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Sample records for transactivates nuclear factor

  1. The C-terminal domain of the nuclear factor I-B2 isoform is glycosylated and transactivates the WAP gene in the JEG-3 cells

    International Nuclear Information System (INIS)

    Mukhopadhyay, Sudit S.; Rosen, Jeffrey M.

    2007-01-01

    The transcription factor nuclear factor I (NFI) has been shown previously both in vivo and in vitro to be involved in the cooperative regulation of whey acidic protein (WAP) gene transcription along with the glucocorticoid receptor and STAT5. In addition, one of the specific NFI isoforms, NFI-B2, was demonstrated in transient co-transfection experiments in JEG cells, which lack endogenous NFI, to be preferentially involved in the cooperative regulation of WAP gene expression. A comparison of the DNA-binding specificities of the different NFI isoforms only partially explained their differential ability to activate the WAP gene transcription. Here, we analyzed the transactivation regions of two NFI isoforms by making chimeric proteins between the NFI-A and B isoforms. Though, their DNA-binding specificities were not altered as compared to the corresponding wild-type transcription factors, the C-terminal region of the NFI-B isoform was shown to preferentially activate WAP gene transcription in cooperation with GR and STAT5 in transient co-transfection assays in JEG-3 cells. Furthermore, determination of serine and threonine-specific glycosylation (O-linked N-acetylglucosamine) of the C-terminus of the NFI-B isoform suggested that the secondary modification by O-GlcNAc might play a role in the cooperative regulation of WAP gene transcription by NFI-B2 and STAT5

  2. Molecular basis for gene-specific transactivation by nuclear receptors

    DEFF Research Database (Denmark)

    Jørgensen, Mads Aagaard; Siersbæk, Rasmus; Mandrup, Susanne

    2010-01-01

    Nuclear receptors (NRs) are key transcriptional regulators of metazoan physiology and metabolism. Different NRs bind to similar or even identical core response elements; however, they regulate transcription in a highly receptor- and gene-specific manner. These differences in gene activation can m...... on the recent advances in the molecular mechanisms responsible for receptor- and gene-specific transcriptional activation. This article is part of a Special Issue entitled: Translating nuclear receptors from health to disease....... most likely be accounted for by mechanisms involving receptor-specific interactions with DNA as well as receptor-specific interactions with protein complexes binding to adjacent and distant DNA sequences. Here, we review key molecular aspects of transactivation by NRs with special emphasis...

  3. The aryl hydrocarbon receptor and estrogen receptor alpha differentially modulate nuclear factor erythroid-2-related factor 2 transactivation in MCF-7 breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Lo, Raymond; Matthews, Jason, E-mail: jason.matthews@utoronto.ca

    2013-07-15

    Nuclear factor erythroid-2-related factor 2 (NRF2; NFE2L2) plays an important role in mediating cellular protection against reactive oxygen species. NRF2 signaling is positively modulated by the aryl hydrocarbon receptor (AHR) but inhibited by estrogen receptor alpha (ERα). In this study we investigated the crosstalk among NRF2, AHR and ERα in MCF-7 breast cancer cells treated with the NRF2 activator sulforaphane (SFN), a dual AHR and ERα activator, 3,3′-diindolylmethane (DIM), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or 17β-estradiol (E2). SFN-dependent increases in NADPH-dependent oxidoreductase 1 (NQO1) and heme oxygenase I (HMOX1) mRNA levels were significantly reduced after co-treatment with E2. E2-dependent repression of NQO1 and HMOX1 was associated with increased ERα but reduced p300 recruitment and reduced histone H3 acetylation at both genes. In contrast, DIM + SFN or TCDD + SFN induced NQO1 and HMOX1 mRNA expression to levels higher than SFN alone, which was prevented by RNAi-mediated knockdown of AHR. DIM + SFN but not TCDD + SFN also induced recruitment of ERα to NQO1 and HMOX1. However, the presence of AHR at NQO1 and HMOX1 restored p300 recruitment and histone H3 acetylation, thereby reversing the ERα-dependent repression of NRF2. Taken together, our study provides further evidence of functional interplay among NRF2, AHR and ERα signaling pathways through altered p300 recruitment to NRF2-regulated target genes. - Highlights: • We examined crosstalk among ERα, AHR, and NRF2 in MCF-7 breast cancer cells. • AHR enhanced the mRNA expression levels of two NRF2 target genes – HMOX1 and NQO1. • ERα repressed HMOX1 and NQO1 expression via decreased histone acetylation. • AHR prevented ERα-dependent repression of HMOX1 and NQO1.

  4. Nuclear Factor Kappa B Activation and Peroxisome Proliferator-activated Receptor Transactivational Effects of Chemical Components of the Roots of Polygonum multiflorum.

    Science.gov (United States)

    Sun, Ya Nan; Li, Wei; Song, Seok Bean; Yan, Xi Tao; Yang, Seo Young; Kim, Young Ho

    2016-01-01

    Polygonum multiflorum is well-known as "Heshouwu" in traditional Chinese herbal medicine. In Northeast Asia, it is often used as a tonic to prevent premature aging of the kidney and liver, tendons, and bones and strengthening of the lower back and knees. To research the anti-inflammatory activities of components from P. multiflorum. The compounds were isolated by a combination of silica gel and YMC R-18 column chromatography, and their structures were identified by analysis of spectroscopic data (1D, 2D-nuclear magnetic resonance, and mass spectrometry). The anti-inflammatory activities of the isolated compounds 1-15 were evaluated by luciferase reporter gene assays. Fifteen compounds (1-15) were isolated from the roots of P. multiflorum. Compounds 1-5 and 14-15 significantly inhibited tumor necrosis factor-α-induced nuclear factor kappa B-luciferase activity, with IC50 values of 24.16-37.56 μM. Compounds 1-5 also greatly enhanced peroxisome proliferator-activated receptors transcriptional activity with EC50 values of 18.26-31.45 μM. The anthraquinone derivatives were the active components from the roots of P. multiflorum as an inhibitor on inflammation-related factors in human hepatoma cells. Therefore, we suggest that the roots of P. multiflorum can be used to treat natural inflammatory diseases. This study presented that fifteen compounds (1-15) isolated from the roots of Polygonum multiflrum exert signifiant anti inflmmatory effects by inhibiting TNF α induced NF κB activation and PPARs transcription. Abbreviation used: NF κB: Nuclear factor kappa B, PPARs: Peroxisome proliferator activated receptors, PPREs: Peroxisome proliferator response elements, TNF α: Tumor necrosis factor α, ESI-MS: Electrospray ionization mass spectrometry, HepG2: Human hepatoma cells.

  5. Co-factors necessary for PPAR mediated transactivation of endogenous target genes

    DEFF Research Database (Denmark)

    Grøntved, Lars; Nielsen, Ronni; Stunnenberg, Henk

    of endogenous target gene in different cell types are elusive. To mutually compare the ability of the PPAR subtypes to activate endogenous target genes in a given cell, PPARa, PPARb/d and PPARg2 were HA tagged and rapidly, equally and synchronously expressed using adenoviral delivery. Within a few hours after...... subtype specific activation of target genes. Accumulating evidence suggests that transcriptional co-factors can function as master regulators for nuclear receptors and impose promoter selectivity. To study co-factor necessity for PPAR mediated transactivation of endogenous target genes, specific co...

  6. The proteosome inhibitor MG132 attenuates Retinoic Acid Receptor trans-activation and enhances trans-repression of Nuclear Factor κB. Potential relevance to chemo-preventive interventions with retinoids

    Directory of Open Access Journals (Sweden)

    Rosier Randy N

    2004-03-01

    Full Text Available Abstract Background Nuclear factor kappa B (NFκB is a pro-malignant transcription factor with reciprocal effects on pro-metastatic and anti-metastatic gene expression. Interestingly, NFκB blockade results in the reciprocal induction of retinoic acid receptors (RARs. Given the established property of RARs as negative regulators of malignant progression, we postulated that reciprocal interactions between NFκB and RARs constitute a signaling module in metastatic gene expression and malignant progression. Using Line 1 tumor cells as a model for signal regulation of metastatic gene expression, we investigated the reciprocal interactions between NFκB and RARs in response to the pan-RAR agonist, all-trans retinoic acid (at-RA and the pan-RAR antagonist, AGN193109. Results At-RA [0.1–1 μM] dose-dependently activated RAR and coordinately trans-repressed NFκB, while AGN193109 [1–10 μM] dose-dependently antagonized the effects of at-RA. At-RA and AGN193109 reciprocally regulate pro-metastatic matrix metalloprotease 9 (MMP 9 and its endogenous inhibitor, the tissue inhibitor of metalloprotease 1 (TIMP 1, in a manner consistent with the putative roles of NFκB and RAR in malignant progression. Activation of RAR concurs with its ubiquitination and proteosomal degradation. Accordingly, the proteosome inhibitor, MG132 [5 μM], blocked RAR degradation, quelled RAR trans-activation and enhanced RAR trans-repression of NFκB. Conclusion We conclude that reciprocal interactions between NFκB and RARs constitute a signaling module in metastatic gene expression and malignant progression and propose that the dissociative effect of proteosome inhibitors could be harnessed towards enhancing the anticancer activity of retinoids.

  7. The nucleotide-binding domain of NLRC5 is critical for nuclear import and transactivation activity

    Energy Technology Data Exchange (ETDEWEB)

    Meissner, Torsten B. [Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02215 (United States); Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02215 (United States); Li, Amy; Liu, Yuen-Joyce [Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02215 (United States); Gagnon, Etienne [Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02215 (United States); Institut de Recherche en Immunologie et Cancerologie, Departement de Microbiologie et Immunologie, Universite de Montreal, Montreal, Canada H3T1J4 (Canada); Kobayashi, Koichi S., E-mail: Koichi_Kobayashi@dfci.harvard.edu [Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02215 (United States); Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02215 (United States)

    2012-02-24

    Highlights: Black-Right-Pointing-Pointer NLRC5 requires an intact NLS for its function as MHC class I transactivator. Black-Right-Pointing-Pointer Nuclear presence of NLRC5 is required for MHC class I induction. Black-Right-Pointing-Pointer Nucleotide-binding controls nuclear import and transactivation activity of NLRC5. -- Abstract: Major histocompatibility complex (MHC) class I and class II are crucial for the function of the human adaptive immune system. A member of the NLR (nucleotide-binding domain, leucine-rich repeat) protein family, NLRC5, has recently been identified as a transcriptional regulator of MHC class I and related genes. While a 'master regulator' of MHC class II genes, CIITA, has long been known, NLRC5 specifically associates with and transactivates the proximal promoters of MHC class I genes. In this study, we analyzed the molecular requirements of NLRC5 nuclear import and transactivation activity. We show that NLRC5-mediated MHC class I gene induction requires an intact nuclear localization signal and nuclear distribution of NLRC5. In addition, we find that the nucleotide-binding domain (NBD) of NLRC5 is critical not only for nuclear translocation but also for the transactivation of MHC class I genes. Changing the cellular localization of NLRC5 is likely to immediately impact MHC class I expression as well as MHC class I-mediated antigen presentation. NLRC5 may thus provide a promising target for the modulation of MHC class I antigen presentation, especially in the setting of transplant medicine.

  8. The nuclear cofactor RAC3/AIB1/SRC-3 enhances Nrf2 signaling by interacting with transactivation domains.

    Science.gov (United States)

    Kim, J-H; Yu, S; Chen, J D; Kong, A N

    2013-01-24

    Nuclear factor erythroid 2-related factor 2 (Nrf2, NM 006164, 605 AA) is essential for the antioxidant responsive element (ARE)-mediated expression of a group of detoxifying antioxidant genes that detoxify carcinogens and protect against oxidative stress. Several proteins have been identified as Nrf2-interacting molecules. In this study, we found that the overexpression of receptor-associated coactivator 3 (RAC3)/AIB-1/steroid receptor coactivator-3, a nuclear coregulator and oncogene frequently amplified in human breast cancers, induced heme oxygenase-1 (HO-1) through Nrf2 transactivation in HeLa cells. Next, we determined the interaction between RAC3 and Nrf2 proteins using a co-immunoprecipitation assay and fluorescence resonance energy transfer analysis. The results showed that RAC3 bound directly to the Nrf2 protein in the nucleus. Subsequently, we identified the interacting domains of Nrf2 and RAC3 using a glutathione S-transferase pull-down assay. The results showed that both the N-terminal RAC3-pasB and C-terminal RAC3-R3B3 domains were tightly bound to the Neh4 and Neh5 transactivation domains. Furthermore, chromatin immunoprecipitation showed that RAC3 bound tightly to the ARE enhancer region of the HO-1 promoter via Nrf2 binding. These data suggest that Nrf2 activation is modulated and directly controlled through interactions with the RAC3 protein in HeLa cells.

  9. Effects of nuclear receptor transactivation on steroid hormone synthesis and gene expression in porcine Leydig cells.

    Science.gov (United States)

    Gray, Matthew A; Squires, E James

    2013-01-01

    Male pigs are routinely castrated at a young age to prevent the formation of androstenone, a 16-androstene testicular steroid that is a major component of boar taint. The practice of castration has been increasingly viewed as unfavorable, due to both economic considerations and animal welfare concerns. Other means of controlling boar taint, including reducing the synthesis of androstenone in the testes, would eliminate the need for castration. In this study, we determined the effects of transactivation of three nuclear receptors, the constitutive androstane receptor (CAR), pregnane X receptor (PXR), and farnesoid X receptor (FXR), on gene expression and steroid hormone metabolism in primary porcine Leydig cells. Primary cells were isolated from mature boars, and transcript expression levels were assayed using real-time PCR. The transcripts of interest included porcine orthologs of common phase I and phase II metabolic enzymes, enzymes involved in steroidogenesis, and transcripts previously shown to be differentially expressed in boars with high androstenone and boar taint levels. Transactivation of CAR, PXR, or FXR increased the expression of several genes involved in steroidogenesis, including cytochrome B5A (CYB5A) and cytochrome B5 reductase 1 (CYB5R1), as well as hydroxysteroid (17-beta) dehydrogenase 4 (HSD17B4) and retinol dehydrogenase 12 (RDH12). Treatment with (6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde-O-(3,4-dichlorobenzyl)oxime (CITCO), a CAR agonist, or rifampicin (RIF), a PXR agonist, resulted in significantly (pnuclear receptors may lead to increased levels of 16-androstene steroids, likely by altering the activity of CYP17A1 through CYB5A and CYB5R1 to the andien-β synthase reaction and away from the 17α-hydroxylase and C17, 20 lyase reactions. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Differential transactivation by orphan nuclear receptor NOR1 and its fusion gene product EWS/NOR1: possible involvement of poly(ADP-ribose) polymerase I, PARP-1.

    Science.gov (United States)

    Ohkura, Naganari; Nagamura, Yuko; Tsukada, Toshihiko

    2008-10-15

    In extraskeletal myxoid chondrosarcoma, a chromosomal translocation creates a gene fusion between EWS and an orphan nuclear receptor, NOR1. The resulting fusion protein EWS/NOR1 has been believed to lead to malignant transformation by functioning as a transactivator for NOR1-target genes. By comparing the gene expression profiles of NOR1- and EWS/NOR1-overexpressing cells, we found that they largely shared up-regulated genes, but no significant correlation was observed with respect to the transactivation levels of each gene. In addition, the proteins associated with NOR1 and EWS/NOR1 were mostly the same in these cells. The results suggest that these proteins differentially transactivate overlapping target genes through a similar transcriptional machinery. To clarify the mechanisms underlying the transcriptional divergence between NOR1 and EWS/NOR1, we searched for alternatively associated proteins, and identified poly(ADP-ribose) polymerase I (PARP-1) as an NOR1-specific binding protein. Consistent with its binding properties, PARP-1 acted as a transcriptional repressor of NOR1, but not EWS/NOR1, in a luciferase reporter assay employing PARP-1(-/-) fibroblasts. Interestingly, suppressive activity of PARP-1 was observed in a DNA response element-specific manner, and in a subtype-specific manner toward the NR4A family (Nur77, Nurr1, and NOR1), suggesting that PARP-1 plays a role in the diversity of transcriptional regulation mediated by the NR4A family in normal cells. Altogether, our findings suggest that NOR1 and EWS/NOR1 regulate overlapping target genes differently by utilizing associated proteins, including PARP-1; and that EWS/NOR1 may acquire oncogenic activities by avoiding (or gaining) transcription factor-specific modulation by the associated proteins. (c) 2008 Wiley-Liss, Inc.

  11. Structural characterization of a noncovalent complex between ubiquitin and the transactivation domain of the erythroid-specific factor EKLF.

    Science.gov (United States)

    Raiola, Luca; Lussier-Price, Mathieu; Gagnon, David; Lafrance-Vanasse, Julien; Mascle, Xavier; Arseneault, Genevieve; Legault, Pascale; Archambault, Jacques; Omichinski, James G

    2013-11-05

    Like other acidic transactivation domains (TAD), the minimal TAD from the erythroid-specific transcription factor EKLF (EKLFTAD) has been shown to contribute both to its transcriptional activity as well as to its ubiquitin(UBI)-mediated degradation. In this article, we examine the activation-degradation role of the acidic TAD of EKLF and demonstrate that the first 40 residues (EKLFTAD1) within this region form a noncovalent interaction with UBI. Nuclear magnetic resonance (NMR) structural studies of an EKLFTAD1-UBI complex show that EKLFTAD1 adopts a 14-residue α helix that forms the recognition interface with UBI in a similar manner as the UBI-interacting helix of Rabex5. We also identify a similar interaction between UBI and the activation-degradation region of SREBP1a, but not with the activation-degradation regions of p53, GAL4, and VP16. These results suggest that select activation-degradation regions like the ones found in EKLF and SREBP1a function in part through their ability to form noncovalent interactions with UBI. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Resveratrol prevents angiotensin II-induced hypertrophy of vascular smooth muscle cells through the transactivation of growth factor receptors.

    Science.gov (United States)

    Hossain, Ekhtear; Anand-Srivastava, Madhu B

    2017-08-01

    We previously showed that augmented levels of endogenous angiotensin II (AngII) contribute to vascular smooth muscle cell (VSMC) hypertrophy through the transactivation of growth factor receptors in spontaneously hypertensive rats. Resveratrol (RV), a polyphenolic component of red wine, has also been shown to attenuate AngII-evoked VSMC hypertrophy; however, the molecular mechanism mediating this response is obscure. The present study was therefore undertaken to examine whether RV could prevent AngII-induced VSMC hypertrophy through the transactivation of growth factor receptor and associated signaling pathways. AngII treatment of VSMC enhanced the protein synthesis that was attenuated towards control levels by RV pretreatment as well as by the inhibitors of NADPH oxidase, c-Src, and growth factor receptors. Furthermore, RV pretreatment also inhibited enhanced levels of superoxide anion, NADPH oxidase activity, increased expression of NADPH oxidase subunits, and phosphorylation of c-Src, EGF-R, PDGE-R, ERK1/2, and AKT1/2. In conclusion, these results indicate that RV attenuates AngII-induced VSMC hypertrophy through the inhibition of enhanced oxidative stress and activation of c-Src, growth factor receptors, and MAPK/AKT signaling. We suggest that RV could be used as a therapeutic agent in the treatment of vascular complications associated with hypertension and hypertrophy.

  13. Nuclear receptor corepressor-dependent repression of peroxisome-proliferator-activated receptor delta-mediated transactivation

    DEFF Research Database (Denmark)

    Krogsdam, Anne-M; Nielsen, Curt A F; Neve, Søren

    2002-01-01

    delta-RXR alpha heterodimer bound to an acyl-CoA oxidase (ACO)-type peroxisome-proliferator response element recruited a glutathione S-transferase-NCoR fusion protein in a ligand-independent manner. Contrasting with most other nuclear receptors, PPAR delta was found to interact equally well......The nuclear receptor corepressor (NCoR) was isolated as a peroxisome-proliferator-activated receptor (PPAR) delta interacting protein using the yeast two-hybrid system. NCoR interacted strongly with the ligand-binding domain of PPAR delta, whereas interactions with the ligand-binding domains...

  14. Newly developed quantitative transactivation system shows difference in activation by Vitis CBF transcription factors on DRE/CRT elements.

    Science.gov (United States)

    Nassuth, Annette; Siddiqua, Mahbuba; Xiao, Huogen; Moody, Michelle A; Carlow, Chevonne E

    2014-01-01

    Agroinfiltration-based transactivation systems can determine if a protein functions as a transcription factor, and via which promoter element. However, this activation is not always a yes or no proposition. Normalization for variation in plasmid delivery into plant cells, sample collection and protein extraction is desired to allow for a quantitative comparison between transcription factors or promoter elements. We developed new effector and reporter plasmids which carry additional reporter genes, as well as a procedure to assay all three reporter enzymes from a single extract. The applicability of these plasmids was demonstrated with the analysis of CBF transcription factors and their target promoter sequence, DRE/CRT. Changes in the core DRE/CRT sequence abolished activation by Vitis CBF1 or Vitis CBF4, whereas changes in the surrounding sequence lowered activation by Vitis CBF1 but much less so for Vitis CBF4. The system also detected a reduction in activation due to one amino acid change in Vitis CBF1. The newly developed effector and reporter plasmids improve the ability to quantitatively compare the activation on two different promoter elements by the same transcription factor, or between two different transcription factors on the same promoter element. The quantitative difference in activation by VrCBF1 and VrCBF4 on various DRE/CRT elements support the hypothesis that these transcription factors have unique roles in the cold acclimation process.

  15. The MHC-II transactivator CIITA, a restriction factor against oncogenic HTLV-1 and HTLV-2 retroviruses: similarities and differences in the inhibition of Tax-1 and Tax-2 viral transactivators

    Science.gov (United States)

    Forlani, Greta; Abdallah, Rawan; Accolla, Roberto S.; Tosi, Giovanna

    2013-01-01

    The activation of CD4+ T helper cells is strictly dependent on the presentation of antigenic peptides by MHC class II (MHC-II) molecules. MHC-II expression is primarily regulated at the transcriptional level by the AIR-1 gene product CIITA (class II transactivator). Thus, CIITA plays a pivotal role in the triggering of the adaptive immune response against pathogens. Besides this well known function, we recently found that CIITA acts as an endogenous restriction factor against HTLV-1 (human T cell lymphotropic virus type 1) and HTLV-2 oncogenic retroviruses by targeting their viral transactivators Tax-1 and Tax-2, respectively. Here we review our findings on CIITA-mediated inhibition of viral replication and discuss similarities and differences in the molecular mechanisms by which CIITA specifically counteracts the function of Tax-1 and Tax-2 molecules. The dual function of CIITA as a key regulator of adaptive and intrinsic immunity represents a rather unique example of adaptation of host-derived factors against pathogen infections during evolution. PMID:23986750

  16. Overexpression of ERβ is sufficient to inhibit hypoxia-inducible factor-1 transactivation

    Energy Technology Data Exchange (ETDEWEB)

    Park, Choa; Lee, YoungJoo, E-mail: yjlee@sejong.ac.kr

    2014-07-18

    Highlights: • We examined the effect of ERβ specific ligand on HIF-1 inhibition. • DPN down-regulates the ARNT protein levels in PC3 cells. • DPN did not show additional effect in ERβ transfected MCF-7 cells. • Our study shows that unliganded ERβ is sufficient to inhibit HIF-1 in systems of overexpression. - Abstract: Estrogen receptor (ER) β is predicted to play an important role in the prevention of breast cancer development and progression. We have previously shown that ERβ suppresses hypoxia inducible factor (HIF)-1-mediated transcription through aryl hydrocarbon receptor nuclear translocator (ARNT) degradation via ubiquitination processes. In this study, we attempted to examine the effect of ERβ specific ligand on HIF-1 inhibition in ERβ positive PC3 cells and ERβ transfected MCF-7 cells. ERβ specific agonist diarylpropionitrile (DPN) stimulated estrogen response element (ERE)-luciferase activity in a similar fashion to estradiol in PC3 cells. We observed that DPN down-regulates the ARNT protein levels leading to an attenuation of hypoxia-induced hypoxia response element (HRE)-driven luciferase reporter gene activation in PC3 cells. Treatment of DPN reduced vascular endothelial growth factor (VEGF) expression and co-treatment with ERβ specific antagonist PHTPP abrogated the effect in PC3 cells. We then examined the effect of DPN in ERβ transfected MCF-7 cells. HIF-1 transcriptional activity repression by ERβ was not further reduced by DPN, as examined by HRE-driven luciferase assays. Expression of ERβ significantly decreased VEGF secretion and ARNT expression under hypoxic conditions. However, DPN did not additionally affect this suppression in MCF-7 cells transfected with ERβ. This result shows that unliganded ERβ is sufficient to inhibit HIF-1 in systems of overexpression.

  17. DNA binding domains and nuclear localization signal of LEDGF: contribution of two helix-turn-helix (HTH)-like domains and a stretch of 58 amino acids of the N-terminal to the trans-activation potential of LEDGF.

    Science.gov (United States)

    Singh, Dhirendra P; Kubo, E; Takamura, Y; Shinohara, T; Kumar, A; Chylack, Leo T; Fatma, N

    2006-01-20

    Lens epithelium derived growth factor (LEDGF), a nuclear protein, plays a role in regulating the transcription of stress-associated genes such as heat shock proteins by binding to consensus core DNA sequences nAGGn or nGAAn or their repeats, and in doing so helps to provide cyto-protection. However, additional information is required to identify the specific structural features of LEDGF involved in gene transcription. Here we have investigated the functional domains activating and repressing DNA-binding modules, by using a DNA binding assay and trans-activation experiments performed by analyzing proteins prepared from deletion constructs. The results disclosed the DNA-binding domain of N-terminal LEDGF mapped between amino acid residues 5 and 62, a 58 amino acid residue stretch PWWP domain which binds to stress response elements (STRE; A/TGGGGA/T). C-terminal LEDGF contains activation domains, an extensive loop-region (aa 418-530) with two helix-turn-helix (HTH)-like domains, and binds to a heat shock element (HSE; nGAAn). A trans-activation assay using Hsp27 promoter revealed that both HTH domains contribute in a cooperative manner to the trans-activation potential of LEDGF. Interestingly, removal of N-terminal LEDGF (aa 1-187) significantly enhances the gene activation potential of C-terminal LEDGF (aa 199-530); thus the N-terminal domain (aa 5-62), exhibits auto-transcriptional repression activity. It appears that this domain is involved in stabilizing the LEDGF-DNA binding complex. Collectively, our results demonstrate that LEDGF contains three DNA-binding domains, which regulate gene expression depending on cellular microenvironment and thus modify the physiology of cells to maintain cellular homeostasis.

  18. Epidermal Growth Factor Receptor Transactivation Is Required for Mitogen-Activated Protein Kinase Activation by Muscarinic Acetylcholine Receptors in HaCaT Keratinocytes

    Directory of Open Access Journals (Sweden)

    Wymke Ockenga

    2014-11-01

    Full Text Available Non-neuronal acetylcholine plays a substantial role in the human skin by influencing adhesion, migration, proliferation and differentiation of keratinocytes. These processes are regulated by the Mitogen-Activated Protein (MAP kinase cascade. Here we show that in HaCaT keratinocytes all five muscarinic receptor subtypes are expressed, but M1 and M3 are the subtypes involved in mitogenic signaling. Stimulation with the cholinergic agonist carbachol leads to activation of the MAP kinase extracellular signal regulated kinase, together with the protein kinase Akt. The activation is fully dependent on the transactivation of the epidermal growth factor receptor (EGFR, which even appears to be the sole pathway for the muscarinic receptors to facilitate MAP kinase activation in HaCaT cells. The transactivation pathway involves a triple-membrane-passing process, based on activation of matrix metalloproteases, and extracellular ligand release; whereas phosphatidylinositol 3-kinase, Src family kinases or protein kinase C do not appear to be involved in MAP kinase activation. Furthermore, phosphorylation, ubiquitination and endocytosis of the EGF receptor after cholinergic transactivation are different from that induced by a direct stimulation with EGF, suggesting that ligands other than EGF itself mediate the cholinergic transactivation.

  19. Transcription factor Nrf1 is topologically repartitioned across membranes to enable target gene transactivation through its acidic glucose-responsive domains.

    Science.gov (United States)

    Zhang, Yiguo; Ren, Yonggang; Li, Shaojun; Hayes, John D

    2014-01-01

    The membrane-bound Nrf1 transcription factor regulates critical homeostatic and developmental genes. The conserved N-terminal homology box 1 (NHB1) sequence in Nrf1 targets the cap'n'collar (CNC) basic basic-region leucine zipper (bZIP) factor to the endoplasmic reticulum (ER), but it is unknown how its activity is controlled topologically within membranes. Herein, we report a hitherto unknown mechanism by which the transactivation activity of Nrf1 is controlled through its membrane-topology. Thus after Nrf1 is anchored within ER membranes, its acidic transactivation domains (TADs), including the Asn/Ser/Thr-rich (NST) glycodomain situated between acidic domain 1 (AD1) and AD2, are transiently translocated into the lumen of the ER, where NST is glycosylated in the presence of glucose to yield an inactive 120-kDa Nrf1 glycoprotein. Subsequently, portions of the TADs partially repartition across membranes into the cyto/nucleoplasmic compartments, whereupon an active 95-kDa form of Nrf1 accumulates, a process that is more obvious in glucose-deprived cells and may involve deglycosylation. The repartitioning of Nrf1 out of membranes is monitored within this protein by its acidic-hydrophobic amphipathic glucose-responsive domains, particularly the Neh5L subdomain within AD1. Therefore, the membrane-topological organization of Nrf1 dictates its post-translational modifications (i.e. glycosylation, the putative deglycosylation and selective proteolysis), which together control its ability to transactivate target genes.

  20. E1A-dependent trans-activation of the human MYC promoter is mediated by the E2F factor

    International Nuclear Information System (INIS)

    Hiebert, S.W.; Lipp, M.; Nevins, J.R.

    1989-01-01

    E2F is a cellular transcription factor that binds to two sites in the adenovirus E2 promoter. Previous experiments have implicated E2F in the E1A-dependent transactivation of the E2 gene since levels of active E2F increase markedly during adenovirus infection in parallel with the increase in E2 transcription, and an E2F binding site can confer E1A inducibility to a heterologous promoter. Here the authors show that E2F binds to two sequence elements within the P2 promoter of the human MYC gene which are within a region that is critical for promoter activity. The MYC promoter can be trans-activated in an E1A-dependent manner and site-directed mutagenesis demonstrates that these E2F elements are essential for trans-activation. Finally, they also find that adenovirus infection of quiescent cells results in a stimulation of the endogenous MYC gene. They conclude that the activation of the E2F factor, which is likely responsible for the activation of viral E2 transcription, is also responsible for the E1A-dependent induction of MYC transcription

  1. Transactivation of the TIEG1 confers growth inhibition of transforming growth factor-β-susceptible hepatocellular carcinoma cells

    Science.gov (United States)

    Jiang, Lei; Lai, Yiu-Kay; Zhang, Jin-Fang; Chan, Chu-Yan; Lu, Gang; Lin, Marie CM; He, Ming-Liang; Li, Ji-Cheng; Kung, Hsiang-Fu

    2012-01-01

    AIM: To investigate the role of transforming growth factor (TGF)-β-inducible early gene 1 (TIEG1) in TGF-β-induced growth inhibition in hepatocellular carcinoma (HCC) cells. METHODS: Human hepatocyte and HCC cell lines with varied susceptibilities to TGF-β1 were tested by methylthiazoletetrazolium (MTT) assay. The expression changes of Smad2, Smad3, Smad4, Smad7, TIEG1 and TIEG2 gene following treatment with TGF-β1 in a TGF-β-sensitive hepatocyte cell line (MIHA), a TGF-β-sensitive hepatoma cell line (Hep3B) and two TGF-β-insensitive hepatoma cell lines (HepG2 and Bel7404) were examined. SiRNA targeting TIEG1 was transfected into Hep3B cells and the sensitivity of cells to TGF-β1 was examined. Overexpression of TIEG1 was induced by lentiviral-mediated transduction in TGF-β1-resistant hepatoma cell lines (Bel7404 and HepG2). MTT assay and 4’,6-Diamidino-2-phenylindole staining were used to identify cell viability and apoptosis, respectively. The expression level of stathmin was measured by reverse transcriptase polymerase chain reaction and Western-blotting analysis, and stathmin promoter activity by TIEG1 was monitored by a luciferase reporter gene system. RESULTS: TIEG1 was significantly upregulated by TGF-β1 in the TGF-β1-sensitive HCC cell line, Hep3B, but not in the resistant cell lines. The suppression of TIEG1 by siRNAs decreased the sensitivity of Hep3B cells to TGF-β1, whereas the overexpression of TIEG1 mediated growth inhibition and apoptosis in TGF-β1-resistant HCC cell lines, which resembled those of TGF-β1-sensitive HCC cells treated with TGF-β1. Our data further suggested that stathmin was a direct target of TIEG1, as stathmin was significantly downregulated by TIEG1 overexpression, and stathmin promoter activity was inhibited by TIEG1 in a dose-dependent manner. CONCLUSION: Our data suggest that transactivation of TIEG1 conferred growth inhibition of TGF-β-susceptible human HCC cells. PMID:22563190

  2. Factors affecting nuclear development

    International Nuclear Information System (INIS)

    Stevens, G.H.; Girouard, P.

    1995-01-01

    Among the factors affecting nuclear development, some depend more or less on public authorities, but many are out of public authorities control (foreign policies, market and deregulation, socials and environmental impacts, public opinion). As far as possible, the following study tries to identify those factors. (D.L.). 2 photos

  3. Nuclear localization and transactivating capacities of the papillary renal cell carcinoma-associated TFE3 and PRCC (fusion) proteins

    NARCIS (Netherlands)

    Weterman, M. A. J.; van Groningen, J. J.; Jansen, A.; van Kessel, A. G.

    2000-01-01

    The papillary renal cell carcinoma-associated t(X;1)(p11;q21) leads to fusion of the transcription factor TFE3 gene on the X-chromosome to a novel gene, PRCC, on chromosome 1. As a result, two putative fusion proteins are formed: PRCCTFE3, which contains all known domains for DNA binding,

  4. Identification of transactivation-responsive DNA-binding protein 43 (TARDBP43; TDP-43) as a novel factor for TNF-α expression upon lipopolysaccharide stimulation in human monocytes.

    Science.gov (United States)

    Murata, H; Hattori, T; Maeda, H; Takashiba, S; Takigawa, M; Kido, J; Nagata, T

    2015-08-01

    Tumor necrosis factor alpha (TNF-α) is a major cytokine implicated in various inflammatory diseases. The nature of the nuclear factors associated with human TNF-α gene regulation is not well elucidated. We previously identified a novel region located from -550 to -487 in human TNF-α promoter that did not contain the reported binding sites for nuclear factor kappa B (NF-κB) but showed lipopolysaccharide (LPS)-induced transcriptional activity. The purpose of this study is to identify novel factors that bind to the promoter region and regulate TNF-α expression. To identify DNA-binding proteins that bound to the target region of TNF-α promoter, a cDNA library from LPS-stimulated human monocytic cell line THP-1 was screened using a yeast one-hybrid system. Cellular localizations of the DNA-binding protein in the cells were examined by subcellular immunocytochemistry. Nuclear amounts of the protein in LPS-stimulated THP-1 cells were identified by western blot analysis. Expression of mRNA of the protein in the cells was quantified by real-time polymerase chain reaction. Electrophoretic mobility shift assays were performed to confirm the DNA-binding profile. Overexpression of the protein and knockdown of the gene were also performed to investigate the role for TNF-α expression. Several candidates were identified from the cDNA library and transactivation-responsive DNA-binding protein 43 (TARDBP43; TDP-43) was focused on. Western blot analysis revealed that nuclear TDP-43 protein was increased in the LPS-stimulated THP-1 cells. Expression of TDP-43 mRNA was already enhanced before TNF-α induction by LPS. Electrophoretic mobility shift assay analysis showed that nuclear extracts obtained by overexpressing FLAG-tagged TDP-43 bound to the -550 to -487 TNF-α promoter fragments. Overexpression of TDP-43 in THP-1 cells resulted in an increase of TNF-α expression. Knockdown of TDP-43 in THP-1 cells downregulated TNF-α expression. We identified TDP-43 as one of the novel

  5. Interferon Regulatory Factor 1 Transactivates Expression of Human DNA Polymerase η in Response to Carcinogen N-Methyl-N′-nitro-N-nitrosoguanidine*

    Science.gov (United States)

    Qi, Hongyan; Zhu, Huifang; Lou, Meng; Fan, Yanfeng; Liu, Hong; Shen, Jing; Li, Zhongjie; Lv, Xue; Shan, Jianzhen; Zhu, Lijun; Chin, Y. Eugene; Shao, Jimin

    2012-01-01

    DNA polymerase η (Polη) implements translesion DNA synthesis but has low fidelity in replication. We have previously shown that Polη plays an important role in the genesis of nontargeted mutations at undamaged DNA sites in cells exposed to the carcinogen N-methyl-N′-nitro-N-nitrosoguanidine (MNNG). Here, we report that MNNG-induced Polη expression in an interferon regulatory factor 1 (IRF1)-dependent manner in human cells. Mutagenesis analysis showed that four critical residues (Arg-82, Cys-83, Asn-86, and Ser-87) located in the IRF family conserved DNA binding domain-helix α3 were involved in DNA binding and POLH transactivation by IRF1. Furthermore, Polη up-regulation induced by IRF1 was responsible for the increase of mutation frequency in a SupF shuttle plasmid replicated in the MNNG-exposed cells. Interestingly, IRF1 was acetylated by the histone acetyltransferase CBP in these cells. Lys → Arg substitution revealed that Lys-78 of helix α3 was the major acetylation site, and the IRF1-K78R mutation partially inhibited DNA binding and its transcriptional activity. Thus, we propose that IRF1 activation is responsible for MNNG-induced Polη up-regulation, which contributes to mutagenesis and ultimately carcinogenesis in cells. PMID:22367195

  6. Stromal cell-derived factor-1α (SDF-1α/CXCL12) stimulates ovarian cancer cell growth through the EGF receptor transactivation

    International Nuclear Information System (INIS)

    Porcile, Carola; Bajetto, Adriana; Barbieri, Federica; Barbero, Simone; Bonavia, Rudy; Biglieri, Marianna; Pirani, Paolo; Florio, Tullio; Schettini, Gennaro

    2005-01-01

    Ovarian cancer (OC) is the leading cause of death in gynecologic diseases in which there is evidence for a complex chemokine network. Chemokines are a family of proteins that play an important role in tumor progression influencing cell proliferation, angiogenic/angiostatic processes, cell migration and metastasis, and, finally, regulating the immune cells recruitment into the tumor mass. We previously demonstrated that astrocytes and glioblastoma cells express both the chemokine receptor CXCR4 and its ligand stromal cell-derived factor-1 (SDF-1), and that SDF-1α treatment induced cell proliferation, supporting the hypothesis that chemokines may play an important role in tumor cells' growth in vitro. In the present study, we report that CXCR4 and SDF-1 are expressed in OC cell lines. We demonstrate that SDF-1α induces a dose-dependent proliferation in OC cells, by the specific interaction with CXCR4 and a biphasic activation of ERK1/2 and Akt kinases. Our results further indicate that CXCR4 activation induces EGF receptor (EGFR) phosphorylation that in turn was linked to the downstream intracellular kinases activation, ERK1/2 and Akt. In addition, we provide evidence for cytoplasmic tyrosine kinase (c-Src) involvement in the SDF-1/CXCR4-EGFR transactivation. These results suggest a possible important 'cross-talk' between SDF-1/CXCR4 and EGFR intracellular pathways that may link signals of cell proliferation in ovarian cancer

  7. TGFβ induces proHB-EGF shedding and EGFR transactivation through ADAM activation in gastric cancer cells

    International Nuclear Information System (INIS)

    Ebi, Masahide; Kataoka, Hiromi; Shimura, Takaya; Kubota, Eiji; Hirata, Yoshikazu; Mizushima, Takashi; Mizoshita, Tsutomu; Tanaka, Mamoru; Mabuchi, Motoshi; Tsukamoto, Hironobu; Tanida, Satoshi; Kamiya, Takeshi; Higashiyama, Shigeki; Joh, Takashi

    2010-01-01

    Research highlights: → TGFβ induces EGFR transactivation through proHB-EGF shedding by activated ADAM members in gastric cancer cells. → TGFβ induces nuclear translocation of HB-EGF-CTF cleaved by ADAM members. → TGFβ enhances cell growth by EGFR transactivation and HB-EGF-CTF nuclear translocation and ADAM inhibitors block these effects. → Silencing of ADAM17 also blocks EGFR transactivation, HB-EGF-CTF nuclear translocation and cancer cell growth by TGFβ. → ADAM17 may play a crucial role in this TGFβ-HB-EGF signal transduction. -- Abstract: Background and aims: Transforming growth factor-beta (TGFβ) is known to potently inhibit cell growth. Loss of responsiveness to TGFβ inhibition on cell growth is a hallmark of many types of cancer, yet its mechanism is not fully understood. Membrane-anchored heparin-binding EGF-like growth factor (proHB-EGF) ectodomain is cleaved by a disintegrin and metalloproteinase (ADAM) members and is implicated in epidermal growth factor receptor (EGFR) transactivation. Recently, nuclear translocation of the C-terminal fragment (CTF) of pro-HB-EGF was found to induce cell growth. We investigated the association between TGFβ and HB-EGF signal transduction via ADAM activation. Materials and methods: The CCK-8 assay in two gastric cancer cell lines was used to determine the effect for cell growth by TGFβ. The effect of two ADAM inhibitors was also evaluated. Induction of EGFR phosphorylation by TGFβ was analyzed and the effect of the ADAM inhibitors was also examined. Nuclear translocation of HB-EGF-CTF by shedding through ADAM activated by TGFβ was also analyzed. EGFR transactivation, HB-EGF-CTF nuclear translocation, and cell growth were examined under the condition of ADAM17 knockdown. Result: TGFβ-induced EGFR phosphorylation of which ADAM inhibitors were able to inhibit. TGFβ induced shedding of proHB-EGF allowing HB-EGF-CTF to translocate to the nucleus. ADAM inhibitors blocked this nuclear translocation. TGF

  8. TGF{beta} induces proHB-EGF shedding and EGFR transactivation through ADAM activation in gastric cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Ebi, Masahide [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan); Kataoka, Hiromi, E-mail: hkataoka@med.nagoya-cu.ac.jp [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan); Shimura, Takaya; Kubota, Eiji; Hirata, Yoshikazu; Mizushima, Takashi; Mizoshita, Tsutomu; Tanaka, Mamoru; Mabuchi, Motoshi; Tsukamoto, Hironobu; Tanida, Satoshi; Kamiya, Takeshi [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan); Higashiyama, Shigeki [Department of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime (Japan); Joh, Takashi [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan)

    2010-11-19

    Research highlights: {yields} TGF{beta} induces EGFR transactivation through proHB-EGF shedding by activated ADAM members in gastric cancer cells. {yields} TGF{beta} induces nuclear translocation of HB-EGF-CTF cleaved by ADAM members. {yields} TGF{beta} enhances cell growth by EGFR transactivation and HB-EGF-CTF nuclear translocation and ADAM inhibitors block these effects. {yields} Silencing of ADAM17 also blocks EGFR transactivation, HB-EGF-CTF nuclear translocation and cancer cell growth by TGF{beta}. {yields} ADAM17 may play a crucial role in this TGF{beta}-HB-EGF signal transduction. -- Abstract: Background and aims: Transforming growth factor-beta (TGF{beta}) is known to potently inhibit cell growth. Loss of responsiveness to TGF{beta} inhibition on cell growth is a hallmark of many types of cancer, yet its mechanism is not fully understood. Membrane-anchored heparin-binding EGF-like growth factor (proHB-EGF) ectodomain is cleaved by a disintegrin and metalloproteinase (ADAM) members and is implicated in epidermal growth factor receptor (EGFR) transactivation. Recently, nuclear translocation of the C-terminal fragment (CTF) of pro-HB-EGF was found to induce cell growth. We investigated the association between TGF{beta} and HB-EGF signal transduction via ADAM activation. Materials and methods: The CCK-8 assay in two gastric cancer cell lines was used to determine the effect for cell growth by TGF{beta}. The effect of two ADAM inhibitors was also evaluated. Induction of EGFR phosphorylation by TGF{beta} was analyzed and the effect of the ADAM inhibitors was also examined. Nuclear translocation of HB-EGF-CTF by shedding through ADAM activated by TGF{beta} was also analyzed. EGFR transactivation, HB-EGF-CTF nuclear translocation, and cell growth were examined under the condition of ADAM17 knockdown. Result: TGF{beta}-induced EGFR phosphorylation of which ADAM inhibitors were able to inhibit. TGF{beta} induced shedding of proHB-EGF allowing HB-EGF-CTF to

  9. DEPENDENCE OF PPAR LIGAND-INDUCED MAPK SIGNALING ON EPIDERMAL GROWTH FACTOR RECEPTOR TRANSACTIVATION HEPARIN-BINDING EGF CLEAVAGE MEDIATES ZINC-INDUCED EGF RECEPTOR PHOSPHORYLATION

    Science.gov (United States)

    Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that function as ligand-activated transcription factors regulating lipid metabolism and homeostasis. In addition to their ability to regulate PPAR-mediated gene transcription, PPARalpha and gamma li...

  10. Inhibitory effects of omega-3 fatty acids on injury-induced epidermal growth factor receptor transactivation contribute to delayed wound healing.

    Science.gov (United States)

    Turk, Harmony F; Monk, Jennifer M; Fan, Yang-Yi; Callaway, Evelyn S; Weeks, Brad; Chapkin, Robert S

    2013-05-01

    Epidermal growth factor receptor (EGFR)-mediated signaling is required for optimal intestinal wound healing. Since n-3 polyunsaturated fatty acids (PUFA), specifically docosahexaenoic acid (DHA), alter EGFR signaling and suppress downstream activation of key signaling pathways, we hypothesized that DHA would be detrimental to the process of intestinal wound healing. Using a mouse immortalized colonocyte model, DHA uniquely reduced EGFR ligand-induced receptor activation, whereas DHA and its metabolic precursor eicosapentaenoic acid (EPA) reduced wound-induced EGFR transactivation compared with control (no fatty acid or linoleic acid). Under wounding conditions, the suppression of EGFR activation was associated with a reduction in downstream activation of cytoskeletal remodeling proteins (PLCγ1, Rac1, and Cdc42). Subsequently, DHA and EPA reduced cell migration in response to wounding. Mice were fed a corn oil-, DHA-, or EPA-enriched diet prior to intestinal wounding (2.5% dextran sodium sulfate for 5 days followed by termination after 0, 3, or 6 days of recovery). Mortality was increased in EPA-fed mice and colonic histological injury scores were increased in EPA- and DHA-fed mice compared with corn oil-fed (control) mice. Although kinetics of colonic EGFR activation and downstream signaling (PLCγ1, Rac1, and Cdc42) were delayed by both n-3 PUFA, colonic repair was increased in EPA- relative to DHA-fed mice. These results indicate that, during the early response to intestinal wounding, DHA and EPA uniquely delay the activation of key wound-healing processes in the colon. This effect is mediated, at least in part, via suppression of EGFR-mediated signaling and downstream cytoskeletal remodeling.

  11. SAR of PXR transactivation in benzimidazole-based IGF-1R kinase inhibitors.

    Science.gov (United States)

    Zimmermann, Kurt; Wittman, Mark D; Saulnier, Mark G; Velaparthi, Upender; Sang, Xiaopeng; Frennesson, David B; Struzynski, Charles; Seitz, Steven P; He, Liqi; Carboni, Joan M; Li, Aixin; Greer, Ann F; Gottardis, Marco; Attar, Ricardo M; Yang, Zheng; Balimane, Praveen; Discenza, Lorell N; Lee, Francis Y; Sinz, Michael; Kim, Sean; Vyas, Dolatrai

    2010-03-01

    The SAR of PXR transactivation by 3-(benzimidazol-2-yl)-pyridine-2-one based ATP competitive inhibitors of Insulin-like Growth Factor 1 Receptor kinase (IGF-1R) is discussed. Compounds without PXR transactivation, with in vivo antitumor activity, reduced protein binding and improved oral exposure are presented. Copyright 2010 Elsevier Ltd. All rights reserved.

  12. BS69 : A novel adenovirus E1A-associated protein that inhibits E1A transactivation

    NARCIS (Netherlands)

    Hateboer, G.; Gennissen, A.M.C.; Ramos, Y.F.M.; Kerkhoven, R.; Sonntag-Buck, V.; Stunnenberg, H.G.; Bernards, R.A.

    1995-01-01

    The adenovirus ElA gene products are nuclear phosphoproteins that can transactivate the other adenovirus early genes as well as several cellular genes, and can transform primary rodent cells in culture. Transformation and transactivation by ElA proteins is most likely to be mediated through

  13. Endothelin B Receptors on Primary Chicken Müller Cells and the Human MIO-M1 Müller Cell Line Activate ERK Signaling via Transactivation of Epidermal Growth Factor Receptors.

    Directory of Open Access Journals (Sweden)

    Mohammad Harun-Or-Rashid

    Full Text Available Injury to the eye or retina triggers Müller cells, the major glia cell of the retina, to dedifferentiate and proliferate. In some species they attain retinal progenitor properties and have the capacity to generate new neurons. The epidermal growth factor receptor (EGFR system and extracellular signal-regulated kinase (ERK signaling are key regulators of these processes in Müller cells. The extracellular signals that modulate and control these processes are not fully understood. In this work we studied whether endothelin receptor signaling can activate EGFR and ERK signaling in Müller cells. Endothelin expression is robustly upregulated at retinal injury and endothelin receptors have been shown to transactivate EGFRs in other cell types. We analyzed the endothelin signaling system in chicken retina and cultured primary chicken Müller cells as well as the human Müller cell line MIO-M1. The Müller cells were stimulated with receptor agonists and treated with specific blockers to key enzymes in the signaling pathway or with siRNAs. We focused on endothelin receptor mediated transactivation of EGFRs by using western blot analysis, quantitative reverse transcriptase PCR and immunocytochemistry. The results showed that chicken Müller cells and the human Müller cell line MIO-M1 express endothelin receptor B. Stimulation by the endothelin receptor B agonist IRL1620 triggered phosphorylation of ERK1/2 and autophosphorylation of (Y1173 EGFR. The effects could be blocked by Src-kinase inhibitors (PP1, PP2, EGFR-inhibitor (AG1478, EGFR-siRNA and by inhibitors to extracellular matrix metalloproteinases (GM6001, consistent with a Src-kinase mediated endothelin receptor response that engage ligand-dependent and ligand-independent EGFR activation. Our data suggest a mechanism for how injury-induced endothelins, produced in the retina, may modulate the Müller cell responses by Src-mediated transactivation of EGFRs. The data give support to a view in

  14. Quantitative Analysis of NF-κB Transactivation Specificity Using a Yeast-Based Functional Assay.

    Directory of Open Access Journals (Sweden)

    Vasundhara Sharma

    Full Text Available The NF-κB transcription factor family plays a central role in innate immunity and inflammation processes and is frequently dysregulated in cancer. We developed an NF-κB functional assay in yeast to investigate the following issues: transactivation specificity of NF-κB proteins acting as homodimers or heterodimers; correlation between transactivation capacity and in vitro DNA binding measurements; impact of co-expressed interacting proteins or of small molecule inhibitors on NF-κB-dependent transactivation. Full-length p65 and p50 cDNAs were cloned into centromeric expression vectors under inducible GAL1 promoter in order to vary their expression levels. Since p50 lacks a transactivation domain (TAD, a chimeric construct containing the TAD derived from p65 was also generated (p50TAD to address its binding and transactivation potential. The p50TAD and p65 had distinct transactivation specificities towards seventeen different κB response elements (κB-REs where single nucleotide changes could greatly impact transactivation. For four κB-REs, results in yeast were predictive of transactivation potential measured in the human MCF7 cell lines treated with the NF-κB activator TNFα. Transactivation results in yeast correlated only partially with in vitro measured DNA binding affinities, suggesting that features other than strength of interaction with naked DNA affect transactivation, although factors such as chromatin context are kept constant in our isogenic yeast assay. The small molecules BAY11-7082 and ethyl-pyruvate as well as expressed IkBα protein acted as NF-κB inhibitors in yeast, more strongly towards p65. Thus, the yeast-based system can recapitulate NF-κB features found in human cells, thereby providing opportunities to address various NF-κB functions, interactions and chemical modulators.

  15. miR-16 targets transcriptional corepressor SMRT and modulates NF-kappaB-regulated transactivation of interleukin-8 gene.

    Directory of Open Access Journals (Sweden)

    Rui Zhou

    Full Text Available The signaling pathways associated with the Toll-like receptors (TLRs and nuclear factor-kappaB (NF-κB are essential to pro-inflammatory cytokine and chemokine expression, as well as initiating innate epithelial immune responses. The TLR/NF-κB signaling pathways must be stringently controlled through an intricate network of positive and negative regulatory elements. MicroRNAs (miRNAs are non-coding small RNAs that regulate the stability and/or translation of protein-coding mRNAs. Herein we report that miR-16 promotes NF-κB-regulated transactivation of the IL-8 gene by suppression of the silencing mediator for retinoid and thyroid hormone receptor (SMRT. LPS stimulation activated miR-16 gene transcription in human monocytes (U937 and biliary epithelial cells (H69 through MAPK-dependent mechanisms. Transfection of cells with the miR-16 precursor promoted LPS-induced production of IL-8, IL-6, and IL-1α, without a significant effect on their RNA stability. Instead, an increase in NF-κB-regulated transactivation of the IL-8 gene was confirmed in cells following transfection of miR-16 precursor. Importantly, miR-16 targeted the 3'-untranslated region of SMRT and caused translational suppression of SMRT. LPS decreased SMRT expression via upregulation of miR-16. Moreover, functional manipulation of SMRT altered NF-κB-regulated transactivation of LPS-induced IL-8 expression. These data suggest that miR-16 targets SMRT and modulates NF-κB-regulated transactivation of the IL-8 gene.

  16. Human factors in nuclear power plant operations

    International Nuclear Information System (INIS)

    Swain, A.D.

    1980-08-01

    This report describes some of the human factors problems in nuclear power plants and the technology that can be employed to reduce those problems. Many of the changes to improve the human factors in existing plants are inexpensive, and the expected gain in human reliability is substantial. The human factors technology is well-established and there are practitioners in most countries that have nuclear power plants

  17. Human factors in nuclear power plants

    International Nuclear Information System (INIS)

    Swain, A.D.

    1981-01-01

    This report describes some of the human factors problems in nuclear power plants and the technology that can be employed to reduce those problems. Many of the changes to improve the human factors in existing plants are inexpensive, and the expected gain in human reliability is substantial. The human factors technology is well-established and there are practitioners in most countries that have nuclear power plants. (orig.) [de

  18. EGFR transactivation: mechanisms, pathophysiology and potential therapies in cardiovascular system

    Science.gov (United States)

    Forrester, Steven J.; Kawai, Tatsuo; Elliott, Katherine J.; O’Brien, Shannon; Thomas, Walter; Harris, Raymond C.; Eguchi, Satoru

    2017-01-01

    Accumulating studies suggest that the epidermal growth factor receptor (EGFR) activation is associated with the physiology and pathophysiology of the cardiovascular system, and inhibition of EGFR activity is emerging as a potential therapeutic strategy to treat diseases, including hypertension, cardiac hypertrophy, renal fibrosis and abdominal aortic aneurysm. The capacity of G protein-coupled receptor (GPCR) agonists, such as angiotensin II (AngII), to promote EGFR signaling is well described – a process termed EGFR “transactivation” – yet delineating the molecular processes and functional relevance of this crosstalk has been challenging. Moreover, these critical findings are dispersed among many different fields. The aim of our review is to highlight the recent advancement of the signaling cascades and downstream consequences of EGFR transactivation within the cardiovascular renal system in vitro and in vivo. We will also focus on linking EGFR transactivation to animal models of the disease as well as the potential therapeutic applications. PMID:26566153

  19. Nucleon form factors in the nuclear medium

    Science.gov (United States)

    Park, Chanyong; Lee, Jung Hun

    2018-01-01

    By using the AdS/CFT correspondence, we investigate various form factors between nucleons and mesons in a nuclear medium. In order to describe a nuclear medium holographically, we take into account the thermal charged AdS geometry with an appropriate IR cutoff. After introducing an anomalous dimension as a free parameter, we investigate how the nucleon’s mass is affected by the change of the anomalous dimension. Moreover, we study how the form factors of nucleons rely on the properties of the nuclear medium. We show that in a nuclear medium with different numbers of proton and neutron, the degenerated nucleon form factor in the vacuum is split into four different values depending on the isospin charges of nucleon and meson.

  20. I-mfa domain proteins specifically interact with HTLV-1 Tax and repress its transactivating functions

    Energy Technology Data Exchange (ETDEWEB)

    Kusano, Shuichi, E-mail: skusano@m2.kufm.kagoshima-u.ac.jp [Division of Persistent and Oncogenic Viruses, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Yoshimitsu, Makoto; Hachiman, Miho [Division of Hematology and Immunology, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Ikeda, Masanori [Division of Persistent and Oncogenic Viruses, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan)

    2015-12-15

    The I-mfa domain proteins HIC (also known as MDFIC) and I-mfa (also known as MDFI) are candidate tumor suppressor genes that are involved in cellular and viral transcriptional regulation. Here, we show that HIC and I-mfa directly interact with human T-cell leukemia virus type-1 (HTLV-1) Tax protein in vitro. In addition, HIC and I-mfa repress Tax-dependent transactivation of an HTLV-1 long terminal repeat (LTR) reporter construct in COS-1, Jurkat and high-Tax-producing HTLV-1-infected T cells. HIC also interacts with Tax through its I-mfa domain in vivo and represses Tax-dependent transactivation of HTLV-1 LTR and NF-κB reporter constructs in an interaction-dependent manner. Furthermore, we show that HIC decreases the nuclear distribution and stimulates the proteasomal degradation of Tax. These data reveal that HIC specifically interacts with HTLV-1 Tax and negatively regulates Tax transactivational activity by altering its subcellular distribution and stability. - Highlights: • I-mfa domain proteins, HIC and I-mfa, specifically interact with HTLV-1 Tax. • HIC and I-mfa repress the Tax-dependent transactivation of HTLV-1 LTR. • HIC represses the Tax-dependent transactivation of NF-κΒ. • HIC decreases the nuclear distribution of Tax. • HIC stimulates the proteasomal degradation of Tax.

  1. Human Factor on Gravelines Nuclear Power Plants

    International Nuclear Information System (INIS)

    Duboc, Gerard

    1998-01-01

    In a first part, the documents describes the commitments by EDF nuclear power plan operations to demands made by the Safety Authority regarding actions in the field of human factors (concerns expressed by the Authority, in-depth analysis, positions on different points raised by the Authority). In a second part, it presents the various actions undertaken in the Gravelines nuclear power station regarding human factors: creation of an 'operator club' (mission and objectives, methods and means, first meetings, tracking file), development of risk analysis strategy, setting up of a human factor engineering mission and example of action in case of a significant event

  2. Human factor problem in nuclear power generation

    International Nuclear Information System (INIS)

    Yoshino, Kenji; Fujimoto, Junzo

    1999-01-01

    Since a nuclear power plant accident at Threemile Island in U.S.A. occurred in March, 1979, twenty years have passed. After the accident, the human factor problem became focussed in nuclear power, to succeed its research at present. For direct reason of human error, most of factors at individual level or work operation level are often listed at their center. Then, it is natural that studies on design of a machine or apparatus suitable for various human functions and abilities and on improvement of relationship between 'human being and machine' and 'human being and working environment' are important in future. Here was, as first, described on outlines of the human factor problem in a nuclear power plant developed at a chance of past important accident, and then was described on educational training for its countermeasure. At last, some concrete researching results obtained by human factor research were introduced. (G.K.)

  3. Cardiac GPCR-Mediated EGFR Transactivation: Impact and Therapeutic Implications.

    Science.gov (United States)

    Grisanti, Laurel A; Guo, Shuchi; Tilley, Douglas G

    2017-07-01

    G protein-coupled receptors (GPCRs) remain primary therapeutic targets for numerous cardiovascular disorders, including heart failure (HF), because of their influence on cardiac remodeling in response to elevated neurohormone signaling. GPCR blockers have proven to be beneficial in the treatment of HF by reducing chronic G protein activation and cardiac remodeling, thereby extending the lifespan of patients with HF. Unfortunately, this effect does not persist indefinitely, thus next-generation therapeutics aim to selectively block harmful GPCR-mediated pathways while simultaneously promoting beneficial signaling. Transactivation of epidermal growth factor receptor (EGFR) has been shown to be mediated by an expanding repertoire of GPCRs in the heart, and promotes cardiomyocyte survival, thus may offer a new avenue of HF therapeutics. However, GPCR-dependent EGFR transactivation has also been shown to regulate cardiac hypertrophy and fibrosis by different GPCRs and through distinct molecular mechanisms. Here, we discuss the mechanisms and impact of GPCR-mediated EGFR transactivation in the heart, focusing on angiotensin II, urotensin II, and β-adrenergic receptor systems, and highlight areas of research that will help us to determine whether this pathway can be engaged as future therapeutic strategy.

  4. Inhibitory effects of omega-3 fatty acids on injury-induced epidermal growth factor receptor transactivation contribute to delayed wound healing

    OpenAIRE

    Turk, Harmony F.; Monk, Jennifer M.; Fan, Yang-Yi; Callaway, Evelyn S.; Weeks, Brad; Chapkin, Robert S.

    2013-01-01

    Epidermal growth factor receptor (EGFR)-mediated signaling is required for optimal intestinal wound healing. Since n-3 polyunsaturated fatty acids (PUFA), specifically docosahexaenoic acid (DHA), alter EGFR signaling and suppress downstream activation of key signaling pathways, we hypothesized that DHA would be detrimental to the process of intestinal wound healing. Using a mouse immortalized colonocyte model, DHA uniquely reduced EGFR ligand-induced receptor activation, whereas DHA and its m...

  5. Human factors in nuclear power plants

    International Nuclear Information System (INIS)

    Hennig, J.; Bohr, E.

    1976-04-01

    This annotated bibliography is a first attempt to give a survey of the kind of literature which is relevant for the ergonomic working conditions in nuclear power plants. Such a survey seems to be useful in view of the fact that the 'factor human being' comes recently more and more to the fore in nuclear power plants. In this context, the necessity is often pointed out to systematically include our knowledge of the performance capacity and limits of human beings when designing the working conditions for the personnel of nuclear power plants. For this reason, the bibliography is so much intended for the ergonomics experts as for the experts of nuclear engineering. (orig./LN) [de

  6. Rac1 augments Wnt signaling by stimulating β-catenin–lymphoid enhancer factor-1 complex assembly independent of β-catenin nuclear import

    Science.gov (United States)

    Jamieson, Cara; Lui, Christina; Brocardo, Mariana G.; Martino-Echarri, Estefania; Henderson, Beric R.

    2015-01-01

    ABSTRACT β-Catenin transduces the Wnt signaling pathway and its nuclear accumulation leads to gene transactivation and cancer. Rac1 GTPase is known to stimulate β-catenin-dependent transcription of Wnt target genes and we confirmed this activity. Here we tested the recent hypothesis that Rac1 augments Wnt signaling by enhancing β-catenin nuclear import; however, we found that silencing/inhibition or up-regulation of Rac1 had no influence on nuclear accumulation of β-catenin. To better define the role of Rac1, we employed proximity ligation assays (PLA) and discovered that a significant pool of Rac1–β-catenin protein complexes redistribute from the plasma membrane to the nucleus upon Wnt or Rac1 activation. More importantly, active Rac1 was shown to stimulate the formation of nuclear β-catenin–lymphoid enhancer factor 1 (LEF-1) complexes. This regulation required Rac1-dependent phosphorylation of β-catenin at specific serines, which when mutated (S191A and S605A) reduced β-catenin binding to LEF-1 by up to 50%, as revealed by PLA and immunoprecipitation experiments. We propose that Rac1-mediated phosphorylation of β-catenin stimulates Wnt-dependent gene transactivation by enhancing β-catenin–LEF-1 complex assembly, providing new insight into the mechanism of cross-talk between Rac1 and canonical Wnt/β-catenin signaling. PMID:26403202

  7. The human factor in the nuclear industry

    International Nuclear Information System (INIS)

    Colas, Armand

    1998-01-01

    After having evoked the progressive reduction and stabilization of significant incidents occurring every year in French nuclear power plants, and the challenges faced by nuclear energy (loss of public confidence, loss of competitiveness), and then outlined the importance of safety to overcome these challenges, the author comments EDF's approach to the human factor. He first highlights the importance of information and communication towards the population. He briefly discusses the meaning of human factors for the nuclear industry, sometimes perceived as the contribution people to the company's safety and performance. He comments the evolution observed in the perception of human error in different industrial or technical environments and situations, and outlines what is at stake to reduce the production of faults and organize a 'hunt for latent defects'

  8. Human factors methods in DOE nuclear facilities

    International Nuclear Information System (INIS)

    Bennett, C.T.; Banks, W.W.; Waters, R.J.

    1993-01-01

    The US Department of Energy (DOE) is in the process of developing a series of guidelines for the use of human factors standards, procedures, and methods to be used in nuclear facilities. This paper discusses the philosophy and process being used to develop a DOE human factors methods handbook to be used during the design cycle. The following sections will discuss: (1) basic justification for the project; (2) human factors design objectives and goals; and (3) role of human factors engineering (HFE) in the design cycle

  9. Uranium, a factor limiting nuclear energy?

    International Nuclear Information System (INIS)

    2006-01-01

    Nuclear power has been back as a topic of public debate since early this year. A special subject under discussion is the extension of nuclear power plant life. Hardly had it been on the agenda, when interested parties announced that this step was impossible because uranium reserves were no longer sufficient. A variety of terms are being used in this discussion without their meaning being taken into account: stocks, resources, and reserves. To clarify the situation, this article outlines important aspects of short and long term uranium supplies, and analyzes their meaning. Here are some of the most important issues under consideration: - For what period of time is there really enough uranium? - Is uranium becoming the limiting factor in the use of nuclear power? - Is uranium really a 'sustainable' energy resource? - Will higher prices extend the range? - What is the influence of the price of uranium on the cost of electricity generation? Among other results, it is found that comprehensive sources of low-price uranium and nuclear fuels are, or can be made, available worldwide. Consequently, the 'range' is beyond the time frames currently mentioned, also as a function of technological factors, i.e. reaching several hundred years. It is also important to note that nuclear power - ensures greater independence of volatile imported sources, - guarantees reliably low electricity prices, - has a huge potential of environmental protection, and - is a clean source of energy. (orig./GL)

  10. Review of EPRI Nuclear Human Factors Program

    International Nuclear Information System (INIS)

    Hanes, L.F.; O'Brien, J.F.

    1996-01-01

    The Electric Power Research Institute (EPRI) Human Factors Program, which is part of the EPRI Nuclear Power Group, was established in 1975. Over the years, the Program has changed emphasis based on the shifting priorities and needs of the commercial nuclear power industry. The Program has produced many important products that provide significant safety and economic benefits for EPRI member utilities. This presentation will provide a brief history of the Program and products. Current projects and products that have been released recently will be mentioned

  11. Human and organizational factors in nuclear safety

    International Nuclear Information System (INIS)

    Garcia, A.; Barrientos, M.; Gil, B.

    2015-01-01

    Nuclear installations are socio technical systems where human and organizational factors, in both utilities and regulators, have a significant impact on safety. Three Mile Island (TMI) accident, original of several initiatives in the human factors field, nevertheless became a lost opportunity to timely acquire lessons related to the upper tiers of the system. Nowadays, Spanish nuclear installations have integrated in their processes specialists and activities in human and organizational factors, promoted by the licensees After many years of hard work, Spanish installations have achieved a better position to face new challenges, such as those posed by Fukushima. With this experience, only technology-centered action plan would not be acceptable, turning this accident in yet another lost opportunity. (Author)

  12. Uranium - a factor limiting nuclear energy?

    International Nuclear Information System (INIS)

    Ohnemus, J.

    2006-01-01

    Nuclear power has been back as a topic of public debate since early this year. A special subject under discussion is the extension of nuclear power plant life. Hardly had it been on the agenda, when interested parties announced that this st ep was impossible because uranium reserves were no longer sufficient. A variety of terms are being used in this discussion without their meaning being taken int o account: stocks, resources, and reserves. To clarify the situation, this artic le outlines important aspects of short and long term uranium supplies, and analy zes their meaning. Here are some of the most important issues under consideration: - For what period of time is there really enough uranium? - Is uranium becoming the limiting factor in the use of nuclear power? - Is uranium really a 'sustainable' energy resource? - Will higher prices extend the range? - What is the in fluence of the price of uranium on the cost of electricity generation? Among oth er results, it is found that comprehensive sources of low-price uranium and nucl ear fuels are, or can be made, available worldwide. Consequently, the 'range' is beyond the time frames currently mentioned, also as a function of technological factors, i.e. reaching several hundred years. It is also important to note that nuclear power - ensures greater independence of volatile imported sources, - guarantees reliably low electricity prices, - has a huge potential of environmental protection, and - is a clean source of energy. (orig.)

  13. Human factors in nuclear safety oversight

    International Nuclear Information System (INIS)

    Taylor, K.

    1989-01-01

    The mission of the nuclear safety oversight function at the Savannah River Plant is to enhance the process and nuclear safety of site facilities. One of the major goals surrounding this mission is the reduction of human error. It is for this reason that several human factors engineers are assigned to the Operations assessment Group of the Facility Safety Evaluation Section (FSES). The initial task of the human factors contingent was the design and implementation of a site wide root cause analysis program. The intent of this system is to determine the most prevalent sources of human error in facility operations and to assist in determining where the limited human factors resources should be focused. In this paper the strategy used to educate the organization about the field of human factors is described. Creating an awareness of the importance of human factors engineering in all facets of design, operation, and maintenance is considered to be an important step in reducing the rate of human error

  14. Inhibition of E2F-1 transactivation by direct binding of the retinoblastoma protein

    DEFF Research Database (Denmark)

    Helin, K; Harlow, E; Fattaey, A

    1993-01-01

    to transcription factor E2F has provided a model for the mechanism of pRB-mediated growth regulation. Since adenovirus E1A proteins dissociate the pRB-E2F complexes and stimulate E2F-dependent transcription, it has been suggested that pRB inhibits E2F transactivation. Although some evidence for this hypothesis has...... been provided, it has not been possible to determine the mechanism of pRB-mediated inhibition of E2F transactivation. In this study, we constructed mutants of E2F-1 that do not bind to pRB yet retain the ability to transactivate the adenovirus E2 promoter through E2F DNA-binding sites. We demonstrated...

  15. Multiple phosphorylation events control chicken ovalbumin upstream promoter transcription factor I orphan nuclear receptor activity.

    Science.gov (United States)

    Gay, Frédérique; Baráth, Peter; Desbois-Le Péron, Christine; Métivier, Raphaël; Le Guével, Rémy; Birse, Darcy; Salbert, Gilles

    2002-06-01

    Chicken ovalbumin upstream promoter transcription factor I (COUP-TFI) is an orphan member of the nuclear hormone receptor superfamily that comprises key regulators of many biological functions, such as embryonic development, metabolism, homeostasis, and reproduction. Although COUP-TFI can both actively silence gene transcription and antagonize the functions of various other nuclear receptors, the COUP-TFI orphan receptor also acts as a transcriptional activator in certain contexts. Moreover, COUP-TFI has recently been shown to serve as an accessory factor for some ligand-bound nuclear receptors, suggesting that it may modulate, both negatively and positively, a wide range of hormonal responses. In the absence of any identified cognate ligand, the mechanisms involved in the regulation of COUP-TFI activity remain unclear. The elucidation of several putative phosphorylation sites for MAPKs, PKC, and casein kinase II within the sequence of this orphan receptor led us to investigate phosphorylation events regulating the various COUP-TFI functions. After showing that COUP-TFI is phosphorylated in vivo, we provide evidence that in vivo inhibition of either MAPK or PKC signaling pathway leads to a specific and pronounced decrease in COUP-TFI-dependent transcriptional activation of the vitronectin gene promoter. Focusing on the molecular mechanisms underlying the MAPK- and PKC-mediated regulation of COUP-TFI activity, we show that COUP-TFI can be directly targeted by PKC and MAPK. These phosphorylation events differentially modulate COUP-TFI functions: PKC-mediated phosphorylation enhances COUP-TFI affinity for DNA and MAPK-mediated phosphorylation positively regulates the transactivation function of COUP-TFI, possibly through enhancing specific coactivator recruitment. These data provide evidence that COUP-TFI is likely to integrate distinct signaling pathways and raise the possibility that multiple extracellular signals influence biological processes controlled by COUP-TFI.

  16. Human Factors in Nuclear Reactor Accidents

    International Nuclear Information System (INIS)

    Mustafa, M.E.

    2016-01-01

    While many people would blame nature for the disaster of the “Fukushima Daiichi” accident, experts considered this accident to be also a human-induced disaster. This confirmed the importance of human errors which have been getting a growing interest in the nuclear field after the Three Mile Island accident. Personnel play an important role in design, operation, maintenance, planning, and management. The interface between machine and man is known as a human factor. In the present work, the human factors that have to be considered were discussed. The effect of the control room configuration and equipment design effect on the human behavior was also discussed. Precise reviewing of person’s qualifications and experience was focused. Insufficient training has been a major cause of human error in the nuclear field. The effective training issues were introduced. Avoiding complicated operational processes and non responsive management systems was stressed. Distinguishing between the procedures for normal and emergency operations was emphasised. It was stated that human error during maintenance and testing activities could cause a serious accident. This is because safety systems do not cover much more risk probabilities in the maintenance and testing activities like they do in the normal operation. In nuclear industry, the need for a classification and identification of human errors has been well recognised. As a result of this, human reliability must be assessed. These errors are analyzed by a probabilistic safety assessment which deals with errors in reading, listening and implementing procedures but not with cognitive errors. Much efforts must be accomplished to consider cognitive errors in the probabilistic safety assessment. The ways of collecting human factor data were surveyed. The methods for identifying safe designs, helping decision makers to predict how proposed or current policies will affect safety, and comprehensive understanding of the relationship

  17. Hepatitis B virus DNA integration and transactivation of cellular genes

    Directory of Open Access Journals (Sweden)

    Vijay Kumar

    2007-02-01

    transactivator can stimulate a wide range of cellular genes and displays oncogenic potential in cell culture as well as in a transgenic environment.

    The HBs transactivators are encoded by the preS/S region of S gene and may involve carboxy terminal truncation to gain transactivation function. Expression of host genes by viral transactivators is mediated by regulatory elements of the cellular transcription factors like c-fos, c-myc, NF-kappa B, SRE and Sp1. Thus, during hepatitis B infection, the tendency of rearrangement of hepatocyte chromosomes is combined with the forcible turnover of cells. This is a constantly operating system for the selection of cells that grow better than normal cells, possibly involving important steps in multi-staged hepatocarcinogeneses. Gene expression profiling and proteomic techniques may help to characterize the molecular mechanisms driving HBV-associated carcinogenesis, and thus potentially identify new strategies in diagnosis and therapy.

     

    REFERENCES

    1. Kekule AS, Lauer U, Meyer M, Caselmann WH, Hofschneider PH, Koshy R. (1990 The preS2/S region of integrated hepatitis B virus DNA encodes a transcriptional transactivator. Nature 343, 457-461.

    2. Caselmann WH. (1996 Trans-activation of cellular genes by hepatitis B virus proteins: a possible mechanism of hepatocarcinogenesis. Adv Virus Res 47, 253-302.

    3. Matsubara K, Tokino T. (1990 Integration of hepatitis B virus DNA and its implications for hepatocarcinogenesis. Mol Biol

  18. Nuclear factor-Y and Epstein Barr virus in nasopharyngeal cancer.

    Science.gov (United States)

    Chia, Marie C; Leung, Abby; Krushel, Tiffany; Alajez, Nehad M; Lo, Kwok W; Busson, Pierre; Klamut, Henry J; Bastianutto, Carlo; Liu, Fei-Fei

    2008-02-15

    The Epstein Barr virus (EBV) is intimately associated with nasopharyngeal cancer (NPC) in a latent state expressing a limited number of genes. The process of switching from latency to replication is not well understood, particularly in response to DNA stress; hence, the focus of this study is on an EBV-positive NPC model. C666-1 cells were exposed to radiation (2-15 Gy) or cisplatin (0.1-50 microg/mL) assayed subsequently for relative EBV copy number (BamHI) and lytic gene expression (BRLF1 and BZLF1) using quantitative real-time PCR. Chromatin immunoprecipitation was conducted to assess the interaction of the transcription factor nuclear factor-Y (NF-Y) with promoter sequences. Radiation-induced and cisplatin-induced BamHI expression, along with increased levels of BRLF1 and BZLF1 in a dose-dependent and time-dependent manner, associated with the immediate nuclear transactivation of the transcription factor NF-Y and its own increased transcription of NF-Y subunits 8 h posttreatment. In silico analysis revealed three putative NF-Y consensus-binding sequences in the promoter region of BRLF1, which all interacted with NF-Y in response to radiation and cisplatin, confirmed using chromatin immunoprecipitation. Introduction of dominant-negative NF-YA reduced BRLF1 expression after radiation and cisplatin by 2.8-fold; in turn, overexpression of NF-YA resulted in a 2-fold increase in both BRLF1 and BZLF1 expression. These results show that NF-Y is an important mediator of EBV stress response in switching from a latent to lytic state. This novel insight could provide a potential therapeutic strategy to enhance NPC response to radiation and cisplatin.

  19. Transcriptional regulation of the human Liver X Receptor α gene by Hepatocyte Nuclear Factor

    Energy Technology Data Exchange (ETDEWEB)

    Theofilatos, Dimitris; Anestis, Aristomenis [University of Crete Medical School and Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology of Hellas, Heraklion, 71003, Crete (Greece); Hashimoto, Koshi [Department of Preemptive Medicine and Metabolism, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-city, Tokyo, 113-8510 (Japan); Kardassis, Dimitris, E-mail: kardasis@imbb.forth.gr [University of Crete Medical School and Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology of Hellas, Heraklion, 71003, Crete (Greece)

    2016-01-15

    Liver X Receptors (LXRs) are sterol-activated transcription factors that play major roles in cellular cholesterol homeostasis, HDL biogenesis and reverse cholesterol transport. The aim of the present study was to investigate the mechanisms that control the expression of the human LXRα gene in hepatic cells. A series of reporter plasmids containing consecutive 5′ deletions of the hLXRα promoter upstream of the luciferase gene were constructed and the activity of each construct was measured in HepG2 cells. This analysis showed that the activity of the human LXRα promoter was significantly reduced by deleting the −111 to −42 region suggesting the presence of positive regulatory elements in this short proximal fragment. Bioinformatics data including motif search and ChIP-Seq revealed the presence of a potential binding motif for Hepatocyte Nuclear Factor 4 α (HNF-4α) in this area. Overexpression of HNF-4α in HEK 293T cells increased the expression of all LXRα promoter constructs except −42/+384. In line, silencing the expression of endogenous HNF-4α in HepG2 cells was associated with reduced LXRα protein levels and reduced activity of the −111/+384 LXRα promoter but not of the −42/+384 promoter. Using ChiP assays in HepG2 cells combined with DNAP assays we mapped the novel HNF-4α specific binding motif (H4-SBM) in the −50 to −40 region of the human LXRα promoter. A triple mutation in this H4-SBM abolished HNF-4α binding and reduced the activity of the promoter to 65% relative to the wild type. Furthermore, the mutant promoter could not be transactivated by HNF-4α. In conclusion, our data indicate that HNF-4α may have a wider role in cell and plasma cholesterol homeostasis by controlling the expression of LXRα in hepatic cells. - Highlights: • The human LXRα promoter contains a HNF-4α specific binding motif in the proximal −50/−40 region. • Mutations in this motif abolished HNF4α binding and transactivation of the h

  20. Transcriptional regulation of the human Liver X Receptor α gene by Hepatocyte Nuclear Factor

    International Nuclear Information System (INIS)

    Theofilatos, Dimitris; Anestis, Aristomenis; Hashimoto, Koshi; Kardassis, Dimitris

    2016-01-01

    Liver X Receptors (LXRs) are sterol-activated transcription factors that play major roles in cellular cholesterol homeostasis, HDL biogenesis and reverse cholesterol transport. The aim of the present study was to investigate the mechanisms that control the expression of the human LXRα gene in hepatic cells. A series of reporter plasmids containing consecutive 5′ deletions of the hLXRα promoter upstream of the luciferase gene were constructed and the activity of each construct was measured in HepG2 cells. This analysis showed that the activity of the human LXRα promoter was significantly reduced by deleting the −111 to −42 region suggesting the presence of positive regulatory elements in this short proximal fragment. Bioinformatics data including motif search and ChIP-Seq revealed the presence of a potential binding motif for Hepatocyte Nuclear Factor 4 α (HNF-4α) in this area. Overexpression of HNF-4α in HEK 293T cells increased the expression of all LXRα promoter constructs except −42/+384. In line, silencing the expression of endogenous HNF-4α in HepG2 cells was associated with reduced LXRα protein levels and reduced activity of the −111/+384 LXRα promoter but not of the −42/+384 promoter. Using ChiP assays in HepG2 cells combined with DNAP assays we mapped the novel HNF-4α specific binding motif (H4-SBM) in the −50 to −40 region of the human LXRα promoter. A triple mutation in this H4-SBM abolished HNF-4α binding and reduced the activity of the promoter to 65% relative to the wild type. Furthermore, the mutant promoter could not be transactivated by HNF-4α. In conclusion, our data indicate that HNF-4α may have a wider role in cell and plasma cholesterol homeostasis by controlling the expression of LXRα in hepatic cells. - Highlights: • The human LXRα promoter contains a HNF-4α specific binding motif in the proximal −50/−40 region. • Mutations in this motif abolished HNF4α binding and transactivation of the h

  1. Organizational factors and nuclear power plant safety

    International Nuclear Information System (INIS)

    Haber, S.B.

    1995-01-01

    There are many organizations in our society that depend on human performance to avoid incidents involving significant adverse consequences. As our culture and technology have become more sophisticated, the management of risk on a broad basis has become more and more critical. The safe operation of military facilities, chemical plants, airlines, and mass transit, to name a few, are substantially dependent on the performance of the organizations that operate those facilities. The nuclear power industry has, within the past 15 years, increased the attention given to the influence of human performance in the safe operation of nuclear power plants (NPP). While NPPs have been designed through engineering disciplines to intercept and mitigate events that could cause adverse consequences, it has been clear from various safety-related incidents that human performance also plays a dominant role in preventing accidents. Initial efforts following the 1979 Three Mile Island incident focused primarily on ergonomic factors (e.g., the best design of control rooms for maximum performance). Greater attention was subsequently directed towards cognitive processes involved in the use of NPP decision support systems and decision making in general, personnel functions such as selection systems, and the influence of work scheduling and planning on employees' performance. Although each of these approaches has contributed to increasing the safety of NPPS, during the last few years, there has been a growing awareness that particular attention must be paid to how organizational processes affect NPP personnel performance, and thus, plant safety. The direct importance of organizational factors on safety performance in the NPP has been well-documented in the reports on the Three Mile Island and Chernobyl accidents as well as numerous other events, especially as evaluated by the U.S. Nuclear Regulatory Commission (NRC)

  2. Regression analysis of nuclear plant capacity factors

    International Nuclear Information System (INIS)

    Stocks, K.J.; Faulkner, J.I.

    1980-07-01

    Operating data on all commercial nuclear power plants of the PWR, HWR, BWR and GCR types in the Western World are analysed statistically to determine whether the explanatory variables size, year of operation, vintage and reactor supplier are significant in accounting for the variation in capacity factor. The results are compared with a number of previous studies which analysed only United States reactors. The possibility of specification errors affecting the results is also examined. Although, in general, the variables considered are statistically significant, they explain only a small portion of the variation in the capacity factor. The equations thus obtained should certainly not be used to predict the lifetime performance of future large reactors

  3. The leukemia associated ETO nuclear repressor gene is regulated by the GATA-1 transcription factor in erythroid/megakaryocytic cells

    Directory of Open Access Journals (Sweden)

    Gullberg Urban

    2010-05-01

    Full Text Available Abstract Background The Eight-Twenty-One (ETO nuclear co-repressor gene belongs to the ETO homologue family also containing Myeloid Translocation Gene on chromosome 16 (MTG16 and myeloid translocation Gene-Related protein 1 (MTGR1. By chromosomal translocations ETO and MTG16 become parts of fusion proteins characteristic of morphological variants of acute myeloid leukemia. Normal functions of ETO homologues have as yet not been examined. The goal of this work was to identify structural and functional promoter elements upstream of the coding sequence of the ETO gene in order to explore lineage-specific hematopoietic expression and get hints to function. Results A putative proximal ETO promoter was identified within 411 bp upstream of the transcription start site. Strong ETO promoter activity was specifically observed upon transfection of a promoter reporter construct into erythroid/megakaryocytic cells, which have endogeneous ETO gene activity. An evolutionary conserved region of 228 bp revealed potential cis-elements involved in transcription of ETO. Disruption of the evolutionary conserved GATA -636 consensus binding site repressed transactivation and disruption of the ETS1 -705 consensus binding site enhanced activity of the ETO promoter. The promoter was stimulated by overexpression of GATA-1 into erythroid/megakaryocytic cells. Electrophoretic mobility shift assay with erythroid/megakaryocytic cells showed specific binding of GATA-1 to the GATA -636 site. Furthermore, results from chromatin immunoprecipitation showed GATA-1 binding in vivo to the conserved region of the ETO promoter containing the -636 site. The results suggest that the GATA -636 site may have a role in activation of the ETO gene activity in cells with erythroid/megakaryocytic potential. Leukemia associated AML1-ETO strongly suppressed an ETO promoter reporter in erythroid/megakaryocytic cells. Conclusions We demonstrate that the GATA-1 transcription factor binds and

  4. Development of human factors engineering guide for nuclear power project

    International Nuclear Information System (INIS)

    Wu Dangshi; Sheng Jufang

    1997-01-01

    'THE PRACTICAL GUIDE FOR APPLICATION OF HUMAN FACTORS ENGINEERING TO NUCLEAR POWER PROJECT (First Draft, in Chinese)', which was developed under a research program sponsored by National Nuclear Safety Administration (NNSA) is described briefly. It is hoped that more conscious, more systematical and more comprehensive application of Human Factors Engineering to the nuclear power projects from the preliminary feasibility studies up to the commercial operation will benefit the safe, efficient and economical operations of nuclear power plants in China

  5. Proteomic analysis of the herpes simplex virus 1 virion protein 16 transactivator protein in infected cells.

    Science.gov (United States)

    Suk, Hyung; Knipe, David M

    2015-06-01

    The herpes simplex virus 1 virion protein 16 (VP16) tegument protein forms a transactivation complex with the cellular proteins host cell factor 1 (HCF-1) and octamer-binding transcription factor 1 (Oct-1) upon entry into the host cell. VP16 has also been shown to interact with a number of virion tegument proteins and viral glycoprotein H to promote viral assembly, but no comprehensive study of the VP16 proteome has been performed at early times postinfection. We therefore performed a proteomic analysis of VP16-interacting proteins at 3 h postinfection. We confirmed the interaction of VP16 with HCF-1 and a large number of cellular Mediator complex proteins, but most surprisingly, we found that the major viral protein associating with VP16 is the infected cell protein 4 (ICP4) immediate-early (IE) transactivator protein. These results raise the potential for a new function for VP16 in associating with the IE ICP4 and playing a role in transactivation of early and late gene expression, in addition to its well-documented function in transactivation of IE gene expression. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Human and organizational factors in nuclear safety; Factores humanos y organizativos en la seguridad nuclear

    Energy Technology Data Exchange (ETDEWEB)

    Garcia, A.; Barrientos, M.; Gil, B.

    2015-07-01

    Nuclear installations are socio technical systems where human and organizational factors, in both utilities and regulators, have a significant impact on safety. Three Mile Island (TMI) accident, original of several initiatives in the human factors field, nevertheless became a lost opportunity to timely acquire lessons related to the upper tiers of the system. Nowadays, Spanish nuclear installations have integrated in their processes specialists and activities in human and organizational factors, promoted by the licensees After many years of hard work, Spanish installations have achieved a better position to face new challenges, such as those posed by Fukushima. With this experience, only technology-centered action plan would not be acceptable, turning this accident in yet another lost opportunity. (Author)

  7. Mutations that abrogate transactivational activity of the feline leukemia virus long terminal repeat do not affect virus replication

    International Nuclear Information System (INIS)

    Abujamra, Ana L.; Faller, Douglas V.; Ghosh, Sajal K.

    2003-01-01

    The U3 region of the LTR of oncogenic Moloney murine leukemia virus (Mo-MuLV) and feline leukemia viruses (FeLV) have been previously reported to activate expression of specific cellular genes in trans, such as MHC class I, collagenase IV, and MCP-1, in an integration-independent manner. It has been suggested that transactivation of these specific cellular genes by leukemia virus U3-LTR may contribute to the multistage process of leukemogenesis. The U3-LTR region, necessary for gene transactivational activity, also contains multiple transcription factor-binding sites that are essential for normal virus replication. To dissect the promoter activity and the gene transactivational activity of the U3-LTR, we conducted mutational analysis of the U3-LTR region of FeLV-A molecular clone 61E. We identified minimal nucleotide substitution mutants on the U3 LTR that did not disturb transcription factor-binding sites but abrogated its ability to transactivate the collagenase gene promoter. To determine if these mutations actually have altered any uncharacterized important transcription factor-binding site, we introduced these U3-LTR mutations into the full-length infectious molecular clone 61E. We demonstrate that the mutant virus was replication competent but could not transactivate cellular gene expression. These results thus suggest that the gene transactivational activity is a distinct property of the LTR and possibly not related to its promoter activity. The cellular gene transactivational activity-deficient mutant FeLV generated in this study may also serve as a valuable reagent for testing the biological significance of LTR-mediated cellular gene activation in the tumorigenesis caused by leukemia viruses

  8. Functional defect of truncated hepatocyte nuclear factor-1α (G554fsX556) associated with maturity-onset diabetes of the young

    International Nuclear Information System (INIS)

    Kooptiwut, Suwattanee; Sujjitjoon, Jatuporn; Plengvidhya, Nattachet; Boonyasrisawat, Watip; Chongjaroen, Nalinee; Jungtrakoon, Prapapron; Semprasert, Namoiy; Furuta, Hiroto; Nanjo, Kishio; Banchuin, Napatawn; Yenchitsomanus, Pa-thai

    2009-01-01

    A novel frameshift mutation attributable to 14-nucleotide insertion in hepatocyte nuclear factor-1α (HNF-1α) encoding a truncated HNF-1α (G554fsX556) with 76-amino acid deletion at its carboxyl terminus was identified in a Thai family with maturity-onset diabetes of the young (MODY). The wild-type and mutant HNF-1α proteins were expressed by in vitro transcription and translation (TNT) assay and by transfection in HeLa cells. The wild-type and mutant HNF-1α could similarly bind to human glucose-transporter 2 (GLUT2) promoter examined by electrophoretic mobility shift assay (EMSA). However, the transactivation activities of mutant HNF-1α on human GLUT2 and rat L-type pyruvate kinase (L-PK) promoters in HeLa cells determined by luciferase reporter assay were reduced to approximately 55-60% of the wild-type protein. These results suggested that the functional defect of novel truncated HNF-1α (G554fsX556) on the transactivation of its target-gene promoters would account for the β-cell dysfunction associated with the pathogenesis of MODY.

  9. Functional defect of truncated hepatocyte nuclear factor-1{alpha} (G554fsX556) associated with maturity-onset diabetes of the young

    Energy Technology Data Exchange (ETDEWEB)

    Kooptiwut, Suwattanee, E-mail: S_kooptiwut@hotmail.com [Department of Physiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Sujjitjoon, Jatuporn [Department of Immunology and Immunology Graduate Program, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Plengvidhya, Nattachet [Department of Immunology and Immunology Graduate Program, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Division of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Boonyasrisawat, Watip; Chongjaroen, Nalinee; Jungtrakoon, Prapapron [Department of Immunology and Immunology Graduate Program, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Semprasert, Namoiy [Department of Physiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Furuta, Hiroto; Nanjo, Kishio [The First Department, Wakayama Medical University (Japan); Banchuin, Napatawn [Department of Immunology and Immunology Graduate Program, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Yenchitsomanus, Pa-thai [Division of Medical Molecular Biology, Medicine Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Medical Biotechnology Unit, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Bangkok (Thailand)

    2009-05-22

    A novel frameshift mutation attributable to 14-nucleotide insertion in hepatocyte nuclear factor-1{alpha} (HNF-1{alpha}) encoding a truncated HNF-1{alpha} (G554fsX556) with 76-amino acid deletion at its carboxyl terminus was identified in a Thai family with maturity-onset diabetes of the young (MODY). The wild-type and mutant HNF-1{alpha} proteins were expressed by in vitro transcription and translation (TNT) assay and by transfection in HeLa cells. The wild-type and mutant HNF-1{alpha} could similarly bind to human glucose-transporter 2 (GLUT2) promoter examined by electrophoretic mobility shift assay (EMSA). However, the transactivation activities of mutant HNF-1{alpha} on human GLUT2 and rat L-type pyruvate kinase (L-PK) promoters in HeLa cells determined by luciferase reporter assay were reduced to approximately 55-60% of the wild-type protein. These results suggested that the functional defect of novel truncated HNF-1{alpha} (G554fsX556) on the transactivation of its target-gene promoters would account for the {beta}-cell dysfunction associated with the pathogenesis of MODY.

  10. AKT increases VEGF expression in tumor cells by transactivating the proximal VEGF promoter

    International Nuclear Information System (INIS)

    Pore, N.; Bernhard, E.J.; Shu, H.-K.; Li, B.; O'Rourke, D.M.; Maity, A.; Haas-Kogan, D.

    2003-01-01

    Vascular endothelial growth factor (VEGF) is overexpressed in many cancers including glioblastomas and may contribute to their growth. Epidermal growth factor receptor (EGFR) amplification and loss of PTEN, commonly found in glioblastomas leading to increase phosphatidylinositol-3-kinase (PI3K) activity and VEGF expression. In the current study we show that AKT, which is downstream of PI3K, regulates VEGF expression. U87MG human glioblastoma cells lack wildtype PTEN and express high levels of phosphorylated AKT. Over expression of AKT either by stable expression in immortalized human astrocytes or by transduction with adenovirus containing activated myristoylated AKT in SF188 glioblastoma cells increases VEGF expression. Moreover the elevation of angiogenesis by constitutively expressed AKT is further confirmed by in vivo matrigel plug assay in nude mice. The upregulation of VEGF by AKT is mediated through a region in the proximal promoter located between -88 and -70 (+1 is transcription start site). In transient transfection activity of a luciferase reporter containing the -88/+54 region of the VEGF promoter is increased by cotransfection with myristoylated AKT and downregulated by a dominant negative AKT expression vector. Mutation of the putative Sp1 binding sites located in the -88/-70 region we show that AKT acts through Sp1 to transactivate the VEGF promoter. Cotransfection of the VEGF promoter reporter with both Sp1 and myristoylated AKT expression vectors increases promoter activity to a greater extent than either Sp1 or Akt by itself. In vivo phosphate labeling of proteins reveals that AKT leads to increased Sp1 phosphorylation. Gel shift assays using a radio labeled probe corresponding to nucleotides -88 through -66 in the promoter show increased binding with nuclear extracts from cells transduced with adenovirus expressing myristoylated AKT. In conclusion, our results suggest that loss of PTEN leads to increased VEGF expression by increasing AKT

  11. BFV activates the NF-κB pathway through its transactivator (BTas) to enhance viral transcription

    International Nuclear Information System (INIS)

    Wang Jian; Tan Juan; Zhang Xihui; Guo Hongyan; Zhang Qicheng; Guo Tingting; Geng Yunqi; Qiao Wentao

    2010-01-01

    Multiple families of viruses have evolved sophisticated strategies to regulate nuclear factor-κB (NF-κB) signaling, which plays a pivotal role in diverse cellular events, including virus-host interactions. In this study, we report that bovine foamy virus (BFV) is able to activate the NF-κB pathway through the action of its transactivator, BTas. Both cellular IKKβ and IκBα also participate in this activation. In addition, we demonstrate that BTas induces the processing of p100, which implies that BTas can activate NF-κB through a noncanonical pathway as well. Co-immunoprecipitation analysis shows that BTas interacts with IKK catalytic subunits (IKKα and IKKβ), which may be responsible for regulation of IKK kinase activity and persistent NF-κB activation. Furthermore, our results indicate that the level of BTas-mediated LTR transcription correlates with the activity of cellular NF-κB. Together, this study suggests that BFV activates the NF-κB pathway through BTas to enhance viral transcription.

  12. The viral transactivator HBx protein exhibits a high potential for regulation via phosphorylation through an evolutionarily conserved mechanism

    Directory of Open Access Journals (Sweden)

    Hernández Sergio

    2012-10-01

    Full Text Available Abstract Background Hepatitis B virus (HBV encodes an oncogenic factor, HBx, which is a multifunctional protein that can induce dysfunctional regulation of signaling pathways, transcription, and cell cycle progression, among other processes, through interactions with target host factors. The subcellular localization of HBx is both cytoplasmic and nuclear. This dynamic distribution of HBx could be essential to the multiple roles of the protein at different stages during HBV infection. Transactivational functions of HBx may be exerted both in the nucleus, via interaction with host DNA-binding proteins, and in the cytoplasm, via signaling pathways. Although there have been many studies describing different pathways altered by HBx, and its innumerable binding partners, the molecular mechanism that regulates its different roles has been difficult to elucidate. Methods In the current study, we took a bioinformatics approach to investigate whether the viral protein HBx might be regulated via phosphorylation by an evolutionarily conserved mechanism. Results We found that the phylogenetically conserved residues Ser25 and Ser41 (both within the negative regulatory domain, and Thr81 (in the transactivation domain are predicted to be phosphorylated. By molecular 3D modeling of HBx, we further show these residues are all predicted to be exposed on the surface of the protein, making them easily accesible to these types of modifications. Furthermore, we have also identified Yin Yang sites that might have the potential to be phosphorylated and O-β-GlcNAc interplay at the same residues. Conclusions Thus, we propose that the different roles of HBx displayed in different subcellular locations might be regulated by an evolutionarily conserved mechanism of posttranslational modification, via phosphorylation.

  13. Human factors in nuclear power plants

    International Nuclear Information System (INIS)

    Bohr, E.; Hennig, J.; Preuss, W.; Thau, G.

    1977-01-01

    This report describes the results of a study on the functions of operating and maintenance personnel in nuclear power plants. Since an effective power plant design must take into systematic account the possibilities and limitations of the human element, the basic aim of the study was to identify what the human operators are required to do and how they achieve it. Information was acquired by direct observation and by interviews as well as by evaluation of written documents (e.g. incident reports, procedures manuals, work regulations) and of working conditions (e.g. equipment and workplace design). A literature search and evaluation carried out within the scope of this study has been published as a separate document. The main part of the report is devoted to discussions and conclusions on selected areas of potential improvements. The topics include control room design, factors of the physical environment including radiation, problems of maintainability, design of written documents, problems in communicating information, design and control of tasks, placement and training. A separate section deals with problems of recording human errors. (orig.) [de

  14. Diametrically opposed effects of hypoxia and oxidative stress on two viral transactivators

    Directory of Open Access Journals (Sweden)

    Aiyar Ashok

    2010-05-01

    Full Text Available Abstract Background Many pathogens exist in multiple physiological niches within the host. Differences between aerobic and anaerobic conditions are known to alter the expression of bacterial virulence factors, typically through the conditional activity of transactivators that modulate their expression. More recently, changes in physiological niches have been shown to affect the expression of viral genes. For many viruses, differences in oxygen tension between hypoxia and normoxia alter gene expression or function. Oxygen tension also affects many mammalian transactivators including AP-1, NFkB, and p53 by affecting the reduced state of critical cysteines in these proteins. We have recently determined that an essential cys-x-x-cys motif in the EBNA1 transactivator of Epstein-Barr virus is redox-regulated, such that transactivation is favoured under reducing conditions. The crucial Tat transactivator of human immunodeficiency virus (HIV has an essential cysteine-rich region, and is also regulated by redox. Contrary to EBNA1, it is reported that Tat's activity is increased by oxidative stress. Here we have compared the effects of hypoxia, oxidative stress, and cellular redox modulators on EBNA1 and Tat. Results Our results indicate that unlike EBNA1, Tat is less active during hypoxia. Agents that generate hydroxyl and superoxide radicals reduce EBNA1's activity but increase transactivation by Tat. The cellular redox modulator, APE1/Ref-1, increases EBNA1's activity, without any effect on Tat. Conversely, thioredoxin reductase 1 (TRR1 reduces Tat's function without any effect on EBNA1. Conclusions We conclude that oxygen partial pressure and oxidative stress affects the functions of EBNA1 and Tat in a dramatically opposed fashion. Tat is more active during oxidative stress, whereas EBNA1's activity is compromised under these conditions. The two proteins respond to differing cellular redox modulators, suggesting that the oxidized cysteine adduct is a

  15. Human Factors in Nuclear Power Engineering in Polish Conditions

    Directory of Open Access Journals (Sweden)

    Agnieszka Kaczmarek-Kacprzak

    2014-09-01

    Full Text Available The paper “Human factors in nuclear power engineering in Polish conditions” focuses on analysis of dynamics of preparing Polish society to build fi rst nuclear power plant in XXI century in Poland. Authors compare experience from constructing nuclear power plant Sizewell B (Great Britain and Sizewell C, which is in preparation phase with polish nuclear power program. Paper includes aspects e.g. of creating nuclear safety culture and social opinion about investment. Human factors in nuclear power engineering are as well important as relevant economical and technical factors, but very often negligible. In Poland where history about Czarnobyl is still alive, and social opinion is created on emotions after accident in Fukushima, human factors are crucial and should be under comprehensive consideration.

  16. Factors in public perception of nuclear energy

    International Nuclear Information System (INIS)

    Hore-Lacy, I.

    1999-01-01

    Public communication about nuclear energy needs to relate to the cultural undercurrents which determine how people perceive the environment. The paper discusses some of these and suggests ways of responding to them. It also outlines major ethical considerations relevant to uranium mining and nuclear energy and communication about both and shows that competent discourse about values is fundamental

  17. Public opinion factors regarding nuclear power

    International Nuclear Information System (INIS)

    Benson, B.

    1991-01-01

    This paper is an effort to identify, as comprehensively as possible, public concerns about nuclear power, and to assess, where possible, the relative importance of these concerns as they relate to government regulation of and policy towards nuclear power. It is based on some two dozen in-depth interviews with key communicators representing the nuclear power industry, the environmental community, and government, as well as on the parallel efforts in our research project: (1) review of federal court case law, (2) a selective examination of the Nuclear Regulatory Commission (NRC) administrative process, and (3) the preceding George Mason University research project in this series. The paper synthesizes our findings about public attitudes towards nuclear power as expressed through federal court case law, NRC administrative law, public opinion surveys, and direct personal interviews. In so doing, we describe the public opinion environment in which the nuclear regulatory process must operate. Our premise is that public opinion ultimately underlies the approaches government agencies take towards regulating nuclear power, and that, to the degree that the nuclear power industry's practices are aligned with public opinion, a more favorable regulatory climate is possible

  18. Public opinion factors regarding nuclear power

    Energy Technology Data Exchange (ETDEWEB)

    Benson, B.

    1991-01-01

    This paper is an effort to identify, as comprehensively as possible, public concerns about nuclear power, and to assess, where possible, the relative importance of these concerns as they relate to government regulation of and policy towards nuclear power. It is based on some two dozen in-depth interviews with key communicators representing the nuclear power industry, the environmental community, and government, as well as on the parallel efforts in our research project: (1) review of federal court case law, (2) a selective examination of the Nuclear Regulatory Commission (NRC) administrative process, and (3) the preceding George Mason University research project in this series. The paper synthesizes our findings about public attitudes towards nuclear power as expressed through federal court case law, NRC administrative law, public opinion surveys, and direct personal interviews. In so doing, we describe the public opinion environment in which the nuclear regulatory process must operate. Our premise is that public opinion ultimately underlies the approaches government agencies take towards regulating nuclear power, and that, to the degree that the nuclear power industry's practices are aligned with public opinion, a more favorable regulatory climate is possible.

  19. Public opinion factors regarding nuclear power

    Energy Technology Data Exchange (ETDEWEB)

    Benson, B.

    1991-12-31

    This paper is an effort to identify, as comprehensively as possible, public concerns about nuclear power, and to assess, where possible, the relative importance of these concerns as they relate to government regulation of and policy towards nuclear power. It is based on some two dozen in-depth interviews with key communicators representing the nuclear power industry, the environmental community, and government, as well as on the parallel efforts in our research project: (1) review of federal court case law, (2) a selective examination of the Nuclear Regulatory Commission (NRC) administrative process, and (3) the preceding George Mason University research project in this series. The paper synthesizes our findings about public attitudes towards nuclear power as expressed through federal court case law, NRC administrative law, public opinion surveys, and direct personal interviews. In so doing, we describe the public opinion environment in which the nuclear regulatory process must operate. Our premise is that public opinion ultimately underlies the approaches government agencies take towards regulating nuclear power, and that, to the degree that the nuclear power industry`s practices are aligned with public opinion, a more favorable regulatory climate is possible.

  20. Ergonomics in nuclear and human factors engineering

    International Nuclear Information System (INIS)

    Muench, E.; Schultheiss, G.F.

    1988-01-01

    The work situation including man-machine-relationships in nuclear power plants is described. The overview gives only a compact summary of some important ergonomic parameters, i.e. human body dimension, human load, human characteristics and human knowledge. (DG)

  1. Δ-9,11 modification of glucocorticoids dissociates nuclear factor-κB inhibitory efficacy from glucocorticoid response element-associated side effects.

    Science.gov (United States)

    Baudy, Andreas R; Reeves, Erica K M; Damsker, Jesse M; Heier, Christopher; Garvin, Lindsay M; Dillingham, Blythe C; McCall, John; Rayavarapu, Sree; Wang, Zuyi; Vandermeulen, Jack H; Sali, Arpana; Jahnke, Vanessa; Duguez, Stephanie; DuBois, Debra; Rose, Mary C; Nagaraju, Kanneboyina; Hoffman, Eric P

    2012-10-01

    Glucocorticoids are standard of care for many inflammatory conditions, but chronic use is associated with a broad array of side effects. This has led to a search for dissociative glucocorticoids--drugs able to retain or improve efficacy associated with transrepression [nuclear factor-κB (NF-κB) inhibition] but with the loss of side effects associated with transactivation (receptor-mediated transcriptional activation through glucocorticoid response element gene promoter elements). We investigated a glucocorticoid derivative with a Δ-9,11 modification as a dissociative steroid. The Δ-9,11 analog showed potent inhibition of tumor necrosis factor-α-induced NF-κB signaling in cell reporter assays, and this transrepression activity was blocked by 17β-hydroxy-11β-[4-dimethylamino phenyl]-17α-[1-propynyl]estra-4,9-dien-3-one (RU-486), showing the requirement for the glucocorticoid receptor (GR). The Δ-9,11 analog induced the nuclear translocation of GR but showed the loss of transactivation as assayed by GR-luciferase constructs as well as mRNA profiles of treated cells. The Δ-9,11 analog was tested for efficacy and side effects in two mouse models of muscular dystrophy: mdx (dystrophin deficiency), and SJL (dysferlin deficiency). Daily oral delivery of the Δ-9,11 analog showed a reduction of muscle inflammation and improvements in multiple muscle function assays yet no reductions in body weight or spleen size, suggesting the loss of key side effects. Our data demonstrate that a Δ-9,11 analog dissociates the GR-mediated transcriptional activities from anti-inflammatory activities. Accordingly, Δ-9,11 analogs may hold promise as a source of safer therapeutic agents for chronic inflammatory disorders.

  2. Cyclin D1 represses p300 transactivation through a cyclin-dependent kinase-independent mechanism.

    Science.gov (United States)

    Fu, Maofu; Wang, Chenguang; Rao, Mahadev; Wu, Xiaofang; Bouras, Toula; Zhang, Xueping; Li, Zhiping; Jiao, Xuanmao; Yang, Jianguo; Li, Anping; Perkins, Neil D; Thimmapaya, Bayar; Kung, Andrew L; Munoz, Alberto; Giordano, Antonio; Lisanti, Michael P; Pestell, Richard G

    2005-08-19

    Cyclin D1 encodes a regulatory subunit, which with its cyclin-dependent kinase (Cdk)-binding partner forms a holoenzyme that phosphorylates and inactivates the retinoblastoma protein. In addition to its Cdk binding-dependent functions, cyclin D1 regulates cellular differentiation in part by modifying several transcription factors and nuclear receptors. The molecular mechanism through which cyclin D1 regulates the function of transcription factors involved in cellular differentiation remains to be clarified. The histone acetyltransferase protein p300 is a co-integrator required for regulation of multiple transcription factors. Here we show that cyclin D1 physically interacts with p300 and represses p300 transactivation. We demonstrated further that the interaction of the two proteins occurs at the peroxisome proliferator-activated receptor gamma-responsive element of the lipoprotein lipase promoter in the context of the local chromatin structure. We have mapped the domains in p300 and cyclin D1 involved in this interaction. The bromo domain and cysteine- and histidine-rich domains of p300 were required for repression by cyclin D1. Cyclin D1 repression of p300 was independent of the Cdk- and retinoblastoma protein-binding domains of cyclin D1. Cyclin D1 inhibits histone acetyltransferase activity of p300 in vitro. Microarray analysis identified a signature of genes repressed by cyclin D1 and induced by p300 that promotes cellular differentiation and induces cell cycle arrest. Together, our results suggest that cyclin D1 plays an important role in cellular proliferation and differentiation through regulation of p300.

  3. The human factor in nuclear reactor operation

    International Nuclear Information System (INIS)

    Bertron, L.

    1982-05-01

    The principal operating characteristics of nuclear power plants are summarized. A description of major hazards relating to operator fallibility in normal and abnormal operating conditions is followed by a specific analysis of control room hazards, shift organization and selection and training of management personnel

  4. Nuclear transport factors: global regulation of mitosis.

    Science.gov (United States)

    Forbes, Douglass J; Travesa, Anna; Nord, Matthew S; Bernis, Cyril

    2015-08-01

    The unexpected repurposing of nuclear transport proteins from their function in interphase to an equally vital and very different set of functions in mitosis was very surprising. The multi-talented cast when first revealed included the import receptors, importin alpha and beta, the small regulatory GTPase RanGTP, and a subset of nuclear pore proteins. In this review, we report that recent years have revealed new discoveries in each area of this expanding story in vertebrates: (a) The cast of nuclear import receptors playing a role in mitotic spindle regulation has expanded: both transportin, a nuclear import receptor, and Crm1/Xpo1, an export receptor, are involved in different aspects of spindle assembly. Importin beta and transportin also regulate nuclear envelope and pore assembly. (b) The role of nucleoporins has grown to include recruiting the key microtubule nucleator - the γ-TuRC complex - and the exportin Crm1 to the mitotic kinetochores of humans. Together they nucleate microtubule formation from the kinetochores toward the centrosomes. (c) New research finds that the original importin beta/RanGTP team have been further co-opted by evolution to help regulate other cellular and organismal activities, ranging from the actual positioning of the spindle within the cell perimeter, to regulation of a newly discovered spindle microtubule branching activity, to regulation of the interaction of microtubule structures with specific actin structures. (d) Lastly, because of the multitudinous roles of karyopherins throughout the cell cycle, a recent large push toward testing their potential as chemotherapeutic targets has begun to yield burgeoning progress in the clinic. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Human factors aspects of advanced instrumentation in the nuclear industry

    International Nuclear Information System (INIS)

    Carter, R.J.

    1989-01-01

    An important consideration in regards to the use of advanced instrumentation in the nuclear industry is the interface between the instrumentation system and the human. A survey, oriented towards identifying the human factors aspects of digital instrumentation, was conducted at a number of United States (US) and Canadian nuclear vendors and utilities. Human factors issues, subsumed under the categories of computer-generated displays, controls, organizational support, training, and related topics were identified. 20 refs., 2 tabs

  6. Orphan Nuclear Receptor Small Heterodimer Partner Negatively Regulates Growth Hormone-mediated Induction of Hepatic Gluconeogenesis through Inhibition of Signal Transducer and Activator of Transcription 5 (STAT5) Transactivation*

    Science.gov (United States)

    Kim, Yong Deuk; Li, Tiangang; Ahn, Seung-Won; Kim, Don-Kyu; Lee, Ji-Min; Hwang, Seung-Lark; Kim, Yong-Hoon; Lee, Chul-Ho; Lee, In-Kyu; Chiang, John Y. L.; Choi, Hueng-Sik

    2012-01-01

    Growth hormone (GH) is a key metabolic regulator mediating glucose and lipid metabolism. Ataxia telangiectasia mutated (ATM) is a member of the phosphatidylinositol 3-kinase superfamily and regulates cell cycle progression. The orphan nuclear receptor small heterodimer partner (SHP: NR0B2) plays a pivotal role in regulating metabolic processes. Here, we studied the role of ATM on GH-dependent regulation of hepatic gluconeogenesis in the liver. GH induced phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase gene expression in primary hepatocytes. GH treatment and adenovirus-mediated STAT5 overexpression in hepatocytes increased glucose production, which was blocked by a JAK2 inhibitor, AG490, dominant negative STAT5, and STAT5 knockdown. We identified a STAT5 binding site on the PEPCK gene promoter using reporter assays and point mutation analysis. Up-regulation of SHP by metformin-mediated activation of the ATM-AMP-activated protein kinase pathway led to inhibition of GH-mediated induction of hepatic gluconeogenesis, which was abolished by an ATM inhibitor, KU-55933. Immunoprecipitation studies showed that SHP physically interacted with STAT5 and inhibited STAT5 recruitment on the PEPCK gene promoter. GH-induced hepatic gluconeogenesis was decreased by either metformin or Ad-SHP, whereas the inhibition by metformin was abolished by SHP knockdown. Finally, the increase of hepatic gluconeogenesis following GH treatment was significantly higher in the liver of SHP null mice compared with that of wild-type mice. Overall, our results suggest that the ATM-AMP-activated protein kinase-SHP network, as a novel mechanism for regulating hepatic glucose homeostasis via a GH-dependent pathway, may be a potential therapeutic target for insulin resistance. PMID:22977252

  7. Examining Factors Affecting Attitudes toward Nuclear Power in Taiwan

    Science.gov (United States)

    Chan, Tzu-Jen

    Nuclear power has become a major issue in Taiwan for several decades. The objective of the present study is to obtain evidence about the major determinants contributing to attitudes toward nuclear power, by investigating socioeconomic factors, environmental attitudes, knowledge of issues, trust, and risk perception, in shaping nuclear attitudes. A face-to-face survey was conducted using paper-based questionnaires from July 2014 to September 2014. Finally, 364 surveys were collected, of which 356 met validation requirements. The findings showed (1) knowledge of issues, trust in university scientists, trust in environmental groups, and risk perception directly influence attitudes toward nuclear power. (2) Risk perception is directly influenced by trust in nuclear authorities, trust in environmental groups, environmental attitudes, and party preference. (3) Gender, age, and party preference directly influence knowledge, trust in nuclear authorities, or trust in university scientists. The potential explanations and implications of findings are discussed.

  8. U.S. Nuclear Regulatory Commission human factors program plan

    International Nuclear Information System (INIS)

    1986-04-01

    The purpose of the U.S. Nuclear Regulatory Commission (NRC) Human Factors Program Plan is to ensure that proper consideration is given to human factors in the design and operation of nuclear facilities. This revised plan addresses human factors issues related to the operation of nuclear power plants (NPPs). The three issues of concern are (1) the activities planned to provide the technical bases to resolve the remaining tasks related to human factors as described in NUREG-0660, The NRC Action Plan Developed as a Result of the TMI-2 Accident, and NUREG-0737, Clarification of TMI Action Plan Requirements; (2) the need to address the additional human factors efforts that were identified during implementation of the Action Plan; and (3) the actual fulfillment of those developmental activities specified in Revision 1 of this plan. The plan represents a systematic approach for addressing high priority human factors concerns important to NPP safety in FY 1986 through 1987

  9. Human factor analysis and preventive countermeasures in nuclear power plant

    International Nuclear Information System (INIS)

    Li Ye

    2010-01-01

    Based on the human error analysis theory and the characteristics of maintenance in a nuclear power plant, human factors of maintenance in NPP are divided into three different areas: human, technology, and organization. Which is defined as individual factors, including psychological factors, physiological characteristics, health status, level of knowledge and interpersonal skills; The technical factors including technology, equipment, tools, working order, etc.; The organizational factors including management, information exchange, education, working environment, team building and leadership management,etc The analysis found that organizational factors can directly or indirectly affect the behavior of staff and technical factors, is the most basic human error factor. Based on this nuclear power plant to reduce human error and measures the response. (authors)

  10. Phosphorylation of Src by phosphoinositide 3-kinase regulates beta-adrenergic receptor-mediated EGFR transactivation.

    Science.gov (United States)

    Watson, Lewis J; Alexander, Kevin M; Mohan, Maradumane L; Bowman, Amber L; Mangmool, Supachoke; Xiao, Kunhong; Naga Prasad, Sathyamangla V; Rockman, Howard A

    2016-10-01

    β2-Adrenergic receptors (β2AR) transactivate epidermal growth factor receptors (EGFR) through formation of a β2AR-EGFR complex that requires activation of Src to mediate signaling. Here, we show that both lipid and protein kinase activities of the bifunctional phosphoinositide 3-kinase (PI3K) enzyme are required for β2AR-stimulated EGFR transactivation. Mechanistically, the generation of phosphatidylinositol (3,4,5)-tris-phosphate (PIP3) by the lipid kinase function stabilizes β2AR-EGFR complexes while the protein kinase activity of PI3K regulates Src activation by direct phosphorylation. The protein kinase activity of PI3K phosphorylates serine residue 70 on Src to enhance its activity and induce EGFR transactivation following βAR stimulation. This newly identified function for PI3K, whereby Src is a substrate for the protein kinase activity of PI3K, is of importance since Src plays a key role in pathological and physiological signaling. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Non-transactivational, dual pathways for LPA-induced Erk1/2 activation in primary cultures of brown pre-adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Holmstroem, Therese E.; Mattsson, Charlotte L.; Wang, Yanling; Iakovleva, Irina; Petrovic, Natasa [Department of Physiology, The Wenner-Gren Institute, Stockholm University, SE-106 91 Stockholm (Sweden); Nedergaard, Jan, E-mail: jan@metabol.su.se [Department of Physiology, The Wenner-Gren Institute, Stockholm University, SE-106 91 Stockholm (Sweden)

    2010-10-01

    In many cell types, G-protein-coupled receptor (GPCR)-induced Erk1/2 MAP kinase activation is mediated via receptor tyrosine kinase (RTK) transactivation, in particular via the epidermal growth factor (EGF) receptor. Lysophosphatidic acid (LPA), acting via GPCRs, is a mitogen and MAP kinase activator in many systems, and LPA can regulate adipocyte proliferation. The mechanism by which LPA activates the Erk1/2 MAP kinase is generally accepted to be via EGF receptor transactivation. In primary cultures of brown pre-adipocytes, EGF can induce Erk1/2 activation, which is obligatory and determinant for EGF-induced proliferation of these cells. Therefore, we have here examined whether LPA, via EGF transactivation, can activate Erk1/2 in brown pre-adipocytes. We found that LPA could induce Erk1/2 activation. However, the LPA-induced Erk1/2 activation was independent of transactivation of EGF receptors (or PDGF receptors) in these cells (whereas in transformed HIB-1B brown adipocytes, the LPA-induced Erk1/2 activation indeed proceeded via EGF receptor transactivation). In the brown pre-adipocytes, LPA instead induced Erk1/2 activation via two distinct non-transactivational pathways, one G{sub i}-protein dependent, involving PKC and Src activation, the other, a PTX-insensitive pathway, involving PI3K (but not Akt) activation. Earlier studies showing LPA-induced Erk1/2 activation being fully dependent on RTK transactivation have all been performed in cell lines and transfected cells. The present study implies that in non-transformed systems, RTK transactivation may not be involved in the mediation of GPCR-induced Erk1/2 MAP kinase activation.

  12. Research of human factor in nuclear power plants

    International Nuclear Information System (INIS)

    Nopp, I.

    1983-01-01

    The question is discussed of the study of the human factor with regard to the reliability of nuclear power plant operation. The reliability of the human factor is the result of the functional fitness, motivation, working conditions and working regime of personnel. (J.B.)

  13. Economic benefits of power factor correction at a nuclear facility

    International Nuclear Information System (INIS)

    Boger, R.M.; Dalos, W.; Juguilon, M.E.

    1986-01-01

    The economic benefits of correcting poor power factor at an operating nuclear facility are shown. A project approach for achieving rapid return of investment without disrupting plant availability is described. Examples of technical problems associated with using capacitors for power factor correction are presented

  14. Consideration of Human Factors (HF) by the nuclear supervisory authorities

    International Nuclear Information System (INIS)

    Schaeffler, L.

    1999-01-01

    The general responsibilities of the German nuclear supervisory authorities are laid down in section 19 AtG (Atomic Energy Act). The authorities are to ensure and examine compliance with the provisions of the act as well as relevant subordinate legislation, orders of the regulatory authorities and provisions of the nuclear licensing documents, including post-licensing, supplementary directives. The paper explains the supervisory functions to be performed by the authorities with respect to proper consideration of advances in the state of the art in nuclear safety, which include research and implementation of results relating to human factors in power plant operation. (orig./CB) [de

  15. Nuclear energy - stabilising factor in the world economy

    International Nuclear Information System (INIS)

    Legassov, V.; Feoktistov, L.; Kouzmine, I.

    1986-01-01

    One of the most important factors for international stability is the development of the economy, reducing the risk of local armed conflicts which could escalate into world-wide nuclear war. Economic progress which plays such a vital part is in turn heavily dependent on energy supplies. The article takes a brief look at the role of nuclear power in this context. (B.M.S.)

  16. Key Factors for Nuclear Being Economic after Fukushima

    International Nuclear Information System (INIS)

    Roh, Myung Sub; Park, Seo Yeon

    2012-01-01

    It is hard to overstate the importance of electricity to the standard of living and the quality of life in a country. Electricity demand grows with population and with the changing nature, level and composition of economic and social activity. Civilization, industrialization and urbanization are, of course, key factors. It, historically, has shown that each major nuclear accident has caused a re-examination of the risk of nuclear power leading to more stringent safety requirement and higher costs. The Fukushima accident and its likely impact on future nuclear power development are difficult to foresee. The accident was a tragedy for the people affected and seriously undermined public confidence in the safety of nuclear power. A number of countries announced reviews of their programs, some took steps toward phasing out nuclear power entirely, and others reemphasized their expansion plans. The Korean nuclear community is carry out many ambitious projects for last three decades continuously and facing the another challenges relating to the future nuclear power economics and difficulty in financing new investment. In order to meet the above economic objective, it is strongly recommended that great emphasis should be placed on maintaining the nuclear economics without jeopardizing safety such as design simplification, standardization, shortening of construction period, increased availability, etc

  17. Inhibition of Nuclear Transcription Factor-κB and Activation of Peroxisome Proliferator-Activated Receptors in HepG2 Cells by Cucurbitane-Type Triterpene Glycosides from Momordica charantia

    Science.gov (United States)

    Nhiem, Nguyen Xuan; Yen, Pham Hai; Ngan, Nguyen Thi Thanh; Quang, Tran Hong; Kiem, Phan Van; Minh, Chau Van; Tai, Bui Huu; Cuong, Nguyen Xuan; Song, Seok Bean

    2012-01-01

    Abstract Momordica charantia: is used to treat various diseases, including inflammatory conditions. Previous reports indicated that the extract of this plant inhibits activation of nuclear transcription factor-κB (NF-κB) but activates peroxisome proliferator-activated receptor (PPAR). Additionally, cucurbitane-type triterpene glycosides are the main bioactive components of the fruit of M. charantia. Therefore, we investigated the anti-inflammatory activity of 17 cucurbitane-type triterpene glycosides (1–17) isolated from this plant. Their inhibition of NF-κB and activation of PPAR activities in HepG2 cells were measured using luciferase reporter and PPAR subtype transactivation assays. Compounds 6 and 8 were found to inhibit NF-κB activation stimulated by tumor necrosis factor-α (TNFα) in a dose-dependent manner. With 50% inhibition concentration (IC50) values of 0.4 μM, compounds 6 and 8 were more potent inhibitors than the positive control, sulfasalazine (IC50=0.9 μM). Compounds 4, 6, and 8 also inhibited TNFα-induced expressions of inducible nitric oxide synthase and cyclooxygenase-2 mRNA. However, only compound 13 significantly increased PPARγ transactivation. PMID:22248180

  18. Transfer factors for nuclear emergency preparedness

    International Nuclear Information System (INIS)

    Kostiainen, E.; Haenninen, R.; Rosen, K.; Haak, E.; Eriksson, Aa.; Nielsen, S.P.; Keith-Roach, M.; Salbu, B.

    2002-12-01

    This report by the NKS/BOK-1.4 project subgroup describes transfer factors for radiocaesium and radiostrontium for the fallout year and the years after the fallout. The intention has been to collect information on tools to assess the order of magnitude of radioactive contamination of agricultural products in an emergency situation in Nordic environment. The report describes transfer paths from fallout to plant, from soil to plant and to animal products. The transfer factors of radionuclides (Sr, Cs, I) given in the report are intended to be used for making rough estimates of the contamination of agricultural products soon after the heaviness and composition of the deposition (Bq m -2 ) is known. (au)

  19. Transfer factors for nuclear emergency preparedness

    Energy Technology Data Exchange (ETDEWEB)

    Kostiainen, E.; Haenninen, R. [Radiation and Nuclear Safety Authority (STUK) (Finland); Rosen, K.; Haak, E.; Eriksson, Aa. [Swedish Univ. of Agricultural Science (Sweden); Nielsen, S.P.; Keith-Roach, M. [Risoe National Lab. (Denmark); Salbu, B. [Agricultural Univ. of Norway (Norway)

    2002-12-01

    This report by the NKS/BOK-1.4 project subgroup describes transfer factors for radiocaesium and radiostrontium for the fallout year and the years after the fallout. The intention has been to collect information on tools to assess the order of magnitude of radioactive contamination of agricultural products in an emergency situation in Nordic environment. The report describes transfer paths from fallout to plant, from soil to plant and to animal products. The transfer factors of radionuclides (Sr, Cs, I) given in the report are intended to be used for making rough estimates of the contamination of agricultural products soon after the heaviness and composition of the deposition (Bq m{sup -2}) is known. (au)

  20. Human factor engineering applied to nuclear power plant design

    International Nuclear Information System (INIS)

    Manrique, A.; Valdivia, J.C.; Jimenez, A.

    2001-01-01

    For the design and construction of new nuclear power plants as well as for maintenance and operation of the existing ones new man-machine interface designs and modifications are been produced. For these new designs Human Factor Engineering must be applied the same as for any other traditional engineering discipline. Advantages of implementing adequate Human Factor Engineering techniques in the design of nuclear reactors have become not only a fact recognized by the majority of engineers and operators but also an explicit requirement regulated and mandatory for the new designs of the so called advanced reactors. Additionally, the big saving achieved by a nuclear power plant having an operating methodology which significantly decreases the risk of operating errors makes it necessary and almost vital its implementation. The first step for this is preparing a plan to incorporate all the Human Factor Engineering principles and developing an integral design of the Instrumentation and Control and Man-machine interface systems. (author)

  1. NLRC5: a newly discovered MHC class I transactivator (CITA)

    OpenAIRE

    Meissner, Torsten B.; Li, Amy; Kobayashi, Koichi S.

    2011-01-01

    Major histocompatibility complex (MHC) class I and class II are crucial for the function of the human adaptive immune system. An NLR protein, CIITA (MHC class II transactivator), is a master regulator of MHC class II gene expression as well as of some of the genes involved in MHC class II antigen presentation. It has recently been discovered that another member of the NLR protein family, NLRC5, transcriptionally activates MHC class I genes, and thus acts as “CITA” (MHC class I transactivator)...

  2. Economic Conditions and Factors Affecting New Nuclear Power Deployment

    Energy Technology Data Exchange (ETDEWEB)

    Harrison, Thomas J [ORNL

    2014-10-01

    This report documents work performed in support of the US Department of Energy Office of Nuclear Energy’s Advanced Small Modular Reactor (AdvSMR) program. The report presents information and results from economic analyses to describe current electricity market conditions and those key factors that may impact the deployment of AdvSMRs or any other new nuclear power plants. Thus, this report serves as a reference document for DOE as it moves forward with its plans to develop advanced reactors, including AdvSMRs. For the purpose of this analysis, information on electricity markets and nuclear power plant operating costs will be combined to examine the current state of the nuclear industry and the process required to successfully move forward with new nuclear power in general and AdvSMRs in particular. The current electricity market is generally unfavorable to new nuclear construction, especially in deregulated markets with heavy competition from natural gas and subsidized renewables. The successful and profitable operation of a nuclear power plant (or any power plant) requires the rate at which the electricity is sold to be sufficiently greater than the cost to operate. The wholesale rates in most US markets have settled into values that provide profits for most operating nuclear power plants but are too low to support the added cost of capital recovery for new nuclear construction. There is a strong geographic dependence on the wholesale rate, with some markets currently able to support new nuclear construction. However, there is also a strong geographic dependence on pronuclear public opinion; the areas where power prices are high tend to have unfavorable views on the construction of new nuclear power plants. The use of government-backed incentives, such as subsidies, can help provide a margin to help justify construction projects that otherwise may not seem viable. Similarly, low interest rates for the project will also add a positive margin to the economic

  3. Nuclear modification factor using Tsallis non-extensive statistics

    Energy Technology Data Exchange (ETDEWEB)

    Tripathy, Sushanta; Garg, Prakhar; Kumar, Prateek; Sahoo, Raghunath [Indian Institute of Technology Indore, Discipline of Physics, School of Basic Sciences, Simrol (India); Bhattacharyya, Trambak; Cleymans, Jean [University of Cape Town, UCT-CERN Research Centre and Department of Physics, Rondebosch (South Africa)

    2016-09-15

    The nuclear modification factor is derived using Tsallis non-extensive statistics in relaxation time approximation. The variation of the nuclear modification factor with transverse momentum for different values of the non-extensive parameter, q, is also observed. The experimental data from RHIC and LHC are analysed in the framework of Tsallis non-extensive statistics in a relaxation time approximation. It is shown that the proposed approach explains the R{sub AA} of all particles over a wide range of transverse momentum but does not seem to describe the rise in R{sub AA} at very high transverse momenta. (orig.)

  4. Correction factors for photon spectrometry in nuclear parameters study

    International Nuclear Information System (INIS)

    Patrao, Karla Cristina de Souza

    2004-10-01

    The goal of this work was the determination, using metrologic severity, the factors of correction for coincidences XX, Xγ and γγ and the factors of transference of efficiency for use in gamma spectrometry. On this way, it was carried through by determination of nuclear parameters of a nuclide used in medicine diagnostic ( 201 Tl) and the standardization of two environmental samples, of regular and irregular geometry, proceeding from the residual (ashes and slag) from the nuclear industry. The results shows that this adopted methodology is valid, and it allows its application for many different nuclides, including complex decay schema nuclides, using only photons spectrometry techniques on semiconductor detectors. (author)

  5. Inhibitory effect on activator protein-1, nuclear factor-kappaB, and cell transformation by extracts of strawberries (Fragaria x ananassa Duch.).

    Science.gov (United States)

    Wang, Shiow Y; Feng, Rentian; Lu, Yongju; Bowman, Linda; Ding, Min

    2005-05-18

    The inhibitory effects of strawberry (Fragaria x ananassa Duch.) antioxidant enzymes on tetradecanoylphorbol-13-acetate (TPA) or ultraviolet-B (UVB) induced activator protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB) were studied. The inhibitory effects of strawberry extracts on the proliferation and transformation of human and mouse cancer cells were also evaluated. Strawberries had high activities of glutathione peroxidase, superoxide dismutase, guaiacol peroxidase, ascorbate peroxidase, and glutathione reductase. Strawberry extracts inhibited the proliferation of human lung epithelial cancer cell line A549 and decreased TPA-induced neoplastic transformation of JB6 P+ mouse epidermal cells. Pretreatment of JB6 P+ mouse epidermal cells with strawberry extract resulted in the inhibition of both UVB- and TPA-induced AP-1 and NF-kappaB transactivation. Furthermore, strawberry extract also blocked TPA-induced phosphorylation of extracellular signal-regulated kinases (ERKs) and UVB-induced phosphorylation of ERKs and JNK kinase in JB6 P+ mouse epidermal cell culture. These results suggest that the ability of strawberries to block UVB- and TPA-induced AP-1 and NF-kappaB activation may be due to their antioxidant properties and their ability to reduce oxidative stress. The oxidative events that regulate AP-1 and NF-kappaB transactivation can be important molecular targets for cancer prevention. The strawberries may be highly effective as a chemopreventive agent that acts by targeting the down-regulation of AP-1 and NF-kappaB activities, blocking MAPK signaling, and suppressing cancer cell proliferation and transformation.

  6. Human factor in the problem of Russian nuclear industry safety

    International Nuclear Information System (INIS)

    Abramova, V.

    2002-01-01

    The approach to human factor definition, considered in the paper, consists of recognition of as many as possible factors for developing a complete list of factors, which have influence on mistakes or successful work of NPP personnel. Safety culture is considered as the main factor. The enhancement in nuclear power industry includes an optimization of organizational structures and development of personnel safety attitudes. The organizational factors, as possible root causes for human errors, need to be identified, assessed and improved. The organizational activities taken in Russia are presented

  7. US Nuclear Regulatory Commission human-factors program plan

    International Nuclear Information System (INIS)

    1983-08-01

    The purpose of the NRC Human Factors Program Plan is to ensure that proper consideration is given to human factors in the design, operation, and maintenance of nuclear facilities. This initial plan addresses nuclear power plants (NPP) and describes (1) the technical assistance and research activities planned to provide the technical bases for the resolution of the remaining human factors related tasks described in NUREG-0660, The NRC Action Plan Developed as a Result of the TMI-2 Accident, and NUREG-0737, Clarification of TMI Action Plan Requirements, and (2) the additional human factors efforts identified during implementation of the Action Plan that should receive NRC attention. The plan represents a systematic and comprehensive approach for addressing human factors concerns important to NPP safety in the FY-83 through FY-85 time frame

  8. Factors which could limit the nuclear fuel cycle development

    International Nuclear Information System (INIS)

    Pecqueur, M.; Barre, B.

    1977-01-01

    The nuclear fuel cycle is a most important industry for the energy future of the world. It has also a leading part as regards the physical continuity of energy supply of the countries engaged in the nuclear field. The development of this industry is subject to the economic or political constraints involved by the availability of raw materials, technologies or production means. The various limiting factors which could affect the different stages of the fuel cycle are linked with the technical, economic and financial aspects, with the impact on the environment, nuclear safety, risks of non-pacific uses and proliferation of arms. Interesting to note is also the correlation between the fuel cycle development and the problems of energy independence and security of nuclear programs. As a conclusion, the nuclear fuel cycle industry is confronted to difficulties due to its extremely rapid growth (doubling time 5 years) which only few heavy industries have encountered for long periods. It is more over submitted to the political and safety constraints always linked with nuclear matters. The task is therefore a difficult one. But the objective is worth-while since it is a condition to the development of nuclear industry [fr

  9. Properties of virion transactivator proteins encoded by primate cytomegaloviruses

    Directory of Open Access Journals (Sweden)

    Barry Peter A

    2009-05-01

    Full Text Available Abstract Background Human cytomegalovirus (HCMV is a betaherpesvirus that causes severe disease in situations where the immune system is immature or compromised. HCMV immediate early (IE gene expression is stimulated by the virion phosphoprotein pp71, encoded by open reading frame (ORF UL82, and this transactivation activity is important for the efficient initiation of viral replication. It is currently recognized that pp71 acts to overcome cellular intrinsic defences that otherwise block viral IE gene expression, and that interactions of pp71 with the cell proteins Daxx and ATRX are important for this function. A further property of pp71 is the ability to enable prolonged gene expression from quiescent herpes simplex virus type 1 (HSV-1 genomes. Non-human primate cytomegaloviruses encode homologs of pp71, but there is currently no published information that addresses their effects on gene expression and modes of action. Results The UL82 homolog encoded by simian cytomegalovirus (SCMV, strain Colburn, was identified and cloned. This ORF, named S82, was cloned into an HSV-1 vector, as were those from baboon, rhesus monkey and chimpanzee cytomegaloviruses. The use of an HSV-1 vector enabled expression of the UL82 homologs in a range of cell types, and permitted investigation of their abilities to direct prolonged gene expression from quiescent genomes. The results show that all UL82 homologs activate gene expression, and that neither host cell type nor promoter target sequence has major effects on these activities. Surprisingly, the UL82 proteins specified by non-human primate cytomegaloviruses, unlike pp71, did not direct long term expression from quiescent HSV-1 genomes. In addition, significant differences were observed in the intranuclear localization of the UL82 homologs, and in their effects on Daxx. Strikingly, S82 mediated the release of Daxx from nuclear domain 10 substructures much more rapidly than pp71 or the other proteins tested. All

  10. Human factors engineering plan for reviewing nuclear plant modernization programs

    Energy Technology Data Exchange (ETDEWEB)

    O' Hara, John; Higgins, James [Brookhaven National Laboratory, Upton, NY (United States)

    2004-12-01

    The Swedish Nuclear Power Inspectorate reviews the human factors engineering (HFE) aspects of nuclear power plants (NPPs) involved in the modernization of the plant systems and control rooms. The purpose of a HFE review is to help ensure personnel and public safety by verifying that accepted HFE practices and guidelines are incorporated into the program and nuclear power plant design. Such a review helps to ensure the HFE aspects of an NPP are developed, designed, and evaluated on the basis of a structured top-down system analysis using accepted HFE principles. The review addresses eleven HFE elements: HFE Program Management, Operating Experience Review, Functional Requirements Analysis and Allocation, Task Analysis, Staffing, Human Reliability Analysis, Human-System Interface Design, Procedure Development, Training Program Development, Human Factors Verification and Validation, and Design Implementation.

  11. Human factors engineering plan for reviewing nuclear plant modernization programs

    International Nuclear Information System (INIS)

    O'Hara, John; Higgins, James

    2004-12-01

    The Swedish Nuclear Power Inspectorate reviews the human factors engineering (HFE) aspects of nuclear power plants (NPPs) involved in the modernization of the plant systems and control rooms. The purpose of a HFE review is to help ensure personnel and public safety by verifying that accepted HFE practices and guidelines are incorporated into the program and nuclear power plant design. Such a review helps to ensure the HFE aspects of an NPP are developed, designed, and evaluated on the basis of a structured top-down system analysis using accepted HFE principles. The review addresses eleven HFE elements: HFE Program Management, Operating Experience Review, Functional Requirements Analysis and Allocation, Task Analysis, Staffing, Human Reliability Analysis, Human-System Interface Design, Procedure Development, Training Program Development, Human Factors Verification and Validation, and Design Implementation

  12. Personality Factors and Nuclear Power Plant Operators: Initial License Success

    Science.gov (United States)

    DeVita-Cochrane, Cynthia

    Commercial nuclear power utilities are under pressure to effectively recruit and retain licensed reactor operators in light of poor candidate training completion rates and recent candidate failures on the Nuclear Regulatory Commission (NRC) license exam. One candidate failure can cost a utility over $400,000, making the successful licensing of new operators a critical path to operational excellence. This study was designed to discover if the NEO-PI-3, a 5-factor measure of personality, could improve selection in nuclear utilities by identifying personality factors that predict license candidate success. Two large U.S. commercial nuclear power corporations provided potential participant contact information and candidate results on the 2014 NRC exam from their nuclear power units nation-wide. License candidates who participated (n = 75) completed the NEO-PI-3 personality test and results were compared to 3 outcomes on the NRC exam: written exam, simulated operating exam, and overall exam result. Significant correlations were found between several personality factors and both written and operating exam outcomes on the NRC exam. Further, a regression analysis indicated that personality factors, particularly Conscientiousness, predicted simulated operating exam scores. The results of this study may be used to support the use of the NEO-PI-3 to improve operator selection as an addition to the current selection protocol. Positive social change implications from this study include support for the use of a personality measure by utilities to improve their return-on-investment in candidates and by individual candidates to avoid career failures. The results of this study may also positively impact the public by supporting the safe and reliable operation of commercial nuclear power utilities in the United States.

  13. Flavonoid glycosides from Olax mannii: Structure elucidation and effect on the nuclear factor kappa B pathway.

    Science.gov (United States)

    Okoye, Festus B C; Sawadogo, Wamtinga Richard; Sendker, Jandirk; Aly, Amal H; Quandt, Bettina; Wray, Victor; Hensel, Andreas; Esimone, Charles O; Debbab, Abdessamad; Diederich, Marc; Proksch, Peter

    2015-12-24

    Olax mannii Oliv. (Olacaceae) is among the many medicinal plants used in Nigeria for the ethnomedicinal management of both cancer and inflammation. Such plants represent potential sources of innovative therapeutic agents for the treatment of cancer and other malignant disorders. While the majority of medicinal plants exert their anticancer effects by direct cytotoxicity on tumor cells, it is important that other mechanisms through which these plants can exhibit anticancer effects are investigated. Preliminary studies indicated that Olax mannii leaves are rich sources of novel flavonoid glycosides. The detailed chemistry as well the mechanisms through which these flavonoid constituents may exert their cancer chemo-preventive and therapeutic effects are, however, not yet investigated. The aim of this study is to carry out a detailed chemical investigation of Olax mannii leaves and the effects of the isolated constituents on the nuclear factor kappa B (NF-κB) pathway. A methanol leaf extract was subjected to various chromatographic separations to achieve isolation of flavonoid glycosides and the structures of the isolated compounds were elucidated by a combination of 1D and 2D NMR and high resolution mass spectrometry. Biological activities were assessed by measurement of cellular viability and proliferation using quantitative IncuCyte videomicroscopy, trypan blue staining and by quantification of the number of metabolically active K562 cells based on quantitation of ATP. The effect of the compounds on the inhibition of the NF-κB pathway as well as toxicity towards peripheral blood mononuclear cells to evaluate differential toxicity was also assayed. Chemical investigation of the methanol leaf extract of the plant material led to the isolation of three new flavonoid triglycosides, kaempferol 3-O-[α-D-apiofuranosyl-(1 → 2)-α-L-arabinofuranoside]-7-O-α-L-rhamnopyranoside (1), kaempferol 3-O-[β-D-glucopyranosyl-(1 → 2)-α-L-arabinofuranoside]-7-O

  14. A report on human factors in nuclear safety

    International Nuclear Information System (INIS)

    1983-03-01

    Following the Three Mile Island incident of 1979, studies were undertaken by the Atomic Energy Control Board (AECB), in-house and through outside consultants, to address the role of human factors in the regulatory process. This report by the Advisory Committee on Nuclear Safety (ACNS) comments briefly on these studies and offers suggestions which would promote a more formal treatment of human factors by the AECB

  15. Dissecting the signaling events that impact classical nuclear import and target nuclear transport factors.

    Directory of Open Access Journals (Sweden)

    Mohamed Kodiha

    2009-12-01

    Full Text Available Signaling through MEK-->ERK1/2 and PI3 kinases is implicated in many aspects of cell physiology, including the survival of oxidant exposure. Oxidants play a role in numerous physiological and pathophysiological processes, many of which rely on transport in and out of the nucleus. However, how oxidative stress impacts nuclear trafficking is not well defined.To better understand the effect of stress on nucleocytoplasmic trafficking, we exposed cells to the oxidant diethyl maleate. This treatment activated MEK-->ERK1/2 as well as PI3 kinase-->Akt cascades and triggered the inhibition of classical nuclear import. To define the molecular mechanisms that regulate nuclear transport, we examined whether MEK and PI3 kinase signaling affected the localization of key transport factors. Using recently developed tools for image acquisition and analysis, the subcellular distributions of importin-alpha, CAS, and nucleoporins Nup153 and Nup88 were quantified in different cellular compartments. These studies identified specific profiles for the localization of transport factors in the nucleus and cytoplasm, and at the nuclear envelope. Our results demonstrate that MEK and PI3 kinase signaling as well as oxidative stress control nuclear trafficking and the localization of transport components. Furthermore, stress not only induced changes in transport factor distribution, but also upregulated post-translational modification of transport factors. Our results are consistent with the idea that the phosphorylation of importin-alpha, CAS, Nup153, and Nup88, and the O-GlcNAc modification of Nup153 increase when cells are exposed to oxidant.Our studies defined the complex regulation of classical nuclear import and identified key transport factors that are targeted by stress, MEK, and PI3 kinase signaling.

  16. Full trans-activation mediated by the immediate-early protein of equine herpesvirus 1 requires a consensus TATA box, but not its cognate binding sequence.

    Science.gov (United States)

    Kim, Seong K; Shakya, Akhalesh K; O'Callaghan, Dennis J

    2016-01-04

    The immediate-early protein (IEP) of equine herpesvirus 1 (EHV-1) has extensive homology to the IEP of alphaherpesviruses and possesses domains essential for trans-activation, including an acidic trans-activation domain (TAD) and binding domains for DNA, TFIIB, and TBP. Our data showed that the IEP directly interacted with transcription factor TFIIA, which is known to stabilize the binding of TBP and TFIID to the TATA box of core promoters. When the TATA box of the EICP0 promoter was mutated to a nonfunctional TATA box, IEP-mediated trans-activation was reduced from 22-fold to 7-fold. The IEP trans-activated the viral promoters in a TATA motif-dependent manner. Our previous data showed that the IEP is able to repress its own promoter when the IEP-binding sequence (IEBS) is located within 26-bp from the TATA box. When the IEBS was located at 100 bp upstream of the TATA box, IEP-mediated trans-activation was very similar to that of the minimal IE(nt -89 to +73) promoter lacking the IEBS. As the distance from the IEBS to the TATA box decreased, IEP-mediated trans-activation progressively decreased, indicating that the IEBS located within 100 bp from the TATA box sequence functions as a distance-dependent repressive element. These results indicated that IEP-mediated full trans-activation requires a consensus TATA box of core promoters, but not its binding to the cognate sequence (IEBS). Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Nuclear tristetraprolin acts as a corepressor of multiple steroid nuclear receptors in breast cancer cells

    Directory of Open Access Journals (Sweden)

    Tonatiuh Barrios-García

    2016-06-01

    Full Text Available Tristetraprolin (TTP is a 34-kDa, zinc finger-containing factor that in mammalian cells acts as a tumor suppressor protein through two different mechanisms. In the cytoplasm TTP promotes the decay of hundreds of mRNAs encoding cell factors involved in inflammation, tissue invasion, and metastasis. In the cell nucleus TTP has been identified as a transcriptional corepressor of the estrogen receptor alpha (ERα, which has been associated to the development and progression of the majority of breast cancer tumors. In this work we report that nuclear TTP modulates the transactivation activity of progesterone receptor (PR, glucocorticoid receptor (GR and androgen receptor (AR. In recent years these steroid nuclear receptors have been shown to be of clinical and therapeutical relevance in breast cancer. The functional association between TTP and steroid nuclear receptors is supported by the finding that TTP physically interacts with ERα, PR, GR and AR in vivo. We also show that TTP overexpression attenuates the transactivation of all the steroid nuclear receptors tested. In contrast, siRNA-mediated reduction of endogenous TTP expression in MCF-7 cells produced an increase in the transcriptional activities of ERα, PR, GR and AR. Taken together, these results suggest that the function of nuclear TTP in breast cancer cells is to act as a corepressor of ERα, PR, GR and AR. We propose that the reduction of TTP expression observed in different types of breast cancer tumors may contribute to the development of this disease by producing a dysregulation of the transactivation activity of multiple steroid nuclear receptors.

  18. Quality management in the nuclear industry: the human factor

    Energy Technology Data Exchange (ETDEWEB)

    1990-01-01

    In the nuclear industry it is vital to understand the 'human factor' with regard to plant performance and plant safety. A proper management system ensures that personnel perform their duties correctly. 'Quality Management in the Nuclear Industry: the Human Factor', was a conference organized by the Institution of Mechanical Engineers in October 1990. The conference covered a wide range of topics on an international level including: standards, licensing and regulatory procedures; selection assessment and training of personnel; feedback from experience of good practice and of deviations; management and support of personnel performance; modelling and evaluation of human factors. The papers presented at the conference are contained in this volume. All twenty papers are indexed separately. (author).

  19. US Nuclear Regulatory Commission Human Factors Program Plan. Revision 1

    International Nuclear Information System (INIS)

    1984-09-01

    The purpose of the NRC Human Factors Program Plan (NUREG-0985) is to ensure that proper consideration is given to human factors in the design, operation, and maintenance of nuclear facilities. This revised plan addresses nuclear power plants (NPPs) and describes (1) the technical assistance and research activities planned to provide the technical bases for the resolution of the remaining human factors related tasks described in NUREG-0660, THE NRC Action Plan developed as a result of the TMI-2 Accident, and NUREG-0737, Clarification of TMI Action Plan Requirements; (2) the additional human factors efforts identified during implementation of the Action Plan that should receive NRC attention; (3) conduct of developmental activities specified in NUREG-0985 during FY-83; and (4) the impact of Section 306 of the Nuclear Waste Policy Act of 1982, PL 97-425. The plan represents a systematic and comprehensive approach for addressing human factors concerns important to NPP safety in the FY-84 through FY-86 time frame

  20. Agmatine inhibits nuclear factor-jB nuclear translocation in acute ...

    African Journals Online (AJOL)

    Secondary damage after acute spinal cord compression injury (SCCI) exacerbates initial insult. Nuclear factor kappa-B (NF-jB)-p65 activation is involved in SCCI deleterious effects. Agmatine (Agm) showed neuroprotection against various CNS injuries. However, Agm impact on NF-jB signaling in acute SCCI remains to be ...

  1. Nuclear Factor-kappaB in Autoimmunity: Man and Mouse.

    Science.gov (United States)

    Miraghazadeh, Bahar; Cook, Matthew C

    2018-01-01

    NF-κB (nuclear factor-kappa B) is a transcription complex crucial for host defense mediated by innate and adaptive immunity, where canonical NF-κB signaling, mediated by nuclear translocation of RelA, c-Rel, and p50, is important for immune cell activation, differentiation, and survival. Non-canonical signaling mediated by nuclear translocation of p52 and RelB contributes to lymphocyte maturation and survival and is also crucial for lymphoid organogenesis. We outline NF-κB signaling and regulation, then summarize important molecular contributions of NF-κB to mechanisms of self-tolerance. We relate these mechanisms to autoimmune phenotypes described in what is now a substantial catalog of immune defects conferred by mutations in NF-κB pathways in mouse models. Finally, we describe Mendelian autoimmune syndromes arising from human NF-κB mutations, and speculate on implications for understanding sporadic autoimmune disease.

  2. Factors affecting the next generation of nuclear power

    International Nuclear Information System (INIS)

    Remick, F.J.

    1990-01-01

    For both financial, environmental and health reasons, and because of external and internal factors affecting this nation's energy supply, nuclear power will likely play a part in supplying this nation's energy in the coming decades. I believe this to be true for some other parts of the world as well. Even some severe critics of the nuclear power industry and the NRC might agree with me on this point. Increasing concern with the environmental consequences of the burning of fossil fuels has led some former opponents of the use of nuclear power to balance anew the risks and benefits of nuclear power and to modify to some degree their former opposition. A related concern with the adequacy of the energy supply is leading others to modify their positions. According to analyses done by the U.S. Department of Energy, after 1994 the United States will no longer be able to assure all its citizens a reliable supply of electricity. Already, many areas of the country are in need of additional electric capacity. In both Sweden and Switzerland, similar concerns have led to the adoption by many of more compromising positions. Some critics of nuclear power may in the end still reject it as an alternative, but, with the increased pressures on the environment and on our energy supply, nuclear power is an alternative which cannot be rejected without the most serious consideration. This should be, I believe, a point of consensus among us. In sum, there is a future for nuclear power in the sense that there is a use for it

  3. Major factors influencing craft productivity in nuclear power plant construction

    International Nuclear Information System (INIS)

    Borcherding, J.D.; Sebastian, S.J.

    1980-01-01

    This paper reports on a research study whose objective was to determine the most influential factors adversely affecting craft productivity in nuclear power plant construction from the perspective of the tradesmen employed at the sites. Data were collected through the use of a questionnaire survey and group interview sessions, predominantly with workmen, at six nuclear power plant construction projects. Craftsmen were chosen as the major data base because of their awareness of how their time would actually be spent on the project. Topics considered include the factors influencing craft productivity, material availability, redoing work, crew interfacing, overcrowded work areas, instruction time, inspection delays, craft turnover, craft absenteeism, foreman changes, foreman incompetence, engineering design lead time, comprehensive scheduling of the design function, the responsibility of the utility, value engineering, plant standardization, the effective utilization of the planning and scheduling system, and the labor-management committee

  4. Human factor engineering applied to nuclear power plant design

    International Nuclear Information System (INIS)

    Manrique, A.; Valdivia, J.C.

    2007-01-01

    Advantages of implementing adequate Human Factor Engineering techniques in the design of nuclear reactors have become not only a fact recognized by the majority of engineers and operators but also an explicit requirement regulated and mandatory for the new designs of the so called advanced reactors. The first step for this is preparing a plan to incorporate all the Human Factor Engineering principles and developing an integral design of the Instrumentation and Control and Man-machine interface systems. Such a plan should state: -) Activities to be performed, and -) Creation of a Human Factor Engineering team adequately qualified. The Human Factor Engineering team is an integral part of the design team and is strongly linked to the engineering organizations but simultaneously has independence to act and is free to evaluate designs and propose changes in order to enhance human behavior. TECNATOM S.A. (a Spanish company) has been a part of the Design and Human Factor Engineering Team and has collaborated in the design of an advanced Nuclear Power Plant, developing methodologies and further implementing those methodologies in the design of the plant systems through the development of the plant systems operational analysis and of the man-machine interface design. The methodologies developed are made up of the following plans: -) Human Factor Engineering implementation in the Man-Machine Interface design; -) Plant System Functional Requirement Analysis; -) Allocation of Functions to man/machine; -) Task Analysis; -) Human-System Interface design; -) Control Room Verification and -) Validation

  5. Nuclear Regulatory Commission Human Factors Program Plan. Revision 2

    International Nuclear Information System (INIS)

    1986-04-01

    This document is the Second Annual Revision to the NRC Human Factors Program Plan. The first edition was published in August 1983. Revision 1 was published in July of 1984. Purpose of the NRC Human Factors Program is to ensure that proper consideration is given to human factors in the design and operation of nuclear power plants. This document describes the plans of the Office of Nuclear Reactor Regulation to address high priority human factors concerns of importance to reactor safety in FY 1986 and FY 1987. Revision 2 of the plan incorporates recent Commission decisions and policies bearing on the human factors aspects of reactor safety regulation. With a few exceptions, the principal changes from prior editions reflect a shift from developing new requirements to staff evaluation of industry progress in resolving human factors issues. The plan addresses seven major program elements: (1) Training, (2) Licensing Examinations, (3) Procedures, (4) Man-Machine Interface, (5) Staffing and Qualifications, (6) Management and Organization, and (7) Human Performance

  6. HTLV-1 subgroups associated with the risk of HAM/TSP are related to viral and host gene expression in peripheral blood mononuclear cells, independent of the transactivation functions of the viral factors.

    Science.gov (United States)

    Yasuma, Keiko; Matsuzaki, Toshio; Yamano, Yoshihisa; Takashima, Hiroshi; Matsuoka, Masao; Saito, Mineki

    2016-08-01

    Among human T cell leukemia virus type 1 (HTLV-1)-infected individuals, the risk of developing HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) across lifetime differs between ethnic groups. There is an association between HTLV-1 tax gene subgroups (subgroup-A or subgroup-B) and the risk of HAM/TSP in the Japanese population. In this study, we investigated the full-length proviral genome sequences of various HTLV-1-infected cell lines and patient samples. The functional differences in the viral transcriptional regulators Tax and HTLV-1 bZIP factor (HBZ) between each subgroup and the relationships between subgroups and the clinical and laboratory characteristics of HAM/TSP patients were evaluated. The results of these analyses indicated the following: (1) distinct nucleotide substitutions corresponding to each subgroup were associated with nucleotide substitutions in viral structural, regulatory, and accessory genes; (2) the HBZ messenger RNA (mRNA) expression in HTLV-1-infected cells was significantly higher in HAM/TSP patients with subgroup-B than in those with subgroup-A; (3) a positive correlation was observed between the expression of HBZ mRNA and its target Foxp3 mRNA in HAM/TSP patients with subgroup-B, but not in patients with subgroup-A; (4) no clear differences were noted in clinical and laboratory characteristics between HAM/TSP patients with subgroup-A and subgroup-B; and (5) no functional differences were observed in Tax and HBZ between each subgroup based on reporter gene assays. Our results indicate that although different HTLV-1 subgroups are characterized by different patterns of viral and host gene expression in HAM/TSP patients via independent mechanisms of direct transcriptional regulation, these differences do not significantly affect the clinical and laboratory characteristics of HAM/TSP patients.

  7. The MHC-II transactivator CIITA inhibits Tat function and HIV-1 replication in human myeloid cells.

    Science.gov (United States)

    Forlani, Greta; Turrini, Filippo; Ghezzi, Silvia; Tedeschi, Alessandra; Poli, Guido; Accolla, Roberto S; Tosi, Giovanna

    2016-04-18

    We previously demonstrated that the HLA class II transactivator CIITA inhibits HIV-1 replication in T cells by competing with the viral transactivator Tat for the binding to Cyclin T1 subunit of the P-TEFb complex. Here, we analyzed the anti-viral function of CIITA in myeloid cells, another relevant HIV-1 target cell type. We sinvestigated clones of the U937 promonocytic cell line, either permissive (Plus) or non-permissive (Minus) to HIV-1 replication. This different phenotype has been associated with the expression of TRIM22 in U937 Minus but not in Plus cells. U937 Plus cells stably expressing CIITA were generated and HLA-II positive clones were selected by cell sorting and cloning. HLA and CIITA proteins were analyzed by cytofluorometry and western blotting, respectively. HLA-II DR and CIITA mRNAs were quantified by qRT-PCR. Tat-dependent transactivation was assessed by performing the HIV-1 LTR luciferase gene reporter assay. Cells were infected with HIV-1 and viral replication was evaluated by measuring the RT activity in culture supernatants. CIITA was expressed only in HLA-II-positive U937 Minus cells, and this was strictly correlated with inhibition of Tat-dependent HIV-1 LTR transactivation in Minus but not in Plus cells. Overexpression of CIITA in Plus cells restored the suppression of Tat transactivation, confirming the inhibitory role of CIITA. Importantly, HIV-1 replication was significantly reduced in Plus-CIITA cells with respect to Plus parental cells. This effect was independent of TRIM22 as CIITA did not induce TRIM22 expression in Plus-CIITA cells. U937 Plus and Minus cells represent an interesting model to study the role of CIITA in HIV-1 restriction in the monocytic/macrophage cell lineage. The differential expression of CIITA in CIITA-negative Plus and CIITA-positive Minus cells correlated with their capacity to support or not HIV-1 replication, respectively. In Minus cells CIITA targeted the viral transactivator Tat to inhibit HIV-1

  8. Key Response Planning Factors for the Aftermath of Nuclear Terrorism

    Energy Technology Data Exchange (ETDEWEB)

    Buddemeier, B R; Dillon, M B

    2009-01-21

    Despite hundreds of above-ground nuclear tests and data gathered from Hiroshima and Nagasaki, the effects of a ground-level, low-yield nuclear detonation in a modern urban environment are still the subject of considerable scientific debate. Extensive review of nuclear weapon effects studies and discussions with nuclear weapon effects experts from various federal agencies, national laboratories, and technical organizations have identified key issues and bounded some of the unknowns required to support response planning for a low-yield, ground-level nuclear detonation in a modern U.S. city. This study, which is focused primarily upon the hazards posed by radioactive fallout, used detailed fallout predictions from the advanced suite of three-dimensional (3-D) meteorology and plume/fallout models developed at Lawrence Livermore National Laboratory (LLNL), including extensive global Key Response Planning Factors for the Aftermath of Nuclear Terrorism geographical and real-time meteorological databases to support model calculations. This 3-D modeling system provides detailed simulations that account for complex meteorology and terrain effects. The results of initial modeling and analysis were presented to federal, state, and local working groups to obtain critical, broad-based review and feedback on strategy and messaging. This effort involved a diverse set of communities, including New York City, National Capitol Regions, Charlotte, Houston, Portland, and Los Angeles. The largest potential for reducing casualties during the post-detonation response phase comes from reducing exposure to fallout radiation. This can be accomplished through early, adequate sheltering followed by informed, delayed evacuation.B The response challenges to a nuclear detonation must be solved through multiple approaches of public education, planning, and rapid response actions. Because the successful response will require extensive coordination of a large number of organizations, supplemented by

  9. Human factors methods for nuclear control room design. Volume I. Human factors enhancement of existing nuclear control rooms. Final report

    International Nuclear Information System (INIS)

    Seminara, J.L.; Seidenstein, S.; Eckert, S.K.; Smith, D.L.

    1979-11-01

    Human factors engineering is an interdisciplinary specialty concerned with influencing the design of equipment systems, facilities, and operational environments to promote safe, efficient, and reliable operator performance. Human factors approaches were applied in the design of representative nuclear power plant control panels. First, methods for upgrading existing operational control panels were examined. Then, based on detailed human factors analyses of operator information and control requirements, designs of reactor, feedwater, and turbine-generator control panels were developed to improve the operator-control board interface, thereby reducing the potential for operator errors. In addition to examining present-generation concepts, human factors aspects of advanced systems and of hybrid combinations of advanced and conventional designs were investigated. Special attention was given to warning system designs. Also, a survey was conducted among control board designers to (1) develop an overview of design practices in the industry, and (2) establish appropriate measures leading to a more systematic concern for human factors in control board design

  10. Transactivation activity and nucleocytoplasmic transport of β-catenin are independently regulated by its C-terminal end.

    Science.gov (United States)

    Maturana, J L; Niechi, I; Silva, E; Huerta, H; Cataldo, R; Härtel, S; Barros, L F; Galindo, M; Tapia, J C

    2015-11-15

    The key protein in the canonical Wnt pathway is β-catenin, which is phosphorylated both in absence and presence of Wnt signals by different kinases. Upon activation in the cytoplasm, β-catenin can enter into the nucleus to transactivate target gene expression, many of which are cancer-related genes. The mechanism governing β-catenin's nucleocytoplasmic transport has been recently unvealed, although phosphorylation at its C-terminal end and its functional consequences are not completely understood. Serine 646 of β-catenin is a putative CK2 phosphorylation site and lies in a region which has been proposed to be important for its nucleocytoplasmic transport and transactivation activity. This residue was mutated to aspartic acid mimicking CK2-phosphorylation and its effects on β-catenin activity as well as localization were explored. β-Catenin S6464D did not show significant differences in both transcriptional activity and nuclear localization compared to the wild-type form, but displayed a characteristic granular nuclear pattern. Three-dimensional models of nuclei were constructed which showed differences in number and volume of granules, being those from β-catenin S646D more and smaller than the wild-type form. FRAP microscopy was used to compare nuclear export of both proteins which showed a slightly higher but not significant retention of β-catenin S646D. Altogether, these results show that C-terminal phosphorylation of β-catenin seems to be related with its nucleocytoplasmic transport but not transactivation activity. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Molecular geometric phase from the exact electron-nuclear factorization

    Science.gov (United States)

    Requist, Ryan; Tandetzky, Falk; Gross, E. K. U.

    2016-04-01

    The Born-Oppenheimer electronic wave function ΦRBO(r ) picks up a topological phase factor ±1 , a special case of Berry phase, when it is transported around a conical intersection of two adiabatic potential energy surfaces in R space. We show that this topological quantity reverts to a geometric quantity ei γ if the geometric phase γ =∮Im .d Rμ is evaluated with the conditional electronic wave function ΦR(r ) from the exact electron-nuclear factorization ΦR(r ) χ (R ) instead of the adiabatic function ΦRBO(r ) . A model of a pseudorotating triatomic molecule, also applicable to dynamical Jahn-Teller ions in bulk crystals, provides examples of nontrivial induced vector potentials and molecular geometric phase from the exact factorization. The induced vector potential gives a contribution to the circulating nuclear current that cannot be removed by a gauge transformation. The exact potential energy surface is calculated and found to contain a term depending on the Fubini-Study metric for the conditional electronic wave function.

  12. Human Factors Considerations in New Nuclear Power Plants: Detailed Analysis.

    Energy Technology Data Exchange (ETDEWEB)

    OHara,J.; Higgins, J.; Brown, W.; Fink, R.

    2008-02-14

    This Nuclear Regulatory Commission (NRC) sponsored study has identified human-performance issues in new and advanced nuclear power plants. To identify the issues, current industry developments and trends were evaluated in the areas of reactor technology, instrumentation and control technology, human-system integration technology, and human factors engineering (HFE) methods and tools. The issues were organized into seven high-level HFE topic areas: Role of Personnel and Automation, Staffing and Training, Normal Operations Management, Disturbance and Emergency Management, Maintenance and Change Management, Plant Design and Construction, and HFE Methods and Tools. The issues where then prioritized into four categories using a 'Phenomena Identification and Ranking Table' methodology based on evaluations provided by 14 independent subject matter experts. The subject matter experts were knowledgeable in a variety of disciplines. Vendors, utilities, research organizations and regulators all participated. Twenty issues were categorized into the top priority category. This Brookhaven National Laboratory (BNL) technical report provides the detailed methodology, issue analysis, and results. A summary of the results of this study can be found in NUREG/CR-6947. The research performed for this project has identified a large number of human-performance issues for new control stations and new nuclear power plant designs. The information gathered in this project can serve as input to the development of a long-term strategy and plan for addressing human performance in these areas through regulatory research. Addressing human-performance issues will provide the technical basis from which regulatory review guidance can be developed to meet these challenges. The availability of this review guidance will help set clear expectations for how the NRC staff will evaluate new designs, reduce regulatory uncertainty, and provide a well-defined path to new nuclear power plant

  13. Nuclear factor-kappa B family member RelB inhibits human immunodeficiency virus-1 Tat-induced tumor necrosis factor-alpha production.

    Directory of Open Access Journals (Sweden)

    Michelle Kiebala

    2010-07-01

    Full Text Available Human Immunodeficiency Virus-1 (HIV-1-associated neurocognitive disorder (HAND is likely neuroinflammatory in origin, believed to be triggered by inflammatory and oxidative stress responses to cytokines and HIV protein gene products such as the HIV transactivator of transcription (Tat. Here we demonstrate increased messenger RNA for nuclear factor-kappa B (NF-kappaB family member, transcription factor RelB, in the brain of doxycycline-induced Tat transgenic mice, and increased RelB synthesis in Tat-exposed microglial cells. Since genetic ablation of RelB in mice leads to multi-organ inflammation, we hypothesized that Tat-induced, newly synthesized RelB inhibits cytokine production by microglial cells, possibly through the formation of transcriptionally inactive RelB/RelA complexes. Indeed, tumor necrosis factor-alpha (TNFalpha production in monocytes isolated from RelB deficient mice was significantly higher than in monocytes isolated from RelB expressing controls. Moreover, RelB overexpression in microglial cells inhibited Tat-induced TNFalpha synthesis in a manner that involved transcriptional repression of the TNFalpha promoter, and increased phosphorylation of RelA at serine 276, a prerequisite for increased RelB/RelA protein interactions. The Rel-homology-domain within RelB was necessary for this interaction. Overexpression of RelA itself, in turn, significantly increased TNFalpha promoter activity, an effect that was completely blocked by RelB overexpression. We conclude that RelB regulates TNFalpha cytokine synthesis by competitive interference binding with RelA, which leads to downregulation of TNFalpha production. Moreover, because Tat activates both RelB and TNFalpha in microglia, and because Tat induces inflammatory TNFalpha synthesis via NF-kappaB, we posit that RelB serves as a cryoprotective, anti-inflammatory, counter-regulatory mechanism for pathogenic NF-kappaB activation. These findings identify a novel regulatory pathway for

  14. A gene-specific role for the Ssu72 RNAPII CTD phosphatase in HIV-1 Tat transactivation.

    Science.gov (United States)

    Chen, Yupeng; Zhang, Lirong; Estarás, Conchi; Choi, Seung H; Moreno, Luis; Karn, Jonathan; Moresco, James J; Yates, John R; Jones, Katherine A

    2014-10-15

    HIV-1 Tat stimulates transcription elongation by recruiting the P-TEFb (positive transcription elongation factor-b) (CycT1:CDK9) C-terminal domain (CTD) kinase to the HIV-1 promoter. Here we show that Tat transactivation also requires the Ssu72 CTD Ser5P (S5P)-specific phosphatase, which mediates transcription termination and intragenic looping at eukaryotic genes. Importantly, HIV-1 Tat interacts directly with Ssu72 and strongly stimulates its CTD phosphatase activity. We found that Ssu72 is essential for Tat:P-TEFb-mediated phosphorylation of the S5P-CTD in vitro. Interestingly, Ssu72 also stimulates nascent HIV-1 transcription in a phosphatase-dependent manner in vivo. Chromatin immunoprecipitation (ChIP) experiments reveal that Ssu72, like P-TEFb and AFF4, is recruited by Tat to the integrated HIV-1 proviral promoter in TNF-α signaling 2D10 T cells and leaves the elongation complex prior to the termination site. ChIP-seq (ChIP combined with deep sequencing) and GRO-seq (genome-wide nuclear run-on [GRO] combined with deep sequencing) analysis further reveals that Ssu72 predominantly colocalizes with S5P-RNAPII (RNA polymerase II) at promoters in human embryonic stem cells, with a minor peak in the terminator region. A few genes, like NANOG, also have high Ssu72 at the terminator. Ssu72 is not required for transcription at most cellular genes but has a modest effect on cotranscriptional termination. We conclude that Tat alters the cellular function of Ssu72 to stimulate viral gene expression and facilitate the early S5P-S2P transition at the integrated HIV-1 promoter. © 2014 Chen et al.; Published by Cold Spring Harbor Laboratory Press.

  15. Factors determining the UK's back-end nuclear fuel cycle strategy and future nuclear systems

    International Nuclear Information System (INIS)

    Dunn, M.J.; Ainsworth, Z.E.

    2002-01-01

    Nuclear generating capacity in the UK is static with no units currently under construction. The AGRs and the UK's only PWR, Sizewell B, are operated by British Energy Generation Ltd (BEGL) and British Energy Generation (UK) Ltd (BEG(UK)L), who are subsidiaries of British Energy plc (BE) which was privatised in July 1996. Ownership of the Magnox stations, which were excluded from this privatisation, has now been transferred to BNFL.Government policy on spent fuel management in the UK is that it is for the owners of the spent fuel to decide on the appropriate spent fuel management options, based on their own commercial judgement, subject to meeting the necessary regulatory requirements. The main factors which have predominantly determined UK utility decisions on spent fuel management, to date, have been based on the technical considerations of the spent fuel characteristics, economic attractiveness of the options and at reactor site spent fuel storage capacities. To date, reprocessing has been the dominant form of spent fuel treatment in the UK. Spent fuel storage facilities consist of a mixture of at-reactor stores and large, centralised ponds associated with the reprocessing activities which take place at the Sellafield site. BEGL and BEG(UK)L have contracts for the lifetime arisings of AGR fuel which allow for all AGR spent fuel to be sent to Sellafield for reprocessing or long-term storage. The prompt reprocessing of all Magnox fuel will continue, and spent PWR fuel will continue to be stored at the reactor site in the short to medium term. It is likely that a combination of factors, which are discussed later in this paper, will continue to affect back-end nuclear fuel cycle strategy and future nuclear systems. (author)

  16. Influence factors on etching rate of PET nuclear pore membrane

    International Nuclear Information System (INIS)

    Zuo Zhenzhong; Wu Zhendong; Liang Haiying; Ju Wei; Chen Dongfeng; Fu Yuanyong; Qu Guopu

    2014-01-01

    Background: The nuclear pore membrane is a kind of liquid filtration material manufactured by irradiation and chemical etching. Various conditions in etch process have a great influence on etch rate. Purpose: The influence factors of concentration and temperature of etch solution and the irradiation energy of heavy ions on etch rate was studied. Methods: Four layers of PET (polyethylene terephthalate) films were stacked together and were irradiated with 140-MeV 32 S ions at room temperature under vacuum conditions. Utilizing conductivity measurement technique, the electrical current changes through the u:radiated PET film were monitored during etching, from which the breakthrough time and therefore the track etching rate was calculated. Results: The results show that there is an exponential correlation between etch rate and temperature, and a linear correlation between etch rate and concentration. The track etching rate increases linearly with energy loss rate. Empirical formula for the bulk etching rate as a function of etchant concentration and temperature was also established via fitting of measurements. Conclusion: It is concluded that by using 1.6-MeV·u -1 32 S ions, PET nuclear pore membrane with cylindrical pore shape can be prepared at 85℃ with etchant concentration of l mol·L -1 . (authors)

  17. The glucocorticoid RU24858 does not distinguish between transrepression and transactivation in primary human eosinophils

    Directory of Open Access Journals (Sweden)

    Zhang Xianzhi

    2006-07-01

    Full Text Available Abstract Background Glucocorticoids are used to treat chronic inflammatory diseases such as asthma. Induction of eosinophil apoptosis is considered to be one of the main mechanisms behind the anti-asthmatic effect of glucocorticoids. Glucocorticoid binding to its receptor (GR can have a dual effect on gene transcription. Activated GR can activate transcription (transactivation, or by interacting with other transcription factors such as NF-κB suppress transcription (transrepression. RU24858 has been reported to transrepress but to have little or no transactivation capability in other cell types. The dissociated properties of RU24858 have not been previously studied in non-malignant human cells. As the eosinophils have a very short lifetime and many of the modern molecular biological methods cannot be used, a "dissociated steroid" would be a valuable tool to evaluate the mechanism of action of glucocorticoids in human eosinophils. The aim of this study was to elucidate the ability of RU24858 to activate and repress gene expression in human eosinophils in order to see whether it is a dissociated steroid in human eosinophils. Methods Human peripheral blood eosinophils were isolated under sterile conditions and cultured in the presence and/or absence RU24858. For comparison, dexamethasone and mometasone were used. We measured chemokine receptor-4 (CXCR4 and Annexin 1 expression by flow cytometry and cytokine production by ELISA. Apoptosis was measured by DNA fragmentation and confirmed by morphological analysis. Results RU24858 (1 μM increased CXCR4 and Annexin 1 expression on eosinophils to a similar extent as mometasone (1 μM and dexamethasone (1 μM. Like dexamethasone and mometasone, RU24858 did suppress IL-8 and MCP-1 production in eosinophils. RU24858 also increased spontaneous eosinophil apoptosis to a similar degree as dexamethasone and mometasone, but unlike dexamethasone and mometasone it did not reverse IL-5- or GM

  18. Inhibitor of nuclear factor kappaB kinase beta is a key regulator of synovial inflammation

    NARCIS (Netherlands)

    Tak, P. P.; Gerlag, D. M.; Aupperle, K. R.; van de Geest, D. A.; Overbeek, M.; Bennett, B. L.; Boyle, D. L.; Manning, A. M.; Firestein, G. S.

    2001-01-01

    Inhibitor of nuclear factor kappaB kinase beta (IkappaB kinase beta, or IKKbeta) has emerged as a key regulator of the transcription factor nuclear factor kappaB (NF-kappaB). Since IKKbeta could have both pro- and antiinflammatory activity, we examined whether its constitutive activation was

  19. Glycogen synthase kinase-3β inactivation inhibits tumor necrosis factor-α production in microglia by modulating nuclear factor κB and MLK3/JNK signaling cascades

    Directory of Open Access Journals (Sweden)

    Chen Wu-Fu

    2010-12-01

    Full Text Available Abstract Background Deciphering the mechanisms that modulate the inflammatory response induced by microglial activation not only improves our insight into neuroinflammation but also provides avenues for designing novel therapies that could halt inflammation-induced neuronal degeneration. Decreasing glycogen synthase kinase-3β (GSK-3β activity has therapeutic benefits in inflammatory diseases. However, the exact molecular mechanisms underlying GSK-3β inactivation-mediated suppression of the inflammatory response induced by microglial activation have not been completely clarified. Tumor necrosis factor-α (TNF-α plays a central role in injury caused by neuroinflammation. We investigated the regulatory effect of GSK-3β on TNF-α production by microglia to discern the molecular mechanisms of this modulation. Methods Lipopolysaccharide (LPS was used to induce an inflammatory response in cultured primary microglia or murine BV-2 microglial cells. Release of TNF-α was measured by ELISA. Signaling molecules were analyzed by western blotting, and activation of NF-κB and AP-1 was measured by ELISA-based DNA binding analysis and luciferase reporter assay. Protein interaction was examined by coimmunoprecipitation. Results Inhibition of GSK-3β by selective GSK-3β inhibitors or by RNA interference attenuated LPS-induced TNF-α production in cultured microglia. Exploration of the mechanisms by which GSK-3β positively regulates inflammatory response showed that LPS-induced IκB-α degradation, NF-κBp65 nuclear translocation, and p65 DNA binding activity were not affected by inhibition of GSK-3β activity. However, GSK-3β inactivation inhibited transactivation activity of p65 by deacetylating p65 at lysine 310. Furthermore, we also demonstrated a functional interaction between mixed lineage kinase 3 (MLK3 and GSK-3β during LPS-induced TNF-α production in microglia. The phosphorylated levels of MLK3, MKK4, and JNK were increased upon LPS treatment

  20. Factors relevant to the sealing of nuclear facilities

    International Nuclear Information System (INIS)

    1991-05-01

    This report reviews and summaries the factors to be considered in the design, construction and surveillance of confinement structures for damaged nuclear facilities. General engineering, design and environmental considerations are included, both from the standpoint of the mitigation of near-term effects by virtue of interim confinement, and from the standpoint of the acceptability of the structure for long-term confinement. Factors which influence optimization of the design and the construction sequence are reviewed, including the nature of the accident, natural conditions of the site, and thermal and radiation effects. Safety criteria are presented from the standpoint of regulatory requirements, radiological consequences, and monitoring/surveillance requirements for both interim and long-term confinement. Methodologies related to concrete fabrication technology and other construction techniques appropriate for building confinement structures are discussed. Long-term considerations relative to the future of the site for in-place storage/disposal of the waste, and possible future reuse of the site are also included

  1. Bim nuclear translocation and inactivation by viral interferon regulatory factor.

    Directory of Open Access Journals (Sweden)

    Young Bong Choi

    2010-08-01

    Full Text Available Viral replication efficiency is in large part governed by the ability of viruses to counteract pro-apoptotic signals induced by infection of the host cell. Human herpesvirus 8 (HHV-8 uses several strategies to block the host's innate antiviral defenses via interference with interferon and apoptotic signaling. Contributors include the four viral interferon regulatory factors (vIRFs 1-4, which function in dominant negative fashion to block cellular IRF activities in addition to targeting IRF signaling-induced proteins such as p53 and inhibiting other inducers of apoptosis such as TGFbeta receptor-activated Smad transcription factors. Here we identify direct targeting by vIRF-1 of BH3-only pro-apoptotic Bcl-2 family member Bim, a key negative regulator of HHV-8 replication, to effect its inactivation via nuclear translocation. vIRF-1-mediated relocalization of Bim was identified in transfected cells, by both immunofluorescence assay and western analysis of fractionated cell extracts. Also, co-localization of vIRF-1 and Bim was detected in nuclei of lytically infected endothelial cells. In vitro co-precipitation assays using purified vIRF-1 and Bim revealed direct interaction between the proteins, and Bim-binding residues of vIRF-1 were mapped by deletion and point mutagenesis. Generation and experimental utilization of Bim-refractory vIRF-1 variants revealed the importance of vIRF-1:Bim interaction, specifically, in pro-replication and anti-apoptotic activity of vIRF-1. Furthermore, blocking of the interaction with cell-permeable peptide corresponding to the Bim-binding region of vIRF-1 confirmed the relevance of vIRF-1:Bim association to vIRF-1 pro-replication activity. To our knowledge, this is the first report of an IRF protein that interacts with a Bcl-2 family member and of nuclear sequestration of Bim or any other member of the family as a means of inactivation. The data presented reveal a novel mechanism utilized by a virus to control

  2. The human factor in the operation of nuclear powered submarines

    International Nuclear Information System (INIS)

    Dambier, M.

    1982-05-01

    The conditions characterizing the operation of nuclear powered submarines are described and the precautionary measures suitable to reduce the incidence of human errors and their consequences are explained

  3. Factors affecting nuclear research reactor utilization across countries

    International Nuclear Information System (INIS)

    Hien, P.D.

    2000-01-01

    In view of the worldwide declining trend of research reactor utilization and the fact that many reactors in developing countries are under-utilised, a question naturally arises as to whether the investment in a research reactor is justifiable. Statistical analyses were applied to reveal relationships between the status of reactor utilization and socio-economic conditions among countries, that may provide a guidance for reactor planning and cost benefit assessment. The reactor power has significant regression relationships with size indicators such as GNP, electricity consumption and R and D expenditure. Concerning the effectiveness of investment in research reactors, the number of reactor operation days per year only weakly correlates with electricity consumption and R and D expenditure, implying that there are controlling factors specific of each group of countries. In the case of less developed countries, the low customer demands on reactor operation may be associated with the failure in achieving quality assurance for the reactor products and services, inadequate investment in the infrastructure for reactor exploitation, the shortage of R and D funding and well trained manpower and the lack of measures to get the scientific community involved in the application of nuclear techniques. (author)

  4. The human factors specialist in nuclear control centre design

    International Nuclear Information System (INIS)

    Wilson, R.B.; Beattie, J.D.

    The main focus at Ontario Hydro for man-machine interface design is in the design of control centres. Because the control of a nuclear generating unit is highly centralized there is an increasing need for effective information display and control layout. Control panel design innovations such as the use of CRT displays and the extended use of computerized control in the Darlington station have made it possible for Ontario Hydro to continue to have one first operator for each generating unit. The human factors specialist involved in control panel design must deal with people who know much more about the specific systems being controlled, and must become a generalist in all these systems as well. Designers have to use conceptual techniques such as task analysis, systems design, panel mock-ups, anthropometric data, and personal judgement based on experience as they design panels. They must find a balance between becoming locked into existing technology and methods, slavishly following the latest technological trends, and forgetting that real people will be using what they design

  5. AML1/ETO trans-activates c-KIT expression through the long range interaction between promoter and intronic enhancer.

    Science.gov (United States)

    Tian, Ying; Wang, Genjie; Hu, Qingzhu; Xiao, Xichun; Chen, Shuxia

    2018-04-01

    The AML1/ETO onco-fusion protein is crucial for the genesis of t(8;21) acute myeloid leukemia (AML) and is well documented as a transcriptional repressor through dominant-negative effect. However, little is known about the transactivation mechanism of AML1/ETO. Through large cohort of patient's expression level data analysis and a series of experimental validation, we report here that AML1/ETO transactivates c-KIT expression through directly binding to and mediating the long-range interaction between the promoter and intronic enhancer regions of c-KIT. Gene expression analyses verify that c-KIT expression is significantly high in t(8;21) AML. Further ChIP-seq analysis and motif scanning identify two regulatory regions located in the promoter and intronic enhancer region of c-KIT, respectively. Both regions are enriched by co-factors of AML1/ETO, such as AML1, CEBPe, c-Jun, and c-Fos. Further luciferase reporter assays show that AML1/ETO trans-activates c-KIT promoter activity through directly recognizing the AML1 motif and the co-existence of co-factors. The induction of c-KIT promoter activity is reinforced with the existence of intronic enhancer region. Furthermore, ChIP-3C-qPCR assays verify that AML1/ETO mediates the formation of DNA-looping between the c-KIT promoter and intronic enhancer region through the long-range interaction. Collectively, our data uncover a novel transcriptional activity mechanism of AML1/ETO and enrich our knowledge of the onco-fusion protein mediated transcription regulation. © 2017 Wiley Periodicals, Inc.

  6. Role of Bioavailable Iron in Coal Dust-Induced Activation of Activator Protein-1 and Nuclear Factor of Activated T Cells

    Science.gov (United States)

    Huang, Chuanshu; Li, Jingxia; Zhang, Qi; Huang, Xi

    2010-01-01

    Activator protein-1 (AP-1) and nuclear factor of activated T cells (NFAT) are two important transcription factors responsible for the regulation of cytokines, which are involved in cell proliferation and inflammation. Coal workers’ pneumoconiosis (CWP) is an occupational lung disease that may be related to chronic inflammation caused by coal dust exposure. In the present study, we demonstrate that coal from the Pennsylvania (PA) coalmine region, which has a high prevalence of CWP, can activate both AP-1 and NFAT in JB6 mouse epidermal cells. In contrast, coal from the Utah (UT) coalmine region, which has a low prevalence of CWP, has no such effects. The PA coal stimulates mitogen-activated protein kinase (MAPK) family members of extracellular signal-regulated kinases (ERKs) and p38 MAPK but not c-Jun-NH2-terminal kinases, as determined by the phosphorylation assay. The increase in AP-1 by the PA coal was completely eliminated by the pretreatment of cells with PD98059, a specific MAPK kinase inhibitor, and SB202190, a p38 kinase inhibitor, further confirming that the PA coal-induced AP-1 activation is mediated through ERKs and p38 MAPK pathways. Deferoxamine (DFO), an iron chelator, synergistically enhanced the PA coal-induced AP-1 activity, but inhibited NFAT activity. For comparison, cells were treated with ferrous sulfate and/or DFO. We have found that iron transactivated both AP-1 and NFAT, and DFO further enhanced iron-induced AP-1 activation but inhibited NFAT. These results indicate that activation of AP-1 and NFAT by the PA coal is through bioavailable iron present in the coal. These data are in agreement with our previous findings that the prevalence of CWP correlates well with levels of bioavailable iron in coals from various mining regions. PMID:12397016

  7. The Security of Russia's Nuclear Arsenal: The Human Factor

    International Nuclear Information System (INIS)

    Ball, D.Y.

    1999-01-01

    Assertions by the Russian military that all of their nuclear weapons are secure against theft and that nuclear units within the military are somehow insulated from the problems plaguing the Russian military should not be accepted uncritically. Accordingly, we should not give unwarranted credence to the pronouncements of military figures like Cal.-Gen. Igor Valynkin, Chief of the Defense Ministry's 12th Main Directorate, which oversees the country's nuclear arsenal. He contends that ''Russian nuclear weapons are under reliable supervision'' and that ''talk about the unreliability of our control over nuclear weapons has only one pragmatic goal--to convince international society that the country is incapable of maintaining nuclear safety and to introduce international oversight over those weapons, as it is done, for example, in Iraq.'' While the comparison to Iraq is preposterous, many analysts might agree with Valynkin's sanguine appraisal of the security of Russia's nuclear weapons. In contrast, I argue that the numerous difficulties confronting the military as a whole should cause concern in the West over the security of the Russian nuclear arsenal

  8. Nuclear-polarization correction to the bound-electron g factor in heavy hydrogenlike ions.

    Science.gov (United States)

    Nefiodov, A V; Plunien, G; Soff, G

    2002-08-19

    The influence of nuclear polarization on the bound-electron g factor in heavy hydrogenlike ions is investigated. Numerical calculations are performed for the K- and L-shell electrons taking into account the dominant virtual nuclear excitations. This determines the ultimate limit for tests of QED utilizing measurements of the bound-electron g factor in highly charged ions.

  9. Nuclear-polarization correction to the bound-electron g factor in heavy hydrogenlike ions

    OpenAIRE

    Nefiodov, A. V.; Plunien, G.; Soff, G.

    2002-01-01

    The influence of nuclear polarization on the bound-electron $g$ factor in heavy hydrogenlike ions is investigated. Numerical calculations are performed for the K- and L-shell electrons taking into account the dominant virtual nuclear excitations. This determines the ultimate limit for tests of QED utilizing measurements of the bound-electron $g$ factor in highly charged ions.

  10. The transcription elongation factor ELL2 is specifically upregulated in HTLV-1-infected T-cells and is dependent on the viral oncoprotein Tax

    Energy Technology Data Exchange (ETDEWEB)

    Mann, Melanie C., E-mail: melanie.mann@viro.med.uni-erlangen.de; Strobel, Sarah, E-mail: sarah.strobel@viro.med.uni-erlangen.de; Fleckenstein, Bernhard, E-mail: bernhard.fleckenstein@viro.med.uni-erlangen.de; Kress, Andrea K., E-mail: andrea.kress@viro.med.uni-erlangen.de

    2014-09-15

    The oncoprotein Tax of human T-cell leukemia virus type 1 (HTLV-1) is a potent transactivator of viral and cellular transcription. Here, we identified ELL2 as the sole transcription elongation factor to be specifically upregulated in HTLV-1-/Tax-transformed T-cells. Tax contributes to regulation of ELL2, since transient transfection of Tax increases ELL2 mRNA, Tax transactivates the ELL2 promoter, and repression of Tax results in decrease of ELL2 in transformed T-lymphocytes. However, we also measured upregulation of ELL2 in HTLV-1-transformed cells exhibiting undetectable amounts of Tax, suggesting that ELL2 can still be maintained independent of continuous Tax expression. We further show that Tax and ELL2 synergistically activate the HTLV-1 promoter, indicating that ELL2 cooperates with Tax in viral transactivation. This is supported by our findings that Tax and ELL2 accumulate in nuclear fractions and that they co-precipitate upon co-expression in transiently-transfected cells. Thus, upregulation of ELL2 could contribute to HTLV-1 gene regulation. - Highlights: • ELL2, a transcription elongation factor, is upregulated in HTLV-1-positive T-cells. • Tax transactivates the ELL2 promoter. • Tax and ELL2 synergistically activate the HTLV-1 promoter. • Tax and ELL2 interact in vivo.

  11. Separating form factor and nuclear model effects in quasielastic neutrino-nucleus scattering

    Science.gov (United States)

    Wieske, Joseph

    2017-09-01

    When studying neutrino oscillations an understanding of charged current quasielastic (CCQE) neutrino-nucleus scattering is imperative. This interaction depends on a nuclear model as well as knowledge of form factors. In the past, CCQE data from the MiniBooNE experiment was analyzed assuming the Relativistic Fermi Gas (RFG) nuclear model, an axial dipole form factor in, and using the the z-expansion for the axial form factor in. We present the first analysis that combines a non-RFG nuclear model, in particular the Correlated Fermi Gas nuclear model (CFG) of, and the z expansion for the axial form factor. This will allow us to separate form factor and nuclear model effects in CCQE scattering. This project was supported through the Wayne State University REU program under NSF Grant PHY-1460853 and by the DOE Grant DE-SC0007983.

  12. Cholinergic Transactivation of the EGFR in HaCaT Keratinocytes Stimulates a Flotillin-1 Dependent MAPK-Mediated Transcriptional Response

    Directory of Open Access Journals (Sweden)

    Sina Kühne

    2015-03-01

    Full Text Available Acetylcholine and its receptors regulate numerous cellular processes in keratinocytes and other non-neuronal cells. Muscarinic acetylcholine receptors are capable of transactivating the epidermal growth factor receptor (EGFR and, downstream thereof, the mitogen-activated protein kinase (MAPK cascade, which in turn regulates transcription of genes involved in cell proliferation and migration. We here show that cholinergic stimulation of human HaCaT keratinocytes results in increased transcription of matrix metalloproteinase MMP-3 as well as several ligands of the epidermal growth factor family. Since both metalloproteinases and the said ligands are involved in the transactivation of the EGFR, this transcriptional upregulation may provide a positive feed-forward loop for EGFR/MAPK activation. We here also show that the cholinergic EGFR and MAPK activation and the upregulation of MMP-3 and EGF-like ligands are dependent on the expression of flotillin-1 which we have previously shown to be a regulator of MAPK signaling.

  13. Factor Analysis and Framework Development for Incorporating Public Trust on Nuclear Safety issues

    International Nuclear Information System (INIS)

    Cho, Seongkyung; Lee, Gyebong; Lee, Gihyung; Lee, Gyehwi; Jeong, Jina

    2014-01-01

    The Korea Institute of Nuclear Safety (KINS), a regulatory expert organization in charge of nuclear safety in Korea, realized that a more fundamental and systematic analysis of activities is needed to actively meet the greater variety of concerns people have and increase the reliability of the results of regulation. Nuclear safety, a highly specialized field, has previously been discussed primarily from the viewpoint of the engineers who deal with the technology, but now 'public trust in nuclear safety' has to be viewed from the standpoint of the general public and from the socio-cultural perspective. Specific measures must be taken to examine which factors affect public trust and how we can secure and reproduce those factors to gain it. Also, an efficient system for incorporating public trust in nuclear safety must be established. In this study, various case studies were examined to identify the factors that affect public trust in nuclear safety. First, nuclear safety laws and information disclosure systems of major countries were examined by investigating data and conducting in-depth interviews. To explore a public framework concerning nuclear safety, big data of social media were analyzed. Also, Q methodology was used to analyze the risk schemata of the opinion leaders living in areas near nuclear power plants. Several surveys were conducted to analyze the amount of trust the public had in nuclear safety as well as their awareness of nuclear safety issues. Based on these analyses, factors affecting public trust in nuclear safety were extracted, and measures to build systems incorporating public trust in nuclear safety were proposed. This study addresses the public trust in nuclear safety on condition that the safety is ensured technically and mechanically

  14. Factors affecting the future of nuclear power in OECD Europe

    International Nuclear Information System (INIS)

    Thompson, S.

    1997-01-01

    This report provides a brief review of nuclear power in OECD Europe and addresses the prospects for its future over, say, the next quarter century. Most of the data and findings are drawn from studies published by the Nuclear Energy Agency (NEA) of the Organisation for Economic Co-operation and Development (OECD). The NEA is a small agency with a rather modest budget whose 27 members are industrialized countries from North America, Asia and Europe. The Agency works to pool the expertise of our member countries to produce technical, economic and legal work of considerable depth and quality addressing issues of common interest to those countries. Our work covers such fields as nuclear science, nuclear power economics, nuclear safety, radiation protection, waste management and nuclear liability. The studies carried out in the framework of the Agency require fewer resources than would be needed by our member countries if they were to pursue them individually, which is especially important at a time of cut-backs in national programmes in such critical areas as nuclear safety research. (author)

  15. Activation of nuclear factor-kappa B via endogenous tumor necrosis factor alpha regulates survival of axotomized adult sensory neurons

    NARCIS (Netherlands)

    Fernyhough, P; Smith, DR; Schapansky, J; Van Der Ploeg, R; Gardiner, NJ; Tweed, CW; Kontos, A; Freeman, L; Purves-Tyson, TD; Glazner, GW

    2005-01-01

    Embryonic dorsal root ganglion (DRG) neurons die after axonal damage in vivo, and cultured embryonic DRG neurons require exogenous neurotrophic factors that activate the neuroprotective transcription factor nuclear factor-kappaB(NF-kappaB) for survival. In contrast, adult DRG neurons survive

  16. GPCR responses in vascular smooth muscle can occur predominantly through dual transactivation of kinase receptors and not classical Gαq protein signalling pathways.

    Science.gov (United States)

    Little, Peter J

    2013-05-30

    GPCR signalling is well known to proceed through several linear pathways involving activation of G proteins and their downstream signalling pathways such as activation of phospholipase C. In addition, GPCRs signal via transactivation of Protein Tyrosine Kinase receptors such as that for Epidermal Growth Factor (EGF) and Platelet-Derived Growth Factor (PDGF) where GPCR agonists mediate increase levels of phosphorylated Erk (pErk) the immediate downstream product of the activation of EGF receptor. It has recently been shown that this paradigm can be extended to include the GPCR transactivation of a Protein Serine/Threonine Kinase receptor, specifically the Transforming Growth Factor β Type I receptor (also known as Alk V) (TβRI) in which case GPCR activation leads to the formation of carboxy terminal polyphosphorylated Smad2 (phosphoSmad2) being the immediate downstream product of the activation of TβRI. Growth factor and hormone regulation of proteoglycan synthesis in vascular smooth muscle cells represent one component of an in vitro model of atherosclerosis because modified proteoglycans show enhanced binding to lipoproteins as the initiating step in atherosclerosis. In the example of proteoglycan synthesis stimulated by GPCR agonists such as thrombin and endothelin-1, the transactivation pathways for the EGF receptor and TβRI are both active and together account for essentially all of the response to the GPCRs. In contrast, signalling downstream of GPCRs such as increased inositol 1,4,5 trisphosphate (IP3) and intracellular calcium do not have any effect on GPCR stimulated proteoglycan synthesis. These data lead to the conclusion that dual transactivation pathways for protein tyrosine and serine/threonine kinase receptors may play a far greater role in GPCR signalling than currently recognised. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Cloning animals by somatic cell nuclear transfer – biological factors

    Directory of Open Access Journals (Sweden)

    Enright Brian

    2003-11-01

    Full Text Available Abstract Cloning by nuclear transfer using mammalian somatic cells has enormous potential application. However, somatic cloning has been inefficient in all species in which live clones have been produced. High abortion and fetal mortality rates are commonly observed. These developmental defects have been attributed to incomplete reprogramming of the somatic nuclei by the cloning process. Various strategies have been used to improve the efficiency of nuclear transfer, however, significant breakthroughs are yet to happen. In this review we will discuss studies conducted, in our laboratories and those of others, to gain a better understanding of nuclear reprogramming. Because cattle are a species widely used for nuclear transfer studies, and more laboratories have succeeded in cloning cattle than any other specie, this review will be focused on somatic cell cloning of cattle.

  18. Effects of mushroom-derived ß-glucan rich polysaccharide extracts on nitric oxide production by bone marrow-derived macrophages and nuclear factor-kB transactivation in Caco-2 reporter cells: Can effects be explained by structure?

    NARCIS (Netherlands)

    Volman, J.J.; Helsper, J.P.F.G.; Wei, S.; Baars, J.J.P.; Griensven, van L.J.L.D.; Sonnenberg, A.S.M.; Mensink, R.P.; Plat, J.

    2010-01-01

    Mushrooms are known for their immune-modulating and anti-tumour properties. The polysaccharide fraction, mainly -glucans, is responsible for the immune-modulating effects. Fungal -glucans have been shown to activate leukocytes, which depend on structural characteristics of -glucans. As edible

  19. Human factors design guidelines for maintainability of Department of Energy nuclear facilities

    International Nuclear Information System (INIS)

    Bongarra, J.P. Jr.; VanCott, H.P.; Pain, R.F.; Peterson, L.R.; Wallace, R.I.

    1985-01-01

    Intent of these guidelines is to provide design and design review teams of DOE nuclear facilities with human factors principles to enhance the design and aid in the inspection of DOE nuclear facilities, systems, and equipment. These guidelines are concerned with design features of DOE nuclear facilities which can potentially affect preventive and corrective maintenance of systems within DOE nuclear facilities. Maintenance includes inspecting, checking, troubleshooting, adjusting, replacing, repairing, and servicing activities. Other factors which influence maintainability such as repair and maintenance suport facilities, maintenance information, and various aspects of the environment are also addressed

  20. Human factors design guidelines for maintainability of Department of Energy nuclear facilities

    Energy Technology Data Exchange (ETDEWEB)

    Bongarra, J.P. Jr.; VanCott, H.P.; Pain, R.F.; Peterson, L.R.; Wallace, R.I.

    1985-06-18

    Intent of these guidelines is to provide design and design review teams of DOE nuclear facilities with human factors principles to enhance the design and aid in the inspection of DOE nuclear facilities, systems, and equipment. These guidelines are concerned with design features of DOE nuclear facilities which can potentially affect preventive and corrective maintenance of systems within DOE nuclear facilities. Maintenance includes inspecting, checking, troubleshooting, adjusting, replacing, repairing, and servicing activities. Other factors which influence maintainability such as repair and maintenance suport facilities, maintenance information, and various aspects of the environment are also addressed.

  1. Keap1 silencing boosts lipopolysaccharide-induced transcription of interleukin 6 via activation of nuclear factor κB in macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Lv, Peng [Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States); Xue, Peng; Dong, Jian [Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States); Peng, Hui [Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States); Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences (China); Clewell, Rebecca [Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States); Wang, Aiping [Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Wang, Yue [Institute for Medical Device Standardization Administration, National Institutes for Food and Drug Control, Beijing (China); Peng, Shuangqing [Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences (China); Qu, Weidong [Key Laboratory of the Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai (China); Zhang, Qiang; Andersen, Melvin E. [Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States); Pi, Jingbo, E-mail: jpi@thehamner.org [Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States)

    2013-11-01

    Interleukin-6 (IL6) is a multifunctional cytokine that regulates immune and inflammatory responses. Multiple transcription factors, including nuclear factor κB (NF-κB) and nuclear factor E2-related factor 2 (Nrf2), regulate IL6 transcription. Kelch-like ECH-associated protein 1 (Keap1) is a substrate adaptor protein for the Cullin 3-dependent E3 ubiquitin ligase complex, which regulates the degradation of many proteins, including Nrf2 and IκB kinase β (IKKβ). Here, we found that stable knockdown of Keap1 (Keap1-KD) in RAW 264.7 (RAW) mouse macrophages and human monocyte THP-1 cells significantly increased expression of Il6, and Nrf2-target genes, under basal and lipopolysaccharide (LPS, 0.001–0.1 μg/ml)-challenged conditions. However, Nrf2 activation alone, by tert-butylhydroquinone treatment of RAW cells, did not increase expression of Il6. Compared to cells transduced with scrambled non-target negative control shRNA, Keap1-KD RAW cells showed enhanced protein levels of IKKβ and increased expression and phosphorylation of NF-κB p65 under non-stressed and LPS-treated conditions. Because the expression of Il6 in Keap1-KD RAW cells was significantly attenuated by silencing of Ikkβ, but not Nrf2, it appears that stabilized IKKβ is responsible for the enhanced transactivation of Il6 in Keap1-KD cells. This study demonstrated that silencing of Keap1 in macrophages boosts LPS-induced transcription of Il6 via NF-κB activation. Given the importance of IL6 in the inflammatory response, the Keap1–IKKβ–NF-κB pathway may be a novel target for treatment and prevention of inflammation and associated disorders. - Highlights: • Knockdown of Keap1 increases expression of Il6 in macrophages. • Silencing of Keap1 results in protein accumulation of IKKβ and NF-κB p65. • Induction of Il6 resulting from Keap1 silencing is attributed to NF-κB activation.

  2. Transactivation of ErbB receptors by leptin in the cardiovascular system: mechanisms, consequences and target for therapy.

    Science.gov (United States)

    Bełtowski, Jerzy; Jazmroz-Wiśniewska, Anna

    2014-01-01

    Many experimental and clinical studies have demonstrated that elevated leptin concentration in patients with obesity/metabolic syndrome contributes to the pathogenesis of cardiovascular disorders including arterial hypertension, atherosclerosis, restenosis after coronary angioplasty and myocardial hypertrophy. Receptor tyrosine kinases belonging to the ErbB family, especially ErbB1 (epidermal growth factor receptor) and ErbB2 are abundantly expressed in the blood vessels and the heart. EGFR is activated not only by its multiple peptide ligands but also by many other factors including angiotensin II, endothelin-1, norepinephrine, thrombin and prorenin; the phenomenon referred to as "transactivation". Augmented EGFR signaling contributes to abnormalities of vascular tone and renal sodium handling as well as vascular remodeling and myocardial hypertrophy through various intracellular mechanisms, in particular extracellular signal-regulated kinases (ERK) and phosphoinositide 3-kinase (PI3K). Recent experimental studies indicate that chronically elevated leptin transactivates the EGFR through the mechanisms requiring reactive oxygen species and cytosolic tyrosine kinase, c-Src. In addition, hyperleptinemia increases ErbB2 activity in the arterial wall. Stimulation of EGFR and ErbB2 downstream signaling pathways such as ERK and PI3K in the vascular wall and the kidney may contribute to the increase in vascular tone, enhanced tubular sodium reabsorption as well as vascular and renal lesions in hyperleptinemic obese subjects.

  3. Imaging analysis of nuclear antiviral factors through direct detection of incoming adenovirus genome complexes

    Energy Technology Data Exchange (ETDEWEB)

    Komatsu, Tetsuro [Microbiologie Fondamentale et Pathogénicité, MFP CNRS UMR 5234, Université de Bordeaux, Bordeaux 33076 (France); Department of Infection Biology, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575 (Japan); Will, Hans [Department of Tumor Biology, University Hospital Hamburg-Eppendorf, 20246 Hamburg (Germany); Nagata, Kyosuke [Department of Infection Biology, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575 (Japan); Wodrich, Harald, E-mail: harald.wodrich@u-bordeaux.fr [Microbiologie Fondamentale et Pathogénicité, MFP CNRS UMR 5234, Université de Bordeaux, Bordeaux 33076 (France)

    2016-04-22

    Recent studies involving several viral systems have highlighted the importance of cellular intrinsic defense mechanisms through nuclear antiviral proteins that restrict viral propagation. These factors include among others components of PML nuclear bodies, the nuclear DNA sensor IFI16, and a potential restriction factor PHF13/SPOC1. For several nuclear replicating DNA viruses, it was shown that these factors sense and target viral genomes immediately upon nuclear import. In contrast to the anticipated view, we recently found that incoming adenoviral genomes are not targeted by PML nuclear bodies. Here we further explored cellular responses against adenoviral infection by focusing on specific conditions as well as additional nuclear antiviral factors. In line with our previous findings, we show that neither interferon treatment nor the use of specific isoforms of PML nuclear body components results in co-localization between incoming adenoviral genomes and the subnuclear domains. Furthermore, our imaging analyses indicated that neither IFI16 nor PHF13/SPOC1 are likely to target incoming adenoviral genomes. Thus our findings suggest that incoming adenoviral genomes may be able to escape from a large repertoire of nuclear antiviral mechanisms, providing a rationale for the efficient initiation of lytic replication cycle. - Highlights: • Host nuclear antiviral factors were analyzed upon adenovirus genome delivery. • Interferon treatments fail to permit PML nuclear bodies to target adenoviral genomes. • Neither Sp100A nor B targets adenoviral genomes despite potentially opposite roles. • The nuclear DNA sensor IFI16 does not target incoming adenoviral genomes. • PHF13/SPOC1 targets neither incoming adenoviral genomes nor genome-bound protein VII.

  4. Characterization of the regulatory domains of the human skn-1a/Epoc-1/Oct-11 POU transcription factor.

    Science.gov (United States)

    Hildesheim, J; Foster, R A; Chamberlin, M E; Vogel, J C

    1999-09-10

    The Skn-1a POU transcription factor is primarily expressed in keratinocytes of murine embryonic and adult epidermis. Although some POU factors expressed in a tissue-specific manner are important for normal differentiation, the biological function of Skn-1a remains unknown. Previous in vitro studies indicate that Skn-1a has the ability to transactivate markers of keratinocyte differentiation. In this study, we have characterized Skn-1a's transactivation domain(s) and engineered a dominant negative protein that lacked this transactivation domain. Deletional analysis of the human homologue of Skn-1a with three target promoters revealed the presence of two functional domains: a primary C-terminal transactivation domain and a combined N-terminal inhibitory domain and transactivation domain. Skn-1a lacking the C-terminal region completely lost transactivation ability, irrespective of the promoter tested, and was able to block transactivation by normal Skn-1a in competition assays. Compared with full-length, Skn-1a lacking the N-terminal region demonstrated either increased transactivation (bovine cytokeratin 6 promoter), comparable transactivation (human papillomavirus type 1a long control region), or loss of transactivation (human papillomavirus type 18 long control region). The identification of a primary C-terminal transactivation domain enabled us to generate a dominant negative Skn-1a factor, which will be useful in the quest for a better understanding of this keratinocyte-specific gene regulator.

  5. Clinical validation of nuclear factor kappa B expression in invasive breast cancer.

    Science.gov (United States)

    Agrawal, Anil Kumar; Pielka, Ewa; Lipinski, Artur; Jelen, Michal; Kielan, Wojciech; Agrawal, Siddarth

    2018-01-01

    Breast cancer is the most commonly diagnosed cancer in Polish women. The expression of transcription nuclear factor kappa B, a key inducer of inflammatory response promoting carcinogenesis and cancer progression in breast cancer, is not well-established. We assessed the nuclear factor kappa B expression in a total of 119 invasive breast carcinomas and 25 healthy control samples and correlated this expression pattern with several clinical and pathologic parameters including histologic type and grade, tumor size, lymph node status, estrogen receptor status, and progesterone receptor status. The data used for the analysis were derived from medical records. An immunohistochemical analysis of nuclear factor kappa B, estrogen receptor, and progesterone receptor was carried out and evaluation of stainings was performed. The expression of nuclear factor kappa B was significantly higher than that in the corresponding healthy control samples. No statistical difference was demonstrated in nuclear factor kappa B expression in relation to age, menopausal status, lymph node status, tumor size and location, grade and histologic type of tumor, and hormonal status (estrogen receptor and progesterone receptor). Nuclear factor kappa B is significantly overexpressed in invasive breast cancer tissues. Although nuclear factor kappa B status does not correlate with clinicopathological findings, it might provide important additional information on prognosis and become a promising object for targeted therapy.

  6. Study of factors governing US utility nuclear power decisions

    International Nuclear Information System (INIS)

    1980-05-01

    Under DOE contract No. DE-AC02-79ET34009, The S.M. Stoller Corporation has conducted a study of US utility attitudes toward nuclear power. In the course of this study SMSC carried out a utility survey the objectives of which were: (1) to identify and rank in importance the governing considerations in actions taken in the past three years to cancel or defer nuclear projects, and (2) to gain insight into the circumstances and attitudes likely to govern new base-load commitments over the next several years. During the survey, contacts were made at the senior management level with utilities representing approximately half of the country's total electric capacity and two-thirds of its present nuclear commitment. Analysis of the responses led to the conclusion that most, if not all, of the decisions reached by the respondent utilities in the past several years to cancel or defer nuclear projects were triggered by one or a combination of the following four considerations: financial constraints; reduction in expected system load growth; schedule delay in licensing and construction and/or unpredictability; and adverse state government policies or attitudes regarding nuclear power

  7. Study of greenhouse gases emission factor for nuclear power chain of China

    International Nuclear Information System (INIS)

    Ma Zhonghai; Pan Ziqiang; Xie Jianlun; Xiu Binglin

    2001-01-01

    The Greenhouse Gases Emission Factor (GGEF) for nuclear power chain of China is calculated based on Life Cycle Analysis method and the definition of full energy chain. There is no greenhouse gases released directly from nuclear power plant. The greenhouse gases emission from nuclear power plant is mainly from coal-fired electricity supply to nuclear power plant for its normal operation and the production of construction materials those are used in the nuclear power plant. The total GGEF of nuclear power chain in China is 13.71 g-co 2 /kWh. It is necessary to regulate un-rational power source mix and to use the energy sources in rational way for reducing the greenhouse gas effect. Nuclear power for electricity generation is one of effective ways to reduce greenhouse gases emission and retard the greenhouse effect

  8. Sofalcone upregulates the nuclear factor (erythroid-derived 2)-like 2/heme oxygenase-1 pathway, reduces soluble fms-like tyrosine kinase-1, and quenches endothelial dysfunction: potential therapeutic for preeclampsia.

    Science.gov (United States)

    Onda, Kenji; Tong, Stephen; Nakahara, Anzu; Kondo, Mei; Monchusho, Hideaki; Hirano, Toshihiko; Kaitu'u-Lino, Tu'uhevaha; Beard, Sally; Binder, Natalie; Tuohey, Laura; Brownfoot, Fiona; Hannan, Natalie J

    2015-04-01

    Preeclampsia is a severe complication of pregnancy, characterized by hypertension, oxidative stress, and severe endothelial dysfunction. Antiangiogenic factors, soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin, play key pathophysiological roles in preeclampsia. Heme oxygenase-1 (HO-1) is a cytoprotective, antioxidant enzyme reported to be downregulated in preeclampsia. Studies propose that inducing HO-1 may also decrease sFlt-1 production. Sofalcone, a gastric antiulcer agent in clinical use, is known to induce HO-1 in gastric epithelium. We aimed to investigate whether sofalcone induces HO-1 and reduces sFlt-1 release from primary human placental and endothelial cells and blocks endothelial dysfunction in vitro. We isolated human trophoblasts and endothelial cells (human umbilical vein endothelial cells) and also used uterine microvascular cells. We investigated the effects of sofalcone on (1) HO-1 production, (2) activation of the nuclear factor (erythroid-derived 2)-like 2 pathway, (3) sFlt-1 and soluble endoglin release, (4) tumor necrosis factor α-induced monocyte adhesion and vascular cell adhesion molecule upregulation, and (5) endothelial tubule formation. Sofalcone potently increased HO-1 mRNA and protein in both primary trophoblasts and human umbilical vein endothelial cells. Furthermore, sofalcone treatment caused nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 and transactivation of other nuclear factor (erythroid-derived 2)-like 2 responsive genes (NQO1, TXN, and GCLC). Importantly, sofalcone significantly decreased the secretion of sFlt-1 from primary human trophoblasts. Sofalcone potently suppressed endothelial dysfunction in 2 in vitro models, blocking tumor necrosis factor α-induced monocyte adhesion and vascular cell adhesion molecule 1 expression in human umbilical vein endothelial cells. These results indicate that in primary human tissues, sofalcone can potently activate antioxidant nuclear factor

  9. Factors that Affect the Decision of Having Nuclear Energy and Predictions for Turkey

    OpenAIRE

    Bülent, Köksal; Abdülkadir, Civan

    2009-01-01

    Using data for 67 countries for the period 1980-2005, we analyze to what extent do the decisions of having nuclear power and the share of nuclear energy in total energy use depend on economic, politic, social and geographic factors. Our econometric model that takes the selectivity problems of the sample into consideration reveals a positive relationship between per capita real income and the probability of selecting to have nuclear power. This relationship, however, weakens as the level of in...

  10. The human factor in the organisation and regulation of nuclear safety

    International Nuclear Information System (INIS)

    Bordes, F.; Savagner, J.-M.; Snanoudj, G.

    1981-10-01

    The TMI accident has brought to light the importance of the human factor in the safe operation of complex installations such as nuclear power plants. On this basis, the paper outlines the institutional framework for nuclear safety in France and reports on EDF practices in human resources management as well as in the improvement of working premises (control rooms) to optimize human behaviour in accident conditions. Finally, the interaction of labour laws on nuclear law in connection with safety is described. (NEA) [fr

  11. Protective effect of nuclear factor E2-related factor 2 on inflammatory cytokine response to brominated diphenyl ether-47 in the HTR-8/SVneo human first trimester extravillous trophoblast cell line

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hae-Ryung, E-mail: heaven@umich.edu; Loch-Caruso, Rita

    2014-11-15

    Polybrominated diphenyl ethers (PBDEs) are widely used flame retardants, and BDE-47 is a prevalent PBDE congener detected in human tissues. Exposure to PBDEs has been linked to adverse pregnancy outcomes in humans. Although the underlying mechanisms of adverse birth outcomes are poorly understood, critical roles for oxidative stress and inflammation are implicated. The present study investigated antioxidant responses in a human extravillous trophoblast cell line, HTR-8/SVneo, and examined the role of nuclear factor E2-related factor 2 (Nrf2), an antioxidative transcription factor, in BDE-47-induced inflammatory responses in the cells. Treatment of HTR-8/SVneo cells with 5, 10, 15, and 20 μM BDE-47 for 24 h increased intracellular glutathione (GSH) levels compared to solvent control. Treatment of HTR-8/SVneo cells with 20 μM BDE-47 for 24 h induced the antioxidant response element (ARE) activity, indicating Nrf2 transactivation by BDE-47 treatment, and resulted in differential expression of redox-sensitive genes compared to solvent control. Pretreatment with tert-butyl hydroquinone (tBHQ) or sulforaphane, known Nrf2 inducers, reduced BDE-47-stimulated IL-6 release with increased ARE reporter activity, reduced nuclear factor kappa B (NF-κB) reporter activity, increased GSH production, and stimulated expression of antioxidant genes compared to non-Nrf2 inducer pretreated groups, suggesting that Nrf2 may play a protective role against BDE-47-mediated inflammatory responses in HTR-8/SVneo cells. These results suggest that Nrf2 activation significantly attenuated BDE-47-induced IL-6 release by augmentation of cellular antioxidative system via upregulation of Nrf2 signaling pathways, and that Nrf2 induction may be a potential therapeutic target to reduce adverse pregnancy outcomes associated with toxicant-induced oxidative stress and inflammation. - Highlights: • BDE-47 stimulated ARE reporter activity and GSH production. • BDE-47 resulted in differential

  12. Discussion on verification criterion and method of human factors engineering for nuclear power plant controller

    International Nuclear Information System (INIS)

    Yang Hualong; Liu Yanzi; Jia Ming; Huang Weijun

    2014-01-01

    In order to prevent or reduce human error and ensure the safe operation of nuclear power plants, control device should be verified from the perspective of human factors engineering (HFE). The domestic and international human factors engineering guidelines about nuclear power plant controller were considered, the verification criterion and method of human factors engineering for nuclear power plant controller were discussed and the application examples were provided for reference in this paper. The results show that the appropriate verification criterion and method should be selected to ensure the objectivity and accuracy of the conclusion. (authors)

  13. Account of the uncertainty factor in forecasting nuclear power development

    International Nuclear Information System (INIS)

    Chernavskij, S.Ya.

    1979-01-01

    Minimization of total discounted costs for linear constraints is commonly used in forecasting nuclear energy growth. This approach is considered inadequate due to the uncertainty of exogenous variables of the model. A method of forecasting that takes into account the presence of uncertainty is elaborated. An example that demonstrates the expediency of the method and its advantage over the conventional approximation method used for taking uncertainty into account is given. In the framework of the example, the optimal strategy for nuclear energy growth over period of 500 years is determined

  14. Changes in the Factors Influencing Public Acceptance of Nuclear Power Generation in Japan Since the 2011 Fukushima Daiichi Nuclear Disaster.

    Science.gov (United States)

    Tsujikawa, Norifumi; Tsuchida, Shoji; Shiotani, Takamasa

    2016-01-01

    Public support for nuclear power generation has decreased in Japan since the Fukushima Daiichi nuclear accident in March 2011. This study examines how the factors influencing public acceptance of nuclear power changed after this event. The influence factors examined are perceived benefit, perceived risk, trust in the managing bodies, and pro-environmental orientation (i.e., new ecological paradigm). This study is based on cross-sectional data collected from two online nationwide surveys: one conducted in November 2009, before the nuclear accident, and the other in October 2011, after the accident. This study's target respondents were residents of Aomori, Miyagi, and Fukushima prefectures in the Tohoku region of Japan, as these areas were the epicenters of the Great East Japan Earthquake and the locations of nuclear power stations. After the accident, trust in the managing bodies was found to have a stronger influence on perceived risk, and pro-environmental orientation was found to have a stronger influence on trust in the managing bodies; however, perceived benefit had a weaker positive influence on public acceptance. We also discuss the theoretical and practical implications of these findings. © 2015 Society for Risk Analysis.

  15. Transactivation Domain of Human c-Myc Is Essential to Alleviate Poly(Q)-Mediated Neurotoxicity in Drosophila Disease Models.

    Science.gov (United States)

    Raj, Kritika; Sarkar, Surajit

    2017-05-01

    Polyglutamine (poly(Q)) disorders, such as Huntington's disease (HD) and spinocerebellar ataxias, represent a group of neurological disorders which arise due to an atypically expanded poly(Q) tract in the coding region of the affected gene. Pathogenesis of these disorders inside the cells begins with the assembly of these mutant proteins in the form of insoluble inclusion bodies (IBs), which progressively sequester several vital cellular transcription factors and other essential proteins, and finally leads to neuronal dysfunction and apoptosis. We have shown earlier that targeted upregulation of Drosophila myc (dmyc) dominantly suppresses the poly(Q) toxicity in Drosophila. The present study examines the ability of the human c-myc proto-oncogene and also identifies the specific c-Myc isoform which drives the mitigation of poly(Q)-mediated neurotoxicity, so that it could be further substantiated as a potential drug target. We report for the first time that similar to dmyc, tissue-specific induced expression of human c-myc also suppresses poly(Q)-mediated neurotoxicity by an analogous mechanism. Among the three isoforms of c-Myc, the rescue potential was maximally manifested by the full-length c-Myc2 protein, followed by c-Myc1, but not by c-MycS which lacks the transactivation domain. Our study suggests that strategies focussing on the transactivation domain of c-Myc could be a very useful approach to design novel drug molecules against poly(Q) disorders.

  16. MB0 and MBI Are Independent and Distinct Transactivation Domains in MYC that Are Essential for Transformation.

    Science.gov (United States)

    Zhang, Qin; West-Osterfield, Kimberly; Spears, Erick; Li, Zhaoliang; Panaccione, Alexander; Hann, Stephen R

    2017-05-06

    MYC is a transcription factor that is essential for cellular proliferation and development. Deregulation or overexpression of MYC occurs in a variety of human cancers. Ectopic expression of MYC causes hyperproliferation and transformation of cells in culture and tumorigenesis in several transgenic mouse models. Deregulation of MYC can also induce apoptosis through activation of p53 and/or ARF tumor suppressors as a safeguard to prevent tumorigenesis. MYC binds to thousands of genomic sites and regulates hundreds of target genes in a context-dependent fashion to mediate these diverse biological roles. The N-terminal region of MYC contains several conserved domains or MYC Boxes (MB), which influence the different MYC transcriptional and biological activities to varying degrees. However, the specific domains that mediate the ability of MYC to activate transcription remain ill defined. In this report, we have identified a new conserved transactivation domain (TAD), MB0, which is essential for MYC transactivation and target gene induction. We demonstrate that MB0 and MBI represent two distinct and independent TADs within the N-terminal 62 amino acids of MYC. In addition, both MB0 and MBI are essential for MYC transformation of primary fibroblasts in cooperation with activated RAS, while MB0 is necessary for efficient MYC-induced p53-independent apoptosis.

  17. Reprint of "Nuclear transport factors: global regulation of mitosis".

    Science.gov (United States)

    Forbes, Douglass J; Travesa, Anna; Nord, Matthew S; Bernis, Cyril

    2015-06-01

    The unexpected repurposing of nuclear transport proteins from their function in interphase to an equally vital and very different set of functions in mitosis was very surprising. The multi-talented cast when first revealed included the import receptors, importin alpha and beta, the small regulatory GTPase RanGTP, and a subset of nuclear pore proteins. In this review, we report that recent years have revealed new discoveries in each area of this expanding story in vertebrates: (a) The cast of nuclear import receptors playing a role in mitotic spindle regulation has expanded: both transportin, a nuclear import receptor, and Crm1/Xpo1, an export receptor, are involved in different aspects of spindle assembly. Importin beta and transportin also regulate nuclear envelope and pore assembly. (b) The role of nucleoporins has grown to include recruiting the key microtubule nucleator – the γ-TuRC complex – and the exportin Crm1 to the mitotic kinetochores of humans. Together they nucleate microtubule formation from the kinetochores toward the centrosomes. (c) New research finds that the original importin beta/RanGTP team have been further co-opted by evolution to help regulate other cellular and organismal activities, ranging from the actual positioning of the spindle within the cell perimeter, to regulation of a newly discovered spindle microtubule branching activity, to regulation of the interaction of microtubule structures with specific actin structures. (d) Lastly, because of the multitudinous roles of karyopherins throughout the cell cycle, a recent large push toward testing their potential as chemotherapeutic targets has begun to yield burgeoning progress in the clinic. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. The contribution of nuclear training staff to human factors work in the CEGB and Nuclear Electric PLC

    International Nuclear Information System (INIS)

    Madden, V.J.

    1990-01-01

    The staff and simulators of utility's nuclear training function are being utilized in support of a wide range of human factor related activities. In addition to work on man machines interface review, operating procedures, operator support system and VDU format design and validation for the Magnox and AGR series of nuclear power plants, support is also being provided to the PWR Project Team through staff who have undergone extensive and comprehensive overseas PWR training programs. This paper discusses how recent initiatives in connection with a survey on operator stress and the possible use of psychometric testing in support of the selection of reactor desk engineers are also being supported

  19. Social-political factors influencing the expansion of nuclear power

    International Nuclear Information System (INIS)

    Waltar, A.E.; Upson, P.

    1999-01-01

    As humanity marches closer to entering a new millennium, it is crucial that we nuclear professionals take renewed stock in the importance of our role in public interactions. The lack of public support has been very influential in bringing the once robust nuclear power construction program in America, Europe and Russia to a grinding halt. In trying to understand the key forces that shape public opinion on technologies such as ours, it becomes clear that the major force is the media enterprise. If we compare the basic driving forces behind successful media with the basic drivers behind successful science, we quickly come to the realization that the media are fundamentally in the entertainment business. Capturing instant attention and holding it are the principal ingredients of success for newspapers, radio, and television. Recognizing that these success drivers are diametrically opposite of those governing good science, we can readily understand why the antinuclear movement has been so successful in orchestrating their message in a package ideally suited to a receptive media enterprise. However, before blaming all our woes on the media, we need to assess at least four technical areas where additional professional work could be of substantial value. These include determining the real health effects of low-level radiation, further developing intrinsic robustness to enhance reactor safety, refining and articulating the environmental ethic associated with the recycling of nuclear waste, and exposing the myth that burying plutonium solves our nuclear non-proliferation problems. We suggest six key ingredients as necessary steps that merit strong consideration in regaining public support for nuclear power. These include 1) seriously addressing the four technical issues summarized above; 2) expressing our key issues and results in language understandable at the high school (or lower) level; 3) continually striving for an open and honest management of the Industry; 4

  20. Whole-genome cartography of p53 response elements ranked on transactivation potential.

    Science.gov (United States)

    Tebaldi, Toma; Zaccara, Sara; Alessandrini, Federica; Bisio, Alessandra; Ciribilli, Yari; Inga, Alberto

    2015-06-17

    Many recent studies using ChIP-seq approaches cross-referenced to trascriptome data and also to potentially unbiased in vitro DNA binding selection experiments are detailing with increasing precision the p53-directed gene regulatory network that, nevertheless, is still expanding. However, most experiments have been conducted in established cell lines subjected to specific p53-inducing stimuli, both factors potentially biasing the results. We developed p53retriever, a pattern search algorithm that maps p53 response elements (REs) and ranks them according to predicted transactivation potentials in five classes. Besides canonical, full site REs, we developed specific pattern searches for non-canonical half sites and 3/4 sites and show that they can mediate p53-dependent responsiveness of associated coding sequences. Using ENCODE data, we also mapped p53 REs in about 44,000 distant enhancers and identified a 16-fold enrichment for high activity REs within those sites in the comparison with genomic regions near transcriptional start sites (TSS). Predictions from our pattern search were cross-referenced to ChIP-seq, ChIP-exo, expression, and various literature data sources. Based on the mapping of predicted functional REs near TSS, we examined expression changes of thirteen genes as a function of different p53-inducing conditions, providing further evidence for PDE2A, GAS6, E2F7, APOBEC3H, KCTD1, TRIM32, DICER, HRAS, KITLG and TGFA p53-dependent regulation, while MAP2K3, DNAJA1 and potentially YAP1 were identified as new direct p53 target genes. We provide a comprehensive annotation of canonical and non-canonical p53 REs in the human genome, ranked on predicted transactivation potential. We also establish or corroborate direct p53 transcriptional control of thirteen genes. The entire list of identified and functionally classified p53 REs near all UCSC-annotated genes and within ENCODE mapped enhancer elements is provided. Our approach is distinct from, and complementary

  1. Noncanonical DNA motifs as transactivation targets by wild type and mutant p53.

    Directory of Open Access Journals (Sweden)

    Jennifer J Jordan

    2008-06-01

    Full Text Available Sequence-specific binding by the human p53 master regulator is critical to its tumor suppressor activity in response to environmental stresses. p53 binds as a tetramer to two decameric half-sites separated by 0-13 nucleotides (nt, originally defined by the consensus RRRCWWGYYY (n = 0-13 RRRCWWGYYY. To better understand the role of sequence, organization, and level of p53 on transactivation at target response elements (REs by wild type (WT and mutant p53, we deconstructed the functional p53 canonical consensus sequence using budding yeast and human cell systems. Contrary to early reports on binding in vitro, small increases in distance between decamer half-sites greatly reduces p53 transactivation, as demonstrated for the natural TIGER RE. This was confirmed with human cell extracts using a newly developed, semi-in vitro microsphere binding assay. These results contrast with the synergistic increase in transactivation from a pair of weak, full-site REs in the MDM2 promoter that are separated by an evolutionary conserved 17 bp spacer. Surprisingly, there can be substantial transactivation at noncanonical (1/2-(a single decamer and (3/4-sites, some of which were originally classified as biologically relevant canonical consensus sequences including PIDD and Apaf-1. p53 family members p63 and p73 yielded similar results. Efficient transactivation from noncanonical elements requires tetrameric p53, and the presence of the carboxy terminal, non-specific DNA binding domain enhanced transactivation from noncanonical sequences. Our findings demonstrate that RE sequence, organization, and level of p53 can strongly impact p53-mediated transactivation, thereby changing the view of what constitutes a functional p53 target. Importantly, inclusion of (1/2- and (3/4-site REs greatly expands the p53 master regulatory network.

  2. Main factors affecting the fixing work about nuclear engineering and its discussion

    International Nuclear Information System (INIS)

    Zhang Zhihua; Liu Yaoguan; Qian Dazhi; Liu Hangang; Xu Xianqi; Deng Yue

    2010-01-01

    Main factors to the impact of the fixing work about nuclear engineering such as project design, construction, plan program, document, preparation, order, locale management, surveillance, quality assurance system and so on were presented. These factors were analyzed and discussed in this paper. Some measures and suggestions were put forward to accelerate construction fixing plan and insure good quality. We wish provide some references and help for someone engaged with construction of nuclear engineering. (authors)

  3. Incidents at nuclear power plants caused by the human factor

    International Nuclear Information System (INIS)

    Mashin, V. A.

    2012-01-01

    Psychological analysis of the causes of incorrect actions by personnel is discussed as presented in the report “Methodological guidelines for analyzing the causes of incidents in the operation of nuclear power plants.” The types of incorrect actions and classification of the root causes of errors by personnel are analyzed. Recommendations are made for improvements in the psychological analysis of causes of incorrect actions by personnel.

  4. Additional factors of nuclear war potential effect on ecosystems

    International Nuclear Information System (INIS)

    Khatchinson, T.; Kharuehll, M.; Kropper, U.; Grover, G.

    1988-01-01

    Available information on response of organisms and ecosystems to increase of ultraviolet radiation, air borne pollutant concentrations, radiation and fires in case of nuclear war is generalized. The presented data are based on accumulated experience and experimental investigations. Potentiality of arising a great amount of stress effect localized regions is noted. Severe consequences for agriculture and population, particularly in sinergic stress effect, are not excluded. 169 refs.; 5 figs.; 25 tabs

  5. Choosing the nuclear power option: Factors to be considered

    International Nuclear Information System (INIS)

    Gueorguiev, B.; Mahadeva Rao, K.V.

    2000-01-01

    To plan and develop a nuclear power program, policies must be formulated and decided at different stages and at different levels by the government and its organizations, by the utility and by other organizations in industry and research and education, each within its sphere of interest and influence. The purpose of this paper is to highlight areas where policy decisions are needed, the options available, what they mean and the contexts in which they should be considered. (author)

  6. Nuclear recycle: One of the key factors ensuring the sustainable development of China's nuclear power

    International Nuclear Information System (INIS)

    Jiang Yunqing

    2002-01-01

    Since early 1970's China has established a complete nuclear fuel cycle system for defense purpose. CNNC and its formers deal mainly with business in nuclear power and nuclear fuel cycle fields. Now COSTIND (CAEA) implements the governmental functions. Based on the features of energy sources, China is steady developing nuclear power as the appropriate supplement to meet demand of electricity in the southeast coastal regions. In the middle of 1980's, considering a number of elements, covering spent fuel arising from PWR dominantly, uranium source availability, development of FBR, radioactive waste management safely and existing good nuclear industry foundation etc., the closed fuel cycle strategy was formulated and announced internationally. In view of complexity of reprocessing technology and the limited spent fuel arising in the early period of nuclear power growing up, a multi-purpose pilot plant will be first set up. The plant involved in spent fuel AFR storage, and HEU/LEU fuel reprocessing separately has been constructed since 1991. At present more than a half of the project job has been completed while the preparation for long-distance transport of spent fuel is actively pushed on. It is expected that a centralized wet storage facility will be finished at the end of next year but the whole plant will be put into active commissioning in 2003. With the extension of the cumulative arising of spent fuel, a large scale reprocessing plant would be established around 2020. Reprocessed uranium will be surely re-enriched in the past manner while reactor-grade plutonium would be fabricated into MOX fuel to supply to FBR program. (author)

  7. Nuclear Power and Resource Efficiency—A Proposal for a Revised Primary Energy Factor

    Directory of Open Access Journals (Sweden)

    Ola Eriksson

    2017-06-01

    Full Text Available Measuring resource efficiency can be achieved using different methods, of which primary energy demand is commonly used. The primary energy factor (PEF is a figure describing how much energy from primary resources is being used per unit of energy delivered. The PEF for nuclear power is typically 3, which refers to thermal energy released from fission in relation to electricity generated. Fuel losses are not accounted for. However; nuclear waste represents an energy loss, as current plans for nuclear waste management mostly include final disposal. Based on a literature review and mathematical calculations of the power-to-fuel ratio for nuclear power, PEF values for the open nuclear fuel cycle (NFC option of nuclear power and different power mixes are calculated. These calculations indicate that a more correct PEF for nuclear power would be 60 (range 32–88; for electricity in Sweden (41% nuclear power PEF would change from 1.8 to 25.5, and the average PEF for electricity in the European Union (EU would change from 2.5 to 18. The results illustrate the poor resource efficiency of nuclear power, which paves the way for the fourth generation of nuclear power and illustrates the policy implication of using PEFs which are inconsistent with current waste management plans.

  8. Cross-talk between constitutive androstane receptor and hypoxia-inducible factor in the regulation of gene expression.

    Science.gov (United States)

    Shizu, Ryota; Shindo, Sawako; Yoshida, Takemi; Numazawa, Satoshi

    2013-05-23

    Hypoxia inducible factor (HIF) and 5'-AMP-activated protein kinase are often activated under similar physiological conditions. Constitutive androstane receptor (CAR) translocates into the nucleus in accordance with 5'-AMP-activated protein kinase and thus confers transactivation. The aim of the present study was to investigate a possible link between CAR and HIFα. Phenobarbital (PB), a typical CAR activator, increased the gene expression of HIF-target genes in the livers of mice, including erythropoietin, heme oxygenase-1 and vascular endothelial growth factor-a. PB induced an accumulation of nuclear HIF-1α and an increase in the HIF-responsive element-mediated transactivation in HepG2 cells. Cobalt chloride, a typical HIF activator, induced the gene expression of CAR-target genes, including cyp2b9 and cyp2b10, an accumulation of nuclear CAR and an increase in the PB-responsive enhancer module-mediated transactivation in the mouse liver. Immunoprecipitation-immunoblot and chromatin immunoprecipitation analyses suggest that CAR binds to the PB-responsive enhancer module with HIF-1α in the liver of untreated mice and that the complex dissociates upon PB treatment. Taken together these results suggest that CAR and HIF-α interact and reciprocally modulate the functions of each other. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  9. Transactivation of EGFR by LPS induces COX-2 expression in enterocytes.

    Directory of Open Access Journals (Sweden)

    Steven J McElroy

    Full Text Available Necrotizing enterocolitis (NEC is the leading cause of gastrointestinal morbidity and mortality in preterm infants. NEC is characterized by an exaggerated inflammatory response to bacterial flora leading to bowel necrosis. Bacterial lipopolysaccharide (LPS mediates inflammation through TLR4 activation and is a key molecule in the pathogenesis of NEC. However, LPS also induces cyclooxygenase-2 (COX-2, which promotes intestinal barrier restitution through stimulation of intestinal cell survival, proliferation, and migration. Epidermal growth factor receptor (EGFR activation prevents experimental NEC and may play a critical role in LPS-stimulated COX-2 production. We hypothesized that EGFR is required for LPS induction of COX-2 expression. Our data show that inhibiting EGFR kinase activity blocks LPS-induced COX-2 expression in small intestinal epithelial cells. LPS induction of COX-2 requires Src-family kinase signaling while LPS transactivation of EGFR requires matrix metalloprotease (MMP activity. EGFR tyrosine kinase inhibitors block LPS stimulation of mitogen-activated protein kinase ERK, suggesting an important role of the MAPK/ERK pathway in EGFR-mediated COX-2 expression. LPS stimulates proliferation of IEC-6 cells, but this stimulation is inhibited with either the EGFR kinase inhibitor AG1478, or the selective COX-2 inhibitor Celecoxib. Taken together, these data show that EGFR plays an important role in LPS-induction of COX-2 expression in enterocytes, which may be one mechanism for EGF in inhibition of NEC.

  10. Vaccinia Virus Protein C6 Inhibits Type I IFN Signalling in the Nucleus and Binds to the Transactivation Domain of STAT2.

    Directory of Open Access Journals (Sweden)

    Jennifer H Stuart

    2016-12-01

    Full Text Available The type I interferon (IFN response is a crucial innate immune signalling pathway required for defense against viral infection. Accordingly, the great majority of mammalian viruses possess means to inhibit this important host immune response. Here we show that vaccinia virus (VACV strain Western Reserve protein C6, is a dual function protein that inhibits the cellular response to type I IFNs in addition to its published function as an inhibitor of IRF-3 activation, thereby restricting type I IFN production from infected cells. Ectopic expression of C6 inhibits the induction of interferon stimulated genes (ISGs in response to IFNα treatment at both the mRNA and protein level. C6 inhibits the IFNα-induced Janus kinase/signal transducer and activator of transcription (JAK/STAT signalling pathway at a late stage, downstream of STAT1 and STAT2 phosphorylation, nuclear translocation and binding of the interferon stimulated gene factor 3 (ISGF3 complex to the interferon stimulated response element (ISRE. Mechanistically, C6 associates with the transactivation domain of STAT2 and this might explain how C6 inhibits the type I IFN signalling very late in the pathway. During virus infection C6 reduces ISRE-dependent gene expression despite the presence of the viral protein phosphatase VH1 that dephosphorylates STAT1 and STAT2. The ability of a cytoplasmic replicating virus to dampen the immune response within the nucleus, and the ability of viral immunomodulators such as C6 to inhibit multiple stages of the innate immune response by distinct mechanisms, emphasizes the intricacies of host-pathogen interactions and viral immune evasion.

  11. Factor analysis for the adoption of nuclear technology in diagnosis and treatment of chronic diseases

    International Nuclear Information System (INIS)

    Sato, Renato Cesar; Zouain, Desiree Moraes

    2012-01-01

    To identify and evaluate latent variables (variables that are not directly observed) for adopting and using nuclear technologies in diagnosis and treatment of chronic diseases. The measurement and management of these latent factors are important for health care due to complexities of the sector. Methods: An exploratory factor analysis study was conducted among 52 physicians practicing in the areas of Cardiology, Neurology and Oncology in the State of Sao Paulo who agreed to participate in the study between 2009 and 2010. Data were collected using an attitude measurement questionnaire, and analyzed according to the principal component method with Varimax rotation. Results: The component matrix after factor rotation showed three elucidative groups arranged according to demand for nuclear technology: clinical factors, structural factors, and technological factors. Clinical factors included questionnaire answers referring to medical history, previous interventions, complexity and chronicity of the disease. Structural factors included patient age, physician's practice area, and payment ability. Technological factors included prospective growth in the use of nuclear technology and availability of services. Conclusions: The clinical factors group dimension identified in the study included patient history, prior interventions, and complexity and chronicity of the disease. This dimension is the main motivating for adopting nuclear technology in diagnosis and treatment of chronic diseases. (author)

  12. Factor analysis for the adoption of nuclear technology in diagnosis and treatment of chronic diseases.

    Science.gov (United States)

    Sato, Renato Cesar; Zouain, Désirée Moraes

    2012-01-01

    To identify and evaluate latent variables (variables that are not directly observed) for adopting and using nuclear technologies in diagnosis and treatment of chronic diseases. The measurement and management of these latent factors are important for healthcare due to complexities of the sector. An exploratory factor analysis study was conducted among 52 physicians practicing in the areas of Cardiology, Neurology and Oncology in the State of Sao Paulo who agreed to participate in the study between 2009 and 2010. Data were collected using an attitude measurement questionnaire, and analyzed according to the principal component method with Varimax rotation. The component matrix after factor rotation showed three elucidative groups arranged according to demand for nuclear technology: clinical factors, structural factors, and technological factors. Clinical factors included questionnaire answers referring to medical history, previous interventions, complexity and chronicity of the disease. Structural factors included patient age, physician's practice area, and payment ability. Technological factors included prospective growth in the use of nuclear technology and availability of services. The clinical factors group dimension identified in the study included patient history, prior interventions, and complexity and chronicity of the disease. This dimension is the main motivator for adopting nuclear technology in diagnosis and treatment of chronic diseases.

  13. Development of human factors evaluation techniques for nuclear power plants

    International Nuclear Information System (INIS)

    Oh, I.S.; Lee, Y.H.; Lee, J.W.; Sim, B.S.

    1999-01-01

    This paper describes development of an operator task simulation analyzer and human factors evaluation techniques performed recently at Korea Atomic Energy Research Institute. The first is the SACOM (Simulation Analyzer with a Cognitive Operator Model) for the assessment of task performance by simulating control room operation. The latter has two objectives: to establish a human factors experiment facility, the Integrated Test Facility (ITF), and to establish techniques for human factors experiments. (author)

  14. Deletion of hepatocyte nuclear factor-1-beta in an infant with prune belly syndrome.

    Science.gov (United States)

    Haeri, Sina; Devers, Patricia L; Kaiser-Rogers, Kathleen A; Moylan, Vincent J; Torchia, Beth S; Horton, Amanda L; Wolfe, Honor M; Aylsworth, Arthur S

    2010-08-01

    Prune belly syndrome is a rare congenital disorder characterized by deficiency of abdominal wall muscles, cryptorchidism, and urinary tract anomalies. We have had the opportunity to study a baby with prune belly syndrome associated with an apparently de novo 1.3-megabase interstitial 17q12 microdeletion that includes the hepatocyte nuclear factor-1-beta gene at 17q12. One previous patient, an adult, has been reported with prune belly syndrome and a hepatocyte nuclear factor-1-beta microdeletion. Hepatocyte nuclear factor-1-beta is a widely expressed transcription factor that regulates tissue-specific gene expression and is expressed in numerous tissues including mesonephric duct derivatives, the renal tubule of the metanephros, and the developing prostate of the mouse. Mutations in hepatocyte nuclear factor-1-beta cause the "renal cysts and diabetes syndrome," isolated renal cystic dysplasia, and a variety of other malformations. Based on its expression pattern and the observation of two affected cases, we propose that haploinsufficiency of hepatocyte nuclear factor-1-beta may be causally related to the production of the prune belly syndrome phenotype through a mechanism of prostatic and ureteral hypoplasia that results in severe obstructive uropathy with urinary tract and abdominal distension. Copyright Thieme Medical Publishers.

  15. Human factors in the operation of nuclear power plants

    International Nuclear Information System (INIS)

    Swaton, E.; Neboyan, V.; Lederman, L.

    1987-01-01

    In large and complex interactive systems, human error can contribute substantially to system failures. At nuclear power plants, operational experience demonstrates that human error accounts for a considerable proportion of safety-related incidents. However, experience also shows that human intervention can be very effective if there is a thorough understanding of the situation in the plant. Thus, an efficient interface of man and machine is important not only to prevent human errors but also to assist the operator in coping with unforeseen events. Human reliability can be understood as a qualitative as well as a quantitative term. Qualitatively it can be described as the aim for successful human performance of activities necessary for system reliability and availability. Quantitatively, it refers to data on failure rates or error probabilities that can be used, for example, for probabilistic safety assessments

  16. Economic, political, and public acceptance factors influencing the future of nuclear power in the United States

    International Nuclear Information System (INIS)

    Gray, J.E.

    1989-01-01

    Views are presented on the economic, political, and public acceptance factors influencing the future of nuclear power in the United States. Electricity has been the preferred energy choice throughout the world. Nuclear energy must produce a competitive economic result along with energy supply security and environmental impacts. In the United States there exists ample experience and capacity to plan, design, construct, and operate new large nuclear power plants which could be competitive. Even at the lowest level of apparent safety and acceptance there was on the whole enough economic incentive and political support to keep the enterprise going. According to the United States Council for Energy Awareness polls, public acceptance is positive. The long-term outlook of nuclear power should be favorable. The one thing which would preclude nuclear power having a future in the United States would be for all parties to insist on eliminating all risks

  17. Hepatitis B Virus X Protein Up-Regulates AKR1C1 Expression Through Nuclear Factor-Y in Human Hepatocarcinoma Cells.

    Science.gov (United States)

    Li, Kai; Ding, Shijia; Chen, Ke; Qin, Dongdong; Qu, Jialin; Wang, Sen; Sheng, Yanrui; Zou, Chengcheng; Chen, Limin; Tang, Hua

    2013-01-01

    The hepatitis B virus X (HBx) protein has long been recognized as an important transcriptional transactivator of several genes. Human aldo-keto reductase family 1, member C1 (AKR1C1), a member of the family of AKR1CS, is significantly increased in HBx-expressed cells. This study aimed to investigate the possible mechanism of HBx in regulating AKR1C1 expression in HepG2.2.15 cells and the role of AKR1C1 for HBV-induced HCC. RT-PCR was performed to detect AKR1C1 expression on mRNA level in HepG2 and HepG2.2.15 cell. The promoter activity of AKR1C1 was assayed by transient transfection and Dual-luciferase reporter assay system. The AKR1C1 promoter sequence was screened using the TFSEARCH database and the ALIBABA 2.0 software. The potential transcription factors binding sites were identified using 5' functional deletion analysis and site-directed mutagenesis. In this study, we found that HBx promoted AKR1C1 expression in HepG2.2.15 cells. Knockdown of HBx inhibited AKR1C1 activation. The role of HBx expression in regulating the promoter activity of human AKR1C1 gene was analyzed. The 5'functional deletion analysis identified that the region between -128 and -88 was the minimal promoter region of HBx to activate AKR1C1 gene expression. Site-directed mutagenesis studies suggested that nuclear factor-Y (NF-Y) plays an important role in this HBx-induced AKR1C1 activation. In HepG2.2.1.5 cell, HBx can promote AKR1C1 promoter activity and thus activates the basal transcription of AKR1C1 gene. This process is mediated by the transcription factor NF-Y. This study explored the mechanism for the regulation of HBV on AKR1C1 expression and has provided a new understanding of HBV-induced HCC.

  18. p53 transactivation and the impact of mutations, cofactors and small molecules using a simplified yeast-based screening system.

    Directory of Open Access Journals (Sweden)

    Virginia Andreotti

    Full Text Available The p53 tumor suppressor, which is altered in most cancers, is a sequence-specific transcription factor that is able to modulate the expression of many target genes and influence a variety of cellular pathways. Inactivation of the p53 pathway in cancer frequently occurs through the expression of mutant p53 protein. In tumors that retain wild type p53, the pathway can be altered by upstream modulators, particularly the p53 negative regulators MDM2 and MDM4.Given the many factors that might influence p53 function, including expression levels, mutations, cofactor proteins and small molecules, we expanded our previously described yeast-based system to provide the opportunity for efficient investigation of their individual and combined impacts in a miniaturized format. The system integrates i variable expression of p53 proteins under the finely tunable GAL1,10 promoter, ii single copy, chromosomally located p53-responsive and control luminescence reporters, iii enhanced chemical uptake using modified ABC-transporters, iv small-volume formats for treatment and dual-luciferase assays, and v opportunities to co-express p53 with other cofactor proteins. This robust system can distinguish different levels of expression of WT and mutant p53 as well as interactions with MDM2 or 53BP1.We found that the small molecules Nutlin and RITA could both relieve the MDM2-dependent inhibition of WT p53 transactivation function, while only RITA could impact p53/53BP1 functional interactions. PRIMA-1 was ineffective in modifying the transactivation capacity of WT p53 and missense p53 mutations. This dual-luciferase assay can, therefore, provide a high-throughput assessment tool for investigating a matrix of factors that can influence the p53 network, including the effectiveness of newly developed small molecules, on WT and tumor-associated p53 mutants as well as interacting proteins.

  19. The Regulatory Role of Nuclear Factor Kappa B in the Heart of Hereditary Hypertriglyceridemic Rat

    Czech Academy of Sciences Publication Activity Database

    Vranková, S.; Barta, A.; Klimentová, J.; Dovinová, I.; Líšková, Silvia; Dobešová, Zdenka; Pecháňová, O.; Kuneš, Jaroslav; Zicha, Josef

    2016-01-01

    Roč. 2016, č. 2016 (2016), s. 9814038 ISSN 1942-0900 R&D Projects: GA MZd(CZ) NV15-25396A Institutional support: RVO:67985823 Keywords : nuclear factor-kB * nitric oxide * reactive oxygen species * heart * hereditary hypertriglyceridemic rats Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 4.593, year: 2016

  20. Apolipoprotein E isoform dependently affects Tat-mediated HIV-1 LTR transactivation.

    Science.gov (United States)

    Khan, Nabab; Datta, Gaurav; Geiger, Jonathan D; Chen, Xuesong

    2018-03-20

    Apolipoprotein E (ApoE) is the major carrier protein that mediates the transport and delivery of cholesterol and other lipids in the brain. Three isoforms of ApoE (ApoE2, ApoE3, ApoE4) exist in humans, and their relative expression levels impact HIV-1 infection, HIV-1/AIDS disease progression, and cognitive decline associated with HIV-1-associated neurocognitive disorder. Because HIV-1 Tat, a viral protein essential for HIV-1 replication, can bind to low-density lipoprotein receptor-related protein 1 (LRP1) that controls ApoE uptake in the brain, we determined the extent to which different isoforms of ApoE affected Tat-mediated HIV-1 LTR transactivation. Using U87MG glioblastoma cells expressing LTR-driven luciferase, we determined the extent to which LRP1 as well as ApoE2, ApoE3, and ApoE4 affected Tat-mediated HIV-1 LTR transactivation. A specific LRP1 antagonist and siRNA knockdown of LRP1 both restricted significantly Tat-mediated LTR transactivation. Of the three ApoEs, ApoE4 was the least potent and effective at preventing HIV-1 Tat internalization and at decreasing Tat-mediated HIV-1 LTR transactivation. Further, Tat-mediated LTR transactivation was attenuated by an ApoE mimetic peptide, and ApoE4-induced restriction of Tat-mediated LTR transactivation was potentiated by an ApoE4 structure modulator that changes ApoE4 into an ApoE3-like phenotype. These findings help explain observed differential effects of ApoEs on HIV-1 infectivity and the prevalence of HAND in people living with HIV-1 infection and suggest that ApoE mimetic peptides and ApoE4 structure modulator might be used as a therapeutic strategy against HIV-1 infection and associated neurocognitive disorders.

  1. Negative transcriptional regulation of mitochondrial transcription factor A (TFAM) by nuclear TFAM

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Jin; Kang, Young Cheol; Park, Wook-Ha; Jeong, Jae Hoon; Pak, Youngmi Kim, E-mail: ykpak@khu.ac.kr

    2014-07-18

    Highlights: • TFAM localizes in nuclei and mitochondria of neuronal cells. • Nuclear TFAM does not bind the Tfam promoter. • Nuclear TFAM reduced the Tfam promoter activity via suppressing NRF-1 activity. • A novel self-negative feedback regulation of Tfam gene expression is explored. • FAM may play different roles depending on its subcellular localizations. - Abstract: The nuclear DNA-encoded mitochondrial transcription factor A (TFAM) is synthesized in cytoplasm and transported into mitochondria. TFAM enhances both transcription and replication of mitochondrial DNA. It is unclear, however, whether TFAM plays a role in regulating nuclear gene expression. Here, we demonstrated that TFAM was localized to the nucleus and mitochondria by immunostaining, subcellular fractionation, and TFAM-green fluorescent protein hybrid protein studies. In HT22 hippocampal neuronal cells, human TFAM (hTFAM) overexpression suppressed human Tfam promoter-mediated luciferase activity in a dose-dependent manner. The mitochondria targeting sequence-deficient hTFAM also repressed Tfam promoter activity to the same degree as hTFAM. It indicated that nuclear hTFAM suppressed Tfam expression without modulating mitochondrial activity. The repression required for nuclear respiratory factor-1 (NRF-1), but hTFAM did not bind to the NRF-1 binding site of its promoter. TFAM was co-immunoprecipitated with NRF-1. Taken together, we suggest that nuclear TFAM down-regulate its own gene expression as a NRF-1 repressor, showing that TFAM may play different roles depending on its subcellular localizations.

  2. Towards high precision measurements of nuclear g-factors for the Be isotopes

    Energy Technology Data Exchange (ETDEWEB)

    Takamine, A., E-mail: icot@riken.jp [RIKEN, Nishina Center for Accelerator Based Science, Wako City, Saitama (Japan); Wada, M. [RIKEN, Nishina Center for Accelerator Based Science, Wako City, Saitama (Japan); Okada, K. [Department of Physics, Sophia University, Chiyoda Ward, Tokyo (Japan); Ito, Y. [RIKEN, Nishina Center for Accelerator Based Science, Wako City, Saitama (Japan); Schury, P.; Arai, F. [RIKEN, Nishina Center for Accelerator Based Science, Wako City, Saitama (Japan); Institute of Physics, University of Tsukuba, Tsukuba City, Ibaraki (Japan); Katayama, I. [RIKEN, Nishina Center for Accelerator Based Science, Wako City, Saitama (Japan); Imamura, K. [RIKEN, Nishina Center for Accelerator Based Science, Wako City, Saitama (Japan); Department of Physics, Meiji University, Kawasaki City, Kanagawa (Japan); Ichikawa, Y.; Ueno, H. [RIKEN, Nishina Center for Accelerator Based Science, Wako City, Saitama (Japan); Wollnik, H. [Department of Chemistry and BioChemistry, New Mexico State University, Las Cruces, NM (United States); Schuessler, H.A. [Department of Physics, Texas A& M University, College Station, TX (United States)

    2016-06-01

    We describe the present status of future high-precision measurements of nuclear g-factors utilizing laser-microwave double and laser-microwave-rf triple resonance methods for online-trapped, laser-cooled radioactive beryllium isotope ions. These methods have applicability to other suitably chosen isotopes and for beryllium show promise in deducing the hyperfine anomaly of {sup 11}Be with a sufficiently high precision to study the nuclear magnetization distribution of this one-neutron halo nucleus in a nuclear-model-independent manner.

  3. Nuclear Power and Resource Efficiency—A Proposal for a Revised Primary Energy Factor

    OpenAIRE

    Ola Eriksson

    2017-01-01

    Measuring resource efficiency can be achieved using different methods, of which primary energy demand is commonly used. The primary energy factor (PEF) is a figure describing how much energy from primary resources is being used per unit of energy delivered. The PEF for nuclear power is typically 3, which refers to thermal energy released from fission in relation to electricity generated. Fuel losses are not accounted for. However; nuclear waste represents an energy loss, as current plans for ...

  4. Human factors design review guidelines for advanced nuclear control room technologies

    International Nuclear Information System (INIS)

    O'Hara, J.; Brown, W.; Granda, T.; Baker, C.

    1991-01-01

    Advanced control rooms (ACRs) for future nuclear power plants are being designed utilizing computer-based technologies. The US Nuclear Regulatory Commission reviews the human engineering aspects of such control rooms to ensure that they are designed to good human factors engineering principles and that operator performance and reliability are appropriately supported in order to protect public health and safety. This paper describes the rationale, general approach, and initial development of an NRC Advanced Control Room Design Review Guideline. 20 refs., 1 fig

  5. Human factors in maintenance: development and research in Swedish nuclear power plants

    International Nuclear Information System (INIS)

    Salo, I.; Svenson, O.

    2001-11-01

    The report investigated previously completed, ongoing, and planned research and development projects focusing human factors and maintenance work carried out at Swedish nuclear power plants and SKI. In addition, needs for future research and development works were also investigated. Participants from all nuclear power plants and SKI were included in the study. Participants responded to a set of questions in an interview. The interviews also generated a list of future research and development projects. (au)

  6. Human factors in maintenance: Development and research in Swedish nuclear power plants

    International Nuclear Information System (INIS)

    Salo, I.; Svensson, Ola

    2001-11-01

    The present report investigated previously completed, ongoing, and planned research and development projects focusing human factors and maintenance work carried out at Swedish nuclear power plants and SKI. In addition, needs for future research and development works were also investigated. Participants from all nuclear power plants and SKI were included in the study. Participants responded to a set of questions in an interview. The interviews also generated a list of future research and development projects

  7. Human factors in maintenance: Development and research in Swedish nuclear power plants

    Energy Technology Data Exchange (ETDEWEB)

    Salo, I. [Lund Univ. (Sweden). Dept. of Psychology; Svensson, Ola [Stockholm Univ. (Sweden). Dept. of Psychology

    2001-11-01

    The present report investigated previously completed, ongoing, and planned research and development projects focusing human factors and maintenance work carried out at Swedish nuclear power plants and SKI. In addition, needs for future research and development works were also investigated. Participants from all nuclear power plants and SKI were included in the study. Participants responded to a set of questions in an interview. The interviews also generated a list of future research and development projects.

  8. Contribution to the investigation of the p53 in vivo and in vitro trans-activation activity

    International Nuclear Information System (INIS)

    Meiller, A.

    2004-03-01

    Among the body's defence mechanisms, the programmed cellular death or apoptosis is an important safeguard way which allows the body to get rid of the injured cells before they acquire steady genetic modifications leading to an anarchistic multiplication. As p53 tumor suppressor gene plays a predominant role within this process, this research report first presents the p53 protein, its structure, its activities as a transcription factor, its modifications and the implications on its functional activities, its biological activities, and describes the p53 intracellular rate regulation and the use of this protein in radiology, particularly in 'in vivo' investigations on irradiated mice. It also presents the p53 family. Then, the author reports experimental investigations on possible other genes which could be trans-activated by p53. A gene is identified as a new target gene. She also demonstrates a new p53 activation path induced by another member of the p53 family, the p73 alpha protein

  9. Human factors estimation methods in nuclear power plant

    International Nuclear Information System (INIS)

    Takano, Kenichi; Yoshino, Kenji; Nagasaka, Akihiko; Ishii, Keichiro; Nakasa, Hiroyasu

    1985-01-01

    To improve the operational and maintenance work reliability, it is neccessary for workers to maintain his performance always at high level, that leads to decreasing mistaken judgements and operations. This paper inuolves the development and evaluation of ''Multi-Purpose Physiological Information Measurement system'' to estimate human performance and conditions with a highly fixed quantity. The following itemes is mentioned : (1) Most suitable physiological informations are selected to measure worker' performance in nuclear power plant with none-disturbance, ambulatory, continual, and multi channel measurement. (2) Relatively important physiological informations are measured with the real-time monitoring functions. (electrocardiogram, respirometric functions and EMG (electromyogram) pulse rete). (3) It is made to optimize the measurement condition and analysing methods in the use of a noise-cut function and a D.C. drift cutting method. (4) As a example, it is clear that, when the different weight is loaded to the arm and make it strech-bend motion, the EMG signal is measured and analysed by this system, the analysed EMG pulse rate and maximum amplitude is related to the arm loaded weight. (author)

  10. Computerized aids and human factors in nuclear power plant operation

    International Nuclear Information System (INIS)

    Bastl, W.

    1988-01-01

    When guiding a complex process and associated intermeshed systems in a nuclear power plant, a primary issue consists of the call for excellent information. Technically speaking, today's centralized control rooms are at the end of a development phase which has been governed by the introduction of remote information and remote control systems. But by centralization, an information overload problem arose, and it has been solved by dividing panels according to systems, operational phases and specific tasks. In addition, the overview and relationship of systems have been visualized by mimic diagrams. It is attempted to make transparent the technical back-ground of the processes and systems to be controlled, thus to provide the necessary basis for understanding the problems of operators. Practical examples are used for the purpose. The information dilemma, the systems for high level information, automation and information, plant safety and information, and the problem of where to go from here are described. Computerized operator aids must be discussed along assistance in information and assistance in automatic control. (Kako, I.)

  11. Relationship between organizational factors, safety culture and PSA in nuclear power plant operations

    International Nuclear Information System (INIS)

    Joksimovich, V.; Orvis, D.D.

    1997-01-01

    There are four nuclear safety imperatives or ''4Ms'': machine (hardware, design, QA/QC), milieux (operating conditions, environment, natural phenomena), man (human reliability) and management (organizational and management influences). Nuclear safety evaluations as well as evolution of its most powerful tool, Probabilistic Safety Assessment (PSA), followed chronologically the 4M constituents. The nuclear industry worldwide, and the nuclear safety regulators in particular, have been preoccupied with the first M almost to the point of obsession with belated and only intuitive interest in the third and fourth M (human dimension). Human factors or economics in the nuclear industry was an afterthought. Human reliability was essentially born in the aftermath of the Three Mile Island (TMI) accident. Impact of organizational factors on nuclear safety is only in the early stages of R and D. This paper describes some of the concepts being pursued by APG to link organizational factors and safety culture to Human Reliability Analysis (HRA) and to integrate such into probabilistic safety assessment (PSA), e.g. [APG, 1993]. (author). 11 refs, 4 figs, 1 tab

  12. Evironmental assessment factors relating to reprocessing of spent nuclear fuel

    International Nuclear Information System (INIS)

    1978-05-01

    This document is in two parts. Part I presents the criteria and evaluation factors, based primarily on US experience, which may be used to carry out an environmental assessment of spent fuel reprocessing. The concept of As Low as is Reasonably Achievable (ALARA) is introduced in limiting radiation exposure. The factors influencing both occupational and general public radiation exposure are reviewed. Part II provides information on occupational and general public radiation exposure in relation to reprocessing taken from various sources including UNSCEAR and GESMO. Some information is provided in relation to potential accidents at reprocessing or MOX fuel refabrication plants. The magnitude of the services, energy, land use and non-radiological effluents for the reference design of reprocessing plant are also presented

  13. Efficiency factor of a chemical nuclear reactor with gamma sources

    International Nuclear Information System (INIS)

    Anguis T, C.

    1975-01-01

    A chemonuclear reactor is simulated in order to calculate the efficiency factor of molecular species in chemical reactions induced by gamma radiation, with the purpose to obtain information for its design and consider the electromagnetic energy as a possible solution to the present problem of energy. The research is based on a mathematical model of succesive Compton processes applied to spherical and cylindrical geometry and corroborated through the absorbed dose and the experimental date of the increase factor, for the radioisotopic sources Co-60 and Cs-137 relating the quantity of energy deposited into various cylinders with the G value, the relation radius/height of the reactor is optimized according to the molecular production. This is illustrated with the radiolysis of a solution of CH 3 OH/H 2 O which forms H 2 and with the obtainment of C 2 H 5 Br that represents and industrial process induced radioactively. The results show a greater energy deposition with Cs-137 but a larger production of H 2 /hr with Co-60, and besides we can find high production values of C 2 H 5 Br. The cylinder with more advantages is that whose relation R/H is of 0.5. It can be concluded that the final selection of the reactor should be made after a more intense study of the used isotope and the source activity. The efficiency factor of H 2 can be increased selecting the appropriate type and concentration of solute of the irradiated aqueous solutions

  14. Analysis on nuclear power plant control room system design and improvement based on human factor engineering

    International Nuclear Information System (INIS)

    Gao Feng; Liu Yanzi; Sun Yongbin

    2014-01-01

    The design of nuclear power plant control room system is a process of improvement with the implementation of human factor engineering theory and guidance. The method of implementation human factor engineering principles into the nuclear power plant control room system design and improvement was discussed in this paper. It is recommended that comprehensive address should be done from control room system function, human machine interface, digital procedure, control room layout and environment design based on the human factor engineering theory and experience. The main issues which should be paid more attention during the control room system design and improvement also were addressed in this paper, and then advices and notices for the design and improvement of the nuclear power plant control room system were afforded. (authors)

  15. Human factors engineering applied to Control Centre Design of a research nuclear reactor

    Energy Technology Data Exchange (ETDEWEB)

    Farias, Larissa P. de; Santos, Isaac J.A. Luquetti dos; Carvalho, Paulo V.R., E-mail: larissapfarias@ymail.com [Instituto de Engenharia Nuclear (DENN/SEESC/IEN/CNEN-RJ), Rio de Janeiro, RJ (Brazil). Lab, de Usabilidade e Confiabilidade Humana; Monteiro, Beany G. [Universidade Federal do Rio Janeiro (UFRJ), Rio Janeiro, RJ (Brazil). Departamento de Desenho Industrial

    2017-07-01

    The Human Factors Engineering (HFE) program is an essential aspect for the design of nuclear installations. The overall aim of the HFE program is the improvement of the operational reliability and safety of plant operation. The HFE program main purpose is to ensure that human factor practices are incorporated into the plant design, emphasizing man-machine interface issues and design improvement of the nuclear reactor Control Centre. The Control Centre of nuclear reactor is a combination of control rooms, control suites and local control stations, which are functionally connected and located on the reactor site. The objective of this paper is to present a design approach for the Control Centre of a nuclear reactor used to produce radioisotopes and for nuclear research, including human factor issues. The design approach is based on participatory design principles, using human factor standards, ergonomic guidelines, and the participation of a multidisciplinary team during all design phases. Using the information gathered, an initial sketch 3D of the Control Centre was developed. (author)

  16. Human factors engineering applied to Control Centre Design of a research nuclear reactor

    International Nuclear Information System (INIS)

    Farias, Larissa P. de; Santos, Isaac J.A. Luquetti dos; Carvalho, Paulo V.R.; Monteiro, Beany G.

    2017-01-01

    The Human Factors Engineering (HFE) program is an essential aspect for the design of nuclear installations. The overall aim of the HFE program is the improvement of the operational reliability and safety of plant operation. The HFE program main purpose is to ensure that human factor practices are incorporated into the plant design, emphasizing man-machine interface issues and design improvement of the nuclear reactor Control Centre. The Control Centre of nuclear reactor is a combination of control rooms, control suites and local control stations, which are functionally connected and located on the reactor site. The objective of this paper is to present a design approach for the Control Centre of a nuclear reactor used to produce radioisotopes and for nuclear research, including human factor issues. The design approach is based on participatory design principles, using human factor standards, ergonomic guidelines, and the participation of a multidisciplinary team during all design phases. Using the information gathered, an initial sketch 3D of the Control Centre was developed. (author)

  17. The E3 ubiquitin ligase WWP2 facilitates RUNX2 protein transactivation in a mono-ubiquitination manner during osteogenic differentiation.

    Science.gov (United States)

    Zhu, Wei; He, Xinyu; Hua, Yue; Li, Qian; Wang, Jiyong; Gan, Xiaoqing

    2017-07-07

    Poly-ubiquitination-mediated RUNX2 degradation is an important cause of age- and inflammation-related bone loss. NEDD4 family E3 ubiquitin protein ligases are thought to be the major regulators of RUNX2 poly-ubiquitination. However, we observed a mono-ubiquitination of RUNX2 that was catalyzed by WWP2, a member of the NEDD4 family of E3 ubiquitin ligases. WWP2 has been reported to catalyze the mono-ubiquitination of Goosecoid in chondrocytes, facilitating craniofacial skeleton development. In this study, we found that osteogenic differentiation of mesenchymal stem cells promoted WWP2 expression and nuclear accumulation. Knockdown of Wwp2 in mesenchymal stem cells and osteoblasts led to significant deficiencies of osteogenesis, including decreased mineral deposition and down-regulation of osteogenic marker genes. Co-immunoprecipitation experiments showed the interaction of WWP2 with RUNX2 in vitro and in vivo Mono-ubiquitination by WWP2 leads to RUNX2 transactivation, as evidenced by the wild type of WWP2, but not its ubiquitin ligase-dead mutant, augmenting RUNX2-reponsive reporter activity. Moreover, deletion of WWP2-dependent mono-ubiquitination resulted in striking defects of RUNX2 osteoblastic activity. In addition, ectopic expression of the constitutively active type 1A bone morphogenetic protein receptor enhanced WWP2-dependent RUNX2 ubiquitination and transactivation, demonstrating a regulatory role of bone morphogenetic protein signaling in the WWP2-RUNX2 axis. Taken together, our results provide evidence that WWP2 serves as a positive regulator of osteogenesis by augmenting RUNX2 transactivation in a non-proteolytic mono-ubiquitination manner. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. Economic assessment factors relating to spent nuclear fuel reprocessing

    International Nuclear Information System (INIS)

    This paper is in two parts. Part I discusses the factors to be applied in an economic assessment of reprocessing. It sets forth three basic cost components, namely capital costs, operating costs and the cost of capital utilization. It lists the various components of each cost area. Part II proposes a relationship between these respective cost areas, tabulates a range of costs and then develops unit costs for reprocessing operations. Finally, an addendum to the paper gives a more detailed breakdown of the capital costs of a reprocessing plant

  19. Psychological factors affecting public acceptance of nuclear energy. Comparative analysis focusing on regional characteristics and degree of knowledge

    International Nuclear Information System (INIS)

    Kimura, Hiroshi; Suzuki, Atsuyuki; Furuta, Kazuo

    2003-01-01

    The purpose of this research is to clarify how psychological factors' impact on public acceptance of nuclear energy varies with where they live and their degree of knowledge. For this purpose, we carried out questionnaire survey about nuclear energy at three urban areas and two nuclear power plant siting areas. After collecting data, we applied factor analysis to the data, and found four factors which construct cognitive structure of nuclear energy. Using multiple regression analysis, we evaluated the impact of the four factors on two issues: the decision for or against nuclear policy and the reaction to nuclear power plant siting, and compared changes of the impact by where respondents live and their degree of knowledge. Consequently, we found that the impact of all four factors on the two issues varies with where respondents live. We also found that the impact of respondents' degree of knowledge to four factors varies with where they live. (author)

  20. Safe Operation of Nuclear Power Plants: Impacts of Human and Organisational Factors and Emerging Technologies

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-07-01

    In co-operation with the OECD Nuclear Energy Agency (NEA), the Halden Reactor Project organised a Summer School on ''Safe Operation of Nuclear Power Plants: Impacts of Human and Organisational Factors and Emerging Technologies'' in the period August 27-August 31, 2001. The Summer School was intended for scientists, engineers and technicians working for nuclear installations, engineering companies, industry and members of universities and research institutes, who wanted to broaden their nuclear background by getting acquainted with Man-Technology-Organisation-related subjects and issues. The Summer School should also serve to transfer knowledge to the ''young generation'' in the nuclear field. The following presentations were given: (1) Overview of the Nuclear Community and Current issues, (2) The Elements of Safety Culture; Evaluation of Events, (3) Quality Management (QM), (4) Probabilistic Risk Assessment (PSA), (5) Human Behaviour from the Viewpoint of Industrial Psychology, (6) Technical tour of the Halden Project Experimental Facilities, (7) Human Factors in Control Room Design, (8) Computerised Operator Support Systems (COSSs) and (9) Artificial Intelligence; a new Approach. Most of the contributions are overhead figures from spoken lectures.

  1. Safe Operation of Nuclear Power Plants: Impacts of Human and Organisational Factors and Emerging Technologies

    International Nuclear Information System (INIS)

    2001-01-01

    In co-operation with the OECD Nuclear Energy Agency (NEA), the Halden Reactor Project organised a Summer School on ''Safe Operation of Nuclear Power Plants: Impacts of Human and Organisational Factors and Emerging Technologies'' in the period August 27-August 31, 2001. The Summer School was intended for scientists, engineers and technicians working for nuclear installations, engineering companies, industry and members of universities and research institutes, who wanted to broaden their nuclear background by getting acquainted with Man-Technology-Organisation-related subjects and issues. The Summer School should also serve to transfer knowledge to the ''young generation'' in the nuclear field. The following presentations were given: (1) Overview of the Nuclear Community and Current issues, (2) The Elements of Safety Culture; Evaluation of Events, (3) Quality Management (QM), (4) Probabilistic Risk Assessment (PSA), (5) Human Behaviour from the Viewpoint of Industrial Psychology, (6) Technical tour of the Halden Project Experimental Facilities, (7) Human Factors in Control Room Design, (8) Computerised Operator Support Systems (COSSs) and (9) Artificial Intelligence; a new Approach. Most of the contributions are overhead figures from spoken lectures

  2. Global Developmental Gene Programing Involves a Nuclear Form of Fibroblast Growth Factor Receptor-1 (FGFR1.

    Directory of Open Access Journals (Sweden)

    Christopher Terranova

    Full Text Available Genetic studies have placed the Fgfr1 gene at the top of major ontogenic pathways that enable gastrulation, tissue development and organogenesis. Using genome-wide sequencing and loss and gain of function experiments the present investigation reveals a mechanism that underlies global and direct gene regulation by the nuclear form of FGFR1, ensuring that pluripotent Embryonic Stem Cells differentiate into Neuronal Cells in response to Retinoic Acid. Nuclear FGFR1, both alone and with its partner nuclear receptors RXR and Nur77, targets thousands of active genes and controls the expression of pluripotency, homeobox, neuronal and mesodermal genes. Nuclear FGFR1 targets genes in developmental pathways represented by Wnt/β-catenin, CREB, BMP, the cell cycle and cancer-related TP53 pathway, neuroectodermal and mesodermal programing networks, axonal growth and synaptic plasticity pathways. Nuclear FGFR1 targets the consensus sequences of transcription factors known to engage CREB-binding protein, a common coregulator of transcription and established binding partner of nuclear FGFR1. This investigation reveals the role of nuclear FGFR1 as a global genomic programmer of cell, neural and muscle development.

  3. Global Developmental Gene Programing Involves a Nuclear Form of Fibroblast Growth Factor Receptor-1 (FGFR1).

    Science.gov (United States)

    Terranova, Christopher; Narla, Sridhar T; Lee, Yu-Wei; Bard, Jonathan; Parikh, Abhirath; Stachowiak, Ewa K; Tzanakakis, Emmanuel S; Buck, Michael J; Birkaya, Barbara; Stachowiak, Michal K

    2015-01-01

    Genetic studies have placed the Fgfr1 gene at the top of major ontogenic pathways that enable gastrulation, tissue development and organogenesis. Using genome-wide sequencing and loss and gain of function experiments the present investigation reveals a mechanism that underlies global and direct gene regulation by the nuclear form of FGFR1, ensuring that pluripotent Embryonic Stem Cells differentiate into Neuronal Cells in response to Retinoic Acid. Nuclear FGFR1, both alone and with its partner nuclear receptors RXR and Nur77, targets thousands of active genes and controls the expression of pluripotency, homeobox, neuronal and mesodermal genes. Nuclear FGFR1 targets genes in developmental pathways represented by Wnt/β-catenin, CREB, BMP, the cell cycle and cancer-related TP53 pathway, neuroectodermal and mesodermal programing networks, axonal growth and synaptic plasticity pathways. Nuclear FGFR1 targets the consensus sequences of transcription factors known to engage CREB-binding protein, a common coregulator of transcription and established binding partner of nuclear FGFR1. This investigation reveals the role of nuclear FGFR1 as a global genomic programmer of cell, neural and muscle development.

  4. DMPD: Nuclear factor-kappaB: activation and regulation during toll-like receptorsignaling. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17349209 Nuclear factor-kappaB: activation and regulation during toll-like receptorsign...clear factor-kappaB: activation and regulation during toll-like receptorsignaling. PubmedID 17349209 Title N...uclear factor-kappaB: activation and regulation during toll-like receptorsignalin

  5. Factor analysis for the adoption of nuclear technology in diagnosis and treatment of chronic diseases

    Directory of Open Access Journals (Sweden)

    Renato Cesar Sato

    2012-03-01

    Full Text Available Objective: To identify and evaluate latent variables (variables that are not directly observed for adopting and using nuclear technologiesin diagnosis and treatment of chronic diseases. The measurementand management of these latent factors are important for healthcaredue to complexities of the sector. Methods: An exploratory factoranalysis study was conducted among 52 physicians practicing in theareas of Cardiology, Neurology and Oncology in the State of Sao Paulowho agreed to participate in the study between 2009 and 2010. Datawere collected using an attitude measurement questionnaire, andanalyzed according to the principal component method with Varimaxrotation. Results: The component matrix after factor rotation showedthree elucidative groups arranged according to demand for nucleartechnology: clinical factors, structural factors, and technologicalfactors. Clinical factors included questionnaire answers referring tomedical history, previous interventions, complexity and chronicityof the disease. Structural factors included patient age, physician’spractice area, and payment ability. Technological factors includedprospective growth in the use of nuclear technology and availabilityof services. Conclusions: The clinical factors group dimensionidentified in the study included patient history, prior interventions,and complexity and chronicity of the disease. This dimension is themain motivator for adopting nuclear technology in diagnosis andtreatment of chronic diseases.

  6. Trans-activation of an artificial dTam3 transposable element in transgenic tobacco plants

    NARCIS (Netherlands)

    Haring, Michel A.; Teeuwen-de Vroomen, Marianne J.; Nijkamp, H. John J.; Hille, Jacques

    1991-01-01

    In Antirrhinum majus only autonomous Tam3 transposons have been characterized. We investigated whether an artificial dTam3 element, with a deletion in the presumptive transposase coding region, can be trans-activated in tobacco by an activator Tam3 element, which was immobilized by the deletion of

  7. The unit cost factors and calculation methods for decommissioning - Cost estimation of nuclear research facilities

    International Nuclear Information System (INIS)

    Kwan-Seong Jeong; Dong-Gyu Lee; Chong-Hun Jung; Kune-Woo Lee

    2007-01-01

    Available in abstract form only. Full text of publication follows: The uncertainties of decommissioning costs increase high due to several conditions. Decommissioning cost estimation depends on the complexity of nuclear installations, its site-specific physical and radiological inventories. Therefore, the decommissioning costs of nuclear research facilities must be estimated in accordance with the detailed sub-tasks and resources by the tasks of decommissioning activities. By selecting the classified activities and resources, costs are calculated by the items and then the total costs of all decommissioning activities are reshuffled to match with its usage and objectives. And the decommissioning cost of nuclear research facilities is calculated by applying a unit cost factor method on which classification of decommissioning works fitted with the features and specifications of decommissioning objects and establishment of composition factors are based. Decommissioning costs of nuclear research facilities are composed of labor cost, equipment and materials cost. Of these three categorical costs, the calculation of labor costs are very important because decommissioning activities mainly depend on labor force. Labor costs in decommissioning activities are calculated on the basis of working time consumed in decommissioning objects and works. The working times are figured out of unit cost factors and work difficulty factors. Finally, labor costs are figured out by using these factors as parameters of calculation. The accuracy of decommissioning cost estimation results is much higher compared to the real decommissioning works. (authors)

  8. In brown adipocytes, adrenergically induced β1-/β3-(Gs)-, α2-(Gi)- and α1-(Gq)-signalling to Erk1/2 activation is not mediated via EGF receptor transactivation

    International Nuclear Information System (INIS)

    Wang, Yanling; Fälting, Johanna M.; Mattsson, Charlotte L.; Holmström, Therése E.; Nedergaard, Jan

    2013-01-01

    Brown adipose tissue is unusual in that the neurotransmitter norepinephrine influences cell destiny in ways generally associated with effects of classical growth factors: regulation of cell proliferation, of apoptosis, and progression of differentiation. The norepinephrine effects are mediated through G-protein-coupled receptors; further mediation of such stimulation to e.g. Erk1/2 activation is in cell biology in general accepted to occur through transactivation of the EGF receptor (by external or internal pathways). We have examined here the significance of such transactivation in brown adipocytes. Stimulation of mature brown adipocytes with cirazoline (α 1 -adrenoceptor coupled via G q ), clonidine (α 2 via G i ) or CL316243 (β 3 via G s ) or via β 1 -receptors significantly activated Erk1/2. Pretreatment with the EGF receptor kinase inhibitor AG1478 had, remarkably, no significant effect on Erk1/2 activation induced by any of these adrenergic agonists (although it fully abolished EGF-induced Erk1/2 activation), demonstrating absence of EGF receptor-mediated transactivation. Results with brown preadipocytes (cells in more proliferative states) were not qualitatively different. Joint stimulation of all adrenoceptors with norepinephrine did not result in synergism on Erk1/2 activation. AG1478 action on EGF-stimulated Erk1/2 phosphorylation showed a sharp concentration–response relationship (IC 50 0.3 µM); a minor apparent effect of AG1478 on norepinephrine-stimulated Erk1/2 phosphorylation showed nonspecific kinetics, implying caution in interpretation of partial effects of AG1478 as reported in other systems. Transactivation of the EGF receptor is clearly not a universal prerequisite for coupling of G-protein coupled receptors to Erk1/2 signalling cascades. - Highlights: • In brown adipocytes, norepinephrine regulates proliferation, apoptosis, differentiation. • EGF receptor transactivation is supposed to mediate GPCR-induced Erk1/2 activation. •

  9. DNA alkylating agents alleviate silencing of class II transactivator gene expression in L1210 lymphoma cells.

    Science.gov (United States)

    Murphy, Shawn P; Holtz, Renae; Lewandowski, Nicole; Tomasi, Thomas B; Fuji, Hiroshi

    2002-09-15

    MHC class II (Ia) Ag expression is inversely correlated with tumorigenicity and directly correlated with immunogenicity in clones of the mouse L1210 lymphoma (1 ). Understanding the mechanisms by which class II Ag expression is regulated in L1210 lymphoma may facilitate the development of immunotherapeutic approaches for the treatment of some types of lymphoma and leukemia. This study demonstrates that the variation in MHC class II Ag expression among clones of L1210 lymphoma is due to differences in the expression of the class II transactivator (CIITA). Analysis of stable hybrids suggests that CIITA expression is repressed by a dominant mechanism in class II-negative L1210 clones. DNA-alkylating agents such as ethyl methanesulfonate and the chemotherapeutic drug melphalan activate CIITA and class II expression in class II negative L1210 cells, and this effect appears to be restricted to transformed cell lines derived from the early stages of B cell ontogeny. Transient transfection assays demonstrated that the CIITA type III promoter is active in class II(-) L1210 cells, despite the fact that the endogenous gene is not expressed, which suggests that these cells have all of the transacting factors necessary for CIITA transcription. An inverse correlation between methylation of the CIITA transcriptional regulatory region and CIITA expression was observed among L1210 clones. Furthermore, 5-azacytidine treatment activated CIITA expression in class II-negative L1210 cells. Collectively, our results suggest that 1) CIITA gene expression is repressed in class II(-) L1210 cells by methylation of the CIITA upstream regulatory region, and 2) treatment with DNA-alkylating agents overcomes methylation-based silencing of the CIITA gene in L1210 cells.

  10. FOXM1 regulates glycolysis in hepatocellular carcinoma by transactivating glucose transporter 1 expression.

    Science.gov (United States)

    Shang, Runze; Pu, Meng; Li, Yu; Wang, Desheng

    2017-04-01

    The Forkhead box M1 (FOXM1) transcription factor plays crucial roles in the initiation and progression of various malignancies, including hepatocellular carcinoma (HCC). However, the mechanism by which FOXM1 regulates cancer metabolism remains unclear. In the present study, overexpression and RNA interference (RNAi) approaches were used to investigate the role of FOXM1 in the regulation of glycolysis in vitro. Luciferase reporter assays were used to explore the transcriptional regulation of the glucose transporter 1 (GLUT1) promoter by FOXM1. Then, immunohistochemical staining was used to examine the expression of FOXM1 and GLUT1 in 100 paired HCC and adjacent non-cancerous liver tissues. Chi-square test and logistic regression analysis were performed to evaluate the association between FOXM1 and GLUT1 expression with clinicopathological characteristics. Our data showed that FOXM1 promoted glycolysis in the HCC cells. FOXM1 knockdown significantly reduced the expression of GLUT1 among key glycolysis-related molecules in the different HCC cell lines. Glucose uptake and lactate production assay showed that FOXM1 positively regulated glycolysis based on GLUT1 expression. Moreover, FOXM1 overexpression increased and knockdown decreased GLUT1 expression. Luciferase reporter assays showed that the -206 to -199 bp region of the GLUT1 promoter is important for FOXM1 to enhance GLUT1 promoter activity. The results of the IHC analysis showed that the protein expression of FOXM1 and GLUT1 was closely related to the tumor histological grade and TNM stage. In addition, GLUT1 expression was also related to microvascular invasion. In conclusion, overexpression of FOXM1 and GLUT1 may play critical roles in HCC. FOXM1 promotes HCC glycolysis by transactivating GLUT1 expression.

  11. Discovery of porcine maternal factors related to nuclear reprogramming and early embryo development by proteomic analysis.

    Science.gov (United States)

    Zhao, Qi; Guo, Zheng; Piao, Shanhua; Wang, Chunsheng; An, Tiezhu

    2015-01-01

    Differentiated cell nuclei can be reprogrammed to a pluripotent state in several ways, including incubation with oocyte extracts, transfer into enucleated oocytes, and induced pluripotent stem cell technology. Nuclear transfer-mediated reprogramming has been proven to be the most efficient method. Maternal factors stored in oocytes have critical roles on nuclear reprogramming and early embryo development, but remain elusive. In this study, we showed most of porcine oocytes became nuclear matured at 33 h of IVM and the rate had no significant difference with oocytes at 42 h of IVM (p > 0.05). Moreover, the cleavage and blastocyst rates of SCNT and PA embryos derived from 42O were significantly higher than that of 33O (p embryo development with higher cleavage and blastocyst rates comparing to 42O (p development potential difference between 33O and 42O, 18 differentially expressed proteins were identified by proteomic analysis, and randomly selected proteins were confirmed by Western blot. Bioinformatic analysis of these proteins revealed that 33O highly synthesized proteins related to fertilization, and 42O was rich in nuclear reprogramming factors. These results present a unique insight into maternal factors related to nuclear reprogramming and early embryo development.

  12. Role of PU.1 in MHC class II expression through transcriptional regulation of class II transactivator pI in dendritic cells.

    Science.gov (United States)

    Kitamura, Nao; Yokoyama, Hokuto; Yashiro, Takuya; Nakano, Nobuhiro; Nishiyama, Makoto; Kanada, Shunsuke; Fukai, Tatsuo; Hara, Mutsuko; Ikeda, Shigaku; Ogawa, Hideoki; Okumura, Ko; Nishiyama, Chiharu

    2012-03-01

    PU.1 is a hematopoietic cell-specific transcription factor belonging to the Ets family. We hypothesized that PU.1 is involved in MHC class II expression in dendritic cells (DCs). The role of PU.1 in MHC class II expression in DCs was analyzed. Transcriptional regulation of the DC-specific pI promoter of the class II transactivator (CIITA) gene and subsequent MHC class II expression was investigated by using PU.1 small interfering RNA (siRNA) and reporter, chromatin immunoprecipitation, and electrophoretic mobility shift assays. PU.1 siRNA introduction suppressed MHC class II expression, allogeneic and syngeneic T-cell activation activities of bone marrow-derived DCs (BMDCs) with reduction of CIITA mRNA driven by the DC-specific promoter pI, and MHC class II mRNA. The chromatin immunoprecipitation assay showed constitutive binding of PU.1 to the pI region in BMDCs, whereas acetylation of histone H3 on pI was suppressed by LPS stimulation in parallel with shutdown of CIITA transcription. PU.1 transactivated the pI promoter through cis-elements at -47/-44 and -30/-27 in a reporter assay and to which PU.1 directly bound in an electrophoretic mobility shift assay. Acetylation of histones H3 and H4 on pI was reduced in PU.1 siRNA-introduced BMDCs. Knockdown of interferon regulatory factor 4 or 8, which is a heterodimer partner of PU.1, by siRNA did not affect pI-driven CIITA transcription or MHC class II expression. PU.1 basally transactivates the CIITA pI promoter in DCs by functioning as a monomeric transcription factor and by affecting histone modification, resulting in the subsequent expression and function of MHC class II. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  13. Human factors estimation method in nuclear power plants

    International Nuclear Information System (INIS)

    Takano, Kenichi; Yoshino, Kenji; Nagasaka, Akihiko

    1987-01-01

    It is need for improving a NPS reliability to prevent human-errors of operators in a control room. Especially, the time error or omission error may be often caused by a exceed of the mental work load. Therefore, in order to decrease such kinds of human errors, not only the planning of an equipment and a console is well considered about proper level of mental work load but also the exceeded mental work load must be let down by trainning etc. This paper present measurement techniques of the mental work load by physiological informations and the relation between the error rate and mental work load on the basis of the experiment by various modeled tasks. Following results are obtained. (1) TSF, the indicator of the mental work load, is well correlated to the subsidary task reaction time. Therefore it is able to estimate the TSF by subsidary tasks if the task was loaded instanteniously with main task. (2) The relation between the TSF and GSR pulses rate has a 0.81 correlation factor except the case of a parallel processing task. Because we can evaluate the mental work load by the measurement of the GSR pulses rate if the task was processed by a single channel. But if uses GSR, the atomospheric condition is kept constant and the arousal level must be at the well stage. (3) The human error is greatly increase when the TSF exceed above 60 %, that values are almost agreed to the tolerance limit of the TTS methods. (author)

  14. b-jet tagged nuclear modification factors in heavy ion collisions with CMS

    CERN Document Server

    Jung, Kurt

    2014-01-01

    The energy loss of jets in heavy-ion collisions is expected to depend on the flavor of the fragmenting parton. Thus, measurements of jet quenching as a function of flavor place powerful constraints on the thermodynamical and transport properties of the hot and dense medium. Measurements of the nuclear modification factors of the heavy-flavor-tagged jets in both PbPb and pPb collisions can quantify such energy loss effects. Specifically, pPb measurements provide crucial insights into the behavior of the cold nuclear matter effect, which is required to fully understand the hot and dense medium effects on jets in PbPb collisions. In this talk, we present the b-jet spectra and the first measurement of the nuclear modification factors as a function of transverse momentum and pseudorapidity, using the high statistics pp, pPb and PbPb data taken in 2011 and 2013.

  15. Assessing State Nuclear Weapons Proliferation: Using Bayesian Network Analysis of Social Factors

    Energy Technology Data Exchange (ETDEWEB)

    Coles, Garill A.; Brothers, Alan J.; Olson, Jarrod; Whitney, Paul D.

    2010-04-16

    A Bayesian network (BN) model of social factors can support proliferation assessments by estimating the likelihood that a state will pursue a nuclear weapon. Social factors including political, economic, nuclear capability, security, and national identity and psychology factors may play as important a role in whether a State pursues nuclear weapons as more physical factors. This paper will show how using Bayesian reasoning on a generic case of a would-be proliferator State can be used to combine evidence that supports proliferation assessment. Theories and analysis by political scientists can be leveraged in a quantitative and transparent way to indicate proliferation risk. BN models facilitate diagnosis and inference in a probabilistic environment by using a network of nodes and acyclic directed arcs between the nodes whose connections, or absence of, indicate probabilistic relevance, or independence. We propose a BN model that would use information from both traditional safeguards and the strengthened safeguards associated with the Additional Protocol to indicate countries with a high risk of proliferating nuclear weapons. This model could be used in a variety of applications such a prioritization tool and as a component of state safeguards evaluations. This paper will discuss the benefits of BN reasoning, the development of Pacific Northwest National Laboratory’s (PNNL) BN state proliferation model and how it could be employed as an analytical tool.

  16. High molecular weight FGF2: the biology of a nuclear growth factor

    Czech Academy of Sciences Publication Activity Database

    Chlebová, K.; Bryja, Vítězslav; Dvořák, Petr; Kozubík, Alois; Wilcox, W.R.; Krejčí, Pavel

    2009-01-01

    Roč. 66, č. 2 (2009), s. 225-235 ISSN 1420-682X Grant - others:GA MŠk(CZ) LC06077 Program:LC Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : high molecular weight * FGF2 * nuclear Subject RIV: BO - Biophysics Impact factor: 6.090, year: 2009

  17. Improving performance of high risk organizations Spanish nuclear sector from the analysis of organizational culture factors

    International Nuclear Information System (INIS)

    La Salabarnada, E.; German, S.; Silla, I.; Navajas, J.

    2012-01-01

    This paper presents the research project funded by UNESA and conducted by the CISOT-CIEMAT that aims to contribute to improving the operating performance of the Spanish nuclear power plants. This paper aims to identify the factors and key organizational processes to improve efficiency, in order to advance knowledge about the influence of organizational culture on the safety of high reliability organizations.

  18. Vitamin D3 transactivates the zinc and manganese transporter SLC30A10 via the Vitamin D receptor.

    Science.gov (United States)

    Claro da Silva, Tatiana; Hiller, Christian; Gai, Zhibo; Kullak-Ublick, Gerd A

    2016-10-01

    competition EMSA revealed binding of select sequences, namely, nt -1623/-1588 and nt -1758/-1723 relative to the transcription start site, to VDR-containing nuclear extracts. In conclusion, we have shown that vitamin D3 transactivates the SLC30A10 gene in a VDR-dependent manner, resulting in increased ZnT10 protein expression. Because SLC30A10 is highly expressed in the small intestine, it is possible that the control of zinc and manganese systemic levels is regulated by vitamin D3 in the intestine. Zinc, manganese and vitamin D are important for bone metabolism and brain health. Future examination of a possible role for supplementation or chelation of zinc and manganese, alongside vitamin D3 administration, will further our understanding of its potential benefit in the treatment of specific illnesses, such as osteoporosis and Parkinson's disease. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  19. Preventive behaviours against radiation and related factors among general workers after Fukushima's nuclear disasters.

    Science.gov (United States)

    Kanda, Hideyuki; Hayakawa, Takehito; Koyama, Kikuo

    2013-04-01

    The nuclear power plant accidents in Fukushima resulted in a widespread release of radioactive substances in the Fukushima prefecture. To clarify what factors led to precautions among general workers who displayed preventive behaviours against radiation following the nuclear disasters in Fukushima. Descriptive study of preventive behaviours among general workers 3-5 months following the nuclear disasters. The subjects were 1394 regular workers who took part in radiation seminars conducted by the Fukushima Occupational Health Promotion Center between July and August 2011. Of 1217 responses, 1110 eligible responses were included in this study. This anonymous questionnaire survey was asking for characteristics and questions on preventive behaviours following the nuclear disasters. The authors assessed the contribution of each variable by a logistic regression analysis. Keeping track of environmental radiation levels and washing hands and gargling were significantly more frequent among female subjects, older age and workers residing up to approximately 80 km away from the power plants. Washing hands and gargling were also related with living with children. Wearing a mask when leaving home and buying bottled water were significantly more often observed with female subjects and workers residing up to 80 km. Refraining from going outdoors was positively associated with workers residing up to 80 km and workers living with children. These results provide information that may help with the targeting of health information after a nuclear disaster. This may contribute to determining an order of priority when distributing information after a nuclear disaster.

  20. Fibroblast growth factor receptor-1 (FGFR1) nuclear dynamics reveal a novel mechanism in transcription control.

    Science.gov (United States)

    Dunham-Ems, Star M; Lee, Yu-Wei; Stachowiak, Ewa K; Pudavar, Haridas; Claus, Peter; Prasad, Paras N; Stachowiak, Michal K

    2009-05-01

    Nuclear FGFR1 acts as a developmental gene regulator in cooperation with FGF-2, RSK1, and CREB-binding protein (CBP). FRAP analysis revealed three nuclear FGFR1 populations: i) a fast mobile, ii) a slower mobile population reflecting chromatin-bound FGFR1, and iii) an immobile FGFR1 population associated with the nuclear matrix. Factors (cAMP, CBP) that induce FGFR1-mediated gene activation shifted FGFR1 from the nuclear matrix (immobile) to chromatin (slow) and reduced the movement rate of the chromatin-bound population. Transcription inhibitors accelerated FGFR1 movement; the content of the chromatin-bound slow FGFR1 decreased, whereas the fast population increased. The transcriptional activation appears to involve conversion of the immobile matrix-bound and the fast nuclear FGFR1 into a slow chromatin-binding population through FGFR1's interaction with CBP, RSK1, and the high-molecular-weight form of FGF-2. Our findings support a general mechanism in which gene activation is governed by protein movement and collisions with other proteins and nuclear structures.

  1. An improvement of the applicability of human factors guidelines for coping with human factors issues in nuclear power plants

    International Nuclear Information System (INIS)

    Lee, Y. H.; Lee, J. Y.

    2003-01-01

    Human factors have been well known as one of the key factors to the system effectiveness as well as the efficiency and safety of nuclear power plants(NPPs). Human factors engineering(HFE) are included in periodic safety review(PSR) on the existing NPPs and the formal safety assessment for the new ones. However, HFE for NPPs is still neither popular in practice nor concrete in methodology. Especially, the human factors guidelines, which are the most frequent form of human factors engineering in practice, reveal the limitations in their applications. We discuss the limitations and their casual factors found in human factors guidelines in order to lesson the workload of HFE practitioners and to improve the applicability of human factors guidelines. According to the purposes and the phases of HFE for NPPs, more selective items and specified criteria should be prepared carefully in the human factors guidelines for the each HFE applications in practice. These finding on the human factors guidelines can be transferred to the other HFE application field, such as military, aviation, telecommunication, HCI, and product safety

  2. Development of a Pilot Program for Human Factors Management in Operating Nuclear Power plants

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jung-Woon; Lee, Yong-Hee; Jang, Tong-Il; Kim, Dae-Ho [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2007-07-01

    The human factors of operating NPPs have been reviewed as a part of Periodic Safety Reviews (PSRs). This human factors PSR covers a wide range of human factors including control room man-machine interfaces (MMIs), procedures, working conditions, qualification, training, information requirements and workload. Korea Atomic Energy Research Institute (KAERI) has performed human factors PSRs from the first PSR for Kori 1. It was determined in 2005 that for a Continuous Operation of the Korean NPPs an enhanced PSR should be performed and issues raised from the PSRs should be resolved. From the results of the PSR for Kori 1, several safety enhancement issues related to human factors were raised. KAERI is working on a resolution of some of the human factors issues for the Korea Hydro and Nuclear Power Co. (KHNP). As a part of the resolution, we are developing a human factors management program (HFMP) for Kori 1. This paper introduces the status of our development of HFMP.

  3. Nuclear localization of Src-family tyrosine kinases is required for growth factor-induced euchromatinization

    International Nuclear Information System (INIS)

    Takahashi, Akinori; Obata, Yuuki; Fukumoto, Yasunori; Nakayama, Yuji; Kasahara, Kousuke; Kuga, Takahisa; Higashiyama, Yukihiro; Saito, Takashi; Yokoyama, Kazunari K.; Yamaguchi, Naoto

    2009-01-01

    Src-family kinases (SFKs), which participate in various signaling events, are found at not only the plasma membrane but also several subcellular compartments, including the nucleus. Nuclear structural changes are frequently observed during transcription, cell differentiation, senescence, tumorigenesis, and cell cycle. However, little is known about signal transduction in the alteration of chromatin texture. Here, we develop a pixel imaging method for quantitatively evaluating chromatin structural changes. Growth factor stimulation increases euchromatic hypocondensation and concomitant heterochromatic hypercondensation in G 1 phase, and the levels reach a plateau by 30 min, sustain for at least 5 h and return to the basal levels after 24 h. Serum-activated SFKs in the nucleus were more frequently detected in the euchromatin areas than the heterochromatin areas. Nuclear expression of kinase-active SFKs, but not unrelated Syk kinase, drastically increases both euchromatinization and heterochromatinization in a manner dependent on the levels of nuclear tyrosine phosphorylation. However, growth factor stimulation does not induce chromatin structural changes in SYF cells lacking SFKs, and reintroduction of one SFK member into SYF cells can, albeit insufficiently, induce chromatin structural changes. These results suggest that nuclear tyrosine phosphorylation by SFKs plays an important role in chromatin structural changes upon growth factor stimulation.

  4. Safety, reliability, risk management and human factors: an integrated engineering approach applied to nuclear facilities

    International Nuclear Information System (INIS)

    Vasconcelos, Vanderley de; Silva, Eliane Magalhaes Pereira da; Costa, Antonio Carlos Lopes da; Reis, Sergio Carneiro dos

    2009-01-01

    Nuclear energy has an important engineering legacy to share with the conventional industry. Much of the development of the tools related to safety, reliability, risk management, and human factors are associated with nuclear plant processes, mainly because the public concern about nuclear power generation. Despite the close association between these subjects, there are some important different approaches. The reliability engineering approach uses several techniques to minimize the component failures that cause the failure of the complex systems. These techniques include, for instance, redundancy, diversity, standby sparing, safety factors, and reliability centered maintenance. On the other hand system safety is primarily concerned with hazard management, that is, the identification, evaluation and control of hazards. Rather than just look at failure rates or engineering strengths, system safety would examine the interactions among system components. The events that cause accidents may be complex combinations of component failures, faulty maintenance, design errors, human actions, or actuation of instrumentation and control. Then, system safety deals with a broader spectrum of risk management, including: ergonomics, legal requirements, quality control, public acceptance, political considerations, and many other non-technical influences. Taking care of these subjects individually can compromise the completeness of the analysis and the measures associated with both risk reduction, and safety and reliability increasing. Analyzing together the engineering systems and controls of a nuclear facility, their management systems and operational procedures, and the human factors engineering, many benefits can be realized. This paper proposes an integration of these issues based on the application of systems theory. (author)

  5. Safety, reliability, risk management and human factors: an integrated engineering approach applied to nuclear facilities

    Energy Technology Data Exchange (ETDEWEB)

    Vasconcelos, Vanderley de; Silva, Eliane Magalhaes Pereira da; Costa, Antonio Carlos Lopes da; Reis, Sergio Carneiro dos [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)], e-mail: vasconv@cdtn.br, e-mail: silvaem@cdtn.br, e-mail: aclc@cdtn.br, e-mail: reissc@cdtn.br

    2009-07-01

    Nuclear energy has an important engineering legacy to share with the conventional industry. Much of the development of the tools related to safety, reliability, risk management, and human factors are associated with nuclear plant processes, mainly because the public concern about nuclear power generation. Despite the close association between these subjects, there are some important different approaches. The reliability engineering approach uses several techniques to minimize the component failures that cause the failure of the complex systems. These techniques include, for instance, redundancy, diversity, standby sparing, safety factors, and reliability centered maintenance. On the other hand system safety is primarily concerned with hazard management, that is, the identification, evaluation and control of hazards. Rather than just look at failure rates or engineering strengths, system safety would examine the interactions among system components. The events that cause accidents may be complex combinations of component failures, faulty maintenance, design errors, human actions, or actuation of instrumentation and control. Then, system safety deals with a broader spectrum of risk management, including: ergonomics, legal requirements, quality control, public acceptance, political considerations, and many other non-technical influences. Taking care of these subjects individually can compromise the completeness of the analysis and the measures associated with both risk reduction, and safety and reliability increasing. Analyzing together the engineering systems and controls of a nuclear facility, their management systems and operational procedures, and the human factors engineering, many benefits can be realized. This paper proposes an integration of these issues based on the application of systems theory. (author)

  6. A novel bipartite nuclear localization signal with an atypically long linker in DOF transcription factors.

    Science.gov (United States)

    Krebs, Jonas; Mueller-Roeber, Bernd; Ruzicic, Slobodan

    2010-05-01

    Large molecules require a nuclear localization signal (NLS) for translocation into the nucleus. Classical NLSs are rich in basic amino acids and they represent three groups, based on their structural features: SV40 T-antigen-type, yeast mating factor Matalpha-2-type, and bipartite NLSs. DNA-binding-with-one-finger (DOF) transcription factors play important roles in plants, and although their nuclear localization has been demonstrated in several cases, public protein localization prediction tools fail to detect NLS motifs in these proteins. Here, we demonstrate that an atypical bipartite NLS with a 17 amino acid long linker between its flanking basic regions directs Arabidopsis thaliana DOF proteins to the cell nucleus. The novel bipartite NLS is highly conserved in plant DOF transcription factors, including the single DOF protein in the green alga Chlamydomonas reinhardtii. Copyright 2010 Elsevier GmbH. All rights reserved.

  7. Inhibition of the TEF/TEAD transcription factor activity by nuclear calcium and distinct kinase pathways.

    Science.gov (United States)

    Thompson, M; Andrade, V A; Andrade, S J; Pusl, T; Ortega, J M; Goes, A M; Leite, M F

    2003-02-07

    Transcription enhancer factor (TEF/TEAD) is a family of four transcription factors that share a common TEA-DNA binding domain and are involved in similar cellular functions, such as cell differentiation and proliferation. All adult tissues express at least one of the four TEAD genes, so this family of transcription factors may be of widespread importance, yet little is known about their regulation. Here we examine the factors that regulate TEAD activity in CHO cells. RT-PCR indicated the presence of TEAD-1, TEAD-3, and both isoforms of TEAD-4, but not TEAD-2. Quantitative measurements showed that TEAD-4 is most abundant, followed by TEAD-3, then TEAD-1. We examined the relative effects of nuclear and cytosolic Ca(2+) on TEAD activity, since TEAD proteins are localized to the nucleus and since free Ca(2+) within the nucleus selectively regulates transcription in some systems. Chelation of nuclear but not cytosolic Ca(2+) increased TEAD activity two times above control. Inhibition of mitogen-activated protein kinase (MAPK) also increased TEAD activity, while cAMP decreased TEAD activity, and protein kinase C had no effect. Together, these results show that nuclear Ca(2+), MAPK, and cAMP each negatively regulate the activity of the TEAD transcription factor.

  8. Selective nuclear morphometry as a prognostic factor of survival in renal cell carcinoma.

    Science.gov (United States)

    Monge, J M; Val-Bernal, J F; Buelta, L; García-Castrillo, L; Asensio, L

    1999-01-01

    In the present study, we sought to determine the predictive value of selective nuclear morphometry (SNM) for patient outcome in renal cell carcinoma (RCC). Tumor samples of 140 renal adenocarcinomas diagnosed and treated with radical nephrectomy and hilar lymphadenectomy between 1970 and 1988 with a minimum follow up of 5 years in all the cases were studied by SNM. The morphometric analysis was performed in the most malignant tumor selected zone. Selection was based on cytological criteria including nuclear grade. Nuclear morphometric features analyzed were: area, perimeter, major diameter, major and minor diameter of the equivalent ellipse, volume of the equivalent ellipse and sphere, circumference diameter, and shape factors. The results showed that in the selected zone tumor nuclei were larger than in the zones selected at random. There was an inverse correlation between morphometric parameters and survival and a direct one between tumoral grade and stage. Tumors of the long-term survival group of patients presented nuclei with smaller morphometric measurements than tumors of short term survival group, with significant differences between them (p < 0.05). In the survival analysis carried out by the Kaplan-Meier method significant differences existed between different groups formed from break point for: area, perimeter, major diameter, major and minor diameter of the ellipse, volume of the ellipse and sphere, circumference diameter and perimeter shape factor. In the multivariate analysis carried out by the Cox method, the feature with the most predictable value related to survival, was the tumor stage. Morphometric value with the highest punctuation in the test was major nuclear diameter. The rest of the morphometric values (except elliptic shape factor and elongation factor) were also significant but they did not improve prognostic information of the major nuclear diameter. SNM offers a useful aid in a more objective grading of RCC. Multivariate Cox analysis

  9. Engineering factors influencing Corbicula fouling in nuclear-service water systems

    International Nuclear Information System (INIS)

    Henager, C.H.; Johnson, K.I.; Page, T.L.

    1983-06-01

    Corbicula fouling is a continuing problem in nuclear-service water systems. More knowledge of biological and engineering factors is needed to develop effective detection and control methods. A data base on Corbicula fouling was compiled from nuclear and non-nuclear power stations and industries using raw water. This data base was used in an analysis to identify systems and components which are conducive to fouling by Corbicula. Bounds on several engineering parameters such as velocity and temperature which support Corbicula growth are given. Service water systems found in BWR and PWR reactors are listed and those that show fouling are identified. Possible safety implications of Corbicula fouling are discussed for specific service water systems. Several effective control methods in current use include backflushing with heated water, centrifugal strainers, and continuous chlorination during spawning seasons

  10. FTZ-Factor1 and Fushi tarazu interact via conserved nuclear receptor and coactivator motifs

    Science.gov (United States)

    Schwartz, Carol J.E.; Sampson, Heidi M.; Hlousek, Daniela; Percival-Smith, Anthony; Copeland, John W.R.; Simmonds, Andrew J.; Krause, Henry M.

    2001-01-01

    To activate transcription, most nuclear receptor proteins require coactivators that bind to their ligand-binding domains (LBDs). The Drosophila FTZ-Factor1 (FTZ-F1) protein is a conserved member of the nuclear receptor superfamily, but was previously thought to lack an AF2 motif, a motif that is required for ligand and coactivator binding. Here we show that FTZ-F1 does have an AF2 motif and that it is required to bind a coactivator, the homeodomain-containing protein Fushi tarazu (FTZ). We also show that FTZ contains an AF2-interacting nuclear receptor box, the first to be found in a homeodomain protein. Both interaction motifs are shown to be necessary for physical interactions in vitro and for functional interactions in developing embryos. These unexpected findings have important implications for the conserved homologs of the two proteins. PMID:11157757

  11. Critical factors supporting the confidence in U.S. nuclear power industries

    International Nuclear Information System (INIS)

    Yoshida, Tomoaki

    2004-01-01

    The risk informed regulation in U.S. is summarized and factors supporting the confidence in U.S. nuclear power industries are thought to be helpful to our country for improving the state of nuclear power industries. In U.S., on the basis of clear Regulatory Guide, an entrepreneur constructs and practices corrective action of nonconformance. A regulatory commission submitted by the nation watches their movements. The movements related to regulatory are opened to the people and they make a thousand preparations for the rule to make correct the insufficient part. These above system get good results in U.S. It is important in Japan that we are not going to get away with anything on the system satisfied above conditions and practice. The risk informed regulation, effectiveness of risk informed regulation supporting conditions, a part of NRC (Nuclear Regulatory Commission) and entrepreneur are described. (S.Y.)

  12. IRSN-ANCCLI partnership. Organizational and human factors in nuclear safety - April 2014

    International Nuclear Information System (INIS)

    Jeffroy, Francois; Garron, Joel; Mercel, Philippe; Compagnat, Gilles; Gaucher, Eric; Gaillard, Pierre; Fanchini, Henri; Jacquemont, Vincent

    2013-06-01

    The contributions (Power Point presentations) of this seminar first address the history of the taking into account of organizational and human factors until the Fukushima accident (history of their taking into account in nuclear safety expertise in France, history of the development of policy of organizational and human factors by an operator). The next contributions discuss the main issues regarding these factors after Fukushima: report by a work-group, work performed by the the Comite d'Orientation sur les Facteurs Sociaux, Organisationnels et Humains (Committee of orientation on social, organizational and human factors). The third session addresses the implication of stakeholders in expertise on these factors: analysis of organizational and human factors by a local information commission or by a CHSCT (committee of hygiene, safety and working conditions)

  13. Inhibition of CRM1-mediated nuclear export of transcription factors by leukemogenic NUP98 fusion proteins.

    Science.gov (United States)

    Takeda, Akiko; Sarma, Nayan J; Abdul-Nabi, Anmaar M; Yaseen, Nabeel R

    2010-05-21

    NUP98 is a nucleoporin that plays complex roles in the nucleocytoplasmic trafficking of macromolecules. Rearrangements of the NUP98 gene in human leukemia result in the expression of numerous fusion oncoproteins whose effect on nucleocytoplasmic trafficking is poorly understood. The present study was undertaken to determine the effects of leukemogenic NUP98 fusion proteins on CRM1-mediated nuclear export. NUP98-HOXA9, a prototypic NUP98 fusion, inhibited the nuclear export of two known CRM1 substrates: mutated cytoplasmic nucleophosmin and HIV-1 Rev. In vitro binding assays revealed that NUP98-HOXA9 binds CRM1 through the FG repeat motif in a Ran-GTP-dependent manner similar to but stronger than the interaction between CRM1 and its export substrates. Two NUP98 fusions, NUP98-HOXA9 and NUP98-DDX10, whose fusion partners are structurally and functionally unrelated, interacted with endogenous CRM1 in myeloid cells as shown by co-immunoprecipitation. These leukemogenic NUP98 fusion proteins interacted with CRM1, Ran, and the nucleoporin NUP214 in a manner fundamentally different from that of wild-type NUP98. NUP98-HOXA9 and NUP98-DDX10 formed characteristic aggregates within the nuclei of a myeloid cell line and primary human CD34+ cells and caused aberrant localization of CRM1 to these aggregates. These NUP98 fusions caused nuclear accumulation of two transcription factors, NFAT and NFkappaB, that are regulated by CRM1-mediated export. The nuclear entrapment of NFAT and NFkappaB correlated with enhanced transcription from promoters responsive to these transcription factors. Taken together, the results suggest a new mechanism by which NUP98 fusions dysregulate transcription and cause leukemia, namely, inhibition of CRM1-mediated nuclear export with aberrant nuclear retention of transcriptional regulators.

  14. Absence of prognostic value of nuclear shape factor analysis in colorectal carcinoma: relevance of interobserver and intraobserver variability.

    Science.gov (United States)

    Di Fabio, Francesco; Shrier, Ian; Bégin, Louis R; Gordon, Philip H

    2008-12-01

    Several retrospective studies, including our previous investigation, have shown a prognostic value of nuclear shape factor in colorectal carcinomas. This prospective study was designed to assess the reliability of nuclear shape factor determined by nuclear morphometry and to confirm its prognostic value. Ninety-eight patients who underwent colorectal carcinoma resection were prospectively enrolled. Measurement of nuclear shape factor was performed by using a computer-based image analysis system. Nuclear shape factor was defined as the degree of circularity of the nucleus (1.0 for a perfect circle and values by American Joint Committee on Cancer stage were: 0.73 (0.07) in Stage I, 0.74 (0.06) in Stage II, and 0.75 (0.05) in Stage III carcinomas (P = 0.78, ANOVA). The intraobserver agreement was poor for observer A (r = 0.28) and practically nonexistent for observer B (r = -0.004, Pearson correlation). The intraclass coefficient for interobserver agreement was practically nonexistent. No significant association between nuclear shape factor and ten-year survival was found. Our prospective results, as opposed to our previous retrospective results, suggest that the reliability for nuclear shape factor morphometric analysis is very poor. We failed to confirm a prognostic value for nuclear shape factor in colorectal carcinoma.

  15. A HUMAN FACTORS META MODEL FOR U.S. NUCLEAR POWER PLANT CONTROL ROOM MODERNIZATION

    Energy Technology Data Exchange (ETDEWEB)

    Joe, Jeffrey C.

    2017-03-01

    Over the last several years, the United States (U.S.) Department of Energy (DOE) has sponsored human factors research and development (R&D) and human factors engineering (HFE) activities through its Light Water Reactor Sustainability (LWRS) program to modernize the main control rooms (MCR) of commercial nuclear power plants (NPP). Idaho National Laboratory (INL), in partnership with numerous commercial nuclear utilities, has conducted some of this R&D to enable the life extension of NPPs (i.e., provide the technical basis for the long-term reliability, productivity, safety, and security of U.S. NPPs). From these activities performed to date, a human factors meta model for U.S. NPP control room modernization can now be formulated. This paper discusses this emergent HFE meta model for NPP control room modernization, with the goal of providing an integrated high level roadmap and guidance on how to perform human factors R&D and HFE for those in the U.S. nuclear industry that are engaging in the process of upgrading their MCRs.

  16. Organizational factors and reoccurrence protection on the JCO nuclear critical accident

    International Nuclear Information System (INIS)

    Takano, Kenichi

    2000-01-01

    A nuclear critical accident formed at a nuclear fuel conversion factory in Tokai-mura on September, 1999 became gradually clear not to be a simple human error formed at a level of workmen but to be an organizational error or accident relating to various organizational factors. As a nuclear power facility adopts a depth protection system fundamentally, a large accident with serious danger would not form only by a single trouble and a human error and unless some factors overlaps. By reviewing recent serious accidents and troubles, all of them seem to have a keyword of 'organizational factor'. In the JCO accident, there are some organizational factors such as a climate deviating from a manual, insufficient and loose check against change of procedure, reduction of operators from a reason of profit priority, attitude on priority of working efficiency, and so forth, which are partially common to the Chernobyl accident. Recently, accidents and troubles impossible to make them a cause of simple human error by a person but to have to say an organizational error, have increased. This trend seems to depend upon not only complication and scale-up of technology system but also graduate change of social and management systems operating them. Therefore, it seems to be necessary to introduce a concept of depth protection (multiple protection) in order to keep its reliability and safety when complicating and scaling-up of system. (G.K.)

  17. Establishing a value chain for human factors in nuclear power plantcontrol room modernization

    Energy Technology Data Exchange (ETDEWEB)

    Joe, Jeffrey Clark [Idaho National Laboratory; Thomas, Kenneth David [Idaho National Laboratory; Boring, Ronald Laurids [Idaho National Laboratory

    2015-07-01

    Commercial nuclear power plants in the United States (U.S.) have operated reliably and efficiently for decades. With the life extensions of plants now being planned for operation beyond their original operating licenses, there are opportunities to achieve even greater efficiencies, while maintaining high operational reliabilities, with strategic, risk- and economically-informed, upgrades to plant systems and infrastructure. The U.S. Department of Energy’s Light Water Reactor Sustainability (LWRS) program supports the commercial nuclear industry’s modernization efforts through research and development (R&D) activities across many areas to help establish the technical and economic bases for modernization activities. The Advanced Instrumentation, Information, and Control Systems Technologies pathway is one R&D focus area for the LWRS program, and has researchers at Idaho National Laboratory working with select utility partners to use human factors and instrumentation and controls R&D to help modernize the plant’s main control room. However, some in the nuclear industry have not been as enthusiastic about using human factors R&D to inform life extension decision making. Part of the reason for this may stem from uncertainty decision-makers have regarding how human factors fits into the value chain for nuclear power plant control room modernization. This paper reviews past work that has attempted to demonstrate the value of human factors, and then describes the value chain concept, how it applies to control room modernization, and then makes a case for how and why human factors is an essential link in the modernization value chain.

  18. An improved reprogrammable mouse model harbouring the reverse tetracycline-controlled transcriptional transactivator 3

    Directory of Open Access Journals (Sweden)

    S. Alaei

    2016-07-01

    Full Text Available Reprogrammable mouse models engineered to conditionally express Oct-4, Klf-4, Sox-2 and c-Myc (OKSM have been instrumental in dissecting molecular events underpinning the generation of induced pluripotent stem cells. However, until now these models have been reported in the context of the m2 reverse tetracycline-controlled transactivator, which results in low reprogramming efficiency and consequently limits the number of reprogramming intermediates that can be isolated for downstream profiling. Here, we describe an improved OKSM mouse model in the context of the reverse tetracycline-controlled transactivator 3 with enhanced reprogramming efficiency (>9-fold and increased numbers of reprogramming intermediate cells albeit with similar kinetics, which we believe will facilitate mechanistic studies of the reprogramming process.

  19. The study of method for calculating the accident atmospheric dispersion factor and accident washout factor for coastal nuclear power plant

    International Nuclear Information System (INIS)

    Hu Erbang; Gao Zhanrong; Jiang Gang; Wang Shuxian; Wang Shoushu; Zhang Maoshuan; Chen Jiayi; Jia Peirong

    1998-12-01

    A model to estimate the accident probabilistic dispersion factor in which the effect of internal boundary layer is considered and a set of deterministic and probabilistic models to estimate the accident washout factor are set up based on the models of accident dispersion factor given by current guides. The accident probabilistic dispersion factor, the deterministic washout factor for different time interval after accident release, the accident probabilistic washout factor and the dose corresponding to various pathway are estimated based on the measured meteorological data on the site of a coastal nuclear power plant to be built in the east part of China. The result shows that: the value of accident probabilistic dispersion factor given by the proposed model are 5.9 times of those given by the common model; for the dose obtained during 0 to 8 h after accident release, the external exposure dose from washout deposition given by deterministic model is about 5.50 times of those from dry deposition; the ratio between external exposure dose from washout and dry deposition given by conservative probabilistic model with and without considering the effect from internal boundary layer is 9.56 and 56.7 respectively; for the realistic probabilistic model the value of above ratio is 1.93 and 11.4

  20. Cell-Surface Receptors Transactivation Mediated by G Protein-Coupled Receptors

    Science.gov (United States)

    Cattaneo, Fabio; Guerra, Germano; Parisi, Melania; De Marinis, Marta; Tafuri, Domenico; Cinelli, Mariapia; Ammendola, Rosario

    2014-01-01

    G protein-coupled receptors (GPCRs) are seven transmembrane-spanning proteins belonging to a large family of cell-surface receptors involved in many intracellular signaling cascades. Despite GPCRs lack intrinsic tyrosine kinase activity, tyrosine phosphorylation of a tyrosine kinase receptor (RTK) occurs in response to binding of specific agonists of several such receptors, triggering intracellular mitogenic cascades. This suggests that the notion that GPCRs are associated with the regulation of post-mitotic cell functions is no longer believable. Crosstalk between GPCR and RTK may occur by different molecular mechanism such as the activation of metalloproteases, which can induce the metalloprotease-dependent release of RTK ligands, or in a ligand-independent manner involving membrane associated non-receptor tyrosine kinases, such as c-Src. Reactive oxygen species (ROS) are also implicated as signaling intermediates in RTKs transactivation. Intracellular concentration of ROS increases transiently in cells stimulated with GPCR agonists and their deliberated and regulated generation is mainly catalyzed by enzymes that belong to nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family. Oxidation and/or reduction of cysteine sulfhydryl groups of phosphatases tightly controls the activity of RTKs and ROS-mediated inhibition of cellular phosphatases results in an equilibrium shift from the non-phosphorylated to the phosphorylated state of RTKs. Many GPCR agonists activate phospholipase C, which catalyze the hydrolysis of phosphatidylinositol 4,5-bis-phosphate to produce inositol 1,4,5-triphosphate and diacylglicerol. The consequent mobilization of Ca2+ from endoplasmic reticulum leads to the activation of protein kinase C (PKC) isoforms. PKCα mediates feedback inhibition of RTK transactivation during GPCR stimulation. Recent data have expanded the coverage of transactivation to include Serine/Threonine kinase receptors and Toll-like receptors. Herein, we

  1. NLRC5/MHC class I transactivator is a target for immune evasion in cancer

    OpenAIRE

    Yoshihama, Sayuri; Roszik, Jason; Downs, Isaac; Meissner, Torsten B.; Vijayan, Saptha; Chapuy, Bjoern; Sidiq, Tabasum; Shipp, Margaret A.; Lizee, Gregory A.; Kobayashi, Koichi S.

    2016-01-01

    Tumor antigen presentation to CD8+ T cells by MHC class I molecules is crucial for immune responses against cancers, whereas the loss of MHC class I is a common immune evasion strategy used by cancers. However, the molecular mechanisms leading to MHC class I deficiency have remained poorly defined. We demonstrate here that MHC class I transactivator (CITA)/NOD-like receptor (NLR) family, caspase recruitment (CARD) domain containing 5 (NLRC5) is a major target for cancer immune evasion. Reduce...

  2. Identification of Essential Genetic Baculoviral Elements for Recombinant Protein Expression by Transactivation in Sf21 Insect Cells.

    Directory of Open Access Journals (Sweden)

    Maren Bleckmann

    Full Text Available The Baculovirus Expression Vector System (BEVS is widely used to produce high amounts of recombinant proteins. Nevertheless, generating recombinant baculovirus in high quality is rather time-consuming and labor-intensive. Alternatively, virus-free expression in insect cells did not achieve similar expression levels for most proteins so far. The transactivation method is a promising approach for protein expression in Sf21 cells. It combines advantages of BEVS and plasmid-based expression by activating strong virus-dependent promoters on a transfected plasmid by baculoviral coinfection. Here, we identified expression elements required for transactivation. Therefore, we designed several vectors comprising different viral promoters or promoter combinations and tested them for eGFP expression using the automated BioLector microcultivation system. Remarkably, only the combination of the very late promoter p10 together with the homologous region 5 (hr5 could boost expression during transactivation. Other elements, like p10 alone or the late viral promoter polH, did not respond to transactivation. A new combination of hr5 and p10 with the strongest immediate early OpMNPV viral promoter OpIE2 improved the yield of eGFP by ~25% in comparison to the previous applied hr5-IE1-p10 expression cassette. Furthermore, we observed a strong influence of the transcription termination sequence and vector backbone on the level of expression. Finally, the expression levels for transactivation, BEVS and solely plasmid-based expression were compared for the marker protein eGFP, underlining the potential of transactivation for fast recombinant protein expression in Sf21 cells. In conclusion, essential elements for transactivation could be identified. The optimal elements were applied to generate an improved vector applicable in virus-free plasmid-based expression, transactivation and BEVS.

  3. Identification of Essential Genetic Baculoviral Elements for Recombinant Protein Expression by Transactivation in Sf21 Insect Cells

    Science.gov (United States)

    Chen, Fang-Fang; Yen, Zen-Zen; Lindemann, Nils; Meyer, Steffen; Spehr, Johannes; van den Heuvel, Joop

    2016-01-01

    The Baculovirus Expression Vector System (BEVS) is widely used to produce high amounts of recombinant proteins. Nevertheless, generating recombinant baculovirus in high quality is rather time-consuming and labor-intensive. Alternatively, virus-free expression in insect cells did not achieve similar expression levels for most proteins so far. The transactivation method is a promising approach for protein expression in Sf21 cells. It combines advantages of BEVS and plasmid-based expression by activating strong virus-dependent promoters on a transfected plasmid by baculoviral coinfection. Here, we identified expression elements required for transactivation. Therefore, we designed several vectors comprising different viral promoters or promoter combinations and tested them for eGFP expression using the automated BioLector microcultivation system. Remarkably, only the combination of the very late promoter p10 together with the homologous region 5 (hr5) could boost expression during transactivation. Other elements, like p10 alone or the late viral promoter polH, did not respond to transactivation. A new combination of hr5 and p10 with the strongest immediate early OpMNPV viral promoter OpIE2 improved the yield of eGFP by ~25% in comparison to the previous applied hr5-IE1-p10 expression cassette. Furthermore, we observed a strong influence of the transcription termination sequence and vector backbone on the level of expression. Finally, the expression levels for transactivation, BEVS and solely plasmid-based expression were compared for the marker protein eGFP, underlining the potential of transactivation for fast recombinant protein expression in Sf21 cells. In conclusion, essential elements for transactivation could be identified. The optimal elements were applied to generate an improved vector applicable in virus-free plasmid-based expression, transactivation and BEVS. PMID:26934632

  4. The Major Histocompatibility Complex Class II Transactivator CIITA Inhibits the Persistent Activation of NF-κB by the Human T Cell Lymphotropic Virus Type 1 Tax-1 Oncoprotein.

    Science.gov (United States)

    Forlani, Greta; Abdallah, Rawan; Accolla, Roberto S; Tosi, Giovanna

    2016-01-20

    Human T cell lymphotropic virus type 1 (HTLV-1) Tax-1, a key protein in HTLV-1-induced T cell transformation, deregulates diverse cell signaling pathways. Among them, the NF-κB pathway is constitutively activated by Tax-1, which binds to NF-κB proteins and activates the IκB kinase (IKK). Upon phosphorylation-dependent IκB degradation, NF-κB migrates into the nucleus, mediating Tax-1-stimulated gene expression. We show that the transcriptional regulator of major histocompatibility complex class II genes CIITA (class II transactivator), endogenously or ectopically expressed in different cells, inhibits the activation of the canonical NF-κB pathway by Tax-1 and map the region that mediates this effect. CIITA affects the subcellular localization of Tax-1, which is mostly retained in the cytoplasm, and this correlates with impaired migration of RelA into the nucleus. Cytoplasmic and nuclear mutant forms of CIITA reveal that CIITA exploits different strategies to suppress Tax-1-mediated NF-κB activation in both subcellular compartments. CIITA interacts with Tax-1 without preventing Tax-1 binding to both IKKγ and RelA. Nevertheless, CIITA affects Tax-1-induced IKK activity, causing retention of the inactive p50/RelA/IκB complex in the cytoplasm. Nuclear CIITA associates with Tax-1/RelA in nuclear bodies, blocking Tax-1-dependent activation of NF-κB-responsive genes. Thus, CIITA inhibits cytoplasmic and nuclear steps of Tax-1-mediated NF-κB activation. These results, together with our previous finding that CIITA acts as a restriction factor inhibiting Tax-1-promoted HTLV-1 gene expression and replication, indicate that CIITA is a versatile molecule that might also counteract Tax-1 transforming activity. Unveiling the molecular basis of CIITA-mediated inhibition of Tax-1 functions may be important in defining new strategies to control HTLV-1 spreading and oncogenic potential. HTLV-1 is the causative agent of human adult T cell leukemia-lymphoma (ATLL). The viral

  5. Quality factors in the life cycle of software oriented to safety systems in nuclear power plants

    International Nuclear Information System (INIS)

    Nunez McLeod, J.E.; Rivera, S.S.

    1997-01-01

    The inclusion of software in safety related systems for nuclear power plants, makes it necessary to include the software quality assurance concept. The software quality can be defined as the adjustment degree between the software and the specified requirements and user expectations. To guarantee a certain software quality level it is necessary to make a systematic and planned set of tasks, that constitute a software quality guaranty plan. The application of such a plan involves activities that should be performed all along the software life cycle, and that can be evaluated through the so called quality factors, due to the fact that the quality itself cannot be directly measured, but indirectly as some of it manifestations. In this work, a software life cycle model is proposed, for nuclear power plant safety related systems. A set os software quality factors is also proposed , with its corresponding classification according to the proposed model. (author) [es

  6. The human factor in operating nuclear power plants during crisis situations

    International Nuclear Information System (INIS)

    Schnauder, H.; Smidt, D.

    1981-10-01

    Human factors in nuclear power plant operation are a main part of safety analyses. A considerable reduction in the influence of human factors has been obtained through ergonomic control room design, automation, clearly formulated operating manuals, and appropriate personnel education and training. These precautions are directed primarily at skill- and rule-based behaviour and are intended for normal operation and design accidents. In addition, one can construct an area of uncommon and very rare events where a partial failure of the safety systems is assumed. This is an area of knowledge-based behaviour. This report describes and assesses the present situation in German nuclear power plants. Recommendations for further research activity are made and, as a main result, for improvements in knowledge-based behaviour. (orig.) [de

  7. Development of safety factors to be used for evaluation of cracked nuclear components

    International Nuclear Information System (INIS)

    Brickstad, B.; Bergman, M.

    1996-10-01

    A modified concept for safety evaluation is introduced which separately accounts for the failure mechanisms fracture and plastic collapse. For application on nuclear components a set of safety factors are also proposed that retain the safety margins expressed in ASME, section III and XI. By performing comparative studies of the acceptance levels for surface cracks in pipes and a pressure vessel, it is shown that some of the anomalies connected with the old safety procedures are removed. It is the authors belief that the outlined safety evaluation procedure has the capability of treating cracks in a consistent way and that the procedure together with the proposed safety factors fulfill the basic safety requirements for nuclear components. Hopefully, it is possible in the near future to develop a probabilistic safety assessment procedure in Sweden, which enables a systematic treatment of uncertainties in the involved data. 14 refs

  8. Research and development on the human factors technologies for nuclear power plants in Korea

    International Nuclear Information System (INIS)

    Sim, B.S.; Lee, J.W.; Cheon, S.W.

    1996-01-01

    This paper introduces our research project on the development of human factors technologies for nuclear power plants in Korea. The project is divided into two sub-projects. The first sub-project is the development of human factors experimental evaluation techniques, which aims to develop the techniques for experimental design, experimental measurement and data collection/analysis, and to construct an integrated test facility (ITF) suitable for the experimental evaluation of man-machine interfaces (MMIs) at an advanced control room. The second is the development of human behavior analysis techniques, which has two research areas: one is the development of a task simulation analyzer and the other is human error case studies for nuclear power plants. (author)

  9. Inhibitors of nuclear factor kappa B cause apoptosis in cultured macrophages

    Directory of Open Access Journals (Sweden)

    E. E. Mannick

    1997-01-01

    Full Text Available The precise role of the transcription factor nuclear factor kappa B (NF- κB in the regulation of cell survival and cell death is still unresolved and may depend on cell type and position in the cell cycle. The aim of this study was to determine if three pharmacologic inhibitors of NF-κB, pyrrolidine dithiocarbamate, N-tosyl-L-lysl chloromethyl ketone and calpain I inhibitor, induce apoptosis in a murine macrophage cell line (RAW 264.7 at doses similar to those required for NF-κB inhibition. We found that each of the three inhibitors resulted in a dose- and time-dependent increase in morphologic indices of apoptosis in unstimulated, LPS-stimulated and TNF-stimulated cells. Lethal doses were consistent with those required for NF- κB inhibition. We conclude that nuclear NF-κB activation may represent an important survival mechanism in macrophages.

  10. Critical human-factors issues in nuclear-power regulation and a recommended comprehensive human-factors long-range plan. Executive summary

    International Nuclear Information System (INIS)

    Hopkins, C.O.; Snyder, H.L.; Price, H.E.; Hornick, R.J.; Mackie, R.R.; Smillie, R.J.; Sugarman, R.C.

    1982-08-01

    This comprehensive long-range human factors plan for nuclear reactor regulation was developed by a Study Group of the Human Factors Society, Inc. This Study Group was selected by the Executive Council of the Society to provide a balanced, experienced human factors perspective to the applications of human factors scientific and engineering knowledge to nuclear power generation. The report is presented in three volumes. Volume 1 contains an Executive Summary of the 18-month effort and its conclusions. Volume 2 summarizes all known nuclear-related human factors activities, evaluates these activities wherever adequate information is available, and describes the recommended long-range (10-year) plan for human factors in regulation. Volume 3 elaborates upon each of the human factors issues and areas of recommended human factors involvement contained in the plan, and discusses the logic that led to the recommendations

  11. Proceedings of the international topical meeting on advances in human factors in nuclear power systems

    International Nuclear Information System (INIS)

    Anon.

    1986-01-01

    This book presents the papers given at a conference on the human factors engineering of nuclear power plants. Topics considered at the conference included human modeling, artificial intelligence, expert systems, robotics and teleoperations, organizational issues, innovative applications, testing and evaluation, training systems technology, a modeling framework for crew decisions during reactor accident sequences, intelligent operator support systems, control algorithms for robot navigation, and personnel management

  12. The economics of nuclear power plants as they age: Production (capacity factors), variable costs, and retirement

    International Nuclear Information System (INIS)

    Heinze-Fry, G.R.

    1989-01-01

    This study examines, using multiple regression analyses, production at nuclear power plants, the variable costs involved, and estimate to dismantle reactors. Variable costs generally follow U-shaped curves as reactors age. Performance is modelled with polynomial equations, using chiefly intercept, age and age .5 terms, interacting with various reactor characteristics, plus time and operating experience. US nuclear capacity factors (actual output/possible) averaged 60% for 13 of 15 years during 1971-1985. Output generally peaked during ages 3-12. Capacity factors were much lower, or aging was faster, for reactors that are-from the worst-non-light water types, prototypes, salt water cooled, expensive to build, large, and boiling water reactors (BWRs). Expected nuclear capacity factors average 56% and reactor lives average 30 years. Outside America, generally capacity factors are much higher and reactor aging is slower. Heavy water reactors perform best, gas cooled ones worst, and BWRs do as well as pressurized water reactors. Capital addition costs have risen fastest and were most affected by aging. Fuel costs were almost constant. Repairs and O and M led the 15.3% real annual increase in nuclear variable costs/kW during 1978-1984. Forecast variable costs rise more slowly. If owners retire reactors when variable costs exceed alternatives, the last reactor should close about 2010. Then expected future lifetime levelized real variable costs range, by reactor, from 2 to 8 cents/kWh, median 4.4 (twice 1983 levels). Expected reactor lives average 24 years. At closed reactors, owners estimate costs to dismantle averaging $760/kW (1985$), or 53% of construction cost. Analysis of owner opinions for all American reactors suggests actual costs may average $200/kW. Higher burial prices could increase that substantially

  13. SUMOylation of the Forkhead transcription factor FOXL2 promotes its stabilization/activation through transient recruitment to PML bodies.

    Directory of Open Access Journals (Sweden)

    Adrien Georges

    Full Text Available BACKGROUND: FOXL2 is a transcription factor essential for ovarian development and maintenance. It is mutated in the genetic condition called Blepharophimosis Ptosis Epicantus inversus Syndrome (BPES and in cases of isolated premature ovarian failure. We and others have previously shown that FOXL2 undergoes several post-translational modifications. METHODS AND PRINCIPAL FINDINGS: Here, using cells in culture, we show that interference with FOXL2 SUMOylation leads to a robust inhibition of its transactivation ability, which correlates with a decreased stability. Interestingly, FOXL2 SUMOylation promotes its transient recruitment to subnuclear structures that we demonstrate to be PML (Promyelocytic Leukemia Nuclear Bodies. Since PML bodies are known to be sites where post-translational modifications of nuclear factors take place, we used tandem mass spectrometry to identify new post-translational modifications of FOXL2. Specifically, we detected four phosphorylated, one sulfated and three acetylated sites. CONCLUSIONS: By analogy with other transcription factors, we propose that PML Nuclear Bodies might transiently recruit FOXL2 to the vicinity of locally concentrated enzymes that could be involved in the post-translational maturation of FOXL2. FOXL2 acetylation, sulfation, phosphorylation as well as other modifications yet to be discovered might alter the transactivation capacity of FOXL2 and/or its stability, thus modulating its global intracellular activity.

  14. Quenching factor for low-energy nuclear recoils in a plastic scintillator

    Science.gov (United States)

    Reichhart, L.; Akimov, D. Yu.; Araújo, H. M.; Barnes, E. J.; Belov, V. A.; Burenkov, A. A.; Chepel, V.; Currie, A.; DeViveiros, L.; Edwards, B.; Francis, V.; Ghag, C.; Hollingsworth, A.; Horn, M.; Kalmus, G. E.; Kobyakin, A. S.; Kovalenko, A. G.; Lebedenko, V. N.; Lindote, A.; Lopes, M. I.; Lüscher, R.; Majewski, P.; Murphy, A. St J.; Neves, F.; Paling, S. M.; Pinto da Cunha, J.; Preece, R.; Quenby, J. J.; Scovell, P. R.; Silva, C.; Solovov, V. N.; Smith, N. J. T.; Smith, P. F.; Stekhanov, V. N.; Sumner, T. J.; Thorne, C.; Walker, R. J.

    2012-06-01

    Plastic scintillators are widely used in industry, medicine, and scientific research, including nuclear and particle physics. Although one of their most common applications is in neutron detection, experimental data on their response to low-energy nuclear recoils are scarce. Here, the relative scintillation efficiency for neutron-induced nuclear recoils in a polystyrene-based plastic scintillator (UPS-923A) is presented, exploring recoil energies between 125 and 850 keV. Monte Carlo simulations, incorporating light collection efficiency and energy resolution effects, are used to generate neutron scattering spectra which are matched to observed distributions of scintillation signals to parameterize the energy-dependent quenching factor. At energies above 300 keV the dependence is reasonably described using the semiempirical formulation of Birks and a kB factor of (0.014±0.002) g MeV-1 cm-2 has been determined. Below that energy, the measured quenching factor falls more steeply than predicted by the Birks formalism.

  15. Effects of different ligands on epidermal growth factor receptor (EGFR) nuclear translocation

    Energy Technology Data Exchange (ETDEWEB)

    Faria, Jerusa A.Q.A.; Andrade, Carolina de; Goes, Alfredo M. [Department of Biochemistry and Immunology, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, Belo Horizonte, MG, 31270-901 (Brazil); Rodrigues, Michele A. [Department of Biochemistry and Immunology, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, Belo Horizonte, MG, 31270-901 (Brazil); Department of General Pathology, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, Belo Horizonte, MG, 31270-901 (Brazil); Gomes, Dawidson A., E-mail: dawidson@ufmg.br [Department of Biochemistry and Immunology, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, Belo Horizonte, MG, 31270-901 (Brazil)

    2016-09-09

    The epidermal growth factor receptor (EGFR) is activated through binding to specific ligands and generates signals for proliferation, differentiation, migration, and cell survival. Recent data show the role of nuclear EGFR in tumors. Although many EGFR ligands are upregulated in cancers, little is known about their effects on EGFR nuclear translocation. We have compared the effects of six EGFR ligands (EGF, HB-EGF, TGF-α, β-Cellulin, amphiregulin, and epiregulin) on nuclear translocation of EGFR, receptor phosphorylation, migration, and proliferation. Cell fractionation and confocal immunofluorescence detected EGFR in the nucleus after EGF, HB-EGF, TGF-α and β-Cellulin stimulation in a dose-dependent manner. In contrast, amphiregulin and epiregulin did not generate nuclear translocation of EGFR. EGF, HB-EGF, TGF-α and β-Cellulin showed correlations between a higher rate of wound closure and increased phosphorylation of residues in the carboxy-terminus of EGFR, compared to amphiregulin and epiregulin. The data indicate that EGFR is translocated to the nucleus after stimulation with EGF, HB-EGF, TGF-α and β-Cellulin, and that these ligands are related to increased phosphorylation of EGFR tyrosine residues, inducing migration of SkHep-1 cells. - Highlights: • EGF, HB-EGF, TGF-α, β-Cellulin are involved in the EGFR nuclear translocation. • Amphiregulin and epiregulin did not promote nuclear translocation of EGFR. • EGF, HB-EGF, TGF-α and β-Cellulin have a role in SkHep-1 cells migration. • EGFR ligands associated with better prognosis don't stimulate EGFR translocation.

  16. Effects of different ligands on epidermal growth factor receptor (EGFR) nuclear translocation

    International Nuclear Information System (INIS)

    Faria, Jerusa A.Q.A.; Andrade, Carolina de; Goes, Alfredo M.; Rodrigues, Michele A.; Gomes, Dawidson A.

    2016-01-01

    The epidermal growth factor receptor (EGFR) is activated through binding to specific ligands and generates signals for proliferation, differentiation, migration, and cell survival. Recent data show the role of nuclear EGFR in tumors. Although many EGFR ligands are upregulated in cancers, little is known about their effects on EGFR nuclear translocation. We have compared the effects of six EGFR ligands (EGF, HB-EGF, TGF-α, β-Cellulin, amphiregulin, and epiregulin) on nuclear translocation of EGFR, receptor phosphorylation, migration, and proliferation. Cell fractionation and confocal immunofluorescence detected EGFR in the nucleus after EGF, HB-EGF, TGF-α and β-Cellulin stimulation in a dose-dependent manner. In contrast, amphiregulin and epiregulin did not generate nuclear translocation of EGFR. EGF, HB-EGF, TGF-α and β-Cellulin showed correlations between a higher rate of wound closure and increased phosphorylation of residues in the carboxy-terminus of EGFR, compared to amphiregulin and epiregulin. The data indicate that EGFR is translocated to the nucleus after stimulation with EGF, HB-EGF, TGF-α and β-Cellulin, and that these ligands are related to increased phosphorylation of EGFR tyrosine residues, inducing migration of SkHep-1 cells. - Highlights: • EGF, HB-EGF, TGF-α, β-Cellulin are involved in the EGFR nuclear translocation. • Amphiregulin and epiregulin did not promote nuclear translocation of EGFR. • EGF, HB-EGF, TGF-α and β-Cellulin have a role in SkHep-1 cells migration. • EGFR ligands associated with better prognosis don't stimulate EGFR translocation.

  17. Insertion of a nuclear factor kappa B DNA nuclear-targeting sequence potentiates suicide gene therapy efficacy in lung cancer cell lines

    DEFF Research Database (Denmark)

    Cramer, F; Christensen, C L; Poulsen, T T

    2012-01-01

    Lung cancer currently causes the majority of cancer-related deaths worldwide and new treatments are in high demand. Gene therapy could be a promising treatment but currently lacks sufficient efficiency for clinical use, primarily due to limited cellular and nuclear DNA delivery. In the present...... study, we investigated whether it was possible to exploit the endogenous nuclear-shuttling activity by the nuclear factor kappa B (NFκB) system, which is highly prominent in many cancers as well as lung cancer. We observed that insertion of a DNA nuclear-targeting sequence (DTS) recognized by NFκB could...... improve plasmid nuclear delivery and enhance the therapeutic effect of a validated transcriptionally cancer-targeted suicide gene therapy system. A clear correlation between the number of inserted NFκB-binding sites and the therapeutic effect of the suicide system was observed in both small cell lung...

  18. Quality factors quantification/assurance for software related to safety in nuclear power plants

    International Nuclear Information System (INIS)

    Nunez McLeod, J.E.; Rivera, S.S.

    1997-01-01

    Quality assurance plan is needed to guarantee the software quality. The use of such a plan involves activities that should take place all along the life cycle, and which can be evaluated using the so called quality factors. This is due to the fact that the quality itself cannot be measured, but some of its manifestations can be used for this purpose. In the present work, a methodology to quantify a set of quality factors is proposed, for software based systems to be used in safety related areas in nuclear power plants. (author) [es

  19. Organisational factors. Their definition and influence on nuclear safety. Final report

    International Nuclear Information System (INIS)

    Baumont, G.; Wahlstroem, B.; Sola, R.; Williams, J.; Frischknecht, A.; Wilpert, B.; Rollenhagen, C.

    2000-12-01

    The importance of organisational factors in the operational safety and efficiency of nuclear power plants (NPP) has been recognised by many organisations around the world. Despite this recognition, however, there are as yet very few methods by which organisational factors can be systematically assessed and improved. The majority of research efforts applied so far have tended to be modest and scattered. The ORFA project was created as a remedy to these problems. The objective of the project is to create a better understanding of how organisation and management factors influence nuclear safety. A key scientific objective of the project is to identify components of a theoretical framework, which would help in understanding the relationships between organisational factors and nuclear safety. Three work packages were planned. First, a review of literature listed out the identified factors and methods for assessing them. Then, a draft version of the present report was prepared to clarify the environment context and the main issues of the topics. This draft was discussed at the ORFA seminar in Madrid 21-22 October 1999. During the seminar views and comments were collected on preliminary results of the project. Finally, this information has been integrated in the present and other reports and will be used to give further guidance to the European Commission in the development of forthcoming research programmes in the field. The project has addressed nuclear safety taking a broad perspective, which reflected and took into account the views of senior NPP management and regulators. The questions discussed during the project have been: how can organisational factors be included in safety assessments, how can good and bad operational practices be identified, which methods can be used for detecting weak signals of deteriorating performance, how should incidents be analysed with respect to organisational factors to give the largest learning benefit, how can data on organisational

  20. MiRNA-Based Regulation of Hemostatic Factors through Hepatic Nuclear Factor-4 Alpha.

    Directory of Open Access Journals (Sweden)

    Salam Salloum-Asfar

    Full Text Available MiRNAs have been reported as CIS-acting elements of several hemostatic factors, however, their mechanism as TRANS-acting elements mediated by a transcription factor is little known and could have important effects. HNF4α has a direct and important role in the regulation of multiple hepatic coagulation genes. Previous in vitro studies have demonstrated that miR-24-3p and miR-34a-5p regulate HNF4A expression. Here we aimed to investigate the molecular mechanisms of miR-24 and miR-34a on coagulation through HNF4A. Transfections with miR-24 and miR-34a in HepG2 cells decreased not only HNF4A but also F10, F12, SERPINC1, PROS1, PROC, and PROZ transcripts levels. Positive and significant correlations were observed between levels of HNF4A and several hemostatic factors (F5, F8, F9, F11, F12, SERPINC1, PROC, and PROS1 in human liver samples (N = 104. However, miR-24 and miR-34a levels of the low (10th and high (90th percentiles of those liver samples were inversely correlated with HNF4A and almost all hemostatic factors expression levels. These outcomes suggest that miR-24 and miR-34a might be two indirect elements of regulation of several hemostatic factors. Additionally, variations in miRNA expression profiles could justify, at least in part, changes in HNF4A expression levels and its downstream targets of coagulation.

  1. The Impact of Organizational Factors on Safety. The Perspective of Experts from the Spanish Nuclear Sector

    International Nuclear Information System (INIS)

    German, S.; Silla, I.; Navajas, J.

    2014-01-01

    Previous research supports the importance of organizational factors on safety in high reliability organizations. This study aims to determine the impact of those factors in the Spanish nuclear sector. Particularly, this study focuses on examining the role of performance indicators, organizational culture, organizational factors, and organizational context. With that purpose, an electronic survey addressed to experts from the Spanish nuclear sector was carried out. Results showed that performance indicators are well-known among industry experts and are perceived as useful for improving performance. Behavioural norms that influence safety and some relevant factors that promote problem identification were identified. Additionally, findings suggested that organizational context must be taken into account to better understand the role of organizational culture. Moreover, industry experts pointed out organizational factors to be improved: organizational communication processes within the organization, positive reinforcement, and field supervisors practices. Finally, findings supported the influence of organizational context on safety. It is noteworthy the role of the social impact of international events (e.g., Chernobyl...), the relationship with the regulator and the legislative and governmental framework. (Author)

  2. Human factors evaluation of man-machine interface for periodic safety review of nuclear power plants

    International Nuclear Information System (INIS)

    Lee, Yong Hee; Lee, Jung Woon; Park, Jae Chang; Hwang, In Koo; Lee, Hyun Cheol; Jang, Tong Il; Ku, Jin Young; Kim, Soo Jin

    2004-12-01

    This report describes the research results of human factors assessment on the MMI(Man Machine Interface) equipment as part of Periodic Safety Review(PSR) of Nuclear Power Plants(NPPs). As MMI is a key factor among human factors to be reviewed in PSR, we reviewed the MMI components of nuclear power plants in aspect of human factors engineering. The availability, suitability, and effectiveness of the MMI devices were chosen to be reviewed. The MMI devices were investigated through the review of design documents related to the MMI, survey of control panels, evaluation of experts, and experimental assessment. Checklists were used to perform this assessment and record the review results. The items mentioned by the expert comments to review in detail in relation with task procedures were tested by experiments with operators' participation. For some questionable issues arisen during this MMI review, operator workload and possibility of errors in operator actions were analysed. The reviewed MMI devices contain MCR(Main Control Room), SPDS(Safety Parameter Display System), RSP(Remote Shutdown Panel), and the selected LCBs(Local Control Boards) importantly related to safety. As results of the assessments, any significant problem challenging the safety was not found on human factors in the MMI devices. However, several small items to be changed and improved in suitability of MMI devices were discovered. An action plan is recommended to accommodate the suggestions and review comments. It will enhance the plant safety on MMI area

  3. The Nuclear Factor of Activated T Cells (Nfat) Transcription Factor Nfatp (Nfatc2) Is a Repressor of Chondrogenesis

    Science.gov (United States)

    Ranger, Ann M.; Gerstenfeld, Louis C.; Wang, Jinxi; Kon, Tamiyo; Bae, Hyunsu; Gravallese, Ellen M.; Glimcher, Melvin J.; Glimcher, Laurie H.

    2000-01-01

    Nuclear factor of activated T cells (NFAT) transcription factors regulate gene expression in lymphocytes and control cardiac valve formation. Here, we report that NFATp regulates chondrogenesis in the adult animal. In mice lacking NFATp, resident cells in the extraarticular connective tissues spontaneously differentiate to cartilage. These cartilage cells progressively differentiate and the tissue undergoes endochondral ossification, recapitulating the development of endochondral bone. Proliferation of already existing articular cartilage cells also occurs in some older animals. At both sites, neoplastic changes in the cartilage cells occur. Consistent with these data, NFATp expression is regulated in mesenchymal stem cells induced to differentiate along a chondrogenic pathway. Lack of NFATp in articular cartilage cells results in increased expression of cartilage markers, whereas overexpression of NFATp in cartilage cell lines extinguishes the cartilage phenotype. Thus, NFATp is a repressor of cartilage cell growth and differentiation and also has the properties of a tumor suppressor. PMID:10620601

  4. Prescribing safety, negotiating expertise. Building of nuclear safety human factors expertise

    International Nuclear Information System (INIS)

    Rolina, Gregory

    2008-01-01

    This Ph.D thesis is dedicated to a specific type of expertise, the safety of nuclear installations in the field of human and organisational factors. Empirical work is at the foundation of this thesis: the monitoring of experts 'in action', allowed a detailed reconstruction of three cases they were examining. The analysis, at the core of which lies the definition of what an efficient expertise can be, emphasizes the incompleteness of the knowledge that links together the nuclear facilities' organisational characteristics and their safety. This leads us to identify the expert's three ranges of actions (rhetorical, cognitive, operative). Defined from objectives and constraints likely to influence the expert's behaviour, those three ranges each require specific skills. A conception of expertise based on these ranges seems adaptable to other sectors and allows an enrichment of models of expertise cited in literature. Historical elements from French institutions of nuclear safety are also called upon to take into consideration some of the determinants of the expertise; its efficiency relies on the upholding of a continuous dialogue between the regulators (the experts and the control authority) and the regulated (the operators). This type of historically inherited regulation makes up a specificity of the French system of external control of nuclear risks. (author) [fr

  5. A Review on the Regulatory Strategy of Human Factors Engineering Consideration in Pakistan Nuclear Facilities

    Energy Technology Data Exchange (ETDEWEB)

    Sohail, Sabir [Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of); Choi, Seong Nam [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

    2013-10-15

    In this paper, the legal and regulatory infrastructure available in Pakistan for HFE requirements is assessed, and the methodology for strengthening of legal infrastructure is presented. The regulatory strategy on evaluation of HFE consideration should provide reviewers with guidance on review process. Therefore, the suggested methodology is based on preparation of guidance documents such as checklist, working procedures, S and Gs etc.; incorporation of PRM elements in regulatory system; and finally the development of PRM implementation criteria. Altogether, the scheme provide the enhancement in regulatory infrastructure and also the effective and efficient review process. The Three Mile Island (TMI) accident brought the general consensus among the nuclear community on the integration of human factors engineering (HFE) principles in all phases of nuclear power. This notion has further strengthened after the recent Fukushima nuclear accident. Much effort has been put over to incorporate the lesson learned and continuous technical evolution on HFE to device different standards. The total of 174 ergonomics standards are alone identified by Dul et al. (2004) published by International Organization for Standardization (ISO) and the European Committee for Standardization (CEN) and number of standards and HFE guidelines (S and Gs) are also published by organizations like Institute for Electrical and Electronics Engineering (IEEE), International Electrotechnical Commission (IEC), International Atomic Energy Agency (IAEA), United States Nuclear Regulatory Commission (USNRC), etc. The ambition of effective review on HFE integration in nuclear facility might be accomplished through the development of methodology for systematic implementation of S and Gs. Such kind of methodology would also be beneficial for strengthening the regulatory framework and practices for countries new in the nuclear arena and with small scale nuclear program. The objective of paper is to review the

  6. The dependence of the nuclear charge form factor on short range correlations and surface fluctuation effects

    International Nuclear Information System (INIS)

    Massen, S. E.; Garistov, V. P.; Grypeos, M. E.

    1996-01-01

    The effects of nuclear surface fluctuations on harmonic oscillator elastic charge form factor of light nuclei are investigated, simultaneously approximating the short-range correlations through a Jastrow correlation factor. Inclusion of the surface fluctuation effects within this description, by truncating the cluster expansion at the two-body part, is found to improve somewhat the fit to the elastic charge form-factor of 16 O and 40 Ca. However, the convergence of the cluster expansion is expected to deteriorate. An additional finding is that surface-fluctuation correlations produce a drastic change in the asymptotic behaviour of the point-proton form-factor, which now falls off quite slowly (i.e. as const.q -4 ) at large values of the momentum transfer q

  7. Critique of the Council on Economic Priorities test ''power plant performance: nuclear and coal capacity factors and economics''

    International Nuclear Information System (INIS)

    Simard, R.L.

    1977-01-01

    The Council on Economic Priorities (CEP) has assembled capacity factor data on most U.S. nuclear and coal-fired units in operation, performed a regression analysis upon capacity factor as a function of intrinsic unit variables such as size and age, and attempted a comparison of the economics of typical nuclear and coal-fired units using the resultant fitted-capacity factors. The report points out inadequacies in the CEP data base, the lack of predictive value in the results of the regression analysis, and inconsistencies in the economic evaluation of nuclear and coal-fired units

  8. Ac-mediated trans-activation of the Ds element in rice (Oryza sativa L.) cells as revealed by GUS assay.

    Science.gov (United States)

    Solis, R; Takumi, S; Mori, N; Nakamura, C

    1999-01-01

    A method using particle bombardment and beta-glucuronidase (GUS) assay was applied to rice callus for detecting the excision of the maize Ds element trans-activated by the Ac transposase source. Excision of Ds biolistically introduced into rice callus resulted in the restoration of the interrupted gus gene expression, allowing visual detection of trans-activation two days after bombardment. Only the transgenic callus lines expressing the Ac transposase gene and the wild-type callus co-transformed with Ac and Ds revealed GUS activity. Frequency of excision, estimated based on the relative GUS activity, ranged from 0.3% to 2.2%. Callus lines showing different levels of Ac transcripts revealed varying excision frequencies. At the later stages of callus growth after selection for the Ac/Ds transformed lines, excision events were detected by GUS assay and confirmed by PCR and sequence analyses of the excision sites in individual colonies. GUS activity was also demonstrated in the primary regenerants from the Ac/Ds-transformed callus colonies. The method described in this study may be used as an approach for rapid detection of excision events and assessment of various factors limiting Ac/Ds activity in rice cells.

  9. Basic factors to forecast maintenance cost and failure processes for nuclear power plants

    International Nuclear Information System (INIS)

    Popova, Elmira; Yu, Wei; Kee, Ernie; Sun, Alice; Richards, Drew; Grantom, Rick

    2006-01-01

    Two types of maintenance interventions are usually administered at nuclear power plants: planned and corrective. The cost incurred includes the labor (manpower) cost, cost for new parts, or emergency order of expensive items. At the plant management level there is a budgeted amount of money to be spent every year for such operations. It is very important to have a good forecast for this cost since unexpected events can trigger it to a very high level. In this research we present a statistical factor model to forecast the maintenance cost for the incoming month. One of the factors is the expected number of unplanned (due to failure) maintenance interventions. We introduce a Bayesian model for the failure rate of the equipment, which is input to the cost forecasting model. The importance of equipment reliability and prediction in the commercial nuclear power plant is presented along with applicable governmental and industry organization requirements. A detailed statistical analysis is performed on a set of maintenance cost and failure data gathered at the South Texas Project Nuclear Operating Company (STPNOC) in Bay City, Texas, USA

  10. Variation near the hepatocyte nuclear factor (HNF)-4alpha gene associates with type 2 diabetes in the Danish population

    DEFF Research Database (Denmark)

    Hansen, S K; Rose, C S; Glümer, C

    2005-01-01

    The hepatocyte nuclear factor (HNF)-4alpha is an orphan nuclear receptor, which plays crucial roles in regulating hepatic gluconeogenesis and insulin secretion. The gene encoding HNF-4alpha (HNF4A) is located on chromosome 20q12-q13 in a region that in several studies has shown linkage with type 2...

  11. Incorporating organizational factors into probabilistic safety assessment of nuclear power plants through canonical probabilistic models

    International Nuclear Information System (INIS)

    Galan, S.F.; Mosleh, A.; Izquierdo, J.M.

    2007-01-01

    The ω-factor approach is a method that explicitly incorporates organizational factors into Probabilistic safety assessment of nuclear power plants. Bayesian networks (BNs) are the underlying formalism used in this approach. They have a structural part formed by a graph whose nodes represent organizational variables, and a parametric part that consists of conditional probabilities, each of them quantifying organizational influences between one variable and its parents in the graph. The aim of this paper is twofold. First, we discuss some important limitations of current procedures in the ω-factor approach for either assessing conditional probabilities from experts or estimating them from data. We illustrate the discussion with an example that uses data from Licensee Events Reports of nuclear power plants for the estimation task. Second, we introduce significant improvements in the way BNs for the ω-factor approach can be constructed, so that parameter acquisition becomes easier and more intuitive. The improvements are based on the use of noisy-OR gates as model of multicausal interaction between each BN node and its parents

  12. Incorporating organizational factors into probabilistic safety assessment of nuclear power plants through canonical probabilistic models

    Energy Technology Data Exchange (ETDEWEB)

    Galan, S.F. [Dpto. de Inteligencia Artificial, E.T.S.I. Informatica (UNED), Juan del Rosal, 16, 28040 Madrid (Spain)]. E-mail: seve@dia.uned.es; Mosleh, A. [2100A Marie Mount Hall, Materials and Nuclear Engineering Department, University of Maryland, College Park, MD 20742 (United States)]. E-mail: mosleh@umd.edu; Izquierdo, J.M. [Area de Modelado y Simulacion, Consejo de Seguridad Nuclear, Justo Dorado, 11, 28040 Madrid (Spain)]. E-mail: jmir@csn.es

    2007-08-15

    The {omega}-factor approach is a method that explicitly incorporates organizational factors into Probabilistic safety assessment of nuclear power plants. Bayesian networks (BNs) are the underlying formalism used in this approach. They have a structural part formed by a graph whose nodes represent organizational variables, and a parametric part that consists of conditional probabilities, each of them quantifying organizational influences between one variable and its parents in the graph. The aim of this paper is twofold. First, we discuss some important limitations of current procedures in the {omega}-factor approach for either assessing conditional probabilities from experts or estimating them from data. We illustrate the discussion with an example that uses data from Licensee Events Reports of nuclear power plants for the estimation task. Second, we introduce significant improvements in the way BNs for the {omega}-factor approach can be constructed, so that parameter acquisition becomes easier and more intuitive. The improvements are based on the use of noisy-OR gates as model of multicausal interaction between each BN node and its parents.

  13. The transcription elongation factor ELL2 is specifically upregulated in HTLV-1-infected T-cells and is dependent on the viral oncoprotein Tax.

    Science.gov (United States)

    Mann, Melanie C; Strobel, Sarah; Fleckenstein, Bernhard; Kress, Andrea K

    2014-09-01

    The oncoprotein Tax of human T-cell leukemia virus type 1 (HTLV-1) is a potent transactivator of viral and cellular transcription. Here, we identified ELL2 as the sole transcription elongation factor to be specifically upregulated in HTLV-1-/Tax-transformed T-cells. Tax contributes to regulation of ELL2, since transient transfection of Tax increases ELL2 mRNA, Tax transactivates the ELL2 promoter, and repression of Tax results in decrease of ELL2 in transformed T-lymphocytes. However, we also measured upregulation of ELL2 in HTLV-1-transformed cells exhibiting undetectable amounts of Tax, suggesting that ELL2 can still be maintained independent of continuous Tax expression. We further show that Tax and ELL2 synergistically activate the HTLV-1 promoter, indicating that ELL2 cooperates with Tax in viral transactivation. This is supported by our findings that Tax and ELL2 accumulate in nuclear fractions and that they co-precipitate upon co-expression in transiently-transfected cells. Thus, upregulation of ELL2 could contribute to HTLV-1 gene regulation. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Fluctuation factors of ambient dose rates in the vicinity of Hamaoka nuclear power plant

    International Nuclear Information System (INIS)

    Yoshida, Hideyuki; Ibuki, Yuko; Goto, Rensuke; Aika, Masahiro; Iki, Akio

    2004-01-01

    It is important to clearly distinguish between variations in natural ambient dose rates and those by small accidents at nuclear facilities from the viewpoint of radiation control. Therefore, we must have exact data of ambient dose rates during daily life. Ambient dose rates are influenced by meteorological conditions as well as geographical and geological features. We investigated the factors which cause fluctuations in ambient dose rates on fine and rainy days around Hamaoka nuclear power plant in Shizuoka Prefecture. Fluctuations in ambient dose rates depended on the concentration of radon daughters on fine days, whereas on rainy days they depended on gamma-rays from the uranium-series. Contributions of gamma-rays from the thorium-series and potassium-40 to fluctuations in ambient dose rates were not observed. (author)

  15. Organizational factors in design and implementation of technological and organizational solutions in the nuclear industry

    International Nuclear Information System (INIS)

    Macchi, L.; Reiman, T.; Savioja, P.; Kahlbom, U.; Rollenhagen, C.

    2012-02-01

    Design is often found as one of the contributing factors in accident in the nuclear industry. The design of new technological systems and organisational structures has to take into account and be driven by the future users' needs and has to consider how their role and work practices within the organisation will be affected. The SADE project explores to which extend the concepts of safety culture and resilience engineering can contribute to the prevention of design errors when no hindsight data are available. In 2011, the SADE project focused on gathering experience and clarifying the current issues and challenges related to the design process. During 2011 seventeen interviews have been conducted in Finland and Sweden to identify some of the major challenges the nuclear industry is currently facing. At the same time a literature review has been conducted to establish a sound common theoretical ground. This progress report presents some of the relevant theoretical findings and preliminary results from the interviews. (Author)

  16. Thyroid hormone and retinoic acid nuclear receptors: specific ligand-activated transcription factors

    International Nuclear Information System (INIS)

    Brtko, J.

    1998-01-01

    Transcriptional regulation by both the thyroid hormone and the vitamin A-derived 'retinoid hormones' is a critical component in controlling many aspects of higher vertebrate development and metabolism. Their functions are mediated by nuclear receptors, which comprise a large super-family of ligand-inducible transcription factors. Both the thyroid hormone and the retinoids are involved in a complex arrangement of physiological and development responses in many tissues of higher vertebrates. The functions of 3,5,3'-triiodothyronine (T 3 ), the thyromimetically active metabolite of thyroxine as well as all-trans retinoic acid, the biologically active vitamin A metabolite are mediated by nuclear receptor proteins that are members of the steroid/thyroid/retinoid hormone receptor family. The functions of all members of the receptor super family are discussed. (authors)

  17. SUV39H1 interacts with HTLV-1 Tax and abrogates Tax transactivation of HTLV-1 LTR

    Directory of Open Access Journals (Sweden)

    Tanaka Yuetsu

    2006-01-01

    Full Text Available Abstract Background Tax is the oncoprotein of HTLV-1 which deregulates signal transduction pathways, transcription of genes and cell cycle regulation of host cells. Transacting function of Tax is mainly mediated by its protein-protein interactions with host cellular factors. As to Tax-mediated regulation of gene expression of HTLV-1 and cellular genes, Tax was shown to regulate histone acetylation through its physical interaction with histone acetylases and deacetylases. However, functional interaction of Tax with histone methyltransferases (HMTase has not been studied. Here we examined the ability of Tax to interact with a histone methyltransferase SUV39H1 that methylates histone H3 lysine 9 (H3K9 and represses transcription of genes, and studied the functional effects of the interaction on HTLV-1 gene expression. Results Tax was shown to interact with SUV39H1 in vitro, and the interaction is largely dependent on the C-terminal half of SUV39H1 containing the SET domain. Tax does not affect the methyltransferase activity of SUV39H1 but tethers SUV39H1 to a Tax containing complex in the nuclei. In reporter gene assays, co-expression of SUV39H1 represses Tax transactivation of HTLV-1 LTR promoter activity, which was dependent on the methyltransferase activity of SUV39H1. Furthermore, SUV39H1 expression is induced along with Tax in JPX9 cells. Chromatin immunoprecipitation (ChIP analysis shows localization of SUV39H1 on the LTR after Tax induction, but not in the absence of Tax induction, in JPX9 transformants retaining HTLV-1-Luc plasmid. Immunoblotting shows higher levels of SUV39H1 expression in HTLV-1 transformed and latently infected cell lines. Conclusion Our study revealed for the first time the interaction between Tax and SUV39H1 and apparent tethering of SUV39H1 by Tax to the HTLV-1 LTR. It is speculated that Tax-mediated tethering of SUV39H1 to the LTR and induction of the repressive histone modification on the chromatin through H3 K9

  18. SUV39H1 interacts with HTLV-1 Tax and abrogates Tax transactivation of HTLV-1 LTR.

    Science.gov (United States)

    Kamoi, Koju; Yamamoto, Keiyu; Misawa, Aya; Miyake, Ariko; Ishida, Takaomi; Tanaka, Yuetsu; Mochizuki, Manabu; Watanabe, Toshiki

    2006-01-13

    Tax is the oncoprotein of HTLV-1 which deregulates signal transduction pathways, transcription of genes and cell cycle regulation of host cells. Transacting function of Tax is mainly mediated by its protein-protein interactions with host cellular factors. As to Tax-mediated regulation of gene expression of HTLV-1 and cellular genes, Tax was shown to regulate histone acetylation through its physical interaction with histone acetylases and deacetylases. However, functional interaction of Tax with histone methyltransferases (HMTase) has not been studied. Here we examined the ability of Tax to interact with a histone methyltransferase SUV39H1 that methylates histone H3 lysine 9 (H3K9) and represses transcription of genes, and studied the functional effects of the interaction on HTLV-1 gene expression. Tax was shown to interact with SUV39H1 in vitro, and the interaction is largely dependent on the C-terminal half of SUV39H1 containing the SET domain. Tax does not affect the methyltransferase activity of SUV39H1 but tethers SUV39H1 to a Tax containing complex in the nuclei. In reporter gene assays, co-expression of SUV39H1 represses Tax transactivation of HTLV-1 LTR promoter activity, which was dependent on the methyltransferase activity of SUV39H1. Furthermore, SUV39H1 expression is induced along with Tax in JPX9 cells. Chromatin immunoprecipitation (ChIP) analysis shows localization of SUV39H1 on the LTR after Tax induction, but not in the absence of Tax induction, in JPX9 transformants retaining HTLV-1-Luc plasmid. Immunoblotting shows higher levels of SUV39H1 expression in HTLV-1 transformed and latently infected cell lines. Our study revealed for the first time the interaction between Tax and SUV39H1 and apparent tethering of SUV39H1 by Tax to the HTLV-1 LTR. It is speculated that Tax-mediated tethering of SUV39H1 to the LTR and induction of the repressive histone modification on the chromatin through H3 K9 methylation may be the basis for the dose

  19. Antidepressant drugs transactivate TrkB neurotrophin receptors in the adult rodent brain independently of BDNF and monoamine transporter blockade.

    Directory of Open Access Journals (Sweden)

    Tomi Rantamäki

    Full Text Available BACKGROUND: Antidepressant drugs (ADs have been shown to activate BDNF (brain-derived neurotrophic factor receptor TrkB in the rodent brain but the mechanism underlying this phenomenon remains unclear. ADs act as monoamine reuptake inhibitors and after prolonged treatments regulate brain bdnf mRNA levels indicating that monoamine-BDNF signaling regulate AD-induced TrkB activation in vivo. However, recent findings demonstrate that Trk receptors can be transactivated independently of their neurotrophin ligands. METHODOLOGY: In this study we examined the role of BDNF, TrkB kinase activity and monoamine reuptake in the AD-induced TrkB activation in vivo and in vitro by employing several transgenic mouse models, cultured neurons and TrkB-expressing cell lines. PRINCIPAL FINDINGS: Using a chemical-genetic TrkB(F616A mutant and TrkB overexpressing mice, we demonstrate that ADs specifically activate both the maturely and immaturely glycosylated forms of TrkB receptors in the brain in a TrkB kinase dependent manner. However, the tricyclic AD imipramine readily induced the phosphorylation of TrkB receptors in conditional bdnf⁻/⁻ knock-out mice (132.4±8.5% of control; P = 0.01, indicating that BDNF is not required for the TrkB activation. Moreover, using serotonin transporter (SERT deficient mice and chemical lesions of monoaminergic neurons we show that neither a functional SERT nor monoamines are required for the TrkB phosphorylation response induced by the serotonin selective reuptake inhibitors fluoxetine or citalopram, or norepinephrine selective reuptake inhibitor reboxetine. However, neither ADs nor monoamine transmitters activated TrkB in cultured neurons or cell lines expressing TrkB receptors, arguing that ADs do not directly bind to TrkB. CONCLUSIONS: The present findings suggest that ADs transactivate brain TrkB receptors independently of BDNF and monoamine reuptake blockade and emphasize the need of an intact tissue context for the

  20. Importance of nuclear station load factor in applied ro energy policies

    International Nuclear Information System (INIS)

    Gomes, Daniel de Souza

    2015-01-01

    Load factor is the ration between the energy produced by a station and the energy it would have produced running at maximum power. The factor intends for all types of commercial reactors. Nuclear plants continuously provide over 11% of the world's electricity. The reactors for which data were available generated 618.7 TWh of electricity in 2014. Typical load factor was around 75% in worldwide during the first quarter of 2015. In this manner, it obtained from an average, three-monthly or yearly. The regular load factor of the reactors in operation was around 56% in 1970. While, in 1980's decade, we have an increase to 63%, the same situation occurred in next the decade and suffering increasing to 73%. Currently, the load factor reaches 78%. Accidents are seasonal factors, with the occurrence of reduction of power generation plants. In 2015 in January, there are over 437 operable commercial reactors in 31 countries, with over 377,728 MWe of full capacity. In Brazil, total capacity is 1901 MWe, with around 2.8% of electricity energy consumed. The primary objective of this study was to find a forecast model that express the evolution of the load factor in the next years. In recent years occur an extensive development of pressurized water reactors in Asia. The periodicity of seasonal effects on the performance of nuclear power plants due to aging. However, the impact of plant age depended on new technologies that allow the growth of the performance. The accident of Fukushima was an inflection point for energy policies. The event produced a trend that reduced the load in the world. (author)

  1. A protective role of nuclear factor-erythroid 2-related factor-2 (Nrf2) in inflammatory disorders

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jiyoung [National Research Laboratory, College of Pharmacy, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 151-742 (Korea, Republic of); Cha, Young-Nam [Inha University College of Medicine, Incheon 382-751 (Korea, Republic of); Surh, Young-Joon, E-mail: surh@plaza.snu.ac.kr [National Research Laboratory, College of Pharmacy, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 151-742 (Korea, Republic of); Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 151-742 (Korea, Republic of); Cancer Research Institute, Seoul National University, Seoul 110-799 (Korea, Republic of)

    2010-08-07

    Nuclear factor-erythroid 2-related factor-2 (Nrf2) is a key transcription factor that plays a central role in cellular defense against oxidative and electrophilic insults by timely induction of antioxidative and phase-2 detoxifying enzymes and related stress-response proteins. The 5'-flanking regions of genes encoding these cytoprotective proteins contain a specific consensus sequence termed antioxidant response element (ARE) to which Nrf2 binds. Recent studies have demonstrated that Nrf2-ARE signaling is also involved in attenuating inflammation-associated pathogenesis, such as autoimmune diseases, rheumatoid arthritis, asthma, emphysema, gastritis, colitis and atherosclerosis. Thus, disruption or loss of Nrf2 signaling causes enhanced susceptibility not only to oxidative and electrophilic stresses but also to inflammatory tissue injuries. During the early-phase of inflammation-mediated tissue damage, activation of Nrf2-ARE might inhibit the production or expression of pro-inflammatory mediators including cytokines, chemokines, cell adhesion molecules, matrix metalloproteinases, cyclooxygenase-2 and inducible nitric oxide synthase. It is likely that the cytoprotective function of genes targeted by Nrf2 may cooperatively regulate the innate immune response and also repress the induction of pro-inflammatory genes. This review highlights the protective role of Nrf2 in inflammation-mediated disorders with special focus on the inflammatory signaling modulated by this redox-regulated transcription factor.

  2. A protective role of nuclear factor-erythroid 2-related factor-2 (Nrf2) in inflammatory disorders

    International Nuclear Information System (INIS)

    Kim, Jiyoung; Cha, Young-Nam; Surh, Young-Joon

    2010-01-01

    Nuclear factor-erythroid 2-related factor-2 (Nrf2) is a key transcription factor that plays a central role in cellular defense against oxidative and electrophilic insults by timely induction of antioxidative and phase-2 detoxifying enzymes and related stress-response proteins. The 5'-flanking regions of genes encoding these cytoprotective proteins contain a specific consensus sequence termed antioxidant response element (ARE) to which Nrf2 binds. Recent studies have demonstrated that Nrf2-ARE signaling is also involved in attenuating inflammation-associated pathogenesis, such as autoimmune diseases, rheumatoid arthritis, asthma, emphysema, gastritis, colitis and atherosclerosis. Thus, disruption or loss of Nrf2 signaling causes enhanced susceptibility not only to oxidative and electrophilic stresses but also to inflammatory tissue injuries. During the early-phase of inflammation-mediated tissue damage, activation of Nrf2-ARE might inhibit the production or expression of pro-inflammatory mediators including cytokines, chemokines, cell adhesion molecules, matrix metalloproteinases, cyclooxygenase-2 and inducible nitric oxide synthase. It is likely that the cytoprotective function of genes targeted by Nrf2 may cooperatively regulate the innate immune response and also repress the induction of pro-inflammatory genes. This review highlights the protective role of Nrf2 in inflammation-mediated disorders with special focus on the inflammatory signaling modulated by this redox-regulated transcription factor.

  3. Human factors engineering measures taken by nuclear power plant owners/operators for optimisation of the man-machine interface

    International Nuclear Information System (INIS)

    Eisgruber, H.

    1996-01-01

    Both operating results and human factors studies show that man is able to meet the requirements in this working environment. Hence the degree of human reliability required by the design basis of nuclear power plants is ensured. This means: - Nuclear technology for electricity generation is justifiable from the human factors point of view. - The chief opponent is not right in saying that man is not able to cope with the risks and challenges brought about by nuclear technology applications. The human factors concept for optimisation or configuration of the man-machine systems represents an additional endeavor on the part of nuclear power plant operators within the framework of their responsibilities. Human factors analyses meet with good response by the personnel, as analysis results and clarification of causes of accident scenarios contribute to relieve the personnel (exoneration) and find ways for remedial action. (orig./DG) [de

  4. An Adenovirus DNA Replication Factor, but Not Incoming Genome Complexes, Targets PML Nuclear Bodies.

    Science.gov (United States)

    Komatsu, Tetsuro; Nagata, Kyosuke; Wodrich, Harald

    2016-02-01

    Promyelocytic leukemia protein nuclear bodies (PML-NBs) are subnuclear domains implicated in cellular antiviral responses. Despite the antiviral activity, several nuclear replicating DNA viruses use the domains as deposition sites for the incoming viral genomes and/or as sites for viral DNA replication, suggesting that PML-NBs are functionally relevant during early viral infection to establish productive replication. Although PML-NBs and their components have also been implicated in the adenoviral life cycle, it remains unclear whether incoming adenoviral genome complexes target PML-NBs. Here we show using immunofluorescence and live-cell imaging analyses that incoming adenovirus genome complexes neither localize at nor recruit components of PML-NBs during early phases of infection. We further show that the viral DNA binding protein (DBP), an early expressed viral gene and essential DNA replication factor, independently targets PML-NBs. We show that DBP oligomerization is required to selectively recruit the PML-NB components Sp100 and USP7. Depletion experiments suggest that the absence of one PML-NB component might not affect the recruitment of other components toward DBP oligomers. Thus, our findings suggest a model in which an adenoviral DNA replication factor, but not incoming viral genome complexes, targets and modulates PML-NBs to support a conducive state for viral DNA replication and argue against a generalized concept that PML-NBs target incoming viral genomes. The immediate fate upon nuclear delivery of genomes of incoming DNA viruses is largely unclear. Early reports suggested that incoming genomes of herpesviruses are targeted and repressed by PML-NBs immediately upon nuclear import. Genome localization and/or viral DNA replication has also been observed at PML-NBs for other DNA viruses. Thus, it was suggested that PML-NBs may immediately sense and target nuclear viral genomes and hence serve as sites for deposition of incoming viral genomes and

  5. A preliminary study on related factors of mental health in nuclear power plant operators

    International Nuclear Information System (INIS)

    Dai Tingting; Liu Yulong; Li Yuan; Liao Haihong; Qiu Mengyue; Bian Huahui; Chen Weibo; Liu Chunfeng

    2012-01-01

    Objective: To explore the status of nuclear power plant operators in mental health and its correlation with emotional stability, liveliness, anxiety and urgency. Methods: 255 male operators were randomly selected from three nuclear power bases, meanwhile 61 undergraduates were used as control group. The mental health and neurobehavioral evaluation system of Chinese nuclear power plant operators was developed by Second Affiliated Hospital of Soochow University, which was used to assess mental health of the subjects. The scores of mental health personality factors were recorded, together with four main personality factors including emotional stability, liveliness, anxiety and urgency. Results: The score of lie was lower than 8 which showed all inspected groups were normal. 1.57% (4/255) operators had psychological disorders, 3.92% (10/255) had poor mental health, 27.84% (71/255) had general mental health, 66.7% (170/255) had excellent mental health, whereas 9.84% (6/61) for control group had psychological disorders. Obvious difference was observed in the final scores between the nuclear power plant operators and control group. The former gained higher scores on mental health,emotional stability,and lower scores on anxiety and urgency (t=3.437, 4.423, -2.493, -2.093, P<0.05). Both groups aged over 27 years and with length of service over 5 years were awarded higher scores on mental health, emotional stability (t=2.585, 2.349; t=2.606, 2.947, P<0.05), lower scores on anxiety and urgency (t=-3.407, -2.138; t=- 2.941, -2.256, P<0.05). The mental health was positively correlated with emotional stability and liveliness (r=0.721, 0.650, P<0.05), but negatively correlated with anxiety and urgency (r=-0.809, -0.693, P<0.05). Conclusions: The majority of nuclear power plant operators had excellent psychological quality, but some factors should be paid more attention, such as different ages and length of service time. (authors)

  6. The human factor data management system of Daya Bay Nuclear Power Station

    International Nuclear Information System (INIS)

    Zhang Li; Zhang Ning; Guo Jianbing; Huang Weigang; Zhu Minhong; Wang Jin

    1999-12-01

    The collection, analysis and quantification of human factor data are very important parts of human reliability analysis and probabilistic risk assessment. Therefore various human databases have been created. But a human data management system with the functions of data collection, classification, analysis, computation and forecast is scarcely seen at home and abroad. So the authors have developed the human data management system of Daya Bay Nuclear Power Station. The system includes three modules and four databases. The authors firstly set forth some basic problems on the human factor data, which are concerned during the development of the system. Then the structure and function of the system are described. In view of the important role of human factor databases in the system, the authors also discuss the structure problems of the data in the databases in detail

  7. Human factor analysis and preventive countermeasures of maintenance in nuclear power plant

    International Nuclear Information System (INIS)

    Zhang Li; Hu Chao

    2008-01-01

    Based on the human error analysis theory and the characteristics of maintenance in a nuclear power plant, human factors of maintenance in NPP are divided into three different areas: human, technology, and organization, in which human refers to the individual factors, mainly including psychological quality, physiological characteristic, state of health, knowledge, skill level, and interpersonal relationship. Technology includes the maintenance technology, maintenance strategy, maintenance tool, maintenance interface, maintenance regulation, and work environment. Organization includes task arrangement, information communication, training, personnel external environment, team construction, and leadership. The analysis also reveals that the organization factors, which can indirectly influence personnel performance, are the primary initiators of human error. Based on these, some countermeasures are brought forward in order to reduce human errors. (authors)

  8. Potential human factors research relating to modern technology in nuclear power plants

    International Nuclear Information System (INIS)

    Ketchel, J.; Fink, R.; Hanes, L.; Williges, R.; Williges, B.

    1994-01-01

    This paper discusses proposed human factors research to address advanced human-machine interface technology in nuclear power plants. It relates to a current EPRI project to identify a prioritized list of specific research issues that could be assessed to improve control room and other user interface areas. The project seeks to bridge the gap between the functional requirements of advanced design initiatives and the human factors research needed to support them. It seeks to identify potential benefits to be expected, as well as potential problems that might be introduced by advanced technology. It provides an organized approach to identifying human factors research needs, information already available, and measures of performance and effectiveness that might be used to assess the value of potential improvements. Those parts of the proposed plan that are subsequently approved by EPRI management and by the utility advisory committee will provide a basis for recommending research priorities

  9. p63 Transcription Factor Regulates Nuclear Shape and Expression of Nuclear Envelope-Associated Genes in Epidermal Keratinocytes.

    Science.gov (United States)

    Rapisarda, Valentina; Malashchuk, Igor; Asamaowei, Inemo E; Poterlowicz, Krzysztof; Fessing, Michael Y; Sharov, Andrey A; Karakesisoglou, Iakowos; Botchkarev, Vladimir A; Mardaryev, Andrei

    2017-10-01

    The maintenance of a proper nuclear architecture and three-dimensional organization of the genes, enhancer elements, and transcription machinery plays an essential role in tissue development and regeneration. Here we show that in the developing skin, epidermal progenitor cells of mice lacking p63 transcription factor display alterations in the nuclear shape accompanied by a marked decrease in expression of several nuclear envelope-associated components (Lamin B1, Lamin A/C, Sun1, Nesprin-3, Plectin) compared with controls. Furthermore, chromatin immunoprecipitation-quantitative PCR assay showed enrichment of p63 on Sun1, Syne3, and Plec promoters, suggesting them as p63 targets. Alterations in the nuclei shape and expression of nuclear envelope-associated proteins were accompanied by altered distribution patterns of the repressive histone marks trimethylation on lysine 27 of histone H3, trimethylation on lysine 9 of histone H3, and heterochromatin protein 1-alpha in p63-null keratinocytes. These changes were also accompanied by downregulation of the transcriptional activity and relocation of the keratinocyte-specific gene loci away from the sites of active transcription toward the heterochromatin-enriched repressive nuclear compartments in p63-null cells. These data demonstrate functional links between the nuclear envelope organization, chromatin architecture, and gene expression in keratinocytes and suggest nuclear envelope-associated genes as important targets mediating p63-regulated gene expression program in the epidermis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  10. APOBEC3G inhibits HIV-1 RNA elongation by inactivating the viral trans-activation response element.

    Science.gov (United States)

    Nowarski, Roni; Prabhu, Ponnandy; Kenig, Edan; Smith, Yoav; Britan-Rosich, Elena; Kotler, Moshe

    2014-07-29

    Deamination of cytidine residues in viral DNA is a major mechanism by which APOBEC3G (A3G) inhibits vif-deficient human immunodeficiency virus type 1 (HIV-1) replication. dC-to-dU transition following RNase-H activity leads to viral cDNA degradation, production of non-functional proteins, formation of undesired stop codons and decreased viral protein synthesis. Here, we demonstrate that A3G provides an additional layer of defense against HIV-1 infection dependent on inhibition of proviral transcription. HIV-1 transcription elongation is regulated by the trans-activation response (TAR) element, a short stem-loop RNA structure required for elongation factors binding. Vif-deficient HIV-1-infected cells accumulate short viral transcripts and produce lower amounts of full-length HIV-1 transcripts due to A3G deamination of the TAR apical loop cytidine, highlighting the requirement for TAR loop integrity in HIV-1 transcription. We further show that free single-stranded DNA (ssDNA) termini are not essential for A3G activity and a gap of CCC motif blocked with juxtaposed DNA or RNA on either or 3'+5' ends is sufficient for A3G deamination. These results identify A3G as an efficient mutator and that deamination of (-)SSDNA results in an early block of HIV-1 transcription. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. A Human Factors Study on an Information Visualization System for Nuclear Power Plants Decommissioning Engineering

    International Nuclear Information System (INIS)

    Yang, Chih Wei; Yang, Li Chen

    2014-01-01

    Most nuclear power plants (NPPs) in the world have an operating life of up to 40 years. The utility should prepare a comprehensive decommissioning plan with purpose to document and to display how decommissioning activities can be safely performed. In the past, most studies related to NPPs decommissioning planning put emphasis on technical issues, little attention have been given to human factors in decommissioning activities. In fact, human factors are a critical factor to successful NPPs decommissioning. NPPs decommissioning will face potential risks. These risks include not only dismantling and moving large equipment but also treating with the radioactive materials. Using information visualization system, such as virtual reality (VR) technology, for staff training can improve decommissioning work safety and economy. Therefore, this study presents a study using VR to solve real world problems in the nuclear plant decommissioning. Then appropriate cases for introducing VR systems are summarized and future prospects are given. This study assesses availability and performance of the work training system by using heuristic evaluation and actual experiment. In the result, block type of radiation visibility was found relatively better both in performance and person's preference than other types. The results presented in this paper illustrate the VR applications a NPP decommissioning perspective

  12. A Human Factors Study on an Information Visualization System for Nuclear Power Plants Decommissioning Engineering

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Chih Wei; Yang, Li Chen [Institute of Nuclear Energy Research, Atomic Energy Council, Longtan (China)

    2014-08-15

    Most nuclear power plants (NPPs) in the world have an operating life of up to 40 years. The utility should prepare a comprehensive decommissioning plan with purpose to document and to display how decommissioning activities can be safely performed. In the past, most studies related to NPPs decommissioning planning put emphasis on technical issues, little attention have been given to human factors in decommissioning activities. In fact, human factors are a critical factor to successful NPPs decommissioning. NPPs decommissioning will face potential risks. These risks include not only dismantling and moving large equipment but also treating with the radioactive materials. Using information visualization system, such as virtual reality (VR) technology, for staff training can improve decommissioning work safety and economy. Therefore, this study presents a study using VR to solve real world problems in the nuclear plant decommissioning. Then appropriate cases for introducing VR systems are summarized and future prospects are given. This study assesses availability and performance of the work training system by using heuristic evaluation and actual experiment. In the result, block type of radiation visibility was found relatively better both in performance and person's preference than other types. The results presented in this paper illustrate the VR applications a NPP decommissioning perspective.

  13. Nuclear Expression of Snail Is an Independent Negative Prognostic Factor in Human Breast Cancer

    Directory of Open Access Journals (Sweden)

    S. Muenst

    2013-01-01

    Full Text Available Background. Snail is a key regulator of epithelial-mesenchymal transition of tumor cells. Several studies have shown nuclear Snail expression to be a negative prognostic factor in human cancer, where it is generally associated with more aggressive tumor behavior and worse survival. Objectives and Methods. To further explore the role of Snail expression in breast cancer, we conducted a study on a tissue microarray, encompassing 1043 breast cancer cases. Results. A total of 265 (25.4% breast cancers were positive for Snail. Snail expression was significantly associated with greater tumor size, higher tumor stage and grade, positive lymph node status, and hormone receptor negative status and was differently expressed in the intrinsic subtypes of breast cancer, being the highest in the basal-like subtype and the lowest in the luminal A subtype. In multivariate analysis, Snail proved to be an independent negative prognostic factor for OS. In the intrinsic subtypes, Snail expression was a negative prognostic factor for OS in the luminal B HER2−, the luminal B HER2+, and the basal-like subtype. Conclusions. This is the first study demonstrating that nuclear Snail expression is an independent negative predictor of prognosis in breast cancer, thus suggesting that it may represent a potential therapeutic target.

  14. Analysis of chemical factors affecting marine ecosystem around nuclear power plant

    International Nuclear Information System (INIS)

    Chun, Kwan Sik; Choi, Yoon Dong; Chun, Ki Jeong; Kim, Jin Kyu; Jung, Kyeong Chai; Lee, Yeong Keun; Park, Hyo Kook

    1994-06-01

    The ecological data of the coastal area of Youngkwang nuclear power plant from 1987 to 1993 were comprehensively analyzed, and various physical and chemical properties of sea water and sediments were measured. Major factors affecting phytoplankton standing crops were suspended substances, nitrate, and silicate. The contents of iron, chromium, copper, and sulfur in sediments sampled from the discharge channel were slightly higher than those in the other areas. In order to qantify the chemical impacts on marine ecosystem, it is desirable that a systematic survey be made through the whole year cycle to assure the consistency and confidence of the related data. (Author)

  15. Radiation factors and smoking interaction at lung cancer incidence for workers at a nuclear enterprise

    International Nuclear Information System (INIS)

    Tokarskaya, Z.B.; Khokhryakov, V.F.; Okladnikova, N.D.; Belyaeva, Z.D.; Zhuntova, G.V.

    1997-01-01

    It was shown on the basis of retrospective investigation of 500 workers at a nuclear enterprise (162 cases of lung cancer, 338 persons as matching control) that the interaction of external gamma-irradiation (> 2.0 Gy) and the body - burden of 239 Pu (> 9.3 kBq) at lung cancer is characterized as the multiplicative effect. Combined influence of smoking and radiation factors dependent on smoking index (SI): it changed from additive up to multiplicative and than to antagonistic with the increase of the smoking effect. The received results could be explained on the basis of a two - mutation model of radiation carcinogenesis

  16. Transcriptional Networks in the Liver: Hepatocyte Nuclear Factor 6 Function Is Largely Independent of Foxa2

    OpenAIRE

    Rubins, Nir E.; Friedman, Joshua R.; Le, Phillip P.; Zhang, Liping; Brestelli, John; Kaestner, Klaus H.

    2005-01-01

    A complex network of hepatocyte nuclear transcription factors, including HNF6 and Foxa2, regulates the expression of liver-specific genes. The current model, based on in vitro studies, suggests that HNF6 and Foxa2 interact physically. This interaction is thought to synergistically stimulate Foxa2-dependent transcription through the recruitment of p300/CBP by HNF6 and to inhibit HNF6-mediated transcription due to the interference of Foxa2 with DNA binding by HNF6. To test this model in vivo, w...

  17. Applying Human Factors Evaluation and Design Guidance to a Nuclear Power Plant Digital Control System

    Energy Technology Data Exchange (ETDEWEB)

    Thomas Ulrich; Ronald Boring; William Phoenix; Emily Dehority; Tim Whiting; Jonathan Morrell; Rhett Backstrom

    2012-08-01

    The United States (U.S.) nuclear industry, like similar process control industries, has moved toward upgrading its control rooms. The upgraded control rooms typically feature digital control system (DCS) displays embedded in the panels. These displays gather information from the system and represent that information on a single display surface. In this manner, the DCS combines many previously separate analog indicators and controls into a single digital display, whereby the operators can toggle between multiple windows to monitor and control different aspects of the plant. The design of the DCS depends on the function of the system it monitors, but revolves around presenting the information most germane to an operator at any point in time. DCSs require a carefully designed human system interface. This report centers on redesigning existing DCS displays for an example chemical volume control system (CVCS) at a U.S. nuclear power plant. The crucial nature of the CVCS, which controls coolant levels and boration in the primary system, requires a thorough human factors evaluation of its supporting DCS. The initial digital controls being developed for the DCSs tend to directly mimic the former analog controls. There are, however, unique operator interactions with a digital vs. analog interface, and the differences have not always been carefully factored in the translation of an analog interface to a replacement DCS. To ensure safety, efficiency, and usability of the emerging DCSs, a human factors usability evaluation was conducted on a CVCS DCS currently being used and refined at an existing U.S. nuclear power plant. Subject matter experts from process control engineering, software development, and human factors evaluated the DCS displays to document potential usability issues and propose design recommendations. The evaluation yielded 167 potential usability issues with the DCS. These issues should not be considered operator performance problems but rather opportunities

  18. A structural explanation of the effects of dissociated glucocorticoids on glucocorticoid receptor transactivation.

    Science.gov (United States)

    Dezitter, Xavier; Fagart, Jérôme; Taront, Solenne; Fay, Michel; Masselot, Bernadette; Hétuin, Dominique; Formstecher, Pierre; Rafestin-Oblin, Marie-Edith; Idziorek, Thierry

    2014-02-01

    There is a therapeutic need for glucocorticoid receptor (GR) ligands that distinguish between the transrepression and transactivation activity of the GR, the later thought to be responsible for side effects. These ligands are known as "dissociated glucocorticoids" (dGCs). The first published dGCs, RU24782 (9α-fluoro-11β-hydroxy-16α-methylpregna-21-thiomethyl-1,4-diene-3,20-dione) and RU24858 (9α-fluoro-11β-hydroxy-16α-methylpregna-21-cyanide-1,4-diene-3,20-dione), do not have the 17α-hydroxyl group that characterizes dexamethasone (Dex; 9α-fluoro-11β,17α,21-trihydroxy-16α-methylpregna-1,4-diene-3,20-dione), and they differ from one another by having C21-thiomethyl and C21-cyanide moieties, respectively. Our aim was therefore to establish the structural basis of their activity. Both RU24782 and RU24858 induced a transactivation activity highly dependent on the GR expression level but always lower than dexamethasone. They also display less ability than dexamethasone to trigger steroid receptor coactivator 1 (SRC-1) recruitment and histone H3 acetylation. Docking studies, validated by mutagenesis experiments, revealed that dGCs are not anchored by Gln642, in contrast to Dex, which is hydrogen bonded to this residue via its 17α-hydroxyl group. This contact is essential for SRC-1 recruitment and subsequent dexamethasone-induced GR transactivation, but not transrepression. The ability of dGCs to make contacts with Ile747, for both RU24858 and RU24782 and with Asn564 for RU24858 are not strong enough to maintain GR in a conformation able to efficiently recruit SRC-1, unless SRC-1 is overexpressed. Overall, our findings provide some structural guidelines for the synthesis of potential new dissociated glucocorticoids with a better therapeutic ratio.

  19. Screening of the target genes trans-activated by HLA-HA8 in hepatocytes

    Directory of Open Access Journals (Sweden)

    Qi WANG

    2011-06-01

    Full Text Available Objective To clone and identify the target genes trans-activated by human minor histocompatibility antigen HLA-HA8 in hepatocytes with suppression subtractive hybridization(SSH and bioinfomatics technique.Methods mRNA was isolated from HepG2 cells transfected by pcDNA3.1(--HLA-HA8 and pcDNA3.1(- empty vector,and then used to synthesize the double-stranded cDNA(marked as Tester and Driver,respectively by reverse transcription.After being digested with restriction enzyme Rsa I,the tester cDNA was divided into two parts and ligated to the specific adaptor 1 and adaptor 2,respectively,and then hybridized with driver cDNA twice and underwent PCR twice.The production was subcloned into pEGM-Teasy plasmid vectors to set up the subtractive library.The library was then amplified by transfection into E.coli strain DH5α.The cDNA was sequenced and analyzed in GenBank with Blast search after PCR amplification.Results The subtractive library of genes trans-activated by HLA-HA8 was constructed successfully.The amplified library contained 101 positive clones.Colony PCR showed that all these clones contained 200-1000bp inserts.Twenty eight clones were selected randomly to analyze the sequences.The result of homologous analysis showed that altogether 16 coding sequences were gotten,of which 4 sequences were with unknown function.Conclusions The obtained sequences trans-activated by HLA-HA8 may code different proteins and play important roles in cell growth and metabolism,energy synthesis and metabolism,material transport and signal transduction.This finding will bring some new clues for the studies not only on the biological functions of HLA-HA8,but also on the HBV infection mechanism.

  20. The far and distal enhancers in the CYP3A4 gene co-ordinate the proximal promoter in responding similarly to the pregnane X receptor but differentially to hepatocyte nuclear factor-4alpha.

    Science.gov (United States)

    Liu, Fu-Jun; Song, Xiulong; Yang, Dongfang; Deng, Ruitang; Yan, Bingfang

    2008-01-01

    CYP3A4 (cytochrome P450 3A4) is involved in the metabolism of more than 50% of drugs and other xenobiotics. The expression of CYP3A4 is induced by many structurally dissimilar compounds. The PXR (pregnane X receptor) is recognized as a key regulator for the induction, and the PXR-directed transactivation of the CYP3A4 gene is achieved through a co-ordinated mechanism of the distal module with the proximal promoter. Recently, a far module was found to support constitutive expression of CYP3A4. The far module, like the distal module, is structurally clustered by a PXR response element (F-ER6) and elements recognized by HNF-4alpha (hepatocyte nuclear receptor-4alpha). We hypothesized that the far module supports PXR transactivation of the CYP3A4 gene. Consistent with the hypothesis, fusion of the far module to the proximal promoter of CYP3A4 markedly increased rifampicin-induced reporter activity. The increase was synergistically enhanced when both the far and distal modules were fused to the proximal promoter. The increase, however, was significantly reduced when the F-ER6 was disrupted. Chromatin immunoprecipitation detected the presence of PXR in the far module. Interestingly, HNF-4alpha increased the activity of the distal-proximal fused promoter, but decreased the activity of the far-proximal fused promoter. Given the fact that induction of CYP3A4 represents an important detoxification mechanism, the functional redundancy and synergistic interaction in supporting PXR transactivation suggest that the far and distal modules ensure the induction of CYP3A4 during chemical insults. The difference in responding to HNF-4alpha suggests that the magnitude of the induction is under control through various transcriptional networks.

  1. Changes at the nuclear lamina alter binding of pioneer factor Foxa2 in aged liver.

    Science.gov (United States)

    Whitton, Holly; Singh, Larry N; Patrick, Marissa A; Price, Andrew J; Osorio, Fernando G; López-Otín, Carlos; Bochkis, Irina M

    2018-02-27

    Increasing evidence suggests that regulation of heterochromatin at the nuclear envelope underlies metabolic disease susceptibility and age-dependent metabolic changes, but the mechanism is unknown. Here, we profile lamina-associated domains (LADs) using lamin B1 ChIP-Seq in young and old hepatocytes and find that, although lamin B1 resides at a large fraction of domains at both ages, a third of lamin B1-associated regions are bound exclusively at each age in vivo. Regions occupied by lamin B1 solely in young livers are enriched for the forkhead motif, bound by Foxa pioneer factors. We also show that Foxa2 binds more sites in Zmpste24 mutant mice, a progeroid laminopathy model, similar to increased Foxa2 occupancy in old livers. Aged and Zmpste24-deficient livers share several features, including nuclear lamina abnormalities, increased Foxa2 binding, de-repression of PPAR- and LXR-dependent gene expression, and fatty liver. In old livers, additional Foxa2 binding is correlated to loss of lamin B1 and heterochromatin (H3K9me3 occupancy) at these loci. Our observations suggest that changes at the nuclear lamina are linked to altered Foxa2 binding, enabling opening of chromatin and de-repression of genes encoding lipid synthesis and storage targets that contribute to etiology of hepatic steatosis. © 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  2. Modification of the ASME code z-factor for circumferential surface crack in nuclear ferritic pipings

    International Nuclear Information System (INIS)

    Choi, Young Hwan; Chung, Yon Ki; Koh, Wan Young; Lee, Joung Bae

    1996-01-01

    The purpose of this paper is to modify the ASME Code Z-Factor, which is used in the evaluation of circumferential surface crack in nuclear ferritic pipings. The ASME Code Z-Factor is a load multiplier to compensate plastic load with elasto-plastic load. The current ASME Code Z-Factor underestimates pipe maximum load. In this study, the original SC. TNP method is modified first because the original SC. TNP method has a problem that the maximum allowable load predicted from the original SC. TNP method is slightly higher than that measured from the experiment. Then the new Z-Factor is developed using the modified SC. TNP method. The desirability of both the modified SC. TNP method and the new Z-Factor is examined using the experimental results for the circumferential surface crack in pipings. The results show that (1) the modified SC. TNP method is good for predicting the circumferential surface crack behavior in pipings, and (2) the Z-Factor obtained from the modified SC. TNP method well predicts the behavior of circumferential surface crack in ferritic pipings. 30 refs., 13 figs., 4 tabs. (author)

  3. Factor analysis for imperfect maintenance planning at nuclear power plants by cognitive task analysis

    International Nuclear Information System (INIS)

    Takagawa, Kenichi; Iida, Hiroyasu

    2011-01-01

    Imperfect maintenance planning was frequently identified in domestic nuclear power plants. To prevent such an event, we analyzed causal factors in maintenance planning stages and showed the directionality of countermeasures in this study. There is a pragmatic limit in finding the causal factors from the items based on report descriptions. Therefore, the idea of the systemic accident model, which is used to monitor the performance variability in normal circumstances, is taken as a new concept instead of investigating negative factors. As an actual method for analyzing usual activities, cognitive task analysis (CTA) was applied. Persons who experienced various maintenance activities at one electric power company were interviewed about sources related to decision making during maintenance planning, and then usual factors affecting planning were extracted as performance variability factors. The tendency of domestic events was analyzed using the classification item of those factors, and the directionality of countermeasures was shown. The following are critical for preventing imperfect maintenance planning: the persons in charge should fully understand the situation of the equipment for which they are responsible in the work planning and maintenance evaluation stages, and they should definitely understand, for example, the maintenance bases of that equipment. (author)

  4. Nuclear factor E2-related factor 2 knockdown enhances glucose uptake and alters glucose metabolism in AML12 hepatocytes.

    Science.gov (United States)

    Yuan, Xiaoyang; Huang, Huijing; Huang, Yi; Wang, Jinli; Yan, Jinhua; Ding, Ling; Zhang, Cuntai; Zhang, Le

    2017-05-01

    Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor known to induce the expression of a variety of antioxidant and detoxification genes. Recently, increasing evidence has revealed roles for Nrf2 in glucose, lipid, and energy metabolism; however, the exact functions of Nrf2 in hepatocyte biology are largely unclear. In the current study, the transient knockdown of Nrf2 via siRNA transfection enhanced the glucose uptake of fasting AML12 hepatocytes to 325.3 ± 11.1% ( P glucose metabolism were then examined in AML12 cells under both high-glucose (33 mmol/L) and low-glucose (4.5 mmol/L) conditions. NK lowered the gene and protein expression of the anti-oxidases heme oxygenase-1 and NAD(P)H: quinone oxidoreductase 1 and increased p-eukaryotic initiation factor-2α S51 , p-nuclear factor-κB p65 S276 , and its downstream proinflammatory factors, including interleukin-1 beta, tumor necrosis factor-α, matrix metalloproteinase 2, and matrix metalloproteinase 9, at the protein level. NK also altered the protein expression of fibroblast growth factor 21, glucose transporter type 4, insulin-like growth factor 1, forkhead box protein O1, p-AKT S473 , and p-GSK3α/β Y279/Y216 , which are involved in glucose uptake, glycogenesis, and gluconeogenesis in AML12 cells. Our results provide a comprehensive understanding of the central role of Nrf2 in the regulation of glucose metabolism in AML12 hepatocytes, in addition to its classical roles in the regulation of redox signaling, endoplasmic reticulum stress and proinflammatory responses, and support the potential of Nrf2 as a therapeutic target for the prevention and treatment of obesity and other associated metabolic syndromes. Impact statement Increasing evidence supports the complexity of Nrf2 functions beyond the antioxidant and detoxification response. Previous in vivo studies employing either Nrf2-knockout or Nrf2-activated mice have achieved a similar endpoint: protection against an obese and

  5. CD151, a novel host factor of nuclear export signaling in influenza virus infection.

    Science.gov (United States)

    Qiao, Yongkang; Yan, Yan; Tan, Kai Sen; Tan, Sheryl S L; Seet, Ju Ee; Arumugam, Thiruma Valavan; Chow, Vincent T K; Wang, De Yun; Tran, Thai

    2017-12-21

    Despite advances in our understanding of the mechanisms of influenza A virus (IAV) infection, the crucial virus-host interactions during the viral replication cycle still remain incomplete. Tetraspanin CD151 is highly expressed in the human respiratory tract, but its pathological role in IAV infection is unknown. We sought to characterize the functional role and mechanisms of action of CD151 in IAV infection of the upper and lower respiratory tracts with H1N1 and H3N2 strains. We used CD151-null mice in an in vivo model of IAV infection and clinical donor samples of in vitro-differentiated human nasal epithelial cells cultured at air-liquid interface. As compared with wild-type infected mice, CD151-null infected mice exhibited a significant reduction in virus titer and improvement in survival that is associated with pronounced host antiviral response and inflammasome activation together with accelerated lung repair. Interestingly, we show that CD151 complexes newly synthesized viral proteins with host nuclear export proteins and stabilizes microtubule complexes, which are key processes necessary for the polarized trafficking of viral progeny to the host plasma membrane for assembly. Our results provide new mechanistic insights into our understanding of IAV infection. We show that CD151 is a critical novel host factor of nuclear export signaling whereby the IAV nuclear export uses it to complement its own nuclear export proteins (a site not targeted by current therapy), making this regulation unique, and holds promise for the development of novel alternative/complementary strategies to reduce IAV severity. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  6. Association of hepatic nuclear factor-4 in the apolipoprotein B promoter: a preliminary report

    Directory of Open Access Journals (Sweden)

    Nóvak E.M.

    1998-01-01

    Full Text Available Previous studies have examined the arrangement of regulatory elements along the apolipoprotein B (apoB promoter region (-3067 to +940 and a promoter fragment extending from nucleotides -150 to +124 has been demonstrated to be essential for transcriptional activation of the apoB gene in hepatic and intestinal cells. It has also been shown that transcriptional activation of apoB requires a synergistic interaction between hepatic nuclear factor-4 (HNF-4 and CCAAT/enhancer-binding protein a (C/EBPa transcription factors. Here, we have examined the hypothesis that HNF-4 factor binding to DNA may induce a DNA helix bend, thus facilitating the communication with a C/EBPa factor located one helix turn from this HNF-4 factor in the apoB promoter. A gel electrophoretic mobility shift assay using wild type double-stranded oligonucleotides or modified wild type duplex oligonucleotides with 10 nucleotides inserted between HNF-4 and C/EBPa factor motifs showed similar retarded complexes, indicating that HNF-4 and C/EBPa factors interact independently of the distance between binding sites. However, when only one base, a thymidine, was inserted at the -71 position of the apoB promoter, the complex shift was completely abolished. In conclusion, these results regarding the study of the mechanisms involving the interaction between HNF-4 and C/EBPa factors in the apoB promoter suggest that the perfect 5'-CCCTTTGGA-3' motif is needed in order to facilitate the interaction between the two factors.

  7. System dynamics modeling of social/political factors in nuclear power plant operations

    International Nuclear Information System (INIS)

    Hansen, K.F.; Turek, M.G.; Eubanks, C.K.

    1995-01-01

    The safety and performance of nuclear power plants are a function of many technical factors such as initial design, service and maintenance programs, and utility investment in improvements. Safety and performance are also a function of the social/political influences that affect requirements on personnel, practices and procedures, and resource availability. This paper describes a process for constructing models of the social/political influences on plant operations using the system dynamics technique. The model incorporates representation of internal utility actions and decisions as affected by external factors such as public opinion, intervenor actions, safety and economic regulation, and the financial community. The feedback between external agents and plant performance is explicitly modeled. The resulting model can be used to simulate performance under a variety of different external and internal policy choices. In particular, the model can be used to study means of improving performance in response to externally imposed regulations

  8. The human factor in the design and operation of french light water nuclear power plants

    International Nuclear Information System (INIS)

    Gomolinski, M.

    1986-10-01

    The accident which occurred at Three Mile Island (TMI 2) on March 28, 1979 is considered rightfully as the outset of the approach taking the human factor explicitly into account in nuclear safety, both in the design of the plants and in their operational use. In this paper, we shall endeavour to explain how this human factor has been taken into account in France. For this purpose, in the first part, we shall define the requirements, i.e. describe the sectors in which improvements were deemed necessary. In the second part, we shall describe the structures set up both at EDF and at the CEA to handle these problems. Lastly, in the third part, we shall describe the principal actions taken or in progress [fr

  9. Psychological and social factors influencing the choice of strategy after a nuclear accident

    International Nuclear Information System (INIS)

    Heriard-Dubreuil, G.F.

    1995-01-01

    The analysis of the post-accident situation in Chernobyl provides information that focuses on social and psychological factors in the management of nuclear accidents. This paper concentrates on the short term countermeasures. It presents the main conclusions of a field survey carried out in Ukraine. The issues talked are the concern about extend of post-response in Chernobyl, the worries over health, contamination, the concern over the future and the complexity of post-accident situation. In a second part, the paper analyses and models the factors that caused the 1993 post-accident situation. Finally, several advices are given concerning the public information and behaviour focusing on the social and psychological aspect of short-term decisions (a constant effort should always be, for example, limiting the element of surprise in order to reduce the stress of population). (TEC). 3 figs

  10. Statistical analysis on the fluence factor of surveillance test data of Korean nuclear power plants

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Gyeong Geun; Kim, Min Chul; Yoon, Ji Hyun; Lee, Bong Sang; Lim, Sang Yeob; Kwon, Jun Hyun [Nuclear Materials Safety Research Division, Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2017-06-15

    The transition temperature shift (TTS) of the reactor pressure vessel materials is an important factor that determines the lifetime of a nuclear power plant. The prediction of the TTS at the end of a plant’s lifespan is calculated based on the equation of Regulatory Guide 1.99 revision 2 (RG1.99/2) from the US. The fluence factor in the equation was expressed as a power function, and the exponent value was determined by the early surveillance data in the US. Recently, an advanced approach to estimate the TTS was proposed in various countries for nuclear power plants, and Korea is considering the development of a new TTS model. In this study, the TTS trend of the Korean surveillance test results was analyzed using a nonlinear regression model and a mixed-effect model based on the power function. The nonlinear regression model yielded a similar exponent as the power function in the fluence compared with RG1.99/2. The mixed-effect model had a higher value of the exponent and showed superior goodness of fit compared with the nonlinear regression model. Compared with RG1.99/2 and RG1.99/3, the mixed-effect model provided a more accurate prediction of the TTS.

  11. Non-nuclear Pool of Splicing Factor SFPQ Regulates Axonal Transcripts Required for Normal Motor Development.

    Science.gov (United States)

    Thomas-Jinu, Swapna; Gordon, Patricia M; Fielding, Triona; Taylor, Richard; Smith, Bradley N; Snowden, Victoria; Blanc, Eric; Vance, Caroline; Topp, Simon; Wong, Chun-Hao; Bielen, Holger; Williams, Kelly L; McCann, Emily P; Nicholson, Garth A; Pan-Vazquez, Alejandro; Fox, Archa H; Bond, Charles S; Talbot, William S; Blair, Ian P; Shaw, Christopher E; Houart, Corinne

    2017-04-19

    Recent progress revealed the complexity of RNA processing and its association to human disorders. Here, we unveil a new facet of this complexity. Complete loss of function of the ubiquitous splicing factor SFPQ affects zebrafish motoneuron differentiation cell autonomously. In addition to its nuclear localization, the protein unexpectedly localizes to motor axons. The cytosolic version of SFPQ abolishes motor axonal defects, rescuing key transcripts, and restores motility in the paralyzed sfpq null mutants, indicating a non-nuclear processing role in motor axons. Novel variants affecting the conserved coiled-coil domain, so far exclusively found in fALS exomes, specifically affect the ability of SFPQ to localize in axons. They broadly rescue morphology and motility in the zebrafish mutant, but alter motor axon morphology, demonstrating functional requirement for axonal SFPQ. Altogether, we uncover the axonal function of the splicing factor SFPQ in motor development and highlight the importance of the coiled-coil domain in this process. VIDEO ABSTRACT. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  12. Evaluation of response factors for seismic probabilistic safety assessment of nuclear power plants

    International Nuclear Information System (INIS)

    Ebisawa, K.; Abe, K.; Muramatsu, K.; Itoh, M.; Kohno, K.; Tanaka, T.

    1994-01-01

    This paper presents a method for evaluating 'response factors' of components in nuclear power plants for use in a seismic probabilistic safety assessment (PSA). The response factor here is a measure of conservatism included in response calculations in seismic design analysis of components and is defined as a ratio of conservative design resonse to actual response. This method has the following characteristic features: (1) The components are classified into several groups based on the differences in their location and in the vibration models used in design response analyses; (2) the response factors are decomposed into subfactors corresponding to the stages of the seismic response analyses in the design practices; (3) the response factors for components are calculated as products of subfactors; (4) the subfactors are expressed either as a single value or as a function of parameters that influence the response of components. This paper describes the outline of this method and results from an application to a sample problem in which response factors were quantified for examples of components selected from the groups. (orig.)

  13. Over-expression of SR-cyclophilin, an interaction partner of nuclear pinin, releases SR family splicing factors from nuclear speckles

    International Nuclear Information System (INIS)

    Lin, C.-L.; Leu, Steve; Lu, M.-C.; Ouyang Pin

    2004-01-01

    Pre-mRNA splicing takes place within a dynamic ribonucleoprotein particle called the spliceosome and occurs in an ordered pathway. Although it is known that spliceosome consists of five small nuclear RNAs and at least 50 proteins, little is known about how the interaction among the proteins changes during splicing. Here we identify that SR-cyp, a Moca family of nuclear cyclophilin, interacts and colocalizes with nuclear pinin (pnn), a SR-related protein involving in pre-mRNA splicing. Nuclear pnn interacts with SR-cyp via its C-terminal RS domain. Upon SR-cyp over-expression, however, the subnuclear distribution of nuclear pnn is altered, resulting in its redistribution from nuclear speckles to a diffuse nucleoplasmic form. The diffuse subnuclear distribution of nuclear pnn is not due to epitope masking, accelerated protein turnover or post-translational modification. Furthermore, we find that SR-cyp regulates the subnuclear distribution of other SR family proteins, including SC35 and SRm300, in a similar manner as it does on nuclear pnn. This result is significant because it suggests that SR-cyp plays a general role in modulating the distribution pattern of SR-like and SR proteins, similar to that of Clk (cdc2-like kinase)/STY on SR family splicing factors. SR-cyp might direct its effect via either alteration of protein folding/conformation or of protein-protein interaction and thus may add another control level of regulation of SR family proteins and modification of their functions

  14. DMPD: Manipulation of mitogen-activated protein kinase/nuclear factor-kappaB-signalingcascades during intracellular Toxoplasma gondii infection. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 15361242 Manipulation of mitogen-activated protein kinase/nuclear factor-kappaB-sig...mmunol Rev. 2004 Oct;201:191-205. (.png) (.svg) (.html) (.csml) Show Manipulation of mitogen-activated protein kinase/nuclear... gondii infection. PubmedID 15361242 Title Manipulation of mitogen-activated protein kinase/nuclear factor-k

  15. NLRC5/MHC class I transactivator is a target for immune evasion in cancer.

    Science.gov (United States)

    Yoshihama, Sayuri; Roszik, Jason; Downs, Isaac; Meissner, Torsten B; Vijayan, Saptha; Chapuy, Bjoern; Sidiq, Tabasum; Shipp, Margaret A; Lizee, Gregory A; Kobayashi, Koichi S

    2016-05-24

    Cancer cells develop under immune surveillance, thus necessitating immune escape for successful growth. Loss of MHC class I expression provides a key immune evasion strategy in many cancers, although the molecular mechanisms remain elusive. MHC class I transactivator (CITA), known as "NLRC5" [NOD-like receptor (NLR) family, caspase recruitment (CARD) domain containing 5], has recently been identified as a critical transcriptional coactivator of MHC class I gene expression. Here we show that the MHC class I transactivation pathway mediated by CITA/NLRC5 constitutes a target for cancer immune evasion. In all the 21 tumor types we examined, NLRC5 expression was highly correlated with the expression of MHC class I, with cytotoxic T-cell markers, and with genes in the MHC class I antigen-presentation pathway, including LMP2/LMP7, TAP1, and β2-microglobulin. Epigenetic and genetic alterations in cancers, including promoter methylation, copy number loss, and somatic mutations, were most prevalent in NLRC5 among all MHC class I-related genes and were associated with the impaired expression of components of the MHC class I pathway. Strikingly, NLRC5 expression was significantly associated with the activation of CD8(+) cytotoxic T cells and patient survival in multiple cancer types. Thus, NLRC5 constitutes a novel prognostic biomarker and potential therapeutic target of cancers.

  16. NLRC5/MHC class I transactivator is a target for immune evasion in cancer

    Science.gov (United States)

    Yoshihama, Sayuri; Roszik, Jason; Downs, Isaac; Meissner, Torsten B.; Vijayan, Saptha; Chapuy, Bjoern; Sidiq, Tabasum; Shipp, Margaret A.; Lizee, Gregory A.; Kobayashi, Koichi S.

    2016-01-01

    Cancer cells develop under immune surveillance, thus necessitating immune escape for successful growth. Loss of MHC class I expression provides a key immune evasion strategy in many cancers, although the molecular mechanisms remain elusive. MHC class I transactivator (CITA), known as “NLRC5” [NOD-like receptor (NLR) family, caspase recruitment (CARD) domain containing 5], has recently been identified as a critical transcriptional coactivator of MHC class I gene expression. Here we show that the MHC class I transactivation pathway mediated by CITA/NLRC5 constitutes a target for cancer immune evasion. In all the 21 tumor types we examined, NLRC5 expression was highly correlated with the expression of MHC class I, with cytotoxic T-cell markers, and with genes in the MHC class I antigen-presentation pathway, including LMP2/LMP7, TAP1, and β2-microglobulin. Epigenetic and genetic alterations in cancers, including promoter methylation, copy number loss, and somatic mutations, were most prevalent in NLRC5 among all MHC class I-related genes and were associated with the impaired expression of components of the MHC class I pathway. Strikingly, NLRC5 expression was significantly associated with the activation of CD8+ cytotoxic T cells and patient survival in multiple cancer types. Thus, NLRC5 constitutes a novel prognostic biomarker and potential therapeutic target of cancers. PMID:27162338

  17. Clusterin is a critical downstream mediator of stress-induced YB-1 transactivation in prostate cancer.

    Science.gov (United States)

    Shiota, Masaki; Zoubeidi, Amina; Kumano, Masafumi; Beraldi, Eliana; Naito, Seiji; Nelson, Colleen C; Sorensen, Poul H B; Gleave, Martin E

    2011-12-01

    Clusterin is a stress-activated, cytoprotective chaperone that confers broad-spectrum treatment resistance in cancer. However, the molecular mechanisms mediating CLU transcription following anticancer treatment stress remain incompletely defined. We report that Y-box binding protein-1 (YB-1) directly binds to CLU promoter regions to transcriptionally regulate clusterin expression. In response to endoplasmic reticulum stress inducers, including paclitaxel, YB-1 is translocated to the nucleus to transactivate clusterin. Furthermore, higher levels of activated YB-1 and clusterin are seen in taxane-resistant, compared with parental, prostate cancer cells. Knockdown of either YB-1 or clusterin sensitized prostate cancer cells to paclitaxel, whereas their overexpression increased resistance to taxane. Clusterin overexpression rescued cells from increased paclitaxel-induced apoptosis following YB-1 knockdown; in contrast, however, YB-1 overexpression did not rescue cells from increased paclitaxel-induced apoptosis following clusterin knockdown. Collectively, these data indicate that YB-1 transactivation of clusterin in response to stress is a critical mediator of paclitaxel resistance in prostate cancer.

  18. Synergistic nuclear import of NeuroD1 and its partner transcription factor, E47, via heterodimerization

    Energy Technology Data Exchange (ETDEWEB)

    Mehmood, Rashid; Yasuhara, Noriko [Department of Frontier Biosciences, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565-0871 (Japan); Oe, Souichi; Nagai, Masahiro [Department of Biochemistry, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan); Yoneda, Yoshihiro, E-mail: yyoneda@anat3.med.osaka-u.ac.jp [Department of Frontier Biosciences, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565-0871 (Japan); Department of Biochemistry, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan)

    2009-06-10

    The transition from undifferentiated pluripotent cells to terminally differentiated neurons is coordinated by a repertoire of transcription factors. NeuroD1 is a type II basic helix loop helix (bHLH) transcription factor that plays critical roles in neuronal differentiation and maintenance in the central nervous system. Its dimerization with E47, a type I bHLH transcription factor, leads to the transcriptional regulation of target genes. Mounting evidence suggests that regulating the localization of transcription factors contributes to the regulation of their activity during development as defects in their localization underlie a variety of developmental disorders. In this study, we attempted to understand the nuclear import mannerisms of NeuroD1 and E47. We found that the nuclear import of NeuroD1 and E47 is energy-dependent and involves the Ran-mediated pathway. Herein, we demonstrate that NeuroD1 and E47 can dimerize inside the cytoplasm before their nuclear import. Moreover, this dimerization promotes nuclear import as the nuclear accumulation of NeuroD1 was enhanced in the presence of E47 in an in vitro nuclear import assay, and NLS-deficient NeuroD1 was successfully imported into the nucleus upon E47 overexpression. NeuroD1 also had a similar effect on the nuclear accumulation of NLS-deficient E47. These findings suggest a novel role for dimerization that may promote, at least partially, the nuclear import of transcription factors allowing them to function efficiently in the nucleus.

  19. Synergistic nuclear import of NeuroD1 and its partner transcription factor, E47, via heterodimerization

    International Nuclear Information System (INIS)

    Mehmood, Rashid; Yasuhara, Noriko; Oe, Souichi; Nagai, Masahiro; Yoneda, Yoshihiro

    2009-01-01

    The transition from undifferentiated pluripotent cells to terminally differentiated neurons is coordinated by a repertoire of transcription factors. NeuroD1 is a type II basic helix loop helix (bHLH) transcription factor that plays critical roles in neuronal differentiation and maintenance in the central nervous system. Its dimerization with E47, a type I bHLH transcription factor, leads to the transcriptional regulation of target genes. Mounting evidence suggests that regulating the localization of transcription factors contributes to the regulation of their activity during development as defects in their localization underlie a variety of developmental disorders. In this study, we attempted to understand the nuclear import mannerisms of NeuroD1 and E47. We found that the nuclear import of NeuroD1 and E47 is energy-dependent and involves the Ran-mediated pathway. Herein, we demonstrate that NeuroD1 and E47 can dimerize inside the cytoplasm before their nuclear import. Moreover, this dimerization promotes nuclear import as the nuclear accumulation of NeuroD1 was enhanced in the presence of E47 in an in vitro nuclear import assay, and NLS-deficient NeuroD1 was successfully imported into the nucleus upon E47 overexpression. NeuroD1 also had a similar effect on the nuclear accumulation of NLS-deficient E47. These findings suggest a novel role for dimerization that may promote, at least partially, the nuclear import of transcription factors allowing them to function efficiently in the nucleus.

  20. Improvements of the Regulatory Framework for Nuclear Installations in the Areas of Human and Organizational Factors and Safety Culture

    International Nuclear Information System (INIS)

    Tronea, M.; Ciurea, C.

    2016-01-01

    The paper presents the development of regulatory requirements in the area of human and organizational factors taking account of the lessons learned from major accidents in the nuclear industry and in particular of the factors that contributed to the Fukushima Daiichi accident and the improvement of the regulatory oversight of nuclear safety culture. New requirements have been elaborated by the National Commission for Nuclear Activities Control (CNCAN) on the nuclear safety policy of licencees for nuclear installations, on independent nuclear safety oversight, on safety conscious work environment and on the assessment of nuclear safety culture. The regulatory process for the oversight of nuclear safety culture within licencees’ organizations operating nuclear installations and the associated procedure and guidelines, based on the IAEA Safety Standards, have been developed in 2010-2011. CNCAN has used the 37 IAEA attributes for a strong safety culture, grouped into five areas corresponding to safety culture characteristics, as the basis for its regulatory guidelines providing support to the reviewers and inspectors, in their routine activities, for recognising and gathering information relevant to safety culture. The safety culture oversight process, procedure and guidelines are in process of being reviewed and revised to improve their effectiveness and to align with the current international practices, using lessons learned from the Fukushima Daiichi accident. Starting with July 2014, Romania has a National Strategy for Nuclear Safety and Security, which includes strategic objectives, associated directions for action and concrete actions for promoting nuclear safety culture in all the organizations in the nuclear sector. The progress with the implementation of this strategy with regard to nuclear safety culture is described in the paper. CNCAN started to define its own organizational culture model and identifying the elements that promote and support safety

  1. Human factors analysis and design methods for nuclear waste retrieval systems. Volume II. A compendium of human factors design data

    International Nuclear Information System (INIS)

    Casey, S.M.

    1980-04-01

    This document is a compilation of human factors engineering design recommendations and data, selected and organized to assist in the design of a nuclear waste retrieval system. Design guidelines from a variety of sources have been evaluated, edited, and expanded for inclusion in this document, and, where appropriate, portions of text from selected sources have been included in their entirety. A number of human factors engineering guidelines for equipment designers have been written over the past three decades, each tailored to the needs of the specific system being designed. In the case of this particular document, a review of the preliminary human operator functions involved in each phase of the retrieval process was performed, resulting in the identification of areas of design emphasis upon which this document should be based. Documents containing information and design data on each of these areas were acquired, and data and design guidelines related to the previously identified areas of emphasis were extracted and reorganized. For each system function, actions were first assigned to operator and/or machine, and the operator functions were then described. Separate lists of operator functions were developed for each of the areas of retrieval activities - survey and mapping, remining, floor flange emplacement, plug and canister overcoring, plug and canister removal and transport, and CWSRS activity. These functions and the associated man-machine interface were grouped into categories based on task similarity, and the principal topics of human factors design emphasis were extracted. These topic areas are reflected in the contents of the 12 sections of this document

  2. Human factors analysis and design methods for nuclear waste retrieval systems. Human factors design methodology and integration plan

    International Nuclear Information System (INIS)

    Casey, S.M.

    1980-06-01

    The purpose of this document is to provide an overview of the recommended activities and methods to be employed by a team of human factors engineers during the development of a nuclear waste retrieval system. This system, as it is presently conceptualized, is intended to be used for the removal of storage canisters (each canister containing a spent fuel rod assembly) located in an underground salt bed depository. This document, and the others in this series, have been developed for the purpose of implementing human factors engineering principles during the design and construction of the retrieval system facilities and equipment. The methodology presented has been structured around a basic systems development effort involving preliminary development, equipment development, personnel subsystem development, and operational test and evaluation. Within each of these phases, the recommended activities of the human engineering team have been stated, along with descriptions of the human factors engineering design techniques applicable to the specific design issues. Explicit examples of how the techniques might be used in the analysis of human tasks and equipment required in the removal of spent fuel canisters have been provided. Only those techniques having possible relevance to the design of the waste retrieval system have been reviewed. This document is intended to provide the framework for integrating human engineering with the rest of the system development effort. The activities and methodologies reviewed in this document have been discussed in the general order in which they will occur, although the time frame (the total duration of the development program in years and months) in which they should be performed has not been discussed

  3. Human factors analysis and design methods for nuclear waste retrieval systems. Human factors design methodology and integration plan

    Energy Technology Data Exchange (ETDEWEB)

    Casey, S.M.

    1980-06-01

    The purpose of this document is to provide an overview of the recommended activities and methods to be employed by a team of human factors engineers during the development of a nuclear waste retrieval system. This system, as it is presently conceptualized, is intended to be used for the removal of storage canisters (each canister containing a spent fuel rod assembly) located in an underground salt bed depository. This document, and the others in this series, have been developed for the purpose of implementing human factors engineering principles during the design and construction of the retrieval system facilities and equipment. The methodology presented has been structured around a basic systems development effort involving preliminary development, equipment development, personnel subsystem development, and operational test and evaluation. Within each of these phases, the recommended activities of the human engineering team have been stated, along with descriptions of the human factors engineering design techniques applicable to the specific design issues. Explicit examples of how the techniques might be used in the analysis of human tasks and equipment required in the removal of spent fuel canisters have been provided. Only those techniques having possible relevance to the design of the waste retrieval system have been reviewed. This document is intended to provide the framework for integrating human engineering with the rest of the system development effort. The activities and methodologies reviewed in this document have been discussed in the general order in which they will occur, although the time frame (the total duration of the development program in years and months) in which they should be performed has not been discussed.

  4. Heat and nuclear radiation as risk factors for male infertility: results of a French case-control study

    International Nuclear Information System (INIS)

    Thonneau, P.F.; Rachou, E.; Ducot, B.; Multigner, L.; Velez de la Calle, J.P.; Le Martelot, M.T.

    1998-01-01

    Very few studies have investigated the possible effects of environmental radiation and heat exposure on male reproductive function. We conducted a case control study to evaluate the various infertility risk factors in the military population of the french town of Brest to investigate an apparently high incidence of infertility in couples in which the man may have been exposed to occupational nuclear radiation. These findings suggest that in addition to well known medical factors, 'potential' exposure to heat or nuclear radiation could also be risk factors for infertility. (N.C.)

  5. Heat and nuclear radiation as risk factors for male infertility: results of a French case-control study

    Energy Technology Data Exchange (ETDEWEB)

    Thonneau, P.F.; Rachou, E.; Ducot, B.; Multigner, L. [Institut National de la Sante et de la Recherche Medicale (INSERM) - Hopital de Bicetre, 94 - Le Kremlin-Bicetre (France); Velez de la Calle, J.P. [Clinique Pasteur Saint-Esprit, 29 - Brest (France); Le Martelot, M.T. [Centre Hospitalier Universitaire, 29 - Brest (France)

    1998-08-01

    Very few studies have investigated the possible effects of environmental radiation and heat exposure on male reproductive function. We conducted a case control study to evaluate the various infertility risk factors in the military population of the french town of Brest to investigate an apparently high incidence of infertility in couples in which the man may have been exposed to occupational nuclear radiation. These findings suggest that in addition to well known medical factors, `potential` exposure to heat or nuclear radiation could also be risk factors for infertility. (N.C.)

  6. A formal design verification and validation on the human factors of a computerized information system in nuclear power plants

    International Nuclear Information System (INIS)

    Lee, Yong Hee; Park, Jae Chang; Cheon, Se Woo; Jung, Kwang Tae; Baek, Seung Min; Han, Seung; Park, Hee Suk; Son, Ki Chang; Kim, Jung Man; Jung Yung Woo

    1999-11-01

    This report describe a technical transfer under the title of ''A formal design verification and validation on the human factors of a computerized information system in nuclear power plants''. Human factors requirements for the information system designs are extracted from various regulatory and industrial standards and guidelines, and interpreted into a more specific procedures and checklists for verifying the satisfaction of those requirements. A formalized implementation plan is established for human factors verification and validation of a computerized information system in nuclear power plants. Additionally, a Computer support system, named as DIMS-web (design Issue Management System), is developed based upon web internet environment so as to enhance the implementation of the human factors activities. DIMS-Web has three maine functions: supporting requirements review, tracking design issues, and management if issues screening evaluation. DIMS-Web shows its benefits in practice through a trial application to the design review of CFMS for YGN nuclear unit 5 and 6. (author)

  7. Development of new Z-factors for the evaluation of the circumferential surface crack in nuclear pipes

    International Nuclear Information System (INIS)

    Choi, Y.H.; Chung, Y.K.; Park, Y.W.; Lee, J.B.

    1997-01-01

    The purpose of this study is to develop new Z-factors to evaluate the behavior of a circumferential surface crack in nuclear pipe. Z-factor is a load multiplier used in the Z-factor method, which is one of the ASME Code Sec. XI's recommendations for the estimation of a surface crack in nuclear pipe. It has been reported that the load carrying capacities predicted from the current ASME Code Z-factors, are not well in agreement with the experimental results for nuclear pipes with a surface crack. In this study, new Z-factors for ferritic base metal, ferritic submerged arc welding (SAW) weld metal, austenitic base metal, and austenitic SAW weld metal are obtained by use of the surface crack for thin pipe (SC.TNP) method based on GE/EPRI method. The desirability of both the SC.TNP method and the new Z-factors is examined using the results from 48 pipe fracture experiments for nuclear pipes with a circumferential surface crack. The results show that the SC.TNP method is good for describing the circumferential surface crack behavior and the new Z-factors are well in agreement with the measured Z-factors for both ferritic and austenitic pipes. (orig.)

  8. Measurement and evaluation of human factor training in nuclear power plants

    International Nuclear Information System (INIS)

    Hamasaki, Kenichi

    2006-01-01

    The purpose of this study is to measure and evaluate the effectiveness of human factor training aimed at awareness and behavioral changes, conducted by electric power company for the nuclear power plant staff. As the first step, the researcher investigated recent trends in training measurement and evaluation methods in the United States. It was found that many instances of training measurement/evaluation had been reported, and that the ROI model was the mainstream method for such measurement and evaluation. However, there had been no instances reported in which the effectiveness of human factor training for plant staff had been measured. The researcher therefore developed a new questionnaire-type of effectiveness measurement/evaluation method, based on the framework of the ROI model. Two-years of research was then conducted, in which the effectiveness of a human factor training program was measured using the newly developed method. This research revealed that participants' overall satisfaction and knowledge/skill acquisition levels were high. The percentage of participants who demonstrated awareness/behavioral change after returning to the workplace increased from 50% at first measurement to 81% at second measurement. It can therefore be concluded that the effectiveness of the second training is greater than that of the first training. Use of the new effectiveness measurement/evaluation method will enable quantification of human factor training effectiveness and help improve training quality. (author)

  9. Analyzing and sense making of human factors in the Malaysian radiation and nuclear emergency planning framework

    Science.gov (United States)

    Hamid, A. H. A.; Rozan, M. Z. A.; Deris, S.; Ibrahim, R.; Abdullah, W. S. W.; Rahman, A. A.; Yunus, M. N. M.

    2016-01-01

    The evolution of current Radiation and Nuclear Emergency Planning Framework (RANEPF) simulator emphasizes on the human factors to be analyzed and interpreted according to the stakeholder's tacit and explicit knowledge. These human factor criteria are analyzed and interpreted according to the "sense making theory" and Disaster Emergency Response Management Information System (DERMIS) design premises. These criteria are corroborated by the statistical criteria. In recent findings, there were no differences of distributions among the stakeholders according to gender and organizational expertise. These criteria are incrementally accepted and agreed the research elements indicated in the respective emergency planning frameworks and simulator (i.e. 78.18 to 84.32, p-value <0.05). This paper suggested these human factors criteria in the associated analyses and theoretical perspectives to be further acomodated in the future simulator development. This development is in conjunction with the proposed hypothesis building of the process factors and responses diagram. We proposed that future work which implies the additional functionality of the simulator, as strategized, condensed and concise, comprehensive public disaster preparedness and intervention guidelines, to be a useful and efficient computer simulation.

  10. Analyzing and sense making of human factors in the Malaysian radiation and nuclear emergency planning framework

    International Nuclear Information System (INIS)

    Hamid, A. H. A.; Rozan, M. Z. A.; Ibrahim, R.; Deris, S.; Abdullah, W. S. W.; Yunus, M. N. M.; Rahman, A. A.

    2016-01-01

    The evolution of current Radiation and Nuclear Emergency Planning Framework (RANEPF) simulator emphasizes on the human factors to be analyzed and interpreted according to the stakeholder’s tacit and explicit knowledge. These human factor criteria are analyzed and interpreted according to the “sense making theory” and Disaster Emergency Response Management Information System (DERMIS) design premises. These criteria are corroborated by the statistical criteria. In recent findings, there were no differences of distributions among the stakeholders according to gender and organizational expertise. These criteria are incrementally accepted and agreed the research elements indicated in the respective emergency planning frameworks and simulator (i.e. 78.18 to 84.32, p-value <0.05). This paper suggested these human factors criteria in the associated analyses and theoretical perspectives to be further acomodated in the future simulator development. This development is in conjunction with the proposed hypothesis building of the process factors and responses diagram. We proposed that future work which implies the additional functionality of the simulator, as strategized, condensed and concise, comprehensive public disaster preparedness and intervention guidelines, to be a useful and efficient computer simulation

  11. Estimation of radon progeny equilibrium factors and their uncertainty bounds using solid state nuclear track detectors

    International Nuclear Information System (INIS)

    Eappen, K.P.; Mayya, Y.S.; Patnaik, R.L.; Kushwaha, H.S.

    2006-01-01

    For the assessment of inhalation doses due to radon and its progeny to uranium mine workers, it is necessary to have information on the time integrated gas concentrations and equilibrium factors. Passive single cup dosimeters using solid state nuclear track detectors (SSNTD) are best suited for this purpose. These generally contain two SSNTDs, one placed inside the cup to measure only the radon gas concentration and other outside the cup for recording tracks due to both radon gas and the progeny species. However, since one obtains only two numbers by this method whereas information on four quantities is required for an unambiguous estimation of dose, there is a need for developing an optimal methodology for extracting information on the equilibrium factors. Several techniques proposed earlier have essentially been based on deterministic approaches, which do not fully take into account all the possible uncertainties in the environmental parameters. Keeping this in view, a simple 'mean of bounds' methodology is proposed to extract equilibrium factors based on their absolute bounds and the associated uncertainties as obtained from general arguments of radon progeny disequilibrium. This may be considered as reasonable estimates of the equilibrium factors in the absence of a knowledge of fluctuation in the environmental variables. The results are compared with those from direct measurements both in the laboratory and in real field situations. In view of the good agreement found between these, it is proposed that the simple mean of bounds estimate may be useful for practical applications in inhalation dosimetry of mine workers

  12. Analyzing and sense making of human factors in the Malaysian radiation and nuclear emergency planning framework

    Energy Technology Data Exchange (ETDEWEB)

    Hamid, A. H. A., E-mail: amyhamijah@gmail.com, E-mail: amyhamijah@nm.gov.my [Faculty of Computing, Universiti Teknologi Malaysia (UTM), Skudai, 81310 Johor Bahru, Johor (Malaysia); Universiti Malaysia Kelantan (UMK), Pengkalan Chepa, 16100 Kota Bharu, Kelantan (Malaysia); Rozan, M. Z. A., E-mail: drmohdzaidi@gmail.com; Ibrahim, R. [Faculty of Computing, Universiti Teknologi Malaysia (UTM), Skudai, 81310 Johor Bahru, Johor (Malaysia); Deris, S. [Universiti Malaysia Kelantan (UMK), Pengkalan Chepa, 16100 Kota Bharu, Kelantan (Malaysia); Abdullah, W. S. W.; Yunus, M. N. M. [Malaysian Nuclear Agency (NM), Bangi, 43000 Kajang, Selangor (Malaysia); Rahman, A. A. [Faculty of Medicine and Health Sciences, Universiti Putra Malaysia (UPM), 43400 Serdang, Selangor (Malaysia)

    2016-01-22

    The evolution of current Radiation and Nuclear Emergency Planning Framework (RANEPF) simulator emphasizes on the human factors to be analyzed and interpreted according to the stakeholder’s tacit and explicit knowledge. These human factor criteria are analyzed and interpreted according to the “sense making theory” and Disaster Emergency Response Management Information System (DERMIS) design premises. These criteria are corroborated by the statistical criteria. In recent findings, there were no differences of distributions among the stakeholders according to gender and organizational expertise. These criteria are incrementally accepted and agreed the research elements indicated in the respective emergency planning frameworks and simulator (i.e. 78.18 to 84.32, p-value <0.05). This paper suggested these human factors criteria in the associated analyses and theoretical perspectives to be further acomodated in the future simulator development. This development is in conjunction with the proposed hypothesis building of the process factors and responses diagram. We proposed that future work which implies the additional functionality of the simulator, as strategized, condensed and concise, comprehensive public disaster preparedness and intervention guidelines, to be a useful and efficient computer simulation.

  13. Critical human-factors issues in nuclear-power regulation and a recommended comprehensive human-factors long-range plan. Critical discussion of human factors areas of concern

    International Nuclear Information System (INIS)

    Hopkins, C.O.; Snyder, H.L.; Price, H.E.; Hornick, R.J.; Mackie, R.R.; Smillie, R.J.; Sugarman, R.C.

    1982-08-01

    This comprehensive long-range human factors plan for nuclear reactor regulation was developed by a Study Group of the Human Factors Society, Inc. This Study Group was selected by the Executive Council of the Society to provide a balanced, experienced human factors perspective to the applications of human factors scientific and engineering knowledge to nuclear power generation. The report is presented in three volumes. Volume 1 contains an Executive Summary of the 18-month effort and its conclusions. Volume 2 summarizes all known nuclear-related human factors activities, evaluates these activities wherever adequate information is available, and describes the recommended long-range (10-year) plan for human factors in regulation. Volume 3 elaborates upon each of the human factors issues and areas of recommended human factors involvement contained in the plan, and discusses the logic that led to the recommendations

  14. Bioaccumulation factors and the steady state assumption for cesium isotopes in aquatic foodwebs near nuclear facilities

    International Nuclear Information System (INIS)

    Rowan, D.J.

    2013-01-01

    Steady state approaches, such as transfer coefficients or bioaccumulation factors, are commonly used to model the bioaccumulation of 137 Cs in aquatic foodwebs from routine operations and releases from nuclear generating stations and other nuclear facilities. Routine releases from nuclear generating stations and facilities, however, often consist of pulses as liquid waste is stored, analyzed to ensure regulatory compliance and then released. The effect of repeated pulse releases on the steady state assumption inherent in the bioaccumulation factor approach has not been evaluated. In this study, I examine the steady state assumption for aquatic biota by analyzing data for two cesium isotopes in the same biota, one isotope in steady state (stable 133 Cs) from geologic sources and the other released in pulses ( 137 Cs) from reactor operations. I also compare 137 Cs bioaccumulation factors for similar upstream populations from the same system exposed solely to weapon test 137 Cs, and assumed to be in steady state. The steady state assumption appears to be valid for small organisms at lower trophic levels (zooplankton, rainbow smelt and 0+ yellow perch) but not for older and larger fish at higher trophic levels (walleye). Attempts to account for previous exposure and retention through a biokinetics approach had a similar effect on steady state, upstream and non-steady state, downstream populations of walleye, but were ineffective in explaining the more or less constant deviation between fish with steady state exposures and non-steady state exposures of about 2-fold for all age classes of walleye. These results suggest that for large, piscivorous fish, repeated exposure to short duration, pulse releases leads to much higher 137 Cs BAFs than expected from 133 Cs BAFs for the same fish or 137 Cs BAFs for similar populations in the same system not impacted by reactor releases. These results suggest that the steady state approach should be used with caution in any situation

  15. Bioaccumulation factors and the steady state assumption for cesium isotopes in aquatic foodwebs near nuclear facilities.

    Science.gov (United States)

    Rowan, D J

    2013-07-01

    Steady state approaches, such as transfer coefficients or bioaccumulation factors, are commonly used to model the bioaccumulation of (137)Cs in aquatic foodwebs from routine operations and releases from nuclear generating stations and other nuclear facilities. Routine releases from nuclear generating stations and facilities, however, often consist of pulses as liquid waste is stored, analyzed to ensure regulatory compliance and then released. The effect of repeated pulse releases on the steady state assumption inherent in the bioaccumulation factor approach has not been evaluated. In this study, I examine the steady state assumption for aquatic biota by analyzing data for two cesium isotopes in the same biota, one isotope in steady state (stable (133)Cs) from geologic sources and the other released in pulses ((137)Cs) from reactor operations. I also compare (137)Cs bioaccumulation factors for similar upstream populations from the same system exposed solely to weapon test (137)Cs, and assumed to be in steady state. The steady state assumption appears to be valid for small organisms at lower trophic levels (zooplankton, rainbow smelt and 0+ yellow perch) but not for older and larger fish at higher trophic levels (walleye). Attempts to account for previous exposure and retention through a biokinetics approach had a similar effect on steady state, upstream and non-steady state, downstream populations of walleye, but were ineffective in explaining the more or less constant deviation between fish with steady state exposures and non-steady state exposures of about 2-fold for all age classes of walleye. These results suggest that for large, piscivorous fish, repeated exposure to short duration, pulse releases leads to much higher (137)Cs BAFs than expected from (133)Cs BAFs for the same fish or (137)Cs BAFs for similar populations in the same system not impacted by reactor releases. These results suggest that the steady state approach should be used with caution in any

  16. Nuclear modification factor of charged particles and light-flavour hadrons in p--Pb collisions measured by ALICE

    CERN Document Server

    Bencedi, Gyula

    2016-01-01

    The hot and dense strongly interacting Quark-Gluon Plasma (sQGP) created in ultra-relativistic heavy-ion collisions can be probed by studying high-$p_{\\rm T}$ particle production and parton energy loss. Similar measurements performed in p-Pb collisions may help in determining whether initial or final state nuclear effects play a role in the observed suppression of hadron production at high-$p_{\\rm T}$ in Pb--Pb collisions. By examining the nuclear modification factors through the comparison of identified hadron yields in different collision systems one can gain insight into particle production mechanisms and nuclear effects.

  17. Greenhouse gas emission factor for coal power chain in China and the comparison with nuclear power chain

    International Nuclear Information System (INIS)

    Ma Zhonghai; Pan Ziqiang; He Huimin

    1999-01-01

    The Greenhouse Gas Emission for coal power chain in China is analyzed in detail and comprehensively by using the Life Cycle Analysis method. The Greenhouse Gas Emission Factors (GGEF) in each link and for the total power chain are calculated. The total GGEF for coal power chain is 1302.3 gCO 2 /kWh, about 40 times more than that for nuclear power chain. And consequently greenhouse effect could not be aggravated further by nuclear power. The energy strategy for nuclear power development is one of reality ways to retard the greenhouse effect, put resources into rational use and protect environment

  18. Knowledge Sharing Through Virtual Mode: The Influenced Factors for KM Development Among the Researchers in Nuclear Malaysia

    International Nuclear Information System (INIS)

    Adnan, H.; Sulaiman, M.S.; Yusof, M.H.; Ali, I.

    2014-01-01

    Conclusion: • The primary contribution of this study is to assess the influence of virtual mode as a KM medium in Nuclear Malaysia. • Direct relationship between the researchers and the used of virtual mode in the knowledge sharing process. • Finding reveals that virtual mode contributes significant factors in influencing researchers’ knowledge sharing behaviour. • The findings from the study may be used by the management of Nuclear Malaysia to improve or enhance the capacity of virtual mode provided by the organisation

  19. Estimation of physiological parameters using knowledge-based factor analysis of dynamic nuclear medicine image sequences

    International Nuclear Information System (INIS)

    Yap, J.T.; Chen, C.T.; Cooper, M.

    1995-01-01

    The authors have previously developed a knowledge-based method of factor analysis to analyze dynamic nuclear medicine image sequences. In this paper, the authors analyze dynamic PET cerebral glucose metabolism and neuroreceptor binding studies. These methods have shown the ability to reduce the dimensionality of the data, enhance the image quality of the sequence, and generate meaningful functional images and their corresponding physiological time functions. The new information produced by the factor analysis has now been used to improve the estimation of various physiological parameters. A principal component analysis (PCA) is first performed to identify statistically significant temporal variations and remove the uncorrelated variations (noise) due to Poisson counting statistics. The statistically significant principal components are then used to reconstruct a noise-reduced image sequence as well as provide an initial solution for the factor analysis. Prior knowledge such as the compartmental models or the requirement of positivity and simple structure can be used to constrain the analysis. These constraints are used to rotate the factors to the most physically and physiologically realistic solution. The final result is a small number of time functions (factors) representing the underlying physiological processes and their associated weighting images representing the spatial localization of these functions. Estimation of physiological parameters can then be performed using the noise-reduced image sequence generated from the statistically significant PCs and/or the final factor images and time functions. These results are compared to the parameter estimation using standard methods and the original raw image sequences. Graphical analysis was performed at the pixel level to generate comparable parametric images of the slope and intercept (influx constant and distribution volume)

  20. Updating Human Factors Engineering Guidelines for Conducting Safety Reviews of Nuclear Power Plants

    International Nuclear Information System (INIS)

    O'Hara, J.M.; Higgins, J.; Fleger, Stephen

    2011-01-01

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

  1. HTLV-1 Tax upregulates early growth response protein 1 through nuclear factor-κB signaling.

    Science.gov (United States)

    Huang, Qingsong; Niu, Zhiguo; Han, Jingxian; Liu, Xihong; Lv, Zhuangwei; Li, Huanhuan; Yuan, Lixiang; Li, Xiangping; Sun, Shuming; Wang, Hui; Huang, Xinxiang

    2017-08-01

    Human T cell leukemia virus type 1 (HTLV-1) is a complex retrovirus that causes adult T cell leukemia (ATL) in susceptible individuals. The HTLV-1-encoded oncoprotein Tax induces persistent activation of the nuclear factor-κB (NF-κB) pathway. Early growth response protein 1 (EGR1) is overexpressed in HTLV-1-infected T cell lines and ATL cells. Here, we showed that both Tax expression and HTLV-1 infection promoted EGR1 overexpression. Loss of the NF-κB binding site in the EGR1 promotor or inhibition of NF-κB activation reduced Tax-induced EGR1 upregulation. Tax mutants unable to activate NF-κB induced only slight EGR1 upregulation as compared with wild-type Tax, confirming NF-κB pathway involvement in EGR1 regulation. Tax also directly interacted with the EGR1 protein and increased endogenous EGR1 stability. Elevated EGR1 in turn promoted p65 nuclear translocation and increased NF-κB activation. These results demonstrate a positive feedback loop between EGR1 expression and NF-κB activation in HTLV-1-infected and Tax-expressing cells. Both NF-κB activation and Tax-induced EGR1 stability upregulated EGR1, which in turn enhanced constitutive NF-κB activation and facilitated ATL progression in HTLV-1-infected cells. These findings suggest EGR1 may be an effective anti-ATL therapeutic target.

  2. Transcriptional activation of nuclear-related factor 2 by FK506 in Jurkat T cells.

    Science.gov (United States)

    Chung, Y W; Jeong, Y M; Chung, M W; Choi, S K; Choi, S J N; Chung, S Y

    2015-04-01

    We investigated the effect of FK506 in transcriptional activation of nuclear factor (erythroid-derived 2)-like2 (Nrf2) in human Jurkat T cells. FK506 treatment increased the generation of reactive oxygen species and reactive nitrogen species in Jurkat cells in a dose-dependent manner. Generation of nitric oxide was also increased after treatment with FK506 in Jurkat cells. Peak levels of endothelial nitricoxide synthase expression occurred at 24 hours and then decreased after 48 hours. We found that a marked dissociation of Nrf 2 from Kelch-like ECH-associated protein-1 and subsequently Nrf 2 nuclear translocation occurred in Jurkat cells treated with FK506 during 48 hours. Immunohistochemistry and Western blot analysis data revealed that the FK506 treatment increased expression of heme oxygenase-1 (HO-1) in Jurkat cells in a dose-dependent manner. HO-1 expression was induced after 6 hours of treatment of FK506 to Jurkat cells, peaked at 24 hours, and then decreased after 48 hours. These results suggest that FK506 induces Nrf 2-driven transcriptional activation of the antioxidant response element by activating HO-1 and free radicals such as reactive oxygen species and nitric oxide. Copyright © 2015. Published by Elsevier Inc.

  3. Primer on Durability of Nuclear Power Plant Reinforced Concrete Structures - A Review of Pertinent Factors

    Energy Technology Data Exchange (ETDEWEB)

    Naus, Dan J [ORNL

    2007-02-01

    The objective of this study was to provide a primer on the environmental effects that can affect the durability of nuclear power plant concrete structures. As concrete ages, changes in its properties will occur as a result of continuing microstructural changes (i.e., slow hydration, crystallization of amorphous constituents, and reactions between cement paste and aggregates), as well as environmental influences. These changes do not have to be detrimental to the point that concrete will not be able to meet its performance requirements. Concrete, however, can suffer undesirable changes with time because of improper specifications, a violation of specifications, or adverse performance of its cement paste matrix or aggregate constituents under either physical or chemical attack. Contained in this report is a discussion on concrete durability and the relationship between durability and performance, a review of the historical perspective related to concrete and longevity, a description of the basic materials that comprise reinforced concrete, and information on the environmental factors that can affect the performance of nuclear power plant concrete structures. Commentary is provided on the importance of an aging management program.

  4. Design engineer perceptions and attitudes regarding human factors application to nuclear power plant design

    International Nuclear Information System (INIS)

    Ma, R.; Jones, J. M.

    2006-01-01

    With the renewed interest in nuclear power and the possibility of constructing new reactors within the next decade in the U.S., there are several challenges for the regulators, designers, and vendors. One challenge is to ensure that Human Factors Engineering (HFE) is involved, and correctly applied in the life-cycle design of the Nuclear Power Plant (NPP). As an important part of the effort, people would ask: 'is the system-design engineer effectively incorporating HFE in the NPPs design?' The present study examines the sagacity of Instrumentation and Control design engineers on issues relating to awareness, attitude, and application of HFE in NPP design. A questionnaire was developed and distributed, focusing on the perceptions and attitudes of the design engineers. The responses revealed that, while the participants had a relatively high positive attitude about HFE, their awareness and application of HFE were moderate. The results also showed that senior engineers applied HFE more frequently in their design work than young engineers. This study provides some preliminary results and implications for improved HFE education and application in NPP design. (authors)

  5. Organizational factors in design and implementation of technological and organizational solutions in the nuclear industry

    Energy Technology Data Exchange (ETDEWEB)

    Macchi, L.; Reiman, T.; Savioja, P. (VTT Technical Research Centre of Finland (Finland)); Kahlbom, U. (Risk Pilot AB, Stockholm (Sweden)); Rollenhagen, C. (Vattenfall (Sweden))

    2012-03-15

    Design is often found as one of the contributing factors in accident in the nuclear industry. The design of new technological systems and organisational structures has to take into account and be driven by the future users' needs and has to consider how their role and work practices within the organisation will be affected. The SADE project explores to which extend the concepts of safety culture and resilience engineering can contribute to the prevention of design errors when no hindsight data are available. In 2011, the SADE project focused on gathering experience and clarifying the current issues and challenges related to the design process. During 2011 seventeen interviews have been conducted in Finland and Sweden to identify some of the major challenges the nuclear industry is currently facing. At the same time a literature review has been conducted to establish a sound common theoretical ground. This progress report presents some of the relevant theoretical findings and preliminary results from the interviews. (Author)

  6. Economic and regulatory factors affecting the maintenance of nuclear power plants

    International Nuclear Information System (INIS)

    Hewlett, J.G.

    1996-01-01

    This paper examines the factors causing the escalation in the 1980s and subsequent leveling off of nuclear power plant non-fuel Operating and Maintenance (O ampersand M) costs. Over the period 1974-93, real (inflation-adjusted) non-fuel costs escalated form about $23 to about $97 per kilowatt of installed capacity (kW). However, much of the escalation in costs occurred in the 1980s. Over the period 1975-87, real O ampersand M costs escalated at an annual rate of about 11 percent. Since then, the annual growth rate in real O ampersand M costs fell to about 1 percent. The research found that the escalation in O ampersand M costs was primarily due to increased regulatory activity by the Nuclear Regulatory Commission. More important, there is little evidence that the moderation in the growth in O ampersand M costs was regulatory induced, but instead was due to changes in the economic incentives to improve plant performance. 28 refs., 3 figs., 6 tabs

  7. Primer on Durability of Nuclear Power Plant Reinforced Concrete Structures - A Review of Pertinent Factors

    International Nuclear Information System (INIS)

    Naus, Dan J.

    2007-01-01

    The objective of this study was to provide a primer on the environmental effects that can affect the durability of nuclear power plant concrete structures. As concrete ages, changes in its properties will occur as a result of continuing microstructural changes (i.e., slow hydration, crystallization of amorphous constituents, and reactions between cement paste and aggregates), as well as environmental influences. These changes do not have to be detrimental to the point that concrete will not be able to meet its performance requirements. Concrete, however, can suffer undesirable changes with time because of improper specifications, a violation of specifications, or adverse performance of its cement paste matrix or aggregate constituents under either physical or chemical attack. Contained in this report is a discussion on concrete durability and the relationship between durability and performance, a review of the historical perspective related to concrete and longevity, a description of the basic materials that comprise reinforced concrete, and information on the environmental factors that can affect the performance of nuclear power plant concrete structures. Commentary is provided on the importance of an aging management program

  8. Organizational factors influencing human performance in nuclear power plants. Report of a technical committee meeting

    International Nuclear Information System (INIS)

    1997-05-01

    In 1991 a Safety Series report on Safety Culture of the International Nuclear Safety Advisory Group (INSAG) was published as 75-INSAG-4 by the IAEA. This report deals with the concept of Safety Culture as it relates to organizations and individuals involved in the operations of nuclear power plants (NPPs). Generally, the role of management and organization in assuring the safe operation of NPPs has been widely recognized and its importance accepted. However, the understanding of what constitutes effective management and organization the area of safety is less developed than the understanding of most of the technical issues which plant operators and regulatory bodies are confronted with. The Technical Committee meeting provided a forum for a broad exchange of information on practices and experiences in the area of organization and management to accomplish operational safety in NPPs and thus enhance Safety Culture. This report and the papers presented at the meeting discuss those factors which influence and improve human performance covering both aspects, i.e. the basic requirements imposed on the operator and the ways of managerial support which enhance the reliable and safety oriented performance of operators. Refs, figs, tabs

  9. CSNI technical opinion papers no.10. The role of human and organisational factors in nuclear power plant modifications

    International Nuclear Information System (INIS)

    2009-01-01

    Nuclear power plant modifications may be needed for a number of different reasons. These include physical ageing of plant systems, structures and components; obsolescence in hardware and software; feedback from operating experience; and opportunities for improved plant safety, reliability or capability. However, experience has also shown that weaknesses in the design and/or implementation of modifications can present significant challenges to plant safety. They can also have a considerable impact on the commercial performance of the plant. It is therefore important that the plant modification process reflect a recognition of the potential impact of human errors and that it incorporate suitable measures to minimise the potential for such errors. In this context, the NEA Committee on the Safety of Nuclear Installations (CSNI) and its Working Group on Human and Organisational Factors organised an international workshop in 2003 to discuss the role of human and organisational performance in the nuclear plant modification process. This technical opinion paper represents the consensus of specialists in human and organisational factors (HOF) in the NEA member countries on commendable practices and approaches to dealing with nuclear plant modifications. It considers factors that should be taken into account when developing a modification process and identifies some lessons learnt from application of the process. The paper should be of particular interest of nuclear safety regulators and nuclear power plant operators. (author)

  10. Hepatocyte nuclear factor 1alpha is an accessory factor required for activation of glucose-6-phosphatase gene transcription by glucocorticoids.

    Science.gov (United States)

    Lin, B; Morris, D W; Chou, J Y

    1998-11-01

    Deficiency of glucose-6-phosphatase (G6Pase), a key enzyme in glucose homeostasis, causes glycogen storage disease type 1a (GSD-1a), also know as von Gierke disease. Expression of the G6Pase gene is regulated by multiple hormones, including glucocorticoids. The synthetic glucocorticoid dexamethasone increased G6Pase mRNA abundance and gene transcription in H4-IIE hepatoma cells. Transient transfection assays demonstrated that the G6Pase promoter was active in H4-IIE cells only in the presence of dexamethasone. The minimal G6Pase promoter was contained within nucleotides -234/+3, which has two putative glucocorticoid response elements (GREs) at nucleotides -178/-164 (site 1) and -154/-140 (site 2). Electromobility shift and transient transfection assays showed that only GRE site 1 was required for glucocorticoid-activated transcription from the G6Pase promoter. Deletion analysis demonstrated that the DNA elements absolutely essential for glucocorticoid-stimulated transcription from the G6Pase promoter were contained within nucleotides -234/-212, encompassing binding motifs for hepatocyte nuclear factors (HNFs) 1 (-226/-212) and 4 (-231/-220). Electromobility shift and cotransfection assays showed that HNF1alpha bound to its cognate site and mediated transcription activation of the G6Pase gene by glucocorticoids.

  11. Diclofenac inhibits tumor necrosis factor-α-induced nuclear factor-κB activation causing synergistic hepatocyte apoptosis.

    Science.gov (United States)

    Fredriksson, Lisa; Herpers, Bram; Benedetti, Giulia; Matadin, Quraisha; Puigvert, Jordi C; de Bont, Hans; Dragovic, Sanja; Vermeulen, Nico P E; Commandeur, Jan N M; Danen, Erik; de Graauw, Marjo; van de Water, Bob

    2011-06-01

    Drug-induced liver injury (DILI) is an important clinical problem. It involves crosstalk between drug toxicity and the immune system, but the exact mechanism at the cellular hepatocyte level is not well understood. Here we studied the mechanism of crosstalk in hepatocyte apoptosis caused by diclofenac and the proinflammatory cytokine tumor necrosis factor α (TNF-α). HepG2 cells were treated with diclofenac followed by TNF-α challenge and subsequent evaluation of necrosis and apoptosis. Diclofenac caused a mild apoptosis of HepG2 cells, which was strongly potentiated by TNF-α. A focused apoptosis machinery short interference RNA (siRNA) library screen identified that this TNF-α-mediated enhancement involved activation of caspase-3 through a caspase-8/Bid/APAF1 pathway. Diclofenac itself induced sustained activation of c-Jun N-terminal kinase (JNK) and inhibition of JNK decreased both diclofenac and diclofenac/TNF-α-induced apoptosis. Live cell imaging of GFPp65/RelA showed that diclofenac dampened the TNF-α-mediated nuclear factor kappaB (NF-κB) translocation oscillation in association with reduced NF-κB transcriptional activity. This was associated with inhibition by diclofenac of the TNF-α-induced phosphorylation of the inhibitor of NF-κB alpha (IκBα). Finally, inhibition of IκB kinase β (IKKβ) with BMS-345541 as well as stable lentiviral short hairpin RNA (shRNA)-based knockdown of p65/RelA sensitized hepatocytes towards diclofenac/TNF-α-induced cytotoxicity. Together, our data suggest a model whereby diclofenac-mediated stress signaling suppresses TNF-α-induced survival signaling routes and sensitizes cells to apoptosis. Copyright © 2011 American Association for the Study of Liver Diseases.

  12. Hepatocyte nuclear factor 4 alpha is a key factor related to depression and physiological homeostasis in the mouse brain.

    Directory of Open Access Journals (Sweden)

    Kyosuke Yamanishi

    Full Text Available Major depressive disorder (MDD is a common psychiatric disorder that involves marked disabilities in global functioning, anorexia, and severe medical comorbidities. MDD is associated with not only psychological and sociocultural problems, but also pervasive physical dysfunctions such as metabolic, neurobiological and immunological abnormalities. Nevertheless, the mechanisms underlying the interactions between these factors have yet to be determined in detail. The aim of the present study was to identify the molecular mechanisms responsible for the interactions between MDD and dysregulation of physiological homeostasis, including immunological function as well as lipid metabolism, coagulation, and hormonal activity in the brain. We generated depression-like behavior in mice using chronic mild stress (CMS as a model of depression. We compared the gene expression profiles in the prefrontal cortex (PFC of CMS and control mice using microarrays. We subsequently categorized genes using two web-based bioinformatics applications: Ingenuity Pathway Analysis and The Database for Annotation, Visualization, and Integrated Discovery. We then confirmed significant group-differences by analyzing mRNA and protein expression levels not only in the PFC, but also in the thalamus and hippocampus. These web tools revealed that hepatocyte nuclear factor 4 alpha (Hnf4a may exert direct effects on various genes specifically associated with amine synthesis, such as genes involved in serotonin metabolism and related immunological functions. Moreover, these genes may influence lipid metabolism, coagulation, and hormonal activity. We also confirmed the significant effects of Hnf4a on both mRNA and protein expression levels in the brain. These results suggest that Hnf4a may have a critical influence on physiological homeostasis under depressive states, and may be associated with the mechanisms responsible for the interactions between MDD and the dysregulation of

  13. Participation of nuclear factor (erythroid 2-related), factor 2 in ameliorating lithocholic acid-induced cholestatic liver injury in mice.

    Science.gov (United States)

    Tan, K P; Wood, G A; Yang, M; Ito, S

    2010-11-01

    Lithocholic acid (LCA), the most toxic bile acid, induces cholestatic liver injury in rodents. We previously showed that LCA activates the oxidative stress-responsive nuclear factor (erythroid-2 like), factor 2 (Nrf2) in cultured liver cells, triggering adaptive responses that reduce cell injury. In this study, we determined whether Nrf2 protects the liver against LCA-induced toxicity in vivo. Nrf2 disrupted (Nrf2(-/-) ) and wild-type mice were treated with LCA (125 mg·kg(-1) body weight) to induce liver injury. Levels of mRNA, protein and function of important Nrf2 target genes coupled with liver histology and injury biomarkers of mice were examined. In 4 day LCA treatments, we observed a significantly higher hepatic induction of Nrf2 target, cytoprotective genes including thioredoxin reductase 1, glutamate cysteine ligase subunits, glutathione S-transferases, haeme oxygenase-1 and multidrug resistance-associated proteins 3 and 4 in the wild type as compared with the Nrf2(-/-) mice. Moreover, basal and LCA-induced hepatic glutathione and activities of glutathione S-transferases and thioredoxin reductases were higher in wild-type than in Nrf2(-/-) mice. This reduced production of cytoprotective genes against LCA toxicity rendered Nrf2(-/-) mice more susceptible to severe liver damage with the presence of multifocal liver necrosis, inflamed bile ducts and elevation of lipid peroxidation and liver injury biomarkers, such as alanine aminotransferase and alkaline phosphatase. Nrf2 plays a crucial cytoprotective role against LCA-induced liver injury by orchestrating adaptive responses. The pharmacological potential of targeting liver Nrf2 in the management of cholestatic liver diseases is proposed. © 2010 The Authors. British Journal of Pharmacology © 2010 The British Pharmacological Society.

  14. Apple, Cherry, and Blackcurrant Increases Nuclear Factor Kappa B Activation in Liver of Transgenic Mice

    DEFF Research Database (Denmark)

    Balstad, Trude; Paur, Ingvild; Poulsen, Morten

    2010-01-01

    Nuclear factor kappa B (NF-B) is essential in normal physiology, and several human disorders involve inappropriate regulation of NF-B. Diets dominated by plant-based foods protect against chronic diseases, and several food derived compounds have been identified as promising NF-B modulators. We...... investigated the effects of diets supplemented with apple, blackcurrant, or cherries on lipopolysaccharide (LPS)-induced NF-B activation in transgenic NF-B-luciferase mice. Whole body and organ specific NF-B activities were determined. The mice had ad libitum access to the respective experimental diets for 7...... slightly higher whole-body NF-B activation at 4 h, and all 3 experimental groups had higher NF-B activation at 6 h. LPS-induced NF-B activation in liver was increased with all 3 experimental diets, but no effects were observed in other organs. Our findings indicate that high intakes of lyophilized fruits...

  15. The human factors and job task analysis in nuclear power plant operation

    International Nuclear Information System (INIS)

    Stefanescu, Petre; Mihailescu, Nicolae; Dragusin, Octavian

    1999-01-01

    After a long period of time, during the development of the NPP technology, where the plant hardware has been considered to be the main factor for a safe, reliable and economic operation, the industry is now changing to an adequate responsibility of plant hardware and operation. Since the human factors has been not discussed methodically so far, there is still a lack of improved classification systems for human errors as well as a lack of methods for the systematic approach in designing the operator's working system, as for instance by using the job task analysis (J.T.A.). The J.T.A. appears to be an adequate method to study the human factor in the nuclear power plant operation, enabling an easy conversion to operational improvements. While the results of the analysis of human errors tell 'what' is to be improved, the J.T.A. shows 'how' to improve, for increasing the quality of the work and the safety of the operator's working system. The paper analyses the issue of setting the task and displays four criteria used to select aspects in NPP operation which require special consideration as personal training, design of control room, content and layout of the procedure manual, or organizing the operating personnel. The results are given as three tables giving: 1- Evaluation of deficiencies in the Working System; 2- Evaluation of the Deficiencies of Operator's Disposition; 3- Evaluation of the Mental Structure of Operation

  16. Scaling factors for the activity determination of radioactive waste from nuclear power reactors

    International Nuclear Information System (INIS)

    Medici, Marcela A.; Piumetti, Elsa H.

    2007-01-01

    Specific information of the total activity and activity concentration of the radionuclides contained is required for conditioning, transporting and final disposal of radioactive waste. Due to the complexity associated to alpha and beta measurements for these emitters it is worldwide used, particularly in the case of heterogeneous radioactive waste, the Scaling Factor Method. As in other cases, inputs of the results of the analysis of waste samples taking from waste streams are necessary. The Scaling Factor Method is based on the determination of averaged correlations between the activity concentrations of Difficult to Measure (DTM) nuclides (i.e. alpha and beta emitters) and the activity concentration of easy to measure nuclides (i.e. strong gamma emitters) called Key Nuclides (KN). In the application of this method two phases may be identified: in the first one the degree of correlation between averaged activities of DTM and a given KN is verified, and specific Scaling Factors are derived for every DTM radionuclide. In the second stage the total activity and the activity concentration of the selected KN is determined in each waste item and, by applying the SFs obtained previously, the activities of DTM nuclides are calculated. It is concluded that this method is appropriate and cost-effective and it is stressed that it is only applicable while the Nuclear Power Reactor is in operation. (author)

  17. Applying human factors to the design of control centre and workstation of a nuclear reactor

    International Nuclear Information System (INIS)

    Santos, Isaac J.A. Luquetti dos; Carvalho, Paulo V.R.; Goncalves, Gabriel de L.; Souza, Tamara D.M.F.; Falcao, Mariana A.

    2013-01-01

    Human factors is a body of scientific factors about human characteristics, covering biomedical, psychological and psychosocial considerations, including principles and applications in the personnel selection areas, training, job performance aid tools and human performance evaluation. Control Centre is a combination of control rooms, control suites and local control stations which are functionally related and all on the same site. Digital control room includes an arrangement of systems, equipment such as computers and communication terminals and workstations at which control and monitoring functions are conducted by operators. Inadequate integration between control room and operators reduces safety, increases the operation complexity, complicates operator training and increases the likelihood of human errors occurrence. The objective of this paper is to present a specific approach for the conceptual and basic design of the control centre and workstation of a nuclear reactor used to produce radioisotope. The approach is based on human factors standards, guidelines and the participation of a multidisciplinary team in the conceptual and basic phases of the design. Using the information gathered from standards and from the multidisciplinary team, an initial sketch 3D of the control centre and workstation are being developed. (author)

  18. Eudesmane-Type Sesquiterpene Lactones Inhibit Nuclear Translocation of the Nuclear Factor κB Subunit RelB in Response to a Lymphotoxin β Stimulation.

    Science.gov (United States)

    Quach, Hue Tu; Kondo, Tetsuya; Watanabe, Megumi; Tamura, Ryuichi; Yajima, Yoshiki; Sayama, Shinsei; Ando, Masayoshi; Kataoka, Takao

    2017-01-01

    The transcription factor nuclear factor κB (NF-κB) regulates various biological processes, including inflammatory responses. We previously reported that eudesmane-type sesquiterpene lactones inhibited multiple steps in the canonical NF-κB signaling pathway induced by tumor necrosis factor-α and interleukin-1α. In contrast, the biological activities of eudesmane-type sesquiterpene lactones on the non-canonical NF-κB signaling pathway remain unclear. In the present study, we found that (11S)-2α-bromo-3-oxoeudesmano-12,6α-lactone, designated santonin-related compound 2 (SRC2), inhibited NF-κB luciferase reporter activity induced by lymphotoxin β (LTβ) in human lung carcinoma A549 cells. Although SRC2 did not prevent the processing of the NF-κB subunit p100 induced by LTβ, it inhibited the nuclear translocation of RelB and p52 in response to the LTβ stimulation. In contrast to (-)-dehydroxymethylepoxyquinomicin, SRC2 inhibited the LTβ-induced nuclear translocation of the RelB (C144S) mutant in a manner similar to wild-type RelB. While eudesmane derivatives possessing an α-bromoketone moiety or α,β-unsaturated carbonyl moieties inhibited LTβ-induced NF-κB luciferase reporter activity, eudesmane derivatives possessing an α-bromoketone moiety exhibited stronger inhibitory activity on the LTβ-induced nuclear translocation of RelB than those possessing a single α-methylene-γ-lactone moiety. The results of the present study revealed that SRC2 inhibits the nuclear translocation of RelB in the non-canonical NF-κB signaling pathway induced by LTβ.

  19. Tumor necrosis factor-α induces MMP-9 expression via p42/p44 MAPK, JNK, and nuclear factor-κB in A549 cells

    International Nuclear Information System (INIS)

    Lin, C.-C.; Tseng, Hsiao-Wei; Hsieh, Hsi-Lung; Lee, Chiang-Wen; Wu, C.-Y.; Cheng, C.-Y.; Yang, C.-M.

    2008-01-01

    Matrix metalloproteinases (MMPs), in particular MMP-9, have been shown to be induced by cytokines including tumor necrosis factor-α (TNF-α) and contributes to airway inflammation. However, the mechanisms underlying MMP-9 expression induced by TNF-α in human A549 cells remain unclear. Here, we showed that TNF-α induced production of MMP-9 protein and mRNA is determined by zymographic, Western blotting, RT-PCR and ELISA assay, which were attenuated by inhibitors of MEK1/2 (U0126), JNK (SP600125), and NF-κB (helenalin), and transfection with dominant negative mutants of ERK2 (ΔERK) and JNK (ΔJNK), and siRNAs for MEK1, p42 and JNK2. TNF-α-stimulated phosphorylation of p42/p44 MAPK and JNK were attenuated by pretreatment with the inhibitors U0126 and SP600125 or transfection with dominant negative mutants of ΔERK and ΔJNK. Furthermore, the involvement of NF-κB in TNF-α-induced MMP-9 production was consistent with that TNF-α-stimulated degradation of IκB-α and translocation of NF-κB into the nucleus which were blocked by helenalin, but not by U0126 and SP600125, revealed by immunofluorescence staining. The regulation of MMP-9 gene transcription by MAPKs and NF-κB was further confirmed by gene luciferase activity assay. MMP-9 promoter activity was enhanced by TNF-α in A549 cells transfected with wild-type MMP-9-Luc, which was inhibited by helenalin, U0126, or SP600125. In contrast, TNF-α-stimulated MMP-9 luciferase activity was totally lost in cells transfected with mutant-NF-κB MMP-9-luc. Moreover, pretreatment with actinomycin D and cycloheximide attenuated TNF-α-induced MMP-9 expression. These results suggest that in A549 cells, phosphorylation of p42/p44 MAPK, JNK, and transactivation of NF-κB are essential for TNF-α-induced MMP-9 gene expression

  20. Nuclear respiratory factor-1 and bioenergetics in tamoxifen-resistant breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Radde, Brandie N.; Ivanova, Margarita M.; Mai, Huy Xuan; Alizadeh-Rad, Negin; Piell, Kellianne; Van Hoose, Patrick; Cole, Marsha P.; Muluhngwi, Penn; Kalbfleisch, Ted S. [Department of Biochemistry & Molecular Genetics, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY 40292 (United States); Rouchka, Eric C. [Bioinformatics and Biomedical Computing Laboratory, Department of Computer Engineering and Computer Science, University of Louisville, Louisville, KY 40292 (United States); Hill, Bradford G. [Department of Medicine, University of Louisville School of Medicine, Louisville, KY 40292 (United States); Klinge, Carolyn M., E-mail: carolyn.klinge@louisville.edu [Department of Biochemistry & Molecular Genetics, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY 40292 (United States)

    2016-09-10

    Acquired tamoxifen (TAM) resistance is a significant clinical problem in treating patients with estrogen receptor α (ERα)+ breast cancer. We reported that ERα increases nuclear respiratory factor-1 (NRF-1), which regulates nuclear-encoded mitochondrial gene transcription, in MCF-7 breast cancer cells and NRF-1 knockdown stimulates apoptosis. Whether NRF-1 and target gene expression is altered in endocrine resistant breast cancer cells is unknown. We measured NRF-1and metabolic features in a cell model of progressive TAM-resistance. NRF-1 and its target mitochondrial transcription factor A (TFAM) were higher in TAM-resistant LCC2 and LCC9 cells than TAM-sensitive MCF-7 cells. Using extracellular flux assays we observed that LCC1, LCC2, and LCC9 cells showed similar oxygen consumption rate (OCR), but lower mitochondrial reserve capacity which was correlated with lower Succinate Dehydrogenase Complex, Subunit B in LCC1 and LCC2 cells. Complex III activity was lower in LCC9 than MCF-7 cells. LCC1, LCC2, and LCC9 cells had higher basal extracellular acidification (ECAR), indicating higher aerobic glycolysis, relative to MCF-7 cells. Mitochondrial bioenergetic responses to estradiol and 4-hydroxytamoxifen were reduced in the endocrine-resistant cells compared to MCF-7 cells. These results suggest the acquisition of altered metabolic phenotypes in response to long term antiestrogen treatment may increase vulnerability to metabolic stress. - Highlights: • NRF-1 and TFAM expression are higher in endocrine-resistant breast cancer cells. • Oxygen consumption rate is similar in endocrine-sensitive and resistant cells. • Mitochondrial reserve capacity is lower in endocrine-resistant cells. • Endocrine-resistant breast cancer cells have increased glycolysis. • Bioenergetic responses to E2 and tamoxifen are lower in endocrine-resistant cells.

  1. Cholesterol Sulfate and Cholesterol Sulfotransferase Inhibit Gluconeogenesis by Targeting Hepatocyte Nuclear Factor

    Science.gov (United States)

    Shi, Xiongjie; Cheng, Qiuqiong; Xu, Leyuan; Yan, Jiong; Jiang, Mengxi; He, Jinhan; Xu, Meishu; Stefanovic-Racic, Maja; Sipula, Ian; O'Doherty, Robert Martin; Ren, Shunlin

    2014-01-01

    Sulfotransferase (SULT)-mediated sulfation represents a critical mechanism in regulating the chemical and functional homeostasis of endogenous and exogenous molecules. The cholesterol sulfotransferase SULT2B1b catalyzes the sulfoconjugation of cholesterol to synthesize cholesterol sulfate (CS). In this study, we showed that the expression of SULT2B1b in the liver was induced in obese mice and during the transition from the fasted to the fed state, suggesting that the regulation of SULT2B1b is physiologically relevant. CS and SULT2B1b inhibited gluconeogenesis by targeting the gluconeogenic factor hepatocyte nuclear factor 4α (HNF4α) in both cell cultures and transgenic mice. Treatment of mice with CS or transgenic overexpression of the CS-generating enzyme SULT2B1b in the liver inhibited hepatic gluconeogenesis and alleviated metabolic abnormalities both in mice with diet-induced obesity (DIO) and in leptin-deficient (ob/ob) mice. Mechanistically, CS and SULT2B1b inhibited gluconeogenesis by suppressing the expression of acetyl coenzyme A (acetyl-CoA) synthetase (Acss), leading to decreased acetylation and nuclear exclusion of HNF4α. Our results also suggested that leptin is a potential effector of SULT2B1b in improving metabolic function. We conclude that SULT2B1b and its enzymatic by-product CS are important metabolic regulators that control glucose metabolism, suggesting CS as a potential therapeutic agent and SULT2B1b as a potential therapeutic target for metabolic disorders. PMID:24277929

  2. Virtual reality technology as a tool for human factors requirements evaluation in design of the nuclear reactors control desks

    International Nuclear Information System (INIS)

    Grecco, Claudio H.S.; Santos, Isaac J.A.L.; Mol, Antonio C.A.; Carvalho, Paulo V.R.; Silva, Antonio C.F.; Ferreira, Francisco J.O.; Dutra, Marco A.M.

    2007-01-01

    The Virtual Reality (VR) is an advanced computer interface technology that allows the user to internet or to explore a three-dimensional environment through the computer, as was part of the virtual world. This technology presents great applicability in the most diverse areas of the human knowledge. This paper presents a study on the use of the VR as tool for human factors requirements evaluation in design of the nuclear reactors control desks. Moreover, this paper presents a case study: a virtual model of the control desk, developed using virtual reality technology to be used in the human factors requirements evaluation. This case study was developed in the Virtual Reality Laboratory at IEN, and understands the stereo visualization of the Argonauta research nuclear reactor control desk for a static ergonomic evaluation using check-lists, in accordance to the standards and human factors nuclear international guides (IEC 1771, NUREG-0700). (author)

  3. Potential human factors deficiencies in the design of local control stations and operator interfaces in nuclear power plants

    International Nuclear Information System (INIS)

    Hartley, C.S.; Levy, I.S.; Fecht, B.A.

    1984-04-01

    The Pacific Northwest Laboratory has completed a project to identify human factors deficiencies in safety-significant control stations outside the control room of a nuclear power plant and to determine whether NUREG-0700, Guidelines for Control Room Design Reviews, would be sufficient for reviewing those local control stations (LCSs). The project accomplished this task by first, reviewing existing data pertaining to human factors deficiencies in LCSs involved in significant safety actions; second, surveying LCSs environments and design features at several operating nuclear power plants; and third, assessing the results of that survey relative to the contents of NUREG-0700

  4. In brown adipocytes, adrenergically induced β{sub 1}-/β{sub 3}-(G{sub s})-, α{sub 2}-(G{sub i})- and α{sub 1}-(G{sub q})-signalling to Erk1/2 activation is not mediated via EGF receptor transactivation

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yanling; Fälting, Johanna M.; Mattsson, Charlotte L.; Holmström, Therése E.; Nedergaard, Jan, E-mail: jan@metabol.su.se

    2013-10-15

    Brown adipose tissue is unusual in that the neurotransmitter norepinephrine influences cell destiny in ways generally associated with effects of classical growth factors: regulation of cell proliferation, of apoptosis, and progression of differentiation. The norepinephrine effects are mediated through G-protein-coupled receptors; further mediation of such stimulation to e.g. Erk1/2 activation is in cell biology in general accepted to occur through transactivation of the EGF receptor (by external or internal pathways). We have examined here the significance of such transactivation in brown adipocytes. Stimulation of mature brown adipocytes with cirazoline (α{sub 1}-adrenoceptor coupled via G{sub q}), clonidine (α{sub 2} via G{sub i}) or CL316243 (β{sub 3} via G{sub s}) or via β{sub 1}-receptors significantly activated Erk1/2. Pretreatment with the EGF receptor kinase inhibitor AG1478 had, remarkably, no significant effect on Erk1/2 activation induced by any of these adrenergic agonists (although it fully abolished EGF-induced Erk1/2 activation), demonstrating absence of EGF receptor-mediated transactivation. Results with brown preadipocytes (cells in more proliferative states) were not qualitatively different. Joint stimulation of all adrenoceptors with norepinephrine did not result in synergism on Erk1/2 activation. AG1478 action on EGF-stimulated Erk1/2 phosphorylation showed a sharp concentration–response relationship (IC{sub 50} 0.3 µM); a minor apparent effect of AG1478 on norepinephrine-stimulated Erk1/2 phosphorylation showed nonspecific kinetics, implying caution in interpretation of partial effects of AG1478 as reported in other systems. Transactivation of the EGF receptor is clearly not a universal prerequisite for coupling of G-protein coupled receptors to Erk1/2 signalling cascades. - Highlights: • In brown adipocytes, norepinephrine regulates proliferation, apoptosis, differentiation. • EGF receptor transactivation is supposed to mediate GPCR

  5. Use of cryopreserved transiently transfected cells in high-throughput pregnane X receptor transactivation assay.

    Science.gov (United States)

    Zhu, Zhengrong; Puglisi, Jaime; Connors, David; Stewart, Jeremy; Herbst, John; Marino, Anthony; Sinz, Michael; O'Connell, Jonathan; Banks, Martyn; Dickinson, Kenneth; Cacace, Angela

    2007-03-01

    Cryopreserved, transiently transfected HepG2 cells were compared to freshly transfected HepG2 cells for use in a pregnane X receptor (PXR) transactivation assay. Assay performance was similar for both cell preparations; however, cryopreserved cells demonstrated less interassay variation. Validation with drugs of different PXR activation potencies and efficacies demonstrated an excellent correlation (r(2) > 0.95) between cryopreserved and fresh cells. Cryopreservation did not change the effect of known CYP3A4 inducers that have poor cell permeability, indicating that cryopreservation had little effect on membrane permeability. In addition, cryopreserved HepG2 cells did not exhibit enhanced susceptibility to cytotoxic compounds compared to transiently transfected control cells. The use of cryopreserved cells enables this assay to run with enhanced efficiency.

  6. Factors relevant to the recycling or reuse of components arising from the decommissioning and refurbishment of nuclear facilities

    International Nuclear Information System (INIS)

    1988-01-01

    The decommissioning and decontamination of nuclear facilities is a topic of great interest to many Member States of the International Atomic Energy Agency (IAEA) because of the large number of older nuclear facilities which are or soon will be retired from service. To assist in the development of the required decommissioning expertise, the IAEA is developing reports and recommendations which will eventually form an integrated information base covering in a systematic way the wide range of topics associated with decommissioning. This information is required so that Member States can decommission their nuclear facilities in a safe, timely and cost effective manner and the IAEA can effectively respond to requests for assistance. One area which warrants more detailed analyses is an assessment of the factors important to the recycling or reuse of components arising from the refurbishment or decommissioning of nuclear plants, the topic of the present report. The document provides an up to date review of the engineering, social, scientific and administrative factors relevant to the safe recycling or reuse of components arising from decommissioning or refurbishment of nuclear facilities. This report should be of interest to owners, operators, policy makers and regulators involved with nuclear facilities, especially those in developing countries. Refs, figs and tabs

  7. Nickel(II) Complex of Polyhydroxybenzaldehyde N4-Thiosemicarbazone Exhibits Anti-Inflammatory Activity by Inhibiting NF-κB Transactivation

    Science.gov (United States)

    Loh, Sheng Wei; Looi, Chung Yeng; Hassandarvish, Pouya; Phan, Alicia Yi Ling; Wong, Won Fen; Wang, Hao; Paterson, Ian C.; Ea, Chee Kwee; Mustafa, Mohd Rais; Maah, Mohd Jamil

    2014-01-01

    Background The biological properties of thiosemicarbazone have been widely reported. The incorporation of some transition metals such as Fe, Ni and Cu to thiosemicarbazone complexes is known to enhance its biological effects. In this study, we incorporated nickel(II) ions into thiosemicarbazone with N4-substitution groups H3L (H; H3L1, CH3; H3L2, C6H5; H3L3 and C2H5; H3L4) and examined its potential anti-inflammatory activity. Methodology/Principal Findings Four ligands (1–4) and their respective nickel-containing complexes (5–8) were synthesized and characterized. The compounds synthesized were tested for their effects on NF-κB nuclear translocation, pro-inflammatory cytokines secretion and NF-κB transactivation activity. The active compound was further evaluated on its ability to suppress carrageenan-induced acute inflammation in vivo. A potential binding target of the active compound was also predicted by molecular docking analysis. Conclusions/Significance Among all synthesized compounds tested, we found that complex [Ni(H2L1)(PPh3)]Cl (5) (complex 5), potently inhibited IκBα degradation and NF-κB p65 nuclear translocation in LPS-stimulated RAW264.7 cells as well as TNFα-stimulated HeLa S3 cells. In addition, complex 5 significantly down-regulated LPS- or TNFα-induced transcription of NF-κB target genes, including genes that encode the pro-inflammatory cytokines TNFα, IFNβ and IL6. Luciferase reporter assays confirmed that complex 5 inhibited the transactivation activity of NF-κB. Furthermore, the anti-inflammatory effect of complex 5 was also supported by its suppressive effect on carrageenan-induced paw edema formation in wild type C57BL/6 mice. Interestingly, molecular docking study showed that complex 5 potentially interact with the active site of IKKβ. Taken together, we suggest complex 5 as a novel NF-κB inhibitor with potent anti-inflammatory effects. PMID:24977407

  8. Factors determining the long term back end nuclear fuel cycle strategy and future nuclear systems. Proceedings of a technical committee meeting

    International Nuclear Information System (INIS)

    2002-05-01

    The Technical Committee Meeting (TCM) was held in Vienna on 8-10 November 1999; it was organized by the International Atomic Energy Agency and attended by 26 participants from 16 Member States. The purpose of the meeting was to exchange information among experts on the back end fuel cycle strategies adopted by Member States; to identify key factors determining the long-term back end fuel cycle strategies; and to assess the applicability of these factors to future nuclear systems. Issues associated with the back end fuel cycle supporting a country's nuclear power programme are technical, economic, institutional and political. This TCM provided an opportunity to address these issues and their impacts to the back end fuel cycles, as well as to identify and assess factors affecting the back end fuel cycle strategies. The discussion was organized ib the following topical sessions: the nuclear fuel cycle; spent fuel management; waste management and repository; plutonium management. This document contains a summary of the meeting and 22 individual papers presented by participants. Each of the papers was indexed separately

  9. Hypo- and hypermorphic FOXC1 mutations in dominant glaucoma: transactivation and phenotypic variability.

    Directory of Open Access Journals (Sweden)

    Cristina Medina-Trillo

    Full Text Available Dominant glaucoma, a heterogeneous, infrequent and irreversible optic neuropathy, is often associated with elevated intraocular pressure and early-onset. The role of FOXC1 in this type of glaucoma was investigated in twelve Spanish probands via nucleotide variation screening of its proximal promoter and unique exon. Functional evaluations of the identified variants included analyses of the transcriptional activity, protein stability, DNA binding ability and subcellular localization. Four different mutations that were identified in four probands (33.3% were associated with remarkable phenotypic variability and were functionally classified as either hypermorphic (p.Y47X, p.Q106X and p.G447_G448insDG or hypomorphic (p.I126S alleles. To the best of our knowledge, three of the variants are novel (p.Y47X, p.I126S and p.G447_G448insDG and, in addition, hypermorphic FOXC1 mutations are reported herein for the first time. The presence of an intact N-terminal activation domain in the truncated proteins p.Y47X and p.Q106X may underlie their associated transactivation hyperactivity by a gain-of-function mechanism involving dysregulated protein-protein interactions. Similarly, altered molecular interactions may also lead to increased p.G447_G448insDG activity. In contrast, the partial loss-of-function associated with p.I126S was due to impaired protein stability, DNA binding, protein phosphorylation and subcellular distribution. These results support that moderate and variable FOXC1 transactivation changes are associated with moderate goniodysgenesis, dominant glaucoma and remarkable phenotypic variability.

  10. Hypo- and Hypermorphic FOXC1 Mutations in Dominant Glaucoma: Transactivation and Phenotypic Variability

    Science.gov (United States)

    Medina-Trillo, Cristina; Sánchez-Sánchez, Francisco; Aroca-Aguilar, José-Daniel; Ferre-Fernández, Jesús-José; Morales, Laura; Méndez-Hernández, Carmen-Dora; Blanco-Kelly, Fiona; Ayuso, Carmen; García-Feijoo, Julián; Escribano, Julio

    2015-01-01

    Dominant glaucoma, a heterogeneous, infrequent and irreversible optic neuropathy, is often associated with elevated intraocular pressure and early-onset. The role of FOXC1 in this type of glaucoma was investigated in twelve Spanish probands via nucleotide variation screening of its proximal promoter and unique exon. Functional evaluations of the identified variants included analyses of the transcriptional activity, protein stability, DNA binding ability and subcellular localization. Four different mutations that were identified in four probands (33.3%) were associated with remarkable phenotypic variability and were functionally classified as either hypermorphic (p.Y47X, p.Q106X and p.G447_G448insDG) or hypomorphic (p.I126S) alleles. To the best of our knowledge, three of the variants are novel (p.Y47X, p.I126S and p.G447_G448insDG) and, in addition, hypermorphic FOXC1 mutations are reported herein for the first time. The presence of an intact N-terminal activation domain in the truncated proteins p.Y47X and p.Q106X may underlie their associated transactivation hyperactivity by a gain-of-function mechanism involving dysregulated protein-protein interactions. Similarly, altered molecular interactions may also lead to increased p.G447_G448insDG activity. In contrast, the partial loss-of-function associated with p.I126S was due to impaired protein stability, DNA binding, protein phosphorylation and subcellular distribution. These results support that moderate and variable FOXC1 transactivation changes are associated with moderate goniodysgenesis, dominant glaucoma and remarkable phenotypic variability. PMID:25786029

  11. Studies of safety and critical work situations in nuclear power plants: A human factors perspective

    International Nuclear Information System (INIS)

    Jacobsson Kecklund, L.

    1998-05-01

    The purpose of this thesis was to develop and apply different approaches for analyzing safety in critical work situations in real work settings in nuclear power plants, and also to identify safety enhancing measures by using the framework of interaction between human, organizational and technical subsystems. A Cognitive Psychology as well as a Stress Psychology framework was used. All studies were related to the annual outage operational state where the need for coping with many infrequent tasks, often carried out under high time pressure, puts great strain on the staff and organisation of the plant. In three studies the natural variations in the plant state, normal operation and annual outage operation, were used to explore human performance, work-related factors as well as coping and the operators' own resources and the relationship between them. In the annual outage condition high work demands, decreased sleepiness at night shift, more errors and less satisfaction with work performance quality was reported by maintenance as well as by control room operators. A relationship between high work demands and more organizational problems and reports of more frequent human errors and lower satisfactions with work performance quality was also identified in the annual outage condition. Moreover, a relationship between increased sleepiness during night shift, more frequent use of coping strategies and a higher frequency of human errors was reported. In two studies the Event and Barrier Function Model was applied to analyze the safety of barrier function systems inserted into work process sequences to protect the systems from the negative consequences of failures and errors. The model was also used to assess safety in relation to a technical and organizational change. The last study addressed changes in work performance and work-related factors in relation to a technical and organizational change of a safety significant work process involving increased automation and new

  12. Spectroscopic factors with coupled-cluster connecting ab initio nuclear structure to reactions

    International Nuclear Information System (INIS)

    Jensen, Oeyvind

    2011-02-01

    This thesis has two parts. Tools and theory are presented in the first part, and papers with specific applications to nuclear physics are collected in the second part. A synopsis of theoretical foundations and basic techniques for many body quantum physics is presented in the context of a computer implementation of Wick's theorem for the symbolic algebra system SymPy. A pedagogical introduction to the implemented Python module is presented, and non-trivial aspects of the implemented simplification algorithms are discussed. Computer aided manipulations of second quantization expressions relieves practitioners of laborious and error-prone hand calculations necessary for the derivation of programmable equations. Theoretical developments of the Coupled-Cluster method (CCM) at Singles- and-Doubles level (CCSD) for the calculation of spectroscopic factors (SF) and radial overlap functions are presented. Algebraic expressions are derived from novel diagram techniques. CCM is one of the most successful methods for accurate numerical quantum mechanical simulations of medium sized many-body systems studied within Chemistry and Nuclear Physics. The recently developed spherical formulation of CCM is presented and alternative coupling schemes of quantum mechanical angular momentum are discussed in the context of a computer implementation for Racah algebra with SymPy. A pedagogical introduction to this functionality is given and it is used to derive angular momentum coupled expressions for efficient calculation of the spectroscopic factor diagrams. The first research paper presents a calculation of spectroscopic factors with CCSD. Details of the calculation is presented and convergence properties, as well as the dependence on various model parameters are discussed. Interactions with different cut-offs are employed and the dependence of the SF on the interactions are studied. In the second paper we employ the angular momentum coupled SF expressions and the spherical formulation

  13. miR-370 suppresses HBV gene expression and replication by targeting nuclear factor IA.

    Science.gov (United States)

    Fan, Hongxia; Lv, Ping; Lv, Jing; Zhao, Xiaopei; Liu, Min; Zhang, Guangling; Tang, Hua

    2017-05-01

    Hepatitis B virus (HBV) infection is a major health problem worldwide. The roles of microRNAs in the regulation of HBV expression are being increasingly recognized. In this study, we found that overexpression of miR-370 suppressed HBV gene expression and replication in Huh7 cells, whereas antisense knockdown of endogenous miR-370 enhanced HBV gene expression and replication in Huh7 cells and HepG2.2.15 cells. Further, we identified the transcription factor nuclear factor IA (NFIA) as a new host target of miR-370. Overexpression and knockdown studies showed that NFIA stimulated HBV gene expression and replication. Importantly, overexpression of NFIA counteracted the effect of miR-370 on HBV gene expression and replication. Further mechanistic studies showed that miR-370 suppressed HBV replication and gene expression by repressing HBV Enhancer I activity, and one of the NFIA binding site in the Enhancer I element was responsible for the repressive effect of miR-370 on HBV Enhancer I activity. Altogether, our results demonstrated that miR-370 suppressed HBV gene expression and replication through repressing NFIA expression, which stimulates HBV replication via direct regulation on HBV Enhancer I activities. Our findings may provide a new antiviral strategy for HBV infection. J. Med. Virol. 89:834-844, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  14. Hepatocyte nuclear factor 4 alpha polymorphisms and the metabolic syndrome in French-Canadian youth.

    Science.gov (United States)

    Marcil, Valérie; Amre, Devendra; Seidman, Ernest G; Boudreau, François; Gendron, Fernand P; Ménard, Daniel; Beaulieu, Jean François; Sinnett, Daniel; Lambert, Marie; Levy, Emile

    2015-01-01

    Hepatocyte nuclear factor 4 alpha (HNF4α) is a transcription factor involved in the regulation of serum glucose and lipid levels. Several HNF4A gene variants have been associated with the risk of developing type 2 diabetes mellitus. However, no study has yet explored its association with insulin resistance and the cardiometabolic risk in children. We aimed to investigate the relationship between HNF4A genetic variants and the presence of metabolic syndrome (MetS) and metabolic parameters in a pediatric population. Our study included 1,749 French-Canadians aged 9, 13 and 16 years and evaluated 24 HNF4A polymorphisms that were previously identified by sequencing. Analyses revealed that, after correction for multiple testing, one SNP (rs736824; PFrench Canadian children and adolescents. This study, the first exploring the relation between HNF4A genetic variants and MetS and metabolic variables in a pediatric cohort, suggests that HNF4α could represent an early marker for the risk of developing type 2 diabetes mellitus.

  15. Human factors and nuclear space technology in long-term exploration

    International Nuclear Information System (INIS)

    Brown-VanHoozer, S.A.; VanHoozer, W.R.

    2000-01-01

    Allocation of manual versus automated tasks for operation and maintenance of nuclear power systems in space will be crucial at the onset and at the return of a space flight. Such factors as space adaptation syndrome (SAS), a temporary space motion sickness that has affected 40 to 50% of crew members on past space flights, can result in lost effort ranging from a few hours to a full day. This could have a significant impact on manual performance where high levels of execution are likely to be required in the very early stages of the mission. Other considerations involving higher-level behavioral phenomena such as interpersonal and group processes, individual belief systems, social and motivational factors, and (subjective) cognitive function have received little attention; nevertheless these will be essential elements for success in long-term exploration. Understanding that long-term space flight missions may create groups that become unique societies distinct unto themselves will test current ethical, moral, and social belief systems, requiring one to examine the amalgamation as well as organizational structures for the safety and balance of the crew

  16. Molecular imaging of nuclear factor-Y transcriptional activity maps proliferation sites in live animals.

    Science.gov (United States)

    Goeman, Frauke; Manni, Isabella; Artuso, Simona; Ramachandran, Balaji; Toietta, Gabriele; Bossi, Gianluca; Rando, Gianpaolo; Cencioni, Chiara; Germoni, Sabrina; Straino, Stefania; Capogrossi, Maurizio C; Bacchetti, Silvia; Maggi, Adriana; Sacchi, Ada; Ciana, Paolo; Piaggio, Giulia

    2012-04-01

    In vivo imaging involving the use of genetically engineered animals is an innovative powerful tool for the noninvasive assessment of the molecular and cellular events that are often targets of therapy. On the basis of the knowledge that the activity of the nuclear factor-Y (NF-Y) transcription factor is restricted in vitro to proliferating cells, we have generated a transgenic reporter mouse, called MITO-Luc (for mitosis-luciferase), in which an NF-Y-dependent promoter controls luciferase expression. In these mice, bioluminescence imaging of NF-Y activity visualizes areas of physiological cell proliferation and regeneration during response to injury. Using this tool, we highlight for the first time a role of NF-Y activity on hepatocyte proliferation during liver regeneration. MITO-Luc reporter mice should facilitate investigations into the involvement of genes in cell proliferation and provide a useful model for studying aberrant proliferation in disease pathogenesis. They should be also useful in the development of new anti/proproliferative drugs and assessment of their efficacy and side effects on nontarget tissues.

  17. Nuclear Wiskott–Aldrich syndrome protein co-regulates T cell factor 1-mediated transcription in T cells

    Directory of Open Access Journals (Sweden)

    Nikolai V. Kuznetsov

    2017-10-01

    Full Text Available Abstract Background The Wiskott–Aldrich syndrome protein (WASp family of actin-nucleating factors are present in the cytoplasm and in the nucleus. The role of nuclear WASp for T cell development remains incompletely defined. Methods We performed WASp chromatin immunoprecipitation and deep sequencing (ChIP-seq in thymocytes and spleen CD4+ T cells. Results WASp was enriched at genic and intergenic regions and associated with the transcription start sites of protein-coding genes. Thymocytes and spleen CD4+ T cells showed 15 common WASp-interacting genes, including the gene encoding T cell factor (TCF12. WASp KO thymocytes had reduced nuclear TCF12 whereas thymocytes expressing constitutively active WASpL272P and WASpI296T had increased nuclear TCF12, suggesting that regulated WASp activity controlled nuclear TCF12. We identify a putative DNA element enriched in WASp ChIP-seq samples identical to a TCF1-binding site and we show that WASp directly interacted with TCF1 in the nucleus. Conclusions These data place nuclear WASp in proximity with TCF1 and TCF12, essential factors for T cell development.

  18. Land and Water Use, CO2 Emissions, and Worker Radiological Exposure Factors for the Nuclear Fuel Cycle

    Energy Technology Data Exchange (ETDEWEB)

    Brett W Carlsen; Brent W Dixon; Urairisa Pathanapirom; Eric Schneider; Bethany L. Smith; Timothy M. AUlt; Allen G. Croff; Steven L. Krahn

    2013-08-01

    The Department of Energy Office of Nuclear Energy’s Fuel Cycle Technologies program is preparing to evaluate several proposed nuclear fuel cycle options to help guide and prioritize Fuel Cycle Technology research and development. Metrics are being developed to assess performance against nine evaluation criteria that will be used to assess relevant impacts resulting from all phases of the fuel cycle. This report focuses on four specific environmental metrics. • land use • water use • CO2 emissions • radiological Dose to workers Impacts associated with the processes in the front-end of the nuclear fuel cycle, mining through enrichment and deconversion of DUF6 are summarized from FCRD-FCO-2012-000124, Revision 1. Impact estimates are developed within this report for the remaining phases of the nuclear fuel cycle. These phases include fuel fabrication, reactor construction and operations, fuel reprocessing, and storage, transport, and disposal of associated used fuel and radioactive wastes. Impact estimates for each of the phases of the nuclear fuel cycle are given as impact factors normalized per unit process throughput or output. These impact factors can then be re-scaled against the appropriate mass flows to provide estimates for a wide range of potential fuel cycles. A companion report, FCRD-FCO-2013-000213, applies the impact factors to estimate and provide a comparative evaluation of 40 fuel cycles under consideration relative to these four environmental metrics.

  19. Factors determining nuclear expansion in Poland till 2020, their analysis and projected nuclear power expansion as a consequence of these factors

    International Nuclear Information System (INIS)

    Kerner, Andrzej; Kumanowski, Marek

    1999-01-01

    Coal plays a dominant role in Polish economy. The share of hard coal and lignite in Poland's total primary energy supply and in portfolio of public electricity/heat production in 1996 amounted to 73% and 97%, respectively. So high shares result: - low energy security index connected with very low fuel diversity; - high level of environmental pollution i.e. air emissions (dusts, SO 2 , NO x and CO 2 ) as well as solid wastes dumping. Electricity demand forecasts performed by different organizations show that in the time horizon 2020 a considerable growth of electricity consumption is projected, estimated within a range of 60-120% in comparison with the 1996 level. In the case of continuation of the present energy policy Poland will not be able to meet international obligations in the field of environmental protection, in particular the Kyoto Protocol. Practically there are two energy carries that might present improve the fuel structure for electricity generation: natural gas and nuclear fuel. Now, with very high discount rate, natural gas has an significant advantage over all other fuels as much less capital and time consuming in power plant investments. The advantage of nuclear power is total reduction of CO 2 emissions. Analyses of electricity generation strategies, under condition that energy policy is kept as it is now, show that nuclear power is not competitive against other sources. With an environmental coal tax or external costs in electricity production modelled, nuclear power plants become competitive since 2015. (author)

  20. Improving performance of high risk organizations Spanish nuclear sector from the analysis of organizational culture factors; Mejora del desempeno de las organizaciones de alto riesgo del sector nuclear espanol a partir del analisis de los factores de cultura organizativa

    Energy Technology Data Exchange (ETDEWEB)

    La Salabarnada, E.; German, S.; Silla, I.; Navajas, J.

    2012-07-01

    This paper presents the research project funded by UNESA and conducted by the CISOT-CIEMAT that aims to contribute to improving the operating performance of the Spanish nuclear power plants. This paper aims to identify the factors and key organizational processes to improve efficiency, in order to advance knowledge about the influence of organizational culture on the safety of high reliability organizations.

  1. Psychological factors in the perception and acceptablilty of risk: implications for nuclear waste management

    International Nuclear Information System (INIS)

    Slovic, P.

    1976-01-01

    Public perception and acceptance of nuclear energy is now the most critical question concerning the future of nuclear energy. This is a review of the dynamics of societal risk taking as applied to nuclear power. It is shown that the human intellect is not well equipped for making decisions about risky activities. Risk-benefit relations are discussed. Some of the possible reasons why nuclear power is presently unpopular are described. Responses to a Battelle questionnaire on attitudes toward nuclear waste disposal are discussed

  2. Heterogeneous nuclear ribonucleoprotein K inhibits heat shock-induced transcriptional activity of heat shock factor 1.

    Science.gov (United States)

    Kim, Hee-Jung; Lee, Jae-Jin; Cho, Jin-Hwan; Jeong, Jaeho; Park, A Young; Kang, Wonmo; Lee, Kong-Joo

    2017-08-04

    When cells are exposed to heat shock and various other stresses, heat shock factor 1 (HSF1) is activated, and the heat shock response (HSR) is elicited. To better understand the molecular regulation of the HSR, we used 2D-PAGE-based proteome analysis to screen for heat shock-induced post-translationally modified cellular proteins. Our analysis revealed that two protein spots typically present on 2D-PAGE gels and containing heterogeneous nuclear ribonucleoprotein K (hnRNP K) with trioxidized Cys 132 disappeared after the heat shock treatment and reappeared during recovery, but the total amount of hnRNP K protein remained unchanged. We next tested whether hnRNP K plays a role in HSR by regulating HSF1 and found that hnRNP K inhibits HSF1 activity, resulting in reduced expression of hsp70 and hsp27 mRNAs. hnRNP K also reduced binding affinity of HSF1 to the heat shock element by directly interacting with HSF1 but did not affect HSF1 phosphorylation-dependent activation or nuclear localization. hnRNP K lost its ability to induce these effects when its Cys 132 was substituted with Ser, Asp, or Glu. These findings suggest that hnRNP K inhibits transcriptional activity of HSF1 by inhibiting its binding to heat shock element and that the oxidation status of Cys 132 in hnRNP K is critical for this inhibition. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Importin α-importin β complex mediated nuclear translocation of insulin-like growth factor binding protein-5.

    Science.gov (United States)

    Sun, Min; Long, Juan; Yi, Yuxin; Xia, Wei

    2017-10-28

    Insulin-like growth factor-binding protein (IGFBP)-5 is a secreted protein that binds to IGFs and modulates IGF actions, as well as regulates cell proliferation, migration, and apoptosis independent of IGF. Proper cellular localization is critical for the effective function of most signaling molecules. In previous studies, we have shown that the nuclear IGFBP-5 comes from ER-cytosol retro-translocation. In this study, we further investigated the pathway mediating IGFBP-5 nuclear import after it retro-translocation. Importin-α5 was identified as an IGFBP-5-interacting protein with a yeast two-hybrid system, and its interaction with IGFBP-5 was further confirmed by GST pull down and co-immunoprecipitation. Binding affinity of IGFBP-5 and importins were determined by surface plasmon resonance (IGFBP-5/importin-β: K D =2.44e-7, IGFBP-5/importin-α5: K D =3.4e-7). Blocking the importin-α5/importin-β nuclear import pathway using SiRNA or dominant negative impotin-β dramatically inhibited IGFBP-5-EGFP nuclear import, though importin-α5 overexpress does not affect IGFBP-5 nuclear import. Furthermore, nuclear IGFBP-5 was quantified using luciferase report assay. When deleted the IGFBP-5 nuclear localization sequence (NLS), IGFBP-5 ΔNLS loss the ability to translocate into the nucleus and accumulation of IGFBP-5 ΔNLS was visualized in the cytosol. Altogether, our findings provide a substantially evidence showed that the IGFBP-5 nuclear import is mediated by importin-α/importin-β complex, and NLS is critical domain in IGFBP-5 nuclear translocation.

  4. p35 regulates the CRM1-dependent nucleocytoplasmic shuttling of nuclear hormone receptor coregulator-interacting factor 1 (NIF-1.

    Directory of Open Access Journals (Sweden)

    Xiao-Su Zhao

    Full Text Available Cyclin-dependent kinase 5 (Cdk5 is a proline-directed serine/threonine kinase, which plays critical roles in a wide spectrum of neuronal functions including neuronal survival, neurite outgrowth, and synapse development and plasticity. Cdk5 activity is controlled by its specific activators: p35 or p39. While knockout studies reveal that Cdk5/p35 is critical for neuronal migration during early brain development, functions of Cdk5/p35 have been unraveled through the identification of the interacting proteins of p35, most of which are Cdk5/p35 substrates. However, it remains unclear whether p35 can regulate neuronal functions independent of Cdk5 activity. Here, we report that a nuclear protein, nuclear hormone receptor coregulator (NRC-interacting factor 1 (NIF-1, is a new interacting partner of p35. Interestingly, p35 regulates the functions of NIF-1 independent of Cdk5 activity. NIF-1 was initially discovered as a transcriptional regulator that enhances the transcriptional activity of nuclear hormone receptors. Our results show that p35 interacts with NIF-1 and regulates its nucleocytoplasmic trafficking via the nuclear export pathway. Furthermore, we identified a nuclear export signal on p35; mutation of this site or blockade of the CRM1/exportin-dependent nuclear export pathway resulted in the nuclear accumulation of p35. Intriguingly, blocking the nuclear export of p35 attenuated the nuclear accumulation of NIF-1. These findings reveal a new p35-dependent mechanism in transcriptional regulation that involves the nucleocytoplasmic shuttling of transcription regulators.

  5. p35 regulates the CRM1-dependent nucleocytoplasmic shuttling of nuclear hormone receptor coregulator-interacting factor 1 (NIF-1).

    Science.gov (United States)

    Zhao, Xiao-Su; Fu, Wing-Yu; Chien, Winnie W Y; Li, Zhen; Fu, Amy K Y; Ip, Nancy Y

    2014-01-01

    Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase, which plays critical roles in a wide spectrum of neuronal functions including neuronal survival, neurite outgrowth, and synapse development and plasticity. Cdk5 activity is controlled by its specific activators: p35 or p39. While knockout studies reveal that Cdk5/p35 is critical for neuronal migration during early brain development, functions of Cdk5/p35 have been unraveled through the identification of the interacting proteins of p35, most of which are Cdk5/p35 substrates. However, it remains unclear whether p35 can regulate neuronal functions independent of Cdk5 activity. Here, we report that a nuclear protein, nuclear hormone receptor coregulator (NRC)-interacting factor 1 (NIF-1), is a new interacting partner of p35. Interestingly, p35 regulates the functions of NIF-1 independent of Cdk5 activity. NIF-1 was initially discovered as a transcriptional regulator that enhances the transcriptional activity of nuclear hormone receptors. Our results show that p35 interacts with NIF-1 and regulates its nucleocytoplasmic trafficking via the nuclear export pathway. Furthermore, we identified a nuclear export signal on p35; mutation of this site or blockade of the CRM1/exportin-dependent nuclear export pathway resulted in the nuclear accumulation of p35. Intriguingly, blocking the nuclear export of p35 attenuated the nuclear accumulation of NIF-1. These findings reveal a new p35-dependent mechanism in transcriptional regulation that involves the nucleocytoplasmic shuttling of transcription regulators.

  6. Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen Inhibits Major Histocompatibility Complex Class II Expression by Disrupting Enhanceosome Assembly through Binding with the Regulatory Factor X Complex.

    Science.gov (United States)

    Thakker, Suhani; Purushothaman, Pravinkumar; Gupta, Namrata; Challa, Shanthan; Cai, Qiliang; Verma, Subhash C

    2015-05-01

    Major histocompatibility complex class II (MHC-II) molecules play a central role in adaptive antiviral immunity by presenting viral peptides to CD4(+) T cells. Due to their key role in adaptive immunity, many viruses, including Kaposi's sarcoma-associated herpesvirus (KSHV), have evolved multiple strategies to inhibit the MHC-II antigen presentation pathway. The expression of MHC-II, which is controlled mainly at the level of transcription, is strictly dependent upon the binding of the class II transactivator (CIITA) to the highly conserved promoters of all MHC-II genes. The recruitment of CIITA to MHC-II promoters requires its direct interactions with a preassembled MHC-II enhanceosome consisting of cyclic AMP response element-binding protein (CREB) and nuclear factor Y (NF-Y) complex and regulatory factor X (RFX) complex proteins. Here, we show that KSHV-encoded latency-associated nuclear antigen (LANA) disrupts the association of CIITA with the MHC-II enhanceosome by binding to the components of the RFX complex. Our data show that LANA is capable of binding to all three components of the RFX complex, RFX-associated protein (RFXAP), RFX5, and RFX-associated ankyrin-containing protein (RFXANK), in vivo but binds more strongly with the RFXAP component in in vitro binding assays. Levels of MHC-II proteins were significantly reduced in KSHV-infected as well as LANA-expressing B cells. Additionally, the expression of LANA in a luciferase promoter reporter assay showed reduced HLA-DRA promoter activity in a dose-dependent manner. Chromatin immunoprecipitation assays showed that LANA binds to the MHC-II promoter along with RFX proteins and that the overexpression of LANA disrupts the association of CIITA with the MHC-II promoter. These assays led to the conclusion that the interaction of LANA with RFX proteins interferes with the recruitment of CIITA to MHC-II promoters, resulting in an inhibition of MHC-II gene expression. Thus, the data presented here identify a novel

  7. Bovine Lhx8, a Germ Cell-Specific Nuclear Factor, Interacts with Figla.

    Directory of Open Access Journals (Sweden)

    Liyuan Fu

    Full Text Available LIM homeobox 8 (Lhx8 is a germ cell-specific transcription factor essential for the development of oocytes during early oogenesis. In mice, Lhx8 deficiency causes postnatal oocyte loss and affects the expression of many oocyte-specific genes. The aims of this study were to characterize the bovine Lhx8 gene, determine its mRNA expression during oocyte development and early embryogenesis, and evaluate its interactions with other oocyte-specific transcription factors. The bovine Lhx8 gene encodes a protein of 377 amino acids. A splice variant of Lhx8 (Lhx8_v1 was also identified. The predicted bovine Lhx8 protein contains two LIM domains and one homeobox domain. However, one of the LIM domains in Lhx8_v1 is incomplete due to deletion of 83 amino acids near the N terminus. Both Lhx8 and Lhx8_v1 transcripts were only detected in the gonads but none of the somatic tissues examined. The expression of Lhx8 and Lhx8_v1 appears to be restricted to oocytes as none of the transcripts was detectable in granulosa or theca cells. The maternal Lhx8 transcript is abundant in GV and MII stage oocytes as well as in early embryos but disappear by morula stage. A nuclear localization signal that is required for the import of Lhx8 into nucleus was identified, and Lhx8 is predominantly localized in the nucleus when ectopically expressed in mammalian cells. Finally, a novel interaction between Lhx8 and Figla, another transcription factor essential for oogenesis, was detected. The results provide new information for studying the mechanisms of action for Lhx8 in oocyte development and early embryogenesis.

  8. The splicing factor U1-70K interacts with the SMN complex and is required for nuclear gem integrity

    Czech Academy of Sciences Publication Activity Database

    Stejskalová, Eva; Staněk, David

    2014-01-01

    Roč. 127, č. 18 (2014), s. 3909-3915 ISSN 0021-9533 R&D Projects: GA ČR GAP302/11/1910 Institutional support: RVO:68378050 Keywords : nuclear gems * SMN * U1-70K Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.432, year: 2014

  9. Close or renew? Factors affecting local community support for rebuilding nuclear power plants in the Czech Republic

    Czech Academy of Sciences Publication Activity Database

    Frantál, Bohumil; Malý, Jiří

    2017-01-01

    Roč. 140, č. 140 (2017), s. 134-143 ISSN 0301-4215 R&D Projects: GA ČR GA16-04483S Institutional support: RVO:68145535 Keywords : nuclear power plants * rebuilding * community acceptance Subject RIV: DE - Earth Magnetism, Geodesy, Geography Impact factor: 4.140, year: 2016 http://www.sciencedirect.com/science/article/pii/S0301421517300599

  10. The Astrophysical S-factor for the 2H(α, γ)6Li Nuclear Reaction at ...

    Indian Academy of Sciences (India)

    1Department of Physics, Faculty of Science, Arak University, Arak 8349-8-38156, Iran. 2Physics Department, Payame Noor ... and available laboratory data, excellent agreement is achieved for the astrophysical S-factor of this ... a target of high nuclear charge. The time-reversed reaction is then studied using virtual photons.

  11. Assessment of theoretical and experimental results in the calculation of atmospheric dilution factors in the Atucha I nuclear power plant

    International Nuclear Information System (INIS)

    Quintana, E.E.; Tossi, M.H.; Telleria, D.M.

    1990-01-01

    Collective doses produced during the normal working of the Atucha I Nuclear Power Plant are calculated using annual atmospheric factors. This work studies the behaviour of the dilution factors in different periods of the year in order to fit the calculated dose model applying factors from seasonal, monthly or weekly periods. The Radiation Protection Group of the C.N.E.A. have carried out continuous environmental monitoring in the surroundings of the Atucha I Nuclear Power Plant. These studies include the measurement of air tritium concentration, radionuclide that is found principally as tritiated water vapour. This isotope, normally released by the nuclear power plant was used as a tracer to assess the atmospheric dilution factors. Factors were calculated by two methods: an experimental one, based on environmental measurements of the tritium concentration in the surroundings of the nuclear power plant and another one by applying a theoretical model based on information from the micrometeorological tower located in the mentioned place. To carry out the environmental monitoring, four monitoring stations in the surroundings of the power plant were chosen. Three of them are approximately one kilometer from the plant and the fourth is 7.5 km away, near the city of Lima. To condense and collect the atmospheric water vapour, an overcooling system was used. The measurement was performed by liquid scintillation counting, previous alkaline electrolytical enrichment of the samples. The theoretical model uses hourly values of direction and wind intensity, as well as the atmospheric dispersive properties. Values obtained during the period 1976 to 1988 allowed, applying statistical tests, to validate the theoretical model and to observe seasonal variation of the dilution factors throughout the same year and between different years. Finally, results and graphics are presented showing that the behaviour of the dilution factors in different periods of the year. It is recommended to

  12. Upregulation of Nuclear Factor of Activated T-Cells by Nerve Injury Contributes to Development of Neuropathic Pain

    OpenAIRE

    Cai, You-Qing; Chen, Shao-Rui; Pan, Hui-Lin

    2013-01-01

    Nerve injury induces long-term changes in gene expression in the nociceptive circuitry and can lead to chronic neuropathic pain. However, the transcriptional mechanism involved in neuropathic pain is poorly understood. Nuclear factor of activated T-cells (NFATc) is a transcriptional factor regulated by the Ca2+-dependent protein phosphatase calcineurin. In this study, we determined nerve injury–induced changes in the expression of NFATc1–c4 in the dorsal root ganglia (DRG) and spinal cords an...

  13. Vitamin D inhibits the growth of and virulence factor gene expression by Porphyromonas gingivalis and blocks activation of the nuclear factor kappa B transcription factor in monocytes.

    Science.gov (United States)

    Grenier, D; Morin, M-P; Fournier-Larente, J; Chen, H

    2016-06-01

    Increasing evidence suggests that 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3 ), a fat-soluble secosteroid hormone, has a positive impact on periodontal health through diverse mechanisms. The present study was aimed at investigating the effect of 1,25(OH)2 D3 on the growth of and virulence factor gene expression by the periodontopathogenic bacterium Porphyromonas gingivalis. The effect of 1,25(OH)2 D3 on P. gingivalis-mediated activation of nuclear factor kappa B (NF-κB) transcription factor in monocytes was also assessed. A broth microdilution assay was used to determine the antibacterial activity of 1,25(OH)2 D3 . The modulation of virulence factor gene expression in P. gingivalis was assessed by quantitative reverse transcription-polymerase chain reaction. NF-κB activation was assessed using a human monocytic cell line stably transfected with a luciferase reporter containing NF-κB binding sites. Minimal inhibitory concentrations of 1,25(OH)2 D3 against P. gingivalis ranged from 3.125 to 6.25 μg/mL. Moreover, a partial synergistic effect was observed when 1,25(OH)2 D3 was used in association with metronidazole. 1,25(OH)2 D3 attenuated the virulence of P. gingivalis by reducing the expression of genes coding for important virulence factors, including adhesins (fimA, hagA and hagB) and proteinases (rgpA, rgpB and kgp). 1,25(OH)2 D3 dose-dependently prevented P. gingivalis-induced NF-κB activation in a monocyte model. Our study suggested that 1,25(OH)2 D3 selectively inhibits the growth of and virulence factor gene expression by P. gingivalis, in addition to attenuating NF-κB activation by this periodontopathogen. This dual action on P. gingivalis and the inflammatory response of host cells may be of particular interest with a view to developing a novel and inexpensive preventive/therapeutic strategy. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Competition of nuclear factor-erythroid 2 factors related transcription factor isoforms, Nrf1 and Nrf2, in antioxidant enzyme induction

    Directory of Open Access Journals (Sweden)

    Nikolai L. Chepelev

    2013-01-01

    Full Text Available Although the Nrf2 (nuclear factor-erythroid 2 p45 subunit-related factor 2 regulated expression of multiple antioxidant and cytoprotective genes through the electrophile responsive element (EpRE is well established, interaction of Nrf2/EpRE with Nrf1, a closely-related transcription factor, is less well understood. Due to either proteolysis or alternative translation, Nrf1 has been found as proteins of varying size, p120, p95, and p65, which have been described as either activators of EpRE or competitive inhibitors of Nrf2. We investigated the effect of Nrf1 on EpRE-regulated gene expression using the catalytic and modifier subunits of glutamate cysteine ligase (GCLC and GCLM as models and explored the potential role of Nrf1 in altering their expression in aging and upon chronic exposure to airborne nano-sized particulate matter (nPM. Nrf1 knockout resulted in the increased expression of GCLC and GCLM in human bronchial epithelial (HBE1 cells. Overexpression Nrf2 in combination with either p120 or p65 diminished or failed to further increase the GCLC- and GLCM-EpRE luciferase activity. All known forms of Nrf1 protein, remained unchanged in the lungs of mice with age or in response to nPM. Our study shows that Nrf1 could inhibit EpRE activity in vitro, whereas the precise role of Nrf1 in vivo requires further investigations. We conclude that Nrf1 may not be directly responsible for the loss of Nrf2-dependent inducibility of antioxidant and cytoprotective genes observed in aged animals.

  15. Project management, an important factor to the successful implementation of a nuclear power plant

    International Nuclear Information System (INIS)

    Zuo Hu.

    1986-01-01

    Project management is a key problem in construction of nuclear power plant. Underestimation of complexity of a nuclear power plant and shortcomings in performance of QA activities may result in delay of schedule and cost overruns. The owner's management competency is vital to the successful implementation of a nuclear power plant. The owner's organization must build up its own project management capability and make efforts in indepedently managing the performance of the overall QA responsibility of the project

  16. Human factor - an important reserve in increasing efficiency and safety of nuclear power plants

    International Nuclear Information System (INIS)

    Simunek, P.

    1982-01-01

    It is demonstrated that the relationship between man and technical equipment in a nuclear power plant should be studied using the systems analysis approach. The consistent use of ergonomic knowledge in nuclear power plants makes it possible with relatively small additional expenditure to achieve considerable economic effect. The establishment is therefore suggested of a workplace to coordinate the use of applied ergonomics in nuclear power plants. (Ha)

  17. Pharmacological stimulation of nuclear factor (erythroid-derived 2)-like 2 translation activates antioxidant responses.

    Science.gov (United States)

    Perez-Leal, Oscar; Barrero, Carlos Alberto; Merali, Salim

    2017-08-25

    Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the master regulator of the antioxidant response, and its function is tightly regulated at the transcriptional, translational, and post-translational levels. It is well-known that Nrf2 is regulated at the protein level by proteasomal degradation via Kelch-like ECH-associated protein 1 (Keap1), but how Nrf2 is regulated at the translational level is less clear. Here, we show that pharmacological stimulation increases Nrf2 levels by overcoming basal translational repression. We developed a novel reporter assay that enabled identification of natural compounds that induce Nrf2 translation by a mechanism independent of Keap1-mediated degradation. Apigenin, resveratrol, and piceatannol all induced Nrf2 translation. More importantly, the pharmacologically induced Nrf2 overcomes Keap1 regulation, translocates to the nucleus, and activates the antioxidant response. We conclude that translational regulation controls physiological levels of Nrf2, and this can be modulated by apigenin, resveratrol, and piceatannol. Also, targeting this mechanism with novel compounds could provide new insights into prevention and treatment of multiple diseases in which oxidative stress plays a significant role. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. Supply and cost factors for metals in the Canadian nuclear fuel waste immobilization program

    International Nuclear Information System (INIS)

    McConnell, D.B.

    1982-11-01

    Estimates have been made of the demand for immobilization containers to accommodate the irradiated fuel bundles arising from Canadian nuclear generating stations to the year 2020. The resulting estimates for container shells and container-filling alloys were compared to estimates for Canadian and Western World production of the candiate metals. The results indicate that, among the container shell metals, supply difficulties might arise only for Grade 7 titanium. Among the filling metals, only lead-antimony alloy might present supply problems. Current cost figures for plate made of each shell metal, and bulk quantities of filling metals, were compared. Materials costs would be least for a supported shell of stainless steel, followed by copper, titanium alloys Grades 2, 12 and 7, and Inconel 625. Aluminum-silicon is the lowest-cost filling matrix, followed by zinc, lead, and lead-antimony. Container durability, vault conditions, groundwater composition and other factors may play an overriding role in the final selection of materials for container construction

  19. Spongiatriol Inhibits Nuclear Factor Kappa B Activation and Induces Apoptosis in Pancreatic Cancer Cells

    Science.gov (United States)

    Guzmán, Esther; Maher, Michael; Temkin, Alexis; Pitts, Tara; Wright, Amy

    2013-01-01

    Pancreatic cancer, the fourth leading cause of cancer death in the US, is highly resistant to all current chemotherapies, and its growth is facilitated by chronic inflammation. The majority of pro-inflammatory cytokines initiate signaling cascades that converge at the activation of the Nuclear Factor Kappa B (NFκB), a signal transduction molecule that promotes cell survival, proliferation and angiogenesis. In an effort to identify novel inhibitors of NFκB, the HBOI library of pure compounds was screened using a reporter cell line that produces luciferin under the transcriptional control of NFκB. Seven compounds were identified through this screen, but in the case of five of them, their reported mechanism of action made them unlikely to be specific NFκB inhibitors. Spongiatriol, a marine furanoditerpenoid that was first isolated in the 1970s, is shown here to inhibit NFκB transcriptional activity in a reporter cell line, to reduce levels of phosphorylated (active) NFκB in the AsPC-1 cell line, to have an IC50 for cytotoxicity in the low micromolar range against the AsPC-1, BxPC-3, MiaPaCa-2 and Panc-1 pancreatic cancer cell lines, and to induce moderate but significant apoptosis in both the AsPC-1 and the Panc-1 cell lines. PMID:23549285

  20. Circumvention of nuclear factor kappaB-induced chemoresistance by cytoplasmic-targeted anthracyclines.

    Science.gov (United States)

    Bilyeu, Jennifer D; Panta, Ganesh R; Cavin, Lakita G; Barrett, Christina M; Turner, Eddie J; Sweatman, Trevor W; Israel, Mervyn; Lothstein, Leonard; Arsura, Marcello

    2004-04-01

    Nuclear factor kappaB (NF-kappaB) has been implicated in inducible chemoresistance against anthracyclines. In an effort to improve the cytotoxicity of anthracyclines while reducing their cardiotoxic effects, we have developed a novel class of extranuclear-localizing 14-O-acylanthracyclines that bind to the phorbol ester/diacylglycerol-binding C1b domain of conventional and novel protein kinase C (PKC) isoforms, thereby promoting an apoptotic response. Because PKCs have been shown to be involved in NF-kappaB activation, in this report, we determined the mechanism of NF-kappaB activation by N-benzyladriamycin-14-valerate (AD 198) and N-benzyladriamycin-14-pivalate (AD 445), two novel 14-O-acylanthracylines. We show that the induction of NF-kappaB activity in response to drug treatment relies on the activation of PKC-delta and NF-kappaB-activating kinase (NAK), independent of ataxia telengectasia mutated and p53 activities. In turn, NAK activates the IKK complex through phosphorylation of the IKK-2 subunit. We find that neither NF-kappaB activation nor ectopic expression of Bcl-X(L) confers protection from AD 198-induced cell killing. Overall, our data indicate that activation of novel PKC isoforms by cytoplasmic-targeted 14-O-acylanthracyclines promotes an apoptotic response independent of DNA damage, which is unimpeded by inducible activation of NF-kappaB.

  1. A study on the human factors of nuclear power plants man-machine interface

    International Nuclear Information System (INIS)

    Shin, Hyun Kook; Lee, Jeong Woon; Lee, Yong Hee; Oh, In Suk; Park, Geun Ok

    1991-01-01

    Approaches of the MMIS design were analysed in this project. Both systems approach and experimental approach were studied. In addition, guidelines for the design of MMI are discussed. The methodology of experimental approach studied in this project can be useful for establishing experimental criteria on MMI design items. The framework of a computer code was developed by utilizing function-based task analysis and procedure information requirements. This can be further developed as a tool useful for the verification and validation of MMI designs. A test facility was designed in compliance with the purpose of experimental approach by considering specific conditions and factors inherent in nuclear power plants. Test facility can be used for conducting experiments which provide detailed human performance and characteristics data at the low level of systems approach. An experimental study was performed to obtain a range of illumination levels suitable for the operation in VDU-based control rooms. Existing design guidelines were tested by this experimental study. A conceptual design of MMIS was developed in accordance with the established MMIS design approach and was evaluated through the comparison to other advanced control room designs. (Author)

  2. Phenotypic screening of hepatocyte nuclear factor (HNF) 4-γ receptor knockout mice

    International Nuclear Information System (INIS)

    Gerdin, Anna Karin; Surve, Vikas V.; Joensson, Marie; Bjursell, Mikael; Bjoerkman, Maria; Edenro, Anne; Schuelke, Meint; Saad, Alaa; Bjurstroem, Sivert; Lundgren, Elisabeth Jensen; Snaith, Michael; Fransson-Steen, Ronny; Toernell, Jan; Berg, Anna-Lena; Bohlooly-Y, Mohammad

    2006-01-01

    Using the mouse as a model organism in pharmaceutical research presents unique advantages as its physiology in many ways resembles the human physiology, it also has a relatively short generation time, low breeding and maintenance costs, and is available in a wide variety of inbred strains. The ability to genetically modify mouse embryonic stem cells to generate mouse models that better mimic human disease is another advantage. In the present study, a comprehensive phenotypic screening protocol is applied to elucidate the phenotype of a novel mouse knockout model of hepatocyte nuclear factor (HNF) 4-γ. HNF4-γ is expressed in the kidneys, gut, pancreas, and testis. First level of the screen is aimed at general health, morphologic appearance, normal cage behaviour, and gross neurological functions. The second level of the screen looks at metabolic characteristics and lung function. The third level of the screen investigates behaviour more in-depth and the fourth level consists of a thorough pathological characterisation, blood chemistry, haematology, and bone marrow analysis. When compared with littermate wild-type mice (HNF4-γ +/+ ), the HNF4-γ knockout (HNF4-γ -/- ) mice had lowered energy expenditure and locomotor activity during night time that resulted in a higher body weight despite having reduced intake of food and water. HNF4-γ -/- mice were less inclined to build nest and were found to spend more time in a passive state during the forced swim test

  3. Psychological factors of professional success of nuclear power plant main control room operators

    Directory of Open Access Journals (Sweden)

    Kosenkov A.A.

    2014-12-01

    Full Text Available Aim: to conduct a comparative analysis of the psychological characteristics of the most and least successful main control room operators. Material and Methods. Two NPP staff groups: the most and least successful main control room operators, who worked in routine operating conditions, were surveyed. Expert evaluation method has been applied to identify the groups. The subjects were administered the Minnesota Multiphasic Personality Inventory (MMPI, Cattell's Sixteen Personality Factor Questionnaire (16PF form A and Raven's Progressive Matrices test. Results. Numerous significant psychological differences between the groups of most and least successful control room operators were obtained: the best operators were significantly more introverted and correctly solved more logical tasks with smaller percentage of mistakes under time pressure than worst ones. Conclusions: 1. The psychodiagnostic methods used in the study were adequate to meet research objective 2. Tendency to introversion, as well as developed the ability to solve logic problems undertime pressure, apparently, are important professional qualities for control room operators. These indicators should be considered in the process of psychological selection and professional guidance of nuclear power plant operators.

  4. Operational readiness decisions at nuclear power plants. Which factors influence the decisions?

    International Nuclear Information System (INIS)

    Kecklund, Lena; Petterson, Sara

    2007-11-01

    The purpose of this project has been to propose a model for how operational readiness decisions are made and to identify important factors influencing these decisions. The project has also studied the support from the management system for decision making, and made a comparison to how decisions are made in practice. This is mainly an explorative study, but it also deals with relevant research and theories about decision making. The project consists of several parts. The first part is composed of descriptions of important notations and terms, and a summary of relevant research about decision making and its relation to the management system. The project proposes a model for the decision making process. The second part consists of analyses of reports from SKI about operational readiness decisions. The last part is a case study at a nuclear power plant. The case study describes the support from work method theories at the nuclear power plant to the decision maker. Decision makers with different roles in the safety management system were interviewed to give a description of the decision making process and of factors influencing the decisions made in practice. The case study also consists of an analysis of decisions in some real events at the nuclear power plant, as well as of making interviews in connection with these. To sum up, this report presents a model for the decision process and describes the work method theories that support the different parts in the process, how the different parts are applied in practice and circumstances that influence the decision process. The results of the project give an understanding for decision making in operational readiness decisions and the factors that influence the decision. The results are meant to be used as a basis for further studies in other nuclear power plants. The results indicate that the decision process is facilitated if there are clear criteria and work methods, if the work methods are well established and if the

  5. Analysis of factors related to man-induced hazard for nuclear facilities

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Young Soon; Jung, Jea Hee; Lee, Keun O; Son, Ki Sang; Wang, Sang Chul; Lee, Chang Jin; Ku, Min Ho; Park, Nam Young [Seoul National Univ. of Technology, Seoul (Korea, Republic of)

    2003-03-15

    This study is to show a guide for installing hazardous facilities adjoined atomic power plant after finding out how much these facilities could impact to the atomic plant. Nuclear power plant is an important facility which is closely connected with public life, industrial activity, and the conduct of public business, so it should not be damaged. Therefore, if there are hazardous and harmful facilities near the plant, then they must be evaluated by the size, the type, and the shape. First of all, any factors that could cause man induced accident must be investigated. And they must be exactly evaluated from how much it will damage the plant facilities. The purpose of this study is to set a technical standard for the installation of these facilities by evaluating the man induced accident. Also, it is to make out the evaluation methods by investigating the hazardous facilities which are placed near the plant. Our country is now using CFR standard : reg. guide and IAEA safety series. However, not only the standard of technology which is related to man induced accident but also the evaluation methods for facilities are not yet layed down. As It was mentioned above, we should evaluate these facilities adequately, and these methods must be made out.

  6. Phenotypic screening of hepatocyte nuclear factor (HNF) 4-gamma receptor knockout mice.

    Science.gov (United States)

    Gerdin, Anna Karin; Surve, Vikas V; Jönsson, Marie; Bjursell, Mikael; Björkman, Maria; Edenro, Anne; Schuelke, Meint; Saad, Alaa; Bjurström, Sivert; Lundgren, Elisabeth Jensen; Snaith, Michael; Fransson-Steen, Ronny; Törnell, Jan; Berg, Anna-Lena; Bohlooly-Y, Mohammad

    2006-10-20

    Using the mouse as a model organism in pharmaceutical research presents unique advantages as its physiology in many ways resembles the human physiology, it also has a relatively short generation time, low breeding and maintenance costs, and is available in a wide variety of inbred strains. The ability to genetically modify mouse embryonic stem cells to generate mouse models that better mimic human disease is another advantage. In the present study, a comprehensive phenotypic screening protocol is applied to elucidate the phenotype of a novel mouse knockout model of hepatocyte nuclear factor (HNF) 4-gamma. HNF4-gamma is expressed in the kidneys, gut, pancreas, and testis. The first level of the screen is aimed at general health, morphologic appearance, normal cage behaviour, and gross neurological functions. The second level of the screen looks at metabolic characteristics and lung function. The third level of the screen investigates behaviour more in-depth and the fourth level consists of a thorough pathological characterisation, blood chemistry, haematology, and bone marrow analysis. When compared with littermate wild-type mice (HNF4-gamma(+/+)), the HNF4-gamma knockout (HNF4-gamma(-/-)) mice had lowered energy expenditure and locomotor activity during night time that resulted in a higher body weight despite having reduced intake of food and water. HNF4-gamma(-/-) mice were less inclined to build nest and were found to spend more time in a passive state during the forced swim test.

  7. Leishmania donovani activates nuclear transcription factor-κB in macrophages through reactive oxygen intermediates

    International Nuclear Information System (INIS)

    Km Singh, Vandana; Balaraman, Sridevi; Tewary, Poonam; Madhubala, Rentala

    2004-01-01

    Interaction of Leishmania donovani with macrophages antagonizes host defense mechanisms by interfering with a cascade of cell signaling processes in the macrophages. An early intracellular signaling event that follows receptor engagement is the activation of transcription factor NF-κB. It has been reported earlier that NF-κB-dependent signaling pathway regulates proinflammatory cytokine release. We therefore investigated the effect of L. donovani infectivity on this nuclear transcription factor in macrophage cell line J774A.1. Both L. donovani and its surface molecule lipophosphoglycan (LPG) resulted in a dose- and time-dependent activation of NF-κB-DNA binding activity in an electrophoretic mobility shift assay. We also report the involvement of IκB-α and IκB-β in the persistent activation of NF-κB by L. donovani. We demonstrate that the NF-κB activation was independent of viability of the parasite. Electrophoretic mobility supershift assay indicated that the NF-κB complex consists of p65 and c-rel subunits. The interaction of parasite with the macrophages and not the cellular uptake was important for NF-κB activation. Both p38 and ERK mitogen activated protein kinase (MAP) activation appears to be necessary for NF-κB activation by LPG. Preincubation of cells with antioxidants resulted in inhibition of L. donovani induced NF-κB activation, thereby suggesting a potential role of reactive oxygen species in L. donovani induced intracellular signaling. The present data indicate that antioxidants could play an important role in working out various therapeutic modalities to control leishmaniasis

  8. Proliferating cell nuclear antigen (PCNA): a key factor in DNA replication and cell cycle regulation.

    Science.gov (United States)

    Strzalka, Wojciech; Ziemienowicz, Alicja

    2011-05-01

    PCNA (proliferating cell nuclear antigen) has been found in the nuclei of yeast, plant and animal cells that undergo cell division, suggesting a function in cell cycle regulation and/or DNA replication. It subsequently became clear that PCNA also played a role in other processes involving the cell genome. This review discusses eukaryotic PCNA, with an emphasis on plant PCNA, in terms of the protein structure and its biochemical properties as well as gene structure, organization, expression and function. PCNA exerts a tripartite function by operating as (1) a sliding clamp during DNA synthesis, (2) a polymerase switch factor and (3) a recruitment factor. Most of its functions are mediated by its interactions with various proteins involved in DNA synthesis, repair and recombination as well as in regulation of the cell cycle and chromatid cohesion. Moreover, post-translational modifications of PCNA play a key role in regulation of its functions. Finally, a phylogenetic comparison of PCNA genes suggests that the multi-functionality observed in most species is a product of evolution. Most plant PCNAs exhibit features similar to those found for PCNAs of other eukaryotes. Similarities include: (1) a trimeric ring structure of the PCNA sliding clamp, (2) the involvement of PCNA in DNA replication and repair, (3) the ability to stimulate the activity of DNA polymerase δ and (4) the ability to interact with p21, a regulator of the cell cycle. However, many plant genomes seem to contain the second, probably functional, copy of the PCNA gene, in contrast to PCNA pseudogenes that are found in mammalian genomes.

  9. Nuclear Factor kappa B is required for the production of infectious human herpesvirus 8 virions

    Directory of Open Access Journals (Sweden)

    Negin N Blattman

    2014-04-01

    Full Text Available Human herpesvirus 8 (HHV8 infection leads to potent activation of nuclear factor kappa B (NFB in primary and transformed cells. We used recombinant HHV8 (rKSHV.219 expressing green fluorescent protein under the constitutive cellular promoter elongation factor 2 and red fluorescent protein under an early HHV8 lytic gene promoter T1.1, to monitor replication during infection of human foreskin fibroblasts (HF, noting changes in NFB activity. In primary HF, NFB levels do not affect HHV8 ability to establish infection or maintain latency. Furthermore, there was no effect on the percent of cells undergoing reactivation from latency, and there were similar numbers of released and cell associated HHV8 viral particles following reactivation in the presence of inhibitors. Reactivation of HHV8 in latently infected HF in the presence of NFB inhibitors resulted in production of viral particles that did not efficiently establish infection, due to deficiencies in binding and/or entry into normally permissive cells. Exogenous expression of glycoprotein M, an envelope protein involved in viral binding and entry was able to partially overcome the deficiency induced by NFB inhibitors. Our data indicate that in primary cells, NFB is not required for infection, establishment of latency, or entry into the lytic cycle, but is required for the expression of virion associated genes involved in the initial steps of virion infectivity. These studies suggest that strategies to inhibit NFB may prevent HHV8 spread and should be considered as a potential therapeutic target for preventing HHV8 associated diseases.

  10. Dextromethorphan inhibits osteoclast differentiation by suppressing RANKL-induced nuclear factor-κB activation.

    Science.gov (United States)

    Wu, Karl; Lin, Tzu-Hung; Liou, Houng-Chi; Lu, Dai-Hua; Chen, Yi-Ru; Fu, Wen-Mei; Yang, Rong-Sen

    2013-08-01

    Dextromethorphan (DXM), a commonly used antitussive, is a dextrorotatory morphinan. Here, we report that DXM inhibits the receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclastogenesis and bone resorption by abrogating the activation of NF-κB signalling in vitro. Oral administration of DXM ameliorates ovariectomy (OVX)-induced osteoporosis in vivo. DXM was reported to possess anti-inflammatory properties through inhibition of the release of pro-inflammatory factors. However, the potential role and action mechanism of DXM on osteoclasts and osteoblasts remain unclear. In this study, in vitro and in vivo studies were performed to investigate the potential effects of DXM on osteoclastogenesis and OVX-induced bone loss. Osteoclastogenesis was examined by the TRAP staining, pit resorption, TNF-α release, and CCR2 and CALCR gene expression. Osteoblast differentiation was analyzed by calcium deposition. Osteogenic and adipogenic genes were measured by real-time PCR. Signaling pathways were explored using Western blot. ICR mice were used in an OVX-induced osteoporosis model. Tibiae were measured by µCT and serum markers were examined with ELISA kits. DXM inhibited RANKL-induced osteoclastogenesis. DXM mainly inhibited osteoclastogenesis via abrogation of IKK-IκBα-NF-κB pathways. However, a higher dosage of DXM antagonized the differentiation of osteoblasts via the inhibition of osteogenic signals and increase of adipogenic signals. Oral administration of DXM (20 mg/kg/day) partially reduced trabecular bone loss in ovariectomized mice. DXM inhibits osteoclast differentiation and activity by affecting NF-κB signaling. Therefore, DXM at suitable doses may have new therapeutic applications for the treatment of diseases associated with excessive osteoclastic activity.

  11. Ghrelin Attenuated Lipotoxicity via Autophagy Induction and Nuclear Factor-κB Inhibition

    Directory of Open Access Journals (Sweden)

    Yuqing Mao

    2015-09-01

    Full Text Available Background/Aims: Nonalcoholic fatty liver disease (NAFLD is the most common chronic liver disease worldwide. Autophagy is associated with NAFLD. Ghrelin is a gut hormone with various functions including energy metabolism and inflammation inhibition. We investigated the therapeutic effect of ghrelin on NAFLD and its association with autophagy. Methods: C57bl/6 mice were fed a high-fat diet for 8 weeks to induce a model of chronic NAFLD, with ghrelin (10 µg/kg administrated subcutaneously twice weekly from weeks 6 to 8. LO2 cells were pretreated with ghrelin (10-8 M before stimulation with free fatty acid (palmitic and oleic acids; 1 mM. Lipid droplets were identified by hematoxylin and eosin and Red O staining and quantified by triglyceride test kits. LC3I/II, an important biomarker protein of autophagy was detected by western blotting, real-time polymerase chain reaction, immunohistochemistry and immunofluorescence. Tumor necrosis factor (TNF-a and interleukin (IL-6 were detected by ELISA and immunohistochemistry. Nuclear factor (NF-κB p65 was detected by western blotting and immunofluorescence. AMP-activated protein kinase (AMPK and mammalian target of rapamycin (mTOR were detected by western blotting. Results: Ghrelin reduced the triglyceride content in high fat diet (HFD group in vivo and free fatty acid (FFA group in vitro. TNF-a and IL-6 were significantly reduced in the ghrelin-treated mice compared with the control group. Autophagy induction was accompanied with intracellular lipid reduction in ghrelin-treated mice. Ghrelin upregulated autophagy via AMPK/mTOR restoration and inhibited translocation of NF-κB into the nucleus. Conclusions: The results indicate that ghrelin attenuates lipotoxicity by autophagy stimulation and NF-κB inhibition.

  12. Virus-Like Particles Derived from HIV-1 for Delivery of Nuclear Proteins: Improvement of Production and Activity by Protein Engineering.

    Science.gov (United States)

    Robert, Marc-André; Lytvyn, Viktoria; Deforet, Francis; Gilbert, Rénald; Gaillet, Bruno

    2017-01-01

    Virus-like particles (VLPs) derived from retroviruses and lentiviruses can be used to deliver recombinant proteins without the fear of causing insertional mutagenesis to the host cell genome. In this study we evaluate the potential of an inducible lentiviral vector packaging cell line for VLP production. The Gag gene from HIV-1 was fused to a gene encoding a selected protein and it was transfected into the packaging cells. Three proteins served as model: the green fluorescent protein and two transcription factors-the cumate transactivator (cTA) of the inducible CR5 promoter and the human Krüppel-like factor 4 (KLF4). The sizes of the VLPs were 120-150 nm in diameter and they were resistant to freeze/thaw cycles. Protein delivery by the VLPs reached up to 100% efficacy in human cells and was well tolerated. Gag-cTA triggered up to 1100-fold gene activation of the reporter gene in comparison to the negative control. Protein engineering was required to detect Gag-KLF4 activity. Thus, insertion of the VP16 transactivation domain increased the activity of the VLPs by eightfold. An additional 2.4-fold enhancement was obtained by inserting nuclear export signal. In conclusion, our platform produced VLPs capable of efficient protein transfer, and it was shown that protein engineering can be used to improve the activity of the delivered proteins as well as VLP production.

  13. Costs of construction, operation and maintenance of nuclear power plants - determinant factors

    International Nuclear Information System (INIS)

    Silva, R.A. da

    1981-01-01

    A study about the construction costs of the Angra-1 nuclear power plant, including direct costs, equipment costs, installation and indirect costs such as: engineering, job-training and administration is presented. The operation and maintenance costs of the Angra-1 nuclear power plant and costs of energy generation are still studied. (E.G.) [pt

  14. Roles of PU.1 in monocyte- and mast cell-specific gene regulation: PU.1 transactivates CIITA pIV in cooperation with IFN-gamma.

    Science.gov (United States)

    Ito, Tomonobu; Nishiyama, Chiharu; Nakano, Nobuhiro; Nishiyama, Makoto; Usui, Yoshihiko; Takeda, Kazuyoshi; Kanada, Shunsuke; Fukuyama, Kanako; Akiba, Hisaya; Tokura, Tomoko; Hara, Mutsuko; Tsuboi, Ryoji; Ogawa, Hideoki; Okumura, Ko

    2009-07-01

    Over-expression of PU.1, a myeloid- and lymphoid-specific transcription factor belonging to the Ets family, induces monocyte-specific gene expression in mast cells. However, the effects of PU.1 on each target gene and the involvement of cytokine signaling in PU.1-mediated gene expression are largely unknown. In the present study, PU.1 was over-expressed in two different types of bone marrow-derived cultured mast cells (BMMCs): BMMCs cultured with IL-3 plus stem cell factor (SCF) and BMMCs cultured with pokeweed mitogen-stimulated spleen-conditioned medium (PWM-SCM). PU.1 over-expression induced expression of MHC class II, CD11b, CD11c and F4/80 on PWM-SCM-cultured BMMCs, whereas IL-3/SCF-cultured BMMCs expressed CD11b and F4/80, but not MHC class II or CD11c. When IFN-gamma was added to the IL-3/SCF-based medium, PU.1 transfectant acquired MHC class II expression, which was abolished by antibody neutralization or in Ifngr(-/-) BMMCs, through the induction of expression of the MHC class II transactivator, CIITA. Real-time PCR detected CIITA mRNA driven by the fourth promoter, pIV, and chromatin immunoprecipitation indicated direct binding of PU.1 to pIV in PU.1-over-expressing BMMCs. PU.1-over-expressing cells showed a marked increase in IL-6 production in response to LPS stimulation in both IL-3/SCF and PWM-SCM cultures. These results suggest that PU.1 overproduction alone is sufficient for both expression of CD11b and F4/80 and for amplification of LPS-induced IL-6 production. However, IFN-gamma stimulation is essential for PU.1-mediated transactivation of CIITA pIV. Reduced expression of mast cell-related molecules and transcription factors GATA-1/2 and up-regulation of C/EBPalpha in PU.1 transfectants indicate that enforced PU.1 suppresses mast cell-specific gene expression through these transcription factors.

  15. Visualization of nuclear localization of transcription factors with cyan and green fluorescent proteins in the red alga Porphyra yezoensis.

    Science.gov (United States)

    Uji, Toshiki; Takahashi, Megumu; Saga, Naotsune; Mikami, Koji

    2010-04-01

    Transcription factors play a central role in expression of genomic information in all organisms. The objective of our study is to analyze the function of transcription factors in red algae. One way to analyze transcription factors in eukaryotic cells is to study their nuclear localization, as reported for land plants and green algae using fluorescent proteins. There is, however, no report documenting subcellular localization of transcription factors from red algae. In the present study, using the marine red alga Porphyra yezoensis, we confirmed for the first time successful expression of humanized fluorescent proteins (ZsGFP and ZsYFP) from a reef coral Zoanthus sp. and land plant-adapted sGFP(S65T) in gametophytic cells comparable to expression of AmCFP. Following molecular cloning and characterization of transcription factors DP-E2F-like 1 (PyDEL1), transcription elongation factor 1 (PyElf1) and multiprotein bridging factor 1 (PyMBF1), we then demonstrated that ZsGFP and AmCFP can be used to visualize nuclear localization of PyElf1 and PyMBF1. This is the first report to perform visualization of subcellular localization of transcription factors as genome-encoded proteins in red algae.

  16. Natural radiation - a perspective to radiological risk factors of nuclear energy production

    DEFF Research Database (Denmark)

    Mustonen, R.; Christensen, T.; Stranden, E.

    1992-01-01

    Radiation doses from natural radiation and from man-made modifications on natural radiation, and different natural radiological environments in the Nordic countries are summarized and used as a perspective for the radiological consequences of nuclear energy production. The significance of different...... radiation sources can be judged against the total collective effective dose equivalent from natural radiation in the Nordic countries, 92 000 manSv per year. The collective dose from nuclear energy production during normal operation is estimated to 20 manSv per year and from non-nuclear energy production...... of radionuclides from a final repository of spent nuclear fuel to the consequences of natural radionuclides in different environments. The danger index of natural radiological environments will not be significantly increased by future releases of nuclear fuel radionuclides....

  17. SOX9 governs differentiation stage-specific gene expression in growth plate chondrocytes via direct concomitant transactivation and repression.

    Directory of Open Access Journals (Sweden)

    Victor Y L Leung

    2011-11-01

    Full Text Available Cartilage and endochondral bone development require SOX9 activity to regulate chondrogenesis, chondrocyte proliferation, and transition to a non-mitotic hypertrophic state. The restricted and reciprocal expression of the collagen X gene, Col10a1, in hypertrophic chondrocytes and Sox9 in immature chondrocytes epitomise the precise spatiotemporal control of gene expression as chondrocytes progress through phases of differentiation, but how this is achieved is not clear. Here, we have identified a regulatory element upstream of Col10a1 that enhances its expression in hypertrophic chondrocytes in vivo. In immature chondrocytes, where Col10a1 is not expressed, SOX9 interacts with a conserved sequence within this element that is analogous to that within the intronic enhancer of the collagen II gene Col2a1, the known transactivation target of SOX9. By analysing a series of Col10a1 reporter genes in transgenic mice, we show that the SOX9 binding consensus in this element is required to repress expression of the transgene in non-hypertrophic chondrocytes. Forced ectopic Sox9 expression in hypertrophic chondrocytes in vitro and in mice resulted in down-regulation of Col10a1. Mutation of a binding consensus motif for GLI transcription factors, which are the effectors of Indian hedgehog signaling, close to the SOX9 site in the Col10a1 regulatory element, also derepressed transgene expression in non-hypertrophic chondrocytes. GLI2 and GLI3 bound to the Col10a1 regulatory element but not to the enhancer of Col2a1. In addition to Col10a1, paired SOX9-GLI binding motifs are present in the conserved non-coding regions of several genes that are preferentially expressed in hypertrophic chondrocytes and the occurrence of pairing is unlikely to be by chance. We propose a regulatory paradigm whereby direct concomitant positive and negative transcriptional control by SOX9 ensures differentiation phase-specific gene expression in chondrocytes. Discrimination between

  18. Involvement of nuclear factor {kappa}B in platelet CD40 signaling

    Energy Technology Data Exchange (ETDEWEB)

    Hachem, Ahmed [Laboratory of Thrombosis and Hemostasis, Montreal Heart Institute, 5000 Belanger, Montreal, Quebec, Canada H1T 1C8 (Canada); Yacoub, Daniel [Laboratory of Thrombosis and Hemostasis, Montreal Heart Institute, 5000 Belanger, Montreal, Quebec, Canada H1T 1C8 (Canada); Centre Hospitalier Universite de Montreal, 264 boul. Rene-Levesque est, Montreal, Quebec, Canada H2X 1P1 (Canada); Zaid, Younes [Laboratory of Thrombosis and Hemostasis, Montreal Heart Institute, 5000 Belanger, Montreal, Quebec, Canada H1T 1C8 (Canada); Mourad, Walid [Universite de Montreal, Department of Medicine, 2900 boul. Edouard-Montpetit, Montreal, Quebec, Canada H3T 1J4 (Canada); Centre Hospitalier Universite de Montreal, 264 boul. Rene-Levesque est, Montreal, Quebec, Canada H2X 1P1 (Canada); Merhi, Yahye, E-mail: yahye.merhi@icm-mhi.org [Laboratory of Thrombosis and Hemostasis, Montreal Heart Institute, 5000 Belanger, Montreal, Quebec, Canada H1T 1C8 (Canada); Universite de Montreal, Department of Medicine, 2900 boul. Edouard-Montpetit, Montreal, Quebec, Canada H3T 1J4 (Canada)

    2012-08-17

    Highlights: Black-Right-Pointing-Pointer sCD40L induces TRAF2 association to CD40 and NF-{kappa}B activation in platelets. Black-Right-Pointing-Pointer I{kappa}B{alpha} phosphorylation downstream of CD40L/CD40 signaling is independent of p38 MAPK phosphorylation. Black-Right-Pointing-Pointer I{kappa}B{alpha} is required for sCD40L-induced platelet activation and potentiation of aggregation. -- Abstract: CD40 ligand (CD40L) is a thrombo-inflammatory molecule that predicts cardiovascular events. Platelets constitute the major source of soluble CD40L (sCD40L), which has been shown to potentiate platelet activation and aggregation, in a CD40-dependent manner, via p38 mitogen activated protein kinase (MAPK) and Rac1 signaling. In many cells, the CD40L/CD40 dyad also induces activation of nuclear factor kappa B (NF-{kappa}B). Given that platelets contain NF-{kappa}B, we hypothesized that it may be involved in platelet CD40 signaling and function. In human platelets, sCD40L induces association of CD40 with its adaptor protein the tumor necrosis factor receptor associated factor 2 and triggers phosphorylation of I{kappa}B{alpha}, which are abolished by CD40L blockade. Inhibition of I{kappa}B{alpha} phosphorylation reverses sCD40L-induced I{kappa}B{alpha} phosphorylation without affecting p38 MAPK phosphorylation. On the other hand, inhibition of p38 MAPK phosphorylation has no effect on I{kappa}B{alpha} phosphorylation, indicating a divergence in the signaling pathway originating from CD40 upon its ligation. In functional studies, inhibition of I{kappa}B{alpha} phosphorylation reverses sCD40L-induced platelet activation and potentiation of platelet aggregation in response to a sub-threshold concentration of collagen. This study demonstrates that the sCD40L/CD40 axis triggers NF-{kappa}B activation in platelets. This signaling pathway plays a critical role in platelet activation and aggregation upon sCD40L stimulation and may represent an important target against thrombo

  19. Involvement of nuclear factor κB in platelet CD40 signaling

    International Nuclear Information System (INIS)

    Hachem, Ahmed; Yacoub, Daniel; Zaid, Younes; Mourad, Walid; Merhi, Yahye

    2012-01-01

    Highlights: ► sCD40L induces TRAF2 association to CD40 and NF-κB activation in platelets. ► IκBα phosphorylation downstream of CD40L/CD40 signaling is independent of p38 MAPK phosphorylation. ► IκBα is required for sCD40L-induced platelet activation and potentiation of aggregation. -- Abstract: CD40 ligand (CD40L) is a thrombo-inflammatory molecule that predicts cardiovascular events. Platelets constitute the major source of soluble CD40L (sCD40L), which has been shown to potentiate platelet activation and aggregation, in a CD40-dependent manner, via p38 mitogen activated protein kinase (MAPK) and Rac1 signaling. In many cells, the CD40L/CD40 dyad also induces activation of nuclear factor kappa B (NF-κB). Given that platelets contain NF-κB, we hypothesized that it may be involved in platelet CD40 signaling and function. In human platelets, sCD40L induces association of CD40 with its adaptor protein the tumor necrosis factor receptor associated factor 2 and triggers phosphorylation of IκBα, which are abolished by CD40L blockade. Inhibition of IκBα phosphorylation reverses sCD40L-induced IκBα phosphorylation without affecting p38 MAPK phosphorylation. On the other hand, inhibition of p38 MAPK phosphorylation has no effect on IκBα phosphorylation, indicating a divergence in the signaling pathway originating from CD40 upon its ligation. In functional studies, inhibition of IκBα phosphorylation reverses sCD40L-induced platelet activation and potentiation of platelet aggregation in response to a sub-threshold concentration of collagen. This study demonstrates that the sCD40L/CD40 axis triggers NF-κB activation in platelets. This signaling pathway plays a critical role in platelet activation and aggregation upon sCD40L stimulation and may represent an important target against thrombo-inflammatory disorders.

  20. Phosphatidic acid interacts with a MYB transcription factor and regulates its nuclear localization and function in Arabidopsis.

    Science.gov (United States)

    Yao, Hongyan; Wang, Geliang; Guo, Liang; Wang, Xuemin

    2013-12-01

    Phosphatidic acid (PA) has emerged as a class of cellular mediators involved in various cellular and physiological processes, but little is known about its mechanism of action. Here we show that PA interacts with werewolf (WER), a R2R3 MYB transcription factor involved in root hair formation. The PA-interacting region is confined to the end of the R2 subdomain. The ablation of the PA binding motif has no effect on WER binding to DNA, but abolishes its nuclear localization and its function in regulating epidermal cell fate. Inhibition of PA production by phospholipase Dζ also suppresses WER's nuclear localization, root hair formation, and elongation. These results suggest a role for PA in promoting protein nuclear localization.

  1. Phosphatidic Acid Interacts with a MYB Transcription Factor and Regulates Its Nuclear Localization and Function in Arabidopsis[C][W

    Science.gov (United States)

    Yao, Hongyan; Wang, Geliang; Guo, Liang; Wang, Xuemin

    2013-01-01

    Phosphatidic acid (PA) has emerged as a class of cellular mediators involved in various cellular and physiological processes, but little is known about its mechanism of action. Here we show that PA interacts with WEREWOLF (WER), a R2R3 MYB transcription factor involved in root hair formation. The PA-interacting region is confined to the end of the R2 subdomain. The ablation of the PA binding motif has no effect on WER binding to DNA, but abolishes its nuclear localization and its function in regulating epidermal cell fate. Inhibition of PA production by phospholipase Dζ also suppresses WER’s nuclear localization, root hair formation, and elongation. These results suggest a role for PA in promoting protein nuclear localization. PMID:24368785

  2. Human Factors Engineering Incorporated into the Carolina Power and Light company's nuclear power plant control panel modifications

    International Nuclear Information System (INIS)

    Beith, D.M.; Shoemaker, E.M.; Horn, K.; Boush, D.

    1988-01-01

    Maintaining human factors conventions/practices that were established during the Detailed Control Design Review (DCRDR), is difficult if Human Factors Engineering (HFE) is not incorporated into the plant modification process. This paper presents the approach used at Carolina Power and Light's nuclear power plants that has successfully incorporated human factors engineering into their plant modification process. An HFE Design Guide or HFE Specification was developed which is used by the design engineers or plant engineering support groups in the preparation of plant modifications

  3. First principles calculations of nucleon and pion form factors: understanding the building blocks of nuclear matter from lattice QCD

    International Nuclear Information System (INIS)

    Constantia Alexandrou; Bojan Bistrovic; Robert Edwards; P de Forcrand; George Fleming; Philipp Haegler; John Negele; Konstantinos Orginos; Andrew Pochinsky; Dru Renner; David Richards; Wolfram Schroers; Antonios Tsapalis

    2005-01-01

    Lattice QCD is an essential complement to the current and anticipated DOE-supported experimental program in hadronic physics. In this poster we address several key questions central to our understanding of the building blocks of nuclear matter, nucleons and pions. Firstly, we describe progress at computing the electromagnetic form factors of the nucleon, describing the distribution of charge and current, before considering the role played by the strange quarks. We then describe the study of transition form factors to the Delta resonance. Finally, we present recent work to determine the pion form factor, complementary to the current JLab experimental determination and providing insight into the approach to asymptotic freedom

  4. Report of the Nuclear Energy Agency expert group on gut transfer factors: implications for dose per unit intake

    International Nuclear Information System (INIS)

    1988-01-01

    This note describes the gut transfer factors recommended by an Expert Group of the Nuclear Energy Agency for intakes of certain important elements in food and drinking water. The evidence behind the recommendations is discussed and their implications for dose per unit intake is investigated. It is found that in many cases the dose per unit intake calculated using the gut uptake factor recommended by the Expert Group is similar to that calculated using the recommendations of ICRP Publication 30. However, in some cases there are substantial increases in dose per unit intake. The largest increases are by a factor of fifty for intakes of certain thorium isotopes by infants. (author)

  5. First principles calculations of nucleon and pion form factors: understanding the building blocks of nuclear matter from lattice QCD

    Energy Technology Data Exchange (ETDEWEB)

    Constantia Alexandrou; Bojan Bistrovic; Robert Edwards; P de Forcrand; George Fleming; Philipp Haegler; John Negele; Konstantinos Orginos; Andrew Pochinsky; Dru Renner; David Richards; Wolfram Schroers; Antonios Tsapalis

    2005-10-01

    Lattice QCD is an essential complement to the current and anticipated DOE-supported experimental program in hadronic physics. In this poster we address several key questions central to our understanding of the building blocks of nuclear matter, nucleons and pions. Firstly, we describe progress at computing the electromagnetic form factors of the nucleon, describing the distribution of charge and current, before considering the role played by the strange quarks. We then describe the study of transition form factors to the Delta resonance. Finally, we present recent work to determine the pion form factor, complementary to the current JLab experimental determination and providing insight into the approach to asymptotic freedom.

  6. Identification of a phosphorylation-dependent nuclear localization motif in interferon regulatory factor 2 binding protein 2.

    Directory of Open Access Journals (Sweden)

    Allen C T Teng

    Full Text Available Interferon regulatory factor 2 binding protein 2 (IRF2BP2 is a muscle-enriched transcription factor required to activate vascular endothelial growth factor-A (VEGFA expression in muscle. IRF2BP2 is found in the nucleus of cardiac and skeletal muscle cells. During the process of skeletal muscle differentiation, some IRF2BP2 becomes relocated to the cytoplasm, although the functional significance of this relocation and the mechanisms that control nucleocytoplasmic localization of IRF2BP2 are not yet known.Here, by fusing IRF2BP2 to green fluorescent protein and testing a series of deletion and site-directed mutagenesis constructs, we mapped the nuclear localization signal (NLS to an evolutionarily conserved sequence (354ARKRKPSP(361 in IRF2BP2. This sequence corresponds to a classical nuclear localization motif bearing positively charged arginine and lysine residues. Substitution of arginine and lysine with negatively charged aspartic acid residues blocked nuclear localization. However, these residues were not sufficient because nuclear targeting of IRF2BP2 also required phosphorylation of serine 360 (S360. Many large-scale phosphopeptide proteomic studies had reported previously that serine 360 of IRF2BP2 is phosphorylated in numerous human cell types. Alanine substitution at this site abolished IRF2BP2 nuclear localization in C(2C(12 myoblasts and CV1 cells. In contrast, substituting serine 360 with aspartic acid forced nuclear retention and prevented cytoplasmic redistribution in differentiated C(2C(12 muscle cells. As for the effects of these mutations on VEGFA promoter activity, the S360A mutation interfered with VEGFA activation, as expected. Surprisingly, the S360D mutation also interfered with VEGFA activation, suggesting that this mutation, while enforcing nuclear entry, may disrupt an essential activation function of IRF2BP2.Nuclear localization of IRF2BP2 depends on phosphorylation near a conserved NLS. Changes in phosphorylation status

  7. Phosphorylation of bovine leukemia virus Tax protein is required for in vitro transformation but not for transactivation.

    Science.gov (United States)

    Willems, L; Grimonpont, C; Kerkhofs, P; Capiau, C; Gheysen, D; Conrath, K; Roussef, R; Mamoun, R; Portetelle, D; Burny, A; Adam, E; Lefèbvre, L; Twizere, J C; Heremans, H; Kettmann, R

    1998-04-30

    The Tax proteins of the oncovirinae viruses are phosphorylated transcriptional activators that exhibit oncogenic potential. The role of phosphorylation in their functional activities remains unknown. As a model for the Human T-cell leukemia virus type I (HTLV-I), Bovine Leukemia Virus (BLV) permits the characterization of viral replication and leukemogenesis in vivo. Here, we show that the BLV Tax protein is phosphorylated on serine residues 106 and 293 both in insect and in mammalian cells. These sites can also be efficiently phosphorylated by the cdc2 and MAP kinases in vitro. Mutation of these residues does not affect the capacity of the Tax protein to function as a transactivator. Indeed, the Tax proteins mutated at one or both serines increase LTR-directed viral transcription at levels similar to those obtained with wild-type Tax in cell culture. Moreover, inhibition of Tax phosphorylation by W7, a calmodulin antagonist, does not alter its transactivation activity. Thus, phosphorylation on serines 106 and 293 is not required for transactivation by Tax. However, simultaneous substitution of both serines into alanine residues destroys the capacity of Tax to cooperate with the Ha-ras oncogene to transform primary rat embryo fibroblasts and induce tumors in nude mice. When the serines were replaced with aspartic acid residues, the oncogenic potential of Tax was maintained indicating that the negative charge rather than the phosphate group itself was required for Tax oncogenicity. Finally, to assess the role of the serine residues in vivo, recombinant viruses which express the Tax mutants were constructed and injected into sheep. It appeared that the mutated proviruses replicate at levels similar to the wild-type virus in vivo. We conclude that Tax phosphorylation is dispensable for transactivation and viral replication in vivo but is required for its oncogenic potential in vitro.

  8. Slug suppression induces apoptosis via Puma transactivation in rheumatoid arthritis fibroblast-like synoviocytes treated with hydrogen peroxide

    OpenAIRE

    Cha, Hoon-Suk; Bae, Eun-Kyung; Ahn, Joong Kyong; Lee, Jaejoon; Ahn, Kwang-Sung; Koh, Eun-Mi

    2010-01-01

    Inadequate apoptosis contributes to synovial hyperplasia in rheumatoid arthritis (RA). Recent study shows that low expression of Puma might be partially responsible for the decreased apoptosis of fibroblast-like synoviocytes (FLS). Slug, a highly conserved zinc finger transcriptional repressor, is known to antagonize apoptosis of hematopoietic progenitor cells by repressing Puma transactivation. In this study, we examined the expression and function of Slug in RA FLS. Slug mRNA expression was...

  9. A formal design verification and validation on the human factors of a computerized information system in nuclear power plants

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Yong Hee; Park, Jae Chang; Cheon, Se Woo; Jung, Kwang Tae; Baek, Seung Min; Han, Seung; Park, Hee Suk; Son, Ki Chang; Kim, Jung Man; Jung Yung Woo

    1999-11-01

    This report describe a technical transfer under the title of ''A formal design verification and validation on the human factors of a computerized information system in nuclear power plants''. Human factors requirements for the information system designs are extracted from various regulatory and industrial standards and guidelines, and interpreted into a more specific procedures and checklists for verifying the satisfaction of those requirements. A formalized implementation plan is established for human factors verification and validation of a computerized information system in nuclear power plants. Additionally, a Computer support system, named as DIMS-web (design Issue Management System), is developed based upon web internet environment so as to enhance the implementation of the human factors activities. DIMS-Web has three maine functions: supporting requirements review, tracking design issues, and management if issues screening evaluation. DIMS-Web shows its benefits in practice through a trial application to the design review of CFMS for YGN nuclear unit 5 and 6. (author)

  10. Integrated System Validation of Barakah Nuclear Power Plant in UAE for The Human Factor Engineering

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Munsoo [KHNP CRI, Daejeon (Korea, Republic of)

    2016-10-15

    APR1400 simulator has been developed based on the state-of-the-art object-oriented simulation technology of TH(Thermo-Hydraulic) and Reactor Core model, which is applied for the first time in the our country and for the exportation, to well simulate characteristics of APR1400. Barakah unit 1,2 simulator are constructed and supplied with this type simulator model. Integrated system validation was performed using a simulator to verify the HFE(Human Factor Engineering) design of the MCR(Maim Control Room) for instrumentation and control system validation of the UAE nuclear power plant. APR1400 for the Barakah unit 1,2 has many specific features such as digital I and C, and digitalized main control room (MCR) design. From January 2016 to February, during six weeks, the tests carried out three times repeatedly and the various proposals for ergonomical satisfactation were derived. However, the HFE errors that cause significant change of validation target for APR1400 MCR design safety fidelity wasn't found. This has resulted in the conclusion to prove the stability of the basic design of APR1400 MCR. In the future, using the simulator derives the HFE requirements of the MCR systems and continually improve the simulator will be built in close to real high-fidelity power plant. These Integrated system validations are likely to be a great help in operating safety and preventing human errors by operators. Therefore successful completion of the Integrated System Validation for BNPP simulation will be effective to promotion the distinction of our simulator and APR1400 NPP.

  11. Radiation damping and reciprocity in nuclear magnetic resonance: the replacement of the filling factor.

    Science.gov (United States)

    Tropp, James; Van Criekinge, Mark

    2010-09-01

    The basic equation describing radiation damping in nuclear magnetic resonance (NMR) is rewritten by means of the reciprocity principle, to remove the dependence of the damping constant upon filling factor - a parameter which is neither uniquely defined for easily measured. The new equation uses instead the transceive efficiency, i.e. the peak amplitude of the radiofrequency B field in laboratory coordinates, divided by the square root of the resistance of the detection coil, for which a simple and direct means of measurement exists. We use the efficiency to define the intrinsic damping constant, i.e. that which obtains when both probe and preamplifier are perfectly matched to the system impedance. For imperfect matching of the preamp, it is shown that the damping constant varies with electrical distance to the probe, and equations are given and simulations performed, to predict the distance dependence, which (for lossless lines) is periodic modulo a half wavelength. Experimental measurements of the radiation-damped free induction NMR signal of protons in neat water are performed at a static B field strength of 14.1T; and an intrinsic damping constant measured using the variable line method. For a sample of 5mm diameter, in an inverse detection probe we measure an intrinsic damping constant of 204 s(-1), corresponding to a damping linewidth of 65 Hz for small tip angles. The predicted intrinsic linewidth, based upon three separate measurements of the efficiency, is 52.3 Hz, or 80% of the measured value. (c) 2010 Elsevier Inc. All rights reserved.

  12. Human factors design of nuclear power plant control rooms including computer-based operator aids

    International Nuclear Information System (INIS)

    Bastl, W.; Felkel, L.; Becker, G.; Bohr, E.

    1983-01-01

    The scientific handling of human factors problems in control rooms began around 1970 on the basis of safety considerations. Some recent research work deals with the development of computerized systems like plant balance calculation, safety parameter display, alarm reduction and disturbance analysis. For disturbance analysis purposes it is necessary to homogenize the information presented to the operator according to the actual plant situation in order to supply the operator with the information he most urgently needs at the time. Different approaches for solving this problem are discussed, and an overview is given on what is being done. Other research projects concentrate on the detailed analysis of operators' diagnosis strategies in unexpected situations, in order to obtain a better understanding of their mental processes and the influences upon them when such situations occur. This project involves the use of a simulator and sophisticated recording and analysis methods. Control rooms are currently designed with the aid of mock-ups. They enable operators to contribute their experience to the optimization of the arrangement of displays and controls. Modern control rooms are characterized by increasing use of process computers and CRT (Cathode Ray Tube) displays. A general concept for the integration of the new computerized system and the conventional control panels is needed. The technical changes modify operators' tasks, and future ergonomic work in nuclear plants will need to consider the re-allocation of function between man and machine, the incorporation of task changes in training programmes, and the optimal design of information presentation using CRTs. Aspects of developments in control room design are detailed, typical research results are dealt with, and a brief forecast of the ergonomic contribution to be made in the Federal Republic of Germany is given

  13. Nuclear translocation of doublecortin-like protein kinase and phosphorylation of a transcription factor JDP2

    Energy Technology Data Exchange (ETDEWEB)

    Nagamine, Tadashi; Nomada, Shohgo; Onouchi, Takashi; Kameshita, Isamu; Sueyoshi, Noriyuki, E-mail: sueyoshi@ag.kagawa-u.ac.jp

    2014-03-28

    Highlights: • Doublecortin-like protein kinase (DCLK) is a microtubule-associated protein kinase. • In living cells, DCLK was cleaved into two functional fragments. • zDCLK(kinase) was translocated into the nucleus by osmotic stresses. • Jun dimerization protein 2 (JDP2) was identified as zDCLK(kinase)-binding protein. • JDP2 was efficiently phosphorylated by zDCLK(kinase) only when histone was present. - Abstract: Doublecortin-like protein kinase (DCLK) is a microtubule-associated protein kinase predominantly expressed in brain. In a previous paper, we reported that zebrafish DCLK2 (zDCLK) was cleaved into two functional fragments; the N-terminal zDCLK(DC + SP) with microtubule-binding activity and the C-terminal zDCLK(kinase) with a Ser/Thr protein kinase activity. In this study, we demonstrated that zDCLK(kinase) was widely distributed in the cytoplasm and translocated into the nucleus when the cells were treated under hyperosmotic conditions with NaCl or mannitol. By two-hybrid screening using the C-terminal domain of DCLK, Jun dimerization protein 2 (JDP2), a nuclear transcription factor, was identified as zDCLK(kinase)-binding protein. Furthermore, JDP2 served as an efficient substrate for zDCLK(kinase) only when histone was present. These results suggest that the kinase fragment of DCLK is translocated into the nucleus upon hyperosmotic stresses and that the kinase efficiently phosphorylates JDP2, a possible target in the nucleus, with the aid of histones.

  14. Nuclear factor-kappa B regulates pain and COMT expression in a rodent model of inflammation.

    Science.gov (United States)

    Hartung, Jane E; Eskew, Olivia; Wong, Terrence; Tchivileva, Inna E; Oladosu, Folabomi A; O'Buckley, Sandra C; Nackley, Andrea G

    2015-11-01

    Nuclear factor-kappa B (NF-κB) is a ubiquitously expressed protein complex regulating the transcription of genes involved in inflammation and pain. Increased NF-κB activity in immune and nervous system cells is linked to several chronic pain conditions in humans as well as inflammation and nerve injury-evoked pain in animals. A recent in vitro study further demonstrates that increased NF-κB activity in astrocytes decreases transcription of catechol-o-methyltransferase (COMT), an enzyme that inactivates catecholamines that cause pain. The purpose of the present study was to examine the relationship between systemic and astrocytic NF-κB activity, pain, and COMT expression in an animal model of inflammation. Results demonstrated that administration of the inflammatory stimulant complete Freund's adjuvant (CFA) led to increased pain and decreased COMT protein expression in an NF-κB-dependent manner. Specifically, we found that rats and mice receiving intraplantar CFA exhibited increased behavioral responses to mechanical and thermal heat stimuli. CFA-evoked pain was blocked in rats receiving a pre-emptive systemic dose of the NF-κB inhibitor MG132 and exacerbated in IKKca mice with constitutive NF-κB activity in astrocytes. Furthermore, we observed NF-κB-linked reductions in COMT expression in midbrain at 6h and 1d following CFA in rats and at 1h and 1d in forebrain and midbrain following CFA in IKKca mice. Collectively, these results demonstrate that systemic and astrocytic NF-κB activity drive inflammatory pain and regulate the expression of COMT in forebrain and midbrain structures. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Genetic variation near the hepatocyte nuclear factor-4 alpha gene predicts susceptibility to type 2 diabetes.

    Science.gov (United States)

    Silander, Kaisa; Mohlke, Karen L; Scott, Laura J; Peck, Erin C; Hollstein, Pablo; Skol, Andrew D; Jackson, Anne U; Deloukas, Panagiotis; Hunt, Sarah; Stavrides, George; Chines, Peter S; Erdos, Michael R; Narisu, Narisu; Conneely, Karen N; Li, Chun; Fingerlin, Tasha E; Dhanjal, Sharanjeet K; Valle, Timo T; Bergman, Richard N; Tuomilehto, Jaakko; Watanabe, Richard M; Boehnke, Michael; Collins, Francis S

    2004-04-01

    The Finland-United States Investigation Of NIDDM Genetics (FUSION) study aims to identify genetic variants that predispose to type 2 diabetes by studying affected sibling pair families from Finland. Chromosome 20 showed our strongest initial evidence for linkage. It currently has a maximum logarithm of odds (LOD) score of 2.48 at 70 cM in a set of 495 families. In this study, we searched for diabetes susceptibility variant(s) at 20q13 by genotyping single nucleotide polymorphism (SNP) markers in case and control DNA pools. Of 291 SNPs successfully typed in a 7.5-Mb interval, the strongest association confirmed by individual genotyping was with SNP rs2144908, located 1.3 kb downstream of the primary beta-cell promoter P2 of hepatocyte nuclear factor-4 alpha (HNF4A). This SNP showed association with diabetes disease status (odds ratio [OR] 1.33, 95% CI 1.06-1.65, P = 0.011) and with several diabetes-related traits. Most of the evidence for linkage at 20q13 could be attributed to the families carrying the risk allele. We subsequently found nine additional associated SNPs spanning a 64-kb region, including the P2 and P1 promoters and exons 1-3. Our results and the independent observation of association of SNPs near the P2 promoter with diabetes in a separate study population of Ashkenazi Jewish origin suggests that variant(s) located near or within HNF4A increases susceptibility to type 2 diabetes.

  16. Exploratory study of the major factors influencing craft productivity in nuclear power plant construction. Volume I

    International Nuclear Information System (INIS)

    Sebastian, S.J.; Borcherding, J.D.

    1979-05-01

    The data for this study were collected at six nuclear power plant construction sites spread throughout the United States. The geographical distribution included two projects from the Midwest and one site from each the Deep South, North Central, Southwest, and Northeast regions of the nation. The range for stage of completion varied from between approximately four and seventy-seven percent. Two of the projects were utilizing boiling water reactors (BWR) while the balance of the sites made use of the pressurized water reactor (PWR) systems. All of the installations had generating capacities approximately equal to 1200 megawatts per unit. The primary objective of the study was to provide a comprehensive investigation of the most influential factors adversely affecting craft productivity by means of a sampling comprised of five hundred seventy-six union and open shop carpenters, electricians, and pipefitters. The overall average amount of time lost due to delays obtaining materials and tools, overcrowded working conditions, interferences between crews, postponements relating to quality control inspections, and waiting for and/or receiving instructions was estimated by the tradesmen to be 24.12 manhours per individual on a weekly basis. Thus, a minimum of 60.3% of each tradesman's time is lost due to one of the aforementioned predicaments. Conversely, this figure accounts for a maximum possible level of direct work activity equal to 39.7% and is not inclusive of any personal breaks or late starts/early quits. The combined mean duration that was speculated for rework activities at all six sites totaled 5.77 manhours per craftsman per week. The summation of these two estimates yields a value of 29.89 manhours showing that only slightly more than twenty-five percent of each worker's time is allocated to productive endeavors for activities being engaged in for the first time

  17. Crisis Stability and Nuclear Exchange Risks on the Subcontinent: Major Trends and the Iran Factor

    Science.gov (United States)

    2013-11-01

    Nuclear Deterrence,” in Nuclear Proliferation in South Asia: Crisis Behaviour and the Bomb, ed. Sumit Ganguly and S. Paul Kapur, 117–143 (London...Iran’s paid advertisement , “An Unnecessary Crisis—Setting the Record Straight about Iran’s Nuclear Program,” The New York Times, November 18, 2005...American and Western economic sanctions that followed Pakistan’s May 1998 response test. Riedel, “Saudi Arabia”; and Tomlinson. 100 See “Saudis ‘Mull Buying

  18. Immediate-early gene region of human cytomegalovirus trans-activates the promoter of human immunodeficiency virus

    Energy Technology Data Exchange (ETDEWEB)

    Davis, M.G.; Kenney, S.C.; Kamine, J.; Pagano, J.S.; Huang, E.S.

    1987-12-01

    Almost all homosexual patients with acquired immunodeficiency syndrome are also actively infected with human cytomegalovirus (HCMV). The authors have hypothesized that an interaction between HCMV and human immunodeficiency virus (HIV), the agent that causes acquired immunodeficiency syndrome, may exist at a molecular level and contribute to the manifestations of HIV infection. In this report, they demonstrate that the immediate-early gene region of HCMV, in particular immediate-early region 2, trans-activates the expression of the bacterial gene chloramphenicol acetyltransferase that is fused to the HIV long terminal repeat and carried by plasmid pHIV-CAT. The HCMV immediate-early trans-activator increases the level of mRNA from the plamid pHIV-CAT. The sequences of HIV that are responsive to trans-activation by the HDMV immediate-early region are distinct from HIV sequences that are required for response to the HIV tat. The stimulation of HIV gene expression by HDMV gene functions could enhance the consequences of HIV infection in persons with previous or concurrent HCMV infection.

  19. Immediate-early gene region of human cytomegalovirus trans-activates the promoter of human immunodeficiency virus

    International Nuclear Information System (INIS)

    Davis, M.G.; Kenney, S.C.; Kamine, J.; Pagano, J.S.; Huang, E.S.

    1987-01-01

    Almost all homosexual patients with acquired immunodeficiency syndrome are also actively infected with human cytomegalovirus (HCMV). The authors have hypothesized that an interaction between HCMV and human immunodeficiency virus (HIV), the agent that causes acquired immunodeficiency syndrome, may exist at a molecular level and contribute to the manifestations of HIV infection. In this report, they demonstrate that the immediate-early gene region of HCMV, in particular immediate-early region 2, trans-activates the expression of the bacterial gene chloramphenicol acetyltransferase that is fused to the HIV long terminal repeat and carried by plasmid pHIV-CAT. The HCMV immediate-early trans-activator increases the level of mRNA from the plamid pHIV-CAT. The sequences of HIV that are responsive to trans-activation by the HDMV immediate-early region are distinct from HIV sequences that are required for response to the HIV tat. The stimulation of HIV gene expression by HDMV gene functions could enhance the consequences of HIV infection in persons with previous or concurrent HCMV infection

  20. Implementation and test of proposals to integrate human factors in reporting and causal analysis in nuclear power plants

    International Nuclear Information System (INIS)

    Wilpert; Maimer, H.; Miller, R.; Fahlbruch, B.; Leiber, I.; Szameitat, S.; Baggen, R.; Gans, A.; Becker, G.

    1998-01-01

    The research project 'Implementation and Test of Proposals to integrate Human Factors in Reporting and Causal Analysis in Nuclear Power Plants' ('Implementation and Test', SR 2039/8) is based on two antecedent projects: 'Reporting System' (SR 2039/1) and 'Causal Analysis' (SR 2039/2). The project 'Implementation and Test' conducted various tests and introductory programs in cooperation with different target groups concerning the event analysis methodology 'SOL - Safety through Organizational Learning': Regulators, consultant organizations, union/works councillors and utilities. Thus, SOL was concurrently optimized and [apted for the practice in the German nuclear power industry. SOL was also validated in a German nuclear power plant using a concrete event. Results of the 'Implementation and Test' project demonstrate that SOL is fit to conduct event analyses practicably and economically with appropriate comprehensiveness and depth. SOL facilitates the identification of relevant contributing factors of events. This report concludes with various concrete proposals for the further development of the Program of the Federal Ministry of Environment, Nature Protection and Reactor Safety (BMU) and the Federal Agency of R[iation Protection (BfS) concerning 'The Contribution of Humans to Safety of Nuclear Power Plants'. (orig.) [de

  1. Brain-targeted delivery of trans-activating transcriptor-conjugated magnetic PLGA/lipid nanoparticles.

    Directory of Open Access Journals (Sweden)

    Xiangru Wen

    Full Text Available Magnetic poly (D,L-lactide-co-glycolide (PLGA/lipid nanoparticles (MPLs were fabricated from PLGA, L-α-phosphatidylethanolamine (DOPE, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-amino (polyethylene glycol (DSPE-PEG-NH2, and magnetic nanoparticles (NPs, and then conjugated to trans-activating transcriptor (TAT peptide. The TAT-MPLs were designed to target the brain by magnetic guidance and TAT conjugation. The drugs hesperidin (HES, naringin (NAR, and glutathione (GSH were encapsulated in MPLs with drug loading capacity (>10% and drug encapsulation efficiency (>90%. The therapeutic efficacy of the drug-loaded TAT-MPLs in bEnd.3 cells was compared with that of drug-loaded MPLs. The cells accumulated higher levels of TAT-MPLs than MPLs. In addition, the accumulation of QD-loaded fluorescein isothiocyanate (FITC-labeled TAT-MPLs in bEnd.3 cells was dose and time dependent. Our results show that TAT-conjugated MPLs may function as an effective drug delivery system that crosses the blood brain barrier to the brain.

  2. Enhanced human somatic cell reprogramming efficiency by fusion of the MYC transactivation domain and OCT4

    Directory of Open Access Journals (Sweden)

    Ling Wang

    2017-12-01

    Full Text Available The development of human induced pluripotent stem cells (iPSCs holds great promise for regenerative medicine. However the iPSC induction efficiency is still very low and with lengthy reprogramming process. We utilized the highly potent transactivation domain (TAD of MYC protein to engineer the human OCT4 fusion proteins. Applying the MYC-TAD-OCT4 fusion proteins in mouse iPSC generation leads to shorter reprogramming dynamics, with earlier activation of pluripotent markers in reprogrammed cells than wild type OCT4 (wt-OCT4. Dramatic enhancement of iPSC colony induction efficiency and shortened reprogramming dynamics were observed when these MYC-TAD-OCT4 fusion proteins were used to reprogram primary human cells. The OCT4 fusion proteins induced human iPSCs are pluripotent. We further show that the MYC Box I (MBI is dispensable while both MBII and the linking region between MBI/II are essential for the enhanced reprogramming activity of MYC-TAD-OCT4 fusion protein. Consistent with an enhanced transcription activity, the engineered OCT4 significantly stimulated the expression of genes specifically targeted by OCT4-alone, OCT4/SOX2, and OCT4/SOX2/KLF4 during human iPSC induction, compared with the wt-OCT4. The MYC-TAD-OCT4 fusion proteins we generated will be valuable tools for studying the reprogramming mechanisms and for efficient iPSC generation for humans as well as for other species.

  3. Crystal Structure of the CLOCK Transactivation Domain Exon19 in Complex with a Repressor

    Energy Technology Data Exchange (ETDEWEB)

    Hou, Zhiqiang; Su, Lijing; Pei, Jimin; Grishin, Nick V.; Zhang, Hong (UTSMC)

    2017-08-01

    In the canonical clock model, CLOCK:BMAL1-mediated transcriptional activation is feedback regulated by its repressors CRY and PER and, in association with other coregulators, ultimately generates oscillatory gene expression patterns. How CLOCK:BMAL1 interacts with coregulator(s) is not well understood. Here we report the crystal structures of the mouse CLOCK transactivating domain Exon19 in complex with CIPC, a potent circadian repressor that functions independently of CRY and PER. The Exon19:CIPC complex adopts a three-helical coiled-coil bundle conformation containing two Exon19 helices and one CIPC. Unique to Exon19:CIPC, three highly conserved polar residues, Asn341 of CIPC and Gln544 of the two Exon19 helices, are located at the mid-section of the coiled-coil bundle interior and form hydrogen bonds with each other. Combining results from protein database search, sequence analysis, and mutagenesis studies, we discovered for the first time that CLOCK Exon19:CIPC interaction is a conserved transcription regulatory mechanism among mammals, fish, flies, and other invertebrates.

  4. Nuclear insulin-like growth factor 1 receptor phosphorylates proliferating cell nuclear antigen and rescues stalled replication forks after DNA damage.

    Science.gov (United States)

    Waraky, Ahmed; Lin, Yingbo; Warsito, Dudi; Haglund, Felix; Aleem, Eiman; Larsson, Olle

    2017-11-03

    We have previously shown that the insulin-like growth factor 1 receptor (IGF-1R) translocates to the cell nucleus, where it binds to enhancer-like regions and increases gene transcription. Further studies have demonstrated that nuclear IGF-1R (nIGF-1R) physically and functionally interacts with some nuclear proteins, i.e. the lymphoid enhancer-binding factor 1 (Lef1), histone H3, and Brahma-related gene-1 proteins. In this study, we identified the proliferating cell nuclear antigen (PCNA) as a nIGF-1R-binding partner. PCNA is a pivotal component of the replication fork