCID/IL-2R{gamma}{sup null} (NOG) mice. Hypoxic culture (1% O{sub 2}) for 6 days efficiently supported the maintenance of HSCs, although cell proliferation was suppressed compared to the normoxic culture. In contrast, hypoxia did not affect in vitro colony-forming ability. Upregulation of a cell cycle inhibitor, p21, was observed in hypoxic culture. Immunohistochemical analysis of recipient bone marrow revealed that engrafted CD34{sup +}CD38{sup -} cord blood HSCs were hypoxic. Taken together, these results demonstrate the significance of hypoxia in the maintenance of quiescent human cord blood HSCs.

  9. The FBXW7 {beta}-form is suppressed in human glioma cells

    SciTech Connect (OSTI)

    Gu, Zhaodi; Inomata, Kenichi; Ishizawa, Kota; Horii, Akira . E-mail: horii@mail.tains.tohoku.ac.jp

    2007-03-23

    FBXW7 (F-box and WD40 domain protein 7) is an F-box protein with 7 tandem WDs (tryptophan-aspartic acid) that functions as a phosphoepitope-specific substrate recognition component of SCF (Skp1-Cul1-F-box protein) ubiquitin ligases and catalyzes the ubiquitination of proteins promoting cell proliferation, such as CCNE1, MYC, AURKA, NOTCH1, and JUN, which are frequently activated in a wide range of human cancers. FBXW7 is a candidate tumor suppressor, and mutations have been reported in some human tumors. In this study, we analyzed 84 human tumor cell lines in search for genetic alterations of FBXW7, as well as mRNA and protein expressional changes, and compared them with expression levels of the CCNE1, MYC, and AURKA proteins. We found a novel nonsense mutation in a colon cancer cell line SCC and confirmed the missense mutations in SKOV3, an ovarian cancer cell line, and LoVo, a colon cancer cell line. Moreover, suppressed expression of FBXW7 accompanied by activation of the target proteins were observed in ovarian, colon, endometrial, gastric, and prostate cancers. It is notable that highly suppressed mRNA expression of the FBXW7 {beta}-form was found in all the human glioma cell lines analyzed; enhanced expressions of CCNE1, MYC, and AURKA were observed in these cells. Our present results imply that FBXW7 plays a pivotal role in many tissues by controlling the amount of cell cycle promoter proteins and that dysfunction of this protein is one of the essential steps in carcinogenesis in multiple organs.

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

    SciTech Connect (OSTI)

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

    2008-03-10

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

  11. Induction of apoptosis by epigallocatechin-3-gallate in human lymphoblastoid B cells

    SciTech Connect (OSTI)

    Noda, Chiseko He, Jinsong; Takano, Tomoko; Tanaka, Chisato; Kondo, Toshinori; Tohyama, Kaoru; Yamamura, Hirohei; Tohyama, Yumi

    2007-11-03

    (-)-Epigallocatechin-3-gallate (EGCG), a major constituent of green tea polyphenols, has been shown to suppress cancer cell proliferation and induce apoptosis. In this study we investigated its efficacy and the mechanism underlying its effect using human B lymphoblastoid cell line Ramos, and effect of co-treatment with EGCG and a chemotherapeutic agent on apoptotic cell death. EGCG induced dose- and time-dependent apoptotic cell death accompanied by loss of mitochondrial transmembrane potential, release of cytochrome c into the cytosol, and cleavage of pro-caspase-9 to its active form. EGCG also enhanced production of intracellular reactive oxygen species (ROS). Pretreatment with diphenylene iodonium chloride, an inhibitor of NAD(P)H oxidase and an antioxidant, partially suppressed both EGCG-induced apoptosis and production of ROS, implying that oxidative stress is involved in the apoptotic response. Furthermore, we showed that combined-treatment with EGCG and a chemotherapeutic agent, etoposide, synergistically induced apoptosis in Ramos cells.

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

    SciTech Connect (OSTI)

    Garcia-Becerra, Rocio; Diaz, Lorenza; Camacho, Javier; Barrera, David; Ordaz-Rosado, David; Morales, Angelica; Ortiz, Cindy Sharon; Avila, Euclides; Bargallo, Enrique; Arrecillas, Myrna; Halhali, Ali; Larrea, Fernando

    2010-02-01

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

  13. Monoclonal antibodies to human hemoglobin S and cell lines for the production thereof

    DOE Patents [OSTI]

    Jensen, R.H.; Vanderlaan, M.; Bigbee, W.L.; Stanker, L.H.; Branscomb, E.W.; Grabske, R.J.

    1984-11-29

    The present invention provides monoclonal antibodies specific to and distinguishing between hemoglobin S and hemoglobin A and methods for their production and use. These antibodies are capable of distinguishing between two hemoglobin types which differ from each other by only a single amino acid residue. The antibodies produced according to the present method are useful as immunofluorescent markers to enumerate circulating red blood cells which have the property of altered expression of the hemoglobin gene due to somatic mutation in stem cells. Such a measurement is contemplated as an assay for in vivo cellular somatic mutations in humans. Since the monoclonal antibodies produced in accordance with the instant invention exhibit a high degree of specificity to and greater affinity for hemoglobin S, they are suitable for labeling human red blood cells for flow cytometric detection of hemoglobin genotype. 4 figs.

  14. Monoclonal antibodies to human hemoglobin S and cell lines for the production thereof

    DOE Patents [OSTI]

    Jensen, Ronald H.; Vanderlaan, Martin; Bigbee, William L.; Stanker, Larry H.; Branscomb, Elbert W.; Grabske, Robert J.

    1988-01-01

    The present invention provides monoclonal antibodies specific to and distinguish between hemoglobin S and hemoglobin A and methods for their production and use. These antibodies are capable of distinguishing between two hemoglobin types which differ from each other by only a single amino acid residue. The antibodies produced according to the present method are useful as immunofluorescent markers to enumerate circulating red blood cells which have the property of altered expression of the hemoglobin gene due to somatic mutation in stem cells. Such a measurement is contemplated as an assay for in vivo cellular somatic mutations in humans. Since the monoclonal antibodies produced in accordance with the instant invention exhibit a high degree of specificity to and greater affinity for hemoglobin S, they are suitable for labeling human red blood cells for flow cytometric detection of hemoglobin genotype.

  15. Sprayed skin turbine component

    DOE Patents [OSTI]

    Allen, David B

    2013-06-04

    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.

  16. BDNF/TrkB signaling protects HT-29 human colon cancer cells from EGFR inhibition

    SciTech Connect (OSTI)

    Brunetto de Farias, Caroline; Children's Cancer Institute, 90420-140 Porto Alegre, RS; Laboratory of Neuropharmacology and Neural Tumor Biology, Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, 90050-170 Porto Alegre, RS; National Institute for Translational Medicine , 90035-003 Porto Alegre, RS ; Heinen, Tiago Elias; Pereira dos Santos, Rafael; Laboratory of Neuropharmacology and Neural Tumor Biology, Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, 90050-170 Porto Alegre, RS; National Institute for Translational Medicine , 90035-003 Porto Alegre, RS ; Abujamra, Ana Lucia; Children's Cancer Institute, 90420-140 Porto Alegre, RS; National Institute for Translational Medicine , 90035-003 Porto Alegre, RS ; Schwartsmann, Gilberto; National Institute for Translational Medicine , 90035-003 Porto Alegre, RS; Department of Internal Medicine, School of Medicine, Federal University of Rio Grande do Sul, 90035-003 Porto Alegre, RS ; and others

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer BDNF protected HT-29 colorectal cancer cells from the antitumor effect of cetuximab. Black-Right-Pointing-Pointer TrkB inhibition potentiated the antitumor effect of cetuximab. Black-Right-Pointing-Pointer BDNF/TrkB signaling might be involved in resistance to anti-EGFR therapy. -- Abstract: The clinical success of targeted treatment of colorectal cancer (CRC) is often limited by resistance to anti-epidermal growth factor receptor (EGFR) therapy. The neurotrophin brain-derived neurotrophic factor (BDNF) and its receptor TrkB have recently emerged as anticancer targets, and we have previously shown increased BDNF levels in CRC tumor samples. Here we report the findings from in vitro experiments suggesting that BDNF/TrkB signaling can protect CRC cells from the antitumor effects of EGFR blockade. The anti-EGFR monoclonal antibody cetuximab reduced both cell proliferation and the mRNA expression of BDNF and TrkB in human HT-29 CRC cells. The inhibitory effect of cetuximab on cell proliferation and survival was counteracted by the addition of human recombinant BDNF. Finally, the Trk inhibitor K252a synergistically enhanced the effect of cetuximab on cell proliferation, and this effect was blocked by BDNF. These results provide the first evidence that increased BDNF/TrkB signaling might play a role in resistance to EGFR blockade. Moreover, it is possible that targeting TrkB could potentiate the anticancer effects of anti-EGFR therapy.

  17. STAT3 signaling pathway is necessary for cell survival and tumorsphere forming capacity in ALDH{sup +}/CD133{sup +} stem cell-like human colon cancer cells

    SciTech Connect (OSTI)

    Lin, Li; Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030 ; Fuchs, James; Li, Chenglong; Olson, Veronica; Bekaii-Saab, Tanios; Lin, Jiayuh

    2011-12-16

    Highlights: Black-Right-Pointing-Pointer The phosphorylated or activated form of STAT3 was expressed in colon cancer stem-like cells. Black-Right-Pointing-Pointer STAT3 inhibitor, FLLL32 inhibits P-STAT3 and STAT3 target genes in colon cancer stem-like cells. Black-Right-Pointing-Pointer Inhibition of STAT3 resulted in decreased cell viability and reduced numbers of tumorspheres. Black-Right-Pointing-Pointer STAT3 is required for survival and tumorsphere forming capacity in colon cancer stem-like cells. Black-Right-Pointing-Pointer Targeting STAT3 in cancer stem-like cells may offer a novel treatment approach for colon cancer. -- Abstract: Persistent activation of Signal Transducers and Activators of Transcription 3 (STAT3) is frequently detected in colon cancer. Increasing evidence suggests the existence of a small population of colon cancer stem or cancer-initiating cells may be responsible for tumor initiation, metastasis, and resistance to chemotherapy and radiation. Whether STAT3 plays a role in colon cancer-initiating cells and the effect of STAT3 inhibition is still unknown. Flow cytometry was used to isolate colon cancer stem-like cells from three independent human colon cancer cell lines characterized by both aldehyde dehydrogenase (ALDH)-positive and CD133-positive subpopulation (ALDH{sup +}/CD133{sup +}). The effects of STAT3 inhibition in colon cancer stem-like cells were examined. The phosphorylated or activated form of STAT3 was expressed in colon cancer stem-like cells and was reduced by a STAT3-selective small molecular inhibitor, FLLL32. FLLL32 also inhibited the expression of potential STAT3 downstream target genes in colon cancer stem-like cells including survivin, Bcl-XL, as well as Notch-1, -3, and -4, which may be involved in stem cell function. Furthermore, FLLL32 inhibited cell viability and tumorsphere formation as well as induced cleaved caspase-3 in colon cancer stem-like cells. FLLL32 is more potent than curcumin as evidenced with lower IC50 in colon cancer stem-like cells. In summary, our results indicate that STAT3 is a novel therapeutic target in colon cancer stem-like cells and inhibition of STAT3 in cancer stem-like cells may offer a potential treatment for colorectal cancer.

  18. Mono-2-ethylhexyl phthalate induces oxidative stress responses in human placental cells in vitro

    SciTech Connect (OSTI)

    Tetz, Lauren M.; Cheng, Adrienne A.; Korte, Cassandra S.; Giese, Roger W.; Wang, Poguang; Harris, Craig; Meeker, John D.; Loch-Caruso, Rita

    2013-04-01

    Di-2-ethylhexyl phthalate (DEHP) is an environmental contaminant commonly used as a plasticizer in polyvinyl chloride products. Exposure to DEHP has been linked to adverse pregnancy outcomes in humans including preterm birth, low birth-weight, and pregnancy loss. Although oxidative stress is linked to the pathology of adverse pregnancy outcomes, effects of DEHP metabolites, including the active metabolite, mono-2-ethylhexyl phthalate (MEHP), on oxidative stress responses in placental cells have not been previously evaluated. The objective of the current study is to identify MEHP-stimulated oxidative stress responses in human placental cells. We treated a human placental cell line, HTR-8/SVneo, with MEHP and then measured reactive oxygen species (ROS) generation using the dichlorofluorescein assay, oxidized thymine with mass-spectrometry, redox-sensitive gene expression with qRT-PCR, and apoptosis using a luminescence assay for caspase 3/7 activity. Treatment of HTR-8 cells with 180 ?M MEHP increased ROS generation, oxidative DNA damage, and caspase 3/7 activity, and resulted in differential expression of redox-sensitive genes. Notably, 90 and 180 ?M MEHP significantly induced mRNA expression of prostaglandin-endoperoxide synthase 2 (PTGS2), an enzyme important for synthesis of prostaglandins implicated in initiation of labor. The results from the present study are the first to demonstrate that MEHP stimulates oxidative stress responses in placental cells. Furthermore, the MEHP concentrations used were within an order of magnitude of the highest concentrations measured previously in human umbilical cord or maternal serum. The findings from the current study warrant future mechanistic studies of oxidative stress, apoptosis, and prostaglandins as molecular mediators of DEHP/MEHP-associated adverse pregnancy outcomes. - Highlights: ? MEHP increased reactive oxygen species, oxidative DNA damage, and caspase activity. ? MEHP induced expression of PTGS2, a gene important in pregnancy and parturition ? MEHP treatment resulted in differential expression of GLRX2, TXNRD1, and DHCR24.

  19. Soft inertial microfluidics for high throughput separation of bacteria from human blood cells

    SciTech Connect (OSTI)

    Wu, Zhigang; Willing, Ben; Bjerketorp, Joakim; Jansson, Janet K.; Hjort, Klas

    2009-01-05

    We developed a new approach to separate bacteria from human blood cells based on soft inertial force induced migration with flow defined curved and focused sample flow inside a microfluidic device. This approach relies on a combination of an asymmetrical sheath flow and proper channel geometry to generate a soft inertial force on the sample fluid in the curved and focused sample flow segment to deflect larger particles away while the smaller ones are kept on or near the original flow streamline. The curved and focused sample flow and inertial effect were visualized and verified using a fluorescent dye primed in the device. First the particle behavior was studied in detail using 9.9 and 1.0 {micro}m particles with a polymer-based prototype. The prototype device is compact with an active size of 3 mm{sup 2}. The soft inertial effect and deflection distance were proportional to the fluid Reynolds number (Re) and particle Reynolds number (Re{sub p}), respectively. We successfully demonstrated separation of bacteria (Escherichia coli) from human red blood cells at high cell concentrations (above 10{sup 8}/mL), using a sample flow rate of up to 18 {micro}L/min. This resulted in at least a 300-fold enrichment of bacteria at a wide range of flow rates with a controlled flow spreading. The separated cells were proven to be viable. Proteins from fractions before and after cell separation were analyzed by gel electrophoresis and staining to verify the removal of red blood cell proteins from the bacterial cell fraction. This novel microfluidic process is robust, reproducible, simple to perform, and has a high throughput compared to other cell sorting systems. Microfluidic systems based on these principles could easily be manufactured for clinical laboratory and biomedical applications.

  20. Nukbone promotes proliferation and osteoblastic differentiation of mesenchymal stem cells from human amniotic membrane

    SciTech Connect (OSTI)

    Rodrguez-Fuentes, Nayeli; Rodrguez-Hernndez, Ana G.; Enrquez-Jimnez, Juana; Alcntara-Quintana, Luz E.; Fuentes-Mera, Lizeth; Pia-Barba, Mara C.; Zepeda-Rodrguez, Armando; and others

    2013-05-10

    Highlights: Nukbone showed to be a good scaffold for adhesion, proliferation and differentiation of stem cells. Nukbone induced osteoblastic differentiation of human mesenchymal stem cells. Results showed that Nukbone offer an excellent option for bone tissue regeneration due to properties. -- Abstract: Bovine bone matrix Nukbone (NKB) is an osseous tissue-engineering biomaterial that retains its mineral and organic phases and its natural bone topography and has been used as a xenoimplant for bone regeneration in clinics. There are not studies regarding its influence of the NKB in the behavior of cells during the repairing processes. The aim of this research is to demonstrate that NKB has an osteoinductive effect in human mesenchymal stem cells from amniotic membrane (AM-hMSCs). Results indicated that NKB favors the AM-hMSCs adhesion and proliferation up to 7 days in culture as shown by the scanning electron microscopy and proliferation measures using an alamarBlue assay. Furthermore, as demonstrated by reverse transcriptase polymerase chain reaction, it was detected that two gene expression markers of osteoblastic differentiation: the core binding factor and osteocalcin were higher for AM-hMSCs co-cultured with NKB in comparison with cultivated cells in absence of the biomaterial. As the results indicate, NKB possess the capability for inducing successfully the osteoblastic differentiation of AM-hMSC, so that, NKB is an excellent xenoimplant option for repairing bone tissue defects.

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

    SciTech Connect (OSTI)

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

    2005-12-30

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

  2. CDK-associated Cullin 1 promotes cell proliferation with activation of ERK1/2 in human lung cancer A549 cells

    SciTech Connect (OSTI)

    Chen, Tian Jun; Gao, Fei; Yang, Tian; Thakur, Asmitanand; Ren, Hui; Li, Yang; Zhang, Shuo; Wang, Ting; Chen, Ming Wei

    2013-07-19

    Highlights: CDK-associated Cullin 1 (CAC1) expression increases in human lung carcinoma. CAC1 promotes the proliferation of lung cancer A549 cells. CAC1 promotes human lung cancer A549 cell proliferation with activation of ERK1/2. -- Abstract: Lung cancer is one of the most common causes of cancer-related death in the world, but the mechanisms remain unknown. In this study, we investigated the expression of CDK-associated Cullin 1 (CAC1) in lung cancer, the effect of CAC1 on the proliferation of human lung cancer A549 cells, and the activation of signaling pathways of mitogen-activated protein kinases (MAPKs). Results showed that CAC1 expression was higher levels in human lung carcinoma than normal lung tissue, and CAC1 siRNA reduced the proliferation of lung cancer A549 cells by decreasing cell activity and cell division in vitro. The proportion of cells treated with CAC1 siRNA increased in the G1 phase and decreased in the S and G2/M phase, indicative of G1 cell cycle arrest. Furthermore, the proportions of early/late apoptosis in lung cancer A549 cells were enhanced with CAC1 siRNA treatment. It was also found that activation of extracellular signal-regulated protein kinase (ERK) and p38 signaling pathways were involved in the proliferation of A549 cells. After CAC1 siRNA treatment, p-ERK1/2 levels decreased, and meanwhile p-p38 level increased, A549 cell proliferation increased when ERK1/2 signaling is activated by PMA. Our findings demonstrated that CAC1 promoted the proliferation of human lung cancer A549 cells with activation of ERK1/2 signaling pathways, suggesting a potential cure target for treatment of human lung cancer.

  3. Inhibition of Sirt1 promotes neural progenitors toward motoneuron differentiation from human embryonic stem cells

    SciTech Connect (OSTI)

    Zhang, Yun; Wang, Jing; Clinical Stem Cell Center, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 ; Chen, Guian; Reproductive Medical Center, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 ; Fan, Dongsheng; Clinical Stem Cell Center, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 ; Deng, Min; Clinical Stem Cell Center, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191

    2011-01-14

    Research highlights: {yields} Nicotinamide inhibit Sirt1. {yields} MASH1 and Ngn2 activation. {yields} Increase the expression of HB9. {yields} Motoneurons formation increases significantly. -- Abstract: Several protocols direct human embryonic stem cells (hESCs) toward differentiation into functional motoneurons, but the efficiency of motoneuron generation varies based on the human ESC line used. We aimed to develop a novel protocol to increase the formation of motoneurons from human ESCs. In this study, we tested a nuclear histone deacetylase protein, Sirt1, to promote neural precursor cell (NPC) development during differentiation of human ESCs into motoneurons. A specific inhibitor of Sirt1, nicotinamide, dramatically increased motoneuron formation. We found that about 60% of the cells from the total NPCs expressed HB9 and {beta}III-tubulin, commonly used motoneuronal markers found in neurons derived from ESCs following nicotinamide treatment. Motoneurons derived from ESC expressed choline acetyltransferase (ChAT), a positive marker of mature motoneuron. Moreover, we also examined the transcript levels of Mash1, Ngn2, and HB9 mRNA in the differentiated NPCs treated with the Sirt1 activator resveratrol (50 {mu}M) or inhibitor nicotinamide (100 {mu}M). The levels of Mash1, Ngn2, and HB9 mRNA were significantly increased after nicotinamide treatment compared with control groups, which used the traditional protocol. These results suggested that increasing Mash1 and Ngn2 levels by inhibiting Sirt1 could elevate HB9 expression, which promotes motoneuron differentiation. This study provides an alternative method for the production of transplantable motoneurons, a key requirement in the development of hESC-based cell therapy in motoneuron disease.

  4. Noscapine induces mitochondria-mediated apoptosis in human colon cancer cells in vivo and in vitro

    SciTech Connect (OSTI)

    Yang, Zi-Rong; Liu, Meng; Peng, Xiu-Lan; Lei, Xiao-Fei; Zhang, Ji-Xiang; Dong, Wei-Guo

    2012-05-11

    Highlights: Black-Right-Pointing-Pointer Noscapine inhibited cell viability of colon cancer in a time- and dose- dependent manner. Black-Right-Pointing-Pointer G{sub 2}/M phase arrest and chromatin condensation and nuclear fragmentation were induced. Black-Right-Pointing-Pointer Noscapine promoted apoptosis via mitochondrial pathways. Black-Right-Pointing-Pointer Tumorigenicity was inhibited by noscapine. -- Abstract: Noscapine, a phthalide isoquinoline alkaloid derived from opium, has been widely used as a cough suppressant for decades. Noscapine has recently been shown to potentiate the anti-cancer effects of several therapies by inducing apoptosis in various malignant cells without any detectable toxicity in cells or tissues. However, the mechanism by which noscapine induces apoptosis in colon cancer cells remains unclear. The signaling pathways by which noscapine induces apoptosis were investigated in colon cancer cell lines treated with various noscapine concentrations for 72 h, and a dose-dependent inhibition of cell viability was observed. Noscapine effectively inhibited the proliferation of LoVo cells in vitro (IC{sub 50} = 75 {mu}M). This cytotoxicity was reflected by cell cycle arrest at G{sub 2}/M and subsequent apoptosis, as indicated by increased chromatin condensation and fragmentation, the upregulation of Bax and cytochrome c (Cyt-c), the downregulation of survivin and Bcl-2, and the activation of caspase-3 and caspase-9. Moreover, in a xenograft tumor model in mice, noscapine injection clearly inhibited tumor growth via the induction of apoptosis, which was demonstrated using a TUNEL assay. These results suggest that noscapine induces apoptosis in colon cancer cells via mitochondrial pathways. Noscapine may be a safe and effective chemotherapeutic agent for the treatment of human colon cancer.

  5. Skin contamination dosimeter

    DOE Patents [OSTI]

    Hamby, David M. (Corvallis, OR); Farsoni, Abdollah T. (Corvallis, OR); Cazalas, Edward (Corvallis, OR)

    2011-06-21

    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. Chlorobenzene induces oxidative stress in human lung epithelial cells in vitro

    SciTech Connect (OSTI)

    Feltens, Ralph; Moegel, Iljana; Roeder-Stolinski, Carmen; Simon, Jan-Christoph; Herberth, Gunda; Lehmann, Irina

    2010-01-01

    Chlorobenzene is a volatile organic compound (VOC) that is widely used as a solvent, degreasing agent and chemical intermediate in many industrial settings. Occupational studies have shown that acute and chronic exposure to chlorobenzene can cause irritation of the mucosa of the upper respiratory tract and eyes. Using in vitro assays, we have shown in a previous study that human bronchial epithelial cells release inflammatory mediators such as the cytokine monocyte chemoattractant protein-1 (MCP-1) in response to chlorobenzene. This response is mediated through the NF-kappaB signaling pathway. Here, we investigated the effects of monochlorobenzene on human lung cells, with emphasis on potential alterations of the redox equilibrium to clarify whether the chlorobenzene-induced inflammatory response in lung epithelial cells is caused via an oxidative stress-dependent mechanism. We found that expression of cellular markers for oxidative stress, such as heme oxygenase 1 (HO-1), glutathione S-transferase pi1 (GSTP1), superoxide dismutase 1 (SOD1), prostaglandin-endoperoxide synthase 2 (PTGS2) and dual specificity phosphatase 1 (DUSP1), were elevated in the presence of monochlorobenzene. Likewise, intracellular reactive oxygen species (ROS) were increased in response to exposure. However, in the presence of the antioxidants N-(2-mercaptopropionyl)-glycine (MPG) or bucillamine, chlorobenzene-induced upregulation of marker proteins and release of the inflammatory mediator MCP-1 are suppressed. These results complement our previous findings and point to an oxidative stress-mediated inflammatory response following chlorobenzene exposure.

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

    SciTech Connect (OSTI)

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

    2013-09-06

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

  8. Reprogramming of human fibroblasts to pluripotent stem cells using mRNA of four transcription factors

    SciTech Connect (OSTI)

    Yakubov, Eduard; Rechavi, Gidi; Rozenblatt, Shmuel; Givol, David

    2010-03-26

    Reprogramming of differentiated cells into induced pluripotent cells (iPS) was accomplished in 2006 by expressing four, or less, embryonic stem cell (ESC)-specific transcription factors. Due to the possible danger of DNA damage and the potential tumorigenicity associated with such DNA damage, attempts were made to minimize DNA integration by the vectors involved in this process without complete success. Here we present a method of using RNA transfection as a tool for reprogramming human fibroblasts to iPS. We used RNA synthesized in vitro from cDNA of the same reprogramming four transcription factors. After transfection of the RNA, we show intracellular expression and nuclear localization of the respective proteins in at least 70% of the cells. We used five consecutive transfections to support continuous protein expression resulting in the formation of iPS colonies that express alkaline phosphatase and several ESC markers and that can be expanded. This method completely avoids DNA integration and may be developed to replace the use of DNA vectors in the formation of iPS.

  9. Sialic acid-dependent cell entry of human enterovirus D68

    SciTech Connect (OSTI)

    Liu, Yue; Sheng, Ju; Baggen, Jim; Meng, Geng; Xiao, Chuan; Thibaut, Hendrik J.; van Kuppeveld, Frank J. M.; Rossmann, Michael G.

    2015-11-13

    Human enterovirus D68 (EV-D68) is a causative agent of childhood respiratory diseases and has now emerged as a global public health threat. Nevertheless, knowledge of the tissue tropism and pathogenesis of EV-D68 has been hindered by a lack of studies on the receptor-mediated EV-D68 entry into host cells. Here we demonstrate that cell surface sialic acid is essential for EV-D68 to bind to and infect susceptible cells. Crystal structures of EV-D68 in complex with sialylated glycan receptor analogues show that they bind into the canyon on the virus surface. The sialic acid receptor induces a cascade of conformational changes in the virus to eject a fatty-acid-like molecule that regulates the stability of the virus. Furthermore, virus binding to a sialic acid receptor and to immunoglobulin-like receptors used by most other enteroviruses share a conserved mechanism for priming viral uncoating and facilitating cell entry.

  10. Sialic acid-dependent cell entry of human enterovirus D68

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

    Liu, Yue; Sheng, Ju; Baggen, Jim; Meng, Geng; Xiao, Chuan; Thibaut, Hendrik J.; van Kuppeveld, Frank J. M.; Rossmann, Michael G.

    2015-11-13

    Human enterovirus D68 (EV-D68) is a causative agent of childhood respiratory diseases and has now emerged as a global public health threat. Nevertheless, knowledge of the tissue tropism and pathogenesis of EV-D68 has been hindered by a lack of studies on the receptor-mediated EV-D68 entry into host cells. Here we demonstrate that cell surface sialic acid is essential for EV-D68 to bind to and infect susceptible cells. Crystal structures of EV-D68 in complex with sialylated glycan receptor analogues show that they bind into the ‘canyon’ on the virus surface. The sialic acid receptor induces a cascade of conformational changes inmore » the virus to eject a fatty-acid-like molecule that regulates the stability of the virus. Furthermore, virus binding to a sialic acid receptor and to immunoglobulin-like receptors used by most other enteroviruses share a conserved mechanism for priming viral uncoating and facilitating cell entry.« less

  11. 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 Radiometric, Surface Properties Instruments The above measurement is considered scientifically relevant for the following instruments. Refer to the

  12. MRG15 activates the cdc2 promoter via histone acetylation in human cells

    SciTech Connect (OSTI)

    Pena, AndreAna N.; Tominaga, Kaoru; Pereira-Smith, Olivia M.; Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, TX

    2011-07-01

    Chromatin remodeling is required for transcriptional activation and repression. MRG15 (MORF4L1), a chromatin modulator, is a highly conserved protein and is present in complexes containing histone acetyltransferases (HATs) as well as histone deacetylases (HDACs). Loss of expression of MRG15 in mice and Drosophila results in embryonic lethality and fibroblast and neural stem/progenitor cells cultured from Mrg15 null mouse embryos exhibit marked proliferative defects when compared with wild type cells. To determine the role of MRG15 in cell cycle progression we performed chromatin immunoprecipitation with an antibody to MRG15 on normal human fibroblasts as they entered the cell cycle from a quiescent state, and analyzed various cell cycle gene promoters. The results demonstrated a 3-fold increase in MRG15 occupancy at the cdc2 promoter during S phase of the cell cycle and a concomitant increase in acetylated histone H4. H4 lysine 12 was acetylated at 24 h post-serum stimulation while there was no change in acetylation of lysine 16. HDAC1 and 2 were decreased at this promoter during cell cycle progression. Over-expression of MRG15 in HeLa cells activated a cdc2 promoter-reporter construct in a dose-dependent manner, whereas knockdown of MRG15 resulted in decreased promoter activity. In order to implicate HAT activity, we treated cells with the HAT inhibitor anacardic acid and determined that HAT inhibition results in loss of expression of cdc2 mRNA. Further, chromatin immunoprecipitation with Tip60 localizes the protein to the same 110 bp stretch of the cdc2 promoter pulled down by MRG15. Additionally, we determined that cotransfection of MRG15 with the known associated HAT Tip60 had a cooperative effect in activating the cdc2 promoter. These results suggest that MRG15 is acting in a HAT complex involving Tip60 to modify chromatin via acetylation of histone H4 at the cdc2 promoter to activate transcription.

  13. Cell cycle regulation of human immunodeficiency virus type 1 integration in T cells: antagonistic effects of nuclear envelope breakdown and chromatin condensation

    SciTech Connect (OSTI)

    Mannioui, Abdelkrim . E-mail: karim.mannioui@chu-stlouis.fr; Schiffer, Cecile . E-mail: cecile.schiffer@voila.fr; Felix, Nathalie . E-mail: nathalie.felix@chu-stlouis.fr

    2004-11-10

    We examined the influence of mitosis on the kinetics of human immunodeficiency virus type 1 integration in T cells. Single-round infection of cells arrested in G1b or allowed to synchronously proceed through division showed that mitosis delays virus integration until 18-24 h postinfection, whereas integration reaches maximum levels by 15 h in G1b-arrested cells. Subcellular fractionation of metaphase-arrested cells indicated that, while nuclear envelope disassembly facilitates docking of viral DNA to chromatin, chromosome condensation directly antagonizes and therefore delays integration. As a result of the balance between the two effects, virus integration efficiency is eventually up to threefold greater in dividing cells. At the single-cell level, using a green fluorescent protein-expressing reporter virus, we found that passage through mitosis leads to prominent asymmetric segregation of the viral genome in daughter cells without interfering with provirus expression.

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

    SciTech Connect (OSTI)

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

    2009-02-01

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

  15. 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)...

  16. Role of reactive oxygen species in arsenic-induced transformation of human lung bronchial epithelial (BEAS-2B) cells

    SciTech Connect (OSTI)

    Zhang, Zhuo; Pratheeshkumar, Poyil; Budhraja, Amit; Son, Young-Ok; Kim, Donghern; Shi, Xianglin

    2015-01-09

    Highlights: Short term exposure of cells to arsenic causes ROS generation. Chronical exposure of cells to arsenic causes malignant cell transformation. Inhibition of ROS generation reduces cell transformation by arsenic. Arsenic-transformed cells exhibit reduced capacity of generating ROS. Arsenic-transformed cells exhibit increased levels of antioxidants. - Abstract: Arsenic is an environmental carcinogen, its mechanisms of carcinogenesis remain to be investigated. Reactive oxygen species (ROS) are considered to be important. A previous study (Carpenter et al., 2011) has measured ROS level in human lung bronchial epithelial (BEAS-2B) cells and arsenic-transformed BEAS-2B cells and found that ROS levels were higher in transformed cells than that in parent normal cells. Based on these observations, the authors concluded that cell transformation induced by arsenic is mediated by increased cellular levels of ROS. This conclusion is problematic because this study only measured the basal ROS levels in transformed and parent cells and did not investigate the role of ROS in the process of arsenic-induced cell transformation. The levels of ROS in arsenic-transformed cells represent the result and not the cause of cell transformation. Thus question concerning whether ROS are important in arsenic-induced cell transformation remains to be answered. In the present study, we used expressions of catalase (antioxidant against H{sub 2}O{sub 2}) and superoxide dismutase 2 (SOD2, antioxidant against O{sub 2}{sup ?}) to decrease ROS level and investigated their role in the process of arsenic-induced cell transformation. Our results show that inhibition of ROS by antioxidant enzymes decreased arsenic-induced cell transformation, demonstrating that ROS are important in this process. We have also shown that in arsenic-transformed cells, ROS generation was lower and levels of antioxidants are higher than those in parent cells, in a disagreement with the previous report. The present study has also shown that the arsenic-transformed cells acquired apoptosis resistance. The inhibition of catalase to increase ROS level restored apoptosis capability of arsenic-transformed BEAS-2B cells, further showing that ROS levels are low in these cells. The apoptosis resistance due to the low ROS levels may increase cells proliferation, providing a favorable environment for tumorigenesis of arsenic-transformed cells.

  17. Human metastatic melanoma cell lines express high levels of growth hormone receptor and respond to GH treatment

    SciTech Connect (OSTI)

    Sustarsic, Elahu G.; Department of Biological Sciences, Ohio University, Athens, OH ; Junnila, Riia K.; Kopchick, John J.

    2013-11-08

    Highlights: Most cancer types of the NCI60 have sub-sets of cell lines with high GHR expression. GHR is highly expressed in melanoma cell lines. GHR is elevated in advanced stage IV metastatic tumors vs. stage III. GH treatment of metastatic melanoma cell lines alters growth and cell signaling. -- Abstract: Accumulating evidence implicates the growth hormone receptor (GHR) in carcinogenesis. While multiple studies show evidence for expression of growth hormone (GH) and GHR mRNA in human cancer tissue, there is a lack of quantification and only a few cancer types have been investigated. The National Cancer Institutes NCI60 panel includes 60 cancer cell lines from nine types of human cancer: breast, CNS, colon, leukemia, melanoma, non-small cell lung, ovarian, prostate and renal. We utilized this panel to quantify expression of GHR, GH, prolactin receptor (PRLR) and prolactin (PRL) mRNA with real-time RT qPCR. Both GHR and PRLR show a broad range of expression within and among most cancer types. Strikingly, GHR expression is nearly 50-fold higher in melanoma than in the panel as a whole. Analysis of human metastatic melanoma biopsies confirmed GHR gene expression in melanoma tissue. In these human biopsies, the level of GHR mRNA is elevated in advanced stage IV tumor samples compared to stage III. Due to the novel finding of high GHR in melanoma, we examined the effect of GH treatment on three NCI60 melanoma lines (MDA-MB-435, UACC-62 and SK-MEL-5). GH increased proliferation in two out of three cell lines tested. Further analysis revealed GH-induced activation of STAT5 and mTOR in a cell line dependent manner. In conclusion, we have identified cell lines and cancer types that are ideal to study the role of GH and PRL in cancer, yet have been largely overlooked. Furthermore, we found that human metastatic melanoma tumors express GHR and cell lines possess active GHRs that can modulate multiple signaling pathways and alter cell proliferation. Based on this data, GH could be a new therapeutic target in melanoma.

  18. 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

    2014-02-15

    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.

  19. Conditionally immortalized human pancreatic stellate cell lines demonstrate enhanced proliferation and migration in response to IGF-I

    SciTech Connect (OSTI)

    Rosendahl, Ann H.; Gundewar, Chinmay; Said Hilmersson, Katarzyna; Ni, Lan; Saleem, Moin A.; Andersson, Roland

    2015-01-15

    Pancreatic stellate cells (PSCs) play a key role in the dense desmoplastic stroma associated with pancreatic ductal adenocarcinoma. Studies on human PSCs have been minimal due to difficulty in maintaining primary PSC in culture. We have generated the first conditionally immortalized human non-tumor (NPSC) and tumor-derived (TPSC) pancreatic stellate cells via transformation with the temperature-sensitive SV40 large T antigen and human telomerase (hTERT). These cells proliferate at 33C. After transfer to 37C, the SV40LT is switched off and the cells regain their primary PSC phenotype and growth characteristics. NPSC contained cytoplasmic vitamin A-storing lipid droplets, while both NPSC and TPSC expressed the characteristic markers ?SMA, vimentin, desmin and GFAP. Proteome array analysis revealed that of the 55 evaluated proteins, 27 (49%) were upregulated ?3-fold in TPSC compared to NPSC, including uPA, pentraxin-3, endoglin and endothelin-1. Two insulin-like growth factor binding proteins (IGFBPs) were inversely expressed. Although discordant IGFBP-2 and IGFBP-3 levels, IGF-I was found to stimulate proliferation of both NPSC and TPSC. Both basal and IGF-I stimulated motility was significantly enhanced in TPSC compared to NPSC. In conclusion, these cells provide a unique resource that will facilitate further study of the active stroma compartment associated with pancreatic cancer. - Highlights: Generation of human conditionally immortalized human pancreatic stellate cell lines. Temperature-sensitive SV40LT allows switch to primary PSC phenotype characteristics. Proteome profiling revealed distinct expression patterns between TPSC and NPSC. Enhanced IGF-I-stimulated proliferation and motility by TPSC compared to NPSC.

  20. Comparative study of the chondrogenic potential of human bone marrow stromal cells, neonatal chondrocytes and adult chondrocytes

    SciTech Connect (OSTI)

    Saha, Sushmita; Kirkham, Jennifer; NIHR Leeds Musculoskeletal Biomedical Research Unit, University of Leeds, Chapel Allerton Hospital, Leeds LS74SA ; Wood, David; Curran, Stephen; Yang, Xuebin; NIHR Leeds Musculoskeletal Biomedical Research Unit, University of Leeds, Chapel Allerton Hospital, Leeds LS74SA

    2010-10-22

    Research highlights: {yields} This study has characterised three different cell types under conditions similar to those used for autologous chondrocyte implantation (ACI) for applications in cartilage repair/regeneration. {yields} Compared for the first time the chondrogenic potential of neonatal chondrocytes with human bone marrow stromal cells (HBMSCs) and adult chondrocytes. {yields} Demonstrated that adult chondrocytes hold greatest potential for use in ACI based on their higher proliferation rates, lower alkaline phosphatise activity and enhanced expression of chondrogenic genes. {yields} Demonstrated the need for chondroinduction as a necessary pre-requisite to efficient chondrogenesis in vitro and, by extrapolation, for cell based therapy (e.g. ACI or cartilage tissue engineering). -- Abstract: Cartilage tissue engineering is still a major clinical challenge with optimisation of a suitable source of cells for cartilage repair/regeneration not yet fully addressed. The aims of this study were to compare and contrast the differences in chondrogenic behaviour between human bone marrow stromal cells (HBMSCs), human neonatal and adult chondrocytes to further our understanding of chondroinduction relative to cell maturity and to identify factors that promote chondrogenesis and maintain functional homoeostasis. Cells were cultured in monolayer in either chondrogenic or basal medium, recapitulating procedures used in existing clinical procedures for cell-based therapies. Cell doubling time, morphology and alkaline phosphatase specific activity (ALPSA) were determined at different time points. Expression of chondrogenic markers (SOX9, ACAN and COL2A1) was compared via real time polymerase chain reaction. Amongst the three cell types studied, HBMSCs had the highest ALPSA in basal culture and lowest ALPSA in chondrogenic media. Neonatal chondrocytes were the most proliferative and adult chondrocytes had the lowest ALPSA in basal media. Gene expression analysis revealed a difference in the temporal expression of chondrogenic markers which were up regulated in chondrogenic medium compared to levels in basal medium. Of the three cell types studied, adult chondrocytes offer a more promising cell source for cartilage tissue engineering. This comparative study revealed differences between the microenvironment of all three cell types and provides useful information to inform cell-based therapies for cartilage regeneration.

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

    SciTech Connect (OSTI)

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

    2014-08-01

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

  2. MiR-18a regulates the proliferation, migration and invasion of human glioblastoma cell by targeting neogenin

    SciTech Connect (OSTI)

    Song, Yichen; Wang, Ping; Zhao, Wei; Yao, Yilong; Liu, Xiaobai; Ma, Jun; Xue, Yixue; Liu, Yunhui

    2014-05-15

    MiR-17-92 cluster has recently been reported as an oncogene in some tumors. However, the association of miR-18a, an important member of this cluster, with glioblastoma remains unknown. Therefore, this study aims to investigate the expression of miR-18a in glioblastoma and its role in biological behavior of U87 and U251 human glioblastoma cell lines. Quantitative RT-PCR results showed that miR-18a was highly expressed in glioblastoma tissues and U87 and U251 cell lines compared with that in human brain tissues and primary normal human astrocytes, and the expression levels were increased along with the rising pathological grades of glioblastoma. Neogenin was identified as the target gene of miR-18a by dual-luciferase reporter assays. RT-PCR and western blot results showed that its expression levels were decreased along with the rising pathological grades of glioblastoma. Inhibition of miR-18a expression was established by transfecting exogenous miR-18a inhibitor into U87 and U251 cells, and its effects on the biological behavior of glioblastoma cells were studied using CCK-8 assay, transwell assay and flow cytometry. Inhibition of miR-18a expression in U87 and U251 cells significantly up-regulated neogenin, and dramatically suppressed the abilities of cell proliferation, migration and invasion, induced cell cycle arrest and promoted cellular apoptosis. Collectively, these results suggest that miR-18a may regulate biological behavior of human glioblastoma cells by targeting neogenin, and miR-18a can serve as a potential target in the treatment of glioblastoma. - Highlights: MiR-18a was highly expressed in glioblastoma tissues and U87 and U251 cell lines. Neogenin was identified as the target gene of miR-18a. Neogenin expressions were decreased along with the rising pathological grades of glioblastoma. Inhibition of miR-18a suppressed biological behavior of glioma cells by up-regulating neogenin.

  3. PPAR{gamma} ligands induce growth inhibition and apoptosis through p63 and p73 in human ovarian cancer cells

    SciTech Connect (OSTI)

    Kim, Soyeon; Innovative Research Institute for Cell Therapy, Seoul National University College of Medicine and Hospital, Seoul ; Lee, Jae-Jung; Heo, Dae Seog

    2011-03-18

    Research highlights: {yields} PPAR{gamma} ligands increased the rate of apoptosis and inhibition of proliferation in ovarian cancer cells. {yields} PPAR{gamma} ligands induced p63 and p73 expression, but not p53. {yields} p63 and p73 leads to an increase in p21 expression and apoptosis in ovarian cancer cells with treatment PPAR{gamma} ligands. {yields} These findings suggest that PPAR{gamma} ligands suppressed growth of ovarian cancer cells through upregulation of p63 and p73. -- Abstract: Peroxisome proliferator-activated receptor gamma (PPAR{gamma}) agonists, including thiazolidinediones (TZDs), can induce anti-proliferation, differentiation, and apoptosis in various cancer cell types. This study investigated the mechanism of the anticancer effect of TZDs on human ovarian cancer. Six human ovarian cancer cell lines (NIH:OVCAR3, SKOV3, SNU-251, SNU-8, SNU-840, and 2774) were treated with the TZD, which induced dose-dependent inhibition of cell growth. Additionally, these cell lines exhibited various expression levels of PPAR{gamma} protein as revealed by Western blotting. Flow cytometry showed that the cell cycle was arrested at the G1 phase, as demonstrated by the appearance of a sub-G1 peak. This observation was corroborated by the finding of increased levels of Bax, p21, PARP, and cleaved caspase 3 in TGZ-treated cells. Interestingly, when we determined the effect of p53-induced growth inhibition in these three human ovarian cancer cells, we found that they either lacked p53 or contained a mutant form of p53. Furthermore, TGZ induced the expression of endogenous or exogenous p63 and p73 proteins and p63- or p73-directed short hairpin (si) RNAs inhibited the ability of TGZ to regulate expression of p21 in these cells. Thus, our results suggest that PPAR{gamma} ligands can induce growth suppression of ovarian cancer cells and mediate p63 and p73 expression, leading to enhanced growth inhibition and apoptosis. The tumor suppressive effects of PPAR{gamma} ligands may have applications for the treatment of ovarian cancer.

  4. MicroRNA-320a suppresses human colon cancer cell proliferation by directly targeting {beta}-catenin

    SciTech Connect (OSTI)

    Sun, Jian-Yong; State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 710032 Xi'an ; Huang, Yi; Li, Ji-Peng; Zhang, Xiang; Wang, Lei; Meng, Yan-Ling; Yan, Bo; Bian, Yong-Qian; Zhao, Jing; Wang, Wei-Zhong; and others

    2012-04-20

    Highlights: Black-Right-Pointing-Pointer miR-320a is downregulated in human colorectal carcinoma. Black-Right-Pointing-Pointer Overexpression of miR-320a inhibits colon cancer cell proliferation. Black-Right-Pointing-Pointer {beta}-Catenin is a direct target of miR-320a in colon cancer cells. Black-Right-Pointing-Pointer miR-320a expression inversely correlates with mRNA expression of {beta}-catenin's target genes in human colon carcinoma. -- Abstract: Recent profile studies of microRNA (miRNA) expression have documented a deregulation of miRNA (miR-320a) in human colorectal carcinoma. However, its expression pattern and underlying mechanisms in the development and progression of colorectal carcinoma has not been elucidated clearly. Here, we performed real-time PCR to examine the expression levels of miR-320a in colon cancer cell lines and tumor tissues. And then, we investigated its biological functions in colon cancer cells by a gain of functional strategy. Further more, by the combinational approaches of bioinformatics and experimental validation, we confirmed target associations of miR-320a in colorectal carcinoma. Our results showed that miR-320a was frequently downregulated in cancer cell lines and colon cancer tissues. And we demonstrated that miR-320a restoration inhibited colon cancer cell proliferation and {beta}-catenin, a functionally oncogenic molecule was a direct target gene of miR-320a. Finally, the data of real-time PCR showed the reciprocal relationship between miR-320a and {beta}-catenin's downstream genes in colon cancer tissues. These findings indicate that miR-320a suppresses the growth of colon cancer cells by directly targeting {beta}-catenin, suggesting its application in prognosis prediction and cancer treatment.

  5. Study the cytotoxicity of different kinds of water-soluble nanoparticles in human osteoblast-like MG-63 cells

    SciTech Connect (OSTI)

    Niu, Lu; Li, Yang; Li, Xiaojie; Gao, Xue; Su, Xingguang

    2012-11-15

    Highlights: ? Preparation of three kinds of water-soluble QDs: CdTe, CdTe@SiO{sub 2}, Mn:ZnSe. ? Evaluated the cytotoxicity qualitatively and quantitatively. ? Fluorescent staining. ? Detected the total intracellular cadmium in cells. -- Abstract: Quantum nanoparticles have been applied extensively in biological and medical fields, the cytotoxicity of nanoparticles becomes the key point we should concern. In this paper, the cytotoxicity of three kinds of water-soluble nanoparticles: CdTe, CdTe@SiO{sub 2} and Mn:ZnSe was studied. We evaluated the nanoparticles toxicity qualitatively by observing the morphological changes of human osteoblast-like MG-63 cells at different incubation times and colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays were carried out to detect the cell viability quantitatively. The results showed that CdTe nanoparticles with high concentrations caused cells to die largely while CdTe@SiO{sub 2} and Mn:ZnSe nanoparticles had no obvious effect. For further study, we studied the relation between the cell viability and the total cadmium concentration in cells and found that the viability of cells treated with CdTe@SiO{sub 2} nanoparticles was higher than that treated with CdTe nanoparticles. We also discovered that the death rate of cells co-incubated with CdTe nanoparticles was proportional to the total intracellular cadmium concentrations.

  6. Three-dimensional Invasion of Human Glioblastoma Cells Remains Unchanged by X-ray and Carbon Ion Irradiation In Vitro

    SciTech Connect (OSTI)

    Eke, Iris; Storch, Katja; Kaestner, Ina; Vehlow, Anne; Faethe, Christina; Mueller-Klieser, Wolfgang; Taucher-Scholz, Gisela; Temme, Achim; Schackert, Gabriele; Department of Radiation Oncology, Medical Faculty Carl Gustav Carus, Dresden University of Technology, Dresden

    2012-11-15

    Purpose: Cell invasion represents one of the major determinants that treatment has failed for patients suffering from glioblastoma. Contrary findings have been reported for cell migration upon exposure to ionizing radiation. Here, the migration and invasion capability of glioblastoma cells on and in collagen type I were evaluated upon irradiation with X-rays or carbon ions. Methods and Materials: Migration on and invasion in collagen type I were evaluated in four established human glioblastoma cell lines exposed to either X-rays or carbon ions. Furthermore, clonogenic radiation survival, proliferation (5-bromo-2-deoxyuridine positivity), DNA double-strand breaks ({gamma}H2AX/53BP1-positive foci), and expression of invasion-relevant proteins (eg, {beta}1 integrin, FAK, MMP2, and MMP9) were explored. Migration and invasion assays for primary glioblastoma cells also were carried out with X-ray irradiation. Results: Neither X-ray nor carbon ion irradiation affected glioblastoma cell migration and invasion, a finding similarly observed in primary glioblastoma cells. Intriguingly, irradiated cells migrated unhampered, despite DNA double-strand breaks and reduced proliferation. Clonogenic radiation survival was increased when cells had contact with extracellular matrix. Specific inhibition of the {beta}1 integrin or proliferation-associated signaling molecules revealed a critical function of JNK, PI3K, and p38 MAPK in glioblastoma cell invasion. Conclusions: These findings indicate that X-rays and carbon ion irradiation effectively reduce proliferation and clonogenic survival without modifying the migration and invasion ability of glioblastoma cells in a collagen type I environment. Addition of targeted agents against members of the MAPK and PI3K signaling axis to conventional chemoradiation therapy seems potentially useful to optimize glioblastoma therapy.

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

    SciTech Connect (OSTI)

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

    2014-12-17

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

  8. Up-regulation of E-cadherin by small activating RNA inhibits cell invasion and migration in 5637 human bladder cancer cells

    SciTech Connect (OSTI)

    Mao Qiqi; Li Yubing; Zheng Xiangyi; Yang Kai; Shen Huafeng; Qin Jie; Bai Yu; Kong Debo; Jia Xiaolong [Department of Urology, First Affiliated Hospital, School of Medicine, Zhejiang University, Qingchun Road 79, Hangzhou 310003, Zhejiang Province (China); Xie Liping [Department of Urology, First Affiliated Hospital, School of Medicine, Zhejiang University, Qingchun Road 79, Hangzhou 310003, Zhejiang Province (China)], E-mail: xielp@zjuem.zju.edu.cn

    2008-10-31

    Recent studies have reported that chemically synthesized small duplex RNAs complementary to promoters of target genes can specifically induce gene expression in several cancer cell lines. Such dsRNA, referred to as small activating RNA (saRNA), are involved in the recently described phenomenon called RNA activation (RNAa). Recent findings show that saRNA can inhibit cell proliferation and viability via up-regulation of p21{sup WAF1/CIP1} (p21) in human bladder cancer cells. In the present study, we demonstrate that induction of E-cadherin expression by saRNA leads to suppression of migration and invasion of 5637 human bladder cancer cells in vitro. The elevated E-cadherin expression was confirmed at transcriptional and protein levels after transfection of a 21-nucleotide dsRNA targeting the E-cadherin promoter (dsEcad). Furthermore, this inhibitory effect was associated with relocalization of {beta}-catenin from the nucleus to the plasma membrane and decreased {beta}-catenin-mediated transactivation. These data suggest that activation of E-cadherin by saRNA may have a therapeutic benefit for bladder and other types of cancer.

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

    SciTech Connect (OSTI)

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

    2012-03-09

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

  10. Turbine vane with high temperature capable skins

    DOE Patents [OSTI]

    Morrison, Jay A.

    2012-07-10

    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.

  11. Plant cyclopeptide RA-V kills human breast cancer cells by inducing mitochondria-mediated apoptosis through blocking PDK1AKT interaction

    SciTech Connect (OSTI)

    Fang, Xian-Ying; Chen, Wei; Fan, Jun-Ting; Song, Ran; Wang, Lu; Gu, Yan-Hong; Zeng, Guang-Zhi; Shen, Yan; Wu, Xue-Feng; Tan, Ning-Hua; Xu, Qiang; Sun, Yang

    2013-02-15

    In the present paper, we examined the effects of a natural cyclopeptide RA-V on human breast cancer cells and the underlying mechanisms. RA-V significantly inhibited the growth of human breast cancer MCF-7, MDA-MB-231 cells and murine breast cancer 4T1 cells. In addition, RA-V triggered mitochondrial apoptotic pathway which was indicated by the loss of mitochondrial membrane potential, the release of cytochrome c, and the activation of caspase cascade. Further study showed that RA-V dramatically inhibited phosphorylation of AKT and 3-phosphoinositide dependent protein kinase 1 (PDK1) in MCF-7 cells. Moreover, RA-V disrupted the interaction between PDK1 and AKT in MCF-7 cells. Furthermore, RA-V-induced apoptosis could be enhanced by phosphatidylinositol 3-kinase inhibitor or attenuated by over-expression of AKT in all the three kinds of breast cancer cells. Taken together, this study shows that RA-V, which can induce mitochondria-mediated apoptosis, exerts strong anti-tumor activity against human breast cancer. The underlying anti-cancer mechanism of RA-V is related to the blockage of the interaction between PDK1 and AKT. - Highlights: ? Plant cyclopeptide RA-V kills human breast cancer cells. ? RA-V triggered mitochondrial apoptotic pathway in human breast cancer cells. ? RA-V inhibited phosphorylation of AKT and PDK1 in breast cancer MCF-7 cells. ? Its mechanism is related to the blockage of the interaction between PDK1 and AKT.

  12. Dissecting Biological Dark Matter: Single Cell Genetic Analysis of TM7, a Rare and Uncultivated Microbe from the Human Mouth

    SciTech Connect (OSTI)

    Fenner, Marsha W; Marcy, Yann; Ouverney, Cleber; Bik, Elisabeth M.; Losekann, Tina; Ivanova, Natalia; Martin, H. Garcia; Szeto, E.; Platt, Darren; Hugenholtz, Philip; Relman, David A.; Quake, Stephen R.

    2007-07-01

    We have developed a microfluidic device that allows the isolation and genome amplification of individual microbial cells, thereby enabling organism-level genomic analysis of complex microbial ecosystems without the need for culture. This device was used to perform a directed survey of the human subgingival crevice and to isolate bacteria having rod-like morphology. Several isolated microbes had a 16S rRNA sequence that placed them in candidate phylum TM7, which has no cultivated or sequenced members. Genome amplification from individual TM7 cells allowed us to sequence and assemble >1,000 genes, providing insight into the physiology of members of this phylum. This approach enables single-cell genetic analysis of any uncultivated minority member of a microbial community.

  13. Tumor exosomes induce tunneling nanotubes in lipid raft-enriched regions of human mesothelioma cells

    SciTech Connect (OSTI)

    Thayanithy, Venugopal; Babatunde, Victor; Dickson, Elizabeth L.; Wong, Phillip; Oh, Sanghoon; Ke, Xu; Barlas, Afsar; Fujisawa, Sho; Romin, Yevgeniy; Moreira, Andr L.; Downey, Robert J.; Steer, Clifford J.; Subramanian, Subbaya; Manova-Todorova, Katia; Moore, Malcolm A.S.; Lou, Emil

    2014-04-15

    Tunneling nanotubes (TnTs) are long, non-adherent, actin-based cellular extensions that act as conduits for transport of cellular cargo between connected cells. The mechanisms of nanotube formation and the effects of the tumor microenvironment and cellular signals on TnT formation are unknown. In the present study, we explored exosomes as potential mediators of TnT formation in mesothelioma and the potential relationship of lipid rafts to TnT formation. Mesothelioma cells co-cultured with exogenous mesothelioma-derived exosomes formed more TnTs than cells cultured without exosomes within 2448 h; and this effect was most prominent in media conditions (low-serum, hyperglycemic medium) that support TnT formation (1.31.9-fold difference). Fluorescence and electron microscopy confirmed the purity of isolated exosomes and revealed that they localized predominantly at the base of and within TnTs, in addition to the extracellular environment. Time-lapse microscopic imaging demonstrated uptake of tumor exosomes by TnTs, which facilitated intercellular transfer of these exosomes between connected cells. Mesothelioma cells connected via TnTs were also significantly enriched for lipid rafts at nearly a 2-fold higher number compared with cells not connected by TnTs. Our findings provide supportive evidence of exosomes as potential chemotactic stimuli for TnT formation, and also lipid raft formation as a potential biomarker for TnT-forming cells. - Highlights: Exosomes derived from malignant cells can stimulate an increased rate in the formation of tunneling nanotubes. Tunneling nanotubes can serve as conduits for intercellular transfer of these exosomes. Most notably, exosomes derived from benign mesothelial cells had no effect on nanotube formation. Cells forming nanotubes were enriched in lipid rafts at a greater number compared with cells not forming nanotubes. Our findings suggest causal and potentially synergistic association of exosomes and tunneling nanotubes in cancer.

  14. Potential role of 20S proteasome in maintaining stem cell integrity of human bone marrow stromal cells in prolonged culture expansion

    SciTech Connect (OSTI)

    Lu, Li; Song, Hui-Fang; Zhang, Wei-Guo; Liu, Xue-Qin; Zhu, Qian; Cheng, Xiao-Long; Yang, Gui-Jiao; Li, Ang; Xiao, Zhi-Cheng; Monash Immunology and Stem Cell Laboratories, Monash University, Clayton, Melbourne 3800

    2012-05-25

    Highlights: Black-Right-Pointing-Pointer Prolonged culture expansion retards proliferation and induces senescence of hBMSCs. Black-Right-Pointing-Pointer Reduced 20S proteasomal activity and expression potentially contribute to cell aging. Black-Right-Pointing-Pointer MG132-mediated 20S proteasomal inhibition induces senescence-like phenotype. Black-Right-Pointing-Pointer 18{alpha}-GA stimulates proteasomal activity and restores replicative senescence. Black-Right-Pointing-Pointer 18{alpha}-GA retains differentiation without affecting stem cell characterizations. -- Abstract: Human bone marrow stromal cells (hBMSCs) could be used in clinics as precursors of multiple cell lineages following proper induction. Such application is impeded by their characteristically short lifespan, together with the increasing loss of proliferation capability and progressive reduction of differentiation potential after the prolonged culture expansion. In the current study, we addressed the possible role of 20S proteasomes in this process. Consistent with prior reports, long-term in vitro expansion of hBMSCs decreased cell proliferation and increased replicative senescence, accompanied by reduced activity and expression of the catalytic subunits PSMB5 and PSMB1, and the 20S proteasome overall. Application of the proteasome inhibitor MG132 produced a senescence-like phenotype in early passages, whereas treating late-passage cells with 18{alpha}-glycyrrhetinic acid (18{alpha}-GA), an agonist of 20S proteasomes, delayed the senescence progress, enhancing the proliferation and recovering the capability of differentiation. The data demonstrate that activation of 20S proteasomes assists in counteracting replicative senescence of hBMSCs expanded in vitro.

  15. Identification of stem cells from human umbilical cord blood with embryonic and hematopoietic characteristics

    SciTech Connect (OSTI)

    Zhao Yong . E-mail: yongzhao@uic.edu; Wang Honglan; Mazzone, Theodore

    2006-08-01

    We identified stem cells from the umbilical cord blood, designated cord blood-stem cells (CB-SC). CB-SC displayed important embryonic stem (ES) cell characteristics including expression of ES-cell-specific molecular markers including transcription factors OCT-4 and Nanog, along with stage-specific embryonic antigen (SSEA)-3 and SSEA-4. CB-SC also expressed hematopoietic cell antigens including CD9, CD45 and CD117, but were negative for CD34. CB-SC displayed very low immunogenicity as indicated by expression of a very low level of major histocompatibility complex (MHC) antigens and failure to stimulate the proliferation of allogeneic lymphocytes. CB-SC could give rise to cells with endothelial-like and neuronal-like characteristics in vitro, as demonstrated by expression of lineage-associated markers. Notably, CB-SC could be stimulated to differentiate into functional insulin-producing cells in vivo and eliminated hyperglycemia after transplantation into a streptozotocin-induced diabetic mouse model. These findings may have significant potential to advance stem-cell-based therapeutics.

  16. Targeting miR-21 enhances the sensitivity of human colon cancer HT-29 cells to chemoradiotherapy in vitro

    SciTech Connect (OSTI)

    Deng, Jun; Lei, Wan; Fu, Jian-Chun; Zhang, Ling; Li, Jun-He; Xiong, Jian-Ping

    2014-01-17

    Highlight: MiR-21 plays a significant role in 5-FU resistance. This role might be attributed to targeting of hMSH2 as well as TP and DPD via miR-21 targeted hMSH2. Indirectly targeted TP and DPD to influence 5-FU chemotherapy sensitivity. -- Abstract: 5-Fluorouracil (5-FU) is a classic chemotherapeutic drug that has been widely used for colorectal cancer treatment, but colorectal cancer cells are often resistant to primary or acquired 5-FU therapy. Several studies have shown that miR-21 is significantly elevated in colorectal cancer. This suggests that this miRNA might play a role in this resistance. In this study, we investigated this possibility and the possible mechanism underlying this role. We showed that forced expression of miR-21 significantly inhibited apoptosis, enhanced cell proliferation, invasion, and colony formation ability, promoted G1/S cell cycle transition and increased the resistance of tumor cells to 5-FU and X radiation in HT-29 colon cancer cells. Furthermore, knockdown of miR-21 reversed these effects on HT-29 cells and increased the sensitivity of HT-29/5-FU to 5-FU chemotherapy. Finally, we showed that miR-21 targeted the human mutS homolog2 (hMSH2), and indirectly regulated the expression of thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD). These results demonstrate that miR-21 may play an important role in the 5-FU resistance of colon cancer cells.

  17. The protein pheromone Er-1 of the ciliate Euplotes raikovi stimulates human T-cell activity: Involvement of interleukin-2 system

    SciTech Connect (OSTI)

    Cervia, Davide; Department of Biomedical and Clinical Sciences, Luigi Sacco University Hospital, University of Milan, Milano ; Catalani, Elisabetta; Belardinelli, Maria Cristina; Perrotta, Cristiana; Picchietti, Simona; Alimenti, Claudio; Casini, Giovanni; Fausto, Anna Maria; Vallesi, Adriana

    2013-02-01

    Water-soluble protein signals (pheromones) of the ciliate Euplotes have been supposed to be functional precursors of growth factors and cytokines that regulate cellcell interaction in multi-cellular eukaryotes. This work provides evidence that native preparations of the Euplotes raikovi pheromone Er-1 (a helical protein of 40 amino acids) specifically increases viability, DNA synthesis, proliferation, and the production of interferon-?, tumor necrosis factor-?, interleukin (IL)-1?, IL-2, and IL-13 in human Jurkat T-cells. Also, Er-1 significantly decreases the mRNA levels of the ? and ? subunits of IL-2 receptor (IL-2R), while the mRNA levels of the ? subunit appeared to be not affected. Jurkat T-cell treatments with Er-1 induced the down-regulation of the IL-2R? subunit by a reversible and time-dependent endocytosis, and increased the levels of phosphorylation of the extracellular signal-regulated kinases (ERK). The cell-type specificity of these effects was supported by the finding that Er-1, although unable to directly influence the growth of human glioma U-373 cells, induced Jurkat cells to synthesize and release factors that, in turn, inhibited the U-373 cell proliferation. Overall, these findings imply that Er-1 coupling to IL-2R and ERK immuno-enhances T-cell activity, and that this effect likely translates to an inhibition of glioma cell growth. -- Highlights: ? Euplotes pheromone Er-1 increases the growth of human Jurkat T-cells. ? Er-1 increases the T-cell production of specific cytokines. ? Er-1 activates interleukin-2 receptor and extracellular signal-regulated kinases. ? The immuno-enhancing effect of Er-1 on Jurkat cells translates to an inhibition of human glioma cell growth.

  18. Bio-inspired nanocomposite assemblies as smart skin components...

    Office of Scientific and Technical Information (OSTI)

    automatically detect and respond to chemical and biological threats without the need for human intervention. In living systems, cell membranes perform such functions on a routine...

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

    SciTech Connect (OSTI)

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

    2014-08-31

    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)

  20. Induction of human microsomal prostaglandin E synthase 1 by activated oncogene RhoA GTPase in A549 human epithelial cancer cells

    SciTech Connect (OSTI)

    Choi, Hye Jin; Lee, Dong-Hyung; Park, Seong-Hwan; Kim, Juil; Do, Kee Hun; An, Tae Jin; Ahn, Young Sup; Park, Chung Berm; Moon, Yuseok; Medical Research Institute and Research Institute for Basic Sciences, Pusan National University, Busan

    2011-09-30

    Highlights: {yields} As a target of oncogene RhoA-linked signal, a prostaglandin metabolism is assessed. {yields} RhoA activation increases PGE{sub 2} levels and its metabolic enzyme mPGES-1. {yields} RhoA-activated NF-{kappa}B and EGR-1 are positively involved in mPGES-1 induction. -- Abstract: Oncogenic RhoA GTPase has been investigated as a mediator of pro-inflammatory responses and aggressive carcinogenesis. Among the various targets of RhoA-linked signals, pro-inflammatory prostaglandin E{sub 2} (PGE{sub 2}), a major prostaglandin metabolite, was assessed in epithelial cancer cells. RhoA activation increased PGE{sub 2} levels and gene expression of the rate-limiting PGE{sub 2} producing enzymes, cyclooxygenase-2 and microsomal prostaglandin E synthase 1 (mPGES-1). In particular, human mPGES-1 was induced by RhoA via transcriptional activation in control and interleukin (IL)-1{beta}-activated cancer cells. To address the involvement of potent signaling pathways in RhoA-activated mPGES-1 induction, various signaling inhibitors were screened for their effects on mPGES-1 promoter activity. RhoA activation enhanced basal and IL-1{beta}-mediated phosphorylated nuclear factor-{kappa}B and extracellular signal-regulated kinase1/2 proteins, all of which were positively involved in RhoA-induced gene expression of mPGES-1. As one potent down-stream transcription factor of ERK1/2 signals, early growth response gene 1 product also mediated RhoA-induced gene expression of mPGES-1 by enhancing transcriptional activity. Since oncogene-triggered PGE{sub 2} production is a critical modulator of epithelial tumor cells, RhoA-associated mPGES-1 represents a promising chemo-preventive or therapeutic target for epithelial inflammation and its associated cancers.

  1. Leptin upregulates telomerase activity and transcription of human telomerase reverse transcriptase in MCF-7 breast cancer cells

    SciTech Connect (OSTI)

    Ren, He; Zhao, Tiansuo; Wang, Xiuchao; Gao, Chuntao; Wang, Jian; Yu, Ming; Hao, Jihui

    2010-03-26

    The aim was to analyze the mechanism of leptin-induced activity of telomerase in MCF-7 breast cancer cells. We found that leptin activated telomerase in a dose-dependent manner; leptin upregulated the expression of Human Telomerase Reverse Transcriptase (hTERT) at mRNA and protein levels; blockade of signal transducer and activator of transcription 3 (STAT3) phosphorylation significantly counteracted leptin-induced hTERT transcription and protein expression; chromatin immunoprecipitation analysis showed that leptin enhanced the binding of STAT3 to the hTERT promoter. This study uncovers a new mechanism of the proliferative effect of leptin on breast cancer cells and provides a new explanation of obesity-related breast cancer.

  2. Effects of FGF-2 on human adipose tissue derived adult stem cells morphology and chondrogenesis enhancement in Transwell culture

    SciTech Connect (OSTI)

    Kabiri, Azadeh; Esfandiari, Ebrahim; Hashemibeni, Batool; Kazemi, Mohammad; Mardani, Mohammad; Esmaeili, Abolghasem

    2012-07-27

    Highlights: Black-Right-Pointing-Pointer We investigated effects of FGF-2 on hADSCs. Black-Right-Pointing-Pointer We examine changes in the level of gene expressions of SOX-9, aggrecan and collagen type II and type X. Black-Right-Pointing-Pointer FGF-2 induces chondrogenesis in hADSCs, which Bullet Increasing information will decrease quality if hospital costs are very different. Black-Right-Pointing-Pointer The result of this study may be beneficial in cartilage tissue engineering. -- Abstract: Injured cartilage is difficult to repair due to its poor vascularisation. Cell based therapies may serve as tools to more effectively regenerate defective cartilage. Both adult mesenchymal stem cells (MSCs) and human adipose derived stem cells (hADSCs) are regarded as potential stem cell sources able to generate functional cartilage for cell transplantation. Growth factors, in particular the TGF-b superfamily, influence many processes during cartilage formation, including cell proliferation, extracellular matrix synthesis, maintenance of the differentiated phenotype, and induction of MSCs towards chondrogenesis. In the current study, we investigated the effects of FGF-2 on hADSC morphology and chondrogenesis in Transwell culture. hADSCs were obtained from patients undergoing elective surgery, and then cultured in expansion medium alone or in the presence of FGF-2 (10 ng/ml). mRNA expression levels of SOX-9, aggrecan and collagen type II and type X were quantified by real-time polymerase chain reaction. The morphology, doubling time, trypsinization time and chondrogenesis of hADSCs were also studied. Expression levels of SOX-9, collagen type II, and aggrecan were all significantly increased in hADSCs expanded in presence of FGF-2. Furthermore FGF-2 induced a slender morphology, whereas doubling time and trypsinization time decreased. Our results suggest that FGF-2 induces hADSCs chondrogenesis in Transwell culture, which may be beneficial in cartilage tissue engineering.

  3. Cytotoxicity and inhibitory effects of low-concentration triclosan on adipogenic differentiation of human mesenchymal stem cells

    SciTech Connect (OSTI)

    Guo, Li-Wu; Wu, Qiangen; Green, Bridgett; Nolen, Greg; Shi, Leming; LoSurdo, Jessica; Deng, Helen; Bauer, Steven; Fang, Jia-Long; Ning, Baitang

    2012-07-15

    Humans at all ages are continually exposed to triclosan (TCS), a widely used antimicrobial agent that can be found in many daily hygiene products, such as toothpastes and shampoos; however, the toxicological and biological effects of TCS in the human body after long-term and low-concentration exposure are far from being well understood. In the current study, we investigated the effects of TCS on the differentiation of human mesenchymal stem cells (hMSCs) by measuring the cytotoxicity, morphological changes, lipid accumulation, and the expression of adipocyte differentiation biomarkers during 21-day adipogenesis. Significant cytotoxicity was observed in un-induced hMSCs treated with high-concentration TCS (? 5.0 ?M TCS), but not with low-concentration treatments (? 2.5 ?M TCS). TCS inhibited adipocyte differentiation of hMSCs in a concentration-dependent manner in the 0.156 to 2.5 ?M range as indicated by morphological changes with Oil Red O staining, which is an index of lipid accumulation. The inhibitory effect was confirmed by a decrease in gene expression of specific adipocyte differentiation biomarkers including adipocyte protein 2, lipoprotein lipase, and adiponectin. Our study demonstrates that TCS inhibits adipocyte differentiation of hMSCs under concentrations that are not cytotoxic and in the range observed in human blood. -- Highlights: ? TCS is cytotoxic to un-induced hMSCs at concentrations ? 5.0 ?M. ? TCS at concentrations ? 2.5 ?M is not cytotoxic to induced hMSCs. ? TCS at non-cytotoxic concentrations inhibits lipid formation in induced hMSCs. ? TCS decreases the expression of specific biomarkers of adipocyte differentiation. ? TCS at concentrations observed in human blood inhibits adipogenesis of hMSCs.

  4. 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: sungw@dicp.ac.cn [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: maxj@dicp.ac.cn [Laboratory of Biomedical Material Engineering, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023 (China)

    2013-08-15

    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.

  5. Stationary turbine component with laminated skin

    DOE Patents [OSTI]

    James, Allister W. (Orlando, FL)

    2012-08-14

    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.

  6. Assessment of beating parameters in human induced pluripotent stem cells enables quantitative in vitro screening for cardiotoxicity

    SciTech Connect (OSTI)

    Sirenko, Oksana; Cromwell, Evan F.; Crittenden, Carole; Wignall, Jessica A.; Wright, Fred A.; Rusyn, Ivan

    2013-12-15

    Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes show promise for screening during early drug development. Here, we tested a hypothesis that in vitro assessment of multiple cardiomyocyte physiological parameters enables predictive and mechanistically-interpretable evaluation of cardiotoxicity in a high-throughput format. Human iPSC-derived cardiomyocytes were exposed for 30 min or 24 h to 131 drugs, positive (107) and negative (24) for in vivo cardiotoxicity, in up to 6 concentrations (3 nM to 30 uM) in 384-well plates. Fast kinetic imaging was used to monitor changes in cardiomyocyte function using intracellular Ca{sup 2+} flux readouts synchronous with beating, and cell viability. A number of physiological parameters of cardiomyocyte beating, such as beat rate, peak shape (amplitude, width, raise, decay, etc.) and regularity were collected using automated data analysis. Concentrationresponse profiles were evaluated using logistic modeling to derive a benchmark concentration (BMC) point-of-departure value, based on one standard deviation departure from the estimated baseline in vehicle (0.3% dimethyl sulfoxide)-treated cells. BMC values were used for cardiotoxicity classification and ranking of compounds. Beat rate and several peak shape parameters were found to be good predictors, while cell viability had poor classification accuracy. In addition, we applied the Toxicological Prioritization Index (ToxPi) approach to integrate and display data across many collected parameters, to derive cardiosafety ranking of tested compounds. Multi-parameter screening of beating profiles allows for cardiotoxicity risk assessment and identification of specific patterns defining mechanism-specific effects. These data and analysis methods may be used widely for compound screening and early safety evaluation in drug development. - Highlights: Induced pluripotent stem cell-derived cardiomyocytes are promising in vitro models. We tested if evaluation of cardiotoxicity is possible in a high-throughput format. The assay shows benefits of automated data integration across multiple parameters. Quantitative assessment of concentrationresponse is possible using iPSCs. Multi-parametric screening allows for cardiotoxicity risk assessment.

  7. Low Dose Radiation Response Curves, Networks and Pathways in Human Lymphoblastoid Cells Exposed from 1 to 10 cGy of Acute Gamma Radiation

    SciTech Connect (OSTI)

    Wyrobek, A. J.; Manohar, C. F.; Nelson, D. O.; Furtado, M. R.; Bhattacharya, M. S.; Marchetti, F.; Coleman, M.A.

    2011-04-18

    We investigated the low dose dependency of the transcriptional response of human cells to characterize the shape and biological functions associated with the dose response curve and to identify common and conserved functions of low dose expressed genes across cells and tissues. Human lymphoblastoid (HL) cells from two unrelated individuals were exposed to graded doses of radiation spanning the range of 1-10 cGy were analyzed by transcriptome profiling, qPCR and bioinformatics, in comparison to sham irradiated samples. A set of {approx}80 genes showed consistent responses in both cell lines; these genes were associated with homeostasis mechanisms (e.g., membrane signaling, molecule transport), subcellular locations (e.g., Golgi, and endoplasmic reticulum), and involved diverse signal transduction pathways. The majority of radiation-modulated genes had plateau-like responses across 1-10 cGy, some with suggestive evidence that transcription was modulated at doses below 1 cGy. MYC, FOS and TP53 were the major network nodes of the low-dose response in HL cells. Comparison our low dose expression findings in HL cells with those of prior studies in mouse brain after whole body exposure, in human keratinocyte cultures, and in endothelial cells cultures, indicates that certain components of the low dose radiation response are broadly conserved across cell types and tissues, independent of proliferation status.

  8. SIRT1 inactivation induces inflammation through the dysregulation of autophagy in human THP-1 cells

    SciTech Connect (OSTI)

    Takeda-Watanabe, Ai; Kitada, Munehiro; Kanasaki, Keizo; Koya, Daisuke

    2012-10-12

    Highlights: Black-Right-Pointing-Pointer SIRT1 inactivation decreases autophagy in THP-1 cell. Black-Right-Pointing-Pointer Inhibition of autophagy induces inflammation. Black-Right-Pointing-Pointer SIRT1 inactivation induces inflammation through NF-{kappa}B activation. Black-Right-Pointing-Pointer The p62/Sqstm1 accumulation by impairment of autophagy is related to NF-{kappa}B activation. Black-Right-Pointing-Pointer SIRT1 inactivation is involved in the activation of mTOR and decreased AMPK activation. -- Abstract: Inflammation plays a crucial role in atherosclerosis. Monocytes/macrophages are some of the cells involved in the inflammatory process in atherogenesis. Autophagy exerts a protective effect against cellular stresses like inflammation, and it is regulated by nutrient-sensing pathways. The nutrient-sensing pathway includes SIRT1, a NAD{sup +}-dependent histone deacetylase, which is implicated in the regulation of a variety of cellular processes including inflammation and autophagy. The mechanism through which the dysfunction of SIRT1 contributes to the regulation of inflammation in relation to autophagy in monocytes/macrophages is unclear. In the present study, we demonstrate that treatment with 2-[(2-Hydroxynaphthalen-1-ylmethylene)amino]-N-(1-phenethyl)benzamide (Sirtinol), a chemical inhibitor of SIRT1, induces the overexpression of inflammation-related genes such as tumor necrosis factor (TNF)-{alpha} and interleukin (IL)-6 through nuclear factor (NF)-{kappa}B signaling activation, which is associated with autophagy dysfunction, as shown through p62/Sqstm1 accumulation and decreased expression of light chain (LC) 3 II in THP-1 cells. The autophagy inhibitor, 3-methyladenine, also induces inflammation-related NF-{kappa}B activation. In p62/Sqstm1 knockdown cells, Sirtinol-induced inflammation through NF-{kappa}B activation is blocked. In addition, inhibition of SIRT1 is involved in the activation of the mammalian target of rapamycin (mTOR) pathway and is implicated in decreased 5 Prime -AMP activated kinase (AMPK) activation, leading to the impairment of autophagy. The mTOR inhibitor, rapamycin, abolishes Sirtinol-induced inflammation and NF-{kappa}B activation associated with p62/Sqstm1 accumulation. In summary, SIRT1 inactivation induces inflammation through NF-{kappa}B activation and dysregulates autophagy via nutrient-sensing pathways such as the mTOR and AMPK pathways, in THP-1 cells.

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

    SciTech Connect (OSTI)

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

    2011-06-01

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

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

    SciTech Connect (OSTI)

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

    2012-06-27

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

  11. miR-21 modulates tumor outgrowth induced by human adipose tissue-derived mesenchymal stem cells in vivo

    SciTech Connect (OSTI)

    Shin, Keun Koo; Lee, Ae Lim; Kim, Jee Young; Medical Research Center for Ischemic Tissue Engineering, Pusan National University, Yangsan, Gyeongnam 626-870; BK21 Medical Science Education Center, School of Medicine, Pusan National University, Yangsan, Gyeongnam 626-870 ; Lee, Sun Young; Medical Research Center for Ischemic Tissue Engineering, Pusan National University, Yangsan, Gyeongnam 626-870 ; Bae, Yong Chan; Jung, Jin Sup

    2012-06-15

    Highlights: Black-Right-Pointing-Pointer miR-21 modulates hADSC-induced increase of tumor growth. Black-Right-Pointing-Pointer The action is mostly mediated by the modulation of TGF-{beta} signaling. Black-Right-Pointing-Pointer Inhibition of miR-21 enhances the blood flow recovery in hindlimb ischemia. -- Abstract: Mesenchymal stem cells (MSCs) have generated a great deal of interest in clinical situations, due principally to their potential use in regenerative medicine and tissue engineering applications. However, the therapeutic application of MSCs remains limited, unless the favorable effects of MSCs on tumor growth in vivo, and the long-term safety of the clinical applications of MSCs, can be more thoroughly understood. In this study, we determined whether microRNAs can modulate MSC-induced tumor outgrowth in BALB/c nude mice. Overexpression of miR-21 in human adipose-derived stem cells (hADSCs) inhibited hADSC-induced tumor growth, and inhibition of miR-21 increased it. Downregulation of transforming growth factor beta receptor II (TGFBR2), but not of signal transducer and activator of transcription 3, in hADSCs showed effects similar to those of miR-21 overexpression. Downregulation of TGFBR2 and overexpression of miR21 decreased tumor vascularity. Inhibition of miR-21 and the addition of TGF-{beta} increased the levels of vascular endothelial growth factor and interleukin-6 in hADSCs. Transplantation of miR-21 inhibitor-transfected hADSCs increased blood flow recovery in a hind limb ischemia model of nude mice, compared with transplantation of control oligo-transfected cells. These findings indicate that MSCs might favor tumor growth in vivo. Thus, it is necessary to study the long-term safety of this technique before MSCs can be used as therapeutic tools in regenerative medicine and tissue engineering.

  12. Overexpression of the human BCL-2 gene product results in growth enhancement of Epstein-Barr virus-immortalized B cells

    SciTech Connect (OSTI)

    Tsujimoto, Yoshihide (Wistar Institute of Anatomy and Biology, Philadelphia, PA (USA))

    1989-03-01

    The biological activity of the human BCL-2 gene product was analyzed in an Epstein-Barr virus (EBV)-infected human lymphoblastoid B-cell line transfected with BCL-2 sequences driven by the simian virus 40 promoter and enhancer. Overproduction of the BCL-2 protein conferred a selective growth advantage to the EBV-infected B cells as compared with control transfectants in low-serum medium and also after seeding at limiting dilution but did not render the cells tumorigenic in athymic nude mice. This growth enhancement was also seen in cells transfected with the BCL-2 gene with its own promoter juxtaposed to the immunoglobulin heavy chain gene enhancer, which represents the translocated form of the BCL-2 gene observed in follicular lymphomas with the t(14;18) translocation. The growth advantage of EBV-infected B cells overproducing the BCL-2 protein is neither due to the enhanced growth factor production nor due to an enhanced sensitivity of the BCL-2 transfectants to interleukins 1 or 6, although both lymphokines are known to stimulate proliferation of EBV-infected B-cell lines. The growth advantage of EBV-infected B-cell lines. The growth advantage of EBV-infected B cells by overproduction of the BCL-2 protein suggests the direct involvement of the BCL-2 gene product in the pathogenesis of follicular lymphoma.

  13. The candidate tumor suppressor CST6 alters the gene expression profile of human breast carcinoma cells: Down-regulation of the potent mitogenic, motogenic, and angiogenic factor autotaxin

    SciTech Connect (OSTI)

    Song Jin; Jie Chunfa; Polk, Paula; Shridhar, Ravi; Clair, Timothy; Zhang, Jun; Yin, Lijia; Keppler, Daniel . E-mail: dkeppl@lsuhsc.edu

    2006-02-03

    We recently coined CST6 as a novel candidate tumor suppressor gene for breast cancer. CST6 indeed is expressed in the normal human breast epithelium, but little or not at all in breast carcinomas and breast cancer cell lines. Moreover, ectopic expression of CST6 in human breast cancer cells suppressed cell proliferation, migration, invasion, and orthotopic tumor growth. To obtain insights into the molecular mechanism by which CST6 exhibits its pleiotropic effects on tumor cells, we compared global gene expression profiles in mock- and CST6-transfected human MDA-MB-435S cells. Out of 12,625 transcript species, 61 showed altered expression. These included genes for extracellular matrix components, cytokines, kinases, and phosphatases, as well as several key transcription factors. TaqMan PCR assays were used to confirm the microarray data for 7 out of 11 genes. One down-regulated gene product, secreted autotaxin/lyso-phospholipase D, was of particular interest because its down-regulation by CST6 could explain most of CST6's effect on the breast cancer cells. This study thus provides First evidence that CST6 plays a role in the modulation of genes, particularly, genes that are highly relevant to breast cancer progression.

  14. Cytoplasmic sequestration of the tumor suppressor p53 by a heat shock protein 70 family member, mortalin, in human colorectal adenocarcinoma cell lines

    SciTech Connect (OSTI)

    Gestl, Erin E.; Anne Boettger, S.

    2012-06-29

    Highlights: Black-Right-Pointing-Pointer Eight human colorectal cell lines were evaluated for p53 and mortalin localization. Black-Right-Pointing-Pointer Six cell lines displayed cytoplasmic sequestration of the tumor suppressor p53. Black-Right-Pointing-Pointer Direct interaction between mortalin and p53 was shown in five cell lines. Black-Right-Pointing-Pointer Cell lines positive for p53 sequestration yielded elevated p53 expression levels. Black-Right-Pointing-Pointer This study yields the first evidence of cytoplasmic sequestration p53 by mortalin. -- Abstract: While it is known that cytoplasmic retention of p53 occurs in many solid tumors, the mechanisms responsible for this retention have not been positively identified. Since heatshock proteins like mortalin have been associated with p53 inactivation in other tumors, the current study sought to characterize this potential interaction in never before examined colorectal adenocarcinoma cell lines. Six cell lines, one with 3 different fractions, were examined to determine expression of p53 and mortalin and characterize their cellular localization. Most of these cell lines displayed punctate p53 and mortalin localization in the cell cytoplasm with the exception of HCT-8 and HCT116 379.2 cells, where p53 was not detected. Nuclear p53 was only observed in HCT-116 40-16, LS123, and HT-29 cell lines. Mortalin was only localized in the cytoplasm in all cell lines. Co-immunoprecipitation and immunohistochemistry revealed that p53 and mortalin were bound and co-localized in the cytoplasmic fraction of four cell lines, HCT-116 (40-16 and 386; parental and heterozygous fractions respectively of the same cell line), HT-29, LS123 and LoVo, implying that p53 nuclear function is limited in those cell lines by being restricted to the cytoplasm. Mortalin gene expression levels were higher than gene expression levels of p53 in all cell lines. Cell lines with cytoplasmic sequestration of p53, however, also displayed elevated p53 gene expression levels compared to cell lines without p53 sequestration. Our data reveal the characteristic cytoplasmic sequestration of p53 by the heat shock protein mortalin in human colorectal adenocarcinoma cell lines, as is the case for other cancers, such as glioblastomas and hepatocellular carcinomas.

  15. Cytochrome P450 2A13 enhances the sensitivity of human bronchial epithelial cells to aflatoxin B1-induced DNA damage

    SciTech Connect (OSTI)

    Yang, Xuejiao; Zhang, Zhan; Wang, Xichen; Wang, Yun; Zhang, Xiaoming; Lu, Huiyuan; Wang, Shou-Lin

    2013-07-15

    Cytochrome P450 2A13 (CYP2A13) mainly expresses in human respiratory system and mediates the metabolic activation of aflatoxin B1 (AFB1). Our previous study suggested that CYP2A13 could increase the cytotoxic and apoptotic effects of AFB1 in immortalized human bronchial epithelial cells (BEAS-2B). However, the role of CYP2A13 in AFB1-induced DNA damage is unclear. Using BEAS-2B cells that stably express CYP2A13 (B-2A13), CYP1A2 (B-1A2), and CYP2A6 (B-2A6), we compared their effects in AFB1-induced DNA adducts, DNA damage, and cell cycle changes. BEAS-2B cells that were transfected with vector (B-vector) were used as a control. The results showed that AFB1 (580 nM) dose- and time-dependently induced DNA damage in B-2A13 cells. AFB1 at 10 and 80 nM significantly augmented this effect in B-2A13 and B-1A2 cells, respectively. B-2A6 cells showed no obvious DNA damage, similar to B-vector cells and the vehicle control. Similarly, compared with B-vector, B-1A2 or B-2A6 cells, B-2A13 cells showed more sensitivity in AFB1-induced ?H2AX expression, DNA adduct 8-hydroxy-deoxyguanosine formation, and S-phase cell-cycle arrest. Furthermore, AFB1 activated the proteins related to DNA damage responses, such as ATM, ATR, Chk2, p53, BRCA1, and H2AX, rather than the proteins related to DNA repair. These effects could be almost completely inhibited by 100 ?M nicotine (a substrate of CYP2A13) or 1 ?M 8-methoxypsoralen (8-MOP; an inhibitor of CYP enzyme). Collectively, these findings suggest that CYP2A13 plays an important role in low-concentration AFB1-induced DNA damage, possibly linking environmental airborne AFB1 to genetic injury in human respiratory system. - Highlights: CYP2A13 plays a critical role in low concentration of AFB1-induced DNA damage. B-2A13 cells were more sensitive to AFB1 than B-1A2 cells and B-2A6 cells. AFB1 dose- and time-dependently induced DNA damage in B-2A13 cells AFB1-induced DNA adducts and damage can be inhibited by nicotine and 8-MOP.

  16. Skin thickness effects on in vivo LXRF

    SciTech Connect (OSTI)

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

    1995-12-31

    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.

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

    SciTech Connect (OSTI)

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

    2012-04-15

    Carbon nanotube (CNT) has a promising usage in the field of material science for industrial purposes because of its unique physicochemical property. However, intraperitoneal administration of CNT was reported to cause mesothelioma in experimental animals. Chronic inflammation may contribute to carcinogenesis induced by fibrous materials. 8-Nitroguanine is a mutagenic DNA lesion formed during inflammation and may play a role in CNT-induced carcinogenesis. In this study, we examined 8-nitroguanine formation in A549 human lung alveolar epithelial cells treated with multi-walled CNT (MWCNT) by fluorescent immunocytochemistry. Both MWCNTs with diameter of 2030 nm (CNT20) and 4070 nm (CNT40) significantly induced 8-nitroguanine formation at 5 and 10 ?g/ml (p < 0.05), which persisted for 24 h, although there was no significant difference in DNA-damaging abilities of these MWCNTs. MWCNTs significantly induced the expression of inducible nitric oxide synthase (iNOS) for 24 h (p < 0.05). MWCNTs also significantly increased the level of nitrite, a hydrolysis product of oxidized NO, in the culture supernatant at 4 and 8 h (p < 0.05). MWCNT-induced 8-nitroguanine formation and iNOS expression were largely suppressed by inhibitors of iNOS (1400 W), nuclear factor-?B (Bay11-7082), actin polymerization (cytochalasin D), caveolae-mediated endocytosis (methyl-?-cyclodextrin, MBCD) and clathrin-mediated endocytosis (monodansylcadaverine, MDC). Electron microscopy revealed that MWCNT was mainly located in vesicular structures in the cytoplasm, and its cellular internalization was reduced by MBCD and MDC. These results suggest that MWCNT is internalized into cells via clathrin- and caveolae-mediated endocytosis, leading to inflammatory reactions including iNOS expression and resulting nitrative DNA damage, which may contribute to carcinogenesis. Highlights: ?Multi-walled carbon nanotube (MWCNT) caused DNA damage in A549 cells. ?MWCNT formed 8-nitroguanine, a DNA lesion associated with inflammatory response. ?MWCNT was internalized into cells via caveolin- and clathrin-mediated endocytosis. ?8-Nitroguanine formation and iNOS expression involved these types of endocytosis. ?Internalized MWCNT plays a key role in inflammatory response and DNA damage.

  18. First Evaluation of the Biologic Effectiveness Factors of Boron Neutron Capture Therapy (BNCT) in a Human Colon Carcinoma Cell Line

    SciTech Connect (OSTI)

    Dagrosa, Maria Alejandra; Crivello, Martin; Perona, Marina; Thorp, Silvia; Santa Cruz, Gustavo Alberto; Pozzi, Emiliano; Casal, Mariana; Thomasz, Lisa; Cabrini, Romulo; Kahl, Steven; Juvenal, Guillermo Juan; Pisarev, Mario Alberto

    2011-01-01

    Purpose: DNA lesions produced by boron neutron capture therapy (BNCT) and those produced by gamma radiation in a colon carcinoma cell line were analyzed. We have also derived the relative biologic effectiveness factor (RBE) of the neutron beam of the RA-3- Argentine nuclear reactor, and the compound biologic effectiveness (CBE) values for p-boronophenylalanine ({sup 10}BPA) and for 2,4-bis ({alpha},{beta}-dihydroxyethyl)-deutero-porphyrin IX ({sup 10}BOPP). Methods and Materials: Exponentially growing human colon carcinoma cells (ARO81-1) were distributed into the following groups: (1) BPA (10 ppm {sup 10}B) + neutrons, (2) BOPP (10 ppm {sup 10}B) + neutrons, (3) neutrons alone, and (4) gamma rays ({sup 60}Co source at 1 Gy/min dose-rate). Different irradiation times were used to obtain total absorbed doses between 0.3 and 5 Gy ({+-}10%) (thermal neutrons flux = 7.5 10{sup 9} n/cm{sup 2} sec). Results: The frequency of micronucleated binucleated cells and the number of micronuclei per micronucleated binucleated cells showed a dose-dependent increase until approximately 2 Gy. The response to gamma rays was significantly lower than the response to the other treatments (p < 0.05). The irradiations with neutrons alone and neutrons + BOPP showed curves that did not differ significantly from, and showed less DNA damage than, irradiation with neutrons + BPA. A decrease in the surviving fraction measured by 3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetrazolium bromide (MTT) assay as a function of the absorbed dose was observed for all the treatments. The RBE and CBE factors calculated from cytokinesis block micronucleus (CBMN) and MTT assays were, respectively, the following: beam RBE: 4.4 {+-} 1.1 and 2.4 {+-} 0.6; CBE for BOPP: 8.0 {+-} 2.2 and 2.0 {+-} 1; CBE for BPA: 19.6 {+-} 3.7 and 3.5 {+-} 1.3. Conclusions: BNCT and gamma irradiations showed different genotoxic patterns. To our knowledge, these values represent the first experimental ones obtained for the RA-3 in a biologic model and could be useful for future experimental studies for the application of BNCT to colon carcinoma.

  19. Long-term low-dose ?-particle enhanced the potential of malignant transformation in human bronchial epithelial cells through MAPK/Akt pathway

    SciTech Connect (OSTI)

    Liu, Weili; Xiao, Linlin; Dong, Chen; He, Mingyuan; Pan, Yan; Xie, Yuexia; Tu, Wenzhi; Fu, Jiamei; Shao, Chunlin

    2014-05-09

    Highlights: Multi-exposures of 25 mGy ?-ray enhanced cell proliferation, adhesion, and invasion. MAPK/Akt but not JNK/P66 was positively correlated with cell invasive phenotypes. LDR of ?-irradiation triggers cell malignant transformation through MAPK/Akt. - Abstract: Since the wide usage of ionizing radiation, the cancer risk of low dose radiation (LDR) (<0.1 Gy) has become attractive for a long time. However, most results are derived from epidemiologic studies on atomic-bomb survivors and nuclear accidents surrounding population, and the molecular mechanism of this risk is elusive. To explore the potential of a long-term LDR-induced malignant transformation, human bronchial epithelial cells Beas-2B were fractionally irradiated with 0.025 Gy ?-particles for 8 times in total and then further cultured for 12 months. It was found that the cell proliferation, the abilities of adhesion and invasion, and the protein expressions of p-ERK, p-Akt, especially p-P38 were not only increased in the multiply-irradiated cells but also in their offspring 12 months after the final exposure, indicating high potentiality of cell malignant transformation. On opposite, the expressions of p-JNK and p-P66 were diminished in the subcultures of irradiated cells and thus may play a role of negative regulation in canceration. When the cells were transferred with p38 siRNA, the LDR-induced enhancements of cell adhesion and invasion were significantly reduced. These findings suggest that long-term LDR of ?-particles could enhance the potential of malignant transformation incidence in human bronchial epithelial cells through MAPK/Akt pathway.

  20. TiBor Skin - Energy Innovation Portal

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

    Startup America Startup America Advanced Materials Advanced Materials Find More Like This Return to Search TiBor Skin Y-12 National Security Complex Contact Y12 About This Technology Publications: PDF Document Publication Fact Sheet (336 KB) PDF Document Publication Presentation (400 KB) PDF Document Publication Patent Application Publication (2,825 KB) Technology Marketing Summary Y-12 invites interested companies to license its patent-pending method known as TiBor Skin. This two-part

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

    SciTech Connect (OSTI)

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

    2013-02-15

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

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

    SciTech Connect (OSTI)

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

    2014-10-29

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

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

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

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

    2014-10-29

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

  4. Ghrelin inhibits proliferation and increases T-type Ca{sup 2+} channel expression in PC-3 human prostate carcinoma cells

    SciTech Connect (OSTI)

    Diaz-Lezama, Nundehui; Hernandez-Elvira, Mariana; Sandoval, Alejandro; Monroy, Alma; Felix, Ricardo; Monjaraz, Eduardo

    2010-12-03

    Research highlights: {yields} Ghrelin decreases prostate carcinoma PC-3 cells proliferation. {yields} Ghrelin favors apoptosis in PC-3 cells. {yields} Ghrelin increase in intracellular free Ca{sup 2+} levels in PC-3 cells. {yields} Grelin up-regulates expression of T-type Ca{sup 2+} channels in PC-3 cells. {yields} PC-3 cells express T-channels of the Ca{sub V}3.1 and Ca{sub V}3.2 subtype. -- Abstract: Ghrelin is a multifunctional peptide hormone with roles in growth hormone release, food intake and cell proliferation. With ghrelin now recognized as important in neoplastic processes, the aim of this report is to present findings from a series of in vitro studies evaluating the cellular mechanisms involved in ghrelin regulation of proliferation in the PC-3 human prostate carcinoma cells. The results showed that ghrelin significantly decreased proliferation and induced apoptosis. Consistent with a role in apoptosis, an increase in intracellular free Ca{sup 2+} levels was observed in the ghrelin-treated cells, which was accompanied by up-regulated expression of T-type voltage-gated Ca{sup 2+} channels. Interestingly, T-channel antagonists were able to prevent the effects of ghrelin on cell proliferation. These results suggest that ghrelin inhibits proliferation and may promote apoptosis by regulating T-type Ca{sup 2+} channel expression.

  5. Breakthrough antibacterial approach could resolve serious skin infections

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

    Antibacterial approach could resolve skin infections Breakthrough antibacterial approach could resolve serious skin infections Like a protective tent over a colony of harmful bacteria, biofilms make the treatment of skin infections especially difficult. August 26, 2014 Artist's rendition of a cross section of skin layers (stratum corneum, epidermis and dermis) showing topical application of an ionic liquid for combating a skin-borne bacterial infection. The ionic liquid can be formulated with

  6. Understanding the origins of human cancer

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

    Alexandrov, L. B.

    2015-12-04

    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

  7. Self-cleaning skin-like prosthetic polymer surfaces

    DOE Patents [OSTI]

    Simpson, John T. (Clinton, TN); Ivanov, Ilia N. (Knoxville, TN); Shibata, Jason (Manhattan Beach, CA)

    2012-03-27

    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.

  8. 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...

  9. MiR-145 is downregulated in human ovarian cancer and modulates cell growth and invasion by targeting p70S6K1 and MUC1

    SciTech Connect (OSTI)

    Wu, Huijuan; Xiao, ZhengHua; Wang, Ke; Liu, Wenxin; Hao, Quan

    2013-11-29

    Highlights: MiR-145 is downregulated in human ovarian cancer. MiR-145 targets p70S6K1 and MUC1. p70S6K1 and MUC1 are involved in miR-145 mediated tumor cell growth and cell invasion, respectively. -- Abstract: MicroRNAs (miRNAs) are a family of small non-coding RNA molecules that regulate gene expression at post-transcriptional levels. Previous studies have shown that miR-145 is downregulated in human ovarian cancer; however, the roles of miR-145 in ovarian cancer growth and invasion have not been fully demonstrated. In the present study, Northern blot and qRT-PCR analysis indicate that miR-145 is downregulated in ovarian cancer tissues and cell lines, as well as in serum samples of ovarian cancer, compared to healthy ovarian tissues, cell lines and serum samples. Functional studies suggest that miR-145 overexpression leads to the inhibition of colony formation, cell proliferation, cell growth viability and invasion, and the induction of cell apoptosis. In accordance with the effect of miR-145 on cell growth, miR-145 suppresses tumor growth in vivo. MiR-145 is found to negatively regulate P70S6K1 and MUC1 protein levels by directly targeting their 3?UTRs. Importantly, the overexpression of p70S6K1 and MUC1 can restore the cell colony formation and invasion abilities that are reduced by miR-145, respectively. MiR-145 expression is increased after 5-aza-CdR treatment, and 5-aza-CdR treatment results in the same phenotype as the effect of miR-145 overexpression. Our study suggests that miR-145 modulates ovarian cancer growth and invasion by suppressing p70S6K1 and MUC1, functioning as a tumor suppressor. Moreover, our data imply that miR-145 has potential as a miRNA-based therapeutic target for ovarian cancer.

  10. Heritable Genetic Changes in Cells Recovered From Irradiated 3D Tissue Constructs

    SciTech Connect (OSTI)

    Michael Cornforth

    2012-03-26

    Combining contemporary cytogenetic methods with DNA CGH microarray technology and chromosome flow-sorting increases substantially the ability to resolve exchange breakpoints associated with interstitial deletions and translocations, allowing the consequences of radiation damage to be directly measured at low doses, while also providing valuable insights into molecular mechanisms of misrepair processes that, in turn, identify appropriate biophysical models of risk at low doses. Specific aims apply to cells recovered from 3D tissue constructs of human skin and, for the purpose of comparison, the same cells irradiated in traditional 2D cultures. The project includes research complementary to NASA/HRP space radiation project.

  11. A polysaccharide fraction of adlay seed (Coixlachryma-jobi L.) induces apoptosis in human non-small cell lung cancer A549 cells

    SciTech Connect (OSTI)

    Lu, Xiangyi; Liu, Wei; Wu, Junhua; Li, Mengxian [Key Laboratory of Food Nutrition and Safety, Ministry of Education, School of Food Engineering and Biotechnology, Tianjin University of Science and Technology, Tianjin 300457 (China)] [Key Laboratory of Food Nutrition and Safety, Ministry of Education, School of Food Engineering and Biotechnology, Tianjin University of Science and Technology, Tianjin 300457 (China); Wang, Juncheng; Wu, Jihui [School of Life Science, University of Science and Technology of China, Hefei 230022 (China)] [School of Life Science, University of Science and Technology of China, Hefei 230022 (China); Luo, Cheng, E-mail: Luo58@yahoo.com [Key Laboratory of Food Nutrition and Safety, Ministry of Education, School of Food Engineering and Biotechnology, Tianjin University of Science and Technology, Tianjin 300457 (China)] [Key Laboratory of Food Nutrition and Safety, Ministry of Education, School of Food Engineering and Biotechnology, Tianjin University of Science and Technology, Tianjin 300457 (China)

    2013-01-11

    Highlights: Black-Right-Pointing-Pointer A polysaccharide from adlay seed, its molecular mass, optical rotation and sugars was determined. Black-Right-Pointing-Pointer We demonstrated that a polysaccharide from adlay can induce apoptosis in cancer cells. Black-Right-Pointing-Pointer The polysaccharide inhibited the metabolism and proliferation of NSCLC A549 cells. Black-Right-Pointing-Pointer The polysaccharide may trigger apoptosis via the mitochondria-dependent pathway. -- Abstract: Different seed extracts from Coix lachryma-jobi (adlay seed) have been used for the treatment of various cancers in China, and clinical data support the use of these extracts for cancer therapy; however, their underlying molecular mechanisms have not been well defined. A polysaccharide fraction, designated as CP-1, was extracted from the C.lachryma-jobi L. var. using the ethanol subsiding method. CP-1 induced apoptosis in A549 cells in a dose-dependent manner, as determined by MTT assay. Apoptotic bodies were observed in the cells by scanning electronic microscopy. Apoptosis and DNA accumulation during S-phase of the cell cycle were determined by annexin V-FITC and PI staining, respectively, and measured by flow cytometry. CP-1 also extended the comet tail length on single cell gel electrophoresis, and disrupted the mitochondrial membrane potential. Further analysis by western blotting showed that the expression of caspase-3 and caspase-9 proteins was increased. Taken together, our results demonstrate that CP-1 is capable of inhibiting A549 cell proliferation and inducing apoptosis via a mechanism primarily involving the activation of the intrinsic mitochondrial pathway. The assay data suggest that in addition to its nutritional properties, CP-1 is a very promising candidate polysaccharide for the development of anti-cancer medicines.

  12. Ran GTPase protein promotes human pancreatic cancer proliferation by deregulating the expression of Survivin and cell cycle proteins

    SciTech Connect (OSTI)

    Deng, Lin; Department of Oncology, Tangdu Hospital, Fourth Military Medical University, Xian, Shaanxi 710038 ; Lu, Yuanyuan; Zhao, Xiaodi; Sun, Yi; Shi, Yongquan; Fan, Hongwei; Liu, Changhao; Zhou, Jinfeng; Nie, Yongzhan; Wu, Kaichun; Fan, Daiming; Guo, Xuegang

    2013-10-18

    Highlights: Overexpression of Ran in pancreatic cancer was correlated with histological grade. Downregulation of Ran could induce cell apoptosis and inhibit cell proliferation. The effects were mediated by cell cycle proteins, Survivin and cleaved Caspase-3. -- Abstract: Ran, a member of the Ras GTPase family, has important roles in nucleocytoplasmic transport. Herein, we detected Ran expression in pancreatic cancer and explored its potential role on tumour progression. Overexpressed Ran in pancreatic cancer tissues was found highly correlated with the histological grade. Downregulation of Ran led to significant suppression of cell proliferation, cell cycle arrest at the G1/S phase and induction of apoptosis. In vivo studies also validated that result. Further studies revealed that those effects were at least partly mediated by the downregulation of Cyclin A, Cyclin D1, Cyclin E, CDK2, CDK4, phospho-Rb and Survivin proteins and up regulation of cleaved Caspase-3.

  13. 7,12-Dimethylbenzanthracene induces apoptosis in RL95-2 human endometrial cancer cells: Ligand-selective activation of cytochrome P450 1B1

    SciTech Connect (OSTI)

    Kim, Ji Young; Medical Research Science Center, Dong-A University, Busan 602-714 ; Lee, Seung Gee; Mitochondria Hub Regulation Center, Dong-A University, Busan 602-714 ; Chung, Jin-Yong; Medical Research Science Center, Dong-A University, Busan 602-714 ; Kim, Yoon-Jae; Mitochondria Hub Regulation Center, Dong-A University, Busan 602-714 ; Park, Ji-Eun; Medical Research Science Center, Dong-A University, Busan 602-714 ; Oh, Seunghoon; Lee, Se Yong; Choi, Hong Jo; Yoo, Young Hyun; and others

    2012-04-15

    7,12-Dimethylbenzanthracene (DMBA), a polycyclic aromatic hydrocarbon, exhibits mutagenic, carcinogenic, immunosuppressive, and apoptogenic properties in various cell types. To achieve these functions effectively, DMBA is modified to its active form by cytochrome P450 1 (CYP1). Exposure to DMBA causes cytotoxicity-mediated apoptosis in bone marrow B cells and ovarian cells. Although uterine endometrium constitutively expresses CYP1A1 and CYP1B1, their apoptotic role after exposure to DMBA remains to be elucidated. Therefore, we chose RL95-2 endometrial cancer cells as a model system for studying DMBA-induced cytotoxicity and cell death and hypothesized that exposure to DMBA causes apoptosis in this cell type following CYP1A1 and/or CYP1B1 activation. We showed that DMBA-induced apoptosis in RL95-2 cells is associated with activation of caspases. In addition, mitochondrial changes, including decrease in mitochondrial potential and release of mitochondrial cytochrome c into the cytosol, support the hypothesis that a mitochondrial pathway is involved in DMBA-induced apoptosis. Exposure to DMBA upregulated the expression of AhR, Arnt, CYP1A1, and CYP1B1 significantly; this may be necessary for the conversion of DMBA to DMBA-3,4-diol-1,2-epoxide (DMBA-DE). Although both CYP1A1 and CYP1B1 were significantly upregulated by DMBA, only CYP1B1 exhibited activity. Moreover, knockdown of CYP1B1 abolished DMBA-induced apoptosis in RL95-2 cells. Our data show that RL95-2 cells are susceptible to apoptosis by exposure to DMBA and that CYP1B1 plays a pivotal role in DMBA-induced apoptosis in this system. -- Highlights: ? Cytotoxicity-mediated apoptogenic action of DMBA in human endometrial cancer cells. ? Mitochondrial pathway in DMBA-induced apoptosis of RL95-2 endometrial cancer cells. ? Requirement of ligand-selective activation of CYP1B1 in DMBA-induced apoptosis.

  14. miR-421 induces cell proliferation and apoptosis resistance in human nasopharyngeal carcinoma via downregulation of FOXO4

    SciTech Connect (OSTI)

    Chen, Liang; Department of Otolaryngology, Guangzhou General Hospital of PLA Guangzhou Command, Guangzhou 510010 ; Tang, Yanping; Wang, Jian; Yan, Zhongjie; Xu, Ruxiang

    2013-06-14

    Highlights: •miR-421 is upregulated in nasopharyngeal carcinoma. •miR-421 induces cell proliferation and apoptosis resistance. •FOXO4 is a direct and functional target of miR-421. -- Abstract: microRNAs have been demonstrated to play important roles in cancer development and progression. Hence, identifying functional microRNAs and better understanding of the underlying molecular mechanisms would provide new clues for the development of targeted cancer therapies. Herein, we reported that a microRNA, miR-421 played an oncogenic role in nasopharyngeal carcinoma. Upregulation of miR-421 induced, whereas inhibition of miR-421 repressed cell proliferation and apoptosis resistance. Furthermore, we found that upregulation of miR-421 inhibited forkhead box protein O4 (FOXO4) signaling pathway following downregulation of p21, p27, Bim and FASL expression by directly targeting FOXO4 3′UTR. Additionally, we demonstrated that FOXO4 expression is critical for miR-421-induced cell growth and apoptosis resistance. Taken together, our findings not only suggest that miR-421 promotes nasopharyngeal carcinoma cell proliferation and anti-apoptosis, but also uncover a novel regulatory mechanism for inactivation of FOXO4 in nasopharyngeal carcinoma.

  15. Estrogen induced concentration dependent differential gene expression in human breast cancer (MCF7) cells: Role of transcription factors

    SciTech Connect (OSTI)

    Chandrasekharan, Sabarinath; Kandasamy, Krishna Kumar; Dayalan, Pavithra; Ramamurthy, Viraragavan

    2013-08-02

    Highlights: Estradiol (E2) at low dose induced cell proliferation in breast cancer cells. E2 at high concentration induced cell stress in breast cancer cells. Estrogen receptor physically interacts only with a few transcription factors. Differential expression of genes with Oct-1 binding sites increased under stress. Transcription factor binding sites showed distinct spatial distribution on genes. -- Abstract: Background: Breast cancer cells respond to estrogen in a concentration dependent fashion, resulting in proliferation or apoptosis. The mechanism of this concentration dependent differential outcome is not well understood yet. Methodology: Meta-analysis of the expression data of MCF7 cells treated with low (1 nM) or high (100 nM) dose of estradiol (E2) was performed. We identified genes differentially expressed at the low or the high dose, and examined the nature of regulatory elements in the vicinity of these genes. Specifically, we looked for the difference in the presence, abundance and spatial distribution of binding sites for estrogen receptor (ER) and selected transcription factors (TFs) in the genomic region up to 25 kb upstream and downstream from the transcription start site (TSS) of these genes. Results: It was observed that at high dose E2 induced the expression of stress responsive genes, while at low dose, genes involved in cell cycle were induced. We found that the occurrence of transcription factor binding regions (TFBRs) for certain factors such as Sp1 and SREBP1 were higher on regulatory regions of genes expressed at low dose. At high concentration of E2, genes with a higher frequency of Oct-1 binding regions were predominantly involved. In addition, there were differences in the spatial distribution pattern of the TFBRs in the genomic regions among the two sets of genes. Discussion: E2 induced predominantly proliferative/metabolic response at low concentrations; but at high concentration, stressrescue responses were induced. At high E2 concentration, classical genomic pathway involving ER binding to the regulatory regions was reduced, and alternate or indirect activation of genes through Oct-1 became more prominent.

  16. Extracellular acidification induces connective tissue growth factor production through proton-sensing receptor OGR1 in human airway smooth muscle cells

    SciTech Connect (OSTI)

    Matsuzaki, Shinichi; Ishizuka, Tamotsu; Yamada, Hidenori; Kamide, Yosuke; Hisada, Takeshi; Ichimonji, Isao; Aoki, Haruka; Yatomi, Masakiyo; Komachi, Mayumi; Tsurumaki, Hiroaki; Ono, Akihiro; Koga, Yasuhiko; Dobashi, Kunio; Mogi, Chihiro; Sato, Koichi; Tomura, Hideaki; Mori, Masatomo; Okajima, Fumikazu

    2011-10-07

    Highlights: {yields} The involvement of extracellular acidification in airway remodeling was investigated. {yields} Extracellular acidification alone induced CTGF production in human ASMCs. {yields} Extracellular acidification enhanced TGF-{beta}-induced CTGF production in human ASMCs. {yields} Proton-sensing receptor OGR1 was involved in acidic pH-stimulated CTGF production. {yields} OGR1 may play an important role in airway remodeling in asthma. -- Abstract: Asthma is characterized by airway inflammation, hyper-responsiveness and remodeling. Extracellular acidification is known to be associated with severe asthma; however, the role of extracellular acidification in airway remodeling remains elusive. In the present study, the effects of acidification on the expression of connective tissue growth factor (CTGF), a critical factor involved in the formation of extracellular matrix proteins and hence airway remodeling, were examined in human airway smooth muscle cells (ASMCs). Acidic pH alone induced a substantial production of CTGF, and enhanced transforming growth factor (TGF)-{beta}-induced CTGF mRNA and protein expression. The extracellular acidic pH-induced effects were inhibited by knockdown of a proton-sensing ovarian cancer G-protein-coupled receptor (OGR1) with its specific small interfering RNA and by addition of the G{sub q/11} protein-specific inhibitor, YM-254890, or the inositol-1,4,5-trisphosphate (IP{sub 3}) receptor antagonist, 2-APB. In conclusion, extracellular acidification induces CTGF production through the OGR1/G{sub q/11} protein and inositol-1,4,5-trisphosphate-induced Ca{sup 2+} mobilization in human ASMCs.

  17. Antibacterial agent triclosan suppresses RBL-2H3 mast cell function

    SciTech Connect (OSTI)

    Palmer, Rachel K.; Hutchinson, Lee M.; Burpee, Benjamin T.; Tupper, Emily J.; Pelletier, Jonathan H.; Kormendy, Zsolt; Hopke, Alex R.; Malay, Ethan T.; Evans, Brieana L.; Velez, Alejandro; Gosse, Julie A.

    2012-01-01

    Triclosan is a broad-spectrum antibacterial agent, which has been shown previously to alleviate human allergic skin disease. The purpose of this study was to investigate the hypothesis that the mechanism of this action of triclosan is, in part, due to effects on mast cell function. Mast cells play important roles in allergy, asthma, parasite defense, and carcinogenesis. In response to various stimuli, mast cells degranulate, releasing allergic mediators such as histamine. In order to investigate the potential anti-inflammatory effect of triclosan on mast cells, we monitored the level of degranulation in a mast cell model, rat basophilic leukemia cells, clone 2H3. Having functional homology to human mast cells, as well as a very well defined signaling pathway leading to degranulation, this cell line has been widely used to gain insight into mast-cell driven allergic disorders in humans. Using a fluorescent microplate assay, we determined that triclosan strongly dampened the release of granules from activated rat mast cells starting at 2 ?M treatment, with dose-responsive suppression through 30 ?M. These concentrations were found to be non-cytotoxic. The inhibition was found to persist when early signaling events (such as IgE receptor aggregation and tyrosine phosphorylation) were bypassed by using calcium ionophore stimulation, indicating that the target for triclosan in this pathway is likely downstream of the calcium signaling event. Triclosan also strongly suppressed F-actin remodeling and cell membrane ruffling, a physiological process that accompanies degranulation. Our finding that triclosan inhibits mast cell function may explain the clinical data mentioned above and supports the use of triclosan or a mechanistically similar compound as a topical treatment for allergic skin disease, such as eczema. -- Highlights: ?The effects of triclosan on mast cell function using a murine mast cell model. ?Triclosan strongly inhibits degranulation of mast cells. ?Triclosan suppresses membrane ruffling of activated mast cells. ?Triclosan's effects persist when early mast cell signaling events are bypassed. ?Supports use of triclosan as a topical treatment for eczema.

  18. Turbine blade having a constant thickness airfoil skin

    DOE Patents [OSTI]

    Marra, John J

    2012-10-23

    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.

  19. Quantitative proteomic analysis of the inhibitory effects of CIL-102 on viability and invasiveness in human glioma cells

    SciTech Connect (OSTI)

    Teng, Chih-Chuan; Kuo, Hsing-Chun; Sze, Chun-I

    2013-11-01

    CIL-102 (1-[4-(furo[2,3-b]quinolin-4-ylamino)phenyl]ethanone), the major active agent of the alkaloid derivative, has been demonstrated to exert anticancer effects. Herein, we present an investigation focused on the identification of the target(s) of CIL-102's action and the mechanism of its action in apoptotic and anti-invasive pathways. Proteomic approaches were used to purify and identify the protein substrates using 2D difference gel electrophoresis (2D SDS-PAGE) to assess changes in the expression of relevant protein treatment with CIL-102 that resulted in the inhibition of viability and invasion. Our results demonstrate that CIL-102 treatment of U87 cells decreased cell proliferation and invasiveness. CIL-102 dose-dependent induction of apoptosis and inhibitory invasiveness were accompanied by sustained phosphorylation of JNK1/2 and p70S6K as well as generation of the reactive oxygen species. In addition, differential proteins displayed between CIL-102-treated and untreated U87 were determined and validated. There were 11 differentially expressed proteins between the CIL-102-treated and untreated groups. Furthermore, we demonstrated that CIL-102 inhibited cancer cell proliferation and reduced anti-invasion properties by up-regulating the levels of FUMH (Fumarate hydratase). The investigation demonstrated that there was an increase in the cellular levels of FUMH in the CIL-102 reduction in viability and invasion via the activation of JNK1/2 and mTOR signaling modules. NAC administration and shRNA FUMH conferred resistance to CIL-102-inhibited HIF1? and MMP-2 levels via inhibition of JNK1/2 and mTOR activation. We concluded that CIL-102-induced an apoptosis cascade and decreased aggressiveness in astrocytoma cells by modulation of mitochondria function, providing a new mechanism for CIL-102 treatment. - Highlights: We found the effect of CIL-102 on neuroblastoma cells. Fumarate hydratase as a CIL-102's target by proteomic differential displays. CIL-102 regulated-FUMH stimulates apoptosis-related protein and inactivation HIF1.

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

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

    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...

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

    DOE Patents [OSTI]

    Dickey, Fred M. (Albuquerque, NM); Holswade, Scott C. (Albuquerque, NM)

    2002-01-01

    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.

  2. STS map of genes and anonymous DNA fragments on human chromosome 18 using a panel of somatic cell hybrids

    SciTech Connect (OSTI)

    Overhauser, J.; Mewar, R.; Rojas, K.; Kline, A.D. ); Lia, K.; Silverman, G.A. )

    1993-02-01

    Somatic cell hybrids containing different deleted regions of chromosome 18 derived form patients with balanced translocations or terminal deletions were used to create a deletion mapping panel. Twenty-four sequence-tagged sites (STSs) for 17 genes and 7 anonymous polymorphic DNA fragments were identified. These STSs were used to map the 24 loci to 18 defined regions of chromosome 18. Both ERV1, previously mapped to 18q22-q23, and YES1, previously mapped to 18q21.3, were found to map to 18p11.21-pter. Several genes previously mapped to 18q21 were found to be in the order cen-SSAV1-DCC-FECH-GRP-BCL2-PLANH2-tel. The precise mapping of genes to chromosome 18 should help in determining whether these genes may be involved in the etiology of specific chromosomal syndromes associated with chromosome 18. The mapping of the poloymorphic loci will assist in the integration of the physical map with the recombination map of chromosome 18. 43 refs., 2 figs., 1 tab.

  3. 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

    2012-08-01

    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 receiving adjuvant breast RT.

  4. 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: I.Meijerman@pharm.uu.nl

    2006-02-15

    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.

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

    SciTech Connect (OSTI)

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

    2015-01-01

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

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

    SciTech Connect (OSTI)

    Reizner, G.T. )

    1993-05-01

    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.

  7. OSU-A9 inhibits angiogenesis in human umbilical vein endothelial cells via disrupting AktNF-?B and MAPK signaling pathways

    SciTech Connect (OSTI)

    Omar, Hany A.; Arafa, El-Shaimaa A.; Salama, Samir A.; Arab, Hany H.; Wu, Chieh-Hsi; Weng, Jing-Ru

    2013-11-01

    Since the introduction of angiogenesis as a useful target for cancer therapy, few agents have been approved for clinical use due to the rapid development of resistance. This problem can be minimized by simultaneous targeting of multiple angiogenesis signaling pathways, a potential strategy in cancer management known as polypharmacology. The current study aimed at exploring the anti-angiogenic activity of OSU-A9, an indole-3-carbinol-derived pleotropic agent that targets mainly Aktnuclear factor-kappa B (NF-?B) signaling which regulates many key players of angiogenesis such as vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs). Human umbilical vein endothelial cells (HUVECs) were used to study the in vitro anti-angiogenic effect of OSU-A9 on several key steps of angiogenesis. Results showed that OSU-A9 effectively inhibited cell proliferation and induced apoptosis and cell cycle arrest in HUVECs. Besides, OSU-A9 inhibited angiogenesis as evidenced by abrogation of migration/invasion and Matrigel tube formation in HUVECs and attenuation of the in vivo neovascularization in the chicken chorioallantoic membrane assay. Mechanistically, Western blot, RT-PCR and ELISA analyses showed the ability of OSU-A9 to inhibit MMP-2 production and VEGF expression induced by hypoxia or phorbol-12-myristyl-13-acetate. Furthermore, dual inhibition of AktNF-?B and mitogen-activated protein kinase (MAPK) signaling, the key regulators of angiogenesis, was observed. Together, the current study highlights evidences for the promising anti-angiogenic activity of OSU-A9, at least in part through the inhibition of AktNF-?B and MAPK signaling and their consequent inhibition of VEGF and MMP-2. These findings support OSU-A9's clinical promise as a component of anticancer therapy. - Highlights: The antiangiogenic activity of OSU-A9 in HUVECs was explored. OSU-A9 inhibited HUVECs proliferation, migration, invasion and tube formation. OSU-A9 targeted signaling pathways mediated by Akt-NF-kB, VEGF, and MMP-2. The anti-angiogenic activity of OSU-A9 supports its clinical promise.

  8. Phototoxicity of nano titanium dioxides in HaCaT keratinocytesGeneration of reactive oxygen species and cell damage

    SciTech Connect (OSTI)

    Yin, Jun-Jie; Liu, Jun; Ehrenshaft, Marilyn; Roberts, Joan E.; Fu, Peter P.; Mason, Ronald P.; Zhao, Baozhong

    2012-08-15

    Nano-sized titanium dioxide (TiO{sub 2}) is among the top five widely used nanomaterials for various applications. In this study, we determine the phototoxicity of TiO{sub 2} nanoparticles (nano-TiO{sub 2}) with different molecular sizes and crystal forms (anatase and rutile) in human skin keratinocytes under UVA irradiation. Our results show that all nano-TiO{sub 2} particles caused phototoxicity, as determined by the MTS assay and by cell membrane damage measured by the lactate dehydrogenase (LDH) assay, both of which were UVA dose- and nano-TiO{sub 2} dose-dependent. The smaller the particle size of the nano-TiO{sub 2} the higher the cell damage. The rutile form of nano-TiO{sub 2} showed less phototoxicity than anatase nano-TiO{sub 2}. The level of photocytotoxicity and cell membrane damage is mainly dependent on the level of reactive oxygen species (ROS) production. Using polyunsaturated lipids in plasma membranes and human serum albumin as model targets, and employing electron spin resonance (ESR) oximetry and immuno-spin trapping as unique probing methods, we demonstrated that UVA irradiation of nano-TiO{sub 2} can induce significant cell damage, mediated by lipid and protein peroxidation. These overall results suggest that nano-TiO{sub 2} is phototoxic to human skin keratinocytes, and that this phototoxicity is mediated by ROS generated during UVA irradiation. Highlights: ? We evaluate the phototoxicity of nano-TiO{sub 2} with different sizes and crystal forms. ? The smaller the particle size of the nano-TiO{sub 2} the higher the cell damage. ? The rutile form of nano-TiO{sub 2} showed less phototoxicity than anatase nano-TiO{sub 2}. ? ESR oximetry and immuno-spin trapping techniques confirm UVA-induced cell damage. ? Phototoxicity is mediated by ROS generated during UVA irradiation of nano-TiO{sub 2}.

  9. Effects of Low-Dose Alpha-Particle Irradiation in Human Cells: The Role of Induced Genes and the Bystander Effect. Final Technical Report (9/15/1998-5/31/2005)

    SciTech Connect (OSTI)

    Little, John B.

    2013-09-17

    This grant was designed to examine the cellular and molecular mechanisms for the bystander effect of radiation (initially described in this laboratory) whereby damage signals are passed from irradiated to non-irradiated cells in a population. These signals induce genetic effects including DNA damage, mutations and chromosomal aberrations in the nonirradiated cells. Experiments were carried out in cultured mammalian cells, primarily human diploid cells, irradiated with alpha particles. This research resulted in 17 publications in the refereed literature and is described in the Progress Report where it is keyed to the publication list. This project was initiated at the Harvard School of Public Health (HSPH) and continued in collaboration with students/fellows at Colorado State University (CSU) and the New Jersey Medical School (NJMS).

  10. Insulin-Like Growth Factor-Type 1 Receptor Inhibitor NVP-AEW541 Enhances Radiosensitivity of PTEN Wild-Type but Not PTEN-Deficient Human Prostate Cancer Cells

    SciTech Connect (OSTI)

    Isebaert, Sofie F.; Swinnen, Johannes V.; McBride, William H.; Haustermans, Karin M.

    2011-09-01

    Purpose: During the past decade, many clinical trials with both monoclonal antibodies and small molecules that target the insulin-like growth factor-type 1 receptor (IGF-1R) have been launched. Despite the important role of IGF-1R signaling in radioresistance, studies of such agents in combination with radiotherapy are lagging behind. Therefore, the aim of this study was to investigate the effect of the small molecule IGF-1R kinase inhibitor NVP-AEW541 on the intrinsic radioresistance of prostate cancer cells. Methods and Materials: The effect of NVP-AEW541 on cell proliferation, cell viability, IGF-1R signaling, radiosensitivity, cell cycle distribution, and double strand break repair was determined in three human prostate cancer cell lines (PC3, DU145, 22Rv1). Moreover, the importance of the PTEN pathway status was explored by means of transfection experiments with constitutively active Akt or inactive kinase-dead Akt. Results: NVP-AEW541 inhibited cell proliferation and decreased cell viability in a time-and dose-dependent manner in all three cell lines. Radiosensitization was observed in the PTEN wild-type cell lines DU145 and 22Rv1 but not in the PTEN-deficient PC3 cell line. NVP-AEW541-induced radiosensitization coincided with downregulation of phospho-Akt levels and high levels of residual double strand breaks. The importance of PTEN status in the radiosensitization effect was confirmed by transfection experiments with constitutively active Akt or inactive kinase-dead Akt. Conclusions: NVP-AEW541 enhances the effect of ionizing radiation in PTEN wild-type, but not in PTEN-deficient, prostate cancer cells. Proper patient selection based on the PTEN status of the tumor will be critical to the achievement of optimal results in clinical trials in which the combination of radiotherapy and this IGF-1R inhibitor is being explored.

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

    DOE Patents [OSTI]

    Duchane, David V. (Los Alamos, NM); Barthell, Barry L. (Los Alamos, NM)

    1985-01-01

    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.

  12. 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

    2014-06-01

    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.

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

    SciTech Connect (OSTI)

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

    2010-12-22

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

  14. 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.

    2011-02-15

    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.

  15. A component of green tea (-)-epigallocatechin-3-gallate, promotes apoptosis in T24 human bladder cancer cells via modulation of the PI3K/Akt pathway and Bcl-2 family proteins

    SciTech Connect (OSTI)

    Qin Jie [Department of Urology, First Affiliated Hospital, Medical College, Zhejiang University, Qingchun Road 79, Hangzhou 310003, Zhejiang Province (China); Xie Liping [Department of Urology, First Affiliated Hospital, Medical College, Zhejiang University, Qingchun Road 79, Hangzhou 310003, Zhejiang Province (China)]. E-mail: xielp@zjuem.zju.edu.cn; Zheng Xiangyi [Department of Urology, First Affiliated Hospital, Medical College, Zhejiang University, Qingchun Road 79, Hangzhou 310003, Zhejiang Province (China); Wang Yunbin [Department of Urology, First Affiliated Hospital, Medical College, Zhejiang University, Qingchun Road 79, Hangzhou 310003, Zhejiang Province (China); Bai Yu [Department of Urology, First Affiliated Hospital, Medical College, Zhejiang University, Qingchun Road 79, Hangzhou 310003, Zhejiang Province (China); Shen Huafeng [Department of Urology, First Affiliated Hospital, Medical College, Zhejiang University, Qingchun Road 79, Hangzhou 310003, Zhejiang Province (China); Li Longcheng [Department of Urology, University of California San Francisco and Veteran Affairs Medical Center San Francisco, San Francisco, CA (United States); Dahiya, Rajvir [Department of Urology, University of California San Francisco and Veteran Affairs Medical Center San Francisco, San Francisco, CA (United States)

    2007-03-23

    Bladder cancer is the fourth most common cancer in men and ninth most common in women. It has a protracted course of progression and is thus an ideal candidate for chemoprevention strategies and trials. This study was conducted to evaluate the chemopreventive/antiproliferative potential of (-)-epigallocatechin gallate (EGCG, the major phytochemical in green tea) against bladder cancer and its mechanism of action. Using the T24 human bladder cancer cell line, we found that EGCG treatment caused dose- and time-dependent inhibition of cellular proliferation and cell viability, and induced apoptosis. Mechanistically, EGCG inhibits phosphatidylinositol 3'-kinase/Akt activation that, in turn, results in modulation of Bcl-2 family proteins, leading to enhanced apoptosis of T24 cells. These findings suggest that EGCG may be an important chemoprevention agent for the management of bladder cancer.

  16. (4-Methoxyphenyl)(3,4,5-trimethoxyphenyl)methanone inhibits tubulin polymerization, induces G{sub 2}/M arrest, and triggers apoptosis in human leukemia HL-60 cells

    SciTech Connect (OSTI)

    Magalhes, Hemerson I.F.; Wilke, Diego V.; Bezerra, Daniel P.; Cavalcanti, Bruno C.; Rotta, Rodrigo; Lima, Dnis P. de; Beatriz, Adilson; Moraes, Manoel O.; Diniz-Filho, Jairo; Pessoa, Claudia

    2013-10-01

    (4-Methoxyphenyl)(3,4,5-trimethoxyphenyl)methanone (PHT) is a known cytotoxic compound belonging to the phenstatin family. However, the exact mechanism of action of PHT-induced cell death remains to be determined. The aim of this study was to investigate the mechanisms underlying PHT-induced cytotoxicity. We found that PHT displayed potent cytotoxicity in different tumor cell lines, showing IC{sub 50} values in the nanomolar range. Cell cycle arrest in G{sub 2}/M phase along with the augmented metaphase cells was found. Cells treated with PHT also showed typical hallmarks of apoptosis such as cell shrinkage, chromatin condensation, phosphatidylserine exposure, increase of the caspase 3/7 and 8 activation, loss of mitochondrial membrane potential, and internucleosomal DNA fragmentation without affecting membrane integrity. Studies conducted with isolated tubulin and docking models confirmed that PHT binds to the colchicine site and interferes in the polymerization of microtubules. These results demonstrated that PHT inhibits tubulin polymerization, arrests cancer cells in G{sub 2}/M phase of the cell cycle, and induces their apoptosis, exhibiting promising anticancer therapeutic potential. - Highlights: PHT inhibits tubulin polymerization. PHT arrests cancer cells in G{sub 2}/M phase of the cell cycle. PHT induces caspase-dependent apoptosis.

  17. The PIKfyveArPIKfyveSac3 triad in human breast cancer: Functional link between elevated Sac3 phosphatase and enhanced proliferation of triple negative cell lines

    SciTech Connect (OSTI)

    Ikonomov, Ognian C. Filios, Catherine Sbrissa, Diego Chen, Xuequn Shisheva, Assia

    2013-10-18

    Highlights: We assess PAS complex proteins and phosphoinositide levels in breast cancer cells. Sac3 and ArPIKfyve are markedly elevated in triple-negative breast cancer cells. Sac3 silencing inhibits proliferation in triple-negative breast cancer cell lines. Phosphoinositide profiles are altered in breast cancer cells. This is the first evidence linking high Sac3 with breast cancer cell proliferation. -- Abstract: The phosphoinositide 5-kinase PIKfyve and 5-phosphatase Sac3 are scaffolded by ArPIKfyve in the PIKfyveArPIKfyveSac3 (PAS) regulatory complex to trigger a unique loop of PtdIns3PPtdIns(3,5)P{sub 2} synthesis and turnover. Whereas the metabolizing enzymes of the other 3-phosphoinositides have already been implicated in breast cancer, the role of the PAS proteins and the PtdIns3PPtdIns(3,5)P{sub 2} conversion is unknown. To begin elucidating their roles, in this study we monitored the endogenous levels of the PAS complex proteins in cell lines derived from hormone-receptor positive (MCF7 and T47D) or triple-negative breast cancers (TNBC) (BT20, BT549 and MDA-MB-231) as well as in MCF10A cells derived from non-tumorigenic mastectomy. We report profound upregulation of Sac3 and ArPIKfyve in the triple negative vs. hormone-sensitive breast cancer or non-tumorigenic cells, with BT cell lines showing the highest levels. siRNA-mediated knockdown of Sac3, but not that of PIKfyve, significantly inhibited proliferation of BT20 and BT549 cells. In these cells, knockdown of ArPIKfyve had only a minor effect, consistent with a primary role for Sac3 in TNBC cell proliferation. Intriguingly, steady-state levels of PtdIns(3,5)P{sub 2} in BT20 and T47D cells were similar despite the 6-fold difference in Sac3 levels between these cell lines. However, steady-state levels of PtdIns3P and PtdIns5P, both regulated by the PAS complex, were significantly reduced in BT20 vs. T47D or MCF10A cell lines, consistent with elevated Sac3 affecting directly or indirectly the homeostasis of these lipids in TNBC. Together, our results uncover an unexpected role for Sac3 phosphatase in TNBC cell proliferation. Database analyses, discussed herein, reinforce the involvement of Sac3 in breast cancer pathogenesis.

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

    SciTech Connect (OSTI)

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

    2013-11-15

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

  19. Human radiation studies: Remembering the early years: Oral history of cell biologist Don Francis Petersen, Ph.D., conducted November 29, 1994

    SciTech Connect (OSTI)

    1995-08-01

    This report is a transcript of an interview of Dr. Don Francis Petersen by representatives of the US DOE Office of Human Radiation Experiments. Dr. Petersen was selected for this interview because of his long research career at Los Alamos and his knowledge of the Atomic Energy Commission`s biomedical program. Dr. Petersen did not personally conduct research on human subjects. After a brief biographical sketch Dr. Petersen discusses his remembrances of the early use of radionuclides as biological tracers, aspects of nuclear weapons testing in the 1940`s and 1950`s including fallout studies, the means by which research projects were approved, use of humans in the whole-body counter, and the Health Division Biomedical responsibilities.

  20. Activation of the PI3K-Akt pathway by human T cell leukemia virus type 1 (HTLV-1) oncoprotein Tax increases Bcl3 expression, which is associated with enhanced growth of HTLV-1-infected T cells

    SciTech Connect (OSTI)

    Saito, Kousuke; Saito, Mineki; Taniura, Naoko; Okuwa, Takako; Ohara, Yoshiro

    2010-08-01

    Bcl3 is a member of the I{kappa}B family that regulates genes involved in cell proliferation and apoptosis. Recent reports indicated that Bcl3 is overexpressed in HTLV-1-infected T cells via Tax-mediated transactivation, and acts as a negative regulator of viral transcription. However, the role of Bcl3 in cellular signal transduction and the growth of HTLV-1-infected T cells have not been reported. In this study, we showed that the knockdown of Bcl3 by short hairpin RNA inhibited the growth of HTLV-1-infected T cells. Although phosphatidylinositol-3 kinase (PI3K) inhibitor reduced Bcl3 expression, inactivation of glycogen synthase kinase 3 (GSK3), an effector kinase of the PI3K/Akt signaling pathway, restored Bcl3 expression in Tax-negative but not in Tax-positive T cells. Our results indicate that the overexpression of Bcl3 in HTLV-1-infected T cells is regulated not only by transcriptional but also by post-transcriptional mechanisms, and is involved in overgrowth of HTLV-1-infected T cells.

  1. 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.

    2013-12-06

    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.

  2. Assay for mutagenesis in heterozygous diploid human lymphoblasts

    DOE Patents [OSTI]

    Skopek, Thomas R. (Somerville, MA); Liber, Howard L. (Brookline, MA); Penman, Bruce W. (Cambridge, MA); Thilly, William G. (Cambridge, MA); Hoppe, IV, Henry (Arlington, MA)

    1981-01-01

    An assay is disclosed for determining mutagenic damage caused by the administration of a known or suspected mutagen to diploid human lymphoblastoid cell lines. The gene locus employed for this assay is the gene for thymidine kinase, uridine kinase, or cytidine deaminase. Since human lymphoblastoid cells contain two genes for these enzymes, heterozygotes of human lymphoblastoid cells are used in this assay.

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

    SciTech Connect (OSTI)

    Erez, Neta; Glanz, Sarah; Raz, Yael; Department of Obstetrics and Gynecology, LIS Maternity Hospital, Tel Aviv Sourasky Medical Center, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv ; Avivi, Camilla; Barshack, Iris; Department of Pathology, Sheba Medical Center, Tel Hashomer, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv

    2013-08-02

    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-?b 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-?B targets and we show that NF-?B 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.

  4. Two natural products, trans-phytol and (22E)-ergosta-6,9,22-triene-3β,5α,8α-triol, inhibit the biosynthesis of estrogen in human ovarian granulosa cells by aromatase (CYP19)

    SciTech Connect (OSTI)

    Guo, Jiajia; Yuan, Yun; Lu, Danfeng; Du, Baowen; Xiong, Liang; Shi, Jiangong; Yang, Lijuan; Liu, Wanli; Yuan, Xiaohong; Zhang, Guolin; Wang, Fei

    2014-08-15

    Aromatase is the only enzyme in vertebrates to catalyze the biosynthesis of estrogens. Although inhibitors of aromatase have been developed for the treatment of estrogen-dependent breast cancer, the whole-body inhibition of aromatase causes severe adverse effects. Thus, tissue-selective aromatase inhibitors are important for the treatment of estrogen-dependent cancers. In this study, 63 natural products with diverse structures were examined for their effects on estrogen biosynthesis in human ovarian granulosa-like KGN cells. Two compounds—trans-phytol (SA-20) and (22E)-ergosta-6,9,22-triene-3β,5α,8α-triol (SA-48)—were found to potently inhibit estrogen biosynthesis (IC{sub 50}: 1 μM and 0.5 μM, respectively). Both compounds decreased aromatase mRNA and protein expression levels in KGN cells, but had no effect on the aromatase catalytic activity in aromatase-overexpressing HEK293A cells and recombinant expressed aromatase. The two compounds decreased the expression of aromatase promoter I.3/II. Neither compound affected intracellular cyclic AMP (cAMP) levels, but they inhibited the phosphorylation or protein expression of cAMP response element-binding protein (CREB). The effects of these two compounds on extracellular regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinases (MAPKs), and AKT/phosphoinositide 3-kinase (PI3K) pathway were examined. Inhibition of p38 MAPK could be the mechanism underpinning the actions of these compounds. Our results suggests that natural products structurally similar to SA-20 and SA-48 may be a new source of tissue-selective aromatase modulators, and that p38 MAPK is important in the basal control of aromatase in ovarian granulosa cells. SA-20 and SA-48 warrant further investigation as new pharmaceutical tools for the prevention and treatment of estrogen-dependent cancers. - Highlights: • Two natural products inhibited estrogen biosynthesis in human ovarian granulosa cells. • They inhibited aromatase transcription without affecting its catalytic activity. • They decreased the transcription or protein expression of CREB. • They inhibited p38 MAPK to exert their inhibitory effects on aromatase expression.

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

    SciTech Connect (OSTI)

    Nakamura, Masaaki Chida, Koichi; Zuguchi, Masayuki

    2014-10-15

    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 [60120 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, and it is a candidate for an x-ray scintillator for such a skin dosimeter.

  6. The eukaryotic translation elongation factor eEF1A2 induces neoplastic properties and mediates tumorigenic effects of ZNF217 in precursor cells of human ovarian carcinomas

    SciTech Connect (OSTI)

    Sun, Yu; Wong, Nicholas; Guan, Yinghui; Salamanca, Clara M.; Cheng, Jung Chien; Lee, Jonathan M.; Gray, Joe W.; Auersperg, Nelly

    2008-04-25

    Ovarian epithelial carcinomas (OEC) frequently exhibit amplifications at the 20q13 locus which is the site of several oncogenes, including the eukaryotic elongation factor EEF1A2 and the transcription factor ZNF217. We reported previously that overexpressed ZNF217 induces neoplastic characteristics in precursor cells of OEC. Unexpectedly, ZNF217, which is a transcriptional repressor, enhanced expression of eEF1A2. In this study, array comparative genomic hybridization, single nucleotide polymorphism and Affymetrix analysis of ZNF217-overexpressing cell lines confirmed consistently increased expression of eEF1A2 but not of other oncogenes, and revealed early changes in EEF1A2 gene copy numbers and increased expression at crisis during immortalization. We defined the influence of eEF1A2 overexpression on immortalized ovarian surface epithelial cells, and investigated interrelationships between effects of ZNF217 and eEF1A2 on cellular phenotypes. Lentivirally induced eEF1A2 overexpression caused delayed crisis, apoptosis resistance and increases in serum-independence, saturation densities, and anchorage independence. siRNA to eEF1A2 reversed apoptosis resistance and reduced anchorage independence in eEF1A2-overexpressing lines. Remarkably, siRNA to eEF1A2 was equally efficient in inhibiting both anchorage independence and resistance to apoptosis conferred by ZNF217 overexpression. Our data define neoplastic properties that are caused by eEF1A2 in nontumorigenic ovarian cancer precursor cells, and suggest that eEF1A2 plays a role in mediating ZNF217-induced neoplastic progression.

  7. Apparatus for testing skin samples or the like

    DOE Patents [OSTI]

    Holland, J.M.

    1982-08-31

    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.

  8. Human MSH2 protein

    DOE Patents [OSTI]

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

    1997-01-01

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

  9. Human MSH2 protein

    DOE Patents [OSTI]

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

    1997-01-07

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

  10. OCT4A contributes to the stemness and multi-potency of human umbilical cord blood-derived multipotent stem cells (hUCB-MSCs)

    SciTech Connect (OSTI)

    Seo, Kwang-Won; Lee, Sae-Rom; Bhandari, Dilli Ram; Roh, Kyoung-Hwan; Park, Sang-Bum; So, Ah-Young; Jung, Ji-Won; Seo, Min-Soo; Laboratory of Stem Cell and Tumor Biology, Department of Veterinary Public Health, College of Veterinary Medicine, and BK21 Program for Veterinary Science, Seoul National University 151-742, Seoul ; Kang, Soo-Kyung; Laboratory of Biotechnology, College of Veterinary Medicine, and BK21 Program for Veterinary Science, Seoul National University 151-742, Seoul ; Lee, Yong-Soon; Laboratory of Stem Cell and Tumor Biology, Department of Veterinary Public Health, College of Veterinary Medicine, and BK21 Program for Veterinary Science, Seoul National University 151-742, Seoul ; Kang, Kyung-Sun; Laboratory of Stem Cell and Tumor Biology, Department of Veterinary Public Health, College of Veterinary Medicine, and BK21 Program for Veterinary Science, Seoul National University 151-742, Seoul

    2009-06-19

    The OCT4A gene, a POU homeodomain transcription factor, has been shown to be expressed in embryonic stem cells (ESC) as well as hUCB-MSCs. In this study, the roles played by OCT4A in hUCB-MSCs were determined by stably inhibiting OCT4A with lenti-viral vector-based small hairpin RNA (shRNA). A decreased rate of cell proliferation was observed in OCT4-inhibited hUCB-MSCs. Down-regulation of CCNA2 expression in OCT4-inhibited hUCB-MSCs was confirmed by RT-PCR and real-time RT-PCR analysis in three genetically independent hUCB-MSC clones. Adipogenic differentiation was also suppressed in OCT4-inhibited hUCB-MSCs. The up-regulation of DTX1 and down-regulation of HDAC1, 2, and 4 expressions may be related to this differentiation deformity. The expression of other transcription factors, including SOX2, REX1 and c-MYC, was also affected by OCT4 inhibition in hUCB-MSCs. In conclusion, these finding suggest that OCT4A performs functionally conserved roles in hUCB-MSCs, making its expression biologically important for ex vivo culture of hUCB-MSCs.

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

    SciTech Connect (OSTI)

    Inakura, Tsunenori; Nakatsukasa, Takashi; Yabana, Kazuhiro

    2011-08-15

    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}.

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

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

    news.sciencemag.org/sciencenow/2012/03/physicists-measure-the-skin-of-a.html?ref=hp Submitted: Friday, March 2, 2012 - 1

  13. Effects of radioactive hot particles on pig skin

    SciTech Connect (OSTI)

    Kaurin, D.G.; Baum, J.W.; Schaefer, C.W. [and others

    1997-06-01

    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.

  14. 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.

    2012-10-20

    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.

  15. Biomolecular interactions and responses of human epithelial and macrophage

    Office of Scientific and Technical Information (OSTI)

    cells to engineered nanomaterials. (Technical Report) | SciTech Connect Biomolecular interactions and responses of human epithelial and macrophage cells to engineered nanomaterials. Citation Details In-Document Search Title: Biomolecular interactions and responses of human epithelial and macrophage cells to engineered nanomaterials. Engineered nanomaterials (ENMs) are increasingly being used in commercial products, particularly in the biomedical, cosmetic, and clothing industries. For

  16. Heritable Genetic Changes in Cells Recovered From Irradiated 3D Tissue Contracts. Final report

    SciTech Connect (OSTI)

    Cornforth, Michael N.

    2013-05-03

    Combining contemporary cytogenetic methods with DNA CGH microarray technology and chromosome flow-sorting increases substantially the ability to resolve exchange breakpoints associated with interstitial deletions and translocations, allowing the consequences of radiation damage to be directly measured at low doses, while also providing valuable insights into molecular mechanisms of misrepair processes that, in turn, identify appropriate biophysical models of risk at low doses. The aims of this work apply to cells recovered from 3D tissue constructs of human skin and, for the purpose of comparison, the same cells irradiated in traditional 2D cultures. These aims are: to analyze by multi-flour fluorescence in situ hybridization (mFISH) the chromosomes in clonal descendents of individual human fibroblasts that were previously irradiated; to examine irradiated clones from Aim 1 for submicroscopic deletions by subjecting their DNA to comparative genomic hybridization (CGH) microarray analysis; and to flow-sort aberrant chromosomes from clones containing stable radiation-induced translocations and map the breakpoints to within an average resolution of 100 kb using the technique of 'array painting'.

  17. 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.

    2011-05-04

    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.

  18. Method for preparing dosimeter for measuring skin dose

    DOE Patents [OSTI]

    Jones, Donald E. (Idaho Falls, ID); Parker, DeRay (Idaho Falls, ID); Boren, Paul R. (Idaho Falls, ID)

    1982-01-01

    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.

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

    DOE Patents [OSTI]

    Jones, Donald E. (Idaho Falls, ID); Parker, DeRay (Idaho Falls, ID); Boren, Paul R. (Idaho Falls, ID)

    1981-01-01

    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.

  20. 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.

    2012-10-20

    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].

  1. Laser speckle contrast imaging of skin blood perfusion responses induced by

    Office of Scientific and Technical Information (OSTI)

    laser coagulation (Journal Article) | SciTech Connect SciTech Connect Search Results Journal Article: 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 blood perfusion responses induced by laser coagulation We report application of laser speckle contrast imaging (LSCI), i.e., a fast imaging technique utilising backscattered light to distinguish such moving objects as

  2. EXPLORING THE POTENTIAL OF SHORT-TIME FOURIER TRANSFORMS FOR ANALYZING SKIN CONDUCTANCE AND PUPILLOMETRY IN REAL-TIME APPLICATIONS

    SciTech Connect (OSTI)

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

    2008-09-01

    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.

  3. 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

    2014-06-01

    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.

  4. Human dopamine receptor and its uses

    DOE Patents [OSTI]

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

    1999-01-01

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

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

    SciTech Connect (OSTI)

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

    2009-04-03

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

  6. Primary Radiation Therapy for Head-and-Neck Cancer in the Setting of Human Immunodeficiency Virus

    SciTech Connect (OSTI)

    Klein, Emily A.; Guiou, Michael; Farwell, D. Gregory; Luu, Quang; Lau, Derick H.; Stuart, Kerri; Vaughan, Andrew; Vijayakumar, Srinivasan; Chen, Allen M.

    2011-01-01

    Purpose: To analyze outcomes after radiation therapy for head-and-neck cancer among a cohort of patients with human immunodeficiency virus (HIV). Methods and Materials: The medical records of 12 patients with serologic evidence of HIV who subsequently underwent radiation therapy to a median dose of 68 Gy (range, 64-72 Gy) for newly diagnosed squamous cell carcinoma of the head and neck were reviewed. Six patients (50%) received concurrent chemotherapy. Intensity-modulated radiotherapy was used in 6 cases (50%). All patients had a Karnofsky performance status of 80 or 90. Nine patients (75%) were receiving antiretroviral therapies at the time of treatment, and the median CD4 count was 460 (range, 266-800). Toxicity was graded according to the Radiation Therapy Oncology Group / European Organization for the Treatment of Cancer toxicity criteria. Results: The 3-year estimates of overall survival and local-regional control were 78% and 92%, respectively. Acute Grade 3+ toxicity occurred in 7 patients (58%), the most common being confluent mucositis (5 patients) and moist skin desquamation (4 patients). Two patients experienced greater than 10% weight loss, and none experienced more than 15% weight loss from baseline. Five patients (42%) experienced treatment breaks in excess of 10 cumulative days, although none required hospitalization. There were no treatment-related fatalities. Conclusions: Radiation therapy for head-and-neck cancer seems to be relatively well tolerated among appropriately selected patients with HIV. The observed rates of toxicity were comparable to historical controls without HIV.

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

    SciTech Connect (OSTI)

    Simpson, John B. Godwin, Guy A.

    2011-10-01

    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.

  8. Advanced Electrocatalysts for PEM Fuel Cells

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

    Webinar on PEM Fuel Cells 2-12-2013 Advanced Electrocatalysts for PEM Fuel Cells Nenad M. Markovic Vojislav R. Stamenkovic Materials Science Division Argonne National Laboratory 1 st Layer 2 nd Layer 3 rd Layer Pt=100 at.% Pt=48 at.% Ni=52 at.% Pt=87 at.% Ni=13 at.% Pt[111]-Skin surface 5 nm (111) (100) 3 nm Size distribution c-15 nm Shape Bulk composition Surface structure ? HR-TEM: Characterization of Nanoscale Pt/C Catalyst x 15 x 5 Surface composition ? 2 Surface Science Approach design,

  9. 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.

    2014-06-15

    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.

  10. 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 institutions, whether supported with DOE funds or performed by DOE employees, addresses the protection of human subjects. The Oak Ridge Institute for Science and Education (ORISE) supports DOE in its efforts to protect human subject by providing a number of capabilities and resources. Human Subjects Research Database Human

  11. Nanosegregated Surfaces as Catalysts for Fuel Cells (IN-07-054) - Energy

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

    Innovation Portal Hydrogen and Fuel Cell Hydrogen and Fuel Cell Energy Storage Energy Storage Advanced Materials Advanced Materials Find More Like This Return to Search Nanosegregated Surfaces as Catalysts for Fuel Cells (IN-07-054) Argonne National Laboratory Contact ANL About This Technology <p> <strong><em>Schematic illustration of the nanosegregated Pt(111)-Skin near surface atomic layers with oscillatory compositional profile</em></strong></p>

  12. Restoration of normal phenotype in cancer cells

    DOE Patents [OSTI]

    Bissell, M.J.; Weaver, V.M.

    1998-12-08

    A method for reversing expression of malignant phenotype in cancer cells is described. The method comprises applying {beta}{sub 1} integrin function-blocking antibody to the cells. The method can be used to assess the progress of cancer therapy. Human breast epithelial cells were shown to be particularly responsive. 14 figs.

  13. Restoration of normal phenotype in cancer cells

    DOE Patents [OSTI]

    Bissell, Mina J.; Weaver, Valerie M.

    1998-01-01

    A method for reversing expression of malignant phenotype in cancer cells is described. The method comprises applying .beta..sub.1 integrin function-blocking antibody to the cells. The method can be used to assess the progress of cancer therapy. Human breast epithelial cells were shown to be particularly responsive.

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

    SciTech Connect (OSTI)

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

    1984-08-01

    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.

  15. Human-machine interactions

    DOE Patents [OSTI]

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

    2009-04-28

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

  16. Beta Radiation

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

    Beta Radiation 1. Beta radiation may travel meters in air and is moderately penetrating. 2. Beta radiation can penetrate human skin to the "germinal layer," where new skin cells...

  17. ORISE: Human Subjects Protection

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

    Human Subjects Protection The Oak Ridge Institute for Science and Education (ORISE) performs technical assessments to assist U.S. Department of Energy (DOE) laboratories involved in human subjects research projects. Under DOE Order and Policy 443.1A, Protection of Human Subjects, and 10 CFR 745, DOE employees and contractors are expected to protect the rights and welfare of human research subjects. In support of the DOE Office of Science and the Human Subjects Protection Program (HSPP), ORISE

  18. 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 PDF icon Corporate Human Resources Information Services (CHIRS) PIA, Office of Human Capitol Management More Documents & Publications MOX Services Unclassified

  19. Core-Protected Platinum Monolayer Shell High-Stability Electrocatalysts for Fuel-Cell Cathodes

    SciTech Connect (OSTI)

    Adzic, R.R.; Sasaki, K.; Naohara, H.; Cai, Y.; Choi, Y.M.; Liu, P.; Vukmirovic, M.B.; Wang, J.X.

    2010-11-08

    More than skin deep: Platinum monolayers can act as shells for palladium nanoparticles to lead to electrocatalysts with high activities and an ultralow platinum content, but high platinum utilization. The stability derives from the core protecting the shell from dissolution. In fuel-cell tests, no loss of platinum was observed in 200?000 potential cycles, whereas loss of palladium was significant.

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

    SciTech Connect (OSTI)

    Kawamori, Eiichirou; Ono, Yasushi

    2005-08-19

    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.

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

    Office of Scientific and Technical Information (OSTI)

    ... The dynamics of the human infant gut microbiome in development and in progression toward type 1 diabetes. Cell Host Microbe. 2015;17(2):260-73. 40. MetaHIT. Metagenomics of the ...

  2. Cytometric Therapies for Cell Delivery - Energy Innovation Portal

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

    Advanced Materials Advanced Materials Find More Like This Return to Search Cytometric Therapies for Cell Delivery Maximizing Efficacy of Cell Delivery Oak Ridge National Laboratory Contact ORNL About This Technology Technology Marketing Summary Stem cell therapies are a viable treatment options for some human diseases. Efficacy of such therapies can be maximized by addressing critical issues such as cell delivery and cell survival post delivery. Conventional methods for cell delivery do not

  3. Mutation assays involving blood cells that metabolize toxic substances

    DOE Patents [OSTI]

    Crespi, Charles L. (Downers Grove, IL); Thilly, William G. (Winchester, MA)

    1985-01-01

    A line of human blood cells which have high levels of oxidative activity (such as oxygenase, oxidase, peroxidase, and hydroxylase activity) is disclosed. Such cells grow in suspension culture, and are useful to determine the mutagenicity of xenobiotic substances that are metabolized into toxic or mutagenic substances. Mutation assays using these cells, and other cells with similar characteristics, are also disclosed.

  4. 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

    2013-08-15

    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 cells and IgE, but the others did not. The allergic drugs commonly induced germinal center hyperplasia in lymphoid tissues. Some of these allergic drugs transiently increased CD4{sup +}CD25{sup +} T cells in the spleen.

  5. ARM - Human Causes

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

    ListHuman Causes Outreach Home Room News Publications Traditional Knowledge Kiosks Barrow, Alaska Tropical Western Pacific Site Tours Contacts Students 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 climate variability and other associated causes to climate change will be discussed here and these include: increased emission of greenhouse gases, development for human

  6. The carboxyl-terminal of BRCA1 is required for subnuclear assembly of RAD51 after treatment with cisplatin but not ionizing radiation in human breast and ovarian cancer cells

    SciTech Connect (OSTI)

    Zhou Chenyi; Huang Peng; Liu Jinsong . E-mail: jliu@mdanderson.org

    2005-10-28

    BRCA1 plays an important role in maintaining genomic stability through its involvement in DNA repair. Although it is known that BRCA1 and RAD51 form distinct DNA repair subnuclear complexes, or foci, following environmental insults to the DNA, the role of BRCA1 in this process remains to be characterized. The purpose of the study was therefore to determine the role of BRCA1 in the formation of RAD51 foci following treatment with cisplatin and ionizing radiation. We found that although a functional BRCA1 is required for the subnuclear assembly of BRCA1 foci following treatment with either ionizing radiation or cisplatin, a functional BRCA1 is required for RAD51 foci to form following treatment with cisplatin but not with ionizing radiation. Similar results were obtained in SKOV-3 cells when the level of BRCA1 expression was knocked down by stable expression of a retrovirus-mediated small-interfering RNA against BRCA1. We also found that the carboxyl-terminal of BRCA1 contains uncharacterized phosphorylation sites that are responsive to cisplatin. The functional BRCA1 is also required for breast and ovarian cancer cells to mount resistance to cisplatin. These results suggest that the carboxyl-terminal of BRCA1 is required for the cisplatin-induced recruitment of RAD51 to the DNA-damage site, which may contribute to cisplatin resistance.

  7. 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.

    2015-05-15

    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.

  8. 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.

    2014-09-01

    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.

  9. 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

    2008-08-11

    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.

  10. Fuel Cells

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

    Fuel Cells Fact Sheets Research Team Members Key Contacts Fuel Cells The Solid State Energy Conversion Alliance (SECA) program is responsible for coordinating Federal efforts to facilitate development of a commercially relevant and robust solid oxide fuel cell (SOFC) system. Specific objectives include achieving an efficiency of greater than 60 percent, meeting a stack cost target of $175 per kW, and demonstrating lifetime performance degradation of less than 0.2 percent per 1000 hours over a

  11. Human Resources | Jefferson Lab

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

    Employee Relations Human Resources Installation Of A Cryomodule Workers prepare to install a cryomodule in Jefferson Lab's accelerator. Read more Business Services Human Resources Jefferson Lab Business Services Jefferson Lab provides opportunities for both large and small businesses to engage with the lab and its scientific mission. Read more Training Human Resources Training Programs at Jefferson Lab There exist many exciting career opportunities at Jefferson Lab, and the lab provides training

  12. ORISE: Human Subjects Protection

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

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

  13. 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....

  14. Mesenchymal Stem Cells Retain Their Defining Stem Cell Characteristics After Exposure to Ionizing Radiation

    SciTech Connect (OSTI)

    Nicolay, Nils H.; Sommer, Eva; Lopez, Ramon; Wirkner, Ute; Trinh, Thuy; Sisombath, Sonevisay; Debus, Jrgen; Ho, Anthony D.; Saffrich, Rainer; Huber, Peter E.

    2013-12-01

    Purpose: Mesenchymal stem cells (MSCs) have the ability to migrate to lesion sites and undergo differentiation into functional tissues. Although this function may be important for tissue regeneration after radiation therapy, the influence of ionizing radiation (IR) on cellular survival and the functional aspects of differentiation and stem cell characteristics of MSCs have remained largely unknown. Methods and Materials: Radiation sensitivity of human primary MSCs from healthy volunteers and primary human fibroblast cells was examined, and cellular morphology, cell cycle effects, apoptosis, and differentiation potential after exposure to IR were assessed. Stem cell gene expression patterns after exposure to IR were studied using gene arrays. Results: MSCs were not more radiosensitive than human primary fibroblasts, whereas there were considerable differences regarding radiation sensitivity within individual MSCs. Cellular morphology, cytoskeletal architecture, and cell motility were not markedly altered by IR. Even after high radiation doses up to 10 Gy, MSCs maintained their differentiation potential. Compared to primary fibroblast cells, MSCs did not show an increase in irradiation-induced apoptosis. Gene expression analyses revealed an upregulation of various genes involved in DNA damage response and DNA repair, but expression of established MSC surface markers appeared only marginally influenced by IR. Conclusions: These data suggest that human MSCs are not more radiosensitive than differentiated primary fibroblasts. In addition, upon photon irradiation, MSCs were able to retain their defining stem cell characteristics both on a functional level and regarding stem cell marker expression.

  15. Protection of Human Subjects

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

    2007-12-20

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

  16. Protection of Human Subjects

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

    2000-05-15

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

  17. The human genome project

    SciTech Connect (OSTI)

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

    1994-04-01

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

  18. Method for restoration of normal phenotype in cancer cells

    DOE Patents [OSTI]

    Bissell, Mina J.; Weaver, Valerie M.

    2000-01-01

    A method for reversing expression of malignant phenotype in cancer cells is described. The method comprises applying .beta..sub.1 integrin function-blocking antibody to the cells. The method can be used to assess the progress of cancer therapy. Human breast epithelial cells were shown to be particularly responsive.

  19. 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

    2012-10-20

    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.

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

    SciTech Connect (OSTI)

    Dalton, Mark M.

    2013-11-01

    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.

  1. Electrochemical cell

    DOE Patents [OSTI]

    Redey, Laszlo I.; Vissers, Donald R.; Prakash, Jai

    1994-01-01

    An electrochemical cell having a bimodal positive electrode, a negative electrode of an alkali metal, and a compatible electrolyte including an alkali metal salt molten at the cell operating temperature. The positive electrode has an electrochemically active layer of at least one transition metal chloride at least partially present as a charging product, and additives of bromide and/or iodide and sulfur in the positive electrode or the electrolyte. Electrode volumetric capacity is in excess of 400 Ah/cm.sup.3 ; the cell can be 90% recharged in three hours and can operate at temperatures below 160.degree. C. There is also disclosed a method of reducing the operating temperature and improving the overall volumetric capacity of an electrochemical cell and for producing a positive electrode having a BET area greater than 6.times.10.sup.4 cm.sup.2 /g of Ni.

  2. Electrochemical cell

    DOE Patents [OSTI]

    Redey, L.I.; Vissers, D.R.; Prakash, J.

    1996-07-16

    An electrochemical cell is described having a bimodal positive electrode, a negative electrode of an alkali metal, and a compatible electrolyte including an alkali metal salt molten at the cell operating temperature. The positive electrode has an electrochemically active layer of at least one transition metal chloride at least partially present as a charging product, and additives of bromide and/or iodide and sulfur in the positive electrode or the electrolyte. Electrode volumetric capacity is in excess of 400 Ah/cm{sup 3}; the cell can be 90% recharged in three hours and can operate at temperatures below 160 C. There is also disclosed a method of reducing the operating temperature and improving the overall volumetric capacity of an electrochemical cell and for producing a positive electrode having a BET area greater than 6{times}10{sup 4}cm{sup 2}/g of Ni. 6 figs.

  3. Electrochemical cell

    DOE Patents [OSTI]

    Redey, Laszlo I. (6851 Carpenter St., Downers Grove, IL 60516); Vissers, Donald R. (611 Clover Ct., Naperville, IL 60540); Prakash, Jai (2205 Arbor Cir. 8, Downers Grove, IL 60515)

    1996-01-01

    An electrochemical cell having a bimodal positive electrode, a negative electrode of an alkali metal, and a compatible electrolyte including an alkali metal salt molten at the cell operating temperature. The positive electrode has an electrochemically active layer of at least one transition metal chloride at least partially present as a charging product, and additives of bromide and/or iodide and sulfur in the positive electrode or the electrolyte. Electrode volumetric capacity is in excess of 400 Ah/cm.sup.3 ; the cell can be 90% recharged in three hours and can operate at temperatures below 160.degree. C. There is also disclosed a method of reducing the operating temperature and improving the overall volumetric capacity of an electrochemical cell and for producing a positive electrode having a BET area greater than 6.times.10.sup.4 cm.sup.2 /g of Ni.

  4. Electrochemical cell

    DOE Patents [OSTI]

    Redey, L.I.; Vissers, D.R.; Prakash, J.

    1994-02-01

    An electrochemical cell is described having a bimodal positive electrode, a negative electrode of an alkali metal, and a compatible electrolyte including an alkali metal salt molten at the cell operating temperature. The positive electrode has an electrochemically active layer of at least one transition metal chloride at least partially present as a charging product, and additives of bromide and/or iodide and sulfur in the positive electrode or the electrolyte. Electrode volumetric capacity is in excess of 400 Ah/cm[sup 3]; the cell can be 90% recharged in three hours and can operate at temperatures below 160 C. There is also disclosed a method of reducing the operating temperature and improving the overall volumetric capacity of an electrochemical cell and for producing a positive electrode having a BET area greater than 6[times]10[sup 4] cm[sup 2]/g of Ni. 8 figures.

  5. Electrochemical cell

    DOE Patents [OSTI]

    Redey, Laszlo I.; Vissers, Donald R.; Prakash, Jai

    1994-01-01

    An electrochemical cell having an alkali metal negative electrode such as sodium and a positive electrode including Ni or transition metals, separated by a .beta." alumina electrolyte and NaAlCl.sub.4 or other compatible material. Various concentrations of a bromine, iodine and/or sulfur containing additive and pore formers are disclosed, which enhance cell capacity and power. The pore formers may be the ammonium salts of carbonic acid or a weak organic acid or oxamide or methylcellulose.

  6. Load cell

    DOE Patents [OSTI]

    Spletzer, B.L.

    1998-12-15

    A load cell combines the outputs of a plurality of strain gauges to measure components of an applied load. Combination of strain gauge outputs allows measurement of any of six load components without requiring complex machining or mechanical linkages to isolate load components. An example six axis load cell produces six independent analog outputs, each directly proportional to one of the six general load components. 16 figs.

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

    SciTech Connect (OSTI)

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

    1984-08-01

    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.

  8. Human Resource Management Delegation

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

    1996-06-28

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

  9. Protection of Human Subjects

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

    2007-12-20

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

  10. Protection of Human Subjects

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

    2000-05-15

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

  11. 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 Employee Concerns and Grievances Employee Concerns Program (EDP)

  12. Human Reliability Program Overview

    SciTech Connect (OSTI)

    Bodin, Michael

    2012-09-25

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

  13. 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 integrity. For general HR inquiries, contact (757) 269-7598. Announcements TIAA-CREF Retirement Counseling Session: To sign up for an appointment with Robert Jean, the TIAA-CREF Individual Consultant, go to http://www.tiaa-cref.org click on Meetings & Counseling and follow the menu. The sessions will be held in Support

  14. Jefferson Lab Human Resources

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

    Human Resources Human Resources Forms Benefits 2011 Anthem Information Anthem General Mail Order Form (For KeyCare, BlueCare & HealthKeepers) Anthem Customer Claim Form Anthem Enrollment Form Anthem HealthKeepers Vision Claim Form Anthem Member Change Form Anthem Vision Services Claim Form (For KeyCare & BlueCare) 2011 Optima Information Optima Enrollment Form Prescription Home Delivery Order Form (For Optima) 2011 Delta Dental Information Delta Dental Change Form Delta Dental

  15. Electrochemical cell

    DOE Patents [OSTI]

    Redey, Laszlo I.; Myles, Kevin M.; Vissers, Donald R.; Prakash, Jai

    1996-01-01

    An electrochemical cell with a positive electrode having an electrochemically active layer of at least one transition metal chloride. A negative electrode of an alkali metal and a compatible electrolyte including an alkali metal salt molten at cell operating temperature is included in the cell. The electrolyte is present at least partially as a corrugated .beta." alumina tube surrounding the negative electrode interior to the positive electrode. The ratio of the volume of liquid electrolyte to the volume of the positive electrode is in the range of from about 0.1 to about 3. A plurality of stacked electrochemical cells is disclosed each having a positive electrode, a negative electrode of an alkali metal molten at cell operating temperature, and a compatible electrolyte. The electrolyte is at least partially present as a corrugated .beta." alumina sheet separating the negative electrode and interior to the positive electrodes. The alkali metal is retained in a porous electrically conductive ceramic, and seals for sealing the junctures of the electrolyte and the adjacent electrodes at the peripheries thereof.

  16. Electrochemical cell

    DOE Patents [OSTI]

    Redey, L.I.; Myles, K.M.; Vissers, D.R.; Prakash, J.

    1996-07-02

    An electrochemical cell is described with a positive electrode having an electrochemically active layer of at least one transition metal chloride. A negative electrode of an alkali metal and a compatible electrolyte including an alkali metal salt molten at cell operating temperature is included in the cell. The electrolyte is present at least partially as a corrugated {beta}{double_prime} alumina tube surrounding the negative electrode interior to the positive electrode. The ratio of the volume of liquid electrolyte to the volume of the positive electrode is in the range of from about 0.1 to about 3. A plurality of stacked electrochemical cells is disclosed each having a positive electrode, a negative electrode of an alkali metal molten at cell operating temperature, and a compatible electrolyte. The electrolyte is at least partially present as a corrugated {beta}{double_prime} alumina sheet separating the negative electrode and interior to the positive electrodes. The alkali metal is retained in a porous electrically conductive ceramic, and seals for sealing the junctures of the electrolyte and the adjacent electrodes at the peripheries thereof. 8 figs.

  17. Electrochemical cell

    DOE Patents [OSTI]

    Nagy, Z.; Yonco, R.M.; You, H.; Melendres, C.A.

    1992-08-25

    An electrochemical cell has a layer-type or sandwich configuration with a Teflon center section that houses working, reference and counter electrodes and defines a relatively narrow electrolyte cavity. The center section is surrounded on both sides with thin Teflon membranes. The membranes are pressed in place by a pair of Teflon inner frames which are in turn supported by a pair of outer metal frames. The pair of inner and outer frames are provided with corresponding, appropriately shaped slits that are in plane generally transverse to the plane of the working electrode and permit X-ray beams to enter and exit the cell through the Teflon membranes that cover the slits so that the interface between the working electrode and the electrolyte within the cell may be analyzed by transmission geometry. In one embodiment, the center section consists of two parts, one on top of the other. Alternatively, the center section of the electrochemical cell may consist of two intersliding pieces or may be made of a single piece of Teflon sheet material. The electrolyte cavity is shaped so that the electrochemical cell can be rotated 90[degree] in either direction while maintaining the working and counter electrodes submerged in the electrolyte. 5 figs.

  18. Highly conductive thermoplastic composites for rapid production of fuel cell bipolar plates

    DOE Patents [OSTI]

    Huang, Jianhua [Blacksburg, VA; Baird, Donald G [Blacksburg, VA; McGrath, James E [Blacksburg, VA

    2008-04-29

    A low cost method of fabricating bipolar plates for use in fuel cells utilizes a wet lay process for combining graphite particles, thermoplastic fibers, and reinforcing fibers to produce a plurality of formable sheets. The formable sheets are then molded into a bipolar plates with features impressed therein via the molding process. The bipolar plates formed by the process have conductivity in excess of 150 S/cm and have sufficient mechanical strength to be used in fuel cells. The bipolar plates can be formed as a skin/core laminate where a second polymer material is used on the skin surface which provides for enhanced conductivity, chemical resistance, and resistance to gas permeation.

  19. Antibody library project could unlock mysteries of human gene function

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

    Mysteries of human gene function Antibody library project could unlock mysteries of human gene function By looking at antibodies, researchers can identify where, in a cell, genes are active and under what conditions they increase or decrease their expression. October 31, 2011 Los Alamos National Laboratory sits on top of a once-remote mesa in northern New Mexico with the Jemez mountains as a backdrop to research and innovation covering multi-disciplines from bioscience, sustainable energy

  20. DOE Strategic Human Capital Plan

    Broader source: Energy.gov [DOE]

    The Strategic Human Capital Plan sets forth the framework for managing the Department of Energy’s (DOE) human capital system through 2015.

  1. 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...

  2. Mutation assays involving blood cells that metabolize toxic substances

    DOE Patents [OSTI]

    Crespi, Charles L. (Marblehead, MA); Thilly, William G. (Winchester, MA)

    1999-01-01

    The present invention pertains to a line of human blood cells which have high levels of oxidative activity (such as oxygenase, oxidase, peroxidase, and hydroxylase activity). Such cells grow in suspension culture, and are useful to determine the mutagenicity of xenobiotic substances that are metabolized into toxic or mutagenic substances. The invention also includes mutation assays using these cells, and other cells with similar characteristics.

  3. Mutation assays involving blood cells that metabolize toxic substances

    DOE Patents [OSTI]

    Crespi, C.L.; Thilly, W.G.

    1999-08-10

    The present invention pertains to a line of human blood cells which have high levels of oxidative activity (such as oxygenase, oxidase, peroxidase, and hydroxylase activity). Such cells grow in suspension culture, and are useful to determine the mutagenicity of xenobiotic substances that are metabolized into toxic or mutagenic substances. The invention also includes mutation assays using these cells, and other cells with similar characteristics. 3 figs.

  4. Electrochemical cell

    DOE Patents [OSTI]

    Redey, L.I.; Vissers, D.R.; Prakash, J.

    1994-08-23

    An electrochemical cell is described having an alkali metal negative electrode such as sodium and a positive electrode including Ni or transition metals, separated by a [beta] alumina electrolyte and NaAlCl[sub 4] or other compatible material. Various concentrations of a bromine, iodine and/or sulfur containing additive and pore formers are disclosed, which enhance cell capacity and power. The pore formers may be the ammonium salts of carbonic acid or a weak organic acid or oxamide or methylcellulose. 6 figs.

  5. Electrochemical cell

    DOE Patents [OSTI]

    Kaun, Thomas D. (New Lenox, IL)

    1984-01-01

    An improved secondary electrochemical cell is disclosed having a negative electrode of lithium aluminum, a positive electrode of iron sulfide, a molten electrolyte of lithium chloride and potassium chloride, and the combination that the fully charged theoretical capacity of the negative electrode is in the range of 0.5-1.0 that of the positive electrode. The cell thus is negative electrode limiting during discharge cycling. Preferably, the negative electrode contains therein, in the approximate range of 1-10 volume % of the electrode, an additive from the materials of graphitized carbon, aluminum-iron alloy, and/or magnesium oxide.

  6. 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.

    2015-05-15

    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-ray imaging.

  7. Evaluation of gamma-Induced Apoptosis in Human Peripheral Blood Lymphocytes

    SciTech Connect (OSTI)

    Baranova, Elena; Boreyko, Alla; Ravnachka, Ivanka; Saveleva, Maria

    2010-01-05

    Several experiments have been performed to study regularities in the induction of apoptotic cells in human lymphocytes by {sup 60}Cogamma-rays at different times after irradiation. Apoptosis induction by {sup 60}Cogamma-rays in human lymphocytes in different cell cycle phases (G{sub 0}, S, G{sub 1}, and G{sub 2}) has been studied. The maximal apoptosis output in lymphocyte cells was observed in the S phase. Modifying effect of replicative and reparative DNA synthesis inhibitors - 1-beta-D-arabinofuranosylcytosine (Ara-C) and hydroxyurea (Hu) - on the kinetics of {sup 60}Cogamma-rays induced apoptosis in human lymphocytes has been studied.

  8. Noninvasive Imaging of Administered Progenitor Cells

    SciTech Connect (OSTI)

    Steven R Bergmann, M.D., Ph.D.

    2012-12-03

    The objective of this research grant was to develop an approach for labeling progenitor cells, specifically those that we had identified as being able to replace ischemic heart cells, so that the distribution could be followed non-invasively. In addition, the research was aimed at determining whether administration of progenitor cells resulted in improved myocardial perfusion and function. The efficiency and toxicity of radiolabeling of progenitor cells was to be evaluated. For the proposed clinical protocol, subjects with end-stage ischemic coronary artery disease were to undergo a screening cardiac positron emission tomography (PET) scan using N-13 ammonia to delineate myocardial perfusion and function. If they qualified based on their PET scan, they would undergo an in-hospital protocol whereby CD34+ cells were stimulated by the administration of granulocytes-colony stimulating factor (G-CSF). CD34+ cells would then be isolated by apharesis, and labeled with indium-111 oxine. Cells were to be re-infused and subjects were to undergo single photon emission computed tomography (SPECT) scanning to evaluate uptake and distribution of labeled progenitor cells. Three months after administration of progenitor cells, a cardiac PET scan was to be repeated to evaluate changes in myocardial perfusion and/or function. Indium oxine is a radiopharmaceutical for labeling of autologous lymphocytes. Indium-111 (In-111) decays by electron capture with a t{sub } of 67.2 hours (2.8 days). Indium forms a saturated complex that is neutral, lipid soluble, and permeates the cell membrane. Within the cell, the indium-oxyquinolone complex labels via indium intracellular chelation. Following leukocyte labeling, ~77% of the In-111 is incorporated in the cell pellet. The presence of red cells and /or plasma reduces the labeling efficacy. Therefore, the product needed to be washed to eliminate plasma proteins. This repeated washing can damage cells. The CD34 selected product was a 90-99% pure population of leukocytes. Viability was assessed using Trypan blue histological analysis. We successfully isolated and labeled ~25-30 x 10{sup 7} CD34+ lymphocytes in cytokine mobilized progenitor cell apharesis harvests. Cells were also subjected to a stat gram stain to look for bacterial contamination, stat endotoxin LAL to look for endotoxin contamination, flow cytometry for evaluation of the purity of the cells and 14-day sterility culture. Colony forming assays confirm the capacity of these cells to proliferate and function ex-vivo with CFU-GM values of 26 colonies/ 1 x 10{sup 4} cells plated and 97% viability in cytokine augmented methylcellulose at 10-14 days in CO{sub 2} incubation. We developed a closed-processing system for the product labeling prior to infusion to maintain autologous cell integrity and sterility. Release criteria for the labeled product were documented for viability, cell count and differential, and measured radiolabel. We were successful in labeling the cells with up to 500 uCi/10{sup 8} cells, with viability of >98%. However, due to delays in getting the protocol approved by the FDA, the cells were not infused in humans in this location (although we did successfully use CD34+ cells in humans in a study in Australia). The approach developed should permit labeling of progenitor cells that can be administered to human subjects for tracking. The labeling approach should be useful for all progenitor cell types, although this would need to be verified since different cell lines may have differential radiosensitivity.

  9. Photovoltaic cell

    DOE Patents [OSTI]

    Gordon, Roy G.; Kurtz, Sarah

    1984-11-27

    In a photovoltaic cell structure containing a visibly transparent, electrically conductive first layer of metal oxide, and a light-absorbing semiconductive photovoltaic second layer, the improvement comprising a thin layer of transition metal nitride, carbide or boride interposed between said first and second layers.

  10. Photoelectrodialytic cell

    DOE Patents [OSTI]

    Murphy, G.W.

    1983-09-13

    A multicompartment photoelectrodialytic demineralization cell is provided with a buffer compartment interposed between the product compartment and a compartment containing an electrolyte solution. Semipermeable membranes separate the buffer compartment from the product and electrolyte compartments. The buffer compartment is flushed to prevent leakage of the electrolyte compartment from entering the product compartment. 3 figs.

  11. Photoelectrodialytic cell

    DOE Patents [OSTI]

    Murphy, George W. (2328 Ashwood, Norman, OK 73069)

    1983-01-01

    A multicompartment photoelectrodialytic demineralization cell is provided with a buffer compartment interposed between the product compartment and a compartment containing an electrolyte solution. Semipermeable membranes separate the buffer compartment from the product and electrolyte compartments. The buffer compartment is flushed to prevent leakage of the electrolyte compartment from entering the product compartment.

  12. BigNeuron: Unlocking the Secrets of the Human Brain

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

    BigNeuron: Unlocking the Secrets of the Human Brain BigNeuron: Unlocking the Secrets of the Human Brain Berkeley Researchers and Supercomputers to Help Create a Standard 3D Neuron Model March 31, 2015 Linda Vu, +1 510 495 2402, lvu@lbl.gov n11.jpg Neuron Image courtesy of The Allen Institute for Brain Science Before scientists can unlock the secrets of the human brain, they must fully understand neurons-the cells of our brain, spinal cord and overall nervous system. Thousands of detailed neuron

  13. Human Genome: DOE Origins

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

    DOE Origins Resources with Additional Information Charles DeLisi Charles DeLisi The genesis of the Department of Energy (DOE) human genome project took place when "Charles DeLisi ... conceived of a concerted effort to sequence the human genome under the aegis of the ... DOE. ... In 1985, DeLisi took the reins of DOE's Office of Health and Environmental Research [OHER], the program that supported most Biology in the Department. The origins of DOE's biology program traced to the Manhattan

  14. Human Papillomavirus (HPV) Infection in Squamous Cell Carcinomas...

    Office of Scientific and Technical Information (OSTI)

    in disease incidence. We evaluated the prevalence of HPV infection and the reliability of different diagnostic tools using primary tumor samples from a cohort of 50 patients. ...

  15. Neutrons provide new insights into human cell behavior

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

    one potential application is to help prevent circulatory blockages that occur with diabetes and other serious illnesses. In addition to the researchers above, Mary Jo Waltman...

  16. 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.

    2014-04-15

    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.

  17. 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.

    1993-05-13

    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.

  18. New light on human evolution

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

    New 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 human evolutionary split took place 10 million years ago. February 19, 2016 Human-gorilla divergence may have occurred two million years earlier than thought (Photo : Flickr: Rod Waddington) Human-gorilla divergence may have occurred two million years earlier than thought (Photo : Flickr: Rod Waddington) "Our

  19. Electrochemical cell

    SciTech Connect (OSTI)

    Walsh, F.M.

    1986-12-23

    This patent describes an electrochemical cell having a metal anode wherein the metal is selected from zinc and cadmium; a bromine cathode; and an aqueous electrolyte containing a metal bromide, the metal bromide having the same metal as the metal of the anode. The improvement described here comprises: a bromine complexing agent in the aqueous metal bromide electrolyte, the complexing agent consisting solely of a quaternary ammonium salt of an N-organo substituted alpha amino acid, ester, or betaine.

  20. Fuel Cells

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

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

  1. 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, Judith M.

    2014-01-01

    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.

  2. The Cell Processor

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

    2005 IBM Corporation The Cell Processor Architecture & Issues 2 2005 IBM Corporation Agenda Cell Processor Overview Programming the Cell Processor Concluding Remarks 3 ...

  3. 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

    2014-06-01

    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.

  4. Diagnostic Studies on Lithium Battery Cells and Cell Components...

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

    Studies on Lithium Battery Cells and Cell Components Diagnostic Studies on Lithium Battery Cells and Cell Components 2012 DOE Hydrogen and Fuel Cells Program and Vehicle ...

  5. Hydrogen and Fuel Cell Technologies Program: Fuel Cells Fact...

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

    Hydrogen and Fuel Cell Technologies Program: Fuel Cells Fact Sheet Hydrogen and Fuel Cell Technologies Program: Fuel Cells Fact Sheet Fact sheet produced by the Fuel Cell...

  6. Fuel Cell Buses

    Broader source: Energy.gov [DOE]

    Presentation slides from the Fuel Cell Technologies Office webinar Fuel Cell Buses Development held September 12, 2013.

  7. Human Factors Engineering Analysis Tool

    Energy Science and Technology Software Center (OSTI)

    2002-03-04

    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.

  8. Development and Optimization of Viable Human Platforms through 3D Printing

    SciTech Connect (OSTI)

    Parker, Paul R.; Moya, Monica L.; Wheeler, Elizabeth K.

    2015-08-21

    3D printing technology offers a unique method for creating cell cultures in a manner far more conducive to accurate representation of human tissues and systems. Here we print cellular structures capable of forming vascular networks and exhibiting qualities of natural tissues and human systems. This allows for cheaper and readily available sources for further study of biological and pharmaceutical agents.

  9. 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

  10. Human Capital Management Accountability Program

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

    2008-08-01

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

  11. Photoelectrochemical cell

    DOE Patents [OSTI]

    Rauh, R. David (Newton, MA); Boudreau, Robert A. (Norton, MA)

    1983-06-14

    A photoelectrochemical cell comprising a sealed container having a light-transmitting window for admitting light into the container across a light-admitting plane, an electrolyte in the container, a photoelectrode in the container having a light-absorbing surface arranged to receive light from the window and in contact with the electrolyte, the surface having a plurality of spaced portions oblique to the plane, each portion having dimensions at least an order of magnitude larger than the maximum wavelength of incident sunlight, the total surface area of the surface being larger than the area of the plane bounded by the container, and a counter electrode in the container in contact with the electrolyte.

  12. 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.

    2014-11-14

    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.

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

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

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

    2014-11-14

    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 cultivablemore » 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.« less

  14. Alternative splicing variants of human Fbx4 disturb cyclin D1 proteolysis in human cancer

    SciTech Connect (OSTI)

    Chu, Xiufeng; Zhang, Ting; Wang, Jie; Li, Meng; Zhang, Xiaolei; Tu, Jing; Sun, Shiqin; Chen, Xiangmei; Lu, Fengmin

    2014-04-25

    Highlights: The expression of Fbx4 was significantly lower in HCC tissues. Novel splicing variants of Fbx4 were identified. These novel variants are much more abundant in human cancer tissues and cells. The novel Fbx4 isoforms could promote cell proliferation and migration in vitro. These isoforms showed less capability for cyclin D1 binding and degradation. - Abstract: Fbx4 is a specific substrate recognition component of SCF ubiquitin ligases that catalyzes the ubiquitination and subsequent degradation of cyclin D1 and Trx1. Two isoforms of human Fbx4 protein, the full length Fbx4? and the C-terminal truncated Fbx4? have been identified, but their functions remain elusive. In this study, we demonstrated that the mRNA level of Fbx4 was significantly lower in hepatocellular carcinoma tissues than that in the corresponding non-tumor tissues. More importantly, we identified three novel splicing variants of Fbx4: Fbx4? (missing 168245nt of exon1), Fbx4? (missing exon6) and a N-terminal reading frame shift variant (missing exon2). Using cloning sequencing and RT-PCR, we demonstrated these novel splice variants are much more abundant in human cancer tissues and cell lines than that in normal tissues. When expressed in Sk-Hep1 and NIH3T3 cell lines, Fbx4?, Fbx4? and Fbx4? could promote cell proliferation and migration in vitro. Concordantly, these isoforms could disrupt cyclin D1 degradation and therefore increase cyclin D1 expression. Moreover, unlike the full-length isoform Fbx4? that mainly exists in cytoplasm, Fbx4?, Fbx4?, and Fbx4? locate in both cytoplasm and nucleus. Since cyclin D1 degradation takes place in cytoplasm, the nuclear distribution of these Fbx4 isoforms may not be involved in the down-regulation of cytoplasmic cyclin D1. These results define the impact of alternative splicing on Fbx4 function, and suggest that the attenuated cyclin D1 degradation by these novel Fbx4 isoforms provides a new insight for aberrant cyclin D1 expression in human cancers.

  15. Electromicroinjection of particles into living cells

    DOE Patents [OSTI]

    Ray, F. Andrew (Los Alamos, NM); Cram, L. Scott (Los Alamos, NM); Galey, William R. (Albuquerque, NM)

    1988-01-01

    Method and apparatus for introducing particles into living cells. Fluorescently-stained human chromosomes are introduced into cultured, mitotic Chinese hamster cells using electromicroinjection. The recipient cells frequently survived the physiological perturbation imposed by a successful chromosome injection. Successfully injected recipient cells maintained viability as evidenced by their ability to be expanded. The technique relies on the surface charge of fluorescently stained chromosomes and their ability to be attracted and repelled to and from the tip of a micropipette. The apparatus includes a micropipette having a tip suitable for piercing the membrane of a target cell and an electrode inserted into the lumen thereof. The target cells and suspended particles are located in an electrically conducted solution, and the lumen of the micropipette is filled with an electrically conducting solution which contacts the electrode located therein. A second electrode is also located in the conducting solution containing the target cells and particles. Voltages applied to the electrode within the micropipette attract the particles to the region of the tip thereof. The particles adhere to the surface of the micropipette with sufficient force that insertion of the micropipette tip and attached particle through the membrane of a target cell will not dislodge the particle. By applying a voltage having the opposite polarity of the attraction voltage, the particles are expelled from the micropipette to which is then withdrawn from the cell body.

  16. Human Genome Program

    SciTech Connect (OSTI)

    Not Available

    1993-01-01

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

  17. Human portable preconcentrator system

    DOE Patents [OSTI]

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

    2003-01-01

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

  18. HUMAN MACHINE COOPERATIVE TELEROBOTICS

    SciTech Connect (OSTI)

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

    2003-06-30

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

  19. Current trends in mapping human genes

    SciTech Connect (OSTI)

    Mckusick, V.A. )

    1991-01-01

    The human is estimated to have at least 50,000 expressed genes (gene loci). Some information is available concerning about 5,000 of these gene loci and about 1,900 have been mapped, i.e., assigned to specific chromosomes (and in most instances particular chromosome regions). Progress has been achieved by a combination of physical mapping (e.g., study of somatic cell hybrids and chromosomal in situ hybridization) and genetic mapping (e.g., genetic linkage studies). New methods for both physical and genetic mapping are expanding the armamentarium. The usefulness of the mapping information is already evident; the spin-off from the Human Genome Project (HGP) begins immediately. the complete nucleotide sequence is the ultimate map of the human genome. Sequencing, although already under way for limited segments of the genome, will await further progress in gene mapping, and in particular creation of contig maps for each chromosome. Meanwhile the technology of sequencing and sequence information handling will be developed.

  20. Human Capital Management Accountability Program (HCMAP) | Department...

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

    Human Capital Management Accountability Program (HCMAP) Human Capital Management Accountability Program (HCMAP) Human Capital Management Accountability Program (HCMAP) is an online ...

  1. Fuel cell arrangement

    DOE Patents [OSTI]

    Isenberg, A.O.

    1987-05-12

    A fuel cell arrangement is provided wherein cylindrical cells of the solid oxide electrolyte type are arranged in planar arrays where the cells within a plane are parallel. Planes of cells are stacked with cells of adjacent planes perpendicular to one another. Air is provided to the interior of the cells through feed tubes which pass through a preheat chamber. Fuel is provided to the fuel cells through a channel in the center of the cell stack; the fuel then passes the exterior of the cells and combines with the oxygen-depleted air in the preheat chamber. 3 figs.

  2. Fuel cell arrangement

    DOE Patents [OSTI]

    Isenberg, Arnold O. (Forest Hills Boro, PA)

    1987-05-12

    A fuel cell arrangement is provided wherein cylindrical cells of the solid oxide electrolyte type are arranged in planar arrays where the cells within a plane are parallel. Planes of cells are stacked with cells of adjacent planes perpendicular to one another. Air is provided to the interior of the cells through feed tubes which pass through a preheat chamber. Fuel is provided to the fuel cells through a channel in the center of the cell stack; the fuel then passes the exterior of the cells and combines with the oxygen-depleted air in the preheat chamber.

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

    SciTech Connect (OSTI)

    1996-01-30

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

  4. SU-E-I-22: Dependence On Calibration Phantom and Field Area of the Conversion Factor Used to Calculate Skin Dose During Neuro-Interventional Fluoroscopic Procedures

    SciTech Connect (OSTI)

    Rana, V K; Vijayan, S; Rudin, S R; Bednarek, D R

    2014-06-01

    Purpose: To determine the appropriate calibration factor to use when calculating skin dose with our real-time dose-tracking system (DTS) during neuro-interventional fluoroscopic procedures by evaluating the difference in backscatter from different phantoms and as a function of entrance-skin field area. Methods: We developed a dose-tracking system to calculate and graphically display the cumulative skin-dose distribution in real time. To calibrate the DTS for neuro-interventional procedures, a phantom is needed that closely approximates the scattering properties of the head. We compared the x-ray backscatter from eight phantoms: 20-cm-thick solid water, 16-cm diameter water-filled container, 16-cm CTDI phantom, modified-ANSI head phantom, 20-cm-thick PMMA, Kyoto-Kagaku PBU- 50 head, Phantom-Labs SK-150 head, and RSD RS-240T head. The phantoms were placed on the patient table with the entrance surface at 15 cm tube-side from the isocenter of a Toshiba Infinix C-arm, and the entrance-skin exposure was measured with a calibrated 6-cc PTW ionization chamber. The measurement included primary radiation, backscatter from the phantom and forward scatter from the table and pad. The variation in entrance-skin exposure was also measured as a function of the skin-entrance area for a 30x30 cm by 20-cm-thick PMMA phantom and the SK-150 head phantom using four different added beam filters. Results: The entranceskin exposure values measured for eight different phantoms differed by up to 12%, while the ratio of entrance exposure of all phantoms relative to solid water showed less than 3% variation with kVp. The change in entrance-skin exposure with entrance-skin area was found to differ for the SK-150 head compared to the 20-cm PMMA phantom and the variation with field area was dependent on the added beam filtration. Conclusion: To accurately calculate skin dose for neuro-interventional procedures with the DTS, the phantom for calibration should be carefully chosen since different phantoms can contribute different backscatter for identical exposure parameters. Research supported in part by Toshiba Medical Systems and NIH Grants R43FD0158401, R44FD0158402 and R01EB002873.

  5. Human Reliability Program Workshop

    SciTech Connect (OSTI)

    Landers, John; Rogers, Erin; Gerke, Gretchen

    2014-05-18

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

  6. Human-computer interface

    DOE Patents [OSTI]

    Anderson, Thomas G.

    2004-12-21

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

  7. Human portable preconcentrator system

    DOE Patents [OSTI]

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

    2003-08-12

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

  8. Human Performance Modeling for Dynamic Human Reliability Analysis

    SciTech Connect (OSTI)

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

    2015-08-01

    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.

  9. Fuel cell-fuel cell hybrid system

    DOE Patents [OSTI]

    Geisbrecht, Rodney A.; Williams, Mark C.

    2003-09-23

    A device for converting chemical energy to electricity is provided, the device comprising a high temperature fuel cell with the ability for partially oxidizing and completely reforming fuel, and a low temperature fuel cell juxtaposed to said high temperature fuel cell so as to utilize remaining reformed fuel from the high temperature fuel cell. Also provided is a method for producing electricity comprising directing fuel to a first fuel cell, completely oxidizing a first portion of the fuel and partially oxidizing a second portion of the fuel, directing the second fuel portion to a second fuel cell, allowing the first fuel cell to utilize the first portion of the fuel to produce electricity; and allowing the second fuel cell to utilize the second portion of the fuel to produce electricity.

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

    Energy Savers [EERE]

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

  11. DOE Fuel Cell Technologies Office: 2013 Fuel Cell Seminar and...

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

    Office: 2013 Fuel Cell Seminar and Energy Exposition DOE Fuel Cell Technologies Office: 2013 Fuel Cell Seminar and Energy Exposition Overview of DOE's Fuel Cell Technologies Office...

  12. 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 and U.S. Department of Energy (DOE) Orders 443.1 and 481.1 require the maintenance of information on all research projects that involve human subjects and that are funded by DOE, conducted in DOE facilities, performed by DOE personnel or involve DOE or contract personnel. The Oak Ridge Institute for Science and Education (ORISE) maintains the Human Subjects Research Database (HSRD) for the Office of

  13. Protection of Human Research Subjects

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

    2015-07-20

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

  14. Quantum physics and human values

    SciTech Connect (OSTI)

    Stapp, H.P.

    1989-09-01

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

  15. Ohio Fuel Cell Initiative

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

    Top 5 Fuel Cell States: Why Local Policies Mean Green Growth Jun 21 st , 2011 2 * Ohio Fuel Cell Initiative * Ohio Fuel Cell Coalition * Accomplishments * Ohio Successes Discussion Areas 3 Ohio's Fuel Cell Initiative * Announced on 5/9/02 * Part of Ohio Third Frontier Initiative * $85 million investment to date * Core focus areas: 1) Expand the state's research capabilities; 2) Participate in demonstration projects; and 3) Expand the fuel cell industry in Ohio 4 OHIO'S FUEL CELL INITIATIVE

  16. CHL1 is involved in human breast tumorigenesis and progression

    SciTech Connect (OSTI)

    He, Li-Hong; Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin ; Ma, Qin; Shi, Ye-Hui; Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin ; Ge, Jie; Zhao, Hong-Meng; Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin ; Li, Shu-Fen; Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin ; Tong, Zhong-Sheng; Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin

    2013-08-23

    Highlights: CHL1 is down-regulation in breast cancer tissues. Down-regulation of CHL1 is related to high grade. Overexpression of CHL1 inhibits breast cancer cell proliferation and invasion in vitro. CHL1 deficiency induces breast cancer cell proliferation and invasion both in vitro and in vivo. -- Abstract: Neural cell adhesion molecules (CAM) play important roles in the development and regeneration of the nervous system. The L1 family of CAMs is comprised of L1, Close Homolog of L1 (CHL1, L1CAM2), NrCAM, and Neurofascin, which are structurally related trans-membrane proteins in vertebrates. Although the L1CAM has been demonstrated play important role in carcinogenesis and progression, the function of CHL1 in human breast cancer is limited. Here, we found that CHL1 is down-regulated in human breast cancer and related to lower grade. Furthermore, overexpression of CHL1 suppresses proliferation and invasion in MDA-MB-231 cells and knockdown of CHL1 expression results in increased proliferation and invasion in MCF7 cells in vitro. Finally, CHL1 deficiency promotes tumor formation in vivo. Our results may provide a strategy for blocking breast carcinogenesis and progression.

  17. Cellular morphometry of the bronchi of human and dog lungs

    SciTech Connect (OSTI)

    Robbins, E.S.

    1992-09-01

    Quantitative data of the human bronchial epithelial cells at possible risk for malignant transformation in lung cancer is crucial for accurate radon dosimetry and risk analysis. The locations and other parameters of the nuclei which may be damaged by [alpha] particles must be determined and compared in different airway generations, among smokers, non-smokers and ex-smokers, between men and women and in people of different ages. This proposal includes extended morphometric studies on electron micrographs of human epithelium of defined airway generations and in parallel on electron micrographs of the dog bronchial lining. The second part of this proposal describes studies to quantitate the cycling bronchial epithelial population(s) using proliferation markers and immunocytochemistry on frozen and paraffin sections and similar labeling of isolated bronchial epithelial cells sorted flow cytometry.

  18. The Human Genome Diversity Project

    SciTech Connect (OSTI)

    Cavalli-Sforza, L.

    1994-12-31

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

  19. Human Reliability Analysis for Digital Human-Machine Interfaces

    SciTech Connect (OSTI)

    Ronald L. Boring

    2014-06-01

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

  20. 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

    2011-03-18

    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 mM range induced increasing structural perturbation to DMPC, but no effects on DMPE multibilayers were detected.

  1. Molten carbonate fuel cell

    DOE Patents [OSTI]

    Kaun, T.D.; Smith, J.L.

    1986-07-08

    A molten electrolyte fuel cell is disclosed with an array of stacked cells and cell enclosures isolating each cell except for access to gas manifolds for the supply of fuel or oxidant gas or the removal of waste gas. The cell enclosures collectively provide an enclosure for the array and effectively avoid the problems of electrolyte migration and the previous need for compression of stack components. The fuel cell further includes an inner housing about and in cooperation with the array enclosure to provide a manifold system with isolated chambers for the supply and removal of gases. An external insulated housing about the inner housing provides thermal isolation to the cell components.

  2. Molten carbonate fuel cell

    DOE Patents [OSTI]

    Kaun, Thomas D. (New Lenox, IL); Smith, James L. (Lemont, IL)

    1987-01-01

    A molten electrolyte fuel cell with an array of stacked cells and cell enclosures isolating each cell except for access to gas manifolds for the supply of fuel or oxidant gas or the removal of waste gas, the cell enclosures collectively providing an enclosure for the array and effectively avoiding the problems of electrolyte migration and the previous need for compression of stack components, the fuel cell further including an inner housing about and in cooperation with the array enclosure to provide a manifold system with isolated chambers for the supply and removal of gases. An external insulated housing about the inner housing provides thermal isolation to the cell components.

  3. Crystallization and preliminary crystallographic analysis of recombinant human galectin-1

    SciTech Connect (OSTI)

    Scott, Stacy A.; Scott, Ken; Blanchard, Helen

    2007-11-01

    Human galectin-1 has been cloned, expressed in E. coli, purified and crystallized in the presence of both lactose (ligand) and ?-mercaptoethanol under six different conditions. The X-ray diffraction data obtained have enabled the assignment of unit-cell parameters for two novel crystal forms of human galectin-1. Galectin-1 is considered to be a regulator protein as it is ubiquitously expressed throughout the adult body and is responsible for a broad range of cellular regulatory functions. Interest in galectin-1 from a drug-design perspective is founded on evidence of its overexpression by many cancers and its immunomodulatory properties. The development of galectin-1-specific inhibitors is a rational approach to the fight against cancer because although galectin-1 induces a plethora of effects, null mice appear normal. X-ray crystallographic structure determination will aid the structure-based design of galectin-1 inhibitors. Here, the crystallization and preliminary diffraction analysis of human galectin-1 crystals generated under six different conditions is reported. X-ray diffraction data enabled the assignment of unit-cell parameters for crystals grown under two conditions, one belongs to a tetragonal crystal system and the other was determined as monoclinic P2{sub 1}, representing two new crystal forms of human galectin-1.

  4. Fuel Cell Technologies Overview: 2011 Fuel Cell Seminar | Department...

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

    2011 Fuel Cell Seminar Fuel Cell Technologies Overview: 2011 Fuel Cell Seminar Presentation by Sunita Satyapal at the Fuel Cell Seminar on November 1, 2011. PDF icon Fuel Cell...

  5. Anandamide inhibits adhesion and migration of breast cancer cells

    SciTech Connect (OSTI)

    Grimaldi, Claudia; Pisanti, Simona; Laezza, Chiara; Malfitano, Anna Maria; Santoro, Antonietta; Vitale, Mario; Caruso, Maria Gabriella; Notarnicola, Maria; Iacuzzo, Irma; Portella, Giuseppe; Di Marzo, Vincenzo . E-mail: vdimarzo@icmib.na.cnr.it; Bifulco, Maurizio . E-mail: maubiful@unina.it

    2006-02-15

    The endocannabinoid system regulates cell proliferation in human breast cancer cells. We reasoned that stimulation of cannabinoid CB{sub 1} receptors could induce a non-invasive phenotype in breast mtastatic cells. In a model of metastatic spreading in vivo, the metabolically stable anandamide analogue, 2-methyl-2'-F-anandamide (Met-F-AEA), significantly reduced the number and dimension of metastatic nodes, this effect being antagonized by the selective CB{sub 1} antagonist SR141716A. In MDA-MB-231 cells, a highly invasive human breast cancer cell line, and in TSA-E1 cells, a murine breast cancer cell line, Met-F-AEA inhibited adhesion and migration on type IV collagen in vitro without modifying integrin expression: both these effects were antagonized by SR141716A. In order to understand the molecular mechanism involved in these processes, we analyzed the phosphorylation of FAK and Src, two tyrosine kinases involved in migration and adhesion. In Met-F-AEA-treated cells, we observed a decreased tyrosine phosphorylation of both FAK and Src, this effect being attenuated by SR141716A. We propose that CB{sub 1} receptor agonists inhibit tumor cell invasion and metastasis by modulating FAK phosphorylation, and that CB{sub 1} receptor activation might represent a novel therapeutic strategy to slow down the growth of breast carcinoma and to inhibit its metastatic diffusion in vivo.

  6. Hydrogen and Fuel Cell Technologies Program: Fuel Cells Fact Sheet |

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

    Department of Energy Hydrogen and Fuel Cell Technologies Program: Fuel Cells Fact Sheet Hydrogen and Fuel Cell Technologies Program: Fuel Cells Fact Sheet Fact sheet produced by the Fuel Cell Technologies Program describing hydrogen fuel cell technology. PDF icon Fuel Cells Fact Sheet More Documents & Publications Comparison of Fuel Cell Technologies: Fact Sheet Fuel Cells Fact Sheet 2011 Pathways to Commercial Success: Technologies and Products Supported by the Fuel Cell Technologies

  7. Human Genome Education Program

    SciTech Connect (OSTI)

    Richard Myers; Lane Conn

    2000-05-01

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

  8. Human genome. 1993 Program report

    SciTech Connect (OSTI)

    Not Available

    1994-03-01

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

  9. Contractor Human Resource Management Programs

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

    1996-09-30

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

  10. Contractor Human Resource Management Programs

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

    1996-09-30

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

  11. 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 and U.S. Department of Energy (DOE) Orders 443.1 and 481.1 require the maintenance of...

  12. Protection of Human Research Subjects

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

    2009-12-09

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

  13. 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 - 6:30 PM WHERE: Eldorado Hotel 309 W San Francisco Street, Santa Fe SPEAKER: Robert Davis, University of Virginia CONTACT: Shermonta Grant (202) 777-7329 CATEGORY: Community Science TYPE: Lecture INTERNAL: Calendar Login Event Description The main reason we are concerned about human-induced climate change is that climate shifts might impact the health of Earth's populace. These impacts can be direct, such as

  14. 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 characterized by a fair treatment of staff, open communications, personal accountability, trust and mutual respect. We will seek and provide practical services and solutions to workplace issues that enhance the overall mission of the Ames Laboratory in support of science to address the nation's future energy needs. Image

  15. 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 characterized by a fair treatment of staff, open communications, personal accountability, trust and mutual respect. We will seek and provide practical services and solutions to workplace issues that enhance the overall mission of the Ames Laboratory in support of science to address the nation's future energy needs. Image New

  16. T Cell Allorecognition via Molecular Mimicry

    SciTech Connect (OSTI)

    Macdonald, Whitney A.; Chen, Zhenjun; Gras, Stephanie; Archbold, Julia K.; Tynan, Fleur E.; Clements, Craig S.; Bharadwaj, Mandvi; Kjer-Nielsen, Lars; Saunders, Philippa M.; Wilce, Matthew C.J.; Crawford, Fran; Stadinsky, Brian; Jackson, David; Brooks, Andrew G.; Purcell, Anthony W.; Kappler, John W.; Burrows, Scott R.; Rossjohn, Jamie; McCluskey, James

    2010-08-16

    T cells often alloreact with foreign human leukocyte antigens (HLA). Here we showed the LC13 T cell receptor (TCR), selected for recognition on self-HLA-B*0801 bound to a viral peptide, alloreacts with B44 allotypes (HLA-B*4402 and HLA-B*4405) bound to two different allopeptides. Despite extensive polymorphism between HLA-B*0801, HLA-B*4402, and HLA-B*4405 and the disparate sequences of the viral and allopeptides, the LC13 TCR engaged these peptide-HLA (pHLA) complexes identically, accommodating mimicry of the viral peptide by the allopeptide. The viral and allopeptides adopted similar conformations only after TCR ligation, revealing an induced-fit mechanism of molecular mimicry. The LC13 T cells did not alloreact against HLA-B*4403, and the single residue polymorphism between HLA-B*4402 and HLA-B*4403 affected the plasticity of the allopeptide, revealing that molecular mimicry was associated with TCR specificity. Accordingly, molecular mimicry that is HLA and peptide dependent is a mechanism for human T cell alloreactivity between disparate cognate and allogeneic pHLA complexes.

  17. Diagnostic Studies on Lithium Battery Cells and Cell Components |

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

    Department of Energy Studies on Lithium Battery Cells and Cell Components Diagnostic Studies on Lithium Battery Cells and Cell Components 2012 DOE Hydrogen and Fuel Cells Program and Vehicle Technologies Program Annual Merit Review and Peer Evaluation Meeting PDF icon es032_abraham_2012_o.pdf More Documents & Publications Mitigating Performance Degradation of High-Energy Lithium-Ion Cells Diagnostic studies on Li-battery cells and cell components Cell Fabrication Facility Team Production

  18. Inhibition of glycogen synthase kinase-3 enhances the differentiation and reduces the proliferation of adult human olfactory epithelium neural precursors

    SciTech Connect (OSTI)

    Manceur, Aziza P.; Donnelly Centre, University of Toronto, Toronto, Ontario ; Tseng, Michael; Department of Psychiatry, University of Toronto, Toronto, ON; Institute of Medical Science, University of Toronto, Toronto, ON ; Holowacz, Tamara; Witterick, Ian; Department of Otolaryngology, Head and Neck Surgery, University of Toronto, ON ; Weksberg, Rosanna; The Hospital for Sick Children, Research Institute, Program in Genetics and Genomic Biology, Toronto, Ontario Canada ; McCurdy, Richard D.; Warsh, Jerry J.; Department of Psychiatry, University of Toronto, Toronto, ON; Institute of Medical Science, University of Toronto, Toronto, ON ; Audet, Julie; Donnelly Centre, University of Toronto, Toronto, Ontario

    2011-09-10

    The olfactory epithelium (OE) contains neural precursor cells which can be easily harvested from a minimally invasive nasal biopsy, making them a valuable cell source to study human neural cell lineages in health and disease. Glycogen synthase kinase-3 (GSK-3) has been implicated in the etiology and treatment of neuropsychiatric disorders and also in the regulation of murine neural precursor cell fate in vitro and in vivo. In this study, we examined the impact of decreased GSK-3 activity on the fate of adult human OE neural precursors in vitro. GSK-3 inhibition was achieved using ATP-competitive (6-bromoindirubin-3'-oxime and CHIR99021) or substrate-competitive (TAT-eIF2B) inhibitors to eliminate potential confounding effects on cell fate due to off-target kinase inhibition. GSK-3 inhibitors decreased the number of neural precursor cells in OE cell cultures through a reduction in proliferation. Decreased proliferation was not associated with a reduction in cell survival but was accompanied by a reduction in nestin expression and a substantial increase in the expression of the neuronal differentiation markers MAP1B and neurofilament (NF-M) after 10 days in culture. Taken together, these results suggest that GSK-3 inhibition promotes the early stages of neuronal differentiation in cultures of adult human neural precursors and provide insights into the mechanisms by which alterations in GSK-3 signaling affect adult human neurogenesis, a cellular process strongly suspected to play a role in the etiology of neuropsychiatric disorders.

  19. Rocky Mountain Humane Investing | Open Energy Information

    Open Energy Info (EERE)

    Rocky Mountain Humane Investing Jump to: navigation, search Name: Rocky Mountain Humane Investing Place: Allenspark, Colorado Zip: 80510 Product: Allenspark-based investment...

  20. Habitat for Humanity | Open Energy Information

    Open Energy Info (EERE)

    Habitat for Humanity Jump to: navigation, search Name: Habitat for Humanity Place: Americus, GA Website: www.habitat.org References: NREL Technical Report: Zero Energy Home1...

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

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

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

  2. Climate Human Capital | Open Energy Information

    Open Energy Info (EERE)

    Human Capital Jump to: navigation, search Name: Climate Human Capital Place: London, United Kingdom Zip: W1K 6NG Sector: Carbon, Renewable Energy, Services Product: Green executive...

  3. Hydrogen and Fuel Cell Technologies Update: 2010 Fuel Cell Seminar...

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

    Update: 2010 Fuel Cell Seminar and Exposition Hydrogen and Fuel Cell Technologies Update: 2010 Fuel Cell Seminar and Exposition Presentation by Sunita Satyapal at the 2010 Fuel...

  4. Th Cell Gene Expression and Function in Response to Low Dose and Acute Radiation

    SciTech Connect (OSTI)

    Daila S. Gridley, PhD

    2012-03-30

    FINAL TECHNICAL REPORT Supported by the Low Dose Radiation Research Program, Office of Science U.S. Department of Energy Grant No. DE-FG02-07ER64345 Project ID: 0012965 Award Register#: ER64345 Project Manager: Noelle F. Metting, Sc.D. Phone: 301-903-8309 Division SC-23.2 noelle.metting@science.doe.gov Submitted March 2012 To: https://www.osti.gov/elink/241.3.jsp Title: Th Cell Gene Expression and Function in Response to Low Dose and Acute Radiation PI: Daila S. Gridley, Ph.D. Human low dose radiation data have been derived primarily from studies of space and airline flight personnel, nuclear plant workers and others exposed occupationally, as well as victims in the vicinity of atomic bomb explosions. The findings remain inconclusive due to population inconsistencies and complex interactions among total dose, dose rate, radiation quality and age at exposure. Thus, safe limits for low dose occupational irradiation are currently based on data obtained with doses far exceeding the levels expected for the general population and health risks have been largely extrapolated using the linear-nonthreshold dose-response model. The overall working hypothesis of the present study is that priming with low dose, low-linear energy transfer (LET) radiation can ameliorate the response to acute high-dose radiation exposure. We also propose that the efficacy of low-dose induced protection will be dependent upon the form and regimen of the high-dose exposure: photons versus protons versus simulated solar particle event protons (sSPE). The emphasis has been on gene expression and function of CD4+ T helper (Th) lymphocytes harvested from spleens of whole-body irradiated C57BL/6 mice, a strain that provides the genetic background for many genetically engineered strains. Evaluations of the responses of other selected cells, tissues such as skin, and organs such as lung, liver and brain were also initiated (partially funded by other sources). The long-term goal is to provide information that will be useful in estimating human health risks due to radiation that may occur during exposures in the work environment, nuclear/radiological catastrophes, as well as radiotherapy. Several papers have been published, accepted for publication or are in preparation. A number of poster and oral presentations have been made at scientific conferences and workshops. Archived tissues of various types will continue to be evaluated via funding from other sources (the DoE Low Dose Radiation Research Program, Office of Science and this specific grant will be appropriately included in the Acknowledgements of all subsequent publications/presentations). A post-doc and several students have participated in this study. More detailed description of the accomplishments is described in attached file.

  5. Fuel Cell Technical Publications

    Broader source: Energy.gov [DOE]

    Technical information about fuel cells published in technical reports, conference proceedings, journal articles, and websites is provided here.

  6. The SACADA database for human reliability and human performance

    SciTech Connect (OSTI)

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

    2014-05-01

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

  7. Biomarkers of cell senescence

    DOE Patents [OSTI]

    Dimri, G.P.; Campisi, J.; Peacocke, M.

    1998-08-18

    The present invention provides a biomarker system for the in vivo and in vitro assessment of cell senescence. In the method of the present invention, {beta}-galactosidase activity is utilized as a means by which cell senescence may be assessed either in vitro cell cultures or in vivo. 1 fig.

  8. Biomarkers of cell senescence

    DOE Patents [OSTI]

    Dimri, Goberdhan P. (Simli U.P., IN); Campisi, Judith (Berkeley, CA); Peacocke, Monica (Newton, MA)

    1998-01-01

    The present invention provides a biomarker system for the in vivo and in vitro assessment of cell senescence. In the method of the present invention, .beta.-galactosidase activity is utilized as a means by which cell senescence may be assessed either in vitro cell cultures or in vivo.

  9. Biomarkers of cell senescence

    DOE Patents [OSTI]

    Dirmi, Goberdhan P. (Simli U.P., IN); Campisi, Judith (Berkeley, CA); Peacocke, Monica (Newton, MA)

    1996-01-01

    The present invention provides a biomarker system for the in vivo and in vitro assessment of cell senescence. In the method of the present invention, .beta.-galactosidase activity is utilized as a means by which cell senescence may be assessed either in in vitro cell cultures or in vivo.

  10. Rapidly refuelable fuel cell

    DOE Patents [OSTI]

    Joy, Richard W. (Santa Clara, CA)

    1983-01-01

    This invention is directed to a metal-air fuel cell where the consumable metal anode is movably positioned in the cell and an expandable enclosure, or bladder, is used to press the anode into contact with separating spacers between the cell electrodes. The bladder may be depressurized to allow replacement of the anode when consumed.

  11. Biomarkers of cell senescence

    DOE Patents [OSTI]

    Dirmi, G.P.; Campisi, J.; Peacocke, M.

    1996-02-13

    The present invention provides a biomarker system for the in vivo and in vitro assessment of cell senescence. In the method of the present invention, {beta}-galactosidase activity is utilized as a means by which cell senescence may be assessed either in in vitro cell cultures or in vivo. 1 fig.

  12. Appendix K Disposal Cell Groundwater Monitoring Plan

    Office of Legacy Management (LM)

    Disposal Cell Groundwater Monitoring Plan

  13. Development of realistic physical breast phantoms matched to virtual breast phantoms based on human subject data

    SciTech Connect (OSTI)

    Kiarashi, Nooshin; Nolte, Adam C.; Sturgeon, Gregory M.; Ghate, Sujata V.; Segars, William P.; Nolte, Loren W.; Samei, Ehsan; and others

    2015-07-15

    Purpose: Physical phantoms are essential for the development, optimization, and evaluation of x-ray breast imaging systems. Recognizing the major effect of anatomy on image quality and clinical performance, such phantoms should ideally reflect the three-dimensional structure of the human breast. Currently, there is no commercially available three-dimensional physical breast phantom that is anthropomorphic. The authors present the development of a new suite of physical breast phantoms based on human data. Methods: The phantoms were designed to match the extended cardiac-torso virtual breast phantoms that were based on dedicated breast computed tomography images of human subjects. The phantoms were fabricated by high-resolution multimaterial additive manufacturing (3D printing) technology. The glandular equivalency of the photopolymer materials was measured relative to breast tissue-equivalent plastic materials. Based on the current state-of-the-art in the technology and available materials, two variations were fabricated. The first was a dual-material phantom, the Doublet. Fibroglandular tissue and skin were represented by the most radiographically dense material available; adipose tissue was represented by the least radiographically dense material. The second variation, the Singlet, was fabricated with a single material to represent fibroglandular tissue and skin. It was subsequently filled with adipose-equivalent materials including oil, beeswax, and permanent urethane-based polymer. Simulated microcalcification clusters were further included in the phantoms via crushed eggshells. The phantoms were imaged and characterized visually and quantitatively. Results: The mammographic projections and tomosynthesis reconstructed images of the fabricated phantoms yielded realistic breast background. The mammograms of the phantoms demonstrated close correlation with simulated mammographic projection images of the corresponding virtual phantoms. Furthermore, power-law descriptions of the phantom images were in general agreement with real human images. The Singlet approach offered more realistic contrast as compared to the Doublet approach, but at the expense of air bubbles and air pockets that formed during the filling process. Conclusions: The presented physical breast phantoms and their matching virtual breast phantoms offer realistic breast anatomy, patient variability, and ease of use, making them a potential candidate for performing both system quality control testing and virtual clinical trials.

  14. ATHENA, the Desktop Human "Body"

    SciTech Connect (OSTI)

    Iyer, Rashi; Harris, Jennifer

    2014-09-29

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

  15. ATHENA, the Desktop Human "Body"

    ScienceCinema (OSTI)

    Iyer, Rashi; Harris, Jennifer

    2015-01-05

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

  16. Human Resources | U.S. DOE Office of Science (SC)

    Office of Science (SC) Website

    Human Resources Human Resources and Administration (HRA) HRA Home About Human Resources Administration SC Correspondence Control Center (SC CCC) Contact Information Human Resources...

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

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

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

  18. Induction of cytochromes P450 1A1 and 1A2 by tanshinones in human HepG2

    Office of Scientific and Technical Information (OSTI)

    hepatoma cell line (Journal Article) | SciTech Connect SciTech Connect Search Results Journal Article: Induction of cytochromes P450 1A1 and 1A2 by tanshinones in human HepG2 hepatoma cell line Citation Details In-Document Search Title: Induction of cytochromes P450 1A1 and 1A2 by tanshinones in human HepG2 hepatoma cell line Diterpenoid tanshinones including tanshinone IIA (TIIA), cryptotanshinone (CTS), tanshinone I (TI) and dihydrotanshinone I (DHTI) are the major bioactive components

  19. Differentiation within autologous fibrin scaffolds of porcine dermal cells with the mesenchymal stem cell phenotype

    SciTech Connect (OSTI)

    Puente, Pilar de la

    2013-02-01

    Porcine mesenchymal stem cells (pMSCs) are an attractive source of cells for tissue engineering because their properties are similar to those of human stem cells. pMSCs can be found in different tissues but their dermal origin has not been studied in depth. Additionally, MSCs differentiation in monolayer cultures requires subcultured cells, and these cells are at risk of dedifferentiation when implanting them into living tissue. Following this, we attempted to characterize the MSCs phenotype of porcine dermal cells and to evaluate their cellular proliferation and differentiation in autologous fibrin scaffolds (AFSs). Dermal biopsies and blood samples were obtained from 12 pigs. Dermal cells were characterized by flow cytometry. Frozen autologous plasma was used to prepare AFSs. pMSC differentiation was studied in standard structures (monolayers and pellets) and in AFSs. The pMSCs expressed the CD90 and CD29 markers of the mesenchymal lineage. AFSs afforded adipogenic, osteogenic and chondrogenic differentiation. The porcine dermis can be proposed to be a good source of MSCs with adequate proliferative capacity and a suitable expression of markers. The pMSCs also showed optimal proliferation and differentiation in AFSs, such that these might serve as a promising autologous and implantable material for use in tissue engineering. -- Highlights: ► Low fibrinogen concentration provides a suitable matrix for cell migration and differentiation. ► Autologous fibrin scaffolds is a promising technique in tissue engineering. ► Dermal cells are an easily accessible mesenchymal stem cell source. ► Fibrin scaffolds afforded adipogenic, osteogenic and chondrogenic differentiation.

  20. 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

    2014-06-15

    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, R44FD0158402 and R01EB002873.

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

    SciTech Connect (OSTI)

    Wang, Ruoxing; Guo, Yan-Lin

    2012-10-01

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

  2. WILD PIG ATTACKS ON HUMANS

    SciTech Connect (OSTI)

    Mayer, J.

    2013-04-12

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

  3. Fuel Cell Technologies Overview: 2012 Flow Cells for Energy Storage

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

    Workshop | Department of Energy Overview: 2012 Flow Cells for Energy Storage Workshop Fuel Cell Technologies Overview: 2012 Flow Cells for Energy Storage Workshop Presentation by Sunita Satyapal and Dimitrios Papageorgopoulos, U.S. Department of Energy Fuel Cell Technologies Program, at the Flow Cells for Energy Storage Workshop held March 7-8, 2012, in Washington, DC. PDF icon Fuel Cell Technologies Overview More Documents & Publications DOE Fuel Cell Technologies Office: 2013 Fuel Cell

  4. Low-Income Weatherization: The Human Dimension

    Broader source: Energy.gov [DOE]

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

  5. Human Capital Organization | Department of Energy

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

    Human Capital Organization Human Capital Organization HC Organizational Chart HC Organizational Chart Printable Version The Office of the Chief Human Capital Officer provides leadership to the Department of Energy (DOE) on the impact and use of policies, proposals, programs, and partnerships related to all aspects of Human Capital Management (HCM).

  6. Solid Oxide Fuel Cells FAQs

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

    further information, see: - Fuel Cell Handbook (Seventh Edition) SOLID OXIDE FUEL CELLS - ENVIRONMENT Q: How are fuel cells used? A: Fuel cells may be used to power anything that...

  7. Cell migration or cytokinesis and proliferation? Revisiting the go or grow hypothesis in cancer cells in vitro

    SciTech Connect (OSTI)

    Garay, Tams; Juhsz, va; Molnr, Eszter; Eisenbauer, Maria; Czirk, Andrs; Dekan, Barbara; Lszl, Viktria; Hoda, Mir Alireza; Dme, Balzs; Tmr, Jzsef; Klepetko, Walter; Berger, Walter; Heged?s, Balzs

    2013-12-10

    The mortality of patients with solid tumors is mostly due to metastasis that relies on the interplay between migration and proliferation. The go or grow hypothesis postulates that migration and proliferation spatiotemporally excludes each other. We evaluated this hypothesis on 35 cell lines (12 mesothelioma, 13 melanoma and 10 lung cancer) on both the individual cell and population levels. Following three-day-long videomicroscopy, migration, proliferation and cytokinesis-length were quantified. We found a significantly higher migration in mesothelioma cells compared to melanoma and lung cancer while tumor types did not differ in mean proliferation or duration of cytokinesis. Strikingly, we found in melanoma and lung cancer a significant positive correlation between mean proliferation and migration. Furthermore, non-dividing melanoma and lung cancer cells displayed slower migration. In contrast, in mesothelioma there were no such correlations. Interestingly, negative correlation was found between cytokinesis-length and migration in melanoma. FAK activation was higher in melanoma cells with high motility. We demonstrate that the cancer cells studied do not defer proliferation for migration. Of note, tumor cells from various organ systems may differently regulate migration and proliferation. Furthermore, our data is in line with the observation of pathologists that highly proliferative tumors are often highly invasive. - Highlights: We investigated the go or grow hypothesis in human cancer cells in vitro. Proliferation and migration positively correlate in melanoma and lung cancer cells. Duration of cytokinesis and migration shows inverse correlation. Increased FAK activation is present in highly motile melanoma cells.

  8. Human Capital Management | Department of Energy

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

    Management Human Capital Management The strategic management of human capital requires comprehensive planning and analysis in order to develop, implement, and evaluate programs that support every facet of employee work life. DOE human capital initiatives are designed to support continuous improvement and accountability in accordance with the DOE Human Capital Management Accountability Program (HCMAP), which is an internal DOE audit process of servicing human resources offices and addresses those

  9. Careers in Fuel Cell Technologies

    Broader source: Energy.gov [DOE]

    Fact sheet produced by the Fuel Cell Technologies Office describing job growth potential in existing and emerging fuel cell applications.

  10. Arsenite suppression of BMP signaling in human keratinocytes

    SciTech Connect (OSTI)

    Phillips, Marjorie A.; Qin, Qin; Hu, Qin; Zhao, Bin; Rice, Robert H.

    2013-06-15

    Arsenic, a human skin carcinogen, suppresses differentiation of cultured keratinocytes. Exploring the mechanism of this suppression revealed that BMP-6 greatly increased levels of mRNA for keratins 1 and 10, two of the earliest differentiation markers expressed, a process prevented by co-treatment with arsenite. BMP also stimulated, and arsenite suppressed, mRNA for FOXN1, an important transcription factor driving early keratinocyte differentiation. Keratin mRNAs increased slowly after BMP-6 addition, suggesting they are indirect transcriptional targets. Inhibition of Notch1 activation blocked BMP induction of keratins 1 and 10, while FOXN1 induction was largely unaffected. Supporting a requirement for Notch1 signaling in keratin induction, BMP increased levels of activated Notch1, which was blocked by arsenite. BMP also greatly decreased active ERK, while co-treatment with arsenite maintained active ERK. Inhibition of ERK signaling mimicked BMP by inducing keratin and FOXN1 mRNAs and by increasing active Notch1, effects blocked by arsenite. Of 6 dual-specificity phosphatases (DUSPs) targeting ERK, two were induced by BMP unless prevented by simultaneous exposure to arsenite and EGF. Knockdown of DUSP2 or DUSP14 using shRNAs greatly reduced FOXN1 and keratins 1 and 10 mRNA levels and their induction by BMP. Knockdown also decreased activated Notch1, keratin 1 and keratin 10 protein levels, both in the presence and absence of BMP. Thus, one of the earliest effects of BMP is induction of DUSPs, which increases FOXN1 transcription factor and activates Notch1, both required for keratin gene expression. Arsenite prevents this cascade by maintaining ERK signaling, at least in part by suppressing DUSP expression. - Highlights: BMP induces FOXN1 transcription. BMP induces DUSP2 and DUSP14, suppressing ERK activation. Arsenite suppresses levels of phosphorylated Smad1/5 and FOXN1 and DUSP mRNA. These actions rationalize arsenite suppression of keratinocyte differentiation.

  11. Characterization of the human oncogene SCL/TAL1 interrupting locus (Stil) mediated Sonic hedgehog (Shh) signaling transduction in proliferating mammalian dopaminergic neurons

    SciTech Connect (OSTI)

    Sun, Lei; Carr, Aprell L.; Li, Ping; Lee, Jessica; McGregor, Mary; Li, Lei

    2014-07-11

    Highlights: Stil is a human oncogene that is conserved in vertebrate species. Stil functions in the Shh pathway in mammalian cells. The expression of Stil is required for mammalian dopaminergic cell proliferation. - Abstract: The human oncogene SCL/TAL1 interrupting locus (Stil) is highly conserved in all vertebrate species. In humans, the expression of Stil is involved in cancer cell survival, apoptosis and proliferation. In this research, we investigated the roles of Stil expression in cell proliferation of mammalian dopaminergic (DA) PC12 cells. Stil functions through the Sonic hedgehog (Shh) signal transduction pathway. Co-immunoprecipitation tests revealed that STIL interacts with Shh downstream components, which include SUFU and GLI1. By examining the expression of Stil, Gli1, CyclinD2 (cell-cycle marker) and PCNA (proliferating cell nuclear antigen), we found that up-regulation of Stil expression (transfection with overexpression plasmids) increased Shh signaling transduction and PC12 cell proliferation, whereas down-regulation of Stil expression (by shRNA) inhibited Shh signaling transduction, and thereby decreased PC12 cell proliferation. Transient transfection of PC12 cells with Stil knockdown or overexpression plasmids did not affect PC12 cell neural differentiation, further indicating the specific roles of Stil in cell proliferation. The results from this research suggest that Stil may serve as a bio-marker for neurological diseases involved in DA neurons, such as Parkinsons disease.

  12. Human retroviruses and AIDS 1994

    SciTech Connect (OSTI)

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

    1995-01-01

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

  13. Human factors in software development

    SciTech Connect (OSTI)

    Curtis, B.

    1986-01-01

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

  14. Analysis of Human Genetic Linkage

    SciTech Connect (OSTI)

    Boehnke, M.

    1991-01-01

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

  15. A Literary Human Exinction Scenario

    SciTech Connect (OSTI)

    Tonn, Bruce Edward

    2009-11-01

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

  16. Human AZU-1 gene, variants thereof and expressed gene products

    DOE Patents [OSTI]

    Chen, Huei-Mei; Bissell, Mina

    2004-06-22

    A human AZU-1 gene, mutants, variants and fragments thereof. Protein products encoded by the AZU-1 gene and homologs encoded by the variants of AZU-1 gene acting as tumor suppressors or markers of malignancy progression and tumorigenicity reversion. Identification, isolation and characterization of AZU-1 and AZU-2 genes localized to a tumor suppressive locus at chromosome 10q26, highly expressed in nonmalignant and premalignant cells derived from a human breast tumor progression model. A recombinant full length protein sequences encoded by the AZU-1 gene and nucleotide sequences of AZU-1 and AZU-2 genes and variant and fragments thereof. Monoclonal or polyclonal antibodies specific to AZU-1, AZU-2 encoded protein and to AZU-1, or AZU-2 encoded protein homologs.

  17. Fuel Cell Technologies Overview

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

    7/21/2015 eere.energy.gov Fuel Cell Technologies Overview States Energy Advisory Board (STEAB) Washington, DC Dr. Sunita Satyapal U.S. Department of Energy Fuel Cell Technologies Program Program Manager 3/14/2012 Outline * Introduction - Technology and Market Overview * DOE Program Overview - Mission & Structure - R&D Progress - Demonstration & Deployments * State Activities - Examples of potential opportunities 2 | Fuel Cell Technologies Program Source: US DOE 7/21/2015

  18. Direct hydrocarbon fuel cells

    DOE Patents [OSTI]

    Barnett, Scott A.; Lai, Tammy; Liu, Jiang

    2010-05-04

    The direct electrochemical oxidation of hydrocarbons in solid oxide fuel cells, to generate greater power densities at lower temperatures without carbon deposition. The performance obtained is comparable to that of fuel cells used for hydrogen, and is achieved by using novel anode composites at low operating temperatures. Such solid oxide fuel cells, regardless of fuel source or operation, can be configured advantageously using the structural geometries of this invention.

  19. Heterojunction solar cell

    DOE Patents [OSTI]

    Olson, Jerry M. (Lakewood, CO)

    1994-01-01

    A high-efficiency single heterojunction solar cell wherein a thin emitter layer (preferably Ga.sub.0.52 In.sub.0.48 P) forms a heterojunction with a GaAs absorber layer. The conversion effiency of the solar cell is at least 25.7%. The solar cell preferably includes a passivating layer between the substrate and the absorber layer. An anti-reflection coating is preferably disposed over the emitter layer.

  20. Fuel Cell Technologies Overview

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

    States Energy Advisory Board (STEAB) Washington, DC Dr. Sunita Satyapal U.S. Department of Energy Fuel Cell Technologies Program Program Manager 3/14/2012 2 | Fuel Cell Technologies Program Source: US DOE 3/19/2013 eere.energy.gov * Introduction - Technology and Market Overview * DOE Program Overview - Mission & Structure - R&D Progress - Demonstration & Deployments * State Activities - Examples of potential opportunities Outline 3 | Fuel Cell Technologies Program Source: US DOE

  1. Fuel Cells Fact Sheet

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

    Cells Fuel cells are the most energy efficient devices for extracting power from fuels. Capable of running on a variety of fuels, including hydrogen, natural gas, and biogas, fuel cells can provide clean power for applications ranging from less than a watt to multiple megawatts. Our transportation-including personal vehicles, trucks, buses, marine vessels, and other specialty vehicles such as lift trucks and ground support equipment, as well as auxiliary power units for traditional

  2. Heterojunction solar cell

    DOE Patents [OSTI]

    Olson, J.M.

    1994-08-30

    A high-efficiency single heterojunction solar cell is described wherein a thin emitter layer (preferably Ga[sub 0.52]In[sub 0.48]P) forms a heterojunction with a GaAs absorber layer. The conversion efficiency of the solar cell is at least 25.7%. The solar cell preferably includes a passivating layer between the substrate and the absorber layer. An anti-reflection coating is preferably disposed over the emitter layer. 1 fig.

  3. Fuel Cell Financing Options

    Broader source: Energy.gov [DOE]

    Presented at the Clean Energy States Alliance and U.S. Department of Energy Webinar: Financing Fuel Cell Installations, August 30, 2011.

  4. Financing Fuel Cells

    Broader source: Energy.gov [DOE]

    Presented at the Clean Energy States Alliance and U.S. Department of Energy Webinar: Financing Fuel Cell Installations, August 30, 2011.

  5. Micro fuel cell

    SciTech Connect (OSTI)

    Zook, L.A.; Vanderborgh, N.E. [Los Alamos National Lab., NM (United States); Hockaday, R. [Energy Related Devices Inc., Los Alamos, NM (United States)

    1998-12-31

    An ambient temperature, liquid feed, direct methanol fuel cell device is under development. A metal barrier layer was used to block methanol crossover from the anode to the cathode side while still allowing for the transport of protons from the anode to the cathode. A direct methanol fuel cell (DMFC) is an electrochemical engine that converts chemical energy into clean electrical power by the direct oxidation of methanol at the fuel cell anode. This direct use of a liquid fuel eliminates the need for a reformer to convert the fuel to hydrogen before it is fed into the fuel cell.

  6. Fuel Cell Technologies Budget

    SciTech Connect (OSTI)

    EERE

    2012-03-16

    The Fuel Cell Technologies Office receives appropriations from Energy and Water Development. The offices's major activities and budget are outlined in this Web page.

  7. Hydrogen Fuel Cells

    Fuel Cell Technologies Publication and Product Library (EERE)

    The fuel cell — an energy conversion device that can efficiently capture and use the power of hydrogen — is the key to making it happen.

  8. Opportunities with Fuel Cells

    Reports and Publications (EIA)

    1994-01-01

    The concept for fuel cells was discovered in the nineteenth century. Today, units incorporating this technology are becoming commercially available for cogeneration applications.

  9. Microcomposite Fuel Cell Membranes

    Broader source: Energy.gov [DOE]

    Summary of microcomposite fuel cell membrane work presented to the High Temperature Membrane Working Group Meeting, Orlando FL, October 17, 2003

  10. Electrochemical cell method

    DOE Patents [OSTI]

    Kaun, T.D.; Eshman, P.F.

    1980-05-09

    A secondary electrochemical cell is prepared by providing positive and negative electrodes having outer enclosures of rigid perforated electrically conductive material defining an internal compartment containing the electrode material in porous solid form. The electrodes are each immersed in molten electrolyte salt prior to cell assembly to incorporate the cell electrolyte. Following solidification of the electrolyte substantially throughout the porous volume of the electrode material, the electrodes are arranged in an alternating positive-negative array with interelectrode separators of porous frangible electrically insulative material. The completed array is assembled into the cell housing and sealed such that on heating the solidified electrolyte flows into the interelectrode separator.

  11. Molten salt lithium cells

    DOE Patents [OSTI]

    Raistrick, Ian D. (Menlo Park, CA); Poris, Jaime (Portola Valley, CA); Huggins, Robert A. (Stanford, CA)

    1983-01-01

    Lithium-based cells are promising for applications such as electric vehicles and load-leveling for power plants since lithium is very electropositive and light weight. One type of lithium-based cell utilizes a molten salt electrolyte and is operated in the temperature range of about 400.degree.-500.degree. C. Such high temperature operation accelerates corrosion problems and a substantial amount of energy is lost through heat transfer. The present invention provides an electrochemical cell (10) which may be operated at temperatures between about 100.degree.-170.degree. C. Cell (10) comprises an electrolyte (16), which preferably includes lithium nitrate, and a lithium or lithium alloy electrode (12).

  12. Molten salt lithium cells

    DOE Patents [OSTI]

    Raistrick, Ian D. (Menlo Park, CA); Poris, Jaime (Portola Valley, CA); Huggins, Robert A. (Stanford, CA)

    1982-02-09

    Lithium-based cells are promising for applications such as electric vehicles and load-leveling for power plants since lithium is very electropositive and light weight. One type of lithium-based cell utilizes a molten salt electrolyte and is operated in the temperature range of about 400.degree.-500.degree. C. Such high temperature operation accelerates corrosion problems and a substantial amount of energy is lost through heat transfer. The present invention provides an electrochemical cell (10) which may be operated at temperatures between about 100.degree.-170.degree. C. Cell (10) comprises an electrolyte (16), which preferably includes lithium nitrate, and a lithium or lithium alloy electrode (12).

  13. Fuel Cell Technologies Overview

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

    Fuel Cell Seminar Orlando, FL Dr. Sunita Satyapal U.S. Department of Energy Fuel Cell Technologies Program Program Manager 11/1/2011 2 | Fuel Cell Technologies Program Source: US DOE 3/19/2013 eere.energy.gov DOE Program Overview Budget Progress Next Steps Agenda 3 | Fuel Cell Technologies Program Source: US DOE 3/19/2013 eere.energy.gov DOE Program Structure The Program is an integrated effort, structured to address all the key challenges and obstacles facing widespread commercialization. The

  14. Molten salt lithium cells

    DOE Patents [OSTI]

    Raistrick, I.D.; Poris, J.; Huggins, R.A.

    1980-07-18

    Lithium-based cells are promising for applications such as electric vehicles and load-leveling for power plants since lithium is very electropositive and light weight. One type of lithium-based cell utilizes a molten salt electrolyte and is operated in the temperature range of about 400 to 500/sup 0/C. Such high temperature operation accelerates corrosion problems and a substantial amount of energy is lost through heat transfer. The present invention provides an electrochemical cell which may be operated at temperatures between about 100 to 170/sup 0/C. The cell is comprised of an electrolyte, which preferably includes lithium nitrate, and a lithium or lithium alloy electrode.

  15. Indoor Chemical Exposures: Humans' Non-respiratory Interactions with Room Air

    ScienceCinema (OSTI)

    Charles Weschler

    2010-09-01

    March 18, 2010 Berkeley Lab Environmental Energy Technology Division distinguished lecture: The marked difference in pollutant concentrations between an occupied and un-occupied room are only partially explained by human bio-effluents. Humans alter levels of ozone and related oxidants such as nitrate and hydroxyl radicals in the rooms they inhabit; in effect, they change the oxidative capacity of room air. Ozone-initiated reactions on exposed skin, hair and clothing generate products, including potentially irritating chemicals whose concentrations are much higher in the occupant's breathing zone than in the core of the room. Charles J. Weschler is a Professor at the School of Public Health, the Department of Environmental and Occupational Medicine and the Environmental and Occupational Health Sciences Institute (EOHSI) at the University of Medicine and Dentistry of New Jersey (UMDNJ)/Robert Wood Johnson Medical School & Rutgers University (New Jersey). He is also a Visiting Professor at the International Centre for Indoor Environment and Energy, Technical University of Denmark (DTU, Lyngby, Denmark).

  16. Contractor Human Resource Management Programs

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

    1996-09-29

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

  17. Contractor Human Resource Management Programs

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

    1996-09-30

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

  18. Human factors in waste management

    SciTech Connect (OSTI)

    Moray, N.

    1994-10-01

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

  19. Human Resources | Argonne National Laboratory

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

    Human Resources Louise LernerMarch 8, 2016 Science Writer Read more about Louise Lerner The secret lives of scientists & engineers: Matt KwiatkowskiMarch 7, 2016 In this series, meet researchers from Argonne with unusual hobbies and interests. Today we're interviewing Matt Kwiatkowski, cyber security manager-and a pilot who built his own plane. Read more about The secret lives of scientists & engineers: Matt Kwiatkowski Women in STEM careers: Breaking down barriersMarch 7, 2016 Three

  20. Fuel Cells in the States

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

    in the Fuel Cells in the States States State and Regional State and Regional Initiatives Working Group Initiatives Working Group July 12, 2006 July 12, 2006 Jennifer Gangi Jennifer Gangi Program Director Program Director Fuel Cells 2000 Fuel Cells 2000 Fuel Cells 2000 / BTI Fuel Cells 2000 / BTI U.S. nonprofit organization U.S. nonprofit organization Established in 1993 Established in 1993 Promotes fuel cells from public Promotes fuel cells from public interest perspective. interest perspective.

  1. Fuel cells and fuel cell catalysts

    DOE Patents [OSTI]

    Masel, Richard I.; Rice, Cynthia A.; Waszczuk, Piotr; Wieckowski, Andrzej

    2006-11-07

    A direct organic fuel cell includes a formic acid fuel solution having between about 10% and about 95% formic acid. The formic acid is oxidized at an anode. The anode may include a Pt/Pd catalyst that promotes the direct oxidation of the formic acid via a direct reaction path that does not include formation of a CO intermediate.

  2. Integrating Human Performance and Technology

    SciTech Connect (OSTI)

    Ronald K. Farris; Heather Medema

    2012-05-01

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

  3. Electrochemical cell stack assembly

    DOE Patents [OSTI]

    Jacobson, Craig P.; Visco, Steven J.; De Jonghe, Lutgard C.

    2010-06-22

    Multiple stacks of tubular electrochemical cells having a dense electrolyte disposed between an anode and a cathode preferably deposited as thin films arranged in parallel on stamped conductive interconnect sheets or ferrules. The stack allows one or more electrochemical cell to malfunction without disabling the entire stack. Stack efficiency is enhanced through simplified gas manifolding, gas recycling, reduced operating temperature and improved heat distribution.

  4. Metal halogen electrochemical cell

    DOE Patents [OSTI]

    Bellows, Richard J. (Hampton, NJ); Kantner, Edward (E. Brunswick, NJ)

    1988-08-23

    It has now been discovered that reduction in the coulombic efficiency of metal halogen cells can be minimized if the microporous separator employed in such cells is selected from one which is preferably wet by the aqueous electrolyte and is not wet substantially by the cathodic halogen.

  5. Fuel cell market applications

    SciTech Connect (OSTI)

    Williams, M.C.

    1995-12-31

    This is a review of the US (and international) fuel cell development for the stationary power generation market. Besides DOE, GRI, and EPRI sponsorship, the US fuel cell program has over 40% cost-sharing from the private sector. Support is provided by user groups with over 75 utility and other end-user members. Objectives are to develop and demonstrate cost-effective fuel cell power generation which can initially be commercialized into various market applications using natural gas fuel by the year 2000. Types of fuel cells being developed include PAFC (phosphoric acid), MCFC (molten carbonate), and SOFC (solid oxide); status of each is reported. Potential international applications are reviewed also. Fuel cells are viewed as a force in dispersed power generation, distributed power, cogeneration, and deregulated industry. Specific fuel cell attributes are discussed: Fuel cells promise to be one of the most reliable power sources; they are now being used in critical uninterruptible power systems. They need hydrogen which can be generated internally from natural gas, coal gas, methanol landfill gas, or other fuels containing hydrocarbons. Finally, fuel cell development and market applications in Japan are reviewed briefly.

  6. Programmed cell death

    SciTech Connect (OSTI)

    1995-12-31

    The purpose of this conference to provide a multidisciplinary forum for exchange of state-of-the-art information on the role programmed cell death plays in normal development and homeostasis of many organisms. This volume contains abstracts of papers in the following areas: invertebrate development; immunology/neurology; bcl-2 family; biochemistry; programmed cell death in viruses; oncogenesis; vertebrate development; and diseases.

  7. Tilted fuel cell apparatus

    DOE Patents [OSTI]

    Cooper, John F.; Cherepy, Nerine; Krueger, Roger L.

    2005-04-12

    Bipolar, tilted embodiments of high temperature, molten electrolyte electrochemical cells capable of directly converting carbon fuel to electrical energy are disclosed herein. The bipolar, tilted configurations minimize the electrical resistance between one cell and others connected in electrical series. The tilted configuration also allows continuous refueling of carbon fuel.

  8. Dengue Virus Infection Perturbs Lipid Homeostasis in Infected Mosquito Cells

    SciTech Connect (OSTI)

    Perera, Rushika M.; Riley, Catherine; Isaac, Georgis; Hopf- Jannasch, Amber; Moore, Ronald J.; Weitz, Karl K.; Pasa-Tolic, Ljiljana; Metz, Thomas O.; Adamec, Jiri; Kuhn, Richard J.

    2012-03-22

    Dengue virus causes {approx}50-100 million infections per year and thus is considered one of the most aggressive arthropod-borne human pathogen worldwide. During its replication, dengue virus induces dramatic alterations in the intracellular membranes of infected cells. This phenomenon is observed both in human and vector-derived cells. Using high-resolution mass spectrometry of mosquito cells, we show that this membrane remodeling is directly linked to a unique lipid repertoire induced by dengue virus infection. Specifically, 15% of the metabolites detected were significantly different between DENV infected and uninfected cells while 85% of the metabolites detected were significantly different in isolated replication complex membranes. Furthermore, we demonstrate that intracellular lipid redistribution induced by the inhibition of fatty acid synthase, the rate-limiting enzyme in lipid biosynthesis, is sufficient for cell survival but is inhibitory to dengue virus replication. Lipids that have the capacity to destabilize and change the curvature of membranes as well as lipids that change the permeability of membranes are enriched in dengue virus infected cells. Several sphingolipids and other bioactive signaling molecules that are involved in controlling membrane fusion, fission, and trafficking as well as molecules that influence cytoskeletal reorganization are also up regulated during dengue infection. These observations shed light on the emerging role of lipids in shaping the membrane and protein environments during viral infections and suggest membrane-organizing principles that may influence virus-induced intracellular membrane architecture.

  9. Photovoltaic solar cell

    DOE Patents [OSTI]

    Nielson, Gregory N.; Gupta, Vipin P.; Okandan, Murat; Watts, Michael R.

    2015-09-08

    A photovoltaic solar concentrator is disclosed with one or more transverse-junction solar cells (also termed point contact solar cells) and a lens located above each solar cell to concentrate sunlight onto the solar cell to generate electricity. Piezoelectric actuators tilt or translate each lens to track the sun using a feedback-control circuit which senses the electricity generated by one or more of the solar cells. The piezoelectric actuators can be coupled through a displacement-multiplier linkage to provide an increased range of movement of each lens. Each lens in the solar concentrator can be supported on a frame (also termed a tilt plate) having three legs, with the movement of the legs being controlled by the piezoelectric actuators.

  10. Receptor tyrosine kinase EphA5 is a functional molecular target in human lung cancer

    SciTech Connect (OSTI)

    Staquicini, Fernanda I.; Qian, Ming D.; Salameh, Ahmad; Dobroff, Andrey S.; Edwards, Julianna K.; Cimino, Daniel F.; Moeller, Benjamin J.; Kelly, Patrick; Nunez, Maria I.; Tang, Ximing; Liu, Diane D.; Lee, J. Jack; Hong, Waun Ki; Ferrara, Fortunato; Bradbury, Andrew R. M.; Lobb, Roy R.; Edelman, Martin J.; Sidman, Richard L.; Wistuba, Ignacio I.; Arap, Wadih; Pasqualini, Renata

    2015-03-20

    Lung cancer is often refractory to radiotherapy, but molecular mechanisms of tumor resistance remain poorly defined. Here we show that the receptor tyrosine kinase EphA5 is specifically overexpressed in lung cancer and is involved in regulating cellular responses to genotoxic insult. In the absence of EphA5, lung cancer cells displayed a defective G1/S cell cycle checkpoint, were unable to resolve DNA damage, and became radiosensitive. Upon irradiation, EphA5 was transported into the nucleus where it interacted with activated ATM (ataxia-telangiectasia mutated) at sites of DNA repair. In conclusion, we demonstrate that a new monoclonal antibody against human EphA5 sensitized lung cancer cells and human lung cancer xenografts to radiotherapy and significantly prolonged survival, thus suggesting the likelihood of translational applications.

  11. Receptor tyrosine kinase EphA5 is a functional molecular target in human lung cancer

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

    Staquicini, Fernanda I.; Qian, Ming D.; Salameh, Ahmad; Dobroff, Andrey S.; Edwards, Julianna K.; Cimino, Daniel F.; Moeller, Benjamin J.; Kelly, Patrick; Nunez, Maria I.; Tang, Ximing; et al

    2015-03-20

    Lung cancer is often refractory to radiotherapy, but molecular mechanisms of tumor resistance remain poorly defined. Here we show that the receptor tyrosine kinase EphA5 is specifically overexpressed in lung cancer and is involved in regulating cellular responses to genotoxic insult. In the absence of EphA5, lung cancer cells displayed a defective G1/S cell cycle checkpoint, were unable to resolve DNA damage, and became radiosensitive. Upon irradiation, EphA5 was transported into the nucleus where it interacted with activated ATM (ataxia-telangiectasia mutated) at sites of DNA repair. In conclusion, we demonstrate that a new monoclonal antibody against human EphA5 sensitized lungmore » cancer cells and human lung cancer xenografts to radiotherapy and significantly prolonged survival, thus suggesting the likelihood of translational applications.« less

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

    SciTech Connect (OSTI)

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

    2014-01-17

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

  13. 6.20 Mapping Human Brain Function

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

    0 612011 6.20 Mapping Human Brain Function Many mysteries of the human brain have been unraveled by positron emission tomography (PET), an imaging tool used worldwide to diagnose ...

  14. GDB - Human Genome Database final report

    SciTech Connect (OSTI)

    Talbot, C. Conover, Jr.

    2002-01-08

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

  15. Identification of Human Repetitive DNA Elements

    Energy Science and Technology Software Center (OSTI)

    1995-11-01

    PYTHIA identifies the subfamily membership of Alu sequences, occurrences of repetitive human DNA elements, and simple DNA sequences.

  16. Solid oxide fuel cell generator

    DOE Patents [OSTI]

    Di Croce, A.M.; Draper, R.

    1993-11-02

    A solid oxide fuel cell generator has a plenum containing at least two rows of spaced apart, annular, axially elongated fuel cells. An electrical conductor extending between adjacent rows of fuel cells connects the fuel cells of one row in parallel with each other and in series with the fuel cells of the adjacent row. 5 figures.

  17. Solid oxide fuel cell generator

    DOE Patents [OSTI]

    Di Croce, A. Michael (Murrysville, PA); Draper, Robert (Churchill Boro, PA)

    1993-11-02

    A solid oxide fuel cell generator has a plenum containing at least two rows of spaced apart, annular, axially elongated fuel cells. An electrical conductor extending between adjacent rows of fuel cells connects the fuel cells of one row in parallel with each other and in series with the fuel cells of the adjacent row.

  18. Fuel Cells for Supermarkets: Cleaner Energy with Fuel Cell Combined...

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

    Fuel Cells for Supermarkets: Cleaner Energy with Fuel Cell Combined Heat and Power Systems ... U.S. Department of Energy Webinar: Fuel Cells for Supermarkets, April 4, 2011. PDF icon ...

  19. Human factors: a necessary tool for industry

    SciTech Connect (OSTI)

    Starcher, K.O.

    1984-03-09

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

  20. NREL: Hydrogen and Fuel Cells Research - Fuel Cells

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

    Fuel Cells Photo of scientific equipment in a laboratory setting. NREL scientist applies catalyst layer to a fuel cell through a spray process that delivers a more even distribution of material, improving performance. Photo by Dennis Schroeder, NREL What is a fuel cell? A single fuel cell consists of an electrolyte sandwiched between two electrodes. Bipolar plates on either side of the cell help distribute gases and serve as current collectors. Depending on the application, a fuel cell stack may

  1. NREL: Hydrogen and Fuel Cells Research - Early Fuel Cell Market

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

    Demonstrations Early Fuel Cell Market Demonstrations Photo of fuel cell backup power system in outdoor setting. Photo of fuel cell forklifts in warehouse setting. Fuel cell backup power systems offer longer continuous runtimes and greater durability than traditional batteries in harsh outdoor environments. For specialty vehicles such as forklifts, fuel cells can be a cost-competitive alternative to traditional lead-acid batteries. Learn More Subscribe to the biannual Fuel Cell and Hydrogen

  2. NREL: Hydrogen and Fuel Cells Research - Fuel Cell Technology Status

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

    Analysis Fuel Cell Technology Status Analysis Get Involved Fuel cell developers interested in collaborating with NREL on fuel cell technology status analysis should send an email to NREL's Technology Validation Team at techval@nrel.gov. NREL's analysis of fuel cell technology provides objective and credible information about new fuel cell technologies with a focus on performance, durability, and price. As demand for fuel cells grows, U.S. manufacturers are developing these technologies for a

  3. Bipolar fuel cell

    DOE Patents [OSTI]

    McElroy, James F. (Suffield, CT)

    1989-01-01

    The present invention discloses an improved fuel cell utilizing an ion transporting membrane having a catalytic anode and a catalytic cathode bonded to opposite sides of the membrane, a wet-proofed carbon sheet in contact with the cathode surface opposite that bonded to the membrane and a bipolar separator positioned in electrical contact with the carbon sheet and the anode of the adjacent fuel cell. Said bipolar separator and carbon sheet forming an oxidant flowpath, wherein the improvement comprises an electrically conductive screen between and in contact with the wet-proofed carbon sheet and the bipolar separator improving the product water removal system of the fuel cell.

  4. Simulation of human decision making

    DOE Patents [OSTI]

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

    2008-05-06

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

  5. Contractor Human Resource Management Programs

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

    1996-09-30

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

  6. DOE Hydrogen & Fuel Cell Overview

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

    t t 1 | Fuel Cell Technologies Program eere.energy.gov Fuel Cell Technologies Program DOE Hydrogen & Fuel Cell Overview Dr. Sunita Satyapal Program Manager U S D f E Overview U.S....

  7. Air Liquide - Biogas & Fuel Cells

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

    and the environment PT Loma WWTP, Biogas to Fuel Cell Power BioFuels Energy Biogas to BioMethane to 4.5 MW Fuel Cell Power 3 FCE Fuel Cells 2 via directed...

  8. Suppressing the Skin-Core Structure of Injection-Molded Isotactic Polypropylene via Combination of an in situ Microfibrillar Network and an Interfacial Compatibilizer

    SciTech Connect (OSTI)

    X Yi; C Chen; G Zhong; L Xu; J Tang; X Ji; B Hsiao; Z Li

    2011-12-31

    Injection-molded semicrystalline polymer parts generally exhibited a so-called skin-core structure basically as a result of the large gradients of temperature, shear rate, stress, and pressure fields created by the boundary conditions of injection molding. Suppression of the skin-core structure is a long-term practical challenge. In the current work, the skin-core structure of the conventional injection-molded isotactic polypropylene (iPP) was largely relieved by the cooperative effects of an in situ microfibrillar network and interfacial compatibilizer. The in situ poly(ethylene terephthalate) microfibrils of 1-8 {micro}m in diameter and large aspect ratios of above 40 tended to entangle with each other to generate a microfibrillar network in the iPP melt. During injection molding, the iPP molecules experienced confined flow in the microchannels or pores formed by the microfibrillar network, which could redistribute and homogenize the flow field of polymer melt. Addition of the compatibilizer, glycidyl methacrylate-grafted iPP, restrained the molecular orientation but facilitated preservation of oriented molecules due to the chemical bonds at the interface between PET microfibrils and iPP. The cooperative effects of in situ microfibrillar network and interfacial compatibilizer led to almost the same molecular orientation across the whole thickness of the injection-molded parts. Additionally, the content of {beta} crystals in different layers of injection-molded iPP parts depended on the combined effects of the molecular orientation, the amount of oriented crystals, and the crystallization time between 105 and 140 C. The presence of the interfacial compatibilizer facilitated formation of the {beta} crystals because of preservation of the oriented molecules.

  9. Four-Dimensional Measurement of the Displacement of Internal Fiducial and Skin Markers During 320-Multislice Computed Tomography Scanning of Breast Cancer

    SciTech Connect (OSTI)

    Yamashita, Hideomi; Okuma, Kae; Tada, Keiichiro; Shiraishi, Kenshiro; Takahashi, Wataru; Shibata-Mobayashi, Shino; Sakumi, Akira; Saotome, Naoya; Haga, Akihiro; Onoe, Tsuyoshi; Ino, Kenji; Akahane, Masaaki; Ohtomo, Kuni; Nakagawa, Keiichi

    2012-10-01

    Purpose: To study the three-dimensional movement of internal tumor bed fiducial and breast skin markers, using 320-multislice computed tomography (CT); and to analyze intrafractional errors for breast cancer patients undergoing breast irradiation. Methods and Materials: This study examined 280 markers on the skin of the breast (200 markers) and on the primary tumor bed (80 markers) of 20 patients treated by external-beam photon radiotherapy. Motion assessment was analyzed in 41 respiratory phases during 20 s of cine CT in the radiotherapy position. To assess intrafractional errors resulting from respiratory motion, four-dimensional CT scans were acquired for 20 patients. Results: Motion in the anterior-posterior (A/P) and superior-inferior (S/I) directions showed a strong correlation (|r| > 0.7) with the respiratory curve for most markers (79% and 70%, respectively). The average marker displacements between maximum and minimum value during 20 s for the 200 breast skin metal markers were 1.1 {+-} 0.3 mm, 2.1 {+-} 0.6 mm, and 1.6 {+-} 0.4 mm in the left-right, A/P, and S/I directions, respectively. For the 80 tumor bed clips, displacements were 0.9 {+-} 0.2 mm in left-right, 1.7 {+-} 0.5 mm in A/P, and 1.1 {+-} 0.3 mm in S/I. There was no significant difference in the motion between breast quadrant regions or between the primary site and the other regions. Conclusions: Motion in primary breast tumors was evaluated with 320-multislice CT. Very little change was detected during individual radiation treatment fractions.

  10. Fuel Cell Technologies Program Overview

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

    IEA HIA Hydrogen Safety Stakeholder Workshop Bethesda, Maryland Fuel Cell Technologies Program Overview Dr. Sunita Satyapal U.S. Department of Energy Fuel Cell Technologies Program Program Manager 10/2/2012 2 | Fuel Cell Technologies Program eere.energy.gov Overview Fuel Cells - An Emerging Global Industry Clean Energy Patent Growth Index [1] shows that fuel cell patents lead in the clean energy field with over 950 fuel cell patents issued in 2011. * Nearly double the second place holder, solar,

  11. Human Resources and Administration Homepage | U.S. DOE Office...

    Office of Science (SC) Website

    Home Human Resources and Administration (HRA) HRA Home About Human Resources Administration SC Correspondence Control Center (SC CCC) Contact Information Human Resources and...

  12. Irradiation Effects on Human Cortical Bone Fracture Behavior

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

    Irradiation Effects on Human Cortical Bone Fracture Behavior Irradiation Effects on Human Cortical Bone Fracture Behavior Print Wednesday, 28 July 2010 00:00 Human bone is strong...

  13. Solar cell array interconnects

    DOE Patents [OSTI]

    Carey, P.G.; Thompson, J.B.; Colella, N.J.; Williams, K.A.

    1995-11-14

    Electrical interconnects are disclosed for solar cells or other electronic components using a silver-silicone paste or a lead-tin (Pb-Sn) no-clean fluxless solder cream, whereby the high breakage of thin (<6 mil thick) solar cells using conventional solder interconnect is eliminated. The interconnects of this invention employs copper strips which are secured to the solar cells by a silver-silicone conductive paste which can be used at room temperature, or by a Pb-Sn solder cream which eliminates undesired residue on the active surfaces of the solar cells. Electrical testing using the interconnects of this invention has shown that no degradation of the interconnects developed under high current testing, while providing a very low contact resistance value. 4 figs.

  14. Thin film photovoltaic cells

    DOE Patents [OSTI]

    Rothwarf, Allen (Philadelphia, PA)

    1981-01-01

    A solar cell has as its transparent electrical contact a grid made from a non-noble metal by providing a layer of copper oxide between the transparent electrical contact and the absorber-generator.

  15. Fuel cell water transport

    DOE Patents [OSTI]

    Vanderborgh, Nicholas E. (Los Alamos, NM); Hedstrom, James C. (Los Alamos, NM)

    1990-01-01

    The moisture content and temperature of hydrogen and oxygen gases is regulated throughout traverse of the gases in a fuel cell incorporating a solid polymer membrane. At least one of the gases traverses a first flow field adjacent the solid polymer membrane, where chemical reactions occur to generate an electrical current. A second flow field is located sequential with the first flow field and incorporates a membrane for effective water transport. A control fluid is then circulated adjacent the second membrane on the face opposite the fuel cell gas wherein moisture is either transported from the control fluid to humidify a fuel gas, e.g., hydrogen, or to the control fluid to prevent excess water buildup in the oxidizer gas, e.g., oxygen. Evaporation of water into the control gas and the control gas temperature act to control the fuel cell gas temperatures throughout the traverse of the fuel cell by the gases.

  16. Hydrogen Fuel Cell Demonstration ...

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

    Brothers, Ltd., at their facility in the Port of Honolulu. The pilot hydrogen fuel cell unit will be used in place of a diesel generator currently used to provide power for...

  17. Solar cell array interconnects

    DOE Patents [OSTI]

    Carey, Paul G. (Mountain View, CA); Thompson, Jesse B. (Brentwood, CA); Colella, Nicolas J. (Livermore, CA); Williams, Kenneth A. (Livermore, CA)

    1995-01-01

    Electrical interconnects for solar cells or other electronic components using a silver-silicone paste or a lead-tin (Pb-Sn) no-clean fluxless solder cream, whereby the high breakage of thin (<6 mil thick) solar cells using conventional solder interconnect is eliminated. The interconnects of this invention employs copper strips which are secured to the solar cells by a silver-silicone conductive paste which can be used at room temperature, or by a Pb-Sn solder cream which eliminates undesired residue on the active surfaces of the solar cells. Electrical testing using the interconnects of this invention has shown that no degradation of the interconnects developed under high current testing, while providing a very low contact resistance value.

  18. Photovoltaic solar cell

    DOE Patents [OSTI]

    Nielson, Gregory N; Cruz-Campa, Jose Luis; Okandan, Murat; Resnick, Paul J

    2014-05-20

    A photovoltaic solar cell for generating electricity from sunlight is disclosed. The photovoltaic solar cell comprises a plurality of spaced-apart point contact junctions formed in a semiconductor body to receive the sunlight and generate the electricity therefrom, the plurality of spaced-apart point contact junctions having a first plurality of regions having a first doping type and a second plurality of regions having a second doping type. In addition, the photovoltaic solar cell comprises a first electrical contact electrically connected to each of the first plurality of regions and a second electrical contact electrically connected to each of the second plurality of regions, as well as a passivation layer covering major surfaces and sidewalls of the photovoltaic solar cell.

  19. Photovoltaic solar cell

    DOE Patents [OSTI]

    Nielson, Gregory N; Okandan, Murat; Cruz-Campa, Jose Luis; Resnick, Paul J

    2013-11-26

    A photovoltaic solar cell for generating electricity from sunlight is disclosed. The photovoltaic solar cell comprises a plurality of spaced-apart point contact junctions formed in a semiconductor body to receive the sunlight and generate the electicity therefrom, the plurality of spaced-apart point contact junctions having a first plurality of regions having a first doping type and a second plurality of regions having a second doping type. In addition, the photovoltaic solar cell comprises a first electrical contact electrically connected to each of the first plurality of regions and a second electrical contact electrically connected to each of the second plurality of regions, as well as a passivation layer covering major surfaces and sidewalls of the photovoltaic solar cell.

  20. Reversible Fuel Cells Workshop

    Broader source: Energy.gov [DOE]

    The National Renewable Energy Laboratory hosted a workshop addressing the current state-of-the-art of reversible fuel cells that use hydrogen/air or hydrogen/oxygen on April 19, 2011, at the...

  1. Exposure of Jurkat cells to bis (tri-n-butyltin) oxide (TBTO) induces transcriptomics changes indicative for ER- and oxidative stress, T cell activation and apoptosis

    SciTech Connect (OSTI)

    Katika, Madhumohan R.; Hendriksen, Peter J.M.; Loveren, Henk van; Peijnenburg, Ad

    2011-08-01

    Tributyltin oxide (TBTO) is an organotin compound that is widely used as a biocide in agriculture and as an antifouling agent in paints. TBTO is toxic for many cell types, particularly immune cells. The present study aimed to identify the effects of TBTO on the human T lymphocyte cell line Jurkat. Cells were treated with 0.2 and 0.5 {mu}M TBTO for 3, 6, 12 and 24 h and then subjected to whole genome gene expression microarray analysis. The biological interpretation of the gene expression profiles revealed that endoplasmic reticulum (ER) stress is among the earliest effects of TBTO. Simultaneously or shortly thereafter, oxidative stress, activation of NFKB and NFAT, T cell activation, and apoptosis are induced. The effects of TBTO on genes involved in ER stress, NFAT pathway, T cell activation and apoptosis were confirmed by qRT-PCR. Activation and nuclear translocation of NFATC1 and the oxidative stress response proteins NRF2 and KEAP1 were confirmed by immunocytology. Taking advantage of previously published microarray data, we demonstrated that the induction of ER stress, oxidative stress, T cell activation and apoptosis by TBTO is not unique for Jurkat cells but does also occur in mouse thymocytes both ex vivo and in vivo and rat thymocytes ex vivo. We propose that the induction of ER stress leading to a T cell activation response is a major factor in the higher sensitivity of immune cells above other types of cells for TBTO. - Research Highlights: > The human T lymphocyte cell line Jurkat was exposed to TBTO. > Whole-genome microarray experiments were performed. > Data analysis revealed the induction of ER stress and activation of NFAT and NFKB. > Exposure to TBTO also led to T cell activation, oxidative stress and apoptosis.

  2. Composite fuel cell membranes

    DOE Patents [OSTI]

    Plowman, Keith R. (Lake Jackson, TX); Rehg, Timothy J. (Lake Jackson, TX); Davis, Larry W. (West Columbia, TX); Carl, William P. (Marble Falls, TX); Cisar, Alan J. (Cypress, TX); Eastland, Charles S. (West Columbia, TX)

    1997-01-01

    A bilayer or trilayer composite ion exchange membrane suitable for use in a fuel cell. The composite membrane has a high equivalent weight thick layer in order to provide sufficient strength and low equivalent weight surface layers for improved electrical performance in a fuel cell. In use, the composite membrane is provided with electrode surface layers. The composite membrane can be composed of a sulfonic fluoropolymer in both core and surface layers.

  3. Composite fuel cell membranes

    DOE Patents [OSTI]

    Plowman, K.R.; Rehg, T.J.; Davis, L.W.; Carl, W.P.; Cisar, A.J.; Eastland, C.S.

    1997-08-05

    A bilayer or trilayer composite ion exchange membrane is described suitable for use in a fuel cell. The composite membrane has a high equivalent weight thick layer in order to provide sufficient strength and low equivalent weight surface layers for improved electrical performance in a fuel cell. In use, the composite membrane is provided with electrode surface layers. The composite membrane can be composed of a sulfonic fluoropolymer in both core and surface layers.

  4. Ice electrode electrolytic cell

    DOE Patents [OSTI]

    Glenn, D.F.; Suciu, D.F.; Harris, T.L.; Ingram, J.C.

    1993-04-06

    This invention relates to a method and apparatus for removing heavy metals from waste water, soils, or process streams by electrolytic cell means. The method includes cooling a cell cathode to form an ice layer over the cathode and then applying an electric current to deposit a layer of the heavy metal over the ice. The metal is then easily removed after melting the ice. In a second embodiment, the same ice-covered electrode can be employed to form powdered metals.

  5. Aluminum reduction cell electrode

    DOE Patents [OSTI]

    Goodnow, W.H.; Payne, J.R.

    1982-09-14

    The invention is directed to cathode modules comprised of refractory hard metal materials, such as TiB[sub 2], for an electrolytic cell for the reduction of alumina wherein the modules may be installed and replaced during operation of the cell and wherein the structure of the cathode modules is such that the refractory hard metal materials are not subjected to externally applied forces or rigid constraints. 9 figs.

  6. Compliant fuel cell system

    DOE Patents [OSTI]

    Bourgeois, Richard Scott (Albany, NY); Gudlavalleti, Sauri (Albany, NY)

    2009-12-15

    A fuel cell assembly comprising at least one metallic component, at least one ceramic component and a structure disposed between the metallic component and the ceramic component. The structure is configured to have a lower stiffness compared to at least one of the metallic component and the ceramic component, to accommodate a difference in strain between the metallic component and the ceramic component of the fuel cell assembly.

  7. Aluminum reduction cell electrode

    DOE Patents [OSTI]

    Goodnow, Warren H. (Palo Alto, CA); Payne, John R. (Pleasanton, CA)

    1982-01-01

    The invention is directed to cathode modules comprised of refractory hard metal materials, such as TiB.sub.2, for an electrolytic cell for the reduction of alumina wherein the modules may be installed and replaced during operation of the cell and wherein the structure of the cathode modules is such that the refractory hard metal materials are not subjected to externally applied forces or rigid constraints.

  8. Fuel Cells at NASCAR

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

    Fuel Cells at NASCAR Ned Stetson U.S. Department of Energy Fuel Cell Technologies Office Catherine Kummer - NASCAR Green Norm Bessette - Acumentrics Question and Answer * Please type your question into the question box hydrogenandfuelcells.energy.gov 3 Selected Milestone Accomplishments * 5 years of NASCAR Green with now most impactful sustainability platform in history of U.S. based on numbers; most impactful in sports * 75% of avid NASCAR fans are now aware of NASCAR green and believe the

  9. Fuel Cells in Telecommunications

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

    Fuel Cells Simply Powerful Fuel Cells in Telecommunications J. Blanchard December 2011 - ~ ReliOn Overview Markets Backup, grid supplement, and off grid power systems for critical communications infrastructure spanning telecom, transportation, government, utility, and OEM customers throughout the world. Products Purpose designed product portfolio of 175W to 2.5kW building blocks providing solutions up to 30kW for target markets. Broad range of hydrogen storage solutions supported by major

  10. Financing Fuel Cells

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

    organized by: ◦ US Department of Energy Fuel Cell Technologies Program ◦ Clean Energy States Alliance ◦ Technology Transition Corporation  Also briefing papers and materials for state policymakers and others on the Hydrogen and Fuel Cells Project page at www.cleanenergystates.org 2  A nonprofit coalition of state and sub-national clean energy funds and programs working together to develop and promote clean energy technologies and markets. www.cleanenergystates.org 3  For more

  11. Ice electrode electrolytic cell

    DOE Patents [OSTI]

    Glenn, David F. (Idaho Falls, ID); Suciu, Dan F. (Idaho Falls, ID); Harris, Taryl L. (Idaho Falls, ID); Ingram, Jani C. (Idaho Falls, ID)

    1993-01-01

    This invention relates to a method and apparatus for removing heavy metals from waste water, soils, or process streams by electrolytic cell means. The method includes cooling a cell cathode to form an ice layer over the cathode and then applying an electric current to deposit a layer of the heavy metal over the ice. The metal is then easily removed after melting the ice. In a second embodiment, the same ice-covered electrode can be employed to form powdered metals.

  12. Fuel Cell Technologies Office: Publications

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

    Fuel Cell Technologies Office EERE Fuel Cell Technologies Office Share this resource Publications Advanced Search Browse by Topic Mail Requests Help Feature featured product...

  13. Hydrogen and Fuel Cell Activities

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

    Activities Mr. Pete Devlin U.S. Department of Energy Fuel Cell Technologies Program Market Transformation Manager Stationary Fuel Cell Applications First National Bank of Omaha...

  14. Fuel Cell Handbook (Seventh Edition)

    Office of Scientific and Technical Information (OSTI)

    ... In addition, because combustion is avoided, fuel cells produce power with minimal ... The only liquid in this fuel cell is water; thus, corrosion problems are minimal. ...

  15. KPNA7, a nuclear transport receptor, promotes malignant properties of pancreatic cancer cells in vitro

    SciTech Connect (OSTI)

    Laurila, Eeva; Vuorinen, Elisa; Savinainen, Kimmo; Rauhala, Hanna; Kallioniemi, Anne

    2014-03-10

    Pancreatic cancer is an aggressive malignancy and one of the leading causes of cancer deaths. The high mortality rate is mostly due to the lack of appropriate tools for early detection of the disease and a shortage of effective therapies. We have previously shown that karyopherin alpha 7 (KPNA7), the newest member of the alpha karyopherin family of nuclear import receptors, is frequently amplified and overexpressed in pancreatic cancer. Here, we report that KPNA7 expression is absent in practically all normal human adult tissues but elevated in several pancreatic cancer cell lines. Inhibition of KPNA7 expression in AsPC-1 and Hs700T pancreatic cancer cells led to a reduction in cell growth and decreased anchorage independent growth, as well as increased autophagy. The cell growth effects were accompanied by an induction of the cell cycle regulator p21 and a G1 arrest of the cell cycle. Interestingly, the p21 induction was caused by increased mRNA synthesis and not defective nuclear transport. These data strongly demonstrate that KPNA7 silencing inhibits the malignant properties of pancreatic cancer cells in vitro and thereby provide the first evidence on the functional role for KPNA7 in human cancer. - Highlights: KPNA7 expression is elevated in several pancreatic cancer cell lines. KPNA7 silencing in high expressing cancer cells leads to growth inhibition. The cell growth reduction is associated with p21 induction and G1 arrest. KPNA7 silencing is also accompanied with increased autophagy.

  16. Tumor necrosis factor: specific binding and internalization in sensitive and resistant cells

    SciTech Connect (OSTI)

    Tsujimoto, M.; Yip, Y.K.; Vilcek, J.

    1985-11-01

    Highly purified, Escherichia coli-derived recombinant human tumor necrosis factor (TNF) was labeled with /sup 125/I and employed to determine receptor binding, internalization, and intracellular degradation in murine L929 cells (highly sensitive to the cytotoxic action of TNF) and in diploid human FS-4 cells (resistant to TNF cytotoxicity). /sup 125/I-labeled TNF bound specifically to high-affinity receptors on both L929 and FS-4 cells. Scatchard analysis of the binding data indicated the presence of 2200 binding sites per L929 cell and 7500 binding sites per FS-4 cell. The calculated dissociation constants are 6.1 x 10/sup -10/ M and 3.2 x 10/sup -10/ M for L929 and FS-4 cells, respectively. In both L929 and FS-4 cells, incubation at 37/sup 0/C resulted in a rapid internalization of the bulk of the cell-bound TNF, followed by the appearance of trichloroacetic acid-soluble /sup 125/I radioactivity in the tissue culture medium, due to degradation of TNF. Degradation but not cellular uptake of TNF was inhibited in the presence of chloroquine (an inhibitor of lysosomal proteases) in both L929 and FS-4 cells, suggesting that degradation occurs intracellularly, probably within lysosomes. These results show that resistance of FS-4 cells to TNF cytotoxicity is not due to a lack of receptors or their inability to internalize and degrade TNF.

  17. Solar Cells Hellas SA | Open Energy Information

    Open Energy Info (EERE)

    Cells Hellas SA Jump to: navigation, search Name: Solar Cells Hellas SA Place: Athens, Greece Product: Greek manufacturer of PV wafers, cells and modules. References: Solar Cells...

  18. Fuel Cells Fact Sheet | Department of Energy

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

    Fact Sheet Fact sheet produced by the Fuel Cell Technologies Office describing hydrogen fuel cell technology. Fuel Cells More Documents & Publications Hydrogen and Fuel Cell...

  19. Fuel Cells Fact Sheet | Department of Energy

    Energy Savers [EERE]

    Cells Fact Sheet Fuel Cells Fact Sheet Fact sheet produced by the Fuel Cell Technologies Office describing fuel cell technologies. PDF icon Fuel Cells Fact Sheet More Documents & Publications Comparison of Fuel Cell Technologies: Fact Sheet Hydrogen and Fuel Cell Technologies Program: Fuel Cells Fact Sheet 2011 Pathways to Commercial Success: Technologies and Products Supported by the Fuel Cell Technologies Program

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

    SciTech Connect (OSTI)

    Ronald Laurids Boring

    2010-11-01

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

  1. Fuel cell system

    DOE Patents [OSTI]

    Early, Jack (Perth Amboy, NJ); Kaufman, Arthur (West Orange, NJ); Stawsky, Alfred (Teaneck, NJ)

    1982-01-01

    A fuel cell system is comprised of a fuel cell module including sub-stacks of series-connected fuel cells, the sub-stacks being held together in a stacked arrangement with cold plates of a cooling means located between the sub-stacks to function as electrical terminals. The anode and cathode terminals of the sub-stacks are connected in parallel by means of the coolant manifolds which electrically connect selected cold plates. The system may comprise a plurality of the fuel cell modules connected in series. The sub-stacks are designed to provide a voltage output equivalent to the desired voltage demand of a low voltage, high current DC load such as an electrolytic cell to be driven by the fuel cell system. This arrangement in conjunction with switching means can be used to drive a DC electrical load with a total voltage output selected to match that of the load being driven. This arrangement eliminates the need for expensive voltage regulation equipment.

  2. Microbial Cell Imaging

    SciTech Connect (OSTI)

    Doktycz, Mitchel John; Sullivan, Claretta; Mortensen, Ninell P; Allison, David P

    2011-01-01

    Atomic force microscopy (AFM) is finding increasing application in a variety of fields including microbiology. Until the emergence of AFM, techniques for ivnestigating processes in single microbes were limited. From a biologist's perspective, the fact that AFM can be used to generate high-resolution images in buffers or media is its most appealing feature as live-cell imaging can be pursued. Imaging living cells by AFM allows dynamic biological events to be studied, at the nanoscale, in real time. Few areas of biological research have as much to gain as microbiology from the application of AFM. Whereas the scale of microbes places them near the limit of resolution for light microscopy. AFM is well suited for the study of structures on the order of a micron or less. Although electron microscopy techniques have been the standard for high-resolution imaging of microbes, AFM is quickly gaining favor for several reasons. First, fixatives that impair biological activity are not required. Second, AFM is capable of detecting forces in the pN range, and precise control of the force applied to the cantilever can be maintained. This combination facilitates the evaluation of physical characteristics of microbes. Third, rather than yielding the composite, statistical average of cell populations, as is the case with many biochemical assays, the behavior of single cells can be monitored. Despite the potential of AFM in microbiology, there are several limitations that must be considered. For example, the time required to record an image allows for the study of gross events such as cell division or membrane degradation from an antibiotic but precludes the evaluation of biological reactions and events that happen in just fractions of a second. Additionally, the AFM is a topographical tool and is restricted to imaging surfaces. Therefore, it cannot be used to look inside cells as with opticla and transmission electron microscopes. other practical considerations are the limitation on the maximum scan size (roughly 100 x 100 {mu}m) and the restricted movement of the cantilever in the Z (or height) direction. In most commercial AFMs, the Z range is restricted to roughly 10 {mu}m such that the height of cells to be imaged must be seriously considered. Nevertheless, AFM can provide structural-functional information at nanometer resolution and do so in physiologically relevant environments. Further, instrumentation for scanning probe microscopy continues to advance. Systems for high-speed imaging are becoming available, and techniques for looking inside the cells are being demonstrated. The ability to combine AFM with other imaging modalities is likely to have an even greater impact on microbiological studies. AFM studies of intact microbial cells started to appear in the literature in the 1990s. For example, AFM studies of Saccharomyces cerevisiae examined buddings cars after cell division and detailed changes related to cell growth processes. Also, the first AFM studies of bacterial biofilms appeared. In the late 1990s, AFM studies of intact fungal spores described clear changes in spore surfaces upon germination, and studies of individual bacterial cells were also described. These early bacterial imaging studies examined changes in bacterial morphology due to antimicrobial peptides exposure and bacterial adhesion properties. The majority of these early studies were carried out on dried samples and took advantage of the resolving power of AFM. The lack of cell mounting procedures presented an impediment for cell imaging studies. Subsequently, several approaches to mounting microbial cells have been developed, and these techniques are described later. Also highlighted are general considerations for microbial imaging and a description of some of the various applications of AFM to microbiology.

  3. Using Genomics to Study Human Biology and Disease

    SciTech Connect (OSTI)

    Myers, Ricard M.

    2005-04-06

    The Human Genome Project culminated in April 2003 with the finished DNA sequence of all of the human chromosomes. This book of information, particularly in conjunction with the genome sequences of many other organisms, has already begun to revolutionize the way that biomedical scientists study our species. The identification of essentially all of our genes has provided a template upon which researchers can discover basic processes that govern cells, organs, and the whole organism, and to understand the fundamental causes of the diseases that occur when something goes wrong with a gene or a set of genes. The Genome Project has already made it possible to identify the genes that are defective in more than 1,000 rare inherited diseases, and these discoveries have helped to understand the mechanisms of the more common forms of these disorders. This understanding of primary defects in diseases - which is translated as mutations in genes that encode proteins that serve specific functions - is transforming the way that biotechnology and pharmaceutical companies identify drug targets, and a few notable cases have already had a striking impact on specific diseases. In addition, it has become clear that the differential response to drugs in human populations is heavily influenced by genes, and a whole field called pharmacogenetics has begun to identify these genetic factors. Such knowledge will allow physicians to prescribe drugs targeted to each individual, with the potential to increase efficacy and decrease side-effects. Determining the DNA sequence of the human genome and identifying the genes has been an exciting endeavor, but we are only just beginning to understand the treasures present in all of our DNA. My presentation will briefly describe the road we took to get the sequence, as well as the tools that we are developing to unlock its secrets.

  4. Fuel Cell Animation - Fuel Cell Components (Text Version) | Department of

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

    Energy Components (Text Version) Fuel Cell Animation - Fuel Cell Components (Text Version) This text version of the fuel cell animation demonstrates how a fuel cell uses hydrogen to produce electricity, with only water and heat as byproducts. Fuel cell shown with its inputs and outputs. Hydrogen input on top, oxygen input in front, water and heat outputs out the back, with an electrical circuit going around the top. Polymer Electrolyte Membrane (PEM) in center, cathode/catalyst to the right

  5. TJ Solar Cell

    SciTech Connect (OSTI)

    Friedman, Daniel

    2009-04-17

    This talk will discuss recent developments in III-V multijunction photovoltaic technology which have led to the highest-efficiency solar cells ever demonstrated. The relationship between the materials science of III-V semiconductors and the achievement of record solar cell efficiencies will be emphasized. For instance, epitaxially-grown GAInP has been found to form a spontaneously-ordered GaP/InP (111) superlattice. This ordering affects the band gap of the material, which in turn affects the design of solar cells which incorporate GaInP. For the next generation of ultrahigh-efficiency III-V solar cells, we need a new semiconductor which is lattice-matched to GaAs, has a band gap of 1 eV, and has long minority-carrier diffusion lengths. Out of a number of candidate materials, the recently-discovered alloy GaInNAs appears to have the greatest promise. This material satisfies the first two criteria, but has to date shown very low diffusion lengths, a problem which is our current focus in the development of these next-generation cells.

  6. Breakthrough Vehicle Development - Fuel Cells

    Fuel Cell Technologies Publication and Product Library (EERE)

    Document describing research and development program for fuel cell power systems for transportation applications.

  7. Seventh Edition Fuel Cell Handbook

    SciTech Connect (OSTI)

    NETL

    2004-11-01

    Provides an overview of fuel cell technology and research projects. Discusses the basic workings of fuel cells and their system components, main fuel cell types, their characteristics, and their development status, as well as a discussion of potential fuel cell applications.

  8. Electrochemical cell operation and system

    DOE Patents [OSTI]

    Maru, Hansraj C. (Brookfield Center, CT)

    1980-03-11

    Thermal control in fuel cell operation is affected through sensible heat of process gas by providing common input manifolding of the cell gas flow passage in communication with the cell electrolyte and an additional gas flow passage which is isolated from the cell electrolyte and in thermal communication with a heat-generating surface of the cell. Flow level in the cell gas flow passage is selected based on desired output electrical energy and flow level in the additional gas flow passage is selected in accordance with desired cell operating temperature.

  9. Device for monitoring cell voltage

    DOE Patents [OSTI]

    Doepke, Matthias (Garbsen, DE); Eisermann, Henning (Edermissen, DE)

    2012-08-21

    A device for monitoring a rechargeable battery having a number of electrically connected cells includes at least one current interruption switch for interrupting current flowing through at least one associated cell and a plurality of monitoring units for detecting cell voltage. Each monitoring unit is associated with a single cell and includes a reference voltage unit for producing a defined reference threshold voltage and a voltage comparison unit for comparing the reference threshold voltage with a partial cell voltage of the associated cell. The reference voltage unit is electrically supplied from the cell voltage of the associated cell. The voltage comparison unit is coupled to the at least one current interruption switch for interrupting the current of at least the current flowing through the associated cell, with a defined minimum difference between the reference threshold voltage and the partial cell voltage.

  10. Project ATHENA creates surrogate human organ systems

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

    Project ATHENA creates surrogate human organ systems Alumni Link: Opportunities, News and Resources for Former Employees Latest Issue:September 2015 all issues All Issues » submit Project ATHENA creates surrogate human organ systems The development of miniature surrogate human organs, coupled with highly sensitive mass spectrometry technologies, could one day revolutionize the way new drugs and toxic agents are studied. July 1, 2015 ATHENA prototype undergoes testing. ATHENA prototype undergoes

  11. Linking Humans and Systems in Nuclear Power

    SciTech Connect (OSTI)

    Jacques Hugo

    2013-02-01

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

  12. Project ATHENA creates surrogate human organ systems

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

    Project ATHENA creates surrogate human organ systems Project ATHENA creates surrogate human organ systems The development of miniature surrogate human organs, coupled with highly sensitive mass spectrometry technologies, could one day revolutionize the way new drugs and toxic agents are studied. June 15, 2015 ATHENA prototype undergoes testing. ATHENA prototype undergoes testing. Contact Los Alamos National Laboratory Kevin Roark Communications Office (505) 665-9202 Email "By developing

  13. DOE Human Resources Management Division - Hanford Site

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

    Management About Us About Hanford Cleanup Hanford History Hanford Site Wide Programs DOE Human Resources Management Division DOE Employment Recognition and Awards Program Federal Employees Union (AFGE Local 788) Work Schedules / Pay and Leave Benefits and Services EEO & Diversity Contact Us DOE Human Resources Management Division Email Email Page | Print Print Page |Text Increase Font Size Decrease Font Size Richland Operations Office / Office of River Protection The Human Resources

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

    SciTech Connect (OSTI)

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

    2013-08-09

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

  15. Frizzled-8 as a putative therapeutic target in human lung cancer

    SciTech Connect (OSTI)

    Wang, Hua-qing; Department of Medical Oncology, Tianjin Medical University Cancer Hospital, Tianjin 300060 ; Xu, Mei-lin; Ma, Jie; Zhang, Yi; Xie, Cong-hua

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer Fzd-8 is over-expressed in human lung cancer. Black-Right-Pointing-Pointer shRNA knock-down of Fzd-8 inhibits proliferation and Wnt pathway in lung cancer cells. Black-Right-Pointing-Pointer shRNA knock-down of Fzd-8 suppresses tumor growth in vivo. Black-Right-Pointing-Pointer shRNA knock-down Fzd-8 sensitizes lung cancer cells to chemotherapy Taxotere. -- Abstract: Lung cancer is the leading cause of cancer related deaths worldwide. It is necessary to better understand the molecular mechanisms involved in lung cancer in order to develop more effective therapeutics for the treatment of this disease. Recent reports have shown that Wnt signaling pathway is important in a number of cancer types including lung cancer. However, the role of Frizzled-8 (Fzd-8), one of the Frizzled family of receptors for the Wnt ligands, in lung cancer still remains to be elucidated. Here in this study we showed that Fzd-8 was over-expressed in human lung cancer tissue samples and cell lines. To investigate the functional importance of the Fzd-8 over-expression in lung cancer, we used shRNA to knock down Fzd-8 mRNA in lung cancer cells expressing the gene. We observed that Fzd-8 shRNA inhibited cell proliferation along with decreased activity of Wnt pathway in vitro, and also significantly suppressed A549 xenograft model in vivo (p < 0.05). Furthermore, we found that knocking down Fzd-8 by shRNA sensitized the lung cancer cells to chemotherapy Taxotere. These data suggest that Fzd-8 is a putative therapeutic target for human lung cancer and over-expression of Fzd-8 may be important for aberrant Wnt activation in lung cancer.

  16. Cell Phone Detection Techniques

    SciTech Connect (OSTI)

    Pratt, Richard M.; Bunch, Kyle J.; Puzycki, David J.; Slaugh, Ryan W.; Good, Morris S.; McMakin, Douglas L.

    2007-10-01

    A team composed of Rick Pratt, Dave Puczyki, Kyle Bunch, Ryan Slaugh, Morris Good, and Doug McMakin teamed together to attempt to exploit cellular telephone features and detect if a person was carrying a cellular telephone into a Limited Area. The cell phones electromagnetic properties were measured, analyzed, and tested in over 10 different ways to determine if an exploitable signature exists. The method that appears to have the most potential for success without adding an external tag is to measure the RF spectrum, not in the cell phone band, but between 240 and 400MHz. Figures 1- 7 show the detected signal levels from cell phones from three different manufacturers.

  17. Multiscale Simulations of Human Pathologies | Argonne Leadership...

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

    apex. Inset shows the time evolution of thrombus formation. George Karniadakis, Brown University Multiscale Simulations of Human Pathologies PI Name: George Karniadakis PI...

  18. Human factors challenges for advanced process control

    SciTech Connect (OSTI)

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

    1996-08-01

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

  19. History of the DOE Human Genome Program

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

    of the DOE Human Genome Program The following history is taken from the U.S. Department of Energy 1991-91 Human Genome Program Report (June 1992). This is an archived item. A brief history of the U.S. Department of Energy (DOE) Human Genome Program will be useful in a discussion of the objectives of the DOE program as well as those of the collaborative U.S. Human Genome Project. The Office of Health and Environmental Research (OHER) of DOE and its predecessor agencies--the Atomic Energy

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

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

    More Documents & Publications PIA - INL PeopleSoft - Human Resource System PIA - INL SECURITY INFORMATION MANAGEMENT SYSTEM BUSINESS ENCLAVE Integrated Safety Management Workshop ...

  1. INSPECTION REPORT Procurement Administration and Human Reliability...

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

    These agents participate in the Human Reliability Program (HRP), a security and safety reliability program designed to ensure that agents meet the highest standards of reliability ...

  2. Immunogenic compositions comprising human immunodeficiency virus...

    Office of Scientific and Technical Information (OSTI)

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

  3. Human Capital Management Accountability Program (HCMAP)

    Broader source: Energy.gov [DOE]

    Human Capital Management Accountability Program (HCMAP) is an online program which serves as the vehicle for identifying and measuring these three factors, effectiveness, efficiency, and timeliness...

  4. Apparatus and methods for a human extender

    DOE Patents [OSTI]

    Jansen, John F. (Knoxville, TN)

    2001-01-01

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

  5. Report: Human Capital Discussion and Observations

    Office of Environmental Management (EM)

    Human Capital Discussion, Observations, and Recommendations August 24, 2006 Submitted by: Mr. A. James Barnes and Mr. Dennis Ferrigno Background: During the March 23-24, 2006 EMAB...

  6. Interband Cascade Photovoltaic Cells

    SciTech Connect (OSTI)

    Yang, Rui Q.; Santos, Michael B.; Johnson, Matthew B.

    2014-09-24

    In this project, we are performing basic and applied research to systematically investigate our newly proposed interband cascade (IC) photovoltaic (PV) cells [1]. These cells follow from the great success of infrared IC lasers [2-3] that pioneered the use of quantum-engineered IC structures. This quantum-engineered approach will enable PV cells to efficiently convert infrared radiation from the sun or other heat source, to electricity. Such cells will have important applications for more efficient use of solar energy, waste-heat recovery, and power beaming in combination with mid-infrared lasers. The objectives of our investigations are to: achieve extensive understanding of the fundamental aspects of the proposed PV structures, develop the necessary knowledge for making such IC PV cells, and demonstrate prototype working PV cells. This research will focus on IC PV structures and their segments for utilizing infrared radiation with wavelengths from 2 to 5 ?m, a range well suited for emission by heat sources (1,000-2,000 K) that are widely available from combustion systems. The long-term goal of this project is to push PV technology to longer wavelengths, allowing for relatively low-temperature thermal sources. Our investigations address material quality, electrical and optical properties, and their interplay for the different regions of an IC PV structure. The tasks involve: design, modeling and optimization of IC PV structures, molecular beam epitaxial growth of PV structures and relevant segments, material characterization, prototype device fabrication and testing. At the end of this program, we expect to generate new cutting-edge knowledge in the design and understanding of quantum-engineered semiconductor structures, and demonstrate the concepts for IC PV devices with high conversion efficiencies.

  7. Dense pattern optical multipass cell

    DOE Patents [OSTI]

    Silver, Joel A [Santa Fe, NM

    2009-01-13

    A multiple pass optical cell and method comprising providing a pair of opposed cylindrical mirrors having curved axes with substantially equal focal lengths, positioning an entrance hole for introducing light into the cell and an exit hole for extracting light from the cell, wherein the entrance hole and exit hole are coextensive or non-coextensive, introducing light into the cell through the entrance hole, and extracting light from the cell through the exit hole.

  8. Dense pattern multiple pass cells

    DOE Patents [OSTI]

    Silver, Joel A. (Santa Fe, NM); Bomse, David S. (Santa Fe, NM)

    2010-09-21

    An optical cell and a method of operating an optical cell comprising employing a first mirror comprising a first hole therein at approximately a center of the first mirror and through which laser light enters the cell, employing a second mirror comprising a second hole therein at approximately a center of the second mirror and through which laser light exits the cell, and forming a Lissajous pattern of spots on the mirrors by repeated reflection of laser light entering the cell.

  9. Electrode for electrochemical cell

    DOE Patents [OSTI]

    Kaun, T.D.; Nelson, P.A.; Miller, W.E.

    1980-05-09

    An electrode structure for a secondary electrochemical cell includes an outer enclosure defining a compartment containing electrochemical active material. The enclosure includes a rigid electrically conductive metal sheet with perforated openings over major side surfaces. The enclosure can be assembled as first and second trays each with a rigid sheet of perforated electrically conductive metal at major side surfaces and normally extending flanges at parametric margins. The trays can be pressed together with moldable active material between the two to form an expandable electrode. A plurality of positive and negative electrodes thus formed are arranged in an alternating array with porous frangible interelectrode separators within the housing of the secondary electrochemical cell.

  10. Fuel cell stack arrangements

    DOE Patents [OSTI]

    Kothmann, Richard E. (Churchill Boro, PA); Somers, Edward V. (Murrysville, PA)

    1982-01-01

    Arrangements of stacks of fuel cells and ducts, for fuel cells operating with separate fuel, oxidant and coolant streams. An even number of stacks are arranged generally end-to-end in a loop. Ducts located at the juncture of consecutive stacks of the loop feed oxidant or fuel to or from the two consecutive stacks, each individual duct communicating with two stacks. A coolant fluid flows from outside the loop, into and through cooling channels of the stack, and is discharged into an enclosure duct formed within the loop by the stacks and seals at the junctures at the stacks.

  11. Aluminum reduction cell electrode

    DOE Patents [OSTI]

    Payne, John R. (Pleasanton, CA)

    1983-09-20

    The invention is directed to an anode-cathode structure for an electrolytic cell for the reduction of alumina wherein the structure is comprised of a carbon anode assembly which straddles a wedge-shaped refractory hard metal cathode assembly having steeply sloped cathodic surfaces, each cathodic surface being paired in essentially parallel planar relationship with an anode surface. The anode-cathode structure not only takes into account the structural weakness of refractory hard metal materials but also permits the changing of the RHM assembly during operation of the cell. Further, the anode-cathode structure enhances the removal of anode gas from the interpolar gap between the anode and cathode surfaces.

  12. Fuel Cells Go Live

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

    green h y d r o g e n f u e l i n g POWer Fuel Cells Go live A closer look at the requirements to create a hydrogen-based warehouse M anagers of distribution centers are always on the lookout for new ways to gain competitive advantage through increased operational efficiency, productivity and worker safety. Around North America, some are finding success by integrating commercially available hydrogen fuel cell systems into their lift truck fleets. For operations with large fleets of electric lift

  13. Monolithic tandem solar cell

    DOE Patents [OSTI]

    Wanlass, Mark W. (Golden, CO)

    1991-01-01

    A single-crystal, monolithic, tandem, photovoltaic solar cell is described which includes (a) an InP substrate having upper and lower surfaces, (b) a first photoactive subcell on the upper surface of the InP substrate, and (c) a second photoactive subcell on the first subcell. The first photoactive subcell is GaInAsP of defined composition. The second subcell is InP. The two subcells are lattice matched. The solar cell can be provided as a two-terminal device or a three-terminal device.

  14. Separators for electrochemical cells

    DOE Patents [OSTI]

    Carlson, Steven Allen; Anakor, Ifenna Kingsley

    2014-11-11

    Provided are separators for use in an electrochemical cell comprising (a) an inorganic oxide and (b) an organic polymer, wherein the inorganic oxide comprises organic substituents. Preferably, the inorganic oxide comprises an hydrated aluminum oxide of the formula Al.sub.2O.sub.3.xH.sub.2O, wherein x is less than 1.0, and wherein the hydrated aluminum oxide comprises organic substituents, preferably comprising a reaction product of a multifunctional monomer and/or organic carbonate with an aluminum oxide, such as pseudo-boehmite and an aluminum oxide. Also provided are electrochemical cells comprising such separators.

  15. Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes

    SciTech Connect (OSTI)

    Elferink, M.G.L., E-mail: m.g.l.elferink@rug.nl [Department of Pharmacokinetics, Toxicology and Targeting, Groningen Research Institute for Pharmacy, University of Groningen (Netherlands); Olinga, P. [Department of Pharmacokinetics, Toxicology and Targeting, Groningen Research Institute for Pharmacy, University of Groningen (Netherlands); van Leeuwen, E.M.; Bauerschmidt, S.; Polman, J. [Molecular Design and Informatics, MSD, Oss (Netherlands); Schoonen, W.G. [Toxicology and Drug Disposition, MSD, Oss (Netherlands); Heisterkamp, S.H. [Biostatistics and Research Decision Sciences MSD, Oss (Netherlands); Bioinformatics Centre, University of Groningen (Netherlands); Groothuis, G.M.M. [Department of Pharmacokinetics, Toxicology and Targeting, Groningen Research Institute for Pharmacy, University of Groningen (Netherlands)

    2011-05-15

    In the process of drug development it is of high importance to test the safety of new drugs with predictive value for human toxicity. A promising approach of toxicity testing is based on shifts in gene expression profiling of the liver. Toxicity screening based on animal liver cells cannot be directly extrapolated to humans due to species differences. The aim of this study was to evaluate precision-cut human liver slices as in vitro method for the prediction of human specific toxicity by toxicogenomics. The liver slices contain all cell types of the liver in their natural architecture. This is important since drug-induced toxicity often is a multi-cellular process. Previously we showed that toxicogenomic analysis of rat liver slices is highly predictive for rat in vivo toxicity. In this study we investigated the levels of gene expression during incubation up to 24 h with Affymetrix microarray technology. The analysis was focused on a broad spectrum of genes related to stress and toxicity, and on genes encoding for phase-I, -II and -III metabolizing enzymes and transporters. Observed changes in gene expression were associated with cytoskeleton remodeling, extracellular matrix and cell adhesion, but for the ADME-Tox related genes only minor changes were observed. PCA analysis showed that changes in gene expression were not associated with age, sex or source of the human livers. Slices treated with acetaminophen showed patterns of gene expression related to its toxicity. These results indicate that precision-cut human liver slices are relatively stable during 24 h of incubation and represent a valuable model for human in vitro hepatotoxicity testing despite the human inter-individual variability.

  16. Atomic magnetometer for human magnetoencephalograpy.

    SciTech Connect (OSTI)

    Schwindt, Peter; Johnson, Cort N.

    2010-12-01

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

  17. Solar Cell Simulation

    K-12 Energy Lesson Plans and Activities Web site (EERE)

    Students model the flow of energy from the sun as it enters a photovoltaic cell, moves along a wire and powers a load. The game-like atmosphere involves the younger students and helps them understand the continuous nature of the flow of energy. For a related lesson, please see the activity “Solar Powered System” (PDF 430 KB).

  18. Thin film photovoltaic cell

    DOE Patents [OSTI]

    Meakin, John D. (Newark, DE); Bragagnolo, Julio (Newark, DE)

    1982-01-01

    A thin film photovoltaic cell having a transparent electrical contact and an opaque electrical contact with a pair of semiconductors therebetween includes utilizing one of the electrical contacts as a substrate and wherein the inner surface thereof is modified by microroughening while being macro-planar.

  19. Fuel Cell Case Study

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

    Kathy Loftus Global Leader, Sustainable Engineering, Maintenance & Energy Management Whole Foods Market, Inc. Fuel Cell Case Study 2 Holistic Approach from Development to Operation WFM Energy Management Negotiation Awareness Load Shaping Engineering Refrigeration HVAC Electrical Maintenance Performance Based Retailers Operational Practices Store Design & Construction Consultants Specifications Procurement Equipment Selection Life Cycle Costing Energy & Maintenance team can feedback

  20. Amorphous semiconductor solar cell

    DOE Patents [OSTI]

    Dalal, Vikram L. (Newark, DE)

    1981-01-01

    A solar cell comprising a back electrical contact, amorphous silicon semiconductor base and junction layers and a top electrical contact includes in its manufacture the step of heat treating the physical junction between the base layer and junction layer to diffuse the dopant species at the physical junction into the base layer.

  1. Analysis of human HPRT deletion mutations with X-linked probes and pulsed field gel electrophoresis

    SciTech Connect (OSTI)

    Nicklas, J.A.; Lippert, M.J.; Hunter, T.C.; O'Neil, J.P.; Albertini, R.J. )

    1991-01-01

    Because the human hprt gene is used in numerous mutation studies, it is important to fully characterize this gene. Therefore, the authors laboratory has undertaken to map the region around the hprt gene at band q26 of the human X chromosome. Utilizing hprt mutant T-cell clones isolated using the hprt clonal assay, which have deletions of all of part of the hprt gene, the authors have ordered 5 anonymous probes previously known to map in Xq26. Results suggest that this region include between 460 kb and 18 Mb of DNA, which is at least 10 times the size of the hprt gene itself (43 kb). Pulsed field gel analysis of the region is underway to determine the exact distances between each of the anonymous probes and hprt and to determine deletion sizes in the mutant T-cell clones.

  2. Fuel Cell Systems | Department of Energy

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

    Cells » Fuel Cell Systems Fuel Cell Systems The design of fuel cell systems is complex, and can vary significantly depending upon fuel cell type and application. However, several basic components are found in many fuel cell systems: Fuel cell stack Fuel processor Power conditioners Air compressors Humidifiers Fuel Cell Stack The fuel cell stack is the heart of a fuel cell power system. It generates electricity in the form of direct current (DC) from electro-chemical reactions that take place in

  3. 2009 Fuel Cell Market Report

    SciTech Connect (OSTI)

    Vincent, Bill; Gangi, Jennifer; Curtin, Sandra; Delmont, Elizabeth

    2010-11-01

    Fuel cells are electrochemical devices that combine hydrogen and oxygen to produce electricity, water, and heat. Unlike batteries, fuel cells continuously generate electricity, as long as a source of fuel is supplied. Moreover, fuel cells do not burn fuel, making the process quiet, pollution-free and two to three times more efficient than combustion. Fuel cell systems can be a truly zero-emission source of electricity, if the hydrogen is produced from non-polluting sources. Global concerns about climate change, energy security, and air pollution are driving demand for fuel cell technology. More than 630 companies and laboratories in the United States are investing $1 billion a year in fuel cells or fuel cell component technologies. This report provides an overview of trends in the fuel cell industry and markets, including product shipments, market development, and corporate performance. It also provides snapshots of select fuel cell companies, including general.

  4. Careers/ Human Resources | Princeton Plasma Physics Lab

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

    Employment Opportunities Directory Environment, Safety & Health Furth Plasma Physics Library Lab Leadership Organization Chart Technology Transfer Contact Us Business Operations Careers/ Human Resources Employment Opportunities Directory Environment, Safety & Health Furth Plasma Physics Library Lab Leadership Organization Chart Technology Transfer Careers/ Human Resources Join Princeton's TALENT NETWORK to enhance your job search and the application process for Princeton University and

  5. Contractor Human Resources Management | Department of Energy

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

    Contractor Human Resources Management Contractor Human Resources Management Value Study Desk Manual & Cost Study Manual PDF icon Memo from Robert Myers regarding DOE Benefit Value Desk Manual PDF icon Value Study Desk Manual PDF icon Cost study manual 06 29 2012.pdf More Documents & Publications Value Study Desk Manual VALUE STUDY VALUE STUDY

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

    SciTech Connect (OSTI)

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

    2013-11-01

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

  7. Pancreatic stellate cells enhance stem cell-like phenotypes in pancreatic cancer cells

    SciTech Connect (OSTI)

    Hamada, Shin [Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai (Japan)] [Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai (Japan); Masamune, Atsushi, E-mail: amasamune@med.tohoku.ac.jp [Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai (Japan)] [Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai (Japan); Takikawa, Tetsuya; Suzuki, Noriaki; Kikuta, Kazuhiro; Hirota, Morihisa [Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai (Japan)] [Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai (Japan); Hamada, Hirofumi [Laboratory of Oncology, Department of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji (Japan)] [Laboratory of Oncology, Department of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji (Japan); Kobune, Masayoshi [Fourth Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo (Japan)] [Fourth Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo (Japan); Satoh, Kennichi [Division of Cancer Stem Cell, Miyagi Cancer Center Research Institute, Natori (Japan)] [Division of Cancer Stem Cell, Miyagi Cancer Center Research Institute, Natori (Japan); Shimosegawa, Tooru [Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai (Japan)] [Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai (Japan)

    2012-05-04

    Highlights: Black-Right-Pointing-Pointer Pancreatic stellate cells (PSCs) promote the progression of pancreatic cancer. Black-Right-Pointing-Pointer Pancreatic cancer cells co-cultured with PSCs showed enhanced spheroid formation. Black-Right-Pointing-Pointer Expression of stem cell-related genes ABCG2, Nestin and LIN28 was increased. Black-Right-Pointing-Pointer Co-injection of PSCs enhanced tumorigenicity of pancreatic cancer cells in vivo. Black-Right-Pointing-Pointer This study suggested a novel role of PSCs as a part of the cancer stem cell niche. -- Abstract: The interaction between pancreatic cancer cells and pancreatic stellate cells (PSCs), a major profibrogenic cell type in the pancreas, is receiving increasing attention. There is accumulating evidence that PSCs promote the progression of pancreatic cancer by increasing cancer cell proliferation and invasion as well as by protecting them from radiation- and gemcitabine-induced apoptosis. Recent studies have identified that a portion of cancer cells, called 'cancer stem cells', within the entire cancer tissue harbor highly tumorigenic and chemo-resistant phenotypes, which lead to the recurrence after surgery or re-growth of the tumor. The mechanisms that maintain the 'stemness' of these cells remain largely unknown. We hypothesized that PSCs might enhance the cancer stem cell-like phenotypes in pancreatic cancer cells. Indirect co-culture of pancreatic cancer cells with PSCs enhanced the spheroid-forming ability of cancer cells and induced the expression of cancer stem cell-related genes ABCG2, Nestin and LIN28. In addition, co-injection of PSCs enhanced tumorigenicity of pancreatic cancer cells in vivo. These results suggested a novel role of PSCs as a part of the cancer stem cell niche.

  8. Hydrogen and Fuel Cell Activities

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

    5/2011 eere.energy.gov 5 th International Conference on Polymer Batteries & Fuel Cells Argonne, Illinois Hydrogen and Fuel Cell Activities Dr. Sunita Satyapal U.S. Department of Energy Fuel Cell Technologies Program Program Manager August 4, 2011 2 | Fuel Cell Technologies Program Source: US DOE 8/5/2011 eere.energy.gov Fuel Cells: Benefits & Market Potential The Role of Fuel Cells Key Benefits Very High Efficiency Reduced CO 2 Emissions * 35-50%+ reductions for CHP systems (>80% with

  9. Fuel Cell Technologies Program Overview

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

    US DOE Non-Metallic Materials Meeting Washington, DC Fuel Cell Technologies Program Overview Dr. Sunita Satyapal U.S. Department of Energy Fuel Cell Technologies Program Program Manager 10/17/2012 2 | Fuel Cell Technologies Program eere.energy.gov Overview Fuel Cells - An Emerging Global Industry Clean Energy Patent Growth Index [1] shows that fuel cell patents lead in the clean energy field with over 950 fuel cell patents issued in 2011. * Nearly double the second place holder, solar, which has

  10. DOE Fuel Cell Technologies Office

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

    DOE Fuel Cell Technologies Office Fuel Cell Seminar & Energy Exposition Columbus, Ohio Dr. Sunita Satyapal Director Fuel Cell Technologies Office Energy Efficiency and Renewable Energy U.S. Department of Energy October 22, 2013 2 | Fuel Cell Technologies Office eere.energy.gov This award is being accepted on behalf of the U.S. Department of Energy fuel cell and hydrogen programs Acknowledgements 3 | Fuel Cell Technologies Office eere.energy.gov 2000 * DOE Hydrogen R&D Program 2002 * DOE

  11. Fuel Cells | Department of Energy

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

    Cells Fuel Cells A fuel cell uses the chemical energy of hydrogen or another fuel to cleanly and efficiently produce electricity. If hydrogen is the fuel, electricity, water, and heat are the only products. Fuel cells are unique in terms of the variety of their potential applications; they can provide power for systems as large as a utility power station and as small as a laptop computer. Why Study Fuel Cells Fuel cells can be used in a wide range of applications, including transportation,

  12. Human retroviruses and AIDS 1997

    SciTech Connect (OSTI)

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

    1997-12-01

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

  13. NREL: Hydrogen and Fuel Cells Research - Fuel Cell Manufacturing

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

    Cell Manufacturing Photo of scientific equipment in laboratory setting. NREL's in-line diagnostics help industry identify defects in fuel cell components. This small-scale manufacturing line at NREL's Energy Systems Integration Facility can convey fuel cell component materials at speeds of 100 feet per minute. NREL's fuel cell manufacturing R&D focuses on improving quality-inspection practices for high-volume manufacturing processes to enable higher production volumes, increased reliability,

  14. Solar Cells: Spin-Cast Bulk Heterojunction Solar Cells: A Dynamical...

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

    Solar Cells: Spin-Cast Bulk Heterojunction Solar Cells: A Dynamical Investigation Solar Cells: Spin-Cast Bulk Heterojunction Solar Cells: A Dynamical Investigation Print Wednesday,...

  15. Fuel Cell Handbook, Fourth Edition

    SciTech Connect (OSTI)

    Stauffer, D.B; Hirschenhofer, J.H.; Klett, M.G.; Engleman, R.R.

    1998-11-01

    Robust progress has been made in fuel cell technology since the previous edition of the Fuel Cell Handbook was published in January 1994. This Handbook provides a foundation in fuel cells for persons wanting a better understanding of the technology, its benefits, and the systems issues that influence its application. Trends in technology are discussed, including next-generation concepts that promise ultra high efficiency and low cost, while providing exceptionally clean power plant systems. Section 1 summarizes fuel cell progress since the last edition and includes existing power plant nameplate data. Section 2 addresses the thermodynamics of fuel cells to provide an understanding of fuel cell operation at two levels (basic and advanced). Sections 3 through 6 describe the four major fuel cell types and their performance based on cell operating conditions. The section on polymer electrolyte membrane fuel cells has been added to reflect their emergence as a significant fuel cell technology. Phosphoric acid, molten carbonate, and solid oxide fuel cell technology description sections have been updated from the previous edition. New information indicates that manufacturers have stayed with proven cell designs, focusing instead on advancing the system surrounding the fuel cell to lower life cycle costs. Section 7, Fuel Cell Systems, has been significantly revised to characterize near-term and next-generation fuel cell power plant systems at a conceptual level of detail. Section 8 provides examples of practical fuel cell system calculations. A list of fuel cell URLs is included in the Appendix. A new index assists the reader in locating specific information quickly.

  16. Inhibition of cell-cell binding by lipid assemblies

    DOE Patents [OSTI]

    Nagy, Jon O. (Rodeo, CA); Bargatze, Robert F. (Bozeman, MT)

    2001-05-22

    This invention relates generally to the field of therapeutic compounds designed to interfere between the binding of ligands and their receptors on cell surface. More specifically, it provides products and methods for inhibiting cell migration and activation using lipid assemblies with surface recognition elements that are specific for the receptors involved in cell migration and activation.

  17. Compact fuel cell

    DOE Patents [OSTI]

    Jacobson, Craig (Moraga, CA); DeJonghe, Lutgard C. (Lafayette, CA); Lu, Chun (Richland, WA)

    2010-10-19

    A novel electrochemical cell which may be a solid oxide fuel cell (SOFC) is disclosed where the cathodes (144, 140) may be exposed to the air and open to the ambient atmosphere without further housing. Current collector (145) extends through a first cathode on one side of a unit and over the unit through the cathode on the other side of the unit and is in electrical contact via lead (146) with housing unit (122 and 124). Electrical insulator (170) prevents electrical contact between two units. Fuel inlet manifold (134) allows fuel to communicate with internal space (138) between the anodes (154 and 156). Electrically insulating members (164 and 166) prevent the current collector from being in electrical contact with the anode.

  18. Electrochemical cell design

    DOE Patents [OSTI]

    Arntzen, John D.

    1978-01-01

    An electrochemical cell includes two outer electrodes and a central electrode of opposite polarity, all nested within a housing having two symmetrical halves which together form an offset configuration. The outer electrodes are nested within raised portions within the side walls of each housing half while the central electrode sealingly engages the perimetric margins of the side-wall internal surfaces. Suitable interelectrode separators and electrical insulating material electrically isolate the central electrode from the housing and the outer electrodes. The outer electrodes are electrically connected to the internal surfaces of the cell housing to provide current collection. The nested structure minimizes void volume that would otherwise be filled with gas or heavy electrolyte and also provides perimetric edge surfaces for sealing and supporting at the outer margins of frangible interelectrode separator layers.

  19. Electrocapturing flow cell

    DOE Patents [OSTI]

    Morozov, Victor (Manassas, VA)

    2011-04-05

    A flow cell for electrophoretically-assisted capturing analytes from a flow. The flow cell includes a specimen chamber, a first membrane, a second membrane, a first electrode chamber, and a second electrode chamber. The specimen chamber may have a sample inlet and a sample outlet. A first portion of the first membrane may be coupled to a first portion of the specimen chamber. A first portion of the second membrane may be coupled to a second portion of the specimen chamber. The first electrode chamber may be configured to accept a charge. A portion of the first electrode chamber may be coupled to a second portion of the first membrane. A second electrode chamber may be configured to accept an opposite charge. A portion of the second electrode chamber may be coupled to a second portion of the second membrane.

  20. Fuel cell CO sensor

    DOE Patents [OSTI]

    Grot, Stephen Andreas (Rochester, NY); Meltser, Mark Alexander (Pittsford, NY); Gutowski, Stanley (Pittsford, NY); Neutzler, Jay Kevin (Rochester, NY); Borup, Rodney Lynn (East Rochester, NY); Weisbrod, Kirk (Los Alamos, NM)

    1999-12-14

    The CO concentration in the H.sub.2 feed stream to a PEM fuel cell stack is monitored by measuring current and/or voltage behavior patterns from a PEM-probe communicating with the reformate feed stream. Pattern recognition software may be used to compare the current and voltage patterns from the PEM-probe to current and voltage telltale outputs determined from a reference cell similar to the PEM-probe and operated under controlled conditions over a wide range of CO concentrations in the H.sub.2 fuel stream. A CO sensor includes the PEM-probe, an electrical discharge circuit for discharging the PEM-probe to monitor the CO concentration, and an electrical purging circuit to intermittently raise the anode potential of the PEM-probe's anode to at least about 0.8 V (RHE) to electrochemically oxidize any CO adsorbed on the probe's anode catalyst.