National Library of Energy BETA

Sample records for mammary epithelial cells

  1. Bone morphogenetic protein-4 strongly potentiates growth factor-induced proliferation of mammary epithelial cells

    SciTech Connect (OSTI)

    Montesano, Roberto Sarkoezi, Rita; Schramek, Herbert

    2008-09-12

    Bone morphogenetic proteins (BMPs) are multifunctional cytokines that elicit pleiotropic effects on biological processes such as cell proliferation, cell differentiation and tissue morphogenesis. With respect to cell proliferation, BMPs can exert either mitogenic or anti-mitogenic activities, depending on the target cells and their context. Here, we report that in low-density cultures of immortalized mammary epithelial cells, BMP-4 did not stimulate cell proliferation by itself. However, when added in combination with suboptimal concentrations of fibroblast growth factor (FGF)-2, FGF-7, FGF-10, epidermal growth factor (EGF) or hepatocyte growth factor (HGF), BMP-4 potently enhanced growth factor-induced cell proliferation. These results reveal a hitherto unsuspected interplay between BMP-4 and growth factors in the regulation of mammary epithelial cell proliferation. We suggest that the ability of BMP-4 to potentiate the mitogenic activity of multiple growth factors may contribute to mammary gland ductal morphogenesis as well as to breast cancer progression.

  2. Self-organization is a dynamic and lineage-intrinsic property of mammary epithelial cells

    SciTech Connect (OSTI)

    Chanson, L.; Brownfield, D.; Garbe, J. C.; Kuhn, I.; Stampfer, M. R.; Bissell, M. J.; LaBarge, M. A.

    2011-02-07

    Loss of organization is a principle feature of cancers; therefore it is important to understand how normal adult multilineage tissues, such as bilayered secretory epithelia, establish and maintain their architectures. The self-organization process that drives heterogeneous mixtures of cells to form organized tissues is well studied in embryology and with mammalian cell lines that were abnormal or engineered. Here we used a micropatterning approach that confined cells to a cylindrical geometry combined with an algorithm to quantify changes of cellular distribution over time to measure the ability of different cell types to self-organize relative to each other. Using normal human mammary epithelial cells enriched into pools of the two principal lineages, luminal and myoepithelial cells, we demonstrated that bilayered organization in mammary epithelium was driven mainly by lineage-specific differential E-cadherin expression, but that P-cadherin contributed specifically to organization of the myoepithelial layer. Disruption of the actomyosin network or of adherens junction proteins resulted in either prevention of bilayer formation or loss of preformed bilayers, consistent with continual sampling of the local microenvironment by cadherins. Together these data show that self-organization is an innate and reversible property of communities of normal adult human mammary epithelial cells.

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

    DOE Patents [OSTI]

    Stampfer, Martha R.; Smith, Helene S.; Hackett, Adeline J.

    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.

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

    SciTech Connect (OSTI)

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

    2005-03-03

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

  5. EGF stimulates Mg{sup 2+} influx in mammary epithelial cells

    SciTech Connect (OSTI)

    Trapani, Valentina; Arduini, Daniela; Luongo, Francesca; Wolf, Federica I.

    2014-11-28

    Highlights: EGF stimulation potentiates Mg{sup 2+} influx into epithelial cells. EGF-induced Mg{sup 2+} influx does not depend on the concomitantly induced Ca{sup 2+} signal. EGF-induced Ca{sup 2+} signal is dependent on the presence of extracellular Mg{sup 2+}. New players in EGF-mediated signaling might be exploited as therapeutic targets. - Abstract: Magnesium is well established as a fundamental factor that regulates cell proliferation. However, the molecular mechanisms linking mitogenic signals, extracellular magnesium availability and intracellular effectors are still largely unknown. In the present study we sought to determine whether EGF regulates magnesium homeostasis in normal HC11 mammary epithelial cells. To this end, we measured Mg{sup 2+} and Ca{sup 2+} fluxes by confocal imaging in live cells loaded with specific fluorescent ion indicators (Mag-Fluo-4 and Fluo-4, respectively). EGF stimulation induces a rapid and sustained increase in intracellular Mg{sup 2+}, concomitantly with a rise in intracellular calcium. The increase in intracellular Mg{sup 2+} derives from an influx from the extracellular compartment, and does not depend on Ca{sup 2+}. On the contrary, the increase in intracellular Ca{sup 2+} derives from intracellular stores, and is impaired in the absence of extracellular magnesium. Inhibition of the EGF receptor tyrosine kinase by Tyrphostin AG1478 markedly inhibits EGF-induced Mg{sup 2+} and Ca{sup 2+} signals. These findings demonstrate that not only does Mg{sup 2+} influx represent an important step in the physiological response of epithelial cells to EGF, but unexpectedly the EGF-induced Mg{sup 2+} influx is essential for the Ca{sup 2+} signal to occur.

  6. Matrix Metalloproteinase Stromelysin-1 Triggers a Cascade of Molecular Alterations that leads to stable epithelial-to-Mesenchymal Conversion and a Premalignant Phenotype in Mammary Epithelial Cells

    SciTech Connect (OSTI)

    Lochter, A.; Galosy, S.; Muschler, J.; Freedman, N.; Werb, Z.; Bissell, M.J.

    1997-08-11

    Matrix metalloproteinases (MMPs) regulate ductal morphogenesis, apoptosis, and neoplastic progression in mammary epithelial cells. To elucidate the direct effects of MMPs on mammary epithelium, we generated functionally normal cells expressing an inducible autoactivating stromelysin-1 (SL-1) transgene. Induction of SL-1 expression resulted in cleavage of E-cadherin, and triggered progressive phenotypic conversion characterized by disappearance of E-cadherin and catenins from cell-cell contacts, downregulation of cytokeratins, upregulation of vimentin, induction of keratinocyte growth factor expression and activation, and upregulation of endogenous MMPs. Cells expressing SL-1 were unable to undergo lactogenic differentiation and became invasive. Once initiated, this phenotypic conversion was essentially stable, and progressed even in the absence of continued SL-1 expression. These observations demonstrate that inappropriate expression of SL-1 initiates a cascade of events that may represent a coordinated program leading to loss of the differentiated epithelial phenotype and gain of some characteristics of tumor cells. Our data provide novel insights into how MMPs function in development and neoplastic conversion.

  7. Stepwise DNA Methylation Changes Are Linked to Escape from Defined Proliferation Barriers and Mammary Epithelial Cell Immortalization

    SciTech Connect (OSTI)

    Novak, Petr; Jensen, Taylor J.; Garbe, James C.; Stampfer, Martha R.; Futscher, Bernard W.

    2009-04-20

    The timing and progression of DNA methylation changes during carcinogenesis are not completely understood. To develop a timeline of aberrant DNA methylation events during malignant transformation, we analyzed genome-wide DNA methylation patterns in an isogenic human mammary epithelial cell (HMEC) culture model of transformation. To acquire immortality and malignancy, the cultured finite lifespan HMEC must overcome two distinct proliferation barriers. The first barrier, stasis, is mediated by the retinoblastoma protein and can be overcome by loss of p16(INK4A) expression. HMEC that escape stasis and continue to proliferate become genomically unstable before encountering a second more stringent proliferation barrier, telomere dysfunction due to telomere attrition. Rare cells that acquire telomerase expression may escape this barrier, become immortal, and develop further malignant properties. Our analysis of HMEC transitioning from finite lifespan to malignantly transformed showed that aberrant DNA methylation changes occur in a stepwise fashion early in the transformation process. The first aberrant DNA methylation step coincides with overcoming stasis, and results in few to hundreds of changes, depending on how stasis was overcome. A second step coincides with immortalization and results in hundreds of additional DNA methylation changes regardless of the immortalization pathway. A majority of these DNA methylation changes are also found in malignant breast cancer cells. These results show that large-scale epigenetic remodeling occurs in the earliest steps of mammary carcinogenesis, temporally links DNA methylation changes and overcoming cellular proliferation barriers, and provides a bank of potential epigenetic biomarkers that mayprove useful in breast cancer risk assessment.

  8. Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells

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

    Severson, Paul L.; Vrba, Lukas; Stampfer, Martha R.; Futscher, Bernard W.

    2014-11-04

    Genetic mutations are known to drive cancer progression and certain tumors have mutation signatures that reflect exposures to environmental carcinogens. Benzo[a]pyrene (BaP) has a known mutation signature and has proven capable of inducing changes to DNA sequence that drives normal pre-stasis human mammary epithelial cells (HMEC) past a first tumor suppressor barrier (stasis) and toward immortality. We analyzed normal, pre-stasis HMEC, three independent BaP-derived post-stasis HMEC strains (184Aa, 184Be, 184Ce) and two of their immortal derivatives(184A1 and 184BE1) by whole exome sequencing. The independent post-stasis strains exhibited between 93 and 233 BaP-induced mutations in exons. Seventy percent of the mutationsmore » were C:G>A:T transversions, consistent with the known mutation spectrum of BaP. Mutations predicted to impact protein function occurred in several known and putative cancer drivers including p16, PLCG1, MED12, TAF1 in 184Aa; PIK3CG, HSP90AB1, WHSC1L1, LCP1 in 184Be and FANCA, LPP in 184Ce. Biological processes that typically harbor cancer driver mutations such as cell cycle, regulation of cell death and proliferation, RNA processing, chromatin modification and DNA repair were found to have mutations predicted to impact function in each of the post-stasis strains. Spontaneously immortalized HMEC lines derived from two of the BaP-derived post-stasis strains shared greater than 95% of their BaP-induced mutations with their precursor cells. These immortal HMEC had 10 or fewer additional point mutations relative to their post-stasis precursors, but acquired chromosomal anomalies during immortalization that arose independent of BaP. In conclusion, the results of this study indicate that acute exposures of HMEC to high dose BaP recapitulate mutation patterns of human tumors and can induce mutations in a number of cancer driver genes.« less

  9. 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.

  10. 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

  11. 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.

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

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

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

    2014-10-02

    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 tomore » 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.« less

  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. 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. ...

  15. 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.

  16. A tool for the quantitative spatial analysis of mammary gland epithelium

    SciTech Connect (OSTI)

    Ortiz de Solorzano, Carlos; Fernandez-Gonzalez, Rodrigo

    2004-04-09

    In this paper we present a method for the spatial analysis of complex cellular systems based on a multiscale study of neighborhood relationships. A function to measure those relationships, M, is introduced. The refined Relative Neighborhood Graph is then presented as a method to establish vicinity relationships within layered cellular structures, and particularized to epithelial cell nuclei in the mammary gland. Finally, the method is illustrated with two examples that show interactions within one population of epithelial cells and between two different populations.

  17. 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.

  18. Ionizing radiation predisposes non-malignant human mammaryepithelial cells to undergo TGF beta-induced epithelial to mesenchymaltransition

    SciTech Connect (OSTI)

    Andarawewa, Kumari L.; Erickson, Anna C.; Chou, William S.; Costes, Sylvain; Gascard, Philippe; Mott, Joni D.; Bissell, Mina J.; Barcellos-Hoff, Mary Helen

    2007-04-06

    Transforming growth factor {beta}1 (TGF{beta}) is a tumor suppressor during the initial stage of tumorigenesis, but it can switch to a tumor promoter during neoplastic progression. Ionizing radiation (IR), both a carcinogen and a therapeutic agent, induces TGF{beta}, activation in vivo. We now show that IR sensitizes human mammary epithelial cells (HMEC) to undergo TGF{beta}-mediated epithelial to mesenchymal transition (EMT). Non-malignant HMEC (MCF10A, HMT3522 S1 and 184v) were irradiated with 2 Gy shortly after attachment in monolayer culture, or treated with a low concentration of TGF{beta} (0.4 ng/ml), or double-treated. All double-treated (IR+TGF{beta}) HMEC underwent a morphological shift from cuboidal to spindle-shaped. This phenotype was accompanied by decreased expression of epithelial markers E-cadherin, {beta}-catenin and ZO-1, remodeling of the actin cytoskeleton, and increased expression of mesenchymal markers N-cadherin, fibronectin and vimentin. Furthermore, double-treatment increased cell motility, promoted invasion and disrupted acinar morphogenesis of cells subsequently plated in Matrigel{trademark}. Neither radiation nor TGF{beta} alone elicited EMT, even though IR increased chronic TGF{beta} signaling and activity. Gene expression profiling revealed that double treated cells exhibit a specific 10-gene signature associated with Erk/MAPK signaling. We hypothesized that IR-induced MAPK activation primes non-malignant HMEC to undergo TGF{beta}-mediated EMT. Consistent with this, Erk phosphorylation were transiently induced by irradiation, persisted in irradiated cells treated with TGF{beta}, and treatment with U0126, a Mek inhibitor, blocked the EMT phenotype. Together, these data demonstrate that the interactions between radiation-induced signaling pathways elicit heritable phenotypes that could contribute to neoplastic progression.

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

    SciTech Connect (OSTI)

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

    2008-10-20

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

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

    SciTech Connect (OSTI)

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

    2003-10-31

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

  1. Epithelialmesenchymal transition during oncogenic transformation induced by hexavalent chromium involves reactive oxygen species-dependent mechanism in lung epithelial cells

    SciTech Connect (OSTI)

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

    2013-05-15

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

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

    SciTech Connect (OSTI)

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

    2013-02-01

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

  3. Chronic inorganic arsenic exposure in vitro induces a cancer cell phenotype in human peripheral lung epithelial cells

    SciTech Connect (OSTI)

    Person, Rachel J.; Olive Ngalame, Ntube N.; Makia, Ngome L.; Bell, Matthew W.; Waalkes, Michael P.; Tokar, Erik J.

    2015-07-01

    Inorganic arsenic is a human lung carcinogen. We studied the ability of chronic inorganic arsenic (2 μM; as sodium arsenite) exposure to induce a cancer phenotype in the immortalized, non-tumorigenic human lung peripheral epithelial cell line, HPL-1D. After 38 weeks of continuous arsenic exposure, secreted matrix metalloproteinase-2 (MMP2) activity increased to over 200% of control, levels linked to arsenic-induced cancer phenotypes in other cell lines. The invasive capacity of these chronic arsenic-treated lung epithelial (CATLE) cells increased to 320% of control and colony formation increased to 280% of control. CATLE cells showed enhanced proliferation in serum-free media indicative of autonomous growth. Compared to control cells, CATLE cells showed reduced protein expression of the tumor suppressor gene PTEN (decreased to 26% of control) and the putative tumor suppressor gene SLC38A3 (14% of control). Morphological evidence of epithelial-to-mesenchymal transition (EMT) occurred in CATLE cells together with appropriate changes in expression of the EMT markers vimentin (VIM; increased to 300% of control) and e-cadherin (CDH1; decreased to 16% of control). EMT is common in carcinogenic transformation of epithelial cells. CATLE cells showed increased KRAS (291%), ERK1/2 (274%), phosphorylated ERK (p-ERK; 152%), and phosphorylated AKT1 (p-AKT1; 170%) protein expression. Increased transcript expression of metallothioneins, MT1A and MT2A and the stress response genes HMOX1 (690%) and HIF1A (247%) occurred in CATLE cells possibly in adaptation to chronic arsenic exposure. Thus, arsenic induced multiple cancer cell characteristics in human peripheral lung epithelial cells. This model may be useful to assess mechanisms of arsenic-induced lung cancer. - Highlights: • Chronic arsenic exposure transforms a human peripheral lung epithelia cell line. • Cells acquire characteristics in common with human lung adenocarcinoma cells. • These transformed cells provide a

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

    SciTech Connect (OSTI)

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

    1998-04-24

    Extracellular matrix and extracellular matrix-degrading matrix metalloproteinases play a key role in interactions between the epithelium and the mesenchyme during mammary gland development and disease. In patients with breast cancer, the mammary mesenchyme undergoes a stromal reaction, the etiology of which is unknown. We previously showed that targeting of an autoactivating mutant of the matrix metalloproteinase stromelysin-1 to mammary epithelia of transgenic mice resulted in reduced mammary function during pregnancy and development of preneoplastic and neoplastic lesions. Here we examine the cascade of alterations before breast tumor formation in the mammary gland stroma once the expression of the stromelysin-1 transgene commences. Beginning in postpubertal virgin animals, low levels of transgene expression in mammary epithelia led to increased expression of endogenous stromelysin-1 in stromal fibroblasts and up-regulation of other matrix metalloproteinases, without basement membrane disruption. These changes were accompanied by the progressive development of a compensatory reactive stroma, characterized by increased collagen content and vascularization in glands from virgin mice. This remodeling of the gland affected epithelial-mesenchymal communication as indicated by inappropriate expression of tenascin-C starting by day 6 of pregnancy. This, together with increased transgene expression, led to basement membrane disruption starting by day 15 of pregnancy. We propose that the highly reactive stroma provides a prelude to breast epithelial tumors observed in these animals. Epithelial development depends on an exquisite series of inductive and instructive interactions between the differentiating epithelium and the mesenchymal (stromal) compartment. The epithelium, which consists of luminal and myoepithelial cells, is separated from the stroma by a basement membrane (BM), which plays a central role in mammary gland homeostasis and gene expression. In vivo, stromal

  5. A 3-D Model of Signaling and Transport Pathways in Epithelial Cells

    SciTech Connect (OSTI)

    Quong, A A; Westbrook, C K

    2005-04-01

    A 3-dimensional computer model was developed to simulate the spatial and chemical evolution of calcium ions inside an array of human epithelial kidney cells. This is a prototype model, intended to develop a methodology to incorporate much more complex interactions of metabolic and other processes within many types of cells and lead to increased ability to predict cellular responses to disease as well as to chemical and biological warfare situations. Preliminary tests of the model are described.

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

    SciTech Connect (OSTI)

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

    2011-08-19

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

  7. 14-3-3{sigma} controls corneal epithelial cell proliferation and differentiation through the Notch signaling pathway

    SciTech Connect (OSTI)

    Xin, Ying; Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, 301 E. Muhammad Ali Blvd., Louisville, KY 40202 ; Lu, Qingxian; Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, 301 E. Muhammad Ali Blvd., Louisville, KY 40202; Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, 301 E. Muhammad Ali Blvd., Louisville, KY 40202 ; Li, Qiutang; Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, 301 E. Muhammad Ali Blvd., Louisville, KY 40202

    2010-02-19

    14-3-3{sigma} (also called stratifin) is specifically expressed in the stratified squamous epithelium and its function was recently shown to be linked to epidermal stratification and differentiation in the skin. In this study, we investigated its role in corneal epithelium cell proliferation and differentiation. We showed that the 14-3-3{sigma} mutation in repeated epilation (Er) mutant mice results in a dominant negative truncated protein. Primary corneal epithelial cells expressing the dominant negative protein failed to undergo high calcium-induced cell cycle arrest and differentiation. We further demonstrated that blocking endogenous 14-3-3{sigma} activity in corneal epithelial cells by overexpressing dominative negative 14-3-3{sigma} led to reduced Notch activity and Notch1/2 transcription. Significantly, expression of the active Notch intracellular domain overcame the block in epithelial cell differentiation in 14-3-3{sigma} mutant-expressing corneal epithelial cells. We conclude that 14-3-3{sigma} is critical for regulating corneal epithelial proliferation and differentiation by regulating Notch signaling activity.

  8. 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.

  9. The effect of retinal pigment epithelial cell patch size on growth factor expression

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

    Vargis, Elizabeth A.; Peterson, Cristen B.; Morrell-Falvey, Jennifer L.; Retterer, Scott T.; Collier, Charles Patrick

    2014-01-30

    The spatial organization of retinal pigment epithelial (RPE) cells grown in culture was controlled using micropatterning techniques in order to examine the effect of patch size on cell health and differentiation. Understanding this effect is a critical step in the development of multiplexed high throughput fluidic assays and provides a model for replicating disease states associated with the deterioration of retinal tissue during age-related macular degeneration (AMD). Microcontact printing of fibronectin on polystyrene and glass substrates was used to promote cell attachment, forming RPE patches of controlled size and shape. These colonies mimic the effect of atrophy and loss-of-function thatmore » occurs in the retina during degenerative diseases such as AMD. After 72 hours of cell growth, levels of vascular endothelial growth factor (VEGF), an important biomarker of AMD, were measured. Cells were counted and morphological indicators of cell viability and tight junction formation were assessed via fluorescence microscopy. As a result, up to a twofold increase of VEGF expression per cell was measured as colony size decreased, suggesting that the local microenvironment of, and connections between, RPE cells influences growth factor expression leading to the initiation and progression of diseases such as AMD.« less

  10. Controlling Retinal Pigment Epithelial Cell Patch Size Influences Growth Factor Expression

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

    Vargis, Elizabeth A; Peterson, Cristen B; Morrell-Falvey, Jennifer L; Retterer, Scott T; Collier, Pat

    2014-01-01

    The spatial organization of retinal pigment epithelial (RPE) cells grown in culture was controlled using micropatterning techniques in order to examine the effect of patch size on cell health and differentiation. Understanding this effect is a critical step in the development of multiplexed high throughput fluidic assays and provides a model for replicating disease states associated with the deterioration of retinal tissue during age-related macular degeneration (AMD). Microcontact printing of fibronectin on polystyrene and glass substrates was used to promote cell attachment, forming RPE patches of controlled size and shape. These colonies mimic the effect of atrophy and loss-of-function thatmore » occurs in the retina during degenerative diseases such as AMD. After 72 hours of cell growth, levels of vascular endothelial growth factor (VEGF), an important biomarker of AMD, were measured. Cells were counted and morphological indicators of cell viability and tight junction formation were assessed via fluorescence microscopy. Up to a twofold increase of VEGF expression per cell was measured as colony size decreased, suggesting that the local microenvironment of, and connections between, RPE cells influences growth factor expression leading to the initiation and progression of diseases such as AMD.« less

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

    SciTech Connect (OSTI)

    Machiguchi, Toshihiko Nakamura, Tatsuo

    2013-06-07

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

  12. 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.

  13. Quantitative proteomic analysis of human breast epithelial cells with differential telomere length

    SciTech Connect (OSTI)

    Yu, Li-Rong . E-mail: lyu@ncifcrf.gov; Chan, King C.; Tahara, Hidetoshi; Lucas, David A.; Chatterjee, Koushik; Issaq, Haleem J.; Veenstra, Timothy D. . E-mail: veenstra@ncifcrf.gov

    2007-05-18

    Telomeres play important functional roles in cell proliferation, cell cycle regulation, and genetic stability, in which telomere length is critical. In this study, quantitative proteome comparisons for the human breast epithelial cells with short and long telomeres (184-hTERT{sub L} vs. 184-hTERT{sub S} and 90P-hTERT{sub L} vs. 90P-hTERT{sub S}), resulting from transfection of the human telomerase reverse transcriptase (hTERT) gene, were performed using cleavable isotope-coded affinity tags. More than 2000 proteins were quantified in each comparative experiment, with approximately 77% of the proteins identified in both analyses. In the cells with long telomeres, significant and consistent alterations were observed in metabolism (amino acid, nucleotide, and lipid metabolism), genetic information transmission (transcription and translation regulation, spliceosome and ribosome complexes), and cell signaling. Interestingly, the DNA excision repair pathway is enhanced, while integrin and its ligands are downregulated in the cells with long telomeres. These results may provide valuable information related to telomere functions.

  14. Continuous human cell lines and method of making same

    DOE Patents [OSTI]

    Stampfer, Martha R.

    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.

  15. 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.

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

    SciTech Connect (OSTI)

    Polyak, Kornelia; Hu, Min

    2005-11-18

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

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

    SciTech Connect (OSTI)

    Qayyum, M

    2014-06-01

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

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

    SciTech Connect (OSTI)

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

    2012-11-15

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

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

    SciTech Connect (OSTI)

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

    1980-07-01

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

  20. Effects of phenol on barrier function of a human intestinal epithelial cell line correlate with altered tight junction protein localization

    SciTech Connect (OSTI)

    McCall, Ingrid C.; Betanzos, Abigail; Weber, Dominique A.; Nava, Porfirio; Miller, Gary W.; Parkos, Charles A.

    2009-11-15

    Phenol contamination of soil and water has raised concerns among people living near phenol-producing factories and hazardous waste sites containing the chemical. Phenol, particularly in high concentrations, is an irritating and corrosive substance, making mucosal membranes targets of toxicity in humans. However, few data on the effects of phenol after oral exposure exist. We used an in vitro model employing human intestinal epithelial cells (SK-CO15) cultured on permeable supports to examine effects of phenol on epithelial barrier function. We hypothesized that phenol disrupts epithelial barrier by altering tight junction (TJ) protein expression. The dose-response effect of phenol on epithelial barrier function was determined using transepithelial electrical resistance (TER) and FITC-dextran permeability measurements. We studied phenol-induced changes in cell morphology and expression of several tight junction proteins by immunofluorescence and Western blot analysis. Effects on cell viability were assessed by MTT, Trypan blue, propidium iodide and TUNEL staining. Exposure to phenol resulted in decreased TER and increased paracellular flux of FITC-dextran in a dose-dependent manner. Delocalization of claudin-1 and ZO-1 from TJs to cytosol correlated with the observed increase in permeability after phenol treatment. Additionally, the decrease in TER correlated with changes in the distribution of a membrane raft marker, suggesting phenol-mediated effects on membrane fluidity. Such observations were independent of effects of phenol on cell viability as enhanced permeability occurred at doses of phenol that did not cause cell death. Overall, these findings suggest that phenol may affect transiently the lipid bilayer of the cell membrane, thus destabilizing TJ-containing microdomains.

  1. Biomolecular interactions and responses of human epithelial and macrophage cells to engineered nanomaterials.

    SciTech Connect (OSTI)

    Kotula, Paul Gabriel; Brozik, Susan Marie; Achyuthan, Komandoor E.; Greene, Adrienne Celeste; Timlin, Jerilyn Ann; Bachand, George David; Bachand, Marlene; Aaron, Jesse S.; Allen, Amy; Seagrave, Jean-Clare

    2011-12-01

    Engineered nanomaterials (ENMs) are increasingly being used in commercial products, particularly in the biomedical, cosmetic, and clothing industries. For example, pants and shirts are routinely manufactured with silver nanoparticles to render them 'wrinkle-free.' Despite the growing applications, the associated environmental health and safety (EHS) impacts are completely unknown. The significance of this problem became pervasive within the general public when Prince Charles authored an article in 2004 warning of the potential social, ethical, health, and environmental issues connected to nanotechnology. The EHS concerns, however, continued to receive relatively little consideration from federal agencies as compared with large investments in basic nanoscience R&D. The mounting literature regarding the toxicology of ENMs (e.g., the ability of inhaled nanoparticles to cross the blood-brain barrier; Kwon et al., 2008, J. Occup. Health 50, 1) has spurred a recent realization within the NNI and other federal agencies that the EHS impacts related to nanotechnology must be addressed now. In our study we proposed to address critical aspects of this problem by developing primary correlations between nanoparticle properties and their effects on cell health and toxicity. A critical challenge embodied within this problem arises from the ability to synthesize nanoparticles with a wide array of physical properties (e.g., size, shape, composition, surface chemistry, etc.), which in turn creates an immense, multidimensional problem in assessing toxicological effects. In this work we first investigated varying sizes of quantum dots (Qdots) and their ability to cross cell membranes based on their aspect ratio utilizing hyperspectral confocal fluorescence microscopy. We then studied toxicity of epithelial cell lines that were exposed to different sized gold and silver nanoparticles using advanced imaging techniques, biochemical analyses, and optical and mass spectrometry methods

  2. Computational modeling predicts simultaneous targeting of fibroblasts and epithelial cells is necessary for treatment of pulmonary fibrosis

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

    Warsinske, Hayley C.; Wheaton, Amanda K.; Kim, Kevin K.; Linderman, Jennifer J.; Moore, Bethany B.; Kirschner, Denise E.

    2016-06-23

    Pulmonary fibrosis is pathologic remodeling of lung tissue that can result in difficulty breathing, reduced quality of life, and a poor prognosis for patients. Fibrosis occurs as a result of insult to lung tissue, though mechanisms of this response are not well-characterized. The disease is driven in part by dysregulation of fibroblast proliferation and differentiation into myofibroblast cells, as well as pro-fibrotic mediator-driven epithelial cell apoptosis. The most well-characterized pro-fibrotic mediator associated with pulmonary fibrosis is TGF-β1. Excessive synthesis of, and sensitivity to, pro-fibrotic mediators as well as insufficient production of and sensitivity to anti-fibrotic mediators has been credited withmore » enabling fibroblast accumulation. Available treatments neither halt nor reverse lung damage. In this study we have two aims: to identify molecular and cellular scale mechanisms driving fibroblast proliferation and differentiation as well as epithelial cell survival in the context of fibrosis, and to predict therapeutic targets and strategies. We combine in vitro studies with a multi-scale hybrid agent-based computational model that describes fibroblasts and epithelial cells in co-culture. Within this model TGF-β1 represents a pro-fibrotic mediator and we include detailed dynamics of TGFβ1 receptor ligand signaling in fibroblasts. PGE2 represents an anti-fibrotic mediator. Using uncertainty and sensitivity analysis we identify TGF-β1 synthesis, TGF-β1 activation, and PGE2 synthesis among the key mechanisms contributing to fibrotic outcomes. We further demonstrate that intervention strategies combining potential therapeutics targeting both fibroblast regulation and epithelial cell survival can promote healthy tissue repair better than individual strategies. Combinations of existing drugs and compounds may provide significant improvements to the current standard of care for pulmonary fibrosis. In conclusion, a two-hit therapeutic

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

    SciTech Connect (OSTI)

    Gudjonsson, Thorarinn; Ronnov-Jessen, Lone; Villadsen, Rene; Rank, Fritz; Bissell, Mina J.; Petersen, Ole William

    2001-10-04

    The signals that determine the correct polarity of breast epithelial structures in vivo are not understood. We have shown previously that luminal epithelial cells can be polarized when cultured within a reconstituted basement membrane gel. We reasoned that such cues in vivo may be given by myoepithelial cells. Accordingly, we used an assay where luminal epithelial cells are incorrectly polarized to test this hypothesis. We show that culturing human primary luminal epithelial cells within collagen-I gels leads to formation of structures with no lumina and with reverse polarity as judged by dual stainings for sialomucin, epithelial specific antigen or occludin. No basement membrane is deposited, and {beta}4-integrin staining is negative. Addition of purified human myoepithelial cells isolated from normal glands corrects the inverse polarity, and leads to formation of double-layered acini with central lumina. Among the laminins present in the human breast basement membrane (laminin-1, -5 and -10/11), laminin-1 was unique in its ability to substitute for myoepithelial cells in polarity reversal. Myoepithelial cells were purified also from four different breast cancer sources including a biphasic cell line. Three out of four samples either totally lacked the ability to interact with luminal epithelial cells, or conveyed only correction of polarity in a fraction of acini. This behavior was directly related to the ability of the tumor myoepithelial cells to produce {alpha}-1 chain of laminin. In vivo, breast carcinomas were either negative for laminin-1 (7/12 biopsies) or showed a focal, fragmented deposition of a less intensely stained basement membrane (5/12 biopsies). Dual staining with myoepithelial markers revealed that tumorassociated myoepithelial cells were either negative or weakly positive for expression of laminin-1, establishing a strong correlation between loss of laminin-1 and breast cancer. We conclude that the double-layered breast acinus may be

  4. Reprogramming of cell junction modules during stepwise epithelial to mesenchymal transition and accumulation of malignant features in vitro in a prostate cell model

    SciTech Connect (OSTI)

    Ke, Xi-song; Department of Microbiology, Haukeland, University Hospital, Bergen ; Li, Wen-cheng; Urological Department, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 ; Hovland, Randi; Department of Molecular Biology, University of Bergen, Bergen ; Qu, Yi; Liu, Run-hui; McCormack, Emmet; Thorsen, Frits; Olsen, Jan Roger; Molven, Anders; Department of Pathology, Haukeland University Hospital, Bergen ; Kogan-Sakin, Ira; Rotter, Varda; Akslen, Lars A.; Department of Pathology, Haukeland University Hospital, Bergen ; Oyan, Anne Margrete; Department of Microbiology, Haukeland, University Hospital, Bergen ; Kalland, Karl-Henning; Department of Microbiology, Haukeland, University Hospital, Bergen

    2011-01-15

    Epithelial to mesenchymal transition (EMT) is pivotal in tumor metastasis. Our previous work reported an EMT model based on primary prostate epithelial cells (EP156T) which gave rise to cells with mesenchymal phenotype (EPT1) without malignant transformation. To promote prostate cell transformation, cells were maintained in saturation density cultures to select for cells overriding quiescence. Foci formed repeatedly following around 8 weeks in confluent EPT1 monolayers. Only later passage EPT1, but not EP156T cells of any passage, could form foci. Cells isolated from the foci were named EPT2 and formed robust colonies in soft agar, a malignant feature present neither in EP156T nor in EPT1 cells. EPT2 cells showed additional malignant traits in vitro, including higher ability to proliferate following confluence, higher resistance to apoptosis and lower dependence on exogenous growth factors than EP156T and EPT1 cells. Microarray profiling identified gene sets, many of which belong to cell junction modules, that changed expression from EP156T to EPT1 cells and continued to change from EPT1 to EPT2 cells. Our findings provide a novel stepwise cell culture model in which EMT emerges independently of transformation and is associated with subsequent accumulation of malignant features in prostate cells. Reprogramming of cell junction modules is involved in both steps.

  5. A chemically defined culture medium containing Rho kinase inhibitor Y-27632 for the fabrication of stratified squamous epithelial cell grafts

    SciTech Connect (OSTI)

    Aslanova, Afag; Takagi, Ryo; Yamato, Masayuki; Okano, Teruo; Yamamoto, Masakazu

    2015-05-01

    With the development of a culture method for stratified squamous epithelial cells, tissue-engineered epithelial cell sheets have been successfully applied as clinical cell grafts. However, the implementation of these cell sheets without the use of any animal-derived materials is highly desirable. In this study, Rho-associated protein kinase inhibitor Y-27632 was used to develop a chemically defined culture medium for the fabrication of stratified epithelial cell grafts consisting of human epidermal and oral keratinocytes, and the proliferation activity, cell morphology, and gene expressions of the keratinocytes were analyzed. The results of a colorimetric assay indicated that Y-27632 significantly promoted the proliferation of the keratinocytes in culture media both with and without fetal bovine serum (FBS), although there were no indications of Y-27632 efficacy on cell morphology and stratification of the keratinocytes in culture medium without any animal-derived materials. The results of quantitative RT-PCR revealed that gene expressions correlated with cell adhesion, cell–cell junction, proliferation markers, and stem/progenitor markers in cultured keratinocytes were not strongly affected by the addition of Y-27632 to the culture medium. Moreover, gene expressions of differentiation markers in stratified keratinocytes cultured in medium without FBS were nearly identical to those of keratinocytes co-cultured with 3T3 feeder cells. Interestingly, the expressions of differentiation markers in cultured stratified keratinocytes were suppressed by FBS, whereas they were reconstructed by either co-culture of a 3T3 feeder layer or addition of Y-27632 into the culture medium containing FBS. These findings indicate that Y-27632 is a useful supplement for the development of a chemically defined culture medium for fabrication of stratified epithelial cell grafts for clinical applications for the purpose of developing the culture medium with a lower risk of pathogen

  6. NiO nanoparticles induce apoptosis through repressing SIRT1 in human bronchial epithelial cells

    SciTech Connect (OSTI)

    Duan, Wei-Xia; He, Min-Di; Mao, Lin; Qian, Feng-Hua; Li, Yu-Ming; Pi, Hui-Feng; Liu, Chuan; Chen, Chun-Hai; Lu, Yong-Hui; Cao, Zheng-Wang; Zhang, Lei; Yu, Zheng-Ping; Zhou, Zhou

    2015-07-15

    With application of nano-sized nickel-containing particles (Nano-Ni) expanding, the health concerns about their adverse effects on the pulmonary system are increasing. However, the mechanisms for the pulmonary toxicity of these materials remain unclear. In the present study, we focused on the impacts of NiO nanoparticles (NiONPs) on sirtuin1 (SIRT1), a NAD-dependent deacetylase, and investigated whether SIRT1 was involved in NiONPs-induced apoptosis. Although the NiONPs tended to agglomerate in fluid medium, they still entered into the human bronchial epithelial cells (BEAS-2B) and released Ni{sup 2+} inside the cells. NiONPs at doses of 5, 10, and 20 μg/cm{sup 2} inhibited the cell viability. NiONPs' produced cytotoxicity was demonstrated through an apoptotic process, indicated by increased numbers of Annexin V positive cells and caspase-3 activation. The expression of SIRT1 was markedly down-regulated by the NiONPs, accompanied by the hyperacetylation of p53 (tumor protein 53) and overexpression of Bax (Bcl-2-associated X protein). However, overexpression of SIRT1 through resveratrol treatment or transfection clearly attenuated the NiONPs-induced apoptosis and activation of p53 and Bax. Our results suggest that the repression of SIRT1 may underlie the NiONPs-induced apoptosis via p53 hyperacetylation and subsequent Bax activation. Because SIRT1 participates in multiple biologic processes by deacetylation of dozens of substrates, this knowledge of the impact of NiONPs on SIRT1 may lead to an improved understanding of the toxic mechanisms of Nano-Ni and provide a molecular target to antagonize Nano-Ni toxicity. - Highlights: • NiONPs were taken up by BEAS-2B cells and released Ni{sup 2+}. • NiONPs produced cytotoxicity was demonstrated through an apoptotic process. • NiONPs repressed SIRT1 expression and activated p53 and Bax. • Overexpression of SIRT1 attenuated NiONPs-induced apoptosis via deacetylation p53.

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

    SciTech Connect (OSTI)

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

    2012-08-31

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

  8. Decoupling Internalization, Acidification and Phagosmal-Endosomal/Iysosomal Phagocytosis of Internalin A coated Beads in epithelial cells

    SciTech Connect (OSTI)

    Blanchette, C D; Woo, Y; Thomas, C; Shen, N; Sulchek, T A; Hiddessen, A L

    2008-12-22

    Phagocytosis has been extensively examined in 'professional' phagocytic cells using pH sensitive dyes. However, in many of the previous studies, a separation between the end of internalization, beginning of acidification and completion of phagosomal-endosomal/lysosomal fusion was not clearly established, and in several cases, it was treated as a one-step process. In addition, very little work has been done to systematically examine phagosomal maturation in 'non-professional' phagocytic cells, such as epithelial cells. Therefore, in this study, we developed a simple and novel method to decouple and accurately measure particle internalization, phagosomal acidification and phagosomal-endosomal/lysosomal fusion in Madin-Darby Canine Kidney (MDCK) and Caco-2 epithelial cells. Our method was developed using a pathogen mimetic system consisting of polystyrene beads coated with Internalin A (InlA), a membrane surface protein from Listeria monocytogenes known to trigger receptor-mediated internalization. We achieved independent measurements of the rates of internalization, phagosomal acidification and phagosomal-endosomal/lysosomal fusion in epithelial cells by combining the InlA-coated beads (InlA-beads) with antibody quenching, pH sensitive dyes and endosomal/lysosomal dyes, as follows: the rate of InlA bead internalization was measured via antibody quenching of a pH independent dye (Alexa488) conjugated to InlA-beads, the rate at which phagosomes containing internalized InlA beads became acidified was measured using a pH dependent dye (FITC) conjugated to the beads and the rate of phagosomal-endosomal/lysosomal fusion was measured using a combination of unlabeled InlA-beads and an endosomal/lysosomal dye. By performing these independent measurements under identical experimental conditions, we were able to decouple the three processes and establish time scales for each. In a separate set of experiments, we also exploited the phagosomal acidification process to demonstrate

  9. 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

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

    SciTech Connect (OSTI)

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

    2013-10-01

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

  11. Cell shape regulates global histone acetylation in human mammaryepithelial cells

    SciTech Connect (OSTI)

    Le Beyec, Johanne; Xu, Ren; Lee, Sun-Young; Nelson, Celeste M.; Rizki, Aylin; Alcaraz, Jordi; Bissell, Mina J.

    2007-02-28

    Extracellular matrix (ECM) regulates cell morphology and gene expression in vivo; these relationships are maintained in three-dimensional (3D) cultures of mammary epithelial cells. In the presence of laminin-rich ECM (lrECM), mammary epithelial cells round up and undergo global histone deacetylation, a process critical for their functional differentiation. However, it remains unclear whether lrECM-dependent cell rounding and global histone deacetylation are indeed part of a common physical-biochemical pathway. Using 3D cultures as well as nonadhesive and micropatterned substrata, here we showed that the cell 'rounding' caused by lrECM was sufficient to induce deacetylation of histones H3 and H4 in the absence of biochemical cues. Microarray and confocal analysis demonstrated that this deacetylation in 3D culture is associated with a global increase in chromatin condensation and a reduction in gene expression. Whereas cells cultured on plastic substrata formed prominent stress fibers, cells grown in 3D lrECM or on micropatterns lacked these structures. Disruption of the actin cytoskeleton with cytochalasin D phenocopied the lrECM-induced cell rounding and histone deacetylation. These results reveal a novel link between ECM-controlled cell shape and chromatin structure, and suggest that this link is mediated by changes in the actin cytoskeleton.

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

    SciTech Connect (OSTI)

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

    2015-09-15

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

  13. Silencing heme oxygenase-1 gene expression in retinal pigment epithelial cells inhibits proliferation, migration and tube formation of cocultured endothelial cells

    SciTech Connect (OSTI)

    Zhang, Wenjie; Zhang, Xiaomei; Lu, Hong; Matsukura, Makoto; Zhao, Jien; Shinohara, Makoto

    2013-05-10

    Highlights: •HO-1 is highly induced in RPE cells by hypoxia. •Inhibition of HO-1 activity and knockdown of HO-1 expression inhibit VEGF expression in RPE cells under hypoxia. •Knockdown of HO-1 in RPE cells inhibits angiogenesis of endothelial cells in vitro. -- Abstract: Heme oxygenase-1 (HO-1) plays an important role in the vasculature and in the angiogenesis of tumors, wounds and other environments. Retinal pigment epithelial (RPE) cells and choroidal endothelial cells (CECs) are the main cells involved in choroidal neovascularization (CNV), a process in which hypoxia plays an important role. Our aim was to evaluate the role of human RPE-cell HO-1 in the angiogenic activities of cocultured endothelial cells under hypoxia. Small interfering RNA (siRNA) for HO-1 was transfected into human RPE cell line ARPE-19, and zinc protoporphyrin (ZnPP) was used to inhibit HO-1 activity. Knockdown of HO-1 expression and inhibition of HO-1 activity resulted in potent reduction of the expression of vascular endothelial growth factor (VEGF) under hypoxia. Furthermore, knockdown of HO-1 suppressed the proliferation, migration and tube formation of cocultured endothelial cells. These findings indicated that HO-1 might have an angiogenic effect in CNV through modulation of VEGF expression and might be a potential target for treating CNV.

  14. Luteolin inhibits Cr(VI)-induced malignant cell transformation of human lung epithelial cells by targeting ROS mediated multiple cell signaling pathways

    SciTech Connect (OSTI)

    Pratheeshkumar, Poyil; Son, Young-Ok; Divya, Sasidharan Padmaja; Roy, Ram Vinod; Hitron, John Andrew; Wang, Lei; Kim, Donghern; Dai, Jin; Asha, Padmaja; Zhang, Zhuo; Wang, Yitao; Shi, Xianglin

    2014-12-01

    Hexavalent chromium [Cr(VI)] is a well-known human carcinogen associated with the incidence of lung cancer. Inhibition of metal induced carcinogenesis by a dietary antioxidant is a novel approach. Luteolin, a natural dietary flavonoid found in fruits and vegetables, possesses potent antioxidant and anti-inflammatory activity. We found that short term exposure of human bronchial epithelial cells (BEAS-2B) to Cr(VI) (5 μM) showed a drastic increase in ROS generation, NADPH oxidase (NOX) activation, lipid peroxidation, and glutathione depletion, which were significantly inhibited by the treatment with luteolin in a dose dependent manner. Treatment with luteolin decreased AP-1, HIF-1α, COX-2, and iNOS promoter activity induced by Cr(VI) in BEAS-2B cells. In addition, luteolin protected BEAS-2B cells from malignant transformation induced by chronic Cr(VI) exposure. Moreover, luteolin also inhibited the production of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α) and VEGF in chronic Cr(VI) exposed BEAS-2B cells. Western blot analysis showed that luteolin inhibited multiple gene products linked to survival (Akt, Fak, Bcl-2, Bcl-xL), inflammation (MAPK, NF-κB, COX-2, STAT-3, iNOS, TNF-α) and angiogenesis (HIF-1α, VEGF, MMP-9) in chronic Cr(VI) exposed BEAS-2B cells. Nude mice injected with BEAS-2B cells chronically exposed to Cr(VI) in the presence of luteolin showed reduced tumor incidence compared to Cr(VI) alone treated group. Overexpression of catalase (CAT) or SOD2, eliminated Cr(VI)-induced malignant transformation. Overall, our results indicate that luteolin protects BEAS-2B cells from Cr(VI)-induced carcinogenesis by scavenging ROS and modulating multiple cell signaling mechanisms that are linked to ROS. Luteolin, therefore, serves as a potential chemopreventive agent against Cr(VI)-induced carcinogenesis. - Highlights: • Luteolin inhibited Cr(VI)-induced oxidative stress. • Luteolin inhibited chronic Cr(VI)-induced malignant transformation.

  15. EGFR tyrosine kinase inhibitory peptide attenuates Helicobacter pylori-mediated hyper-proliferation in AGS enteric epithelial cells

    SciTech Connect (OSTI)

    Himaya, S.W.A.; Dewapriya, Pradeep; Kim, Se-Kwon

    2013-06-15

    Helicobacter pylori infection is one of the most critical causes of stomach cancer. The current study was conducted to explore the protective effects of an isolated active peptide H-P-6 (Pro-Gln-Pro-Lys-Val-Leu-Asp-Ser) from microbial hydrolysates of Chlamydomonas sp. against H. pylori-induced carcinogenesis. The peptide H-P-6 has effectively suppressed H. pylori-induced hyper-proliferation and migration of gastric epithelial cells (AGS). However, the peptide did not inhibit the viability of the bacteria or invasion into AGS cells. Therefore, the effect of the peptide on regulating H. pylori-induced molecular signaling was investigated. The results indicated that H. pylori activates the EGFR tyrosine kinase signaling and nuclear translocation of the ?-catenin. The EGFR activation has led to the up-regulation of PI3K/Akt signaling pathway. Moreover, the nuclear translocation levels of ?-catenin were significantly increased as a result of Akt mediated down-regulation of GSK3/? protein levels in the cytoplasm. Both of these consequences have resulted in increased expression of cell survival and migration related genes such as c-Myc, cyclin-D, MMP-2 and matrilysin. Interestingly, the isolated peptide potently inhibited H. pylori-mediated EGFR activation and thereby down-regulated the subsequent P13K/Akt signaling leading to ?-catenin nuclear translocation. The effect of the peptide was confirmed with the use of EGFR tyrosine kinase inhibitor AG1487 and molecular docking studies. Collectively this study identifies a potent peptide which regulates the H. pylori-induced hyper-proliferation and migration of AGS cells at molecular level. - Highlights: Chlamydomonas sp. derived peptide H-P-6 inhibits H. pylori-induced pathogenesis. H-P-6 suppresses H. pylori-induced hyper-proliferation and migration of AGS cells. The peptide inhibits H. pylori-induced EGFR activation.

  16. Mammalian aPKC/Par polarity complex mediated regulation of epithelial division orientation and cell fate

    SciTech Connect (OSTI)

    Vorhagen, Susanne; Niessen, Carien M.

    2014-11-01

    Oriented cell division is a key regulator of tissue architecture and crucial for morphogenesis and homeostasis. Balanced regulation of proliferation and differentiation is an essential property of tissues not only to drive morphogenesis but also to maintain and restore homeostasis. In many tissues orientation of cell division is coupled to the regulation of differentiation producing daughters with similar (symmetric cell division, SCD) or differential fate (asymmetric cell division, ACD). This allows the organism to generate cell lineage diversity from a small pool of stem and progenitor cells. Division orientation and/or the ratio of ACD/SCD need to be tightly controlled. Loss of orientation or an altered ratio can promote overgrowth, alter tissue architecture and induce aberrant differentiation, and have been linked to morphogenetic diseases, cancer and aging. A key requirement for oriented division is the presence of a polarity axis, which can be established through cell intrinsic and/or extrinsic signals. Polarity proteins translate such internal and external cues to drive polarization. In this review we will focus on the role of the polarity complex aPKC/Par3/Par6 in the regulation of division orientation and cell fate in different mammalian epithelia. We will compare the conserved function of this complex in mitotic spindle orientation and distribution of cell fate determinants and highlight common and differential mechanisms in which this complex is used by tissues to adapt division orientation and cell fate to the specific properties of the epithelium.

  17. Exploring the potential role of tungsten carbide cobalt (WC-Co) nanoparticle internalization in observed toxicity toward lung epithelial cells in vitro

    SciTech Connect (OSTI)

    Armstead, Andrea L.; Arena, Christopher B.; Li, Bingyun

    2014-07-01

    Tungsten carbide cobalt (WC-Co) has been recognized as a workplace inhalation hazard in the manufacturing, mining and drilling industries by the National Institute of Occupational Safety and Health. Exposure to WC-Co is known to cause “hard metal lung disease” but the relationship between exposure, toxicity and development of disease remain poorly understood. To better understand this relationship, the present study examined the role of WC-Co particle size and internalization on toxicity using lung epithelial cells. We demonstrated that nano- and micro-WC-Co particles exerted toxicity in a dose- and time-dependent manner and that nano-WC-Co particles caused significantly greater toxicity at lower concentrations and shorter exposure times compared to micro-WC-Co particles. WC-Co particles in the nano-size range (not micron-sized) were internalized by lung epithelial cells, which suggested that internalization may play a key role in the enhanced toxicity of nano-WC-Co particles over micro-WC-Co particles. Further exploration of the internalization process indicated that there may be multiple mechanisms involved in WC-Co internalization such as actin and microtubule based cytoskeletal rearrangements. These findings support our hypothesis that WC-Co particle internalization contributes to cellular toxicity and suggest that therapeutic treatments inhibiting particle internalization may serve as prophylactic approaches for those at risk of WC-Co particle exposure. - Highlights: • Hard metal (WC-Co) particle toxicity was established in lung epithelial cells. • Nano-WC-Co particles caused greater toxicity than micro-WC-Co particles. • Nano- and micro-WC-Co particles were capable of inducing cellular apoptosis. • Nano-WC-Co particles were internalized by lung epithelial cells. • WC-Co particle internalization was mediated by actin dynamics.

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. Sofalcone, a gastric mucosa protective agent, increases vascular endothelial growth factor via the Nrf2-heme-oxygenase-1 dependent pathway in gastric epithelial cells

    SciTech Connect (OSTI)

    Shibuya, Akiko; Onda, Kenji; Kawahara, Hirofumi; Uchiyama, Yuka; Nakayama, Hiroko; Omi, Takamasa; Nagaoka, Masayoshi; Matsui, Hirofumi; Hirano, Toshihiko

    2010-07-30

    Research highlights: {yields} Sofalcone increases HO-1 in gastric epithelial cells. {yields} The induction of HO-1 by sofalcone treatment follows the activation of Nrf2. {yields} The production of VEGF by sofalcone treatment is mediated by HO-1 induction. -- Abstract: Sofalcone, 2'-carboxymethoxy-4,4-bis(3-methyl-2-butenyloxy)chalcone, is an anti-ulcer agent that is classified as a gastric mucosa protective agent. Recent studies indicate heat shock proteins such as HSP32, also known as heme-oxygenase-1(HO-1), play important roles in protecting gastrointestinal tissues from several stresses. We have previously reported that sofalcone increases the expression of HO-1 in adipocytes and pre-adipocytes, although the effect of sofalcone on HO-1 induction in gastrointestinal tissues is not clear. In the current study, we investigated the effects of sofalcone on the expression of HO-1 and its functional role in rat gastric epithelial (RGM-1) cells. We found that sofalcone increased HO-1 expression in RGM-1 cells in both time- and concentration-dependent manners. The HO-1 induction was associated with the nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in RGM-1 cells. We also observed that sofalcone increased vascular endothelial growth factor (VEGF) production in the culture medium. Treatment of RGM-1 cells with an HO-1 inhibitor (tin-protoporphyrin), or HO-1 siRNA inhibited sofalcone-induced VEGF production, suggesting that the effect of sofalcone on VEGF expression is mediated by the HO-1 pathway. These results suggest that the gastroprotective effects of sofalcone are partly exerted via Nrf2-HO-1 activation followed by VEGF production.

  3. The effect of DDT and its metabolite (DDE) on prostaglandin secretion from epithelial cells and on contractions of the smooth muscle of the bovine oviduct in vitro

    SciTech Connect (OSTI)

    Wrobel, Michal H.; Mlynarczuk, Jaroslaw; Kotwica, Jan

    2012-03-01

    The insecticide DDT and its metabolite (DDE), due to their lipolytic nature and resistance to biodegradation, are accumulated in the living tissues. In cows, DDT and DDE were found to affect prostaglandin (PG) secretion from the endometrium and contractions of the myometrium. In this study, the impact of both xenobiotics (0.1, 1, 10 or 100 ng/ml) on the function of epithelial cells and muscle strips of bovine oviducts from 1 to 5 day of the oestrous cycle was examined. Therefore the concentration of PGE2 and PGFM (a metabolite of PGF2α) in culture media, mRNA expression of genes involved in PGs synthesis in epithelial cells and the force and amplitude of strips contractions were measured after 2 and 24 or 48 h of incubation. Neither DDT nor DDE affected the viability of cells after 48 h (P > 0.05). Both DDT and DDE increased the concentrations of PGFM in culture medium and secretion of PGE2 after only 2 h of cell culture (P < 0.05). Similar effects were seen for the influence of DDE on amount of PGFM after 48 h, while DDT decreased secretion of PGE2 (P < 0.05). DDT after 2 h increased (P < 0.05) mRNA expression of PGF2α synthase (PGFS), while both xenobiotics decreased (P < 0.05) mRNA expression of cyclooxygenase-2 (COX-2) after 24 h. DTT also increased the force of isthmus contractions after 2 h, as did both xenobiotics after 48 h (P < 0.05). Moreover, after 2 and 48 h, DDE stimulated the amplitude of contractions of the isthmus as well as the ampulla, (P < 0.05). The effect of both compounds on oviduct contractions was diminished by indomethacin, which blocks PG synthesis. We conclude that oviductal secretion of prostaglandins is affected, by DDT and DDE. The influence of these xenobiotics on PGF2α and PGE2 secretion and ratio may be part of the mechanism by which both DDT and its metabolite disturb the contractions of oviductal muscle. -- Highlights: ► DDT and its metabolite – DDE are accumulated in the living tissues. ► The insecticides affected PGF2

  4. 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.

  5. Development of Na/sup +/-dependent hexose transport in cultured renal epithelial cells (LLC-PK/sub 1/)

    SciTech Connect (OSTI)

    Weiss, E.R.; Amsler, K.; Dawson, W.D.; Cook, J.S.

    1984-01-01

    A number of factors were explored to analyze how they interact to yield the increasing transport capacity in differentiating cell populations. These factors include the number of functional transporters in the population, the distribution of these transporters among the individual cells, the Na/sup +/ chemical gradient, the transmembrane potential, the pathways and activities of these pathways for efflux of glucoside, and cell-cell coupling between accumulating and non-accumulating cells. 35 references, 9 figures, 2 tables. (ACR)

  6. Disruption of polyubiquitin gene Ubc leads to defective proliferation of hepatocytes and bipotent fetal liver epithelial progenitor cells

    SciTech Connect (OSTI)

    Park, Hyejin; Yoon, Min-Sik; Ryu, Kwon-Yul

    2013-06-07

    Highlights: Proliferation capacity of Ubc{sup ?/?} FLCs was reduced during culture in vitro. Ubc is required for proliferation of both hepatocytes and bipotent FLEPCs. Bipotent FLEPCs exhibit highest Ubc transcription and proliferation capacity. Cell types responsible for Ubc{sup ?/?} fetal liver developmental defect were identified. -- Abstract: We have previously demonstrated that disruption of polyubiquitin gene Ubc leads to mid-gestation embryonic lethality most likely due to a defect in fetal liver development, which can be partially rescued by ectopic expression of Ub. In a previous study, we assessed the cause of embryonic lethality with respect to the fetal liver hematopoietic system. We confirmed that Ubc{sup ?/?} embryonic lethality could not be attributed to impaired function of hematopoietic stem cells, which raises the question of whether or not FLECs such as hepatocytes and bile duct cells, the most abundant cell types in the liver, are affected by disruption of Ubc and contribute to embryonic lethality. To answer this, we isolated FLCs from E13.5 embryos and cultured them in vitro. We found that proliferation capacity of Ubc{sup ?/?} cells was significantly reduced compared to that of control cells, especially during the early culture period, however we did not observe the increased number of apoptotic cells. Furthermore, levels of Ub conjugate, but not free Ub, decreased upon disruption of Ubc expression in FLCs, and this could not be compensated for by upregulation of other poly- or mono-ubiquitin genes. Intriguingly, the highest Ubc expression levels throughout the entire culture period were observed in bipotent FLEPCs. Hepatocytes and bipotent FLEPCs were most affected by disruption of Ubc, resulting in defective proliferation as well as reduced cell numbers in vitro. These results suggest that defective proliferation of these cell types may contribute to severe reduction of fetal liver size and potentially mid-gestation lethality of Ubc

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

    SciTech Connect (OSTI)

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

    2002-06-30

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

  8. 3,5,4?-Trimethoxystilbene, a natural methoxylated analog of resveratrol, inhibits breast cancer cell invasiveness by downregulation of PI3K/Akt and Wnt/?-catenin signaling cascades and reversal of epithelialmesenchymal transition

    SciTech Connect (OSTI)

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

    2013-11-01

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

  9. 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.

  10. High-Dose Estrogen and Clinical Selective Estrogen Receptor Modulators Induce Growth Arrest, p21, and p53 in Primate Ovarian Surface Epithelial Cells

    SciTech Connect (OSTI)

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

    2005-06-09

    Ovarian cancer is the most lethal gynecological cancer affecting women. Hormone-based therapies are variably successful in treating ovarian cancer, but the reasoning behind these therapies is paradoxical. Clinical reagents such as tamoxifen are considered to inhibit or reverse tumor growth by competitive inhibition of the estrogen receptor (ER); however high dose estrogen is as clinically effective as tamoxifen, and it is unlikely that estrogen is acting by blocking ER activity; however, it may be activating a unique function of the ER that is nonmitogenic. For poorly defined reasons, 90% of varian cancers derive from the ovarian surface epithelium (OSE). In vivo the ER-positive OSE is exposed to high estrogen levels, reaching micromolar concentrations in dominant ovarian follicles. Using cultured OSE cells in vitro, we show that these levels of estradiol (1 ug/ml; {approx}3um) block the actions of serum growth factors, activate the G1 phase retinoblastoma AQ:A checkpoint, and induce p21, an inhibitor of kinases that normally inactivate the retinoblastoma checkpoint. We also show that estradiol increases p53 levels, which may contribute to p21 induction. Supporting the hypothesis that clinical selective ER modulators activate this novel ER function, we find that micromolar doses of tamoxifen and the ''pure antiestrogen'' ICI 182,780 elicit the same effects as estradiol. We propose that, in the context of proliferation, these data clarify some paradoxical aspects of hormone-based therapy and suggest that fuller understanding of normal ER function is necessary to improve therapeutic strategies that target the ER. (J Clin Endocrinol Metab 90: 0000-0000, 2005)

  11. Alveolocapillary model system to study alveolar re-epithelialization

    SciTech Connect (OSTI)

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

    2013-01-01

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

  12. Distinct Luminal-Type Mammary Carcinomas Arise from Orthotopic Trp53-Null Mammary Transplantation of Juvenile versus Adult Mice

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

    Nguyen, David H.; Ouyang, Haoxu; Mao, Jian-Hua; Hlatky, Lynn; Barcellos-Hoff, M. H.

    2014-12-01

    Age and physiologic status, such as menopause, are risk factors for breast cancer. Less clear is what factors influence the diversity of breast cancer. In this study, we investigated the effect of host age on the distribution of tumor subtypes in mouse mammary chimera consisting of wild-type hosts and Trp53 nullizygous epithelium, which undergoes a high rate of neoplastic transformation. Wild-type mammary glands cleared of endogenous epithelium at 3 weeks of age were subsequently transplanted during puberty (5 weeks) or at maturation (10 weeks) with syngeneic Trp53-null mammary tissue fragments and monitored for one year. Tumors arose sooner from adultmore » hosts (AH) compared with juvenile hosts (JH). However, compared with AH tumors, JH tumors grew several times faster, were more perfused, exhibited a two-fold higher mitotic index, and were more highly positive for insulin-like growth factor receptor phosphorylation. Most tumors in each setting were estrogen receptor (ER)-positive (80% JH vs. 70% AH), but JH tumors were significantly more ER-immunoreactive (P = 0.0001) than AH tumors. A differential expression signature (JvA) of juvenile versus adult tumors revealed a luminal transcriptional program. Centroids of the human homologs of JvA genes showed that JH tumors were more like luminal A tumors and AH tumors were more like luminal B tumors. Hierarchical clustering with the JvA human ortholog gene list segregated luminal A and luminal B breast cancers across datasets. Lastly, these data support the notion that age-associated host physiology greatly influences the intrinsic subtype of breast cancer.« less

  13. A new role of SNAI2 in postlactational involution of the mammary gland links it to luminal breast cancer development

    SciTech Connect (OSTI)

    Castillo-Lluva, Sonia; Hontecillas-Prieto, Lourdes; Blanco-Gómez, Adrian; del Mar Sáez-Freire, María; García-Cenador, Begona; García-Criado, Javier; Pérez-Andrés, Martín; Orfao, Alberto; Cañamero, Marta; Mao, Jian-Hua; Gridley, Thomas; Castellanos-Martín, Andres; Pérez-Losada, Jesus

    2015-06-22

    Breast cancer is a major cause of mortality in women. The transcription factor SNAI2 has been implicated in the pathogenesis of several types of cancer, including breast cancer of basal origin. Here we show that SNAI2 is also important in the development of breast cancer of luminal origin in MMTV-ErbB2 mice. SNAI2 deficiency leads to longer latency and fewer luminal tumors, both of these being characteristics of pretumoral origin. These effects were associated with reduced proliferation and a decreased ability to generate mammospheres in normal mammary glands. However, the capacity to metastasize was not modified. Under conditions of increased ERBB2 oncogenic activity after pregnancy plus SNAI2 deficiency, both pretumoral defects-latency and tumor load-were compensated. However, the incidence of lung metastases was dramatically reduced. Furthermore, SNAI2 was required for proper postlactational involution of the breast. At 3 days post lactational involution, the mammary glands of Snai2-deficient mice exhibited lower levels of pSTAT3 and higher levels of pAKT1, resulting in decreased apoptosis. Abundant noninvoluted ducts were still present at 30 days post lactation, with a greater number of residual ERBB2+ cells. These results suggest that this defect in involution leads to an increase in the number of susceptible target cells for transformation, to the recovery of the capacity to generate mammospheres and to an increase in the number of tumors. In conclusion, our work demonstrates the participation of SNAI2 in the pathogenesis of luminal breast cancer, and reveals an unexpected connection between the processes of postlactational involution and breast tumorigenesis in Snai2-null mutant mice.

  14. A new role of SNAI2 in postlactational involution of the mammary gland links it to luminal breast cancer development

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

    Castillo-Lluva, Sonia; Hontecillas-Prieto, Lourdes; Blanco-Gómez, Adrian; del Mar Sáez-Freire, María; García-Cenador, Begona; García-Criado, Javier; Pérez-Andrés, Martín; Orfao, Alberto; Cañamero, Marta; Mao, Jian-Hua; et al

    2015-06-22

    Breast cancer is a major cause of mortality in women. The transcription factor SNAI2 has been implicated in the pathogenesis of several types of cancer, including breast cancer of basal origin. Here we show that SNAI2 is also important in the development of breast cancer of luminal origin in MMTV-ErbB2 mice. SNAI2 deficiency leads to longer latency and fewer luminal tumors, both of these being characteristics of pretumoral origin. These effects were associated with reduced proliferation and a decreased ability to generate mammospheres in normal mammary glands. However, the capacity to metastasize was not modified. Under conditions of increased ERBB2more » oncogenic activity after pregnancy plus SNAI2 deficiency, both pretumoral defects-latency and tumor load-were compensated. However, the incidence of lung metastases was dramatically reduced. Furthermore, SNAI2 was required for proper postlactational involution of the breast. At 3 days post lactational involution, the mammary glands of Snai2-deficient mice exhibited lower levels of pSTAT3 and higher levels of pAKT1, resulting in decreased apoptosis. Abundant noninvoluted ducts were still present at 30 days post lactation, with a greater number of residual ERBB2+ cells. These results suggest that this defect in involution leads to an increase in the number of susceptible target cells for transformation, to the recovery of the capacity to generate mammospheres and to an increase in the number of tumors. In conclusion, our work demonstrates the participation of SNAI2 in the pathogenesis of luminal breast cancer, and reveals an unexpected connection between the processes of postlactational involution and breast tumorigenesis in Snai2-null mutant mice.« less

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

    SciTech Connect (OSTI)

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

    2015-03-09

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

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

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

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

    2015-03-09

    The interplay between host genetics, tumor microenvironment and environmental exposure in cancer susceptibility remains poorly understood. Here we assessed the genetic control of stromal mediation of mammary tumor susceptibility to low dose ionizing radiation (LDIR) using backcrossed F1 into BALB/c (F1Bx) between cancer susceptible (BALB/c) and resistant (SPRET/EiJ) mouse strains. Tumor formation was evaluated after transplantation of non-irradiated Trp53-/- BALB/c mammary gland fragments into cleared fat pads of F1Bx hosts. Genome-wide linkage analysis revealed 2 genetic loci that constitute the baseline susceptibility via host microenvironment. However, once challenged with LDIR, we discovered 13 additional loci that were enriched for genesmore » involved in cytokines, including TGFβ1 signaling. Surprisingly, LDIR-treated F1Bx cohort significantly reduced incidence of mammary tumors from Trp53-/- fragments as well as prolonged tumor latency, compared to sham-treated controls. We demonstrated further that plasma levels of specific cytokines were significantly correlated with tumor latency. Using an ex vivo 3-D assay, we confirmed TGFβ1 as a strong candidate for reduced mammary invasion in SPRET/EiJ, which could explain resistance of this strain to mammary cancer risk following LDIR. Our results open possible new avenues to understand mechanisms of genes operating via the stroma that affect cancer risk from external environmental exposures.« less

  17. Ganodermanontriol (GDNT) exerts its effect on growth and invasiveness of breast cancer cells through the down-regulation of CDC20 and uPA

    SciTech Connect (OSTI)

    Jiang, Jiahua; Jedinak, Andrej; Sliva, Daniel; Department of Medicine, School of Medicine, Indiana University, Indianapolis, IN; Indiana University Simon Cancer Center, School of Medicine, Indiana University, Indianapolis, IN

    2011-11-18

    Highlights: Black-Right-Pointing-Pointer Ganodermanontriol (GDNT), a Ganoderma mushroom alcohol, inhibits growth of breast cancer cells. Black-Right-Pointing-Pointer CDC20 is over-expressed in tumors but not in the tumor surrounding tissue in breast cancer patients. Black-Right-Pointing-Pointer GDNT inhibits expression of CDC20 in breast cancer cells. Black-Right-Pointing-Pointer GDNT inhibits cell adhesion, cell migration and cell invasion of breast cancer cells. Black-Right-Pointing-Pointer GDNT inhibits secretion of uPA and down-regulates expression of uPAR in breast cancer cells. -- Abstract: Ganoderma lucidum is a medicinal mushroom that has been recognized by Traditional Chinese Medicine (TCM). Although some of the direct anticancer activities are attributed to the presence of triterpenes-ganoderic and lucidenic acids-the activity of other compounds remains elusive. Here we show that ganodermanontriol (GDNT), a Ganoderma alcohol, specifically suppressed proliferation (anchorage-dependent growth) and colony formation (anchorage-independent growth) of highly invasive human breast cancer cells MDA-MB-231. GDNT suppressed expression of the cell cycle regulatory protein CDC20, which is over-expressed in precancerous and breast cancer cells compared to normal mammary epithelial cells. Moreover, we found that CDC20 is over-expressed in tumors when compared to the tissue surrounding the tumor in specimens from breast cancer patients. GDNT also inhibited invasive behavior (cell adhesion, cell migration, and cell invasion) through the suppression of secretion of urokinase-plasminogen activator (uPA) and inhibited expression of uPA receptor. In conclusion, mushroom GDNT is a natural agent that has potential as a therapy for invasive breast cancers.

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

    DOE Patents [OSTI]

    Hu, Zhi; Kuo, Wen-Lin; Neve, Richard M.; Gray, Joe W.

    2012-06-12

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

  19. Sox5 induces epithelial to mesenchymal transition by transactivation of Twist1

    SciTech Connect (OSTI)

    Pei, Xin-Hong; Lv, Xin-Quan; Li, Hui-Xiang

    2014-03-28

    Highlights: • Depletion of Sox5 inhibits breast cancer proliferation, migration, and invasion. • Sox5 transactivates Twist1 expression. • Sox5 induces epithelial to mesenchymal transition through transactivation of Twist1 expression. - Abstract: The epithelial to mesenchymal transition (EMT), a highly conserved cellular program, plays an important role in normal embryogenesis and cancer metastasis. Twist1, a master regulator of embryonic morphogenesis, is overexpressed in breast cancer and contributes to metastasis by promoting EMT. In exploring the mechanism underlying the increased Twist1 in breast cancer cells, we found that the transcription factor SRY (sex-determining region Y)-box 5(Sox5) is up-regulation in breast cancer cells and depletion of Sox5 inhibits breast cancer cell proliferation, migration, and invasion. Furthermore, depletion of Sox5 in breast cancer cells caused a dramatic decrease in Twist1 and chromosome immunoprecipitation assay showed that Sox5 can bind directly to the Twist1 promoter, suggesting that Sox5 transactivates Twist1 expression. We further demonstrated that knockdown of Sox5 up-regulated epithelial phenotype cell biomarker (E-cadherin) and down-regulated mesenchymal phenotype cell biomarkers (N-cadherin, Vimentin, and Fibronectin 1), resulting in suppression of EMT. Our study suggests that Sox5 transactivates Twist1 expression and plays an important role in the regulation of breast cancer progression.

  20. 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.

  1. A lincRNA connected to cell mortality and epigenetically-silenced in most common human cancers

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

    Vrba, Lukas; Garbe, James C.; Stampfer, Martha R.; Futscher, Bernard W.

    2015-10-19

    Immortality is an essential characteristic of human carcinoma cells. We recently developed an efficient, reproducible method that immortalizes human mammary epithelial cells (HMEC) in the absence of gross genomic changes by targeting 2 critical senescence barriers. Consistent transcriptomic changes associated with immortality were identified using microarray analysis of isogenic normal finite pre-stasis, abnormal finite post-stasis, and immortal HMECs from 4 individuals. A total of 277 genes consistently changed in cells that transitioned from post-stasis to immortal. Gene ontology analysis of affected genes revealed biological processes significantly altered in the immortalization process. These immortalization-associated changes showed striking similarity to the genemore » expression changes seen in The Cancer Genome Atlas (TCGA) clinical breast cancer data. The most dramatic change in gene expression seen during the immortalization step was the downregulation of an unnamed, incompletely annotated transcript that we called MORT, for mortality, since its expression was closely associated with the mortal, finite lifespan phenotype. We show here that MORT (ZNF667-AS1) is expressed in all normal finite lifespan human cells examined to date and is lost in immortalized HMEC. MORT gene silencing at the mortal/immortal boundary was due to DNA hypermethylation of its CpG island promoter. This epigenetic silencing is also seen in human breast cancer cell lines and in a majority of human breast tumor tissues. The functional importance of DNA hypermethylation in MORT gene silencing is supported by the ability of 5-aza-2'- deoxycytidine to reactivate MORT expression. Analysis of TCGA data revealed deregulation of MORT expression due to DNA hypermethylation in 15 out of the 17 most common human cancers. In conclusion, the epigenetic silencing of MORT in a large majority of the common human cancers suggests a potential fundamental role in cellular immortalization during human

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

    SciTech Connect (OSTI)

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

    2015-06-24

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

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

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

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

    2015-06-24

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

  4. YY1 modulates taxane response in epithelial ovarian cancer

    SciTech Connect (OSTI)

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

    2008-10-10

    The results of this study show that a high YY1 gene signature (characterized by coordinate elevated expression of transcription factor YY1 and putative YY1 target genes) within serous epithelial ovarian cancers is associated with enhanced response to taxane-based chemotherapy and improved survival. If confirmed in a prospective study, these results have important implications for the potential future use of individualized therapy in treating patients with ovarian cancer. Identification of the YY1 gene signature profile within a tumor prior to initiation of chemotherapy may provide valuable information about the anticipated response of these tumors to taxane-based drugs, leading to better informed decisions regarding chemotherapeutic choice. Survival of ovarian cancer patients is largely dictated by their response to chemotherapy, which depends on underlying molecular features of the malignancy. We previously identified YIN YANG 1 (YY1) as a gene whose expression is positively correlated with ovarian cancer survival. Herein we investigated the mechanistic basis of this association. Epigenetic and genetic characteristics of YY1 in serous epithelial ovarian cancer (SEOC) were analyzed along with YY1 mRNA and protein. Patterns of gene expression in primary SEOC and in the NCI60 database were investigated using computational methods. YY1 function and modulation of chemotherapeutic response in vitro was studied using siRNA knockdown. Microarray analysis showed strong positive correlation between expression of YY1 and genes with YY1 and transcription factor E2F binding motifs in SEOC and in the NCI60 cancer cell lines. Clustering of microarray data for these genes revealed that high YY1/E2F3 activity positively correlates with survival of patients treated with the microtubule stabilizing drug paclitaxel. Increased sensitivity to taxanes, but not to DNA crosslinking platinum agents, was also characteristic of NCI60 cancer cell lines with a high YY1/E2F signature. YY1

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

    SciTech Connect (OSTI)

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

    2008-02-13

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

  6. Controlling Retinal Pigment Epithelial Cell Patch Size Influences...

    Office of Scientific and Technical Information (OSTI)

    ... Close Cite: Bibtex Format Close 0 pages in this document matching the terms "" Search For Terms: Enter terms in the toolbar above to search the full text of this document for ...

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

    SciTech Connect (OSTI)

    Inman, J.L.; Bissell, Mina

    2010-01-21

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

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

    SciTech Connect (OSTI)

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

    2013-05-29

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

  9. 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.

  10. 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.

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

    SciTech Connect (OSTI)

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

    2014-12-17

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

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

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

    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.; et al

    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 reactionmore » monitoring (SRM) quantification. The PRISM-SRM approach enabled direct quantification of ERK phosphorylation in human mammary epithelial cells (HMEC) from as little as 25 µg tryptic peptides from whole cell lysates. Compared to immobilized metal-ion affinity chromatography, PRISM provided >10-fold improvement in signal intensities, presumably due to the better peptide recovery of PRISM for handling small size samples. This approach was applied to quantify ERK phosphorylation dynamics in HMEC treated by different doses of EGF at both the peak activation (10 min) and steady state (2 h). At 10 min, the maximal ERK activation was observed with 0.3 ng/mL dose, whereas the maximal steady state level of ERK activation at 2 h was at 3 ng/ml dose, corresponding to 1200 and 9000 occupied receptors, respectively. At 10 min, the maximally activated pTpY isoform represented ~40% of total ERK, falling to less than 10% at 2 h. The time course and dose-response profiles of individual phosphorylated ERK isoforms indicated that singly phosphorylated pT-ERK never increases significantly, while the increase of pY-ERK paralleled that of pTpY-ERK. This data supports for a processive, rather than

  13. Chemical chaperones reduce ionizing radiation-induced endoplasmic reticulum stress and cell death in IEC-6 cells

    SciTech Connect (OSTI)

    Lee, Eun Sang; Lee, Hae-June; Lee, Yoon-Jin; Jeong, Jae-Hoon; Kang, Seongman; Lim, Young-Bin

    2014-07-25

    Highlights: UPR activation precedes caspase activation in irradiated IEC-6 cells. Chemical ER stress inducers radiosensitize IEC-6 cells. siRNAs that targeted ER stress responses ameliorate IR-induced cell death. Chemical chaperons prevent cell death in irradiated IEC-6 cells. - Abstract: Radiotherapy, which is one of the most effective approaches to the treatment of various cancers, plays an important role in malignant cell eradication in the pelvic area and abdomen. However, it also generates some degree of intestinal injury. Apoptosis in the intestinal epithelium is the primary pathological factor that initiates radiation-induced intestinal injury, but the mechanism by which ionizing radiation (IR) induces apoptosis in the intestinal epithelium is not clearly understood. Recently, IR has been shown to induce endoplasmic reticulum (ER) stress, thereby activating the unfolded protein response (UPR) signaling pathway in intestinal epithelial cells. However, the consequences of the IR-induced activation of the UPR signaling pathway on radiosensitivity in intestinal epithelial cells remain to be determined. In this study, we investigated the role of ER stress responses in IR-induced intestinal epithelial cell death. We show that chemical ER stress inducers, such as tunicamycin or thapsigargin, enhanced IR-induced caspase 3 activation and DNA fragmentation in intestinal epithelial cells. Knockdown of Xbp1 or Atf6 with small interfering RNA inhibited IR-induced caspase 3 activation. Treatment with chemical chaperones prevented ER stress and subsequent apoptosis in IR-exposed intestinal epithelial cells. Our results suggest a pro-apoptotic role of ER stress in IR-exposed intestinal epithelial cells. Furthermore, inhibiting ER stress may be an effective strategy to prevent IR-induced intestinal injury.

  14. 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.

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

    SciTech Connect (OSTI)

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

    2012-10-01

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

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

    Office of Scientific and Technical Information (OSTI)

    of inhaled nanoparticles to cross the blood-brain barrier; Kwon et al., 2008, J. Occup. ... AND NANOTECHNOLOGY; ASPECT RATIO; BLOOD-BRAIN BARRIER; CELL MEMBRANES; CHEMISTRY; ...

  17. Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor

    SciTech Connect (OSTI)

    Coppé, Jean-Philippe; Patil, Christopher; Rodier, Francis; Sun, Yu; Munoz, Denise; Goldstein, Joshua; Nelson, Peter; Desprez, Pierre-Yves; Campisi, Judith

    2008-10-24

    Cellular senescence suppresses cancer by arresting cell proliferation, essentially permanently, in response to oncogenic stimuli, including genotoxic stress. We modified the use of antibody arrays to provide a quantitative assessment of factors secreted by senescent cells. We show that human cells induced to senesce by genotoxic stress secrete myriad factors associated with inflammation and malignancy. This senescence-associated secretory phenotype (SASP) developed slowly over several days and only after DNA damage of sufficient magnitude to induce senescence. Remarkably similar SASPs developed in normal fibroblasts, normal epithelial cells, and epithelial tumor cells after genotoxic stress in culture, and in epithelial tumor cells in vivo after treatment of prostate cancer patients with DNA-damaging chemotherapy. In cultured premalignant epithelial cells, SASPs induced an epithelial-mesenchyme transition and invasiveness, hallmarks of malignancy, by a paracrine mechanism that depended largely on the SASP factors interleukin (IL)-6 and IL-8. Strikingly, two manipulations markedly amplified, and accelerated development of, the SASPs: oncogenic RAS expression, which causes genotoxic stress and senescence in normal cells, and functional loss of the p53 tumor suppressor protein. Both loss of p53 and gain of oncogenic RAS also exacerbated the promalignant paracrine activities of the SASPs. Our findings define a central feature of genotoxic stress-induced senescence. Moreover, they suggest a cell-nonautonomous mechanism by which p53 can restrain, and oncogenic RAS can promote, the development of age-related cancer by altering the tissue microenvironment.

  18. COMMD1 regulates the delta epithelial sodium channel ({delta}ENaC) through trafficking and ubiquitination

    SciTech Connect (OSTI)

    Chang, Tina; Ke, Ying; Ly, Kevin; McDonald, Fiona J.

    2011-08-05

    Highlights: {yields} The COMM domain of COMMD1 mediates binding to {delta}ENaC. {yields} COMMD1 reduces the cell surface population of {delta}ENaC. {yields} COMMD1 increases the population of {delta}ENaC-ubiquitin. {yields} Both endogenous and transfected {delta}ENaC localize with COMMD1 and transferrin suggesting they are located in early/recycling endosomes. -- Abstract: The delta subunit of the epithelial sodium channel ({delta}ENaC) is a member of the ENaC/degenerin family of ion channels. {delta}ENaC is distinct from the related {alpha}-, {beta}- and {gamma}ENaC subunits, known for their role in sodium homeostasis and blood pressure control, as {delta}ENaC is expressed in brain neurons and activated by external protons. COMMD1 (copper metabolism Murr1 domain 1) was previously found to associate with and downregulate {delta}ENaC activity. Here, we show that COMMD1 interacts with {delta}ENaC through its COMM domain. Co-expression of {delta}ENaC with COMMD1 significantly reduced {delta}ENaC surface expression, and led to an increase in {delta}ENaC ubiquitination. Immunocytochemical and confocal microscopy studies show that COMMD1 promoted localization of {delta}ENaC to the early/recycling endosomal pool where the two proteins were localized together. These results suggest that COMMD1 downregulates {delta}ENaC activity by reducing {delta}ENaC surface expression through promoting internalization of surface {delta}ENaC to an intracellular recycling pool, possibly via enhanced ubiquitination.

  19. A bioinformatics prediction approach towards analyzing the glycosylation, co-expression and interaction patterns of epithelial membrane antigen (EMA/MUC1)

    SciTech Connect (OSTI)

    Kalra, Rajkumar S. Wadhwa, Renu

    2015-02-27

    Epithelial membrane antigen (EMA or MUC1) is a heavily glycosylated, type I transmembrane glycoprotein commonly expressed by epithelial cells of duct organs. It has been shown to be aberrantly glycosylated in several diseases including cancer. Protein sequence based annotation and analysis of glycosylation profile of glycoproteins by robust computational and comprehensive algorithms provides possible insights to the mechanism(s) of anomalous glycosylation. In present report, by using a number of bioinformatics applications we studied EMA/MUC1 and explored its trans-membrane structural domain sequence that is widely subjected to glycosylation. Exploration of different extracellular motifs led to prediction of N and O-linked glycosylation target sites. Based on the putative O-linked target sites, glycosylated moieties and pathways were envisaged. Furthermore, Protein network analysis demonstrated physical interaction of EMA with a number of proteins and confirmed its functional involvement in cell growth and proliferation pathways. Gene Ontology analysis suggested an involvement of EMA in a number of functions including signal transduction, protein binding, processing and transport along with glycosylation. Thus, present study explored potential of bioinformatics prediction approach in analyzing glycosylation, co-expression and interaction patterns of EMA/MUC1 glycoprotein.

  20. Ballistic transfection of mammalian cells in vivo

    SciTech Connect (OSTI)

    Kolesnikov, V.A.; Zelenin, A.V.; Zelenina, I.A.

    1995-11-01

    The method of ballistic transfection initially proposed for genetic transformation of plants was used for animal cells in vitro and in situ. The method consists in bombarding the transfected cells with microparticles of heavy metals carrying foreign DNA. Penetrating the cell nucleus, the microparticles transport the introduced gene. Successful genetic transformation of the cultured mouse cells and fish embryos was realized, and this allowed the study of mammalian cells in situ. The performed studies allowed us to demonstrate expression of the reporter genes of chloramphenicol acetyltransferase, galactosidase, and neomycin phosphotransferase in the mouse liver, mammary gland and kidney explants, in the liver and cross-striated muscle of mouse and rat in situ, and in developing mouse embryos at the stages of two-cell embryo, morula, and blastocyst. All these genes were introduced by ballistic transfection. In the liver and cross-striated muscle the transgene activity was detected within two to three months after transfection. Thus, the ballistic introduction of the foreign genes in the cells in situ was demonstrated, and this opens possibilities for the use of this method in gene therapy. Methodical aspects of the bombarding and transfection are considered in detail, and the published data on transfection and genetic transformation of mammalian cells are discussed. 41 refs., 13 figs., 1 tab.

  1. Link Alpha M

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

    m A B C D E F G H I J K L M N O P Q R S T U V W Y Z Filter by alpha... A B C D E F G H I J K L M N O P Q R S T U V W Y Z Macintosh User Group (LBNL-MUG) Mail Services (Facilities Dep't.) Malware/Virus Protection and Prevention Mammary: Human Mammary Epithelial Cell (HMEC) Map: Berkeley Lab Global Talent Map Map: Lab Shuttle Bus Map Maps: Berkeley Lab Interactive Site Map Maps: Berkeley Lab Printable Site Map Massage Material Safety Data Sheets (Safety Data Sheets, SDS) Material Transfer

  2. Stabilization of gene expression and cell morphology after explant recycling during fin explant culture in goldfish

    SciTech Connect (OSTI)

    Chenais, Nathalie; Lareyre, Jean-Jacques; Le Bail, Pierre-Yves; Labbe, Catherine

    2015-07-01

    The development of fin primary cell cultures for in vitro cellular and physiological studies is hampered by slow cell outgrowth, low proliferation rate, poor viability, and sparse cell characterization. Here, we investigated whether the recycling of fresh explants after a first conventional culture could improve physiological stability and sustainability of the culture. The recycled explants were able to give a supplementary cell culture showing faster outgrowth, cleaner cell layers and higher net cell production. The cells exhibited a highly stabilized profile for marker gene expression including a low cytokeratin 49 (epithelial marker) and a high collagen 1a1 (mesenchymal marker) expression. Added to the cell spindle-shaped morphology, motility behavior, and actin organization, this suggests that the cells bore stable mesenchymal characteristics. This contrast with the time-evolving expression pattern observed in the control fresh explants during the first 2 weeks of culture: a sharp decrease in cytokeratin 49 expression was concomitant with a gradual increase in col1a1. We surmise that such loss of epithelial features for the benefit of mesenchymal ones was triggered by an epithelial to mesenchymal transition (EMT) process or by way of a progressive population replacement process. Overall, our findings provide a comprehensive characterization of this new primary culture model bearing mesenchymal features and whose stability over culture time makes those cells good candidates for cell reprogramming prior to nuclear transfer, in a context of fish genome preservation. - Highlights: • Recycled fin explants outgrow cells bearing stable mesenchymal traits. • Cell production and quality is enhanced in the recycled explant culture system. • Fresh fin primary culture is highly variable and loose epithelial traits over time.

  3. Evaluation of Common Angling-Induced Sources of Epithelial Damage for Popular Freshwater Sport Fish using Fluorescein

    SciTech Connect (OSTI)

    Colotelo, Alison HA; Cooke, Steven J.

    2011-05-01

    Angling is a popular recreational activity across the globe and a large proportion of fish captured by anglers are released due to voluntary or mandatory catch-and-release practices. The handling associated with hook removal and return of the fish to their environment can cause physical damage to the epidermal layer of the fish which may affect the condition and survival of released fish. This study investigated possible sources of epithelial damage associated with several different handling methods (i.e. landing net types, interactions with different boat floor surfaces, tournament procedures) commonly used in recreational angling for two popular freshwater sport fish species, largemouth bass (Micropterus salmoides) and northern pike (Esox lucius). Epithelial damage was examined using fluorescein, a non-toxic dye, which has been shown to detect latent epithelial damage. Northern pike exhibited extensive epithelial damage after exposure to several of the induced treatments (i.e., interaction with a carpeted surface, knotted nylon net, and line rolling) but relatively little epithelial damage when exposed to others (i.e., knotless rubber nets, smooth boat surfaces, or lip gripping devices). Largemouth bass did not show significant epithelial damage for any of the treatments, with the exception of fish caught in a semi-professional live release tournament. The detection of latent injuries using fluorescein can be an important management tool as it provides visual examples of potential damage that can be caused by different handling methods. Such visualizations can be used to encourage fish friendly angler behaviour and enhance the survival and welfare of released fish. It can also be used to test new products that are intended to or claim to reduce injury to fish that are to be released. Future research should evaluate the relationship between different levels of epithelial damage and mortality across a range of environmental conditions.

  4. Comparative Evaluation of Four Presumptive Tests for Blood to Detect Epithelial Injury on Fish

    SciTech Connect (OSTI)

    Colotelo, Alison HA; Smokorowski, Karen; Haxton, Tim; Cooke, Steven J.

    2014-06-01

    Current methods of fish epithelial injury detection are limited to gross macroscopic examination that has a subjective bias as well as an inability to reliably quantify the degree of injury. Fluorescein, a presumptive test for blood, has been shown to have the capability to detect and quantify fish epithelial injury. However, there are several other presumptive tests for blood (Bluestar*, phenolphthalein, and HemastixH) that may have benefits over the use of fluorescein, particularly for field research on wild fish. This study investigated the capabilities of these four tests to detect and quantify a variety of injuries commonly encountered by fish (abrasion, cuts, fin frays, and punctures) using the freshwater bluegill Lepomis macrochirus as a model. Fluorescein was consistently found to be the most reliable (i.e., detected the highest proportion of true positive results and rarely detected false positive reactions) of the four presumptive tests for blood compared. Further testing was conducted to examine the reliability of fluorescein. By 24 h after an injury was inflicted, the injury was no longer detectable by fluorescein, and when fluorescein was applied to an injured fish, the fluorescein was no longer detectable 3 h after application. In a comparison of two common anaesthetics used in fisheries research, there was no significant difference in the proportion of injury detected when 3- aminobenzoic acid ethyl ester methanesulfate (tricaine) was used compared with a clove oil and ethanol (1:9) solution. In summary, fluorescein was the most reliable presumptive test for blood examined in this study for the detection and quantification of recent (hours) fish epithelial injury.

  5. Stable knockdown of Kif5b in MDCK cells leads to epithelial–mesenchymal transition

    SciTech Connect (OSTI)

    Cui, Ju; Jin, Guoxiang; Yu, Bin; Wang, Zai; Lin, Raozhou; Huang, Jian-Dong

    2015-07-17

    Polarization of epithelial cells requires vectorial sorting and transport of polarity proteins to apical or basolateral domains. Kif5b is the mouse homologue of the human ubiquitous Kinesin Heavy Chain (uKHC). To investigate the function of Kif5b in epithelial cells, we examined the phenotypes of Kif5b-deficient MDCK cells. Stable knockdown of Kif5b in MDCK cells resulted in reduced cell proliferation rate, profound changes in cell morphology, loss of epithelial cell marker, and gain of mesenchymal marker, as well as increased cell migration, invasion, and tumorigenesis abilities. E-cadherin and NMMIIA could interact with Kif5b in polarized MDCK cells, and their expression levels were decreased in Kif5b-deficient MDCK cells. Overexpression of E-cadherin and NMMIIA in Kif5b depleted MDCK cells could decrease mesenchymal marker expression and cell migration ability. These results indicate that stable knockdown of Kif5b in MDCK cells can lead to epithelial–mesenchymal transition, which is mediated by defective E-cadherin and NMMIIA expression. - Highlights: • Knockdown of Kif5b in MDCK cells resulted in reduced cell proliferation rate. • Kif5b deficient MDCK cells underwent epithelial–mesenchymal transition. • E-cadherin and NMMIIA could interact with Kif5b in polarized MDCK cells. • Decreased E-cadherin and NMMIIA levels mediate EMT in Kif5b deficient MDCK cells. • Overexpression of E-cadherin and NMMIIA reverse the effects of Kif5b knockdown.

  6. TGFβ loss activates ADAMTS-1-mediated EGF-dependent invasion in a model of esophageal cell invasion

    SciTech Connect (OSTI)

    Le Bras, Grégoire F.; Taylor, Chase; Koumangoye, Rainelli B.; Revetta, Frank; Loomans, Holli A.; Andl, Claudia D.

    2015-01-01

    The TGFβ signaling pathway is essential to epithelial homeostasis and is often inhibited during progression of esophageal squamous cell carcinoma. Recently, an important role for TGFβ signaling has been described in the crosstalk between epithelial and stromal cells regulating squamous tumor cell invasion in mouse models of head-and-neck squamous cell carcinoma (HNSCC). Loss of TGFβ signaling, in either compartment, leads to HNSCC however, the mechanisms involved are not well understood. Using organotypic reconstruct cultures (OTC) to model the interaction between epithelial and stromal cells that occur in dysplastic lesions, we show that loss of TGFβ signaling promotes an invasive phenotype in both fibroblast and epithelial compartments. Employing immortalized esophageal keratinocytes established to reproduce common mutations of esophageal squamous cell carcinoma, we show that treatment of OTC with inhibitors of TGFβ signaling (A83-01 or SB431542) enhances invasion of epithelial cells into a fibroblast-embedded Matrigel/collagen I matrix. Invasion induced by A83-01 is independent of proliferation but relies on protease activity and expression of ADAMTS-1 and can be altered by matrix density. This invasion was associated with increased expression of pro-inflammatory cytokines, IL1 and EGFR ligands HB-EGF and TGFα. Altering EGF signaling prevented or induced epithelial cell invasion in this model. Loss of expression of the TGFβ target gene ROBO1 suggested that chemorepulsion may regulate keratinocyte invasion. Taken together, our data show increased invasion through inhibition of TGFβ signaling altered epithelial-fibroblasts interactions, repressing markers of activated fibroblasts, and altering integrin-fibronectin interactions. These results suggest that inhibition of TGFβ signaling modulates an array of pathways that combined promote multiple aspects of tumor invasion. - Highlights: • Chemical inhibition of TGFβ signaling advances collective invasion

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

    SciTech Connect (OSTI)

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

    2013-08-01

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

  8. Low Dose IR Creates an Oncogenic Microenvironment by Inducing Premature

    SciTech Connect (OSTI)

    Yuan, Zhi-Min

    2013-04-28

    Introduction Much of the work addressing ionizing radiation-induced cellular response has been carried out mainly with the traditional cell culture technique involving only one cell type, how cellular response to IR is influenced by the tissue microenvironment remains elusive. By use of a three-dimensional (3D) co-culture system to model critical interactions of different cell types with their neighbors and with their environment, we recently showed that low-dose IR-induced extracellular signaling via the tissue environment affects profoundly cellular responses. This proposal aims at determining the response of mammary epithelial cells in a tissue-like setting.

  9. Characterization of mechanical behavior of an epithelial monolayer in response to epidermal growth factor stimulation

    SciTech Connect (OSTI)

    Yang, Ruiguo; Chen, Jennifer Y.; Xi, Ning; Lai, King Wai Chiu; Qu, Chengeng; Fung, Carmen Kar Man; Penn, Lynn S.; Xi, Jun

    2012-03-10

    Cell signaling often causes changes in cellular mechanical properties. Knowledge of such changes can ultimately lead to insight into the complex network of cell signaling. In the current study, we employed a combination of atomic force microscopy (AFM) and quartz crystal microbalance with dissipation monitoring (QCM-D) to characterize the mechanical behavior of A431 cells in response to epidermal growth factor receptor (EGFR) signaling. From AFM, which probes the upper portion of an individual cell in a monolayer of cells, we observed increases in energy dissipation, Young's modulus, and hysteresivity. Increases in hysteresivity imply a shift toward a more fluid-like mechanical ordering state in the bodies of the cells. From QCM-D, which probes the basal area of the monolayer of cells collectively, we observed decreases in energy dissipation factor. This result suggests a shift toward a more solid-like state in the basal areas of the cells. The comparative analysis of these results indicates a regionally specific mechanical behavior of the cell in response to EGFR signaling and suggests a correlation between the time-dependent mechanical responses and the dynamic process of EGFR signaling. This study also demonstrates that a combination of AFM and QCM-D is able to provide a more complete and refined mechanical profile of the cells during cell signaling. -- Highlights: Black-Right-Pointing-Pointer The EGF-induced cellular mechanical response is regionally specific. Black-Right-Pointing-Pointer The EGF-induced cellular mechanical response is time and dose dependent. Black-Right-Pointing-Pointer A combination of AFM and QCM-D provides a more complete mechanical profile of cells.

  10. Rab27a regulates epithelial sodium channel (ENaC) activity through synaptotagmin-like protein (SLP-5) and Munc13-4 effector mechanism

    SciTech Connect (OSTI)

    Saxena, Sunil K. . E-mail: ssaxena@stevens.edu; Horiuchi, Hisanori; Fukuda, Mitsunori

    2006-06-02

    Liddle's syndrome (excessive absorption of sodium ions) and PHA-1 (pseudohypoaldosteronism type 1) with decreased sodium absorption are caused by the mutations in the amiloride-sensitive epithelial sodium channel ENaC. Rab proteins are small GTPases involved in vesicle transport, docking, and fusion. Earlier, we reported that Rab27a inhibits ENaC-mediated currents through protein-protein interaction in HT-29 cells. We hereby report that Rab27a-dependent inhibition is associated with the GTP/GDP status as constitutively active or GTPase-deficient mutant Q78L inhibits amiloride-sensitive currents whereas GDP-locked inactive mutant T23N showed no effect. In order to further explore the molecular mechanism of this regulation, we performed competitive assays with two Rab27a-binding proteins: synaptotagmin-like protein (SLP-5) and Munc13-4 (a putative priming factor for exocytosis). Both proteins eliminate negative modulation of Rab27a on ENaC function. The SLP-5 reversal of Rab27a effect was restricted to C-terminal C2A/C2B domains assigned for putative phospholipids-binding function while the Rab27a-binding SHD motif imparted higher inhibition. The ENaC-mediated currents remain unaffected by Rab27a though SLP-5 appears to strongly bind it. The immunoprecipitation experiments suggest that in the presence of excessive Munc13-4 and SLP-5 proteins, Rab27a interaction with ENaC is diminished. Munc13-4 and SLP-5 limit the Rab27a availability to ENaC, thus minimizing its effect on channel function. These observations decisively prove that Rab27a inhibits ENaC function through a complex mechanism that involves GTP/GDP status, and protein-protein interactions involving Munc13-4 and SLP-5 effector proteins.

  11. Id-1 and Id-2 genes and products as markers of epithelial cancer

    DOE Patents [OSTI]

    Desprez, Pierre-Yves; Campisi, Judith

    2008-09-30

    A method for detection and prognosis of breast cancer and other types of cancer. The method comprises detecting expression, if any, for both an Id-1 and an Id-2 genes, or the ratio thereof, of gene products in samples of breast tissue obtained from a patient. When expressed, Id-1 gene is a prognostic indicator that breast cancer cells are invasive and metastatic, whereas Id-2 gene is a prognostic indicator that breast cancer cells are localized and noninvasive in the breast tissue.

  12. Id-1 and Id-2 genes and products as markers of epithelial cancer

    DOE Patents [OSTI]

    Desprez, Pierre-Yves; Campisi, Judith

    2011-10-04

    A method for detection and prognosis of breast cancer and other types of cancer. The method comprises detecting expression, if any, for both an Id-1 and an Id-2 genes, or the ratio thereof, of gene products in samples of breast tissue obtained from a patient. When expressed, Id-1 gene is a prognostic indicator that breast cancer cells are invasive and metastatic, whereas Id-2 gene is a prognostic indicator that breast cancer cells are localized and noninvasive in the breast tissue.

  13. Modelling breast cancer requires identification and correction of a critical cell lineage-dependent transduction bias

    SciTech Connect (OSTI)

    Hines, William C.; Yaswen, Paul; Bissell, Mina J.

    2015-04-21

    When trying to explore the biology and etiology of human cancers, clinically relevant human culture models are essential. Current breast tumour models, such as those from oncogenically transformed primary breast cells, produce predominantly basal-like properties, whereas the more common phenotype expressed by the vast majority of breast tumours are luminal. Reasons for this puzzling, yet important phenomenon, are not understood. We show here that luminal epithelial cells are significantly more resistant to viral transduction than their myoepithelial counterparts. Here, we suggest that this is a significant barrier to generating luminal cell lines and experimental tumours in vivo and to accurate interpretation of results. We show that the resistance is due to lower affinity of luminal cells for virus attachment, which can be overcome by pretreating cells—or virus—with neuraminidase. We present an analytical method for quantifying transductional differences between cell types and an optimized protocol for transducing unsorted primary human breast cells in context.

  14. NanoLC-FT-ICR MS improves proteome coverage attainable for ~3000 laser microdissected breast carcinoma cells

    SciTech Connect (OSTI)

    Umar, Arzu; Luider, Theo N.; Foekens, J. A.; Pasa-Tolic, Liljiana

    2007-01-29

    Genomics and proteomics assays hold great promise for unrevealing molecular events that underlie human disease. Essential to this quest is the ability to effectively analyze clinical samples, but this task is considerably complicated by tissue heterogeneity. Laser capture microdissection (LCM) can be used to selectively isolate targeted cell populations (such as tumor cells) from their native tissue environment. However, the small number of cells that are typically procured by LCM severely limits the proteome coverage and biomarker discovery potential achievable by conventional proteomics platforms. Herein, we report on the use of a nano liquid chromatography-Fourier transform ion clyclotron resonance mass spectrometry (nLC-FTICR MS) platform for analyzing protein digests of approximately 3,000 LCM-derived tumor cells from breast carcinoma tissue, which corresponds to approximately 300 ng of total protein. A total of 2,836 peptides were identified by matching LC-MS data to accurate mass and time (AMT) tag databases that were previously established for the human mammary epithelium and several breast cancer cell lines. The peptide identifications correspond to 1,139 unique proteins confidently identified with 2 or more peptides. Based on categorization by Gene Ontology, identified proteins appear to cover a wide variety of biological functions and cellular compartments. This work demonstrates that a substantial number of proteins can be identified from a limited number of cells using the AMT tag approach and opens a door for high throughput in-depth proteomics analysis of clinical samples.

  15. Knockdown of TWIST1 enhances arsenic trioxide- and ionizing radiation-induced cell death in lung cancer cells by promoting mitochondrial dysfunction

    SciTech Connect (OSTI)

    Seo, Sung-Keum; Kim, Jae-Hee; Choi, Ha-Na; Choe, Tae-Boo; Hong, Seok-Il; Yi, Jae-Youn; Hwang, Sang-Gu; Lee, Hyun-Gyu; Lee, Yun-Han; Park, In-Chul

    2014-07-11

    Highlights: • Knockdown of TWIST1 enhanced ATO- and IR-induced cell death in NSCLCs. • Intracellular ROS levels were increased in cells treated with TWIST1 siRNA. • TWIST1 siRNA induced MMP loss and mitochondrial fragmentation. • TWIST1 siRNA upregulated the fission-related proteins FIS1 and DRP1. - Abstract: TWIST1 is implicated in the process of epithelial mesenchymal transition, metastasis, stemness, and drug resistance in cancer cells, and therefore is a potential target for cancer therapy. In the present study, we found that knockdown of TWIST1 by small interfering RNA (siRNA) enhanced arsenic trioxide (ATO)- and ionizing radiation (IR)-induced cell death in non-small-cell lung cancer cells. Interestingly, intracellular reactive oxygen species levels were increased in cells treated with TWIST1 siRNA and further increased by co-treatment with ATO or IR. Pretreatment of lung cancer cells with the antioxidant N-acetyl-cysteine markedly suppressed the cell death induced by combined treatment with TWIST1 siRNA and ATO or IR. Moreover, treatment of cells with TWIST1 siRNA induced mitochondrial membrane depolarization and significantly increased mitochondrial fragmentation (fission) and upregulated the fission-related proteins FIS1 and DRP1. Collectively, our results demonstrate that siRNA-mediated TWIST1 knockdown induces mitochondrial dysfunction and enhances IR- and ATO-induced cell death in lung cancer cells.

  16. Context dependent reversion of tumor phenotype by connexin-43 expression in MDA-MB231 cells and MCF-7 cells: Role of ?-catenin/connexin43 association

    SciTech Connect (OSTI)

    Talhouk, Rabih S.; Fares, Mohamed-Bilal; Rahme, Gilbert J.; Hariri, Hanaa H.; Rayess, Tina; Dbouk, Hashem A.; Bazzoun, Dana; Al-Labban, Dania; El-Sabban, Marwan E.

    2013-12-10

    Connexins (Cx), gap junction (GJ) proteins, are regarded as tumor suppressors, and Cx43 expression is often down regulated in breast tumors. We assessed the effect of Cx43 over-expression in 2D and 3D cultures of two breast adenocarcinoma cell lines: MCF-7 and MDA-MB-231. While Cx43 over-expression decreased proliferation of 2D and 3D cultures of MCF-7 by 56% and 80% respectively, MDA-MB-231 growth was not altered in 2D cultures, but exhibited 35% reduction in 3D cultures. C-terminus truncated Cx43 did not alter proliferation. Untransfected MCF-7 cells formed spherical aggregates in 3D cultures, and MDA-MB-231 cells formed stellar aggregates. However, MCF-7 cells over-expressing Cx43 formed smaller sized clusters and Cx43 expressing MDA-MB-231 cells lost their stellar morphology. Extravasation ability of both MCF-7 and MDA-MB-231 cells was reduced by 60% and 30% respectively. On the other hand, silencing Cx43 in MCF10A cells, nonneoplastic human mammary cell line, increased proliferation in both 2D and 3D cultures, and disrupted acinar morphology. Although Cx43 over-expression did not affect total levels of ?-catenin, ?-catenin and ZO-2, it decreased nuclear levels of ?-catenin in 2D and 3D cultures of MCF-7 cells, and in 3D cultures of MDA-MB-231 cells. Cx43 associated at the membrane with ?-catenin, ?-catenin and ZO-2 in 2D and 3D cultures of MCF-7 cells, and only in 3D conditions in MDA-MB-231 cells. This study suggests that Cx43 exerts tumor suppressive effects in a context-dependent manner where GJ assembly with ?-catenin, ?-catenin and ZO-2 may be implicated in reducing growth rate, invasiveness, and, malignant phenotype of 2D and 3D cultures of MCF-7 cells, and 3D cultures of MDA-MB-231 cells, by sequestering ?-catenin away from nucleus. - Highlights: Cx43 over-expressing MCF-7 and MDA-MB-231 were grown in 2D and 3D cultures. Proliferation and growth morphology were affected in a context dependent manner. Extravasation ability of both MCF-7 and MDA

  17. Long-term in vitro, cell-type-specific genome-wide reprogramming of gene expression

    SciTech Connect (OSTI)

    Hakelien, Anne-Mari; Gaustad, Kristine G.; Taranger, Christel K.; Skalhegg, Bjorn S.; Kuentziger, Thomas; Collas, Philippe . E-mail: philippe.collas@medisin.uio.no

    2005-09-10

    We demonstrate a cell extract-based, genome-wide and heritable reprogramming of gene expression in vitro. Kidney epithelial 293T cells have previously been shown to take on T cell properties following a brief treatment with an extract of Jurkat T cells. We show here that 293T cells exposed for 1 h to a Jurkat cell extract undergo genome-wide, target cell-type-specific and long-lasting transcriptional changes. Microarray analyses indicate that on any given week after extract treatment, {approx}2500 genes are upregulated >3-fold, of which {approx}900 are also expressed in Jurkat cells. Concomitantly, {approx}1500 genes are downregulated or repressed, of which {approx}500 are also downregulated in Jurkat cells. Gene expression changes persist for over 30 passages ({approx}80 population doublings) in culture. Target cell-type specificity of these changes is shown by the lack of activation or repression of Jurkat-specific genes by extracts of 293T cells or carcinoma cells. Quantitative RT-PCR analysis confirms the long-term transcriptional activation of genes involved in key T cell functions. Additionally, growth of cells in suspended aggregates, expression of CD3 and CD28 T cell surface markers, and interleukin-2 secretion by 293T cells treated with extract of adult peripheral blood T cells illustrate a functional nuclear reprogramming. Therefore, target cell-type-specific and heritable changes in gene expression, and alterations in cell function, can be promoted by extracts derived from transformed cells as well as from adult primary cells.

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

    SciTech Connect (OSTI)

    Chuang, Hsiao-Chi; Cheng, Yi-Ling; Lei, Yu-Chen; Chang, Hui-Hsien; Cheng, Tsun-Jen

    2013-02-01

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

  19. Dummy Run of Quality Assurance Program in a Phase 3 Randomized Trial Investigating the Role of Internal Mammary Lymph Node Irradiation in Breast Cancer Patients: Korean Radiation Oncology Group 08-06 Study

    SciTech Connect (OSTI)

    Chung, Yoonsun; Kim, Jun Won; Shin, Kyung Hwan; Kim, Su Ssan; Ahn, Sung-Ja; Park, Won; Lee, Hyung-Sik; Kim, Dong Won; Lee, Kyu Chan; Suh, Hyun Suk; Kim, Jin Hee; Shin, Hyun Soo; Kim, Yong Bae; Suh, Chang-Ok

    2015-02-01

    Purpose: The Korean Radiation Oncology Group (KROG) 08-06 study protocol allowed radiation therapy (RT) technique to include or exclude breast cancer patients from receiving radiation therapy to the internal mammary lymph node (IMN). The purpose of this study was to assess dosimetric differences between the 2 groups and potential influence on clinical outcome by a dummy run procedure. Methods and Materials: All participating institutions were asked to produce RT plans without irradiation (Arm 1) and with irradiation to the IMN (Arm 2) for 1 breast-conservation treatment case (breast-conserving surgery [BCS]) and 1 mastectomy case (modified radical mastectomy [MRM]) whose computed tomography images were provided. We assessed interinstitutional variations in IMN delineation and evaluated the dose-volume histograms of the IMN and normal organs. A reference IMN was delineated by an expert panel group based on the study guidelines. Also, we analyzed the potential influence of actual dose variation observed in this study on patient survival. Results: Although physicians intended to exclude the IMN within the RT field, the data showed almost 59.0% of the prescribed dose was delivered to the IMN in Arm 1. However, the mean doses covering the IMN in Arm 1 and Arm 2 were significantly different for both cases (P<.001). Due to the probability of overdose in Arm 1, the estimated gain in 7-year disease-free survival rate would be reduced from 10% to 7.9% for BCS cases and 7.1% for MRM cases. The radiation doses to the ipsilateral lung, heart, and coronary artery were lower in Arm 1 than in Arm 2. Conclusions: Although this dummy run study indicated that a substantial dose was delivered to the IMN, even in the nonirradiation group, the dose differences between the 2 groups were statistically significant. However, this dosimetric profile should be studied further with actual patient samples and be taken into consideration when analyzing clinical outcomes according to IMN

  20. Role for DNA methylation in the regulation of miR-200c and miR-141 expression in normal and cancer cells

    SciTech Connect (OSTI)

    Vrba, Lukas; Jensen, Taylor J.; Garbe, James C.; Heimark, Ronald L.; Cress, Anne E.; Dickinson, Sally; Stampfer, Martha R.; Futscher, Bernard W.

    2009-12-23

    BACKGROUND: The microRNA-200 family participates in the maintenance of an epithelial phenotype and loss of its expression can result in epithelial to mesenchymal transition (EMT). Furthermore, the loss of expression of miR-200 family members is linked to an aggressive cancer phenotype. Regulation of the miR-200 family expression in normal and cancer cells is not fully understood. METHODOLOGY/ PRINCIPAL FINDINGS: Epigenetic mechanisms participate in the control of miR-200c and miR-141 expression in both normal and cancer cells. A CpG island near the predicted mir-200c/mir-141 transcription start site shows a striking correlation between miR-200c and miR-141 expression and DNA methylation in both normal and cancer cells, as determined by MassARRAY technology. The CpG island is unmethylated in human miR-200/miR-141 expressing epithelial cells and in miR-200c/miR-141 positive tumor cells. The CpG island is heavily methylated in human miR-200c/miR-141 negative fibroblasts and miR-200c/miR-141 negative tumor cells. Mouse cells show a similar inverse correlation between DNA methylation and miR-200c expression. Enrichment of permissive histone modifications, H3 acetylation and H3K4 trimethylation, is seen in normal miR-200c/miR-141-positive epithelial cells, as determined by chromatin immunoprecipitation coupled to real-time PCR. In contrast, repressive H3K9 dimethylation marks are present in normal miR-200c/miR-141-negative fibroblasts and miR-200c/miR-141 negative cancer cells and the permissive histone modifications are absent. The epigenetic modifier drug, 5-aza-2'-deoxycytidine, reactivates miR-200c/miR-141 expression showing that epigenetic mechanisms play a functional role in their transcriptional control. CONCLUSIONS/ SIGNIFICANCE: We report that DNA methylation plays a role in the normal cell type-specific expression of miR-200c and miR-141 and this role appears evolutionarily conserved, since similar results were obtained in mouse. Aberrant DNA methylation of the

  1. 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.

  2. 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.

  3. Fuel Cells

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

    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 ...

  4. 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.

  5. 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.

  6. 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.

  7. Electrochemical cell

    DOE Patents [OSTI]

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

    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.

  8. Load cell

    DOE Patents [OSTI]

    Spletzer, Barry L.

    2001-01-01

    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 which can be combined to determine any one of the six general load components.

  9. Load cell

    DOE Patents [OSTI]

    Spletzer, Barry L.

    1998-01-01

    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.

  10. 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.

  11. 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.

  12. Ovarian tumor-initiating cells display a flexible metabolism

    SciTech Connect (OSTI)

    Anderson, Angela S.; Roberts, Paul C.; Frisard, Madlyn I.; Hulver, Matthew W.; Schmelz, Eva M.

    2014-10-15

    An altered metabolism during ovarian cancer progression allows for increased macromolecular synthesis and unrestrained growth. However, the metabolic phenotype of cancer stem or tumor-initiating cells, small tumor cell populations that are able to recapitulate the original tumor, has not been well characterized. In the present study, we compared the metabolic phenotype of the stem cell enriched cell variant, MOSE-L{sub FFLv} (TIC), derived from mouse ovarian surface epithelial (MOSE) cells, to their parental (MOSE-L) and benign precursor (MOSE-E) cells. TICs exhibit a decrease in glucose and fatty acid oxidation with a concomitant increase in lactate secretion. In contrast to MOSE-L cells, TICs can increase their rate of glycolysis to overcome the inhibition of ATP synthase by oligomycin and can increase their oxygen consumption rate to maintain proton motive force when uncoupled, similar to the benign MOSE-E cells. TICs have an increased survival rate under limiting conditions as well as an increased survival rate when treated with AICAR, but exhibit a higher sensitivity to metformin than MOSE-E and MOSE-L cells. Together, our data show that TICs have a distinct metabolic profile that may render them flexible to adapt to the specific conditions of their microenvironment. By better understanding their metabolic phenotype and external environmental conditions that support their survival, treatment interventions can be designed to extend current therapy regimens to eradicate TICs. - Highlights: Ovarian cancer TICs exhibit a decreased glucose and fatty acid oxidation. TICs are more glycolytic and have highly active mitochondria. TICs are more resistant to AICAR but not metformin. A flexible metabolism allows TICs to adapt to their microenvironment. This flexibility requires development of specific drugs targeting TIC-specific changes to prevent recurrent TIC outgrowth.

  13. 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.

  14. 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.

  15. Electrochemical cell

    DOE Patents [OSTI]

    Nagy, Zoltan; Yonco, Robert M.; You, Hoydoo; Melendres, Carlos A.

    1992-01-01

    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.

  16. 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.

  17. Comparative Iron Oxide Nanoparticle Cellular Dosimetry and Response in Mice by the Inhalation and Liquid Cell Culture Exposure Routes

    SciTech Connect (OSTI)

    Teeguarden, Justin G.; Mikheev, Vladimir B.; Minard, Kevin R.; Forsythe, William C.; Wang, Wei; Sharma, Gaurav; Karin, Norman J.; Tilton, Susan C.; Waters, Katrina M.; Asgharian, Bahman; Price, Owen; Pounds, Joel G.; Thrall, Brian D.

    2014-01-01

    testing the rapidly growing number of nanomaterials requires large scale use of in vitro systems under the presumption that these systems are sufficiently predictive or descriptive of responses in in vivo systems for effective use in hazard ranking. We hypothesized that improved relationships between in vitro and in vivo models of experimental toxicology for nanomaterials would result from placing response data in vitro and in vivo on the same dose scale, the amount of material associated with cells (target cell dose). Methods: Balb/c mice were exposed nose-only to an aerosol of 12.8 nm (68.6 nm CMD, 19.9 mg/m3, 4 hours) super paramagnetic iron oxide particles, target cell doses were calculated and biomarkers of response anchored with histological evidence were identified by global transcriptomics. Representative murine epithelial and macrophage cell types were exposed in vitro to the same material in liquid suspension for four hours and levels nanoparticle regulated cytokine transcripts identified in vivo were quantified as a function of measured nanoparticle cellular dose. Results. Target tissue doses of 0.009-0.4 μg SPIO/cm2 lung led to an inflammatory response in the alveolar region characterized by interstitial inflammation and macrophage infiltration. In vitro, higher target tissue doses of ~1.2-4 μg SPIO/ cm2 of cells were required to induce transcriptional regulation of markers of inflammation, CXCL2 CCL3, in C10 lung epithelial cells. Estimated in vivo macrophage SPIO nanoparticle doses ranged from 1-100 pg/cell, and induction of inflammatory markers was observed in vitro in macrophages at doses of 8-35 pg/cell. Conclusions: Application of target tissue dosimetry revealed good correspondence between target cell doses triggering inflammatory processes in vitro and in vivo in the alveolar macrophage population, but not in the epithelial cells of the alveolar region. These findings demonstrate the potential for target tissue dosimetry to enable the more

  18. 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.

  19. 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.

  20. CITED2 modulates estrogen receptor transcriptional activity in breast cancer cells

    SciTech Connect (OSTI)

    Lau, Wen Min; Doucet, Michele; Huang, David; Weber, Kristy L.; Kominsky, Scott L.

    2013-07-26

    Highlights: The effects of elevated CITED2 on ER function in breast cancer cells are examined. CITED2 enhances cell growth in the absence of estrogen and presence of tamoxifen. CITED2 functions as a transcriptional co-activator of ER in breast cancer cells. -- Abstract: Cbp/p300-interacting transactivator with Glu/Asp-rich carboxy-terminal domain 2 (CITED2) is a member of the CITED family of non-DNA binding transcriptional co-activators of the p300/CBP-mediated transcription complex. Previously, we identified CITED2 as being overexpressed in human breast tumors relative to normal mammary epithelium. Upon further investigation within the estrogen receptor (ER)-positive subset of these breast tumor samples, we found that CITED2 mRNA expression was elevated in those associated with poor survival. In light of this observation, we investigated the effect of elevated CITED2 levels on ER function. While ectopic overexpression of CITED2 in three ER-positive breast cancer cell lines (MCF-7, T47D, and CAMA-1) did not alter cell proliferation in complete media, growth was markedly enhanced in the absence of exogenous estrogen. Correspondingly, cells overexpressing CITED2 demonstrated reduced sensitivity to the growth inhibitory effects of the selective estrogen receptor modulator, 4-hydroxytamoxifen. Subsequent studies revealed that basal ER transcriptional activity was elevated in CITED2-overexpressing cells and was further increased upon the addition of estrogen. Similarly, basal and estrogen-induced expression of the ER-regulated genes trefoil factor 1 (TFF1) and progesterone receptor (PGR) was higher in cells overexpressing CITED2. Concordant with this observation, ChIP analysis revealed higher basal levels of CITED2 localized to the TFF-1 and PGR promoters in cells with ectopic overexpression of CITED2, and these levels were elevated further in response to estrogen stimulation. Taken together, these data indicate that CITED2 functions as a transcriptional co

  1. 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.

  2. 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.

  3. Photoelectrodialytic cell

    DOE Patents [OSTI]

    Murphy, George W.

    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.

  4. Regulatory T Cells Promote β-Catenin–Mediated Epithelium-to-Mesenchyme Transition During Radiation-Induced Pulmonary Fibrosis

    SciTech Connect (OSTI)

    Xiong, Shanshan; Pan, Xiujie; Xu, Long; Yang, Zhihua; Guo, Renfeng; Gu, Yongqing; Li, Ruoxi; Wang, Qianjun; Xiao, Fengjun; Du, Li; Zhou, Pingkun; Zhu, Maoxiang

    2015-10-01

    Purpose: Radiation-induced pulmonary fibrosis results from thoracic radiation therapy and severely limits radiation therapy approaches. CD4{sup +}CD25{sup +}FoxP3{sup +} regulatory T cells (Tregs) as well as epithelium-to-mesenchyme transition (EMT) cells are involved in pulmonary fibrosis induced by multiple factors. However, the mechanisms of Tregs and EMT cells in irradiation-induced pulmonary fibrosis remain unclear. In the present study, we investigated the influence of Tregs on EMT in radiation-induced pulmonary fibrosis. Methods and Materials: Mice thoraxes were irradiated (20 Gy), and Tregs were depleted by intraperitoneal injection of a monoclonal anti-CD25 antibody 2 hours after irradiation and every 7 days thereafter. Mice were treated on days 3, 7, and 14 and 1, 3, and 6 months post irradiation. The effectiveness of Treg depletion was assayed via flow cytometry. EMT and β-catenin in lung tissues were detected by immunohistochemistry. Tregs isolated from murine spleens were cultured with mouse lung epithelial (MLE) 12 cells, and short interfering RNA (siRNA) knockdown of β-catenin in MLE 12 cells was used to explore the effects of Tregs on EMT and β-catenin via flow cytometry and Western blotting. Results: Anti-CD25 antibody treatment depleted Tregs efficiently, attenuated the process of radiation-induced pulmonary fibrosis, hindered EMT, and reduced β-catenin accumulation in lung epithelial cells in vivo. The coculture of Tregs with irradiated MLE 12 cells showed that Tregs could promote EMT in MLE 12 cells and that the effect of Tregs on EMT was partially abrogated by β-catenin knockdown in vitro. Conclusions: Tregs can promote EMT in accelerating radiation-induced pulmonary fibrosis. This process is partially mediated through β-catenin. Our study suggests a new mechanism for EMT, promoted by Tregs, that accelerates radiation-induced pulmonary fibrosis.

  5. Taurine protects HK-2 cells from oxidized LDL-induced cytotoxicity via the ROS-mediated mitochondrial and p53-related apoptotic pathways

    SciTech Connect (OSTI)

    Chang, Chun-Yu; Shen, Chao-Yu; Kang, Chao-Kai; Sher, Yuh-Pyng; Sheu, Wayne H.-H.; Chang, Chia-Che; Lee, Tsung-Han

    2014-09-15

    Oxidized LDL (oxLDL) induces a pro-oxidative environment and promotes apoptosis, causing the progression of renal diseases in humans. Taurine is a semi-essential amino acid in mammals and has been shown to be a potent endogenous antioxidant. The kidney plays a pivotal role in maintaining the balance of taurine. However, the mechanisms underlying the protective effects of taurine against oxLDL-induced injury in renal epithelial cells have not been clarified. In the present study, we investigated the anti-apoptotic effects of taurine on human proximal tubular epithelial (HK-2) cells exposed to oxLDL and explored the related mechanisms. We observed that oxLDL increased the contents of ROS and of malondialdehyde (MDA), which is a lipid peroxidation by-product that acts as an indicator of the cellular oxidation status. In addition, oxLDL induced cell death and apoptosis in HK-2 cells. Pretreatment with taurine at 100 μM significantly attenuated the oxLDL-induced cytotoxicity. We determined that oxLDL triggered the phosphorylation of ERK and, in turn, the activation of p53 and other apoptosis-related events, including calcium accumulation, destabilization of the mitochondrial permeability and disruption of the balance between pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins. The malfunctions induced by oxLDL were effectively blocked by taurine. Thus, our results suggested that taurine exhibits potential therapeutic activity by preventing oxLDL-induced nephrotoxicity. The inhibition of oxLDL-induced epithelial apoptosis by taurine was at least partially due to its anti-oxidant activity and its ability to modulate the ERK and p53 apoptotic pathways. - Highlights: • Oxidized LDL induced cytotoxicity and apoptosis in HK-2 cells. • Pretreatment with taurine attenuated oxLDL-induced nephrotoxicity. • Taurine protected against renal damages through inhibition of ROS generation. • Taurine prevented apoptosis through modulation of the p53 phosphorylation.

  6. 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.

  7. 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 Energy Defense Waste Management Programs Advanced Nuclear Energy Nuclear

  8. Disruption of canonical TGF?-signaling in murine coronary progenitor cells by low level arsenic

    SciTech Connect (OSTI)

    Allison, Patrick; Huang, Tianfang; Broka, Derrick; Parker, Patti; Barnett, Joey V.; Camenisch, Todd D.

    2013-10-01

    Exposure to arsenic results in several types of cancers as well as heart disease. A major contributor to ischemic heart pathologies is coronary artery disease, however the influences by environmental arsenic in this disease process are not known. Similarly, the impact of toxicants on blood vessel formation and function during development has not been studied. During embryogenesis, the epicardium undergoes proliferation, migration, and differentiation into several cardiac cell types including smooth muscle cells which contribute to the coronary vessels. The TGF? family of ligands and receptors is essential for developmental cardiac epithelial to mesenchymal transition (EMT) and differentiation into coronary smooth muscle cells. In this in vitro study, 18 hour exposure to 1.34 ?M arsenite disrupted developmental EMT programming in murine epicardial cells causing a deficit in cardiac mesenchyme. The expression of EMT genes including TGF?2, TGF? receptor-3, Snail, and Has-2 are decreased in a dose-dependent manner following exposure to arsenite. TGF?2 cell signaling is abrogated as detected by decreases in phosphorylated Smad2/3 when cells are exposed to 1.34 ?M arsenite. There is also loss of nuclear accumulation pSmad due to arsenite exposure. These observations coincide with a decrease in vimentin positive mesenchymal cells invading three-dimensional collagen gels. However, arsenite does not block TGF?2 mediated smooth muscle cell differentiation by epicardial cells. Overall these results show that arsenic exposure blocks developmental EMT gene programming in murine coronary progenitor cells by disrupting TGF?2 signals and Smad activation, and that smooth muscle cell differentiation is refractory to this arsenic toxicity. - Highlights: Arsenic blocks TGF?2 induced expression of EMT genes. Arsenic blocks TGF?2 triggered Smad2/3 phosphorylation and nuclear translocation. Arsenic blocks epicardial cell differentiation into cardiac mesenchyme. Arsenic does not

  9. The Cell Processor

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

    Agenda Cell Processor Overview Programming the Cell Processor Concluding Remarks 3 2005 IBM Corporation Cell Highlights Observed clock speed > 4 GHz Peak performance (single ...

  10. 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 ...

  11. CORONAL CELLS

    SciTech Connect (OSTI)

    Sheeley, N. R. Jr.; Warren, H. P. E-mail: harry.warren@nrl.navy.mil

    2012-04-10

    We have recently noticed cellular features in Fe XII 193 A images of the 1.2 MK corona. They occur in regions bounded by a coronal hole and a filament channel, and are centered on flux elements of the photospheric magnetic network. Like their neighboring coronal holes, these regions have minority-polarity flux that is {approx}0.1-0.3 times their flux of majority polarity. Consequently, the minority-polarity flux is 'grabbed' by the majority-polarity flux to form low-lying loops, and the remainder of the network flux escapes to connect with its opposite-polarity counterpart in distant active regions of the Sun. As these regions are carried toward the limb by solar rotation, the cells disappear and are replaced by linear plumes projecting toward the limb. In simultaneous views from the Solar Terrestrial Relations Observatory and Solar Dynamics Observatory spacecraft, these plumes project in opposite directions, extending away from the coronal hole in one view and toward the hole in the other view, suggesting that they are sky-plane projections of the same radial structures. We conclude that these regions are composed of closely spaced radial plumes, extending upward like candles on a birthday cake and visible as cells when seen from above. We suppose that a coronal hole has this same discrete, cellular magnetic structure, but that it is not seen until the encroachment of opposite-polarity flux closes part or all of the hole.

  12. DNA-cell conjugates

    DOE Patents [OSTI]

    Hsiao, Shih-Chia; Francis, Matthew B.; Bertozzi, Carolyn; Mathies, Richard; Chandra, Ravi; Douglas, Erik; Twite, Amy; Toriello, Nicholas; Onoe, Hiroaki

    2016-05-03

    The present invention provides conjugates of DNA and cells by linking the DNA to a native functional group on the cell surface. The cells can be without cell walls or can have cell walls. The modified cells can be linked to a substrate surface and used in assay or bioreactors.

  13. Photoelectrochemical cell

    DOE Patents [OSTI]

    Rauh, R. David; Boudreau, Robert A.

    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.

  14. Modelling breast cancer requires identification and correction of a critical cell lineage-dependent transduction bias

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

    Hines, William C.; Yaswen, Paul; Bissell, Mina J.

    2015-04-21

    When trying to explore the biology and etiology of human cancers, clinically relevant human culture models are essential. Current breast tumour models, such as those from oncogenically transformed primary breast cells, produce predominantly basal-like properties, whereas the more common phenotype expressed by the vast majority of breast tumours are luminal. Reasons for this puzzling, yet important phenomenon, are not understood. We show here that luminal epithelial cells are significantly more resistant to viral transduction than their myoepithelial counterparts. Here, we suggest that this is a significant barrier to generating luminal cell lines and experimental tumours in vivo and to accuratemore » interpretation of results. We show that the resistance is due to lower affinity of luminal cells for virus attachment, which can be overcome by pretreating cells—or virus—with neuraminidase. We present an analytical method for quantifying transductional differences between cell types and an optimized protocol for transducing unsorted primary human breast cells in context.« less

  15. 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.

  16. Knockdown of dual specificity phosphatase 4 enhances the chemosensitivity of MCF-7 and MCF-7/ADR breast cancer cells to doxorubicin

    SciTech Connect (OSTI)

    Liu, Yu; Du, Feiya; Chen, Wei; Yao, Minya; Lv, Kezhen; Fu, Peifen

    2013-12-10

    Background: Breast cancer is the major cause of cancer-related deaths in females world-wide. Doxorubicin-based therapy has limited efficacy in breast cancer due to drug resistance, which has been shown to be associated with the epithelial-to-mesenchymal transition (EMT). However, the molecular mechanisms linking the EMT and drug resistance in breast cancer cells remain unclear. Dual specificity phosphatase 4 (DUSP4), a member of the dual specificity phosphatase family, is associated with cellular proliferation and differentiation; however, its role in breast cancer progression is controversial. Methods: We used cell viability assays, Western blotting and immunofluorescent staining, combined with siRNA interference, to evaluate chemoresistance and the EMT in MCF-7 and adriamycin-resistant MCF-7/ADR breast cancer cells, and investigate the underlying mechanisms. Results: Knockdown of DUSP4 significantly increased the chemosensitivity of MCF-7 and MCF-7/ADR breast cancer cells to doxorubicin, and MCF-7/ADR cells which expressed high levels of DUSP4 had a mesenchymal phenotype. Furthermore, knockdown of DUSP4 reversed the EMT in MCF-7/ADR cells, as demonstrated by upregulation of epithelial biomarkers and downregulation of mesenchymal biomarkers, and also increased the chemosensitivity of MCF-7/ADR cells to doxorubicin. Conclusions: DUSP4 might represent a potential drug target for inhibiting drug resistance and regulating the process of the EMT during the treatment of breast cancer. - Highlights: We used different technologies to prove our conclusion. DUSP4 knockdown increased doxorubicin chemosensitivity in breast cancer cells. DUSP4 is a potential target for combating drug resistance in breast cancer. DUSP4 is a potential target for regulating the EMT in breast cancer.

  17. Fuel cell arrangement

    DOE Patents [OSTI]

    Isenberg, Arnold 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.

  18. 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.

  19. Research Cell Efficiency Records

    Broader source: Energy.gov [DOE]

    The National Renewable Energy Laboratory maintains a plot of compiled values of highest confirmed conversion efficiencies for research cells, from 1976 to the present, for a range of photovoltaic technologies. This chart highlights cell efficiency results within different families of semiconductors: (1) multijunction cells, (2) single-junction gallium arsenide cells, (3) crystalline silicon cells, (4) thinfilm technologies, and (5) emerging photovoltaics.

  20. Cell Context Dependent p53 Genome-Wide Binding Patterns and Enrichment at Repeats

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

    Botcheva, Krassimira; McCorkle, Sean R.

    2014-11-21

    The p53 ability to elicit stress specific and cell type specific responses is well recognized, but how that specificity is established remains to be defined. Whether upon activation p53 binds to its genomic targets in a cell type and stress type dependent manner is still an open question. Here we show that the p53 binding to the human genome is selective and cell context-dependent. We mapped the genomic binding sites for the endogenous wild type p53 protein in the human cancer cell line HCT116 and compared them to those we previously determined in the normal cell line IMR90. We reportmore » distinct p53 genome-wide binding landscapes in two different cell lines, analyzed under the same treatment and experimental conditions, using the same ChIP-seq approach. This is evidence for cell context dependent p53 genomic binding. The observed differences affect the p53 binding sites distribution with respect to major genomic and epigenomic elements (promoter regions, CpG islands and repeats). We correlated the high-confidence p53 ChIP-seq peaks positions with the annotated human repeats (UCSC Human Genome Browser) and observed both common and cell line specific trends. In HCT116, the p53 binding was specifically enriched at LINE repeats, compared to IMR90 cells. The p53 genome-wide binding patterns in HCT116 and IMR90 likely reflect the different epigenetic landscapes in these two cell lines, resulting from cancer-associated changes (accumulated in HCT116) superimposed on tissue specific differences (HCT116 has epithelial, while IMR90 has mesenchymal origin). In conclusion, our data support the model for p53 binding to the human genome in a highly selective manner, mobilizing distinct sets of genes, contributing to distinct pathways.« less

  1. 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.

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

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

    Mitigating Performance Degradation of High-Energy Lithium-Ion Cells Diagnostic studies on Li-battery cells and cell components Cell Fabrication Facility Team Production and ...

  3. Radiosensitizing Effects of Ectopic miR-101 on Non-Small-Cell Lung Cancer Cells Depend on the Endogenous miR-101 Level

    SciTech Connect (OSTI)

    Chen, Susie; Wang Hongyan; Ng, Wooi Loon; Curran, Walter J.; Wang Ya

    2011-12-01

    Purpose: Previously, we showed that ectopic miR-101 could sensitize human tumor cells to radiation by targeting ATM and DNA-PK catalytic subunit (DNA-PKcs) to inhibit DNA repair, as the endogenous miR-101 levels are low in tumors in general. However, the heterogeneity of human cancers may result in an exception. The purpose of this study was to test the hypothesis that a few tumor cell lines with a high level of endogenous miR-101 would prove less response to ectopic miR-101. Methods and Materials: Fourteeen non-small-cell lung cancer (NSCLC) cell lines and one immortalized non-malignant lung epithelial cell line (NL20) were used for comparing endogenous miR-101 levels by real-time reverse transcription-polymerase chain reaction. Based on the different miR-101 levels, four cell lines with different miR-101 levels were chosen for transfection with a green fluorescent protein-lentiviral plasmid encoding miR-101. The target protein levels were measured by using Western blotting. The radiosensitizing effects of ectopic miR-101 on these NSCLC cell lines were determined by a clonogenic assay and xenograft mouse model. Results: The endogenous miR-101 level was similar or lower in 13 NSCLC cell lines but was 11-fold higher in one cell line (H157) than in NL20 cells. Although ectopic miR-101 efficiently decreased the ATM and DNA-PKcs levels and increased the radiosensitization level in H1299, H1975, and A549 cells, it did not change the levels of the miR-101 targets or radiosensitivity in H157 cells. Similar results were observed in xenograft mice. Conclusions: A small number of NSCLC cell lines could have a high level of endogenous miR-101. The ectopic miR-101 was able to radiosensitize most NSCLC cells, except for the NSCLC cell lines that had a much higher endogenous miR-101 level. These results suggest that when we choose one miRNA as a therapeutic tool, the endogenous level of the miRNA in each tumor should be considered.

  4. 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

  5. Mechanism of Akt1 inhibition of breast cancer cell invasionreveals a protumorigenic role for TSC2

    SciTech Connect (OSTI)

    Liu, Hong; Radisky, Derek C.; Nelson, Celeste M.; Zhang, Hui; Fata, Jimmie; Roth, Richard A.; Bissell, Mina J.

    2006-02-07

    Akt1 is frequently upregulated in human tumors, and has been shown to accelerate cell proliferation and to suppress programmed cell death; consequently, inhibiting the activity of Akt1 has been seen as an attractive target for therapeutic intervention. Paradoxically, hyperactivation of the Akt1 oncogene can also prevent the invasive behavior that underlies progression to metastasis. Here we show that overexpression of activated myr-Akt1 in human breast cancer cells phosphorylates and thereby targets the tumor suppressor tuberous sclerosis complex 2 (TSC2) for degradation, leading to reduced Rho-GTPase activity, decreased actin stress fibers and focal adhesions, and reduced motility and invasion. Overexpression of TSC2 rescues the migration phenotype of myr-Akt1-expressing tumor cells, and high levels of TSC2 in breast cancer patients correlate with increased metastasis and reduced survival. These data indicate that the functional properties of genes designated as oncogenes or tumor suppressor genes depends on the context of the cell type and the tissues studied, and suggest the need for caution in designing therapies targeting the function of individual genes in epithelial tissues.

  6. Transport of tetraethylammonium by a kidney cell line (LLC-PK sub 1 )

    SciTech Connect (OSTI)

    Fauth, C.; Rossier, B.; Roch-Ramel, F. )

    1988-03-01

    The authors investigated whether the LLC-PK{sub 1} epithelial cell lines (which shows many characteristics of proximal tubular cells) also is capable of transporting an organic ion. Suspended LLC-PK{sub 1} cells accumulated tetraethylammonium (TEA). The uptake showed characteristics of a facilitated mechanism; TEA uptake was saturable and temperature-dependent and was inhibited by other organic cations. Quinine and mepiperphenidol were the most potent inhibitors, whereas N{sup 1}-methylnicotinamide and morphine inhibited the transport system only slightly at doses of 10{sup {minus}3} M. Basolateral-to-apical TEA flux through LLC-PK{sub 1} monolayers was five to six times larger than that of mannitol, a nontransported compound, whereas apical-to-basolateral TEA and mannitol fluxes were equal. Only the basolateral-to-apical TEA flux was inhibited by quinine. Under similar experimental conditions, no transport of p-aminohippuric acid was observed. It is concluded that LLC-PK{sub 1} cells are able to transport TEA, as do cells of the proximal tubule.

  7. Electrochemical cell (Patent) | DOEPatents

    Office of Scientific and Technical Information (OSTI)

    Title: Electrochemical cell An electrochemical cell having an alkali metal negative electrode such as sodium and a positive electrode including Ni or transition metals, separated ...

  8. Electrochemical cell (Patent) | DOEPatents

    Office of Scientific and Technical Information (OSTI)

    Title: Electrochemical cell An electrochemical cell having a bimodal positive electrode, a negative electrode of an alkali metal, and a compatible electrolyte including an alkali ...

  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 ...

  10. Down-regulation of Wnt10a affects odontogenesis and proliferation in mesenchymal cells

    SciTech Connect (OSTI)

    Liu, Yang Han, Dong Wang, Lei Feng, Hailan

    2013-05-17

    Highlights: •Down-regulation of Wnt10a in dental mesenchymal cells impairs odontogenesis of reassociated tooth germs. •Dspp is down- and up-regulated after Wnt10a-knockdown and overexpression in dental mesenchymal cells. •Down-regulation of Wnt10a inhibits proliferation of dental mesenchymal cells. -- Abstract: The WNT10a mutation has been found in patients with abnormal odontogenesis. In mice, Wnt10a expression is found in the tooth germ, but its role has not yet been elucidated. We aimed to investigate the role of Wnt10a in odontogenesis. Mesenchymal cells of the first mandibular molar germ at the bell stage were isolated, transfected with Wnt10a SiRNA or plasmid, and reassociated with epithelial part of the molar germ. Scrambled SiRNA or empty vector was used in the control group. The reassociated tooth germs were transplanted into mice subrenal capsules. After gene modification, dental mesenchymal cells cultured in vitro were checked for cell proliferation and the expression of Dspp was examined. All 12 reassociated tooth germs in the control group resumed odontogenesis, while only 5 of 12 in the Wnt10a knockdown group developed into teeth. After Wnt10a knockdown, the mesenchymal cells cultured in vitro presented repressed proliferation. Wnt10a knockdown and overexpression led to both down- and up-regulation of Dspp. We conclude that the down-regulation of Wnt10a impairs odontogensis and cell proliferation, and that Wnt10a regulates Dspp expression in mesenchymal cells. These findings help to elucidate the mechanism of abnormal tooth development in patients with the WNT10A mutation.

  11. 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.

  12. Fuel Cell Bus Workshop

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

    ue Ce ec o o es o a Energy Efficiency & Renewable Energy Fuel Cell Bus Workshop Overview and Purp pose Dimitrios Papageorgopoulos Fuel Cell Technolog gies Prog gram DOE and DOT Joint Fuel Cell Bus Workshop, Washington DC DOE and DOT Joint Fuel Cell Bus Workshop, Washington DC June 7, 2010 June 7, 2010 Fuel Cells - Addressing Energy Challenges Energy Efficiency and Resource Diversity * Fuel cells offer a highly efficient way to use diverse fuels and energy sources Fuel cells offer a highly

  13. Molten carbonate fuel cell

    DOE Patents [OSTI]

    Kaun, Thomas D.; Smith, James L.

    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.

  14. 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.

  15. Fuel Cell Technologies Overview

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

    4/3/2012 eere.energy.gov Fuel Cell Technologies Overview Flow Cell Workshop Washington, DC Dr. Sunita Satyapal & Dr. Dimitrios Papageorgopoulos U.S. Department of Energy Fuel Cell Technologies Program 3/7/2011 Flow Cells for Energy Storage Workshop Purpose To understand the applied research and development needs and the grand challenges for the use of flow cells as energy-storage devices. Objectives 1. Understand the needs for applied research from stakeholders. 2. Gather input for future

  16. 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. Fuel Cells Fact Sheet (545.14 KB) 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

  17. Snail/beta-catenin signaling protects breast cancer cells from hypoxia attack

    SciTech Connect (OSTI)

    Scherbakov, Alexander M.; Stefanova, Lidia B.; Sorokin, Danila V.; Semina, Svetlana E.; Berstein, Lev M.; Krasilnikov, Mikhail A.

    2013-12-10

    The tolerance of cancer cells to hypoxia depends on the combination of different factors from increase of glycolysis (Warburg Effect) to activation of intracellular growth/apoptotic pathways. Less is known about the influence of epithelialmesenchymal transition (EMT) and EMT-associated pathways on the cell sensitivity to hypoxia. The aim of this study was to explore the role of Snail signaling, one of the key EMT pathways, in the mediating of hypoxia response and regulation of cell sensitivity to hypoxia, using as a model in vitro cultured breast cancer cells. Earlier we have shown that estrogen-independent HBL-100 breast cancer cells differ from estrogen-dependent MCF-7 cells with increased expression of Snail1, and demonstrated Snail1 involvement into formation of hormone-resistant phenotype. Because Snail1 belongs to hypoxia-activated proteins, here we studied the influence of Snail1 signaling on the cell tolerance to hypoxia. We found that Snail1-enriched HBL-100 cells were less sensitive to hypoxia-induced growth suppression if compared with MCF-7 line (31% MCF-7 vs. 71% HBL-100 cell viability after 1% O{sub 2} atmosphere for 3 days). Snail1 knock-down enhanced the hypoxia-induced inhibition of cell proliferation giving the direct evidence of Snail1 involvement into cell protection from hypoxia attack. The protective effect of Snail1 was shown to be mediated, at least in a part, via beta-catenin which positively regulated expression of HIF-1-dependent genes. Finally, we found that cell tolerance to hypoxia was accompanied with the failure in the phosphorylation of AMPK the key energy sensor, and demonstrated an inverse relationship between AMPK and Snail/beta-catenin signaling. Totally, our data show that Snail1 and beta-catenin, besides association with loss of hormone dependence, protect cancer cells from hypoxia and may serve as an important target in the treatment of breast cancer. Moreover, we suggest that the level of these proteins as well the

  18. Mixed lineage kinase 3 is required for matrix metalloproteinase expression and invasion in ovarian cancer cells

    SciTech Connect (OSTI)

    Zhan, Yu; Abi Saab, Widian F.; Modi, Nidhi; Stewart, Amanda M.; Liu, Jinsong; Chadee, Deborah N.

    2012-08-15

    Mixed lineage kinase 3 (MLK3) is a mitogen-activated protein kinase kinase kinase (MAP3K) that activates MAPK signaling pathways and regulates cellular responses such as proliferation, migration and apoptosis. Here we report high levels of total and phospho-MLK3 in ovarian cancer cell lines in comparison to immortalized nontumorigenic ovarian epithelial cell lines. Using small interfering RNA (siRNA)-mediated gene silencing, we determined that MLK3 is required for the invasion of SKOV3 and HEY1B ovarian cancer cells. Furthermore, mlk3 silencing substantially reduced matrix metalloproteinase (MMP)-1, -2, -9 and -12 gene expression and MMP-2 and -9 activities in SKOV3 and HEY1B ovarian cancer cells. MMP-1, -2, -9 and-12 expression, and MLK3-induced activation of MMP-2 and MMP-9 requires both extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) activities. In addition, inhibition of activator protein-1 (AP-1) reduced MMP-1, MMP-9 and MMP-12 gene expression. Collectively, these findings establish MLK3 as an important regulator of MMP expression and invasion in ovarian cancer cells. -- Highlights: Black-Right-Pointing-Pointer Ovarian cancer cell lines have high levels of total and phosphorylated MLK3. Black-Right-Pointing-Pointer MLK3 is required for MMP expression and activity in ovarian cancer cells. Black-Right-Pointing-Pointer MLK3 is required for invasion of SKOV3 and HEY1B ovarian cancer cells. Black-Right-Pointing-Pointer MLK3-dependent regulation of MMP-2 and MMP-9 activities requires ERK and JNK.

  19. Bleomycin induced epithelial–mesenchymal transition (EMT) in pleural mesothelial cells

    SciTech Connect (OSTI)

    Chen, Li-Jun; Ye, Hong; Zhang, Qian; Li, Feng-Zhi; Song, Lin-Jie; Yang, Jie; Mu, Qing; Rao, Shan-Shan; Cai, Peng-Cheng; Xiang, Fei; Zhang, Jian-Chu; Su, Yunchao; Xin, Jian-Bao; Ma, Wan-Li

    2015-03-01

    Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease characterized by the development of subpleural foci of myofibroblasts that contribute to the exuberant fibrosis. Recent studies revealed that pleural mesothelial cells (PMCs) undergo epithelial–mesenchymal transition (EMT) and play a pivotal role in IPF. In animal model, bleomycin induces pulmonary fibrosis exhibiting subpleural fibrosis similar to what is seen in human IPF. It is not known yet whether bleomycin induces EMT in PMCs. In the present study, PMCs were cultured and treated with bleomycin. The protein levels of collagen-I, mesenchymal phenotypic markers (vimentin and α-smooth muscle actin), and epithelial phenotypic markers (cytokeratin-8 and E-cadherin) were measured by Western blot. PMC migration was evaluated using wound-healing assay of culture PMCs in vitro, and in vivo by monitoring the localization of PMC marker, calretinin, in the lung sections of bleomycin-induced lung fibrosis. The results showed that bleomycin induced increases in collagen-I synthesis in PMC. Bleomycin induced significant increases in mesenchymal phenotypic markers and decreases in epithelial phenotypic markers in PMC, and promoted PMC migration in vitro and in vivo. Moreover, TGF-β1-Smad2/3 signaling pathway involved in the EMT of PMC was demonstrated. Taken together, our results indicate that bleomycin induces characteristic changes of EMT in PMC and the latter contributes to subpleural fibrosis. - Highlights: • Bleomycin induces collagen-I synthesis in pleural mesothelial cells (PMCs). • Bleomycin induces increases in vimentin and α-SMA protein in PMCs. • Bleomycin induces decreases in cytokeratin-8 and E-cadherin protein in PMCs • TGF-β1-Smad2/3 signaling pathway is involved in the PMC EMT induced by bleomycin.

  20. Endothelial Cell Migration and Vascular Endothelial Growth Factor Expression Are the Result of Loss of Breast Tissue Polarity

    SciTech Connect (OSTI)

    Chen, Amy; Cuevas, Ileana; Kenny, Paraic A; Miyake, Hiroshi; Mace, Kimberley; Ghajar, Cyrus; Boudreau, Aaron; Bissell, Mina; Boudreau, Nancy

    2009-05-26

    Recruiting a new blood supply is a rate-limiting step in tumor progression. In a three-dimensional model of breast carcinogenesis, disorganized, proliferative transformed breast epithelial cells express significantly higher expression of angiogenic genes compared with their polarized, growth-arrested nonmalignant counterparts. Elevated vascular endothelial growth factor (VEGF) secretion by malignant cells enhanced recruitment of endothelial cells (EC) in heterotypic cocultures. Significantly, phenotypic reversion of malignant cells via reexpression of HoxD10, which is lost in malignant progression, significantly attenuated VEGF expression in a hypoxia-inducible factor 1{alpha}-independent fashion and reduced EC migration. This was due primarily to restoring polarity: forced proliferation of polarized, nonmalignant cells did not induce VEGF expression and EC recruitment, whereas disrupting the architecture of growth-arrested, reverted cells did. These data show that disrupting cytostructure activates the angiogenic switch even in the absence of proliferation and/or hypoxia and restoring organization of malignant clusters reduces VEGF expression and EC activation to levels found in quiescent nonmalignant epithelium. These data confirm the importance of tissue architecture and polarity in malignant progression.

  1. 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.

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

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

    Fuel Cell Seminar on November 1, 2011. Fuel Cell Technologies Overview (4.38 MB) More Documents & Publications Fuel Cell Technologies Overview: March 2012 State Energy Advisory ...

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

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

    Overview of DOE's Fuel Cell Technologies Office presented by Sunita Satyapal at the 2013 Fuel Cell Seminar and Energy Exposition in Columbus, Ohio. DOE Fuel Cell Technologies ...

  4. 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 ...

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

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

    smith.pdf (0 B) More Documents & Publications Fuel Cells at Supermarkets: NYSERDA's Perspective Fuel Cell Case Study Hydrogen Production and Storage for Fuel Cells: Current Status

  6. 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

  7. Silicon solar cell assembly

    DOE Patents [OSTI]

    Burgess, Edward L.; Nasby, Robert D.; Schueler, Donald G.

    1979-01-01

    A silicon solar cell assembly comprising a large, thin silicon solar cell bonded to a metal mount for use when there exists a mismatch in the thermal expansivities of the device and the mount.

  8. Development and characterization of a hydrogen peroxide-resistant cholangiocyte cell line: A novel model of oxidative stress-related cholangiocarcinoma genesis

    SciTech Connect (OSTI)

    Thanan, Raynoo; Techasen, Anchalee; Hou, Bo; Jamnongkan, Wassana; Armartmuntree, Napat; Yongvanit, Puangrat; Murata, Mariko

    2015-08-14

    Oxidative stress is a cause of inflammation–related diseases, including cancers. Cholangiocarcinoma is a liver cancer with bile duct epithelial cell phenotypes. Our previous studies in animal and human models indicated that oxidative stress is a major cause of cholangiocarcinoma development. Hydrogen peroxide (H{sub 2}O{sub 2}) can generate hydroxyl radicals, which damage lipids, proteins, and nucleic acids, leading to cell death. However, some cells can survive by adapting to oxidative stress conditions, and selective clonal expansion of these resistant cells would be involved in oxidative stress-related carcinogenesis. The present study aimed to establish H{sub 2}O{sub 2}-resistant cell line from an immortal cholangiocyte cell line (MMNK1) by chronic treatment with low-concentration H{sub 2}O{sub 2} (25 μM). After 72 days of induction, H{sub 2}O{sub 2}-resistant cell lines (ox-MMNK1-L) were obtained. The ox-MMNK1-L cell line showed H{sub 2}O{sub 2}-resistant properties, increasing the expression of the anti-oxidant genes catalase (CAT), superoxide dismutase-1 (SOD1), superoxide dismutase-2 (SOD2), and superoxide dismutase-3 (SOD3) and the enzyme activities of CAT and intracellular SODs. Furthermore, the resistant cells showed increased expression levels of an epigenetics-related gene, DNA methyltransferase-1 (DNMT1), when compared to the parental cells. Interestingly, the ox-MMNK1-L cell line had a significantly higher cell proliferation rate than the MMNK1 normal cell line. Moreover, ox-MMNK1-L cells showed pseudopodia formation and the loss of cell-to-cell adhesion (multi-layers) under additional oxidative stress (100 μM H{sub 2}O{sub 2}). These findings suggest that H{sub 2}O{sub 2}-resistant cells can be used as a model of oxidative stress-related cholangiocarcinoma genesis through molecular changes such as alteration of gene expression and epigenetic changes. - Highlights: • An H{sub 2}O{sub 2}-resistant ox-MMNK1-L cells was established from

  9. NETL: SOFC Cell Development

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

    Cell Development Cell Development-Research is focused on the cell-related technologies critical to the commercialization of SOFC technology. The components of the SOFC - the anode, cathode and electrolyte - are the primary research emphasis of this key technology. The electrochemical performance, durability, and reliability of the solid oxide fuel cell are key determinants in establishing the technical and economic viability of SOFC Power Systems. Thus the SOFC Program maintains a diversified

  10. Electrochemistry Cell Model

    Broader source: Energy.gov [DOE]

    2012 DOE Hydrogen and Fuel Cells Program and Vehicle Technologies Program Annual Merit Review and Peer Evaluation Meeting

  11. Electrochemistry Cell Model

    Broader source: Energy.gov [DOE]

    2011 DOE Hydrogen and Fuel Cells Program, and Vehicle Technologies Program Annual Merit Review and Peer Evaluation

  12. Biomarkers of cell senescence

    DOE Patents [OSTI]

    Dirmi, Goberdhan P.; Campisi, Judith; Peacocke, Monica

    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.

  13. Biomarkers of cell senescence

    DOE Patents [OSTI]

    Dimri, Goberdhan P.; Campisi, Judith; Peacocke, Monica

    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.

  14. 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.

  15. 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.

  16. 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.

  17. EERE Fuel Cell Technologies Program

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

    AudienceEvent Date EERE Fuel Cell Technologies Program Sunita Satyapal Acting Program Manager U.S. Department of Energy Fuel Cell Technologies Program Fuel Cell Project Kickoff ...

  18. Matrigel Basement Membrane Matrix influences expression of microRNAs in cancer cell lines

    SciTech Connect (OSTI)

    Price, Karina J.; School of Medicine and Pharmacology, University of Western Australia, Nedlands, WA 6008 ; Tsykin, Anna; School of Molecular and Biomedical Science, University of Adelaide, Adelaide, SA 5005 ; Giles, Keith M.; Sladic, Rosemary T.; Epis, Michael R.; Ganss, Ruth; Goodall, Gregory J.; School of Molecular and Biomedical Science, University of Adelaide, Adelaide, SA 5005; Department of Medicine, University of Adelaide, Adelaide, SA 5005 ; Leedman, Peter J.

    2012-10-19

    Highlights: Black-Right-Pointing-Pointer Matrigel alters cancer cell line miRNA expression relative to culture on plastic. Black-Right-Pointing-Pointer Many identified Matrigel-regulated miRNAs are implicated in cancer. Black-Right-Pointing-Pointer miR-1290, -210, -32 and -29b represent a Matrigel-induced miRNA signature. Black-Right-Pointing-Pointer miR-32 down-regulates Integrin alpha 5 (ITGA5) mRNA. -- Abstract: Matrigel is a medium rich in extracellular matrix (ECM) components used for three-dimensional cell culture and is known to alter cellular phenotypes and gene expression. microRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression and have roles in cancer. While miRNA profiles of numerous cell lines cultured on plastic have been reported, the influence of Matrigel-based culture on cancer cell miRNA expression is largely unknown. This study investigated the influence of Matrigel on the expression of miRNAs that might facilitate ECM-associated cancer cell growth. We performed miRNA profiling by microarray using two colon cancer cell lines (SW480 and SW620), identifying significant differential expression of miRNAs between cells cultured in Matrigel and on plastic. Many of these miRNAs have previously been implicated in cancer-related processes. A common Matrigel-induced miRNA signature comprised of up-regulated miR-1290 and miR-210 and down-regulated miR-29b and miR-32 was identified using RT-qPCR across five epithelial cancer cell lines (SW480, SW620, HT-29, A549 and MDA-MB-231). Experimental modulation of these miRNAs altered expression of their known target mRNAs involved in cell adhesion, proliferation and invasion, in colon cancer cell lines. Furthermore, ITGA5 was identified as a novel putative target of miR-32 that may facilitate cancer cell interactions with the ECM. We propose that culture of cancer cell lines in Matrigel more accurately recapitulates miRNA expression and function in cancer than culture on plastic and thus is a

  19. 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.

  20. Iron repletion relocalizes hephaestin to a proximal basolateral compartment in polarized MDCK and Caco2 cells

    SciTech Connect (OSTI)

    Lee, Seung-Min [Department of Biological Sciences, University of Columbia, NY (United States) [Department of Biological Sciences, University of Columbia, NY (United States); Department of Nutritional Science and Toxicology, University of California, Berkeley, CA (United States); Attieh, Zouhair K. [Department of Laboratory Science and Technology, American University of Science and Technology, Ashrafieh (Lebanon) [Department of Laboratory Science and Technology, American University of Science and Technology, Ashrafieh (Lebanon); Department of Nutritional Science and Toxicology, University of California, Berkeley, CA (United States); Son, Hee Sook [Department of Food Science and Human Nutrition, College of Human Ecology, Chonbuk National University (Korea, Republic of) [Department of Food Science and Human Nutrition, College of Human Ecology, Chonbuk National University (Korea, Republic of); Department of Nutritional Science and Toxicology, University of California, Berkeley, CA (United States); Chen, Huijun [Medical School, Nanjing University, Nanjing 210008, Jiangsu Province (China) [Medical School, Nanjing University, Nanjing 210008, Jiangsu Province (China); Department of Nutritional Science and Toxicology, University of California, Berkeley, CA (United States); Bacouri-Haidar, Mhenia [Department of Biology, Faculty of Sciences (I), Lebanese University, Hadath (Lebanon) [Department of Biology, Faculty of Sciences (I), Lebanese University, Hadath (Lebanon); Department of Nutritional Science and Toxicology, University of California, Berkeley, CA (United States); Vulpe, Chris D., E-mail: vulpe@berkeley.edu [Department of Nutritional Science and Toxicology, University of California, Berkeley, CA (United States)

    2012-05-11

    Highlights: Black-Right-Pointing-Pointer Hephaestin localizes in the perinuclear space in non-polarized cells. Black-Right-Pointing-Pointer Hephaestin localizes in the perinuclear space in iron deficient and polarized cells. Black-Right-Pointing-Pointer Hephaestin with apical iron moves near to basolateral membrane of polarized cells. Black-Right-Pointing-Pointer Peri-basolateral location of hephaestin is accessible to the extracellular space. Black-Right-Pointing-Pointer Hephaestin is involved in iron mobilization from the intestine to circulation. -- Abstract: While intestinal cellular iron entry in vertebrates employs multiple routes including heme and non-heme routes, iron egress from these cells is exclusively channeled through the only known transporter, ferroportin. Reduced intestinal iron export in sex-linked anemia mice implicates hephaestin, a ferroxidase, in this process. Polarized cells are exposed to two distinct environments. Enterocytes contact the gut lumen via the apical surface of the cell, and through the basolateral surface, to the body. Previous studies indicate both local and systemic control of iron uptake. We hypothesized that differences in iron availability at the apical and/or basolateral surface may modulate iron uptake via cellular localization of hephaestin. We therefore characterized the localization of hephaestin in two models of polarized epithelial cell lines, MDCK and Caco2, with varying iron availability at the apical and basolateral surfaces. Our results indicate that hephaestin is expressed in a supra-nuclear compartment in non-polarized cells regardless of the iron status of the cells and in iron deficient and polarized cells. In polarized cells, we found that both apical (as FeSO{sub 4}) and basolateral iron (as the ratio of apo-transferrin to holo-transferrin) affect mobilization of hephaestin from the supra-nuclear compartment. We find that the presence of apical iron is essential for relocalization of hephaestin to a

  1. 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

  2. Fuel Cell 101

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

    Cell 101 Don Hoffman Don Hoffman Ship Systems & Engineering Research Division March 2011 Distribution Statement A: Approved for public release; distribution is unlimited. Fuel Cell Operation * A Fuel Cell is an electrochemical power source * It supplies electricity by combining hydrogen and oxygen electrochemically without combustion. * It is configured like a battery with anode and cathode. * Unlike a battery, it does not run down or require recharging and will produce electricity and will

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. Heterojunction solar cell

    DOE Patents [OSTI]

    Olson, Jerry M.

    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.

  8. Fuel Cell Case Study

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

    Global Leader, Sustainable Engineering, Maintenance & Energy Management Whole Foods Market, Inc. Fuel Cell Case Study 2 Holistic Approach from Development to Operation WFM Energy ...

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. Molten salt lithium cells

    DOE Patents [OSTI]

    Raistrick, Ian D.; Poris, Jaime; Huggins, Robert A.

    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).

  14. Molten salt lithium cells

    DOE Patents [OSTI]

    Raistrick, Ian D.; Poris, Jaime; Huggins, Robert A.

    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).

  15. 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.

  16. Hot Cell Complex Building

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

    Based on the safety and functional requirements, starting from existing layout and existing safety analyses, the first step of the Hot Cell Complex Building Engineering Contract ...

  17. The cell surface

    SciTech Connect (OSTI)

    Axel, R.; Goodman, C.; Hynes, R.; Stillman, B.

    1992-12-31

    This volume contains abstracts of oral presentations and poster sessions of made at the LVII Cold Springs Symposium on Quantitative Biology, entitled The Cell Surface.

  18. 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.

  19. 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.

  20. Nanocrystal Solar Cells

    SciTech Connect (OSTI)

    Gur, Ilan

    2006-12-15

    This dissertation presents the results of a research agenda aimed at improving integration and stability in nanocrystal-based solar cells through advances in active materials and device architectures. The introduction of 3-dimensional nanocrystals illustrates the potential for improving transport and percolation in hybrid solar cells and enables novel fabrication methods for optimizing integration in these systems. Fabricating cells by sequential deposition allows for solution-based assembly of hybrid composites with controlled and well-characterized dispersion and electrode contact. Hyperbranched nanocrystals emerge as a nearly ideal building block for hybrid cells, allowing the controlled morphologies targeted by templated approaches to be achieved in an easily fabricated solution-cast device. In addition to offering practical benefits to device processing, these approaches offer fundamental insight into the operation of hybrid solar cells, shedding light on key phenomena such as the roles of electrode-contact and percolation behavior in these cells. Finally, all-inorganic nanocrystal solar cells are presented as a wholly new cell concept, illustrating that donor-acceptor charge transfer and directed carrier diffusion can be utilized in a system with no organic components, and that nanocrystals may act as building blocks for efficient, stable, and low-cost thin-film solar cells.

  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. Fuel Cell Demonstration Program

    SciTech Connect (OSTI)

    Gerald Brun

    2006-09-15

    In an effort to promote clean energy projects and aid in the commercialization of new fuel cell technologies the Long Island Power Authority (LIPA) initiated a Fuel Cell Demonstration Program in 1999 with six month deployments of Proton Exchange Membrane (PEM) non-commercial Beta model systems at partnering sites throughout Long Island. These projects facilitated significant developments in the technology, providing operating experience that allowed the manufacturer to produce fuel cells that were half the size of the Beta units and suitable for outdoor installations. In 2001, LIPA embarked on a large-scale effort to identify and develop measures that could improve the reliability and performance of future fuel cell technologies for electric utility applications and the concept to establish a fuel cell farm (Farm) of 75 units was developed. By the end of October of 2001, 75 Lorax 2.0 fuel cells had been installed at the West Babylon substation on Long Island, making it the first fuel cell demonstration of its kind and size anywhere in the world at the time. Designed to help LIPA study the feasibility of using fuel cells to operate in parallel with LIPA's electric grid system, the Farm operated 120 fuel cells over its lifetime of over 3 years including 3 generations of Plug Power fuel cells (Lorax 2.0, Lorax 3.0, Lorax 4.5). Of these 120 fuel cells, 20 Lorax 3.0 units operated under this Award from June 2002 to September 2004. In parallel with the operation of the Farm, LIPA recruited government and commercial/industrial customers to demonstrate fuel cells as on-site distributed generation. From December 2002 to February 2005, 17 fuel cells were tested and monitored at various customer sites throughout Long Island. The 37 fuel cells operated under this Award produced a total of 712,635 kWh. As fuel cell technology became more mature, performance improvements included a 1% increase in system efficiency. Including equipment, design, fuel, maintenance, installation

  3. 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.

  4. 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.

  5. Oatp-associated uptake and toxicity of microcystins in primary murine whole brain cells

    SciTech Connect (OSTI)

    Feurstein, D.; Holst, K.; Fischer, A.; Dietrich, D.R.

    2009-01-15

    Microcystins (MCs) are naturally occurring cyclic heptapeptides that exhibit hepato-, nephro- and possibly neurotoxic effects in mammals. Organic anion transporting polypeptides (rodent Oatp/human OATP) appear to be specifically required for active uptake of MCs into hepatocytes and kidney epithelial cells. Based on symptoms of neurotoxicity in MC-intoxicated patients and the presence of Oatp/OATP at the blood-brain-barrier (BBB) and blood-cerebrospinal-fluid-barrier (BCFB) it is hypothesized that MCs can be transported across the BBB/BCFB in an Oatp/OATP-dependent manner and can induce toxicity in brain cells via inhibition of protein phosphatase (PP). To test these hypotheses, the presence of murine Oatp (mOatp) in primary murine whole brain cells (mWBC) was investigated at the mRNA and protein level. MC transport was tested by exposing mWBCs to three different MC-congeners (MC-LR, -LW, -LF) with/without co-incubation with the OATP/Oatp-substrates taurocholate (TC) and bromosulfophthalein (BSP). Uptake of MCs and cytotoxicity was demonstrated via MC-Western blot analysis, immunocytochemistry, cell viability and PP inhibition assays. All MC congeners bound covalently and inhibited mWBC PP. MC-LF was the most cytotoxic congener followed by -LW and -LR. The lowest toxin concentration significantly reducing mWBC viability after 48 h exposure was 400 nM (MC-LF). Uptake of MCs into mWBCs was inhibited via co-incubation with excess TC (50 and 500 {mu}M) and BSP (50 {mu}M). MC-Western blot analysis demonstrated a concentration-dependent accumulation of MCs. In conclusion, the in vitro data support the assumed MC-congener-dependent uptake in a mOatp-associated manner and cytotoxicity of MCs in primary murine whole brain cells.

  6. 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.

  7. 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.

  8. Fuel cell generator

    DOE Patents [OSTI]

    Isenberg, Arnold O.

    1983-01-01

    High temperature solid oxide electrolyte fuel cell generators which allow controlled leakage among plural chambers in a sealed housing. Depleted oxidant and fuel are directly reacted in one chamber to combust remaining fuel and preheat incoming reactants. The cells are preferably electrically arranged in a series-parallel configuration.

  9. 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.

  10. Metal halogen electrochemical cell

    DOE Patents [OSTI]

    Bellows, Richard J.; Kantner, Edward

    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.

  11. 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.

  12. Photovoltaic solar cell

    SciTech Connect (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.

  13. 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.

  14. Solid oxide fuel cell generator

    DOE Patents [OSTI]

    Di Croce, A. Michael; Draper, Robert

    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.

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

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

    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

  16. 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

  17. 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

  18. Internet Fuel Cells Forum

    SciTech Connect (OSTI)

    Sudhoff, Frederick A.

    1996-08-01

    The rapid development and integration of the Internet into the mainstream of professional life provides the fuel cell industry with the opportunity to share new ideas with unprecedented capabilities. The U.S. Department of Energy's (DOE's) Morgantown Energy Technology Center (METC) has undertaken the task to maintain a Fuel Cell Forum on the Internet. Here, members can exchange ideas and information pertaining to fuel cell technologies. The purpose of this forum is to promote a better understanding of fuel cell concepts, terminology, processes, and issues relating to commercialization of fuel cell power technology. The Forum was developed by METC to provide those interested with fuel cell conference information for its current concept of exchanging ideas and information pertaining to fuel cells. Last August, the Forum expanded to an on-line and world-wide network. There are 250 members, and membership is growing at a rate of several new subscribers per week. The forum currently provides updated conference information and interactive information exchange. Forum membership is encouraged from utilities, industry, universities, and government. Because of the public nature of the internet, business sensitive, confidential, or proprietary information should not be placed on this system. The Forum is unmoderated; therefore, the views and opinions of authors expressed in the forum do not necessarily state or reflect those of the U.S. government or METC.

  19. Fuel Cell Animation- Fuel Cell Stack (Text Version)

    Broader source: Energy.gov [DOE]

    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.

  20. Fuel Cell Animation- Fuel Cell Components (Text Version)

    Broader source: Energy.gov [DOE]

    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.

  1. Bipolar fuel cell

    DOE Patents [OSTI]

    McElroy, James F.

    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.

  2. Solid Oxide Fuel Cells FAQs

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

    SOLID OXIDE FUEL CELLS - BASICS Q: What is a fuel cell? A: A fuel cell is a power generation ... Program research is focused on developing low-cost and highly efficient SOFC power ...

  3. Air Liquide - Biogas & Fuel Cells

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

    ... 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 Biomethane ...

  4. Fuel Cell Technologies Program Overview

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

    US DOE CSD Workshop Washington, DC Fuel Cell Technologies Program Overview Dr. Sunita Satyapal Director, Fuel Cell Technologies Office Energy Efficiency and Renewable Energy U.S. Department of Energy 3/20/2012 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,

  5. 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,

  6. 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...

  7. Ohio Fuel Cell Initiative

    Broader source: Energy.gov [DOE]

    Presented at the Technology Transition Corporation and U.S. Department of Energy Webinar: The Top 5 Fuel Cell States: Why Local Policies Mean Green Growth, June 21, 2011.

  8. Fuel cell water transport

    DOE Patents [OSTI]

    Vanderborgh, Nicholas E.; Hedstrom, James C.

    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.

  9. Hydrogen & Fuel Cells

    Broader source: Energy.gov [DOE]

    Hydrogen is an energy carrier that can be produced from clean, diverse and abundant domestic energy resources. Fuel cells use the energy from hydrogen in a highly efficient way -- with only water and heat as byproducts.

  10. Financing Fuel Cells

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

    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 ...

  11. 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.

  12. 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.

  13. 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.

  14. Solar cell array interconnects

    DOE Patents [OSTI]

    Carey, Paul G.; Thompson, Jesse B.; Colella, Nicolas J.; Williams, Kenneth A.

    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.

  15. Thin film photovoltaic cells

    DOE Patents [OSTI]

    Rothwarf, Allen

    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.

  16. 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...

  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. Appendix K Disposal Cell Groundwater Monitoring Plan

    Office of Legacy Management (LM)

    K Disposal Cell Groundwater Monitoring Plan

  19. Comparison of Fuel Cell Technologies

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

    More Information More information on the Fuel Cell Technologies Offce is available at http:www.hydrogenandfuelcells.energy.gov. Fuel Cell Type Common Electrolyte Operating ...

  20. 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...

  1. 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...

  2. Manufacturing Fuel Cell Manhattan Project

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

    Manufacturing Fuel Cell Manhattan Project Presented by the Benchmarking and Best Practices ... in providing valued information on affordable and implementable fuel cell technology. ...

  3. DOE Fuel Cell Technology Office

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

    Fuel Cell Technology Office - Sandia Energy Energy Search Icon Sandia Home Locations ... SunShot Grand Challenge: Regional Test Centers DOE Fuel Cell Technology Office Home...

  4. Ceramic Fuel Cells (SOFC)

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

    H2/FC Manufacturing R&D Workshop J. David Carter, PhD Chemical Sciences and Engineering Argonne National Laboratory Thursday, August 11, 2011 Ceramic Fuel Cells (SOFC) Manufacturing Fuel Cell Manhattan Project: * Joe Bonadies - Delphi * Rick Kerr - Delphi * David Carter - Argonne * Aaron Crumm - AMI * Randy Petri - Versa Power * Jolyon Rawson - Acumentrics * Marc Gietter - Army-CERDEC * Scott Swartz - NexTech Materials * Eric Stanfield - NIST * Mike Ulsh - NREL / DOE * Matt Steinbroner -

  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. 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.

  7. Fuel Cell Development Status

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

    Development Status Michael Short Systems Engineering Manager United Technologies Corporation Research Center Hamilton Sundstrand UTC Power UTC Fire & Security Fortune 50 corporation $52.9B in annual sales in 2009 ~60% of Sales are in building technologies Transportation Stationary Fuel Cells Space & Defense * Fuel cell technology leader since 1958 * ~ 550 employees * 768+ Active U.S. patents, more than 300 additional U.S. patents pending * Global leader in efficient, reliable, and

  8. 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.

  9. Compliant fuel cell system

    DOE Patents [OSTI]

    Bourgeois, Richard Scott; Gudlavalleti, Sauri

    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.

  10. 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.

  11. 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.

  12. Aluminum reduction cell electrode

    DOE Patents [OSTI]

    Goodnow, Warren H.; Payne, John R.

    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.

  13. Fuel cell system

    DOE Patents [OSTI]

    Early, Jack; Kaufman, Arthur; Stawsky, Alfred

    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.

  14. Fuel cell generator

    DOE Patents [OSTI]

    Makiel, Joseph M.

    1985-01-01

    A high temperature solid electrolyte fuel cell generator comprising a housing means defining a plurality of chambers including a generator chamber and a combustion products chamber, a porous barrier separating the generator and combustion product chambers, a plurality of elongated annular fuel cells each having a closed end and an open end with the open ends disposed within the combustion product chamber, the cells extending from the open end through the porous barrier and into the generator chamber, a conduit for each cell, each conduit extending into a portion of each cell disposed within the generator chamber, each conduit having means for discharging a first gaseous reactant within each fuel cell, exhaust means for exhausting the combustion product chamber, manifolding means for supplying the first gaseous reactant to the conduits with the manifolding means disposed within the combustion product chamber between the porous barrier and the exhaust means and the manifolding means further comprising support and bypass means for providing support of the manifolding means within the housing while allowing combustion products from the first and a second gaseous reactant to flow past the manifolding means to the exhaust means, and means for flowing the second gaseous reactant into the generator chamber.

  15. 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

  16. MicroRNA-134 regulates lung cancer cell H69 growth and apoptosis by targeting WWOX gene and suppressing the ERK1/2 signaling pathway

    SciTech Connect (OSTI)

    Chen, Tianjun; Gao, Fei; Feng, Sifang; Yang, Tian; Chen, Mingwei

    2015-08-28

    MicroRNAs have been shown to act as crucial modulators during carcinogenesis. Recent studies have implied that miR-134 expression associated with epithelial-to-mesenchymal transition phenotype and invasive potential of NSCLC cells. Our study investigated the pathogenic implications of miR-134 in small cell lung cancer (SCLC). Overexpression or inhibition MiR-134 expression by miR-134 mimics or miR-134 inhibitors (anti-miR-134) in SCLC cell lines was detected using qRT-PCR. Lactate dehydrogenase (LDH) assay, MTT assays and flow cytometry were performed in order to clarify the growth and apoptosis of SCLC cells which had been transfected with miR-134 mimics or anti-miR-134. WWOX expression in H69 cells was detected by qRT-PCR and western blot, respectively. The results showed that overexpression miR-134 was significantly promoting SCLC cells growth and inhibit its apoptosis. In addition, reduced miR-134 expression was significantly correlated with cell growth inhibition and apoptosis promotion. Furthermore, transfection of miR-134 mimics into the SCLC cells markedly down-regulated the level of WWOX, whereas, anti-miR-134 up-regulated WWOX expression. We also found that overexpression WWOX attenuate miR-134 induced H69 cells growth, and promote cell apoptosis. Moreover, miR-134 promoted cell proliferation and inhibit apoptosis via the activation of ERK1/2 pathway. These findings suggest that miR-134 may be an ideal diagnostic and prognostic marker, and may be attributed to the molecular therapy of SCLC. - Highlights: • MiR-134 play roles in small cell lung cancer cell growth and apoptosis. • MiR-134 negative regulated the level of WWOX in H69 cells. • WWOX overexpression attenuate miR-134 induced H69 cells growth. • MiR-134 promotes cell growth via the activation of ERK1/2 pathway.

  17. Transitioning from Fuel Cells to Redox Flow Cells

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

    Transitioning From Fuel Cells to Redox Flow Cells T. Zawodzinski and Matt Mench University of Tennessee and ORNL Managed by UT-Battelle for the Department of Energy 2 Acknowledgments $$ DOE-OE EPRI GCEP NSF EPSCOR (TN SCORE) UTK Governor's Chair Fund Partner in Crime Matt Mench Managed by UT-Battelle for the Department of Energy Peeling the Onion' Personalized History of PEM Fuel Cells We May Recapitulate This for RFBs Catalysis Test System * Small Single Cell * Large Single Cell * Stack *

  18. 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.

  19. 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.

  20. 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.

  1. Electrochemical cell operation and system

    DOE Patents [OSTI]

    Maru, Hansraj C.

    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.

  2. Device for monitoring cell voltage

    DOE Patents [OSTI]

    Doepke, Matthias; Eisermann, Henning

    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.

  3. 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.

  4. 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.

  5. Dense pattern multiple pass cells

    DOE Patents [OSTI]

    Silver, Joel A.; Bomse, David S.

    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.

  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 μm, 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. 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.

  8. 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

  9. 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.

  10. Monolithic tandem solar cell

    SciTech Connect (OSTI)

    Wanlass, Mark W.

    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.

  11. Fuel cell stack arrangements

    DOE Patents [OSTI]

    Kothmann, Richard E.; Somers, Edward V.

    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.

  12. 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.

  13. Sulphoraphane, a naturally occurring isothiocyanate induces apoptosis in breast cancer cells by targeting heat shock proteins

    SciTech Connect (OSTI)

    Sarkar, Ruma; Mukherjee, Sutapa [Department of Environmental Carcinogenesis and Toxicology, Chittaranjan National Cancer Institute, 37, SP Mukherjee Road, Kolkata 700 026 (India)] [Department of Environmental Carcinogenesis and Toxicology, Chittaranjan National Cancer Institute, 37, SP Mukherjee Road, Kolkata 700 026 (India); Biswas, Jaydip [Chittaranjan National Cancer Institute, 37, SP Mukherjee Road, Kolkata 700 026 (India)] [Chittaranjan National Cancer Institute, 37, SP Mukherjee Road, Kolkata 700 026 (India); Roy, Madhumita, E-mail: mitacnci@yahoo.co.in [Department of Environmental Carcinogenesis and Toxicology, Chittaranjan National Cancer Institute, 37, SP Mukherjee Road, Kolkata 700 026 (India)] [Department of Environmental Carcinogenesis and Toxicology, Chittaranjan National Cancer Institute, 37, SP Mukherjee Road, Kolkata 700 026 (India)

    2012-10-12

    Highlights: Black-Right-Pointing-Pointer HSPs (27, 70 and 90) and HSF1 are overexpressed in MCF-7 and MDA-MB-231 cells. Black-Right-Pointing-Pointer Sulphoraphane, a natural isothiocyanate inhibited HSPs and HSF1 expressions. Black-Right-Pointing-Pointer Inhibition of HSPs and HSF1 lead to regulation of apoptotic proteins. Black-Right-Pointing-Pointer Alteration of apoptotic proteins activate of caspases particularly caspase 3 and 9 leading to induction of apoptosis. Black-Right-Pointing-Pointer Alteration of apoptotic proteins induce caspases leading to induction of apoptosis. -- Abstract: Heat shock proteins (HSPs) are involved in protein folding, aggregation, transport and/or stabilization by acting as a molecular chaperone, leading to inhibition of apoptosis by both caspase dependent and/or independent pathways. HSPs are overexpressed in a wide range of human cancers and are implicated in tumor cell proliferation, differentiation, invasion and metastasis. HSPs particularly 27, 70, 90 and the transcription factor heat shock factor1 (HSF1) play key roles in the etiology of breast cancer and can be considered as potential therapeutic target. The present study was designed to investigate the role of sulphoraphane, a natural isothiocyanate on HSPs (27, 70, 90) and HSF1 in two different breast cancer cell lines MCF-7 and MDA-MB-231 cells expressing wild type and mutated p53 respectively, vis-a-vis in normal breast epithelial cell line MCF-12F. It was furthermore investigated whether modulation of HSPs and HSF1 could induce apoptosis in these cells by altering the expressions of p53, p21 and some apoptotic proteins like Bcl-2, Bax, Bid, Bad, Apaf-1 and AIF. Sulphoraphane was found to down-regulate the expressions of HSP70, 90 and HSF1, though the effect on HSP27 was not pronounced. Consequences of HSP inhibition was upregulation of p21 irrespective of p53 status. Bax, Bad, Apaf-1, AIF were upregulated followed by down-regulation of Bcl-2 and this effect was prominent

  14. 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

  15. 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).

  16. Thin film photovoltaic cell

    DOE Patents [OSTI]

    Meakin, John D.; Bragagnolo, Julio

    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.

  17. Improved photoelectrodialytic cell

    SciTech Connect (OSTI)

    Murphy, G.W.

    1981-08-14

    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.

  18. Amorphous semiconductor solar cell

    DOE Patents [OSTI]

    Dalal, Vikram L.

    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.

  19. 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.

  20. Metal-sulfide mineral ores, Fenton chemistry and disease. Particle induced inflammatory stress response in lung cells

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

    Harrington, Andrea D.; Smirnov, Alexander; Tsirka, Stella E.; Schoonen, Martin A. A.

    2014-07-10

    The inhalation of mineral particulates and other earth materials, such as coal, can initiate or enhance disease in humans. Workers in occupations with high particulate exposure, such as mining, are particularly at risk. The ability of a material to generate an inflammatory stress response (ISR), a measure of particle toxicity, is a useful tool in evaluating said exposure risk. ISR is defined as the upregulation of cellular reactive oxygen species (ROS) normalized to cell viability. This study compares the ISR of A549 human lung epithelial cells after exposure to well-characterized common metal-sulfide ore mineral separates. The evaluation of the deleteriousmore » nature of ore minerals is based on a range of particle loadings (serial dilutions of 0.002 m2/mL stock) and exposure periods (beginning at 30 min and measured systematically for up to 24 h). There is a wide range in ISR values generated by the ore minerals. The ISR values produced by the sphalerite samples are within the range of inert materials. Arsenopyrite generated a small ISR that was largely driven by cell death. Galena showed a similar, but more pronounced response. Copper-bearing ore minerals generated the greatest ISR, both by upregulating cellular ROS and generating substantial and sustained cell death. Chalcopyrite and bornite, both containing ferrous iron, generated the greatest ISR overall. Particles containing Fenton metals as major constituents produce the highest ISR, while other heavy metals mainly generate cell death. Furthermore, this study highlights the importance of evaluating the chemistry, oxidation states and structure of a material when assessing risk management.« less

  1. Metal-sulfide mineral ores, Fenton chemistry and disease. Particle induced inflammatory stress response in lung cells

    SciTech Connect (OSTI)

    Harrington, Andrea D.; Smirnov, Alexander; Tsirka, Stella E.; Schoonen, Martin A. A.

    2014-07-10

    The inhalation of mineral particulates and other earth materials, such as coal, can initiate or enhance disease in humans. Workers in occupations with high particulate exposure, such as mining, are particularly at risk. The ability of a material to generate an inflammatory stress response (ISR), a measure of particle toxicity, is a useful tool in evaluating said exposure risk. ISR is defined as the upregulation of cellular reactive oxygen species (ROS) normalized to cell viability. This study compares the ISR of A549 human lung epithelial cells after exposure to well-characterized common metal-sulfide ore mineral separates. The evaluation of the deleterious nature of ore minerals is based on a range of particle loadings (serial dilutions of 0.002 m2/mL stock) and exposure periods (beginning at 30 min and measured systematically for up to 24 h). There is a wide range in ISR values generated by the ore minerals. The ISR values produced by the sphalerite samples are within the range of inert materials. Arsenopyrite generated a small ISR that was largely driven by cell death. Galena showed a similar, but more pronounced response. Copper-bearing ore minerals generated the greatest ISR, both by upregulating cellular ROS and generating substantial and sustained cell death. Chalcopyrite and bornite, both containing ferrous iron, generated the greatest ISR overall. Particles containing Fenton metals as major constituents produce the highest ISR, while other heavy metals mainly generate cell death. Furthermore, this study highlights the importance of evaluating the chemistry, oxidation states and structure of a material when assessing risk management.

  2. 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.

  3. 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

  4. Fuel Cells | Department of Energy

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

    Fuel 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,

  5. 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

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

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

    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. ...

  7. NREL: Hydrogen and Fuel Cells Research - Stationary Fuel Cell...

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

    ... 26, 11515 Installed Eligible Cost per kW by Capacity (CHP Fuel Cell) CDP STAT 27, 11515 Range of ... decision making. (June 2016) Hydrogen and Fuel Cells for IT Equipment. ...

  8. 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,...

  9. 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,

  10. Diagnostic Studies on Lithium Battery Cells and Cell Components

    Broader source: Energy.gov [DOE]

    2012 DOE Hydrogen and Fuel Cells Program and Vehicle Technologies Program Annual Merit Review and Peer Evaluation Meeting

  11. High Temperature Fuel Cell Performance High Temperature Fuel Cell

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

    Performance of of Sulfonated Sulfonated Poly(phenylene Poly(phenylene) Proton) Proton Conducting Conducting Polymers | Department of Energy Cell Performance High Temperature Fuel Cell Performance of of Sulfonated Sulfonated Poly(phenylene Poly(phenylene) Proton) Proton Conducting Conducting Polymers High Temperature Fuel Cell Performance High Temperature Fuel Cell Performance of of Sulfonated Sulfonated Poly(phenylene Poly(phenylene) Proton) Proton Conducting Conducting Polymers Presentation

  12. Inhibition of cell-cell binding by lipid assemblies

    DOE Patents [OSTI]

    Nagy, Jon O.; Bargatze, Robert F.

    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.

  13. Energy 101: Fuel Cell Technology | Department of Energy

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

    Fuel Cell Technology Energy 101: Fuel Cell Technology

  14. Fuel Cell Projects Kickoff Meeting

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

    Break Transport 4:10 Transport Studies Enabling Efficiency Optimization of Cost-Competitive Fuel Cell Stacks James Cross, Nuvera 4:30 Fuel Cell Fundamentals at Low and Subzero ...

  15. Fuel Cell Vehicle Basics | NREL

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

    Fuel Cell Vehicle Basics Researchers are developing fuel cells that can be used in vehicles to provide electricity for propulsion as well as for a car's electric and electronic ...

  16. Air Liquide- Biogas & Fuel Cells

    Broader source: Energy.gov [DOE]

    Presentation about Air Liquide's biogas technologies and integration with fuel cells. Presented by Charlie Anderson, Air Liquide, at the NREL/DOE Biogas and Fuel Cells Workshop held June 11-13, 2012, in Golden, Colorado.

  17. Cell boundary fault detection system

    DOE Patents [OSTI]

    Archer, Charles Jens; Pinnow, Kurt Walter; Ratterman, Joseph D.; Smith, Brian Edward

    2009-05-05

    A method determines a nodal fault along the boundary, or face, of a computing cell. Nodes on adjacent cell boundaries communicate with each other, and the communications are analyzed to determine if a node or connection is faulty.

  18. Solar Cells | Open Energy Information

    Open Energy Info (EERE)

    Solar Cells Place: Split, Croatia Zip: 21000 Product: manufacturers of PV modules References: Solar Cells1 This article is a stub. You can help OpenEI by expanding it. Solar...

  19. Fuel Cell Technical Team Roadmap

    SciTech Connect (OSTI)

    2013-06-01

    The Fuel Cell Technical Team promotes the development of a fuel cell power system for an automotive powertrain that meets the U.S. DRIVE Partnership (United States Driving Research and Innovation for Vehicle efficiency and Energy sustainability) goals.

  20. 2009 Fuel Cell Market Report

    Fuel Cell Technologies Publication and Product Library (EERE)

    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

  1. Maritime Hydrogen Fuel Cell project

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

    ... SunShot Grand Challenge: Regional Test Centers Maritime Hydrogen Fuel Cell project HomeTag:Maritime Hydrogen Fuel Cell project - Pete Devlin, of the Department of Energy's Fuel ...

  2. Aluminum reduction cell electrode

    DOE Patents [OSTI]

    Payne, J.R.

    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. 10 figs.

  3. Fuel cell CO sensor

    DOE Patents [OSTI]

    Grot, Stephen Andreas; Meltser, Mark Alexander; Gutowski, Stanley; Neutzler, Jay Kevin; Borup, Rodney Lynn; Weisbrod, Kirk

    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.

  4. Electrocapturing flow cell

    DOE Patents [OSTI]

    Morozov, Victor

    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.

  5. 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.

  6. Broad spectrum solar cell

    DOE Patents [OSTI]

    Walukiewicz, Wladyslaw; Yu, Kin Man; Wu, Junqiao; Schaff, William J.

    2007-05-15

    An alloy having a large band gap range is used in a multijunction solar cell to enhance utilization of the solar energy spectrum. In one embodiment, the alloy is In.sub.1-xGa.sub.xN having an energy bandgap range of approximately 0.7 eV to 3.4 eV, providing a good match to the solar energy spectrum. Multiple junctions having different bandgaps are stacked to form a solar cell. Each junction may have different bandgaps (realized by varying the alloy composition), and therefore be responsive to different parts of the spectrum. The junctions are stacked in such a manner that some bands of light pass through upper junctions to lower junctions that are responsive to such bands.

  7. Compact fuel cell

    DOE Patents [OSTI]

    Jacobson, Craig; DeJonghe, Lutgard C.; Lu, Chun

    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.

  8. Electrocatalysts for Fuel Cells

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

    Electrocatalysts for Fuel Cells June 2012 BROOKHAVEN NATIONAL LABORATORY Technology Description * Core-shell nanoparticles with a palladium or palladium alloy core coated by a monolayer of platinum * All platinum atoms on surface and participate in catalysis * Lattice contraction improves catalytic activity of platinum * Reduction of platinum reduces overall precious metal cost 2 BROOKHAVEN NATIONAL LABORATORY Technology Opportunity * One version of the platinum monolayer core-shell

  9. Miniature ceramic fuel cell

    DOE Patents [OSTI]

    Lessing, Paul A.; Zuppero, Anthony C.

    1997-06-24

    A miniature power source assembly capable of providing portable electricity is provided. A preferred embodiment of the power source assembly employing a fuel tank, fuel pump and control, air pump, heat management system, power chamber, power conditioning and power storage. The power chamber utilizes a ceramic fuel cell to produce the electricity. Incoming hydro carbon fuel is automatically reformed within the power chamber. Electrochemical combustion of hydrogen then produces electricity.

  10. Fuel cell system combustor

    DOE Patents [OSTI]

    Pettit, William Henry

    2001-01-01

    A fuel cell system including a fuel reformer heated by a catalytic combustor fired by anode and cathode effluents. The combustor includes a turbulator section at its input end for intimately mixing the anode and cathode effluents before they contact the combustors primary catalyst bed. The turbulator comprises at least one porous bed of mixing media that provides a tortuous path therethrough for creating turbulent flow and intimate mixing of the anode and cathode effluents therein.

  11. Fuel cell oxygen electrode

    DOE Patents [OSTI]

    Shanks, H.R.; Bevolo, A.J.; Danielson, G.C.; Weber, M.F.

    An oxygen electrode for a fuel cell utilizing an acid electrolyte has a substrate of an alkali metal tungsten bronze of the formula: A/sub x/WO/sub 3/ where A is an alkali metal and x is at least 0.2, which is covered with a thin layer of platinum tungsten bronze of the formula: Pt/sub y/WO/sub 3/ where y is at least 0.8.

  12. Fuel cell oxygen electrode

    DOE Patents [OSTI]

    Shanks, Howard R.; Bevolo, Albert J.; Danielson, Gordon C.; Weber, Michael F.

    1980-11-04

    An oxygen electrode for a fuel cell utilizing an acid electrolyte has a substrate of an alkali metal tungsten bronze of the formula: A.sub.x WO.sub.3 where A is an alkali metal and x is at least 0.2, which is covered with a thin layer of platinum tungsten bronze of the formula: Pt.sub.y WO.sub.3 where y is at least 0.8.

  13. Fuel Cell Financing Options

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

    UTC Power Corporation 195 Governor's Highway South Windsor, CT Fuel Cell Financing Options (CESA/DOE Webinar - August 30, 2011) Paul J. Rescsanski, Manager, Business Finance Paul J. Rescsanski, Manager, Business Finance The UTC Power Advantage Strained Utility Grid, unreliable power * Significant Energy savings through: - 80 - 90% system efficiency - Combined heat and power * Payback in 3-5 years Sustainability and carbon reduction Rising energy costs * Assured power generated on-site: -

  14. Rapidly refuelable fuel cell

    DOE Patents [OSTI]

    Joy, R.W.

    1982-09-20

    A rapidly refuelable dual cell of an electrochemical type is described wherein a single anode cooperates with two cathodes and wherein the anode has a fixed position and the cathodes are urged toward opposite faces of the anodes at constant and uniform force. The associated cathodes are automatically retractable to permit the consumed anode remains to be removed from the housing and a new anode inserted between the two cathodes.

  15. Cell culture compositions

    DOE Patents [OSTI]

    Dunn-Coleman, Nigel; Goedegebuur, Frits; Ward, Michael; Yiao, Jian

    2014-03-18

    The present invention provides a novel endoglucanase nucleic acid sequence, designated egl6 (SEQ ID NO:1 encodes the full length endoglucanase; SEQ ID NO:4 encodes the mature form), and the corresponding endoglucanase VI amino acid sequence ("EGVI"; SEQ ID NO:3 is the signal sequence; SEQ ID NO:2 is the mature sequence). The invention also provides expression vectors and host cells comprising a nucleic acid sequence encoding EGVI, recombinant EGVI proteins and methods for producing the same.

  16. Carbonate fuel cell matrix

    DOE Patents [OSTI]

    Farooque, Mohammad; Yuh, Chao-Yi

    1996-01-01

    A carbonate fuel cell matrix comprising support particles and crack attenuator particles which are made platelet in shape to increase the resistance of the matrix to through cracking. Also disclosed is a matrix having porous crack attenuator particles and a matrix whose crack attenuator particles have a thermal coefficient of expansion which is significantly different from that of the support particles, and a method of making platelet-shaped crack attenuator particles.

  17. Fuel cell system configurations

    DOE Patents [OSTI]

    Kothmann, Richard E.; Cyphers, Joseph A.

    1981-01-01

    Fuel cell stack configurations having elongated polygonal cross-sectional shapes and gaskets at the peripheral faces to which flow manifolds are sealingly affixed. Process channels convey a fuel and an oxidant through longer channels, and a cooling fluid is conveyed through relatively shorter cooling passages. The polygonal structure preferably includes at least two right angles, and the faces of the stack are arranged in opposite parallel pairs.

  18. Carbonate fuel cell matrix

    DOE Patents [OSTI]

    Farooque, M.; Yuh, C.Y.

    1996-12-03

    A carbonate fuel cell matrix is described comprising support particles and crack attenuator particles which are made platelet in shape to increase the resistance of the matrix to through cracking. Also disclosed is a matrix having porous crack attenuator particles and a matrix whose crack attenuator particles have a thermal coefficient of expansion which is significantly different from that of the support particles, and a method of making platelet-shaped crack attenuator particles. 8 figs.

  19. Fuel cell current collector

    DOE Patents [OSTI]

    Katz, Murray; Bonk, Stanley P.; Maricle, Donald L.; Abrams, Martin

    1991-01-01

    A fuel cell has a current collector plate (22) located between an electrode (20) and a separate plate (25). The collector plate has a plurality of arches (26, 28) deformed from a single flat plate in a checkerboard pattern. The arches are of sufficient height (30) to provide sufficient reactant flow area. Each arch is formed with sufficient stiffness to accept compressive load and sufficient resiliently to distribute the load and maintain electrical contact.

  20. Cell Prototyping Facility

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

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

  1. Rapidly refuelable fuel cell

    DOE Patents [OSTI]

    Joy, Richard W. (Santa Clara, CA)

    1985-01-01

    A rapidly refuelable dual cell of an electrochemical type wherein a single anode cooperates with two cathodes and wherein the anode has a fixed position and the cathodes are urged toward opposite faces of the anodes at constant and uniform force. The associated cathodes are automatically retractable to permit the consumed anode remains to be removed from the housing and a new anode inserted between the two cathodes.

  2. Automotive Fuel Cell Corporation

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

    Fuel Cell Corporation n SNL researcher Cy Fujimoto demonstrates his new flexible hydrocarbon polymer electrolyte mem- brane, which could be a key factor in realizing a hydrogen car. The close partnership between Sandia and AFCC has resulted in a very unique and promising technology for future automotive applications. Dr. Rajeev Vohra Manager R&D AFCC Hydrocarbon Membrane Fuels the Suc- cess of Future Generation Vehicles While every car manufacturer, such as GM and Ford, has developed their

  3. Fuel cell system with interconnect

    SciTech Connect (OSTI)

    Goettler, Richard; Liu, Zhien

    2015-08-11

    The present invention includes a fuel cell system having a plurality of adjacent electrochemical cells formed of an anode layer, a cathode layer spaced apart from the anode layer, and an electrolyte layer disposed between the anode layer and the cathode layer. The fuel cell system also includes at least one interconnect, the interconnect being structured to conduct free electrons between adjacent electrochemical cells. Each interconnect includes a primary conductor embedded within the electrolyte layer and structured to conduct the free electrons.

  4. Fuel cell system with interconnect

    SciTech Connect (OSTI)

    Liu, Zhien; Goettler, Richard

    2015-09-29

    The present invention includes a fuel cell system having a plurality of adjacent electrochemical cells formed of an anode layer, a cathode layer spaced apart from the anode layer, and an electrolyte layer disposed between the anode layer and the cathode layer. The fuel cell system also includes at least one interconnect, the interconnect being structured to conduct free electrons between adjacent electrochemical cells. Each interconnect includes a primary conductor embedded within the electrolyte layer and structured to conduct the free electrons.

  5. Fuel cell system with interconnect

    SciTech Connect (OSTI)

    Goettler, Richard; Liu, Zhien

    2015-03-10

    The present invention includes a fuel cell system having a plurality of adjacent electrochemical cells formed of an anode layer, a cathode layer spaced apart from the anode layer, and an electrolyte layer disposed between the anode layer and the cathode layer. The fuel cell system also includes at least one interconnect, the interconnect being structured to conduct free electrons between adjacent electrochemical cells. Each interconnect includes a primary conductor embedded within the electrolyte layer and structured to conduct the free electrons.

  6. ARIA Cell Solenoid Design Considerations

    SciTech Connect (OSTI)

    Schulze, Martin E.

    2015-05-20

    Detailed schematics of the structure of the preliminary ARIA solenoid cell design including overhead and cross section views and dimensions.

  7. Fuel Cell Seminar & Energy Exposition

    Broader source: Energy.gov [DOE]

    The Fuell Cell Seminar & Energy Exposition will be held in Los Angeles, California, November 16–19, 2015.

  8. Manufacturing Fuel Cell Manhattan Project

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

    to DOE Fuel Cell Manufacturing Workshop 2011 John Christensen, PE NREL Consultant DOE Fuel Cell Market Transformation Support August 11, 2011 Manufacturing Fuel Cell Manhattan Project √ Identify manufacturing cost drivers to achieve affordability √ Identify best practices in fuel cell manufacturing technology √ Identify manufacturing technology gaps √ Identify FC projects to address these gaps MFCMP Objectives Completed Final Report due out Nov 2010 B2PCOE Montana Tech SME's Industry

  9. ANL: Prototype Cell Fabrication Facility

    Broader source: Energy.gov [DOE]

    2011 DOE Hydrogen and Fuel Cells Program, and Vehicle Technologies Program Annual Merit Review and Peer Evaluation

  10. Careers in Fuel Cell Technologies

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

    Careers In Fuel Cell Technologies Existing and emerging fuel cell applications hold large job growth potential. Fuel cells are among the promising technologies that are expected to transform our energy sector. They represent highly efficient and fuel- flexible technologies that offer diverse benefits. For example, fuel cells can be used in a wide range of applications- from portable electronics, to combined heat and power (CHP) units used for distributed electricity generation, to passenger

  11. Fuel cell sub-assembly

    DOE Patents [OSTI]

    Chi, Chang V.

    1983-01-01

    A fuel cell sub-assembly comprising a plurality of fuel cells, a first section of a cooling means disposed at an end of the assembly and means for connecting the fuel cells and first section together to form a unitary structure.

  12. Fuel cell report to congress

    SciTech Connect (OSTI)

    None, None

    2003-02-28

    This report describes the status of fuel cells for Congressional committees. It focuses on the technical and economic barriers to the use of fuel cells in transportation, portable power, stationary, and distributed power generation applications, and describes the need for public-private cooperative programs to demonstrate the use of fuel cells in commercial-scale applications by 2012. (Department of Energy, February 2003).

  13. Method for fabricating silicon cells

    DOE Patents [OSTI]

    Ruby, Douglas S.; Basore, Paul A.; Schubert, W. Kent

    1998-08-11

    A process for making high-efficiency solar cells. This is accomplished by forming a diffusion junction and a passivating oxide layer in a single high-temperature process step. The invention includes the class of solar cells made using this process, including high-efficiency solar cells made using Czochralski-grown silicon.

  14. Method for fabricating silicon cells

    DOE Patents [OSTI]

    Ruby, D.S.; Basore, P.A.; Schubert, W.K.

    1998-08-11

    A process is described for making high-efficiency solar cells. This is accomplished by forming a diffusion junction and a passivating oxide layer in a single high-temperature process step. The invention includes the class of solar cells made using this process, including high-efficiency solar cells made using Czochralski-grown silicon. 9 figs.

  15. Fuel cell generator energy dissipator

    DOE Patents [OSTI]

    Veyo, Stephen Emery; Dederer, Jeffrey Todd; Gordon, John Thomas; Shockling, Larry Anthony

    2000-01-01

    An apparatus and method are disclosed for eliminating the chemical energy of fuel remaining in a fuel cell generator when the electrical power output of the fuel cell generator is terminated. During a generator shut down condition, electrically resistive elements are automatically connected across the fuel cell generator terminals in order to draw current, thereby depleting the fuel

  16. Prolonged effect of fluid flow stress on the proliferative activity of mesothelial cells after abrupt discontinuation of fluid streaming

    SciTech Connect (OSTI)

    Aoki, Shigehisa; Ikeda, Satoshi; Takezawa, Toshiaki; Kishi, Tomoya; Makino, Junichi; Uchihashi, Kazuyoshi; Matsunobu, Aki; Noguchi, Mitsuru; Sugihara, Hajime; Toda, Shuji

    2011-12-16

    Highlights: Black-Right-Pointing-Pointer Late-onset peritoneal fibrosis leading to EPS remains to be elucidated. Black-Right-Pointing-Pointer Fluid streaming is a potent factor for peritoneal fibrosis in PD. Black-Right-Pointing-Pointer We focused on the prolonged effect of fluid streaming on mesothelial cell kinetics. Black-Right-Pointing-Pointer A history of fluid streaming exposure promoted mesothelial proliferative activity. Black-Right-Pointing-Pointer We have thus identified a potent new factor for late-onset peritoneal fibrosis. -- Abstract: Encapsulating peritoneal sclerosis (EPS) often develops after transfer to hemodialysis and transplantation. Both termination of peritoneal dialysis (PD) and transplantation-related factors are risks implicated in post-PD development of EPS, but the precise mechanism of this late-onset peritoneal fibrosis remains to be elucidated. We previously demonstrated that fluid flow stress induced mesothelial proliferation and epithelial-mesenchymal transition via mitogen-activated protein kinase (MAPK) signaling. Therefore, we speculated that the prolonged bioactive effect of fluid flow stress may affect mesothelial cell kinetics after cessation of fluid streaming. To investigate how long mesothelial cells stay under the bioactive effect brought on by fluid flow stress after removal of the stress, we initially cultured mesothelial cells under fluid flow stress and then cultured the cells under static conditions. Mesothelial cells exposed to fluid flow stress for a certain time showed significantly high proliferative activity compared with static conditions after stoppage of fluid streaming. The expression levels of protein phosphatase 2A, which dephosphorylates MAPK, in mesothelial cells changed with time and showed a biphasic pattern that was dependent on the duration of exposure to fluid flow stress. There were no differences in the fluid flow stress-related bioactive effects on mesothelial cells once a certain time had passed

  17. Gore Fuel Cell Technologies | Open Energy Information

    Open Energy Info (EERE)

    Gore Fuel Cell Technologies Jump to: navigation, search Name: Gore Fuel Cell Technologies Place: Elkton, Maryland Zip: 21922-1488 Product: Gore Fuel Cell Technologies supplies the...

  18. Hydra Fuel Cell Corporation | Open Energy Information

    Open Energy Info (EERE)

    Fuel Cell Corporation Jump to: navigation, search Name: Hydra Fuel Cell Corporation Place: Beaverton, Oregon Product: Holding company for American Security Resources' fuel cell...

  19. Cornell Fuel Cell Institute | Open Energy Information

    Open Energy Info (EERE)

    Cornell Fuel Cell Institute Jump to: navigation, search Name: Cornell Fuel Cell Institute Place: Ithaca, New York Zip: 14850 Product: The Cornell Fuel Cell Institute (CFCI)...

  20. Fuel Cell Power | Open Energy Information

    Open Energy Info (EERE)

    Fuel Cell Power Place: United Kingdom Product: Information provider of fuel cells and their supporting infrastructure. References: Fuel Cell Power1 This article is a stub. You...

  1. US Fuel Cell Council | Open Energy Information

    Open Energy Info (EERE)

    US Fuel Cell Council Place: Washington DC, Washington, DC Zip: Washington Product: US Fuel Cell Council is a membership association of fuel cell industry dedicated to fostering the...

  2. Cabot Fuel Cells | Open Energy Information

    Open Energy Info (EERE)

    Cabot Fuel Cells Jump to: navigation, search Name: Cabot Fuel Cells Place: Albuquerque, New Mexico Zip: 87113 Product: Cabot develops and manufactures advanced fuel cell...

  3. Computational Challenges for Nanostructure Solar Cells

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

    Challenges for Nanostructure Solar Cells Computational Challenges for Nanostructure Solar Cells ZZ2.jpg Key Challenges: Current nanostructure solar cells often have energy...

  4. Hydrogen and Fuel Cells Success Stories

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

    71 Hydrogen and Fuel Cells Success Stories en Doosan Fuel Cell Takes Closed Plant to Full Production http:energy.goveeresuccess-storiesarticlesdoosan-fuel-cell-takes-closed-p...

  5. Canadian Fuel Cell Commercialization Roadmap Update: Progress...

    Open Energy Info (EERE)

    Fuel Cell Commercialization Roadmap Update: Progress of Canada's Hydrogen and Fuel Cell Industry Jump to: navigation, search Tool Summary LAUNCH TOOL Name: Canadian Fuel Cell...

  6. Financing Fuel Cells | Department of Energy

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

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

  7. Crystalline Silicon Photovolatic Cell Basics | Department of...

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

    Crystalline Silicon Photovolatic Cell Basics Crystalline Silicon Photovolatic Cell Basics ... This lattice comprises the solid material that forms the photovoltaic (PV) cell's ...

  8. Photovoltaic Crystalline Silicon Cell Basics | Department of...

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

    Crystalline Silicon Cell Basics Photovoltaic Crystalline Silicon Cell Basics August 20, 2013 - 2:00pm Addthis To separate electrical charges, crystalline silicon cells must have a ...

  9. Enabling Thin Silicon Solar Cell Technology

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

    Enabling Thin Silicon Solar Cell Technology Enabling Thin Silicon Solar Cell Technology Print Friday, 21 June 2013 10:49 Generic silicon solar cells showing +45, -45, and ...

  10. Fuel Cell Handbook, Fifth Edition

    SciTech Connect (OSTI)

    Energy and Environmental Solutions

    2000-10-31

    Progress continues in fuel cell technology since the previous edition of the Fuel Cell Handbook was published in November 1998. Uppermost, polymer electrolyte fuel cells, molten carbonate fuel cells, and solid oxide fuel cells have been demonstrated at commercial size in power plants. The previously demonstrated phosphoric acid fuel cells have entered the marketplace with more than 220 power plants delivered. Highlighting this commercial entry, the phosphoric acid power plant fleet has demonstrated 95+% availability and several units have passed 40,000 hours of operation. One unit has operated over 49,000 hours. Early expectations of very low emissions and relatively high efficiencies have been met in power plants with each type of fuel cell. Fuel flexibility has been demonstrated using natural gas, propane, landfill gas, anaerobic digester gas, military logistic fuels, and coal gas, greatly expanding market opportunities. Transportation markets worldwide have shown remarkable interest in fuel cells; nearly every major vehicle manufacturer in the U.S., Europe, and the Far East is supporting development. 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 ultrahigh 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 8 describe the six major fuel cell types and their performance based on cell operating conditions. Alkaline and intermediate solid state fuel cells were added to this edition of the Handbook. New information indicates that manufacturers have stayed

  11. Double interconnection fuel cell array

    DOE Patents [OSTI]

    Draper, R.; Zymboly, G.E.

    1993-12-28

    A fuel cell array is made, containing number of tubular, elongated fuel cells which are placed next to each other in rows (A, B, C, D), where each cell contains inner electrodes and outer electrodes, with solid electrolyte between the electrodes, where the electrolyte and outer electrode are discontinuous, having two portions, and providing at least two opposed discontinuities which contain at least two oppositely opposed interconnections contacting the inner electrode, each cell having only three metallic felt electrical connectors which contact surrounding cells, where each row is electrically connected to the other. 5 figures.

  12. Double interconnection fuel cell array

    DOE Patents [OSTI]

    Draper, Robert; Zymboly, Gregory E.

    1993-01-01

    A fuel cell array (10) is made, containing number of tubular, elongated fuel cells (12) which are placed next to each other in rows (A, B, C, D), where each cell contains inner electrodes (14) and outer electrodes (18 and 18'), with solid electrolyte (16 and 16') between the electrodes, where the electrolyte and outer electrode are discontinuous, having two portions, and providing at least two opposed discontinuities which contain at least two oppositely opposed interconnections (20 and 20') contacting the inner electrode (14), each cell (12) having only three metallic felt electrical connectors (22) which contact surrounding cells, where each row is electrically connected to the other.

  13. Self-humidified proton exchange membrane fuel cells: Operation of larger cells and fuel cell stacks

    SciTech Connect (OSTI)

    Dhar, H.P.; Lee, J.H.; Lewinski, K.A.

    1996-12-31

    The PEM fuel cell is promising as the power source for use in mobile and stationary applications primarily because of its high power density, all solid components, and simplicity of operation. For wide acceptability of this power source, its cost has to be competitive with the presently available energy sources. The fuel cell requires continuous humidification during operation as a power source. The humidification unit however, increases fuel cell volume, weight, and therefore decreases its overall power density. Great advantages in terms of further fuel cell simplification can be achieved if the humidification process can be eliminated or minimized. In addition, cost reductions are associated with the case of manufacturing and operation. At BCS Technology we have developed a technology of self-humidified operation of PEM fuel cells based on the mass balance of the reactants and products and the ability of membrane electrode assembly (MEA) to retain water necessary for humidification under the cell operating conditions. The reactants enter the fuel cell chambers without carrying any form of water, whether in liquid or vapor form. Basic principles of self-humidified operation of fuel cells as practiced by BCS Technology, Inc. have been presented previously in literature. Here, we report the operation of larger self-humidified single cells and fuel cell stacks. Fuel cells of areas Up to 100 cm{sup 2} have been operated. We also show the self-humidified operation of fuel cell stacks of 50 and 100 cm{sup 2} electrode areas.

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

    SciTech Connect (OSTI)

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

    2009-09-09

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

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

    SciTech Connect (OSTI)

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

    2012-03-29

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

  16. Quantifying Cell-to-Cell Variations in Lithium Ion Batteries

    SciTech Connect (OSTI)

    Santhanagopalan, S.; White, R. E.

    2012-01-01

    Lithium ion batteries have conventionally been manufactured in small capacities but large volumes for consumer electronics applications. More recently, the industry has seen a surge in the individual cell capacities, as well as the number of cells used to build modules and packs. Reducing cell-to-cell and lot-to-lot variations has been identified as one of the major means to reduce the rejection rate when building the packs as well as to improve pack durability. The tight quality control measures have been passed on from the pack manufactures to the companies building the individual cells and in turn to the components. This paper identifies a quantitative procedure utilizing impedance spectroscopy, a commonly used tool, to determine the effects of material variability on the cell performance, to compare the relative importance of uncertainties in the component properties, and to suggest a rational procedure to set quality control specifications for the various components of a cell, that will reduce cell-to-cell variability, while preventing undue requirements on uniformity that often result in excessive cost of manufacturing but have a limited impact on the cells performance.

  17. Carbonate fuel cell anodes

    DOE Patents [OSTI]

    Donado, Rafael A. (Chicago, IL); Hrdina, Kenneth E. (Glenview, IL); Remick, Robert J. (Bolingbrook, IL)

    1993-01-01

    A molten alkali metal carbonates fuel cell porous anode of lithium ferrite and a metal or metal alloy of nickel, cobalt, nickel/iron, cobalt/iron, nickel/iron/aluminum, cobalt/iron/aluminum and mixtures thereof wherein the total iron content including ferrite and iron of the composite is about 25 to about 80 percent, based upon the total anode, provided aluminum when present is less than about 5 weight percent of the anode. A process for production of the lithium ferrite containing anode by slipcasting.

  18. Fuel cell having electrolyte

    DOE Patents [OSTI]

    Wright, Maynard K. (Bethel Park, PA)

    1989-01-01

    A fuel cell having an electrolyte control volume includes a pair of porous opposed electrodes. A maxtrix is positioned between the pair of electrodes for containing an electrolyte. A first layer of backing paper is positioned adjacent to one of the electrodes. A portion of the paper is substantially previous to the acceptance of the electrolyte so as to absorb electrolyte when there is an excess in the matrix and to desorb electrolyte when there is a shortage in the matrix. A second layer of backing paper is positioned adjacent to the first layer of paper and is substantially impervious to the acceptance of electrolyte.

  19. Hot cell examination table

    DOE Patents [OSTI]

    Gaal, Peter S.; Ebejer, Lino P.; Kareis, James H.; Schlegel, Gary L.

    1991-01-01

    A table for use in a hot cell or similar controlled environment for use in examining specimens. The table has a movable table top that can be moved relative to a table frame. A shaft is fixedly mounted to the frame for axial rotation. A shaft traveler having a plurality of tilted rollers biased against the shaft is connected to the table top such that rotation of the shaft causes the shaft traveler to roll along the shaft. An electromagnetic drive is connected to the shaft and the frame for controllably rotating the shaft.

  20. Carbonate fuel cell anodes

    DOE Patents [OSTI]

    Donado, R.A.; Hrdina, K.E.; Remick, R.J.

    1993-04-27

    A molten alkali metal carbonates fuel cell porous anode of lithium ferrite and a metal or metal alloy of nickel, cobalt, nickel/iron, cobalt/iron, nickel/iron/aluminum, cobalt/iron/aluminum and mixtures thereof wherein the total iron content including ferrite and iron of the composite is about 25 to about 80 percent, based upon the total anode, provided aluminum when present is less than about 5 weight percent of the anode. A process is described for production of the lithium ferrite containing anode by slipcasting.

  1. Metal halogen electrochemical cell

    SciTech Connect (OSTI)

    Walsh, F.M.

    1986-06-03

    An electrochemical cell is described having a metal anode selected from the group consisting of zinc and cadmium; a bromine cathode; and, an aqueous electrolyte containing a metal bromide, the metal having the same metal as the metal of the anode, the improvement comprising: a bromine complexing agent in the aqueous metal bromide electrolyte consisting solely of a tetraorgano substituted ammonium salt, which salt is soluble of water and forms and substantially water immiscible liquid bromine complex at temperatures in the range of about 10/sup 0/C. to about 60/sup 0/C. and wherein the tetraorgano substituted ammonium salt is selected from asymmetric quaternary ammonium compounds.

  2. Monolithic tandem solar cell

    DOE Patents [OSTI]

    Wanlass, M.W.

    1994-06-21

    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, (c) a second photoactive subcell on the first subcell; and (d) an optically transparent prismatic cover layer over the second subcell. The first photoactive subcell is GaInAsP of defined composition. The second subcell is InP. The two subcells are lattice matched. 9 figs.

  3. Monolithic tandem solar cell

    DOE Patents [OSTI]

    Wanlass, Mark W. (Golden, CO)

    1994-01-01

    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, (c) a second photoactive subcell on the first subcell; and (d) an optically transparent prismatic cover layer over the second subcell. The first photoactive subcell is GaInAsP of defined composition. The second subcell is InP. The two subcells are lattice matched.

  4. PV Nano Cell | Open Energy Information

    Open Energy Info (EERE)

    Cell Jump to: navigation, search Name: PV Nano Cell Place: Israel Product: Israel-based firm focused on PV nano cell technology. References: PV Nano Cell1 This article is a stub....

  5. Nickel coated aluminum battery cell tabs

    SciTech Connect (OSTI)

    Bucchi, Robert S.; Casoli, Daniel J.; Campbell, Kathleen M.; Nicotina, Joseph

    2014-07-29

    A battery cell tab is described. The battery cell tab is anodized on one end and has a metal coating on the other end. Battery cells and methods of making battery cell tabs are also described.

  6. Fuel Cells Fact Sheet | Department of Energy

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

    Fact Sheet Fuel Cells Fact Sheet Fact sheet produced by the Fuel Cell Technologies Office describing fuel cell technologies. Fuel Cells Fact Sheet (545.14 KB) More Documents & ...

  7. Fuel Cells at NASCAR | Department of Energy

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

    at NASCAR Fuel Cells at NASCAR Download presentation slides from the DOE Fuel Cell Technologies Office webinar "Fuel Cells at NASCAR" held on April 17, 2014. Fuel Cells at NASCAR ...

  8. Photovoltaic Cell Basics | Department of Energy

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

    Cell Basics Photovoltaic Cell Basics August 16, 2013 - 4:53pm Addthis Photovoltaic (PV) cells, or solar cells, take advantage of the photoelectric effect to produce electricity. PV ...

  9. Homozygous deletions on the short arm of chromosome 9 in ovarian adenocarcinoma cell lines and loss of heterozygosity in sporadic tumors

    SciTech Connect (OSTI)

    Chenevix-Trench, G.; Kerr, J.; Hurst, T.; Sanderson, B.; Coglan, M.; Ward, B.; Khoo, S.K. ); Friedlander, M.; Leary, J.

    1994-07-01

    Rat ovarian surface epithelial cells transformed spontaneously in vitro have been found to have homozygous deletions of the interferon alpha (IFNA) gene. This suggests that inactivation of a tumor-suppressor gene in this region may be crucial for the development of ovarian cancer. The authors therefore used microsatellite markers and Southern analysis to examine the homologous region in humans - the short arm of chromosome 9 - for deletions in sporadic ovarian adenocarcinomas and ovarian tumor cell lines. Loss of heterozygosity occurred in 34 (37%) of 91 informative sporadic tumors, including some benign, low-malignant-potential and early-stage tumors, suggesting that it is an early event in the development of ovarian adenocarcinoma. Furthermore, homozygous deletions on 9p were found in 2 of 10 independent cell lines. Deletion mapping of the tumors and lines indicates that the candidate suppressor gene inactivated as a consequence lies between D9S171 and the IFNA locus, a region that is also deleted in several other tumors and that contains the melanoma predisposition gene, MLM. 52 refs., 4 figs., 1 tab.

  10. Leakage pathway layer for solar cell

    SciTech Connect (OSTI)

    Luan, Andy; Smith, David; Cousins, Peter; Sun, Sheng

    2015-12-01

    Leakage pathway layers for solar cells and methods of forming leakage pathway layers for solar cells are described.

  11. Types of Fuel Cells | Department of Energy

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

    Fuel Cells » Types of Fuel Cells Types of Fuel Cells Fuel cells are classified primarily by the kind of electrolyte they employ. This classification determines the kind of electro-chemical reactions that take place in the cell, the kind of catalysts required, the temperature range in which the cell operates, the fuel required, and other factors. These characteristics, in turn, affect the applications for which these cells are most suitable. There are several types of fuel cells currently under

  12. Advanced Electrocatalysts for PEM Fuel Cells

    Broader source: Energy.gov [DOE]

    Presentation slides from the DOE Fuel Cell Technologies Office webinar, Advanced Electrocatalysts for PEM Fuel Cells, held February 12, 2013.

  13. Ion cyclotron resonance cell

    DOE Patents [OSTI]

    Weller, Robert R. (Aiken, SC)

    1995-01-01

    An ion cyclotron resonance cell having two adjacent sections separated by a center trapping plate. The first section is defined by the center trapping plate, a first end trapping plate, and excitation and detector electrodes. The second section includes a second end trapping plate spaced apart from the center plate, a mirror, and an analyzer. The analyzer includes a wavelength-selective light detector, such as a detector incorporating an acousto-optical device (AOD) and a photodetector. One or more ion guides, grounded plates with holes for the ion beam, are positioned within the vacuum chamber of the mass spectrometer between the ion source and the cell. After ions are trapped and analyzed by ion cyclotron resonance techniques in the first section, the ions of interest are selected according to their mass and passed into the second section for optical spectroscopic studies. The trapped ions are excited by light from a laser and caused thereby to fluoresce. The fluorescent light emitted by the excited ions is reflected by the mirror and directed onto the detector. The AOD is scanned, and the photodetector output is recorded and analyzed. The ions remain in the second section for an extended period, enabling multiple studies to be carried out on the same ensemble of ions.

  14. Ion cyclotron resonance cell

    DOE Patents [OSTI]

    Weller, R.R.

    1995-02-14

    An ion cyclotron resonance cell is disclosed having two adjacent sections separated by a center trapping plate. The first section is defined by the center trapping plate, a first end trapping plate, and excitation and detector electrodes. The second section includes a second end trapping plate spaced apart from the center plate, a mirror, and an analyzer. The analyzer includes a wavelength-selective light detector, such as a detector incorporating an acousto-optical device (AOD) and a photodetector. One or more ion guides, grounded plates with holes for the ion beam, are positioned within the vacuum chamber of the mass spectrometer between the ion source and the cell. After ions are trapped and analyzed by ion cyclotron resonance techniques in the first section, the ions of interest are selected according to their mass and passed into the second section for optical spectroscopic studies. The trapped ions are excited by light from a laser and caused thereby to fluoresce. The fluorescent light emitted by the excited ions is reflected by the mirror and directed onto the detector. The AOD is scanned, and the photodetector output is recorded and analyzed. The ions remain in the second section for an extended period, enabling multiple studies to be carried out on the same ensemble of ions. 5 figs.

  15. DNDO Analysis Cell Concept

    SciTech Connect (OSTI)

    Pagh, Richard T.; Dimmerling, Paul J.; Guillen, Zoe C.; Hoyt, Joel R.; Jarman, Kenneth D.; Kernan, Warnick J.; Reichmuth, Barbara A.; Rohlfing, Kerrie S.; Schweppe, John E.; Sego, Landon H.; Shergur, Jason M.; Siciliano, Edward R.; Woodring, Mitchell L.

    2014-03-12

    The Domestic Nuclear Detection Office (DNDO) has a mission of implementing rad/nuc interdiction capabilities for a managed and coordinated response to threats, integration of federal nuclear forensics programs, and coordinating the development of the global nuclear detection and reporting architecture. In the process of executing this mission, DNDO has generated substantial information, data, technical results, operational workflows and analytical tools. The effective utilization of these resources is an overarching goal of the organization. After nearly a decade of performing work, DNDO faces a challenge in capitalizing on the large amount of data, reports, processes, tools, and people. As new work is being planned, managers and researchers need to have an understating of what information has been collected, what tools are available, the collaborations which can be utilized to propel the work forward, processes to plan and execute, and how to present conclusions and results that can assist the government in making decisions. This type of challenge can be met through the use of a series of organized and connected elements which form a broader structure (cell) that promotes cross utilization of elements such that they can be tailored (analyzed) to fit the context of the problem to be solved. The development of an analysis cell for DNDO will address the challenges of utilizing existing elements, identifying gaps, annually reporting the performance of rad/nuc interdiction instrumentation, and planning the execution of future work.

  16. NREL: Hydrogen and Fuel Cells Research - Fuel Cell Electric Vehicle

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

    Evaluations Fuel Cell Electric Vehicle Evaluations NREL's technology validation team analyzes hydrogen fuel cell electric vehicles (FCEVs) operating in a real-world setting to identify the current status of the technology, compare it to Department of Energy (DOE) performance and durability targets, and evaluate progress between multiple generations of technology, some of which will include commercial FCEVs for the first time. Current fuel cell electric vehicle evaluations build on the

  17. NREL: Hydrogen and Fuel Cells Research - National Fuel Cell Technology

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

    Evaluation Center National Fuel Cell Technology Evaluation Center The National Fuel Cell Technology Evaluation Center (NFCTEC) at NREL's Energy Systems Integration Facility (ESIF) plays a crucial role in NREL's independent, third-party analysis of hydrogen fuel cell technologies in real-world operation. The NFCTEC is designed for secure management, storage, and processing of proprietary data from industry. Access to the off-network NFCTEC is limited to NREL's Technology Validation Team,

  18. NREL: Hydrogen and Fuel Cells Research - Fuel Cell System Contaminants...

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

    System Contaminants Material Screening Data NREL designed this interactive material selector tool to help fuel cell developers and material suppliers explore the results of fuel ...

  19. California: TetraCell Silicon Solar Cell Improves Efficiency...

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

    TetraSun, in partnership with the National Renewable Energy Laboratory, developed a novel crystalline silicon photovoltaic (PV) cell architecture and manufacturing process that ...

  20. NREL: Hydrogen and Fuel Cells Research - Fuel Cell Electric Bus...

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

    Fuel Cell Electric Bus Reliability Surpasses 2016 and Ultimate Technical Targets Project ... Applicable DOE Technical Target DOE and FTA have established performance, cost, and ...

  1. Flexible method for monitoring fuel cell voltage

    DOE Patents [OSTI]

    Mowery, Kenneth D.; Ripley, Eugene V.

    2002-01-01

    A method for equalizing the measured voltage of each cluster in a fuel cell stack wherein at least one of the clusters has a different number of cells than the identical number of cells in the remaining clusters by creating a pseudo voltage for the different cell numbered cluster. The average cell voltage of the all of the cells in the fuel cell stack is calculated and multiplied by a constant equal to the difference in the number of cells in the identical cell clusters and the number of cells in the different numbered cell cluster. The resultant product is added to the actual voltage measured across the different numbered cell cluster to create a pseudo voltage which is equivalent in cell number to the number of cells in the other identical numbered cell clusters.

  2. Hybrid Fuel Cell Technology Overview

    SciTech Connect (OSTI)

    None available

    2001-05-31

    For the purpose of this STI product and unless otherwise stated, hybrid fuel cell systems are power generation systems in which a high temperature fuel cell is combined with another power generating technology. The resulting system exhibits a synergism in which the combination performs with an efficiency far greater than can be provided by either system alone. Hybrid fuel cell designs under development include fuel cell with gas turbine, fuel cell with reciprocating (piston) engine, and designs that combine different fuel cell technologies. Hybrid systems have been extensively analyzed and studied over the past five years by the Department of Energy (DOE), industry, and others. These efforts have revealed that this combination is capable of providing remarkably high efficiencies. This attribute, combined with an inherent low level of pollutant emission, suggests that hybrid systems are likely to serve as the next generation of advanced power generation systems.

  3. Corrugated Membrane Fuel Cell Structures

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

    Corrugated Membrane Fuel Cell Structures Structures 2010 DOE Hydrogen Program Fuel Cell 2010 DOE Hydrogen Program Fuel Cell Project Kick-Off Principle Investigator: Dr. Stephen Grot Presenter: Dr. Walther Grot Ion Power, Inc September 28, 2010 September 28, 2010 This presentation does not contain any proprietary, confidential, or otherwise restricted information t Overview Timeline * Start Sept 1, 2010 E d A 31 2013 * End August 31, 2013 * 0% Complete Budget * * Total project funding Total

  4. Fuel cell design and assembly

    DOE Patents [OSTI]

    Myerhoff, Alfred

    1984-01-01

    The present invention is directed to a novel bipolar cooling plate, fuel cell design and method of assembly of fuel cells. The bipolar cooling plate used in the fuel cell design and method of assembly has discrete opposite edge and means carried by the plate defining a plurality of channels extending along the surface of the plate toward the opposite edges. At least one edge of the channels terminates short of the edge of the plate defining a recess for receiving a fastener.

  5. Fuel cell gas management system

    DOE Patents [OSTI]

    DuBose, Ronald Arthur

    2000-01-11

    A fuel cell gas management system including a cathode humidification system for transferring latent and sensible heat from an exhaust stream to the cathode inlet stream of the fuel cell; an anode humidity retention system for maintaining the total enthalpy of the anode stream exiting the fuel cell equal to the total enthalpy of the anode inlet stream; and a cooling water management system having segregated deionized water and cooling water loops interconnected by means of a brazed plate heat exchanger.

  6. Corrosion resistant PEM fuel cell

    DOE Patents [OSTI]

    Li, Y.; Meng, W.J.; Swathirajan, S.; Harris, S.J.; Doll, G.L.

    1997-04-29

    The present invention contemplates a PEM fuel cell having electrical contact elements (including bipolar plates/septums) comprising a titanium nitride coated light weight metal (e.g., Al or Ti) core, having a passivating, protective metal layer intermediate the core and the titanium nitride. The protective layer forms a barrier to further oxidation/corrosion when exposed to the fuel cell`s operating environment. Stainless steels rich in Cr, Ni, and Mo are particularly effective protective interlayers. 6 figs.

  7. Solar cell module lamination process

    DOE Patents [OSTI]

    Carey, Paul G.; Thompson, Jesse B.; Aceves, Randy C.

    2002-01-01

    A solar cell module lamination process using fluoropolymers to provide protection from adverse environmental conditions and thus enable more extended use of solar cells, particularly in space applications. A laminate of fluoropolymer material provides a hermetically sealed solar cell module structure that is flexible and very durable. The laminate is virtually chemically inert, highly transmissive in the visible spectrum, dimensionally stable at temperatures up to about 200.degree. C. highly abrasion resistant, and exhibits very little ultra-violet degradation.

  8. Cell casing and grommet therefore

    SciTech Connect (OSTI)

    Law, G.H.; Meyler-warlow, I.

    1980-11-11

    A grommet has a central opening and a peripheral groove defining spaced first and second peripheral lips, the opening aligned with the first peripheral lip is of increased width so that the lip may flex inwardly to allow insertion over a cell terminal post after assembly. The first peripheral lip has an inclined surface which cooperates with an inclined surface on the cell casing to facilitate insertion of the grommet. An electric cell including such a grommet is also disclosed.

  9. Microbial fuel cells

    DOE Patents [OSTI]

    Nealson, Kenneth H; Pirbazari, Massoud; Hsu, Lewis

    2013-04-09

    A microbial fuel cell includes an anode compartment with an anode and an anode biocatalyst and a cathode compartment with a cathode and a cathode biocatalyst, with a membrane positioned between the anode compartment and the cathode compartment, and an electrical pathway between the anode and the cathode. The anode biocatalyst is capable of catalyzing oxidation of an organic substance, and the cathode biocatalyst is capable of catalyzing reduction of an inorganic substance. The reduced organic substance can form a precipitate, thereby removing the inorganic substance from solution. In some cases, the anode biocatalyst is capable of catalyzing oxidation of an inorganic substance, and the cathode biocatalyst is capable of catalyzing reduction of an organic or inorganic substance.

  10. FLUORINE CELL ANODE ASSEMBLY

    DOE Patents [OSTI]

    Cable, R.E.; Goode, W.B. Jr.; Henderson, W.K.; Montillon, G.H.

    1962-06-26

    An improved anode assembly is deslgned for use in electrolytlc cells ln the productlon of hydrogen and fluorlne from a moIten electrolyte. The anode assembly comprises a copper post, a copper hanger supported by the post, a plurality of carbon anode members, and bolt means for clamplng half of the anode members to one slde of the hanger and for clamplng the other half of the anode members to the other slde of the hanger. The heads of the clamplng bolts are recessed withln the anode members and carbon plugs are inserted ln the recesses above the bolt heads to protect the boIts agalnst corroslon. A copper washer is provided under the head of each clamplng boIt such that the anode members can be tightly clamped to the hanger with a resultant low anode jolnt resistance. (AEC)

  11. Photovoltaic cell assembly

    DOE Patents [OSTI]

    Beavis, Leonard C.; Panitz, Janda K. G.; Sharp, Donald J.

    1990-01-01

    A photovoltaic assembly for converting high intensity solar radiation into lectrical energy in which a solar cell is separated from a heat sink by a thin layer of a composite material which has excellent dielectric properties and good thermal conductivity. This composite material is a thin film of porous Al.sub.2 O.sub.3 in which the pores have been substantially filled with an electrophoretically-deposited layer of a styrene-acrylate resin. This composite provides electrical breakdown strengths greater than that of a layer consisting essentially of Al.sub.2 O.sub.3 and has a higher thermal conductivity than a layer of styrene-acrylate alone.

  12. Fuel cell membrane humidification

    DOE Patents [OSTI]

    Wilson, Mahlon S.

    1999-01-01

    A polymer electrolyte membrane fuel cell assembly has an anode side and a cathode side separated by the membrane and generating electrical current by electrochemical reactions between a fuel gas and an oxidant. The anode side comprises a hydrophobic gas diffusion backing contacting one side of the membrane and having hydrophilic areas therein for providing liquid water directly to the one side of the membrane through the hydrophilic areas of the gas diffusion backing. In a preferred embodiment, the hydrophilic areas of the gas diffusion backing are formed by sewing a hydrophilic thread through the backing. Liquid water is distributed over the gas diffusion backing in distribution channels that are separate from the fuel distribution channels.

  13. Fuel Cell Power (FCPower) Model

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

    tool for analyzing high-temperature, fuel cell-based tri- generation systems. 1 Key ... Performs hourly energy analysis and detailed grid time of use cost evaluations, which ...

  14. Lux expression in eukaryotic cells

    DOE Patents [OSTI]

    Gupta, Rakesh K.; Patterson, Stacy S.; Sayler, Gary S.; Ripp, Steven A.

    2007-11-27

    The luxA, B, C, D, and E genes from Photorhabdus luminescens have been introduced into Saccharomyces cerevisiae bioluminescent yeast cells.

  15. economic hydrogen fuel cell vehicles

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

    economic hydrogen fuel cell vehicles - Sandia Energy Energy Search Icon Sandia Home Locations Contact Us Employee Locator Energy & Climate Secure & Sustainable Energy Future ...

  16. Molten carbonate fuel cell separator

    DOE Patents [OSTI]

    Nickols, Richard C.

    1986-09-02

    In a stacked array of molten carbonate fuel cells, a fuel cell separator is positioned between adjacent fuel cells to provide isolation as well as a conductive path therebetween. The center portion of the fuel cell separator includes a generally rectangular, flat, electrical conductor. Around the periphery of the flat portion of the separator are positioned a plurality of elongated resilient flanges which form a gas-tight seal around the edges of the fuel cell. With one elongated flange resiliently engaging a respective edge of the center portion of the separator, the sealing flanges, which are preferably comprised of a noncorrosive material such as an alloy of yttrium, iron, aluminum or chromium, form a tight-fitting wet seal for confining the corrosive elements of the fuel cell therein. This arrangement permits a good conductive material which may be highly subject to corrosion and dissolution to be used in combination with a corrosion-resistant material in the fuel cell separator of a molten carbonate fuel cell for improved fuel cell conductivity and a gas-tight wet seal.

  17. Molten carbonate fuel cell separator

    DOE Patents [OSTI]

    Nickols, R.C.

    1984-10-17

    In a stacked array of molten carbonate fuel cells, a fuel cell separator is positioned between adjacent fuel cells to provide isolation as well as a conductive path therebetween. The center portion of the fuel cell separator includes a generally rectangular, flat, electrical conductor. Around the periphery of the flat portion of the separator are positioned a plurality of elongated resilient flanges which form a gas-tight seal around the edges of the fuel cell. With one elongated flange resiliently engaging a respective edge of the center portion of the separator, the sealing flanges, which are preferably comprised of a noncorrosive material such as an alloy of yttrium, iron, aluminum or chromium, form a tight-fitting wet seal for confining the corrosive elements of the fuel cell therein. This arrangement permits a good conductive material which may be highly subject to corrosion and dissolution to be used in combination with a corrosion-resistant material in the fuel cell separator of a molten carbonate fuel cell for improved fuel cell conductivity and a gas-tight wet seal.

  18. LADWP FUEL CELL DEMONSTRATION PROJECT

    SciTech Connect (OSTI)

    Thai Ta

    2003-09-12

    Los Angeles Department of Water and Power (LADWP) is currently one of the most active power utility companies in researching fuel cell technology. Fuel cells offer many benefits and are now used as an alternative to traditional internal combustion engines in power generation. In continuing it's role as the leader in fuel cell research, LADWP has installed a pre-commercial molten carbonate fuel cell on August 2001 at its headquarter, the John Ferraro Building (JFB). The goal of this project is to learn more about the actual behavior of the fuel cell running under real world conditions. The fuel cell ran smoothly through the first year of operation with very high efficiency, but with some minor setbacks. The JFB fuel cell project is funded by the City of Los Angeles Department of Water and Power with partial grant funding from the Department of Defense's Climate Change Fuel Cell Buydown Program. The technical evaluation and the benefit-cost evaluation of the JFB fuel cell are both examined in this report.

  19. CLIMATE CHANGE FUEL CELL PROGRAM

    SciTech Connect (OSTI)

    Steven A. Gabrielle

    2004-12-03

    This report discusses the first year of operation of a fuel cell power plant located at the Sheraton Edison Hotel, Edison, New Jersey. PPL EnergyPlus, LLC installed the plant under a contract with the Starwood Hotels & Resorts Worldwide, Inc. A DFC{reg_sign}300 fuel cell, manufactured by FuelCell Energy, Inc. of Danbury, CT was selected for the project. The fuel cell successfully operated from June 2003 to May 2004. This report discusses the performance of the plant during this period.

  20. Multi-cell storage battery

    DOE Patents [OSTI]

    Brohm, Thomas; Bottcher, Friedhelm

    2000-01-01

    A multi-cell storage battery, in particular to a lithium storage battery, which contains a temperature control device and in which groups of one or more individual cells arranged alongside one another are separated from one another by a thermally insulating solid layer whose coefficient of thermal conductivity lies between 0.01 and 0.2 W/(m*K), the thermal resistance of the solid layer being greater by at least a factor .lambda. than the thermal resistance of the individual cell. The individual cell is connected, at least in a region free of insulating material, to a heat exchanger, the thermal resistance of the heat exchanger in the direction toward the neighboring cell being selected to be greater by at least a factor .lambda. than the thermal resistance of the individual cell and, in addition, the thermal resistance of the heat exchanger toward the temperature control medium being selected to be smaller by at least a factor of about 10 than the thermal resistance of the individual cell, and .lambda. being the ratio of the energy content of the individual cell to the amount of energy that is needed to trigger a thermally induced cell failure at a defined upper operating temperature limit.

  1. disrupting the plant cell wall

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

    disrupting the plant cell wall - Sandia Energy Energy Search Icon Sandia Home Locations ... Stationary Power Energy Conversion Efficiency Solar Energy Wind Energy Water Power ...

  2. Fuel Cell Power Plant Experience Naval Applications

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

    clean Fuel Cell Power Plant Experience Naval Applications US Department of Energy/ Office of Naval Research Shipboard Fuel Cell Workshop Washington, DC March 29, 2011 FuelCell Energy, the FuelCell Energy logo, Direct FuelCell and "DFC" are all registered trademarks (®) of FuelCell Energy, Inc. *FuelCell Energy, Inc. *Renewable and Liquid Fuels Experience *HTPEM Fuel Cell Stack for Shipboard APU *Solid Oxide Experience and Applications DOE-ONR Workshop FuelCell Energy, the FuelCell

  3. 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. Department of Energy Fuel Cell Technologies Program January 13, 2011 Fuel Cells for Diverse Applications 2 | Fuel Cell Technologies Program eere.energy.gov Fuel Cells - Where are we today? F l C ll f Fuel Cells for Stationary Power, Fuel Cells for Transportation In the U.S., there are currently: > 200 fuel cell

  4. T cells stimulate catabolic gene expression by the stromal cells from giant cell tumor of bone

    SciTech Connect (OSTI)

    Cowan, Robert W.; Juravinski Cancer Centre, 699 Concession St., Hamilton, ON, Canada L8V 5C2 ; Ghert, Michelle; Department of Surgery, McMaster University, 1280 Main St. W., Hamilton, ON, Canada L8S 4L8 ; Singh, Gurmit; Juravinski Cancer Centre, 699 Concession St., Hamilton, ON, Canada L8V 5C2

    2012-03-23

    Highlights: Black-Right-Pointing-Pointer Two T cell lines stimulate PTHrP, RANKL, MMP13 gene expression in GCT cell cultures. Black-Right-Pointing-Pointer CD40 expressed by stromal cells; CD40L detected in whole tumor but not cultures. Black-Right-Pointing-Pointer Effect of CD40L treatment on GCT cells increased PTHrP and MMP13 gene expression. Black-Right-Pointing-Pointer PTHrP treatment increased MMP13 expression, while inhibition decreased expression. Black-Right-Pointing-Pointer T cells may stimulate GCT stromal cells and promote the osteolysis of the tumor. -- Abstract: The factors that promote the localized bone resorption by giant cell tumor of bone (GCT) are not fully understood. We investigated whether T cells could contribute to bone resorption by stimulating expression of genes for parathyroid hormone-related protein (PTHrP), matrix metalloproteinase (MMP)-13, and the receptor activator of nuclear-factor {kappa}B ligand (RANKL). Two cell lines, Jurkat clone E6-1 and D1.1, were co-cultured with isolated GCT stromal cells. Real-time PCR analyses demonstrated a significant increase of all three genes following 48 h incubation, and PTHrP and MMP-13 gene expression was also increased at 24 h. Further, we examined the expression of CD40 ligand (CD40L), a protein expressed by activated T cells, and its receptor, CD40, in GCT. Immunohistochemistry results revealed expression of the CD40 receptor in both the stromal cells and giant cells of the tumor. RNA collected from whole GCT tissues showed expression of CD40LG, which was absent in cultured stromal cells, and suggests that CD40L is expressed within GCT. Stimulation of GCT stromal cells with CD40L significantly increased expression of the PTHrP and MMP-13 genes. Moreover, we show that inhibition of PTHrP with neutralizing antibodies significantly decreased MMP13 expression by the stromal cells compared to IgG-matched controls, whereas stimulation with PTHrP (1-34) increased MMP-13 gene expression. These

  5. Cell-to-cell communication and cellular environment alter the somatostatin status of delta cells

    SciTech Connect (OSTI)

    Kelly, Catriona; Flatt, Peter R.; McClenaghan, Neville H.

    2010-08-20

    Research highlights: {yields} TGP52 cells display enhanced functionality in pseudoislet form. {yields} Somatostatin content was reduced, but secretion increased in high glucose conditions. {yields} Cellular interactions and environment alter the somatostatin status of TGP52 cells. -- Abstract: Introduction: Somatostatin, released from pancreatic delta cells, is a potent paracrine inhibitor of insulin and glucagon secretion. Islet cellular interactions and glucose homeostasis are essential to maintain normal patterns of insulin secretion. However, the importance of cell-to-cell communication and cellular environment in the regulation of somatostatin release remains unclear. Methods: This study employed the somatostatin-secreting TGP52 cell line maintained in DMEM:F12 (17.5 mM glucose) or DMEM (25 mM glucose) culture media. The effect of pseudoislet formation and culture medium on somatostatin content and release in response to a variety of stimuli was measured by somatostatin EIA. In addition, the effect of pseudoislet formation on cellular viability (MTT and LDH assays) and proliferation (BrdU ELISA) was determined. Results: TGP52 cells readily formed pseudoislets and showed enhanced functionality in three-dimensional form with increased E-cadherin expression irrespective of the culture environment used. However, culture in DMEM decreased cellular somatostatin content (P < 0.01) and increased somatostatin secretion in response to a variety of stimuli including arginine, calcium and PMA (P < 0.001) when compared with cells grown in DMEM:F12. Configuration of TGP52 cells as pseudoislets reduced the proliferative rate and increased cellular cytotoxicity irrespective of culture medium used. Conclusions: Somatostatin secretion is greatly facilitated by cell-to-cell interactions and E-cadherin expression. Cellular environment and extracellular glucose also significantly influence the function of delta cells.

  6. Fuel Cells Related Links | Department of Energy

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

    Fuel Cells » Fuel Cells Related Links Fuel Cells Related Links The following resources provide details about U.S. Department of Energy (DOE)-funded fuel cell activities, research plans and roadmaps, partnerships, and additional related links. DOE-Funded Fuel Cell Activities Each year, hydrogen and fuel cell projects funded by DOE's Hydrogen and Fuel Cells Program are reviewed for their merit during an Annual Merit Review and Peer Evaluation Meeting. View posters and presentations from the

  7. Ceramic Fuel Cells (SOFC) | Department of Energy

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

    Ceramic Fuel Cells (SOFC) Ceramic Fuel Cells (SOFC) Presented at the NREL Hydrogen and Fuel Cell Manufacturing R&D Workshop in Washington, DC, August 11-12, 2011. Ceramic Fuel Cells (SOFC) (1.09 MB) More Documents & Publications 2011 NREL/DOE Hydrogen and Fuel Cell Manufacturing R&D Workshop Report Manufacturing Fuel Cell Manhattan Project DOE Fuel Cell Pre-Solicitation Workshop - Breakout Group 3: HIGH TEMP (SOFC) SYSTEM AND BOP

  8. Energy 101: Fuel Cell Technology

    SciTech Connect (OSTI)

    2014-03-11

    Learn how fuel cell technology generates clean electricity from hydrogen to power our buildings and transportation-while emitting nothing but water. This video illustrates the fundamentals of fuel cell technology and its potential to supply our homes, offices, industries, and vehicles with sustainable, reliable energy.

  9. Electrochemical cell with calcium anode

    DOE Patents [OSTI]

    Cooper, John F.; Hosmer, Pamela K.; Kelly, Benjamin E.

    1979-01-01

    An electrochemical cell comprising a calcium anode and a suitable cathode in an alkaline electrolyte consisting essentially of an aqueous solution of an hydroxide and a chloride. Specifically disclosed is a mechanically rechargeable calcium/air fuel cell with an aqueous NaOH/NaCl electrolyte.

  10. Heated transportable fuel cell cartridges

    DOE Patents [OSTI]

    Lance, Joseph R. (N. Huntingdon, PA); Spurrier, Francis R. (Whitehall, PA)

    1985-01-01

    A fuel cell stack protective system is made where a plurality of fuel cells, each containing liquid electrolyte subject to crystallization, is enclosed by a containing vessel, and where at least one electric heater is placed in the containing vessel and is capable of preventing electrolyte crystallization.

  11. Bonded polyimide fuel cell package

    DOE Patents [OSTI]

    Morse, Jeffrey D.; Jankowski, Alan; Graff, Robert T.; Bettencourt, Kerry

    2010-06-08

    Described herein are processes for fabricating microfluidic fuel cell systems with embedded components in which micron-scale features are formed by bonding layers of DuPont Kapton.TM. polyimide laminate. A microfluidic fuel cell system fabricated using this process is also described.

  12. Cell boundary fault detection system

    DOE Patents [OSTI]

    Archer, Charles Jens; Pinnow, Kurt Walter; Ratterman, Joseph D.; Smith, Brian Edward

    2011-04-19

    An apparatus and program product determine a nodal fault along the boundary, or face, of a computing cell. Nodes on adjacent cell boundaries communicate with each other, and the communications are analyzed to determine if a node or connection is faulty.

  13. Fuel Cell Powered Lift Truck

    SciTech Connect (OSTI)

    Moulden, Steve

    2015-08-20

    This project, entitled “Recovery Act: Fuel Cell-Powered Lift Truck Sysco (Houston) Fleet Deployment”, was in response to DOE funding opportunity announcement DE-PS36-08GO98009, Topic 7B, which promotes the deployment of fuel cell powered material handling equipment in large, multi-shift distribution centers. This project promoted large-volume commercialdeployments and helped to create a market pull for material handling equipment (MHE) powered fuel cell systems. Specific outcomes and benefits involved the proliferation of fuel cell systems in 5-to 20-kW lift trucks at a high-profile, real-world site that demonstrated the benefits of fuel cell technology and served as a focal point for other nascent customers. The project allowed for the creation of expertise in providing service and support for MHE fuel cell powered systems, growth of existing product manufacturing expertise, and promoted existing fuel cell system and component companies. The project also stimulated other MHE fleet conversions helping to speed the adoption of fuel cell systems and hydrogen fueling technology. This document also contains the lessons learned during the project in order to communicate the successes and difficulties experienced, which could potentially assist others planning similar projects.

  14. Energy 101: Fuel Cell Technology

    ScienceCinema (OSTI)

    None

    2014-06-06

    Learn how fuel cell technology generates clean electricity from hydrogen to power our buildings and transportation-while emitting nothing but water. This video illustrates the fundamentals of fuel cell technology and its potential to supply our homes, offices, industries, and vehicles with sustainable, reliable energy.

  15. Graphite-based photovoltaic cells

    DOE Patents [OSTI]

    Lagally, Max; Liu, Feng

    2010-12-28

    The present invention uses lithographically patterned graphite stacks as the basic building elements of an efficient and economical photovoltaic cell. The basic design of the graphite-based photovoltaic cells includes a plurality of spatially separated graphite stacks, each comprising a plurality of vertically stacked, semiconducting graphene sheets (carbon nanoribbons) bridging electrically conductive contacts.

  16. Photovoltaic cells employing zinc phosphide

    DOE Patents [OSTI]

    Barnett, Allen M.; Catalano, Anthony W.; Dalal, Vikram L.; Masi, James V.; Meakin, John D.; Hall, Robert B.

    1984-01-01

    A photovoltaic cell having a zinc phosphide absorber. The zinc phosphide can be a single or multiple crystal slice or a thin polycrystalline film. The cell can be a Schottky barrier, heterojunction or homojunction device. Methods for synthesizing and crystallizing zinc phosphide are disclosed as well as a method for forming thin films.

  17. Plastic Schottky barrier solar cells

    DOE Patents [OSTI]

    Waldrop, James R.; Cohen, Marshall J.

    1984-01-24

    A photovoltaic cell structure is fabricated from an active medium including an undoped, intrinsically p-type organic semiconductor comprising polyacetylene. When a film of such material is in rectifying contact with a magnesium electrode, a Schottky-barrier junction is obtained within the body of the cell structure. Also, a gold overlayer passivates the magnesium layer on the undoped polyacetylene film.

  18. Bronx Zoo Fuel Cell Project

    SciTech Connect (OSTI)

    Hoang Pham

    2007-09-30

    A 200 kW Fuel Cell has been installed in the Lion House, Bronx Zoo, NY. The Fuel Cell is a 200 kW phosphoric acid type manufactured by United Technologies Corporation (UTC) and will provide thermal energy at 725,000 Btu/hr.

  19. Microaspiration for high-pressure freezing: a new method for ultrastructural preservation of fragile and sparse tissues for TEM and electron tomography

    SciTech Connect (OSTI)

    Auer, Manfred; Triffo, W.J.; Palsdottir, H.; McDonald, K.L.; Inman, J.L.; Bissell, M.J.; Raphael, R.M.; Auer, M.; Lee, J.K.

    2008-02-13

    High-pressure freezing is the preferred method to prepare thick biological specimens for ultrastructural studies. However, the advantages obtained by this method often prove unattainable for samples that are difficult to handle during the freezing and substitution protocols. Delicate and sparse samples are difficult to manipulate and maintain intact throughout the sequence of freezing, infiltration, embedding, and final orientation for sectioning and subsequent TEM imaging. An established approach to surmount these difficulties is the use of cellulose microdialysis tubing to transport the sample. With an inner diameter of 200 micrometers, the tubing protects small and fragile samples within the thickness constraints of high-pressure freezing, and the tube ends can be sealed to avoid loss of sample. Importantly, the transparency of the tubing allows optical study of the specimen at different steps in the process. Here, we describe the use of a micromanipulator and microinjection apparatus to handle and position delicate specimens within the tubing. We report two biologically significant examples that benefit from this approach, 3D cultures of mammary epithelial cells and cochlear outer hair cells. We illustrate the potential for correlative light and electron microscopy as well as electron tomography.

  20. Dye Sensitized Tandem Photovoltaic Cells

    SciTech Connect (OSTI)

    Barber, Greg D.

    2009-12-21

    This work provided a new way to look at photoelectrochemical cells and their performance. Although thought of as low efficiency, a the internal efficiency of a 9% global efficiency dye sensitized solar cell is approximately equal to an 18% efficient silicon cell when each is compared to their useful spectral range. Other work undertaken with this contract also reported the first growth oriented titania and perovskite columns on a transparent conducting oxide. Other work has shown than significant performance enhancement in the performance of dye sensitized solar cells can be obtained through the use of coupling inverse opal photonic crystals to the nanocrystalline dye sensitized solar cell. Lastly, a quick efficient method was developed to bond titanium foils to transparent conducting oxide substrates for anodization.

  1. Electrode for a lithium cell

    DOE Patents [OSTI]

    Thackeray, Michael M.; Vaughey, John T.; Dees, Dennis W.

    2008-10-14

    This invention relates to a positive electrode for an electrochemical cell or battery, and to an electrochemical cell or battery; the invention relates more specifically to a positive electrode for a non-aqueous lithium cell or battery when the electrode is used therein. The positive electrode includes a composite metal oxide containing AgV.sub.3O.sub.8 as one component and one or more other components consisting of LiV.sub.3O.sub.8, Ag.sub.2V.sub.4O.sub.11, MnO.sub.2, CF.sub.x, AgF or Ag.sub.2O to increase the energy density of the cell, optionally in the presence of silver powder and/or silver foil to assist in current collection at the electrode and to improve the power capability of the cell or battery.

  2. Rechargeable lithium-ion cell

    DOE Patents [OSTI]

    Bechtold, Dieter; Bartke, Dietrich; Kramer, Peter; Kretzschmar, Reiner; Vollbert, Jurgen

    1999-01-01

    The invention relates to a rechargeable lithium-ion cell, a method for its manufacture, and its application. The cell is distinguished by the fact that it has a metallic housing (21) which is electrically insulated internally by two half shells (15), which cover electrode plates (8) and main output tabs (7) and are composed of a non-conductive material, where the metallic housing is electrically insulated externally by means of an insulation coating. The cell also has a bursting membrane (4) which, in its normal position, is located above the electrolyte level of the cell (1). In addition, the cell has a twisting protection (6) which extends over the entire surface of the cover (2) and provides centering and assembly functions for the electrode package, which comprises the electrode plates (8).

  3. Ambient pressure fuel cell system

    DOE Patents [OSTI]

    Wilson, Mahlon S.

    2000-01-01

    An ambient pressure fuel cell system is provided with a fuel cell stack formed from a plurality of fuel cells having membrane/electrode assemblies (MEAs) that are hydrated with liquid water and bipolar plates with anode and cathode sides for distributing hydrogen fuel gas and water to a first side of each one of the MEAs and air with reactant oxygen gas to a second side of each one of the MEAs. A pump supplies liquid water to the fuel cells. A recirculating system may be used to return unused hydrogen fuel gas to the stack. A near-ambient pressure blower blows air through the fuel cell stack in excess of reaction stoichiometric amounts to react with the hydrogen fuel gas.

  4. Integrated Experimental and Model-based Analysis Reveals the Spatial Aspects of EGFR Activation Dynamics

    SciTech Connect (OSTI)

    Shankaran, Harish; Zhang, Yi; Chrisler, William B.; Ewald, Jonathan A.; Wiley, H. S.; Resat, Haluk

    2012-10-02

    The epidermal growth factor receptor (EGFR) belongs to the ErbB family of receptor tyrosine kinases, and controls a diverse set of cellular responses relevant to development and tumorigenesis. ErbB activation is a complex process involving receptor-ligand binding, receptor dimerization, phosphorylation, and trafficking (internalization, recycling and degradation), which together dictate the spatio-temporal distribution of active receptors within the cell. The ability to predict this distribution, and elucidation of the factors regulating it, would help to establish a mechanistic link between ErbB expression levels and the cellular response. Towards this end, we constructed mathematical models for deconvolving the contributions of receptor dimerization and phosphorylation to EGFR activation, and to examine the dependence of these processes on sub-cellular location. We collected experimental datasets for EGFR activation dynamics in human mammary epithelial cells, with the specific goal of model parameterization, and used the data to estimate parameters for several alternate models. Model-based analysis indicated that: 1) signal termination via receptor dephosphorylation in late endosomes, prior to degradation, is an important component of the response, 2) less than 40% of the receptors in the cell are phosphorylated at any given time, even at saturating ligand doses, and 3) receptor dephosphorylation rates at the cell surface and early endosomes are comparable. We validated the last finding by measuring EGFR dephosphorylation rates at various times following ligand addition both in whole cells, and in endosomes using ELISAs and fluorescent imaging. Overall, our results provide important information on how EGFR phosphorylation levels are regulated within cells. Further, the mathematical model described here can be extended to determine receptor dimer abundances in cells co-expressing various levels of ErbB receptors. This study demonstrates that an iterative cycle of

  5. Fuel Cell Research

    SciTech Connect (OSTI)

    Weber, Peter M.

    2014-03-30

    Executive Summary In conjunction with the Brown Energy Initiative, research Projects selected for the fuel cell research grant were selected on the following criteria: They should be fundamental research that has the potential to significantly impact the nation’s energy infrastructure. They should be scientifically exciting and sound. They should synthesize new materials, lead to greater insights, explore new phenomena, or design new devices or processes that are of relevance to solving the energy problems. They involve top-caliper senior scientists with a record of accomplishment, or junior faculty with outstanding promise of achievement. They should promise to yield at least preliminary results within the given funding period, which would warrant further research development. They should fit into the overall mission of the Brown Energy Initiative, and the investigators should contribute as partners to an intellectually stimulating environment focused on energy science. Based on these criteria, fourteen faculty across three disciplines (Chemistry, Physics and Engineering) and the Charles Stark Draper Laboratory were selected to participate in this effort.1 In total, there were 30 people supported, at some level, on these projects. This report highlights the findings and research outcomes of the participating researchers.

  6. Calling All Fuel Cells | Department of Energy

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

    Calling All Fuel Cells Calling All Fuel Cells December 7, 2012 - 4:31pm Addthis Altergy had more than 60 fuel cells in the immediate Hurricane Sandy disaster area that acted as backup power for cell phone towers. | Photo courtesy of Altergy. Altergy had more than 60 fuel cells in the immediate Hurricane Sandy disaster area that acted as backup power for cell phone towers. | Photo courtesy of Altergy. Sunita Satyapal Director, Fuel Cell Technologies Office What is a fuel cell? A fuel cell is a

  7. Fuel Cell Animation | Department of Energy

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

    Animation Fuel Cell Animation This fuel cell animation demonstrates how a fuel cell uses hydrogen to produce electricity, with only water and heat as byproducts. Hydrogen fuel cell vehicles emit approximately the same amount of water per mile as conventional vehicles powered by internal combustion engines. Learn more about water emissions from fuel cell vehicles. View text version of animation.

  8. Fuel Cell Technical Publications | Department of Energy

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

    Technical Publications » Fuel Cell Technical Publications Fuel Cell Technical Publications Technical information about fuel cells published in technical reports, conference proceedings, journal articles, and websites is provided here. General Transportation Stationary/Distributed Power Auxiliary and Portable Power Manufacturing Material Handling Equipment General The Business Case for Fuel Cells 2015: Powering Corporate Sustainability (Fuel Cell and Hydrogen Energy Association, January 2016)

  9. The Kanatzidis - Chang Cell: dye sensitized all solid state solar cell |

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

    ANSER Center | Argonne-Northwestern National Laboratory The Kanatzidis - Chang Cell: dye sensitized all solid state solar cell Home > Research > ANSER Research Highlights > The Kanatzidis - Chang Cell: dye sensitized all solid state solar cell

  10. Superstrate sub-cell voltage-matched multijunction solar cells

    DOE Patents [OSTI]

    Mascarenhas, Angelo; Alberi, Kirstin

    2016-03-15

    Voltage-matched thin film multijunction solar cell and methods of producing cells having upper CdTe pn junction layers formed on a transparent substrate which in the completed device is operatively positioned in a superstate configuration. The solar cell also includes a lower pn junction formed independently of the CdTe pn junction and an insulating layer between CdTe and lower pn junctions. The voltage-matched thin film multijunction solar cells further include a parallel connection between the CdTe pn junction and lower pn junctions to form a two-terminal photonic device. Methods of fabricating devices from independently produced upper CdTe junction layers and lower junction layers are also disclosed.

  11. NREL: Hydrogen and Fuel Cells Research - Hydrogen Fuel Cell Electric

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

    Vehicle Learning Demonstration Fuel Cell Electric Vehicle Learning Demonstration Delve deeper into real-world performance data with our Interactive Composite Data Product demo Graphical thumbnail of the Interactive Composite Data Product demo map. Learn More Subscribe to the biannual Fuel Cell and Hydrogen Technology Validation newsletter, which highlights recent technology validation activities at NREL. Initiated in 2004, DOE's Controlled Hydrogen Fleet and Infrastructure Demonstration and

  12. Organic fuel cells and fuel cell conducting sheets

    DOE Patents [OSTI]

    Masel, Richard I.; Ha, Su; Adams, Brian

    2007-10-16

    A passive direct organic fuel cell includes an organic fuel solution and is operative to produce at least 15 mW/cm.sup.2 when operating at room temperature. In additional aspects of the invention, fuel cells can include a gas remover configured to promote circulation of an organic fuel solution when gas passes through the solution, a modified carbon cloth, one or more sealants, and a replaceable fuel cartridge.

  13. Solid oxide fuel cell generator

    DOE Patents [OSTI]

    Draper, R.; George, R.A.; Shockling, L.A.

    1993-04-06

    A solid oxide fuel cell generator has a pair of spaced apart tubesheets in a housing. At least two intermediate barrier walls are between the tubesheets and define a generator chamber between two intermediate buffer chambers. An array of fuel cells have tubes with open ends engaging the tubesheets. Tubular, axially elongated electrochemical cells are supported on the tubes in the generator chamber. Fuel gas and oxidant gas are preheated in the intermediate chambers by the gases flowing on the other side of the tubes. Gas leakage around the tubes through the tubesheets is permitted. The buffer chambers reentrain the leaked fuel gas for reintroduction to the generator chamber.

  14. High temperature sealed electrochemical cell

    DOE Patents [OSTI]

    Valentin Chung, Brice Hoani; Burke, Paul J.; Sadoway, Donald R.

    2015-10-06

    A cell for high temperature electrochemical reactions is provided. The cell includes a container, at least a portion of the container acting as a first electrode. An extension tube has a first end and a second end, the extension tube coupled to the container at the second end forming a conduit from the container to said first end. A second electrode is positioned in the container and extends out of the container via the conduit. A seal is positioned proximate the first end of the extension tube, for sealing the cell.

  15. Micro-Sized Photovoltaic Cells

    Office of Energy Efficiency and Renewable Energy (EERE)

    This photograph features Greg Nielson, a project leader at Sandia National Laboratoies. He holds a solar cell test prototype with a microscale lens array fastened above it. Together, the cell and lens help create a concentrated photovoltaic unit. The tiny cells could turn a person into a walking solar battery charger if they were fastened to flexible substrates molded around unusual shapes, such as clothing. The solar particles, fabricated of crystalline silicon, hold the potential for a variety of new applications. They are expected eventually to be less expensive and have greater efficiencies than current photovoltaic collectors that are pieced together with 6-inch- square solar wafers.

  16. Photovoltaic cell and production thereof

    DOE Patents [OSTI]

    Narayanan, Srinivasamohan; Kumar, Bikash

    2008-07-22

    An efficient photovoltaic cell, and its process of manufacture, is disclosed wherein the back surface p-n junction is removed from a doped substrate having an oppositely doped emitter layer. A front surface and edges and optionally the back surface periphery are masked and a back surface etch is performed. The mask is not removed and acts as an anti-reflective coating, a passivating agent, or both. The photovoltaic cell retains an untextured back surface whether or not the front is textured and the dopant layer on the back surface is removed to enhance the cell efficiency. Optionally, a back surface field is formed.

  17. Reference electrode for electrolytic cell

    DOE Patents [OSTI]

    Kessie, R.W.

    1988-07-28

    A reference electrode device is provided for a high temperature electrolytic cell used to electrolytically recover uranium from spent reactor fuel dissolved in an anode pool, the device having a glass tube to enclose the electrode and electrolyte and serve as a conductive membrane with the cell electrolyte, and an outer metal tube about the glass tube to serve as a shield and basket for any glass sections broken by handling of the tube to prevent their contact with the anode pool, the metal tube having perforations to provide access between the bulk of the cell electrolyte and glass membrane. 4 figs.

  18. Solid oxide fuel cell generator

    DOE Patents [OSTI]

    Draper, Robert; George, Raymond A.; Shockling, Larry A.

    1993-01-01

    A solid oxide fuel cell generator has a pair of spaced apart tubesheets in a housing. At least two intermediate barrier walls are between the tubesheets and define a generator chamber between two intermediate buffer chambers. An array of fuel cells have tubes with open ends engaging the tubesheets. Tubular, axially elongated electrochemical cells are supported on the tubes in the generator chamber. Fuel gas and oxidant gas are preheated in the intermediate chambers by the gases flowing on the other side of the tubes. Gas leakage around the tubes through the tubesheets is permitted. The buffer chambers reentrain the leaked fuel gas for reintroduction to the generator chamber.

  19. Mixed ternary heterojunction solar cell

    SciTech Connect (OSTI)

    Chen, Wen S.; Stewart, John M.

    1992-08-25

    A thin film heterojunction solar cell and a method of making it has a p-type layer of mixed ternary I-III-VI.sub.2 semiconductor material in contact with an n-type layer of mixed binary II-VI semiconductor material. The p-type semiconductor material includes a low resistivity copper-rich region adjacent the back metal contact of the cell and a composition gradient providing a minority carrier mirror that improves the photovoltaic performance of the cell. The p-type semiconductor material preferably is CuInGaSe.sub.2 or CuIn(SSe).sub.2.

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

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

    Exposition | Department of Energy 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 Cell Seminar and Exposition on October 19, 2010. Hydrogen and Fuel Cell Technologies Update (4.81 MB) More Documents & Publications DOE Hydrogen and Fuel Cell Overview: 2011 Waste-to-Energy Using Fuel Cells Workshop 2010 Fuel Cell Project Kick-off Welcome DOE Hydrogen and Fuel

  1. DOE Fuel Cell Technologies Office: 2013 Fuel Cell Seminar and Energy

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

    Exposition | Department of Energy 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 presented by Sunita Satyapal at the 2013 Fuel Cell Seminar and Energy Exposition in Columbus, Ohio. DOE Fuel Cell Technologies Office (2.15 MB) More Documents & Publications Fuel Cell Technologies Program - DOD-DOE Workshop: Shipboard APUs Overview DOE Hydrogen and Fuel Cell

  2. DOE Hydrogen and Fuel Cell Overview: 2011 Waste-to-Energy Using Fuel Cells

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

    Workshop | Department of Energy 2011 Waste-to-Energy Using Fuel Cells Workshop DOE Hydrogen and Fuel Cell Overview: 2011 Waste-to-Energy Using Fuel Cells Workshop Presentation by Sunita Satyapal, DOE Fuel Cell Technologies Program, at the Waste-to-Energy Using Fuel Cells Workshop help January 13, 2011. DOE Hydrogen and Fuel Cell Overview (1.77 MB) More Documents & Publications Fuel Cell Technologies Program - DOD-DOE Workshop: Shipboard APUs Overview DOE Fuel Cell Technologies Office:

  3. SunLine Expands Horizons with Fuel Cell Bus Demo. Hydrogen, Fuel Cells &

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

    Infrastructure Technologies Program, Fuel Cell Bus Demonstration Projects (Fact Sheet). | Department of Energy Expands Horizons with Fuel Cell Bus Demo. Hydrogen, Fuel Cells & Infrastructure Technologies Program, Fuel Cell Bus Demonstration Projects (Fact Sheet). SunLine Expands Horizons with Fuel Cell Bus Demo. Hydrogen, Fuel Cells & Infrastructure Technologies Program, Fuel Cell Bus Demonstration Projects (Fact Sheet). Fact sheet describes the study being conducted on fuel cell

  4. U.S. Fuel Cell Council: The Voice of the Fuel Cell Industry | Department of

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

    Energy Fuel Cell Council: The Voice of the Fuel Cell Industry U.S. Fuel Cell Council: The Voice of the Fuel Cell Industry Presentation to the Fall 2009 High Temperature Membrane Working Group about_usfcc.pdf (152.13 KB) More Documents & Publications Fuel Cell Council Working Group on Aircraft and Aircraft Ground Support Fuel Cell Applications Legislative Update: State and Regional Hydrogen and Fuel Cell Initiatives Conference Call Micro and Man-Portable Fuel Cells

  5. Fuel Cell Buses | Department of Energy

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

    Download presentation slides from the DOE Fuel Cell Technologies Office webinar "Fuel Cell Buses" held on September 12, 2013. Fuel Cell Buses Webinar Slides (2.44 MB) More ...

  6. fuel cell | OpenEI Community

    Open Energy Info (EERE)

    fuel cell Home Dc's picture Submitted by Dc(266) Contributor 19 February, 2015 - 15:08 2016 Toyota Mirai Fuel Cell Car First Drive - HybridCars.com Review 2016 car fuel cell hybrid...

  7. Fuel Cell Europe | Open Energy Information

    Open Energy Info (EERE)

    Name: Fuel Cell Europe Place: FrankfurtM, Germany Zip: D-60313 Product: Fuel Cell Europe was set up to promote the commercial application of fuel cell across Europe. Coordinates:...

  8. EPG Fuel Cell LLc | Open Energy Information

    Open Energy Info (EERE)

    EPG Fuel Cell LLc Jump to: navigation, search Name: EPG Fuel Cell LLc Place: Maryland Product: 50-50 JV between Catamount Energy and Elemental Power. References: EPG Fuel Cell...

  9. Solid Oxide Fuel Cells | Department of Energy

    Energy Savers [EERE]

    Solid Oxide Fuel Cells FE researchers at NETL have developed a unique test platform, called the multi-cell array, to rapidly test multiple fuel cells and determine how they degrade ...

  10. CMR Fuel Cells Ltd | Open Energy Information

    Open Energy Info (EERE)

    CMR Fuel Cells Ltd Jump to: navigation, search Name: CMR Fuel Cells Ltd Place: Cambridge, England, United Kingdom Zip: CB2 5GG Product: Cambridge-based firm developing fuel cell...

  11. Dupont Fuel Cells | Open Energy Information

    Open Energy Info (EERE)

    Dupont Fuel Cells Jump to: navigation, search Name: Dupont Fuel Cells Place: Wilmington, Delaware Zip: DE 19880-0 Product: A subsidiary of Dupont which specializes in fuel cell...

  12. Fuel Cell Markets Ltd | Open Energy Information

    Open Energy Info (EERE)

    Cell Markets Ltd Place: Buckinghamshire, United Kingdom Zip: SL0 9AQ Sector: Hydro, Hydrogen Product: Fuel Cell Markets was set up to assist companies in the fuel cell and...

  13. Air Breathing Direct Methanol Fuel Cell

    DOE Patents [OSTI]

    Ren; Xiaoming

    2003-07-22

    A method for activating a membrane electrode assembly for a direct methanol fuel cell is disclosed. The method comprises operating the fuel cell with humidified hydrogen as the fuel followed by running the fuel cell with methanol as the fuel.

  14. National Fuel Cell Technology Evaluation Center (NFCTEC)

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

    National Fuel Cell Technology Evaluation Center (NFCTEC) Jim Alkire U.S. Department of Energy Fuel Cell Technologies Office Jennifer Kurtz & Sam Sprik National Renewable Energy Laboratory 2 Outline * About NFCTEC * Benefits to the Hydrogen & Fuel Cell Community * New Fuel Cell Cost/Price Aggregation Project About NFCTEC 4 National Fuel Cell Technology Evaluation Center a national resource for hydrogen and fuel cell stakeholders supported through Energy Efficiency and Renewable Energy's

  15. 1986 fuel cell seminar: Program and abstracts

    SciTech Connect (OSTI)

    1986-10-01

    Ninety nine brief papers are arranged under the following session headings: gas industry's 40 kw program, solid oxide fuel cell technology, phosphoric acid fuel cell technology, molten carbonate fuel cell technology, phosphoric acid fuel cell systems, power plants technology, fuel cell power plant designs, unconventional fuels, fuel cell application and economic assessments, and plans for commerical development. The papers are processed separately for the data base. (DLC)

  16. Fuel Cells & Renewable Portfolio Standards

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

    Fuel Cells & Renewable Portfolio Standards Webinar - Jun 9 th , 2011 Ohio Fuel Cell Coalition Ohio Fuel Cell Coalition * Mission - The Ohio Fuel Cell Coalition is a united group of industry, academic, and government leaders working collectively to strengthen Ohio's fuel cell industry and to accelerate the transformation of industry to global leadership in fuel cell technology and applications * Activities - Networking and Collaboration - Education - Marketing and Communications - Advocacy

  17. Fuel Cells for Critical Communications Backup Power

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

    for Critical Communications Backup Power Greg Moreland SENTECH, Inc. Supporting the U.S. Department of Energy August 6, 2008 APCO Annual Conference and Expo 2 2 Fuel cells use hydrogen to create electricity, with only water and heat as byproducts Fuel Cell Overview * An individual fuel cell produces about 1 volt * Hundreds of individual cells can comprise a fuel cell stack * Fuel cells can be used to power a variety of applications -Bibliographic Database * Laptop computers (50-100 W) *

  18. DOE Hydrogen and Fuel Cell Overview

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

    Fuel Cell Technologies Program DOE Hydrogen & Fuel Cell Overview Dr. Sunita Satyapal Program Manager U.S. Department of Energy Fuel Cell Technologies Program January 5, 2011 2 | Fuel Cell Technologies Program eere.energy.gov * Overview - Goals & Objectives - Technology Status & Key Challenges * Progress - Research & Development - Deployments - Recovery Act Projects * Budget * Key Publications Agenda: DOE Fuel Cell Technologies Program 3 | Fuel Cell Technologies Program

  19. Cascade solar cell having conductive interconnects

    DOE Patents [OSTI]

    Borden, Peter G.; Saxena, Ram R.

    1982-10-26

    Direct ohmic contact between the cells in an epitaxially grown cascade solar cell is obtained by means of conductive interconnects formed through grooves etched intermittently in the upper cell. The base of the upper cell is directly connected by the conductive interconnects to the emitter of the bottom cell. The conductive interconnects preferably terminate on a ledge formed in the base of the upper cell.

  20. Hydrogen and Fuel Cells Program Plenary Presentation

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

    U.S. Department of Energy Hydrogen & Fuel Cells Program Annual Merit Review and Peer Evaluation Meeting Dr. Sunita Satyapal Director Fuel Cell Technologies Office U.S. Department of Energy June 2014 2 | Fuel Cell Technologies Office eere.energy.gov Fuel Cell Market Market Growth Fuel cell markets continue to grow * >25% increase in global MWs shipped since 2012 * 35% increase in revenues from fuel cell systems shipped over last year * Consistent ~30% annual growth in global systems

  1. Human papillomavirus 16 E5 induces bi-nucleated cell formation by cell-cell fusion

    SciTech Connect (OSTI)

    Hu Lulin; Plafker, Kendra; Vorozhko, Valeriya; Zuna, Rosemary E.; Hanigan, Marie H.; Gorbsky, Gary J.; Plafker, Scott M.; Angeletti, Peter C.; Ceresa, Brian P.

    2009-02-05

    Human papillomaviruses (HPV) 16 is a DNA virus encoding three oncogenes - E5, E6, and E7. The E6 and E7 proteins have well-established roles as inhibitors of tumor suppression, but the contribution of E5 to malignant transformation is controversial. Using spontaneously immortalized human keratinocytes (HaCaT cells), we demonstrate that expression of HPV16 E5 is necessary and sufficient for the formation of bi-nucleated cells, a common characteristic of precancerous cervical lesions. Expression of E5 from non-carcinogenic HPV6b does not produce bi-nucleate cells. Video microscopy and biochemical analyses reveal that bi-nucleates arise through cell-cell fusion. Although most E5-induced bi-nucleates fail to propagate, co-expression of HPV16 E6/E7 enhances the proliferation of these cells. Expression of HPV16 E6/E7 also increases bi-nucleated cell colony formation. These findings identify a new role for HPV16 E5 and support a model in which complementary roles of the HPV16 oncogenes lead to the induction of carcinogenesis.

  2. Additive Manufacturing for Fuel Cells

    Broader source: Energy.gov [DOE]

    Blake Marshall, AMO's lead for Additive Manufacturing Technologies, will provide an overview of current R&D activities in additive manufacturing and its application to fuel cell prototyping and...

  3. NETL: Solid Oxide Fuel Cells

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

    The NETL Fuel Cell Program maintains a portfolio of RD&D projects that address the technical issues facing the commercialization of SOFC technology and a series of increasingly ...

  4. PEM/SPE fuel cell

    DOE Patents [OSTI]

    Grot, S.A.

    1998-01-13

    A PEM/SPE fuel cell is described including a membrane-electrode assembly (MEA) having a plurality of oriented filament embedded the face thereof for supporting the MEA and conducting current therefrom to contiguous electrode plates. 4 figs.

  5. Multiple Exciton Generation Solar Cells

    SciTech Connect (OSTI)

    Luther, J. M.; Semonin, O. E.; Beard, M. C.; Gao, J.; Nozik, A. J.

    2012-01-01

    Heat loss is the major factor limiting traditional single junction solar cells to a theoretical efficiency of 32%. Multiple Exciton Generation (MEG) enables efficient use of the solar spectrum yielding a theoretical power conversion efficiency of 44% in solar cells under 1-sun conditions. Quantum-confined semiconductors have demonstrated the ability to generate multiple carriers but present-day materials deliver efficiencies far below the SQ limit of 32%. Semiconductor quantum dots of PbSe and PbS provide an active testbed for developing high-efficiency, inexpensive solar cells benefitting from quantum confinement effects. Here, we will present recent work of solar cells employing MEG to yield external quantum efficiencies exceeding 100%.

  6. Fuel Cell Technologies Office Overview

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

    Biological Hydrogen Production Workshop Sara Dillich U.S ... & Renewable Energy Fuel Cell Technologies Office ... a delivered and dispensed cost of 2-4kg H 2 by 2020 P&D ...

  7. Cell Data Sheet Specification (Presentation)

    SciTech Connect (OSTI)

    Kurtz, S.

    2012-03-01

    The presentation shows a brief status report on the development of a specification being considered by IEC TC82 WG7 for a concentrator cell data sheet and solicits suggestions from the community.

  8. CLIMATE CHANGE FUEL CELL PROGRAM

    SciTech Connect (OSTI)

    Mike Walneuski

    2004-09-16

    ChevronTexaco has successfully operated a 200 kW PC25C phosphoric acid fuel cell power plant at the corporate data center in San Ramon, California for the past two years and seven months following installation in December 2001. This site was chosen based on the ability to utilize the combined heat (hot water) and power generation capability of this modular fuel cell power plant in an office park setting . In addition, this project also represents one of the first commercial applications of a stationary fuel cell for a mission critical data center to assess power reliability benefits. This fuel cell power plant system has demonstrated outstanding reliability and performance relative to other comparably sized cogeneration systems.

  9. Imaging Liquids Using Microfluidic Cells

    SciTech Connect (OSTI)

    Yu, Xiao-Ying; Liu, Bingwen; Yang, Li

    2013-05-10

    Chemistry occurring in the liquid and liquid surface is important in many applications. Chemical imaging of liquids using vacuum based analytical techniques is challenging due to the difficulty in working with liquids with high volatility. Recent development in microfluidics enabled and increased our capabilities to study liquid in situ using surface sensitive techniques such as electron microscopy and spectroscopy. Due to its small size, low cost, and flexibility in design, liquid cells based on microfluidics have been increasingly used in studying and imaging complex phenomena involving liquids. This paper presents a review of microfluidic cells that were developed to adapt to electron microscopes and various spectrometers for in situ chemical analysis and imaging of liquids. The following topics will be covered including cell designs, fabrication techniques, unique technical features for vacuum compatible cells, and imaging with electron microscopy and spectroscopy. Challenges are summarized and recommendations for future development priority are proposed.

  10. Interfacing nanostructures to biological cells

    DOE Patents [OSTI]

    Chen, Xing; Bertozzi, Carolyn R.; Zettl, Alexander K.

    2012-09-04

    Disclosed herein are methods and materials by which nanostructures such as carbon nanotubes, nanorods, etc. are bound to lectins and/or polysaccharides and prepared for administration to cells. Also disclosed are complexes comprising glycosylated nanostructures, which bind selectively to cells expressing glycosylated surface molecules recognized by the lectin. Exemplified is a complex comprising a carbon nanotube functionalized with a lipid-like alkane, linked to a polymer bearing repeated .alpha.-N-acetylgalactosamine sugar groups. This complex is shown to selectively adhere to the surface of living cells, without toxicity. In the exemplified embodiment, adherence is mediated by a multivalent lectin, which binds both to the cells and the .alpha.-N-acetylgalactosamine groups on the nanostructure.

  11. Navy fuel cell demonstration project.

    SciTech Connect (OSTI)

    Black, Billy D.; Akhil, Abbas Ali

    2008-08-01

    This is the final report on a field evaluation by the Department of the Navy of twenty 5-kW PEM fuel cells carried out during 2004 and 2005 at five Navy sites located in New York, California, and Hawaii. The key objective of the effort was to obtain an engineering assessment of their military applications. Particular issues of interest were fuel cell cost, performance, reliability, and the readiness of commercial fuel cells for use as a standalone (grid-independent) power option. Two corollary objectives of the demonstration were to promote technological advances and to improve fuel performance and reliability. From a cost perspective, the capital cost of PEM fuel cells at this stage of their development is high compared to other power generation technologies. Sandia National Laboratories technical recommendation to the Navy is to remain involved in evaluating successive generations of this technology, particularly in locations with greater environmental extremes, and it encourages their increased use by the Navy.

  12. Fuel Cell Technologies Program Overview

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

    3 | Fuel Cell Technologies Program eere.energy.gov - 5,000 10,000 15,000 20,000 25,000 2008 2009 2010 2011P Systems ... Storage (NREL) * Showed PEM and alkaline electrolyzers ...

  13. DOE Fuel Cell Subprogram (Presentation)

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

    ... Table 3.4.4 Technical Targets a : Integrated Stationary PEM Fuel Cell Power Systems (5-250kW) Operating on Reformate a Includes fuel processor, stack and all ancillaries. b Ratio ...

  14. Fuel cell electric power production

    DOE Patents [OSTI]

    Hwang, Herng-Shinn; Heck, Ronald M.; Yarrington, Robert M.

    1985-01-01

    A process for generating electricity from a fuel cell includes generating a hydrogen-rich gas as the fuel for the fuel cell by treating a hydrocarbon feed, which may be a normally liquid feed, in an autothermal reformer utilizing a first monolithic catalyst zone having palladium and platinum catalytic components therein and a second, platinum group metal steam reforming catalyst. Air is used as the oxidant in the hydrocarbon reforming zone and a low oxygen to carbon ratio is maintained to control the amount of dilution of the hydrogen-rich gas with nitrogen of the air without sustaining an insupportable amount of carbon deposition on the catalyst. Anode vent gas may be utilized as the fuel to preheat the inlet stream to the reformer. The fuel cell and the reformer are preferably operated at elevated pressures, up to about a pressure of 150 psia for the fuel cell.

  15. Fuel cell system with interconnect

    DOE Patents [OSTI]

    Liu, Zhien; Goettler, Richard; Delaforce, Philip Mark

    2016-03-08

    The present invention includes a fuel cell system having an interconnect that reduces or eliminates diffusion (leakage) of fuel and oxidant by providing an increased densification, by forming the interconnect as a ceramic/metal composite.

  16. Metrology for Fuel Cell Manufacturing

    SciTech Connect (OSTI)

    Stocker, Michael; Stanfield, Eric

    2015-02-04

    The project was divided into three subprojects. The first subproject is Fuel Cell Manufacturing Variability and Its Impact on Performance. The objective was to determine if flow field channel dimensional variability has an impact on fuel cell performance. The second subproject is Non-contact Sensor Evaluation for Bipolar Plate Manufacturing Process Control and Smart Assembly of Fuel Cell Stacks. The objective was to enable cost reduction in the manufacture of fuel cell plates by providing a rapid non-contact measurement system for in-line process control. The third subproject is Optical Scatterfield Metrology for Online Catalyst Coating Inspection of PEM Soft Goods. The objective was to evaluate the suitability of Optical Scatterfield Microscopy as a viable measurement tool for in situ process control of catalyst coatings.

  17. PEM/SPE fuel cell

    DOE Patents [OSTI]

    Grot, Stephen Andreas

    1998-01-01

    A PEM/SPE fuel cell including a membrane-electrode assembly (MEA) having a plurality of oriented filament embedded the face thereof for supporting the MEA and conducting current therefrom to contiguous electrode plates.

  18. Silicon Cells | Open Energy Information

    Open Energy Info (EERE)

    a low cost method of processing silicon to produce a new generation of high energy density batteries. References: Silicon Cells1 This article is a stub. You can help OpenEI...

  19. Water Emissions from Fuel Cell Vehicles | Department of Energy

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

    Fuel Cells Water Emissions from Fuel Cell Vehicles Water Emissions from Fuel Cell Vehicles Hydrogen fuel cell vehicles (FCVs) emit approximately the same amount of water per ...

  20. Hydrogen and Fuel Cells Program Overview: 2013 Annual Merit Review...

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

    DOE Fuel Cell Technologies Office: 2013 Fuel Cell Seminar and Energy Exposition Fuel Cell Technologies Program - DOD-DOE Workshop: Shipboard APUs Overview Hydrogen and Fuel Cells ...