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Sample records for nuclear factor-kb inhibitor

  1. Epigallocatechin-3-gallate regulates cell growth, cell cycle and phosphorylated nuclear factor-KB in human dermal fibroblasts

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    Dong-Wook HAN; Mi Hee LEE; Hak Hee KIM; Suong-Hyu HYON; Jong-Chul PARK

    2011-01-01

    Aim: To investigate the effects of (-)epigallocatechin-3-gallate (EGCG), the main polyphenol in green tea, on cell growth, cell cycle and phosphorylated nuclear factor-kB (pNF-KB) expression in neonatal human dermal fibroblasts (nHDFs).Methods: The proliferation and cell-cycle of nHDFs were determined using WST-8 cell growth assay and flow cytometry, respectively. The apoptosis was examined using DNA ladder and Annexin V-FITC assays. The expression levels of pNF-kB and cell cycle-related genes and proteins in nHDFs were measured using cDNA microarray analyses and Western blot. The cellular uptake of EGCG was examined using fluorescence (FITC)-Iabeled EGCG (FITC-EGCG) in combination with confocal microscopy.Results: The effect of EGCG on the growth of nHDFs depended on the concentration tested. At a low concentration (200 μmol/L), EGCG resulted in a slight decrease in the proportion of ceils in the S and G/M phases of cell cycle with a concomitant increase in the proportion of cells in G/G phase. At the higher doses (400 and 800 pmol/L), apoptosis was induced. The regulation of EGCG on the expression of pNF-kB was also concentration-dependent, whereas it did not affect the unphosphorylated NF-kB expression, cDNA microarray analysis showed that cell cycle-related genes were down-regulated by EGCG (200 μmol/L). The expression of cyclins A/B and cyclin-dependent kinase 1 was reversibly regulated by EGCG (200 μmol/L). FITC-EGCG was found to be internalized into the cyto-plasm and translocated into the nucleus of nHDFs.Conclusion: EGCG, through uptake into cytoplasm, reversibly regulated the cell growth and expression of cell cycle-related proteins and genes in normal fibroblasts.

  2. Expression of nuclear factor-KB in hepatocellular carcinoma and its relation with .the X protein of hepatitis B virus

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    Shuang Ping Guo; Wen Liang Wang; Yu Qiang Zhai; Yi Ling Zhao

    2001-01-01

    AIM In this study we investigated therelationship of the X protein of HBV and nuclearfactor-KB (NF-κB) and the expression of NF-KB inhuman hepatocellular carcinoma tissues.METHODS Immunohistochemistry SP methodwas used to detect the expression of NF-κB and the X protein of HBV in human hepatocellularcarcinoma tissues of 52 cases. Gene transfectionmediated by lipofectamine was used to transfectthe eukaryotic expression vector pCDNA3. 1-HBXof HBV x gene into human hepatocellularcarcinoma cell line HCC-9204 and NF-κB wasdetected.RESULTS NF-κB was widely expressed inhuman hepatocellular carcinoma tissues in atotal of 52 cases and its expression was relatedto the X protein of HBV. NF-KB was localizedboth in the cytoplasm and . The nuclei ofhepatocellular carcinoma cells in 11 cases whichwere positive for the X protein of HBV while in 41cases negative for the X protein of HBV, NF-Kbwas only localized in the cytoplasm ofhepatocellular carcinoma cells but translocatedto the nuclei of hepatocellular carcinoma cellsafter the eukaryotic expression vectorpCDNA3.1-HBX was transfected into HCC-9204cells.CONCLUSION This study strongly suggeststhat the nuclear factor NF-KB is widely expressedin hepatocellular carcinoma tissues in differentstyles according to the expression of the Xprotein of HBV. NF-κB is abnormally activated inhepatocellular carcinoma, which is probablyrelated to the X protein of HBV. The X protein ofHBV can activate NF-κB to translocate into nucleiof hepatocellular carcinoma cells.

  3. Role of Nuclear Transcription Factor-KB in Endotoxin-induced Shock in Rats

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    To investigate the role of NF-κB in endotoxic shock in rats, the model of endotoxinshock rats was induced by intravenous infusion of lipopolysaccharide (LPS). 1 h, 2 h, 4 h and 6h after LPS injection, the activation of NF-κB in blood mononuclear cells and the content of TNF-α and IL-6 in plasma was detected by enzyme-linked immunoadsordent assay (ELISA). The level of mean arterial pressure (MAP) and the histopathological changes of lung and liver were also observed. The activation of NF-κB in mononuclear cells increased 1 h after LPS injection and reached its peak 2 h after the injection, and its level was higher than that of normal group. The level of TNF-α was increased 1 h after the infusion and peaked 2 h after the injection, and its level was higher than that of normal group after LPS infusion. The content of IL-6 increased gradually with time, the IL-6 level was higher than that of normal group after LPS injection. MAP was decreased gradually with time and its level was lower than that of normal group after LPS injection. Pathological examination showed that endotoxic shock could cause pulmonary alveolar hemorrhage, edema and infiltration of inflammatory cell in lung tissue and congestion, edema, capillary dilation and inflammatory cell infiltration in liver tissue. It is concluded that NF-κB can up-regulate the expression of TNF-α and IL-6 in plasma and play an important role in endotoxin-induced shock in rats.

  4. Medicated serum prepared with Chinese herbal medicine Zhizhen Recipe down-regulates activity of nuclear factor-KB and expression of P-glycoprotein in human colorectal cancer multidrug-resistant cell line HCT-8/VCR%至真方含药血清对人大肠癌多药耐药细胞HCT-8/VCR内核因子κB活性及P-糖蛋白表达与功能的抑制作用

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    蔡松柏; 张旭; 陈志霞; 孔令春; 王松坡

    2011-01-01

    To investigate the effects of medicated serum prepared with Chinese herbal medicine Zhizhen Recipe (ZZR) on activity of nuclear factor-kB (NF-kB) and expression and function of P-glycoprotein (P-gp) in human colorectal cancer multidrug-resistant cell line HCT-8/VCR.Methods: The multidrug resistance of HCT-8/VCR cells was detected by cell counting kit-8 method, and the experimental concentrations of ZZR-medicated serum were determined by the same way. HCT-8 and HCT-8/ VCR cells were treated with ZZR-medicated serum of medium dose for 24 h. The activity of NF-kB was determined by enzyme-linked immunosorbent assay. The intracellular distribution of P-gp was detected by laser scanning confocal microscopy, and the mean fluorescence intensity of rhodamine 123 was detected by flow cytometry.Results: ZZR-medicated sera with volume fraction of 8% , 16% and 32% of medium dose were confirmed as the experimental sera. Compared with the untreated group, NF-kB activities of the ZZR-medicated serum groups (ZZR-medicated serum with volume fraction of 8%, 16% and 32% of medium dose) were obviously down-regulated (P<0. 01), which had a negative correlation with the concentrations. After interfering HCT-8/VCR with ZZR-medicated serum of different concentrations for 24 h, P-gp in HCT-8/VCR transmitted gradually from cell membrane to cytoplasm and nuclei. Nuclei became pyknotic and cracking. Compared with the untreated group, the mean fluorescence intensities of ZZR-medicated serum groups declined with concentration gradients (P<0. 01). The efflux of intracellular rhodamine 123 decreased, the wave crest shifted to right, and the intracellular fluorescence intensity strengthened (P<0.01). Conclusion: ZZR-medicated sera of experimental concentrations down-regulate activity of NF-KB and expression and function of P-gp in human colorectal cancer multidrug-resistant cell line HCT-8/VCR and the effect is related to the concentrations.%目的:探讨至真方是

  5. Investigation of Corrosion Inhibitors by Nuclear Quadrupole Resonance Relaxometry Method

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    Nikolay Sinyavsky

    2015-12-01

    Full Text Available The changes taking place with the corrosion-resistant coating, but not the state of the surface subjected to corrosion are investigated in this paper in contrast to traditional approaches. We used the method of nitrogen relaxometry NQR and multi-exponential inversion of decay of longitudinal and transverse components of the nuclear magnetization is applied for the first time for this purpose. The results of experimental studies of changes in the distributions of spin-spin and spin-lattice relaxation of crystallite powder of sodium nitrite and urotropin, the mixture of which is used as a corrosion inhibitor of ferrous metals are considered.

  6. Basic nuclear processes affected by histone acetyltransferases and histone deacetylase inhibitors

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    Legartová, Soňa; Stixová, Lenka; Strnad, Hynek; Kozubek, Stanislav; Martinet, Nadine; Dekker, Frank J; Franek, Michal; Bártová, Eva

    2013-01-01

    AIM: The optimal balance between histone acetylation and deacetylation is important for proper gene function. Therefore, we addressed how inhibitors of histone-modifying enzymes can modulate nuclear events, including replication, transcription, splicing and DNA repair. MATERIALS & METHODS: Changes i

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

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    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.

  8. Unprecedented NES non-antagonistic inhibitor for nuclear export of Rev from Sida cordifolia.

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    Tamura, Satoru; Kaneko, Masafumi; Shiomi, Atsushi; Yang, Guang-Ming; Yamaura, Toshiaki; Murakami, Nobutoshi

    2010-03-15

    Bioassay-guided separation from the MeOH extract of the South American medicinal plant Sida cordifolia resulted in isolation of (10E,12Z)-9-hydroxyoctadeca-10,12-dienoic acid (1) as an unprecedented NES non-antagonistic inhibitor for nuclear export of Rev. This mechanism of action was established by competitive experiment by the biotinylated probe derived from leptomycin B, the known NES antagonistic inhibitor. Additionally, structure-activity relationship analysis by use of the synthesized analogs clarified cooperation of several functionalities in the Rev-export inhibitory activity of 1. Copyright 2010 Elsevier Ltd. All rights reserved.

  9. High-content screening of natural products reveals novel nuclear export inhibitors.

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    Cautain, Bastien; de Pedro, Nuria; Murillo Garzón, Virginia; Muñoz de Escalona, María; González Menéndez, Victor; Tormo, José R; Martin, Jesús; El Aouad, Noureddine; Reyes, Fernando; Asensio, Francisco; Genilloud, Olga; Vicente, Francisca; Link, Wolfgang

    2014-01-01

    Natural products are considered an extremely valuable source for the discovery of new drugs against diverse pathologies. As yet, we have only explored a fraction of the diversity of bioactive compounds, and opportunities for discovering new natural products leading to new drugs are huge. In the present study, U2nesRELOC, a previously established cell-based imaging assay, was employed to screen a collection of extracts of microbial origin for nuclear export inhibition activity. The fluorescent signal of untreated U2nesRELOC cells localizes predominantly to the cytoplasm. Upon treatment with the nuclear export inhibitor leptomycin B, the fluorescent-tagged reporter proteins appear as speckles in the nucleus. A proprietary collection of extracts from fungi, actinomycetes, and unicellular bacteria that covers an uncommonly broad chemical space was used to interrogate this nuclear export assay system. A two-step image-based analysis allowed us to identify 12 extracts with biological activities that are not associated with previously known active metabolites. The fractionation and structural elucidation of active compounds revealed several chemical structures with nuclear export inhibition activity. Here we show that substrates of the nuclear export receptor CRM1, such as Rev, FOXO3a and NF-κB, accumulate in the nucleus in the presence of the fungal metabolite MDN-0105 with an IC50 value of 3.4 µM. Many important processes in tumor formation and progression, as well as in many viral infections, critically depend on the nucleocytoplasmic trafficking of proteins and RNA molecules. Therefore, the disruption of nuclear export is emerging as a novel therapeutic approach with enormous clinical potential. Our work highlights the potential of applying high-throughput phenotypic imaging on natural product extracts to identify novel nuclear export inhibitors.

  10. Intracellular lysyl oxidase: Effect of a specific inhibitor on nuclear mass in proliferating cells

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    Saad, Fawzy A. [Laboratory for the Study of Skeletal Disorders and Rehabilitation, Department of Orthopedics, Children' s Hospital Boston, 300 Longwood Avenue EN926, Boston, MA 02115 (United States); Harvard Medical School, Boston, MA 02115 (United States); Torres, Marie [Laboratory for the Study of Skeletal Disorders and Rehabilitation, Department of Orthopedics, Children' s Hospital Boston, 300 Longwood Avenue EN926, Boston, MA 02115 (United States); Wang, Hao [Laboratory for the Study of Skeletal Disorders and Rehabilitation, Department of Orthopedics, Children' s Hospital Boston, 300 Longwood Avenue EN926, Boston, MA 02115 (United States); Harvard Medical School, Boston, MA 02115 (United States); Graham, Lila, E-mail: lilagraham@cs.com [Laboratory for the Study of Skeletal Disorders and Rehabilitation, Department of Orthopedics, Children' s Hospital Boston, 300 Longwood Avenue EN926, Boston, MA 02115 (United States); Harvard Medical School, Boston, MA 02115 (United States)

    2010-06-11

    LOX, the principal enzyme involved in crosslinking of collagen, was the first of several lysyl oxidase isotypes to be characterized. Its active form was believed to be exclusively extracellular. Active LOX was later reported to be present in cell nuclei; its function there is unknown. LOX expression opposes the effect of mutationally activated Ras, which is present in about 30% of human cancers. The mechanism of LOX in countering the action of Ras is also unknown. In the present work, assessment of nuclear protein for possible effects of lysyl oxidase activity led to the discovery that proliferating cells dramatically increase their nuclear protein content when exposed to BAPN ({beta}-aminopropionitrile), a highly specific lysyl oxidase inhibitor that reportedly blocks LOX inhibition of Ras-induced oocyte maturation. In three cell types (PC12 cells, A7r5 smooth muscle cells, and NIH 3T3 fibroblasts), BAPN caused a 1.8-, 1.7-, and 2.1-fold increase in total nuclear protein per cell, respectively, affecting all major components in both nuclear matrix and chromatin fractions. Since nuclear size is correlated with proliferative status, enzyme activity restricting nuclear growth may be involved in the lysyl oxidase tumor suppressive effect. Evidence is also presented for the presence of apparent lysyl oxidase isotype(s) containing a highly conserved LOX active site sequence in the nuclei of PC12 cells, which do not manufacture extracellular lysyl oxidase substrates. Results reported here support the hypothesis that nuclear lysyl oxidase regulates nuclear growth, and thereby modulates cell proliferation.

  11. Insensible is a novel nuclear inhibitor of Notch activity in Drosophila.

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    Franck Coumailleau

    Full Text Available Notch signalling regulates a wide range of developmental processes. In the Drosophila peripheral nervous system, Notch regulates a series of binary fate decisions that lead to the formation of regularly spaced sensory organs. Each sensory organ is generated by single sensory organ precursor cell (SOP via a series of asymmetric cell divisions. Starting from a SOP-specific Cis-Regulatory Module (CRM, we identified insensible (insb, a.k.a CG6520, as a SOP/neuron-specific gene encoding a nuclear factor that inhibits Notch signalling activity. First, over-expression of Insb led to the transcriptional repression of a Notch reporter and to phenotypes associated with the inhibition of Notch. Second, while the complete loss of insb activity had no significant phenotype, it enhanced the bristle phenotype associated with reduced levels of Hairless, a nuclear protein acting as a co-repressor for Suppressor of Hairless. In conclusion, our work identified Insb as a novel SOP/neuron-specific nuclear inhibitor of Notch activity in Drosophila.

  12. Imaging Nuclear Morphology and Organization in Cleared Plant Tissues Treated with Cell Cycle Inhibitors.

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    de Souza Junior, José Dijair Antonino; de Sa, Maria Fatima Grossi; Engler, Gilbert; Engler, Janice de Almeida

    2016-01-01

    Synchronization of root cells through chemical treatment can generate a large number of cells blocked in specific cell cycle phases. In plants, this approach can be employed for cell suspension cultures and plant seedlings. To identify plant cells in the course of the cell cycle, especially during mitosis in meristematic tissues, chemical inhibitors can be used to block cell cycle progression. Herein, we present a simplified and easy-to-apply protocol to visualize mitotic figures, nuclei morphology, and organization in whole Arabidopsis root apexes. The procedure is based on tissue clearing, and fluorescent staining of nuclear DNA with DAPI. The protocol allows carrying out bulk analysis of nuclei and cell cycle phases in root cells and will be valuable to investigate mutants like overexpressing lines of genes disturbing the plant cell cycle.

  13. Tissue factor pathway inhibitor-2 may interact with nuclear protein RASSF1C

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    Xudong Chen; Zhenwu Li; Jin Zhang; Zuohua Mao; Duan Ma; Huijun Wang

    2012-01-01

    Tissue factor pathway inhibitor-2 (TFPI-2) is a 32 kDa matrix-associated Kunitz-type serine proteinase inhibitor consisting of a short amino-terminal region,three tandem Kunitz-type domains,and a positively charged carboxyterminal tail.Human TFPI-2 (hTFPI-2) inhibits a broad spectrum of serine proteinases (including trypsin,plasmin,plasma kallikrein,XIa,and chymotrypsin) almost exclusively via its first Kunitz-type domain,and potentially plays an important role in the regulation of extracellular matrix digestion and remodeling [1].Reduced TFPI-2 synthesis has been related to numerous pathophysiological processes such as inflammation,angiogenesis,atherosclerosis [2,3],retinal degeneration,and tumor growth/metastasis [4-6].It has been suggested that TFPI-2 is a tumor suppressor gene in some cancers [7,8].However,the specific physiological functions of hTFPI-2 in humans are unclear,particularly its interactions with other proteins.To better understand the physiological function of hTFPI-2,we used yeast two-hybrid system screening and bioinformatics analysis to identify its interacting proteins and confirm its interactions with nuclear protein RASSF1C using confocal microscopy and co-immunoprecipitation.

  14. PML nuclear bodies contribute to the basal expression of the mTOR inhibitor DDIT4

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    Salsman, Jayme; Stathakis, Alex; Parker, Ellen; Chung, Dudley; Anthes, Livia E.; Koskowich, Kara L.; Lahsaee, Sara; Gaston, Daniel; Kukurba, Kimberly R.; Smith, Kevin S.; Chute, Ian C.; Léger, Daniel; Frost, Laura D.; Montgomery, Stephen B.; Lewis, Stephen M.; Eskiw, Christopher; Dellaire, Graham

    2017-01-01

    The promyelocytic leukemia (PML) protein is an essential component of PML nuclear bodies (PML NBs) frequently lost in cancer. PML NBs coordinate chromosomal regions via modification of nuclear proteins that in turn may regulate genes in the vicinity of these bodies. However, few PML NB-associated genes have been identified. PML and PML NBs can also regulate mTOR and cell fate decisions in response to cellular stresses. We now demonstrate that PML depletion in U2OS cells or TERT-immortalized normal human diploid fibroblasts results in decreased expression of the mTOR inhibitor DDIT4 (REDD1). DNA and RNA immuno-FISH reveal that PML NBs are closely associated with actively transcribed DDIT4 loci, implicating these bodies in regulation of basal DDIT4 expression. Although PML silencing did reduce the sensitivity of U2OS cells to metabolic stress induced by metformin, PML loss did not inhibit the upregulation of DDIT4 in response to metformin, hypoxia-like (CoCl2) or genotoxic stress. Analysis of publicly available cancer data also revealed a significant correlation between PML and DDIT4 expression in several cancer types (e.g. lung, breast, prostate). Thus, these findings uncover a novel mechanism by which PML loss may contribute to mTOR activation and cancer progression via dysregulation of basal DDIT4 gene expression. PMID:28332630

  15. Identification of a chemical inhibitor for nuclear speckle formation: Implications for the function of nuclear speckles in regulation of alternative pre-mRNA splicing

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    Kurogi, Yutaro; Matsuo, Yota; Mihara, Yuki; Yagi, Hiroaki; Shigaki-Miyamoto, Kaya; Toyota, Syukichi; Azuma, Yuko [Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, Chuo-ku, Kumamoto 860-8555 (Japan); Igarashi, Masayuki [Laboratory of Disease Biology, Institute of Microbial Chemistry, Shinagawa-ku, Tokyo 141-0021 (Japan); Tani, Tokio, E-mail: ttani@sci.kumamoto-u.ac.jp [Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, Chuo-ku, Kumamoto 860-8555 (Japan)

    2014-03-28

    Highlights: • We identified tubercidin as a compound inducing aberrant formation of the speckles. • Tubercidin causes delocalization of poly (A){sup +}RNAs from nuclear speckles. • Tubercidin induces dispersion of splicing factors from nuclear speckles. • Tubercidin affects alternative pre-mRNA splicing. • Nuclear speckles play a role in regulation of alternative pre-mRNA splicing. - Abstract: Nuclear speckles are subnuclear structures enriched with RNA processing factors and poly (A){sup +} RNAs comprising mRNAs and poly (A){sup +} non-coding RNAs (ncRNAs). Nuclear speckles are thought to be involved in post-transcriptional regulation of gene expression, such as pre-mRNA splicing. By screening 3585 culture extracts of actinomycetes with in situ hybridization using an oligo dT probe, we identified tubercidin, an analogue of adenosine, as an inhibitor of speckle formation, which induces the delocalization of poly (A){sup +} RNA and dispersion of splicing factor SRSF1/SF2 from nuclear speckles in HeLa cells. Treatment with tubercidin also decreased steady-state MALAT1 long ncRNA, thought to be involved in the retention of SRSF1/SF2 in nuclear speckles. In addition, we found that tubercidin treatment promoted exon skipping in the alternative splicing of Clk1 pre-mRNA. These results suggest that nuclear speckles play a role in modulating the concentration of splicing factors in the nucleoplasm to regulate alternative pre-mRNA splicing.

  16. Selective Inhibitor of Nuclear Export (SINE) Compounds Alter New World Alphavirus Capsid Localization and Reduce Viral Replication in Mammalian Cells.

    Science.gov (United States)

    Lundberg, Lindsay; Pinkham, Chelsea; de la Fuente, Cynthia; Brahms, Ashwini; Shafagati, Nazly; Wagstaff, Kylie M; Jans, David A; Tamir, Sharon; Kehn-Hall, Kylene

    2016-11-01

    The capsid structural protein of the New World alphavirus, Venezuelan equine encephalitis virus (VEEV), interacts with the host nuclear transport proteins importin α/β1 and CRM1. Novel selective inhibitor of nuclear export (SINE) compounds, KPT-185, KPT-335 (verdinexor), and KPT-350, target the host's primary nuclear export protein, CRM1, in a manner similar to the archetypical inhibitor Leptomycin B. One major limitation of Leptomycin B is its irreversible binding to CRM1; which SINE compounds alleviate because they are slowly reversible. Chemically inhibiting CRM1 with these compounds enhanced capsid localization to the nucleus compared to the inactive compound KPT-301, as indicated by immunofluorescent confocal microscopy. Differences in extracellular versus intracellular viral RNA, as well as decreased capsid in cell free supernatants, indicated the inhibitors affected viral assembly, which led to a decrease in viral titers. The decrease in viral replication was confirmed using a luciferase-tagged virus and through plaque assays. SINE compounds had no effect on VEEV TC83_Cm, which encodes a mutated form of capsid that is unable to enter the nucleus. Serially passaging VEEV in the presence of KPT-185 resulted in mutations within the nuclear localization and nuclear export signals of capsid. Finally, SINE compound treatment also reduced the viral titers of the related eastern and western equine encephalitis viruses, suggesting that CRM1 maintains a common interaction with capsid proteins across the New World alphavirus genus.

  17. Jumping the nuclear envelop barrier: Improving polyplex-mediated gene transfection efficiency by a selective CDK1 inhibitor RO-3306.

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    Zhou, Xuefei; Liu, Xiangrui; Zhao, Bingxiang; Liu, Xin; Zhu, Dingcheng; Qiu, Nasha; Zhou, Quan; Piao, Ying; Zhou, Zhuxian; Tang, Jianbin; Shen, Youqing

    2016-07-28

    Successful transfection of plasmid DNA (pDNA) requires intranuclear internalization of pDNA effectively and the nuclear envelope appears to be one of the critical intracellular barriers for polymer mediated pDNA delivery. Polyethylenimine (PEI), as the classic cationic polymer, compact the negatively charged pDNA tightly and make up stable polyplexes. The polyplexes are too large to enter the nuclear through nuclear pores and it is believed that the nuclear envelope breakdown in mitosis could facilitate the nuclear entry of polyplexes. To jump the nuclear envelope barrier, we used a selective and reversible CDK1 inhibitor RO-3306 to control the G2/M transition of the cell cycle and increased the proportion of mitotic cells which have disappeared nuclear envelope during transfection. Herein, we show that RO-3306 remarkably increases the transfection efficiency of PEI polyplexes through enhanced nuclear localization of PEI and pDNA. However, RO-3306 is less effective to the charge-reversal polymer poly[(2-acryloyl)ethyl(p-boronic acid benzyl)diethylammonium bromide] (B-PDEAEA) which responses to cellular stimuli and releases free pDNA in cytoplasm. Our findings not only offer new opportunities for improving non-viral based gene delivery but also provide theoretical support for the rational design of novel functional polymers for gene delivery. We also report current data showing that RO-3306 synergizes TRAIL gene induced apoptosis in cancer cells.

  18. Cyclooxygenase-2 inhibitor, celecoxib, inhibits leiomyoma cell proliferation through the nuclear factor κB pathway.

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    Park, Seung Bin; Jee, Byung Chul; Kim, Seok Hyun; Cho, Yeon Jean; Han, Myoungseok

    2014-09-01

    Our aim was to investigate whether celecoxib, a cyclooxygenase 2 (COX-2) inhibitor, decreases the in vitro proliferation of leiomyoma cells if the inflammatory pathway is blocked. Menstruation is an inflammation of uterus that produces cytokines and prostanoids, but the inflammatory mechanism underlying the growth of leiomyoma remains unexplained. Using in vitro cultures of leiomyoma cells obtained from 5 patients who underwent hysterectomy, cell proliferation, inflammatory signaling, transcription factors, growth factors, and extracellular matrix were examined by (4,5-dimethylthiaxol-2-yi)-2,5-diphenyltetraxolium bromide assay, immunoblotting, and quantitative polymerase chain reaction. Prostaglandin E2 was used to induce menstruation-like condition in the cells. We found that celecoxib inhibited COX-2 through the expression of nuclear factor κB in the cells. Celcoxib also decreased the gene expression of interleukin 6, tumor necrosis factor α, collagen A, fibronectin, platelet-derived growth factor, epidermal growth factor, and transforming growth factor β. In conclusion, the present study indicated that celecoxib could inhibit leiomyoma cell proliferation through blocking the inflammatory pathway that is probably one of the mechanisms underlying its pathogenesis.

  19. Development of a cell death-based method for the screening of nuclear factor-kappaB inhibitors.

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    Chopra, Puneet; Bajpai, Malini; Dastidar, Sunanda G; Ray, Abhijit

    2008-06-01

    Nuclear factor kappa B (NF-kappaB) plays a significant role in immunity and inflammation and represents a first choice as pharmacological target for anti-inflammatory therapy. However, research in this field has been hampered by the fact that no convenient assay suitable for large-scale screening procedures is available. The present study provides a cell death-based assay method for screening of nuclear factor-kappaB inhibitors. In this study, we observed that four distinct pharmacologic inhibitors of NF-kappaB, pyrrolidine dithiocarbamate (PDTC), N-tosyl-L-lysyl chloromethyl ketone (TPCK), genistein and BAY11-7082, resulted in the cell death of murine macrophages, J774A.1. DNA-binding experiments showed that lethal doses were consistent with those required for NF-kappaB inhibition. DNA fragmentation analysis showed that cell death is apoptotic in nature. Further studies suggested that NF-kappaB inhibitors induced apoptosis is independent of the involvement of other markers of cell death such as caspases and p38 MAP (Mitogen activated protein) kinase. From this study, we conclude that NF-kappaB activation may represent an important survival mechanism in macrophages. This study also provides a new cell-based screening method, as any compound that will inhibit NF-kappaB activity will result in the death of macrophages.

  20. In vivo islet protection by a nuclear import inhibitor in a mouse model of type 1 diabetes.

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    Daniel J Moore

    Full Text Available BACKGROUND: Insulin-dependent Type 1 diabetes (T1D is a devastating autoimmune disease that destroys beta cells within the pancreatic islets and afflicts over 10 million people worldwide. These patients face life-long risks for blindness, cardiovascular and renal diseases, and complications of insulin treatment. New therapies that protect islets from autoimmune destruction and allow continuing insulin production are needed. Increasing evidence regarding the pathomechanism of T1D indicates that islets are destroyed by the relentless attack by autoreactive immune cells evolving from an aberrant action of the innate, in addition to adaptive, immune system that produces islet-toxic cytokines, chemokines, and other effectors of islet inflammation. We tested the hypothesis that targeting nuclear import of stress-responsive transcription factors evoked by agonist-stimulated innate and adaptive immunity receptors would protect islets from autoimmune destruction. PRINCIPAL FINDINGS: Here we show that a first-in-class inhibitor of nuclear import, cSN50 peptide, affords in vivo islet protection following a 2-day course of intense treatment in NOD mice, which resulted in a diabetes-free state for one year without apparent toxicity. This nuclear import inhibitor precipitously reduces the accumulation of islet-destructive autoreactive lymphocytes while enhancing activation-induced cell death of T and B lymphocytes derived from autoimmune diabetes-prone, non-obese diabetic (NOD mice that develop T1D. Moreover, in this widely used model of human T1D we noted attenuation of pro-inflammatory cytokine and chemokine production in immune cells. CONCLUSIONS: These results indicate that a novel form of immunotherapy that targets nuclear import can arrest inflammation-driven destruction of insulin-producing beta cells at the site of autoimmune attack within pancreatic islets during the progression of T1D.

  1. Heterozygous mutation of cysteine528 in XPO1 is sufficient for resistance to selective inhibitors of nuclear export.

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    Neggers, Jasper Edgar; Vanstreels, Els; Baloglu, Erkan; Shacham, Sharon; Landesman, Yosef; Daelemans, Dirk

    2016-10-18

    Exportin-1 (CRM1/XPO1) is a crucial nuclear export protein that transports a wide variety of proteins from the nucleus to the cytoplasm. These cargo proteins include tumor suppressors and growth-regulatory factors and as such XPO1 is considered a potential anti-cancer target. From this perspective, inhibition of the XPO1-mediated nuclear export by selective inhibitor of nuclear export (SINE) compounds has shown broad-spectrum anti-cancer activity. Furthermore, the clinical candidate SINE, selinexor, is currently in multiple phase I/II/IIb trials for treatment of cancer. Resistance against selinexor has not yet been observed in the clinic, but in vitro selection of resistance did not reveal any mutations in the target protein, XPO1. However, introduction of a homozygous mutation at the drug's target site, the cysteine 528 residue inside the XPO1 cargo-binding pocket, by genetic engineering, confers resistance to selinexor. Here we investigated whether this resistance to selinexor is recessive or dominant. For this purpose we have engineered multiple leukemia cell lines containing heterozygous or homozygous C528S substitutions using CRISPR/Cas9-mediated genome editing. Our findings show that heterozygous mutation confers similar resistance against selinexor as homozygous substitution, demonstrating that SINE resistance can be obtained by a single and dominant mutation of the cysteine528 residue in XPO1.

  2. Anti-tumor activity of selective inhibitor of nuclear export (SINE) compounds, is enhanced in non-Hodgkin lymphoma through combination with mTOR inhibitor and dexamethasone.

    Science.gov (United States)

    Muqbil, Irfana; Aboukameel, Amro; Elloul, Sivan; Carlson, Robert; Senapedis, William; Baloglu, Erkan; Kauffman, Michael; Shacham, Sharon; Bhutani, Divaya; Zonder, Jeffrey; Azmi, Asfar S; Mohammad, Ramzi M

    2016-12-28

    In previous studies we demonstrated that targeting the nuclear exporter protein exportin-1 (CRM1/XPO1) by a selective inhibitor of nuclear export (SINE) compound is a viable therapeutic strategy against Non-Hodgkin Lymphoma (NHL). Our studies along with pre-clinical work from others led to the evaluation of the lead SINE compound, selinexor, in a phase 1 trial in patients with CLL or NHL (NCT02303392). Continuing our previous work, we studied combinations of selinexor-dexamethasone (DEX) and selinexor-everolimus (EVER) in NHL. Combination of selinexor with DEX or EVER resulted in enhanced cytotoxicity in WSU-DLCL2 and WSU-FSCCL cells which was consistent with enhanced apoptosis. Molecular analysis showed enhancement in the activation of apoptotic signaling and down-regulation of XPO1. This enhancement is consistent with the mechanism of action of these drugs in that both selinexor and DEX antagonize NF-κB (p65) and mTOR (EVER target) is an XPO1 cargo protein. SINE compounds, KPT-251 and KPT-276, showed activities similar to CHOP (cyclophosphamide-hydroxydaunorubicin-oncovin-prednisone) regimen in subcutaneous and disseminated NHL xenograft models in vivo. In both animal models the anti-lymphoma activity of selinexor is enhanced through combination with DEX or EVER. The in vivo activity of selinexor and related SINE compounds relative to 'standard of care' treatment is consistent with the objective responses observed in Phase I NHL patients treated with selinexor. Our pre-clinical data provide a rational basis for testing these combinations in Phase II NHL trials.

  3. Effect of histone acetylation modification with MGCD0103, a histone deacetylase inhibitor, on nuclear reprogramming and the developmental competence of porcine somatic cell nuclear transfer embryos.

    Science.gov (United States)

    Jin, Long; Zhu, Hai-Ying; Guo, Qing; Li, Xiao-Chen; Zhang, Yu-Chen; Cui, Cheng-Du; Li, Wen-Xue; Cui, Zheng-Yun; Yin, Xi-Jun; Kang, Jin-Dan

    2017-01-01

    Cloning remains as an important technique to enhance the reconstitution and distribution of animal population with high-genetic merit. One of the major detrimental factors of this technique is the abnormal epigenetic modifications. MGCD0103 is known as a histone deacetylase inhibitor. In this study, we investigated the effect of MGCD0103 on the in vitro blastocyst formation rate in porcine somatic cell nuclear transferred (SCNT) embryos and expression in acetylation of the histone H3 lysine 9 and histone H4 lysine 12. We compared the in vitro embryonic development of SCNT embryos treated with different concentrations of MGCD0103 for 24 hours. Our results reported that treating with 0.2-μM MGCD0103 for 24 hours effectively improved the development of SCNT embryos, in comparison to the control group (blastocyst formation rate, 25.5 vs. 10.7%, P transferred into two surrogate sows, one of whom became pregnant and three fetuses developed. These results suggest that MGCD0103 can enhance the nuclear reprogramming and improve in vitro developmental potential of porcine SCNT embryos.

  4. In silico simulation of inhibitor drug effects on nuclear factor-kappaB pathway dynamics.

    Science.gov (United States)

    Sung, Myong-Hee; Simon, Richard

    2004-07-01

    NF-kappaB is a transcription factor family that activates numerous genes that are related to cell survival, apoptosis, and cell migration. Its persistent activity is associated with tumor formation, growth, metastasis, and drug resistance in many cancer types, including lymphoma, colon cancer, and breast cancer. Current therapeutic efforts for inhibiting this central "switch" include using small molecules to block a selected target in this pathway. Recognizing the regulatory network structure of the NF-kappaB pathway, we examine in silico the effects of inhibitors targeting various network components, using a kinetic model of the pathway. By simulating the corresponding perturbed system dynamics, we show the resulting time course of inhibition has distinct target-specific profiles. In particular, greater oscillatory potential exists for inhibition of upstream events than for direct inhibition of NF-kappaB, at low drug concentrations. This phenomenon is observed also when we examine the dynamic effects of the recently approved proteasome inhibitor, bortezomib (PS-341), and compare it with other inhibitors, taking its pharmacokinetics into consideration. Such kinetic analyses of the "drugged" molecular system will facilitate optimal drug target selection and the development of treatment protocols for a molecularly targeted therapy.

  5. Nuclear quantum effects in a HIV/cancer inhibitor: The case of ellipticine

    Science.gov (United States)

    Sappati, Subrahmanyam; Hassanali, Ali; Gebauer, Ralph; Ghosh, Prasenjit

    2016-11-01

    Ellipticine is a natural product that is currently being actively investigated for its inhibitory cancer and HIV properties. Here we use path-integral molecular dynamics coupled with excited state calculations to characterize the role of nuclear quantum effects on the structural and electronic properties of ellipticine in water, a common biological solvent. Quantum effects collectively enhance the fluctuations of both light and heavy nuclei of the covalent and hydrogen bonds in ellipticine. In particular, for the ellipticine-water system, where the proton donor and acceptor have different proton affinities, we find that nuclear quantum effects (NQEs) strengthen both the strong and the weak H bonds. This is in contrast to what is observed for the cases where the proton affinity of the donors and acceptors is same. These structural fluctuations cause a significant red-shift in the absorption spectra and an increase in the broadening, bringing it into closer agreement with the experiments. Our work shows that nuclear quantum effects alter both qualitatively and quantitatively the optical properties of this biologically relevant system and highlights the importance of the inclusion of these effects in the microscopic understanding of their optical properties. We propose that isotopic substitution will produce a blue shift and a reduction in the broadening of the absorption peak.

  6. Chemoprotective effect of a nuclear factor-kappaB inhibitor, pyrrolidine dithiocarbamate, against cisplatin-induced testicular damage in rats.

    Science.gov (United States)

    Ilbey, Yusuf Ozlem; Ozbek, Emin; Simsek, Abdulmuttalip; Cekmen, Mustafa; Otunctemur, Alper; Somay, Adnan

    2009-01-01

    The objective of this study was to evaluate inducible nitric oxide synthase (iNOS) and nuclear factor-kappaB inhibitor (NF-kappaB) expression and the potential chemoprotective effects of an NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC), against cisplatin-induced testicular damage in rats. Rats were divided into 4 equal groups: group 1, control; group 2, injected with cisplatin (CIS) for 5 days (7 mg/kg/day intraperitoneally [IP]); group 3, injected with PDTC alone; group 4, injected with CIS plus PDTC (100 mg/kg IP). Body and testicular weights, plasma testosterone levels, and histopathologic structure of the testicular tissue were determined. The iNOS and NF-kappaB activity were evaluated immunohistochemically by staining p65 to define NF-kappaB activity. Malondialdehyde (MDA), reduced glutathione (GSH), and nitric oxide (NO) levels and glutathione peroxidase (GSH-Px) activity were assessed in testicular tissue. Body and testicular weights, plasma testosterone levels, activity of GSH-Px, and GSH levels were all significantly decreased, whereas the levels of MDA and NO were significantly increased in rats of the CIS group. PDTC treatment increased plasma testosterone levels. A significant increase in GSH levels and GSH-Px activity and a decrease in MDA and NO levels in testicular tissue were observed in the CIS + PDTC group. Immunohistochemically, there was a marked staining for iNOS and NF-kappaB/p65 expression in rats injected with CIS compared with the control (P < .001). CIS caused irregular seminiferous tubules, reduction of seminiferous epithelial layers, significant arrest of maturation, and perivascular fibrosis. Moreover, PDTC administration to CIS-treated rats significantly prevented these histopathologic chances, as well. CIS induces iNOS expression through activation of NF-kappaB/p65, and CIS-induced testicular toxicity may be prevented by PDTC, which is a selective NF-kappaB inhibitor.

  7. A method for quantification of exportin-1 (XPO1) occupancy by Selective Inhibitor of Nuclear Export (SINE) compounds.

    Science.gov (United States)

    Crochiere, Marsha L; Baloglu, Erkan; Klebanov, Boris; Donovan, Scott; Del Alamo, Diego; Lee, Margaret; Kauffman, Michael; Shacham, Sharon; Landesman, Yosef

    2016-01-12

    Selective Inhibitor of Nuclear Export (SINE) compounds are a family of small-molecules that inhibit nuclear export through covalent binding to cysteine 528 (Cys528) in the cargo-binding pocket of Exportin 1 (XPO1/CRM1) and promote cancer cell death. Selinexor is the lead SINE compound currently in phase I and II clinical trials for advanced solid and hematological malignancies. In an effort to understand selinexor-XPO1 interaction and to establish whether cancer cell response is a function of drug-target engagement, we developed a quantitative XPO1 occupancy assay. Biotinylated leptomycin B (b-LMB) was utilized as a tool compound to measure SINE-free XPO1. Binding to XPO1 was quantitated from SINE compound treated adherent and suspension cells in vitro, dosed ex vivo human peripheral blood mononuclear cells (PBMCs), and PBMCs from mice dosed orally with drug in vivo. Evaluation of a panel of selinexor sensitive and resistant cell lines revealed that resistance was not attributed to XPO1 occupancy by selinexor. Administration of a single dose of selinexor bound XPO1 for minimally 72 hours both in vitro and in vivo. While XPO1 inhibition directly correlates with selinexor pharmacokinetics, the biological outcome of this inhibition depends on modulation of pathways downstream of XPO1, which ultimately determines cancer cell responsiveness.

  8. The p38 MAP kinase inhibitor SB203580 enhances nuclear factor-kappa B transcriptional activity by a non-specific effect upon the ERK pathway

    NARCIS (Netherlands)

    Birkenkamp, KU; Tuyt, LML; Lummen, C; Wierenga, LTJ; Kruijer, W; Vellenga, E

    2000-01-01

    1 In the present study we investigated a possible role for the p38 mitogen-activated protein (MAP) kinase pathway in mediating nuclear factor-kappa B (NF-kappa B) transcriptional activity in the erythroleukaemic cell line TF-1. 2 TF-1 cells stimulated with the phosphatase inhibitor okadaic acid (OA)

  9. High Resolution Nuclear Magnetic Resonance Studies of the Active Site of Chymotrypsin. II. Polarization of Histidine 57 by Substrate Analogues and Competitive Inhibitors

    NARCIS (Netherlands)

    Robillard, G.; Shulman, R.G.

    1974-01-01

    The proton nuclear magnetic resonance signal of the His57-Asp102 hydrogen bonded proton in the charge relay system of chymotrypsinogen A and chymotrypsin Aδ has been monitored to determine the influence of substrate analogues and competitive inhibitors on the electronic state of the active site regi

  10. High Resolution Nuclear Magnetic Resonance Studies of the Active Site of Chymotrypsin. II. Polarization of Histidine 57 by Substrate Analogues and Competitive Inhibitors

    NARCIS (Netherlands)

    Robillard, G.; Shulman, R.G.

    1974-01-01

    The proton nuclear magnetic resonance signal of the His57-Asp102 hydrogen bonded proton in the charge relay system of chymotrypsinogen A and chymotrypsin Aδ has been monitored to determine the influence of substrate analogues and competitive inhibitors on the electronic state of the active site regi

  11. Histone deacetylase inhibitor significantly improved the cloning efficiency of porcine somatic cell nuclear transfer embryos.

    Science.gov (United States)

    Huang, Yongye; Tang, Xiaochun; Xie, Wanhua; Zhou, Yan; Li, Dong; Yao, Chaogang; Zhou, Yang; Zhu, Jianguo; Lai, Liangxue; Ouyang, Hongsheng; Pang, Daxin

    2011-12-01

    Valproic acid (VPA), a histone deacetylase inbibitor, has been shown to generate inducible pluripotent stem (iPS) cells from mouse and human fibroblasts with a significant higher efficiency. Because successful cloning by somatic cell nuclear transfer (SCNT) undergoes a full reprogramming process in which the epigenetic state of a differentiated donor nuclear is converted into an embryonic totipotent state, we speculated that VPA would be useful in promoting cloning efficiency. Therefore, in the present study, we examined whether VPA can promote the developmental competence of SCNT embryos by improving the reprogramming state of donor nucleus. Here we report that 1 mM VPA for 14 to 16 h following activation significantly increased the rate of blastocyst formation of porcine SCNT embryos constructed from Landrace fetal fibroblast cells compared to the control (31.8 vs. 11.4%). However, we found that the acetylation level of Histone H3 lysine 14 and Histone H4 lysine 5 and expression level of Oct4, Sox2, and Klf4 was not significantly changed between VPA-treated and -untreated groups at the blastocyst stage. The SCNT embryos were transferred to 38 surrogates, and the cloning efficiency in the treated group was significantly improved compared with the control group. Taken together, we have demonstrated that VPA can improve both in vitro and in vivo development competence of porcine SCNT embryos.

  12. Oncoprotein p28GANK binds to RelA and retains NF-kB in the cytoplasm through nuclear export

    Institute of Scientific and Technical Information of China (English)

    Yao Chen; Hong Yang Wang; Hong Hai Li; Jing Fu; Xue Feng Wang; Yi Bin Ren; Li Wei Dong; Shan Hua Tang; Shu Qing Liu; Meng Chao Wu

    2007-01-01

    p2gGANK (also known as PSMD10, p28 and gankyrin) is an ankyrin repeat anti-apoptotic oncoprotein that is commonly overexpressed in hepatocellular carcinomas and increases the degradation of p53 and Rb. NF-kB (nuclear factor-KB) is known to be sequestered in the cytoplasm by IkB (inhibitor of NF-kB) proteins [1, 2], but much less is known about the cytoplasmic retention of NF-kB by other cellular proteins. Here we show that p28GANK inhibits NF-kB activity. As a nuclear-cytoplasmic shuttling protein, p28GANK directly binds to NF-KB/RelA and exports RelA from nucleus through a chromosomal region maintenance-1 (CRM-1) dependent pathway, which results in the cytoplasmic retention of NF-KB/RelA. We demonstrate that all the ankyrin repeats of p28GANK are required for the interaction with RelA and that the N terminus of p28GANK, which contains the nuclear export sequence (NES), is responsible for suppressing NF-KB/RelA nuclear translocation. These results suggest that overexpression of p28GANK prevents the nuclear localization and inhibits the activity of NF-KB/RelA.

  13. Combining oral contraceptives with a natural nuclear factor-kappa B inhibitor for the treatment of endometriosis-related pain

    Directory of Open Access Journals (Sweden)

    Maia H Jr

    2013-12-01

    Full Text Available Hugo Maia Jr,1–3 Clarice Haddad,3 Julio Casoy3 1Department of Gynecology and Obstetrics, School of Medicine, Federal University of Bahia, 2Itaigara Memorial Day Hospital, 3Centro de Pesquisas e Assistência em Reprodução Humana (CEPARH, Salvador, Bahia, Brazil Abstract: Endometriosis is a chronic disease in which a persistent state of heightened inflammation is maintained by nuclear factor-kappa B (NF-κB activation. The progestins present in oral contraceptives are potent inhibitors of NF-κB translocation to cell nuclei, while Pycnogenol® (Pinus pinaster acts by blocking post-translational events. In this study, the effects of Pycnogenol on pain scores were investigated in patients with endometriosis using oral contraceptives containing either gestodene or drospirenone in extended regimens. Pain scores were determined using a visual analog scale before and after 3 months of treatment. Oral contraceptives, used alone (groups 1 and 3 or in association with Pycnogenol (groups 2 and 4, resulted in significant decreases in pain scores after 3 months of treatment; however, this reduction was significantly greater in the groups using oral contraceptives + Pycnogenol (groups 2 and 4 compared with those using oral contraceptives alone (groups 1 and 3. In the groups using oral contraceptives alone, 50% of patients became pain-free by the end of the third month of treatment. These results suggest that Pycnogenol increases the efficacy of oral contraceptives for the treatment of endometriosis-related pain. Keywords: Pycnogenol®, aromatase, endometriosis, nuclear factor-kappa B

  14. Virtual screening for potential inhibitors of Mcl-1 conformations sampled by normal modes, molecular dynamics, and nuclear magnetic resonance

    Directory of Open Access Journals (Sweden)

    Glantz-Gashai Y

    2017-06-01

    Full Text Available Yitav Glantz-Gashai,* Tomer Meirson,* Eli Reuveni, Abraham O Samson Faculty of Medicine in the Galilee, Bar Ilan University, Safed, Israel *These authors contributed equally to this work Abstract: Myeloid cell leukemia-1 (Mcl-1 is often overexpressed in human cancer and is an important target for developing antineoplastic drugs. In this study, a data set containing 2.3 million lead-like molecules and a data set of all the US Food and Drug Administration (FDA-approved drugs are virtually screened for potential Mcl-1 ligands using Protein Data Bank (PDB ID 2MHS. The potential Mcl-1 ligands are evaluated and computationally docked on to three conformation ensembles generated by normal mode analysis (NMA, molecular dynamics (MD, and nuclear magnetic resonance (NMR, respectively. The evaluated potential Mcl-1 ligands are then compared with their clinical use. Remarkably, half of the top 30 potential drugs are used clinically to treat cancer, thus partially validating our virtual screen. The partial validation also favors the idea that the other half of the top 30 potential drugs could be used in the treatment of cancer. The normal mode-, MD-, and NMR-based conformation greatly expand the conformational sampling used herein for in silico identification of potential Mcl-1 inhibitors. Keywords: virtual screening, Mcl-1, molecular dynamics, NMR, normal modes

  15. Protective effects of the nuclear factor kappa B inhibitor pyrrolidine dithiocarbamate on experimental testicular torsion and detorsion injury.

    Science.gov (United States)

    Kabay, Sahin; Ozden, Hilmi; Guven, Gul; Burukoglu, Dilek; Ustuner, Mehmet Cengiz; Topal, Fatma; Gunes, Hasan Veysi; Ustuner, Derya; Ozbayer, Cansu

    2014-08-01

    Testicular torsion results with the damage of the testis and it is a surgical emergency. Pyrrolidine dithiocarbamate (PDTC) is a low-molecular-weight antioxidant and potent inhibitor of nuclear factor kappa B (NF-κB) activation. In this study, we aimed to investigate the effects of PDTC to testicular torsion-detorsion (T/D) injury. Forty adult male Sprague-Dawley rats were separated into four groups. A sham operation was performed in group I. In group II, torsion is performed 2 hours by 720 degree extravaginally testis. In group III, 4 h reperfusion of the testis was performed after 2 h of testicular torsion. In group IV, after performing the same surgical procedures as in group III, PDTC (100 mg/kg, intravenous's) was administered before 30 min of detorsion. The testes tissue malondialdehyde (MDA), superoxide dismutase (SOD) catalase (CAT) level was evaluated. Histological evaluations were performed after hematoxylin and eosin staining. Testicular tissue MDA levels were the highest in the T/D groups compared with treatment group. Administration of PDTC prevented a further increase in MDA levels. Significant decrease occurred in CAT and SOD levels in treatment group compared with the control group. The rats in the treatment group had normal testicular architecture. The results suggest that PDTC can be a potential protective agent for preventing the biochemical and histological changes related to oxidative stress in testicular injury caused by testis torsion.

  16. Effects of natural nuclear factor-kappa B inhibitors on anticancer drug efflux transporter human P-glycoprotein.

    Science.gov (United States)

    Nabekura, Tomohiro; Hiroi, Takashi; Kawasaki, Tatsuya; Uwai, Yuichi

    2015-03-01

    Drug efflux transporter P-glycoprotein plays an important role in cancer chemotherapy. The nuclear factor-κB (NF-κB) transcription factors play critical roles in development and progression of cancer. In this study, the effects of natural compounds that can inhibit NF-κB activation on the function of P-glycoprotein were investigated using human MDR1 gene-transfected KB/MDR1 cells. The accumulation of daunorubicin or rhodamine 123, fluorescent substrates of P-glycoprotein, in KB/MDR1 cells increased in the presence of caffeic acid phenetyl ester (CAPE), licochalcone A, anacardic acid, celastrol, xanthohumol, magnolol, and honokiol in a concentration-dependent manner. In contrast, lupeol, zerumbone, thymoquinone, emodin, and anethol had no effects. The ATPase activities of P-glycoprotein were stimulated by CAPE, licochalcone A, anacardic acid, celastrol, xanthohumol, magnolol, and honokiol. Tumor necrosis factor (TNF)-α stimulated NF-κB activation was inhibited by CAPE, licochalcone A, anacardic acid, and xanthohumol. KB/MDR1 cells were sensitized to vinblastine cytotoxicity by CAPE, licochalcone A, anacardic acid, xanthohumol, magnolol, and honokiol, showing that these natural NF-κB inhibitors reverse multidrug resistance. These results suggest that natural compounds, such as CAPE, licochalcone A, and anacardic acid, have dual inhibitory effects on the anticancer drug efflux transporter P-glycoprotein and NF-κB activation, and may become useful to enhance the efficacy of cancer chemotherapy.

  17. Combining oral contraceptives with a natural nuclear factor-kappa B inhibitor for the treatment of endometriosis-related pain

    Science.gov (United States)

    Maia, Hugo; Haddad, Clarice; Casoy, Julio

    2014-01-01

    Endometriosis is a chronic disease in which a persistent state of heightened inflammation is maintained by nuclear factor-kappa B (NF-κB) activation. The progestins present in oral contraceptives are potent inhibitors of NF-κB translocation to cell nuclei, while Pycnogenol® (Pinus pinaster) acts by blocking post-translational events. In this study, the effects of Pycnogenol on pain scores were investigated in patients with endometriosis using oral contraceptives containing either gestodene or drospirenone in extended regimens. Pain scores were determined using a visual analog scale before and after 3 months of treatment. Oral contraceptives, used alone (groups 1 and 3) or in association with Pycnogenol (groups 2 and 4), resulted in significant decreases in pain scores after 3 months of treatment; however, this reduction was significantly greater in the groups using oral contraceptives + Pycnogenol (groups 2 and 4) compared with those using oral contraceptives alone (groups 1 and 3). In the groups using oral contraceptives alone, 50% of patients became pain-free by the end of the third month of treatment. These results suggest that Pycnogenol increases the efficacy of oral contraceptives for the treatment of endometriosis-related pain. PMID:24379702

  18. Reciprocal regulation of nuclear factor kappa B and its inhibitor ZAS3 after peripheral nerve injury

    Directory of Open Access Journals (Sweden)

    Madiai Francesca

    2006-01-01

    Full Text Available Abstract Background NF-κB binds to the κB motif to regulate transcription of genes involved in growth, immunity and inflammation, and plays a pivotal role in the production of pro-inflammatory cytokines after nerve injuries. The zinc finger protein ZAS3 also binds to the κB or similar motif. In addition to competition for common DNA sites, in vitro experiments have shown that ZAS3 can inhibit NF-κB via the association with TRAF2 to inhibit the nuclear translocation of NF-κB. However, the physiological significance of the ZAS3-mediated inhibition of NF-κB has not been demonstrated. The purpose of this study is to characterize ZAS3 proteins in nervous tissues and to use spinal nerve ligation, a neuropathic pain model, to demonstrate a functional relationship between ZAS3 and NF-κB. Results Immunohistochemical experiments show that ZAS3 is expressed in specific regions of the central and peripheral nervous system. Abundant ZAS3 expression is found in the trigeminal ganglion, hippocampal formation, dorsal root ganglia, and motoneurons. Low levels of ZAS3 expressions are also found in the cerebral cortex and in the grey matter of the spinal cord. In those nervous tissues, ZAS3 is expressed mainly in the cell bodies of neurons and astrocytes. Together with results of Western blot analyses, the data suggest that ZAS3 protein isoforms with differential cellular distribution are produced in a cell-specific manner. Further, neuropathic pain confirmed by persistent mechanical allodynia was manifested in rats seven days after L5 and L6 lumbar spinal nerve ligation. Changes in gene expression, including a decrease in ZAS3 and an increase in the p65 subunit of NF-κB were observed in dorsal root ganglion ipsilateral to the ligation when compared to the contralateral side. Conclusion ZAS3 is expressed in nervous tissues involved in cognitive function and pain modulation. The down-regulation of ZAS3 after peripheral nerve injury may lead to activation of

  19. Nuclear localization of CPI-17, a protein phosphatase-1 inhibitor protein, affects histone H3 phosphorylation and corresponds to proliferation of cancer and smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Eto, Masumi, E-mail: masumi.eto@jefferson.edu [Department of Molecular Physiology and Biophysics, and Kimmel Cancer Center, Thomas Jefferson University, 1020 Locust Street, PA 19107 (United States); Kirkbride, Jason A.; Chugh, Rishika; Karikari, Nana Kofi [Department of Molecular Physiology and Biophysics, and Kimmel Cancer Center, Thomas Jefferson University, 1020 Locust Street, PA 19107 (United States); Kim, Jee In [Department of Molecular Physiology and Biophysics, and Kimmel Cancer Center, Thomas Jefferson University, 1020 Locust Street, PA 19107 (United States); Cardiovascular Research Institute, Kyungpook National University School of Medicine, Daegu 700-422 (Korea, Republic of)

    2013-04-26

    Highlights: •Non-canonical roles of the myosin phosphatase inhibitor (CPI-17) were studied. •CPI-17 is localized in the nucleus of hyperplastic cancer and smooth muscle cells. •CPI-17 Ser12 phosphorylation may regulate the nuclear import. •CPI-17 regulates histone H3 phosphorylation and cell proliferation. •The nuclear CPI-17-PP1 axis plays a proliferative role in cells. -- Abstract: CPI-17 (C-kinase-activated protein phosphatase-1 (PP1) inhibitor, 17 kDa) is a cytoplasmic protein predominantly expressed in mature smooth muscle (SM) that regulates the myosin-associated PP1 holoenzyme (MLCP). Here, we show CPI-17 expression in proliferating cells, such as pancreatic cancer and hyperplastic SM cells. Immunofluorescence showed that CPI-17 was concentrated in nuclei of human pancreatic cancer (Panc1) cells. Nuclear accumulation of CPI-17 was also detected in the proliferating vascular SM cell culture and cells at neointima of rat vascular injury model. The N-terminal 21-residue tail domain of CPI-17 was necessary for the nuclear localization. Phospho-mimetic Asp-substitution of CPI-17 at Ser12 attenuated the nuclear import. CPI-17 phosphorylated at Ser12 was not localized at nuclei, suggesting a suppressive role of Ser12 phosphorylation in the nuclear import. Activated CPI-17 bound to all three isoforms of PP1 catalytic subunit in Panc1 nuclear extracts. CPI-17 knockdown in Panc1 resulted in dephosphorylation of histone H3 at Thr3, Ser10 and Thr11, whereas it had no effects on the phosphorylation of myosin light chain and merlin, the known targets of MLCP. In parallel, CPI-17 knockdown suppressed Panc1 proliferation. We propose that CPI-17 accumulated in the nucleus through the N-terminal tail targets multiple PP1 signaling pathways regulating cell proliferation.

  20. Nuclear Factor kB and Inhibitor of kB: Acupuncture Protection Against Acute Focal Cerebral Ischemia in Rodents.

    Science.gov (United States)

    Huang, Wei; Zhou, Zhongyu; Wan, Bijiang; Chen, Guang; Li, Jia

    2017-02-27

    Context • Acute, focal, cerebral ischemic stroke is a leading cause of morbidity and mortality worldwide. Acupuncture is an emerging alternative therapy for treatment of acute brain ischemia. Nevertheless, the precise mechanism underlying the neuroprotective effects of acupuncture has not been elucidated. Nuclear factor κB (NF-κB) and nuclear factor of κ light polypeptide gene enhancer in B cell inhibitor alpha (IκB-α) are involved in cerebral inflammation. However, the involvement of NF-κB and IκB-α in the protective effects of acupuncture on ischemic tolerance remains unknown. Objective • The study evaluated the hypothesis that acupuncture can exert a neuroprotective action in a rat model of middle cerebral artery occlusion (MCAO). Design • The rats were randomly divided into a normal group (N), a sham model group (SM), an MCAO model group (M), a sham acupuncture group (SA), and an acupuncture group (A). Setting • All of processes of this study were conducted at Hubei University of Chinese Medicine (Hubei Shang, China). Animals • The animals were 100 Sprague-Dawley rats, aged 3 mo. Intervention • Craniotomy and electrocoagulation of the middle cerebral artery were conducted to generate acute, focal, cerebral ischemic models in 3 groups, excluding the N and SM groups. The SM group received a surgical fenestration similar to the M group, but the procedure did not include the coagulation of the exposed artery. In the A group, acupuncture was administered at the acupoints Baihui (GV-20) and Renzhong (GV-26). In the SA group, sham acupuncture was performed at a depth of 5 mm at a position close to the left side of the GV-20 and GV-26 points. The N, M, and SM groups received neither the acupuncture nor the sham acupuncture treatment. Outcome Measures • The study (1) evaluated neurological function using the modified neurological severity score; (2) examined the ultrastructure; (3) assessed the infarct volume; (4) determined levels of serum

  1. Dissociation between skeletal muscle inhibitor-{kappa}B kinase/nuclear factor-{kappa}B pathway activity and insulin sensitivity in nondiabetic twins

    DEFF Research Database (Denmark)

    Friedrichsen, Martin; Ribel-Madsen, Rasmus; Wojtaszewski, Jørgen

    2010-01-01

    Context: Several studies suggest a link between increased activity of the inflammatory inhibitor-kappaB kinase/nuclear factor-kappaB (IKK/NF-kappaB) pathway in skeletal muscle and insulin resistance. Objective: We aimed to study the regulation of skeletal muscle IKK/NF-kappaB pathway activity...... as well as the association with glucose metabolism and skeletal muscle insulin signaling. Methods: The study population included a metabolically well-characterized cohort of young and elderly predominantly nondiabetic twins (n = 181). Inhibitor-kappaBbeta (IkappaBbeta) protein levels are negatively...... associated with IKK/NF-kappaB pathway activity and were used to evaluate pathway activity with p65 levels included as loading control. This indirect measure for IKK/NF-kappaB pathway activity was validated by a p65 binding assay. Results: Evaluating the effects of heritability, age, sex, obesity, aerobic...

  2. Auxin responsiveness of the MONOPTEROS-BODENLOS module in primary root initiation critically depends on the nuclear import kinetics of the Aux/IAA inhibitor BODENLOS.

    Science.gov (United States)

    Herud, Ole; Weijers, Dolf; Lau, Steffen; Jürgens, Gerd

    2016-01-01

    Primary root formation in early embryogenesis of Arabidopsis thaliana is initiated with the specification of a single cell called hypophysis. This initial step requires the auxin-dependent release of the transcription factor MONOPTEROS (MP, also known as ARF5) from its inhibition by the Aux/IAA protein BODENLOS (BDL, also known as IAA12). Auxin-insensitive bdl mutant embryos and mp loss-of-function embryos fail to specify the hypophysis, giving rise to rootless seedlings. A suppressor screen of rootless bdl mutant seedlings yielded a mutation in the nuclear import receptor IMPORTIN-ALPHA 6 (IMPα6) that promoted primary root formation through rescue of the embryonic hypophysis defects, without causing additional phenotypic changes. Aux/IAA proteins are continually synthesized and degraded, which is essential for rapid transcriptional responses to changing auxin concentrations. Nuclear translocation of bdl:3×GFP was slowed down in impα6 mutants as measured by fluorescence recovery after photobleaching (FRAP) analysis, which correlated with the reduced inhibition of MP by bdl in transient expression assays in impα6 knock-down protoplasts. The MP-BDL module acts like an auxin-triggered genetic switch because MP activates its own expression as well as the expression of its inhibitor BDL. Using an established simulation model, we determined that the reduced nuclear translocation rate of BDL in impα6 mutant embryos rendered the auxin-triggered switch unstable, impairing the fast response to changes in auxin concentration. Our results suggest that the instability of the inhibitor BDL necessitates a fast nuclear uptake in order to reach the critical threshold level required for auxin responsiveness of the MP-BDL module in primary root initiation.

  3. The statin class of HMG-CoA reductase inhibitors demonstrate differential activation of the nuclear receptors PXR, CAR and FXR, as well as their downstream target genes.

    Science.gov (United States)

    Howe, Katharine; Sanat, Faizah; Thumser, Alfred E; Coleman, Tanya; Plant, Nick

    2011-07-01

    The therapeutic class of HMG-CoA reductase inhibitors, the statins are central agents in the treatment of hypercholesterolaemia and the associated conditions of cardiovascular disease, obesity and metabolic syndrome. Although statin therapy is generally considered safe, a number of known adverse effects do occur, most commonly treatment-associated muscular pain. In vitro evidence also supports the potential for drug-drug interactions involving this class of agents, and to examine this a ligand-binding assay was used to determine the ability of six clinically used statins for their ability to directly activate the nuclear receptors pregnane X-receptor (PXR), farnesoid X-receptor (FXR) and constitutive androstane receptor (CAR), demonstrating a relative activation of PXR>FXR>CAR. Using reporter gene constructs, we demonstrated that this order of activation is mirrored at the transcriptional activation level, with PXR-mediated gene activation being pre-eminent. Finally, we described a novel regulatory loop, whereby activation of FXR by statins increases PXR reporter gene expression, potentially enhancing PXR-mediated responses. Delineating the molecular interactions of statins with nuclear receptors is an important step in understanding the full biological consequences of statin exposure. This demonstration of their ability to directly activate nuclear receptors, leading to nuclear receptor cross-talk, has important potential implications for their use within a polypharmacy paradigm.

  4. Ca2+/calmodulin-dependent kinase II contributes to inhibitor of nuclear factor-kappa B kinase complex activation in Helicobacter pylori infection.

    Science.gov (United States)

    Maubach, Gunter; Sokolova, Olga; Wolfien, Markus; Rothkötter, Hermann-Josef; Naumann, Michael

    2013-09-15

    Helicobacter pylori, a class I carcinogen, induces a proinflammatory response by activating the transcription factor nuclear factor-kappa B (NF-κB) in gastric epithelial cells. This inflammatory condition could lead to chronic gastritis, which is epidemiologically and biologically linked to the development of gastric cancer. So far, there exists no clear knowledge on how H. pylori induces the NF-κB-mediated inflammatory response. In our study, we investigated the role of Ca(2+) /calmodulin-dependent kinase II (CAMKII), calmodulin, protein kinases C (PKCs) and the CARMA3-Bcl10-MALT1 (CBM) complex in conjunction with H. pylori-induced activation of NF-κB via the inhibitor of nuclear factor-kappa B kinase (IKK) complex. We use specific inhibitors and/or RNA interference to assess the contribution of these components. Our results show that CAMKII and calmodulin contribute to IKK complex activation and thus to the induction of NF-κB in response to H. pylori infection, but not in response to TNF-α. Thus, our findings are specific for H. pylori infected cells. Neither the PKCs α, δ, θ, nor the CBM complex itself is involved in the activation of NF-κB by H. pylori. The contribution of CAMKII and calmodulin, but not PKCs/CBM to the induction of an inflammatory response by H. pylori infection augment the understanding of the molecular mechanism involved and provide potential new disease markers for the diagnosis of gastric inflammatory diseases including gastric cancer.

  5. Nuclear receptor co-activators and HER-2/neu are upregulated in breast cancer patients during neo-adjuvant treatment with aromatase inhibitors

    Science.gov (United States)

    Flågeng, M Hauglid; Haugan Moi, L L; Dixon, J M; Geisler, J; Lien, E A; Miller, W R; Lønning, P E; Mellgren, G

    2009-01-01

    Background: Acquired resistance to endocrine therapy in breast cancer is poorly understood. Characterisation of the molecular response to aromatase inhibitors in breast cancer tissue may provide important information regarding development of oestrogen hypersensitivity. Methods: We examined the expression levels of nuclear receptor co-regulators, the orphan nuclear receptor liver receptor homologue-1 and HER-2/neu growth factor receptor using real-time RT-PCR before and after 13–16 weeks of primary medical treatment with the aromatase inhibitors anastrozole or letrozole. Results: mRNA expression of the steroid receptor co-activator 1 (SRC-1) and peroxisome-proliferator-activated receptor γ co-activator-1α (PGC-1α) was correlated (P=0.002), and both co-activators increased during treatment in the patient group as a whole (P=0.008 and P=0.032, respectively), as well as in the subgroup of patients achieving an objective treatment response (P=0.002 and P=0.006). Although we recorded no significant change in SRC-3/amplified in breast cancer 1 level, the expression correlated positively to the change of SRC-1 (P=0.002). Notably, we recorded an increase in HER-2/neu levels during therapy in the total patient group (18 out of 26; P=0.016), but in particular among responders (15 out of 21; P=0.008). Conclusion: Our results show an upregulation of co-activator mRNA and HER-2/neu during treatment with aromatase inhibitors. These mechanisms may represent an early adaption of the breast cancer cells to oestrogen deprivation in vivo. PMID:19755984

  6. Mangiferin, a novel nuclear factor kappa B-inducing kinase inhibitor, suppresses metastasis and tumor growth in a mouse metastatic melanoma model.

    Science.gov (United States)

    Takeda, Tomoya; Tsubaki, Masanobu; Sakamoto, Kotaro; Ichimura, Eri; Enomoto, Aya; Suzuki, Yuri; Itoh, Tatsuki; Imano, Motohiro; Tanabe, Genzoh; Muraoka, Osamu; Matsuda, Hideaki; Satou, Takao; Nishida, Shozo

    2016-09-01

    Advanced metastatic melanoma, one of the most aggressive malignancies, is currently without reliable therapy. Therefore, new therapies are urgently needed. Mangiferin is a naturally occurring glucosylxanthone and exerts many beneficial biological activities. However, the effect of mangiferin on metastasis and tumor growth of metastatic melanoma remains unclear. In this study, we evaluated the effect of mangiferin on metastasis and tumor growth in a mouse metastatic melanoma model. We found that mangiferin inhibited spontaneous metastasis and tumor growth. Furthermore, mangiferin suppressed the nuclear translocation of nuclear factor kappa B (NF-κB) and expression of phosphorylated NF-κB-inducing kinase (NIK), inhibitor of kappa B kinase (IKK), and inhibitor of kappa B (IκB) and increases the expression of IκB protein in vivo. In addition, we found that mangiferin inhibited the expression of matrix metalloproteinases (MMPs) and very late antigens (VLAs) in vivo. Mangiferin treatment also increased the expression of cleaved caspase-3, cleaved Poly ADP ribose polymerase-1 (PARP-1), p53 upregulated modulator of apoptosis (PUMA), p53, and phosphorylated p53 proteins, and decreased the expression of Survivin and Bcl-associated X (Bcl-xL) proteins in vivo. These results indicate that mangiferin selectivity suppresses the NF-κB pathway via inhibition of NIK activation, thereby inhibiting metastasis and tumor growth. Importantly, the number of reported NIK selective inhibitors is limited. Taken together, our data suggest that mangiferin may be a potential therapeutic agent with a new mechanism of targeting NIK for the treatment of metastatic melanoma.

  7. Lapatinib, a dual EGFR and HER2 tyrosine kinase inhibitor, downregulates thymidylate synthase by inhibiting the nuclear translocation of EGFR and HER2.

    Directory of Open Access Journals (Sweden)

    Hwang-Phill Kim

    Full Text Available BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI has been shown to exert a synergistic antitumor effect when combined with fluoropyrimidine. This synergy may be attributable to the downregulation of thymidylate synthase (TS, which is frequently overexpressed in fluoropyrimidine-resistant cancer cells. However, the molecular mechanism underlying the downregulation of TS has yet to be clearly elucidated. METHODOLOGY AND PRINCIPAL FINDINGS: In this study, we demonstrate that lapatinib, a dual TKI of EGFR and HER2 downregulates TS via inhibition of the nuclear translocation of EGFR and HER2. From our cDNA microarray experiments, we determined that a variety of nucleotide synthesis-related genes, including TS, were downregulated with lapatinib, and this was apparent in HER2-amplified cells. Targeted and pharmacologic inhibition assays confirmed that the dual inhibition of EGFR and HER2 is required for the more effective reduction of TS as compared to what was observed with gefitinib or trasutuzumab alone. Additionally, we determined that co-transfected EGFR and HER2 activate the TS gene promoter more profoundly than do either EGFR or HER2 alone. The translocation of EGFR and HER2 into the nucleus and the subsequent activation of the TS promoter were inhibited by lapatinib. CONCLUSIONS AND SIGNIFICANCE: These results demonstrate that lapatinib inhibits the nuclear translocation of EGFR and HER2 and downregulates TS, thus sensitizing cancer cells to fluoropyrimidine.

  8. Preclinical evaluation of the novel, orally bioavailable Selective Inhibitor of Nuclear Export (SINE KPT-335 in spontaneous canine cancer: results of a phase I study.

    Directory of Open Access Journals (Sweden)

    Cheryl A London

    Full Text Available BACKGROUND: The purpose of this study was to evaluate the activity of Selective Inhibitors of Nuclear Export (SINE compounds that inhibit the function of the nuclear export protein Exportin 1 (XPO1/CRM1 against canine tumor cell lines and perform a Phase I clinical trial of KPT-335 in dogs with spontaneous cancer to provide a preliminary assessment of biologic activity and tolerability. METHODS AND FINDINGS: Canine tumor cell lines derived from non-Hodgkin lymphoma (NHL, mast cell tumor, melanoma and osteosarcoma exhibited growth inhibition and apoptosis in response to nanomolar concentrations of SINE compounds; NHL cells were particularly sensitive with IC50 concentrations ranging from 2-42 nM. A Phase I clinical trial of KPT-335 was performed in 17 dogs with NHL (naive or relapsed, mast cell tumor or osteosarcoma. The maximum tolerated dose was 1.75 mg/kg given orally twice/week (Monday/Thursday although biologic activity was observed at 1 mg/kg. Clinical benefit (CB including partial response to therapy (PR, n = 2 and stable disease (SD, n = 7 was observed in 9/14 dogs with NHL with a median time to progression (TTP for responders of 66 days (range 35-256 days. A dose expansion study was performed in 6 dogs with NHL given 1.5 mg/kg KPT-335 Monday/Wednesday/Friday; CB was observed in 4/6 dogs with a median TTP for responders of 83 days (range 35-354 days. Toxicities were primarily gastrointestinal consisting of anorexia, weight loss, vomiting and diarrhea and were manageable with supportive care, dose modulation and administration of low dose prednisone; hepatotoxicity, anorexia and weight loss were the dose limiting toxicities. CONCLUSIONS: This study provides evidence that the novel orally bioavailable XPO1 inhibitor KPT-335 is safe and exhibits activity in a relevant, spontaneous large animal model of cancer. Data from this study provides critical new information that lays the groundwork for evaluation of SINE compounds in human cancer.

  9. Recurrent mutations of the exportin 1 gene (XPO1) and their impact on selective inhibitor of nuclear export compounds sensitivity in primary mediastinal B-cell lymphoma.

    Science.gov (United States)

    Jardin, Fabrice; Pujals, Anais; Pelletier, Laura; Bohers, Elodie; Camus, Vincent; Mareschal, Sylvain; Dubois, Sydney; Sola, Brigitte; Ochmann, Marlène; Lemonnier, François; Viailly, Pierre-Julien; Bertrand, Philippe; Maingonnat, Catherine; Traverse-Glehen, Alexandra; Gaulard, Philippe; Damotte, Diane; Delarue, Richard; Haioun, Corinne; Argueta, Christian; Landesman, Yosef; Salles, Gilles; Jais, Jean-Philippe; Figeac, Martin; Copie-Bergman, Christiane; Molina, Thierry Jo; Picquenot, Jean Michel; Cornic, Marie; Fest, Thierry; Milpied, Noel; Lemasle, Emilie; Stamatoullas, Aspasia; Moeller, Peter; Dyer, Martin J S; Sundstrom, Christer; Bastard, Christian; Tilly, Hervé; Leroy, Karen

    2016-09-01

    Primary mediastinal B-cell lymphoma (PMBL) is an entity of B-cell lymphoma distinct from the other molecular subtypes of diffuse large B-cell lymphoma (DLBCL). We investigated the prevalence, specificity, and clinical relevance of mutations of XPO1, which encodes a member of the karyopherin-β nuclear transporters, in a large cohort of PMBL. PMBL cases defined histologically or by gene expression profiling (GEP) were sequenced and the XPO1 mutational status was correlated to genetic and clinical characteristics. The XPO1 mutational status was also assessed in DLBCL, Hodgkin lymphoma (HL) and mediastinal gray-zone lymphoma (MGZL).The biological impact of the mutation on Selective Inhibitor of Nuclear Export (SINE) compounds (KPT-185/330) sensitivity was investigated in vitro. XPO1 mutations were present in 28/117 (24%) PMBL cases and in 5/19 (26%) HL cases but absent/rare in MGZL (0/20) or DLBCL (3/197). A higher prevalence (50%) of the recurrent codon 571 variant (p.E571K) was observed in GEP-defined PMBL and was associated with shorter PFS. Age, International Prognostic Index and bulky mass were similar in XPO1 mutant and wild-type cases. KPT-185 induced a dose-dependent decrease in cell proliferation and increased cell-death in PMBL cell lines harboring wild type or XPO1 E571K mutant alleles. Experiments in transfected U2OS cells further confirmed that the XPO1 E571K mutation does not have a drastic impact on KPT-330 binding. To conclude the XPO1 E571K mutation represents a genetic hallmark of the PMBL subtype and serves as a new relevant PMBL biomarker. SINE compounds appear active for both mutated and wild-type protein. Am. J. Hematol. 91:923-930, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. The cyclin-dependent kinase inhibitor roscovitine inhibits kinase activity, cell proliferation, multicellular development, and Cdk5 nuclear translocation in Dictyostelium discoideum.

    Science.gov (United States)

    Huber, Robert J; O'Day, Danton H

    2012-03-01

    Roscovitine, a cyclin-dependent kinase (Cdk) inhibitor, inhibited kinase activity and the axenic growth of Dictyostelium discoideum at micromolar concentrations. Growth was almost fully rescued in 50 µM and ≈ 50% rescued in 100 µM roscovitine-treated cultures by the over-expression of Cdk5-GFP. This supports the importance of Cdk5 function during cell proliferation in Dictyostelium and indicates that Cdk5 is a primary target of the drug. Roscovitine did not affect the expression of Cdk5 protein during axenic growth but did inhibit its nuclear translocation. This novel result suggests that the effects of roscovitine could be due in part to altering Cdk5 translocation in other systems as well. Kinase activity was inhibited by roscovitine in assays using AX3 whole cell lysates, but not in assays using lysates from Cdk5-GFP over-expressing cells. At higher concentrations, roscovitine impaired slug and fruiting body formation. Fruiting bodies that did form were small and produced relatively fewer spores many of which were round. However, roscovitine did not affect stalk cell differentiation. Together with previous findings, these data reveal that roscovitine inhibits Cdk5 during growth and as yet undefined Cdks during mid-late development. Copyright © 2011 Wiley Periodicals, Inc.

  11. Statins suppress glucose-induced plasminogen activator inhibitor-1 expression by regulating RhoA and nuclear factor-κB activities in cardiac microvascular endothelial cells.

    Science.gov (United States)

    Ni, Xiao-Qing; Zhu, Jian-Hua; Yao, Ning-Hua; Qian, Juan; Yang, Xiang-Jun

    2013-01-01

    The aim of this study was to investigate the possible proinflammatory signaling pathways involved in statin inhibition of glucose-induced plasminogen activator inhibitor-1 (PAI-1) expression in cardiac microvascular endothelial cells (CMECs). Primary rat CMECs were grown in the presence of 5.7 or 23 mmol/L glucose. PAI-1 mRNA and protein expression levels were measured by realtime polymerase chain reaction, Western blotting and enzyme-linked immunosorbent assay, respectively. A pull-down assay was performed to determine RhoA activity. IκBα protein expression was measured by Western blotting, nuclear factor (NF)-κB activation was detected by electrophoretic mobility shift assay and its transcription activity was determined by a dual luciferase reporter gene assay. PAI-1 mRNA and protein expression levels were both increased with high glucose concentrations, but they were significantly suppressed by simvastatin and atorvastatin treatment (P statins (P statins may occur partly by regulating the RhoA/ROCK-NF-κB pathway. The multifunctional roles of statins may be particularly beneficial for patients with metabolic syndrome.

  12. Amelioration of experimental autoimmune uveoretinitis (EAU) with an inhibitor of nuclear factor-kappaB (NF-kappaB), pyrrolidine dithiocarbamate.

    Science.gov (United States)

    Kitamei, Hirokuni; Iwabuchi, Kazuya; Namba, Kenichi; Yoshida, Kazuhiko; Yanagawa, Yoshiki; Kitaichi, Nobuyoshi; Kitamura, Mizuki; Ohno, Shigeaki; Onoé, Kazunori

    2006-06-01

    Experimental autoimmune uveoretinitis (EAU) is a T helper type 1 cell-mediated autoimmune disease, which serves as a model of human chronic uveitis. In this model, cells of a monocyte/macrophage lineage and retinal antigen (Ag)-specific T cells infiltrate into the retina and cause inflammatory lesion, where proinflammatory cytokines and various stimuli activate a transcriptional factor, nuclear factor-kappaB (NF-kappaB), which modulates inflammation and enhances immune responses. In the present study, the therapeutic effect of administration of a NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC), was examined in a murine EAU model. It was shown that PDTC ameliorated the clinical symptoms of EAU mice and significantly reduced the histopathological score compared with those in untreated mice. mRNA expressions of tumor necrosis factor alpha and interleukin-1beta were suppressed in eyes of PDTC-treated EAU mice. However, when T cells from PDTC-treated EAU mice, Ag-presenting cells (APC), and the retinal Ag peptides were cocultured, these T cells showed the same level of proliferation as those from control mice. Furthermore, addition of PDTC in the culture of T cells from EAU mice, Ag, and APC completely abrogated the T cell-proliferative response and cytokine production. Pretreatment of Ag-primed T cells or APC with PDTC in vitro also reduced these responses. These results indicate that the inhibitory effect of PDTC is attributed mainly to the suppression of effector-phase responses including inflammation but not to the inhibition of T cell priming. Regulation of NF-kappaB pathway in the lesion could be a novel target for the successful control of uveoretinitis.

  13. PARP inhibitors.

    Science.gov (United States)

    Anwar, Maheen; Aslam, Hafiz Muhammad; Anwar, Shahzad

    2015-01-01

    Poly (ADP-ribose) polymerases, abbreviated as PARPs, are a group of familiar proteins that play a central role in DNA repair employing the base excision repair (BER) pathway. There about 17 proteins in this family out of which the primary nuclear PARPs are PARP-1, PARP-2, PARP-3, and tankyrases 1 and 2 (PARP-5a and -5b) .The PARP family members are known to engage in a wide range of cellular activities, for example, DNA repair, transcription, cellular signaling, cell cycle regulation and mitosis amongst others. The chief functional units of PARP-1 are an amino terminal DNA binding domain (DBD), a central auto modification domain (AMD), and a carboxyl-terminal catalytic domain (CD). PARP inhibitors are currently undergoing clinical trials as targeted treatment modalities of breast, uterine, colorectal and ovarian cancer. This review summarizes current insights into the mechanism of action of PARP inhibitors, its recent clinical trials, and potential next steps in the evaluation of this promising class of anti-cancer drugs.

  14. Nuclear magnetic resonance studies on the pKa values and interaction of ionizable groups in bromelain inhibitor VI from pineapple stem.

    Science.gov (United States)

    Hatano, Ken-ichi; Kojima, Masaki; Tanokura, Masaru; Takahashi, Kenji

    2003-01-01

    Bromelain inhibitor VI (BI-VI), a cysteine proteinase inhibitor from pineapple stem, is a unique double-chain molecule composed of two distinct domains A and B. In order to clarify the molecular mechanism of the proteinase-inhibitor interaction, we investigated the electrostatic properties of this inhibitor. The inhibitory activity toward bromelain was revealed to be maximal at pH 3-4 and the gross conformation to be stable over a wide range of pH. Based on these results, pH titration experiments were performed on the proton resonances of BI-VI in the pH range of 1.5-9.9, and pKa values (pKexp) were determined for all carboxyl groups and alpha-amino groups. The pKexp were also compared with theoretical values calculated from the NMR-derived structures of BI-VI. The electrostatic surface potential map constructed using the pKexp values revealed that BI-VI possesses continuous negatively charged and scattered positively charged regions on the molecular surface and both regions appear to serve for docking properly with a basic target enzyme. Furthermore, it was suggested that the ionic interaction of the inhibitor with the target enzyme is primarily important for the inhibition, which seems to involve some carboxyl groups in the inhibitor and a thiol group in the proteinase.

  15. Targeting the Nuclear Cathepsin L CCAAT Displacement Protein/Cut Homeobox Transcription Factor-Epithelial Mesenchymal Transition Pathway in Prostate and Breast Cancer Cells with the Z-FY-CHO Inhibitor

    Science.gov (United States)

    Burton, Liza J.; Dougan, Jodi; Jones, Jasmine; Smith, Bethany N.; Randle, Diandra; Henderson, Veronica

    2016-01-01

    ABSTRACT The epithelial mesenchymal transition (EMT) promotes tumor migration and invasion by downregulating epithelial markers such as E-cadherin and upregulating mesenchymal markers such as vimentin. Cathepsin L (Cat L) is a cysteine protease that can proteolytically activate CCAAT displacement protein/cut homeobox transcription factor (CUX1). We hypothesized that nuclear Cat L may promote EMT via CUX1 and that this could be antagonized with the Cat L-specific inhibitor Z-FY-CHO. Mesenchymal prostate (ARCaP-M and ARCaP-E overexpressing Snail) and breast (MDA-MB-468, MDA-MB-231, and MCF-7 overexpressing Snail) cancer cells expressed lower E-cadherin activity, higher Snail, vimentin, and Cat L activity, and a p110/p90 active CUX1 form, compared to epithelial prostate (ARCaP-E and ARCaP-Neo) and breast (MCF-7 and MCF-7 Neo) cancer cells. There was increased binding of CUX1 to Snail and the E-cadherin promoter in mesenchymal cells compared to epithelial prostate and breast cells. Treatment of mesenchymal cells with the Cat L inhibitor Z-FY-CHO led to nuclear-to-cytoplasmic relocalization of Cat L, decreased binding of CUX1 to Snail and the E-cadherin promoter, reversed EMT, and decreased cell migration/invasion. Overall, our novel data suggest that a positive feedback loop between Snail-nuclear Cat L-CUX1 drives EMT, which can be antagonized by Z-FY-CHO. Therefore, Z-FY-CHO may be an important therapeutic tool to antagonize EMT and cancer progression. PMID:27956696

  16. Targeting the Nuclear Cathepsin L CCAAT Displacement Protein/Cut Homeobox Transcription Factor-Epithelial Mesenchymal Transition Pathway in Prostate and Breast Cancer Cells with the Z-FY-CHO Inhibitor.

    Science.gov (United States)

    Burton, Liza J; Dougan, Jodi; Jones, Jasmine; Smith, Bethany N; Randle, Diandra; Henderson, Veronica; Odero-Marah, Valerie A

    2017-03-01

    The epithelial mesenchymal transition (EMT) promotes tumor migration and invasion by downregulating epithelial markers such as E-cadherin and upregulating mesenchymal markers such as vimentin. Cathepsin L (Cat L) is a cysteine protease that can proteolytically activate CCAAT displacement protein/cut homeobox transcription factor (CUX1). We hypothesized that nuclear Cat L may promote EMT via CUX1 and that this could be antagonized with the Cat L-specific inhibitor Z-FY-CHO. Mesenchymal prostate (ARCaP-M and ARCaP-E overexpressing Snail) and breast (MDA-MB-468, MDA-MB-231, and MCF-7 overexpressing Snail) cancer cells expressed lower E-cadherin activity, higher Snail, vimentin, and Cat L activity, and a p110/p90 active CUX1 form, compared to epithelial prostate (ARCaP-E and ARCaP-Neo) and breast (MCF-7 and MCF-7 Neo) cancer cells. There was increased binding of CUX1 to Snail and the E-cadherin promoter in mesenchymal cells compared to epithelial prostate and breast cells. Treatment of mesenchymal cells with the Cat L inhibitor Z-FY-CHO led to nuclear-to-cytoplasmic relocalization of Cat L, decreased binding of CUX1 to Snail and the E-cadherin promoter, reversed EMT, and decreased cell migration/invasion. Overall, our novel data suggest that a positive feedback loop between Snail-nuclear Cat L-CUX1 drives EMT, which can be antagonized by Z-FY-CHO. Therefore, Z-FY-CHO may be an important therapeutic tool to antagonize EMT and cancer progression.

  17. First-in-Class, First-in-Human Phase I Study of Selinexor, a Selective Inhibitor of Nuclear Export, in Patients With Advanced Solid Tumors

    DEFF Research Database (Denmark)

    Abdul Razak, Albiruni R; Mau-Sørensen, Morten; Gabrail, Nashat Y

    2016-01-01

    PURPOSE: This trial evaluated the safety, pharmacokinetics, pharmacodynamics, and efficacy of selinexor (KPT-330), a novel, oral small-molecule inhibitor of exportin 1 (XPO1/CRM1), and determined the recommended phase II dose. PATIENTS AND METHODS: In total, 189 patients with advanced solid tumors...

  18. Structure-activity relationship studies of chalcone leading to 3-hydroxy-4,3',4',5'-tetramethoxychalcone and its analogues as potent nuclear factor kappaB inhibitors and their anticancer activities.

    Science.gov (United States)

    Srinivasan, Balasubramanian; Johnson, Thomas E; Lad, Rahul; Xing, Chengguo

    2009-11-26

    Chalcone is a privileged structure, demonstrating promising anti-inflammatory and anticancer activities. One potential mechanism is to suppress nuclear factor kappa B (NF-kappaB) activation. The structures of chalcone-based NF-kappaB inhibitors vary significantly that there is minimum information about their structure-activity relationships (SAR). This study aims to establish SAR of chalcone-based compounds to NF-kappaB inhibition, to explore the feasibility of developing simple chalcone-based potent NF-kappaB inhibitors, and to evaluate their anticancer activities. Three series of chalcones were synthesized in one to three steps with the key step being aldol condensation. These candidates demonstrated a wide range of NF-kappaB inhibitory activities, some of low micromolar potency, establishing that structural complexity is not required for NF-kappaB inhibition. Lead compounds also demonstrate potent cytotoxicity against lung cancer cells. Their cytotoxicities correlate moderately well with their NF-kappaB inhibitory activities, suggesting that suppressing NF-kappaB activation is likely responsible for at least some of the cytotoxicities. One lead compound effectively inhibits lung tumor growth with no signs of adverse side effects.

  19. Reduction of hippocampal apoptosis by intracerebroventricular administration of extracellular signal-regulated protein kinase and/or p38 inhibitors in amyloid beta rat model of Alzheimer's disease: involvement of nuclear-related factor-2 and nuclear factor-κB.

    Science.gov (United States)

    Ashabi, Ghorbangol; Alamdary, Shabnam Zeighamy; Ramin, Mahmoudreza; Khodagholi, Fariba

    2013-03-01

    In the present study, we examined the effects of intracerebroventricular administration of extracellular signal-regulated protein kinase- (ERK) and p38-specific inhibitors, U0126 and PD169316, respectively, on apoptosis induced by amyloid beta (Aβ) in rats. To investigate the effects of these compounds, we evaluated intracellular signalling pathways of apoptosis, as well as inflammatory and antioxidant pathways, 7 and 20 days after Aβ injection. We found that caspase-3 and Bax/Bcl-2 ratio, two hallmarks of apoptosis, were significantly decreased in the rats pre-treated with U0126 and PD169316, 7 days after Aβ injection. This observation was in agreement with the results of immunostaining analysis of the hippocampus that showed decreased levels of terminal transferase dUTP nick end labelling positive cells in the hippocampus of U0126 and PD169316 pre-treated rats, compared with the Aβ-injected group. We also chased the changes in the levels of calpain-2 and caspase-12, two ER factors, in the Aβ-injected and treatment groups. Decreased levels of calpain-2 and caspase-12 in U0126 and PD169316 pre-treated rats confirmed the protective effects of these inhibitors. Furthermore, we studied the effect of two stress-sensing transcription factors, nuclear-related factor-2 (Nrf2) and nuclear factor-кB (NF-кB), in Aβ-injected as wells as U0126 and PD169316 pre-treated rats. U0126 and PD169316 activated Nrf2 and suppressed NF-кB pathways, 7 days after Aβ injection. These antioxidant and inflammatory pathways restored to the vehicle level within 20 days. Taken together, our findings reinforce and extend the notion of the potential neuroprotective role of ERK and/or p38 inhibitors against the neuronal toxicity induced by Aβ.

  20. IκBζ, an atypical member of the inhibitor of nuclear factor kappa B family, is induced by γ-irradiation in glioma cells, regulating cytokine secretion and associated with poor prognosis.

    Science.gov (United States)

    Brennenstuhl, Heiko; Armento, Angela; Braczysnki, Anne Kristin; Mittelbronn, Michel; Naumann, Ulrike

    2015-11-01

    The inhibitor of nuclear factor kappa B zeta (IκBζ) is an atypical member of the IκB protein family. Its function in regulating the activity of the transcription factor nuclear factor kappa B (NFκB) as well as its involvement in cancer-associated processes is poorly understood. In glioma patients, enhanced expression of IκBζ in tumor specimen is associated with poor prognosis. Here we report that IκBζ is upregulated in a glioma cell line resistant towards NFκB-dependent non-apoptotic cell death. Upon γ-irradiation of glioma cells, IκBζ expression is enhanced, and subsequently serves as a transcriptional activator of the tumor promoting cytokines interleukin (IL-6), IL-8 and chemokine (C-X-C motif) ligand 1 (CXCL1) that are known to be involved in glioma associated inflammatory processes. In contrast, shRNA-mediated knockdown of IκBζ reduces the expression of the aforementioned cytokines. We propose a previously unappreciated role of IκBζ in the inflammatory micromilieu as well as progression in glioma.

  1. Activity of a selective inhibitor of nuclear export, selinexor (KPT-330), against AML-initiating cells engrafted into immunosuppressed NSG mice.

    Science.gov (United States)

    Etchin, J; Montero, J; Berezovskaya, A; Le, B T; Kentsis, A; Christie, A L; Conway, A S; Chen, W C; Reed, C; Mansour, M R; Ng, C E L; Adamia, S; Rodig, S J; Galinsky, I A; Stone, R M; Klebanov, B; Landesman, Y; Kauffman, M; Shacham, S; Kung, A L; Wang, J C Y; Letai, A; Look, A T

    2016-01-01

    Currently available combination chemotherapy for acute myeloid leukemia (AML) often fails to result in long-term remissions, emphasizing the need for novel therapeutic strategies. We reasoned that targeted inhibition of a prominent nuclear exporter, XPO1/CRM1, could eradicate self-renewing leukemia-initiating cells (LICs) whose survival depends on timely XPO1-mediated transport of specific protein and RNA cargoes. Using an immunosuppressed mouse model bearing primary patient-derived AML cells, we demonstrate that selinexor (KPT-330), an oral antagonist of XPO1 that is currently in clinical trials, has strong activity against primary AML cells while sparing normal stem and progenitor cells. Importantly, limiting dilution transplantation assays showed that this cytotoxic activity is not limited to the rapidly proliferating bulk population of leukemic cells but extends to the LICs, whose inherent drug resistance and unrestricted self-renewal capacity has been implicated in the difficulty of curing AML patients with conventional chemotherapy alone.

  2. The epigenetic effect of glucosamine and a nuclear factor-kappa B (NF-kB) inhibitor on primary human chondrocytes - Implications for osteoarthritis

    Energy Technology Data Exchange (ETDEWEB)

    Imagawa, Kei, E-mail: k.Imagawa@soton.ac.uk [University of Southampton Medical School, Bone and Joint Research Group, Southampton (United Kingdom); Tohoku University School of Medicine, Sendai (Japan); Andres, MC de [University of Southampton Medical School, Bone and Joint Research Group, Southampton (United Kingdom); Hashimoto, Ko [Hospital for Special Surgery, NY (United States); Pitt, Dominic [University of Southampton Medical School, Bone and Joint Research Group, Southampton (United Kingdom); Itoi, Eiji [Tohoku University School of Medicine, Sendai (Japan); Goldring, Mary B. [Hospital for Special Surgery, NY (United States); Roach, Helmtrud I.; Oreffo, Richard O.C. [University of Southampton Medical School, Bone and Joint Research Group, Southampton (United Kingdom)

    2011-02-18

    Research highlights: {yields} Glucosamine and a NF-kB inhibitor reduce inflammation in OA. {yields} Cytokine induced demethylation of CpG site in IL1{beta} promoter prevented by glucosamine. {yields} Glucosamine and NF-kB inhibitor have epigenetic effects on human chondrocytes. -- Abstract: Objective: Idiopathic osteoarthritis is the most common form of osteoarthritis (OA) world-wide and remains the leading cause of disability and the associated socio-economic burden in an increasing aging population. Traditionally, OA has been viewed as a degenerative joint disease characterized by progressive destruction of the articular cartilage and changes in the subchondral bone culminating in joint failure. However, the etiology of OA is multifactorial involving genetic, mechanical and environmental factors. Treatment modalities include analgesia, joint injection with steroids or hyaluronic acid, oral supplements including glucosamine and chondroitin sulfate, as well as physiotherapy. Thus, there is significant interest in the discovery of disease modifying agents. One such agent, glucosamine (GlcN) is commonly prescribed even though the therapeutic efficacy and mechanism of action remain controversial. Inflammatory cytokines, including IL-1{beta}, and proteinases such as MMP-13 have been implicated in the pathogenesis and progression of OA together with an associated CpG demethylation in their promoters. We have investigated the potential of GlcN to modulate NF-kB activity and cytokine-induced abnormal gene expression in articular chondrocytes and, critically, whether this is associated with an epigenetic process. Method: Human chondrocytes were isolated from the articular cartilage of femoral heads, obtained with ethical permission, following fractured neck of femur surgery. Chondrocytes were cultured for 5 weeks in six separate groups; (i) control culture, (ii) cultured with a mixture of 2.5 ng/ml IL-1{beta} and 2.5 ng/ml oncostatin M (OSM), (iii) cultured with 2 mM N

  3. The Nuclear Factor kappaB Inhibitor Pyrrolidine Dithiocarbamate Prevents Cardiac Remodelling and Matrix Metalloproteinase-2 Up-Regulation in Renovascular Hypertension.

    Science.gov (United States)

    Cau, Stefany B A; Guimaraes, Danielle A; Rizzi, Elen; Ceron, Carla S; Gerlach, Raquel F; Tanus-Santos, Jose E

    2015-10-01

    Imbalanced matrix metalloproteinase (MMP) activity is involved in hypertensive cardiac hypertrophy. Pharmacological inhibition of nuclear factor kappaB (NF-кB) with pyrrolidine dithiocarbamate (PDTC) can prevent MMP up-regulation. We suggested that treatment with PDTC could prevent 2-kidney, 1-clip (2K1C) hypertension-induced left ventricular remodelling. Sham-operated controls or 2K1C rats with hypertension received either vehicle or PDTC (100 mg/kg/day) by gavage for 8 weeks. Systolic blood pressure was monitored every week. Histological assessment of left ventricles was carried out with haematoxylin/eosin sections, and fibrosis was quantified in picrosirius red-stained sections. Oxidative stress was evaluated in heart samples with the dihydroethidium probe. Cardiac MMP activity was determined by in situ zymography, and cardiac MMP-2 was assessed by immunofluorescence. 2K1C surgery significantly increased systolic blood pressure in the 2K1C vehicle. PDTC exerted antihypertensive effects after 2 weeks of treatment. Histology revealed increased left ventricular and septum wall thickness associated with augmented myocyte diameter in hypertensive rats, which were reversed by treatment with PDTC. Hypertensive rats developed pronounced cardiac fibrosis with increased interstitial collagen area, increased cardiac reactive oxygen species levels, gelatinase activity and MMP-2 expression. PDTC treatment decreased these alterations. These findings show that PDTC modulates myocardial MMP-2 expression and ameliorates cardiac remodelling in renovascular hypertension. These results suggest that interfering with MMP expression at transcriptional level may be an interesting strategy in the therapy of organ damage associated with hypertension.

  4. Nuclear Medicine

    Science.gov (United States)

    ... for Parents/Teachers Resource Links for Students Glossary Nuclear Medicine What is nuclear medicine? What are radioactive ... NIBIB-funded researchers advancing nuclear medicine? What is nuclear medicine? Nuclear medicine is a medical specialty that ...

  5. 核电厂冷冻水系统更换缓蚀剂的可行性评估%Feasibility of Replacing Inhibitor for Chilled Water System of Nuclear Power Plant

    Institute of Scientific and Technical Information of China (English)

    谢建丽; 卢叶艇; 吴立新

    2015-01-01

    ABSTRACT:Objective To assess the influence of replacing inhibitors on the anti-corrosion treatment of chilled water system. Methods This paper studied the changes of corrosion resistance of A106B and B10 in the replacement process from the original in-hibitor ( NaNO2-Na2 MoO4 ) to a new inhibitor ( LiOH-N2 H4 ) by the means of electrochemical tests and surface analysis methods, such as linear polarization and AC impedance tests, SEM and XRD. Results The electrochemical results showed that the Rp value and Rt value of two pipe materials increased gradually while the Icorr value decreased in the replacement process of inhibitors. The surface analysis results showed that there was little rust on metal surfaces in original inhibitor solution, the rust layers were formed during the replacement process of inhibitors, and the rust layers were not thickened in the new inhibitor solution. Conclusion The original NaNO2-Na2 MoO4 medium had a good protective effect on the metal above by inhibiting anodic corrosion process. A106B carbon steel suffered a uniform corrosion and a rust layer formed on its surface, while B10 copper-nickel ally had a lesser degree of corrosion when the inhibitor was replacing, indicating the anti-corrosion property of the two materials was not decreased. The novel LiOH-N2 H4 medium, which can enhance the compactness of rust, was able to reduce the corrosion rate of rusted metal and increase the corrosion resistance of metals. It is feasible and operable to replace NaNO2-Na2 MoO4 with LiOH-N2 H4 medium for the anti-cor-rosion treatment of chilled water system of nuclear power plant.%目的:评估缓蚀剂更换过程对核电厂冷冻水系统管材防腐的影响。方法采用线性极化、交流阻抗、强极化等电化学方法以及扫描电镜、X 射线衍射等表面分析技术,研究在从原缓蚀剂( NaNO2-Na2MoO4介质)向新缓蚀剂(LiOH-联氨介质)置换过程中,A106B碳钢及B10铜镍合金等两种主体管材的耐蚀性

  6. Nuclear Confidence

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    The Fukushima nuclear accident provides valuable lessons for China national nuclear Corp.as it continues to expand its operations AS Japan’s Fukushima nuclear crisis sparks a global debate over nuclear safety,China National Nuclear Corp. (CNNC),the country’s largest nuclear plant operator, comes under the spotlight.

  7. Nuclear safeguards; Salvaguardias nucleares

    Energy Technology Data Exchange (ETDEWEB)

    Zurron, O.

    2015-07-01

    Safeguards control at the Juzbado Plant is implemented through the joint IAEA/EURATOM partnership approach in force within the European Union for all nuclear facilities. this verification agreement is designed to minimize burden on the operators whilst ensuring that both inspectorate achieve the objectives related to their respective safeguards regimes. This paper outlines the safeguards approaches followed by the inspectorate and the particularities of the Juzbado Plants nuclear material accountancy and control system. (Authors)

  8. Shikonin, a constituent of Lithospermum erythrorhizon exhibits anti-allergic effects by suppressing orphan nuclear receptor Nr4a family gene expression as a new prototype of calcineurin inhibitors in mast cells.

    Science.gov (United States)

    Wang, Xiaoyu; Hayashi, Shusaku; Umezaki, Masahito; Yamamoto, Takeshi; Kageyama-Yahara, Natsuko; Kondo, Takashi; Kadowaki, Makoto

    2014-12-05

    Over the last few decades, food allergy (FA) has become a common disease in infants in advanced countries. However, anti-allergic medicines available in the market have no effect on FA, and consequently effective drug therapies for FA are not yet available. We have already demonstrated that mucosal mast cells play an essential role in the development of FA in a murine model. Thus, we screened many constituents from medicinal herbs for the ability to inhibit rat basophilic leukemia-2H3 mast-like cell degranulation, and found that shikonin, a naphthoquinone dye from Lithospermum erythrorhizon, exhibited the most potent inhibitory effect among them. Furthermore, shikonin extremely inhibited the IgE/antigen-induced and calcium ionophore-induced upregulation of tumor necrosis factor (TNF)-α mRNA expression in mucosal-type bone marrow-derived mast cells (mBMMCs). Global gene expression analysis confirmed by real-time PCR revealed that shikonin drastically inhibited the IgE/antigen-induced and calcium ionophore-induced upregulation of mRNA expression of the nuclear orphan receptor 4a family (Nr4a1, Nr4a2 and Nr4a3) in mBMMCs, and knockdown of Nr4a1 or Nr4a2 suppressed the IgE/antigen-induced upregulation of TNF-α mRNA expression. Computational docking simulation of a small molecule for a target protein is a useful technique to elucidate the molecular mechanisms underlying the effects of drugs. Therefore, the simulation revealed that the predicted binding sites of shikonin to immunophilins (cyclophilin A and FK506 binding protein (FKBP) 12) were almost the same as the binding sites of immunosuppressants (cyclosporin A and FK506) to immunophilins. Indeed, shikonin inhibited the calcineurin activity to a similar extent as cyclosporin A that markedly suppressed the IgE/antigen-enhanced mRNA expression of TNF-α and the Nr4a family in mBMMCs. These findings suggest that shikonin suppresses mucosal mast cell activation by reducing Nr4a family gene expression through the

  9. Nuclear physics

    Energy Technology Data Exchange (ETDEWEB)

    Sang, David (Bishop Luffa Comprehensive School, Chichester (UK))

    1990-01-01

    Nuclear Physics covers the aspects of radioactivity and nuclear physics dealt with in the syllabuses of all the A-level examination boards; in particular, it provides detailed coverage of the Joint Matriculation Board option in nuclear physics. It deals with the discovery of the atomic nucleus, the physics of nuclear processes, and nuclear technology. (author).

  10. PARP Inhibitors for Cancer Therapy.

    Science.gov (United States)

    Lin, Ken Y; Kraus, W Lee

    2017-04-06

    Rucaparib is an inhibitor of nuclear poly (ADP-ribose) polymerases (inhibition of PARP-1 > PARP-2 > PARP-3), following a similar drug, Olaparib. It disrupts DNA repair and replication pathways (and possibly transcription), leading to selective killing of cancer cells with BRCA1/2 mutations. Rucaparib is approved for recurrent ovarian cancers with germline or somatic mutations in BRCA1/2. Copyright © 2017. Published by Elsevier Inc.

  11. Nuclear ventriculography

    Science.gov (United States)

    ... ventriculography (RNV); Multiple gate acquisition scan (MUGA); Nuclear cardiology; Cardiomyopathy - nuclear ventriculography ... 56. Udelson JE, Dilsizian V, Bonow RO. Nuclear cardiology. In: Bonow RO, Mann DL, Zipes DP, Libby ...

  12. Nuclear Medicine.

    Science.gov (United States)

    Badawi, Ramsey D.

    2001-01-01

    Describes the use of nuclear medicine techniques in diagnosis and therapy. Describes instrumentation in diagnostic nuclear medicine and predicts future trends in nuclear medicine imaging technology. (Author/MM)

  13. Nuclear Theory - Nuclear Power

    Science.gov (United States)

    Svenne, J. P.; Canton, L.; Kozier, K. S.

    2008-01-01

    The results from modern nuclear theory are accurate and reliable enough to be used for practical applications, in particular for scattering that involves few-nucleon systems of importance to nuclear power. Using well-established nucleon-nucleon (NN) interactions that fit well the NN scattering data, and the AGS form of the three-body theory, we have performed precise calculations of low-energy neutron-deuteron (n+d) scattering. We show that three-nucleon force effects that have impact on the low-energy vector analyzing powers have no practical effects on the angular distribution of the n+d cross-section. There appear to be problems for this scattering in the evaluated nuclear data file (ENDF) libraries, at the incident neutron energies less than 3.2 MeV. Supporting experimental data in this energy region are rather old (>25 years), sparse and often inconsistent. Our three-body results at low energies, 50 keV to 10.0 MeV, are compared to the ENDF/B-VII.0 and JENDL (Japanese Evaluated Nuclear Data Library) -3.3 evaluated angular distributions. The impact of these results on the calculated reactivity for various critical systems involving heavy water is shown.

  14. Nuclear control

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Wan Kee [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1995-02-01

    International cooperation in nuclear industries requires nuclear control as prerequisites. The concept of nuclear control is based on the Treaty on the Non-proliferation of Nuclear Weapon (NPT). The International Atomic Energy Agency (IAEA) plays central role in implementing nuclear control. Nuclear control consists of nuclear safeguards, physical protection, and export/import control. Each member state of NPT is subject to the IAEA`s safeguards by concluding safeguards agreements with the IAEA. IAEA recommends member states to implement physical protection on nuclear materials by `The Physical Protection of Nuclear Material` and `The Convention on the Physical Protection of Nuclear Material` of IAEA. Export/Import Control is to deter development of nuclear weapons by controlling international trade on nuclear materials, nuclear equipments and technology. Current status of domestic and foreign nuclear control implementation including recent induction of national inspection system in Korea is described and functions of recently set-up Technology Center for Nuclear Control (TCNC) under the Korea Atomic Energy Research Institute (KAERI) are also explained. 6 tabs., 11 refs. (Author).

  15. Nuclear Scans

    Science.gov (United States)

    Nuclear scans use radioactive substances to see structures and functions inside your body. They use a special ... images. Most scans take 20 to 45 minutes. Nuclear scans can help doctors diagnose many conditions, including ...

  16. Nuclear Chemistry.

    Science.gov (United States)

    Chemical and Engineering News, 1979

    1979-01-01

    Provides a brief review of the latest developments in nuclear chemistry. Nuclear research today is directed toward increased activity in radiopharmaceuticals and formation of new isotopes by high-energy, heavy-ion collisions. (Author/BB)

  17. Nuclear weapons, nuclear effects, nuclear war

    Energy Technology Data Exchange (ETDEWEB)

    Bing, G.F.

    1991-08-20

    This paper provides a brief and mostly non-technical description of the militarily important features of nuclear weapons, of the physical phenomena associated with individual explosions, and of the expected or possible results of the use of many weapons in a nuclear war. Most emphasis is on the effects of so-called ``strategic exchanges.``

  18. Nuclear Ambitions

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    China will begin to build the world’s first third-generation nuclear power plant at the Sanmen Nuclear Power Project in Sanmen City, coastal Zhejiang Province, in March 2009, accord-ing to the State Nuclear Power Technology Corp.

  19. Nuclear structure

    CERN Document Server

    Nazarewicz, W

    1999-01-01

    Current developments in nuclear structure are discussed from a theoretical perspective. The studies of the nuclear many-body system provide us with invaluable information about the nature of the nuclear interaction, nucleonic correlations at various energy-distance scales, and the modes of the nucleonic matter.

  20. Nuclear spectroscopy

    CERN Document Server

    Ajzenberg-Selove, Fay

    1960-01-01

    Nuclear Spectroscopy, Part B focuses on the ways in which experimental data may be analyzed to furnish information about nuclear parameters and nuclear models in terms of which the data are interpreted.This book discusses the elastic and inelastic potential scattering amplitudes, role of beta decay in nuclear physics, and general selection rules for electromagnetic transitions. The nuclear shell model, fundamental coupling procedure, vibrational spectra, and empirical determination of the complex potential are also covered. This publication is suitable for graduate students preparing for exper

  1. High-resolution α-amylase assay combined with high-performance liquid chromatography−solid-phase extraction−nuclear magnetic resonance spectroscopy for expedited identification of α-amylase inhibitors – proof of concept and α-amylase inhibitor in cinnamon

    DEFF Research Database (Denmark)

    Okutan, Leyla; Kongstad, Kenneth Thermann; Jäger, Anna

    2014-01-01

    Type 2 diabetes affects millions of people worldwide, and new improved drugs or functional foods containing selective α-amylase inhibitors are needed for improved management of blood glucose. In this article the development of a microplate-based high-resolution α-amylase inhibition assay with dir......Type 2 diabetes affects millions of people worldwide, and new improved drugs or functional foods containing selective α-amylase inhibitors are needed for improved management of blood glucose. In this article the development of a microplate-based high-resolution α-amylase inhibition assay...

  2. Drug design from the cryptic inhibitor envelope.

    Science.gov (United States)

    Lee, Chul-Jin; Liang, Xiaofei; Wu, Qinglin; Najeeb, Javaria; Zhao, Jinshi; Gopalaswamy, Ramesh; Titecat, Marie; Sebbane, Florent; Lemaitre, Nadine; Toone, Eric J; Zhou, Pei

    2016-02-25

    Conformational dynamics plays an important role in enzyme catalysis, allosteric regulation of protein functions and assembly of macromolecular complexes. Despite these well-established roles, such information has yet to be exploited for drug design. Here we show by nuclear magnetic resonance spectroscopy that inhibitors of LpxC--an essential enzyme of the lipid A biosynthetic pathway in Gram-negative bacteria and a validated novel antibiotic target--access alternative, minor population states in solution in addition to the ligand conformation observed in crystal structures. These conformations collectively delineate an inhibitor envelope that is invisible to crystallography, but is dynamically accessible by small molecules in solution. Drug design exploiting such a hidden inhibitor envelope has led to the development of potent antibiotics with inhibition constants in the single-digit picomolar range. The principle of the cryptic inhibitor envelope approach may be broadly applicable to other lead optimization campaigns to yield improved therapeutics.

  3. Drug design from the cryptic inhibitor envelope

    Science.gov (United States)

    Lee, Chul-Jin; Liang, Xiaofei; Wu, Qinglin; Najeeb, Javaria; Zhao, Jinshi; Gopalaswamy, Ramesh; Titecat, Marie; Sebbane, Florent; Lemaitre, Nadine; Toone, Eric J.; Zhou, Pei

    2016-01-01

    Conformational dynamics plays an important role in enzyme catalysis, allosteric regulation of protein functions and assembly of macromolecular complexes. Despite these well-established roles, such information has yet to be exploited for drug design. Here we show by nuclear magnetic resonance spectroscopy that inhibitors of LpxC—an essential enzyme of the lipid A biosynthetic pathway in Gram-negative bacteria and a validated novel antibiotic target—access alternative, minor population states in solution in addition to the ligand conformation observed in crystal structures. These conformations collectively delineate an inhibitor envelope that is invisible to crystallography, but is dynamically accessible by small molecules in solution. Drug design exploiting such a hidden inhibitor envelope has led to the development of potent antibiotics with inhibition constants in the single-digit picomolar range. The principle of the cryptic inhibitor envelope approach may be broadly applicable to other lead optimization campaigns to yield improved therapeutics. PMID:26912110

  4. 抑制核因子-κB受体活化因子及其配体通路治疗牙周炎的研究进展%Research advances on inhibition receptor activator of nuclear factor-κB and its ligand in periodontal treatment

    Institute of Scientific and Technical Information of China (English)

    陈斌

    2012-01-01

    核因子-κB受体活化因子(RANK)及其配体(RANKL)在牙周炎患者的牙槽骨吸收中具有重要的作用,抑制RANKL/RANK通路,可有效抑制破骨细胞的分化和激活,从而抑制牙槽骨的吸收.骨保护蛋白(OPG)可和RANKL结合,干扰RANKL和RANK的结合,从而防止骨组织的过度破坏.本文就RANKL/RANK/OPG轴、RANKL/RANK/OPG与牙周炎、抑制RANKL/RANK通路治疗牙周炎的可行性等研究进展作一综述.%Receptor activator of nuclear factor-KB(RANK) /receptor activator of nuclear factor-KB ligand(RAN-KL)blay a critical role in alveolar bone resorption though affecting osteoclasts formation and activation, therefore, we can inhibit periodontal bone resorption though RANKL/RANK inhibition. Osteoprotegerin(OPG) protects bone from excessive resorption by binding to RANKL and preventing it from binding to RANK. In this paper, we will review the relationship between RANKL/RANK/OPG signaling pathway and periodontal disease, and we will mainly focus on the possibility of periodontal treatment with RANKL/RANK inhibition.

  5. Nuclear Fission

    Science.gov (United States)

    Denschlag, J. O.

    This chapter first gives a survey on the history of the discovery of nuclear fission. It briefly presents the liquid-drop and shell models and their application to the fission process. The most important quantities accessible to experimental determination such as mass yields, nuclear charge distribution, prompt neutron emission, kinetic energy distribution, ternary fragment yields, angular distributions, and properties of fission isomers are presented as well as the instrumentation and techniques used for their measurement. The contribution concentrates on the fundamental aspects of nuclear fission. The practical aspects of nuclear fission are discussed in http://dx.doi.org/10.1007/978-1-4419-0720-2_57 of Vol. 6.

  6. Nuclear Safety

    Energy Technology Data Exchange (ETDEWEB)

    Silver, E G [ed.

    1989-01-01

    This document is a review journal that covers significant developments in the field of nuclear safety. Its scope includes the analysis and control of hazards associated with nuclear energy, operations involving fissionable materials, and the products of nuclear fission and their effects on the environment. Primary emphasis is on safety in reactor design, construction, and operation; however, the safety aspects of the entire fuel cycle, including fuel fabrication, spent-fuel processing, nuclear waste disposal, handling of radioisotopes, and environmental effects of these operations, are also treated.

  7. Inhibitors of protein kinase C

    Institute of Scientific and Technical Information of China (English)

    LIU Shiying; JIANG Yuyang; CAO Jian; LIU Feng; MA Li; ZHAO Yufen

    2005-01-01

    Protein kinase catalyzes the transfer of the γ-phosphoryl group from ATP to the hydroxyl groups of protein side chains, which plays critical roles in signal transduction pathways by transmitting extracellular signals across the plasma membrane and nuclear membrane to the destination sites in the cytoplasm and the nucleus. Protein kinase C (PKC) is a superfamily of phospholipid-dependent Ser/Thr kinase. There are at least 12 isozymes in PKC family. They are distributed in different tissues and play different roles in physiological processes. On account of their concern with a variety of pathophysiologic states, such as cancer, inflammatory conditions, autoimmune disorder, and cardiac diseases, the inhibitors, which can inhibit the activity of PKC and the interaction of cytokine with receptor, and interfere signal transduction pathway, may be candidates of therapeutic drugs. Therefore, intense efforts have been made to develop specific protein kinase inhibitors as biological tools and therapeutic agents. This article reviews the recent development of some of PKC inhibitors based on their interaction with different conserved domains and different inhibition mechanisms.

  8. Proton pump inhibitors

    Science.gov (United States)

    Proton pump inhibitors (PPIs) are medicines that work by reducing the amount of stomach acid made by ... Proton pump inhibitors are used to: Relieve symptoms of acid reflux, or gastroesophageal reflux disease (GERD). This ...

  9. Nuclear Astrophysics

    Science.gov (United States)

    Drago, Alessandro

    2005-04-01

    The activity of the Italian nuclear physicists community in the field of Nuclear Astrophysics is reported. The researches here described have been performed within the project "Fisica teorica del nucleo e dei sistemi a multi corpi", supported by the Ministero dell'Istruzione, dell'Università e della Ricerca.

  10. Nuclear stress test

    Science.gov (United States)

    ... Persantine stress test; Thallium stress test; Stress test - nuclear; Adenosine stress test; Regadenoson stress test; CAD - nuclear stress; Coronary artery disease - nuclear stress; Angina - nuclear ...

  11. Nuclear questions

    Energy Technology Data Exchange (ETDEWEB)

    Durrani, M. [Physics World (United Kingdom)

    2006-01-01

    The future of nuclear power has returned to centre stage. Freezing weather on both sides of the Atlantic and last month's climate-change talks in Montreal have helped to put energy and the future of nuclear power right back on the political agenda. The issue is particularly pressing for those countries where existing nuclear stations are reaching the end of their lives. In the UK, prime minister Tony Blair has commissioned a review of energy, with a view to deciding later this year whether to build new nuclear power plants. The review comes just four years after the Labour government published a White Paper on energy that said the country should keep the nuclear option open but did not follow this up with any concrete action. In Germany, new chancellor and former physicist Angela Merkel is a fan of nuclear energy and had said she would extend the lifetime of its nuclear plants beyond 2020, when they are due to close. However, that commitment has had to be abandoned, at least for the time being, following negotiations with her left-wing coalition partners. The arguments in favour of nuclear power will be familiar to all physicists - it emits almost no carbon dioxide and can play a vital role in maintaining a diverse energy supply. To over-rely on imported supplies of oil and gas can leave a nation hostage to fortune. The arguments against are equally easy to list - the public is scared of nuclear power, it generates dangerous waste with potentially huge clean-up costs, and it is not necessarily cheap. Nuclear plants could also be a target for terrorist attacks. Given political will, many of these problems can be resolved, or at least tackled. China certainly sees the benefits of nuclear power, as does Finland, which is building a new 1600 MW station - the world's most powerful - that is set to open in 2009. Physicists, of course, are essential to such developments. They play a vital role in ensuring the safety of such plants and developing new types of

  12. PARP1 Inhibitors: antitumor drug design.

    Science.gov (United States)

    Malyuchenko, N V; Kotova, E Yu; Kulaeva, O I; Kirpichnikov, M P; Studitskiy, V M

    2015-01-01

    The poly (ADP-ribose) polymerase 1 (PARP1) enzyme is one of the promising molecular targets for the discovery of antitumor drugs. PARP1 is a common nuclear protein (1-2 million molecules per cell) serving as a "sensor" for DNA strand breaks. Increased PARP1 expression is sometimes observed in melanomas, breast cancer, lung cancer, and other neoplastic diseases. The PARP1 expression level is a prognostic indicator and is associated with a poor survival prognosis. There is evidence that high PARP1 expression and treatment-resistance of tumors are correlated. PARP1 inhibitors are promising antitumor agents, since they act as chemo- and radiosensitizers in the conventional therapy of malignant tumors. Furthermore, PARP1 inhibitors can be used as independent, effective drugs against tumors with broken DNA repair mechanisms. Currently, third-generation PARP1 inhibitors are being developed, many of which are undergoing Phase II clinical trials. In this review, we focus on the properties and features of the PARP1 inhibitors identified in preclinical and clinical trials. We also describe some problems associated with the application of PARP1 inhibitors. The possibility of developing new PARP1 inhibitors aimed at DNA binding and transcriptional activity rather than the catalytic domain of the protein is discussed.

  13. Nuclear Physics

    CERN Document Server

    Savage, Martin J

    2016-01-01

    Lattice QCD is making good progress toward calculating the structure and properties of light nuclei and the forces between nucleons. These calculations will ultimately refine the nuclear forces, particularly in the three- and four-nucleon sector and the short-distance interactions of nucleons with electroweak currents, and allow for a reduction of uncertainties in nuclear many-body calculations of nuclei and their reactions. After highlighting their importance, particularly to the Nuclear Physics and High-Energy Physics experimental programs, I discuss the progress that has been made toward achieving these goals and the challenges that remain.

  14. Nuclear reaction

    CERN Multimedia

    Penwarden, C

    2001-01-01

    At the European Research Organization for Nuclear Research, Nobel laureates delve into the mysteries of particle physics. But when they invited artists from across the continent to visit their site in Geneva, they wanted a new kind of experiment.

  15. Nuclear Disarmament.

    Science.gov (United States)

    Johnson, Christopher

    1982-01-01

    Material about nuclear disarmament and the arms race should be included in secondary school curricula. Teachers can present this technical, controversial, and frightening material in a balanced and comprehensible way. Resources for instructional materials are listed. (PP)

  16. Nuclear Data

    Energy Technology Data Exchange (ETDEWEB)

    White, Morgan C. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2014-01-23

    PowerPoint presentation targeted for educational use. Nuclear data comes from a variety of sources and in many flavors. Understanding where the data you use comes from and what flavor it is can be essential to understand and interpret your results. This talk will discuss the nuclear data pipeline with particular emphasis on providing links to additional resources that can be used to explore the issues you will encounter.

  17. Nuclear Structure

    Science.gov (United States)

    Gargano, Angela

    2003-04-01

    An account of recent studies in the field of theoretical nuclear structure is reported. These studies concern essentially research activities performed under the Italian project "Fisica Teorica del Nucleo e dei Sistemi a Molti Corpi". Special attention is addressed to results obtained during the last two years as regards the development of new many-body techniques as well as the interpretation of new experimental aspects of nuclear structure.

  18. Nuclear astrophysics

    Energy Technology Data Exchange (ETDEWEB)

    Arnould, M. [Institut d' Astronomie et d' Astrophysique, Universite Libre de Bruxelles, Bruxelles (Belgium); Takahashi, K. [Max-Planck-Institut fuer Astrophysik, Garching (Germany)

    1999-03-01

    Nuclear astrophysics is that branch of astrophysics which helps understanding of the Universe, or at least some of its many faces, through the knowledge of the microcosm of the atomic nucleus. It attempts to find as many nuclear physics imprints as possible in the macrocosm, and to decipher what those messages are telling us about the varied constituent objects in the Universe at present and in the past. In the last decades much advance has been made in nuclear astrophysics thanks to the sometimes spectacular progress made in the modelling of the structure and evolution of the stars, in the quality and diversity of the astronomical observations, as well as in the experimental and theoretical understanding of the atomic nucleus and of its spontaneous or induced transformations. Developments in other subfields of physics and chemistry have also contributed to that advance. Notwithstanding the accomplishment, many long-standing problems remain to be solved, and the theoretical understanding of a large variety of observational facts needs to be put on safer grounds. In addition, new questions are continuously emerging, and new facts endangering old ideas. This review shows that astrophysics has been, and still is, highly demanding to nuclear physics in both its experimental and theoretical components. On top of the fact that large varieties of nuclei have to be dealt with, these nuclei are immersed in highly unusual environments which may have a significant impact on their static properties, the diversity of their transmutation modes, and on the probabilities of these modes. In order to have a chance of solving some of the problems nuclear astrophysics is facing, the astrophysicists and nuclear physicists are obviously bound to put their competence in common, and have sometimes to benefit from the help of other fields of physics, like particle physics, plasma physics or solid-state physics. Given the highly varied and complex aspects, we pick here some specific nuclear

  19. Nuclear astrophysics

    Science.gov (United States)

    Arnould, M.; Takahashi, K.

    1999-03-01

    Nuclear astrophysics is that branch of astrophysics which helps understanding of the Universe, or at least some of its many faces, through the knowledge of the microcosm of the atomic nucleus. It attempts to find as many nuclear physics imprints as possible in the macrocosm, and to decipher what those messages are telling us about the varied constituent objects in the Universe at present and in the past. In the last decades much advance has been made in nuclear astrophysics thanks to the sometimes spectacular progress made in the modelling of the structure and evolution of the stars, in the quality and diversity of the astronomical observations, as well as in the experimental and theoretical understanding of the atomic nucleus and of its spontaneous or induced transformations. Developments in other subfields of physics and chemistry have also contributed to that advance. Notwithstanding the accomplishment, many long-standing problems remain to be solved, and the theoretical understanding of a large variety of observational facts needs to be put on safer grounds. In addition, new questions are continuously emerging, and new facts endangering old ideas. This review shows that astrophysics has been, and still is, highly demanding to nuclear physics in both its experimental and theoretical components. On top of the fact that large varieties of nuclei have to be dealt with, these nuclei are immersed in highly unusual environments which may have a significant impact on their static properties, the diversity of their transmutation modes, and on the probabilities of these modes. In order to have a chance of solving some of the problems nuclear astrophysics is facing, the astrophysicists and nuclear physicists are obviously bound to put their competence in common, and have sometimes to benefit from the help of other fields of physics, like particle physics, plasma physics or solid-state physics. Given the highly varied and complex aspects, we pick here some specific nuclear

  20. Nuclear Nonproliferation

    Energy Technology Data Exchange (ETDEWEB)

    Atkins-Duffin, C E

    2008-12-10

    With an explosion equivalent of about 20kT of TNT, the Trinity test was the first demonstration of a nuclear weapon. Conducted on July 16, 1945 in Alamogordo, NM this site is now a Registered National Historic Landmark. The concept and applicability of nuclear power was demonstrated on December 20, 1951 with the Experimental Breeder Reactor Number One (EBR-1) lit four light bulbs. This reactor is now a Registered National Historic Landmark, located near Arco, ID. From that moment forward it had been clearly demonstrated that nuclear energy has both peaceful and military applications and that the civilian and military fuel cycles can overlap. For the more than fifty years since the Atoms for Peace program, a key objective of nuclear policy has been to enable the wider peaceful use of nuclear energy while preventing the spread of nuclear weapons. Volumes have been written on the impact of these two actions on the world by advocates and critics; pundits and practioners; politicians and technologists. The nations of the world have woven together a delicate balance of treaties, agreements, frameworks and handshakes that are representative of the timeframe in which they were constructed and how they have evolved in time. Collectively these vehicles attempt to keep political will, nuclear materials and technology in check. This paper captures only the briefest abstract of the more significant aspects on the Nonproliferation Regime. Of particular relevance to this discussion is the special nonproliferation sensitivity associated with the uranium isotope separation and spent fuel reprocessing aspects of the nuclear fuel cycle.

  1. Inner/Outer nuclear membrane fusion in nuclear pore assembly: biochemical demonstration and molecular analysis.

    Science.gov (United States)

    Fichtman, Boris; Ramos, Corinne; Rasala, Beth; Harel, Amnon; Forbes, Douglass J

    2010-12-01

    Nuclear pore complexes (NPCs) are large proteinaceous channels embedded in double nuclear membranes, which carry out nucleocytoplasmic exchange. The mechanism of nuclear pore assembly involves a unique challenge, as it requires creation of a long-lived membrane-lined channel connecting the inner and outer nuclear membranes. This stabilized membrane channel has little evolutionary precedent. Here we mapped inner/outer nuclear membrane fusion in NPC assembly biochemically by using novel assembly intermediates and membrane fusion inhibitors. Incubation of a Xenopus in vitro nuclear assembly system at 14°C revealed an early pore intermediate where nucleoporin subunits POM121 and the Nup107-160 complex were organized in a punctate pattern on the inner nuclear membrane. With time, this intermediate progressed to diffusion channel formation and finally to complete nuclear pore assembly. Correct channel formation was blocked by the hemifusion inhibitor lysophosphatidylcholine (LPC), but not if a complementary-shaped lipid, oleic acid (OA), was simultaneously added, as determined with a novel fluorescent dextran-quenching assay. Importantly, recruitment of the bulk of FG nucleoporins, characteristic of mature nuclear pores, was not observed before diffusion channel formation and was prevented by LPC or OA, but not by LPC+OA. These results map the crucial inner/outer nuclear membrane fusion event of NPC assembly downstream of POM121/Nup107-160 complex interaction and upstream or at the time of FG nucleoporin recruitment.

  2. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... Resources Professions Site Index A-Z Children's (Pediatric) Nuclear Medicine Children’s (pediatric) nuclear medicine imaging uses small ... of Children's Nuclear Medicine? What is Children's (Pediatric) Nuclear Medicine? Nuclear medicine is a branch of medical ...

  3. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... News Physician Resources Professions Site Index A-Z Children's (Pediatric) Nuclear Medicine Children’s (pediatric) nuclear medicine imaging ... the limitations of Children's Nuclear Medicine? What is Children's (Pediatric) Nuclear Medicine? Nuclear medicine is a branch ...

  4. General Nuclear Medicine

    Science.gov (United States)

    ... Physician Resources Professions Site Index A-Z General Nuclear Medicine Nuclear medicine imaging uses small amounts of ... limitations of General Nuclear Medicine? What is General Nuclear Medicine? Nuclear medicine is a branch of medical ...

  5. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... Resources Professions Site Index A-Z Children's (Pediatric) Nuclear Medicine Children’s (pediatric) nuclear medicine imaging uses small ... of Children's Nuclear Medicine? What is Children's (Pediatric) Nuclear Medicine? Nuclear medicine is a branch of medical ...

  6. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... Physician Resources Professions Site Index A-Z Children's (Pediatric) Nuclear Medicine Children’s (pediatric) nuclear medicine imaging uses ... limitations of Children's Nuclear Medicine? What is Children's (Pediatric) Nuclear Medicine? Nuclear medicine is a branch of ...

  7. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... Professions Site Index A-Z Children's (Pediatric) Nuclear Medicine Children’s (pediatric) nuclear medicine imaging uses small amounts ... Children's Nuclear Medicine? What is Children's (Pediatric) Nuclear Medicine? Nuclear medicine is a branch of medical imaging ...

  8. Children's (Pediatric) Nuclear Medicine

    Science.gov (United States)

    ... Professions Site Index A-Z Children's (Pediatric) Nuclear Medicine Children’s (pediatric) nuclear medicine imaging uses small amounts ... Children's Nuclear Medicine? What is Children's (Pediatric) Nuclear Medicine? Nuclear medicine is a branch of medical imaging ...

  9. The nuclear factor-κB inhibitor pyrrolidine dithiocarbamate reduces polyinosinic-polycytidilic acid-induced immune response in pregnant rats and the behavioral defects of their adult offspring

    Directory of Open Access Journals (Sweden)

    Song Xueqin

    2011-12-01

    Full Text Available Abstract Background Epidemiological studies have indicated that maternal infection during pregnancy may lead to a higher incidence of schizophrenia in the offspring. It is assumed that the maternal infection increases the immune response, leading to neurodevelopmental disorders in the offspring. Maternal polyinosinic-polycytidilic acid (PolyI:C treatment induces a wide range of characteristics in the offspring mimicking some schizophrenia symptoms in humans. These observations are consistent with the neurodevelopmental hypothesis of schizophrenia. Methods We examined whether suppression of the maternal immune response could prevent neurodevelopmental disorders in adult offspring. PolyI:C or saline was administered to early pregnant rats to mimic maternal infection, and the maternal immune response represented by tumor necrosis factor alpha (TNF-α and interleukin-10 (IL-10 levels was determined by enzyme-linked immunosorbent assays (ELISA. The NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC was used to suppress the maternal immune response. Neurodevelopmental disorders in adult offspring were examined by prepulse inhibition (PPI, passive avoidance, and active avoidance tests. Results PolyI:C administration to early pregnant rats led to elevated serum cytokine levels as shown by massive increases in serum TNF-α and IL-10 levels. The adult offspring showed defects in prepulse inhibition, and passive avoidance and active avoidance tests. PDTC intervention in early pregnant rats suppressed cytokine increases and reduced the severity of neurodevelopmental defects in adult offspring. Conclusions Our findings suggest that PDTC can suppress the maternal immune response induced by PolyI:C and partially prevent neurodevelopmental disorders of adult offspring.

  10. Nuclear scales

    Energy Technology Data Exchange (ETDEWEB)

    Friar, J.L.

    1998-12-01

    Nuclear scales are discussed from the nuclear physics viewpoint. The conventional nuclear potential is characterized as a black box that interpolates nucleon-nucleon (NN) data, while being constrained by the best possible theoretical input. The latter consists of the longer-range parts of the NN force (e.g., OPEP, TPEP, the {pi}-{gamma} force), which can be calculated using chiral perturbation theory and gauged using modern phase-shift analyses. The shorter-range parts of the force are effectively parameterized by moments of the interaction that are independent of the details of the force model, in analogy to chiral perturbation theory. Results of GFMC calculations in light nuclei are interpreted in terms of fundamental scales, which are in good agreement with expectations from chiral effective field theories. Problems with spin-orbit-type observables are noted.

  11. Nuclear Scales

    CERN Document Server

    Friar, J L

    1998-01-01

    Nuclear scales are discussed from the nuclear physics viewpoint. The conventional nuclear potential is characterized as a black box that interpolates nucleon-nucleon (NN) data, while being constrained by the best possible theoretical input. The latter consists of the longer-range parts of the NN force (e.g., OPEP, TPEP, the $\\pi$-$\\gamma$ force), which can be calculated using chiral perturbation theory and gauged using modern phase-shift analyses. The shorter-range parts of the force are effectively parameterized by moments of the interaction that are independent of the details of the force model, in analogy to chiral perturbation theory. Results of GFMC calculations in light nuclei are interpreted in terms of fundamental scales, which are in good agreement with expectations from chiral effective field theories. Problems with spin-orbit-type observables are noted.

  12. Nuclear astrophysics

    CERN Document Server

    Arnould, M

    1999-01-01

    Nuclear astrophysics is that branch of astrophysics which helps understanding some of the many facets of the Universe through the knowledge of the microcosm of the atomic nucleus. In the last decades much advance has been made in nuclear astrophysics thanks to the sometimes spectacular progress in the modelling of the structure and evolution of the stars, in the quality and diversity of the astronomical observations, as well as in the experimental and theoretical understanding of the atomic nucleus and of its spontaneous or induced transformations. Developments in other sub-fields of physics and chemistry have also contributed to that advance. Many long-standing problems remain to be solved, however, and the theoretical understanding of a large variety of observational facts needs to be put on safer grounds. In addition, new questions are continuously emerging, and new facts endanger old ideas. This review shows that astrophysics has been, and still is, highly demanding to nuclear physics in both its experime...

  13. Nuclear Models

    Science.gov (United States)

    Fossión, Rubén

    2010-09-01

    The atomic nucleus is a typical example of a many-body problem. On the one hand, the number of nucleons (protons and neutrons) that constitute the nucleus is too large to allow for exact calculations. On the other hand, the number of constituent particles is too small for the individual nuclear excitation states to be explained by statistical methods. Another problem, particular for the atomic nucleus, is that the nucleon-nucleon (n-n) interaction is not one of the fundamental forces of Nature, and is hard to put in a single closed equation. The nucleon-nucleon interaction also behaves differently between two free nucleons (bare interaction) and between two nucleons in the nuclear medium (dressed interaction). Because of the above reasons, specific nuclear many-body models have been devised of which each one sheds light on some selected aspects of nuclear structure. Only combining the viewpoints of different models, a global insight of the atomic nucleus can be gained. In this chapter, we revise the the Nuclear Shell Model as an example of the microscopic approach, and the Collective Model as an example of the geometric approach. Finally, we study the statistical properties of nuclear spectra, basing on symmetry principles, to find out whether there is quantum chaos in the atomic nucleus. All three major approaches have been rewarded with the Nobel Prize of Physics. In the text, we will stress how each approach introduces its own series of approximations to reduce the prohibitingly large number of degrees of freedom of the full many-body problem to a smaller manageable number of effective degrees of freedom.

  14. Nuclear Assessment

    Institute of Scientific and Technical Information of China (English)

    CHARLES K.EBINGER; JOHN P.BANKS

    2010-01-01

    @@ In President Barack Obama's State of the Union address in January 2009,he called for the building of "a new generation of safe,clean nuclear power plants" This was followed by his highprofile speech in Prague in April 2009,in which he noted the need "to harness the power of nuclear energy on behalf of our efforts to combat climate change."In December 2009 in Copenhagen,he pledged the United States will reduce carbon dioxide (CO2) emissions 17 percent from 2005 levels by 2020.

  15. Nuclear winter or nuclear fall?

    Science.gov (United States)

    Berger, André

    Climate is universal. If a major modern nuclear war (i.e., with a large number of small-yield weapons) were to happen, it is not even necessary to have a specific part of the world directly involved for there to be cause to worry about the consequences for its inhabitants and their future. Indeed, smoke from fires ignited by the nuclear explosions would be transported by winds all over the world, causing dark and cold. According to the first study, by Turco et al. [1983], air surface temperature over continental areas of the northern mid-latitudes (assumed to be the nuclear war theatre) would fall to winter levels even in summer (hence the term “nuclear winter”) and induce drastic climatic conditions for several months at least. The devastating effects of a nuclear war would thus last much longer than was assumed initially. Discussing to what extent these estimations of long-term impacts on climate are reliable is the purpose of this article.

  16. PARP Inhibition Suppresses Growth of EGFR-Mutant Cancers by Targeting Nuclear PKM2

    Directory of Open Access Journals (Sweden)

    Nan Li

    2016-04-01

    Full Text Available Upon growth factor stimulation or in some EGFR mutant cancer cells, PKM2 translocates into the nucleus to induce glycolysis and cell growth. Here, we report that nuclear PKM2 binds directly to poly-ADP ribose, and this PAR-binding capability is critical for its nuclear localization. Accordingly, PARP inhibition prevents nuclear retention of PKM2 and therefore suppresses cell proliferation and tumor growth. In addition, we found that PAR level correlates with nuclear localization of PKM2 in EGFR mutant brain and lung cancers, suggesting that PAR-dependent nuclear localization of PKM2 likely contributes to tumor progression in EGFR mutant glioblastoma and lung cancers. In addition, some EGFR-inhibitor-resistant lung cancer cells are sensitive to PARP inhibitors. Taken together, our data indicate that suppression of PKM2 nuclear function by PARP inhibitors represents a treatment strategy for EGFR-inhibitor-resistant cancers.

  17. Nuclear Assessment

    Institute of Scientific and Technical Information of China (English)

    CHARLES; K.; EBINGER; JOHN; P.; BANKS

    2010-01-01

    The United States needs a comprehensive policy and market-based solutions to address the challenges and demands of energy provision in President Barack Obama’s State of the Union address in January 2009, he called for the building of "a new generation of safe, clean nuclear power plants." This was followed by his high- profile speech in Prague in April 2009,

  18. Nuclear Science.

    Science.gov (United States)

    Pennsylvania State Dept. of Education, Harrisburg. Bureau of Curriculum Services.

    This document is a report on a course in nuclear science for the high school curriculum. The course is designed to provide a basic but comprehensive understanding of the atom in the light of modern knowledge, and to show how people attempt to harness the tremendous energy liberated through fission and fusion reactions. The course crosses what are…

  19. Nuclear Physics

    Science.gov (United States)

    Contents: V Dinucleons, published in The Physical Review , v93 n4 p908-909, 15 Feb 1954; Concentration of a Cyclotron Beam by Strong Focusing Lenses...published in The Review of Scientific Instruments, v25 n4 p365-367, Apr 1954; and Photon Splitting in a Nuclear Electrostatic Field, published in The Physical Review , v94 n2 p367-368, 15 Apr 1954.

  20. Nuclear Waffles

    CERN Document Server

    Schneider, A S; Briggs, C M; Caplan, M E; Horowitz, C J

    2014-01-01

    The dense neutron-rich matter found in supernovae and neutron stars is expected to form complex nonuniform phases referred to as nuclear pasta. The pasta shapes depend on density, temperature and proton fraction and determine many transport properties in supernovae and neutron star crusts. We use two recently developed hybrid CPU/GPU codes to perform large scale molecular dynamics (MD) simulations with $51200$ and $409600$ nucleons of nuclear pasta. From the output of the MD simulations we characterize the topology and compute two observables, the radial distribution function $g(r)$ and the structure factor $S(q)$, for systems with proton fractions $Y_p=0.10, 0.20, 0.30$ and $0.40$ at about one third of nuclear saturation density and temperatures near $1.0$ MeV. We observe that the two lowest proton fraction systems simulated, $Y_p=0.10$ and $0.20$, equilibrate quickly and form liquid-like structures. Meanwhile, the two higher proton fraction systems, $Y_p=0.30$ and $0.40$, take a longer time to equilibrate a...

  1. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... are the limitations of Children's Nuclear Medicine? What is Children's (Pediatric) Nuclear Medicine? Nuclear medicine is a ... of your child's body. top of page How is the procedure performed? Nuclear medicine imaging is usually ...

  2. CRM1 Inhibitors for Antiviral Therapy

    Directory of Open Access Journals (Sweden)

    Cynthia Mathew

    2017-06-01

    Full Text Available Infectious diseases are a major global concern and despite major advancements in medical research, still cause significant morbidity and mortality. Progress in antiviral therapy is particularly hindered by appearance of mutants capable of overcoming the effects of drugs targeting viral components. Alternatively, development of drugs targeting host proteins essential for completion of viral lifecycle holds potential as a viable strategy for antiviral therapy. Nucleocytoplasmic trafficking pathways in particular are involved in several pathological conditions including cancer and viral infections, where hijacking or alteration of function of key transporter proteins, such as Chromosome Region Maintenance1 (CRM1 is observed. Overexpression of CRM1-mediated nuclear export is evident in several solid and hematological malignancies. Interestingly, CRM1-mediated nuclear export of viral components is crucial in various stages of the viral lifecycle and assembly. This review summarizes the role of CRM1 in cancer and selected viruses. Leptomycin B (LMB is the prototypical inhibitor of CRM1 potent against various cancer cell lines overexpressing CRM1 and in limiting viral infections at nanomolar concentrations in vitro. However, the irreversible shutdown of nuclear export results in high cytotoxicity and limited efficacy in vivo. This has prompted search for synthetic and natural CRM1 inhibitors that can potentially be developed as broadly active antivirals, some of which are summarized in this review.

  3. Nuclear photonics

    Science.gov (United States)

    Habs, D.; Günther, M. M.; Jentschel, M.; Thirolf, P. G.

    2012-07-01

    With the planned new γ-beam facilities like MEGa-ray at LLNL (USA) or ELI-NP at Bucharest (Romania) with 1013 γ/s and a band width of ΔEγ/Eγ≈10-3, a new era of γ beams with energies up to 20MeV comes into operation, compared to the present world-leading HIγS facility at Duke University (USA) with 108 γ/s and ΔEγ/Eγ≈3ṡ10-2. In the long run even a seeded quantum FEL for γ beams may become possible, with much higher brilliance and spectral flux. At the same time new exciting possibilities open up for focused γ beams. Here we describe a new experiment at the γ beam of the ILL reactor (Grenoble, France), where we observed for the first time that the index of refraction for γ beams is determined by virtual pair creation. Using a combination of refractive and reflective optics, efficient monochromators for γ beams are being developed. Thus, we have to optimize the total system: the γ-beam facility, the γ-beam optics and γ detectors. We can trade γ intensity for band width, going down to ΔEγ/Eγ≈10-6 and address individual nuclear levels. The term "nuclear photonics" stresses the importance of nuclear applications. We can address with γ-beams individual nuclear isotopes and not just elements like with X-ray beams. Compared to X rays, γ beams can penetrate much deeper into big samples like radioactive waste barrels, motors or batteries. We can perform tomography and microscopy studies by focusing down to μm resolution using Nuclear Resonance Fluorescence (NRF) for detection with eV resolution and high spatial resolution at the same time. We discuss the dominating M1 and E1 excitations like the scissors mode, two-phonon quadrupole octupole excitations, pygmy dipole excitations or giant dipole excitations under the new facet of applications. We find many new applications in biomedicine, green energy, radioactive waste management or homeland security. Also more brilliant secondary beams of neutrons and positrons can be produced.

  4. Nuclear tele medicine; Telemedicina nuclear

    Energy Technology Data Exchange (ETDEWEB)

    Vargas, L.; Hernandez, F.; Fernandez, R. [Departamento de Medicina Nuclear, Imagenologia Diagnostica, Xalapa, Veracruz (Mexico)

    2005-07-01

    The great majority of the digital images of nuclear medicine are susceptible of being sent through internet. This has allowed that the work in diagnosis cabinets by image it can benefit of this modern technology. We have presented in previous congresses works related with tele medicine, however, due to the speed in the evolution of the computer programs and the internet, becomes necessary to make a current position in this modality of work. (Author)

  5. The nuclear arsenals and nuclear disarmament.

    Science.gov (United States)

    Barnaby, F

    1998-01-01

    Current world stockpiles of nuclear weapons and the status of treaties for nuclear disarmament and the ultimate elimination of nuclear weapons are summarised. The need for including stockpiles of civil plutonium in a programme for ending production and disposing of fissile materials is emphasized, and the ultimate difficulty of disposing of the last few nuclear weapons discussed.

  6. Nuclear energy.

    Science.gov (United States)

    Grandin, Karl; Jagers, Peter; Kullander, Sven

    2010-01-01

    Nuclear energy can play a role in carbon free production of electrical energy, thus making it interesting for tomorrow's energy mix. However, several issues have to be addressed. In fission technology, the design of so-called fourth generation reactors show great promise, in particular in addressing materials efficiency and safety issues. If successfully developed, such reactors may have an important and sustainable part in future energy production. Working fusion reactors may be even more materials efficient and environmental friendly, but also need more development and research. The roadmap for development of fourth generation fission and fusion reactors, therefore, asks for attention and research in these fields must be strengthened.

  7. Applications of nuclear physics

    Science.gov (United States)

    Hayes, A. C.

    2017-02-01

    Today the applications of nuclear physics span a very broad range of topics and fields. This review discusses a number of aspects of these applications, including selected topics and concepts in nuclear reactor physics, nuclear fusion, nuclear non-proliferation, nuclear-geophysics, and nuclear medicine. The review begins with a historic summary of the early years in applied nuclear physics, with an emphasis on the huge developments that took place around the time of World War II, and that underlie the physics involved in designs of nuclear explosions, controlled nuclear energy, and nuclear fusion. The review then moves to focus on modern applications of these concepts, including the basic concepts and diagnostics developed for the forensics of nuclear explosions, the nuclear diagnostics at the National Ignition Facility, nuclear reactor safeguards, and the detection of nuclear material production and trafficking. The review also summarizes recent developments in nuclear geophysics and nuclear medicine. The nuclear geophysics areas discussed include geo-chronology, nuclear logging for industry, the Oklo reactor, and geo-neutrinos. The section on nuclear medicine summarizes the critical advances in nuclear imaging, including PET and SPECT imaging, targeted radionuclide therapy, and the nuclear physics of medical isotope production. Each subfield discussed requires a review article unto itself, which is not the intention of the current review; rather, the current review is intended for readers who wish to get a broad understanding of applied nuclear physics.

  8. Nuclear Photonics

    CERN Document Server

    Habs, D; Jentschel, M; Thirolf, P G

    2012-01-01

    With new gamma-beam facilities like MEGa-ray at LLNL (USA) or ELI-NP at Bucharest with 10^13 g/s and a bandwidth of Delta E_g/E_g ~10^-3, a new era of g-beams with energies <=20 MeV comes into operation, compared to the present world-leading HIGS facility (Duke Univ., USA) with 10^8 g/s and Delta E_g/E_g~0.03. Even a seeded quantum FEL for g-beams may become possible, with much higher brilliance and spectral flux. At the same time new exciting possibilities open up for focused g-beams. We describe a new experiment at the g-beam of the ILL reactor (Grenoble), where we observed for the first time that the index of refraction for g-beams is determined by virtual pair creation. Using a combination of refractive and reflective optics, efficient monochromators for g-beams are being developed. Thus we have to optimize the system of the g-beam facility, the g-beam optics and g-detectors. We can trade g-intensity for band width, going down to Delta E_g/E_g ~ 10^-6 and address individual nuclear levels. 'Nuclear pho...

  9. Dictionary of nuclear engineering

    Energy Technology Data Exchange (ETDEWEB)

    Sube, R.

    1985-01-01

    Ralf Sube, an experienced compiler of three wellknown four-language reference works has now prepared this glossary of nuclear engineering terms in English, German, French and Russian. Based on the proven lexicography of the Technik-Worterbuch series, it comprises about 30,000 terms in each language covering the following: Nuclear and Atomic Physics; Nuclear Radiation and Isotopes; Nuclear Materials; Nuclear Facilties; Nuclear Power Industry; Nuclear Weapons.

  10. Nuclear "waffles"

    Science.gov (United States)

    Schneider, A. S.; Berry, D. K.; Briggs, C. M.; Caplan, M. E.; Horowitz, C. J.

    2014-11-01

    Background: The dense neutron-rich matter found in supernovae and inside neutron stars is expected to form complex nonuniform phases, often referred to as nuclear pasta. The pasta shapes depend on density, temperature and proton fraction and determine many transport properties in supernovae and neutron star crusts. Purpose: To characterize the topology and compute two observables, the radial distribution function (RDF) g (r ) and the structure factor S (q ) , for systems with proton fractions Yp=0.10 ,0.20 ,0.30 , and 0.40 at about one-third of nuclear saturation density, n =0.050 fm-3 , and temperatures near k T =1 MeV . Methods: We use two recently developed hybrid CPU/GPU codes to perform large scale molecular dynamics (MD) simulations with 51 200 and 409 600 nucleons. From the output of the MD simulations we obtain the two desired observables. Results: We compute and discuss the differences in topology and observables for each simulation. We observe that the two lowest proton fraction systems simulated, Yp=0.10 and 0.20 , equilibrate quickly and form liquidlike structures. Meanwhile, the two higher proton fraction systems, Yp=0.30 and 0.40 , take a longer time to equilibrate and organize themselves in solidlike periodic structures. Furthermore, the Yp=0.40 system is made up of slabs, lasagna phase, interconnected by defects while the Yp=0.30 systems consist of a stack of perforated plates, the nuclear waffle phase. Conclusions: The periodic configurations observed in our MD simulations for proton fractions Yp≥0.30 have important consequences for the structure factors S (q ) of protons and neutrons, which relate to many transport properties of supernovae and neutron star crust. A detailed study of the waffle phase and how its structure depends on temperature, size of the simulation, and the screening length showed that finite-size effects appear to be under control and, also, that the plates in the waffle phase merge at temperatures slightly above 1.0 MeV and

  11. Cholinesterase inhibitors from botanicals

    Directory of Open Access Journals (Sweden)

    Faiyaz Ahmed

    2013-01-01

    Full Text Available Alzheimer′s disease (AD is a progressive neurodegenerative disease, wherein a progressive loss of cholinergic synapses occurs in hippocampus and neocortex. Decreased concentration of the neurotransmitter, acetylcholine (ACh, appears to be critical element in the development of dementia, and the most appropriate therapeutic approach to treat AD and other form of dementia is to restore acetylcholine levels by inhibiting both major form of cholinesterase: Acetylcholinesterase (AChE and butyrylcholinesterase (BChE. Consequently, researches have focused their attention towards finding cholinesterase inhibitors from natural products. A large number of such inhibitors have been isolated from medicinal plants. This review presents a comprehensive account of the advances in field of cholinesterase inhibitor phytoconstituents. The structures of some important phytoconstituents (collected through www.Chemspider.com are also presented and the scope for future research is discussed.

  12. Targeting nuclear transporters in cancer: Diagnostic, prognostic and therapeutic potential.

    Science.gov (United States)

    Stelma, Tamara; Chi, Alicia; van der Watt, Pauline J; Verrico, Annalisa; Lavia, Patrizia; Leaner, Virna D

    2016-04-01

    The Karyopherin superfamily is a major class of soluble transport receptors consisting of both import and export proteins. The trafficking of proteins involved in transcription, cell signalling and cell cycle regulation among other functions across the nuclear membrane is essential for normal cellular functioning. However, in cancer cells, the altered expression or localization of nuclear transporters as well as the disruption of endogenous nuclear transport inhibitors are some ways in which the Karyopherin proteins are dysregulated. The value of nuclear transporters in the diagnosis, prognosis and treatment of cancer is currently being elucidated with recent studies highlighting their potential as biomarkers and therapeutic targets.

  13. Nuclear nirvana?

    Energy Technology Data Exchange (ETDEWEB)

    Sacks, T.

    1997-06-10

    This article describes a proposed method of processing high-level radioactive wastes from existing PWR reactors and weapons grade plutonium to produce relatively benign medium-level wastes, which is easier to handle and store. The energy amplifier proposed by Carlo Rubbia, ex-director-general of CERN, causes fission to occur as a result of nuclear cascades, rather than chain reactions, by bombarding a thorium-based mixture of radioactive materials with a high-intensity beam of sub-atomic particles. He claims that, as it depends largely on proven technology it could be in commercial operation with ten years, well ahead of even a prototype fusion reactor and thus provide a viable, sustainable and more environmentally acceptable power source. (Author).

  14. NUCLEAR REACTOR

    Science.gov (United States)

    Miller, H.I.; Smith, R.C.

    1958-01-21

    This patent relates to nuclear reactors of the type which use a liquid fuel, such as a solution of uranyl sulfate in ordinary water which acts as the moderator. The reactor is comprised of a spherical vessel having a diameter of about 12 inches substantially surrounded by a reflector of beryllium oxide. Conventionnl control rods and safety rods are operated in slots in the reflector outside the vessel to control the operation of the reactor. An additional means for increasing the safety factor of the reactor by raising the ratio of delayed neutrons to prompt neutrons, is provided and consists of a soluble sulfate salt of beryllium dissolved in the liquid fuel in the proper proportion to obtain the result desired.

  15. Nuclear exoticism

    Science.gov (United States)

    Penionzhkevich, Yu. E.

    2016-07-01

    Extreme states of nuclearmatter (such that feature high spins, large deformations, high density and temperature, or a large excess of neutrons and protons) play an important role in studying fundamental properties of nuclei and are helpful in solving the problem of constructing the equation of state for nuclear matter. The synthesis of neutron-rich nuclei near the nucleon drip lines and investigation of their properties permit drawing conclusions about the positions of these boundaries and deducing information about unusual states of such nuclei and about their decays. At the present time, experimental investigations along these lines can only be performed via the cooperation of leading research centers that possess powerful heavy-ion accelerators, such as the Large Hadron Collider (LHC) at CERN and the heavy-ion cyclotrons at the Joint Institute for Nuclear Research (JINR, Dubna), where respective experiments are being conducted by physicists from about 20 JINR member countries. The present article gives a survey of the most recent results in the realms of super neutron-rich nuclei. Implications of the change in the structure of such nuclei near the nucleon drip lines are discussed. Information about the results obtained by measuring the masses (binding energies) of exotic nuclei, the nucleon-distribution radii (neutron halo) and momentum distributions in them, and their deformations and quantum properties is presented. It is shown that the properties of nuclei lying near the stability boundaries differ strongly from the properties of other nuclei. The problem of the stability of nuclei that is associated with the magic numbers of 20 and 28 is discussed along with the effect of new magic numbers.

  16. Reconversion of nuclear weapons

    CERN Document Server

    Kapitza, Sergei P

    1993-01-01

    The nuclear predicament or nuclear option. Synopsis of three lectures : 1- The physical basis of nuclear technology. Physics of fission. Chain reaction in reactors and weapons. Fission fragments. Separration of isotopes. Radiochemistry.2- Nuclear reactors with slow and fast neutrons. Power, size, fuel and waste. Plutonium production. Dose rate, shielding and health hazard. The lessons of Chernobyl3- Nuclear weapons. Types, energy, blast and fallout. Fusion and hydrogen bombs. What to do with nuclear weapons when you cannot use them? Testing. Nonmilittary use. Can we get rid of the nuclear weapon? Nuclear proliferation. Is there a nuclear future?

  17. Inhibitors of histone deacetylase

    DEFF Research Database (Denmark)

    2015-01-01

    of the invention are useful for treating, alleviating, and/or preventing various conditions, including for example, a metabolic disorder such as type 1 or type 2 diabetes, dyslipidemias, lipodystrophies, liver disease associated with metabolic syndrome, polycystic ovarian syndrome, or obesity; inflammatory disease...... of making and using them. In one aspect, the invention relates to selective HDAC3 inhibitors useful for protecting beta-cells and improving insulin resistence. The selective HDAC3 inhibitors are also useful for promoting cognitive function and enhancing learning and memory formation. Compounds...

  18. 5-Flurouracil disrupts nuclear export and nuclear pore permeability in a calcium dependent manner.

    Science.gov (United States)

    Higby, Kelly J; Bischak, Melissa M; Campbell, Christina A; Anderson, Rebecca G; Broskin, Sarah A; Foltz, Lauren E; Koper, Jarrett A; Nickle, Audrey C; Resendes, Karen K

    2017-03-01

    Regulation of nuclear transport is an essential component of apoptosis. As chemotherapy induced cell death progresses, nuclear transport and the nuclear pore complex (NPC) are slowly disrupted and dismantled. 5-Fluorouracil (5-FU) and the camptothecin derivatives irinotecan and topotecan, are linked to altered nuclear transport of specific proteins; however, their general effects on the NPC and transport during apoptosis have not been characterized. We demonstrate that 5-FU, but not topotecan, increases NPC permeability, and disrupts Ran-mediated nuclear transport before the disruption of the NPC. This increased permeability is dependent on increased cellular calcium, as the Ca(2+) chelator BAPTA-AM, abolishes the effect. Furthermore, increased calcium alone was sufficient to disrupt the Ran gradient. Combination treatments of 5-FU with topotecan or irinotecan, similarly disrupted nuclear transport before disassembly of the NPC. In both single and combination treatments nuclear transport was disrupted before caspase 9 activation, indicating that 5-FU induces an early caspase-independent increase in NPC permeability and alteration of nuclear transport. Because Crm1-mediated nuclear export of tumor suppressors is linked to drug resistance we also examined the effect of 5-FU on the nuclear export of a specific target, topoisomerase. 5-FU treatment led to accumulation of topoisomerase in the nucleus and recovered the loss nuclear topoisomerase induced by irinotecan or topotecan, a known cause of drug resistance. Furthermore, 5-FU retains its ability to cause nuclear accumulation of p53 in the presence of irinotecan or topotecan. Our results reveal a new mechanism of action for these therapeutics during apoptosis, opening the door to other potential combination chemotherapies that employ 5-FU as a calcium mediated inhibitor of Crm1-induced nuclear export of tumor suppressors.

  19. No Nuclear Worries

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    China National Nuclear Corp.will learn lessons from the Fukushima accident while expanding its operations As Japan’s Fukushima nuclear crisis sparks a global debate over nuclear safety,China National Nuclear Corp.(CNNC),the country’s largest nuclear power operator,comes under

  20. Trends in Nuclear Astrophysics

    OpenAIRE

    Schatz, Hendrik

    2016-01-01

    Nuclear Astrophysics is a vibrant field at the intersection of nuclear physics and astrophysics that encompasses research in nuclear physics, astrophysics, astronomy, and computational science. This paper is not a review. It is intended to provide an incomplete personal perspective on current trends in nuclear astrophysics and the specific role of nuclear physics in this field.

  1. Inhibitors of histone demethylases

    DEFF Research Database (Denmark)

    Lohse, Brian; Kristensen, Jesper L; Kristensen, Line H;

    2011-01-01

    Methylated lysines are important epigenetic marks. The enzymes involved in demethylation have recently been discovered and found to be involved in cancer development and progression. Despite the relative recent discovery of these enzymes a number of inhibitors have already appeared. Most of the i...

  2. Inhibitors of histone deacetylase

    DEFF Research Database (Denmark)

    2015-01-01

    The present invention relates to compounds of formula (I) or a pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, wherein X1, X2, X3, X4, X5, W1, W2, W3, and W4 are as described. The present invention relates generally to inhibitors of histone deacetylase and to methods...

  3. ACE inhibitors and proteinuria

    NARCIS (Netherlands)

    Gansevoort, RT; deZeeuw, D; deJong, PE

    1996-01-01

    This review discusses the clinical consequences of urinary protein loss and the effects of inhibitors of the angiotensin converting enzyme (ACE) on this clinical finding. Proteinuria appears to be an important risk factor for renal function deterioration and for cardiovascular mortality. ACE inhibit

  4. Transglutaminase inhibitor from milk

    NARCIS (Netherlands)

    Jong, G.A.H. de; Wijngaards, G.; Koppelman, S.J.

    2003-01-01

    Cross-linking experiments of skimmed bovine milk with bacterial transglutaminase isolated from Streptoverticillium mobaraense showed only some degree of formation of high-molecular-weight casein polymers. Studies on the nature of this phenomenon revealed that bovine milk contains an inhibitor of tra

  5. Thrombin inhibitor design.

    Science.gov (United States)

    Sanderson, P E; Naylor-Olsen, A M

    1998-08-01

    Recently, iv formulated direct thrombin inhibitors have been shown to be safe and efficacious alternatives to heparin. These results have fueled the hopes for an orally active compound. Such a compound could be a significant advance over warfarin if it had predictable pharmacokinetics and a duration of action sufficient for once or twice a day dosing. In order to develop an orally active compound which meets these criteria, the deficiencies of the prototype inhibitor efegatran have had to be addressed. First, using a combination of structure based design and empirical structure optimization, more selective compounds have been identified by modifying the P1 group or by incorporating different peptidomimetic P2/P3 scaffolds. Secondly, this optimization has resulted in the development of potent and selective non-covalent inhibitors, thus bypassing the liabilities of the serine trap. Thirdly, oral bioavailability has been achieved while maintaining selectivity and efficacy through the incorporation of progressively less basic P1 groups. The duration of action of these compounds remains to be optimized. Other advances in thrombin inhibitor design have included the development of uncharged P1 groups and the discovery of two non-peptide templates.

  6. Nuclear analytical chemistry

    Energy Technology Data Exchange (ETDEWEB)

    Brune, D.; Forkman, B.; Persson, B.

    1984-01-01

    This book covers the general theories and techniques of nuclear chemical analysis, directed at applications in analytical chemistry, nuclear medicine, radiophysics, agriculture, environmental sciences, geological exploration, industrial process control, etc. The main principles of nuclear physics and nuclear detection on which the analysis is based are briefly outlined. An attempt is made to emphasise the fundamentals of activation analysis, detection and activation methods, as well as their applications. The book provides guidance in analytical chemistry, agriculture, environmental and biomedical sciences, etc. The contents include: the nuclear periodic system; nuclear decay; nuclear reactions; nuclear radiation sources; interaction of radiation with matter; principles of radiation detectors; nuclear electronics; statistical methods and spectral analysis; methods of radiation detection; neutron activation analysis; charged particle activation analysis; photon activation analysis; sample preparation and chemical separation; nuclear chemical analysis in biological and medical research; the use of nuclear chemical analysis in the field of criminology; nuclear chemical analysis in environmental sciences, geology and mineral exploration; and radiation protection.

  7. Mean nuclear volume

    DEFF Research Database (Denmark)

    Mogensen, O.; Sørensen, Flemming Brandt; Bichel, P.

    1999-01-01

    We evaluated the following nine parameters with respect to their prognostic value in females with endometrial cancer: four stereologic parameters [mean nuclear volume (MNV), nuclear volume fraction, nuclear index and mitotic index], the immunohistochemical expression of cancer antigen (CA125...

  8. Cold nuclear fusion

    National Research Council Canada - National Science Library

    Huang Zhenqiang Huang Yuxiang

    2013-01-01

    ...... And with a magnetic moment of light nuclei controlled cold nuclear collide fusion, belongs to the nuclear energy research and development in the field of applied technology "cold nuclear collide fusion...

  9. Nuclear Quadrupole Moments and Nuclear Shell Structure

    Science.gov (United States)

    Townes, C. H.; Foley, H. M.; Low, W.

    1950-06-23

    Describes a simple model, based on nuclear shell considerations, which leads to the proper behavior of known nuclear quadrupole moments, although predictions of the magnitudes of some quadrupole moments are seriously in error.

  10. Nuclear energy data 2010

    CERN Document Server

    2010-01-01

    This 2010 edition of Nuclear Energy Data , the OECD Nuclear Energy Agency's annual compilation of official statistics and country reports on nuclear energy, provides key information on plans for new nuclear plant construction, nuclear fuel cycle developments as well as current and projected nuclear generating capacity to 2035 in OECD member countries. This comprehensive overview provides authoritative information for policy makers, experts and other interested stakeholders.

  11. Consolidation: Thwarting Nuclear Theft

    OpenAIRE

    Bunn, Matthew G.; Harrell, Eben

    2013-01-01

    At the first nuclear security summit in April 2010, the assembled leaders agreed on the goal of securing all vulnerable nuclear material worldwide within four years, including consolidating plutonium and highly enriched uranium (HEU) to fewer locations and minimizing the use of HEU “where technically and economically feasible.†Reducing the number of buildings and sites where nuclear weapons and weapons-usable nuclear material exist is a key element of preventing nuclear theft and nuclear ...

  12. Nuclear Fuel Cycle & Vulnerabilities

    Energy Technology Data Exchange (ETDEWEB)

    Boyer, Brian D. [Los Alamos National Laboratory

    2012-06-18

    The objective of safeguards is the timely detection of diversion of significant quantities of nuclear material from peaceful nuclear activities to the manufacture of nuclear weapons or of other nuclear explosive devices or for purposes unknown, and deterrence of such diversion by the risk of early detection. The safeguards system should be designed to provide credible assurances that there has been no diversion of declared nuclear material and no undeclared nuclear material and activities.

  13. Crocodylian nuclear factor kappa B.

    Science.gov (United States)

    Merchant, Mark; Morkotinis, Vasileios; Hale, Amber; White, Mary; Moran, Chris

    2017-11-01

    We deduced the amino acid (aa) sequence of the nuclear factor kappa B (NFκB) protein from genomic data for the American alligator (Alligator mississippiensis), the estuarine crocodile (Crocodylus porosus), and the Indian gharial (Gavialis gangeticus). A 105kDa protein, NFκB1 exhibits complex post-translational processing, multiple mechanisms of activation, and acts as precursor for a p50, a Rel homology transcription factor which influences the expression of key genes for developmental processes, apoptosis, and immune function. The aa sequences of the crocodylian proteins share very high identity with each other (97.2±0.7%), birds (81.0±1.1%, n=6), mammals (75.3±1.6%, n=4), reptiles (80.3±5.1%, n=2), and less identity with fish (55.5±5.5%, n=4) and one amphibian (66.1±0.8%). The crocodylian protein has a well-conserved Rel homology domain, a nuclear localization signal, and a glycine-rich region which facilitates proteasome-mediated generation of p50. The Rel homology domain contains sequences responsible for dimerization, DNA-binding, and nuclear translocation. In addition, seven ankyrin repeats were located, which putatively allow for inhibition of transcriptional regulation by mediating interaction with Inhibitor kappa B. Other features include a death domain, and conserved serine residues, near the C-terminal end, which act as potential phosphorylation sites for activation of the proteolytic generation of p50. Western blot analysis showed both the 105kDa precursor and the 50kDa mature NFκB were expressed in the alligator liver. Nuclear factor κB exhibited diffuse cytoplasmic distribution in alligator hepatocytes, and almost no cytoplasmic localization in infected animals. In addition, nuclear NFκB exhibited specific binding to the consensus NFκB promoter element. Published by Elsevier Inc.

  14. Nuclear Entalpies

    CERN Document Server

    Rozynek, J

    2013-01-01

    In a compressed Nuclear Matter (NM) an increasing pressure between the nucleons starts to increase the ratio of a nucleon Fermi to average single particle energy and in accordance with the Hugenholtz-van Hove theorem the longitudinal Momentum Sum Rule (MSR) is broken in a Relativistic Mean Field (RMF) approach. We propose to benefit from the concept of enthalpy in order to show how to fulfill the MSR above a saturation density with pressure corrections. As a result a nucleon mass can decrease with density, making the Equation of State (EoS) softer. The course of the EoS in our modified RMF model is close to a semi-empirical estimate and to results obtained from extensive DBHF calculations with a Bonn A potential, which produce the EoS stiff enough to describe neutron star properties (mass-radius constraint), especially the most massive known neutron star. The presented model has proper saturation properties, including good values of a compressibility and a spin-orbit term.

  15. Nuclear Data and Nuclear Model Methods

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Developing nuclear data needs towards to sustainable development on fission reactor design and many nuclear applications out the field of fission reactor technology that are growing economicsignificance and that have substantial data requirements are introduced. International standard codes used in nuclear data evaluations and calculations are introduced and compared each other. Generally

  16. Nuclear energy data 2011

    CERN Document Server

    2011-01-01

     . Nuclear Energy Data, the OECD Nuclear Energy Agency's annual compilation of statistics and country reports on nuclear energy, contains official information provided by OECD member country governments on plans for new nuclear plant construction, nuclear fuel cycle developments as well as current and projected nuclear generating capacity to 2035. For the first time, it includes data for Chile, Estonia, Israel and Slovenia, which recently became OECD members. Key elements of this edition show a 2% increase in nuclear and total electricity production and a 0.5% increase in nuclear generating ca

  17. Nuclear weapons modernizations

    Energy Technology Data Exchange (ETDEWEB)

    Kristensen, Hans M. [Federation of American Scientists, Washington, DC (United States)

    2014-05-09

    This article reviews the nuclear weapons modernization programs underway in the world's nine nuclear weapons states. It concludes that despite significant reductions in overall weapons inventories since the end of the Cold War, the pace of reductions is slowing - four of the nuclear weapons states are even increasing their arsenals, and all the nuclear weapons states are busy modernizing their remaining arsenals in what appears to be a dynamic and counterproductive nuclear competition. The author questions whether perpetual modernization combined with no specific plan for the elimination of nuclear weapons is consistent with the nuclear Non-Proliferation Treaty and concludes that new limits on nuclear modernizations are needed.

  18. PARP activation promotes nuclear AID accumulation in lymphoma cells.

    Science.gov (United States)

    Tepper, Sandra; Jeschke, Julia; Böttcher, Katrin; Schmidt, Angelika; Davari, Kathrin; Müller, Peter; Kremmer, Elisabeth; Hemmerich, Peter; Pfeil, Ines; Jungnickel, Berit

    2016-03-15

    Activation-induced cytidine deaminase (AID) initiates immunoglobulin diversification in germinal center B cells by targeted introduction of DNA damage. As aberrant nuclear AID action contributes to the generation of B cell lymphoma, the protein's activity is tightly regulated, e.g. by nuclear/cytoplasmic shuttling and nuclear degradation. In the present study, we asked whether DNA damage may affect regulation of the AID protein. We show that exogenous DNA damage that mainly activates base excision repair leads to prevention of proteasomal degradation of AID and hence its nuclear accumulation. Inhibitor as well as knockout studies indicate that activation of poly (ADP-ribose) polymerase (PARP) by DNA damaging agents promotes both phenomena. These findings suggest that PARP inhibitors influence DNA damage dependent AID regulation, with interesting implications for the regulation of AID function and chemotherapy of lymphoma.

  19. Benzoylurea Chitin Synthesis Inhibitors.

    Science.gov (United States)

    Sun, Ranfeng; Liu, Chunjuan; Zhang, Hao; Wang, Qingmin

    2015-08-12

    Benzoylurea chitin synthesis inhibitors are widely used in integrated pest management (IPM) and insecticide resistance management (IRM) programs due to their low toxicity to mammals and predatory insects. In the past decades, a large number of benzoylurea derivatives have been synthesized, and 15 benzoylurea chitin synthesis inhibitors have been commercialized. This review focuses on the history of commercial benzolyphenylureas (BPUs), synthetic methods, structure-activity relationships (SAR), action mechanism research, environmental behaviors, and ecotoxicology. Furthermore, their disadvantages of high risk to aquatic invertebrates and crustaceans are pointed out. Finally, we propose that the para-substituents at anilide of benzoylphenylureas should be the functional groups, and bipartite model BPU analogues are discussed in an attempt to provide new insight for future development of BPUs.

  20. Sequencing of aromatase inhibitors

    OpenAIRE

    2005-01-01

    Since the development of the third-generation aromatase inhibitors (AIs), anastrozole, letrozole and exemestane, these agents have been the subject of intensive research to determine their optimal use in advanced breast cancer. Not only have they replaced progestins in second-line therapy and challenged the role of tamoxifen in first-line, but there is also evidence for a lack of cross-resistance between the steroidal and nonsteroidal AIs, meaning that they may be used in sequence to obtain p...

  1. Update on Aromatase Inhibitors

    Directory of Open Access Journals (Sweden)

    Seifert-Klauss V

    2015-01-01

    Full Text Available Aromatase inhibitors (AI block the last phase of estrogen production in many types of tissues which express the enzym aromatase, among them muscle, liver, adrenal, brain and fat. The enzyme catalyzes the last step of the biosynthesis of the estrogens, i. e. the aromatisation of testosterone to estradiol and of androstendion to estrone. Aromatase is localized in the membrane of the endoplasmatic reticulum and is also produced in the placenta and the gonads. Mutations in the gene CYP19A1, which codes for aromatase, can lead either to lack or excess of aromatase. Gene polymorphisms also influence the amount of bioavailable estrogen and bone density.br Indications: AI are approved for the treatment of postmenopausal women with hormone receptor positive breast cancer, both in the adjuvant setting as well as after recurrence and in progressive disease. In premenopausal and in perimenopausal women AI cause an increased sensitivity of the ovaries to follicle stimulating hormone (FSH and can thereby lead to a boosted estrogen answer – this effect is particularly pronounced in early perimenopausal women – so that these situations demand a combination with GnRH-analogue if AI treatment is to be initiated. Alternatively, tamoxifene may be used in premenopausal patients, with or without GnRH analogues. Treatment of premenopausal patients with hormone receptor positive breast cancer with aromatase inhibiting therapy alone constitutes an absolute contraindication. Aromatase inhibitors do not lead to estrogen receptor downregulation or block the receptor such as tamoxifene. An exceptional application is the application in reproductive medicine in women who do not have hormone receptor positive breast cancer: because of the higher sensitivity induced by AI-co-therapy, FSH-doses and -costs for assisted reproduction are reduced, and ovarian hyperstimulation syndrome (OHSS may be avoided. For premenopausal diseases which are said to be positively affected by

  2. JPRS Report, Nuclear Developments

    Science.gov (United States)

    2016-03-24

    I Foreign Ministry on Algerian Nuclear Reactor [ZHONGGUO XINWEN SHE] .............................. I...Nuclear Facilities Urged [Seoul YONHAP] .................................................... 5 WPK’s ’Anti- War , Anti-Nuke’ Policy Viewed [KCNA...34 JPRS-TND-91-008 31 May 1991 CHINA 1 Algerian Nuclear Reactor Algeria signed a protocol on nuclear cooperation, in which China agreed

  3. Ensuring Nuclear Safety

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    The Fukushima accident precipitates overall safety inspection by China Guangdong Nuclear Power Holding Corp The Fukushima nuclear accident in Japan had barely made headlines around the world when China Guangdong Nuclear Power Holding Corp.(CGNPC),a nuclear power magnate in China,organized

  4. Novel targeted therapeutics: inhibitors of MDM2, ALK and PARP

    Directory of Open Access Journals (Sweden)

    Hsueh Chung-Tsen

    2011-04-01

    Full Text Available Abstract We reviewed preclinical data and clinical development of MDM2 (murine double minute 2, ALK (anaplastic lymphoma kinase and PARP (poly [ADP-ribose] polymerase inhibitors. MDM2 binds to p53, and promotes degradation of p53 through ubiquitin-proteasome degradation. JNJ-26854165 and RO5045337 are 2 small-molecule inhibitors of MDM2 in clinical development. ALK is a transmembrane protein and a member of the insulin receptor tyrosine kinases. EML4-ALK fusion gene is identified in approximately 3-13% of non-small cell lung cancer (NSCLC. Early-phase clinical studies with Crizotinib, an ALK inhibitor, in NSCLC harboring EML4-ALK have demonstrated promising activity with high response rate and prolonged progression-free survival. PARPs are a family of nuclear enzymes that regulates the repair of DNA single-strand breaks through the base excision repair pathway. Randomized phase II study has shown adding PARP-1 inhibitor BSI-201 to cytotoxic chemotherapy improves clinical outcome in patients with triple-negative breast cancer. Olaparib, another oral small-molecule PARP inhibitor, demonstrated encouraging single-agent activity in patients with advanced breast or ovarian cancer. There are 5 other PARP inhibitors currently under active clinical investigation.

  5. Inhibition of matrix metalloproteinase-2 by PARP inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Nicolescu, Adrian C.; Holt, Andrew; Kandasamy, Arulmozhi D. [Departments of Pharmacology and Pediatrics, Cardiovascular Research Centre, University of Alberta, Edmonton, Alta., Canada T6G 2S2 (Canada); Pacher, Pal [National Institutes of Health, NIAAA, Laboratory of Physiologic Studies, Bethesda, MD (United States); Schulz, Richard, E-mail: richard.schulz@ualberta.ca [Departments of Pharmacology and Pediatrics, Cardiovascular Research Centre, University of Alberta, Edmonton, Alta., Canada T6G 2S2 (Canada)

    2009-10-02

    Matrix metalloproteinase-2 (MMP-2), a ubiquitously expressed zinc-dependent endopeptidase, and poly(ADP-ribosyl) polymerase (PARP), a nuclear enzyme regulating DNA repair, are activated by nitroxidative stress associated with various pathologies. As MMP-2 plays a detrimental role in heart injuries resulting from enhanced nitroxidative stress, where PARP and MMP inhibitors are beneficial, we hypothesized that PARP inhibitors may affect MMP-2 activity. Using substrate degradation assays to determine MMP-2 activity we found that four PARP inhibitors (3-AB, PJ-34, 5-AIQ, and EB-47) inhibited 64 kDa MMP-2 in a concentration-dependent manner. The IC{sub 50} values of PJ-34 and 5-AIQ were in the high micromolar range and comparable to those of known MMP-2 inhibitors doxycycline, minocycline or o-phenanthroline, whereas those for 3-AB and EB-47 were in the millimolar range. Co-incubation of PARP inhibitors with doxycycline showed an additive inhibition of MMP-2 that was significant for 3-AB alone. These data demonstrate that the protective effects of some PARP inhibitors may include inhibition of MMP-2 activity.

  6. Identification of neuron selective androgen receptor inhibitors.

    Science.gov (United States)

    Otto-Duessel, Maya; Tew, Ben Yi; Vonderfecht, Steven; Moore, Roger; Jones, Jeremy O

    2017-05-26

    To identify neuron-selective androgen receptor (AR) signaling inhibitors, which could be useful in the treatment of spinal and bulbar muscular atrophy (SBMA), or Kennedy's disease, a neuromuscular disorder in which deterioration of motor neurons leads to progressive muscle weakness. Cell lines representing prostate, kidney, neuron, adipose, and muscle tissue were developed that stably expressed the CFP-AR-YFP FRET reporter. We used these cells to screen a library of small molecules for cell type-selective AR inhibitors. Secondary screening in luciferase assays was used to identify the best cell-type specific AR inhibitors. The mechanism of action of a neuron-selective AR inhibitor was examined in vitro using luciferase reporter assays, immunofluorescence microscopy, and immunoprecipitations. Rats were treated with the most potent compound and tissue-selective AR inhibition was examined using RT-qPCR of AR-regulated genes and immunohistochemistry. We identified the thiazole class of antibiotics as compounds able to inhibit AR signaling in a neuronal cell line but not a muscle cell line. One of these antibiotics, thiostrepton is able to inhibit the activity of both wild type and polyglutamine expanded AR in neuronal GT1-7 cells with nanomolar potency. The thiazole antibiotics are known to inhibit FOXM1 activity and accordingly, a novel FOXM1 inhibitor FDI-6 also inhibited AR activity in a neuron-selective fashion. The selective inhibition of AR is likely indirect as the varied structures of these compounds would not suggest that they are competitive antagonists. Indeed, we found that FOXM1 expression correlates with cell-type selectivity, FOXM1 co-localizes with AR in the nucleus, and that shRNA-mediated knock down of FOXM1 reduces AR activity and thiostrepton sensitivity in a neuronal cell line. Thiostrepton treatment reduces FOXM1 levels and the nuclear localization of beta-catenin, a known co-activator of both FOXM1 and AR, and reduces the association between beta

  7. Nuclear actin and protein 4.1: Essential interactions during nuclear assembly in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Krauss, Sharon Wald; Chen, Cynthia; Penman, Sheldon; Heald, Rebecca

    2003-06-11

    Structural protein 4.1, which has crucial interactions within the spectin-actin lattice of the human red cell membrane skeleton, also is widely distributed at diverse intracellular sites in nucleated cells. We previously showed that 4.1 is essential for assembly of functional nuclei in vitro and that the capacity of 4.1 to bind actin is required. Here we report that 4.1 and actin colocalize in mammalian cell nuclei using fluorescence microscopy and, by higher resolution cell whole mount electron microscopy, are associated on nuclear filaments. We also devised a cell-free assay using Xenopus egg extract containing fluorescent actin to follow actin during nuclear assembly. By directly imaging actin under non-perturbing conditions, the total nuclear actin population is retained and is visualized in situ relative to intact chromatin. We detected actin initially when chromatin and nuclear pores began assembling. As the nuclear lamina assembled, but preceding DNA synthesis, a discrete actin network formed throughout the nucleus. Protein 4.1 epitopes also were detected when actin began to accumulate in nuclei, producing a diffuse coincident pattern. As nuclei matured, actin was detected both coincident with and also independent of 4.1 epitopes. To test whether acquisition of nuclear actin is required for nuclear assembly, the actin inhibitor latrunculin A was added to Xenopus egg extracts during nuclear assembly. Latrunculin A strongly perturbed nuclear assembly and produced distorted nuclear structures containing neither actin nor protein 4.1. Our results suggest that actin as well as 4.1 is necessary for nuclear assembly and that 4.1-actin interactions may be critical.

  8. Energy from nuclear fission(*

    Directory of Open Access Journals (Sweden)

    Ripani M.

    2015-01-01

    Full Text Available The main features of nuclear fission as physical phenomenon will be revisited, emphasizing its peculiarities with respect to other nuclear reactions. Some basic concepts underlying the operation of nuclear reactors and the main types of reactors will be illustrated, including fast reactors, showing the most important differences among them. The nuclear cycle and radioactive-nuclear-waste production will be also discussed, along with the perspectives offered by next generation nuclear assemblies being proposed. The current situation of nuclear power in the world, its role in reducing carbon emission and the available resources will be briefly illustrated.

  9. [Chilean nuclear policy].

    Science.gov (United States)

    Bobadilla, E

    1996-06-01

    This official document is statement of the President of the Chilean Nuclear Energy Commission, Dr. Eduardo Bobadilla, about the nuclear policy of the Chilean State, Thanks to the international policy adopted by presidents Aylwin (1990-1994) and his successor Frei Ruiz Tagle (1994-), a nuclear development plan, protected by the Chilean entrance to the nuclear weapons non proliferation treaty and Tlatelolco Denuclearization treaty, has started. Chile will be able to develop without interference, an autonomous nuclear electrical system and other pacific uses of nuclear energy. Chile also supports a new international treaty to ban nuclear weapon tests.

  10. ERR Gamma: Does an Orphan Nuclear Receptor Link Steroid Hormone Biogenesis to Endocrine Resistance?

    Science.gov (United States)

    2007-09-01

    Endocr. Relat. Cancer 13 (2006) 1121–1133. [66] R.B. Riggins, A. Zwart, R. Nehra, R. Clarke, The nuclear factor kappa B inhibitor parthenolide ...Clarke. The NFκB inhibitor parthenolide restores ICI 182,780 (Faslodex; Fulvestrant)-induced apoptosis in antiestrogen-resistant breast cancer cells

  11. Nuclear energy data 2005

    CERN Document Server

    Publishing, OECD

    2005-01-01

    This 2005 edition of Nuclear Energy Data, the OECD Nuclear Energy Agency's annual compilation of essential statistics on nuclear energy in OECD countries, offers a projection horizon lengthened to 2025 for the first time.  It presents the reader with a comprehensive overview on the status and trends in nuclear electricity generation in OECD countries and in the various sectors of the nuclear fuel cycle.

  12. 77 FR 70847 - Entergy Nuclear Indian Point 2, LLC; Entergy Nuclear Operations, Inc., Indian Point Nuclear...

    Science.gov (United States)

    2012-11-27

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Entergy Nuclear Indian Point 2, LLC; Entergy Nuclear Operations, Inc., Indian Point Nuclear Generating Unit No. 2, Request for Action AGENCY: Nuclear Regulatory Commission. ACTION: Request for...

  13. IKKβ inhibitor identification: a multi-filter driven novel scaffold

    Directory of Open Access Journals (Sweden)

    Oh Kwang-Seok

    2010-10-01

    Full Text Available Abstract Background Nuclear factor kappa B (NF-κB is a chief nuclear transcription factor that controls the transcription of various genes; and its activation is tightly controlled by Inhibitor kappa B kinase (IKK. The irregular transcription of NF-κB has been linked to auto-immune disorders, cancer and other diseases. The IKK complex is composed of three units, IKKα, IKKβ, and the regulatory domain NEMO, of which IKKβ is well understood in the canonical pathway. Therefore, the inhibition of IKKβ by drugs forms the molecular basis for anti-inflammatory drug research. Results The ligand- and structure-based virtual screening (VS technique has been applied to identify IKKβ inhibitors from the ChemDiv database with 0.7 million compounds. Initially, a 3D-QSAR pharmacophore model has been deployed to greatly reduce the database size. Subsequently, recursive partitioning (RP and docking filters were used to screen the pharmacophore hits. Finally, 29 compounds were selected for IKKβ enzyme inhibition assay to identify a novel small molecule inhibitor of IKKβ protein. Conclusions In the present investigation, we have applied various computational models sequentially to virtually screen the ChemDiv database, and identified a small molecule that has an IC50 value of 20.3μM. This compound is novel among the known IKKβ inhibitors. Further optimization of the hit compound can reveal a more potent anti-inflammatory agent.

  14. Technology Roadmaps: Nuclear Energy

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2010-07-01

    This nuclear energy roadmap has been prepared jointly by the IEA and the OECD Nuclear Energy Agency (NEA). Unlike most other low-carbon energy sources, nuclear energy is a mature technology that has been in use for more than 50 years. The latest designs for nuclear power plants build on this experience to offer enhanced safety and performance, and are ready for wider deployment over the next few years. Several countries are reactivating dormant nuclear programmes, while others are considering nuclear for the first time. China in particular is already embarking on a rapid nuclear expansion. In the longer term, there is great potential for new developments in nuclear energy technology to enhance nuclear's role in a sustainable energy future.

  15. Nuclear export of L-periaxin, mediated by its nuclear export signal in the PDZ domain.

    Directory of Open Access Journals (Sweden)

    Yawei Shi

    Full Text Available Myelinating Schwann cells specifically express L-periaxin (L-PRX in the mammalian peripheral nervous system. Several loss-of-function mutations in periaxin have been described and linked to autosomal recessive Dejerine Sottas neuropathy and to demyelinating Charcot-Marie-Tooth disease. The localization of L-periaxin is developmentally regulated in the nucleus and the plasma membrane of Schwann cells. In this study, L-periaxin, which contains a PDZ domain, a nuclear localization signal (NLS domain, a repeat domain, and an acidic domain, was localized in the cytoplasm of RSC96 cells. By contrast, a mutant L-periaxin with a deleted PDZ domain was localized mainly in the nucleus of RSC96 cells. After a nuclear cyclin A1, which is localized exclusively in the nucleus, was fused with the PDZ domain, cyclinA1was found in the cytoplasm of RSC96 cells. Treatment with leptomycin B (LMB, a specific inhibitor of nuclear export mediated by leucine-rich nuclear export signal (NES, also causes nuclear accumulation of wild-type L-periaxin. Double leucine mutation (L83, 85Q in the putative NES in the PDZ domain prevented L-periaxin nuclear export and induced nuclear accumulation. These results suggested that the localization of L-periaxin in the cytoplasm is supported by NES in the PDZ domain.

  16. Nuclear and radiochemistry

    CERN Document Server

    Konya, Jozsef

    2012-01-01

    The field of nuclear and radiochemistry is wide-reaching, with results having functions and use across a variety of disciplines. Drawing on 40 years of experience in teaching and research, this concise book explains the basic principles and applications of the primary areas of nuclear and radiochemistry. Separate chapters cover each main area of recent radiochemistry. This includes nuclear medicine and chemical aspects of nuclear power plants, namely the problems of nuclear wastes and nuclear analysis (both bulk and surface analysis), with the analytical methods based on the interactions of

  17. Effect of nuclear transcription factor RelB on the proteasome inhibitor-sensitivity of chronic lymphocytic leukemia cells%核转录因子RelB对慢性B淋巴细胞白血病细胞蛋白酶体抑制剂敏感性的影响

    Institute of Scientific and Technical Information of China (English)

    徐晶晶; 周鹏; 孙爱宁; 国风

    2014-01-01

    Objective To investigate the effect of nuclear transcription factor RelB on the proteasome inhibitor-sensitivity of chronic lymphocytic leukemia (CLL) cells.Methods The mRNA expression of RelB in CD5 + CD19 + CLL cells from BM was analyzed by reverse transcription PCR (RT-PCR).The RelB activity was examined by electromobility shift assay (EMSA) and an ELISA-based NF-κd3 family transcription factor activity assay.CLL cells were classified into RelB+ and RelB-groups according to RelB activity.The frequencies of cell death of CLL cells cultured with human bone marrow stromal cells (hBMSCs) after treatment with PS-341,MG-132 or fludarabine were determined by PI staining.Results RelB mRNA expression and RelB activity could be detected in CLL cells at variable levels.Fludarabine (10 μmol/L),MG-132 (1 μmol/L) and PS-341 (1 μmol/L) could induce cell death of RelB+ and RelB-CLL cells co-cultured with hBMSCs in a time dependent manner.There was no significant difference in the fludarabine sensitivity between RelB + and RelB-CLL cells,and the frequencies of cell death of RelB+ and RelB-CLL cells were (61.11 ±6.91)% and (67.57±9.45)%,respectively,when treated with fludarabine for 72 h.RelB+ CLL cells were more sensitive to MG-132 than RelB-CLL cells for 72 h,and the frequencies of cell death were (66.22±3.39) % and (51.07±5.93) %,respectively.RelB+ CLL cells were more sensitive to PS-341 than RelB CLL cells for 24 and 48 h treatment,and the frequencies of cell death of RelB+ and RelB-CLL cells were (75.50±4.66)% and (66.32±10.20)% for 24 h,(92.11±3.14)% and (85.84 ± 5.81)% for 48 h treatment,respectively.Conclusion The alternative NF-κB activity was detected in bone marrow derived CLL cells.Enhancement of RelB activity may increase CLL cells' sensitivity to proteasome inhibitor bortezomib and MG-132.However,the sensitivity of CLL cells to fludarabine had no relationship to RelB activity.%目的 探讨核转录因子RelB对慢性B淋巴细胞白血

  18. Inhibitors of lysosomal cysteine proteases

    Directory of Open Access Journals (Sweden)

    Lyanna O. L.

    2011-04-01

    Full Text Available The review is devoted to the inhibitors of cysteine proteinases which are believed to be very important in many biochemical processes of living organisms. They participate in the development and progression of numerous diseases that involve abnormal protein turnover. One of the main regulators of these proteinases is their specific inhibitors: cystatins. The aim of this review was to present current knowledge about endogenous inhibitors of lysosomal cysteine proteases and their synthetic analogs.

  19. ACE INHIBITORS: A COMPREHENSIVE REVIEW

    Directory of Open Access Journals (Sweden)

    Pradeep Kumar Arora* and Ashish Chauhan

    2013-02-01

    Full Text Available Hypertension is a chronic increase in blood pressure, characterized as primary and secondary hypertension. The disorder is associated with various risk factors like obesity, diabetes, age, lack of exercise etc. Hypertension is being treated since ancient times by Ayurvedic, Chinese and Unani medicine. Now various allopathic drugs are available which include diuretics, calcium channel blockers, α-blockers, β-blockers, vasodilators, central sympatholytics and ACE-inhibitors. Non-pharmacological treatments include weight reduction, dietary sodium reduction, increased potassium intake and reduction in alcohol consumption. ACE-inhibitors are widely used in the treatment of hypertension by inhibiting the angiotensin converting enzyme responsible for the conversion of angiotensin I to angiotensin II (responsible for vasoconstriction. Various structure activity relationship studies led to the synthesis of ACE-inhibitors, some are under clinical development. This comprehensive review gives various guidelines on classification of hypertension, hypertension therapy including ancient, pharmacological, non-pharmacological therapies, pharmacoeconomics, historical perspectives of ACE, renin, renin angiotensin system (circulating vs local RAS, mechanism of ACE inhibitors, and development of ACE inhibitors. Review also emphasizes on the recent advancements on ACE inhibitors including drugs in clinical trials, computational studies on ACE-inhibitors, peptidomimetics, dual, natural, multi-functional ACE inhibitors, and conformational requirements for ACE-inhibitors.

  20. Nuclear domains and the nuclear matrix.

    Science.gov (United States)

    van Driel, R; Wansink, D G; van Steensel, B; Grande, M A; Schul, W; de Jong, L

    1995-01-01

    This overview describes the spatial distribution of several enzymatic machineries and functions in the interphase nucleus. Three general observations can be made. First, many components of the different nuclear machineries are distributed in the nucleus in a characteristic way for each component. They are often found concentrated in specific domains. Second, nuclear machineries for the synthesis and processing of RNA and DNA are associated with an insoluble nuclear structure, called nuclear matrix. Evidently, handling of DNA and RNA is done by immobilized enzyme systems. Finally, the nucleus seems to be divided in two major compartments. One is occupied by compact chromosomes, the other compartment is the space between the chromosomes. In the latter, transcription takes place at the surface of chromosomal domains and it houses the splicing machinery. The relevance of nuclear organization for efficient gene expression is discussed.

  1. Nuclear Security for Floating Nuclear Power Plants

    Energy Technology Data Exchange (ETDEWEB)

    Skiba, James M. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Scherer, Carolynn P. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-10-13

    Recently there has been a lot of interest in small modular reactors. A specific type of these small modular reactors (SMR,) are marine based power plants called floating nuclear power plants (FNPP). These FNPPs are typically built by countries with extensive knowledge of nuclear energy, such as Russia, France, China and the US. These FNPPs are built in one country and then sent to countries in need of power and/or seawater desalination. Fifteen countries have expressed interest in acquiring such power stations. Some designs for such power stations are briefly summarized. Several different avenues for cooperation in FNPP technology are proposed, including IAEA nuclear security (i.e. safeguards), multilateral or bilateral agreements, and working with Russian design that incorporates nuclear safeguards for IAEA inspections in non-nuclear weapons states

  2. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... Nuclear Medicine? Nuclear medicine is a branch of medical imaging that uses small amounts of radioactive material to ... a radiologist or other physician. To locate a medical imaging or radiation oncology provider in your community, you ...

  3. Nuclear fear revisited

    Science.gov (United States)

    Crease, Robert P.

    2010-10-01

    In 1988 the science historian Spencer Weart published a groundbreaking book called Nuclear Fear: A History of Images, which examined visions of radiation damage and nuclear disaster in newspapers, television, film, literature, advertisements and popular culture.

  4. Triangle Universities Nuclear Laboratory

    Energy Technology Data Exchange (ETDEWEB)

    1991-01-01

    This report contains brief papers that discusses the following topics: Fundamental Symmetries in the Nucleus; Internucleon Interactions; Dynamics of Very Light Nuclei; Facets of the Nuclear Many-Body Problem; and Nuclear Instruments and Methods.

  5. Theory of nuclear matter

    Energy Technology Data Exchange (ETDEWEB)

    Avakyan, R.M.; Sarkisyan, A.V.

    1987-07-01

    The properties of degenerate stellar matter in the region of nuclear densities are considered. The threshold of the transition of the electron-nucleus phase to the state of continuous nuclear matter is found.

  6. RBC nuclear scan

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003835.htm RBC nuclear scan To use the sharing features on this page, please enable JavaScript. An RBC nuclear scan uses small amounts of radioactive material to ...

  7. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... Us News Physician Resources Professions Site Index A-Z Children's (Pediatric) Nuclear Medicine Children’s (pediatric) nuclear medicine ... physicians diagnose and evaluate medical conditions. These imaging scans use radioactive materials called radiopharmaceuticals or radiotracers . Depending ...

  8. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... its earliest stages as well as a patient’s immediate response to therapeutic interventions. Children's (pediatric) nuclear medicine ... leaving the nuclear medicine facility. Through the natural process of radioactive decay, the small amount of radiotracer ...

  9. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... Tell your doctor about your child’s recent illnesses, medical conditions, medications and allergies. Depending on the type ... Nuclear Medicine? Nuclear medicine is a branch of medical imaging that uses small amounts of radioactive material ...

  10. Nuclear disarmament verification

    Energy Technology Data Exchange (ETDEWEB)

    DeVolpi, A.

    1993-12-31

    Arms control treaties, unilateral actions, and cooperative activities -- reflecting the defusing of East-West tensions -- are causing nuclear weapons to be disarmed and dismantled worldwide. In order to provide for future reductions and to build confidence in the permanency of this disarmament, verification procedures and technologies would play an important role. This paper outlines arms-control objectives, treaty organization, and actions that could be undertaken. For the purposes of this Workshop on Verification, nuclear disarmament has been divided into five topical subareas: Converting nuclear-weapons production complexes, Eliminating and monitoring nuclear-weapons delivery systems, Disabling and destroying nuclear warheads, Demilitarizing or non-military utilization of special nuclear materials, and Inhibiting nuclear arms in non-nuclear-weapons states. This paper concludes with an overview of potential methods for verification.

  11. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... of page What are some common uses of the procedure? Children's (pediatric) nuclear medicine imaging is performed ... the thyroid gland. top of page How does the nuclear medicine procedure work? With ordinary x-ray ...

  12. Polyphenol Compound as a Transcription Factor Inhibitor

    Directory of Open Access Journals (Sweden)

    Seyeon Park

    2015-10-01

    Full Text Available A target-based approach has been used to develop novel drugs in many therapeutic fields. In the final stage of intracellular signaling, transcription factor–DNA interactions are central to most biological processes and therefore represent a large and important class of targets for human therapeutics. Thus, we focused on the idea that the disruption of protein dimers and cognate DNA complexes could impair the transcriptional activation and cell transformation regulated by these proteins. Historically, natural products have been regarded as providing the primary leading compounds capable of modulating protein–protein or protein-DNA interactions. Although their mechanism of action is not fully defined, polyphenols including flavonoids were found to act mostly as site-directed small molecule inhibitors on signaling. There are many reports in the literature of screening initiatives suggesting improved drugs that can modulate the transcription factor interactions responsible for disease. In this review, we focus on polyphenol compound inhibitors against dimeric forms of transcription factor components of intracellular signaling pathways (for instance, c-jun/c-fos (Activator Protein-1; AP-1, c-myc/max, Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB and β-catenin/T cell factor (Tcf.

  13. Phenosafranin inhibits nuclear localization of transglutaminase 2 without affecting its transamidase activity.

    Science.gov (United States)

    Furutani, Yutaka; Toguchi, Mariko; Shrestha, Rajan; Kojima, Soichi

    2017-03-01

    Transglutaminase 2 (TG2) localizes to the nucleus and induces apoptosis through a crosslinking inactivation of Sp1 in JHH-7 cells treated with acyclic retinoid. We screened an inhibitor suppressing transamidase activity in the nucleus without affecting transamidase activity itself. Phenosafranin was found to inhibit nuclear localization of EGFP-tagged TG2 and dose-dependently reduce nuclear transamidase activity without affecting the activity in a tube. We concluded that phenosafranin was a novel TG2 inhibitor capable of suppressing its nuclear localization.

  14. Nuclear air cushion vehicles.

    Science.gov (United States)

    Anderson, J. L.

    1973-01-01

    This paper serves several functions. It identifies the 'state-of-the-art' of the still-conceptual nuclear air cushion vehicle, particularly the nuclear powerplant. Using mission studies and cost estimates, the report describes some of the advantages of nuclear power for large air cushion vehicles. The paper also summarizes the technology studies on mobile nuclear powerplants and conceptual ACV systems/missions studies that have been performed at NASA Lewis Research Center.

  15. Generalized Nuclear Data

    Energy Technology Data Exchange (ETDEWEB)

    2017-03-15

    This software is code related to reading/writing/manipulating nuclear data in the Generalized Nuclear Data (GND) format, a new format for sharing nuclear data among institutions. In addition to the software and its documentation, notes and documentation from the WPEC Subgroup 43 will be included. WPEC Subgroup 43 is an international committee charged with creating the API for the GND format.

  16. Nuclear fact book

    Energy Technology Data Exchange (ETDEWEB)

    Hill, O. F.; Platt, A. M.; Robinson, J. V. [comps

    1983-05-01

    This reference provides significant highlights and summary facts in the following areas: general energy; nuclear energy; nuclear fuel cycle; uranium supply and enrichment; nuclear reactors; spent fuel and advanced repacking concepts; reprocessing; high-level waste; gaseous waste; transuranic waste; low-level waste; remedial action; transportation; disposal; radiation information; environment; legislation; socio-political aspects; conversion factors; and a glossary. (GHT)

  17. Basic Nuclear Physics.

    Science.gov (United States)

    Bureau of Naval Personnel, Washington, DC.

    Basic concepts of nuclear structures, radiation, nuclear reactions, and health physics are presented in this text, prepared for naval officers. Applications to the area of nuclear power are described in connection with pressurized water reactors, experimental boiling water reactors, homogeneous reactor experiments, and experimental breeder…

  18. Nuclear Power in China

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    China’s vigorous efforts to propel development of nuclear power are paying off as the country’s nuclear power sector advances at an amazing pace. At present, China has set up three enormous nuclear power bases, one each in Qinshan of Zhejiang Province, Dayawan of Guangdong

  19. RETHINKING NUCLEAR POWER SAFETY

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    The Fukushima nuclear accident sounds alarm bells in China’s nuclear power industry In the wake of the Fukushima nucleara ccident caused by the earthquake andt sunami in Japan,the safety of nuclearp ower plants and the development of nuclear power have raised concerns,

  20. Revitalizing Nuclear Safety Research.

    Science.gov (United States)

    National Academy of Sciences - National Research Council, Washington, DC.

    This report covers the general issues involved in nuclear safety research and points out the areas needing detailed consideration. Topics included are: (1) "Principles of Nuclear Safety Research" (examining who should fund, who should conduct, and who should set the agenda for nuclear safety research); (2) "Elements of a Future…

  1. Nuclear energy technology

    Science.gov (United States)

    Buden, David

    1992-01-01

    An overview of space nuclear energy technologies is presented. The development and characteristics of radioisotope thermoelectric generators (RTG's) and space nuclear power reactors are discussed. In addition, the policy and issues related to public safety and the use of nuclear power sources in space are addressed.

  2. Relation between nuclear envelope and nuclear lamina in nuclear assembly in vitro

    Institute of Scientific and Technical Information of China (English)

    蔡树涛; 翟中和

    1997-01-01

    Xenopus laevis egg extracts cell-free nuclear assembly system was used as an experimental model to study the process of nuclear lamina assembly in nuclear reconstitution in vitro. The experimental results showed that lamin was involved in the nuclear assembly in vitro. The assembly of nuclear lamina was preceded by the assembly of nuclear matrix, and probably, inner nuclear matrix assembly provided the basis for nuclear lamina assembly. Inhibition of normal assembly of nuclear lamina, by preincubating egg extracts cell-free system with anti-lamin antibodies, resulted in abnormal assembly of nuclear envelope, suggesting that nuclear envelope assembly is closely associated with nuclear lamina assembly.

  3. Acetylcholinesterase Inhibitors: Pharmacology and Toxicology

    OpenAIRE

    Čolović, Mirjana B.; Krstić, Danijela Z; Lazarević-Pašti, Tamara D; Bondžić, Aleksandra M; Vasić, Vesna M

    2013-01-01

    Acetylcholinesterase is involved in the termination of impulse transmission by rapid hydrolysis of the neurotransmitter acetylcholine in numerous cholinergic pathways in the central and peripheral nervous systems. The enzyme inactivation, induced by various inhibitors, leads to acetylcholine accumulation, hyperstimulation of nicotinic and muscarinic receptors, and disrupted neurotransmission. Hence, acetylcholinesterase inhibitors, interacting with the enzyme as their primary target, are appl...

  4. Progeria, the nucleolus and farnesyltransferase inhibitors.

    Science.gov (United States)

    Mehta, Ishita S; Bridger, Joanna M; Kill, Ian R

    2010-02-01

    HGPS (Hutchinson-Gilford progeria syndrome) is a rare genetic disease affecting children causing them to age and die prematurely. The disease is typically due to a point mutation in the coding sequence for the nuclear intermediate-type filament protein lamin A and gives rise to a dominant-negative splice variant named progerin. Accumulation of progerin within nuclei causes disruption to nuclear structure, causes and premature replicative senescence and increases apoptosis. Now it appears that accumulation of progerin may have more widespread effects than previously thought since the demonstration that the presence and distribution of some nucleolar proteins are also adversely affected in progeria cells. One of the major breakthroughs both in the lamin field and for this syndrome is that many of the cellular defects observed in HGPS patient cells and model systems can be restored after treatment with a class of compounds known as FTIs (farnesyltransferase inhibitors). Indeed, it is demonstrated that FTI-277 is able to completely restore nucleolar antigen localization in treated progeria cells. This is encouraging news for the HGPS patients who are currently undergoing clinical trials with FTI treatment.

  5. Identification and characterization of a new chemotype of noncovalent SENP inhibitors.

    Science.gov (United States)

    Madu, Ikenna G; Namanja, Andrew T; Su, Yang; Wong, Steven; Li, Yi-Jia; Chen, Yuan

    2013-07-19

    Enzymes called SENPs catalyze both the maturation of small ubiquitin-like modifier (SUMO) precursors and removal of SUMO modifications, which regulate essential cellular functions such as cell cycle progression, DNA damage response, and intracellular trafficking. Some members, such as SENP1, are potential targets for developing cancer therapeutics. We searched for small molecule inhibitors of SENPs using in silico screening in conjunction with biochemical assays and identified a new chemotype of small molecule inhibitors that noncovalently inhibit SENPs. The inhibitors confer the noncompetitive inhibitory mechanism, as shown by nuclear magnetic resonance (NMR) and quantitative enzyme kinetic analysis. The NMR data also provided evidence for substrate-assisted inhibitor binding, which indicates the need for caution in using artificial substrates for compound screening, as the inhibitory effects could be significantly different from using the physiological substrates. This finding also suggests the possibility of designing inhibitors for this class of enzymes that are tuned for substrate-specificity.

  6. Proteinase inhibitors in Brazilian leguminosae

    Directory of Open Access Journals (Sweden)

    C. A. M. Sampaio

    1991-01-01

    Full Text Available Serine proteinase inhitors, in the seeds of several Leguminosae from the Pantanal region (West Brazil, were studied using bovine trypsin, a digestive enzyme, Factor XIIa and human plasma Kallikrein, two blood clotting factors. The inhibitors were purified from Enterolobium contortisiliquum (Mr=23,000, Torresea cearensis (Mr = 13,000, Bauhinia pentandra (Mr = 20,000 and Bauhinia bauhinioides (Mr = 20,000. E. contortisiliquum inhibitor inactivates all three enzymes, whereas the T. cearensis inhibitor inactivates trypsin and Factor XSSa, but does nor affect plasma kallikrein; both Bauhinia inhibitors, on the other hand, inactivate trypsin and plasma kallikrein but only the Bpentandra inhibitor affects Factor XIIa. Ki values were calculated between 10 [raised to the power of] -7 and 10 [raised to the power of] -8 M.

  7. Proteinaceous alpha-araylase inhibitors

    DEFF Research Database (Denmark)

    Svensson, Birte; Fukuda, Kenji; Nielsen, P.K.

    2004-01-01

    Proteins that inhibit alpha-amylases have been isolated from plants and microorganisms. These inhibitors can have natural roles in the control of endogenous a-amylase activity or in defence against pathogens and pests; certain inhibitors are reported to be antinutritional factors. The alpha-amylase...... inhibitors belong to seven different protein structural families, most of which also contain evolutionary related proteins without inhibitory activity. Two families include bifunctional inhibitors acting both on alpha-amylases and proteases. High-resolution structures are available of target alpha-amylases...... in complex with inhibitors from five families. These structures indicate major diversity but also some similarity in the structural basis of alpha-amylase inhibition. Mutational analysis of the mechanism of inhibition was performed in a few cases and various protein engineering and biotechnological...

  8. Activities report in nuclear physics

    NARCIS (Netherlands)

    Jansen, J. F. W.; Scholten, O.

    1987-01-01

    Experimental studies of giant resonances, nuclear structure, light mass systems, and heavy mass systems are summarized. Theoretical studies of nuclear structure, and dynamics are described. Electroweak interactions; atomic and surface physics; applied nuclear physics; and nuclear medicine are discus

  9. Nuclear reactor physics

    CERN Document Server

    Stacey, Weston M

    2010-01-01

    Nuclear reactor physics is the core discipline of nuclear engineering. Nuclear reactors now account for a significant portion of the electrical power generated worldwide, and new power reactors with improved fuel cycles are being developed. At the same time, the past few decades have seen an ever-increasing number of industrial, medical, military, and research applications for nuclear reactors. The second edition of this successful comprehensive textbook and reference on basic and advanced nuclear reactor physics has been completely updated, revised and enlarged to include the latest developme

  10. Nuclear Egress of Herpesviruses

    Institute of Scientific and Technical Information of China (English)

    Richard J.Roller

    2008-01-01

    Herpesviruses assemble and fill their capsids in the infected cell nucleus,and must then move this enormous macromolecular assembly across the nuclear membrane and into the cytoplasm.Doing so is a complex,multi-step process that involves envelopment of the capsid at the inner nuclear membrane and de-envelopment by fusion with the outer nuclear membrane.This process is orchestrated by viral proteins,but requires the modification of cellular structures and mechanisms including the nuclear lamina.In this review I summarize recent research on the mechanism of nuclear envelopment and the viral and cellular systems involved in its execution.

  11. Nuclear parton distributions

    Directory of Open Access Journals (Sweden)

    Kulagin S. A.

    2017-01-01

    Full Text Available We review a microscopic model of the nuclear parton distribution functions, which accounts for a number of nuclear effects including Fermi motion and nuclear binding, nuclear meson-exchange currents, off-shell corrections to bound nucleon distributions and nuclear shadowing. We also discuss applications of this model to a number of processes including lepton-nucleus deep inelastic scattering, proton-nucleus Drell-Yan lepton pair production at Fermilab, as well as W± and Z0 boson production in proton-lead collisions at the LHC.

  12. Nuclear energy; Le nucleaire

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2007-07-01

    This digest document was written by members of the union of associations of ex-members and retired people of the Areva group (UARGA). It gives a comprehensive overview of the nuclear industry world, starting from radioactivity and its applications, and going on with the fuel cycle (front-end, back-end, fuel reprocessing, transports), the nuclear reactors (PWR, BWR, Candu, HTR, generation 4 systems), the effluents from nuclear facilities, the nuclear wastes (processing, disposal), and the management and safety of nuclear activities. (J.S.)

  13. Nuclear education and training

    CERN Document Server

    2012-01-01

    The OECD Nuclear Energy Agency (NEA) first published in 2000 Nuclear Education and Training: Cause for Concern? , which highlighted significant issues in the availability of human resources for the nuclear industry. Ten years on, Nuclear Education and Training: From Concern to Capability considers what has changed in that time and finds that, while some countries have taken positive actions, in a number of others human resources could soon be facing serious challenges in coping with existing and potential new nuclear facilities. This is exacerbated by the increasing rate of retirement as the w

  14. A high-throughput screening system targeting the nuclear export pathway via the third nuclear export signal of influenza A virus nucleoprotein.

    Science.gov (United States)

    Kakisaka, Michinori; Mano, Takafumi; Aida, Yoko

    2016-06-02

    Two classes of antiviral drugs, M2 channel inhibitors and neuraminidase (NA) inhibitors, are currently approved for the treatment of influenza; however, the development of resistance against these agents limits their efficacy. Therefore, the identification of new targets and the development of new antiviral drugs against influenza are urgently needed. The third nuclear export signal (NES3) of nucleoprotein (NP) is the most important for viral replication among seven NESs encoded by four viral proteins, NP, M1, NS1, and NS2. NP-NES3 is critical for the nuclear export of NP, and targeting NP-NES3 is therefore a promising strategy that may lead to the development of antiviral drugs. However, a high-throughput screening (HTS) system to identify inhibitors of NP nuclear export has not been established. Here, we developed a novel HTS system to evaluate the inhibitory effects of compounds on the nuclear export pathway mediated by NP-NES3 using a MDCK cell line stably expressing NP-NES3 fused to a green fluorescent protein from aequorea coerulescens (AcGFP-NP-NES3) and a cell imaging analyzer. This HTS system was used to screen a 9600-compound library, leading to the identification of several hit compounds with inhibitory activity against the nuclear export of AcGFP-NP-NES3. The present HTS system provides a useful strategy for the identification of inhibitors targeting the nuclear export of NP via its NES3 sequence.

  15. History of Nuclear India

    Science.gov (United States)

    Chaturvedi, Ram

    2000-04-01

    India emerged as a free and democratic country in 1947, and entered into the nuclear age in 1948 by establishing the Atomic Energy Commission (AEC), with Homi Bhabha as the chairman. Later on the Department of Atomic Energy (DAE) was created under the Office of the Prime Minister Jawahar Lal Nehru. Initially the AEC and DAE received international cooperation, and by 1963 India had two research reactors and four nuclear power reactors. In spite of the humiliating defeat in the border war by China in 1962 and China's nuclear testing in 1964, India continued to adhere to the peaceful uses of nuclear energy. On May 18, 1974 India performed a 15 kt Peaceful Nuclear Explosion (PNE). The western powers considered it nuclear weapons proliferation and cut off all financial and technical help, even for the production of nuclear power. However, India used existing infrastructure to build nuclear power reactors and exploded both fission and fusion devices on May 11 and 13, 1998. The international community viewed the later activity as a serious road block for the Non-Proliferation Treaty and the Comprehensive Test Ban Treaty; both deemed essential to stop the spread of nuclear weapons. India considers these treaties favoring nuclear states and is prepared to sign if genuine nuclear disarmament is included as an integral part of these treaties.

  16. The nuclear symmetry energy

    Science.gov (United States)

    Baldo, M.; Burgio, G. F.

    2016-11-01

    The nuclear symmetry energy characterizes the variation of the binding energy as the neutron to proton ratio of a nuclear system is varied. This is one of the most important features of nuclear physics in general, since it is just related to the two component nature of the nuclear systems. As such it is one of the most relevant physical parameters that affect the physics of many phenomena and nuclear processes. This review paper presents a survey of the role and relevance of the nuclear symmetry energy in different fields of research and of the accuracy of its determination from the phenomenology and from the microscopic many-body theory. In recent years, a great interest was devoted not only to the Nuclear Matter symmetry energy at saturation density but also to its whole density dependence, which is an essential ingredient for our understanding of many phenomena. We analyze the nuclear symmetry energy in different realms of nuclear physics and astrophysics. In particular we consider the nuclear symmetry energy in relation to nuclear structure, astrophysics of Neutron Stars and supernovae, and heavy ion collision experiments, trying to elucidate the connections of these different fields on the basis of the symmetry energy peculiarities. The interplay between experimental and observational data and theoretical developments is stressed. The expected future developments and improvements are schematically addressed, together with most demanded experimental and theoretical advances for the next few years.

  17. Dynamic nuclear spin polarization

    Energy Technology Data Exchange (ETDEWEB)

    Stuhrmann, H.B. [GKSS-Forschungszentrum Geesthacht GmbH (Germany)

    1996-11-01

    Polarized neutron scattering from dynamic polarized targets has been applied to various hydrogenous materials at different laboratories. In situ structures of macromolecular components have been determined by nuclear spin contrast variation with an unprecedented precision. The experiments of selective nuclear spin depolarisation not only opened a new dimension to structural studies but also revealed phenomena related to propagation of nuclear spin polarization and the interplay of nuclear polarisation with the electronic spin system. The observation of electron spin label dependent nuclear spin polarisation domains by NMR and polarized neutron scattering opens a way to generalize the method of nuclear spin contrast variation and most importantly it avoids precontrasting by specific deuteration. It also likely might tell us more about the mechanism of dynamic nuclear spin polarisation. (author) 4 figs., refs.

  18. Overview of nuclear data

    Energy Technology Data Exchange (ETDEWEB)

    Firestone, R.B.

    2003-06-30

    For many years, nuclear structure and decay data have been compiled and disseminated by an International Network of Nuclear Structure and Decay Data (NSDD) evaluators under the auspices of the International Nuclear Data Committee (INDC) of the International Atomic Energy Agency (IAEA). In this lecture I will discuss the kinds of data that are available and describe various ways to obtain this information. We will learn about some of the publications that are available and Internet sources of nuclear data. You will be introduced to Isotope Explorer software for retrieving and displaying nuclear structure and radioactive decay data. The on-line resources Table of Radioactive Isotopes, PGAA Database Viewer, Nuclear Science Reference Search, Table of Isotopes Educational Website, and other information sources will be discussed. Exercises will be provided to increase your ability to understand, access, and use nuclear data.

  19. Cold nuclear fusion

    Directory of Open Access Journals (Sweden)

    Huang Zhenqiang Huang Yuxiang

    2013-10-01

    Full Text Available In normal temperature condition, the nuclear force constraint inertial guidance method, realize the combination of deuterium and tritium, helium and lithium... And with a magnetic moment of light nuclei controlled cold nuclear collide fusion, belongs to the nuclear energy research and development in the field of applied technology "cold nuclear collide fusion". According to the similarity of the nuclear force constraint inertial guidance system, the different velocity and energy of the ion beam mixing control, developed ion speed dc transformer, it is cold nuclear fusion collide, issue of motivation and the nuclear power plant start-up fusion and power transfer system of the important equipment, so the merger to apply for a patent

  20. Nuclear apoptosis induced by isolated mitochondria

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    We isolated and purified mitochondria from mouse livers and spinach leaves. When added into egg extracts of Xenopus laevis, they caused nuclei of mouse liver to undergo apoptotic changes. Chromatin condensation, margination and DNA ladder were observed. After incubating isolated mitochondria in some hypotonic solutions, and centrifuging these mixtures at high speed, we got mitochondrial supernatants. It was found that in the absence of cytosolic factor, the supernatant alone was able to induce apoptotic changes in nuclei. The effective components were partly of protein. DNA fragmentation was partly inhibited by caspase inhibitors AC-DEVD-CHO and AC-YVADCHO. Meanwhile, caspase inhibitors fully blocked chromatin condensation. Primary characterization of the nuclear endonuclease(s) induced by mitochondrial supernatants was also conducted. It was found that this endonuclease is different from endonuclease G, cytochrome c-induced nuclease, or Ca2+-activated endonuclease.

  1. PARP1 inhibitors attenuate AKT phosphorylation via the upregulation of PHLPP1

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Shuai [State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025 (China); Division of Hematology and Oncology, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35205 (United States); Wang, Huibo; Davis, Ben C. [Division of Hematology and Oncology, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35205 (United States); Liang, Jiyong [Department of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77054 (United States); Cui, Rutao [Department of Dermatology, Boston University School of Medicine, Boston, MA 02118 (United States); Chen, Sai-Juan, E-mail: sjchen@stn.sh.cn [State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025 (China); Xu, Zhi-Xiang, E-mail: zhi-xiang.xu@ccc.uab.edu [Division of Hematology and Oncology, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35205 (United States)

    2011-08-26

    Highlights: {yields} PARP1 inhibitors cause a cytotoxic effect independent of DNA repair impairment. {yields} PARP1 inhibitors attenuated AKT-FOXO3A signaling by activating PHLPP1. {yields} PHLPP1 regulates the sensitivity of cancer cells to PARP1 inhibitors. -- Abstract: Poly(ADP-ribose) polymerase-1 (PARP1) inhibitors are emerging as an important class of drugs for treating BRCA-deficient cancers. Recent discoveries have shown that PARP1 inhibitors may treat other cancer patients in addition to the relatively small proportion of patients carrying BRCA mutations. However, the additional targets by which PARP1 inhibitor-mediated tumor suppression remain poorly understood. In this study, we show that two PARP1 inhibitors, PJ-34 and 3-AB, attenuate AKT phosphorylation at serine 473 (S473) independent of DNA repair impairment. These inhibitors decrease the AKT-associated phosphorylation of FOXO3A, enhance the nuclear retention of FOXO3A, and activate its transcriptional activity. We further demonstrate that treatment with PJ-34 or 3-AB dramatically increases the level of PHLPP1. Overexpression of PHLPP1 enhances the PARP1 inhibitor-induced downregulation of AKT phosphorylation and increases tumor cell death. In contrast, knockdown of PHLPP1 abrogates the PARP1 inhibitor-mediated AKT inhibition and desensitizes cells to its treatment. Therefore, our findings not only show the robust role of PARP1 inhibitors in AKT inhibition but also develop a novel strategy to increase the effectiveness of cancer treatment via PARP1 inhibitor-induced PHLPP1 upregulation.

  2. The Nuclear Symmetry Energy

    CERN Document Server

    Baldo, M

    2016-01-01

    The nuclear symmetry energy characterizes the variation of the binding energy as the neutron to proton ratio of a nuclear system is varied. This is one of the most important features of nuclear physics in general, since it is just related to the two component nature of the nuclear systems. As such it is one of the most relevant physical parameters that affect the physics of many phenomena and nuclear processes. This review paper presents a survey of the role and relevance of the nuclear symmetry energy in different fields of research and of the accuracy of its determination from the phenomenology and from the microscopic many-body theory. In recent years, a great interest was devoted not only to the Nuclear Matter symmetry energy at saturation density but also to its whole density dependence, which is an essential ingredient for our understanding of many phenomena. We analyze the nuclear symmetry energy in different realms of nuclear physics and astrophysics. In particular we consider the nuclear symmetry ene...

  3. Nuclear energy efficiency improvements

    Energy Technology Data Exchange (ETDEWEB)

    Lauritzen, B.; Nonboel, E. [Technical Univ. of Denmark. DTU Nutech, Roskilde (Denmark); Kyrki-Rajamaeki, R. [Lappeenranta Univ. of Technology (Finland)

    2012-11-15

    Nuclear energy already today plays an important role in decarbonisation of the electricity sector while providing energy security and being economically competitive. Nuclear energy is characterized by its very high energy density and is well suited for large-scale, baseload electricity supply. Similar to renewable energy sources such as wind, solar or biomass, nuclear power is characterized by an abundant supply of its primary energy source, uranium, but is not limited to the same extent as these renewable energy sources from being an intermittent energy supply or imposing severe restrictions on land-use. Improving energy efficiency of nuclear power plants has contributed to a better utilization of the uranium resources and has helped improving the economic performance of nuclear power plants. This is to a large degree accomplished through optimisation of nuclear fuel assemblies as well as renewing turbines and generators. More importantly however, the overall economy of nuclear power has improved though better plant management leading to higher capacity factors and by extending the lifetimes of existing nuclear power plants. Provided that improved safety, economics and successful waste management can be demonstrated nuclear power is likely to grow in the future. Non-electricity applications may further boost the growth of nuclear energy, especially with the development of new reactor systems allowing for cogeneration of electricity and hydrogen or biofuels for transport. (Author)

  4. Nuclear energy - some aspects; Energia nuclear - alguns aspectos

    Energy Technology Data Exchange (ETDEWEB)

    Bandeira, Fausto de Paula Menezes

    2005-05-15

    This work presents a brief history of research and development concerning to nuclear technology worldwide and in Brazil, also information about radiations and radioactive elements as well; the nuclear technology applications; nuclear reactor types and functioning of thermonuclear power plants; the number of existing nuclear power plants; the nuclear hazards occurred; the national fiscalization of nuclear sector; the Brazilian legislation in effect and the propositions under proceduring at House of Representatives related to the nuclear energy.

  5. Cholinesterase inhibitors and memory.

    Science.gov (United States)

    Pepeu, Giancarlo; Giovannini, Maria Grazia

    2010-09-06

    A consensus exists that cholinesterase inhibitors (ChEIs) are efficacious for mild to moderate Alzheimer's Disease (AD). Unfortunately, the number of non-responders is large and the therapeutic effect is usually short-lasting. In experimental animals, ChEIs exert three main actions: inhibit cholinesterase (ChE), increase extracellular levels of brain acetylcholine (ACh), improve cognitive processes, particularly when disrupted in models of AD. In this overview we shall deal with the cognitive processes that are improved by ChEI treatment because they depend on the integrity of brain cholinergic pathways and their activation. The role of cholinergic system in cognition can be investigated using different approaches. Microdialysis experiments demonstrate the involvement of the cholinergic system in attention, working, spatial and explicit memory, information encoding, sensory-motor gating, skill learning. No involvement in long-term memory has yet been demonstrated. Conversely, memory consolidation is facilitated by low cholinergic activity. Experiments on healthy human subjects, notwithstanding caveats concerning age, dose, and different memory tests, confirm the findings of animal experiments and demonstrate that stimulation of the cholinergic system facilitates attention, stimulus detection, perceptual processing and information encoding. It is not clear whether information retrieval may be improved but memory consolidation is reduced by cholinergic activation. ChEI effects in AD patients have been extensively investigated using rating scales that assess cognitive and behavioural responses. Few attempts have been made to identify which scale items respond better to ChEIs and therefore, presumably, depend on the activity of the cholinergic system. Improvement in attention and executive functions, communication, expressive language and mood stability have been reported. Memory consolidation and retrieval may be impaired by high ACh levels. Therefore, considering

  6. Nuclear Threats and Security

    Directory of Open Access Journals (Sweden)

    Garry Jacobs

    2012-10-01

    Full Text Available This article presents highlights and insights from the International Conference on “Nuclear Threats and Security” organized by the World Academy of Art and Science in association with the European Leadership Network and the Dag Hammarskjöld University College of International Relations and Diplomacy and sponsored by NATO at the Inter-University Centre, Dubrovnik on September 14-16, 2012. The conference examined important issues related to nuclear non-proliferation and disarmament, the legality of nuclear weapons and their use, illicit trade in nuclear materials, the dangers of nuclear terrorism, nuclear- and cyber-security. Papers and video recordings of the major presentations and session summaries can be found here.

  7. Safety and nuclear power

    Energy Technology Data Exchange (ETDEWEB)

    Gittus, John; Gunning, Angela.

    1988-05-01

    Representatives of the supporters and opponents of civil nuclear power put forward the arguments they feel the public should consider when making up their mind about the nuclear industry. The main argument in favour of nuclear power is about the low risk in comparison with other risks and the amount of radiation received on average by the population in the United Kingdom from different sources. The aim is to show that the nuclear industry is fully committed to the cause of safety and this has resulted in a healthy workforce and a safe environment for the public. The arguments against are that the nuclear industry is deceitful, secretive and politically motivated and thus its arguments about safety, risks, etc, cannot be trusted. The question of safety is considered further - in particular the perceptions, definitions and responsibility. The economic case for nuclear electricity is not accepted. (U.K.).

  8. Nuclear power industry

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-04-28

    This press dossier presented in Shanghai (China) in April 1999, describes first the activities of the Framatome group in the people`s republic of China with a short presentation of the Daya Bay power plant and of the future Ling Ao project, and with a description of the technological cooperation with China in the nuclear domain (technology transfers, nuclear fuels) and in other industrial domains (mechanics, oil and gas, connectors, food and agriculture, paper industry etc..). The general activities of the Framatome group in the domain of energy (nuclear realizations in France, EPR project, export activities, nuclear services, nuclear fuels, nuclear equipments, industrial equipments) and of connectors engineering are presented in a second and third part with the 1998 performances. (J.S.)

  9. [ACE inhibitors and the kidney].

    Science.gov (United States)

    Hörl, W H

    1996-01-01

    Treatment with ACE inhibitors results in kidney protection due to reduction of systemic blood pressure, intraglomerular pressure, an antiproliferative effect, reduction of proteinuria and a lipid-lowering effect in proteinuric patients (secondary due to reduction of protein excretion). Elderly patients with diabetes melitus, coronary heart disease or peripheral vascular occlusion are at risk for deterioration of kidney function due to a high frequency of renal artery stenosis in these patients. In patients with renal insufficiency dose reduction of ACE inhibitors is necessary (exception: fosinopril) but more important is the risk for development of hyperkalemia. Patients at risk for renal artery stenosis and patients pretreated with diuretics should receive a low ACE inhibitor dosage initially ("start low - go slow"). For compliance reasons once daily ACE inhibitor dosage is recommended.

  10. [Cancer therapy by PARP inhibitors].

    Science.gov (United States)

    Seimiya, Hiroyuki

    2015-08-01

    Poly(ADP-ribose) polymerases(PARP) synthesize the ADP-ribose polymers onto proteins and play a role in DNA repair. PARP inhibitors block the repair of single-strand breaks, which in turn gives rise to double-strand breaks during DNA replication. Thus, PARP inhibitors elicit synthetic lethality in cancer with BRCA1/2 loss-of-function mutations that hamper homologous recombination repair of double-strand breaks. Olaparib, the first-in-class PARP inhibitor, was approved for treatment of BRCA-mutated ovarian cancer in Europe and the United States in 2014. Other PARP inhibitors under clinical trials include rucaparib, niraparib, veliparib, and the "PARP-trapping" BMN-673. BRCA1/2 sequencing is an FDA-approved companion diagnostics, which predicts the cancer vulnerability to PARP inhibition. Together, synthetic lethal PARP inhibition is a novel promising strategy for cancer intervention even in cases without prominent driver oncogenes.

  11. Nuclear Power Feasibility 2007

    OpenAIRE

    Aragonés Beltrán, José María; Hill, Barrie Frederick; Kadak, Andrew C.; Shultz, Donald F.; Spitalnik, Jorge

    2008-01-01

    Nuclear power is a proven technology and has the potential to generate virtually limitless energy with no significant greenhouse gas emissions. Nuclear power can become one of the main options to contribute to substantial cuts in global greenhouse gas emissions. Modern development of nuclear power technology and the established framework of international agreements and conventions are responding to the major political, economic and environmental issues -high capital costs, the risks posed by ...

  12. Absolute nuclear material assay

    Science.gov (United States)

    Prasad, Manoj K [Pleasanton, CA; Snyderman, Neal J [Berkeley, CA; Rowland, Mark S [Alamo, CA

    2012-05-15

    A method of absolute nuclear material assay of an unknown source comprising counting neutrons from the unknown source and providing an absolute nuclear material assay utilizing a model to optimally compare to the measured count distributions. In one embodiment, the step of providing an absolute nuclear material assay comprises utilizing a random sampling of analytically computed fission chain distributions to generate a continuous time-evolving sequence of event-counts by spreading the fission chain distribution in time.

  13. Nuclear spirals in galaxies

    OpenAIRE

    Maciejewski, Witold

    2006-01-01

    Recent high-resolution observations indicate that nuclear spirals are often present in the innermost few hundred parsecs of disc galaxies. My models show that nuclear spirals form naturally as a gas response to non-axisymmetry in the gravitational potential. Some nuclear spirals take the form of spiral shocks, resulting in streaming motions in the gas, and in inflow comparable to the accretion rates needed to power local Active Galactic Nuclei. Recently streaming motions of amplitude expected...

  14. Nonstrategic Nuclear Weapons

    Science.gov (United States)

    2014-01-03

    William Potter , and Nikolai Sokov, Reducing and Regulating Tactical (Nonstrategic) Nuclear Weapons in Europe, The James Martin Center For...See William C. Potter and Nikolai Sokov, “Nuclear Weapons that People Forget,” International Herald Tribune, May 31, 2000. 87 Sam Nunn, Igor...their security.97 94 Kent Harris , “NATO Allies Want U.S. Nuclear Weapons out of Europe

  15. Nuclear Fabrication Consortium

    Energy Technology Data Exchange (ETDEWEB)

    Levesque, Stephen [EWI, Columbus, OH (United States)

    2013-04-05

    This report summarizes the activities undertaken by EWI while under contract from the Department of Energy (DOE) Office of Nuclear Energy (NE) for the management and operation of the Nuclear Fabrication Consortium (NFC). The NFC was established by EWI to independently develop, evaluate, and deploy fabrication approaches and data that support the re-establishment of the U.S. nuclear industry: ensuring that the supply chain will be competitive on a global stage, enabling more cost-effective and reliable nuclear power in a carbon constrained environment. The NFC provided a forum for member original equipment manufactures (OEM), fabricators, manufacturers, and materials suppliers to effectively engage with each other and rebuild the capacity of this supply chain by : Identifying and removing impediments to the implementation of new construction and fabrication techniques and approaches for nuclear equipment, including system components and nuclear plants. Providing and facilitating detailed scientific-based studies on new approaches and technologies that will have positive impacts on the cost of building of nuclear plants. Analyzing and disseminating information about future nuclear fabrication technologies and how they could impact the North American and the International Nuclear Marketplace. Facilitating dialog and initiate alignment among fabricators, owners, trade associations, and government agencies. Supporting industry in helping to create a larger qualified nuclear supplier network. Acting as an unbiased technology resource to evaluate, develop, and demonstrate new manufacturing technologies. Creating welder and inspector training programs to help enable the necessary workforce for the upcoming construction work. Serving as a focal point for technology, policy, and politically interested parties to share ideas and concepts associated with fabrication across the nuclear industry. The report the objectives and summaries of the Nuclear Fabrication Consortium

  16. Nuclear South Asia

    Science.gov (United States)

    2007-11-02

    nuclear equation in South Asia, the geopolitical and geoeconomic realities will keep China out of the South Asian nuclear picture. As Pakistan...remain unipolar for quite some time with the United States as the global superpower. There is predominance of geoeconomics as against geopolitical...to drag China into the nuclear equation in South Asia, the geopolitical and geoeconomic realities will likely keep China out of the South Asian

  17. Facilitating Global Nuclear Disarmament

    Institute of Scientific and Technical Information of China (English)

    Wu; Junr

    2014-01-01

    <正>I.Introduction Since the advent of nuclear weapons,especially after the United States dropped atomic bombs in Hiroshima and Nagasaki,the capacity of massive and indiscriminate annihilation of nuclear weapons have made people of insight across the world realize that such weapons cannot be used arbitrarily.In the 1960s,the then Chinese leader Mao Zedong said that to throw them(nuclear weapons)about at will is committing a

  18. Nuclear electronic instrumentation; Instrumentacion electronica nuclear

    Energy Technology Data Exchange (ETDEWEB)

    Ramirez J, F. J., E-mail: francisco.ramirez@inin.gob.m [ININ, Departamento de Sistemas Electronicos, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico)

    2010-07-01

    The activities carried out in the Instituto Nacional de Investigaciones Nucleares (ININ) in the field of the nuclear electronic instrumentation included those activities corresponding to the design and production of nuclear instruments in a first stage, as well as the internal activities of design, repair and maintenance that have supported to other projects of the institution during many years. It is mentioned of the presence and constant collaboration of the ININ with the IAEA in different projects and programs. Also, it is mentioned on the establishment of the Radiation Detectors Laboratory, which for their characteristics and repair capacities of radiation detectors of cooled semiconductor, it is only in their specialty. It is emphasized the investigation and the development in the field of new radiation detectors and applications, as well as the important contribution in this field, in institutions like: Mexican Petroleum, National Commission of Nuclear Safety and Safeguards and Federal Commission of Electricity. Finally a position of the future of these activities is made, considering the speed of the advances of the electronic and nuclear technology. (Author)

  19. Nuclear medicine physics

    CERN Document Server

    De Lima, Joao Jose

    2011-01-01

    Edited by a renowned international expert in the field, Nuclear Medicine Physics offers an up-to-date, state-of-the-art account of the physics behind the theoretical foundation and applications of nuclear medicine. It covers important physical aspects of the methods and instruments involved in modern nuclear medicine, along with related biological topics. The book first discusses the physics of and machines for producing radioisotopes suitable for use in conventional nuclear medicine and PET. After focusing on positron physics and the applications of positrons in medicine and biology, it descr

  20. Nuclear safety in perspective

    Directory of Open Access Journals (Sweden)

    J. K. Basson

    1983-03-01

    Full Text Available The impending operation of South Africa’s first nuclear power station, Koeberg, necessitates a thorough analysis of nuclear safety under local conditions. More is known, worldwide, about radiation effects than about any other health hazard, and international norms have already been accepted since 1928. The widespread use of X-rays and radio-isotopes, the extraction and processing of uranium, visits by nuclear-powered ships and, especially, the nuclear-reactor operation in South Africa. Consequently, the pre-operational investigations of Koeberg could be completed thoroughly, with full confidence in its safe commissioning.

  1. Nuclear level density predictions

    Directory of Open Access Journals (Sweden)

    Bucurescu Dorel

    2015-01-01

    Full Text Available Simple formulas depending only on nuclear masses were previously proposed for the parameters of the Back-Shifted Fermi Gas (BSFG model and of the Constant Temperature (CT model of the nuclear level density, respectively. They are now applied for the prediction of the level density parameters of all nuclei with available masses. Both masses from the new 2012 mass table and from different models are considered and the predictions are discussed in connection with nuclear regions most affected by shell corrections and nuclear structure effects and relevant for the nucleosynthesis.

  2. Nuclear power in Europe

    Energy Technology Data Exchange (ETDEWEB)

    Gittus, J. (British Nuclear Forum, London (UK))

    1991-04-01

    The 1990s are turning out to be a most crucial phase for the nuclear industries of Europe. A time of uncertainty, as well as considerable opportunity, lies ahead. Despite a measure of public and political opposition to nuclear power, many are beginning to realise that, as a method of generating electricity that produces only 1% of greenhouse gases compared to coal per unit of electricity, nuclear energy may be the best alternative to the burning of fossil fuels. Although advances have been made in renewable energy, nuclear power is still the main non-fossil fuel source that can cope with today's energy demands. (author).

  3. Nuclear medium effects in $\

    CERN Document Server

    Haider, H; Athar, M Sajjad; Vacas, M J Vicente

    2011-01-01

    We study the nuclear medium effects in the weak structure functions $F_2(x,Q^2)$ and $F_3(x,Q^2)$ in the deep inelastic neutrino/antineutrino reactions in nuclei. We use a theoretical model for the nuclear spectral functions which incorporates the conventional nuclear effects, such as Fermi motion, binding and nucleon correlations. We also consider the pion and rho meson cloud contributions calculated from a microscopic model for meson-nucleus self-energies. The calculations have been performed using relativistic nuclear spectral functions which include nucleon correlations. Our results are compared with the experimental data of NuTeV and CDHSW.

  4. Nuclear physics of stars

    CERN Document Server

    Iliadis, Christian

    2007-01-01

    Thermonuclear reactions in stars is a major topic in the field of nuclear astrophysics, and deals with the topics of how precisely stars generate their energy through nuclear reactions, and how these nuclear reactions create the elements the stars, planets and - ultimately - we humans consist of. The present book treats these topics in detail. It also presents the nuclear reaction and structure theory, thermonuclear reaction rate formalism and stellar nucleosynthesis. The topics are discussed in a coherent way, enabling the reader to grasp their interconnections intuitively. The book serves bo

  5. Nuclear criticality safety guide

    Energy Technology Data Exchange (ETDEWEB)

    Pruvost, N.L.; Paxton, H.C. [eds.

    1996-09-01

    This technical reference document cites information related to nuclear criticality safety principles, experience, and practice. The document also provides general guidance for criticality safety personnel and regulators.

  6. Nuclear structure theory

    CERN Document Server

    Irvine, J M

    1972-01-01

    Nuclear Structure Theory provides a guide to nuclear structure theory. The book is comprised of 23 chapters that are organized into four parts; each part covers an aspect of nuclear structure theory. In the first part, the text discusses the experimentally observed phenomena, which nuclear structure theories need to look into and detail the information that supports those theories. The second part of the book deals with the phenomenological nucleon-nucleon potentials derived from phase shift analysis of nucleon-nucleon scattering. Part III talks about the phenomenological parameters used to de

  7. Technologists for Nuclear Medicine

    Science.gov (United States)

    Barnett, Huey D.

    1974-01-01

    Physicians need support personnel for work with radioisotopes in diagnosing dangerous diseases. The Nuclear Medicine Technology (NMT) Program at Hillsborough Community College in Tampa, Florida, is described. (MW)

  8. Inhibition of CRM1-dependent nuclear export sensitizes malignant cells to cytotoxic and targeted agents.

    Science.gov (United States)

    Turner, Joel G; Dawson, Jana; Cubitt, Christopher L; Baz, Rachid; Sullivan, Daniel M

    2014-08-01

    Nuclear-cytoplasmic trafficking of proteins is a significant factor in the development of cancer and drug resistance. Subcellular localization of exported proteins linked to cancer development include those involved in cell growth and proliferation, apoptosis, cell cycle regulation, transformation, angiogenesis, cell adhesion, invasion, and metastasis. Here, we examined the basic mechanisms involved in the export of proteins from the nucleus to the cytoplasm. All proteins over 40kDa use the nuclear pore complex to gain entry or exit from the nucleus, with the primary nuclear export molecule involved in these processes being chromosome region maintenance 1 (CRM1, exportin 1 or XPO1). Proteins exported from the nucleus must possess a hydrophobic nuclear export signal (NES) peptide that binds to a hydrophobic groove containing an active-site Cys528 in the CRM1 protein. CRM1 inhibitors function largely by covalent modification of the active site Cys528 and prevent binding to the cargo protein NES. In the absence of a CRM1 inhibitor, CRM1 binds cooperatively to the NES of the cargo protein and RanGTP, forming a trimer that is actively transported out of the nucleus by facilitated diffusion. Nuclear export can be blocked by CRM1 inhibitors, NES peptide inhibitors or by preventing post-translational modification of cargo proteins. Clinical trials using the classic CRM1 inhibitor leptomycin B proved too toxic for patients; however, a new generation of less toxic small molecule inhibitors is being used in clinical trials in patients with both hematological malignancies and solid tumors. Additional trials are being initiated using small-molecule CRM1 inhibitors in combination with chemotherapeutics such as pegylated liposomal doxorubicin. In this review, we present evidence that combining the new CRM1 inhibitors with other classes of therapeutics may prove effective in the treatment of cancer. Potential combinatorial therapies discussed include the use of CRM1 inhibitors and

  9. Silibinin induces apoptosis via calpain-dependent AIF nuclear translocation in U87MG human glioma cell death

    Directory of Open Access Journals (Sweden)

    Kim Yong K

    2011-04-01

    Full Text Available Abstract Background Silibinin, a natural polyphenolic flavonoid, has been reported to induce cell death in various cancer cell types. However, the molecular mechanism is not clearly defined. Our previous study showed that silibinin induces glioma cell death and its effect was effectively prevented by calpain inhibitor. The present study was therefore undertaken to examine the role of calpain in the silibinin-induced glioma cell death. Methods U87MG cells were grown on well tissue culture plates and cell viability was measured by MTT assay. ROS generation and △ψm were estimated using the fluorescence dyes. PKC activation and Bax expression were measured by Western blot analysis. AIF nuclear translocation was determined by Western blot and immunocytochemistry. Results Silibinin induced activation of calpain, which was blocked by EGTA and the calpain inhibitor Z-Leu-Leu-CHO. Silibinin caused ROS generation and its effect was inhibited by calpain inhibitor, the general PKC inhibitor GF 109203X, the specific PKCδ inhibitor rottlerin, and catalase. Silibinin-induce cell death was blocked by calpain inhibitor and PKC inhibitors. Silibinin-induced PKCδ activation and disruption of △ψm were prevented by the calpain inhibitor. Silibinin induced AIF nuclear translocation and its effect was prevented by calpain inhibitor. Transfection of vector expressing microRNA of AIF prevented the silibinin-induced cell death. Conclusions Silibinin induces apoptotic cell death through a calpain-dependent mechanism involving PKC, ROS, and AIF nuclear translocation in U87MG human glioma cells.

  10. Commercial nuclear power 1990

    Energy Technology Data Exchange (ETDEWEB)

    1990-09-28

    This report presents the status at the end of 1989 and the outlook for commercial nuclear capacity and generation for all countries in the world with free market economies (FME). The report provides documentation of the US nuclear capacity and generation projections through 2030. The long-term projections of US nuclear capacity and generation are provided to the US Department of Energy's (DOE) Office of Civilian Radioactive Waste Management (OCRWM) for use in estimating nuclear waste fund revenues and to aid in planning the disposal of nuclear waste. These projections also support the Energy Information Administration's annual report, Domestic Uranium Mining and Milling Industry: Viability Assessment, and are provided to the Organization for Economic Cooperation and Development. The foreign nuclear capacity projections are used by the DOE uranium enrichment program in assessing potential markets for future enrichment contracts. The two major sections of this report discuss US and foreign commercial nuclear power. The US section (Chapters 2 and 3) deals with (1) the status of nuclear power as of the end of 1989; (2) projections of nuclear capacity and generation at 5-year intervals from 1990 through 2030; and (3) a discussion of institutional and technical issues that affect nuclear power. The nuclear capacity projections are discussed in terms of two projection periods: the intermediate term through 2010 and the long term through 2030. A No New Orders case is presented for each of the projection periods, as well as Lower Reference and Upper Reference cases. 5 figs., 30 tabs.

  11. Nuclear Manpower Training

    Energy Technology Data Exchange (ETDEWEB)

    Min, B. J.; Han, K. W.; Lee, H. Y. and others

    2006-01-15

    Through the project on nuclear human resources development in 2005, the Nuclear Training Center of KAERI has provided 67 nuclear education and training courses for 3,658 persons from the domestic nuclear related organizations such as Government Agencies, nuclear industries, R and D institutes, universities, and public as well as from IAEA Member States. In addition, 6 students (MS and Ph D.) have taken nuclear technology related courses offered by UST-KAERI. The project has developed 8 programs and 12 courses. They includes programs for IAEA training, bilateral education and training, and in-house training as well as courses dealing with maintenance of nuclear power plants and management of electricity generation, thermal-hydraulics nuclear hydrogen, nuclear safeguards, radiation emergency preparedness and etc. National and international cooperation has been promoted. For ANENT, test operation, data loading and revision of the web-portal have been undertaken. Also the web-portal operation system has been established. For FNCA, NTC has cooperated for the establishment of a model of human resource development and the exchange of information/materials. With WNU, the NTC has made an effort for hosting 2007 WNU Summer Institute. The infrastructure for nuclear education and training has been strengthened. Basic directions for providing the customers with better service, This includes showing kindness to the customer, renovation of the interior of training facilities, and upgrading of web-based management system for learning and using facilities of NTC. Other efforts have resulted in the publication of 25 course materials (10 for international courses and 15 for national courses), and the improvement of education and training equipment. The International Nuclear Training and Education Center (INTEC), which was opened in 2002, has hosted 296 international and domestic events in 2005.

  12. Promising SINEs for embargoing nuclear-cytoplasmic export as an anticancer strategy.

    Science.gov (United States)

    Tan, David S P; Bedard, Philippe L; Kuruvilla, John; Siu, Lillian L; Razak, Albiruni R Abdul

    2014-05-01

    In cancer cells, the nuclear-cytoplasmic transport machinery is frequently disrupted, resulting in mislocalization and loss of function for many key regulatory proteins. In this review, the mechanisms by which tumor cells co-opt the nuclear transport machinery to facilitate carcinogenesis, cell survival, drug resistance, and tumor progression will be elucidated, with a particular focus on the role of the nuclear-cytoplasmic export protein. The recent development of a new generation of selective inhibitors of nuclear export (XPO1 antagonists) and how these novel anticancer drugs may bring us closer to the implementation of this therapeutic strategy in the clinic will be discussed.

  13. Gordon Conference on Nuclear Research

    Energy Technology Data Exchange (ETDEWEB)

    Austin, S.M.

    1983-09-01

    Session topics were: quarks and nuclear physics; anomalons and anti-protons; the independent particle structure of nuclei; relativistic descriptions of nuclear structure and scattering; nuclear structure at high excitation; advances in nuclear astrophysics; properties of nuclear material; the earliest moments of the universe; and pions and spin excitations in nuclei.

  14. Nuclear Energy and the Environment.

    Science.gov (United States)

    International Atomic Energy Agency, Vienna (Austria).

    "Nuclear Energy and the Environment" is a pocket folder of removable leaflets concerned with two major topics: Nuclear energy and Nuclear Techniques. Under Nuclear Energy, leaflets concerning the topics of "Radiation--A Fact of Life,""The Impact of a Fact: 1963 Test Ban Treaty,""Energy Needs and Nuclear Power,""Power Reactor Safety,""Transport,"…

  15. Clinical Nuclear Pharmacy Clerkship

    Science.gov (United States)

    Dunson, George L.; Christopherson, William J., Jr.

    1977-01-01

    The School of Pharmacy, University of the Pacific, and the Pharmacy Service, Letterman Army Medical Center, initiated a 15-week clinical nuclear pharmacy clerkship in 1975. It includes basic nuclear medical science, technical competency, professional competency, and special interest emphasis. (LBH)

  16. The nuclear age

    Energy Technology Data Exchange (ETDEWEB)

    Leclercq, J.

    1986-01-01

    This book is divided into 7 chapters bearing on: (1) Nuclear power: an historical perspective (2) Diversity of reactor designs (3) Safety and the environment (4) Architecture and heavy construction (5) Fabrication and installation (6) Nuclear fuel (7) Working for the electric power industry.

  17. Exotic nuclear matter

    Directory of Open Access Journals (Sweden)

    Lenske H.

    2016-01-01

    Full Text Available Recent developments of nuclear structure theory for exotic nuclei are addressed. The inclusion of hyperons and nucleon resonances is discussed. Nuclear multipole response functions, hyperon interactions in infinite matter and in neutron stars and theoretical aspects of excitations of nucleon resonances in nuclei are discussed.

  18. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... scan being performed, you will receive specific preparation instructions for what your child may eat and drink before the exam, especially ... Epilepsy Images related to Children's (Pediatric) Nuclear Medicine ... Videos related to Children's (Pediatric) Nuclear Medicine Sponsored by Please note RadiologyInfo. ...

  19. Battling Nuclear Proliferation

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    As the North Korean and Iranian nuclear issues develop and efforts to resolve them continue, global attention to anti-nuclear proliferation and the work of the International Atomic Energy Agency (IAEA) has become even more intense. Pang Sen, Chairman of

  20. Nuclear Power Plant Technician

    Science.gov (United States)

    Randall, George A.

    1975-01-01

    The author recognizes a body of basic knowledge in nuclear power plant technoogy that can be taught in school programs, and lists the various courses, aiming to fill the anticipated need for nuclear-trained manpower--persons holding an associate degree in engineering technology. (Author/BP)

  1. Nuclear Power Plants. Revised.

    Science.gov (United States)

    Lyerly, Ray L.; Mitchell, Walter, III

    This publication is one of a series of information booklets for the general public published by the United States Atomic Energy Commission. Among the topics discussed are: Why Use Nuclear Power?; From Atoms to Electricity; Reactor Types; Typical Plant Design Features; The Cost of Nuclear Power; Plants in the United States; Developments in Foreign…

  2. Nonstrategic Nuclear Weapons

    Science.gov (United States)

    2017-02-21

    have eased in recent years, with their nuclear tests in 1998 and continued animosity toward each other, India and Pakistan have joined the list of...could be complex, difficult, and very time- consuming . 137 Given the large disparity in the numbers of U.S. and Russian nonstrategic nuclear weapons

  3. (Nuclear theory: Annual report)

    Energy Technology Data Exchange (ETDEWEB)

    Iachello, F.; Alhassid, Y.; Kusnezov, D.

    1991-01-01

    This report discusses topics on : nuclear structure models; algebraic models of hadronic structure; nuclear reactions; hot rotating nuclei; chaos in nuclei; signatures of the quark-gluon plasma; hadronic spectroscopy; octupole collectivity in nuclei; finite-temperature methods for the many-body problem; and classical limit of algebraic hamiltonians. (LSP)

  4. [Nuclear theory: Annual report

    Energy Technology Data Exchange (ETDEWEB)

    Iachello, F.; Alhassid, Y.; Kusnezov, D.

    1991-12-31

    This report discusses topics on : nuclear structure models; algebraic models of hadronic structure; nuclear reactions; hot rotating nuclei; chaos in nuclei; signatures of the quark-gluon plasma; hadronic spectroscopy; octupole collectivity in nuclei; finite-temperature methods for the many-body problem; and classical limit of algebraic hamiltonians. (LSP)

  5. Vented nuclear fuel element

    Science.gov (United States)

    Grossman, Leonard N.; Kaznoff, Alexis I.

    1979-01-01

    A nuclear fuel cell for use in a thermionic nuclear reactor in which a small conduit extends from the outside surface of the emitter to the center of the fuel mass of the emitter body to permit escape of volatile and gaseous fission products collected in the center thereof by virtue of molecular migration of the gases to the hotter region of the fuel.

  6. Nuclear Power Plant Technician

    Science.gov (United States)

    Randall, George A.

    1975-01-01

    The author recognizes a body of basic knowledge in nuclear power plant technoogy that can be taught in school programs, and lists the various courses, aiming to fill the anticipated need for nuclear-trained manpower--persons holding an associate degree in engineering technology. (Author/BP)

  7. Industrialization of Nuclear Technology

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    1 Overview1.1 Income from operating activities Sale income from application of nuclear technology and non-nuclear products totaled 419million Yuan in 2015,an increase of 23.6%over the previous year,exceeding the target income set at the beginning of 2015.Of the total,sale incomes from iridium source,cobalt source,inspection system

  8. TRAINING NUCLEAR TECHNICIANS.

    Science.gov (United States)

    KOVNER, EDGAR A.

    PROBLEMS CONFRONTED BY PLANNERS OF NUCLEAR PROGRAMS AT THE TECHNICIAN LEVEL INCLUDE (1) LACK OF PRECEDENT IN CURRICULUM, COURSE OUTLINES, AND GRADUATE PLACEMENT, (2) DIFFICULTY IN DETERMINING COSTS OF LABORATORY CONSTRUCTION, EQUIPMENT, AND OPERATION, AND (3) REQUIREMENT OF ATOMIC ENERGY COMMISSION LICENSES IN NUCLEAR OCCUPATIONS. A 92-SEMESTER…

  9. Themes in nuclear law; Temas de Derecho Nuclear

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2003-07-01

    The nuclear law was analyzed during a workshop. The main aspects were: the law of population to access to information on nuclear energy and the relationship between the Regulator Organism and the nuclear power plants managers.

  10. Comprehensive nuclear materials

    CERN Document Server

    Allen, Todd; Stoller, Roger; Yamanaka, Shinsuke

    2012-01-01

    Comprehensive Nuclear Materials encapsulates a panorama of fundamental information on the vast variety of materials employed in the broad field of nuclear technology. The work addresses, in five volumes, 3,400 pages and over 120 chapter-length articles, the full panorama of historical and contemporary international research in nuclear materials, from Actinides to Zirconium alloys, from the worlds' leading scientists and engineers. It synthesizes the most pertinent research to support the selection, assessment, validation and engineering of materials in extreme nuclear environments. The work discusses the major classes of materials suitable for usage in nuclear fission, fusion reactors and high power accelerators, and for diverse functions in fuels, cladding, moderator and control materials, structural, functional, and waste materials.

  11. Nuclear risk management

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-07-01

    This paper gives the list of contributions to Eurosafe 2001 which was organised around two round tables on the first day and five seminars on the second day. The first round table dealt with the technical, organisational and societal aspects of risk management aimed at the prevention of accidents in nuclear power plants. The second round table focused on radiological risks from the normal operation of nuclear installations. Special consideration has been given to the involvement of stakeholders. The five seminars were held in order to provide opportunities for comparing experiences and learning about recent activities of IRSN, GRS and their partners in the European Union and Eastern Europe: - Safety assessment and analysis of nuclear installations; -Nuclear safety research; -Environment and radiation protection; - Waste management; - Nuclear material security. (author)

  12. Nuclear-pumped lasers

    CERN Document Server

    Prelas, Mark

    2016-01-01

    This book focuses on Nuclear-Pumped Laser (NPL) technology and provides the reader with a fundamental understanding of NPLs, a review of research in the field, and exploration of large scale NPL system design and applications. Early chapters look at the fundamental properties of lasers, nuclear-pumping and nuclear reactions that may be used as drivers for nuclear-pumped lasers. The book goes on to explore the efficient transport of energy from the ionizing radiation to the laser medium and then the operational characteristics of existing nuclear-pumped lasers. Models based on Mathematica, explanations and a tutorial all assist the reader’s understanding of this technology. Later chapters consider the integration of the various systems involved in NPLs and the ways in which they can be used, including beyond the military agenda. As readers will discover, there are significant humanitarian applications for high energy/power lasers, such as deflecting asteroids, space propulsion, power transmission and mining....

  13. Nuclear transfer in rodents.

    Science.gov (United States)

    Mullins, Linda J; Wilmut, Ian; Mullins, John J

    2004-01-01

    Cloning is the asexual reproduction of an individual, such that the offspring have an essentially identical nuclear genome. Nuclear transfer and cloning have been achieved in a number of species, namely sheep, cows, goats, rabbits, cats and mice, but have been largely unsuccessful, so far, in dogs, primates and rats. Clearly, contributory factors which affect the outcome of successful cloning experiments are not universally applicable to all species. One theme common to all cloning experiments, however, is the overall inefficiency of the process, typically 0-4%. A number of factors contribute to nuclear transfer inefficiency, and we will review mouse cloning experiments, which address these problems, highlighting the importance of donor nucleus choice (somatic or ES cell, fetal or adult, quiescent or actively dividing). Finally, we will summarize the emerging principles which appear to govern nuclear reprogramming and production of clones, and will consider the application of nuclear transfer to the rat.

  14. Fundamentals of nuclear physics

    CERN Document Server

    Takigawa, Noboru

    2017-01-01

    This book introduces the current understanding of the fundamentals of nuclear physics by referring to key experimental data and by providing a theoretical understanding of principal nuclear properties. It primarily covers the structure of nuclei at low excitation in detail. It also examines nuclear forces and decay properties. In addition to fundamentals, the book treats several new research areas such as non-relativistic as well as relativistic Hartree–Fock calculations, the synthesis of super-heavy elements, the quantum chromodynamics phase diagram, and nucleosynthesis in stars, to convey to readers the flavor of current research frontiers in nuclear physics. The authors explain semi-classical arguments and derivation of its formulae. In these ways an intuitive understanding of complex nuclear phenomena is provided. The book is aimed at graduate school students as well as junior and senior undergraduate students and postdoctoral fellows. It is also useful for researchers to update their knowledge of diver...

  15. Nuclear Pasta Formation

    CERN Document Server

    Schneider, A S; Hughto, J; Berry, D K

    2013-01-01

    The formation of complex nonuniform phases of nuclear matter, known as nuclear pasta, is studied with molecular dynamics simulations containing 51200 nucleons. A phenomenological nuclear interaction is used that reproduces the saturation binding energy and density of nuclear matter. Systems are prepared at an initial density of 0.10fm$^{-3}$ and then the density is decreased by expanding the simulation volume at different rates to densities of 0.01 fm$^{-3}$ or less. An originally uniform system of nuclear matter is observed to form spherical bubbles ("swiss cheese"), hollow tubes, flat plates ("lasagna"), thin rods ("spaghetti") and, finally, nearly spherical nuclei with decreasing density. We explicitly observe nucleation mechanisms, with decreasing density, for these different pasta phase transitions. Topological quantities known as Minkowski functionals are obtained to characterize the pasta shapes. Different pasta shapes are observed depending on the expansion rate. This indicates non equilibrium effects...

  16. World nuclear outlook 1995

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-09-29

    As part of the EIA program to provide energy information, this analysis report presents the current status and projections through 2015 of nuclear capacity, generation, and fuel cycle requirements for all countries in the world using nuclear power to generate electricity for commercial use. It also contains information and forecasts of developments in the uranium market. Long-term projections of US nuclear capacity, generation, and spent fuel discharges for two different scenarios through 2040 are developed for the Department of Energy`s Office of Civilian Radioactive Waste Management (OCRWM). In turn, the OCRWM provides partial funding for preparation of this report. The projections of uranium requirements are provided to the Organization for Economic Cooperation and Development (OECD) for preparation of the Nuclear Energy Agency/OECD report, Summary of Nuclear Power and Fuel Cycle Data in OECD Member Countries.

  17. Nuclear power economics

    Energy Technology Data Exchange (ETDEWEB)

    Emsley, Ian; Cobb, Jonathan [World Nuclear Association, London (United Kingdom)

    2017-04-15

    Many countries recognize the substantial role which nuclear power has played in providing energy security of supply, reducing import dependence and reducing greenhouse gas and polluting emissions. Nevertheless, as such considerations are far from being fully accounted for in liberalized or deregulated power markets, nuclear plants must demonstrate their viability in these markets on commercial criteria as well as their lifecycle advantages. Nuclear plants are operating more efficiently than in the past and unit operating costs are low relative to those of alternative generating technologies. The political risk facing the economic functioning of nuclear in a number of countries has increased with the imposition of nuclear-specific taxes that in some cases have deprived operators of the economic incentive to continue to operate existing plants.

  18. World nuclear outlook 1994

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1994-12-01

    As part of the EIA program to provide energy information, this analysis report presents the current status and projections through 2010 of nuclear capacity, generation, and fuel cycle requirements for all countries in the world using nuclear power to generate electricity for commercial use. It also contains information and forecasts of developments in the uranium market. Long-term projections of US nuclear capacity, generation, and spent fuel discharges for three different scenarios through 2040 are developed for the Department of Energy`s Office of Civilian Radioactive Waste Management (OCRWM). In turn, the OCRWM provides partial funding for preparation of this report. The projections of uranium requirements are provided to the Organization for Economic Cooperation and Development (OECD) for preparation of the Nuclear Energy Agency/OECD report, Summary of Nuclear Power and Fuel Cycle Data in OECD Member Countries.

  19. European Nuclear Features

    Energy Technology Data Exchange (ETDEWEB)

    Barre, B.; Gonzalez, E.; Diaz Diaz, J.L.; Jimenez, J.L.; Velarde, G.; Navarro, J.M.; Hittner, D.; Dominguez, M.T.; Bollini, G.; Martin, A.; Suarez, J.; Traini, E.; Lang-Lenton, J.

    2004-09-01

    ''European Nuclear Features - ENF'' is a joint publication of the three specialized technical journals, Nuclear Espana (Spain), Revue General Nucleaire (France), and atw - International Journal of Nuclear Power (Germany). The ENF support the international Europeen exchange of information and news about energy and nuclear power. News items, comments, and scientific and technical contributions will cover important aspects of the field. The second issue of ENF contains contributions about theses topics, among others: Institutional and Political Changes in the EU. - CIEMAT Department of Nuclear Fission: A General Overview. - Inertial Fusion Energy at DENIM. - High Temperature Reactors. European Research Programme. - On Site Assistance to Khmelnitsky NPP 1 and 2 (Ukraine). - Dismantling and Decommissioning of Vandellos I. (orig.)

  20. Nuclear medicine consensus; Consenso sobre medicina nuclear

    Energy Technology Data Exchange (ETDEWEB)

    Camargo, Edwaldo E.; Marin Neto, Jose Antonio; Naccarato, Alberto F.P.; Ramires, Jose Antonio F.; Castro, Iran de; Paiva, Eleuses Vieira; Thom, Anneliese F.; Barroso, Adelanir; Blum, Bernardo; Hollanda, Ricardo; Mansur, Antonio de Padua

    1995-04-01

    The use of nuclear methods in cardiovascular diseases is studied concerning diagnosis, risk, prognosis, indications and accuracy. Aspects concerning chronic coronary artery disease, myocardial ischemia, myocardial infarction, viable myocardium, valvular heart disease, ventricular dysfunction, heart transplant, congenital heart diseases in adults, are discussed.

  1. Nuclear war, nuclear proliferation, and their consequences

    Energy Technology Data Exchange (ETDEWEB)

    Sanruddin, A.K.

    1986-01-01

    The proceedings of a colloquium convened by the Groupe de Bellerive offers the contributions of Carl Sagan, Gabriel Garcia Marquez, Kenneth Galbraith, Pierre Trudeau, Edward Kennedy, and other eminent scientists, politicians, and strategists on the subject of the proliferation of nuclear weaponry and its potential ramifications.

  2. The Relationship between Nuclear Disarmament and Nuclear Nonproliferation

    Institute of Scientific and Technical Information of China (English)

    Sun; Xiangli

    2015-01-01

    The history of nuclear weapons development since the end of World War II is also one of nuclear arms control.There are two major aspects that represent the global efforts of nuclear arms control,which include limiting on nuclear weapon development in quantities and qualities,and limiting on the proliferation of nuclear weapons and the relevant research and development technologies.The limitation on the nuclear weapons development constitute

  3. [Trypsin inhibitor from Gleditsia triacanthos L. seeds].

    Science.gov (United States)

    Mosolov, V V; Kolosova, G V; Valueva, T A; Dronova, L A

    1982-05-01

    The trypsin inhibitor from Gleditsia triacanthos (L.) seeds was purified by affinity chromatography on a column with trypsin-Sepharose 4B. The isolated inhibitor is a single-chain protein with molecular weight of about 20 000. The inhibitor suppresses bovine trypsin at a molar rate of 1 : 1, but weakly inhibits chymotrypsin in a non-stoichiometric manner. Some properties of the isolated inhibitor closely resembled those of soybean trypsin inhibitor (Kunitz).

  4. 76 FR 19148 - Entergy Nuclear Operations, Inc., Entergy Nuclear Vermont Yankee, LLC, Vermont Yankee Nuclear...

    Science.gov (United States)

    2011-04-06

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Entergy Nuclear Operations, Inc., Entergy Nuclear Vermont Yankee, LLC, Vermont Yankee Nuclear... (10 CFR), Section 2.206, ``Requests for Action under this Subpart,'' the U.S. Nuclear...

  5. 77 FR 7184 - Entergy Nuclear Indian Point 2, LLC; Entergy Nuclear Operations, Inc.; Indian Point Nuclear...

    Science.gov (United States)

    2012-02-10

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Entergy Nuclear Indian Point 2, LLC; Entergy Nuclear Operations, Inc.; Indian Point Nuclear Generating Unit No. 2; Exemption 1.0 Background Entergy Nuclear Operations, Inc. (Entergy or the licensee)...

  6. 77 FR 8904 - Entergy Nuclear Indian Point 3, LLC.; Entergy Nuclear Operations, Inc., Indian Point Nuclear...

    Science.gov (United States)

    2012-02-15

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Entergy Nuclear Indian Point 3, LLC.; Entergy Nuclear Operations, Inc., Indian Point Nuclear Generating Unit 3; Exemption 1.0 Background Entergy Nuclear Operations, Inc. (Entergy or the licensee) is...

  7. 75 FR 39057 - Entergy Nuclear Operations, Inc.; Entergy Nuclear Vermont Yankee, LLC; Vermont Yankee Nuclear...

    Science.gov (United States)

    2010-07-07

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Entergy Nuclear Operations, Inc.; Entergy Nuclear Vermont Yankee, LLC; Vermont Yankee Nuclear... CFR), Section 2.206, ``Requests for Action under this Subpart,'' the U.S. Nuclear...

  8. Your Radiologist Explains Nuclear Medicine

    Medline Plus

    Full Text Available ... Sponsored by Image/Video Gallery Your Radiologist Explains Nuclear Medicine Transcript Welcome to Radiology Info dot org ... I’d like to talk to you about nuclear medicine. Nuclear medicine offers the potential to identify ...

  9. Your Radiologist Explains Nuclear Medicine

    Medline Plus

    Full Text Available ... Sponsored by Image/Video Gallery Your Radiologist Explains Nuclear Medicine Transcript Welcome to Radiology Info dot org ... I’d like to talk to you about nuclear medicine. Nuclear medicine offers the potential to identify ...

  10. Your Radiologist Explains Nuclear Medicine

    Medline Plus

    Full Text Available ... by Image/Video Gallery Your Radiologist Explains Nuclear Medicine Transcript Welcome to Radiology Info dot org Hello! ... d like to talk to you about nuclear medicine. Nuclear medicine offers the potential to identify disease ...

  11. Your Radiologist Explains Nuclear Medicine

    Medline Plus

    Full Text Available ... nuclear medicine. Nuclear medicine offers the potential to identify disease in its earliest stage, often before symptoms ... benefit of an accurate diagnosis far outweighs any risk. To learn more about nuclear medicine, visit Radiology ...

  12. Your Radiologist Explains Nuclear Medicine

    Science.gov (United States)

    ... Sponsored by Image/Video Gallery Your Radiologist Explains Nuclear Medicine Transcript Welcome to Radiology Info dot org Hello! ... I’d like to talk to you about nuclear medicine. Nuclear medicine offers the potential to identify disease ...

  13. Mechanisms of Nuclear Export in Cancer and Resistance to Chemotherapy

    Directory of Open Access Journals (Sweden)

    Mohamed El-Tanani

    2016-03-01

    Full Text Available Tumour suppressor proteins, such as p53, BRCA1, and ABC, play key roles in preventing the development of a malignant phenotype, but those that function as transcriptional regulators need to enter the nucleus in order to function. The export of proteins between the nucleus and cytoplasm is complex. It occurs through nuclear pores and exported proteins need a nuclear export signal (NES to bind to nuclear exportin proteins, including CRM1 (Chromosomal Region Maintenance protein 1, and the energy for this process is provided by the RanGTP/RanGDP gradient. Due to the loss of DNA repair and cell cycle checkpoints, drug resistance is a major problem in cancer treatment, and often an initially successful treatment will fail due to the development of resistance. An important mechanism underlying resistance is nuclear export, and a number of strategies that can prevent nuclear export may reverse resistance. Examples include inhibitors of CRM1, antibodies to the nuclear export signal, and alteration of nuclear pore structure. Each of these are considered in this review.

  14. Nuclear targeting of an endosomal E3 ubiquitin ligase.

    Science.gov (United States)

    Bocock, Jeffrey P; Carmicle, Stephanie; Madamba, Egbert; Erickson, Ann H

    2010-06-01

    Ring finger protein 13 (RNF13) is an E3 ubiquitin ligase embedded in endosome membranes. The protein undergoes constitutive post-translational proteolysis, making its detection difficult unless cells are incubated with a proteasome inhibitor to allow biosynthetic forms to accumulate. When cells were treated with phorbol 12-myristate 13-acetate (PMA), RNF13 avoided proteolysis. A similar stabilization was seen on ionomycin treatment of cells. Drug treatment stabilized both the full-length protein and a membrane-embedded C-terminal fragment generated following ectodomain shedding. Immunofluorescence staining revealed that PMA treatment caused the protein to accumulate in recycling endosomes, where it colocalized with transferrin receptor, and on the inner nuclear membrane, where it colocalized with lamin B. Expression of dominant-negative Rab11 inhibited nuclear localization, suggesting RNF13 was targeted to the inner nuclear membrane through recycling endosomes. New protein synthesis was necessary for this targeting. Nuclear localization was confirmed by immunoelectron microscopy and by purification of the inner nuclear membrane. Stress-induced transport of an endosomal protein to the inner nuclear membrane is a novel mechanism for introduction of regulatory proteins to the DNA environment. RNF13, with its ubiquitin ligase-active RING domain, has the potential to turn over key nuclear proteins in response to signals received at the plasma membrane.

  15. Mechanisms of Nuclear Export in Cancer and Resistance to Chemotherapy.

    Science.gov (United States)

    El-Tanani, Mohamed; Dakir, El-Habib; Raynor, Bethany; Morgan, Richard

    2016-03-14

    Tumour suppressor proteins, such as p53, BRCA1, and ABC, play key roles in preventing the development of a malignant phenotype, but those that function as transcriptional regulators need to enter the nucleus in order to function. The export of proteins between the nucleus and cytoplasm is complex. It occurs through nuclear pores and exported proteins need a nuclear export signal (NES) to bind to nuclear exportin proteins, including CRM1 (Chromosomal Region Maintenance protein 1), and the energy for this process is provided by the RanGTP/RanGDP gradient. Due to the loss of DNA repair and cell cycle checkpoints, drug resistance is a major problem in cancer treatment, and often an initially successful treatment will fail due to the development of resistance. An important mechanism underlying resistance is nuclear export, and a number of strategies that can prevent nuclear export may reverse resistance. Examples include inhibitors of CRM1, antibodies to the nuclear export signal, and alteration of nuclear pore structure. Each of these are considered in this review.

  16. Modelling the nuclear parton distributions

    CERN Document Server

    Kulagin, S A

    2016-01-01

    We review a semi-microscopic model of nuclear parton distributions, which takes into account a number of nuclear effects including Fermi motion and nuclear binding, nuclear meson-exchange currents and off-shell corrections to bound nucleon distributions as well as nuclear shadowing effect. We also discuss applications of the model to the lepton-nuclear deep-inelastic scattering, Drell-Yan process and neutrino total cross sections.

  17. Diverse inhibitors of aflatoxin biosynthesis.

    Science.gov (United States)

    Holmes, Robert A; Boston, Rebecca S; Payne, Gary A

    2008-03-01

    Pre-harvest and post-harvest contamination of maize, peanuts, cotton, and tree nuts by members of the genus Aspergillus and subsequent contamination with the mycotoxin aflatoxin pose a widespread food safety problem for which effective and inexpensive control strategies are lacking. Since the discovery of aflatoxin as a potently carcinogenic food contaminant, extensive research has been focused on identifying compounds that inhibit its biosynthesis. Numerous diverse compounds and extracts containing activity inhibitory to aflatoxin biosynthesis have been reported. Only recently, however, have tools been available to investigate the molecular mechanisms by which these inhibitors affect aflatoxin biosynthesis. Many inhibitors are plant-derived and a few may be amenable to pathway engineering for tissue-specific expression in susceptible host plants as a defense against aflatoxin contamination. Other compounds show promise as protectants during crop storage. Finally, inhibitors with different modes of action could be used in comparative transcriptional and metabolomic profiling experiments to identify regulatory networks controlling aflatoxin biosynthesis.

  18. Corrosion inhibitors from expired drugs.

    Science.gov (United States)

    Vaszilcsin, Nicolae; Ordodi, Valentin; Borza, Alexandra

    2012-07-15

    This paper presents a method of expired or unused drugs valorization as corrosion inhibitors for metals in various media. Cyclic voltammograms were drawn on platinum in order to assess the stability of pharmaceutically active substances from drugs at the metal-corrosive environment interface. Tafel slope method was used to determine corrosion rates of steel in the absence and presence of inhibitors. Expired Carbamazepine and Paracetamol tablets were used to obtain corrosion inhibitors. For the former, the corrosion inhibition of carbon steel in 0.1 mol L(-1) sulfuric acid solution was about 90%, whereas for the latter, the corrosion inhibition efficiency of the same material in the 0.25 mol L(-1) acetic acid-0.25 mol L(-1) sodium acetate buffer solution was about 85%.

  19. Advances in nuclear physics

    CERN Document Server

    Vogt, Erich

    1975-01-01

    Review articles on three topics of considerable current interest make up the present volume. The first, on A-hypernuclei, was solicited by the editors in order to provide nuclear physicists with a general description of the most recent developments in a field which this audience has largely neglected or, perhaps, viewed as a novelty in which a bizarre nuclear system gave some information about the lambda-nuclear intersection. That view was never valid. The very recent developments reviewed here-particularly those pertaining to hypernuclear excitations and the strangeness exchange reactions-emphasize that this field provides important information about the models and central ideas of nuclear physics. The off-shell behavior of the nucleon-nucleon interaction is a topic which was at first received with some embarrassment, abuse, and neglect, but it has recently gained proper attention in many nuclear problems. Interest was first focused on it in nuclear many-body theory, but it threatened nuclear physicists'comf...

  20. Evaluated Nuclear Data

    Energy Technology Data Exchange (ETDEWEB)

    Oblozinsky, P.; Oblozinsky,P.; Herman,M.; Mughabghab,S.F.

    2010-10-01

    This chapter describes the current status of evaluated nuclear data for nuclear technology applications. We start with evaluation procedures for neutron-induced reactions focusing on incident energies from the thermal energy up to 20 MeV, though higher energies are also mentioned. This is followed by examining the status of evaluated neutron data for actinides that play dominant role in most of the applications, followed by coolants/moderators, structural materials and fission products. We then discuss neutron covariance data that characterize uncertainties and correlations. We explain how modern nuclear evaluated data libraries are validated against an extensive set of integral benchmark experiments. Afterwards, we briefly examine other data of importance for nuclear technology, including fission yields, thermal neutron scattering and decay data. A description of three major evaluated nuclear data libraries is provided, including the latest version of the US library ENDF/B-VII.0, European JEFF-3.1 and Japanese JENDL-3.3. A brief introduction is made to current web retrieval systems that allow easy access to a vast amount of up-to-date evaluated nuclear data for nuclear technology applications.

  1. Nuclear forensics: Soil content

    Energy Technology Data Exchange (ETDEWEB)

    Beebe, Merilyn Amy [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-08-31

    Nuclear Forensics is a growing field that is concerned with all stages of the process of creating and detonating a nuclear weapon. The main goal is to prevent nuclear attack by locating and securing nuclear material before it can be used in an aggressive manner. This stage of the process is mostly paperwork; laws, regulations, treaties, and declarations made by individual countries or by the UN Security Council. There is some preliminary leg work done in the form of field testing detection equipment and tracking down orphan materials; however, none of these have yielded any spectacular or useful results. In the event of a nuclear attack, the first step is to analyze the post detonation debris to aid in the identification of the responsible party. This aspect of the nuclear forensics process, while reactive in nature, is more scientific. A rock sample taken from the detonation site can be dissolved into liquid form and analyzed to determine its chemical composition. The chemical analysis of spent nuclear material can provide valuable information if properly processed and analyzed. In order to accurately evaluate the results, scientists require information on the natural occurring elements in the detonation zone. From this information, scientists can determine what percentage of the element originated in the bomb itself rather than the environment. To this end, element concentrations in soils from sixty-nine different cities are given, along with activity concentrations for uranium, thorium, potassium, and radium in various building materials. These data are used in the analysis program Python.

  2. Perspectives of Nuclear Physics

    Science.gov (United States)

    Faessler, Amand

    2003-04-01

    The organizers of this meeting have asked me to present perspectives of nuclear physics. This means to identify the areas where nuclear physics will be expanding in the next future. In six chapters a short overview of these areas will be given, where I expect that nuclear physics will develop quite fast: (1) Quantum Chromodynamics and effective field theories in the confinement region. (2) Nuclear structure at the limits. (3) High energy heavy ion collisions. (4) Nuclear astrophysics. (5) Neutrino physics. (6) Test of physics beyond the standard model by rare processes. After a survey over these six points I will pick out a few topics where I will go more in details. There is no time to give for all six points detailed examples. I shall discuss the following examples of the six topics mentionned above: (1) The perturbative chiral quark model and the nucleon Σ-term. (2) VAMPIR (Variation After Mean field Projection In Realistic model spaces and with realistic forces) as an example of the nuclear structure renaissance. (3) Measurement of important astrophysical nuclear reactions in the Gamow peak. (4) The solar neutrino problem. As examples for testing new physics beyond the standard model by rare processes I had prepared to speak about the measurement of the electric neutron dipole moment and of the neutrinoless double beta decay. But the time is limited and so I have to skip these points, although they are extremely interesting.

  3. Nuclear charge and neutron radii and nuclear matter: trend analysis

    CERN Document Server

    Reinhard, P -G

    2016-01-01

    Radii of charge and neutron distributions are fundamental nuclear properties. They depend on both nuclear interaction parameters related to the equation of state of infinite nuclear matter and on quantal shell effects, which are strongly impacted by the presence of nuclear surface. In this work, by studying the dependence of charge and neutron radii, and neutron skin, on nuclear matter parameters, we assess different mechanisms that drive nuclear sizes. We apply nuclear density functional theory using a family of Skyrme functionals obtained by means of different optimization protocols targeting specific nuclear properties. By performing the Monte-Carlo sampling of reasonable functionals around the optimal parametrization, we study correlations between nuclear matter paramaters and observables characterizing charge and neutron distributions. We demonstrate the existence of the strong converse relation between the nuclear charge radii and the saturation density of symmetric nuclear matter and also between the n...

  4. Virtual nuclear weapons

    Energy Technology Data Exchange (ETDEWEB)

    Pilat, J.F.

    1997-08-01

    The term virtual nuclear weapons proliferation and arsenals, as opposed to actual weapons and arsenals, has entered in recent years the American lexicon of nuclear strategy, arms control, and nonproliferation. While the term seems to have an intuitive appeal, largely due to its cyberspace imagery, its current use is still vague and loose. The author believes, however, that if the term is clearly delineated, it might offer a promising approach to conceptualizing certain current problems of proliferation. The first use is in a reference to an old problem that has resurfaced recently: the problem of growing availability of weapon-usable nuclear materials in civilian nuclear programs along with materials made `excess` to defense needs by current arms reduction and dismantlement. It is argued that the availability of these vast materials, either by declared nuclear-weapon states or by technologically advanced nonweapon states, makes it possible for those states to rapidly assemble and deploy nuclear weapons. The second use has quite a different set of connotations. It is derived conceptually from the imagery of computer-generated reality. In this use, one thinks of virtual proliferation and arsenals not in terms of the physical hardware required to make the bomb but rather in terms of the knowledge/experience required to design, assemble, and deploy the arsenal. Virtual weapons are a physics reality and cannot be ignored in a world where knowledge, experience, materials, and other requirements to make nuclear weapons are widespread, and where dramatic army reductions and, in some cases, disarmament are realities. These concepts are useful in defining a continuum of virtual capabilities, ranging from those at the low end that derive from general technology diffusion and the existence of nuclear energy programs to those at the high end that involve conscious decisions to develop or maintain militarily significant nuclear-weapon capabilities.

  5. Economic Analysis of Nuclear Energy

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Man Ki; Moon, K. H.; Kim, S. S.; Lim, C. Y.; Oh, K. B

    2006-12-15

    It has been well recognized that securing economic viabilities along with technologies are very important elements in the successful implementation of nuclear R and D projects. The objective of the Project is to help nuclear energy to be utilized in an efficient way by analyzing major issues related with nuclear economics. The study covers following subjects: the role of nuclear in the future electric supply system, economic analysis of nuclear R and D project, contribution to the regional economy from nuclear power. In addition, the study introduces the international cooperation in the methodological area of efficient use of nuclear energy by surveying the international activities related with nuclear economics.

  6. American Society of Nuclear Cardiology

    Science.gov (United States)

    ... much more! class="box-li"> Journal of Nuclear Cardiology Official publication of the American Society of Nuclear Cardiology Clinical Guidelines Procedures, Appropriate Use Criteria, Information Statements ...

  7. Nuclear Physics Department annual report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-07-01

    This annual report presents articles and abstracts published in foreign journals, covering the following subjects: nuclear structure, nuclear reactions, applied physics, instrumentation, nonlinear phenomena and high energy physics

  8. Nuclear engineering vocabulary

    Energy Technology Data Exchange (ETDEWEB)

    Dumont, X. [FRAMATOME, Dept. Corporate R and D, 92 - Paris-La-Defence (France); Andrieux, C. [CEA Saclay, Direction des Technologies de l' Information, DTI, 91 - Gif sur Yvette (France)

    2001-07-01

    The members of the CSTNIN - the Special Commission for Nuclear Engineering Terminology and Neology - have just produced a Nuclear Engineering Vocabulary, published by SFEN. A 120-page document which, to date, includes 400 nuclear engineering terms or expressions. For each term or expression, this Glossary gives: the primary and secondary subject field in which it is applied, a possible abbreviation, its definition, a synonym if appropriate, any relevant comments, any associated word(s), the English equivalent, its status on the date of publication of the Glossary. (author)

  9. Theoretical nuclear physics

    CERN Document Server

    Blatt, John M

    2010-01-01

    A classic work by two leading physicists and scientific educators endures as an uncommonly clear and cogent investigation and correlation of key aspects of theoretical nuclear physics. It is probably the most widely adopted book on the subject. The authors approach the subject as ""the theoretical concepts, methods, and considerations which have been devised in order to interpret the experimental material and to advance our ability to predict and control nuclear phenomena.""The present volume does not pretend to cover all aspects of theoretical nuclear physics. Its coverage is restricted to

  10. Nuclear physics of stars

    CERN Document Server

    Iliadis, Christian

    2015-01-01

    Most elements are synthesized, or ""cooked"", by thermonuclear reactions in stars. The newly formed elements are released into the interstellar medium during a star's lifetime, and are subsequently incorporated into a new generation of stars, into the planets that form around the stars, and into the life forms that originate on the planets. Moreover, the energy we depend on for life originates from nuclear reactions that occur at the center of the Sun. Synthesis of the elements and nuclear energy production in stars are the topics of nuclear astrophysics, which is the subject of this book

  11. Nuclear regulation and safety

    Energy Technology Data Exchange (ETDEWEB)

    Hendrie, J.M.

    1982-01-01

    Nuclear regulation and safety are discussed from the standpoint of a hypothetical country that is in the process of introducing a nuclear power industry and setting up a regulatory system. The national policy is assumed to be in favor of nuclear power. The regulators will have responsibility for economic, reliable electric production as well as for safety. Reactor safety is divided into three parts: shut it down, keep it covered, take out the afterheat. Emergency plans also have to be provided. Ways of keeping the core covered with water are discussed. (DLC)

  12. Fictions of nuclear disaster

    Energy Technology Data Exchange (ETDEWEB)

    Dowling, D.

    1987-01-01

    This work is critical study of literary interpretations of the nuclear holocaust. The author examines more than 250 stories and novels dealing with the theme of nuclear power and its devastating potential implications. Addressing such topics as the scientist and Armageddon, the role of religion, future evolution and mutation, and the postnuclear society, the author assesses the response of Bradbury, Lessing, Malamud, Shute, Huxley, Vonnegut, Heinlein, and others to the threat of nuclear apocalypse, with in-depth analyses of Alter Miller's A canticle for Leibowitz and Russell Hoban's Riddley Walker.

  13. Baltic nuclear projects

    Energy Technology Data Exchange (ETDEWEB)

    Adlys, Gediminas; Adliene, Diana [Kaunas Univ. of Technology (Lithuania)

    2009-07-01

    The Authors discuss the Baltic energy policy with respect to new nuclear power plants for Lithuania, Belarus and the Kaliningrad region. The construction of a new nuclear power plant in Lithuania would threaten Russian interests in the region. Therefore Lithuania is looking to Russian plans to build a new nuclear power plant in the Kaliningrad region as an attempt to subvert Lithuania's foreign partners and potential investors from participating in the Visaginas NPP project. However, the authors conclude, that the Visaginas NPP project is and must be the preferential project for the EU and NATO member states.

  14. Practical nuclear medicine

    CERN Document Server

    Gemmell, Howard G; Sharp, Peter F

    2006-01-01

    Nuclear medicine plays a crucial role in patient care, and this book is an essential guide for all practitioners to the many techniques that inform clinical management. The first part covers the scientific basis of nuclear medicine, the rest of the book deals with clinical applications. Diagnostic imaging has an increasingly important role in patient management and, despite advances in other modalities (functional MRI and spiral CT), nuclear medicine continues to make its unique contribution by its ability to demonstrate physiological function. This book is also expanded by covering areas of d

  15. Nuclear energy debate

    CERN Document Server

    Healey, Justin

    2012-01-01

    The debate over the introduction of nuclear power in Australia has recently become more heated in light of safety concerns over the nuclear reactor meltdown emergency in Japan. Australia has also just committed to a carbon trading scheme to address its reliance on coal-fired energy and reduce greenhouse emissions. With 40% of the world's uranium located in Australia, the economic, environmental and health considerations are significant. This book contains an overview of global nuclear energy use and production, and presents a range of current opinions debating the pros and cons of Australia's

  16. Nuclear Medicine Annual, 1989

    Energy Technology Data Exchange (ETDEWEB)

    Freeman, L.M.; Weissmann, H.S.

    1989-01-01

    Among the highlights of Nuclear Medicine Annual, 1989 are a status report on the thyroid scan in clinical practice, a review of functional and structural brain imaging in dementia, an update on radionuclide renal imaging in children, and an article outlining a quality assurance program for SPECT instrumentation. Also included are discussions on current concepts in osseous sports and stress injury scintigraphy and on correlative magnetic resonance and radionuclide imaging of bone. Other contributors assess the role of nuclear medicine in clinical decision making and examine medicolegal and regulatory aspects of nuclear medicine.

  17. Advances in Nuclear Energy

    Science.gov (United States)

    Frois, B.

    2005-04-01

    This paper briefly reviews the next generations of nuclear reactors and the perspectives of development of nuclear energy. Advanced reactors will progressively replace the existing ones during the next two decades. Future systems of the fourth generation are planned to be built beyond 2030. These systems have been studied in the framework of the "Generation IV" International Forum. The goals of these systems is to have a considerable increase in safety, be economically competitive and produce a significantly reduced volume of nuclear wastes. The closed fuel cycle is preferred.

  18. Reporting nuclear cardiology

    DEFF Research Database (Denmark)

    Trägårdh, Elin; Hesse, Birger; Knuuti, Juhani

    2015-01-01

    are available; therefore, an European position statement on how to report nuclear cardiology might be useful. The current paper combines the limited existing evidence with expert consensus, previously published recommendations as well as current clinical practices. For all the applications discussed......, and conclusion of the report. The statement also discusses recommended terminology in nuclear cardiology, image display, and preliminary reports. It is hoped that this statement may lead to more attention to create well-written and standardized nuclear cardiology reports and eventually lead to improved clinical...

  19. Nuclear manpower training

    Energy Technology Data Exchange (ETDEWEB)

    Suh, In Suk; Lee, H. Y.; Joe, B. J.; Lee, S. H.; Lee, E. J.; Yoo, B. H.; Seo, K. W.; Lee, W. K.; Jun, H. I.; Yang, K. N.; Kim, Y. J.; Kim, I. H.; Kim, M. Y.; Ju, Y. C.; Hyun, H. Y.; Choi, I. G.; Hong, C. S.; Won, J. Y.; Nam, J. Y.; Lee, H. J.

    1997-01-01

    This report describes the annual results of training courses. the scope and contents are as follows: 1. Regional and interregional training courses 2. Training courses assisted by foreign experts 3. Training courses for nuclear industry personnel 4. Training courses for internal staff-members 5. Training courses under the law. This Nuclear Training Center executed the open-door training courses for 2,400 engineers/scientists from the regulatory body, nuclear industries, research institutes and other related organizations by means of offering 51 training courses during the fiscal year 1996. (author). 23 refs.

  20. The effect of chemical anti-inhibitors on fibrinolytic enzymes and inhibitors

    DEFF Research Database (Denmark)

    Sidelmann, Johannes Jakobsen; Jespersen, J; Kluft, C;

    1997-01-01

    Fibrinolytic enzyme inhibitors hamper the determination of the specific fibrinolytic serine protease activity. Reportedly, chemical anti-inhibitors eliminate the influence of fibrinolytic inhibitors, but it remains unclear to what extent they change the specific activity of fibrinolytic serine pr...

  1. Suppression of Coronavirus Replication by Cyclophilin Inhibitors

    Directory of Open Access Journals (Sweden)

    Takashi Sasaki

    2013-05-01

    Full Text Available Coronaviruses infect a variety of mammalian and avian species and cause serious diseases in humans, cats, mice, and birds in the form of severe acute respiratory syndrome (SARS, feline infectious peritonitis (FIP, mouse hepatitis, and avian infectious bronchitis, respectively. No effective vaccine or treatment has been developed for SARS-coronavirus or FIP virus, both of which cause lethal diseases. It has been reported that a cyclophilin inhibitor, cyclosporin A (CsA, could inhibit the replication of coronaviruses. CsA is a well-known immunosuppressive drug that binds to cellular cyclophilins to inhibit calcineurin, a calcium-calmodulin-activated serine/threonine-specific phosphatase. The inhibition of calcineurin blocks the translocation of nuclear factor of activated T cells from the cytosol into the nucleus, thus preventing the transcription of genes encoding cytokines such as interleukin-2. Cyclophilins are peptidyl-prolyl isomerases with physiological functions that have been described for many years to include chaperone and foldase activities. Also, many viruses require cyclophilins for replication; these include human immunodeficiency virus, vesicular stomatitis virus, and hepatitis C virus. However, the molecular mechanisms leading to the suppression of viral replication differ for different viruses. This review describes the suppressive effects of CsA on coronavirus replication.

  2. Nuclear Transparency in the lightest nuclear interactions

    CERN Document Server

    Ajaz, M; Khan, K H; Zaman, A

    2012-01-01

    Some experimental results on nuclear transparency effect in pC- and dC-interaction at 4.2 A GeV/c (JINR Dubna) are presented. The "half angle" ({\\theta}1/2) technique was used and the particles with emission angle greater and less than {\\theta}1/2 are considered separately. The results of the experimental study have been compared with the simulation data coming from the Dubna Cascade model. The values of average multiplicity, average momentum, and average transverse momentum of charged pions and protons are analyzed as a function of the number of identified protons in an event. We observed some behaviors for the data which could be considered as some nuclear transparency effects. The lasts have been divided into three main groups depending on their probable behavior: leading effect; cascade effect; medium effect.

  3. Recent Advances in the Development and Application of Radiolabeled Kinase Inhibitors for PET Imaging

    Directory of Open Access Journals (Sweden)

    Vadim Bernard-Gauthier

    2015-12-01

    Full Text Available Over the last 20 years, intensive investigation and multiple clinical successes targeting protein kinases, mostly for cancer treatment, have identified small molecule kinase inhibitors as a prominent therapeutic class. In the course of those investigations, radiolabeled kinase inhibitors for positron emission tomography (PET imaging have been synthesized and evaluated as diagnostic imaging probes for cancer characterization. Given that inhibitor coverage of the kinome is continuously expanding, in vivo PET imaging will likely find increasing applications for therapy monitoring and receptor density studies both in- and outside of oncological conditions. Early investigated radiolabeled inhibitors, which are mostly based on clinically approved tyrosine kinase inhibitor (TKI isotopologues, have now entered clinical trials. Novel radioligands for cancer and PET neuroimaging originating from novel but relevant target kinases are currently being explored in preclinical studies. This article reviews the literature involving radiotracer design, radiochemistry approaches, biological tracer evaluation and nuclear imaging results of radiolabeled kinase inhibitors for PET reported between 2010 and mid-2015. Aspects regarding the usefulness of pursuing selective vs. promiscuous inhibitor scaffolds and the inherent challenges associated with intracellular enzyme imaging will be discussed.

  4. Nuclear Waste and Ethics

    Energy Technology Data Exchange (ETDEWEB)

    Damveld, Herman [Groningen (Netherlands)

    2003-10-01

    In the past years in almost all conferences on storage of nuclear waste, ethics has been considered as an important theme. But what is ethics? We will first give a sketch of this branch of philosophy. We will then give a short explanation of the three principal ethical theories. In the discussion about storage of nuclear waste, the ethical theory of utilitarianism is often implicitly invoked. In this system future generations weigh less heavily than the present generation, so that people of the future are not considered as much as those now living. We reject this form of reasoning. The discussion about nuclear waste is also sometimes pursued from ethical points of departure such as equality and justice. But many loose ends remain in these arguments, which gives rise to the question of whether the production and storage of nuclear waste is responsible.

  5. Nuclear material operations manual

    Energy Technology Data Exchange (ETDEWEB)

    Tyler, R.P.

    1981-02-01

    This manual provides a concise and comprehensive documentation of the operating procedures currently practiced at Sandia National Laboratories with regard to the management, control, and accountability of nuclear materials. The manual is divided into chapters which are devoted to the separate functions performed in nuclear material operations-management, control, accountability, and safeguards, and the final two chapters comprise a document which is also issued separately to provide a summary of the information and operating procedures relevant to custodians and users of radioactive and nuclear materials. The manual also contains samples of the forms utilized in carrying out nuclear material activities. To enhance the clarity of presentation, operating procedures are presented in the form of playscripts in which the responsible organizations and necessary actions are clearly delineated in a chronological fashion from the initiation of a transaction to its completion.

  6. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... beforehand, especially if sedation is to be used. Most nuclear medicine exams will involve an injection in ... PET/CT, SPECT/CT and PET/MR) are most often used in children with cancer, epilepsy and ...

  7. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... the bladder, such as with a vesicoureteral reflux study. It can take several seconds to a few ... until the nuclear physician checks the images in case additional images are needed. top of page What ...

  8. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... nuclear medicine imaging uses small amounts of radioactive materials called radiotracers, a special camera and a computer ... medical imaging that uses small amounts of radioactive material to diagnose and determine the severity of or ...

  9. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... of page What are some common uses of the procedure? Children's (pediatric) nuclear medicine imaging is performed ... the thyroid gland. top of page How does the procedure work? With ordinary x-ray examinations, an ...

  10. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... necessitate sedation for your child. You will receive instructions prior to the exam if your child will ... child has been sedated, you will receive specific instructions to be followed after leaving the nuclear medicine ...

  11. Nuclear Fuel Reprocessing

    Energy Technology Data Exchange (ETDEWEB)

    Michael F. Simpson; Jack D. Law

    2010-02-01

    This is an a submission for the Encyclopedia of Sustainable Technology on the subject of Reprocessing Spent Nuclear Fuel. No formal abstract was required for the article. The full article will be attached.

  12. Desalting and Nuclear Energy

    Science.gov (United States)

    Burwell, Calvin C.

    1971-01-01

    Future use of nuclear energy to produce electricity and desalted water is outlined. Possible desalting processes are analyzed to show economic feasibility and the place in planning in world's economic growth. (DS)

  13. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... of page How does the nuclear medicine procedure work? With ordinary x-ray examinations, an image is ... placed over the patient's body. SPECT involves the rotation of the gamma camera heads around the patient's ...

  14. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... bladder. bones. liver and gallbladder. gastrointestinal tract. heart. lungs. brain. thyroid. Nuclear medicine scans are typically used ... gas via a mask, such as with a lung scan. Bladder: some exams require a catheter to ...

  15. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... help diagnose childhood disorders that are present at birth or that develop during childhood. It provides unique ... diagnose childhood disorders that are congenital (present at birth) or that develop during childhood. Physicians use nuclear ...

  16. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... the procedure. top of page Who interprets the results and how do we get them? A radiologist ... radiotracer administered are small, diagnostic nuclear medicine procedures result in low radiation exposure, acceptable for diagnostic exams. ...

  17. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... placed over the patient's body. SPECT involves the rotation of the gamma camera heads around the patient's ... the child has been sedated, you will receive specific instructions to be followed after leaving the nuclear ...

  18. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... used in children with cancer, epilepsy and back pain. top of page What does the equipment look ... being recorded. Though nuclear imaging itself causes no pain, children may experience some discomfort from having to ...

  19. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... to be followed after leaving the nuclear medicine facility. Through the natural process of radioactive decay, the ... Please note RadiologyInfo.org is not a medical facility. Please contact your physician with specific medical questions ...

  20. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... body. jaundice in newborns and older children. epilepsy . location, anatomy and function of the thyroid gland. top ... to be followed after leaving the nuclear medicine facility. Through the natural process of radioactive decay, the ...

  1. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... used. Most nuclear medicine exams will involve an injection in a vein in your child’s arm or ... are noninvasive and, with the exception of intravenous injections, are usually painless medical tests that help physicians ...

  2. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... top of page What are the benefits vs. risks? Benefits The information provided by nuclear medicine examinations ... diagnosis or to determine appropriate treatment, if any. Risks Because the doses of radiotracer administered are small, ...

  3. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... liver and gallbladder. gastrointestinal tract. heart. lungs. brain. thyroid. Nuclear medicine scans are typically used to help ... children. epilepsy . location, anatomy and function of the thyroid gland. top of page How does the procedure ...

  4. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... jaundice in newborns and older children. epilepsy . location, anatomy and function of the thyroid gland. top of ... full size with caption Related Articles and Media General Nuclear Medicine Children's (Pediatric) CT (Computed Tomography) Epilepsy ...

  5. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... organs and tissues in your body. Hybrid imaging techniques (PET/CT, SPECT/CT and PET/MR) are ... equipment look like? The special camera and imaging techniques used in nuclear medicine include the gamma camera ...

  6. Nuclear Clusters in Astrophysics

    Energy Technology Data Exchange (ETDEWEB)

    Kubono, S.; Binh, Dam N.; Hayakawa, S.; Hashimoto, H.; Kahl, D.; Wakabayashi, Y.; Yamaguchi, H. [Center for Nuclear Study (CNS), University of Tokyo, Wako Branch at RIKEN 2-1 Hirosawa, Wako, Saitama, 351-0198 (Japan); Teranishi, T. [Department of Physics, Kyushu University, Fukuoka, 812-8581 (Japan); Iwasa, N. [Department of Physics, Tohoku University, Sendai, 980-8578 (Japan); Komatsubara, T. [Department of Physics, Tsukuba University, Ibaraki, 305-8571 (Japan); Kato, S. [Department of Physics, Yamagata University, Yamagata, 990-8560 (Japan); Khiem, Le H. [Institute of Physics, Vietnam Academy for Science and Technology, Hanoi (Viet Nam)

    2010-03-01

    The role of nuclear clustering is discussed for nucleosynthesis in stellar evolution with Cluster Nucleosynthesis Diagram (CND) proposed before. Special emphasis is placed on alpha-induced stellar reactions together with molecular states for O and C burning.

  7. THE NUCLEAR ENCOUNTER PROBABILITY

    NARCIS (Netherlands)

    SMULDERS, PJM

    1994-01-01

    This Letter dicusses the nuclear encounter probability as used in ion channeling analysis. A formulation is given, incorporating effects of large beam angles and beam divergence. A critical examination of previous definitions is made.

  8. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... diagnostic nuclear medicine procedures result in low radiation exposure, acceptable for diagnostic exams. Thus, the radiation risk ... long-term adverse effects from such low-dose exposure. For more information about safety in pediatric radiology ...

  9. Low temperature nuclear heat

    Energy Technology Data Exchange (ETDEWEB)

    Kotakorpi, J.; Tarjanne, R. (comps.)

    1977-08-01

    The meeting was concerned with the use of low grade nuclear heat for district heating, desalination, process heat, and agriculture and aquaculture. The sessions covered applications and demand, heat sources, and economics.

  10. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... molecular information. In many centers, nuclear medicine images can be superimposed with computed tomography (CT) or magnetic ... small hand-held device resembling a microphone that can detect and measure the amount of the radiotracer ...

  11. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... painless medical tests that help physicians diagnose and evaluate medical conditions. These imaging scans use radioactive materials called radiopharmaceuticals or radiotracers . Depending on the type of nuclear medicine exam, the radiotracer is either ...

  12. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... including many types of cancers, heart disease, gastrointestinal, endocrine, neurological disorders and other abnormalities within the body. Because nuclear medicine procedures are able to pinpoint molecular activity within ...

  13. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... variety of diseases, including many types of cancers, heart disease, gastrointestinal, endocrine, neurological disorders and other abnormalities ... and bladder. bones. liver and gallbladder. gastrointestinal tract. heart. lungs. brain. thyroid. Nuclear medicine scans are typically ...

  14. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... will be inhaled as a gas via a mask, such as with a lung scan. Bladder: some ... A radiologist or other physician who has specialized training in nuclear medicine will interpret the images and ...

  15. International Nuclear Security

    Energy Technology Data Exchange (ETDEWEB)

    Doyle, James E. [Los Alamos National Laboratory

    2012-08-14

    This presentation discusses: (1) Definitions of international nuclear security; (2) What degree of security do we have now; (3) Limitations of a nuclear security strategy focused on national lock-downs of fissile materials and weapons; (4) What do current trends say about the future; and (5) How can nuclear security be strengthened? Nuclear security can be strengthened by: (1) More accurate baseline inventories; (2) Better physical protection, control and accounting; (3) Effective personnel reliability programs; (4) Minimize weapons-usable materials and consolidate to fewer locations; (5) Consider local threat environment when siting facilities; (6) Implement pledges made in the NSS process; and (7) More robust interdiction, emergency response and special operations capabilities. International cooperation is desirable, but not always possible.

  16. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... determine appropriate treatment, if any. Risks Because the doses of radiotracer administered are small, diagnostic nuclear medicine procedures result in low radiation exposure, acceptable for diagnostic exams. Thus, the radiation ...

  17. Western Nuclear Science Alliance

    Energy Technology Data Exchange (ETDEWEB)

    Steve Reese; George Miller; Stephen Frantz; Denis Beller; Denis Beller; Ed Morse; Melinda Krahenbuhl; Bob Flocchini; Jim Elliston

    2010-12-07

    The primary objective of the INIE program is to strengthen nuclear science and engineering programs at the member institutions and to address the long term goal of the University Reactor Infrastructure and Education Assistance Program.

  18. Desalting and Nuclear Energy

    Science.gov (United States)

    Burwell, Calvin C.

    1971-01-01

    Future use of nuclear energy to produce electricity and desalted water is outlined. Possible desalting processes are analyzed to show economic feasibility and the place in planning in world's economic growth. (DS)

  19. JPRS Report, Nuclear Developments.

    Science.gov (United States)

    2007-11-02

    COMERCIO 21 Aug] 23 NEAR EAST & SOUTH ASIA EGYPT Agreements Signed to Develop Domestic Uranium [AL-JUMHURIYAH 2 Aug] 24 INDIA Two Large...Empresas Nucleares Brasileiras S.A. (Nuclebras) to Industrias Nucleares do Brasil S.A. (INB), and trans- ferred the shares of its capital stock...96.622 authorizes the establishment of Uranium of Brasil S.A. as a subsidiary of INB, with headquarters in the city of Caldas, Minas Gerais State

  20. Nuclear Threats and Security

    OpenAIRE

    Garry Jacobs; Winston P. Nagan

    2012-01-01

    This article presents highlights and insights from the International Conference on “Nuclear Threats and Security” organized by the World Academy of Art and Science in association with the European Leadership Network and the Dag Hammarskjöld University College of International Relations and Diplomacy and sponsored by NATO at the Inter-University Centre, Dubrovnik on September 14-16, 2012. The conference examined important issues related to nuclear non-proliferation and disarmament, the legalit...

  1. Nuclear fuel element

    Science.gov (United States)

    Meadowcroft, Ronald Ross; Bain, Alastair Stewart

    1977-01-01

    A nuclear fuel element wherein a tubular cladding of zirconium or a zirconium alloy has a fission gas plenum chamber which is held against collapse by the loops of a spacer in the form of a tube which has been deformed inwardly at three equally spaced, circumferential positions to provide three loops. A heat resistant disc of, say, graphite separates nuclear fuel pellets within the cladding from the plenum chamber. The spacer is of zirconium or a zirconium alloy.

  2. JPRS Report, Nuclear Developments

    Science.gov (United States)

    2016-03-24

    Pilotless Plane in 1991 [DAVAR 5 Nov] ....................................................... 19 Arens Rules Out Iraqi Nuclear Capability [Jerusalem...islands near is allowed to dispose of nuclear waste on the island, Prachuab Kiri Khan to see if there is any appropriate destroying not only the ecology ...controversial aspects of the issue has to Government was investing much more in the parallel do with a series of charges made by the ecological group

  3. INVAP's Nuclear Calculation System

    OpenAIRE

    Ignacio Mochi

    2011-01-01

    Since its origins in 1976, INVAP has been on continuous development of the calculation system used for design and optimization of nuclear reactors. The calculation codes have been polished and enhanced with new capabilities as they were needed or useful for the new challenges that the market imposed. The actual state of the code packages enables INVAP to design nuclear installations with complex geometries using a set of easy-to-use input files that minimize user errors due to confusion or mi...

  4. JPRS Report, Nuclear Developments

    Science.gov (United States)

    2016-03-24

    50 SWEDEN Poll Surveys Views on Nuclear Power [DAGENS NYHETER 8 Mar] ........................................... 51 JPRS-TND...Indonesian Chong Chun-ki, chairman of the Korean Committee for 0600 GMT 9 Apr 91 Cultural Relations with Foreign Countries, indicated [Text] Indonesia has...taken additional mea- plants. In Sweden , where the nuclear power industry has sures. The leak occurred because of a neuparine plastic been most

  5. Nuclear Plant Inspection

    Science.gov (United States)

    1983-01-01

    Engineers from the Power Authority of the State of New York use a Crack Growth Analysis Program supplied by COSMIC (Computer Software Management and Information Center) in one stage of nuclear plant inspection. Welds of the nuclear steam supply system are checked for cracks; radiographs, dye penetration and visual inspections are performed to locate cracks in the metal structure and welds. The software package includes three separate crack growth analysis models and enables necessary repairs to be planned before serious problems develop.

  6. Biocatalysts with enhanced inhibitor tolerance

    Science.gov (United States)

    Yang, Shihui; Linger, Jeffrey; Franden, Mary Ann; Pienkos, Philip T.; Zhang, Min

    2015-12-08

    Disclosed herein are biocatalysts for the production of biofuels, including microorganisms that contain genetic modifications conferring tolerance to growth and fermentation inhibitors found in many cellulosic feedstocks. Methods of converting cellulose-containing materials to fuels and chemicals, as well as methods of fermenting sugars to fuels and chemicals, using these biocatalysts are also disclosed.

  7. Renal targeting of kinase inhibitors

    NARCIS (Netherlands)

    Dolman, M. E. M.; Fretz, M. M.; Segers, Gj. W.; Lacombe, M.; Prakash, J.; Storm, G.; Hennink, W. E.; Kok, R. J.

    2008-01-01

    Activation of proximal tubular cells by fibrotic and inflammatory mediators is an important hallmark of chronic kidney disease. We have developed a novel strategy to intervene in renal fibrosis, by means of locally delivered kinase inhibitors. Such compounds will display enhanced activity within tub

  8. Biocatalysts with enhanced inhibitor tolerance

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Shihui; Linger, Jeffrey; Franden, Mary Ann; Pienkos, Philip T.; Zhang, Min

    2015-12-08

    Disclosed herein are biocatalysts for the production of biofuels, including microorganisms that contain genetic modifications conferring tolerance to growth and fermentation inhibitors found in many cellulosic feedstocks. Methods of converting cellulose-containing materials to fuels and chemicals, as well as methods of fermenting sugars to fuels and chemicals, using these biocatalysts are also disclosed.

  9. Proton pump inhibitors and gastroenteritis

    NARCIS (Netherlands)

    R.J. Hassing (Robert); A. Verbon (Annelies); H. de Visser (Herman); A. Hofman (Albert); B.H.Ch. Stricker (Bruno)

    2016-01-01

    textabstractAn association between proton pump inhibitor (PPI) therapy and bacterial gastroenteritis has been suggested as well as contradicted. The aim of this study was to examine the association between the use of PPIs and occurrence of bacterial gastroenteritis in the prospective Rotterdam Study

  10. Renal targeting of kinase inhibitors

    NARCIS (Netherlands)

    Dolman, M. E. M.; Fretz, M. M.; Segers, Gj. W.; Lacombe, M.; Prakash, J.; Storm, G.; Hennink, W. E.; Kok, R. J.

    2008-01-01

    Activation of proximal tubular cells by fibrotic and inflammatory mediators is an important hallmark of chronic kidney disease. We have developed a novel strategy to intervene in renal fibrosis, by means of locally delivered kinase inhibitors. Such compounds will display enhanced activity within

  11. Proteasome Inhibitors with Photocontrolled Activity

    NARCIS (Netherlands)

    Hansen, Mickel J.; Velema, Willem A.; de Bruin, Gerjan; Overkleeft, Herman S.; Szymanski, Wiktor; Feringa, Ben L.

    2014-01-01

    Proteasome inhibitors are widely used in cancer treatment as chemotherapeutic agents. However, their employment often results in severe side effects, due to their non-specific cytotoxicity towards healthy tissue. This problem might be overcome by using a photopharmacological approach, that is, by

  12. CORROSION INHIBITOR FOR CARBON STEELS

    African Journals Online (AJOL)

    corrosion inhibitor for carbon steel in 3% ac]neon.s' NaCl solution (pH 6) ... compared to stainless steels (Buchweishaija & Hagen 1997). Organic compounds are ... resistant dust for break and clutch linings, wood binders and mould (Gedam.

  13. Corrosion Inhibitors for Reinforced Concrete

    OpenAIRE

    ECT Team, Purdue

    2007-01-01

    Steel corrosion in reinforced concrete structures has been a major problem across the U.S. Steel-reinforced concrete structures are continually subject to attack by corrosion brought on by naturally occurring environmental conditions. FerroGard, a corrosion inhibitor, developed by Sika Corporation, penetrates hardened concrete to dramatically reduce corrosion by 65% and extend the structure's service life.

  14. Superpower nuclear minimalism

    Energy Technology Data Exchange (ETDEWEB)

    Graben, E.K.

    1992-01-01

    During the Cold War, the United States and the Soviet Union competed in building weapons -- now it seems like America and Russia are competing to get rid of them the fastest. The lengthy process of formal arms control has been replaced by exchanges of unilateral force reductions and proposals for reciprocal reductions not necessarily codified by treaty. Should superpower nuclear strategies change along with force postures President Bush has yet to make a formal pronouncement on post-Cold War American nuclear strategy, and it is uncertain if the Soviet/Russian doctrine of reasonable sufficiency formulated in the Gorbachev era actually heralds a change in strategy. Some of the provisions in the most recent round of unilateral proposals put forth by Presidents Bush and Yeltsin in January 1992 are compatible with a change in strategy. Whether such a change has actually occurred remains to be seen. With the end of the Cold War and the breakup of the Soviet Union, the strategic environment has fundamentally changed, so it would seem logical to reexamine strategy as well. There are two main schools of nuclear strategic thought: a maximalist school, mutual assured destruction (MAD) which emphasizes counterforce superiority and nuclear war- fighting capability, and a MAD-plus school, which emphasizes survivability of an assured destruction capability along with the ability to deliver small, limited nuclear attacks in the event that conflict occurs. The MAD-plus strategy is based on an attempt to conventionalize nuclear weapons which is unrealistic.

  15. Perspectives of Nuclear Physics

    CERN Document Server

    Faessler, A

    2002-01-01

    The organizers of this meeting have asked me to present perspectives of nuclear physics. This means to identify the areas where nuclear physics will be expanding in the next future. In six chapters a short overview of these areas will be given, where I expect that nuclear physics willdevelop quite fast: A. Quantum Chromodynamics and effective field theories in the confinement region; B. Nuclear structure at the limits; C. High energy heavy ion collisions; D. Nuclear astrophysics; E. Neutrino physics; F. Test of physics beyond the standard model by rare processes. After a survey over these six points I will pick out a few topics where I will go more in details. There is no time to give for all six points detailed examples. I shall discuss the following examples of the six topics mentionned above: 1. The perturbative chiral quark model and the nucleon $\\Sigma$-term, 2. VAMPIR (Variation After Mean field Projection In Realistic model spaces and with realistic forces) as an example of the nuclear structure renais...

  16. PARP inhibitors in ovarian cancer.

    Science.gov (United States)

    Ledermann, J A

    2016-04-01

    Slow progress in improving the outcome of ovarian cancer with chemotherapy over the last decade has stimulated research into molecularly targeted therapy. Poly(ADP-ribose) polymerase (PARP) inhibitors target DNA repair and are specifically active in cells that have impaired repair of DNA by the homologous recombination (HR) pathway. Cells with mutated BRCA function have HR deficiency (HRD), which is also present in a significant proportion of non-BRCA-mutated ovarian cancer. In the last decade, olaparib, the first and most-investigated oral PARP inhibitor, has undergone phase I-III trials as a single agent, in comparison with and in addition to chemotherapy, and as a maintenance therapy following chemotherapy. The greatest benefit to-date has been in the maintenance setting, prolonging the progression-free survival of high-grade serous ovarian cancer with a BRCA1/2 mutation. In this group of patients, olaparib has received approval as maintenance following chemotherapy from the EMA, and accelerated approval as a single agent in women who have had three or more lines of therapy. Olaparib can be given for a prolonged period with few significant side-effects in most patients. Similar trials with other PARP inhibitors (rucaparib, niraparib and veliparib) are in progress and include non-BRCA-mutated ovarian cancer. Second-generation studies are exploring the combination of PARP inhibitors with anti-angiogenic drugs. PARP inhibitors represent a step change in the management of ovarian cancer. BRCA mutations are the first genotypic predictive markers in ovarian cancer and can be used to select patients who will most likely benefit from PARP inhibitors. BRCA testing is now becoming a routine part of the evaluation of women with ovarian cancer, and tests for HRD are being used to evaluate PARP inhibitors in an extended population of non-BRCA-mutated ovarian cancer. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical

  17. Phosphodiesterase inhibitors: history of pharmacology.

    Science.gov (United States)

    Schudt, Christian; Hatzelmann, Armin; Beume, Rolf; Tenor, Hermann

    2011-01-01

    The first pharmacological investigations of phosphodiesterase (PDE) inhibitors were developed with the clinical efficacies of drugs isolated from coffee, cacao and tea but only later their relevant ingredients were identified as xanthines that act as PDE. With its diuretic, inotropic and bronchodilating clinical efficacy, use of theophylline anticipated the clinical goals, which were later approached with the first-generation of weakly selective PDE inhibitors in the period from 1980 to 1990. Pharmacological and clinical research with these early compounds provided a vast pool of information regarding desired and adverse actions - although most of these new drugs had to be discontinued due to severe adverse effects. The pharmacological models for cardiac, vascular and respiratory indications were analysed for their PDE isoenzyme profiles, and when biochemical and molecular biological approaches expanded our knowledge of the PDE superfamily, the purified isoenzymes that were now available opened the door for more systematic studies of inhibitors and for generation of highly selective isoenzyme-specific drugs. The development of simple screening models and clinically relevant indication models reflecting the growing knowledge about pathomechanisms of disease are summarised here for today's successful application of highly selective PDE3, PDE4 and PDE5 inhibitors. The interplay of serendipitous discoveries, the establishment of intelligent pharmacological models and the knowledge gain by research results with new substances is reviewed. The broad efficacies of new substances in vitro, the enormous biodiversity of the PDE isoenzyme family and the sophisticated biochemical pharmacology enabled Viagra to be the first success story in the field of PDE inhibitor drug development, but probably more success stories will follow.

  18. Density content of nuclear symmetry energy from nuclear observables

    Indian Academy of Sciences (India)

    B K Agrawal

    2014-11-01

    The nuclear symmetry energy at a given density measures the energy transferred in converting symmetric nuclear matter into the pure neutron matter. The density content of nuclear symmetry energy remains poorly constrained. Our recent results for the density content of the nuclear symmetry energy, around the saturation density, extracted using experimental data for accurately known nuclear masses, giant resonances and neutron-skin thickness in heavy nuclei are summarized.

  19. Radioactive target needs for nuclear reactor physics and nuclear astrophysics

    OpenAIRE

    Jurado, B.; Barreau, G.; Bacri, C. O.

    2010-01-01

    Nuclear Instruments and Methods in Physics Research Section A - In press.; Nuclear reaction cross sections of short-lived nuclei are key inputs for new generation nuclear reactor simulations and for models describing the nucleosynthesis of elements. After discussing various topics of nuclear astrophysics and reactor physics where the demand of nuclear data on unstable nuclei is strong, we describe the general characteristics of the targets needed to measure the requested data. In some cases t...

  20. Panel report: nuclear physics

    Energy Technology Data Exchange (ETDEWEB)

    Carlson, Joseph A [Los Alamos National Laboratory; Hartouni, Edward P [LLNL

    2010-01-01

    Nuclear science is at the very heart of the NNSA program. The energy produced by nuclear processes is central to the NNSA mission, and nuclear reactions are critical in many applications, including National Ignition Facility (NIF) capsules, energy production, weapons, and in global threat reduction. Nuclear reactions are the source of energy in all these applications, and they can also be crucial in understanding and diagnosing the complex high-energy environments integral to the work of the NNSA. Nuclear processes are complex quantum many-body problems. Modeling and simulation of nuclear reactions and their role in applications, coupled tightly with experiments, have played a key role in NNSA's mission. The science input to NNSA program applications has been heavily reliant on experiment combined with extrapolations and physical models 'just good enough' to provide a starting point to extensive engineering that generated a body of empirical information. This body of information lacks the basic science underpinnings necessary to provide reliable extrapolations beyond the domain in which it was produced and for providing quantifiable error bars. Further, the ability to perform additional engineering tests is no longer possible, especially those tests that produce data in the extreme environments that uniquely characterize these applications. The end of testing has required improvements to the predictive capabilities of codes simulating the reactions and associated applications for both well known and well characterized cases as well as incompletely known cases. Developments in high performance computing, computational physics, applied mathematics and nuclear theory have combined to make spectacular advances in the theory of fission, fusion and nuclear reactions. Current research exploits these developments in a number of Office of Science and NNSA programs, and in joint programs such as the SciDAC (Science Discovery through Advanced Computing) that

  1. Thinking About Preventing Nuclear War.

    Science.gov (United States)

    Ground Zero, Washington, DC.

    Potential paths to nuclear war and the available means of prevention of nuclear war are discussed. Presented is a detailed description of six nuclear war scenarios, and brief examples of types of potential deterrents to nuclear war (firebreaks) which are relevant for each. To be effective, the right combination of firebreaks must be used, the…

  2. Nuclear War and Science Teaching.

    Science.gov (United States)

    Hobson, Art

    1983-01-01

    Suggests that science-related material on nuclear war be included in introductory courses. Lists nuclear war topics for physics, psychology, sociology, biology/ecology, chemistry, geography, geology/meteorology, mathematics, and medical science. Also lists 11 lectures on nuclear physics which include nuclear war topics. (JN)

  3. Discovery of a Potent and Selective BCL-XL Inhibitor with in Vivo Activity.

    Science.gov (United States)

    Tao, Zhi-Fu; Hasvold, Lisa; Wang, Le; Wang, Xilu; Petros, Andrew M; Park, Chang H; Boghaert, Erwin R; Catron, Nathaniel D; Chen, Jun; Colman, Peter M; Czabotar, Peter E; Deshayes, Kurt; Fairbrother, Wayne J; Flygare, John A; Hymowitz, Sarah G; Jin, Sha; Judge, Russell A; Koehler, Michael F T; Kovar, Peter J; Lessene, Guillaume; Mitten, Michael J; Ndubaku, Chudi O; Nimmer, Paul; Purkey, Hans E; Oleksijew, Anatol; Phillips, Darren C; Sleebs, Brad E; Smith, Brian J; Smith, Morey L; Tahir, Stephen K; Watson, Keith G; Xiao, Yu; Xue, John; Zhang, Haichao; Zobel, Kerry; Rosenberg, Saul H; Tse, Chris; Leverson, Joel D; Elmore, Steven W; Souers, Andrew J

    2014-10-09

    A-1155463, a highly potent and selective BCL-XL inhibitor, was discovered through nuclear magnetic resonance (NMR) fragment screening and structure-based design. This compound is substantially more potent against BCL-XL-dependent cell lines relative to our recently reported inhibitor, WEHI-539, while possessing none of its inherent pharmaceutical liabilities. A-1155463 caused a mechanism-based and reversible thrombocytopenia in mice and inhibited H146 small cell lung cancer xenograft tumor growth in vivo following multiple doses. A-1155463 thus represents an excellent tool molecule for studying BCL-XL biology as well as a productive lead structure for further optimization.

  4. Nuclear EGFR as a molecular target in cancer.

    Science.gov (United States)

    Brand, Toni M; Iida, Mari; Luthar, Neha; Starr, Megan M; Huppert, Evan J; Wheeler, Deric L

    2013-09-01

    The epidermal growth factor receptor (EGFR) has been one of the most targeted receptors in the field of oncology. While anti-EGFR inhibitors have demonstrated clinical success in specific cancers, most patients demonstrate either intrinsic or acquired resistance within one year of treatment. Many mechanisms of resistance to EGFR inhibitors have been identified, one of these being attributed to alternatively localized EGFR from the cell membrane into the cell's nucleus. Inside the nucleus, EGFR functions as a co-transcription factor for several genes involved in cell proliferation and angiogenesis, and as a tyrosine kinase to activate and stabilize proliferating cell nuclear antigen and DNA dependent protein kinase. Nuclear localized EGFR is highly associated with disease progression, worse overall survival in numerous cancers, and enhanced resistance to radiation, chemotherapy, and the anti-EGFR therapies gefitinib and cetuximab. In this review the current knowledge of how nuclear EGFR enhances resistance to cancer therapeutics is discussed, in addition to highlighting ways to target nuclear EGFR as an anti-cancer strategy in the future.

  5. Nicotinamide phosphoribosyltransferase inhibitors, design, preparation and SAR

    DEFF Research Database (Denmark)

    Christensen, Mette Knak; Erichsen, Kamille Dumong; Olesen, Uffe Hogh;

    2013-01-01

    Existing pharmacological inhibitors for nicotinamide phosphoribosyltransferase (NAMPT) are promising therapeutics for treating cancer. Using medicinal and computational chemistry methods, the structure-activity relationship for novel classes of NAMPT inhibitors is described and compounds optimized....... Compounds are designed inspired by the NAMPT inhibitor APO866 and cyanoguanidine inhibitor scaffolds. In comparison with recently published derivatives the new analogues exhibit an equally potent anti-proliferative activity in vitro and comparable activity in vivo. The best performing compounds from...

  6. NUCLEAR CHEMISTRY ANNUAL REPORT 1970

    Energy Technology Data Exchange (ETDEWEB)

    Authors, Various

    1971-05-01

    Papers are presented for the following topics: (1) Nuclear Structure and Nuclear Properties - (a) Nuclear Spectroscopy and Radioactivity; (b) Nuclear Reactions and Scattering; (c) Nuclear Theory; and (d) Fission. (2) Chemical and Atomic Physics - (a) Atomic and Molecular Spectroscopy; and (b) Hyperfine Interactions. (3) Physical, Inorganic, and Analytical Chemistry - (a) X-Ray Crystallography; (b) Physical and Inorganic Chemistry; (c) Radiation Chemistry; and (d) Chemical Engineering. (4) Instrumentation and Systems Development.

  7. Nuclear Propulsion for Space (Rev.)

    Energy Technology Data Exchange (ETDEWEB)

    Corliss, William R; Schwenk, Francis C

    1971-01-01

    The operation of nuclear rockets and a description of the development of nuclear rockets in the U.S. is given. Early developments and Project Rover, Project Pluto, and the NERVA (Nuclear Engine for Rocket Vehicle Application) Program are detailed. The Nuclear Rocket Development Station facilities in Nevada are described. The possibilities and advantages of using nuclear rockets for missions beginning from an earth orbit and moving outward toward higher earth orbits, the moon, and the planets are discussed.

  8. Let us learn nuclear power

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Wan Sang

    2006-08-15

    This book teach us nuclear power through nine chapters with recommendation and a prolog. The contents of this book are how did Formi become a scientist? what does atom look like? discover of neutron, what is an isotope?, power in the nuclear, various radiation, artificial nuclear transformation, nuclear fission and clinging atomic nucleus. It also has an appendix on SF story ; an atom bomb war. It explains basic nuclear physic in easy way with pictures.

  9. Nuclear Regulatory Commission information digest

    Energy Technology Data Exchange (ETDEWEB)

    None,

    1990-03-01

    The Nuclear Regulatory Commission information digest provides summary information regarding the US Nuclear Regulatory Commission, its regulatory responsibilities, and areas licensed by the commission. This is an annual publication for the general use of the NRC Staff and is available to the public. The digest is divided into two parts: the first presents an overview of the US Nuclear Regulatory Commission and the second provides data on NRC commercial nuclear reactor licensees and commercial nuclear power reactors worldwide.

  10. Endothelial nuclear lamina is not required for glucocorticoid receptor nuclear import but does affect receptor-mediated transcription activation.

    Science.gov (United States)

    Nayebosadri, Arman; Ji, Julie Y

    2013-08-01

    The lamina serves to maintain the nuclear structure and stiffness while acting as a scaffold for heterochromatin and many transcriptional proteins. Its role in endothelial mechanotransduction, specifically how nuclear mechanics impact gene regulation under shear stress, is not fully understood. In this study, we successfully silenced lamin A/C in bovine aortic endothelial cells to determine its role in both glucocorticoid receptor (GR) nuclear translocation and glucocorticoid response element (GRE) transcriptional activation in response to dexamethasone and shear stress. Nuclear translocation of GR, an anti-inflammatory nuclear receptor, in response to dexamethasone or shear stress (5, 10, and 25 dyn/cm(2)) was observed via time-lapse cell imaging and quantified using a Bayesian image analysis algorithm. Transcriptional activity of the GRE promoter was assessed using a dual-luciferase reporter plasmid. We found no dependence on nuclear lamina for GR translocation from the cytoplasm into the nucleus. However, the absence of lamin A/C led to significantly increased expression of luciferase under dexamethasone and shear stress induction as well as changes in histone protein function. PCR results for NF-κB inhibitor alpha (NF-κBIA) and dual specificity phosphatase 1 (DUSP1) genes further supported our luciferase data with increased expression in the absence of lamin. Our results suggest that absence of lamin A/C does not hinder passage of GR into the nucleus, but nuclear lamina is important to properly regulate GRE transcription. Nuclear lamina, rather than histone deacetylase (HDAC), is a more significant mediator of shear stress-induced transcriptional activity, while dexamethasone-initiated transcription is more HDAC dependent. Our findings provide more insights into the molecular pathways involved in nuclear mechanotransduction.

  11. Allosteric small-molecule kinase inhibitors

    DEFF Research Database (Denmark)

    Wu, Peng; Clausen, Mads Hartvig; Nielsen, Thomas E.

    2015-01-01

    current barriers of kinase inhibitors, including poor selectivity and emergence of drug resistance. In spite of the small number of identified allosteric inhibitors in comparison with that of inhibitors targeting the ATP pocket, encouraging results, such as the FDA-approval of the first small...

  12. Nuclear fundamentals remain

    Directory of Open Access Journals (Sweden)

    Stošić Zoran V.

    2012-01-01

    Full Text Available For Japan, the situation has become extremely difficult since counter-measures to deal with the nuclear accident had to be carried out along with dealing with the broader disaster caused by earthquake and the tsunami. In terms of damage, the Tohoku earthquake and the tsunami have caused the most fatalities and the largest economic loss ever from an earthquake and/or tsunami. The impact of this natural disaster is present not only in Japan but world-wide. The state of affairs in the global energy sector is affected by the consequences which may be lasting for decades. These effects are subject of this article dealing not with the nuclear accident at Fukushima Daiichi NPPs itself, but rather with the world-wide consequences and after effect on nuclear energy development. This includes: environmental damages, socio-economic effects, actions of safety authorities, extended protective measures against external events, the impact on global nuclear energy, triggered nuclear phase-outs and changes in new build plans as well as the sustainability of energy mix itself and an outlook.

  13. Nuclear Manpower Development

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, I. A.; Lee, K. B.; Shin, B. C. [KAERI, Daejeon (Korea, Republic of)

    2010-12-15

    The industry-university-research collaborative education is aiming at developing national nuclear human resources to satisfy with the increasing needs from the industry. For this efforts are being made to develop curricula customized to respective industry needs by improving existing ones. As the demand for training programs for the university students and domestic nuclear personnel was increasing owing to revitalization of nuclear industry, Nuclear Training Center (NTC) improved previous education programs to meet the needs. NTC has operated 2 education programs on research reactor experiments for the university students, and 18 programs on nuclear technology related experiment courses in 2010. Furthermore, the NTC developed new education programs related to 'standardized research reactor system design'. Also the request from universities for internship programs was increased by about three times in 2010 compared to those of the previous year, and this required to develop relevant curricula. In 2005, NTC developed KAERI-ACE, as a unique competency-based staff education system of Korea Atomic Energy Research Institute (KAERI). Based on the system, the NTC has performed 'systematic education'. In 2008, NTC was awarded Best HRD(Human Resource Development) in Public sector for the first time as a government-supported research institute. In 2009, the system was improved to become KAERI-ACE 2.0, based on which, in 2010, NTC improved and diversified education programs including various cyber training programs

  14. Basic Nuclear Physics Research Needs for Nuclear Energy

    Science.gov (United States)

    Hill, Tony

    2008-10-01

    Basic nuclear physics research will play a central role in the development of the future nuclear facilities. Federal requirements for higher efficiencies, lower operating and construction costs, and advanced safeguards can all be impacted by the quality of nuclear data used in the fuel cycle calculations for design and licensing. Uncertainties in the underlying nuclear data propagate to uncertainties in integral and operational parameters, which drive margins and cost. Department of Energy (DOE) programs are underway to help develop the necessary nuclear research infrastructure. The Nuclear Energy office of DOE leads the development of new nuclear energy generation technologies to meet energy and climate change goals and advanced, proliferation resistant nuclear fuel technologies that maximize energy from nuclear fuel, while maintaining and enhancing the national nuclear infrastructure. These activities build on important work started over the last three years to deploy new nuclear plants in the United States by early in the next decade, and to develop advanced, next-generation nuclear technology. In this talk, I will discuss some of the foreseen opportunities and needs for basic nuclear research in nuclear energy.

  15. Model Action Plan for Nuclear Forensics and Nuclear Attribution

    Energy Technology Data Exchange (ETDEWEB)

    Dudder, G B; Niemeyer, S; Smith, D K; Kristo, M J

    2004-03-01

    Nuclear forensics and nuclear attribution have become increasingly important tools in the fight against illegal trafficking in nuclear and radiological materials. This technical report documents the field of nuclear forensics and nuclear attribution in a comprehensive manner, summarizing tools and procedures that have heretofore been described independently in the scientific literature. This report also provides national policy-makers, decision-makers, and technical managers with guidance for responding to incidents involving the interdiction of nuclear and radiological materials. However, due to the significant capital costs of the equipment and the specialized expertise of the personnel, work in the field of nuclear forensics has been restricted so far to a handful of national and international laboratories. In fact, there are a limited number of specialists who have experience working with interdicted nuclear materials and affiliated evidence. Most of the laboratories that have the requisite equipment, personnel, and experience to perform nuclear forensic analysis are participants in the Nuclear Smuggling International Technical Working Group or ITWG (see Section 1.8). Consequently, there is a need to disseminate information on an appropriate response to incidents of nuclear smuggling, including a comprehensive approach to gathering evidence that meets appropriate legal standards and to developing insights into the source and routes of nuclear and radiological contraband. Appendix A presents a ''Menu of Options'' for other Member States to request assistance from the ITWG Nuclear Forensics Laboratories (INFL) on nuclear forensic cases.

  16. Proteasome inhibitors in cancer therapy

    Directory of Open Access Journals (Sweden)

    Wioletta Romaniuk

    2015-12-01

    Full Text Available Proteasomes are multisubunit enzyme complexes. They contain three enzymatic active sites which are termed chymotrypsin-like, trypsin-like, and caspase-like. The elementary function of the proteasomes is degradation of damaged proteins. Proteasome inhibition leads to accumulation of damaged protein, which leads to caspase activation and cell death. This relationship is used in cancer therapy. Bortezomib is the first proteasome inhibitor approved by the US Food and Drug Administration for the treatment of relapsed/refractory multiple myeloma. Carfilzomib belongs to the second generation of drugs, which was approved by the US FDA in 2012. Currently in the study phase there are four new inhibitors: ixazomib (MLN9780/MLN2238, delanzomib (CEP-18770, oprozomib (ONX0912/PR-047 and marizomib (NPI-0052.

  17. Nelfinavir: fourth protease inhibitor approved.

    Science.gov (United States)

    1997-01-01

    The Food and Drug Administration (FDA) has granted accelerated approval to nelfinavir in both adult and pediatric formulations. Agouron, the manufacturer, used innovative computerized drug design techniques to discover, design, and refine the nelfinavir molecule. Nelfinavir is marketed under the trade name Viracept, and costs $5,000 per year. Early clinical trials find it to be as powerful as the other protease inhibitors, but with a different resistance profile. The drug has relatively few drug indications; however, several compounds have been contraindicated.

  18. Notch Inhibitors for Cancer Treatment

    OpenAIRE

    Espinoza, Ingrid; Miele, Lucio

    2013-01-01

    Notch signaling is an evolutionarily conserved cell signaling pathway involved in cell fate during development, stem cell renewal and differentiation in postnatal tissues. Roles for Notch in carcinogenesis, in the biology of cancer stem cells and tumor angiogenesis have been reported. These features identify Notch as a potential therapeutic target in oncology. Based on the molecular structure of Notch receptor, Notch ligands and Notch activators, a set of Notch pathway inhibitors have been de...

  19. Conversion of calcineurin inhibitors with mammalian target of rapamycin inhibitors after kidney transplant.

    Science.gov (United States)

    Nikoueinejad, Hassan; Soleimani, Alireza; Mirshafiey, Abbas; Amirzargar, Aliakbar; Sarrafnejad, Abdolfattah; Kamkar, Ideh; Einollahi, Behzad

    2013-02-01

    One way to overcome chronic allograft nephropathy induced by calcineurin inhibitors in immunosuppression protocols for organ transplants is to replace such inhibitors with mammalian target of rapamycin inhibitors, which are not clinically nephrotoxic because they have better renal function. If patients tolerate replacement, there could be a clear preference for mammalian target of rapamycin inhibitors as a maintenance immunosuppressant after renal transplant. This replacement could be sufficient if it were used for a certain time after calcineurin inhibitors. This review considers the conversion effects of calcineurin inhibitors with mammalian target of rapamycin inhibitors from the view point of kidney function during different periods after a kidney transplant.

  20. Exotic Nuclear Shapes:

    Science.gov (United States)

    Dudek, J.; Schunck, N.; Dubray, N.; Góźdź, A.

    After recalling some in principle known but seldom mentioned facts about variety of concepts/notions of the nuclear shapes, we briefly summarize the results of the recent microscopic calculations predicting the existence of the large-elongation (hyper-deformed) nuclear configurations — as well as another series of calculations predicting that some nuclei should exhibit high-rank symmetries: the tetrahedral and the octahedral ones. The latter are associated with 48- and 96- symmetry elements, respectively, of the nuclear mean-field Hamiltonian. Obviously the physics motivations behind the hyper-deformation and the high-rank symmetry studies are not the observations of the new geometrical forms as such; in our opinion these motivations are much deeper and are given in the text.

  1. Nuclear Parton Distribution Functions

    Energy Technology Data Exchange (ETDEWEB)

    I. Schienbein, J.Y. Yu, C. Keppel, J.G. Morfin, F. Olness, J.F. Owens

    2009-06-01

    We study nuclear effects of charged current deep inelastic neutrino-iron scattering in the framework of a {chi}{sup 2} analysis of parton distribution functions (PDFs). We extract a set of iron PDFs which are used to compute x{sub Bj}-dependent and Q{sup 2}-dependent nuclear correction factors for iron structure functions which are required in global analyses of free nucleon PDFs. We compare our results with nuclear correction factors from neutrino-nucleus scattering models and correction factors for charged-lepton--iron scattering. We find that, except for very high x{sub Bj}, our correction factors differ in both shape and magnitude from the correction factors of the models and charged-lepton scattering.

  2. Nuclear and particle physics

    CERN Document Server

    Amsler, Claude

    2015-01-01

    Nuclear and Particle Physics provides an introductory course on nuclear and particle physics for undergraduate and early-graduate students, which the author has taught for several years at the University of Zurich. It contains fundamentals on both nuclear and particle physics, giving emphasis to the discovery and history of developments in the field, and is experimentally/phenomenologically oriented. It contains detailed derivations of formulae such as 2–3 body phase space, the Weinberg-Salam model, and neutrino scattering. Originally published in German as Kern- und Teilchenphysik, several sections have been added to this new English version to cover modern topics, including updates on neutrinos, the Higgs boson, the top quark and bottom quark physics.

  3. Nuclear reactions an introduction

    CERN Document Server

    Paetz gen. Schieck, Hans

    2014-01-01

    Nuclei and nuclear reactions offer a unique setting for investigating three (and in some cases even all four) of the fundamental forces in nature. Nuclei have been shown – mainly by performing scattering experiments with electrons, muons, and neutrinos – to be extended objects with complex internal structures: constituent quarks; gluons, whose exchange binds the quarks together; sea-quarks, the ubiquitous virtual quark-antiquark pairs and, last but not least, clouds of virtual mesons, surrounding an inner nuclear region, their exchange being the source of the nucleon-nucleon interaction.   The interplay between the (mostly attractive) hadronic nucleon-nucleon interaction and the repulsive Coulomb force is responsible for the existence of nuclei; their degree of stability, expressed in the details and limits of the chart of nuclides; their rich structure and the variety of their interactions. Despite the impressive successes of the classical nuclear models and of ab-initio approaches, there is clearly no ...

  4. Pediatric nuclear medicine

    Energy Technology Data Exchange (ETDEWEB)

    1986-01-01

    This symposium presented the latest techniques and approaches to the proper medical application of radionuclides in pediatrics. An expert faculty, comprised of specialists in the field of pediatric nuclear medicine, discussed the major indications as well as the advantages and potential hazards of nuclear medicine procedures compared to other diagnostic modalities. In recent years, newer radiopharmaceuticals labeled with technetium-99m and other short-lived radionuclides with relatively favorable radiation characteristics have permitted a variety of diagnostic studies that are very useful clinically and carry a substantially lower radiation burden then many comparable X-ray studies. This new battery of nuclear medicine procedures is now widely available for diagnosis and management of pediatric patients. Many recent research studies in children have yielded data concerning the effacacy of these procedures, and current recommendations will be presented by those involved in conducting such studies. Individual papers are processed separately for the Energy Data Base.

  5. Nuclear Power in Space

    Science.gov (United States)

    1994-01-01

    In the early years of the United States space program, lightweight batteries, fuel cells, and solar modules provided electric power for space missions. As missions became more ambitious and complex, power needs increased and scientists investigated various options to meet these challenging power requirements. One of the options was nuclear energy. By the mid-1950s, research had begun in earnest on ways to use nuclear power in space. These efforts resulted in the first radioisotope thermoelectric generators (RTGs), which are nuclear power generators build specifically for space and special terrestrial uses. These RTGs convert the heat generated from the natural decay of their radioactive fuel into electricity. RTGs have powered many spacecraft used for exploring the outer planets of the solar system and orbiting the sun and Earth. They have also landed on Mars and the moon. They provide the power that enables us to see and learn about even the farthermost objects in our solar system.

  6. Yeast nuclear RNA processing

    Institute of Scientific and Technical Information of China (English)

    Jade; Bernstein; Eric; A; Toth

    2012-01-01

    Nuclear RNA processing requires dynamic and intricately regulated machinery composed of multiple enzymes and their cofactors.In this review,we summarize recent experiments using Saccharomyces cerevisiae as a model system that have yielded important insights regarding the conversion of pre-RNAs to functional RNAs,and the elimination of aberrant RNAs and unneeded intermediates from the nuclear RNA pool.Much progress has been made recently in describing the 3D structure of many elements of the nuclear degradation machinery and its cofactors.Similarly,the regulatory mechanisms that govern RNA processing are gradually coming into focus.Such advances invariably generate many new questions,which we highlight in this review.

  7. Communication in nuclear emergency

    Energy Technology Data Exchange (ETDEWEB)

    Nozawa, Masao [Research Organization for Information Science and Technology, Tokai, Ibaraki (Japan)

    1996-12-01

    In order to take protection measures smoothly at the time of emergency in nuclear power stations and others, it is necessary to prepare information communication facilities mutually among disaster prevention organizations including the state and information transmission network for residents in surrounding areas. The matters decided in ``the measures to be taken for the time being for the countermeasures to prevent disaster in nuclear power stations and others`` are shown. In order to avoid the congestion of communication, the exclusively used communication systems are adopted for disaster prevention organizations, in which facsimile is used to transmit graphic information. The data communication circuits for distributing SPEEDI are installed between Science and Technology Agency, Nuclear Power Safety Technology Center and respective prefectures. The routes, means and order of notices must be confirmed beforehand mutually among the related organizations. As to the general communication for disaster countermeasures, the communication systems in ministries and agencies are described. (K.I.)

  8. Nuclear Power Plants (Rev.)

    Energy Technology Data Exchange (ETDEWEB)

    Lyerly, Ray L.; Mitchell III, Walter [Southern Nuclear Engineering, Inc.

    1973-01-01

    Projected energy requirements for the future suggest that we must employ atomic energy to generate electric power or face depletion of our fossil-fuel resources—coal, oil, and gas. In short, both conservation and economic considerations will require us to use nuclear energy to generate the electricity that supports our civilization. Until we reach the time when nuclear power plants are as common as fossil-fueled or hydroelectric plants, many people will wonder how the nuclear plants work, how much they cost, where they are located, and what kinds of reactors they use. The purpose of this booklet is to answer these questions. In doing so, it will consider only central station plants, which are those that provide electric power for established utility systems.

  9. Nuclear multifragmentation: Basic concepts

    Indian Academy of Sciences (India)

    G Chaudhuri; S Mallik; S Das Gupta

    2014-05-01

    We present a brief overview of nuclear multifragmentation reaction. Basic formalism of canonical thermodynamical model based on equilibrium statistical mechanics is described. This model is used to calculate basic observables of nuclear multifragmentation like mass distribution, fragment multiplicity, isotopic distribution and isoscaling. Extension of canonical thermodynamical model to a projectile fragmentation model is outlined. Application of the projectile fragmentation model for calculating average number of intermediate mass fragments and the average size of the largest cluster at different bound, differential charge distribution and cross-section of neutron-rich nuclei of different projectile fragmentation reactions at different energies are described. Application of nuclear multifragmentation reaction in basic research as well as in other domains is outlined.

  10. Nuclear reactor neutron shielding

    Energy Technology Data Exchange (ETDEWEB)

    Speaker, Daniel P; Neeley, Gary W; Inman, James B

    2017-09-12

    A nuclear reactor includes a reactor pressure vessel and a nuclear reactor core comprising fissile material disposed in a lower portion of the reactor pressure vessel. The lower portion of the reactor pressure vessel is disposed in a reactor cavity. An annular neutron stop is located at an elevation above the uppermost elevation of the nuclear reactor core. The annular neutron stop comprises neutron absorbing material filling an annular gap between the reactor pressure vessel and the wall of the reactor cavity. The annular neutron stop may comprise an outer neutron stop ring attached to the wall of the reactor cavity, and an inner neutron stop ring attached to the reactor pressure vessel. An excore instrument guide tube penetrates through the annular neutron stop, and a neutron plug comprising neutron absorbing material is disposed in the tube at the penetration through the neutron stop.

  11. Status of nuclear energy and nuclear safety in Slovenia

    Energy Technology Data Exchange (ETDEWEB)

    Grlicarev, I. [Slovenian Nuclear Safety Administration (Slovenia)

    2002-07-01

    Although in Slovenia there is only one nuclear power plant in operation, it represents a substantial share in the production of electrical power in the country. Nuclear fuel cycle in Slovenia comprises the nuclear power plant, a research reactor, a storage for low and intermediate level radioactive waste and uranium mine in decommissioning. The Krsko NPP operation meets the standards of the high level of nuclear safety. Considerable effort has been put into the negotiations in the field of nuclear energy and nuclear safety with the European Commission within the pre-accession activities of Slovenia to European Union. (orig.)

  12. Carbonic anhydrase inhibitors drug design.

    Science.gov (United States)

    McKenna, Robert; Supuran, Claudiu T

    2014-01-01

    Inhibition of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) has pharmacologic applications in the field of antiglaucoma, anticonvulsant, antiobesity, and anticancer agents but is also emerging for designing anti-infectives (antifungal and antibacterial agents) with a novel mechanism of action. As a consequence, the drug design of CA inhibitors (CAIs) is a very dynamic field. Sulfonamides and their isosteres (sulfamates/sulfamides) constitute the main class of CAIs which bind to the metal ion in the enzyme active site. Recently the dithiocarbamates, possessing a similar mechanism of action, were reported as a new class of inhibitors. Other families of CAIs possess a distinct mechanism of action: phenols, polyamines, some carboxylates, and sulfocoumarins anchor to the zinc-coordinated water molecule. Coumarins and five/six-membered lactones are prodrug inhibitors, binding in hydrolyzed form at the entrance of the active site cavity. Novel drug design strategies have been reported principally based on the tail approach for obtaining all these types of CAIs, which exploit more external binding regions within the enzyme active site (in addition to coordination to the metal ion), leading thus to isoform-selective compounds. Sugar-based tails as well as click chemistry were the most fruitful developments of the tail approach. Promising compounds that inhibit CAs from bacterial and fungal pathogens, of the dithiocarbamate, phenol and carboxylate types have also been reported.

  13. Substituted androstanes as aromatase inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Levina, Inna S [N.D.Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow (Russian Federation)

    1998-11-30

    The synthesis and structure-activity relationships of inhibitors of steroid aromatase which catalyses the last stage of a multistep biotransformation of cholesterol into estrogens, viz., aromatisation of C{sub 19}-steroids into C{sub 18}-phenolic steroids, are discussed. Compounds of the androstane series which are structurally related to the natural substrate, viz., androst-4-ene-3,17-dione, are the subjects of consideration. The review encompasses problems of synthesis of various substituted androstanes and their aromatase-inhibiting activities and structural requirements for selective specific aromatase inhibitors based on in vitro and in vivo structure-activity studies of compounds synthesised, their biological properties and the results of clinical trials. Special attention is paid to practical applications of aromatase inhibitors in the treatment of hormone-dependent mammary and ovarian tumours as well as benign prostatic tumours. In writing this report, the author has used all the information currently available in the chemical, biochemical, endocrinological and medicinal literature as well as in patents. The bibliography includes 173 references.

  14. Substituted androstanes as aromatase inhibitors

    Science.gov (United States)

    Levina, Inna S.

    1998-11-01

    The synthesis and structure-activity relationships of inhibitors of steroid aromatase which catalyses the last stage of a multistep biotransformation of cholesterol into estrogens, viz., aromatisation of C19-steroids into C18-phenolic steroids, are discussed. Compounds of the androstane series which are structurally related to the natural substrate, viz., androst-4-ene-3,17-dione, are the subjects of consideration. The review encompasses problems of synthesis of various substituted androstanes and their aromatase-inhibiting activities and structural requirements for selective specific aromatase inhibitors based on in vitro and in vivo structure-activity studies of compounds synthesised, their biological properties and the results of clinical trials. Special attention is paid to practical applications of aromatase inhibitors in the treatment of hormone-dependent mammary and ovarian tumours as well as benign prostatic tumours. In writing this report, the author has used all the information currently available in the chemical, biochemical, endocrinological and medicinal literature as well as in patents. The bibliography includes 173 references.

  15. Accidents in nuclear ships

    Energy Technology Data Exchange (ETDEWEB)

    Oelgaard, P.L. [Risoe National Lab., Roskilde (Denmark)]|[Technical Univ. of Denmark, Lyngby (Denmark)

    1996-12-01

    This report starts with a discussion of the types of nuclear vessels accidents, in particular accidents which involve the nuclear propulsion systems. Next available information on 61 reported nuclear ship events in considered. Of these 6 deals with U.S. ships, 54 with USSR ships and 1 with a French ship. The ships are in almost all cases nuclear submarines. Only events that involve the sinking of vessels, the nuclear propulsion plants, radiation exposures, fires/explosions, sea-water leaks into the submarines and sinking of vessels are considered. For each event a summary of available information is presented, and comments are added. In some cases the available information is not credible, and these events are neglected. This reduces the number of events to 5 U.S. events, 35 USSR/Russian events and 1 French event. A comparison is made between the reported Soviet accidents and information available on dumped and damaged Soviet naval reactors. It seems possible to obtain good correlation between the two types of events. An analysis is made of the accident and estimates are made of the accident probabilities which are found to be of the order of 10{sup -3} per ship reactor years. It if finally pointed out that the consequences of nuclear ship accidents are fairly local and does in no way not approach the magnitude of the Chernobyl accident. It is emphasized that some of the information on which this report is based, may not be correct. Consequently some of the results of the assessments made may not be correct. (au).

  16. Swedish nuclear waste efforts

    Energy Technology Data Exchange (ETDEWEB)

    Rydberg, J.

    1981-09-01

    After the introduction of a law prohibiting the start-up of any new nuclear power plant until the utility had shown that the waste produced by the plant could be taken care of in an absolutely safe way, the Swedish nuclear utilities in December 1976 embarked on the Nuclear Fuel Safety Project, which in November 1977 presented a first report, Handling of Spent Nuclear Fuel and Final Storage of Vitrified Waste (KBS-I), and in November 1978 a second report, Handling and Final Storage of Unreprocessed Spent Nuclear Fuel (KBS II). These summary reports were supported by 120 technical reports prepared by 450 experts. The project engaged 70 private and governmental institutions at a total cost of US $15 million. The KBS-I and KBS-II reports are summarized in this document, as are also continued waste research efforts carried out by KBS, SKBF, PRAV, ASEA and other Swedish organizations. The KBS reports describe all steps (except reprocessing) in handling chain from removal from a reactor of spent fuel elements until their radioactive waste products are finally disposed of, in canisters, in an underground granite depository. The KBS concept relies on engineered multibarrier systems in combination with final storage in thoroughly investigated stable geologic formations. This report also briefly describes other activities carried out by the nuclear industry, namely, the construction of a central storage facility for spent fuel elements (to be in operation by 1985), a repository for reactor waste (to be in operation by 1988), and an intermediate storage facility for vitrified high-level waste (to be in operation by 1990). The R and D activities are updated to September 1981.

  17. Nuclear Energy Policy

    Science.gov (United States)

    2008-01-28

    AFCI to $181 million and shifts the mixed-oxide ( MOX ) fuel program — totaling $281 million — to the nuclear energy program from the nuclear...appropriations act, signed December 26, 2007 (P.L. 110-161), holds AFCI to $181 million and shifts the mixed-oxide ( MOX ) fuel program — totaling $281...million in FY2007 to $395.0 million in FY2008. The FY2008 omnibus appropriation holds AFCI to $181 million and shifts the mixed-oxide ( MOX ) fuel program

  18. Nuclear War Survival Skills

    Energy Technology Data Exchange (ETDEWEB)

    Kearny, C.H.

    2002-06-24

    The purpose of this book is to provide Americans with information and instructions that will significantly increase their chances of surviving a possible nuclear attack. It brings together field-tested instructions that, if followed by a large fraction of Americans during a crisis that preceded an attack, could save millions of lives. The author is convinced that the vulnerability of our country to nuclear threat or attack must be reduced and that the wide dissemination of the information contained in this book would help achieve that objective of our overall defense strategy.

  19. Nuclear Chemistry and Services

    Energy Technology Data Exchange (ETDEWEB)

    Vandevelde, L

    2002-04-01

    The objectives, the programme, and the achievements of R and D at the Belgian Nuclear Research Centre SCK-CEN in the field of nuclear chemistry and analytical techniques are summarized. Major achievement in 2001 included the completion of a project on the measurement of critical radionuclides in reactor waste fluxes (the ARIANE project), the radiochemical characterisation of beryllium material originating from the second matrix of the BR2 reactor as well as to a the organisation of a workshop on the analysis of thorium and its isotopes in workplace materials.

  20. Neutrinos in Nuclear Physics

    CERN Document Server

    McKeown, R D

    2014-01-01

    Since the discovery of nuclear beta decay, nuclear physicists have studied the weak interaction and the nature of neutrinos. Many recent and current experiments have been focused on the elucidation of neutrino oscillations and neutrino mass. The quest for the absolute value of neutrino mass continues with higher precision studies of the tritium beta decay spectrum near the endpoint. Neutrino oscillations are studied through measurements of reactor neutrinos as a function of baseline and energy. And experiments searching for neutrinoless double beta decay seek to discover violation of lepton number and establish the Majorana nature of neutrino masses.

  1. Nuclear structure and astrophysics

    Energy Technology Data Exchange (ETDEWEB)

    Grawe, H [Gesellschaft fuer Schwerionenforschung (GSI), D-64291 Darmstadt (Germany); Langanke, K [Gesellschaft fuer Schwerionenforschung (GSI), D-64291 Darmstadt (Germany); MartInez-Pinedo, G [Gesellschaft fuer Schwerionenforschung (GSI), D-64291 Darmstadt (Germany)

    2007-09-15

    The nuclear structure in regions of the Segre chart which are of astrophysical importance is reviewed. The main emphasis is put on those nuclei that are relevant for stellar nucleosynthesis in fusion processes, and in slow neutron capture, both located close to stability, rapid neutron capture close to the neutron dripline and rapid proton capture near the proton dripline. The basic features of modern nuclear structure, their importance and future potential for astrophysics and their level of predictibility are critically discussed. Recent experimental and theoretical results for shell evolution far off the stability line and consequences for weak interaction processes, proton and neutron capture are reviewed.

  2. Nuclear reactor effluent monitoring

    Energy Technology Data Exchange (ETDEWEB)

    Minns, J.L.; Essig, T.H. [Nuclear Regulatory Commission, Washington, DC (United States)

    1993-12-31

    Radiological environmental monitoring and effluent monitoring at nuclear power plants is important both for normal operations, as well as in the event of an accident. During normal operations, environmental monitoring verifies the effectiveness of in-plant measures for controlling the release of radioactive materials in the plant. Following an accident, it would be an additional mechanism for estimating doses to members of the general public. This paper identifies the U.S. Nuclear Regulatory Commission (NRC) regulatory basis for requiring radiological environmental and effluent monitoring, licensee conditions for effluent and environmental monitoring, NRC independent oversight activities, and NRC`s program results.

  3. Nuclear Innovation Workshops Report

    Energy Technology Data Exchange (ETDEWEB)

    Jackson, John Howard [Idaho National Lab. (INL), Idaho Falls, ID (United States); Allen, Todd Randall [Idaho National Lab. (INL), Idaho Falls, ID (United States); Hildebrandt, Philip Clay [Idaho National Lab. (INL), Idaho Falls, ID (United States); Baker, Suzanne Hobbs [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2015-09-01

    The Nuclear Innovation Workshops were held at six locations across the United States on March 3-5, 2015. The data collected during these workshops has been analyzed and sorted to bring out consistent themes toward enhancing innovation in nuclear energy. These themes include development of a test bed and demonstration platform, improved regulatory processes, improved communications, and increased public-private partnerships. This report contains a discussion of the workshops and resulting themes. Actionable steps are suggested at the end of the report. This revision has a small amount of the data in Appendix C removed in order to avoid potential confusion.

  4. Neutrinos in Nuclear Physics

    Energy Technology Data Exchange (ETDEWEB)

    McKeown, Bob [bmck@jlab.org

    2015-06-01

    Since the discovery of nuclear beta decay, nuclear physicists have studied the weak interaction and the nature of neutrinos. Many recent and current experiments have been focused on the elucidation of neutrino oscillations and neutrino mass. The quest for the absolute value of neutrino mass continues with higher precision studies of the tritium beta decay spectrum near the endpoint. Neutrino oscillations are studied through measurements of reactor neutrinos as a function of baseline and energy. And experiments searching for neutrinoless double beta decay seek to discover violation of lepton number and establish the Majorana nature of neutrino masses.

  5. Nuclear Chemistry and Services

    Energy Technology Data Exchange (ETDEWEB)

    Vandevelde, L

    2002-04-01

    The objectives, the programme, and the achievements of R and D at the Belgian Nuclear Research Centre SCK-CEN in the field of nuclear chemistry and analytical techniques are summarized. Major achievement in 2001 included the completion of a project on the measurement of critical radionuclides in reactor waste fluxes (the ARIANE project), the radiochemical characterisation of beryllium material originating from the second matrix of the BR2 reactor as well as to a the organisation of a workshop on the analysis of thorium and its isotopes in workplace materials.

  6. Focused technology: Nuclear propulsion

    Science.gov (United States)

    Miller, Thomas J.

    1991-01-01

    The topics presented are covered in viewgraph form and include: nuclear thermal propulsion (NTP), which challenges (1) high temperature fuel and materials, (2) hot hydrogen environment, (3) test facilities, (4) safety, (5) environmental impact compliance, and (6) concept development, and nuclear electric propulsion (NEP), which challenges (1) long operational lifetime, (2) high temperature reactors, turbines, and radiators, (3) high fuel burn-up reactor fuels, and designs, (4) efficient, high temperature power conditioning, (5) high efficiency, and long life thrusters, (6) safety, (7) environmental impact compliance, and (8) concept development.

  7. Physics in nuclear medicine

    CERN Document Server

    Cherry, Simon R; Phelps, Michael E

    2012-01-01

    Physics in Nuclear Medicine - by Drs. Simon R. Cherry, James A. Sorenson, and Michael E. Phelps - provides current, comprehensive guidance on the physics underlying modern nuclear medicine and imaging using radioactively labeled tracers. This revised and updated fourth edition features a new full-color layout, as well as the latest information on instrumentation and technology. Stay current on crucial developments in hybrid imaging (PET/CT and SPECT/CT), and small animal imaging, and benefit from the new section on tracer kinetic modeling in neuroreceptor imaging.

  8. Composite nuclear fuel assembly

    Energy Technology Data Exchange (ETDEWEB)

    Dollard, W.J.; Ferrari, H.M.

    1982-04-27

    An open lattice elongated nuclear fuel assembly including small diameter fuel rods disposed in an array spaced a selected distance above an array of larger diameter fuel rods for use in a nuclear reactor having liquid coolant flowing in an upward direction. Plenums are preferably provided in the upper portion of the upper smaller diameter fuel rods and in the lower portion of the lower larger diameter fuel rods. Lattice grid structures provide lateral support for the fuel rods and preferably the lowest grid about the upper rods is directly and rigidly affixed to the highest grid about the lower rods.

  9. Introduction to nuclear physics.

    Science.gov (United States)

    Patton, J A

    1998-01-01

    Photons for counting or imaging applications in nuclear medicine result from several processes. Gamma rays are produced from excited state transitions after beta decay and electron capture. Annihilation photons result from positron decay. The de-excitation of the atom after electron capture results in the production of characteristic x rays or Auger electrons. Metastable state transitions result in gamma ray emission or internal conversion electrons. All radiopharmaceuticals used in diagnostic nuclear medicine applications are tagged with radionuclides that emit photons as a result of one of these processes.

  10. Nuclear order in copper

    DEFF Research Database (Denmark)

    Annila, A.J.; Clausen, K.N.; Lindgård, P-A.

    1990-01-01

    A new ordering vector k=(2π/a)(0, 2/3, 2/3) for fcc antiferromagnets has been found by neutron-diffraction experiments at nanokelvin temperatures in the nuclear-spin system of a 65Cu single crystal. The corresponding reflection together with the previously observed (100) Bragg peak show the prese......A new ordering vector k=(2π/a)(0, 2/3, 2/3) for fcc antiferromagnets has been found by neutron-diffraction experiments at nanokelvin temperatures in the nuclear-spin system of a 65Cu single crystal. The corresponding reflection together with the previously observed (100) Bragg peak show...

  11. Nuclear order in copper

    DEFF Research Database (Denmark)

    Annila, A.J.; Clausen, K.N.; Lindgård, P.-A.

    1990-01-01

    The new antiferromagnetic reflection (02/32/3) has been found by neutron diffraction experiments at nanokelvin temperatures in the nuclear spin system of a 65CU single crystal. The corresponding three-sublattice structure has not been observed previously in any fcc antiferromagnet.......The new antiferromagnetic reflection (02/32/3) has been found by neutron diffraction experiments at nanokelvin temperatures in the nuclear spin system of a 65CU single crystal. The corresponding three-sublattice structure has not been observed previously in any fcc antiferromagnet....

  12. Nuclear safety in perspective

    DEFF Research Database (Denmark)

    Andersson, K.; Sjöberg, B.M.D.; Lauridsen, Kurt

    2003-01-01

    The aim of the NKS/SOS-1 project has been to enhance common understanding about requirements for nuclear safety by finding improved means of communicat-ing on the subject in society. The project, which has been built around a number of seminars, wassupported by limited research in three sub......-projects: Risk assessment Safety analysis Strategies for safety management The report describes an industry in change due to societal factors. The concepts of risk and safety, safety management and systems forregulatory oversight are de-scribed in the nuclear area and also, to widen the perspective, for other...

  13. Particle and nuclear physics

    CERN Document Server

    Faessler, Amand

    1971-01-01

    Progress in Particle and Nuclear Physics, Volume 26 covers the significant advances in understanding the fundamentals of particle and nuclear physics. This volume is divided into four chapters, and begins with a brief overview of the various possible ideas beyond the standard model, the problem they address and their experimental tests. The next chapter deals with the basic physics of neutrino mass based on from a gauge theoretic point of view. This chapter considers the various extensions of the standard electroweak theory, along with their implications for neutrino physics. The discussio

  14. Conformation-specific inhibitors of Raf kinases.

    Science.gov (United States)

    Wang, Xiaolun; Schleicher, Kristin

    2013-01-01

    Since the discovery linking B-Raf mutations to human tumors in 2002, significant advances in the development of Raf inhibitors have been made, leading to the recent approval of two Raf inhibitor drugs. This chapter includes a brief introduction to B-Raf as a validated target and focuses on the three different binding modes observed with Raf small-molecule inhibitors. These various binding modes lock the Raf kinase in different conformations that impact the toxicity profiles of the inhibitors. Possible solutions to mitigate the side effects caused by inhibitor-induced dimerization are also discussed.

  15. A cyclic peptidic serine protease inhibitor

    DEFF Research Database (Denmark)

    Zhao, Baoyu; Xu, Peng; Jiang, Longguang;

    2014-01-01

    Peptides are attracting increasing interest as protease inhibitors. Here, we demonstrate a new inhibitory mechanism and a new type of exosite interactions for a phage-displayed peptide library-derived competitive inhibitor, mupain-1 (CPAYSRYLDC), of the serine protease murine urokinase...... pocket, its carbonyl group aligning improperly relative to Ser195 and the oxyanion hole, explaining why the peptide is an inhibitor rather than a substrate. Substitution of the P1 Arg with novel unnatural Arg analogues with aliphatic or aromatic ring structures led to an increased affinity, depending...... of this peptidic inhibitor, a concept different from conventional attempts at improving inhibitor affinity by reducing the entropic burden....

  16. Security culture for nuclear facilities

    Science.gov (United States)

    Gupta, Deeksha; Bajramovic, Edita

    2017-01-01

    Natural radioactive elements are part of our environment and radioactivity is a natural phenomenon. There are numerous beneficial applications of radioactive elements (radioisotopes) and radiation, starting from power generation to usages in medical, industrial and agriculture applications. But the risk of radiation exposure is always attached to operational workers, the public and the environment. Hence, this risk has to be assessed and controlled. The main goal of safety and security measures is to protect human life, health, and the environment. Currently, nuclear security considerations became essential along with nuclear safety as nuclear facilities are facing rapidly increase in cybersecurity risks. Therefore, prevention and adequate protection of nuclear facilities from cyberattacks is the major task. Historically, nuclear safety is well defined by IAEA guidelines while nuclear security is just gradually being addressed by some new guidance, especially the IAEA Nuclear Security Series (NSS), IEC 62645 and some national regulations. At the overall level, IAEA NSS 7 describes nuclear security as deterrence and detection of, and response to, theft, sabotage, unauthorized access, illegal transfer or other malicious acts involving nuclear, other radioactive substances and their associated facilities. Nuclear security should be included throughout nuclear facilities. Proper implementation of a nuclear security culture leads to staff vigilance and a high level of security posture. Nuclear security also depends on policy makers, regulators, managers, individual employees and members of public. Therefore, proper education and security awareness are essential in keeping nuclear facilities safe and secure.

  17. International nuclear cooperation in Asia

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Yong-Kyu

    1987-01-01

    Nuclear power project traditionally involve huge financial investment, highly sophisticated technology, and long lead time. Many countries, particularly developing ones, find it impossible to implement their nuclear power programs without technical cooperation and assistance from advanced countries. In this Asia and Pacific Region, seven countries have commercial nuclear power units in operation and/or under construction. Korea has six nuclear power units in operation, and three under construction. Active nuclear cooperation has been instrumental in implementing her abmitious nuclear power programs successfully. Nuclear cooperation is one of the widely recognized necessities, which is quite often talked about among the countries of the Asia and Pacific Region. But the differences in nuclear maturity and national interests among those in the region seem to be standing against it. Given the constraints, it is not easy to select appropriate areas for cooperation. There is no doubt, however, that they should include the nuclear policy, nuclear safety, radwaste management, radiological protection, and the management of nuclear units. In order to effectively promote nuclear cooperation in the Region, the scope of RCA activities must be expanded to include the nuclear power area. The Regional Nuclear Data Bank, the Regional Training Center and the Nuclear Emergency Response Center, for example, would be the effective tools for cooperation to meet the demands of the countries in the Region. In view of the technological gap between Japan and all others in the region, we cannot speak of a regional nuclear cooperation without heavily counting on Japan, the most advanced nuclear state in the region. For these reasons, Japan is expected to share an increasing portion of her nuclear technology with others.

  18. Nuclear science and technology

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2014-07-01

    The Program on Nuclear Science and Technology comprehends Nuclear and Condensed Matter Physics, Neutron Activation Analysis, Radiation Metrology, Radioprotection and Radioactive Waste Management. These activities are developed at the Research Reactor Center, the Radiation Metrology Center and the Radioactive Waste Management Laboratory. The Radioprotection activities are developed at all radioactive and nuclear facilities of IPEN-CNEN/SP. The Research Reactor Center at IPEN-CNEN/SP is responsible for the operation and maintenance of the Research Reactor IEA-R1 and has a three-fold mission: promoting basic and applied research in nuclear and neutron related sciences, providing educational opportunities for students in these fields and providing services and applications resulting from the reactor utilization. Specific research programs include nuclear structure study from beta and gamma decay of radioactive nuclei and nuclear reactions, nuclear and neutron metrology, neutron diffraction and neutron multiple-diffraction study for crystalline and magnetic structure determination, perturbed -angular correlation (PAC) using radioactive nuclear probes to study the nuclear hyperfine interactions in solids and instrumental neutron activation analysis, with comparative or ko standardization applied to the fields of health, agriculture, environment, archaeology, reference material production, geology and industry. The research in the areas of applied physics includes neutron radiography, scientific computation and nuclear instrumentation. During the last several years a special effort was made to refurbish the old components and systems of the reactor, particularly those related with the reactor safety improvement, in order to upgrade the reactor power. The primary objective was to modernize the IEA-R1 reactor for safe and sustainable operation to produce primary radioisotopes, such as {sup 99}Mo and {sup 131}I, among several others, used in nuclear medicine, by operating

  19. Effects of ROCK inhibitor Y-27632 on cell fusion through a microslit.

    Science.gov (United States)

    Wada, Ken-Ichi; Hosokawa, Kazuo; Ito, Yoshihiro; Maeda, Mizuo

    2015-11-01

    We previously reported a direct cytoplasmic transfer method using a microfluidic device, in which cell fusion was induced through a microslit (slit-through-fusion) by the Sendai virus envelope (HVJ-E) to prevent nuclear mixing. However, the method was impractical due to low efficiency of slit-through-fusion formation and insufficient prevention of nuclear mixing. The purpose of this study was to establish an efficient method for inducing slit-through-fusion without nuclear mixing. We hypothesized that modulation of cytoskeletal component can decrease nuclear migration through the microslit considering its functions. Here we report that supplementation with Y-27632, a specific ROCK inhibitor, significantly enhances cell fusion induction and prevention of nuclear mixing. Supplementation with Y-27632 increased the formation of slit-through-fusion efficiency by more than twofold. Disruption of F-actin by Y-27632 prevented nuclear migration between fused cells through the microslit. These two effects of Y-27632 led to promotion of the slit-through-fusion without nuclear mixing with a 16.5-fold higher frequency compared to our previous method (i.e., cell fusion induction by HVJ-E without supplementation with Y-27632). We also confirmed that mitochondria were successfully transferred to the fusion partner under conditions of Y-27632 supplementation. These findings demonstrate the practicality of our cell fusion system in producing direct cytoplasmic transfer between live cells.

  20. Inhibitors

    Science.gov (United States)

    ... Project (CHAMP) mutation list: a new online resource. Human Mutation. 2012; E2382-E2392. Li T, Miller CH, Payne AB, Hooper CW. The CDC Hemophilia B mutation project mutation list: a new online resource. Molecular Genetics and Genomic Medicine. 2013; 1(4):238-245. ...

  1. Mechanistic Insights from Structural Analyses of Ran-GTPase-Driven Nuclear Export of Proteins and RNAs.

    Science.gov (United States)

    Matsuura, Yoshiyuki

    2016-05-22

    Understanding how macromolecules are rapidly exchanged between the nucleus and the cytoplasm through nuclear pore complexes is a fundamental problem in biology. Exportins are Ran-GTPase-dependent nuclear transport factors that belong to the karyopherin-β family and mediate nuclear export of a plethora of proteins and RNAs, except for bulk mRNA nuclear export. Exportins bind cargo macromolecules in a Ran-GTP-dependent manner in the nucleus, forming exportin-cargo-Ran-GTP complexes (nuclear export complexes). Transient weak interactions between exportins and nucleoporins containing characteristic FG (phenylalanine-glycine) repeat motifs facilitate nuclear pore complex passage of nuclear export complexes. In the cytoplasm, nuclear export complexes are disassembled, thereby releasing the cargo. GTP hydrolysis by Ran promoted in the cytoplasm makes the disassembly reaction virtually irreversible and provides thermodynamic driving force for the overall export reaction. In the past decade, X-ray crystallography of some of the exportins in various functional states coupled with functional analyses, single-particle electron microscopy, molecular dynamics simulations, and small-angle solution X-ray scattering has provided rich insights into the mechanism of cargo binding and release and also begins to elucidate how exportins interact with the FG repeat motifs. The knowledge gained from structural analyses of nuclear export is being translated into development of clinically useful inhibitors of nuclear export to treat human diseases such as cancer and influenza.

  2. Nuclear power renaissance or demise?

    Energy Technology Data Exchange (ETDEWEB)

    Dossani, Umair

    2010-09-15

    Nuclear power is going through a renaissance or demise is widely debated around the world keeping in mind the facts that there are risks related to nuclear technology and at the same time that is it environmentally friendly. My part of the argument is that there is no better alternative than Nuclear power. Firstly Nuclear Power in comparison to all other alternative fuels is environmentally sustainable. Second Nuclear power at present is at the dawn of a new era with new designs and technologies. Third part of the debate is renovation in the nuclear fuel production, reprocessing and disposal.

  3. Fukushima Nuclear Power Plant Accident and Nuclear Physicists

    Directory of Open Access Journals (Sweden)

    Otsuka Takaharu

    2014-03-01

    Full Text Available I give an overview on the Fukushima Nuclear Power Plant Accident and a report on voluntary activities of Japanese nuclear physicists in this terrible event, including their major outcome.

  4. Nuclear Reactors and Technology

    Energy Technology Data Exchange (ETDEWEB)

    Cason, D.L.; Hicks, S.C. [eds.

    1992-01-01

    This publication Nuclear Reactors and Technology (NRT) announces on a monthly basis the current worldwide information available from the open literature on nuclear reactors and technology, including all aspects of power reactors, components and accessories, fuel elements, control systems, and materials. This publication contains the abstracts of DOE reports, journal articles, conference papers, patents, theses, and monographs added to the Energy Science and Technology Database during the past month. Also included are US information obtained through acquisition programs or interagency agreements and international information obtained through the International Energy Agency`s Energy Technology Data Exchange or government-to-government agreements. The digests in NRT and other citations to information on nuclear reactors back to 1948 are available for online searching and retrieval on the Energy Science and Technology Database and Nuclear Science Abstracts (NSA) database. Current information, added daily to the Energy Science and Technology Database, is available to DOE and its contractors through the DOE Integrated Technical Information System. Customized profiles can be developed to provide current information to meet each user`s needs.

  5. Nuclear Magnetic Resonance Gyroscope

    Science.gov (United States)

    Larsen, Michael; Griffith, Robert; Bulatowicz, Michael

    2014-03-01

    The navigation grade micro Nuclear Magnetic Resonance Gyroscope (micro-NMRG) being developed by the Northrop Grumman Corporation (NGC) has concluded the fourth and final phase of the DARPA Navigation Grade Integrated Micro Gyro (NGIMG) program. Traditional MEMS gyros utilize springs as an inherent part of the sensing mechanism, leading to bias and scale factor sensitivity to acceleration and vibration. As a result, they have not met performance expectations in real world environments and to date have been limited to tactical grade applications. The Nuclear Magnetic Resonance Gyroscope (NMRG) utilizes the fixed precession rate of a nuclear spin in a constant magnetic field as an inertial reference for determining rotation. The nuclear spin precession rate sensitivity to acceleration and vibration is negligible for most applications. Therefore, the application of new micro and batch fabrication methods to NMRG technology holds great promise for navigation grade performance in a low cost and compact gyro. This presentation will describe the operational principles, design basics, and demonstrated performance of the NMRG including an overview of the NGC designs developed and demonstrated in the DARPA gyro development program.

  6. Lasers with nuclear pumping

    CERN Document Server

    Melnikov, S P; Sizov, A N; Miley, George H

    2015-01-01

    This book covers the history of lasers with nuclear pumping (Nuclear Pumped Lasers, NPLs). This book showcases the most important results and stages of NPL development in The Russian Federal Nuclear Center (VNIIEF) as well as other Russian and international laboratories, including laboratories in the United States. The basic science and technology behind NPLs along with potential applications are covered throughout the book. As such, this book: ·         Contains a historical overview of the extensive information developed over the past 40 years of work on NPLs ·         Covers the most important results and stages of NPL development, not just in the Russian Federal Nuclear Center, VNIIEF, but also in other laboratories in Russia, the United States , and some other scattered international laboratories ·         Systematizes the fragmented information accumulated over these years of very active research and development As the first comprehensive discussion of NPLs, students, research...

  7. Topics in nuclear power

    Science.gov (United States)

    Budnitz, Robert J.

    2015-03-01

    The 101 nuclear plants operating in the US today are far safer than they were 20-30 years ago. For example, there's been about a 100-fold reduction in the occurrence of "significant events" since the late 1970s. Although the youngest of currently operating US plants was designed in the 1970s, all have been significantly modified over the years. Key contributors to the safety gains are a vigilant culture, much improved equipment reliability, greatly improved training of operators and maintenance workers, worldwide sharing of experience, and the effective use of probabilistic risk assessment. Several manufacturers have submitted high quality new designs for large reactors to the U.S. Nuclear Regulatory Commission (NRC) for design approval, and several companies are vigorously working on designs for smaller, modular reactors. Although the Fukushima reactor accident in March 2011 in Japan has been an almost unmitigated disaster for the local population due to their being displaced from their homes and workplaces and also due to the land contamination, its "lessons learned" have been important for the broader nuclear industry, and will surely result in safer nuclear plants worldwide - indeed, have already done so, with more safety improvements to come.

  8. Nuclear lattice simulations

    Directory of Open Access Journals (Sweden)

    Epelbaum E.

    2010-04-01

    Full Text Available We review recent progress on nuclear lattice simulations using chiral effective field theory. We discuss lattice results for dilute neutron matter at next-to-leading order, three-body forces at next-to-next-toleading order, isospin-breaking and Coulomb effects, and the binding energy of light nuclei.

  9. The nuclear symmetry energy

    NARCIS (Netherlands)

    Dieperink, AEL; van Neck, D; Suzuki, T; Otsuka, T; Ichimura, M

    2005-01-01

    The role of isospin asymmetry in nuclei and neutron stars is discussed, with an emphasis on the density dependence of the nuclear symmetry energy. Results obtained with the self-consistent Green function method are presented and compared with various other theoretical predictions. Implications for t

  10. Detecting Illicit Nuclear Materials

    Energy Technology Data Exchange (ETDEWEB)

    Kouzes, Richard T.

    2005-09-01

    The threat that weapons of mass destruction might enter the United States has led to a number of efforts for the detection and interdiction of nuclear, radiological, chemical, and biological weapons at our borders. There have been multiple deployments of instrumentation to detect radiation signatures to interdict radiological material, including weapons and weapons material worldwide.

  11. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... like? Special camera or imaging devices used in nuclear medicine include the gamma camera and single-photon emission-computed tomography (SPECT). The gamma camera, also called a scintillation camera, detects radioactive energy that is emitted from the patient's body and ...

  12. Space Nuclear Reactor Engineering

    Energy Technology Data Exchange (ETDEWEB)

    Poston, David Irvin [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-03-06

    We needed to find a space reactor concept that could be attractive to NASA for flight and proven with a rapid turnaround, low-cost nuclear test. Heat-pipe-cooled reactors coupled to Stirling engines long identified as the easiest path to near-term, low-cost concept.

  13. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... diagnoses. In addition, manufacturers are now making single photon emission computed tomography/computed tomography (SPECT/CT) and ... nuclear medicine include the gamma camera and single-photon emission-computed tomography (SPECT). The gamma camera, also ...

  14. JPRS Report Nuclear Developments

    Science.gov (United States)

    2007-11-02

    Text] Furnas Chairman Camilo Pena has said the operation of the Angra I nuclear plant has been delayed once again. Furnas is suing the American...Westinghouse company and is demanding compensation for damages caused by a malfunction in the Angra I power generator. According to Camilo Pena, Angra I

  15. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... exams at the same time. An emerging imaging technology, but not readily available at this time is PET/MRI. top of page What are some common uses of the procedure? Children's (pediatric) nuclear medicine imaging is performed to help diagnose childhood disorders ...

  16. Second Nuclear Era

    Energy Technology Data Exchange (ETDEWEB)

    Weinberg, A.M.; Spiewak, I.; Barkenbus, J.N.; Livingston, R.S.; Phung, D.L.

    1984-03-01

    The Institute for Energy Analysis with support from The Andrew W. Mellon Foundation has studied the decline of the present nuclear era in the United States and the characteristics of a Second Nuclear Era which might be instrumental in restoring nuclear power to an appropriate place in the energy options of our country. The study has determined that reactors operating today are much safer than they were at the time of the TMI accident. A number of concepts for a supersafe reactor were reviewed and at least two were found that show considerable promise, the PIUS, a Swedish pressurized water design, and a gas-cooled modular design of German and US origin. Although new, safer, incrementally improved, conventional reactors are under study by the nuclear industry, the complete lack of new orders in the United States will slow their introduction and they are likely to be more expensive than present designs. The study recommends that supersafe reactors be taken seriously and that federal and private funds both be used to design and, if feasible, to build a prototype reactor of substantial size. 146 references, 8 figures, 2 tables.

  17. Chiral nuclear thermodynamics

    CERN Document Server

    Fiorilla, Salvatore; Weise, Wolfram

    2011-01-01

    We calculate the equation of state of nuclear matter for arbitrary isospin-asymmetry up to three loop order in the free energy density in the framework of in-medium chiral perturbation theory. In our approach 1\\pi- and 2\\pi-exchange dynamics with the inclusion of the \\Delta-isobar excitation as an explicit degree of freedom, corresponding to the long- and intermediate-range correlations, are treated explicitly. Few contact terms fixed to reproduce selected known properties of nuclear matter encode the short-distance physics. Two-body as well as three-body forces are systematically included. We find a critical temperature of about 15 MeV for symmetric nuclear matter. We investigate the dependence of the liquid-gas first-order phase transition on isospin-asymmetry. In the same chiral framework we calculate the chiral condensate of isospin-symmetric nuclear matter at finite temperatures. The contribution of the \\Delta-isobar excitation is essential for stabilizing the condensate. As a result, we find no indicati...

  18. Reducing The Nuclear Danger

    Science.gov (United States)

    1995-10-01

    Conference on Disarmament - Ambassadors tour the Hanford Site (October 1994) - Pacific Northwest - Ensuring effective international nuclear safeguards...requirements of a CTBT by seismic , hydroacoustic and satellite instrumentation capabilities. - Initiation of Project CALIOPE, which is intended to...N excess fissle materials at Hanford for placement under IAEA | National Lab || safeguards. Additionally, develop tutorials on the IAEA I

  19. Politics of nuclear waste

    Energy Technology Data Exchange (ETDEWEB)

    Colglazier, E.W. Jr. (eds.)

    1982-01-01

    In November of 1979, the Program in Science, Technology and Humanism and the Energy Committee of the Aspen Institute organized a conference on resolving the social, political, and institutional conflicts over the permanent siting of radioactive wastes. This book was written as a result of this conference. The chapters provide a comprehensive and up-to-date overview of the governance issues connected with radioactive waste management as well as a sampling of the diverse views of the interested parties. Chapter 1 looks in depth of radioactive waste management in the United States, with special emphasis on the events of the Carter Administration as well as on the issues with which the Reagen administration must deal. Chapter 2 compares waste management policies and programs among the industralized countries. Chapter 3 examines the factional controversies in the last administration and Congress over nuclear waste issues. Chapter 4 examines the complex legal questions involved in the federal-state conflicts over nuclear waste management. Chapter 5 examines the concept of consultation and concurrence from the perspectives of a host state that is a candidate for a repository and an interested state that has special concerns regarding the demonstration of nuclear waste disposal technology. Chapter 6 examines US and European perspectives concerning public participation in nuclear waste management. Chapter 7 discusses propaganda in the issues. The epilogue attempts to assess the prospects for consensus in the United States on national policies for radioactive waste management. All of the chapter in this book should be interpreted as personal assessments. (DP)

  20. Preserving Nuclear Grade Knowledge

    Energy Technology Data Exchange (ETDEWEB)

    Lange, Bob

    2008-02-05

    When people think of the government they think of the President, or Congress, or the Internal Revenue Service (IRS), but there are thousands of people in government-related jobs doing things most don’t really notice everyday. You can find them everywhere, from the space science folks at NASA, to the Federal Bureau of Investigations (FBI) watching out for the bad guys. There are Rangers, and Social Workers, Nurses and Agricultural Managers. They are people working to keep the many facets of the USA rolling. One very diverse bunch is The Department of Energy (DOE) , a group who is expanding the ways we make and save energy to power our cars, homes, and businesses. Tucked away under the DOE is the National Nuclear Security Administration, the NNSA is an agency that maintains the safety, security, and reliability of the U.S. nuclear weapons stockpile. It works to reduce global danger from weapons of mass destruction. It provides the U.S. Navy with safe nuclear propulsion, and it responds to nuclear and radiological emergencies in the United States and abroad, and it supports efforts in science and technology*. (* DOE/NNSA/KCP website info)

  1. Nuclear lamins and neurobiology.

    Science.gov (United States)

    Young, Stephen G; Jung, Hea-Jin; Lee, John M; Fong, Loren G

    2014-08-01

    Much of the work on nuclear lamins during the past 15 years has focused on mutations in LMNA (the gene for prelamin A and lamin C) that cause particular muscular dystrophy, cardiomyopathy, partial lipodystrophy, and progeroid syndromes. These disorders, often called "laminopathies," mainly affect mesenchymal tissues (e.g., striated muscle, bone, and fibrous tissue). Recently, however, a series of papers have identified important roles for nuclear lamins in the central nervous system. Studies of knockout mice uncovered a key role for B-type lamins (lamins B1 and B2) in neuronal migration in the developing brain. Also, duplications of LMNB1 (the gene for lamin B1) have been shown to cause autosome-dominant leukodystrophy. Finally, recent studies have uncovered a peculiar pattern of nuclear lamin expression in the brain. Lamin C transcripts are present at high levels in the brain, but prelamin A expression levels are very low-due to regulation of prelamin A transcripts by microRNA 9. This form of prelamin A regulation likely explains why "prelamin A diseases" such as Hutchinson-Gilford progeria syndrome spare the central nervous system. In this review, we summarize recent progress in elucidating links between nuclear lamins and neurobiology.

  2. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... Most nuclear medicine exams will involve an injection in a vein in your child’s arm or hand. Your child should ... body, they offer the potential to identify disease in its earliest stages as well as a patient’s ...

  3. Teaching About Nuclear War.

    Science.gov (United States)

    Chavez, Linda

    1983-01-01

    Accuses the National Education Association (NEA) of encouraging its teacher-members to indoctrinate children on the benefits of a nuclear freeze. Holds that a new study guide, produced by the Union of Concerned Scientists in conjunction with the NEA, is political propaganda. (GC)

  4. Nuclear motion is classical

    CERN Document Server

    Frank, Irmgard

    2016-01-01

    The notion from ab-initio molecular dynamics simulations that nuclear motion is best described by classical Newton dynamics instead of the time-dependent Schr{\\"o}dinger equation is substantiated. In principle a single experiment should bring clarity. Caution is however necessary, as temperature dependent effects must be eliminated when trying to determine the existence of a zero-point energy.

  5. Meeting report: nuclear receptors

    DEFF Research Database (Denmark)

    Tuckermann, Jan; Bourguet, William; Mandrup, Susanne

    2010-01-01

    The biannual European Molecular Biology Organization (EMBO) conference on nuclear receptors was organized by Beatrice Desvergne and Laszlo Nagy and took place in Cavtat near Dubrovnik on the Adriatic coast of Croatia September 25-29, 2009. The meeting brought together researchers from all over...

  6. Nuclear weapons in Europe

    CERN Document Server

    Calogero, F

    1981-01-01

    Information speech given by Prof. Calogero from the university of Roma to describe the actual situation of nuclear weapons in Europe, the strategical reasons or justifications for this deployment, the prospects of negociations, and what scientists could do and do on this issue.

  7. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... pictures and provides molecular information. In many centers, nuclear medicine images can be superimposed with computed tomography (CT) or magnetic resonance imaging (MRI) to produce special views, a practice known as image fusion or co-registration. These views allow the information ...

  8. Elements of nuclear safety

    CERN Document Server

    Libmann, Jacques

    1996-01-01

    This basically educational book is intended for all involved in nuclear facility safety. It dissects the principles and experiences conducive to the adoption of attitudes compliant with what is now known as "safety culture". This book is accessible to a wide range of readers.

  9. Nuclear Security Futures Scenarios.

    Energy Technology Data Exchange (ETDEWEB)

    Keller, Elizabeth James Kistin [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Warren, Drake Edward [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Hayden, Nancy Kay [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Passell, Howard D. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Malczynski, Leonard A. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Backus, George A. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2017-01-01

    This report provides an overview of the scenarios used in strategic futures workshops conducted at Sandia on September 21 and 29, 2016. The workshops, designed and facilitated by analysts in Center 100, used scenarios to enable thought leaders to think collectively about the changing aspects of global nuclear security and the potential implications for the US Government and Sandia National Laboratories.

  10. Symmetries in nuclear structure

    CERN Document Server

    Allaart, K; Dieperink, A

    1983-01-01

    The 1982 summer school on nuclear physics, organized by the Nuclear Physics Division of the Netherlands' Physical Society, was the fifth in a series that started in 1963. The number of students attending has always been about one hundred, coming from about thirty countries. The theme of this year's school was symmetry in nuclear physics. This book covers the material presented by the enthusi­ astic speakers, who were invited to lecture on this subject. We think they have succeeded in presenting us with clear and thorough introductory talks at graduate or higher level. The time schedule of the school and the location allowed the participants to make many informal contacts during many social activities, ranging from billiards to surf board sailing. We hope and expect that the combination of a relaxed atmosphere during part of the time and hard work during most of the time, has furthered the interest in, and understanding of, nuclear physics. The organization of the summer school was made possible by substantia...

  11. Controlled Nuclear Fusion.

    Science.gov (United States)

    Glasstone, Samuel

    This publication is one of a series of information booklets for the general public published by The United States Atomic Energy Commission. Among the topics discussed are: Importance of Fusion Energy; Conditions for Nuclear Fusion; Thermonuclear Reactions in Plasmas; Plasma Confinement by Magnetic Fields; Experiments With Plasmas; High-Temperature…

  12. Subcritical nuclear assembly

    Energy Technology Data Exchange (ETDEWEB)

    Vega C, H. R., E-mail: fermineutron@yahoo.com [Universidad Autonoma de Zacatecas, Unidad Academica de Estudios Nucleares, Cipres No. 10, Fracc. La Penuela, 98068 Zacatecas (Mexico)

    2014-08-15

    A Subcritical Nuclear Assembly is a device where the nuclear-fission chain reaction is initiated and maintained using an external neutron source. It is a valuable educational and research tool where in a safe way many reactor parameters can be measured. Here, we have used the Wigner-Seitz method in the six-factor formula to calculate the effective multiplication factor of a subcritical nuclear reactor Nuclear Chicago model 9000. This reactor has approximately 2500 kg of natural uranium heterogeneously distributed in slugs. The reactor uses a {sup 239}PuBe neutron source that is located in the center of an hexagonal array. Using Monte Carlo methods, with the MCNP5 code, a three-dimensional model of the subcritical reactor was designed to estimate the effective multiplication factor, the neutron spectra, the total and thermal neutron fluences along the radial and axial axis. With the neutron spectra in two locations outside the reactor the ambient dose equivalent were estimated. (Author)

  13. Minimum Nuclear Deterrence Research

    Science.gov (United States)

    2003-05-15

    délivrer une frappe d’ultime avertissement sur des objectifs navals ou terrestres ." The translation is the SAIC author’s. Projet de loi de finances... orbit .”75 As China’s nuclear force posture has changed, so too have the assigned targets. For example, the DF-2 was initially based to target Japan

  14. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... The special camera and imaging techniques used in nuclear medicine include the gamma camera and single-photon emission-computed tomography (SPECT). The gamma camera, also called a scintillation camera, detects radioactive energy that is emitted from the patient's body and ...

  15. Pakistans Nuclear Weapons

    Science.gov (United States)

    2016-02-12

    Memorandum from Air Commodore Khalid Banuri, 2011. 84 Mahmud Ali Durrani, “Pakistan’s Strategic Thinking and the Role of Nuclear Weapons...Richard P. Cronin , K. Alan Kronstadt, and Sharon Squassoni. Also see CRS Report RL33498, Pakistan-U.S. Relations, by K. Alan Kronstadt. 168 For a

  16. Effect of inhibitors of cellular metabolism on postradiation repair and degradation of DNA in rat thymocytes

    Energy Technology Data Exchange (ETDEWEB)

    Ivannik, B.P.; Golubeva, R.V.; Proskuryakov, S.Ya.; Murzaev, V.I.; Ryabchenko, N.I.

    1979-10-01

    The viscosimetric method was used to determine the molecular weight of high polymer single-stranded DNA in alkaline nuclear lysates for the study of the effects of a number of inhibitors of synthesis of DNA (hydroxyurea), macroergic elements (2,4-dinitrophenol, EDTA) and DNAase (Na/sup +/ citrate, Ca/sup + +/ ions) on the process of repair and secondary post-radiation degradation of DNA of rat thymocytes exposed to radiation in a dosage of 3 kR.

  17. Nuclear Fuel Reprocessing

    Energy Technology Data Exchange (ETDEWEB)

    Harold F. McFarlane; Terry Todd

    2013-11-01

    Reprocessing is essential to closing nuclear fuel cycle. Natural uranium contains only 0.7 percent 235U, the fissile (see glossary for technical terms) isotope that produces most of the fission energy in a nuclear power plant. Prior to being used in commercial nuclear fuel, uranium is typically enriched to 3–5% in 235U. If the enrichment process discards depleted uranium at 0.2 percent 235U, it takes more than seven tonnes of uranium feed to produce one tonne of 4%-enriched uranium. Nuclear fuel discharged at the end of its economic lifetime contains less one percent 235U, but still more than the natural ore. Less than one percent of the uranium that enters the fuel cycle is actually used in a single pass through the reactor. The other naturally occurring isotope, 238U, directly contributes in a minor way to power generation. However, its main role is to transmute into plutoniumby neutron capture and subsequent radioactive decay of unstable uraniumand neptuniumisotopes. 239Pu and 241Pu are fissile isotopes that produce more than 40% of the fission energy in commercially deployed reactors. It is recovery of the plutonium (and to a lesser extent the uranium) for use in recycled nuclear fuel that has been the primary focus of commercial reprocessing. Uraniumtargets irradiated in special purpose reactors are also reprocessed to obtain the fission product 99Mo, the parent isotope of technetium, which is widely used inmedical procedures. Among the fission products, recovery of such expensive metals as platinum and rhodium is technically achievable, but not economically viable in current market and regulatory conditions. During the past 60 years, many different techniques for reprocessing used nuclear fuel have been proposed and tested in the laboratory. However, commercial reprocessing has been implemented along a single line of aqueous solvent extraction technology called plutonium uranium reduction extraction process (PUREX). Similarly, hundreds of types of reactor

  18. Safety culture in the nuclear versus non-nuclear organization

    Energy Technology Data Exchange (ETDEWEB)

    Haber, S.B.; Shurberg, D.A.

    1996-10-01

    The importance of safety culture in the safe and reliable operation of nuclear organizations is not a new concept. The greatest barriers to this area of research are twofold: (1) the definition and criteria of safety culture for a nuclear organization and (2) the measurement of those attributes in an objective and systematic fashion. This paper will discuss a proposed resolution of those barriers as demonstrated by the collection of data across nuclear and non-nuclear facilities over a two year period.

  19. Current Situation of International Nuclear Arms Control and Nuclear Disarmament

    Institute of Scientific and Technical Information of China (English)

    Gong; Xianfu

    2014-01-01

    <正>Currently,international nuclear arms control and nuclear disarmament process is showing both encouraging and frustrating signs,with a stress on the latter.The following is a general picture:First,the new U.S.-Russian nuclear disarmament process faces challenges and prospect of a new round of nuclear disarmament negotiation is grim.As a result of implementing the New START signed in February 2011,as of March 1,2014,the United States has 1585

  20. Chinese Nuclear Science Basic Data Base (CNSBDB)

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    A new research project on "Development of the Chinese Nuclear Science Basic Database (CNSBDB)for Fundamental Researches of Nuclear Physics and Interrelated Subjects, and Requirements of NuclearPower and Nuclear Technologies Application" has been commenced. The CNSBDB contains thefollowing eight segments: 1) Information on Nuclear Science (INFO); 2) Nuclear Structure Data Base(NSDB); 3) Nuclear Decay Data Base (NDDB); 4) Nuclear Reaction Data Base (NRDB); 5) Nuclear

  1. Nuclear material detection techniques

    Science.gov (United States)

    Christian, James F.; Sia, Radia; Dokhale, Purushottam; Shestakova, Irina; Nagarkar, Vivek; Shah, Kanai; Johnson, Erik B.; Stapels, Christopher J.; Ryan, James M.; Macri, John; Bravar, Ulisse; Leung, Ka-Ngo; Squillante, Michael R.

    2008-04-01

    Illicit nuclear materials represent a threat for the safety of the American citizens, and the detection and interdiction of a nuclear weapon is a national problem that has not been yet solved. Alleviating this threat represents an enormous challenge to current detection methods that have to be substantially improved to identify and discriminate threatening from benign incidents. Rugged, low-power and less-expensive radiation detectors and imagers are needed for large-scale wireless deployment. Detecting the gamma rays emitted by nuclear and fissionable materials, particularly special nuclear materials (SNM), is the most convenient way to identify and locate them. While there are detectors that have the necessary sensitivity, none are suitable to meet the present need, primarily because of the high occurrence of false alarms. The exploitation of neutron signatures represents a promising solution to detecting illicit nuclear materials. This work presents the development of several detector configurations such as a mobile active interrogation system based on a compact RF-Plasma neutron generator developed at LBNL and a fast neutron telescope that uses plastic scintillating-fibers developed at the University of New Hampshire. A human-portable improved Solid-State Neutron Detector (SSND) intended to replace pressurized 3He-tubes will be also presented. The SSND uses an ultra-compact CMOS-SSPM (Solid-State Photomultiplier) detector, developed at Radiation Monitoring devices Inc., coupled to a neutron sensitive scintillator. The detector is very fast and can provide time and spectroscopy information over a wide energy range including fast neutrons.

  2. Risks from nuclear waste

    Energy Technology Data Exchange (ETDEWEB)

    Liljenzin, J.O.; Rydberg, J. [Radiochemistry Consultant Group, Vaestra Froelunda (Sweden)

    1996-11-01

    The first part of this review discusses the importance of risk. If there is any relation between the emotional and rational risk perceptions (for example, it is believed that increased knowledge will decrease emotions), it will be a desirable goal for society, and the nuclear industry in particular, to improve the understanding by the laymen of the rational risks from nuclear energy. This review surveys various paths to a more common comprehension - perhaps a consensus - of the nuclear waste risks. The second part discusses radioactivity as a risk factor and concludes that it has no relation in itself to risk, but must be connected to exposure leading to a dose risk, i.e. a health detriment, which is commonly expressed in terms of cancer induction rate. Dose-effect relations are discussed in light of recent scientific debate. The third part of the report describes a number of hazard indexes for nuclear waste found in the literature and distinguishes between absolute and relative risk scales. The absolute risks as well as the relative risks have changed over time due to changes in radiological and metabolic data and by changes in the mode of calculation. To judge from the literature, the risk discussion is huge, even when it is limited to nuclear waste. It would be very difficult to make a comprehensive review and extract the essentials from that. Therefore, we have chosen to select some publications, out of the over 100, which we summarize rather comprehensively; in some cases we also include our remarks. 110 refs, 22 figs.

  3. Condensed Matter Nuclear Science

    Science.gov (United States)

    Biberian, Jean-Paul

    2006-02-01

    1. General. A tribute to gene Mallove - the "Genie" reactor / K. Wallace and R. Stringham. An update of LENR for ICCF-11 (short course, 10/31/04) / E. Storms. New physical effects in metal deuterides / P. L. Hagelstein ... [et al.]. Reproducibility, controllability, and optimization of LENR experiments / D. J. Nagel -- 2. Experiments. Electrochemistry. Evidence of electromagnetic radiation from Ni-H systems / S. Focardi ... [et al.]. Superwave reality / I. Dardik. Excess heat in electrolysis experiments at energetics technologies / I. Dardik ... [et al.]. "Excess heat" during electrolysis in platinum/K[symbol]CO[symbol]/nickel light water system / J. Tian ... [et al.]. Innovative procedure for the, in situ, measurement of the resistive thermal coefficient of H(D)/Pd during electrolysis; cross-comparison of new elements detected in the Th-Hg-Pd-D(H) electrolytic cells / F. Celani ... [et al.]. Emergence of a high-temperature superconductivity in hydrogen cycled Pd compounds as an evidence for superstoihiometric H/D sites / A. Lipson ... [et al.]. Plasma electrolysis. Calorimetry of energy-efficient glow discharge - apparatus design and calibration / T. B. Benson and T. O. Passell. Generation of heat and products during plasma electrolysis / T. Mizuno ... [et al.]. Glow discharge. Excess heat production in Pd/D during periodic pulse discharge current in various conditions / A. B. Karabut. Beam experiments. Accelerator experiments and theoretical models for the electron screening effect in metallic environments / A. Huke, K. Czerski, and P. Heide. Evidence for a target-material dependence of the neutron-proton branching ratio in d+d reactions for deuteron energies below 20keV / A. Huke ... [et al.]. Experiments on condensed matter nuclear events in Kobe University / T. Minari ... [et al.]. Electron screening constraints for the cold fusion / K. Czerski, P. Heide, and A. Huke. Cavitation. Low mass 1.6 MHz sonofusion reactor / R. Stringham. Particle detection. Research

  4. Frontiers in nuclear medicine symposium: Nuclear medicine & molecular biology

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-04-01

    This document contains the abstracts from the American College of Nuclear Physicians 1993 Fall Meeting entitled, `Frontiers in Nuclear Medicine Symposium: Nuclear Medicine and Molecular Biology`. This meeting was sponsored by the US DOE, Office of Health and Environmental Research, Office of Energy Research. The program chairman was Richard C. Reba, M.D.

  5. A Novel Hydrazinecarbothioamide as a Potential Corrosion Inhibitor for Mild Steel in HCl

    Directory of Open Access Journals (Sweden)

    Abu Bakar Mohamad

    2013-04-01

    Full Text Available 2-(1-methyl-4-((E-(2-methylbenzylideneamino-2-phenyl-1H-pyrazol-3(2H-ylidene-hydrazineecarbothioamide (HCB was synthesized as a corrosion inhibitor from the reaction of 4-aminoantipyrine, thiosemicarbazide and 2-methylbenzaldehyde. The corrosion inhibitory effects of HCB on mild steel in 1.0 M HCl were investigated using potentiodynamic polarization (PDP and electrochemical impedance spectroscopy (EIS. The results showed that HCB inhibited mild steel corrosion in acidic solution and inhibition efficiency increased with an increase in the concentration of the inhibitor. The inhibition efficiency was up to 96.5% at 5.0 mM. Changes in the impedance parameters suggested that HCB adsorbed on the surface of mild steel, leading to the formation of a protective film. The novel corrosion inhibitor synthesized in the present study was characterized using Fourier transform infrared spectroscopy (FTIR and nuclear magnetic resonance (NMR spectral data.

  6. Deacetylase inhibitors-focus on non-histone targets and effects

    Institute of Scientific and Technical Information of China (English)

    Matthias; Ocker

    2010-01-01

    Inhibitors of protein deacetylases have recently been established as a novel therapeutic principle for several human diseases,including cancer.The original notion of the mechanism of action of these compounds focused on the epigenetic control of transcriptional processes, especially of tumor suppressor genes,by interfering with the acetylation status of nuclear histone proteins,hence the name histone deacetylase inhibitors was coined.Yet,this view could not explain the high specificity for tumor cells and recent evidence now suggests that non-histone proteins represent major targets for protein deacetylase inhibitors and that the post-translational modification of the acetylome is involved in various cellular processes of differentiation,survival and cell death induction.

  7. The effect of nanoparticle size and NLS density on nuclear targeting in cancer and normal cells; impaired nuclear import and aberrant nanoparticle intracellular trafficking in glioma.

    Science.gov (United States)

    Tammam, Salma N; Azzazy, Hassan M E; Lamprecht, Alf

    2017-02-27

    The cell nucleus is an interesting target in many diseases with particular interest in cancer. Previously, nuclear targeted small and large chitosan nanoparticles (S-NPs≈25nm, and L-NPs≈150nm respectively), modified with low, intermediate and high densities of NLS (L-NLS, I-NLS and H-NLS) were developed and assessed in L929 fibroblasts. However, to evade apoptosis and stimulate tumor growth cancer cells are capable of manipulating the nuclear-cytoplasmic transport on many levels, making NPs that are capable of nuclear targeting in normal cells incapable of doing so in cancer. For such reason, here, the nuclear delivery efficiency of S-NPs and L-NPs was assessed as a function of their NLS density in cancer and non-cancer cells. For S-NPs, in all cells tested, NLS was unnecessary for nuclear delivery; unmodified S-NPs showed higher nuclear delivery than NLS-S-NPs due to their ability to gain nuclear entry in a passive manner. For L-NPs, L-NLS-L-NPs showed ≈ 8.5, 33, 1.8 and 7.2 fold higher nuclear deliveries than H-NLS-L-NPs in L929 fibroblasts, primary human fibroblasts, HEK 293 and lung cancer cells, respectively. In glioma however, unmodified L-NPs showed highest nuclear delivery, whereas NLS-L-NPs were retained in the cytoplasm. Experiments conducted in the presence of inhibitors of the classical nuclear import pathway indicated that due to overexpression of importin α, classical nuclear import in glioma is impaired leading to aberrant NP intracellular trafficking and nuclear import.

  8. Adventures in scientific nuclear diplomacy

    Science.gov (United States)

    Hecker, Siegfried S.

    2014-05-01

    A former director of Los Alamos National Laboratory offers a first-person perspective on the important contributions scientists can make toward improving the safety and security of nuclear materials and reducing the global nuclear dangers in an evolving world.

  9. An introduction to nuclear physics

    CERN Document Server

    Jana, Yatramohan

    2015-01-01

    AN INTRODUCTION TO NUCLEAR PHYSICS explores the nucleus - its size, shape and structure, its static and dynamic properties, its interaction with external system (particles and radiation), and above all the nuclear interaction in the two-nucleon and many-nucleon systems. It covers all aspects of the nucleus, divided into five Parts and nineteen Chapters. Part-1 introduces nuclear binding energy, separation energy and nuclear stability. Part-2 explores the two-nucleon potential through the study of the deuteron problem, nucleon-nucleon scattering, and also presents a meson theoretical description of the nuclear potential. Part-3 deals with the nuclear structure through different models, e.g., liquid-drop model, Fermi gas model, nuclear shell model, collective model. Part-4 develops different theoretical models for nuclear reactions, e.g., compound nucleus, statistical model, continuum model, optical model, direct reaction mechanism.

  10. Adventures in scientific nuclear diplomacy

    Energy Technology Data Exchange (ETDEWEB)

    Hecker, Siegfried S. [Center for International Security and Cooperation, Stanford University, Stanford, California (United States)

    2014-05-09

    A former director of Los Alamos National Laboratory offers a first-person perspective on the important contributions scientists can make toward improving the safety and security of nuclear materials and reducing the global nuclear dangers in an evolving world.

  11. Psychoanalysis and the nuclear threat

    Energy Technology Data Exchange (ETDEWEB)

    Levine, H.B.; Jacobs, D.; Rubin, L.J.

    1988-01-01

    {ital Psychoanalysis and the Nuclear Threat} provides coverage of the dynamic and clinical considerations that follow from life in the nuclear age. Of special clinical interest are chapters dealing with the developmental consequences of the nuclear threat in childhood, adolescence, and adulthood, and those exploring the technical issues raised by the occurrence in analytic and psychotherapeutic hours of material related to the nuclear threat. Additional chapters bring a psychoanalytic perspective to bear on such issues as the need to have enemies, silence as the real crime, love, work, and survival in the nuclear age, the relationship of the nuclear threat to issues of mourning and melancholia, apocalyptic fantasies, the paranoid process, considerations of the possible impact of gender on the nuclear threat, and the application of psychoanalytic thinking to nuclear arms strategy. Finally, the volume includes the first case report in the English language---albeit a brief psychotherapy---involving the treatment of a Hiroshima survivor.

  12. Your Radiologist Explains Nuclear Medicine

    Medline Plus

    Full Text Available ... I-131 Therapy Radiology and You Sponsored by Image/Video Gallery Your Radiologist Explains Nuclear Medicine Transcript ... an accurate diagnosis far outweighs any risk. To learn more about nuclear medicine, visit Radiology Info dot ...

  13. Your Radiologist Explains Nuclear Medicine

    Medline Plus

    Full Text Available ... stage, often before symptoms occur or before abnormalities can be detected with other diagnostic tests. Nuclear medicine ... nuclear medicine exam, there are several things you can do to prepare. First, you may be asked ...

  14. Ultrastructural evidence for differentiation in a human glioblastoma cell line treated with inhibitors of eicosanoid metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, D.E.; Anderson, K.M. (Rush Presbyterian St. Luke' s Medical Center, Chicago, IL (United States)); Seed, T.M. (Argonne National Lab., IL (United States))

    1990-01-01

    Human glioblastoma cells incubated in the presence of inhibitors of eicosanoid biosynthesis show decreased cellular proliferation without cytotoxicity. The authors studied the ultrastructural morphology of a human glioblastoma cell line cultured with nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor, or 5,8,11,14-eicosatetraynoic acid, a cyclooxygenase and lipoxygenase inhibitor. When glioblastoma cells were treated for 3 days with antiproliferative concentrations of either agent, they shared many morphological characteristics, including evidence for increased astrocytic differentiation with only limited signs of toxicity. The inhibited glioma cells demonstrated an increase in the number and length of astrocytic processes containing greater numbers of glial filaments, and the NDGA-treated cells also demonstrated extensive lateral pseudopod formation along the processes. The glioblastoma cell shape also become more elongated, losing the usual nuclear lobularity and nuclear inclusions, especially in NDGA-treated cells. Many cytoplasmic organelles packed the cytosol of the inhibited glioma cells, including prominent Golgi apparatus, dilated smooth endoplasmic reticulum evolving into dilated vesicles, cytoplasmic vacuoles, and numerous concentric laminations. There was limited evidence for toxicity, however, as the mitochondria were more pleomorphic with some mitochondrial distension and disruption of the cristae along with an increase in cytoplasmic vacuolization. The authors conclude that the inhibitors of eicosanoid biosynthesis. NDGA and 5,8,11,14-eicosatetraynoic acid, not only suppress glioblastoma cell proliferation, but also include increased astrocytic differentiation.

  15. Tissue factor pathway inhibitor endocytosis.

    Science.gov (United States)

    Schwartz, A L; Broze, G J

    1997-10-01

    Tissue factor pathway inhibitor (TFPI), a 42 kD protein, provides the physiological inhibition of tissue factor initiated coagulation by inhibition of both factor Xa and factor VIIa/tissue factor. In plasma, most TFPI is lipoprotein bound with an additional "releasable" pool bound to the endothelial cell surface. TFPI clearance is via receptor mediated endocytosis into liver. Heparin sulfate proteoglycans and LRP (low density lipoprotein receptor-related protein), an extremely large (∼600 kD) cell surface protein, primarily mediate this clearance, although additional TFPI binding sites and endocytosis pathways exist. (Trends Cardiovasc Med 1997; 7:234-239). © 1997, Elsevier Science Inc.

  16. Nuclear Proliferation: A Historical Overview

    Science.gov (United States)

    2008-03-01

    Potential. In 1965 President Sukarno publicly declared his support for an Indonesian nuclear weapon. In 1966 General Suharto formally agreed to...Foreign Minister stated that Indonesia had no interest in heading in the direction of nuclear weapons. See Robert M. Cornejo, “When Sukarno Sought...assistance, Indonesia began constructing its first nuclear research facility,. See Robert M. Cornejo, “When Sukarno Sought the Bomb: Indonesian Nuclear

  17. Nuclear medicine technology study guide

    CERN Document Server

    Patel, Dee

    2011-01-01

    Nuclear Medicine Technology Study Guide presents a comprehensive review of nuclear medicine principles and concepts necessary for technologists to pass board examinations. The practice questions and content follow the guidelines of the Nuclear Medicine Technology Certification Board (NMTCB) and American Registry of Radiological Technologists (ARRT), allowing test takers to maximize their success in passing the examinations. The book is organized by sections of increasing difficulty, with over 600 multiple-choice questions covering all areas of nuclear medicine, including radiation safety; radi

  18. Nuclear weapon detection categorization analysis

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-12-01

    This statement of work is for the Proof of Concept for nuclear weapon categories utility in Arms control. The focus of the project will be to collect, analyze and correlate Intrinsic Radiation (INRAD) calculation results for the purpose of defining measurable signatures that differentiate categories of nuclear weapons. The project will support START III negotiations by identifying categories of nuclear weapons. The categories could be used to clarify sub-limits on the total number of nuclear weapons.

  19. Nuclear effects in atomic transitions

    OpenAIRE

    Pálffy, Adriana

    2011-01-01

    Atomic electrons are sensitive to the properties of the nucleus they are bound to, such as nuclear mass, charge distribution, spin, magnetization distribution, or even excited level scheme. These nuclear parameters are reflected in the atomic transition energies. A very precise determination of atomic spectra may thus reveal information about the nucleus, otherwise hardly accessible via nuclear physics experiments. This work reviews theoretical and experimental aspects of the nuclear effects ...

  20. White Paper on Nuclear Astrophysics and Low Energy Nuclear Physics - Part 1. Nuclear Astrophysics

    Energy Technology Data Exchange (ETDEWEB)

    Arcones, Almudena [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Escher, Jutta E. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Others, M. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2016-04-04

    This white paper informs the nuclear astrophysics community and funding agencies about the scientific directions and priorities of the field and provides input from this community for the 2015 Nuclear Science Long Range Plan. It summarizes the outcome of the nuclear astrophysics town meeting that was held on August 21 - 23, 2014 in College Station at the campus of Texas A&M University in preparation of the NSAC Nuclear Science Long Range Plan. It also reflects the outcome of an earlier town meeting of the nuclear astrophysics community organized by the Joint Institute for Nuclear Astrophysics (JINA) on October 9 - 10, 2012 Detroit, Michigan, with the purpose of developing a vision for nuclear astrophysics in light of the recent NRC decadal surveys in nuclear physics (NP2010) and astronomy (ASTRO2010). The white paper is furthermore informed by the town meeting of the Association of Research at University Nuclear Accelerators (ARUNA) that took place at the University of Notre Dame on June 12 - 13, 2014. In summary we find that nuclear astrophysics is a modern and vibrant field addressing fundamental science questions at the intersection of nuclear physics and astrophysics. These questions relate to the origin of the elements, the nuclear engines that drive life and death of stars, and the properties of dense matter. A broad range of nuclear accelerator facilities, astronomical observatories, theory efforts, and computational capabilities are needed. With the developments outlined in this white paper, answers to long-standing key questions are well within reach in the coming decade.