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Sample records for nuclear factor-kb inhibitor

  1. Analysis of employee benefits in Factoring KB, a.s.v

    OpenAIRE

    Vachoušek, Stanislav

    2011-01-01

    The main objective of this work is to analyze employee benefits - benefits of Factoring KB, a.s. The theoretical part of the generally specifies the basic concepts related to employee benefits needed to cope with the analytical part. The content of this section is primarily a system of employee benefits, classification of employee benefits, tax savings and marginally trends in providing benefits. The analytical part is devoted exclusively to Factoring KB, there is an analysis of employee bene...

  2. COPPER-DEPENDENT INFLAMMATION AND NUCLEAR FACTOR-KB ACTIVATION BY PARTICULATE AIR POLLUTION

    Science.gov (United States)

    Particulate air pollution causes increased cardiopulmonary morbidity and mortality, but the chemical determinants responsible for its biologic effects are not understood. We studied the effect of total suspended particulates collected in Provo, Utah, an area where an increase in ...

  3. Inhibitors

    Science.gov (United States)

    ... JM, and the Hemophilia Inhibitor Research Study Investigators. Validation of Nijmegen-Bethesda assay modifications to allow inhibitor ... webinars on blood disorders Language: English (US) Español (Spanish) File Formats Help: How do I view different ...

  4. 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.

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

    Science.gov (United States)

    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.

  6. DOT1L inhibitor improves early development of porcine somatic cell nuclear transfer embryos

    DEFF Research Database (Denmark)

    Tao, Jia; Zhang, Yu; Zuo, Xiaoyuan

    2017-01-01

    Incomplete epigenetic reprogramming of the genome of donor cells causes poor early and full-term developmental efficiency of somatic cell nuclear transfer (SCNT) embryos. Previous research indicate that inhibition of the histone H3 K79 methyltransferase DOT1L, using a selective pharmacological...... inhibitor EPZ004777 (EPZ), significantly improved reprogramming efficiency during the generation of mouse induced pluripotent stem cells. However, the roles of DOT1L in porcine nuclear transfer-mediated cellular reprogramming are not yet known. Here we showed that DOT1L inhibition via 0.5 nM EPZ treatment...

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  8. Combined therapeutic potential of nuclear receptors with receptor tyrosine kinase inhibitors in lung cancer

    International Nuclear Information System (INIS)

    Wairagu, Peninah M.; Park, Kwang Hwa; Kim, Jihye; Choi, Jong-Whan; Kim, Hyun-Won; Yeh, Byung-Il; Jung, Soon-Hee; Yong, Suk-Joong; Jeong, Yangsik

    2014-01-01

    Highlights: • The 48 NR genes and 48 biological anti-cancer targets are profiled in paired-cells. • Growth inhibition by NR ligands or TKIs is target receptor level-dependent. • T0901317 with gefitinib/PHA665752 shows additive growth inhibition in lung cells. - Abstract: Cancer heterogeneity is a big hurdle in achieving complete cancer treatment, which has led to the emergence of combinational therapy. In this study, we investigated the potential use of nuclear receptor (NR) ligands for combinational therapy with other anti-cancer drugs. We first profiled all 48 NRs and 48 biological anti-cancer targets in four pairs of lung cell lines, where each pair was obtained from the same patient. Two sets of cell lines were normal and the corresponding tumor cell lines while the other two sets consisted of primary versus metastatic tumor cell lines. Analysis of the expression profile revealed 11 NRs and 15 cancer targets from the two pairs of normal versus tumor cell lines, and 9 NRs and 9 cancer targets from the primary versus metastatic tumor cell lines had distinct expression patterns in each category. Finally, the evaluation of nuclear receptor ligand T0901317 for liver X receptor (LXR) demonstrated its combined therapeutic potential with tyrosine kinase inhibitors. The combined treatment of cMET inhibitor PHA665752 or EGFR inhibitor gefitinib with T0901317 showed additive growth inhibition in both H2073 and H1993 cells. Mechanistically, the combined treatment suppressed cell cycle progression by inhibiting cyclinD1 and cyclinB expression. Taken together, this study provides insight into the potential use of NR ligands in combined therapeutics with other biological anti-cancer drugs

  9. Deciphering mechanisms of drug sensitivity and resistance to Selective Inhibitor of Nuclear Export (SINE) compounds

    International Nuclear Information System (INIS)

    Crochiere, Marsha; Kashyap, Trinayan; Kalid, Ori; Shechter, Sharon; Klebanov, Boris; Senapedis, William; Saint-Martin, Jean-Richard; Landesman, Yosef

    2015-01-01

    Exportin 1 (XPO1) is a well-characterized nuclear export protein whose expression is up-regulated in many types of cancers and functions to transport key tumor suppressor proteins (TSPs) from the nucleus. Karyopharm Therapeutics has developed a series of small-molecule Selective Inhibitor of Nuclear Export (SINE) compounds, which have been shown to block XPO1 function both in vitro and in vivo. The drug candidate, selinexor (KPT-330), is currently in Phase-II/IIb clinical trials for treatment of both hematologic and solid tumors. The present study sought to decipher the mechanisms that render cells either sensitive or resistant to treatment with SINE compounds, represented by KPT-185, an early analogue of KPT-330. Using the human fibrosarcoma HT1080 cell line, resistance to SINE was acquired over a period of 10 months of constant incubation with increasing concentration of KPT-185. Cell viability was assayed by MTT. Immunofluorescence was used to compare nuclear export of TSPs. Fluorescence activated cell sorting (FACS), quantitative polymerase chain reaction (qPCR), and immunoblots were used to measure effects on cell cycle, gene expression, and cell death. RNA from naïve and drug treated parental and resistant cells was analyzed by Affymetrix microarrays. Treatment of HT1080 cells with gradually increasing concentrations of SINE resulted in > 100 fold decrease in sensitivity to SINE cytotoxicity. Resistant cells displayed prolonged cell cycle, reduced nuclear accumulation of TSPs, and similar changes in protein expression compared to parental cells, however the magnitude of the protein expression changes were more significant in parental cells. Microarray analyses comparing parental to resistant cells indicate that a number of key signaling pathways were altered in resistant cells including expression changes in genes involved in adhesion, apoptosis, and inflammation. While the patterns of changes in transcription following drug treatment are similar in parental

  10. 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.

  11. Nuclear magnetic resonance studies of trypsin inhibitors isolated from seeds of Cucurbitaceae plants

    International Nuclear Information System (INIS)

    Sobczyk, K.; Markley, J.L.

    1986-01-01

    Two-dimensional NMR techniques were used to assign individual protons in two trypsin inhibitors isolated from squash seeds (Cucurbita maxima and C. pepo). The assignments of 1 H NMR signals from these unusually small proteins (29 amino acid residues) were based entirely on the sequences of the proteins plus the analysis of data from two-dimensional 1 H{ 1 H} chemical shift correlation spectroscopy (COSY), relayed COSY, and nuclear Overhauser effect spectroscopy (NOESY). The pH dependence (pH range 1 to 12) of NMR chemical shifts has been analyzed in detail. The complex pH titration profiles exhibited by the 1 H peaks of His-25 and Tyr-27 may be interpreted in terms of side-chain interactions between these residues. The protons of Gly-26 demonstrate a well-resolved AB spin system. These results suggest that this region of the protein has restricted conformational freedom. The kinetics of amide hydrogen/deuterium exchange were measured as a function of pH. The exchange rate for all amide hydrogens is governed by acid/base catalysis

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  13. Restoring conjunctival tolerance by topical nuclear factor-κB inhibitors reduces preservative-facilitated allergic conjunctivitis in mice.

    Science.gov (United States)

    Guzmán, Mauricio; Sabbione, Florencia; Gabelloni, María Laura; Vanzulli, Silvia; Trevani, Analía Silvina; Giordano, Mirta Nilda; Galletti, Jeremías Gastón

    2014-09-04

    To evaluate the role of nuclear factor-κB (NF-κB) activation in eye drop preservative toxicity and the effect of topical NF-κB inhibitors on preservative-facilitated allergic conjunctivitis. Balb/c mice were instilled ovalbumin (OVA) combined with benzalkonium chloride (BAK) and/or NF-κB inhibitors in both eyes. After immunization, T-cell responses and antigen-induced ocular inflammation were evaluated. Nuclear factor-κB activation and associated inflammatory changes also were assessed in murine eyes and in an epithelial cell line after BAK exposure. Benzalkonium chloride promoted allergic inflammation and leukocyte infiltration of the conjunctiva. Topical NF-κB inhibitors blocked the disruptive effect of BAK on conjunctival immunological tolerance and ameliorated subsequent ocular allergic reactions. In line with these findings, BAK induced NF-κB activation and the secretion of IL-6 and granulocyte-monocyte colony-stimulating factor in an epithelial cell line and in the conjunctiva of instilled mice. In addition, BAK favored major histocompatibility complex (MHC) II expression in cultured epithelial cells in an NF-κB-dependent fashion after interaction with T cells. Benzalkonium chloride triggers conjunctival epithelial NF-κB activation, which seems to mediate some of its immune side effects, such as proinflammatory cytokine release and increased MHC II expression. Breakdown of conjunctival tolerance by BAK favors allergic inflammation, and this effect can be prevented in mice by topical NF-κB inhibitors. These results suggest a new pharmacological target for preservative toxicity and highlight the importance of conjunctival tolerance in ocular surface homeostasis. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

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

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    Daniel J Moore

    2010-10-01

    Full Text Available 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.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.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.

  15. Biologic activity of the novel orally bioavailable selective inhibitor of nuclear export (SINE) KPT-335 against canine melanoma cell lines

    Science.gov (United States)

    2014-01-01

    Background Exportin 1 (XPO1, also known as CRM1), is a chaperone protein responsible for the export of over 200 target proteins out of the nucleus. The expression and activity of XPO1 is upregulated in several human cancers and its expression is also linked to the development of chemotherapy resistance. Recent studies using both human and murine cancer cell lines have demonstrated that XPO1 is a relevant target for therapeutic intervention. The present study sought to characterize the biologic activity of an orally bioavailable selective inhibitor of nuclear export (SINE), KPT-335, against canine melanoma cell lines as a prelude to future clinical trials in dogs with melanoma. Results We evaluated the effects of KPT-335 on 4 canine malignant melanoma cell lines and found that KPT-335 inhibited proliferation, blocked colony formation, and induced apoptosis of treated cells at biologically relevant concentrations of drug. Additionally, KPT-335 downregulated XPO1 protein while inducing a concomitant increase in XPO1 messenger RNA. Lastly, KPT-335 treatment of cell lines upregulated the expression of both protein and mRNA for the tumor suppressor proteins p53 and p21, and promoted their nuclear localization. Conclusions KPT-335 demonstrates biologic activity against canine melanoma cell lines at physiologically relevant doses, suggesting that KPT-335 may represent a viable treatment option for dogs with malignant melanoma. PMID:25022346

  16. Proton pump inhibitor Lansoprazole is a nuclear Liver X Receptor agonist

    Science.gov (United States)

    Cronican, Andrea A.; Fitz, Nicholas F.; Pham, Tam; Fogg, Allison; Kifer, Brionna; Koldamova, Radosveta; Lefterov, Iliya

    2010-01-01

    The liver X receptors (LXRα and LXRβ) are transcription factors that control the expression of genes primarily involved in cholesterol metabolism. In brain, in addition to normal neuronal function, cholesterol metabolism is important for APP proteolytic cleavage, secretase activities, Aβ aggregation and clearance. Particularly significant in this respect is the LXR mediated transcriptional control of APOE, which is the only proven risk factor for late onset Alzheimer’s disease. Using a transactivation reporter assay for screening pharmacologically active compounds and off patent drugs we identified the Proton Pump Inhibitor Lansoprazole as an LXR agonist. In secondary screens and counter-screening assays, it was confirmed that Lansoprazole directly activates LXR, increases the expression of LXR target genes in brain-derived human cell lines, and increases Abca1 and Apo-E protein levels in primary astrocytes derived from wild type but not LXRα/β double knockout mice. Other PPIs activate LXR as well, but the efficiency of activation depends on their structural similarities to Lansoprazole. The identification of widely used, drug with LXR agonist-like activity opens the possibility for systematic preclinical testing in at least two diseases – Alzheimer’s disease and atherosclerosis. PMID:20060385

  17. 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.

  18. Role of regulatory subunits and protein kinase inhibitor (PKI) in determining nuclear localization and activity of the catalytic subunit of protein kinase A.

    Science.gov (United States)

    Wiley, J C; Wailes, L A; Idzerda, R L; McKnight, G S

    1999-03-05

    Regulation of protein kinase A by subcellular localization may be critical to target catalytic subunits to specific substrates. We employed epitope-tagged catalytic subunit to correlate subcellular localization and gene-inducing activity in the presence of regulatory subunit or protein kinase inhibitor (PKI). Transiently expressed catalytic subunit distributed throughout the cell and induced gene expression. Co-expression of regulatory subunit or PKI blocked gene induction and prevented nuclear accumulation. A mutant PKI lacking the nuclear export signal blocked gene induction but not nuclear accumulation, demonstrating that nuclear export is not essential to inhibit gene induction. When the catalytic subunit was targeted to the nucleus with a nuclear localization signal, it was not sequestered in the cytoplasm by regulatory subunit, although its activity was completely inhibited. PKI redistributed the nuclear catalytic subunit to the cytoplasm and blocked gene induction, demonstrating that the nuclear export signal of PKI can override a strong nuclear localization signal. With increasing PKI, the export process appeared to saturate, resulting in the return of catalytic subunit to the nucleus. These results demonstrate that both the regulatory subunit and PKI are able to completely inhibit the gene-inducing activity of the catalytic subunit even when the catalytic subunit is forced to concentrate in the nuclear compartment.

  19. 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

  20. Identification of a novel A20-binding inhibitor of nuclear factor-kappa B activation termed ABIN-2.

    Science.gov (United States)

    Van Huffel, S; Delaei, F; Heyninck, K; De Valck, D; Beyaert, R

    2001-08-10

    The nuclear factor kappaB (NF-kappaB) plays a central role in the regulation of genes implicated in immune responses, inflammatory processes, and apoptotic cell death. The zinc finger protein A20 is a cellular inhibitor of NF-kappaB activation by various stimuli and plays a critical role in terminating NF-kappaB responses. The underlying mechanism for NF-kappaB inhibition by A20 is still unknown. A20 has been shown to interact with several proteins including tumor necrosis factor (TNF) receptor-associated factors 2 and 6, as well as the inhibitory protein of kappaB kinase (IKK) gamma protein. Here we report the cloning and characterization of ABIN-2, a previously unknown protein that binds to the COOH-terminal zinc finger domain of A20. NF-kappaB activation induced by TNF and interleukin-1 is inhibited by overexpression of ABIN-2. The latter also inhibits NF-kappaB activation induced by overexpression of receptor-interacting protein or TNF receptor-associated factor 2. In contrast, NF-kappaB activation by overexpression of IKKbeta or direct activators of the IKK complex, such as Tax, cannot be inhibited by ABIN-2. These results indicate that ABIN-2 interferes with NF-kappaB activation upstream of the IKK complex and that it might contribute to the NF-kappaB-inhibitory function of A20.

  1. Pluripotency maintenance in mouse somatic cell nuclear transfer embryos and its improvement by treatment with the histone deacetylase inhibitor TSA.

    Science.gov (United States)

    Hai, Tang; Hao, Jie; Wang, Liu; Jouneau, Alice; Zhou, Qi

    2011-02-01

    Reprogramming of somatic cells to pluripotency can be achieved by nuclear transfer into enucleated oocytes (SCNT). A key event of this process is the demethylation of the Oct4 gene and its temporally and spatially regulated expression. Different studies have shown that it occurs abnormally in some SCNT embryos. TSA is a histone deacetylase inhibitor known to increase the efficiency of development to term of SCNT embryos, but its impact on the developmental features of SCNT embryos is poorly understood. Here, we have followed the fate of the pluripotent cells within SCNT embryos, from the late blastocyst to the early epiblast prior to gastrulation. Our data show a delay in development correlated with a defect in forming and maintaining a correct number of Oct4 expressing ICM and epiblast cells in SCNT embryos. As a consequence, during the outgrowth phase of embryonic stem cell derivation as well as during diapause in vivo, part of the SCNT blastocysts completely lose their ICM cells. Meanwhile, the others display a correctly reprogrammed ICM compatible with the derivation of ES cells and development of the epiblast. Our data also indicate that TSA favors the establishment of pluripotency in SCNT embryos.

  2. 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

  3. 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

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    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.

  4. A novel function for the IκB inhibitor Cactus in promoting Dorsal nuclear localization and activity in the Drosophila embryo.

    Science.gov (United States)

    Cardoso, Maira Arruda; Fontenele, Marcio; Lim, Bomyi; Bisch, Paulo Mascarello; Shvartsman, Stanislav Y; Araujo, Helena Marcolla

    2017-08-15

    The evolutionarily conserved Toll signaling pathway controls innate immunity across phyla and embryonic patterning in insects. In the Drosophila embryo, Toll is required to establish gene expression domains along the dorsal-ventral axis. Pathway activation induces degradation of the IκB inhibitor Cactus, resulting in a ventral-to-dorsal nuclear gradient of the NFκB effector Dorsal. Here, we investigate how cactus modulates Toll signals through its effects on the Dorsal gradient and on Dorsal target genes. Quantitative analysis using a series of loss- and gain-of-function conditions shows that the ventral and lateral aspects of the Dorsal gradient can behave differently with respect to Cactus fluctuations. In lateral and dorsal embryo domains, loss of Cactus allows more Dorsal to translocate to the nucleus. Unexpectedly, cactus loss-of-function alleles decrease Dorsal nuclear localization ventrally, where Toll signals are high. Overexpression analysis suggests that this ability of Cactus to enhance Toll stems from the mobilization of a free Cactus pool induced by the Calpain A protease. These results indicate that Cactus acts to bolster Dorsal activation, in addition to its role as a NFκB inhibitor, ensuring a correct response to Toll signals. © 2017. Published by The Company of Biologists Ltd.

  5. Development and Implementation of a High-Throughput High-Content Screening Assay to Identify Inhibitors of Androgen Receptor Nuclear Localization in Castration-Resistant Prostate Cancer Cells

    Science.gov (United States)

    Nguyen, Minh M.; Dar, Javid A.; Ai, Junkui; Wang, Yujuan; Masoodi, Khalid Z.; Shun, Tongying; Shinde, Sunita; Camarco, Daniel P.; Hua, Yun; Huryn, Donna M.; Wilson, Gabriela Mustata; Lazo, John S.; Nelson, Joel B.; Wipf, Peter

    2016-01-01

    Abstract Patients with castration-resistant prostate cancer (CRPC) can be treated with abiraterone, a potent inhibitor of androgen synthesis, or enzalutamide, a second-generation androgen receptor (AR) antagonist, both targeting AR signaling. However, most patients relapse after several months of therapy and a majority of patients with relapsed CRPC tumors express the AR target gene prostate-specific antigen (PSA), suggesting that AR signaling is reactivated and can be targeted again to inhibit the relapsed tumors. Novel small molecules capable of inhibiting AR function may lead to urgently needed therapies for patients resistant to abiraterone, enzalutamide, and/or other previously approved antiandrogen therapies. Here, we describe a high-throughput high-content screening (HCS) campaign to identify small-molecule inhibitors of AR nuclear localization in the C4-2 CRPC cell line stably transfected with GFP-AR-GFP (2GFP-AR). The implementation of this HCS assay to screen a National Institutes of Health library of 219,055 compounds led to the discovery of 3 small molecules capable of inhibiting AR nuclear localization and function in C4-2 cells, demonstrating the feasibility of using this cell-based phenotypic assay to identify small molecules targeting the subcellular localization of AR. Furthermore, the three hit compounds provide opportunities to develop novel AR drugs with potential for therapeutic intervention in CRPC patients who have relapsed after treatment with antiandrogens, such as abiraterone and/or enzalutamide. PMID:27187604

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

    Energy Technology Data Exchange (ETDEWEB)

    Takeda, Tomoya; Tsubaki, Masanobu; Sakamoto, Kotaro; Ichimura, Eri; Enomoto, Aya; Suzuki, Yuri [Division of Pharmacotherapy, Kinki University School of Pharmacy, Kowakae, Higashi-, Osaka (Japan); Itoh, Tatsuki [Department of Food Science and Nutrition, Kinki University School of Agriculture, Nara, Nara (Japan); Imano, Motohiro [Department of Surgery, Kinki University School of Medicine, Osakasayama, Osaka (Japan); Tanabe, Genzoh; Muraoka, Osamu [Laboratory of Pharmaceutical Organic Chemistry, School of Pharmacy, Kinki University, Kowakae, Higashi-, Osaka (Japan); Matsuda, Hideaki [Department of Natural Drugs Resources, Kinki University School of Pharmacy, Kowakae, Higashi-, Osaka (Japan); Satou, Takao [Department of Pathology, Kinki University School of Medicine, Osakasayama, Osaka (Japan); Nishida, Shozo, E-mail: nishida@phar.kindai.ac.jp [Division of Pharmacotherapy, Kinki University School of Pharmacy, Kowakae, Higashi-, Osaka (Japan)

    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. - Highlights: • Mangiferin prolongs survival in mice by inhibiting metastasis and tumor growth • Mangiferin selectivity suppresses the NF-κB pathway via inhibition of NIK activation • Mangiferin regulates the expression of MMPs, VLAs, and apoptosis regulatory proteins.

  7. Differentiation of human lymphocytes into nuclear vlimata by meiosis. The cytotoxic effect of calcium-activated neutral proteinase inhibitor

    OpenAIRE

    Logothetou-Rella, H.

    1994-01-01

    Phytohaemagglutinin (PHA)-activated lymphocytes differentiated into nuclear vlimata (NVs) in vitro. Lymphocyte attachment was followed by formation and extrusion of cytoplasmic vesicles. nuclear elongation and fragmentation into NVs. NVs and cytoplasmic vesicles were detached and organized into large cell nodules in suspension. Immunocytochemistry showed that T-lymphocytes differentiated mainly to NVs while B-lymphocytes to buds. During differentiation ther...

  8. Nuclear import inhibitor N-(4-hydroxyphenyl) retinamide targets Zika virus (ZIKV) nonstructural protein 5 to inhibit ZIKV infection.

    Science.gov (United States)

    Wang, Chunxiao; Yang, Sundy N Y; Smith, Kate; Forwood, Jade K; Jans, David A

    2017-12-02

    In the absence of approved therapeutics, Zika virus (ZIKV)'s recent prolific outbreaks in the Americas, together with impacts on unborn fetuses of infected mothers, make it a pressing human health concern worldwide. Although a key player in viral replication in the infected host cell cytoplasm, ZIKV non-structural protein 5 (NS5) appears to contribute integrally to pathogenesis by localising in the host cell nucleus, in similar fashion to NS5 from Dengue virus (DENV). We show here for the first time that ZIKV NS5 is recognized with high nanomolar affinity by the host cell importin α/β1 heterodimer, and that this interaction can be blocked by the novel DENV NS5 targeting inhibitor N-(4-hydroxyphenyl) retinamide (4-HPR). Importantly, we show that 4-HPR has potent anti-ZIKV activity at low μM concentrations. With an established safety profile for human use, 4-HPR represents an exciting possibility as an anti-ZIKV agent. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. 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 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.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.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.

  10. Improvement of mouse cloning using nuclear transfer-derived embryonic stem cells and/or histone deacetylase inhibitor.

    Science.gov (United States)

    Wakayama, Sayaka; Wakayama, Teruhiko

    2010-01-01

    Nuclear transfer-derived ES (ntES) cell lines can be established from somatic cell nuclei with a relatively high success rate. Although ntES cells have been shown to be equivalent to ES cells, there are ethical objections concerning human cells, such as the use of fresh oocyte donation from young healthy woman. In contrast, the use of induced pluripotent stem (iPS) cells for cloning poses few ethical problems and is a relatively easy technique compared with nuclear transfer. Therefore, although there are several reports proposing the use of ntES cells as a model of regenerative medicine, the use of these cells in preliminary medical research is waning. However, in theory, 5 to 10 donor cells can establish one ntES cell line and, once established, these cells will propagate indefinitely. These cells can be used to generate cloned animals from ntES cell lines using a second round of NT. Even in infertile and "unclonable" strains of mice, we can generate offspring from somatic cells by combining cloning with ntES technology. Moreover, cloned offspring can be generated potentially even from the nuclei of dead bodies or freeze-dried cells via ntES cells, such as from an extinct frozen animal. Currently, only the ntES technology is available for this purpose, because all other techniques, including iPS cell derivation, require significant numbers of living donor cells. This review describes how to improve the efficiency of cloning, the establishment of clone-derived embryonic stem cells and further applications.

  11. A novel inhibitor of apoptosis protein (IAP)-interacting protein, Vestigial-like (Vgl)-4, counteracts apoptosis-inhibitory function of IAPs by nuclear sequestration

    International Nuclear Information System (INIS)

    Jin, Hyung-Seung; Park, Hyung-Sun; Shin, Jun-Ha; Kim, Dong-Hwan; Jun, Sung-Hun; Lee, Chang-Jun; Lee, Tae H.

    2011-01-01

    Highlights: → We identified a new IAP binding protein Vgl-4. → Vgl-4 is expressed mainly in the nucleus and triggers a relocalization of IAPs from the cytoplasm to the nucleus. → Vgl-4-mediated IAP nuclear localization was blocked by TRAF2 coexpression. → Vgl-4 suppresses the ability of IAPs to prevent cell death, however TRAF2 can revere the effect of Vgl-4. → Vgl-4 functions as an IAP regulator by binding to IAPs and altering their sub-cellular localization. -- Abstract: The inhibitors of apoptosis proteins (IAP), which include cIAP1, cIAP2 and XIAP, suppress apoptosis through the inhibition of caspases, and the activity of IAPs is regulated by a variety of IAP-binding proteins. Herein, we report the identification of a Vestigial-like 4 (Vgl-4), which functions as a transcription cofactor in cardiac myocytes, as a new IAP binding protein. Vgl-4 is expressed predominantly in the nucleus and its overexpression triggers a relocalization of IAPs from the cytoplasm to the nucleus. cIAP1/2-interacting protein TRAF2 (TNF receptor-associated factor 2) prevented the Vgl-4-driven nuclear localization of cIAP2. Accordingly, the forced relocation of IAPs to the nucleus by Vgl-4 significantly reduced their ability to prevent Bax- and TNFα-induced apoptosis, which can be recovered by co-expression with TRAF2. Our results suggest that Vgl-4 may play a role in the apoptotic pathways by regulating translocation of IAPs between different cell compartments.

  12. A chemical genetic screen for mTOR pathway inhibitors based on 4E-BP-dependent nuclear accumulation of eIF4E.

    Science.gov (United States)

    Livingstone, Mark; Larsson, Ola; Sukarieh, Rami; Pelletier, Jerry; Sonenberg, Nahum

    2009-12-24

    The signal transduction pathway wherein mTOR regulates cellular growth and proliferation is an active target for drug discovery. The search for new mTOR inhibitors has recently yielded a handful of promising compounds that hold therapeutic potential. This search has been limited by the lack of a high-throughput assay to monitor the phosphorylation of a direct rapamycin-sensitive mTOR substrate in cells. Here we describe a novel cell-based chemical genetic screen useful for efficiently monitoring mTOR signaling to 4E-BPs in response to stimuli. The screen is based on the nuclear accumulation of eIF4E, which occurs in a 4E-BP-dependent manner specifically upon inhibition of mTOR signaling. Using this assay in a small-scale screen, we have identified several compounds not previously known to inhibit mTOR signaling, demonstrating that this method can be adapted to larger screens. Copyright 2009 Elsevier Ltd. All rights reserved.

  13. Nuclear

    International Nuclear Information System (INIS)

    2014-01-01

    This document proposes a presentation and discussion of the main notions, issues, principles, or characteristics related to nuclear energy: radioactivity (presence in the environment, explanation, measurement, periods and activities, low doses, applications), fuel cycle (front end, mining and ore concentration, refining and conversion, fuel fabrication, in the reactor, back end with reprocessing and recycling, transport), the future of the thorium-based fuel cycle (motivations, benefits and drawbacks), nuclear reactors (principles of fission reactors, reactor types, PWR reactors, BWR, heavy-water reactor, high temperature reactor of HTR, future reactors), nuclear wastes (classification, packaging and storage, legal aspects, vitrification, choice of a deep storage option, quantities and costs, foreign practices), radioactive releases of nuclear installations (main released radio-elements, radioactive releases by nuclear reactors and by La Hague plant, gaseous and liquid effluents, impact of releases, regulation), the OSPAR Convention, management and safety of nuclear activities (from control to quality insurance, to quality management and to sustainable development), national safety bodies (mission, means, organisation and activities of ASN, IRSN, HCTISN), international bodies, nuclear and medicine (applications of radioactivity, medical imagery, radiotherapy, doses in nuclear medicine, implementation, the accident in Epinal), nuclear and R and D (past R and D programmes and expenses, main actors in France and present funding, main R and D axis, international cooperation)

  14. Three-dimensional structure of potato carboxypeptidase inhibitor in solution. A study using nuclear magnetic resonance, distance geometry, and restrained molecular dynamics

    International Nuclear Information System (INIS)

    Clore, G.M.; Gronenborn, A.M.; Nilges, M.; Ryan, C.A.

    1987-01-01

    The solution conformation of potato carboxypeptidase inhibitor (CPI) has been investigated by 1 H NMR spectroscopy. The spectrum is assigned in a sequential manner by using two-dimensional NMR techniques to identify through-bond and through-space (<5 A) connectivities. A set of 309 approximate interproton distance restraints is derived from the two-dimensional nuclear Overhauser enhancement spectra and used as the basis of a three-dimensional structure determination by a combination of metric matrix distance geometry and restrained molecular dynamics calculations. A total of 11 converged distance geometry structures were computed and refined by using restrained molecular dynamics. The average atomic root mean square (rms) difference between the final 11 structures and the mean structure obtained by averaging their coordinates is 1.4 +/- 0.3 A for residues 2-39 and 0.9 +/- 0.2 A for residues 5-37. The corresponding values for all atoms are 1.9 +/- 0.3 and 1.4 +/- 0.2 A, respectively. The computed structures are very close to the X-ray structure of CPI in its complex with carboxypeptidase, and the backbone atomic rms difference between the mean of the computed structures and the X-ray structure is only 1.2 A. Nevertheless, there are some real differences present which are evidenced by significant deviations between the experimental upper interproton distance limits and the corresponding interproton distances derived from the X-ray structure. These principally occur in two regions, residues 18-20 and residues 28-30, the latter comprising part of the region of secondary contact between CPI and carboxypeptidase in the X-ray structure

  15. Nuclear

    International Nuclear Information System (INIS)

    Anon.

    2000-01-01

    The first text deals with a new circular concerning the collect of the medicine radioactive wastes, containing radium. This campaign wants to incite people to let go their radioactive wastes (needles, tubes) in order to suppress any danger. The second text presents a decree of the 31 december 1999, relative to the limitations of noise and external risks resulting from the nuclear facilities exploitation: noise, atmospheric pollution, water pollution, wastes management and fire prevention. (A.L.B.)

  16. 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...

  17. [Syk inhibitors].

    Science.gov (United States)

    Kimura, Yukihiro; Chihara, Kazuyasu; Takeuchi, Kenji; Sada, Kiyonao

    2013-07-01

    Non-receptor type of protein-tyrosine kinase Syk (spleen tyrosine kinase) was isolated in the University of Fukui in 1991. Syk is known to be essential for the various physiological functions, especially in hematopoietic lineage cells. Moreover, ectopic expression of Syk by epigenetic changes is reported to cause retinoblastoma. Recently, novel Syk inhibitors were developed and its usefulness has been evaluated in the treatment of allergic rhinitis, rheumatoid arthritis, and idiopathic thrombocytopenic purpura. In this review, we will summarize the history, structure, and function of Syk, and then describe the novel Syk inhibitors and their current status. Furthermore, we will introduce our findings of the adaptor protein 3BP2 (c-Abl SH3 domain-binding protein-2), as a novel target of Syk.

  18. Syk inhibitors.

    Science.gov (United States)

    Chihara, Kazuyasu; Kimura, Yukihiro; Honjo, Chisato; Takeuchi, Kenji; Sada, Kiyonao

    2013-01-01

    Non-receptor type of protein-tyrosine kinase Syk (spleen tyrosine kinase) was isolated in University of Fukui in 1991. Syk is most highly expressed by haemopoietic cells and known to play crucial roles in the signal transduction through various immunoreceptors of the adaptive immune response. However, recent reports demonstrate that Syk also mediates other biological functions, such as innate immune response, osteoclast maturation, platelet activation and cellular adhesion. Moreover, ectopic expression of Syk by epigenetic changes is reported to cause retinoblastoma. Because of its critical roles on the cellular functions, the development of Syk inhibitors for clinical use has been desired. Although many candidate compounds were produced, none of them had progressed to clinical trials. However, novel Syk inhibitors were finally developed and its usefulness has been evaluated in the treatment of allergic rhinitis, rheumatoid arthritis and idiopathic thrombocytopenic purpura. In this review, we will summarize the history, structure and function of Syk, and then the novel Syk inhibitors and their current status. In addition, we will introduce our research focused on the functions of Syk on Dectin-1-mediated mast cell activation.

  19. Directional Migration in Esophageal Squamous Cell Carcinoma (ESCC) is Epigenetically Regulated by SET Nuclear Oncogene, a Member of the Inhibitor of Histone Acetyltransferase Complex

    OpenAIRE

    Xiang Yuan; Xinshuai Wang; Bianli Gu; Yingjian Ma; Yiwen Liu; Man Sun; Jinyu Kong; Wei Sun; Huizhi Wang; Fuyou Zhou; Shegan Gao

    2017-01-01

    Directional cell migration is of fundamental importance to a variety of biological events, including metastasis of malignant cells. Herein, we specifically investigated SET oncoprotein, a subunit of the recently identified inhibitor of acetyltransferases (INHAT) complex and identified its role in the establishment of front–rear cell polarity and directional migration in Esophageal Squamous Cell Carcinoma (ESCC). We further define the molecular circuits that govern these processes by showing t...

  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. pH and temperature effects on the molecular conformation of the porcine pancreatic secretory trypsin inhibitor as detected by hydrogen-1 nuclear magnetic resonance

    International Nuclear Information System (INIS)

    De Marco, A.; Menegatti, E.; Guarneri, M.

    1982-01-01

    1 H NMR spectra of the porcine pancreatic secretory trypsin inhibitor (PSTI) have been recorded vs. pH and temperature. Of the two tyrosines, one titrates with a pK of 1.25, while the resonances from the other are pH insensitive in the investigated range 4.8 less than or equal to pH less than or equal to 12. This is consistent with PSTI having one Tyr solvent exposed (Try-20) and the other buried (Tyr-31). The resonances from the lysyl epsilon-CH 2 protons titrate with a pK of 10.95. The titration is accompanied by a pronounced line broadening, which starts near pH 8.5. Between pH 11.5 and pH 12 the epsilon-CH 2 resonances recover their low pH line width. Titration curves for the lysines and Tyr-20 reflect single proton ionization equilibria, suggesting that these residues do not interact among themselves. On the basis of double resonance experiments, combined with analysis of chemical shifts, spin-spin couplngs, and line widths, all methyl resonances are identified and followed as functions of pH and temperature. The γ-CH 3 doublet from the N-terminal Thr-1 is assigned by comparison between spectra of forms I and II of the inhibitor, the latter lacking the first four residues of form I. The β-CH 3 resonance from Ala-7 is also assigned. Proton resonance parameters of methyl groups are shown to afford useful NMR probes for the characterization of local nonbonded interactions, microenvironments, and mobilities

  2. Metabolite Regulation of Nuclear Localization of Carbohydrate-response Element-binding Protein (ChREBP): ROLE OF AMP AS AN ALLOSTERIC INHIBITOR.

    Science.gov (United States)

    Sato, Shogo; Jung, Hunmin; Nakagawa, Tsutomu; Pawlosky, Robert; Takeshima, Tomomi; Lee, Wan-Ru; Sakiyama, Haruhiko; Laxman, Sunil; Wynn, R Max; Tu, Benjamin P; MacMillan, John B; De Brabander, Jef K; Veech, Richard L; Uyeda, Kosaku

    2016-05-13

    The carbohydrate-response element-binding protein (ChREBP) is a glucose-responsive transcription factor that plays an essential role in converting excess carbohydrate to fat storage in the liver. In response to glucose levels, ChREBP is regulated by nuclear/cytosol trafficking via interaction with 14-3-3 proteins, CRM-1 (exportin-1 or XPO-1), or importins. Nuclear localization of ChREBP was rapidly inhibited when incubated in branched-chain α-ketoacids, saturated and unsaturated fatty acids, or 5-aminoimidazole-4-carboxamide ribonucleotide. Here, we discovered that protein-free extracts of high fat-fed livers contained, in addition to ketone bodies, a new metabolite, identified as AMP, which specifically activates the interaction between ChREBP and 14-3-3. The crystal structure showed that AMP binds directly to the N terminus of ChREBP-α2 helix. Our results suggest that AMP inhibits the nuclear localization of ChREBP through an allosteric activation of ChREBP/14-3-3 interactions and not by activation of AMPK. AMP and ketone bodies together can therefore inhibit lipogenesis by restricting localization of ChREBP to the cytoplasm during periods of ketosis. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. SUMO Ligase Protein Inhibitor of Activated STAT1 (PIAS1) Is a Constituent Promyelocytic Leukemia Nuclear Body Protein That Contributes to the Intrinsic Antiviral Immune Response to Herpes Simplex Virus 1.

    Science.gov (United States)

    Brown, James R; Conn, Kristen L; Wasson, Peter; Charman, Matthew; Tong, Lily; Grant, Kyle; McFarlane, Steven; Boutell, Chris

    2016-07-01

    Aspects of intrinsic antiviral immunity are mediated by promyelocytic leukemia nuclear body (PML-NB) constituent proteins. During herpesvirus infection, these antiviral proteins are independently recruited to nuclear domains that contain infecting viral genomes to cooperatively promote viral genome silencing. Central to the execution of this particular antiviral response is the small ubiquitin-like modifier (SUMO) signaling pathway. However, the participating SUMOylation enzymes are not fully characterized. We identify the SUMO ligase protein inhibitor of activated STAT1 (PIAS1) as a constituent PML-NB protein. We show that PIAS1 localizes at PML-NBs in a SUMO interaction motif (SIM)-dependent manner that requires SUMOylated or SUMOylation-competent PML. Following infection with herpes simplex virus 1 (HSV-1), PIAS1 is recruited to nuclear sites associated with viral genome entry in a SIM-dependent manner, consistent with the SIM-dependent recruitment mechanisms of other well-characterized PML-NB proteins. In contrast to that of Daxx and Sp100, however, the recruitment of PIAS1 is enhanced by PML. PIAS1 promotes the stable accumulation of SUMO1 at nuclear sites associated with HSV-1 genome entry, whereas the accumulation of other evaluated PML-NB proteins occurs independently of PIAS1. We show that PIAS1 cooperatively contributes to HSV-1 restriction through mechanisms that are additive to those of PML and cooperative with those of PIAS4. The antiviral mechanisms of PIAS1 are counteracted by ICP0, the HSV-1 SUMO-targeted ubiquitin ligase, which disrupts the recruitment of PIAS1 to nuclear domains that contain infecting HSV-1 genomes through mechanisms that do not directly result in PIAS1 degradation. Adaptive, innate, and intrinsic immunity cooperatively and efficiently restrict the propagation of viral pathogens. Intrinsic immunity mediated by constitutively expressed cellular proteins represents the first line of intracellular defense against infection. PML

  4. Directional Migration in Esophageal Squamous Cell Carcinoma (ESCC is Epigenetically Regulated by SET Nuclear Oncogene, a Member of the Inhibitor of Histone Acetyltransferase Complex

    Directory of Open Access Journals (Sweden)

    Xiang Yuan

    2017-11-01

    Full Text Available Directional cell migration is of fundamental importance to a variety of biological events, including metastasis of malignant cells. Herein, we specifically investigated SET oncoprotein, a subunit of the recently identified inhibitor of acetyltransferases (INHAT complex and identified its role in the establishment of front–rear cell polarity and directional migration in Esophageal Squamous Cell Carcinoma (ESCC. We further define the molecular circuits that govern these processes by showing that SET modulated DOCK7/RAC1 and cofilin signaling events. Moreover, a detailed analysis of the spatial distribution of RAC1 and cofilin allowed us to decipher the synergistical contributions of the two in coordinating the advancing dynamics by measuring architectures, polarities, and cytoskeletal organizations of the lamellipodia leading edges. In further investigations in vivo, we identified their unique role at multiple levels of the invasive cascade for SET cell and indicate the necessity for their functional balance to enable efficient invasion as well. Additionally, SET epigenetically repressed miR-30c expression by deacetylating histones H2B and H4 on its promoter, which was functionally important for the biological effects of SET in our cell-context. Finally, we corroborated our findings in vivo by evaluating the clinical relevance of SET signaling in the metastatic burden in mice and a large series of patients with ESCC at diagnosis, observing it's significance in predicting metastasis formation. Our findings uncovered a novel signaling network initiated by SET that epigenetically modulated ESCC properties and suggest that targeting the regulatory axis might be a promising strategy to inhibit migration and metastasis.

  5. Nuclear factor κB inhibitor BAY 11-7082 suppresses oxidative stress induced by endothelin-1 (ET-1) in rat kidney.

    Science.gov (United States)

    Kowalczyk, Agata; Kołodziejczyk, Michał; Gorąca, Anna

    2015-12-31

    The aim of the study was to evaluate the effect of BAY 11-7082, an NF-κB inhibitor, on basal and ET-1-induced production of reactive oxygen species (ROS), TNF-α and p65 protein in rat kidney. The experimental animals were divided into five groups (n=7) receiving: 1) saline (control); 2 and 3) ET-1 in a dose of 3 μg/kg body weight (b.w.) or 12.5 μg/kg b.w.; 4) BAY 11-7082 (10 mg/kg b.w.); 5) BAY 11-7082 (10 mg/kg b.w.) and ET-1 (12.5 μg/kg b.w.), respectively. In kidney homogenates the concentration of thiobarbituric acid reactive substances (TBARS), H2O2, TNF-α, p65 protein and GSH/GSSG ratio were determined. ET-1 resulted in a dose-dependent increase in TBARS and hydrogen peroxide (H2O2) levels, and a decrease in GSH/GSSG ratio when compared to the controls. BAY 11-7082 administered 1 h before ET-1 administration at a dose of 12.5 μg/kg resulted in a decrease (PET-1 groups. The level of TNF-α was increased (PET-1, while BAY 11-7082 reduced the TNF-α level (PET-1 induced oxidative stress in kidney tissue. These actions of BAY 11-7082 may result from reduced activity of NF-κB signaling pathways. Inhibition of the NF-κB pathway may be a promising strategy for preventing the progression of kidney damage.

  6. 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

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

    International Nuclear Information System (INIS)

    Imagawa, Kei; Andres, MC de; Hashimoto, Ko; Pitt, Dominic; Itoi, Eiji; Goldring, Mary B.; Roach, Helmtrud I.; Oreffo, Richard O.C.

    2011-01-01

    Research highlights: → Glucosamine and a NF-kB inhibitor reduce inflammation in OA. → Cytokine induced demethylation of CpG site in IL1β promoter prevented by glucosamine. → 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-1β, 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-1β and 2.5 ng/ml oncostatin M (OSM), (iii) cultured with 2 mM N-acetyl GlcN (Sigma

  8. Enzyme structure and interaction with inhibitors

    International Nuclear Information System (INIS)

    London, R.E.

    1983-01-01

    This article reviews some of the results of studies on the 13 C-labeled enzyme dihydrofolate reductase (DHFR). Nuclear magnetic resonance (NMR) techniques are used in combination with isotopic labeling to learn about the structure and dynamics of this enzyme. 13 C-labeling is used for the purpose of studying enzyme/substrate and enzyme/inhibitor interactions. A second set of studies with DHFR was designed to investigate the basis for the high affinity between the inhibitor methotrexate and DHFR. The label was placed on the inhibitor, rather than the enzyme

  9. Cell-cycle-dependent three-dimensional redistribution of nuclear proteins, P 120, pKi-67, and SC 35 splicing factor, in the presence of the topoisomerase I inhibitor camptothecin.

    Science.gov (United States)

    Elias, Emmanuel; Lalun, Nathalie; Lorenzato, Marianne; Blache, Laurent; Chelidze, Pavel; O'Donohue, Marie-Françoise; Ploton, Dominique; Bobichon, Hélène

    2003-11-15

    Topoisomerase I (Topo I) is mostly known for its role in DNA relaxation, which is required for duplication and transcription. Topo I acts as a protein kinase mainly directed to the mRNA splicing factor SC35. Camptothecin is one of the specific Topo I inhibitors and is effective on the two functions of the enzyme. In this study we demonstrated that treatment of KB cells with camptothecin for only 30 min induced the 3D reorganization and redistribution of three proteins involved in the nucleus machinery, P 120, pKi-67, and SC 35, and this occurred in a cell cycle-dependent manner. Our data were obtained from confocal microscopic studies after immunolabeling, 3D reconstruction, and measurement of the nuclear components volumes. In the presence of camptothecin, P 120, which occupied the nucleolar volume, lost its reticulation and pKi-67 was redistributed within the nucleoplasm and even into the cytoplasm. Finally, for SC 35 the fusion of its dots into bigger volumes was observed specifically during the G1 phase. Variations of volumes were also observed for the nucleolus and for the nucleus. These results pointed out that, depending on the cell cycle phase, Topo I functions were selective toward the three different proteins.

  10. Nature of isomerism of solid isothiourea salts, inhibitors of nitric oxide synthases, as studied by 1H-14N nuclear quadrupole double resonance, X-ray, and density functional theory/quantum theory of atoms in molecules.

    Science.gov (United States)

    Latosińska, J N; Latosińska, M; Seliger, J; Žagar, V; Maurin, J K; Kazimierczuk, Z

    2012-02-09

    Isothioureas, inhibitors of nitric oxide synthases, have been studied experimentally in solid state by nuclear quadrupole double resonance (NQDR) and X-ray methods and theoretically by the quantum theory of atoms in molecules/density functional theory. Resonance frequencies on (14)N have been detected and assigned to particular nitrogen sites in each molecule. The crystal packings of (S)-3,4-dichlorobenzyl-N-methylisothiouronium chloride with the disordered chlorine positions in benzene ring and (S)-butyloisothiouronium bromide have been resolved in X-ray diffraction studies. (14)N NQDR spectra have been found good indicators of isomer type and strength of intra- or intermolecular N-H···X (X = Cl, Br) interactions. From among all salts studied, only for (S)-2,3,4,5,6-pentabromobenzylisothiouronium chloride are both nitrogen sites equivalent, which has been explained by the slow exchange. This unique structural feature can be a key factor in the high biological activity of (S)-2,3,4,5,6-pentabromobenzylisothiouronium salts.

  11. Inhibition of nuclear factor-κB and target genes during combined therapy with proteasome inhibitor bortezomib and reirradiation in patients with recurrent head-and-neck squamous cell carcinoma

    International Nuclear Information System (INIS)

    Van Waes, Carter; Chang, Angela A.; Lebowitz, Peter F.; Druzgal, Colleen H.; Chen, Zhong; Elsayed, Yusri A.; Sunwoo, John B.; Rudy, Susan; Morris, John C.; Mitchell, James B.; Camphausen, Kevin; Gius, David; Adams, Julian; Sausville, Edward A.; Conley, Barbara A.

    2005-01-01

    Purpose: To examine the effects the proteasome inhibitor bortezomib (VELCADE) on transcription factor nuclear factor-κB (NF-κB) and target genes and the feasibility of combination therapy with reirradiation in patients with recurrent head-and-neck squamous cell carcinoma (HNSCC). Methods and Materials: The tolerability and response to bortezomib 0.6 mg/m 2 and 0.9 mg/m 2 given twice weekly concurrent with daily reirradiation to 50-70 Gy was explored. Blood proteasome inhibition and NF-κB-modulated cytokines and factors were measured. Proteasome inhibition, nuclear localization of NF-κB phospho-p65, apoptosis, and expression of NF-κB-modulated mRNAs were compared in serial biopsies from accessible tumors. Results: The maximally tolerated dose was exceeded, and study was limited to 7 and 2 patients, respectively, given bortezomib 0.6 mg/m 2 and 0.9 mg/m 2 /dose with reirradiation. Grade 3 hypotension and hyponatremia were dose limiting. Mucositis was Grade 3 or less and was delayed. The mean blood proteasome inhibition at 1, 24, and 48 h after 0.6 mg/m 2 was 32%, 16%, and 7% and after 0.9 mg/m 2 was 56%, 26%, and 14%, respectively. Differences in proteasome and NF-κB activity, apoptosis, and expression of NF-κB-modulated cell cycle, apoptosis, and angiogenesis factor mRNAs were detected in 2 patients with minor tumor reductions and in serum NF-κB-modulated cytokines in 1 patient with a major tumor reduction. Conclusions: In combination with reirradiation, the maximally tolerated dose of bortezomib was exceeded at a dose of 0.6 mg/m 2 and the threshold of proteasome inhibition. Although this regimen with reirradiation is not feasible, bortezomib induced detectable differences in NF-κB localization, apoptosis, and NF-κB-modulated genes and cytokines in tumor and serum in association with tumor reduction, indicating that other schedules of bortezomib combined with primary radiotherapy or reirradiation may merit future investigation

  12. Vorinostat, a HDAC inhibitor, showed anti-osteoarthritic activities through inhibition of iNOS and MMP expression, p38 and ERK phosphorylation and blocking NF-κB nuclear translocation.

    Science.gov (United States)

    Zhong, Hui-ming; Ding, Qian-hai; Chen, Wei-ping; Luo, Ru-bin

    2013-10-01

    Overproduction of nitric oxide (NO) and matrix metalloproteinases (MMPs) plays an important role in the pathogenesis of osteoarthritis (OA). In present study, we investigated whether vorinostat can inhibit the catabolic effects of IL-1β in vitro, especially the inhibition of MMPs and inducible nitric oxide synthase (iNOS) through the attenuation of nuclear factor kappa-B (NF-κB) and mitogen activated protein kinase (MAPK) pathways in human chondrocytes. Human OA chondrocytes were either left untreated or treated with various concentrations of vorinostat followed by incubation with IL-1β (5ng/mL). Effects of vorinostat on IL-1β-induced gene and protein expression of iNOS, MMP-1, MMP-13 and tissue inhibitors of metalloproteinase-1 (TIMP-1) were verified by quantitative real time-PCR and Western blot analysis. Production of NO, MMP-1, MMP-13 and TIMP-1 released in culture supernatant was estimated using commercially available kits. The roles of NF-κB and MAPK pathways in the regulation of targeted genes and the mechanism involved in vorinostat mediated modulation of these genes were determined by Western blot using specific antibodies. We found that vorinostat down-regulated iNOS, MMP-1 and MMP-13 expression and up-regulated TIMP-1 expression in human OA chondrocytes. In addition, the release of NO, MMP-1 and MMP-13 secreted from IL-1β stimulated chondrocytes was also suppressed by vorinostat. Interestingly, vorinostat selectively inhibited IL-1β-induced p38 and ERK1/2 activation without affecting JNK activation. Furthermore, we observed that vorinostat inhibited NF-κB pathway by suppressing the degradation of I-κBα and attenuating NF-κB p65 translocation to the nucleus. These results suggest that vorinostat may be a promising therapeutic agent for the prevention and treatment of OA. © 2013.

  13. 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

  14. Monoamine Oxidase Inhibitors (MAOIs)

    Science.gov (United States)

    ... health-medications/index.shtml. Accessed May 16, 2016. Hirsch M, et al. Monoamine oxidase inhibitors (MAOIs) for ... www.uptodate.com/home. Accessed May 16, 2016. Hirsch M, et al. Discontinuing antidepressant medications in adults. ...

  15. 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

    . In combination with HPLC–HRMS–SPE–NMR, this provides an analytical platform that allows simultaneous chemical and biological profiling of α-amylase inhibitors in plant extracts. Proof-of-concept with an artificial mixture of six compounds—of which three are known α-amylase inhibitors—showed that the high...

  16. SGLT2 inhibitors.

    Science.gov (United States)

    Dardi, I; Kouvatsos, T; Jabbour, S A

    2016-02-01

    Diabetes mellitus is a serious health issue and an economic burden, rising in epidemic proportions over the last few decades worldwide. Although several treatment options are available, only half of the global diabetic population achieves the recommended or individualized glycemic targets. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic agents with a novel insulin-independent action. SGLT2 is a transporter found in the proximal renal tubules, responsible for the reabsorption of most of the glucose filtered by the kidney. Inhibition of SGLT2 lowers the blood glucose level by promoting the urinary excretion of excess glucose. Due to their insulin-independent action, SGLT2 inhibitors can be used with any degree of beta-cell dysfunction or insulin resistance, related to a very low risk of hypoglycemia. In addition to improving glycemic control, SGLT2 inhibitors have been associated with a reduction in weight and blood pressure when used as monotherapy or in combination with other antidiabetic agents in patients with type 2 diabetes mellitus (T2DM). Treatment with SGLT2 inhibitors is usually well tolerated; however, they have been associated with an increased incidence of urinary tract and genital infections, although these infections are usually mild and easy to treat. SGLT2 inhibitors are a promising new option in the armamentarium of drugs for patients with T2DM. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Aromatase inhibitors in pediatrics.

    Science.gov (United States)

    Wit, Jan M; Hero, Matti; Nunez, Susan B

    2011-10-25

    Aromatase, an enzyme located in the endoplasmic reticulum of estrogen-producing cells, catalyzes the rate-limiting step in the conversion of androgens to estrogens in many tissues. The clinical features of patients with defects in CYP19A1, the gene encoding aromatase, have revealed a major role for this enzyme in epiphyseal plate closure, which has promoted interest in the use of inhibitors of aromatase to improve adult height. The availability of the selective aromatase inhibitors letrozole and anastrozole--currently approved as adjuvant therapy for breast cancer--have stimulated off-label use of aromatase inhibitors in pediatrics for the following conditions: hyperestrogenism, such as aromatase excess syndrome, Peutz-Jeghers syndrome, McCune-Albright syndrome and functional follicular ovarian cysts; hyperandrogenism, for example, testotoxicosis (also known as familial male-limited precocious puberty) and congenital adrenal hyperplasia; pubertal gynecomastia; and short stature and/or pubertal delay in boys. Current data suggest that aromatase inhibitors are probably effective in the treatment of patients with aromatase excess syndrome or testotoxicosis, partially effective in Peutz-Jeghers and McCune-Albright syndrome, but probably ineffective in gynecomastia. Insufficient data are available in patients with congenital adrenal hyperplasia or functional ovarian cysts. Although aromatase inhibitors appear effective in increasing adult height of boys with short stature and/or pubertal delay, safety concerns, including vertebral deformities, a decrease in serum HDL cholesterol levels and increase of erythrocytosis, are reasons for caution.

  18. JAK inhibitors in autoinflammation.

    Science.gov (United States)

    Hoffman, Hal M; Broderick, Lori

    2018-06-11

    Interferonopathies are a subset of autoinflammatory disorders with a prominent type I IFN gene signature. Treatment of these patients has been challenging, given the lack of response to common autoinflammatory therapeutics including IL-1 and TNF blockade. JAK inhibitors (Jakinibs) are a family of small-molecule inhibitors that target the JAK/STAT signaling pathway and have shown clinical efficacy, with FDA and European Medicines Agency (EMA) approval for arthritic and myeloproliferative syndromes. Sanchez and colleagues repurposed baricitinib to establish a significant role for JAK inhibition as a novel therapy for patients with interferonopathies, demonstrating the power of translational rare disease research with lifesaving effects.

  19. Cathepsin D inhibitors

    Directory of Open Access Journals (Sweden)

    M. Gacko

    2007-11-01

    Full Text Available Inhibitors of cathepsin D belong to chemical compounds that estrify carboxyl groups of the Asp33 and Asp231residues of its catalytic site, penta-peptides containing statin, i.e. the amino acid similar in structure to the tetraedric indirectproduct, and polypeptides found in the spare organs of many plants and forming permanent noncovalent complexes withcathepsin. Cathepsin D activity is also inhibited by alpha2-macroglobulin and antibodies directed against this enzyme.Methods used to determine the activity and concentration of these inhibitors and their analytical, preparative and therapeuticapplications are discussed.

  20. Nuclear law - Nuclear safety

    International Nuclear Information System (INIS)

    Pontier, Jean-Marie; Roux, Emmanuel; Leger, Marc; Deguergue, Maryse; Vallar, Christian; Pissaloux, Jean-Luc; Bernie-Boissard, Catherine; Thireau, Veronique; Takahashi, Nobuyuki; Spencer, Mary; Zhang, Li; Park, Kyun Sung; Artus, J.C.

    2012-01-01

    This book contains the contributions presented during a one-day seminar. The authors propose a framework for a legal approach to nuclear safety, a discussion of the 2009/71/EURATOM directive which establishes a European framework for nuclear safety in nuclear installations, a comment on nuclear safety and environmental governance, a discussion of the relationship between citizenship and nuclear, some thoughts about the Nuclear Safety Authority, an overview of the situation regarding the safety in nuclear waste burying, a comment on the Nome law with respect to electricity price and nuclear safety, a comment on the legal consequences of the Fukushima accident on nuclear safety in the Japanese law, a presentation of the USA nuclear regulation, an overview of nuclear safety in China, and a discussion of nuclear safety in the medical sector

  1. 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

  2. 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...

  3. A novel class of small molecule inhibitors of HDAC6.

    Science.gov (United States)

    Inks, Elizabeth S; Josey, Benjamin J; Jesinkey, Sean R; Chou, C James

    2012-02-17

    Histone deacetylases (HDACs) are a family of enzymes that play significant roles in numerous biological processes and diseases. HDACs are best known for their repressive influence on gene transcription through histone deacetylation. Mapping of nonhistone acetylated proteins and acetylation-modifying enzymes involved in various cellular pathways has shown protein acetylation/deacetylation also plays key roles in a variety of cellular processes including RNA splicing, nuclear transport, and cytoskeletal remodeling. Studies of HDACs have accelerated due to the availability of small molecule HDAC inhibitors, most of which contain a canonical hydroxamic acid or benzamide that chelates the metal catalytic site. To increase the pool of unique and novel HDAC inhibitor pharmacophores, a pharmacological active compound screen was performed. Several unique HDAC inhibitor pharmacophores were identified in vitro. One class of novel HDAC inhibitors, with a central naphthoquinone structure, displayed a selective inhibition profile against HDAC6. Here we present the results of a unique class of HDAC6 inhibitors identified using this compound library screen. In addition, we demonstrated that treatment of human acute myeloid leukemia cell line MV4-11 with the selective HDAC6 inhibitors decreases levels of mutant FLT-3 and constitutively active STAT5 and attenuates Erk phosphorylation, all of which are associated with the inhibitor's selective toxicity against leukemia.

  4. Acid corrosion inhibitor

    Energy Technology Data Exchange (ETDEWEB)

    Chen, N G

    1964-04-28

    An acid corrosion inhibitor is prepared by a 2-stage vacuum evaporation of effluents obtained from the ammonia columns of the coking oven plant. The effluent, leaving a scrubber in which the phenols are removed at a temperature of 98$C, passes through a quartz filter and flows into a heated chamber in which it is used for preheating a solution circulating through a vacuum unit, maintaining the temperature of the solution at 55$ to 60$C. The effluent enters a large tank in which it is boiled at 55$ to 60$C under 635 to 640 mm Hg pressure. Double evaporation of this solution yields a very effective acid corrosion inhibitor. Its corrosion-preventing effect is 97.9% compared with 90.1% for thiourea and 88.5% for urotropin under identical conditions.

  5. 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.

  6. Nuclear Medicine

    Science.gov (United States)

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

  7. DGAT inhibitors for obesity.

    Science.gov (United States)

    Matsuda, Daisuke; Tomoda, Hiroshi

    2007-10-01

    Obesity is characterized by the accumulation of triacylglycerol in adipocytes. Diacylglycerol acyltransferase (DGAT) catalyzes the final reaction of triacylgycerol synthesis. Two isozymes of DGAT, DGAT1 and DGAT2, have been reported. Increased DGAT2 activity has a role in steatosis, while DGAT1 plays a role in very (V)LDL synthesis; increased plasma VLDL concentrations may promote obesity and thus DGAT1 is considered a potential therapeutic target of inhibition for obesity control. Several DGAT inhibitors of natural and synthetic origin have been reported, and their future prospect as anti-obesity drugs is discussed in this review.

  8. Nuclear safety. Seguranca nuclear

    Energy Technology Data Exchange (ETDEWEB)

    Aveline, A [Rio Grande do Sul Univ., Porto Alegre, RS (Brazil). Inst. de Fisica

    1981-01-01

    What is nuclear safety Is there any technical way to reduce risks Is it possible to put them at reasonable levels Are there competitiveness and economic reliability to employ the nuclear energy by means of safety technics Looking for answers to these questions the author describes the sources of potential risks to nuclear reactors and tries to apply the answers to the Brazilian Nuclear Programme. (author).

  9. Inhibition of matrix metalloproteinase-2 by PARP inhibitors

    International Nuclear Information System (INIS)

    Nicolescu, Adrian C.; Holt, Andrew; Kandasamy, Arulmozhi D.; Pacher, Pal; Schulz, Richard

    2009-01-01

    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 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.

  10. 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.

  11. 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.

  12. Invisible nuclear; converting nuclear

    International Nuclear Information System (INIS)

    Park, Jongmoon

    1993-03-01

    This book consists of 14 chapters which are CNN era and big science, from East and West to North and South, illusory nuclear strategy, UN and nuclear arms reduction, management of armaments, advent of petroleum period, the track of nuclear power generation, view of energy, internationalization of environment, the war over water in the Middle East, influence of radiation and an isotope technology transfer and transfer armament into civilian industry, the end of nuclear period and the nuclear Nonproliferation, national scientific and technological power and political organ and executive organ.

  13. Pulmonary Toxicity of Cholinesterase Inhibitors

    National Research Council Canada - National Science Library

    Hilmas, Corey; Adler, Michael; Baskin, Steven I; Gupta, Ramesh C

    2006-01-01

    .... Whereas nerve agents were produced primarily for military deployment, other cholinesterase inhibitors were used for treating conditions such as myasthenia gravis and as pretreaunents for nerve agent exposure...

  14. Solution structure of the Grb2 SH2 domain complexed with a high-affinity inhibitor

    International Nuclear Information System (INIS)

    Ogura, Kenji; Shiga, Takanori; Yokochi, Masashi; Yuzawa, Satoru; Burke, Terrence R.; Inagaki, Fuyuhiko

    2008-01-01

    The solution structure of the growth factor receptor-bound protein 2 (Grb2) SH2 domain complexed with a high-affinity inhibitor containing a non-phosphorus phosphate mimetic within a macrocyclic platform was determined by nuclear magnetic resonance (NMR) spectroscopy. Unambiguous assignments of the bound inhibitor and intermolecular NOEs between the Grb2 SH2 domain and the inhibitor was accomplished using perdeuterated Grb2 SH2 protein. The well-defined solution structure of the complex was obtained and compared to those by X-ray crystallography. Since the crystal structure of the Grb2 SH2 domain formed a domain-swapped dimer and several inhibitors were bound to a hinge region, there were appreciable differences between the solution and crystal structures. Based on the binding interactions between the inhibitor and the Grb2 SH2 domain in solution, we proposed a design of second-generation inhibitors that could be expected to have higher affinity

  15. Biological abatement of cellulase inhibitors

    Science.gov (United States)

    Bio-abatement uses a fungus to metabolize and remove fermentation inhibitors. To determine whether bio-abatement could alleviate enzyme inhibitor effects observed in biomass liquors after pretreatment, corn stover at 10% (w/v) solids was pretreated with either dilute acid or liquid hot water. The ...

  16. Proteinaceous alpha-araylase inhibitors

    DEFF Research Database (Denmark)

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

    2004-01-01

    -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...

  17. Corrosion inhibitors. Manufacture and technology

    International Nuclear Information System (INIS)

    Ranney, M.W.

    1976-01-01

    Detailed information is presented relating to corrosion inhibitors. Areas covered include: cooling water, boilers and water supply plants; oil well and refinery operations; fuel and lubricant additives for automotive use; hydraulic fluids and machine tool lubes; grease compositions; metal surface treatments and coatings; and general processes for corrosion inhibitors

  18. [Nuclear theory

    International Nuclear Information System (INIS)

    Haxton, W.

    1990-01-01

    This report discusses research in nuclear physics. Topics covered in this paper are: symmetry principles; nuclear astrophysics; nuclear structure; quark-gluon plasma; quantum chromodynamics; symmetry breaking; nuclear deformation; and cold fusion

  19. Hsp90 inhibitors reduce influenza virus replication in cell culture

    International Nuclear Information System (INIS)

    Chase, Geoffrey; Deng, Tao; Fodor, Ervin; Leung, B.W.; Mayer, Daniel; Schwemmle, Martin; Brownlee, George

    2008-01-01

    The viral RNA polymerase complex of influenza A virus consists of three subunits PB1, PB2 and PA. Recently, the cellular chaperone Hsp90 was shown to play a role in nuclear import and assembly of the trimeric polymerase complex by binding to PB1 and PB2. Here we show that Hsp90 inhibitors, geldanamycin or its derivative 17-AAG, delay the growth of influenza virus in cell culture resulting in a 1-2 log reduction in viral titre early in infection. We suggest that this is caused by the reduced half-life of PB1 and PB2 and inhibition of nuclear import of PB1 and PA which lead to reduction in viral RNP assembly. Hsp90 inhibitors may represent a new class of antiviral compounds against influenza viruses

  20. Nuclear topics

    International Nuclear Information System (INIS)

    Lukner, C.

    1982-07-01

    The pamphlet touches on all aspects of nuclear energy, from the world energy demands and consumption, the energy program of the Federal Government, nuclear power plants in the world, nuclear fusion, nuclear liability up to the nuclear fuel cycle and the shutdown of nuclear power plants. (HSCH) [de

  1. Nuclear power and nuclear weapons

    International Nuclear Information System (INIS)

    Vaughen, V.C.A.

    1983-01-01

    The proliferation of nuclear weapons and the expanded use of nuclear energy for the production of electricity and other peaceful uses are compared. The difference in technologies associated with nuclear weapons and nuclear power plants are described

  2. 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.

  3. Polyphenol Compound as a Transcription Factor Inhibitor.

    Science.gov (United States)

    Park, Seyeon

    2015-10-30

    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)).

  4. [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.

  5. Nuclear rights - nuclear wrongs

    Energy Technology Data Exchange (ETDEWEB)

    Paul, E.F.; Miller, F.D.; Paul, J.; Ahrens, J.

    1986-01-01

    This book contains 11 selections. The titles are: Three Ways to Kill Innocent Bystanders: Some Conundrums Concerning the Morality of War; The International Defense of Liberty; Two Concepts of Deterrence; Nuclear Deterrence and Arms Control; Ethical Issues for the 1980s; The Moral Status of Nuclear Deterrent Threats; Optimal Deterrence; Morality and Paradoxical Deterrence; Immoral Risks: A Deontological Critique of Nuclear Deterrence; No War Without Dictatorship, No Peace Without Democracy: Foreign Policy as Domestic Politics; Marxism-Leninism and its Strategic Implications for the United States; Tocqueveille War.

  6. Nuclear moments

    CERN Document Server

    Kopferman, H; Massey, H S W

    1958-01-01

    Nuclear Moments focuses on the processes, methodologies, reactions, and transformations of molecules and atoms, including magnetic resonance and nuclear moments. The book first offers information on nuclear moments in free atoms and molecules, including theoretical foundations of hyperfine structure, isotope shift, spectra of diatomic molecules, and vector model of molecules. The manuscript then takes a look at nuclear moments in liquids and crystals. Discussions focus on nuclear paramagnetic and magnetic resonance and nuclear quadrupole resonance. The text discusses nuclear moments and nucl

  7. Electronic structure of trypsin inhibitor from squash seeds in aqueous solution

    Science.gov (United States)

    Zheng, Haoping

    2000-10-01

    The electronic structure of the trypsin inhibitor from seeds of the squash Cucurbita maxima (CMTI-I) in aqueous solution is obtained by ab initio, all-electron, full-potential calculations using the self-consistent cluster-embedding (SCCE) method. The reactive site of the inhibitor is explained theoretically, which is in agreement with the experimental results. It is shown that the coordinates of oxygen atoms in the inhibitor, determined by nuclear magnetic resonance and combination of distance geometry and dynamical simulated annealing, are systematically less accurate than that of other kinds of heavy atoms.

  8. Metal corrosion inhibitors and ecology

    International Nuclear Information System (INIS)

    Krasts, H.; Svarce, J.; Berge, B.

    1999-01-01

    The use of metal corrosion inhibitors in water is one of the cheapest method to protect metals against corrosion. However, the used inhibitors can come to surface water in the course of time and can become as source of environmental pollution. It is important to co-ordinate amount of substances in the elaborated inhibitors not only with demands for metal protection, but also with demands for quality of surface water and drinking water according to normative statements: 3.5 mg/l (as PO 4 ) for hexametaphosphate, tripolyphosphate and phosphonate; 40 mg/l (as SiO 2 for silicate, up to 1 mg/l for CU 2+ ; up to 5 mg/l for Zn 2+ ; up to 1 mg/l for B; up to 0.5 mg/l for Mo 2+ . The examples of the elaborated inhibitors are given. Many organic substances can be used as corrosion inhibitors, but there is shortage of standard methods for their analysis in water in Latvia. Removing of salt's deposits from boilers needs elaboration of a separate normative statement for dispersing waste water which content chloride at high concentration and heavy metals. (authors)

  9. Nuclear power

    International Nuclear Information System (INIS)

    Abd Khalik Wood

    2005-01-01

    This chapter discussed the following topics related to the nuclear power: nuclear reactions, nuclear reactors and its components - reactor fuel, fuel assembly, moderator, control system, coolants. The topics titled nuclear fuel cycle following subtopics are covered: , mining and milling, tailings, enrichment, fuel fabrication, reactor operations, radioactive waste and fuel reprocessing. Special topic on types of nuclear reactor highlighted the reactors for research, training, production, material testing and quite detail on reactors for electricity generation. Other related topics are also discussed: sustainability of nuclear power, renewable nuclear fuel, human capital, environmental friendly, emission free, impacts on global warming and air pollution, conservation and preservation, and future prospect of nuclear power

  10. Positron emitter labeled enzyme inhibitors

    International Nuclear Information System (INIS)

    Fowler, J.S.; MacGregor, R.R.; Wolf, A.P.; Langstrom, B.

    1990-01-01

    This invention involves a new strategy for imagining and mapping enzyme activity in the living human and animal body using positron emitter-labeled suicide enzyme inactivators or inhibitors which become covalently bound to the enzyme as a result of enzymatic catalysis. Two such suicide inactivators for monoamine oxidase have been labeled with carbon-11 and used to map the enzyme subtypes in the living human and animal body using PET. By using positron emission tomography to image the distribution of radioactivity produced by the body penetrating radiation emitted by carbon-11, a map of functionally active monoamine oxidase activity is obtained. Clorgyline and L-deprenyl are suicide enzyme inhibitors and irreversibly inhibit monoamine oxidase. When these inhibitors are labeled with carbon-11 they provide selective probes for monoamine oxidase localization and reactivity in vivo using positron emission tomography

  11. ROCK inhibitors in ocular disease

    Directory of Open Access Journals (Sweden)

    Eva Halasz

    2016-12-01

    Full Text Available Rho kinases (ROCKs have a crucial role in actin-cytoskeletal reorganization and thus are involved in broad aspects of cell motility, from smooth muscle contraction to neurite outgrowth. The first marketed ROCK inhibitor, called fasudil, has been used safely for treatment of cerebral vasospasm since 1995 in Japan. During the succeeding decades ROCK inhibitors have been applied in many pathological conditions from central nervous system disorders to cardiovascular disease as potential therapeutic agents or experimental tools to help understand the underlying (pathomechanisms. In 2014, a fasudil derivate named ripasudil was accepted for clinical use in glaucoma and ocular hypertension. Since ROCK kinases are widely expressed in ocular tissues, they have been implicated in the pathology of many ocular conditions such as corneal dysfunction, glaucoma, cataract, diabetic retinopathy, age-related macular degeneration, and retinal detachment. This paper aims to provide an overview of the most recent status/application of ROCK inhibitors in the field of eye disease.

  12. Nuclear Molecular Imaging Strategies in Immune Checkpoint Inhibitor Therapy

    DEFF Research Database (Denmark)

    Guldbrandsen, Kasper F; Hendel, Helle W; Langer, Seppo W

    2017-01-01

    this, new response criteria for evaluating these patients with morphologic imaging have been proposed. The aim of this paper is to review and discuss the current evidence for the use of molecular imaging, e.g., PET/CT (Positron Emission Tomography/Computer Tomography) with18F-Fluorodeoxyglucoes (FDG...

  13. Nuclear science

    International Nuclear Information System (INIS)

    1989-01-01

    This fact sheet answers specific questions about the Department of Energy's possible acquisition and conversion of a partially completed commercial nuclear power plant to a nuclear materials production facility. The nuclear power plant is the Washington Nuclear Plant number sign 1 owned by the Washington Public Power Supply System and is located on DOE's Hanford Reservation near Richland, Washington

  14. Nuclear science

    International Nuclear Information System (INIS)

    1989-04-01

    This report answers questions about the Department of Energy's possible acquisition and conversion of a partially completed commercial nuclear power plant to a nuclear materials production facility. The nuclear power plant is the Washington Nuclear Plant No.1 owned by the Washington Public Power Supply System and is located on DOE's Hanford Reservation near Richland, Washington

  15. Nuclear medicine

    International Nuclear Information System (INIS)

    Lentle, B.C.

    1986-01-01

    Several growth areas for nuclear medicine were defined. Among them were: cardiac nuclear medicine, neuro-psychiatric nuclear medicine, and cancer diagnosis through direct tumor imaging. A powerful new tool, Positron Emission Tomography (PET) was lauded as the impetus for new developments in nuclear medicine. The political environment (funding, degree of autonomy) was discussed, as were the economic and scientific environments

  16. Nuclear option

    Energy Technology Data Exchange (ETDEWEB)

    Kemm, K R

    1978-05-01

    The global outlook is that nuclear reactors are here to stay and South Africa has already entered the nuclear power stakes. This article discusses the rocketing oil prices, and the alternatives that can be used in power generation, the good safety record of the nuclear industry and the effect that South Africa's first nuclear power station should have on the environment.

  17. Nuclear resisters

    International Nuclear Information System (INIS)

    1981-01-01

    The booklet contains six papers by different authors, under the headings: dangers along the nuclear fuel cycle; the nuclear profiteers; the nuclear state is a police state; a non-disposable future (renewable energy sources, energy conservation); nuclear weapons - out of control; man made madness. (U.K.)

  18. Nuclear links

    International Nuclear Information System (INIS)

    1981-01-01

    The subject is dealt with in sections: introduction; energy and the third world; world energy consumption 1978; oil -the energy dilemma; nuclear chains - introduction; uranium; Namibia; enrichment and reprocessing; countries with enrichment and reprocessing facilities; waste; conclusion; why take the nuclear option; third world countries with nuclear reactors; the arms connection; government spending and human resources 1977 (by countries); nuclear power - the final solution; the fascists; world bank; campaigns; community action in Plogoff; Australian labour movement; NUM against nuclear power; Scottish campaign; students against nuclear energy; anti-nuclear campaign; partizans; 3W1 disarmament and development; campaign ATOM; CANUC; 3W1; SANE. (U.K.)

  19. Azidoblebbistatin, a photoreactive myosin inhibitor

    Science.gov (United States)

    Képiró, Miklós; Várkuti, Boglárka H.; Bodor, Andrea; Hegyi, György; Drahos, László; Kovács, Mihály; Málnási-Csizmadia, András

    2012-01-01

    Photoreactive compounds are important tools in life sciences that allow precisely timed covalent crosslinking of ligands and targets. Using a unique technique we have synthesized azidoblebbistatin, which is a derivative of blebbistatin, the most widely used myosin inhibitor. Without UV irradiation azidoblebbistatin exhibits identical inhibitory properties to those of blebbistatin. Using UV irradiation, azidoblebbistatin can be covalently crosslinked to myosin, which greatly enhances its in vitro and in vivo effectiveness. Photo-crosslinking also eliminates limitations associated with the relatively low myosin affinity and water solubility of blebbistatin. The wavelength used for photo-crosslinking is not toxic for cells and tissues, which confers a great advantage in in vivo tests. Because the crosslink results in an irreversible association of the inhibitor to myosin and the irradiation eliminates the residual activity of unbound inhibitor molecules, azidoblebbistatin has a great potential to become a highly effective tool in both structural studies of actomyosin contractility and the investigation of cellular and physiological functions of myosin II. We used azidoblebbistatin to identify previously unknown low-affinity targets of the inhibitor (EC50 ≥ 50 μM) in Dictyostelium discoideum, while the strongest interactant was found to be myosin II (EC50 = 5 μM). Our results demonstrate that azidoblebbistatin, and potentially other azidated drugs, can become highly useful tools for the identification of strong- and weak-binding cellular targets and the determination of the apparent binding affinities in in vivo conditions. PMID:22647605

  20. Biological abatement of cellulase inhibitors.

    Science.gov (United States)

    Cao, Guangli; Ximenes, Eduardo; Nichols, Nancy N; Zhang, Leyu; Ladisch, Michael

    2013-10-01

    Removal of enzyme inhibitors released during lignocellulose pretreatment is essential for economically feasible biofuel production. We tested bio-abatement to mitigate enzyme inhibitor effects observed in corn stover liquors after pretreatment with either dilute acid or liquid hot water at 10% (w/v) solids. Bio-abatement of liquors was followed by enzymatic hydrolysis of cellulose. To distinguish between inhibitor effects on enzymes and recalcitrance of the substrate, pretreated corn stover solids were removed and replaced with 1% (w/v) Solka Floc. Cellulose conversion in the presence of bio-abated liquors from dilute acid pretreatment was 8.6% (0.1x enzyme) and 16% (1x enzyme) higher than control (non-abated) samples. In the presence of bio-abated liquor from liquid hot water pretreated corn stover, 10% (0.1x enzyme) and 13% (1x enzyme) higher cellulose conversion was obtained compared to control. Bio-abatement yielded improved enzyme hydrolysis in the same range as that obtained using a chemical (overliming) method for mitigating inhibitors. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Phosphodiesterase inhibitors in clinical urology.

    Science.gov (United States)

    Ückert, Stefan; Kuczyk, Markus A; Oelke, Matthias

    2013-05-01

    To date, benign diseases of the male and female lower urinary and genital tract, such as erectile dysfunction, bladder overactivity, lower urinary tract symptomatology secondary to benign prostatic hyperplasia and symptoms of female sexual dysfunction (including arousal and orgasmic disorders), can be therapeutically approached by influencing the function of the smooth musculature of the respective tissues. The use of isoenzyme-selective phosphodiesterase (PDE) inhibitors is considered a great opportunity to treat various diseases of the human urogenital tract. PDE inhibitors, in particular the PDE5 (cyclic GMP PDE) inhibitors avanafil, lodenafil, sildenafil, tadalafil, udenafil and vardenafil, are regarded as efficacious, having a fast onset of drug action and an improved effect-to-adverse event ratio, combining a high response rate with the advantage of an on-demand intake. The purpose of this review is to summarize recent as well as potential future indications, namely, erectile dysfunction, Peyronie's disease, overactive bladder, urinary stone disease, lower urinary tract symptomatology secondary to benign prostatic hyperplasia and premature ejaculation, for the use of PDE inhibitors in clinical urology.

  2. Inhibitors of mTOR

    NARCIS (Netherlands)

    Klümpen, Heinz-Josef; Beijnen, Jos H.; Gurney, Howard; Schellens, Jan H. M.

    2010-01-01

    Inhibitors of mammalian target of rapamycin (mTOR) have been approved for the treatment of renal cell carcinoma and appear to have a role in the treatment of other malignancies. The primary objective of this drug review is to provide pharmacokinetic and dynamic properties of the commonly used drugs

  3. Retroviral proteinases and their inhibitors

    Czech Academy of Sciences Publication Activity Database

    Sedláček, Juraj

    2000-01-01

    Roč. 3, 3,4 (2000), s. 23-24 [ Proteolytic enzymes and their inhibitors in physiology and pathogenesis. 14.09.2000, Plzen] Institutional research plan: CEZ:AV0Z5052915 Subject RIV: EB - Genetics ; Molecular Biology

  4. Inhibitor-induced oxidation of the nucleus and cytosol in Arabidopsis thaliana: implications for organelle to nucleus retrograde signalling.

    Science.gov (United States)

    Karpinska, Barbara; Alomrani, Sarah Owdah; Foyer, Christine H

    2017-09-26

    Concepts of organelle-to-nucleus signalling pathways are largely based on genetic screens involving inhibitors of chloroplast and mitochondrial functions such as norflurazon, lincomycin (LINC), antimycin A (ANT) and salicylhydroxamic acid. These inhibitors favour enhanced cellular oxidation, but their precise effects on the cellular redox state are unknown. Using the in vivo reduction-oxidation (redox) reporter, roGFP2, inhibitor-induced changes in the glutathione redox potentials of the nuclei and cytosol were measured in Arabidopsis thaliana root, epidermal and stomatal guard cells, together with the expression of nuclear-encoded chloroplast and mitochondrial marker genes. All the chloroplast and mitochondrial inhibitors increased the degree of oxidation in the nuclei and cytosol. However, inhibitor-induced oxidation was less marked in stomatal guard cells than in epidermal or root cells. Moreover, LINC and ANT caused a greater oxidation of guard cell nuclei than the cytosol. Chloroplast and mitochondrial inhibitors significantly decreased the abundance of LHCA1 and LHCB1 transcripts. The levels of WHY1 , WHY3 and LEA5 transcripts were increased in the presence of inhibitors. Chloroplast inhibitors decreased AOXA1 mRNA levels, while mitochondrial inhibitors had the opposite effect. Inhibitors that are used to characterize retrograde signalling pathways therefore have similar general effects on cellular redox state and gene expression.This article is part of the themed issue 'Enhancing photosynthesis in crop plants: targets for improvement'. © 2017 The Authors.

  5. Monoamine depletion by reuptake inhibitors

    Directory of Open Access Journals (Sweden)

    Hinz M

    2011-10-01

    Full Text Available Marty Hinz1, Alvin Stein2, Thomas Uncini31Clinical Research, NeuroResearch Clinics Inc, Cape Coral, FL; 2Stein Orthopedic Associates, Plantation, FL; 3DBS Labs Inc, Duluth, MN, USABackground: Disagreement exists regarding the etiology of cessation of the observed clinical results with administration of reuptake inhibitors. Traditionally, when drug effects wane, it is known as tachyphylaxis. With reuptake inhibitors, the placebo effect is significantly greater than the drug effect in the treatment of depression and attention deficit hyperactivity disorder, leading some to assert that waning of drug effects is placebo relapse, not tachyphylaxis.Methods: Two groups were retrospectively evaluated. Group 1 was composed of subjects with depression and Group 2 was composed of bariatric subjects treated with reuptake inhibitors for appetite suppression.Results: In Group 1, 200 subjects with depression were treated with citalopram 20 mg per day. A total of 46.5% (n = 93 achieved relief of symptoms (Hamilton-D rating score ≤ 7, of whom 37 (39.8% of whom experienced recurrence of depression symptoms, at which point an amino acid precursor formula was started. Within 1–5 days, 97.3% (n = 36 experienced relief of depression symptoms. In Group 2, 220 subjects were treated with phentermine 30 mg in the morning and citalopram 20 mg at 4 pm. In this group, 90.0% (n = 198 achieved adequate appetite suppression. The appetite suppression ceased in all 198 subjects within 4–48 days. Administration of an amino acid precursor formula restored appetite suppression in 98.5% (n = 195 of subjects within 1–5 days.Conclusion: Reuptake inhibitors do not increase the total number of monoamine molecules in the central nervous system. Their mechanism of action facilitates redistribution of monoamines from one place to another. In the process, conditions are induced that facilitate depletion of monoamines. The "reuptake inhibitor monoamine depletion theory" of this paper

  6. Evaluation of corrosion inhibitors for high temperature decontamination applications

    International Nuclear Information System (INIS)

    Sathyaseelan, V.S.; Rufus, A.L.; Velmurugan, S.

    2015-01-01

    Normally, chemical decontamination of coolant systems of nuclear power reactors is carried out at temperatures less than 90 °C. At these temperatures, though magnetite dissolves effectively, the rate of dissolution of chromium and nickel containing oxides formed over stainless steel and other non-carbon steel coolant system surfaces is not that appreciable. A high temperature dissolution process using 5 mM NTA at 160 °C developed earlier by us was very effective in dissolving the oxides such as ferrites and chromites. However, the corrosion of structural materials such as carbon steel (CS) and stainless steel (SS) also increased beyond the acceptable limits at elevated temperatures. Hence, the control of base metal corrosion during the high temperature decontamination process is very important. In view of this, it was felt essential to investigate and develop a suitable inhibitor to reduce the corrosion that can take place on coolant structural material surfaces during the high temperature decontamination applications with weak organic acids. Three commercial inhibitors viz., Philmplus 5K655, Prosel PC 2116 and Ferroqest were evaluated at ambient and at 160 °C temperature in NTA formulation. Preliminary evaluation of these corrosion inhibitors carried out using electrochemical techniques showed maximum corrosion inhibition efficiency for Philmplus. Hence, it was used for high temperature applications. A concentration of 500 ppm was found to be optimum at 160 °C and at this concentration it showed an inhibition efficiency of 62% for CS. High temperature dissolution of oxides such as Fe 3 O 4 and NiFe 2 O 4 , which are relevant to nuclear reactors, was also carried out and the rate of dissolution observed was less in the presence of Philmplus. Studies were also carried out to evaluate hydrazine as a corrosion inhibitor for high temperature applications. The results revealed that for CS inhibition efficiency of hydrazine is comparable to that of Philmplus, while

  7. Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs)

    Science.gov (United States)

    Serotonin and norepinephrine reuptake inhibitors (SNRIs) Antidepressant SNRIs help relieve depression symptoms, such as irritability and sadness, ... effects they may cause. By Mayo Clinic Staff Serotonin and norepinephrine reuptake inhibitors (SNRIs) are a class ...

  8. Contemporary protease inhibitors and cardiovascular risk

    DEFF Research Database (Denmark)

    Lundgren, Jens; Mocroft, Amanda; Ryom, Lene

    2018-01-01

    PURPOSE OF REVIEW: To review the evidence linking use of HIV protease inhibitors with excess risk of cardiovascular disease (CVD) in HIV+ populations. RECENT FINDINGS: For the two contemporary most frequently used protease inhibitors, darunavir and atazanavir [both pharmacologically boosted...

  9. Improvement of Corrosion Inhibitors of Primary and Secondary Closed Cooling Water System

    International Nuclear Information System (INIS)

    Choi, Byung Seon; Kim, K. M.; Kim, K. H.

    2010-08-01

    In nuclear power plants, the Closed Cooling Water (CCW) system provide cooling to both safety-related and non-safety-related heat exchange equipment. Various chemicals are used to mitigate corrosion, fouling, and microbiological growth in the CCW systems. In nuclear plants, these inhibitors have included chromates, nitrites, molybdates, hydrazine, and silicate. In the case of the CCW of some domestic nuclear power plants, there is during the overhaul period, a saturation of ion exchange resin caused by an inhibitor which has high conductivity for an increase in radiation exposure and radioactive waste. The objective of this study is to evaluate the corrosion behavior of structural materials with various corrosion inhibitors. In the present study, more than 50 ppm hydrazine concentration is needed to reduce the corrosion rate of carbon steel to satisfy the CCW operational guidelines. However, if hydrazine is continuously injected into the CCW system, the critical concentration of hydrazine will be lower. Hydrazine might be an alternative corrosion inhibitor for nitrite in the CCW system of nuclear power plant

  10. Transportin-1-dependent YB-1 nuclear import

    International Nuclear Information System (INIS)

    Mordovkina, Daria A.; Kim, Ekaterina R.; Buldakov, Ilya A.; Sorokin, Alexey V.; Eliseeva, Irina A.; Lyabin, Dmitry N.; Ovchinnikov, Lev P.

    2016-01-01

    The DNA/RNA-binding protein YB-1 (Y-box binding protein 1) performs multiple functions both in the cytoplasm and the nucleus of the cell. Generally localized to the cytoplasm, under certain conditions YB-1 is translocated to the nucleus. Here we report for the first time a transport factor that mediates YB-1 nuclear import – transportin-1. The YB-1/transportin-1 complex can be isolated from HeLa cell extract. Nuclear import of YB-1 and its truncated form YB-1 (1-219) in in vitro transport assay was diminished in the presence of a competitor substrate and ceased in the presence of transportin-1 inhibitor M9M. Inhibitors of importin β1 had no effect on YB-1 transport. Furthermore, transport of YB-1 (P201A/Y202A) and YB-1 (1–219) (P201A/Y202A) bearing inactivating mutations in the transportin-1-dependent nuclear localization signal was practically abolished. Together, these results indicate that transportin-1 mediates YB-1 nuclear translocation. - Highlights: • Transportin-1 mediates YB-1 nuclear import. • YB-1 nuclear translocation is diminished in the presence of transportin-1 inhibitors. • Mutations in the PY motif of YB-1 NLS prevent its translocation to the nucleus.

  11. Reduction rules for reset/inhibitor nets

    NARCIS (Netherlands)

    Verbeek, H.M.W.; Wynn, M.T.; Aalst, van der W.M.P.; Hofstede, ter A.H.M.

    2010-01-01

    Reset/inhibitor nets are Petri nets extended with reset arcs and inhibitor arcs. These extensions can be used to model cancellation and blocking. A reset arc allows a transition to remove all tokens from a certain place when the transition fires. An inhibitor arc can stop a transition from being

  12. 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...

  13. 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.

  14. Nuclear Power

    International Nuclear Information System (INIS)

    Douglas-Hamilton, J.; Home Robertson, J.; Beith, A.J.

    1987-01-01

    In this debate the Government's policy on nuclear power is discussed. Government policy is that nuclear power is the safest and cleanest way of generating electricity and is cheap. Other political parties who do not endorse a nuclear energy policy are considered not to be acting in the people's best interests. The debate ranged over the risks from nuclear power, the UK safety record, safety regulations, and the environmental effects of nuclear power. The Torness nuclear power plant was mentioned specifically. The energy policy of the opposition parties is strongly criticised. The debate lasted just over an hour and is reported verbatim. (UK)

  15. Discovery of HDAC inhibitors with potent activity against multiple malaria parasite life cycle stages.

    Science.gov (United States)

    Hansen, Finn K; Sumanadasa, Subathdrage D M; Stenzel, Katharina; Duffy, Sandra; Meister, Stephan; Marek, Linda; Schmetter, Rebekka; Kuna, Krystina; Hamacher, Alexandra; Mordmüller, Benjamin; Kassack, Matthias U; Winzeler, Elizabeth A; Avery, Vicky M; Andrews, Katherine T; Kurz, Thomas

    2014-07-23

    In this work we investigated the antiplasmodial activity of a series of HDAC inhibitors containing an alkoxyamide connecting-unit linker region. HDAC inhibitor 1a (LMK235), previously shown to be a novel and specific inhibitor of human HDAC4 and 5, was used as a starting point to rapidly construct a mini-library of HDAC inhibitors using a straightforward solid-phase supported synthesis. Several of these novel HDAC inhibitors were found to have potent in vitro activity against asexual stage Plasmodium falciparum malaria parasites. Representative compounds were shown to hyperacetylate P. falciparum histones and to inhibit deacetylase activity of recombinant PfHDAC1 and P. falciparum nuclear extracts. All compounds were also screened in vitro for activity against Plasmodium berghei exo-erythrocytic stages and selected compounds were further tested against late stage (IV and V) P. falciparum gametocytes. Of note, some compounds showed nanomolar activity against all three life cycle stages tested (asexual, exo-erythrocytic and gametocyte stages) and several compounds displayed significantly increased parasite selectivity compared to the reference HDAC inhibitor suberoylanilide hydroxamic acid (SAHA). These data suggest that it may be possible to develop HDAC inhibitors that target multiple malaria parasite life cycle stages. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  16. 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.

  17. JPRS Report, Nuclear Developments

    National Research Council Canada - National Science Library

    1991-01-01

    Partial Contents: Medium Range Missiles, Rocket Engine, Nuclear Submarine, Nuclear Reactor, Nuclear Inspection, Nuclear Weapons, Transfer Technology, Scud, Safety, Nuclear Power, Chernobyl Trial, ,CHemical Weapons...

  18. 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.

  19. Stabilization versus inhibition of TAFIa by competitive inhibitors in vitro

    NARCIS (Netherlands)

    Walker, J.B.; Hughes, B.; James, I.; Haddock, P.; Kluft, C.; Bajzar, L.

    2003-01-01

    Two competitive inhibitors of TAFIa (activated thrombin-activable fibrinolysis inhibitor), 2-guanidinoethyl-mercaptosuccinic acid and potato tuber carboxypeptidase inhibitor, variably affect fibrinolysis of clotted human plasma. Depending on their concentration, the inhibitors shortened, prolonged,

  20. Nuclear forensics

    International Nuclear Information System (INIS)

    Venugopal, V.

    2010-01-01

    Nuclear forensics is the analysis of nuclear materials recovered from either the capture of unused materials, or from the radioactive debris following a nuclear explosion and can contribute significantly to the identification of the sources of the materials and the industrial processes used to obtain them. In the case of an explosion, nuclear forensics can also reconstruct key features of the nuclear device. Nuclear forensic analysis works best in conjunction with other law enforcement, radiological protection dosimetry, traditional forensics, and intelligence work to provide the basis for attributing the materials and/or nuclear device to its originators. Nuclear forensics is a piece of the overall attribution process, not a stand-alone activity

  1. Nuclear power

    International Nuclear Information System (INIS)

    1987-01-01

    ''Nuclear Power'' describes how a reactor works and examines the different designs including Magnox, AGR, RBMK and PWR. It charts the growth of nuclear generation in the world and its contributions to world energy resources. (author)

  2. 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 ...

  3. Nuclear energy

    International Nuclear Information System (INIS)

    Kuhn, W.

    1986-01-01

    This loose-leaf collection is made up of five didactically prepared units covering the following subjects: basic knowledge on nuclear energy, nuclear energy in relation to energy economy, site issues, environmental compatibility of nuclear energy, and nuclear energy in the focus of political and social action. To this was added a comprehensive collection of material: specific scientific background material, a multitude of tables, diagrams, charts etc. for copying, as well as 44 transparent charts, mostly in four colours. (orig./HP) [de

  4. Nuclear structure

    International Nuclear Information System (INIS)

    Eastham, D.A.; Joy, T.

    1986-01-01

    The paper on 'nuclear structure' is the Appendix to the Daresbury (United Kingdom) Annual Report 1985/86, and contains the research work carried out at the Nuclear Structure Facility, Daresbury, within that period. During the year a total of 74 experiments were scheduled covering the main areas of activity including: nuclear collective motion, nuclei far from stability, and nuclear collisions. The Appendix contains brief reports on these experiments and associated theory. (U.K.)

  5. Nuclear terrorism

    International Nuclear Information System (INIS)

    2002-01-01

    Recent reports of alleged terrorist plans to build a 'dirty bomb' have heightened longstanding concerns about nuclear terrorism. This briefing outlines possible forms of attack, such as: detonation of a nuclear weapon; attacks involving radioactive materials; attacks on nuclear facilities. Legislation addressing these risks and the UK's strategy for coping with them are also considered

  6. Nuclear power

    International Nuclear Information System (INIS)

    d'Easum, Lille.

    1976-03-01

    An environmentalist's criticism of nuclear energy is given, on a layman's level. Such subjects as conflict of interest in controlling bodies, low-level radiation, reactor safety, liability insurance, thermal pollution, economics, heavy water production, export of nuclear technology, and the history of the anti-nuclear movement are discussed in a sensationalistic tone. (E.C.B.)

  7. Nuclear alerts

    International Nuclear Information System (INIS)

    Anon.

    1983-01-01

    Anti-nuclear demonstrations against the deployment of new US missiles were held in Nato Europe. As no agreement has yet been reached at the US-Soviet Intermediate Nuclear Forces talks in Geneva, the deployment of nuclear missiles in Europe has started

  8. Nuclear questions

    International Nuclear Information System (INIS)

    Berg, Eugene

    2012-01-01

    Civilian and military nuclear questions fill a multitude of publications these days, especially after the Japanese tsunami and the Fukushima disaster. The author analyses some of them and highlights the links between civil and military nuclear industries, the realities of the nuclear cycle and related industrial questions before concluding on the controversial issue of weapons and their proliferation potential

  9. Nuclear decommissioning

    International Nuclear Information System (INIS)

    Anon.

    1987-01-01

    The paper on nuclear decommissioning was presented by Dr H. Lawton to a meeting of the British Nuclear Energy Society and Institution of Nuclear Engineers, 1986. The decommissioning work currently being undertaken on the Windscale advanced gas cooled reactor (WAGR) is briefly described, along with projects in other countries, development work associated with the WAGR operation and costs. (U.K.)

  10. Nuclear electronics

    International Nuclear Information System (INIS)

    Friese, T.

    1981-09-01

    A short survey is given on nuclear radiation detectors and nuclear electronics. It is written for newcomers and those, who are not very familiar with this technique. Some additional information is given on typical failures in nuclear measurement systems. (orig.) [de

  11. Nucleocytoplasmic shuttling mediates the dynamic maintenance of nuclear Dorsal levels during Drosophila embryogenesis

    DEFF Research Database (Denmark)

    DeLotto, Robert; DeLotto, Yvonne; Steward, Ruth

    2007-01-01

    , including nuclei on the dorsal side. Nuclear export is blocked by leptomycin B, a potent inhibitor of Exportin 1 (CRM1)-mediated nuclear export. We have developed a novel in vivo assay revealing the presence of a functional leucine-rich nuclear export signal within the carboxyterminal 44 amino acids...

  12. Nuclear energy

    International Nuclear Information System (INIS)

    2007-01-01

    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 orientation and nuclear structure

    International Nuclear Information System (INIS)

    Krane, K.S.

    1988-01-01

    The present generation of on-line nuclear orientation facilities promises to revolutionize the gathering of nuclear structure information, especially for the hitherto poorly known and understood nuclei far from stability. Following a brief review of the technological developments that have facilitated these experiments, the nuclear spectroscopic information that can be obtained is summarized. Applications to understanding nuclear structure are reviewed, and challenges for future studies are discussed. (orig.)

  14. Nuclear power

    International Nuclear Information System (INIS)

    Anon.

    1980-01-01

    The committee concludes that the nature of the proliferation problem is such that even stopping nuclear power completely could not stop proliferation completely. Countries can acquire nuclear weapons by means independent of commercial nuclear power. It is reasonable to suppose if a country is strongly motivated to acquire nuclear weapons, it will have them by 2010, or soon thereafter, no matter how nuclear power is managed in the meantime. Unilateral and international diplomatic measures to reduce the motivations that lead to proliferation should be high on the foreign policy agenda of the United States. A mimimum antiproliferation prescription for the management of nuclear power is to try to raise the political barriers against proliferation through misuse of nuclear power by strengthening the Non-Proliferation Treaty, and to seek to raise the technological barriers by placing fuel-cycle operations involving weapons-usable material under international control. Any such measures should be considered tactics to slow the spread of nuclear weapons and thus earn time for the exercise of statesmanship. The committee concludes the following about technical factors that should be considered in formulating nuclear policy: (1) rate of growth of electricity use is a primary factor; (2) growth of conventional nuclear power will be limited by producibility of domestic uranium sources; (3) greater contribution of nuclear power beyond 400 GWe past the year 2000 can only be supported by advanced reactor systems; and (4) several different breeder reactors could serve in principle as candidates for an indefinitely sustainable source of energy

  15. Nuclear physics

    International Nuclear Information System (INIS)

    Kamal, Anwar

    2014-01-01

    Explains the concepts in detail and in depth. Provides step-by-step derivations. Contains numerous tables and diagrams. Supports learning and teaching with numerous worked examples, questions and problems with answers. Sketches also the historical development of the subject. This textbook explains the experimental basics, effects and theory of nuclear physics. It supports learning and teaching with numerous worked examples, questions and problems with answers. Numerous tables and diagrams help to better understand the explanations. A better feeling to the subject of the book is given with sketches about the historical development of nuclear physics. The main topics of this book include the phenomena associated with passage of charged particles and radiation through matter which are related to nuclear resonance fluorescence and the Moessbauer effect., Gamov's theory of alpha decay, Fermi theory of beta decay, electron capture and gamma decay. The discussion of general properties of nuclei covers nuclear sizes and nuclear force, nuclear spin, magnetic dipole moment and electric quadrupole moment. Nuclear instability against various modes of decay and Yukawa theory are explained. Nuclear models such as Fermi Gas Model, Shell Model, Liquid Drop Model, Collective Model and Optical Model are outlined to explain various experimental facts related to nuclear structure. Heavy ion reactions, including nuclear fusion, are explained. Nuclear fission and fusion power production is treated elaborately.

  16. Nuclear chemistry

    International Nuclear Information System (INIS)

    Vertes, A.; Kiss, I.

    1987-01-01

    This book is an introduction to the application of nuclear science in modern chemistry. The first group of chapters discuss the basic phenomena and concepts of nuclear physics with emphasis on their relation to chemical problems, including the main properties and the composition of atomic nuclei, nuclear reactions, radioactive decay and interactions of radiation with matter. These chapters provide the basis for understanding the following chapters which encompass the wide scope of nuclear chemistry. The methods of the investigation of chemical structure based on the interaction of nuclear radiation with matter including positronium chemistry and other exotic atoms is elaborated in particular detail. Separate chapters are devoted to the use of radioactive tracers, the chemical consequences of nuclear processes (i.e. hot atom chemistry), radiation chemistry, isotope effects and their applications, and the operation of nuclear reactors

  17. Nuclear chemistry

    International Nuclear Information System (INIS)

    Vertes, A.; Kiss, I.

    1987-01-01

    This book is an introduction to the application of nuclear science in modern chemistry. The first group of chapters discuss the basic phenomena and concepts of nuclear physics with emphasis on their relation to chemical problems, including the main properties and the composition of atomic nuclei, nuclear reactions, radioactive decay and interactions of radiation with matter. These chapters provide the basis for understanding the following chapters which encompass the wide scope of nuclear chemistry. The methods of the investigation of chemical structure based on the interaction of nuclear radiation with matter including positronium chemistry and other exotic atoms is elaborated in particular detail. Separate chapters are devoted to the use of radioactive tracers, the chemical consequences of nuclear processes (i.e. hot atom chemistry), radiation chemistry, isotope effects and their applications, and the operation of nuclear reactors. (Auth.)

  18. Nuclear forensics

    International Nuclear Information System (INIS)

    Karadeniz, O.; Guenalp, G.

    2010-01-01

    This review discusses the methodology of nuclear forensics and illicit trafficking of nuclear materials. Nuclear forensics is relatively new scientific branch whose aim it is to read out material inherent from nuclear material. Nuclear forensics investigations have to be considered as part of a comprehensive set of measures for detection,interception, categorization and characterization of illicitly trafficking nuclear material. Prevention, detection and response are the main elements in combating illicit trafficking. Forensics is a key element in the response process. Forensic science is defined as the application of a broad spectrum of sciences to answer questions of interest to the legal system. Besides, in this study we will explain age determination of nuclear materials.

  19. Nuclear fuels

    International Nuclear Information System (INIS)

    Gangwani, Saloni; Chakrabortty, Sumita

    2011-01-01

    Nuclear fuel is a material that can be consumed to derive nuclear energy, by analogy to chemical fuel that is burned for energy. Nuclear fuels are the most dense sources of energy available. Nuclear fuel in a nuclear fuel cycle can refer to the fuel itself, or to physical objects (for example bundles composed of fuel rods) composed of the fuel material, mixed with structural, neutron moderating, or neutron reflecting materials. Long-lived radioactive waste from the back end of the fuel cycle is especially relevant when designing a complete waste management plan for SNF. When looking at long-term radioactive decay, the actinides in the SNF have a significant influence due to their characteristically long half-lives. Depending on what a nuclear reactor is fueled with, the actinide composition in the SNF will be different. The following paper will also include the uses. advancements, advantages, disadvantages, various processes and behavior of nuclear fuels

  20. Nuclear networking.

    Science.gov (United States)

    Xie, Wei; Burke, Brian

    2017-07-04

    Nuclear lamins are intermediate filament proteins that represent important structural components of metazoan nuclear envelopes (NEs). By combining proteomics and superresolution microscopy, we recently reported that both A- and B-type nuclear lamins form spatially distinct filament networks at the nuclear periphery of mouse fibroblasts. In particular, A-type lamins exhibit differential association with nuclear pore complexes (NPCs). Our studies reveal that the nuclear lamina network in mammalian somatic cells is less ordered and more complex than that of amphibian oocytes, the only other system in which the lamina has been visualized at high resolution. In addition, the NPC component Tpr likely links NPCs to the A-type lamin network, an association that appears to be regulated by C-terminal modification of various A-type lamin isoforms. Many questions remain, however, concerning the structure and assembly of lamin filaments, as well as with their mode of association with other nuclear components such as peripheral chromatin.

  1. Histone deacetylase inhibitors (HDACIs): multitargeted anticancer agents.

    Science.gov (United States)

    Ververis, Katherine; Hiong, Alison; Karagiannis, Tom C; Licciardi, Paul V

    2013-01-01

    Histone deacetylase (HDAC) inhibitors are an emerging class of therapeutics with potential as anticancer drugs. The rationale for developing HDAC inhibitors (and other chromatin-modifying agents) as anticancer therapies arose from the understanding that in addition to genetic mutations, epigenetic changes such as dysregulation of HDAC enzymes can alter phenotype and gene expression, disturb homeostasis, and contribute to neoplastic growth. The family of HDAC inhibitors is large and diverse. It includes a range of naturally occurring and synthetic compounds that differ in terms of structure, function, and specificity. HDAC inhibitors have multiple cell type-specific effects in vitro and in vivo, such as growth arrest, cell differentiation, and apoptosis in malignant cells. HDAC inhibitors have the potential to be used as monotherapies or in combination with other anticancer therapies. Currently, there are two HDAC inhibitors that have received approval from the US FDA for the treatment of cutaneous T-cell lymphoma: vorinostat (suberoylanilide hydroxamic acid, Zolinza) and depsipeptide (romidepsin, Istodax). More recently, depsipeptide has also gained FDA approval for the treatment of peripheral T-cell lymphoma. Many more clinical trials assessing the effects of various HDAC inhibitors on hematological and solid malignancies are currently being conducted. Despite the proven anticancer effects of particular HDAC inhibitors against certain cancers, many aspects of HDAC enzymes and HDAC inhibitors are still not fully understood. Increasing our understanding of the effects of HDAC inhibitors, their targets and mechanisms of action will be critical for the advancement of these drugs, especially to facilitate the rational design of HDAC inhibitors that are effective as antineoplastic agents. This review will discuss the use of HDAC inhibitors as multitargeted therapies for malignancy. Further, we outline the pharmacology and mechanisms of action of HDAC inhibitors while

  2. Calcineurin-inhibitor pain syndrome.

    Science.gov (United States)

    Prommer, Eric

    2012-07-01

    There has been increased recognition of calcineurin, a phosphoprotein serine/threonine phosphatase enzyme, in the regulation of many physiologic systems. Calcineurin mediates activation of lymphocytes, which play a role in immune response. Widely distributed in the central nervous system, calcinuerin also plays an important role in sensory neural function, via its role in the regulation of newly discovered 2-pore potassium channels, which greatly influence neuronal resting membrane potentials. Calcinuerin inhibition is the mechanism of action of immunomodulatory drugs such as cyclosporine and tacrolimus, which are widely used in transplantation medicine to prevent rejection. While important for immunosuppression, the use of calcineurin inhibitors has been associated with the development of a new pain syndrome called the calcineurin pain syndrome, which appears to be an untoward complication of the interruption of the physiologic function of calcineurin. This is a narrative review focusing on the epidemiology, pathophysiology, characterization of a newly recognized pain syndrome associated with the use of calcineurin inhibitors. The use of immunosuppressants however is associated with several well-known toxicities to which the calcineurin pain syndrome can be added. The development of this syndrome most likely involves altered nociceptive processing due to the effect of calcineurin inhibition on neuronal firing, as well as effects of calcineurin on vascular tone. The most striking aspect of the treatment of this syndrome is the response to calcium channel blockers, which suggest that the effects of calcineurin inhibition on vascular tone play an important role in the development of the calcineurin pain syndrome. The calcineurin syndrome is a newly recognized complication associated with the use of calcineurin inhibitors. There is no standard therapy at this time but anecdotal reports suggest the effectiveness of calcium channel blockers.

  3. Crystallization inhibitors for amorphous oxides

    International Nuclear Information System (INIS)

    Reznitskij, L.A.; Filippova, S.E.

    1993-01-01

    Data for the last 10 years, in which experimental results of studying the temperature stabilization of x-ray amorphous oxides (including R 3 Fe 5 O 12 R-rare earths, ZrO 2 , In 2 O 3 , Sc 2 O 3 ) and their solid solution are presented, are generalized. Processes of amorphous oxide crystallization with the production of simple oxides, solid solutions and chemical compounds with different polyhedral structure, are investigated. Energy and crystallochemical criteria for selecting the doping inhibitor-components stabilizing the amorphous state are ascertained, temperatures and enthalpies of amorpous oxide crystallization are determined, examination of certain provisions of iso,orphous miscibility theory is conducted

  4. Inhibitors of plant hormone transport

    Czech Academy of Sciences Publication Activity Database

    Klíma, Petr; Laňková, Martina; Zažímalová, Eva

    2016-01-01

    Roč. 253, č. 6 (2016), s. 1391-1404 ISSN 0033-183X R&D Projects: GA MŠk(CZ) LD15088 Institutional support: RVO:61389030 Keywords : polar auxin transport * acid-binding protein * gnom arf-gef * equilibrative nucleoside transporter * efflux carrier polarity * plasma-membrane-protein * cultured tobacco cells * arabidopsis-thaliana * gravitropic response * brefeldin-a * Plant hormones * Transport * Inhibitors * Auxin * Cytokinins * Strigolactones * Abscisic acid * Cell biology Subject RIV: ED - Physiology Impact factor: 2.870, year: 2016

  5. Nuclear blackmail and nuclear balance

    International Nuclear Information System (INIS)

    Betts, R.K.

    1987-01-01

    This book raises pointed questions about nuclear saber rattling. More than a dozen cases since the bombing of Hiroshima and Magasaki in which some sort of nuclear threat was used as a sparring technique in tense confrontations are cited. Each incident is described and analyzed. Two theories offered to explain America's use of nuclear threats, the balance of interest theory and the balance of power theory, are contrasted throughout the book. This book helps to fill the gap in the understanding of nuclear weapons and their uses, while pointing out that nuclear bravado could lead to an unintended unleashing of these weapons

  6. Nuclear energy and nuclear weapons

    International Nuclear Information System (INIS)

    Robertson, J.A.L.

    1983-06-01

    We all want to prevent the use of nuclear weapons. The issue before us is how best to achieve this objective; more specifically, whether the peaceful applications of nuclear energy help or hinder, and to what extent. Many of us in the nuclear industry are working on these applications from a conviction that without peaceful nuclear energy the risk of nuclear war would be appreciably greater. Others, however, hold the opposite view. In discussing the subject, a necessary step in allaying fears is understanding some facts, and indeed facing up to some unpalatable facts. When the facts are assessed, and a balance struck, the conclusion is that peaceful nuclear energy is much more part of the solution to preventing nuclear war than it is part of the problem

  7. Laura: Soybean variety lacking Kunitz trypsin inhibitor

    Directory of Open Access Journals (Sweden)

    Srebrić Mirjana

    2010-01-01

    Full Text Available Grain of conventional soybean varieties requires heat processing to break down trypsin inhibitor's activity before using as food or animal feed. At the same time, protein denaturation and other qualitative changes occur in soybean grain, especially if the temperature of heating is not controlled. Two types of trypsin inhibitor were found in soybean grain the Kunitz trypsin inhibitor and the Bowman-Birk inhibitor. Mature grain of soybean Laura is lacking Kunitz trypsin inhibitor. Grain yield of variety Laura is equal to high yielding varieties from the maturity group I, where it belongs. Lacking of Kunitz-trypsin inhibitor makes soybean grain suitable for direct feeding in adult non ruminant animals without previous thermal processing. Grain of variety Laura can be processed for a shorter period of time than conventional soybeans. This way we save energy, and preserve valuable nutritional composition of soybean grain, which is of interest in industrial processing.

  8. Vanadium Compounds as PTP Inhibitors

    Directory of Open Access Journals (Sweden)

    Elsa Irving

    2017-12-01

    Full Text Available Phosphotyrosine signaling is regulated by the opposing actions of protein tyrosine kinases (PTKs and protein tyrosine phosphatases (PTPs. Here we discuss the potential of vanadium derivatives as PTP enzyme inhibitors and metallotherapeutics. We describe how vanadate in the V oxidized state is thought to inhibit PTPs, thus acting as a pan-inhibitor of this enzyme superfamily. We discuss recent developments in the biological and biochemical actions of more complex vanadium derivatives, including decavanadate and in particular the growing number of oxidovanadium compounds with organic ligands. Pre-clinical studies involving these compounds are discussed in the anti-diabetic and anti-cancer contexts. Although in many cases PTP inhibition has been implicated, it is also clear that many such compounds have further biochemical effects in cells. There also remain concerns surrounding off-target toxicities and long-term use of vanadium compounds in vivo in humans, hindering their progress through clinical trials. Despite these current misgivings, interest in these chemicals continues and many believe they could still have therapeutic potential. If so, we argue that this field would benefit from greater focus on improving the delivery and tissue targeting of vanadium compounds in order to minimize off-target toxicities. This may then harness their full therapeutic potential.

  9. Proton pump inhibitors and osteoporosis

    DEFF Research Database (Denmark)

    Andersen, Bjarne Nesgaard; Johansen, Per Birger; Abrahamsen, Bo

    2016-01-01

    PURPOSE OF REVIEW: The purpose of the review is to provide an update on recent advances in the evidence based on proton pump inhibitors (PPI) as a possible cause of osteoporosis and osteoporotic fractures. This review focuses, in particular, on new studies published in the last 18 months and a di......PURPOSE OF REVIEW: The purpose of the review is to provide an update on recent advances in the evidence based on proton pump inhibitors (PPI) as a possible cause of osteoporosis and osteoporotic fractures. This review focuses, in particular, on new studies published in the last 18 months...... and a discussion of these findings and how this has influenced our understanding of this association, the clinical impact and the underlying pathophysiology. RECENT FINDINGS: New studies have further strengthened existing evidence linking use of PPIs to osteoporosis. Short-term use does not appear to pose a lower...... risk than long-term use. There is a continued lack of conclusive studies identifying the pathogenesis. Direct effects on calcium absorption or on osteoblast or osteoclast action cannot at present plausibly explain the mechanism. SUMMARY: The use of PPIs is a risk factor for development of osteoporosis...

  10. Nuclear materials

    International Nuclear Information System (INIS)

    1996-01-01

    In 1998, Nuclear Regulatory Authority of the Slovak Republic (NRA SR) performed 38 inspections, 25 of them were performed in co-operation with IAEA inspectors. There is no fresh nuclear fuel at Bohunice A-1 NPP at present. Fresh fuel of Bohunice V-1 and V-2 NPPs is inspected in the fresh fuel storage.There are 327 fresh fuel assemblies in Mochovce NPP fresh fuel storage. In addition to that, are also 71 small users of nuclear materials in Slovakia. In most cases they use: covers made of depleted uranium for non-destructive works, detection of level in production plants, covers for therapeutical sources at medical facilities. In. 1995, NRA SR issued 4 new licences for nuclear material withdrawal. In the next part manipulation with nuclear materials, spent fuel stores and illegal trafficking in nuclear materials are reported

  11. Nuclear Law

    International Nuclear Information System (INIS)

    Wiesbauer, Bruno

    1978-01-01

    This book is the first attempt of a comprehensive compilation of national Austrian Nuclear Law (Nuclear Liability Act; Radiation protection Act, Radiation Protection Ordinance, Security Control Act, Act on the uses of Nuclear Energy - Zwentendorf Nuclear Power Plant) and the most important international agreements to which Austria is a party. Furthermore, the book contains the most important Nuclear Liability Conventions to which Austria is not yet a party, but which are applicable in neighbouring; the Paris Convention served as a model for the national Nuclear Liability Act and may be used for its interpretation. The author has translated a number of international instruments into German, such as the Expose des Motifs of the Paris Convention. (NEA) [fr

  12. Nuclear nonproliferation

    International Nuclear Information System (INIS)

    Neubert, M.

    1992-01-01

    The following motion was put before the United Kingdom House of Commons on 3rd February 1992 and agreed; that this House, recognising the potential dangers of the rapidly changing world order, welcomes the recent proposals for substantial reductions in nuclear weaponry, the growing support for the non-proliferation treaty and progress in the implementation of the United Nations Security Council Resolutions concerning the dismantling of Iraqi nuclear, chemical and biological capabilities; urges the Government to play their full part in helping the relevant authorities in the Commonwealth of Independent States to dismantle their nuclear devices, to safeguard their nuclear components and to discourage the proliferation of nuclear expertise; and believes it is of the first importance that Britain retains an effective and credible minimum nuclear deterrent as security in a world where there remain many sources of instability. The record of arguments for and against the motion in the debate is presented. (author)

  13. Nuclear energy

    International Nuclear Information System (INIS)

    Panait, A.

    1994-01-01

    This is a general report presenting the section VII entitled Nuclear Power of the National Conference on Energy (CNE '94) held in Neptun, Romania, on 13-16 June 1994. The problems addressed were those relating to electric power produced by nuclear power plant, to heat secondary generation, to quality assurance, to safety, etc. A special attention was paid to the commissioning of the first Romanian nuclear power unit, the Cernavoda-1 reactor of CANDU type. The communications were grouped in four subsections. These were: 1. Quality assurance, nuclear safety, and environmental protection; 2. Nuclear power plant, commissioning, and operation; 3. Nuclear power plant inspection, maintenance, and repairs, heavy water technology; 4. Public opinion education. There were 22 reports, altogether

  14. Nuclear power

    International Nuclear Information System (INIS)

    King, P.

    1990-01-01

    Written from the basis of neutrality, neither for nor against nuclear power this book considers whether there are special features of nuclear power which mean that its development should be either promoted or restrained by the State. The author makes it dear that there are no easy answers to the questions raised by the intervention of nuclear power but calls for openness in the nuclear decision making process. First, the need for energy is considered; most people agree that energy is the power to progress. Then the historicalzed background to the current position of nuclear power is given. Further chapters consider the fuel cycle, environmental impacts including carbon dioxide emission and the greenhouse effect, the costs, safety and risks and waste disposal. No conclusion either for or against nuclear power is made. The various shades of opinion are outlined and the arguments presented so that readers can come to their own conclusions. (UK)

  15. Nuclear power

    International Nuclear Information System (INIS)

    Porter, Arthur.

    1980-01-01

    This chapter of the final report of the Royal Commission on Electric Power Planning in Ontario updates its interim report on nuclear power in Ontario (1978) in the light of the Three Mile Island accident and presents the commission's general conclusions and recommendations relating to nuclear power. The risks of nuclear power, reactor safety with special reference to Three Mile Island and incidents at the Bruce generating station, the environmental effects of uranium mining and milling, waste management, nuclear power economics, uranium supplies, socio-political issues, and the regulation of nuclear power are discussed. Specific recommendations are made concerning the organization and public control of Ontario Hydro, but the commission concluded that nuclear power is acceptable in Ontario as long as satisfactory progress is made in the disposal of uranium mill tailings and spent fuel wastes. (LL)

  16. Nuclear astrophysics

    International Nuclear Information System (INIS)

    Haxton, W.C.

    1992-01-01

    The problem of core-collapse supernovae is used to illustrate the many connections between nuclear astrophysics and the problems nuclear physicists study in terrestrial laboratories. Efforts to better understand the collapse and mantle ejection are also motivated by a variety of interdisciplinary issues in nuclear, particle, and astrophysics, including galactic chemical evolution, neutrino masses and mixing, and stellar cooling by the emission of new particles. The current status of theory and observations is summarized

  17. Nuclear physics

    International Nuclear Information System (INIS)

    Patel, S.B.

    1991-01-01

    This book is a simple and direct introduction to the tools of modern nuclear physics, both experimental and mathematical. Emphasizes physical intuition and illuminating analogies, rather than formal mathematics. Topics covered include particle accelerators, radioactive series, types of nuclear reactions, detection of the neutrino, nuclear isomerism, binding energy of nuclei, fission chain reactions, and predictions of the shell model. Each chapter contains problems and illustrative examples. Pre-requisites are calculus and elementary vector analysis

  18. Nuclear energy

    International Nuclear Information System (INIS)

    Hesketh, Ross.

    1985-01-01

    The subject is treated under the headings: nuclear energy -what is it; fusion (principles; practice); fission (principles); reactor types and systems (fast (neutron) reactors as breeders; fast reactors; thermal reactors; graphite-moderated thermal reactors; the CANDU reactor; light water reactors - the BWR and the PWR); the nuclear fuel cycle (waste storage; fuel element manufacture; enrichment processes; uranium mining); safety and risk assessment; the nuclear power industry and the economy (regulating authorities; economics; advantages and disadvantages). (U.K.)

  19. Nuclear Asia

    National Research Council Canada - National Science Library

    Ferguson, Joseph; Tarleton, Gael

    2004-01-01

    .... This event was an opportunity for policy makers, security analysts, nuclear scientists and engineers, regional experts, and military planners to share perspectives and identify those issues requiring...

  20. Nuclear cardiology

    International Nuclear Information System (INIS)

    Fish, M.B.

    2002-01-01

    Recent advances in nuclear medicine instrumentation and software, including myocardial perfusion imaging, offer increased accuracy in the detection, diagnosis and prognosis of coronary artery disease. (orig.)

  1. Nuclear medicine

    International Nuclear Information System (INIS)

    Anon.

    1993-01-01

    The area of nuclear medicine, the development of artificially produced radioactive isotopes for medical applications, is relatively recent. Among the subjects covered in a lengthy discussion are the following: history of development; impact of nuclear medicine; understanding the most effective use of radioisotopes; most significant uses of nuclear medicine radioimmunoassays; description of equipment designed for use in the field of nuclear medicine (counters, scanning system, display systems, gamma camera); description of radioisotopes used and their purposes; quality control. Numerous historical photographs are included. 52 refs

  2. Nuclear Law

    International Nuclear Information System (INIS)

    Pascal, Maurice.

    1979-01-01

    This book on nuclear law is the first of a series of analytical studies to be published by the French Energy Commission (CEA) concerning all the various nuclear activities. It describes national and international legislation applicable in France covering the following main sectors: the licensing procedure for nuclear installations, the law of the sea and nuclear law, the legal system governing radioisotopes, the transport of radioactive materials, third party liability and insurance and radiation protection. In each chapter, the overall analysis is supplemented by the relevant regulatory texts and by organisation charts in annex. (NEA) [fr

  3. 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.

  4. Nuclear power

    International Nuclear Information System (INIS)

    Bupp, I.C.

    1991-01-01

    Is a nuclear power renaissance likely to occur in the United States? This paper investigates the many driving forces that will determine the answer to that question. This analysis reveals some frequently overlooked truths about the current state of nuclear technology: An examination of the issues also produces some noteworthy insights concerning government regulations and related technologies. Public opinion will play a major role in the unfolding story of the nuclear power renaissance. Some observers are betting that psychological, sociological, and political considerations will hod sway over public attitudes. Others wager that economic and technical concerns will prevail. The implications for the nuclear power renaissance are striking

  5. 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 ...

  6. Inhibiting cancer cell hallmark features through nuclear export inhibition.

    Science.gov (United States)

    Sun, Qingxiang; Chen, Xueqin; Zhou, Qiao; Burstein, Ezra; Yang, Shengyong; Jia, Da

    2016-01-01

    Treating cancer through inhibition of nuclear export is one of the best examples of basic research translation into clinical application. Nuclear export factor chromosomal region maintenance 1 (CRM1; Xpo1 and exportin-1) controls cellular localization and function of numerous proteins that are critical for the development of many cancer hallmarks. The diverse actions of CRM1 are likely to explain the broad ranging anti-cancer potency of CRM1 inhibitors observed in pre-clinical studies and/or clinical trials (phase I-III) on both advanced-stage solid and hematological tumors. In this review, we compare and contrast the mechanisms of action of different CRM1 inhibitors, and discuss the potential benefit of unexplored non-covalent CRM1 inhibitors. This emerging field has uncovered that nuclear export inhibition is well poised as an attractive target towards low-toxicity broad-spectrum potent anti-cancer therapy.

  7. Nuclear physics for nuclear fusion

    International Nuclear Information System (INIS)

    Li Xingzhong; Liu Bin; Wei Qingming; Ren Xianzhe

    2004-01-01

    The D-T fusion cross-section is calculated using quantum mechanics with the model of square nuclear potential well and Coulomb potential barrier. The agreement between ENDF data and the theoretically calculated results is well in the range of 0.2-280 keV. It shows that the application of Breit-Wigner formula is not suitable for the case of the light nuclei fusion reaction. When this model is applied to the nuclear reaction between the charged particles confined in a lattice, it explains the 'abnormal phenomena'. It implies a prospect of nuclear fusion energy without strong nuclear radiations

  8. TYROSINE KINASE INHIBITORS AND PREGNANCY

    Directory of Open Access Journals (Sweden)

    Elisabetta Abruzzese

    2014-04-01

    Full Text Available The management of patients with chronic myeloid leukemia (CML during pregnancy has became recently a matter of continuous debate.  The introduction of the Tyrosine Kinase Inhibitors (TKIs in clinical practice has dramatically changed the prognosis of CML patients.  Patients diagnosed in chronic phase can reasonably expect many years of excellent disease control and good quality of life, as well as a normal life expectancy.  This fact has come the necessity to address issues relating to fertility and pregnancy. Physicians are not infrequently being asked for advice regarding the need for, and or the appropriateness of, stopping treatment in order to conceive. In this report we will review the data published in terms of fertility, conception, pregnancy, pregnancy outcome and illness control for all the approved TKIs, as well as suggest how to manage a planned and/or unplanned pregnancy.

  9. Nuclear installations

    International Nuclear Information System (INIS)

    2001-01-01

    This document presents the fulfilling of the Brazilian obligations under the Convention on Nuclear Safety. The Chapter 2 of the document contains some details about the existing Brazilian nuclear installations. Also, safety improvements at Angra 1 and aspects of Angra 2 and 3 are reported

  10. Nuclear safety

    International Nuclear Information System (INIS)

    1991-02-01

    This book reviews the accomplishments, operations, and problems faced by the defense Nuclear Facilities Safety Board. Specifically, it discusses the recommendations that the Safety Board made to improve safety and health conditions at the Department of Energy's defense nuclear facilities, problems the Safety Board has encountered in hiring technical staff, and management problems that could affect the Safety Board's independence and credibility

  11. Nuclear violence

    International Nuclear Information System (INIS)

    Mullen, R.K.

    1987-01-01

    A great deal of attention has been paid in the past decade or so to the characteristics of terrorists and their apparent goals and objectives, capabilities, and evolving strategy and tactics with respect to nuclear terrorism. In contrast, little has been said about the procedural aspects of nuclear terrorism, and even less about the way in which such endeavors can fail. This latter omission is important because it bears directly on the ability to evaluate credibly the potential for nuclear terrorism. Here, the author addresses the requirements inherent in acquiring a nuclear explosive capability by three routes: separation of plutonium from irradiated light or heavy water reactor (LWR or HWR) fuel, processing, or use of separated fissile material, and theft of a nuclear weapon. In addition, he deals with other potential acts of nuclear terrorism: sabotage of power reactors, uranium enrichment facilities and spent nuclear fuel in transport, and dispersal of radioactive materials, in particular, plutonium. He specifically does not look at the design or production of a nuclear weapon. Finally, the discussion here assumes that the terrorist is subnational; that is, a nation is not involved. Also, the discussion of subnational participation does not address the possibility of collusion with insiders

  12. Nuclear installations

    International Nuclear Information System (INIS)

    1998-01-01

    This document presents the fulfilling of the Brazilian obligations under the Convention on Nuclear Safety. The Chapter 2 of the document contains some details about the existing Brazilian nuclear installations. Also, safety improvements at Angra 1 and aspects of Angra 2 and 3 are reported

  13. Nuclear power

    International Nuclear Information System (INIS)

    Abd Khalik Wood

    2003-01-01

    This chapter discuss on nuclear power and its advantages. The concept of nucleus fission, fusion, electric generation are discussed in this chapter. Nuclear power has big potential to become alternative energy to substitute current conventional energy from coal, oil and gas

  14. Nuclear energy

    International Nuclear Information System (INIS)

    1978-01-01

    This brochure is intended as a contribution to a better and more general understanding of one of the most urgent problems of present society. Emphasis is laid on three issues that are always raised in the nuclear debate: 1) Fuel cycle, 2) environmental effects of nuclear power plants, 3) waste disposal problems. (GL) [de

  15. Nuclear pollution

    International Nuclear Information System (INIS)

    Ramade, Francois

    1979-01-01

    In this chapter devoted to nuclear pollution the following topics were studied: fundamentals of radiobiology (ecological importance of the various radioisotopes, biological effects of ionizing radiations); ecological effects of radioactive fallout (contamination of atmosphere, terrestrial ecosystems, oceans). The electronuclear industry and its environmental impact. PWR type reactors, fuel reprocessing plants, contamination of trophic chains by radionuclides released in the environment from nuclear installations [fr

  16. Nuclear lifetimes

    International Nuclear Information System (INIS)

    Caraca, J.M.G.

    1976-01-01

    The importance of the results obtained in experiments of measurement of lifetimes for a detailed knowledge of nuclear structure is referred. Direct methods of measurement of nuclear lifetimes are described, namely, electronic methods, recoil-distance method, doppler shift atenuation method and blocking-method. A brief reference is made to indirect methods for measurement of life-times

  17. Nuclear facts

    International Nuclear Information System (INIS)

    1982-01-01

    The subject is discussed as follows: the case for using nuclear energy (Britain's energy needs; energy policy); safety; transport of spent fuel; radiation (natural radioactivity); environment (land use of nuclear power plants; storage and disposal of radioactive wastes). (U.K.)

  18. PARP Inhibitors in Ovarian Cancer.

    Science.gov (United States)

    Mittica, Gloria; Ghisoni, Eleonora; Giannone, Gaia; Genta, Sofia; Aglietta, Massimo; Sapino, Anna; Valabrega, Giorgio

    2018-03-05

    Treatment of Epithelial Ovarian Cancer (EOC), historically based on surgery and platinum doublet chemotherapy, is associated with high risk of relapse and poor prognosis for recurrent disease. In this landscape, the innovative treatment with PARP inhibitors (PARPis) demonstrated an outstanding activity in EOC, and is currently changing clinical practice in BRCA mutant patients. To highlight the mechanism of action, pharmacokinetics, clinical activity, indications and current strategies of development of Olaparib, Niraparib, Rucaparib, Talazoparib and Veliparib, the 5 most relevant PARPis. We performed a review on Pubmed using 'ovarian cancer' and the name of each PARPi (PARP inhibitor) discussed in the review as Medical Subject Headings (MeSH) keywords. The same search was performed on "clinicaltrial.gov" to identify ongoing clinical trials and on "google.com/patents" and "uspto.gov" for recent patents exploring PARPIs in ovarian cancer. Olaparib, Niraparib and Rucaparib are already approved for treatment of recurrent EOC and their indications are partially overlapping. Talazoparib and Veliparib are promising PARPis, but currently under investigation in early phase trials. Several studies are evaluating PARPis in monotherapy or in associations, in a wide range of settings (i.e. first line, neoadjuvant, platinum-sensitive and resistant disease). PARPis are valuable options in patients with recurrent ovarian cancer with promising activity in different stages of this disease. Further studies are required to better define optimal clinical settings, predictors of response beyond BRCA mutations and strategies to overcome secondary resistance of PARPis therapy in EOC. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. Nuclear measurements

    International Nuclear Information System (INIS)

    Schenkel, R.

    2005-01-01

    Nuclear measurements play a fundamental role in the development of nuclear technology and the assurance of its peaceful use. They are also required in many non-power nuclear applications such as in nuclear medicine, agriculture, environmental protection, etc. This presentation will show examples of most recent advances in measurement methodology or technology in the areas described below. The Generation IV International Forum has selected six innovative reactor systems as candidates for a next generation of sustainable, economic and safe nuclear energy systems. The choice of the best options relies heavily on the availability of accurate nuclear data that can only be obtained, in an international effort, using highly specialised facilities. Significant efforts are being directed towards the partitioning and transmutation of highly active nuclear waste. Different concepts involving fast reactors or accelerator-driven systems are being studied in view of their transmutation capabilities. State of the art equipment has been developed to assess basic properties of nuclear fuel at very high burn-up; some fine examples of this work will be shown. Physical and chemical methods play a crucial role in the detection and identification of radioisotopes used in various stages of the nuclear fuel cycle. Radiation measurement techniques are used, for example, to monitor the quantities of uranium, plutonium and other actinide elements in fuel enrichment and reprocessing facilities. Another field of application of physical and chemical methods is the characterisation of nuclear material seized from illicit trafficking. Seized material has to be analysed in order to obtain clues on its origin and intended use and to prevent diversion of nuclear material from the same source in the future. A recent highlight in basic physics relates to nuclear fission and transmutation with high intensity lasers. Ultra-fast high intensity lasers can produce high energy (tens of MeV) photons through

  20. Nuclear rockets

    International Nuclear Information System (INIS)

    Sarram, M.

    1972-01-01

    Nuclear energy has found many applications in space projects. This article deals with these applications. The first application is the use of nuclear energy for the production of electricity in space and the second main application is the use of nuclear energy for propulsion purposes in space flight. The main objective is to develop a 75000 pound thrust flight engine call NERVA by heating liquid hydrogen, in a nuclear reactor, from 420F to 4000 0 F. The paper describes in detail the salient features of the NERVA rocket as well as its comparison with the conventional chemical rockets. It is shown that a nuclear rocket using liquid hydrogen as medium is at least 85% more efficient as compared with the chemical rockets such as those used for the APOLLO moon flight

  1. Nuclear rockets

    Energy Technology Data Exchange (ETDEWEB)

    Sarram, M [Teheran Univ. (Iran). Inst. of Nuclear Science and Technology

    1972-02-01

    Nuclear energy has found many applications in space projects. This article deals with these applications. The first application is the use of nuclear energy for the production of electricity in space and the second main application is the use of nuclear energy for propulsion purposes in space flight. The main objective is to develop a 75000 pound thrust flight engine called NERVA by heating liquid hydrogen in a nuclear reactor. The paper describes in detail the salient features of the NERVA rocket as well as its comparison with the conventional chemical rockets. It is shown that a nuclear rocket using liquid hydrogen as medium is at least 85% more efficient as compared with the chemical rockets such as those used for the APOLLO moon flight.

  2. Nuclear haematology

    International Nuclear Information System (INIS)

    Masjhur, J.S.

    1992-01-01

    Nuclear techniques have been applied to study diagnose and treat various haematological disorders for more than five decades. Two scientists are regarded as pioneers in this field, i.e. John Lawrence who in 1938 used 32 P to treat chronic myeloid leukaemia and George Hevessy who used 32 P labelled erythrocytes to measure blood volume in 1939. At present, many nuclear medicine procedures are available for diagnosis and therapy of a variety of haematological disorders. Although nuclear techniques are somewhat complex, they give direct and quantitative assessment of the kinetics of blood elements as compared to other non-isotopic haematological tests. Basically, equipment required for nuclear haematology is very simple such as well scintillation counters to measure radioactivity in blood samples. More sophisticated equipment like rectilinear scanner or gamma camera is required when imaging is necessary. An overview of the basic principles and clinical applications of nuclear haematology is given

  3. Nuclear forensics

    International Nuclear Information System (INIS)

    Venugopal, V.

    2010-01-01

    Increasing threat by terrorists for a possible nuclear attack is particularly alarming in recent years. The likelihood of such an event is highly uncertain but cannot be ruled out. The consequence of such an event would be highly disastrous and the implications could be far-reaching both socially and politically. It is feared that significant amount of nuclear weapons materials may be kept under poor security. Therefore, there is a greater demand with utmost priority to curb nuclear terrorism by adapting proper security measures. One of the most important measures is to stop illicit trafficking of nuclear materials which are the source of building nuclear explosive devices. According to the IAEA illicit trafficking database (ITDB) report, a total number of 252 incidents were reported in 2006, of which 150 occurred in 2006 and the remaining 102 had taken place prior to that year, mainly in 2005

  4. Nuclear Safety

    International Nuclear Information System (INIS)

    1978-09-01

    In this short paper it has only been possible to deal in a rather general way with the standards of safety used in the UK nuclear industry. The record of the industry extending over at least twenty years is impressive and, indeed, unique. No other industry has been so painstaking in protection of its workers and in its avoidance of damage to the environment. Headings are: introduction; how a nuclear power station works; radiation and its effects (including reference to ICRP, the UK National Radiological Protection Board, and safety standards); typical radiation doses (natural radiation, therapy, nuclear power programme and other sources); safety of nuclear reactors - design; key questions (matters of concern which arise in the public mind); safety of operators; safety of people in the vicinity of a nuclear power station; safety of the general public; safety bodies. (U.K.)

  5. Nuclear proliferation

    International Nuclear Information System (INIS)

    Stencel, S.

    1978-01-01

    The terms and reactions to President Carter's nuclear policy, culminating in the 1978 Nuclear Non-Proliferation Act, are reviewed and analyzed. The new law increases restrictions on nuclear exports, encourages continued use of light water reactors in preference to plutonium-fueled reactors, and emphasizes technical solutions to proliferation problems. Critics of the law point out that it will hurt U.S. trade unfairly, that other countries do not have as many fuel options as the U.S. has, and that nuclear sales have as many political and economic as technical solutions. Compromise areas include new international safety guidelines, the possibility of an international nuclear fuel bank, and a willingness to consider each case on its merits. 21 references

  6. Nuclear privatization

    International Nuclear Information System (INIS)

    Jeffs, E.

    1995-01-01

    The United Kingdom government announced in May 1995 plans to privatize the country's two nuclear generating companies, Nuclear Electric and Scottish Nuclear. Under the plan, the two companies will become operating divisions of a unified holding company, to be called British Electric, with headquarters in Scotland. Britain's nuclear plants were left out of the initial privatization in 1989 because the government believed the financial community would be unwilling to accept the open-ended liability of decommissioning the original nine stations based on the Magnox gas-cooled reactor. Six years later, the government has found a way around this by retaining these power stations in state ownership, leaving the new nuclear company with the eight Advanced Gas-cooled Reactor (AGR) stations and the recently completed Sizewell B PWR stations. The operating Magnox stations are to be transferred to BNFL, which operates two Magnox stations of their own at Calder Hall and Chapelcross

  7. Nuclear haematology

    Energy Technology Data Exchange (ETDEWEB)

    Masjhur, J S

    1993-12-31

    Nuclear techniques have been applied to study diagnose and treat various haematological disorders for more than five decades. Two scientists are regarded as pioneers in this field, i.e. John Lawrence who in 1938 used {sup 32}P to treat chronic myeloid leukaemia and George Hevessy who used {sup 32}P labelled erythrocytes to measure blood volume in 1939. At present, many nuclear medicine procedures are available for diagnosis and therapy of a variety of haematological disorders. Although nuclear techniques are somewhat complex, they give direct and quantitative assessment of the kinetics of blood elements as compared to other non-isotopic haematological tests. Basically, equipment required for nuclear haematology is very simple such as well scintillation counters to measure radioactivity in blood samples. More sophisticated equipment like rectilinear scanner or gamma camera is required when imaging is necessary. An overview of the basic principles and clinical applications of nuclear haematology is given

  8. Discovery and SAR of hydantoin TACE inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Wensheng; Guo, Zhuyan; Orth, Peter; Madison, Vincent; Chen, Lei; Dai, Chaoyang; Feltz, Robert J.; Girijavallabhan, Vinay M.; Kim, Seong Heon; Kozlowski, Joseph A.; Lavey, Brian J.; Li, Dansu; Lundell, Daniel; Niu, Xiaoda; Piwinski, John J.; Popovici-Muller, Janeta; Rizvi, Razia; Rosner, Kristin E.; Shankar, Bandarpalle B.; Shih, Neng-Yang; Siddiqui, M.A.; Sun, J.; Tong, L.; Umland, S.; Wong, M.K.; Yang, D.Y.; Zhou, G. (Merck)

    2010-09-03

    We disclose inhibitors of TNF-{alpha} converting enzyme (TACE) designed around a hydantoin zinc binding moiety. Crystal structures of inhibitors bound to TACE revealed monodentate coordination of the hydantoin to the zinc. SAR, X-ray, and modeling designs are described. To our knowledge, these are the first reported X-ray structures of TACE with a hydantoin zinc ligand.

  9. Does plasminogen activator inhibitor-1 drive lymphangiogenesis?

    DEFF Research Database (Denmark)

    Bruyère, Françoise; Melen-Lamalle, Laurence; Blacher, Silvia

    2010-01-01

    The purpose of this study is to explore the function of plasminogen activator inhibitor-1 (PAI-1) during pathological lymphangiogenesis. PAI-1, the main physiological inhibitor of plasminogen activators is involved in pathological angiogenesis at least by controlling extracellular proteolysis and...

  10. Electrochemical Behaviour of Environmentally Friendly Inhibitor of ...

    African Journals Online (AJOL)

    Electrochemical Behaviour of Environmentally Friendly Inhibitor of Aloe Secundiflora Extract in Corrosion Control of Carbon Steel in Soft Water Media. ... The investigation was performed at different inhibitor concentrations under static and dynamic conditions using a Rotating Disk Electrode (RDE). The impedance and ...

  11. Histone deacetylase inhibitors (HDACIs: multitargeted anticancer agents

    Directory of Open Access Journals (Sweden)

    Ververis K

    2013-02-01

    Full Text Available Katherine Ververis,1 Alison Hiong,1 Tom C Karagiannis,1,* Paul V Licciardi2,*1Epigenomic Medicine, Alfred Medical Research and Education Precinct, 2Allergy and Immune Disorders, Murdoch Childrens Research Institute, Melbourne, VIC, Australia*These authors contributed equally to this workAbstract: Histone deacetylase (HDAC inhibitors are an emerging class of therapeutics with potential as anticancer drugs. The rationale for developing HDAC inhibitors (and other chromatin-modifying agents as anticancer therapies arose from the understanding that in addition to genetic mutations, epigenetic changes such as dysregulation of HDAC enzymes can alter phenotype and gene expression, disturb homeostasis, and contribute to neoplastic growth. The family of HDAC inhibitors is large and diverse. It includes a range of naturally occurring and synthetic compounds that differ in terms of structure, function, and specificity. HDAC inhibitors have multiple cell type-specific effects in vitro and in vivo, such as growth arrest, cell differentiation, and apoptosis in malignant cells. HDAC inhibitors have the potential to be used as monotherapies or in combination with other anticancer therapies. Currently, there are two HDAC inhibitors that have received approval from the US FDA for the treatment of cutaneous T-cell lymphoma: vorinostat (suberoylanilide hydroxamic acid, Zolinza and depsipeptide (romidepsin, Istodax. More recently, depsipeptide has also gained FDA approval for the treatment of peripheral T-cell lymphoma. Many more clinical trials assessing the effects of various HDAC inhibitors on hematological and solid malignancies are currently being conducted. Despite the proven anticancer effects of particular HDAC inhibitors against certain cancers, many aspects of HDAC enzymes and HDAC inhibitors are still not fully understood. Increasing our understanding of the effects of HDAC inhibitors, their targets and mechanisms of action will be critical for the

  12. Potential physiological role of plant glycosidase inhibitors

    DEFF Research Database (Denmark)

    Bellincampi, D.; Carmadella, L.; Delcour, J.A.

    2004-01-01

    Carbohydrate-active enzymes including glycosidases, transglycosidases, glycosyltransferases, polysaccharide lyases and carbohydrate esterases are responsible for the enzymatic processing of carbohydrates in plants. A number of carbohydrate-active enzymes are produced by microbial pathogens...... and insects responsible of severe crop losses. Plants have evolved proteinaceous inhibitors to modulate the activity of several of these enzymes. The continuing discovery of new inhibitors indicates that this research area is still unexplored and may lead to new exciting developments. To date, the role...... of the inhibitors is not completely understood. Here we review recent results obtained on the best characterised inhibitors, pointing to their possible biological role in vivo. Results recently obtained with plant transformation technology indicate that this class of inhibitors has potential biotechnological...

  13. 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

  14. Nuclear energy

    International Nuclear Information System (INIS)

    Rippon, S.

    1984-01-01

    Do we need nuclear energy. Is it safe. What are the risks. Will it lead to proliferation. The questions are endless, the answers often confused. In the vigorous debates that surround the siting and operation of nuclear power plants, it is all too easy to lose sight of the central issues amid the mass of arguments and counter-arguments put forward. And there remains the doubt, who do we believe. This book presents the facts, simply, straightforwardly, and comprehensibly. It describes the different types of nuclear reactor, how they work, how energy is produced and transformed into usable power, how nuclear waste is handled, what safeguards are built in to prevent accident, contamination and misuse. More important, it does this in the context of the real world, examining the benefits as well as the dangers of a nuclear power programme, quantifying the risks, and providing an authoritative account of the nuclear industry worldwide. Technically complex and politically controversial, the contribution of nuclear energy to our future energy requirements is a crucial topic of our time. (author)

  15. Nuclear Hostages

    International Nuclear Information System (INIS)

    Cooper, C.L.

    1978-01-01

    The global spread of nuclear reactors for the production of energy seems inevitable. Nuclear power plants will be supplied--if not by the United States, then by one of several other exporters. But other aspects of this development are less certain. One is the relationship between proliferation of nuclear energy plants and that of nuclear weapons. Another is the actual constraint that such vulnerable potential targets as nuclear power plants would have on would-be aggressors. In the last analysis, this would depend on the rationality of a nation's leadership. What can be said for the concept of nuclear power plants as potential hostages is that by installing a reactor on its territory, a country increases its vulnerability to grave, possibly unacceptable damage in the event of war. As a result, that nation's leaders might be inclined to raise the threshold of their sensitivity to provocation by neighbors and to restrain their own inclinations toward aggression. Admittedly this is a frail substitute for robust international agreements, but in the present order of things it is not a trivial consideration. Many incidents once regarded by the great powers as easi belli have more recently been either resolved by diplomacy or ignored altogether. The idea must not be pressed too far. The export of a nuclear power plant to a Third World country cannot be advocated simply as a means to constrain its own military adventurism. Aside from the promise of a vast increase in energy supply for developing nations, nuclear powered generating stations could actually improve relations among countries. The risk of widespread radioactive contamination by nuclear power plants hit by even conventional bombs could introduce a positive new element into the military calculations of powers outside the NATO-Warsaw Pact arena. As they balance military and diplomatic solutions to local conflicts, moderation rather than bellicosity might become the better part of valor

  16. Nuclear medicine

    International Nuclear Information System (INIS)

    Kand, Purushottam

    2012-01-01

    Nuclear medicine is a specialized area of radiology that uses very small amounts of radioactive materials to examine organ function and structure. Nuclear medicine is older than CT, ultrasound and MRI. It was first used in patients over 60-70 years ago. Today it is an established medical specialty and offers procedures that are essential in many medical specialities like nephrology, pediatrics, cardiology, psychiatry, endocrinology and oncology. Nuclear medicine refers to medicine (a pharmaceutical) that is attached to a small quantity of radioactive material (a radioisotope). This combination is called a radiopharmaceutical. There are many radiopharmaceuticals like DTPA, DMSA, HIDA, MIBI and MDP available to study different parts of the body like kidneys, heart and bones etc. Nuclear medicine uses radiation coming from inside a patient's body where as conventional radiology exposes patients to radiation from outside the body. Thus nuclear imaging study is a physiological imaging, whereas diagnostic radiology is anatomical imaging. It combines many different disciplines like chemistry, physics mathematics, computer technology, and medicine. It helps in diagnosis and to treat abnormalities very early in the progression of a disease. The information provides a quick and accurate diagnosis of wide range of conditions and diseases in a person of any age. These tests are painless and most scans expose patients to only minimal and safe amounts of radiation. The amount of radiation received from a nuclear medicine procedure is comparable to, or often many times less than, that of a diagnostic X-ray. Nuclear medicine provides an effective means of examining whether some tissues/organs are functioning properly. Therapy using nuclear medicine in an effective, safe and relatively inexpensive way of controlling and in some cases eliminating, conditions such as overactive thyroid, thyroid cancer and arthritis. Nuclear medicine imaging is unique because it provides doctors with

  17. Nuclear inheritance

    International Nuclear Information System (INIS)

    Delpech, Therese

    1997-01-01

    Since the end of the East-West confronting, the nuclear weapon issue has been focused in an international debate with obvious repercussions in Europe, because it is the European continent which indicated first the significance of nuclear deterrence. This debate refers first upon the past, as the German unification allowed capturing numerous documents of Warsaw treaty which revealed the intentions and the plans of Soviet Union during the cold war, and secondly concerns the future, since the role of nuclear weapons must be re-thought in a new context. This is the subject of this book, which refers also to the problem of the nuclear proliferation in the world and evolution of different countries in a political and regional context. The extension of the non-proliferation treaty for an undefined duration, in May 1995, is a incontestable victory because this treaty rules the renouncement to nuclear weapons of 185 countries. However, it does not solve most sensible problems like the Iraq case, for which a specific inspection regime has been instituted, or the case of Iran, which is suspected to acquire the bomb, although no clear evidence has been provided up to now. This is also the case of Israel, India and Pakistan which allege plainly their willingness of keeping open, from security reasons, their nuclear option. The content is displayed in five chapters: 1. Introduction; 2. The role of the nuclear weapons after the cold war; 3. The nuclear proliferation at crossroads; 4. Undefined extension of the NPT, a striking but fragile victory; 5. Conclusions. An appendix containing the text of the Nuclear Weapon Non-Proliferation Treaty and a chronology are added

  18. Nuclear energy

    International Nuclear Information System (INIS)

    Hladky, S.

    1985-01-01

    This booklet appeared in a series on technical history. It tries to communicate some of the scientific, technical and social stresses, which have been connected with the application of nuclear energy since its discovery. The individual sections are concerned with the following subjects: the search for the 'smallest particles'; the atomic nucleus; nuclear fission; the 'Manhattan Project'; the time after this - from the euphoria of the 1950's via disillusionment and change of opinion to the state of nuclear energy at the start of the 1980's. The booklet contains many details and is generously illustrated. (HSCH) [de

  19. Nuclear transport

    International Nuclear Information System (INIS)

    Anon.

    2003-01-01

    During january and february 2003, a unique event concerning nuclear transport was reported and rated 1 on the INES scale. This event concerns the absence of a maintenance operation on a shipping cask. This shipping cask was used for several years for nuclear transport inside La-hague site before being re-assigned to transport on public thoroughfare. The re-assignment of the cask should have been preceded and conditioned by a maintenance operation whose purpose is to check the efficiency of its radiation shield. During this period 2 on-site inspections concerning the transport of nuclear materials were performed. (A.C.)

  20. Nuclear energy

    International Nuclear Information System (INIS)

    Luxo, Armand.

    1977-01-01

    The reasons and conditions of utilizing nuclear power in developing countries are examined jointly with the present status and future uses already evaluated by some organizations. Some consequences are deduced in the human, financial scientific and technological fields, with provisional suggestions for preparing the nuclear industry development in these countries. As a conclusion trends are given to show how the industrialized countries having gained a long scientific and technological experience in nuclear energy can afford their assistance in this field, to developing countries [fr

  1. Nuclear questions

    International Nuclear Information System (INIS)

    Hohlfeld, W.

    1977-01-01

    This brochure 'nuclear problems' deals with the attitude of the protestant church in the region around the northern Elbe towards further quantitative economic growth, esp. nuclear energy, with the following essays: preaching the Gospel in an environment in danger: the Christian occident and the problems of the third world, facing the problems of exhausted supplies, the role of the prophet, problem of environment - a problem of theology, the political dimension, against ATW, signal Brokdorf, strange effects (defense of the church from unqualified teachings by non-professionals), Christian liberty, church and nuclear energy, violence and robes. (HP) [de

  2. Rotterdam Nuclear

    International Nuclear Information System (INIS)

    Anon.

    1975-01-01

    In 1965 Rotterdam Nuclear received an order for the design, supply of materials, manufacture, testing, inspection and preparation for shipment of one 450MW Boiling Water Reactor pressure vessel. This was one of the first orders for a reactor pressure vessel, ever obtained by a European Manufacturer. The Company has since supplied 19 reactor pressure vessels for nuclear power stations, having a total weight of about 10,000,000kg. The nuclear power stations in which these are installed represent an electrical output of about 15,000MW and they are located in seven different countries (USA, Spain, Switzerland, Argentina, Sweden, Germany and the Netherlands). (Auth.)

  3. Nuclear law

    International Nuclear Information System (INIS)

    Bringuier, P.

    2009-01-01

    The object of this report is to present the evolution of the nuclear law during the period from 2006 to 2008, period that was characterized in France by a real rewriting from the implementation of a control authority. The prescriptive backing of nuclear activities has been deeply changed by numerous texts. In this first part are presented: (1) the institutional aspects, (2) openness and public information, (7) radioactive wastes and (9) liability and insurance. In a next publication will be treated: (3) safety and radiation protection; (4) nuclear matter, inspection, physical protection; (5) transports; (6) trade, non-proliferation; (8) radiological accidents. (N.C.)

  4. Nuclear fuel

    International Nuclear Information System (INIS)

    D Hondt, P.

    1998-01-01

    The research and development programme on nuclear fuel at the Belgian Nuclear Research Centre SCK/CEN is described. The objective of this programme is to enhance the quantitative prediction of the operational limits of nuclear fuel and to assess the behaviour of fuel under incidental and accidental conditions. Progress is described in different domains including the modelling of fission gas release in LWR fuel, thermal conductivity, basic physical phenomena, post-irradiation examination for fuel performance assessment, and conceptual studies of incidental and accidental fuel experiments

  5. Nuclear energy

    International Nuclear Information System (INIS)

    Wethe, Per Ivar

    2009-01-01

    Today we know two forms of nuclear energy: fission and fusion. Fission is the decomposition of heavy nuclei, while fusion is the melting together of light nuclei. Both processes create a large surplus of energy. Technologically, we can currently only use fission to produce energy in today's nuclear power plants, but there is intense research worldwide in order to realize a controlled fusion process. In a practical context, today's nuclear energy is a sustained source of energy since the resource base is virtually unlimited. When fusion technology is realized, the resource supply will be a marginal problem. (AG)

  6. Nuclear electronics

    International Nuclear Information System (INIS)

    Lucero B, E.

    1989-01-01

    The rapid technical development of Colombia over the past years, resulted among others, a considerable increase in the number of measuring instrumentation and testing laboratories, scientific research and metrology centers, in industry, agriculture, public health, education on the nuclear field, etc. IAN is a well organized institution with qualified management, trained staff and reasonably equipped laboratories to carry out tasks as: Metrology, standardization, quality control and maintenance and repair of nuclear instruments. The government of Colombia has adopted a policy to establish and operate through the country maintenance and repair facilities for nuclear instrumentation. This policy is reflected in the organization of electronic laboratories in Bogota-IAN

  7. The Wonders of Phosphodiesterase‑5 Inhibitors: A Majestic History

    African Journals Online (AJOL)

    A milestone in drug discovery was the selective inhibitors of. PDE‑5 that ... the pharmacotherapeutics of PDE‑5 inhibitors and the majestic history that led to their discovery. ..... including HIV protease inhibitors, ketoconazole, itraconazole,.

  8. Nuclear medicine

    International Nuclear Information System (INIS)

    Taylor, A. Jr.

    1996-01-01

    Renovascular hypertension is estimated to affect 1-3% of the unselected hypertension population and from 15-45% of patients referred to a subspecialty center because of refractory hypertension. A large body of literature exists which supports the use of angiotensin converting enzyme (ACE) inhibitors in conjunction with radionuclide renography to enhance the sensitivity and specificity for the detection of renovascular hypertension. The goals of ACE inhibitor renography ar two-fold: (1) detect those patients with hypertension who have renal artery stenosis as the cause of their hypertension and would benefit from revascularization and (2) determine which hypertensive patients do not have renovascular hypertension and thereby obviate the necessity of angiography or revascularization. (EG) 22 refs

  9. Squash inhibitor family of serine proteinases

    International Nuclear Information System (INIS)

    Otlewski, J.; Krowarsch, D.

    1996-01-01

    Squash inhibitors of serine proteinases form an uniform family of small proteins. They are built of 27-33 amino-acid residues and cross-linked with three disulfide bridges. The reactive site peptide bond (P1-P1') is between residue 5 (Lys, Arg or Leu) and 6 (always Ile). High resolution X-ray structures are available for two squash inhibitors complexed with trypsin. NMR solution structures have also been determined for free inhibitors. The major structural motif is a distorted, triple-stranded antiparallel beta-sheet. A similar folding motif has been recently found in a number of proteins, including: conotoxins from fish-hunting snails, carboxypeptidase inhibitor from potato, kalata B1 polypeptide, and in some growth factors (e.g. nerve growth factor, transforming growth factor β2, platelet-derived growth factor). Squash inhibitors are highly stable and rigid proteins. They inhibit a number of serine proteinases: trypsin, plasmin, kallikrein, blood clotting factors: X a and XII a , cathepsin G. The inhibition spectrum can be much broadened if specific amino-acid substitutions are introduced, especially at residues which contact proteinase. Squash inhibitors inhibit proteinases via the standard mechanism. According to the mechanism, inhibitors are substrates which exhibit at neutral pH a high k cat /K m index for hydrolysis and resynthesis of the reactive site, and a low value of the hydrolysis constant. (author)

  10. Histone Deacetylase Inhibitors as Anticancer Drugs.

    Science.gov (United States)

    Eckschlager, Tomas; Plch, Johana; Stiborova, Marie; Hrabeta, Jan

    2017-07-01

    Carcinogenesis cannot be explained only by genetic alterations, but also involves epigenetic processes. Modification of histones by acetylation plays a key role in epigenetic regulation of gene expression and is controlled by the balance between histone deacetylases (HDAC) and histone acetyltransferases (HAT). HDAC inhibitors induce cancer cell cycle arrest, differentiation and cell death, reduce angiogenesis and modulate immune response. Mechanisms of anticancer effects of HDAC inhibitors are not uniform; they may be different and depend on the cancer type, HDAC inhibitors, doses, etc. HDAC inhibitors seem to be promising anti-cancer drugs particularly in the combination with other anti-cancer drugs and/or radiotherapy. HDAC inhibitors vorinostat, romidepsin and belinostat have been approved for some T-cell lymphoma and panobinostat for multiple myeloma. Other HDAC inhibitors are in clinical trials for the treatment of hematological and solid malignancies. The results of such studies are promising but further larger studies are needed. Because of the reversibility of epigenetic changes during cancer development, the potency of epigenetic therapies seems to be of great importance. Here, we summarize the data on different classes of HDAC inhibitors, mechanisms of their actions and discuss novel results of preclinical and clinical studies, including the combination with other therapeutic modalities.

  11. Histone Deacetylase Inhibitors as Anticancer Drugs

    Directory of Open Access Journals (Sweden)

    Tomas Eckschlager

    2017-07-01

    Full Text Available Carcinogenesis cannot be explained only by genetic alterations, but also involves epigenetic processes. Modification of histones by acetylation plays a key role in epigenetic regulation of gene expression and is controlled by the balance between histone deacetylases (HDAC and histone acetyltransferases (HAT. HDAC inhibitors induce cancer cell cycle arrest, differentiation and cell death, reduce angiogenesis and modulate immune response. Mechanisms of anticancer effects of HDAC inhibitors are not uniform; they may be different and depend on the cancer type, HDAC inhibitors, doses, etc. HDAC inhibitors seem to be promising anti-cancer drugs particularly in the combination with other anti-cancer drugs and/or radiotherapy. HDAC inhibitors vorinostat, romidepsin and belinostat have been approved for some T-cell lymphoma and panobinostat for multiple myeloma. Other HDAC inhibitors are in clinical trials for the treatment of hematological and solid malignancies. The results of such studies are promising but further larger studies are needed. Because of the reversibility of epigenetic changes during cancer development, the potency of epigenetic therapies seems to be of great importance. Here, we summarize the data on different classes of HDAC inhibitors, mechanisms of their actions and discuss novel results of preclinical and clinical studies, including the combination with other therapeutic modalities.

  12. Nuclear wastes

    International Nuclear Information System (INIS)

    2002-01-01

    This scientific document presents an introduction to the nuclear wastes problems, the separation process and the transmutation, the political and technical aspects of the storage, the radioprotection standards and the biological effects. (A.L.B.)

  13. 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)

  14. Nuclear analysis

    International Nuclear Information System (INIS)

    1988-01-01

    Basic studies in nuclear analytical techniques include the examination of underlying assumptions and the development and extention of techniques involving the use of ion beams for elemental and mass analysis. 1 ref., 1 tab

  15. 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.

  16. [Nuclear theory

    International Nuclear Information System (INIS)

    1989-06-01

    This report discusses concepts in nuclear theory such as: neutrino nucleosynthesis; double beta decay; neutrino oscillations; chiral symmetry breaking; T invariance; quark propagator; cold fusion; and other related topics

  17. Nuclear constants

    International Nuclear Information System (INIS)

    Foos, J.

    1999-01-01

    This paper is written in two tables. The first one describes the different particles (bosons and fermions). The second one gives the isotopes nuclear constants of the different elements, for Z = 1 to 56. (A.L.B.)

  18. Nuclear constants

    International Nuclear Information System (INIS)

    Foos, J.

    2000-01-01

    This paper is written in two tables. The first one describes the different particles (bosons and fermions). The second one gives the isotopes nuclear constants of the different elements, for Z = 56 to 68. (A.L.B.)

  19. Nuclear constants

    International Nuclear Information System (INIS)

    Foos, J.

    1998-01-01

    This paper is made of two tables. The first table describes the different particles (bosons and fermions) while the second one gives the nuclear constants of isotopes from the different elements with Z = 1 to 25. (J.S.)

  20. Nuclear constants

    International Nuclear Information System (INIS)

    Foos, J.

    1999-01-01

    This paper is written in two tables. The first one describes the different particles (bosons and fermions). The second one gives the isotopes nuclear constants of the different elements, for Z = 56 to 68. (A.L.B.)

  1. Nuclear transmutations

    International Nuclear Information System (INIS)

    Mikulaj, V.

    1992-01-01

    Two types of nuclear transmutations are outlined, namely the radioactive transmutations and nuclear reactions. The basic characteristics are given of radioactive transmutations (gamma transmutations and isomeric transitions, beta, alpha transmutations, spontaneous fission and spontaneous emission of nucleons), their kinetics and the influence of the physical and chemical state of the radionuclide on the transmutation rate. The basic characteristics are described of nuclear reactions (reactions of neutrons including fission, reactions induced by charged particles and photons), their kinetics, effective cross sections and their mechanism. Chemical reactions caused by nuclear transmutations are discussed (recoil energy, properties of hot atoms, Szilard-Chalmers effect). A brief information is given on the behavior of radionuclides in trace concentrations. (Z.S.) 2 tabs., 19 figs., 12 refs

  2. Nuclear waste

    International Nuclear Information System (INIS)

    1992-05-01

    The Nuclear Waste Policy Act of 1982, as amended in 1987, directed the Secretary of Energy to, among other things, investigate Yucca Mountain, Nevada, as a potential site for permanently disposing of highly radioactive wastes in an underground repository. In April 1991, the authors testified on Yucca Mountain project expenditures before your Subcommittee. Because of the significance of the authors findings regrading DOE's program management and expenditures, you asked the authors to continue reviewing program expenditures in depth. As agreed with your office, the authors reviewed the expenditures of project funds made available to the Department of Energy's (DOE) Lawrence Livermore National Laboratory, which is the lead project contractor for developing a nuclear waste package that wold be used for disposing of nuclear waste at Yucca Mountain. This report discusses the laboratory's use of nuclear waste funds to support independent research projects and to manage Yucca Mountain project activities. It also discusses the laboratory's project contracting practices

  3. Nuclear shields

    International Nuclear Information System (INIS)

    Linares, R.C.; Nienart, L.F.; Toelcke, G.A.

    1976-01-01

    A process is described for preparing melt-processable nuclear shielding compositions from chloro-fluoro substituted ethylene polymers, particularly PCTFE and E-CTFE, containing 1 to 75 percent by weight of a gadolinium compound. 13 claims, no drawings

  4. Nuclear option

    International Nuclear Information System (INIS)

    Olson, P.S.

    1983-01-01

    The energy demand complexion of this country is always changing and promises to change in the future. The nuclear industry is responding to changing energy demands through standards writing activities. Since the oil embargo of 1973, there has been a change in the mix of fuels contributing to energy growth in this country; virtually all of the energy growth has come from coal and nuclear power. The predicted expansion of coal use by 1985, over 1977 level, is 37%, while the use of oil is expected to decline by 17%. Use of nuclear power is expected to increase 62% from the 1977 level. The feasibility of using nuclear energy to meet the needs of the USA for electric power is discussed

  5. Nuclear safety

    International Nuclear Information System (INIS)

    Tarride, Bruno

    2015-10-01

    The author proposes an overview of methods and concepts used in the nuclear industry, at the design level as well as at the exploitation level, to ensure an acceptable safety level, notably in the case of nuclear reactors. He first addresses the general objectives of nuclear safety and the notion of acceptable risk: definition and organisation of nuclear safety (relationships between safety authorities and operators), notion of acceptable risk, deterministic safety approach and main safety principles (safety functions and confinement barriers, concept of defence in depth). Then, the author addresses the safety approach at the design level: studies of operational situations, studies of internal and external aggressions, safety report, design principles for important-for-safety systems (failure criterion, redundancy, failure prevention, safety classification). The next part addresses safety during exploitation and general exploitation rules: definition of the operation domain and of its limits, periodic controls and tests, management in case of incidents, accidents or aggressions

  6. Nuclear fission

    International Nuclear Information System (INIS)

    Kodama, T.

    1981-01-01

    The nuclear fission process is pedagogically reviewed from a macroscopic-microscopic point of view. The Droplet model is considered. The fission dynamics is discussed utilizing path integrals and semiclassical methods. (L.C.) [pt

  7. Nuclear physics

    International Nuclear Information System (INIS)

    Connell, K.A.; Warner, D.D.

    1990-01-01

    The first volume of the Annual Report for 1989/90 gives an overview of the Nuclear Structure Facility at Daresbury, its development and a selection of highlights of the year's programme. This volume is complementary, presenting brief specialist reports, submitted by the users, describing the progress and results of each individual proposal. The contents reflect the extremely successful year due in good measure to the performance of the tandem accelerator which provided a record number of hours with ''beam on target''. Reports are grouped in four sections: research into nuclear structure with contributions ordered in increasing Z numbers of the nuclei studied; investigations of nuclear reaction mechanisms; nuclear theory; accelerator operations and development plus experimental instrumentation and techniques. The appendix forms a concise summary of the work at the facility for the year. (author)

  8. Nuclear waste

    International Nuclear Information System (INIS)

    Pligt, J. van der

    1989-01-01

    This chapter present a brief overview of the current situation of siting radioactive wastes. This is followed by an overview of various psychological approaches attempting to analyse public reactions to nuclear facilities. It will be argued that public reactions to nuclear waste factilities must be seen in the context of more general attitudes toward nuclear energy. The latter are not only based upon perceptions of the health and environmental risks but are built on values, and sets of attributes which need not be similar to the representations o the experts and policy-makers. The issue of siting nuclear waste facilities is also embedded in a wider moral and political domain. This is illustrated by the importance of equity issues in siting radioactive wastes. In the last section, the implications of the present line of argument for risk communication and public participation in decisions about siting radioactive wastes will be briefly discussed. (author). 49 refs

  9. Reverse transcriptase inhibitors as microbicides.

    Science.gov (United States)

    Lewi, Paul; Heeres, Jan; Ariën, Kevin; Venkatraj, Muthusamy; Joossens, Jurgen; Van der Veken, Pieter; Augustyns, Koen; Vanham, Guido

    2012-01-01

    The CAPRISA 004 study in South Africa has accelerated the development of vaginal and rectal microbicides containing antiretrovirals that target specific enzymes in the reproduction cycle of HIV, especially reverse transcriptase inhibitors (RTI). In this review we discuss the potential relevance of HIV-1 RTIs as microbicides, focusing in the nucleotide RTI tenofovir and six classes of nonnucleoside RTIs (including dapivirine, UC781, urea and thiourea PETTs, DABOs and a pyrimidinedione). Although tenofovir and dapivirine appear to be most advanced in clinical trials as potential microbicides, several issues remain unresolved, e.g., the importance of nonhuman primates as a "gatekeeper" for clinical trials, the emergence and spread of drug-resistant mutants, the combination of microbicides that target different phases of viral reproduction and the accessibility to microbicides in low-income countries. Thus, here we discuss the latest research on RTI as microbicides in the light of the continuing spread of the HIV pandemic from the point of view of medicinal chemistry, virological, and pharmaceutical studies.

  10. AZT as a telomerase inhibitor

    International Nuclear Information System (INIS)

    Gomez, Daniel E.; Armando, Romina G.; Alonso, Daniel F.

    2012-01-01

    Telomerase is a highly specialized reverse transcriptase (RT) and the maintenance of telomeric length is determined by this specific enzyme. The human holoenzyme telomerase is a ribonucleoprotein composed by a catalytic subunit, hTERT, an RNA component, hTR, and a group of associated proteins. Telomerase is normally expressed in embryonic cells and is repressed during adulthood. The enzyme is reexpressed in around 85% of solid tumors. This observation makes it a potential target for developing drugs that could be developed for therapeutic purposes. The identification of the hTERT as a functional catalytic RT prompted studies of inhibiting telomerase with the HIV RT inhibitor azidothymidine (AZT). Previously, we have demonstrated that AZT binds preferentially to telomeres, inhibits telomerase and enhances tumor cell senescence, and apoptosis after AZT treatment in breast mammary adenocarcinoma cells. Since then, several studies have considered AZT for telomerase inhibition and have led to potential clinical strategies for anticancer therapy. This review covers present thinking of the inhibition of telomerase by AZT and future treatment protocols using the drug.

  11. Proton pump inhibitors and gastroenteritis

    International Nuclear Information System (INIS)

    Hassing, Robert-Jan; Verbon, Annelies; Visser, Herman de; Hofman, Albert; Stricker, Bruno H.

    2016-01-01

    An 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. The Rotterdam Study is a population-based cohort study among 14,926 subjects aged 45 years and older with up to 24 years of follow-up. Analyses were performed with a generalized estimating equations method in participants who handed-in a diagnostic stool sample. Furthermore, a nested case–control analysis was performed using the total cohort as a reference group. A bacterial microorganism was isolated in 125 samples, whereas 1174 samples were culture negative. In the generalized estimating equations analysis, we found that participants with a bacterial gastroenteritis were more likely than controls to be current users of PPIs (adjusted OR 1.94; 95 % CI 1.15–3.25). Different sensitivity analyses did not change this result. A considerably higher effect was observed (adjusted OR 6.14; 95 % CI 3.81–9.91), using the total cohort as a reference in a nested case–control analysis. Current PPI therapy is associated with an increased risk of bacterial gastroenteritis. However, by reducing the risk of selection and information bias in our study design, we demonstrated that the effect is lower than previously assumed.

  12. ALK inhibitors, a pharmaceutical perspective

    Directory of Open Access Journals (Sweden)

    Arturo eGalvani

    2012-02-01

    Full Text Available In 2007, the ALK tyrosine kinase, already known to be translocated and activated in Anaplastic Large Cell Lymphoma, and a few other rare cancers, was described as a potential therapeutic target for a subset of non small-cell lung cancer (NSCLC patients. Clinical proof of concept, culminating in the recent approval by the FDA of the Pfizer drug Xalkori (crizotinib, formerly known as PF-02341066 followed in record time. The drug was approved together with a companion diagnostic, the Vysis ALK Break Apart FISH Probe Kit (Abbott Molecular, Inc. for detection of eligible patients. This remarkable example of the coming of age of personalized medicine in cancer therapy is hopefully only an auspice of things to come in this rapidly developing field. Perhaps unsurprisingly, however, the appearance of clinical acquired resistance to crizotinib has already been observed early on in clinical testing, with the identification of several ALK secondary point mutations which diminish drug efficacy, and which open the way for development of second-generation inhibitors. It is also emerging that acquired resistance to crizotinib may also occur through ALK-independent mechanisms, which still need to be elucidated in detail.

  13. 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 ...

  14. 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 ...

  15. General Nuclear Medicine

    Science.gov (United States)

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

  16. 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 ...

  17. 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 ...

  18. 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 ...

  19. Nuclear instrumentation

    International Nuclear Information System (INIS)

    Weill, Jacky; Fabre, Rene.

    1981-01-01

    This article sums up the Research and Development effort at present being carried out in the five following fields of applications: Health physics and Radioprospection, Control of nuclear reactors, Plant control (preparation and reprocessing of the fuel, testing of nuclear substances, etc.), Research laboratory instrumentation, Detectors. It also sets the place of French industrial activities by means of an estimate of the French market, production and flow of trading with other countries [fr

  20. Nuclear hadrodynamics

    International Nuclear Information System (INIS)

    Geesaman, D.F.

    1984-01-01

    The role of hadron dynamics in the nucleus is illustrated to show the importance of nuclear medium effects in hadron interactions. The low lying hadron spectrum is considered to provide the natural collective variables for nuclear systems. Recent studies of nucleon-nucleon and delta-nucleon interactions are reviewed, with emphasis on the type of experimental phenomena which signal the importance of the many-body dynamics. 28 references

  1. Seguro Nuclear

    International Nuclear Information System (INIS)

    Oliveira, S.C.C. de.

    1978-04-01

    A description of the constitutive elements of insurance and its features in the field of law, and special legislation about the matter are given. The relationship between the liability of the nuclear power plant operator and the international conventions about civil liability on nuclear damage is discussed. Some considerations on damage reparing in the United States, Germany, France and Spain are presented. (A.L.S.L.) [pt

  2. Nuclear medicine

    International Nuclear Information System (INIS)

    Sibille, L.; Nalda, E.; Collombier, L.; Kotzki, P.O.; Boudousq, V.

    2011-01-01

    Nuclear medicine is a medical specialty using the properties of radioactivity. Radioactive markers associated with vectors are used as a tracer or radiopharmaceutical for diagnostic purposes and/or therapy. Since its birth more than half a century ago, it has become essential in the care of many patients, particularly in oncology. After some definitions, this paper presents the main nuclear techniques - imaging for diagnostic, radiopharmaceuticals as therapeutic agents, intra-operative detection, technique of radioimmunoassay - and the future of this field. (authors)

  3. Nuclear waste

    International Nuclear Information System (INIS)

    1988-01-01

    The Department of Energy has proposed a draft plan for investigating the Yucca Mountain, Nevada, site to determine if it suitable for a waste repository. This fact sheet provides information on the status of DOE's and the Nuclear Regulatory Commission's efforts to streamline what NRC expects will be the largest and most complex nuclear-licensing proceeding in history, including the development of an electronic information management system called the Licensing Support System

  4. Nuclear safety

    International Nuclear Information System (INIS)

    Arnott, D.

    1981-01-01

    Dr Arnott, scientific consultant to PANDORA, emphasises our lack of knowledge of the behaviour of highly active radioactive wastes, particularly effluents, and their characteristics. He proposes that they should be stored, preferably in a solidified state, until our knowledge allows their safe disposal. Political aspects and government policies are discussed and human fallibility is stressed. The nuclear establishment and nuclear power programme are severely criticised. (U.K.)

  5. Nuclear astrophysics

    International Nuclear Information System (INIS)

    Lehoucq, Roland; Klotz, Gregory

    2015-11-01

    Astronomy deals with the position and observation of the objects in our Universe, from planets to galaxies. It is the oldest of the sciences. Astrophysics is the study of the physical properties of these objects. It dates from the start of the 20. century. Nuclear astrophysics is the marriage of nuclear physics, a laboratory science concerned with the infinitely small, and astrophysics, the science of what is far away and infinitely large. Its aim is to explain the origin, evolution and abundance of the elements in the Universe. It was born in 1938 with the work of Hans Bethe, an American physicist who won the Nobel Prize for physics in 1967, on the nuclear reactions that can occur at the center of stars. It explains where the incredible energy of the stars and the Sun comes from and enables us to understand how they are born, live and die. The matter all around us and from which we are made, is made up of ninety-two chemical elements that can be found in every corner of the Universe. Nuclear astrophysics explains the origin of these chemical elements by nucleosynthesis, which is the synthesis of atomic nuclei in different astrophysical environments such as stars. Nuclear astrophysics provides answers to fundamental questions: - Our Sun and the stars in general shine because nuclear reactions are taking place within them. - The stars follow a sequence of nuclear reaction cycles. Nucleosynthesis in the stars enables us to explain the origin and abundance of elements essential to life, such as carbon, oxygen, nitrogen and iron. - Star explosions, in the form of supernovae, disperse the nuclei formed by nucleosynthesis into space and explain the formation of the heaviest chemical elements such as gold, platinum and lead. Nuclear astrophysics is still a growing area of science. (authors)

  6. Nuclear physics

    International Nuclear Information System (INIS)

    Spicer, B.M.

    1981-01-01

    Major centres of experimental nuclear physics are at Melbourne University, A.N.U., the A.A.E.C., James Cook University and the University of Western Australia. Groups working in theoretical nuclear physics exist at Melbourne, A.N.U., the A.A.E.C., Flinders and Adelaide Universities and the University of Western Australia. The activities of these groups are summarised

  7. Nuclear energy

    International Nuclear Information System (INIS)

    1996-01-01

    Several issues concerning nuclear energy in France during 1996 are presented: permission of a demand for installing underground laboratories in three sites (Marcoule, Bure and Chapelle-Baton); a report assessing the capacity of Superphenix plant to operate as a research tool; the project of merging between Framatome and Gec-Alsthom companies; the revision of a general report on nuclear energy in France; the issue of military plutonium management

  8. 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.

  9. Nuclear medicine

    International Nuclear Information System (INIS)

    Blanquet, Paul; Blanc, Daniel.

    1976-01-01

    The applications of radioisotopes in medical diagnostics are briefly reviewed. Each organ system is considered and the Nuclear medicine procedures pertinent to that system are discussed. This includes, the principle of the test, the detector and the radiopharmaceutical used, the procedure followed and the clinical results obtained. The various types of radiation detectors presently employed in Nuclear Medicine are surveyed, including scanners, gamma cameras, positron cameras and procedures for obtaining tomographic presentation of radionuclide distributions [fr

  10. Nuclear medicine

    International Nuclear Information System (INIS)

    Chamberlain, M.J.

    1986-01-01

    Despite an aggressive, competitive diagnostic radiology department, the University Hospital, London, Ontario has seen a decline of 11% total (in vivo and in the laboratory) in the nuclear medicine workload between 1982 and 1985. The decline of in vivo work alone was 24%. This trend has already been noted in the U.S.. Nuclear medicine is no longer 'a large volume prosperous specialty of wide diagnostic application'

  11. Nuclear cardiac

    International Nuclear Information System (INIS)

    Slutsky, R.; Ashburn, W.L.

    1982-01-01

    The relationship between nuclear medicine and cardiology has continued to produce a surfeit of interesting, illuminating, and important reports involving the analysis of cardiac function, perfusion, and metabolism. To simplify the presentation, this review is broken down into three major subheadings: analysis of myocardial perfusion; imaging of the recent myocardial infarction; and the evaluation of myocardial function. There appears to be an increasingly important relationship between cardiology, particularly cardiac physiology, and nuclear imaging techniques

  12. Nuclear medicine

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, S M [Bhabha Atomic Research Centre, Bombay (India). Radiation Medicine Centre

    1967-01-01

    The article deals with the growth of nuclear medicine in India. Radiopharmaceuticals both in elemental form and radiolabelled compounds became commercially available in India in 1961. Objectives and educational efforts of the Radiation Medicine Centre setup in Bombay are mentioned. In vivo tests of nuclear medicine such as imaging procedures, dynamic studies, dilution studies, thyroid function studies, renal function studies, linear function studies, blood flow, and absorption studies are reported. Techniques of radioimmunoassay are also mentioned.

  13. Nuclear technology

    International Nuclear Information System (INIS)

    1983-03-01

    This report examines nuclear technology in Canada, with emphasis on Quebec, as a means of revitilizing industry. The historical, present day, and future states of Atomic Energy of Canada Limited are examined. Future research programs are discussed in greatest detail. These range from disposal of porcine wastes to new applications for electricity to nuclear medical techniques (to cite only a few examples). The executive summary is written in English. (23 fig., 16 tab.)

  14. Nuclear risk

    International Nuclear Information System (INIS)

    Mulkers, G.

    1988-01-01

    This file includes data on risks insured by the nuclear insurance pool in Belgium and on the Chernobyl accident covering injury, economic damage and compensation for the latter. Also included are the texts of the IAEA Conventions on Early Notification and on Assistance in Case of a Nuclear Accident as well as that of a Convention on long-distance transfrontier atmospheric pollution signed in Geneva [fr

  15. Nuclear accidents

    International Nuclear Information System (INIS)

    1987-01-01

    On 27 May 1986 the Norwegian government appointed an inter-ministerial committee of senior officials to prepare a report on experiences in connection with the Chernobyl accident. The present second part of the committee's report describes proposals for measures to prevent and deal with similar accidents in the future. The committee's evaluations and proposals are grouped into four main sections: Safety and risk at nuclear power plants; the Norwegian contingency organization for dealing with nuclear accidents; compensation issues; and international cooperation

  16. Nuclear education

    International Nuclear Information System (INIS)

    Kemeny, L.G.

    1987-01-01

    All scientists and technologists are agreed that the coal based fuel cycle is somewhere between 50 to 300 times more dangerous than the uranium fuel cycle. Under these circumstances it is not difficult to show that on a more quantitative basis, the nuclear industry, in all countries, has an unblemished safety record when compared with other energy sources. Various hazards and benefits of nuclear power are analyzed in this paper comparing with other energy sources. (Liu)

  17. Nuclear astrophysics

    International Nuclear Information System (INIS)

    Arnould, M.; Takahashi, K.

    1999-01-01

    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

  18. SGLT2 Inhibitors May Predispose to Ketoacidosis.

    Science.gov (United States)

    Taylor, Simeon I; Blau, Jenny E; Rother, Kristina I

    2015-08-01

    Sodium glucose cotransporter 2 (SGLT2) inhibitors are antidiabetic drugs that increase urinary excretion of glucose, thereby improving glycemic control and promoting weight loss. Since approval of the first-in-class drug in 2013, data have emerged suggesting that these drugs increase the risk of diabetic ketoacidosis. In May 2015, the Food and Drug Administration issued a warning that SGLT2 inhibitors may lead to ketoacidosis. Using PubMed and Google, we conducted Boolean searches including terms related to ketone bodies or ketoacidosis with terms for SGLT2 inhibitors or phlorizin. Priority was assigned to publications that shed light on molecular mechanisms whereby SGLT2 inhibitors could affect ketone body metabolism. SGLT2 inhibitors trigger multiple mechanisms that could predispose to diabetic ketoacidosis. When SGLT2 inhibitors are combined with insulin, it is often necessary to decrease the insulin dose to avoid hypoglycemia. The lower dose of insulin may be insufficient to suppress lipolysis and ketogenesis. Furthermore, SGLT2 is expressed in pancreatic α-cells, and SGLT2 inhibitors promote glucagon secretion. Finally, phlorizin, a nonselective inhibitor of SGLT family transporters decreases urinary excretion of ketone bodies. A decrease in the renal clearance of ketone bodies could also increase the plasma ketone body levels. Based on the physiology of SGLT2 and the pharmacology of SGLT2 inhibitors, there are several biologically plausible mechanisms whereby this class of drugs has the potential to increase the risk of developing diabetic ketoacidosis. Future research should be directed toward identifying which patients are at greatest risk for this side effect and also to optimizing pharmacotherapy to minimize the risk to patients.

  19. Nuclear safety

    International Nuclear Information System (INIS)

    2014-01-01

    The Program on Nuclear Safety comprehends Radioprotection, Radioactive Waste Management and Nuclear Material Control. These activities are developed at the Nuclear Safety Directory. The Radioactive Waste Management Department (GRR) was formally created in 1983, to promote research and development, teaching and service activities in the field of radioactive waste. Its mission is to develop and employ technologies to manage safely the radioactive wastes generated at IPEN and at its customer’s facilities all over the country, in order to protect the health and the environment of today's and future generations. The Radioprotection Service (GRP) aims primarily to establish requirements for the protection of people, as workers, contractors, students, members of the general public and the environment from harmful effects of ionizing radiation. Furthermore, it also aims to establish the primary criteria for the safety of radiation sources at IPEN and planning and preparing for response to nuclear and radiological emergencies. The procedures about the management and the control of exposures to ionizing radiation are in compliance with national standards and international recommendations. Research related to the main activities is also performed. The Nuclear Material Control has been performed by the Safeguard Service team, which manages the accountability and the control of nuclear material at IPEN facilities and provides information related to these activities to ABACC and IAEA. (author)

  20. Nuclear fuel

    Energy Technology Data Exchange (ETDEWEB)

    Nakano, H [Power Reactor and Nuclear Fuel Development Corp., Tokyo (Japan)

    1976-10-01

    It is expected that nuclear power generation will reach 49 million kW in 1985 and 129 million kW in 1995, and the nuclear fuel having to be supplied and processed will increase in proportion to these values. The technical problems concerning nuclear fuel are presented on the basis of the balance between the benefit for human beings and the burden on the human beings. Recently, especially the downstream of nuclear fuel attracts public attention. Enriched uranium as the raw material for light water reactor fuel is almost monopolized by the U.S., and the technical information has not been published for fear of the diversion to nuclear weapons. In this paper, the present situations of uranium enrichment, fuel fabrication, transportation, reprocessing and waste disposal and the future problems are described according to the path of nuclear fuel cycle. The demand and supply of enriched uranium in Japan will be balanced up to about 1988, but afterwards, the supply must rely upon the early establishment of the domestic technology by centrifugal separation method. No problem remains in the fabrication of light water reactor fuel, but for the fabrication of mixed oxide fuel, the mechanization of the production facility and labor saving are necessary. The solution of the capital risk for the construction of the second reprocessing plant is the main problem. Japan must develop waste disposal techniques with all-out efforts.

  1. Nuclear safety

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2014-07-01

    The Program on Nuclear Safety comprehends Radioprotection, Radioactive Waste Management and Nuclear Material Control. These activities are developed at the Nuclear Safety Directory. The Radioactive Waste Management Department (GRR) was formally created in 1983, to promote research and development, teaching and service activities in the field of radioactive waste. Its mission is to develop and employ technologies to manage safely the radioactive wastes generated at IPEN and at its customer’s facilities all over the country, in order to protect the health and the environment of today's and future generations. The Radioprotection Service (GRP) aims primarily to establish requirements for the protection of people, as workers, contractors, students, members of the general public and the environment from harmful effects of ionizing radiation. Furthermore, it also aims to establish the primary criteria for the safety of radiation sources at IPEN and planning and preparing for response to nuclear and radiological emergencies. The procedures about the management and the control of exposures to ionizing radiation are in compliance with national standards and international recommendations. Research related to the main activities is also performed. The Nuclear Material Control has been performed by the Safeguard Service team, which manages the accountability and the control of nuclear material at IPEN facilities and provides information related to these activities to ABACC and IAEA. (author)

  2. Nuclear energy

    International Nuclear Information System (INIS)

    Seidel, J.

    1990-01-01

    This set of questions is based on an inquiry from the years 1987 to 1989. About 250 people af all age groups - primarily, however, young people between 16 and 25 years of age - were asked to state the questions they considered particularly important on the subject of nuclear energy. The survey was carried out without handicaps according to the brain-storming principle. Although the results cannot claim to be representative, they certainly reflect the areas of interest of many citizens and also their expectations, hopes and fears in connection with nuclear energy. The greater part of the questions were aimed at three topic areas: The security of nuclear power-stations, the effects of radioactivity on people and the problem of waste disposal. The book centres around these sets of questions. The introduction gives a general survey of the significance of nuclear energy as a whole. After this follow questions to do with the function of nuclear power stations, for the problems of security and waste disposal - which are dealt with in the following chapters - are easier to explain and to understand if a few physical and technical basics are understood. In the final section of the book there are questions on the so-called rejection debate and on the possibility of replacing nuclear energy with other energy forms. (orig./HP) [de

  3. Nuclear technologies

    International Nuclear Information System (INIS)

    Toyama, Makoto; Hamasaki, Manabu; Kobayashi, Masahiko; Hoshide, Akihiko; Katayama, Kimio; Nozawa, H.; Karigome, Satoshi

    2010-01-01

    In recent days, energy security is becoming a major global concern and it has been recognized that a major reduction in greenhouse-gas emissions is required to combat climate change. Considerable expansion and new introduction of nuclear power generation are currently being planned and considered for the further in various parts of the world. Nuclear technologies of the latest 10 years in Japan were reviewed with their characteristics, advancement and future perspective. Steady efforts have been made to construct new nuclear power stations with computer-aided engineering system and modular and prefabricated structures, extend the interval of periodic inspections under the new inspection system that should improve both safety and reliability, implement advanced measures against aging and develop the next-generation light water reactors including a medium small reactor. Export of nuclear power plants has been promoted with international business alliance or cooperation. Activities to close nuclear fuel cycle to ensure sustainable nuclear energy utilization have been promoted. Decommissioning technologies for Tokai power station have been developed and accumulated know-how will be utilized in light water reactors. (T. Tanaka)

  4. Nuclear watershed

    International Nuclear Information System (INIS)

    Makovich, L.; Parish, T.

    1984-01-01

    In 1979 the accident at Three Mile Island brought nuclear power to the forefront of national attention. Over the last five years there have been no new orders for nuclear plants, construction costs and lead times have increased drastically, and numerous plants have been cancelled. In the coming years many new plants will come on line, and the first round of nuclear plant retirements will begin. Thus, the new set of issues faced by utilities are whether to complete plants currently under construction, how to recover the cost of abandoned plants, how to handle the potential rate shock of bringing costly plants into rate base, and how to accomplish decommissioning and retirement of nuclear plants. This paper presents and analyzes these issues. First, the history of the nuclear electric generation industry is reviewed. Next a case study illustrating the cost momentum built into nuclear power plant construction is presented. The issues involved in plant cancellation are discussed. Finally, a case study involving rate phase-in strategies is analyzed. 1 reference, 7 figures

  5. An Updated Review of Tyrosinase Inhibitors

    Directory of Open Access Journals (Sweden)

    Te-Sheng Chang

    2009-05-01

    Full Text Available Tyrosinase is a multifunctional, glycosylated, and copper-containing oxidase, which catalyzes the first two steps in mammalian melanogenesis and is responsible for enzymatic browning reactions in damaged fruits during post-harvest handling and processing. Neither hyperpigmentation in human skin nor enzymatic browning in fruits are desirable. These phenomena have encouraged researchers to seek new potent tyrosinase inhibitors for use in foods and cosmetics. This article surveys tyrosinase inhibitors newly discovered from natural and synthetic sources. The inhibitory strength is compared with that of a standard inhibitor, kojic acid, and their inhibitory mechanisms are discussed.

  6. Inflammatory Signaling by NOD-RIPK2 Is Inhibited by Clinically Relevant Type II Kinase Inhibitors.

    Science.gov (United States)

    Canning, Peter; Ruan, Qui; Schwerd, Tobias; Hrdinka, Matous; Maki, Jenny L; Saleh, Danish; Suebsuwong, Chalada; Ray, Soumya; Brennan, Paul E; Cuny, Gregory D; Uhlig, Holm H; Gyrd-Hansen, Mads; Degterev, Alexei; Bullock, Alex N

    2015-09-17

    RIPK2 mediates pro-inflammatory signaling from the bacterial sensors NOD1 and NOD2, and is an emerging therapeutic target in autoimmune and inflammatory diseases. We observed that cellular RIPK2 can be potently inhibited by type II inhibitors that displace the kinase activation segment, whereas ATP-competitive type I inhibition was only poorly effective. The most potent RIPK2 inhibitors were the US Food and Drug Administration-approved drugs ponatinib and regorafenib. Their mechanism of action was independent of NOD2 interaction and involved loss of downstream kinase activation as evidenced by lack of RIPK2 autophosphorylation. Notably, these molecules also blocked RIPK2 ubiquitination and, consequently, inflammatory nuclear factor κB signaling. In monocytes, the inhibitors selectively blocked NOD-dependent tumor necrosis factor production without affecting lipopolysaccharide-dependent pathways. We also determined the first crystal structure of RIPK2 bound to ponatinib, and identified an allosteric site for inhibitor development. These results highlight the potential for type II inhibitors to treat indications of RIPK2 activation as well as inflammation-associated cancers. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. The human immunodeficiency virus protease inhibitor ritonavir is potentially active against urological malignancies

    Directory of Open Access Journals (Sweden)

    Sato A

    2015-04-01

    Full Text Available Akinori Sato Department of Urology, National Defense Medical College, Tokorozawa, Japan Abstract: The human immunodeficiency virus protease inhibitor ritonavir has recently been shown to have antineoplastic activity, and its use in urological malignancies is under investigation with an eye toward drug repositioning. Ritonavir is thought to exert its antineoplastic activity by inhibiting multiple signaling pathways, including the Akt and nuclear factor-kappaB pathways. It can increase the amount of unfolded proteins in the cell by inhibiting both the proteasome and heat shock protein 90. Combinations of ritonavir with agents that increase the amount of unfolded proteins, such as proteasome inhibitors, histone deacetylase inhibitors, or heat shock protein 90 inhibitors, therefore, induce endoplasmic reticulum stress cooperatively and thereby kill cancer cells effectively. Ritonavir is also a potent cytochrome P450 3A4 and P-glycoprotein inhibitor, increasing the intracellular concentration of combined drugs by inhibiting their degradation and efflux from cancer cells and thereby enhancing their antineoplastic activity. Furthermore, riotnavir’s antineoplastic activity includes modulation of immune system activity. Therapies using ritonavir are thus an attractive new approach to cancer treatment and, due to their novel mechanisms of action, are expected to be effective against malignancies that are refractory to current treatment strategies. Further investigations using ritonavir are expected to find new uses for clinically available drugs in the treatment of urological malignancies as well as many other types of cancer. Keywords: drug repositioning, novel treatment

  8. Effect of the Flexible Regions of the Oncoprotein Mouse Double Minute X on Inhibitor Binding Affinity.

    Science.gov (United States)

    Qin, Lingyun; Liu, Huili; Chen, Rong; Zhou, Jingjing; Cheng, Xiyao; Chen, Yao; Huang, Yongqi; Su, Zhengding

    2017-11-07

    The oncoprotein MdmX (mouse double minute X) is highly homologous to Mdm2 (mouse double minute 2) in terms of their amino acid sequences and three-dimensional conformations, but Mdm2 inhibitors exhibit very weak affinity for MdmX, providing an excellent model for exploring how protein conformation distinguishes and alters inhibitor binding. The intrinsic conformation flexibility of proteins plays pivotal roles in determining and predicting the binding properties and the design of inhibitors. Although the molecular dynamics simulation approach enables us to understand protein-ligand interactions, the mechanism underlying how a flexible binding pocket adapts an inhibitor has been less explored experimentally. In this work, we have investigated how the intrinsic flexible regions of the N-terminal domain of MdmX (N-MdmX) affect the affinity of the Mdm2 inhibitor nutlin-3a using protein engineering. Guided by heteronuclear nuclear Overhauser effect measurements, we identified the flexible regions that affect inhibitor binding affinity around the ligand-binding pocket on N-MdmX. A disulfide engineering mutant, N-MdmX C25-C110/C76-C88 , which incorporated two staples to rigidify the ligand-binding pocket, allowed an affinity for nutlin-3a higher than that of wild-type N-MdmX (K d ∼ 0.48 vs K d ∼ 20.3 μM). Therefore, this mutant provides not only an effective protein model for screening and designing of MdmX inhibitors but also a valuable clue for enhancing the intermolecular interactions of the pharmacophores of a ligand with pronounced flexible regions. In addition, our results revealed an allosteric ligand-binding mechanism of N-MdmX in which the ligand initially interacts with a compact core, followed by augmenting intermolecular interactions with intrinsic flexible regions. This strategy should also be applicable to many other protein targets to accelerate drug discovery.

  9. Using model complexes to augment and advance metalloproteinase inhibitor design.

    Science.gov (United States)

    Jacobsen, Faith E; Cohen, Seth M

    2004-05-17

    The tetrahedral zinc complex [(Tp(Ph,Me))ZnOH] (Tp(Ph,Me) = hydrotris(3,5-phenylmethylpyrazolyl)borate) was combined with 2-thenylmercaptan, ethyl 4,4,4-trifluoroacetoacetate, salicylic acid, salicylamide, thiosalicylic acid, thiosalicylamide, methyl salicylate, methyl thiosalicyliate, and 2-hydroxyacetophenone to form the corresponding [(Tp(Ph,Me))Zn(ZBG)] complexes (ZBG = zinc-binding group). X-ray crystal structures of these complexes were obtained to determine the mode of binding for each ZBG, several of which had been previously studied with SAR by NMR (structure-activity relationship by nuclear magnetic resonance) as potential ligands for use in matrix metalloproteinase inhibitors. The [(Tp(Ph,Me))Zn(ZBG)] complexes show that hydrogen bonding and donor atom acidity have a pronounced effect on the mode of binding for this series of ligands. The results of these studies give valuable insight into how ligand protonation state and intramolecular hydrogen bonds can influence the coordination mode of metal-binding proteinase inhibitors. The findings here suggest that model-based approaches can be used to augment drug discovery methods applied to metalloproteins and can aid second-generation drug design.

  10. Aphidicolin-induced nuclear elongation in tobacco BY-2 cells.

    Science.gov (United States)

    Yasuhara, Hiroki; Kitamoto, Kazuki

    2014-05-01

    Plant nuclei are known to differentiate into various shapes within a single plant. However, little is known about the mechanisms of nuclear morphogenesis. We found that nuclei of tobacco BY-2 cells were highly elongated on long-term treatment with 5 mg l⁻¹ aphidicolin, an inhibitor of DNA polymerase α. In aphidicolin-treated cells, the nuclear length was correlated with the cell length. During culture in the presence of aphidicolin, the nuclei were elongated in parallel with cell elongation. Nuclear elongation was inhibited by the inhibition of cell elongation with 2,6-dichlorobenzonitrile, a cellulose synthesis inhibitor. However, cell elongation induced in the auxin-depleted medium in the absence of aphidicolin did not cause nuclear elongation, indicating that cell elongation alone is not sufficient for nuclear elongation. Treatment with either latrunculin B or propyzamide inhibited the aphidicolin-induced nuclear elongation, indicating that both actin filaments and microtubules (MTs) are required for nuclear elongation. Observations using BY-YTHCLR2 cells, in which actin filaments, MTs and nuclei were simultaneously visualized, revealed that the longitudinally arranged MT bundles associated with the nucleus play an important role in nuclear elongation, and that actin filaments affect the formation of these MT bundles. In aphidicolin-treated cells, the nuclear DNA contents of the elongated nuclei exceeded 4C, and the nuclear length was highly correlated with the nuclear DNA content. In cells treated with 50 mg l⁻¹ aphidicolin, cells were elongated and nucleus-associated longitudinal MT bundles were formed, but the nuclear DNA contents did not exceed 4C and the nuclei did not elongate. These results indicate that an increase in the nuclear DNA content above 4C is also required for nuclear elongation.

  11. Food as a Source for Quorum Sensing Inhibitors: Iberin from Horseradish Revealed as a Quorum Sensing Inhibitor of Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Jakobsen, Tim Holm; Bragason, Steinn Kristinn; Phipps, Richard Kerry

    2012-01-01

    of traditional antibiotics to treat infections caused by bacterial biofilms and multidrug-resistant bacteria. Several QSIs of natural origin have been identified, and in this study, several common food products and plants were extracted and screened for QSI activity in an attempt to isolate and characterize...... to transcend problems with selective pressures for antibiotic resistance, is to interrupt bacterial communication, also known as quorum sensing (QS), by means of signal antagonists, the so-called QS inhibitors (QSIs). Furthermore, QSI agents offer a potential solution to the deficiencies associated with use......-diode array detector-mass spectrometry (LC-DAD-MS) and nuclear magnetic resonance (NMR) spectroscopy as iberin—an isothiocyanate produced by many members of the Brassicaceae family. Real-time PCR (RT-PCR) and DNA microarray studies showed that iberin specifically blocks expression of QS-regulated genes in P...

  12. Strategies for discontinuation of proton pump inhibitors

    DEFF Research Database (Denmark)

    Haastrup, Peter; Paulsen, Maja S; Begtrup, Luise M

    2014-01-01

    PURPOSE: Proton pump inhibitors (PPIs) are considered to be overprescribed. Consensus on how to attempt discontinuation is, however, lacking. We therefore conducted a systematic review of clinical studies on discontinuation of PPIs. METHODS: Systematic review based on clinical studies investigating...

  13. Predicting the Performance of Organic Corrosion Inhibitors

    Directory of Open Access Journals (Sweden)

    David A. Winkler

    2017-12-01

    Full Text Available The withdrawal of effective but toxic corrosion inhibitors has provided an impetus for the discovery of new, benign organic compounds to fill that role. Concurrently, developments in the high-throughput synthesis of organic compounds, the establishment of large libraries of available chemicals, accelerated corrosion inhibition testing technologies, and the increased capability of machine learning methods have made discovery of new corrosion inhibitors much faster and cheaper than it used to be. We summarize these technical developments in the corrosion inhibition field and describe how data-driven machine learning methods can generate models linking molecular properties to corrosion inhibition that can be used to predict the performance of materials not yet synthesized or tested. We briefly summarize the literature on quantitative structure–property relationships models of small organic molecule corrosion inhibitors. The success of these models provides a paradigm for rapid discovery of novel, effective corrosion inhibitors for a range of metals and alloys in diverse environments.

  14. Novel diamide-based inhibitors of IMPDH.

    Science.gov (United States)

    Gu, Henry H; Iwanowicz, Edwin J; Guo, Junqing; Watterson, Scott H; Shen, Zhongqi; Pitts, William J; Dhar, T G Murali; Fleener, Catherine A; Rouleau, Katherine; Sherbina, N Z; Witmer, Mark; Tredup, Jeffrey; Hollenbaugh, Diane

    2002-05-06

    A series of novel amide-based small molecule inhibitors of inosine monophosphate dehydrogenase is described. The synthesis and the structure-activity relationships (SARs) derived from in vitro studies are presented.

  15. Monoamine Oxidase B Inhibitors in Parkinson's Disease.

    Science.gov (United States)

    Dezsi, Livia; Vecsei, Laszlo

    2017-01-01

    Parkinson's disease (PD) is a neurodegenerative disorder with a prevalence increasing with age. Oxidative stress and glutamate toxicity are involved in its pathomechanism. There are still many unmet needs of PD patients, including the alleviation of motor fluctuations and dyskinesias, and the development of therapies with neuroprotective potential. To give an overview of the pharmacological properties, the efficacy and safety of the monoamine oxidase B (MAO-B) inhibitors in the treatment of PD, with special focus on the results of randomized clinical trials. A literature search was conducted in PubMed for 'PD treatment', 'MAO-B inhibitors', 'selegiline', 'rasagiline', 'safinamide' and 'clinical trials' with 'MAO-B inhibitors' in 'Parkinson' disease'. MAO-B inhibitors have a favorable pharmacokinetic profile, improve the dopamine deficient state and may have neuroprotective properties. Safinamide exhibits an anti-glutamatergic effect as well. When applied as monotherapy, MAO-B inhibitors provide a modest, but significant improvement of motor function and delay the need for levodopa. Rasagiline and safinamide were proven safe and effective when added to a dopamine agonist in early PD. As add-on to levodopa, MAO-B inhibitors significantly reduced off-time and were comparable in efficacy to COMT inhibitors. Improvements were achieved as regards certain non-motor symptoms as well. Due to the efficacy shown in clinical trials and their favorable side-effect profile, MAO-B inhibitors are valuable drugs in the treatment of PD. They are recommended as monotherapy in the early stages of the disease and as add-on therapy to levodopa in advanced PD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. 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

    proteases. We studied the influence of chemical anti-inhibitors (chloramine T, flufenamate, sodium lauryl sulfate, and methylamine) on fibrinolytic serine proteases and fibrinolytic enzyme inhibitors using the physiological substrate fibrin as plasmin substrate. Low concentrations of chloramine T (0.01 mmol......%) and plasminogen activators (apparent recovery > 200%). Sodium lauryl sulfate eliminates the major fibrinolytic enzyme inhibitors, but increases the activity of plasmin (apparent recovery > 200%) and plasminogen activator, urokinase type (apparent recovery 130%). Methylamine affects only plasmin inhibition. We...

  17. Nuclear waste

    International Nuclear Information System (INIS)

    Anon.

    1983-01-01

    The Koeberg nuclear power station, planned to come on stream in 1984, is expected to save South Africa some six million t/annum of coal, and to contribute some 10 per cent of the country's electricity requirements. The use of nuclear energy will provide for growing national energy needs, and reduce high coal transport costs for power generation at the coast. In the long term, however, it gives rise to the controversial question of nuclear waste storage. The Atomic Energy Corporation of South Africa Ltd (AEC) recently announced the purchase of a site in Namaqualand (NW Cape) for the storage of low-level radioactive waste. The Nuclear Development Corporation of South Africa (Pty) Ltd, (NUCOR) will develop and operate the site. The South African Mining and Engineering Journal interviewed Dr P.D. Toens, manager of the Geology Department and Mr P.E. Moore, project engineer, on the subject of nuclear waste, the reasons behind Nucor's choice of site and the storage method

  18. Nuclear risk

    International Nuclear Information System (INIS)

    Levenson, M.

    1989-01-01

    The title of our session, Nuclear Risk Versus Other Power Options, is provocative. It is also a title with different meanings to different people. To the utility chief executive officer, nuclear power is a high-risk financial undertaking because of political and economic barriers to cost recovery. To the utility dispatcher, it is a high-risk future power source since plant completion and start-up dates can be delayed for very long times due to uncertain legal and political issues. To the environmentalist, concerned about global effects such as greenhouse and acid rain, nuclear power is a relatively low risk energy source. To the financial people, nuclear power is a cash cow turned sour because of uncertainties as to what new plants will cost and whether they will even be allowed to operate. The statistics on risk are known and the results of probability risk assessment calculations of risks are known. The challenge is not to make nuclear power safer, it is already one of the safest, if not the safest, source of power currently available. The challenge is to find a way to communicate this to the public

  19. Nuclear recession

    International Nuclear Information System (INIS)

    Speth, G.

    1978-01-01

    The private sector's growing doubts about nuclear power plants, as reflected in the decline in new orders and the number of rescinded orders, will result in an estimated total of under 300 nuclear power plants by the year 2000 rather than the 1200 to 1500 that were projected several years ago. The decline is a result of construction and equipment costs and a lower operating efficiency than anticipated. The growth of electricity demand also declined after 1974 and, although it is increasing again, there are concerns about future growth rates. Besides its noncompetitive position relative to coal, nuclear plant construction suffers from restrictive policies based on the uncertainties of safety, security, waste disposal, and proliferation. Unless these problems can be resolved, many consider nuclear power to be an impractical option as an energy source. The Council on Environmental Quality supports policies that will permit further nuclear or coal development only after a clear demonstration of technical and institutional capacity to handle these problems. A commitment to solar technology is urged

  20. Nuclear fusion

    International Nuclear Information System (INIS)

    Al-zaelic, M.M.

    2013-01-01

    Nuclear fusion can be relied on to solve the global energy crisis if the process of limiting the heat produced by the fusion reaction (Plasma) is successful. Currently scientists are progressively working on this aspect whereas there are two methods to limit the heat produced by fusion reaction, the two methods are auto-restriction using laser beam and magnetic restriction through the use of magnetic fields and research is carried out to improve these two methods. It is expected that at the end of this century the nuclear fusion energy will play a vital role in overcoming the global energy crisis and for these reasons, acquiring energy through the use of nuclear fusion reactors is one of the most urge nt demands of all mankind at this time. The conclusion given is that the source of fuel for energy production is readily available and inexpensive ( hydrogen atoms) and whole process is free of risks and hazards, especially to general health and the environment . Nuclear fusion importance lies in the fact that energy produced by the process is estimated to be about four to five times the energy produced by nuclear fission. (author)

  1. Development of Radiosensitizer using farnesyltransferase inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Jong Seok; Choe, Yong Kyung; Han, Mi Young; Kim, Kwang Dong [Korea Research Institute of Bioscience and Biotechnology, Taejon (Korea)

    1999-03-01

    We selected some compounds that were reported to have an activity of farneyltransferase inhibitor and tested the hypothesis that they might be used to radiosensitize cells transformed by ras oncogenes. The inhibition of ras processing using some, but not all, inhibitors resulted in higher levels of cell death after {gamma}-irradiation and increased radiosensitivity in H-ras-transformed NIH3T3 cells and MCF-10A human tumor cells. They did not induce additional cell death in control cells that doe not have ras mutation. Furthermore, the treatment of inhibitors alone induced a weak G0/G1 block, whereas inhibitors in combination with {gamma}-irradiation induced an additional enrichment in the G2/M phase of the cell cycle that typically represents irradiation-induced growth arrest. At present, the underling mechanism by which the farnesylltransferase inhibitors exert radiosensitizing effect is not known. In summary, our results suggest and lead to the possibility that some of farnesylation inhibitors may prove clinically useful not only as antitumor agents, but also radiosensitizers of tumors whose growth is dependent on ras function. (author). 15 refs., 10 figs., 4 tabs.

  2. Natural inhibitors of tumor-associated proteases

    International Nuclear Information System (INIS)

    Magdolen, U.; Krol, J.; Sato, S.; Schmitt, M.; Magdolen, V.; Krueger, A.; Mueller, M.M.; Sperl, S.

    2002-01-01

    The turnover and remodelling of extracellular matrix (ECM) is an essential part of many normal biological processes including development, morphogenesis, and wound healing. ECM turnover also occurs in severe pathological situations like artherosclerosis, fibrosis, tumor invasion and metastasis. The major proteases involved in this turnover are serine proteases (especially the urokinase-type plasminogen activator/plasmin system), matrix metalloproteases (a family of about 20 zinc-dependent endopeptidases including collagenases, gelatinases, stromelysins, and membrane-type metalloproteases), and cysteine proteases. In vivo, the activity of these proteases is tightly regulated in the extracellular space by zymogen activation and/or controlled inhibition. In the present review, we give an overview on the structure and biochemical properties of important tumor-associated protease inhibitors such as plasminogen activator inhibitor type 1 and type 2 (PAI-1, PAI-2), tissue inhibitors of metalloproteinases (TIMP-1, -2, -3, and -4), and the cysteine protease inhibitor cystatin C. Interestingly, some of these inhibitors of tumor-associated proteases display multiple functions which rather promote than inhibit tumor progression, when the presence of inhibitors in the tumor tissue is not balanced. (author)

  3. Emerging Corrosion Inhibitors for Interfacial Coating

    Directory of Open Access Journals (Sweden)

    Mona Taghavikish

    2017-12-01

    Full Text Available Corrosion is a deterioration of a metal due to reaction with environment. The use of corrosion inhibitors is one of the most effective ways of protecting metal surfaces against corrosion. Their effectiveness is related to the chemical composition, their molecular structures and affinities for adsorption on the metal surface. This review focuses on the potential of ionic liquid, polyionic liquid (PIL and graphene as promising corrosion inhibitors in emerging coatings due to their remarkable properties and various embedment or fabrication strategies. The review begins with a precise description of the synthesis, characterization and structure-property-performance relationship of such inhibitors for anti-corrosion coatings. It establishes a platform for the formation of new generation of PIL based coatings and shows that PIL corrosion inhibitors with various heteroatoms in different form can be employed for corrosion protection with higher barrier properties and protection of metal surface. However, such study is still in its infancy and there is significant scope to further develop new structures of PIL based corrosion inhibitors and coatings and study their behaviour in protection of metals. Besides, it is identified that the combination of ionic liquid, PIL and graphene could possibly contribute to the development of the ultimate corrosion inhibitor based coating.

  4. Discovery of natural mouse serum derived HIV-1 entry inhibitor(s).

    Science.gov (United States)

    Wei, M; Chen, Y; Xi, J; Ru, S; Ji, M; Zhang, D; Fang, Q; Tang, B

    Among rationally designed human immunodeficiency virus 1 (HIV-1) inhibitors, diverse natural factors have showed as potent anti-HIV activity in human blood. We have discovered that the boiled supernatant of healthy mouse serum could suppress HIV-1 entry, and exhibited reduced inhibitory activity after trypsin digestion. Further analysis demonstrated that only the fraction containing 10-25 K proteins could inhibit HIV-1 mediated cell-cell fusion. These results suggest that the 10-25 K protein(s) is novel natural HIV-1 entry inhibitor(s). Our findings provide important information about novel natural HIV entry inhibitors in mouse serum.

  5. Nuclear scales

    International Nuclear Information System (INIS)

    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 π-γ 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

  6. Nuclear forces

    International Nuclear Information System (INIS)

    Holinde, K.

    1990-01-01

    In this paper the present status of the meson theory of nuclear forces is reviewed. After some introductory remarks about the relevance of the meson exchange concept in the era of QCD and the empirical features of the NN interaction, the exciting history of nuclear forces is briefly outlined. In the main part, the author gives the basic physical ideas and sketch the derivation of the one-boson-exchange model of the nuclear force, in the Feynman approach. Secondly we describe, in a qualitative way, various necessary extensions, leading to the Bonn model of the N interaction. Finally, points to some interesting pen questions connected with the extended quark structure of the hadrons, which are topics of current research activity

  7. Nuclear astrophysics

    International Nuclear Information System (INIS)

    Penionzhkevich, Yu. E.

    2010-01-01

    The International Year of Astronomy 2009 (IYA2009) was declared by the 62nd General Assembly of the United Nations and was also endorsed by UNESCO. Investigations in the realms of particle and nuclear physicsmake a large contribution in the development of our ideas of the properties of the Universe. The present article discusses some problems of the evolution of the Universe, nucleosyntheses, and cosmochronology from the point of view of nuclear and particle physics. Processes occurring in the Universe are compared with the mechanisms of the production and decay of nuclei, as well as with the mechanisms of their interaction at high energies. Examples that demonstrate the potential of nuclearphysics methods for studying cosmic objects and the properties of the Universe are given. The results that come from investigations into nuclear reactions induced by beams of radioactive nuclei and which make it possible to take a fresh look at the nucleosynthesis scenario in the range at light nuclei are presented.

  8. 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.

  9. Nuclear waste

    International Nuclear Information System (INIS)

    Anon.

    1996-01-01

    The NEA Nuclear Waste Bulletin has been prepared by the Radiation Protection and Waste Management Division of the OECD Nuclear Energy Agency to provide a means of communication amongst the various technical and policy groups within the waste management community. In particular, it is intended to provide timely and concise information on radioactive waste management activities, policies and programmes in Member countries and at the NEA. It is also intended that the Bulletin assists in the communication of recent developments in a variety of areas contributing to the development of acceptable technology for the management and disposal of nuclear waste (e.g., performance assessment, in-situ investigations, repository engineering, scientific data bases, regulatory developments, etc)

  10. Nuclear policy

    International Nuclear Information System (INIS)

    Ford, G.R.

    1976-01-01

    Then-President Gerald Ford outlines the potential benefits of nuclear power as opposed to the danger of proliferation. He points out that not all nations have the same interest or views toward nuclear energy; but also he says that if a choice must be made, nonproliferation objectives must take precedence over economic and energy benefits. It is pointed out that the management of nuclear energy can be only partial and temporary by technical measures, and that full management can result only if nations realistically face the task prepared to forego preconceived short-term advantages in favor of long-term gains. Coordination of the policies of all nations toward the common goal of nonproliferation is predicted to lead to success

  11. Nuclear proliferation and terrorism

    International Nuclear Information System (INIS)

    Anon.

    1977-01-01

    This section of the book, Part III, has two chapters (9 and 10). Chapter 9, Nuclear Power and Proliferation of Nuclear Weapons, is disucssed under these subjects: nuclear nonproliferation: origins and status; requirements for nuclear weapons manufacture; current nuclear programs and proliferation capabilities; encouraging decisions to forego weapons; arms control; safeguards; attitudes and expectations. Chapter 10, Nuclear Terrorism, discusses these areas: theft of nuclear materials; attacks on nuclear reactors; responding to nuclear terrorism; security and civil liberties

  12. Nuclear politics

    International Nuclear Information System (INIS)

    Hall, Tony.

    1986-01-01

    Written by an arts graduate journalist this is intended for a non-technical general readership. It chronicles the history of the nuclear power industry in Britain from its beginnings, which were inextricably tied to the development of the atomic bomb, to the Sellafield investigation and Sizewell public inquiry. In particular the government decisions which have influenced the present structure and state of the industry are criticised. With important decisions about to be made the author questions the accountability of the nuclear industry and the government's ability to understand the complex technical aspects of the industry. (U.K.)

  13. Nuclear dilemma

    Energy Technology Data Exchange (ETDEWEB)

    Penn, J.

    Declaring nuclear preparedness 'immoral' helps to recreate the pacifism of 50 years ago. War itself is a dilemma, not the weapons with which it is waged. We must ask of the anti-war proposals: whom do they benefit. On the whole people concerned are ordinary citizens who are fearful of nuclear incineration. But marching with them is a spectrum of forces with other motivations and purposes. In a real life situation of international tension or crises, numbers of weapons in combination with their particular charateristics could mean the difference between peace and outbreak of war.

  14. Nuclear energy

    International Nuclear Information System (INIS)

    Lotter, A.C.

    1979-01-01

    The recent, terrifying threat of a major calamity at Pennsylvania's Three Mile Island power plant near Harrisburg reverberated across practically the whole of the civilised world. An almost incredible sequence of human and mechanical failures at this installation had stopped just short of disaster and had brought the unthinkable perilously close to happening. The accident had sprayed radioactive waste into the air and had led to the large scale evacuation of people from the endangered area, disrupted hundreds of thousands of lives and caused a crippling setback to the nuclear industry. In this article the author discusses the impact the Harrisburg incident has had on the nuclear industry

  15. Nuclear cardiology

    International Nuclear Information System (INIS)

    Bashore, T.M.; Shaffer, P.B.

    1985-01-01

    The birth of nuclear cardiology has generally been attributed to a 1927 experiment during which a radium salt was injected in one arm vein and the circulation time calculated by recording the arrival of the radioactivity in the opposite arm. This simple experiment lead to the radiocardiogram in the late 1940s that was used to measure left ventricular function and, later, cardiac output. This chapter provides a brief overview of nuclear cardiology. Methodology is presented when it is important for the understanding of test results. The use of these studies in the diagnosis and evaluation of patients with suspected cardiovascular disease is emphasized

  16. Nuclear fuel

    International Nuclear Information System (INIS)

    Azevedo, J.B.L. de.

    1980-01-01

    All stages of nuclear fuel cycle are analysed with respect to the present situation and future perspectives of supply and demand of services; the prices and the unitary cost estimation of these stages for the international fuel market are also mentioned. From the world resources and projections of uranium consumption, medium-and long term analyses are made of fuel availability for several strategies of use of different reactor types. Finally, the cost of nuclear fuel in the generation of electric energy is calculated to be used in the energetic planning of the electric sector. (M.A.) [pt

  17. Nuclear reactions

    International Nuclear Information System (INIS)

    Lane, A.M.

    1980-01-01

    In reviewing work at Harwell over the past 25 years on nuclear reactions it is stated that a balance has to be struck in both experiment and theory between work on cross-sections of direct practical relevance to reactors and on those relevant to an overall understanding of reaction processes. The compound nucleus and direct process reactions are described. Having listed the contributions from AERE, Harwell to developments in nuclear reaction research in the period, work on the optical model, neutron capture theory, reactions at doorway states with fine structure, and sum-rules for spectroscopic factors are considered in more detail. (UK)

  18. The nuclear

    International Nuclear Information System (INIS)

    2011-01-01

    This report proposes an overview of knowledge and technical aspects regarding nuclear energy. It presents the phenomenon of radioactivity and its measurement and thresholds, describes the fuel cycle, presents the different principles and types of nuclear reactors, and more precisely the pressurized water reactors and their various models (900, 1300, 1400 and 1600 MW). It presents other reactors: boiling water reactors, heavy water reactors, high temperature reactors, fourth generation reactors. It addresses the issues of wastes and releases, presents the OSPAR convention, the issues of management and safety. It presents the national safety bodies (ASN, IRSN, HCTISM) and international bodies

  19. Nuclear medicine

    International Nuclear Information System (INIS)

    Reichelt, H.G.

    1980-01-01

    Nuclear medicine as a complex diagnostical method is used mainly to detect functional organic disorders, to locate disorders and for radioimmunologic assays (RIA) in vitro. In surgery, its indication range comprises the thyroid (in vivo and in vitro), liver and bile ducts, skeletal and joint diseases, disorders of the cerebro-spinal liquor system and the urologic disorders. In the early detection of tumors, the search for metastases and tumor after-care, scintiscanning and the tumor marcher method (CEA) can be of great practical advantage, but the value of myocardial sciritiscanning in cardiac respectively coronary disorders is restricted. The paper is also concerned with the radiation doses in nuclear medicine. (orig.) [de

  20. Inactivation of proteinaceous protease inhibitors of soybeans by isolated fungi

    NARCIS (Netherlands)

    Meijer, M.M.T.; Spekking, W.T.J.; Sijtsma, L.; Bont, de J.A.M.

    1995-01-01

    Proteinaceous protease inhibitors, Kunitz Soybean Trypsin Inhibitor (KSTI) and Bowman Birk Inhibitor (BBI), in legume seeds reduce the digestibility of proteins in feed of monogastric animals. Enzymatic inactivation of these inhibitors will increase the nutritional value of the feed. The aim of this

  1. Nuclear energy and nuclear technology

    International Nuclear Information System (INIS)

    Luescher, E.

    1982-01-01

    This book originated in the training courses for teachers of grammar- and secondary schools in Dillingen (Bavaria). The aim of these courses is to become informed about the latest state in one field of physics. The lectures are well-known experts in the respective fields. In the latest study (1980) of the National Academy of Sciences the experts came to the conclusion that without further development nuclear power plants the utilization of too much coal would become necessary and involve irreversible environmental damage (see chapter 6). There are two important obstacles impeding the further extension of nuclear energy. The first problem to be solved is the processing and storage of radioactive waste. This is a more technical task and can be treated in a satisfactory way. The second obstacle is less easy to take as the population has to be convinced that a nuclear power plant can be operated with almost unbelievable safety (see chapter 5) and be shut down safely in the case of incidents. The most promising possibility of controlled nuclear fusion as energy source is still many decades- if feasible at all- away from being performed (see chapter. 7). In the Soviet Union 25% of the electric energy production shall be proceed from nuclear power plants by the year 1990. (orig./GL) [de

  2. 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.

  3. 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.

  4. Combined effects of EGFR tyrosine kinase inhibitors and vATPase inhibitors in NSCLC cells

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Hyeon-Ok [KIRAMS Radiation Biobank, Korea Institute of Radiological and Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul, 139–706 (Korea, Republic of); Hong, Sung-Eun [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul, 139–706 (Korea, Republic of); Kim, Chang Soon [Department of Microbiological Engineering, Kon-Kuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 143–701 (Korea, Republic of); Park, Jin-Ah; Kim, Jin-Hee; Kim, Ji-Young; Kim, Bora [KIRAMS Radiation Biobank, Korea Institute of Radiological and Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul, 139–706 (Korea, Republic of); Chang, Yoon Hwan; Hong, Seok-Il; Hong, Young Jun [Department of Laboratory Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul, 139–706 (Korea, Republic of); Park, In-Chul, E-mail: parkic@kirams.re.kr [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul, 139–706 (Korea, Republic of); Lee, Jin Kyung, E-mail: jklee@kirams.re.kr [KIRAMS Radiation Biobank, Korea Institute of Radiological and Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul, 139–706 (Korea, Republic of); Department of Laboratory Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul, 139–706 (Korea, Republic of)

    2015-08-15

    Despite excellent initial clinical responses of non-small cell lung cancer (NSCLC) patients to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), many patients eventually develop resistance. According to a recent report, vacuolar H + ATPase (vATPase) is overexpressed and is associated with chemotherapy drug resistance in NSCLC. We investigated the combined effects of EGFR TKIs and vATPase inhibitors and their underlying mechanisms in the regulation of NSCLC cell death. We found that combined treatment with EGFR TKIs (erlotinib, gefitinib, or lapatinib) and vATPase inhibitors (bafilomycin A1 or concanamycin A) enhanced synergistic cell death compared to treatments with each drug alone. Treatment with bafilomycin A1 or concanamycin A led to the induction of Bnip3 expression in an Hif-1α dependent manner. Knock-down of Hif-1α or Bnip3 by siRNA further enhanced cell death induced by bafilomycin A1, suggesting that Hif-1α/Bnip3 induction promoted resistance to cell death induced by the vATPase inhibitors. EGFR TKIs suppressed Hif-1α and Bnip3 expression induced by the vATPase inhibitors, suggesting that they enhanced the sensitivity of the cells to these inhibitors by decreasing Hif-1α/Bnip3 expression. Taken together, we conclude that EGFR TKIs enhance the sensitivity of NSCLC cells to vATPase inhibitors by decreasing Hif-1α/Bnip3 expression. We suggest that combined treatment with EGFR TKIs and vATPase inhibitors is potentially effective for the treatment of NSCLC. - Highlights: • Co-treatment with EGFR TKIs and vATPase inhibitors induces synergistic cell death • EGFR TKIs enhance cell sensitivity to vATPase inhibitors via Hif-1α downregulation • Co-treatment of these inhibitors is potentially effective for the treatment of NSCLC.

  5. Screening of protein kinase inhibitors identifies PKC inhibitors as inhibitors of osteoclastic acid secretion and bone resorption

    Directory of Open Access Journals (Sweden)

    Boutin Jean A

    2010-10-01

    Full Text Available Abstract Background Bone resorption is initiated by osteoclastic acidification of the resorption lacunae. This process is mediated by secretion of protons through the V-ATPase and chloride through the chloride antiporter ClC-7. To shed light on the intracellular signalling controlling extracellular acidification, we screened a protein kinase inhibitor library in human osteoclasts. Methods Human osteoclasts were generated from CD14+ monocytes. The effect of different kinase inhibitors on lysosomal acidification in human osteoclasts was investigated using acridine orange for different incubation times (45 minutes, 4 and 24 hours. The inhibitors were tested in an acid influx assay using microsomes isolated from human osteoclasts. Bone resorption by human osteoclasts on bone slices was measured by calcium release. Cell viability was measured using AlamarBlue. Results Of the 51 compounds investigated only few inhibitors were positive in both acidification and resorption assays. Rottlerin, GF109203X, Hypericin and Ro31-8220 inhibited acid influx in microsomes and bone resorption, while Sphingosine and Palmitoyl-DL-carnitine-Cl showed low levels of inhibition. Rottlerin inhibited lysosomal acidification in human osteoclasts potently. Conclusions In conclusion, a group of inhibitors all indicated to inhibit PKC reduced acidification in human osteoclasts, and thereby bone resorption, indicating that acid secretion by osteoclasts may be specifically regulated by PKC in osteoclasts.

  6. SGLT2 Inhibitors and the Diabetic Kidney.

    Science.gov (United States)

    Fioretto, Paola; Zambon, Alberto; Rossato, Marco; Busetto, Luca; Vettor, Roberto

    2016-08-01

    Diabetic nephropathy (DN) is the most common cause of end-stage renal disease worldwide. Blood glucose and blood pressure control reduce the risk of developing this complication; however, once DN is established, it is only possible to slow progression. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, the most recent glucose-lowering oral agents, may have the potential to exert nephroprotection not only through improving glycemic control but also through glucose-independent effects, such as blood pressure-lowering and direct renal effects. It is important to consider, however, that in patients with impaired renal function, given their mode of action, SGLT2 inhibitors are less effective in lowering blood glucose. In patients with high cardiovascular risk, the SGLT2 inhibitor empagliflozin lowered the rate of cardiovascular events, especially cardiovascular death, and substantially reduced important renal outcomes. Such benefits on DN could derive from effects beyond glycemia. Glomerular hyperfiltration is a potential risk factor for DN. In addition to the activation of the renin-angiotensin-aldosterone system, renal tubular factors, including SGLT2, contribute to glomerular hyperfiltration in diabetes. SGLT2 inhibitors reduce sodium reabsorption in the proximal tubule, causing, through tubuloglomerular feedback, afferent arteriole vasoconstriction and reduction in hyperfiltration. Experimental studies showed that SGLT2 inhibitors reduced hyperfiltration and decreased inflammatory and fibrotic responses of proximal tubular cells. SGLT2 inhibitors reduced glomerular hyperfiltration in patients with type 1 diabetes, and in patients with type 2 diabetes, they caused transient acute reductions in glomerular filtration rate, followed by a progressive recovery and stabilization of renal function. Interestingly, recent studies consistently demonstrated a reduction in albuminuria. Although these data are promising, only dedicated renal outcome trials will clarify whether

  7. Nuclear crime

    International Nuclear Information System (INIS)

    Braun, P.; Ferchland, B.

    1993-01-01

    The article discusses the legal provisions (Criminal Code (StGB), weapons Control Act) applicable in Germany to combat illegal trading of nuclear fuels and other readioactive materials. The authors conclude that part of the provisions are not in live with the rights and duties of the police, and they evolve near-practice proposals for remedy and legal improvement. (hP) [de

  8. Nuclear reactor

    International Nuclear Information System (INIS)

    Mysels, K.J.; Shenoy, A.S.

    1976-01-01

    A nuclear reactor is described in which the core consists of a number of fuel regions through each of which regulated coolant flows. The coolant from neighbouring fuel regions is combined in a manner which results in an averaging of the coolant temperature at the outlet of the core. By this method the presence of hot streaks in the reactor is reduced. (UK)

  9. Nuclear energy

    International Nuclear Information System (INIS)

    Reuss, Paul

    2012-01-01

    With simple and accessible explanations, this book presents the physical principles, the history and industrial developments of nuclear energy. More than 25 years after the Chernobyl accidents and few months only after the Fukushima one, it discusses the pros and cons of this energy source with its assets and its risks. (J.S.)

  10. Nuclear imaging

    International Nuclear Information System (INIS)

    Miller, J.H.; Reid, B.S.

    1985-01-01

    Nuclear imaging, utilizing relatively low photon energy emitting isotopes, allows an assessment of anatomic configuration and organ function. This method of imaging is predicted on the utilization of physiologically active radioisotope-labeled compounds or biologically active radioisotopes. Localization of such isotopes in normal or abnormal concentrations may be due to varying physiological or pathological mechanisms

  11. Nuclear Energy

    International Nuclear Information System (INIS)

    1982-11-01

    A brief indication is given of the United Kingdom nuclear power programme including descriptions of the fission process, the Magnox, AGR and PWR type reactors, the recycling process, waste management and decommissioning, safety precautions, the prototype fast reactor at Dounreay, and the JET fusion experiment. (U.K.)

  12. Nuclear physics

    International Nuclear Information System (INIS)

    Guzman B, O.; Vallejo M, J.I.; Cardenas C, H.F.

    1989-01-01

    A historical review of the evolution of the Nuclear Physics Section at the IAN is presented along the 30 years of existence of the Institute. Objectives, structure, programs and goal are historically examined. Present status of the section and its projection on national development is also analyzed

  13. Nuclear films

    International Nuclear Information System (INIS)

    Malone, Peter.

    1985-01-01

    This booklet is a resource for the study of feature films that highlight the theme of nuclear war. It provides basic credits and brief indication of the theme, treatment, quality and particular notable aspects; and a series of questions raised by the film. Seventy feature films and thirty documentaries are examined

  14. Nuclear reactions

    International Nuclear Information System (INIS)

    Corner, J.; Richardson, K.; Fenton, N.

    1990-01-01

    Nuclear reactions' marks a new development in the study of television as an agency of public policy debate. During the Eighties, nuclear energy became a major international issue. The disasters at Three-mile Island and Chernobyl created a global anxiety about its risks and a new sensitivity to it among politicians and journalists. This book is a case-study into documentary depictions of nuclear energy in television and video programmes and into the interpretations and responses of viewers drawn from many different occupational groupings. How are the complex and specialist arguments about benefit, risk and proof conveyed through the different conventions of commentary, interview and film sequence? What symbolic associations does the visual language of television bring to portrayals of the issue? And how do viewers make sense of various and conflicting accounts, connecting what they see and hear on the screen with their pre-existing knowledge, experience and 'civic' expectations. The authors examine some of the contrasting forms and themes which have been used by programme makers to explain and persuade, and then give a sustained analysis of the nature and sources of viewers' own accounts. 'Nuclear Reactions' inquires into the public meanings surrounding energy and the environment, spelling out in its conclusion some of the implications for future media treatments of this issue. It is also a key contribution to the international literature on 'television knowledge' and the processes of active viewing. (author)

  15. Nuclear fragmentation

    International Nuclear Information System (INIS)

    Chung, K.C.

    1989-01-01

    An introduction to nuclear fragmentation, with emphasis in percolation ideas, is presented. The main theoretical models are discussed and as an application, the uniform expansion approximation is presented and the statistical multifragmentation model is used to calculate the fragment energy spectra. (L.C.)

  16. Nuclear physics

    International Nuclear Information System (INIS)

    1990-01-01

    This work describes the actual situation of nuclear physics in Brazil as well as its perspectives of developments and real needs in the next decade. It discusses the main projects and the financing of brazilian research groups and Universities. (A.C.A.S.)

  17. Nuclear waste

    International Nuclear Information System (INIS)

    1990-06-01

    DOE estimates that disposing of radioactive waste from civilian nuclear power plants and its defense-related nuclear facilities could eventually end up costing $32 billion. To pay for this, DOE collects fees from utilities on electricity generated by nuclear power plants and makes payments from its defense appropriation. This report states that unless careful attention is given to its financial condition, the nuclear waste program is susceptible to future shortfalls. Without a fee increase, the civilian-waste part of the program may already be underfunded by at least $2.4 billion (in discounted 1988 dollars). Also, DOE has not paid its share of cost-about $480 million-nor has it disclosed this liability in its financial records. Indexing the civilian fee to the inflation rate would address one major cost uncertainty. However, while DOE intends to do this at an appropriate time, it does not use a realistic rate of inflation as its most probable scenario in assessing whether that time has arrived

  18. Nuclear safety culture and nuclear safety supervision

    International Nuclear Information System (INIS)

    Chai Jianshe

    2013-01-01

    In this paper, the author reviews systematically and summarizes up the development process and stage characteristics of nuclear safety culture, analysis the connotation and characteristics of nuclear safety culture, sums up the achievements of our country's nuclear safety supervision, dissects the challenges and problems of nuclear safety supervision. This thesis focused on the relationship between nuclear safety culture and nuclear safety supervision, they are essential differences, but there is a close relationship. Nuclear safety supervision needs to introduce some concepts of nuclear safety culture, lays emphasis on humanistic care and improves its level and efficiency. Nuclear safety supervision authorities must strengthen nuclear safety culture training, conduct the development of nuclear safety culture, make sure that nuclear safety culture can play significant roles. (author)

  19. Inhibitor chymotrypsynowy nasion wiechliny łąkowej (Poa pratensis [Chymotrypsin inhibitor from Poa pratensis seeds

    Directory of Open Access Journals (Sweden)

    I. Lorenc-Kubis

    2015-01-01

    Full Text Available A chymotrypsin inhibitor was isolated from Poa pratensis seeds. The inhibitor showed also antytriptic activity. It is a termostable protein, soluble in water, sodium chloride, but insoluble in 5% trichloracetic acid and 0.15 M sulphosalicylic acid.

  20. The Arabidopsis Nuclear Pore and Nuclear Envelope

    OpenAIRE

    Meier, Iris; Brkljacic, Jelena

    2010-01-01

    The nuclear envelope is a double membrane structure that separates the eukaryotic cytoplasm from the nucleoplasm. The nuclear pores embedded in the nuclear envelope are the sole gateways for macromolecular trafficking in and out of the nucleus. The nuclear pore complexes assembled at the nuclear pores are large protein conglomerates composed of multiple units of about 30 different nucleoporins. Proteins and RNAs traffic through the nuclear pore complexes, enabled by the interacting activities...

  1. SGLT2 inhibitors: are they safe?

    Science.gov (United States)

    Filippas-Ntekouan, Sebastian; Filippatos, Theodosios D; Elisaf, Moses S

    2018-01-01

    Sodium-glucose linked transporter type 2 (SGLT2) inhibitors are a relatively new class of antidiabetic drugs with positive cardiovascular and kidney effects. The aim of this review is to present the safety issues associated with SGLT2 inhibitors. Urogenital infections are the most frequently encountered adverse events, although tend to be mild to moderate and are easily manageable with standard treatment. Although no increased acute kidney injury risk was evident in the major trials, the mechanism of action of these drugs requires caution when they are administered in patients with extracellular volume depletion or with drugs affecting renal hemodynamics. Canagliflozin raised the risk of amputations and the rate of fractures in the CANVAS trial, although more data are necessary before drawing definite conclusions. The risk of euglycemic diabetic ketoacidosis seems to be minimal when the drugs are prescribed properly. Regarding other adverse events, SGLT2 inhibitors do not increase the risk of hypoglycemia even when co-administered with insulin, but a decrease in the dose of sulphonylureas may be needed. The available data do not point to a causative role of SGLT2 inhibitors on malignancy risk, however, these drugs should be used with caution in patients with known hematuria or history of bladder cancer. SGLT2 inhibitors seem to be safe and effective in the treatment of diabetes but more studies are required to assess their long-term safety.

  2. Aromatase inhibitors and breast cancer prevention.

    Science.gov (United States)

    Litton, Jennifer Keating; Arun, Banu K; Brown, Powel H; Hortobagyi, Gabriel N

    2012-02-01

    Endocrine therapy with selective estrogen receptor modulators (SERMs) has been the mainstay of breast cancer prevention trials to date. The aromatase inhibitors, which inhibit the final chemical conversion of androgens to estrogens, have shown increased disease-free survival benefit over tamoxifen in patients with primary hormone receptor-positive breast cancer, as well as reducing the risk of developing contralateral breast cancers. The aromatase inhibitors are being actively evaluated as prevention agents for women with a history of ductal carcinoma in situ as well as for women who are considered to be at high risk for developing primary invasive breast cancer. This review evaluates the available prevention data, as evidenced by the decrease in contralateral breast cancers, when aromatase inhibitors are used in the adjuvant setting, as well as the emerging data of the aromatase inhibitors specifically tested in the prevention setting for women at high risk. Exemestane is a viable option for breast cancer prevention. We continue to await further follow-up on exemestane as well as other aromatase inhibitors in the prevention setting for women at high risk of developing breast cancer or with a history of ductal carcinoma in situ.

  3. Janus kinase inhibitors: jackpot or potluck?

    Directory of Open Access Journals (Sweden)

    Pavithran Keechilat

    2012-06-01

    Full Text Available The reports of a unique mutation in the Janus kinase-2 gene (JAK2 in polycythemia vera by several independent groups in 2005 quickly spurred the development of the Janus kinase inhibitors. In one of the great victories of translational research in recent times, the first smallmolecule Janus kinase inhibitor ruxolitinib entered a phase I trial in 2007. With the approval of ruxolitinib by the US Federal Drug Administration in November 2011 for high-risk and intermediate-2 risk myelofibrosis, a change in paradigm has occurred in the management of a subset of myeloproliferative neoplasms (MPN: primary myelofibrosis, post-polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis. Whereas the current evidence for ruxolitinib only covers high-risk and intermediate-2 risk myelofibrosis, inhibitors with greater potency are likely to offer better disease control and survival advantage in patients belonging to these categories, and possibly to the low-risk and intermediate-1 risk categories of MPN as well. But use of the Janus kinase inhibitors also probably has certain disadvantages, such as toxicity, resistance, withdrawal phenomenon, non-reversal of histology, and an implausible goal of disease clone eradication, some of which could offset the gains. In spite of this, Janus kinase inhibitors are here to stay, and for use in more than just myeloproliferative neoplasms.

  4. Inhibition of herpes simplex virus type 1 entry by chloride channel inhibitors tamoxifen and NPPB

    International Nuclear Information System (INIS)

    Zheng, Kai; Chen, Maoyun; Xiang, Yangfei; Ma, Kaiqi; Jin, Fujun; Wang, Xiao; Wang, Xiaoyan; Wang, Shaoxiang; Wang, Yifei

    2014-01-01

    Highlights: • We analyze the anti-HSV potential of chloride channel inhibitors. • Tamoxifen and NPPB show anti-HSV-1 and anti-ACV-resistant HSV-1 activities. • HSV-1 infection induces intracellular chloride concentration increasing. • Tamoxifen and NPPB inhibit HSV-1 early infection. • Tamoxifen and NPPB prevent the fusion process of HSV-1. - Abstract: Herpes simplex virus type 1 (HSV-1) infection is very common worldwide and can cause significant health problems from periodic skin and corneal lesions to encephalitis. Appearance of drug-resistant viruses in clinical therapy has made exploring novel antiviral agents emergent. Here we show that chloride channel inhibitors, including tamoxifen and 5-nitro-2-(3-phenyl-propylamino) benzoic acid (NPPB), exhibited extensive antiviral activities toward HSV-1 and ACV-resistant HSV viruses. HSV-1 infection induced chloride ion influx while treatment with inhibitors reduced the increase of intracellular chloride ion concentration. Pretreatment or treatment of inhibitors at different time points during HSV-1 infection all suppressed viral RNA synthesis, protein expression and virus production. More detailed studies demonstrated that tamoxifen and NPPB acted as potent inhibitors of HSV-1 early entry step by preventing viral binding, penetration and nuclear translocation. Specifically the compounds appeared to affect viral fusion process by inhibiting virus binding to lipid rafts and interrupting calcium homeostasis. Taken together, the observation that tamoxifen and NPPB can block viral entry suggests a stronger potential for these compounds as well as other ion channel inhibitors in antiviral therapy against HSV-1, especially the compound tamoxifen is an immediately actionable drug that can be reused for treatment of HSV-1 infections

  5. Inhibition of herpes simplex virus type 1 entry by chloride channel inhibitors tamoxifen and NPPB

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Kai [Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou (China); College of Life Science and Technology, Jinan University, Guangzhou (China); Chen, Maoyun [Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou (China); College of pharmacy, Jinan University, Guangzhou (China); Xiang, Yangfei; Ma, Kaiqi [Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou (China); Jin, Fujun [Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou (China); College of pharmacy, Jinan University, Guangzhou (China); Wang, Xiao [School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006 (China); Wang, Xiaoyan; Wang, Shaoxiang [Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou (China); Wang, Yifei, E-mail: twang-yf@163.com [Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou (China)

    2014-04-18

    Highlights: • We analyze the anti-HSV potential of chloride channel inhibitors. • Tamoxifen and NPPB show anti-HSV-1 and anti-ACV-resistant HSV-1 activities. • HSV-1 infection induces intracellular chloride concentration increasing. • Tamoxifen and NPPB inhibit HSV-1 early infection. • Tamoxifen and NPPB prevent the fusion process of HSV-1. - Abstract: Herpes simplex virus type 1 (HSV-1) infection is very common worldwide and can cause significant health problems from periodic skin and corneal lesions to encephalitis. Appearance of drug-resistant viruses in clinical therapy has made exploring novel antiviral agents emergent. Here we show that chloride channel inhibitors, including tamoxifen and 5-nitro-2-(3-phenyl-propylamino) benzoic acid (NPPB), exhibited extensive antiviral activities toward HSV-1 and ACV-resistant HSV viruses. HSV-1 infection induced chloride ion influx while treatment with inhibitors reduced the increase of intracellular chloride ion concentration. Pretreatment or treatment of inhibitors at different time points during HSV-1 infection all suppressed viral RNA synthesis, protein expression and virus production. More detailed studies demonstrated that tamoxifen and NPPB acted as potent inhibitors of HSV-1 early entry step by preventing viral binding, penetration and nuclear translocation. Specifically the compounds appeared to affect viral fusion process by inhibiting virus binding to lipid rafts and interrupting calcium homeostasis. Taken together, the observation that tamoxifen and NPPB can block viral entry suggests a stronger potential for these compounds as well as other ion channel inhibitors in antiviral therapy against HSV-1, especially the compound tamoxifen is an immediately actionable drug that can be reused for treatment of HSV-1 infections.

  6. The nuclear controversy

    International Nuclear Information System (INIS)

    Walske, C.; Dobkin, R.A.

    1984-01-01

    The article deals with the nuclear controversy, especially in the United States. To a certain extent the nuclear debate has become heavily politicised. Public opinion and anti-nuclear groups are mentioned as well as nuclear disarmament

  7. Institute for Nuclear Research and Nuclear Energy and Nuclear Science

    International Nuclear Information System (INIS)

    Stamenov, J.

    2004-01-01

    The Institute for Nuclear Research and Nuclear Energy (INRNE) of the Bulgarian Academy of Sciences is the leading Bulgarian Institute for scientific investigations and applications of nuclear science. The main Institute's activities in the field of elementary particles and nuclear physics, high energy physics and nuclear energy, radiochemistry, radioecology, radioactive wastes treatment, monitoring of the environment, nuclear instruments development ect. are briefly described. Several examples for: environmental radiation monitoring; monitoring of the radioactivity and heavy metals in aerosols, 99m Tc clinical use, Boron Neutron Capture Therapy application of IRT-2000 Research Reactor, neutron fluence for reactor vessel embrittlement, NPP safety analysis, nuclear fuel modelling are also presented

  8. Nuclear power without nuclear weapons

    International Nuclear Information System (INIS)

    Kaiser, K.; Klein, F.J.

    1982-01-01

    In this study leading experts summarize the work of a working group meeting during several years, and they represent the state of the art of the international discussion about the non-proliferation of nuclear weapons. The technical basis of proliferation, the relations between energy policy and nuclear energy, as well as the development of the non-proliferation system up to the present are thoroughly studied. Special attention is paid to the further development of the instruments of the non-proliferation policy, and approaches and ways to improving the control of the fuel cycle, e.g. by means of multinational methods or by improving the control requirements are analyzed. Also the field of positive inducements and negative sanctions to prevent the proliferation as well as the question of ensured supply are elucidated in detail. A further section then analyzes the functions of the international organizations active in this field and the nuclear policy of the most important western industrial nations, the RGW-states and the threshold countries of the Third World. This volume pays special attention to the nuclear policy of the Federal Republic of Germany and to the possibilities and necessities of a further development of the non-proliferation policy. (orig.) [de

  9. Nuclear power of Korea

    International Nuclear Information System (INIS)

    Chun Bee-Ho

    2011-01-01

    National nuclear is presented. Nuclear energy safety after Fukushima, international cooperation in nuclear energy is discussed. Nuclear projects with the United Arab Emirates have been developed to build 4 nuclear power plants in the UAE - APR 1400. At the Korea-Bulgaria Industrial Committee Meeting in Sofia (March 2011) Korean side proposed Nuclear Safety Training Program in Korea for Bulgarian government officials and experts transfer of know-how and profound expertise on world-class nuclear technology and nuclear safety

  10. Nuclear power plants

    International Nuclear Information System (INIS)

    1985-01-01

    Data concerning the existing nuclear power plants in the world are presented. The data was retrieved from the SIEN (Nuclear and Energetic Information System) data bank. The information are organized in table forms as follows: nuclear plants, its status and type; installed nuclear power plants by country; nuclear power plants under construction by country; planned nuclear power plants by country; cancelled nuclear power plants by country; shut-down nuclear power plants by country. (E.G.) [pt

  11. 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......, in spite of a less favorable binding entropy and loss of a polar interaction. We conclude that increased flexibility of the peptide allows more favorable exosite interactions, which, in combination with the use of novel Arg analogues as P1 residues, can be used to manipulate the affinity and specificity...

  12. SGLT-2 Inhibitors and Cardiovascular Risk

    DEFF Research Database (Denmark)

    Cavender, Matthew A; Norhammar, Anna; Birkeland, Kåre I

    2018-01-01

    BACKGROUND: Prior studies found patients treated with sodium-glucose co-transporter-2 inhibitors (SGLT-2i) had lower rates of death and heart failure (HF). Whether the benefits of SGLT-2i vary based upon the presence of cardiovascular disease (CVD) is unknown. OBJECTIVES: This study sought...... to determine the association between initiation of SGLT-2i therapy and HF or death in patients with and without CVD. METHODS: The CVD-REAL (Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors) study was a multinational, observational study in which adults with type 2 diabetes...... evidence regarding the benefit of SGLT-2i in patients without established CVD. (Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors [CVD-REAL]; NCT02993614)....

  13. Akt phosphorylation is essential for nuclear translocation and retention in NGF-stimulated PC12 cells

    International Nuclear Information System (INIS)

    Truong Le Xuan Nguyen; Choi, Joung Woo; Lee, Sang Bae; Ye, Keqiang; Woo, Soo-Dong; Lee, Kyung-Hoon; Ahn, Jee-Yin

    2006-01-01

    Nerve growth factor (NGF) elicits Akt translocation into the nucleus, where it phosphorylates nuclear targets. Here, we describe that Akt phosphorylation can promote the nuclear translocation of Akt and is necessary for its nuclear retention. Overexpression of Akt-K179A, T308A, S473A-mutant failed to show either nuclear translocation or nuclear Akt phosphorylation, whereas expression of wild-type counterpart elicited profound Akt phosphorylation and induced nuclear translocation under NGF stimulation. Employing the PI3K inhibitor and a variety of mutants PI3K, we showed that nuclear translocation of Akt was mediated by activation of PI3K, and Akt phosphorylation status in the nucleus required PI3K activity. Thus the activity of PI3K might contribute to the nuclear translocation of Akt, and that Akt phosphorylation is essential for its nuclear retention under NGF stimulation conditions

  14. Nuclear energy and the nuclear industry

    International Nuclear Information System (INIS)

    1979-01-01

    These notes have been prepared by the Department of Energy to provide information and to answer questions often raised about nuclear energy and the nuclear industry and in the hope that they will contribute to the public debate about the future of nuclear energy in the UK. The subject is dealt with under the headings; contribution of nuclear power, energy forecasts, nuclear fuels and reactor types, cost, thermal reactor strategy, planning margin, safety, nuclear licensing, unlike an atomic bomb, radiation, waste disposal, transport of nuclear materials, emergency arrangements at nuclear sites, siting of nuclear stations, security of nuclear installations, world nuclear programmes, international regulation and non-proliferation, IAEA safeguards arrangements in the UK, INFCE, and uranium supplies. (U.K.)

  15. Nuclear astrophysics: An application of nuclear physics

    International Nuclear Information System (INIS)

    Fueloep, Z.

    2005-01-01

    Nuclear astrophysics, a fruitful combination of nuclear physics and astrophysics can be viewed as a special application of nuclear physics where the study of nuclei and their reactions are motivated by astrophysical problems. Nuclear astrophysics is also a good example for the state of the art interdisciplinary research. The origin of elements studied by geologists is explored by astrophysicists using nuclear reaction rates provided by the nuclear physics community. Due to the high interest in the field two recent Nuclear Physics Divisional Conferences of the European Physical Society were devoted to nuclear astrophysics and a new conference series entitled 'Nuclear Physics in Astrophysics' has been established. Selected problems of nuclear astrophysics will be presented emphasizing the interplay between nuclear physics and astrophysics. As an example the role of 14 N(p,r) 15 O reaction rate in the determination of the age of globular clusters will be discussed in details

  16. I wonder nuclear energy

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Cheol

    2009-04-15

    This book consists seven chapters, which are powerful nuclear energy, principle of nuclear fission, nuclear energy in our daily life, is nuclear energy safe?, what is radiation?, radiation spread in pur daily life and radiation like a spy. It adds nuclear energy story through quiz. This book with pictures is for kids to explain nuclear energy easily.

  17. The inhibitors of cyclin-dependent kinases and GSK-3β enhance osteoclastogenesis

    Directory of Open Access Journals (Sweden)

    Yosuke Akiba

    2016-03-01

    Full Text Available Osteoclasts are multinucleated cells with bone resorption activity that is crucial for bone remodeling. RANK‐RANKL (receptor activator of nuclear factor κB ligand signaling has been shown as a main signal pathway for osteoclast differentiation. However, the molecular mechanism and the factors regulating osteoclastogenesis remain to be fully understood. In this study, we performed a chemical genetic screen, and identified a Cdks/GSK-3β (cyclin-dependent kinases/glycogen synthase kinase 3β inhibitor, kenpaullone, and two Cdks inhibitors, olomoucine and roscovitine, all of which significantly enhance osteoclastogenesis of RAW264.7 cells by upregulating NFATc1 (nuclear factor of activated T cells, cytoplasmic 1 levels. We also determined that the all three compounds increase the number of osteoclast differentiated from murine bone marrow cells. Furthermore, the three inhibitors, especially kenpaullone, promoted maturation of cathepsin K, suggesting that the resorption activity of the resultant osteoclasts is also activated. Our findings indicate that inhibition of GSK-3β and/or Cdks enhance osteoclastogenesis by modulating the RANK–RANKL signaling pathway.

  18. Single-molecule supercoil-relaxation assay as a screening tool to determine the mechanism and efficacy of human topoisomerase IB inhibitors

    Science.gov (United States)

    Seol, Yeonee; Zhang, Hongliang; Agama, Keli; Lorence, Nicholas; Pommier, Yves; Neuman, Keir C.

    2015-01-01

    Human nuclear type IB topoisomerase (Top1) inhibitors are widely used and powerful anti-cancer agents. In this study, we introduce and validate a single-molecule supercoil relaxation assay as a molecular pharmacology tool for characterizing therapeutically relevant Top1 inhibitors. Using this assay, we determined the effects on Top1 supercoil relaxation activity of four Top1 inhibitors; three clinically relevant: camptothecin, LMP-400, LMP-776 (both indenoisoquinoline derivatives), and one natural product in preclinical development, lamellarin-D. Our results demonstrate that Top1 inhibitors have two distinct effects on Top1 activity: a decrease in supercoil relaxation rate and an increase in religation inhibition. The type and magnitude of the inhibition mode depend both on the specific inhibitor and on the topology of the DNA substrate. In general, the efficacy of inhibition is significantly higher with supercoiled than with relaxed DNA substrates. Comparing single-molecule inhibition with cell growth inhibition (IC50) measurements showed a correlation between the binding time of the Top1 inhibitors and their cytotoxic efficacy, independent of the mode of inhibition. This study demonstrates that the single-molecule supercoil relaxation assay is a sensitive method to elucidate the detailed mechanisms of Top1 inhibitors and is relevant for the cellular efficacy of Top1 inhibitors. PMID:26351326

  19. Nuclear insurance

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    The yearbook contains among others the figures of the nuclear insurance line. According to these these the DKVG (German nuclear power plant insurance association) has 102 member insurance companies all registered in the Federal Republic of Germany. By using reinsurance capacities of the other pools at present property insurance amounts to 1.5 billion DM and liability insurance to 200 million DM. In 1991 the damage charges on account of DKV amounted to 3.1 (1990 : 4.3) million DM. From these 0.6 million DM are apportioned to payments and 2.5 million DM to reserves. One large damage would cost a maximum gross sum of 2.2 billion DM property and liability insurance; on account of DKVG 750 million DM. (orig./HSCH) [de

  20. Nuclear power

    Energy Technology Data Exchange (ETDEWEB)

    Hodgson, P.

    1985-01-01

    The question 'Do we really need nuclear power' is tackled within the context of Christian beliefs. First, an estimate is made of the energy requirements in the future and whether it can be got in conventional ways. The dangers of all the ways of supplying energy (eg coal mining, oil and gas production) are considered scientifically. Also the cost of each source and its environmental effects are debated. The consequences of developing a new energy source, as well as the consequences of not developing it, are considered. Decisions must also take into account a belief about the ultimate purpose of life, the relation of men to each other and to nature. Each issue is raised and questions for discussion are posed. On the whole the book comes down in favour of nuclear power.

  1. Nuclear reactor

    International Nuclear Information System (INIS)

    Sasaki, Tomozo.

    1987-01-01

    Purpose: To improve the nuclear reactor availability by enabling to continuously exchange fuels in the natural-slightly enriched uranium region during operation. Constitution: A control rod is withdrawn to the midway of a highly enriched uranium region by means of control rod drives and the highly enriched uranium region is burnt to maintain the nuclear reactor always at a critical state. At the same time, fresh uranium-slightly enriched uranium is continuously supplied gravitationally from a fresh fuel reservoir through fuel reservoir to each of fuel pipes in the natural-slightly enriched uranium region. Then, spent fuels reduced with the reactivity by the burn up are successively taken out from the bottom of each of the fuel pipes through an exit duct and a solenoid valve to the inside of a spent fuel reservoir and the burn up in the natural-slightly enriched uranium region is conducted continuously. (Kawakami, Y.)

  2. Nuclear reactors

    International Nuclear Information System (INIS)

    Barre, Bertrand

    2015-10-01

    After some remarks on the nuclear fuel, on the chain reaction control, on fuel loading and unloading, this article proposes descriptions of the design, principles and operations of different types of nuclear reactors as well as comments on their presence and use in different countries: pressurized water reactors (design of the primary and secondary circuits, volume and chemistry control, backup injection circuits), boiling water reactors, heavy water reactors, graphite and boiling water reactors, graphite-gas reactors, fast breeder reactors, and fourth generation reactors (definition, fast breeding). For these last ones, six concepts are presented: sodium-cooled fast reactor, lead-cooled fast reactor, gas-cooled fast reactor, high temperature gas-cooled reactor, supercritical water-cooled reactor, and molten salt reactor

  3. Nuclear waste

    International Nuclear Information System (INIS)

    1991-01-01

    The Privacy Act of 1974 restricts both the type of information on private individuals that federal agencies may maintain in their records and the conditions under which such information may be disclosed. The Nuclear Regulatory Commission, which must approve DOE plans to build a nuclear waste repository at the Yucca Mountain site in Nevada, requires a quality assurance program to guarantee that studies of the site are done by qualified employees. Under such a program, the training and qualifications of DOE and contractor employees would be verified. This report reviews DOE's efforts to identify and resolve the implications of the Privacy Act for DOE's quality assurance program and how the delay in resolving Privacy Act issues may have affected preliminary work on the Yucca Mountain project

  4. Nuclear physics

    International Nuclear Information System (INIS)

    Warner, D.D.; Aitken, T.W.; Rowley, N.

    1989-01-01

    The many diverse programmes of fundamental research and technical development at the Daresbury Nuclear Structure Facility (NSF) have continued at their usual hectic pace throughout the period 1988/89. An overview of the overall programme and of the Facility has been presented in the first volume of this report, along with an expanded discussion of some of the highlights of the year's work. This second volume presents the more technical and detailed reports on the progress and results of individuals proposals and hence will be of most interest to the more expert reader. The reports are grouped in terms of experimental studies aimed at probing the structure of individual nuclei or series of nuclei, studies devoted to probing the primary nuclear reaction mechanism itself, theoretical work and research devoted to the development of the accelerator, and experimental equipment/techniques. Overall, they provide a concise summary of the year's work at the NSF. (author)

  5. Nuclear safeguards

    International Nuclear Information System (INIS)

    Estrampres, J.

    2010-01-01

    Close cooperation with the Ministry of Industry with representation from the UNESA Safeguards Group, has meant that, after almost two years of intense meetings and negotiations, Spain has a specific plant to plant agreement for the application of Safeguards under this new method. This is an agreement which aims to be a benchmark for all other EU countries, as the IAEA tends to apply a generic agreement that, in many cases, majority interferes in the nuclear power plants own processes. (Author).

  6. Nuclear structure

    International Nuclear Information System (INIS)

    Joy, T.; Price, H.G.

    1984-01-01

    The appendix to the Daresbury Annual report contains detailed summaries of experiments carried out, or in progress, for the period 1983/84, using the Nuclear Structure Facility tandem accelerator. The experimental work is carried out by University groups from the UK and abroad, and Daresbury Staff. Developments in instrumentation, and a report on the first year of scheduled operation of the Facility, are also given. (U.K.)

  7. Nuclear terrorism

    International Nuclear Information System (INIS)

    Watson, C.

    2005-01-01

    This article is aimed at those professional scientists and engineers who believe that issues of international peace and security are too important to be left to the politicians. Nuclear Terrorism is a hostile act (or a threat of such an act) involving nuclear materials (fissile or radioactive) performed by a terrorist, a term which covers a wide range of individuals. What they all have in common is that, for some reason they have become motivated to hurt or destroy sections of society which they have come to regard as the enemy; their motivation varies enormously. They also vary enormously in the extent and nature of their technical/scientific education. There are 'PhD terrorists' and 'Peasant terrorists', and they differ greatly in the threat that they represent, and the steps which can appropriately be taken to counter it. The most serious threat comes from the potential ability of terrorists to steal or manufacture nuclear weapons of mass destruction (e.g. capable of causing thousands of deaths). Unless the underlying causes of terrorism can be quickly removed, we have a duty to mankind to make terrorist access to such weapons, and to the nuclear materials which are their essential ingredients, as difficult as possible. Improvements in the arrangements for denying unauthorised access to radioactive material should be made such that the protective measures made are proportionate to the number of Curies at risk and the likelihood of a terrorist initiative. The preventative measures, sadly, need to take account of the possibility that the terrorist will use lethal force to access the material. (author)

  8. Nuclear medicine

    International Nuclear Information System (INIS)

    Casier, Ph.; Lepage, B.

    1998-01-01

    Except for dedicated devices for mobile nuclear cardiology for instance, the market is set on variable angulation dual heads cameras. These cameras are suited for all general applications and their cost effectiveness is optimized. Now, all major companies have such a camera in their of products. But, the big question in nuclear medicine is about the future of coincidence imaging for the monitoring of treatments in oncology. Many companies are focused on WIP assessments to find out the right crustal thickness to perform both high energy FDG procedures and low energy Tc procedures, with the same SPECT camera. The classic thickness is 3/8''. Assessments are made with 1/2'', 5/8'' or 3/4'' crystals. If FDG procedures proved to be of great interest in oncology, it may lead to the design of a dedicated SPECT camera with a 1'' crustal. Due to the short half of FDG, it may be the dawning of slip ring technology. (e.g. Varicam from Elscint). The three small heads camera market seems to be depressed. Will the new three large heads camera unveiled by Picker, reverse that trend? The last important topic in nuclear medicine is the emergence of new flat digital detectors to get rid of the old bulky ones. Digirad is the first company to manufacture a commercial product based on that technology. Bichron, Siemens and General Electric are working on that development, too. But that technology is very expensive and the market for digital detection in nuclear medicine is not as large as the market in digital detection in radiology. (author)

  9. Nuclear transport

    International Nuclear Information System (INIS)

    Anon.

    2002-01-01

    During September and October 2001, 1 event has been reported and classified at the first level of the INES scale. This incident concerns the violation of the European regulation that imposes to any driver of radioactive matter of being the holder of a certificate asserting that he attended a special training. During this period, 13 in-site inspections have been made in places related to nuclear transport. (A.C.)

  10. Nuclear stethoscope

    Energy Technology Data Exchange (ETDEWEB)

    Shen, W.F.; Singer, I.; Hackworthy, R.A.; Morris, J.; Kelly, D.T. (Royal Prince Alfred Hospital, Camperdown (Australia))

    1983-05-14

    A portable, computerized nuclear probe designed to measure left ventricular function is described. The ejection fraction was reproducible and correlated well with that obtained by means of a gamma camera. The limitations of the machine are that it measures the global, rather than the segmental, function of the left ventricle and, when discrete large areas of regional dysfunction occur, the global ejection fraction may be overestimated. An advantage is that continuous beat-to-beat measurements are easily performed and displayed.

  11. Nuclear shelters

    International Nuclear Information System (INIS)

    Prendergast, L.; Prendergast, P.; Prendergast, E.J.; Prendergast, L.J.

    1982-01-01

    An underground nuclear shelter, fabricated from a series of transverse metal hoop frames connected by longitudinal metal members and plates, is described. The shelter chamber has two hatches in the roof each with a shaft fitted with a shield cover. One shaft houses an air inlet and filter, the other is used for access. Two or more shelter units can be linked. (U.K.)

  12. Nuclear decommissioning

    Energy Technology Data Exchange (ETDEWEB)

    Lawton, H.

    1987-02-01

    Sufficient work has now been done, on a world-wide basis, to justify confidence that full decommissioning of nuclear installations, both plant and reactors, can be carried out safely and efficiently. Projects in several countries should confirm this in the next few years. In the UK, good progress has been made with the WAGR and supporting development work is finding solutions to resolve uncertainties. Estimates from several sources suggest that decommissioning costs can be kept to an acceptable level.

  13. Nuclear decommissioning

    International Nuclear Information System (INIS)

    Lawton, H.

    1987-01-01

    Sufficient work has now been done, on a world-wide basis, to justify confidence that full decommissioning of nuclear installations, both plant and reactors, can be carried out safely and efficiently. Projects in several countries should confirm this in the next few years. In the UK, good progress has been made with the WAGR and supporting development work is finding solutions to resolve uncertainties. Estimates from several sources suggest that decommissioning costs can be kept to an acceptable level. (author)

  14. Nuclear reactors

    International Nuclear Information System (INIS)

    Humphreys, P.; Davidson, D.F.; Thatcher, G.

    1980-01-01

    The cooling system of a liquid metal cooled fast breeder nuclear reactor of the pool kind is described. It has an intermediate heat exchange module comprising a tube-in-shell heat exchanger and an electromagnetic flow coupler in the base region of the module. Primary coolant is flowed through the heat exchanger being driven by electromagnetic interaction with secondary liquid metal coolant flow effected by a mechanical pump. (author)

  15. Nuclear reactor

    International Nuclear Information System (INIS)

    Batheja, P.; Huber, R.; Rau, P.

    1985-01-01

    Particularly for nuclear reactors of small output, the reactor pressure vessel contains at least two heat exchangers, which have coolant flowing through them in a circuit through the reactor core. The circuit of at least one heat exchanger is controlled by a slide valve, so that even for low drive forces, particularly in natural circulation, the required even loading of the heat exchanger is possible. (orig./HP) [de

  16. Nuclear therapy

    International Nuclear Information System (INIS)

    Roux, Henry

    1977-01-01

    Having first recalled the biological action of ionizing radiations, the main problems relating to the therapeutical use of radioelements were analyzed. Stressing the good results recorded with this method for the treatment of some diseases, the present limits were also defined, stating however that the progress made in biochemistry in the direction of metabolism, combined with the progress made in nuclear medicine, still allows some hope [fr

  17. Nuclear Britain

    Energy Technology Data Exchange (ETDEWEB)

    Bunyard, P

    1981-01-01

    The subject is dealt with in chapters, entitled: (preface) the new resistance; (1) the weapons connection; (2) the AGR - a bungled programme; (3) reactor choice - a fearful dilemma; (4) the deadly atom (uranium - mining, processing, enrichment of U-235, political and international aspects); (5) the fast reactor - how safe; (6) radiation risk and cancer; (7) atomic waste - the industry's Achilles Heel; (8) accidents - the ever-present threat; (9) the growing opposition; (10) the nuclear state.

  18. Nuclear decisions

    International Nuclear Information System (INIS)

    Dunster, H.J.; Farmer, F.R.; Gaines, M.J.

    1979-01-01

    In the Correspondence section of this issue of Nature three letters are published each of which has a bearing on the article by P. Taylor in the issue of 22 February. In that article Taylor calls for changes in the way decisions are taken on nuclear energy matters. The three articles are by H.J. Dunster of the UKAEA Health and Safety Executive, F.R. Farmer, Safety Adviser to the UKAEA, and M.J. Gaines, National Radiological Protection Board. (UK)

  19. New halogenated phenylcoumarins as tyrosinase inhibitors.

    Science.gov (United States)

    Matos, Maria João; Santana, Lourdes; Uriarte, Eugenio; Delogu, Giovanna; Corda, Marcella; Fadda, Maria Benedetta; Era, Benedetta; Fais, Antonella

    2011-06-01

    With the aim to find out structural features for the tyrosinase inhibitory activity, in the present communication we report the synthesis and pharmacological evaluation of a new series of phenylcoumarin derivatives with different number of hydroxyl or ether groups and bromo substituent in the scaffold. The synthesized compounds 5-12 were evaluated as mushroom tyrosinase inhibitors showing, two of them, lower IC(50) than the umbelliferone. Compound 12 (IC(50)=215 μM) is the best tyrosinase inhibitor of this series. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Green inhibitors. Rare Earth based systems

    International Nuclear Information System (INIS)

    Aballe, A.; Bethencourt, M.; Botana, F.J.; Perez, J.; Rodriguez, M.A.; Marcos, M.

    1997-01-01

    Lanthanum, Cerium and Samarium chlorides have been investigated as uniform and pitting corrosion inhibitors of AISI 434 and AISI 304 stainless steels and AA 5083 Al-Mg alloy in 3.5% Na Cl aerated aqueous solutions. Their inhibitor power was evaluated by using electrochemical techniques such as Linear and Cyclic Polarisation. In each case, the highest protection degree was found in the solution dropped with 500 ppm of CeCl 3 . Similar results were obtained for additions of 500 ppm of LaCl 3 . Scanning Electron Microscopy and Energy Dispersive Spectroscopy allowed us to confirm the cathodic nature of the inhibition process. (Author) 27 refs

  1. 2-Aminobenzimidazoles as potent Aurora kinase inhibitors.

    Science.gov (United States)

    Zhong, Min; Bui, Minna; Shen, Wang; Baskaran, Subramanian; Allen, Darin A; Elling, Robert A; Flanagan, W Michael; Fung, Amy D; Hanan, Emily J; Harris, Shannon O; Heumann, Stacey A; Hoch, Ute; Ivy, Sheryl N; Jacobs, Jeffrey W; Lam, Stuart; Lee, Heman; McDowell, Robert S; Oslob, Johan D; Purkey, Hans E; Romanowski, Michael J; Silverman, Jeffrey A; Tangonan, Bradley T; Taverna, Pietro; Yang, Wenjin; Yoburn, Josh C; Yu, Chul H; Zimmerman, Kristin M; O'Brien, Tom; Lew, Willard

    2009-09-01

    This Letter describes the discovery and key structure-activity relationship (SAR) of a series of 2-aminobenzimidazoles as potent Aurora kinase inhibitors. 2-Aminobenzimidazole serves as a bioisostere of the biaryl urea residue of SNS-314 (1c), which is a potent Aurora kinase inhibitor and entered clinical testing in patients with solid tumors. Compared to SNS-314, this series of compounds offers better aqueous solubility while retaining comparable in vitro potency in biochemical and cell-based assays; in particular, 6m has also demonstrated a comparable mouse iv PK profile to SNS-314.

  2. Nuclear energy

    International Nuclear Information System (INIS)

    1978-01-01

    2 1/2 years ago a consultation group was formed to help the Section for Social Questions of the Council of Churches in the Netherlands, to answer questions in the area of nuclear energy. During this time the character of the questions has changed considerably. In the beginning people spoke of fear and anxiety over the plans for the application of this new technical development but later this fear and anxiety turned to protest and opposition. This brochure has been produced to enlighten people and try and answer their alarm, by exploring the many facets of the problems. Some of these problems are already being deeply discussed by the public, others play no role in the forming of public opinion. The points of view of the churches over nuclear energy are not expressed, the brochure endeavours to express that nuclear energy problems are a concern for the churches. Technical and economic information and the most important social questions are discussed. (C.F.)

  3. Nuclear medicine

    International Nuclear Information System (INIS)

    James, A.E. Jr.; Squire, L.F.

    1977-01-01

    The book presents a number of fundamental imaging principles in nuclear medicine. The fact that low radiation doses are sufficient for the study of normal and changed physiological functions of the body is an important advancement brought about by nuclear medicine. The possibility of quantitative investigations of organs and organ regions and of an assessment of their function as compared to normal values is a fascinating new diagnostic dimension. The possibility of comparing the findings with other pathological findings and of course control in the same patient lead to a dynamic continuity with many research possibilities not even recognized until now. The limits of nuclear scanning methods are presented by the imprecise structural information of the images. When scintiscans are compared with X-ray images or contrast angiography, the great difference in the imaging of anatomical details is clearly seen. But although the present pictures are not optimal, they are a great improvement on the pictures that were considered clinically valuable a few years ago. (orig./AJ) [de

  4. Nuclear physics

    International Nuclear Information System (INIS)

    Dacre, J.

    1990-01-01

    This book fills a gap in current literature by covering the increasing nuclear physics content of various A-level syllabuses. In section 1 we outline the background and early development of the subject, in section 2 we deal with nuclear properties and theories at a level suitable for the pre-university student. The majority of topics have been treated with the limited use of mathematics, this necessitating some simplification which we hope to have accomplished without undue error. A few topics have been developed mathematically, to some extent, e.g. series decay. While it is the purpose of a book at this level to introduce the reader to the facts and theories of nuclear physics, we have to recognise that any teacher of science, at any level, must attempt to instill in the young scientist a sense of responsibility and an understanding of the problems attendant on the technological applications are important. These problems have been touched on in the text but we hope the student will be persuaded to read further; for this purpose we have added a short list of suggested additional reading. A selection of A-level past paper questions has been included. (author)

  5. Nuclear facilities

    International Nuclear Information System (INIS)

    Anon.

    2002-01-01

    During September and October 2001, 15 events were recorded on the first grade and 1 on the second grade of the INES scale. The second grade event is in fact a re-classification of an incident that occurred on the second april 2001 at Dampierre power plant. This event happened during core refueling, a shift in the operation sequence led to the wrong positioning of 113 assemblies. A preliminary study of this event shows that this wrong positioning could have led, in other circumstances, to the ignition of nuclear reactions. Even in that case, the analysis made by EDF shows that the consequences on the staff would have been limited. Nevertheless a further study has shown that the existing measuring instruments could not have detected the power increase announcing the beginning of the chain reaction. The investigation has shown that there were deficiencies in the control of the successive operations involved in refueling. EDF has proposed a series of corrective measures to be implemented in all nuclear power plants. The other 15 events are described in the article. During this period 121 inspections have been made in nuclear facilities. (A.C.)

  6. Saururus cernuus lignans-Potent small molecule inhibitors of hypoxia-inducible factor-1

    International Nuclear Information System (INIS)

    Hossain, Chowdhury Faiz; Kim, Yong-Pil; Baerson, Scott R.; Zhang Lei; Bruick, Richard K.; Mohammed, Kaleem A.; Agarwal, Ameeta K.; Nagle, Dale G.; Zhou Yudong

    2005-01-01

    Hypoxia-inducible factor-1 (HIF-1) represents an important tumor-selective therapeutic target for solid tumors. In search of novel small molecule HIF-1 inhibitors, 5400 natural product-rich extracts from plants, marine organisms, and microbes were examined for HIF-1 inhibitory activities using a cell-based reporter assay. Bioassay-guided fractionation and isolation, followed by structure elucidation, yielded three potent natural product-derived HIF-1 inhibitors and two structurally related inactive compounds. In a T47D cell-based reporter assay, manassantin B 1 , manassantin A, and 4-O-methylsaucerneol inhibited hypoxia-induced HIF-1 activation with IC 50 values of 3, 3, and 20 nM, respectively. All three compounds are relatively hypoxia-specific inhibitors of HIF-1 activation, in comparison to other stimuli. The hypoxic induction of HIF-1 target genes CDKN1A, VEGF, and GLUT-1 were also inhibited. These compounds inhibit HIF-1 by blocking hypoxia-induced nuclear HIF-1α protein accumulation without affecting HIF-1α mRNA levels. In addition, preliminary structure-activity studies suggest specific structural requirements for this class of HIF-1 inhibitors

  7. Nuclear fuels

    International Nuclear Information System (INIS)

    2008-01-01

    The nuclear fuel is one of the key component of a nuclear reactor. Inside it, the fission reactions of heavy atoms, uranium and plutonium, take place. It is located in the core of the reactor, but also in the core of the whole nuclear system. Its design and properties influence the behaviour, the efficiency and the safety of the reactor. Even if it represents a weak share of the generated electricity cost, its proper use represents an important economic stake. Important improvements remain to be made to increase its residence time inside the reactor, to supply more energy, and to improve its robustness. Beyond the economical and safety considerations, strategical questions have to find an answer, like the use of plutonium, the management of resources and the management of nuclear wastes and real technological challenges have to be taken up. This monograph summarizes the existing knowledge about the nuclear fuel, its behaviour inside the reactor, its limits of use, and its R and D tracks. It illustrates also the researches in progress and presents some key results obtained recently. Content: 1 - Introduction; 2 - The fuel of water-cooled reactors: aspect, fabrication, behaviour of UO 2 and MOX fuels inside the reactor, behaviour in loss of tightness situation, microscopic morphology of fuel ceramics and evolution under irradiation - migration and localisation of fission products in UOX and MOX matrices, modeling of fuels behaviour - modeling of defects and fission products in the UO 2 ceramics by ab initio calculations, cladding and assembly materials, pellet-cladding interaction, advanced UO 2 and MOX ceramics, mechanical behaviour of the fuel assembly, fuel during a loss of coolant accident, fuel during a reactivity accident, fuel during a serious accident, fuel management inside reactor cores, fuel cycle materials balance, long-term behaviour of the spent fuel, fuel of boiling water reactors; 3 - the fuel of liquid metal fast reactors: fast neutrons radiation

  8. 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.

  9. Nuclear power and the nuclear fuel cycle

    International Nuclear Information System (INIS)

    Hardy, C.J.; Silver, J.M.

    1985-09-01

    The report provides data and assessments of the status and prospects of nuclear power and the nuclear fuel cycle. The report discusses the economic competitiveness of nuclear electricity generation, the extent of world uranium resources, production and requirements, uranium conversion and enrichment, fuel fabrication, spent fuel treatment and radioactive waste management. A review is given of the status of nuclear fusion research

  10. Nuclear power economic database

    International Nuclear Information System (INIS)

    Ding Xiaoming; Li Lin; Zhao Shiping

    1996-01-01

    Nuclear power economic database (NPEDB), based on ORACLE V6.0, consists of three parts, i.e., economic data base of nuclear power station, economic data base of nuclear fuel cycle and economic database of nuclear power planning and nuclear environment. Economic database of nuclear power station includes data of general economics, technique, capital cost and benefit, etc. Economic database of nuclear fuel cycle includes data of technique and nuclear fuel price. Economic database of nuclear power planning and nuclear environment includes data of energy history, forecast, energy balance, electric power and energy facilities

  11. Synergistic apoptosis induction in leukemic cells by the phosphatase inhibitor salubrinal and proteasome inhibitors.

    Directory of Open Access Journals (Sweden)

    Hannes C A Drexler

    Full Text Available Cells adapt to endoplasmic reticulum (ER-stress by arresting global protein synthesis while simultaneously activating specific transcription factors and their downstream targets. These processes are mediated in part by the phosphorylation-dependent inactivation of the translation initiation factor eIF2alpha. Following restoration of homeostasis protein synthesis is resumed when the serine/threonine-protein phosphatase PP1 dephosphorylates and reactivates eIF2alpha. Proteasome inhibitors, used to treat multiple myeloma patients evoke ER-stress and apoptosis by blocking the ER-associated degradation of misfolded proteins (ERAD, however, the role of eIF2alpha phosphorylation in leukemic cells under conditions of proteasome inhibitor-mediated ER stress is currently unclear.Bcr-Abl-positive and negative leukemic cell lines were used to investigate the functional implications of PP1-related phosphatase activities on eIF2alpha phosphorylation in proteasome inhibitor-mediated ER stress and apoptosis. Rather unexpectedly, salubrinal, a recently identified PP1 inhibitor capable to protect against ER stress in various model systems, strongly synergized with proteasome inhibitors to augment apoptotic death of different leukemic cell lines. Salubrinal treatment did not affect the phosphorlyation status of eIF2alpha. Furthermore, the proapoptotic effect of salubrinal occurred independently from the chemical nature of the proteasome inhibitor, was recapitulated by a second unrelated phosphatase inhibitor and was unaffected by overexpression of a dominant negative eIF2alpha S51A variant that can not be phosphorylated. Salubrinal further aggravated ER-stress and proteotoxicity inflicted by the proteasome inhibitors on the leukemic cells since characteristic ER stress responses, such as ATF4 and CHOP synthesis, XBP1 splicing, activation of MAP kinases and eventually apoptosis were efficiently abrogated by the translational inhibitor cycloheximide.Although PP1

  12. Nuclear danger and nuclear history

    International Nuclear Information System (INIS)

    Howard, M.

    1988-01-01

    This article makes a review of the books Danger and Survival: Choices about the Bomb in the First Fifty Years written by McGeorge Bundy, and War and Peace in the Nuclear Age written by John Newhouse. A history of political decisions on weapon development is given, along with a what if analysis of other options. The lesson of these two books is that it has proved considerably easier to live with nuclear weapons and the Soviet Union than anyone expected forty years ago. It is all the easier if arms control issues, based on worst case analyses, are kept in their place, which is firmly in the background of the overall conduct of foreign policy

  13. Nuclear Law: A Key Against Nuclear Terrorism

    International Nuclear Information System (INIS)

    Cardozo, P.

    2004-01-01

    The role of the legal instruments in the war against nuclear terrorism. Control of radioactive sources. Elements of Nuclear Law: Definition: it is the body of special legislation that regulates the pacific uses of nuclear energy and the conduct of the persons engaged in activities related to fissionable materials and ionizing radiation . Objective: to provide a legal framework in order to protect individuals , property and the environment against the harmful effects of the use of nuclear energy and ionising radiation. Principles of nuclear energy legislation: safety principle, exclusively operator responsibility, authorization, independence of the regulatory body, inspections and enforcement, nuclear damage compensation, international cooperation. National regulatory infrastructure. Establishment of special law in Emergency Preparedness for nuclear or radiological disaster. IAEA Conventions. Transportation of nuclear material. IAEA regulations on radioactive material. Compensation for nuclear damage. Nuclear safety, security and terrorism. International and domestic instruments. Anti terrorism acts. International agreements on Safety Cooperation. (Author)

  14. 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)

  15. 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.

  16. Applications of nuclear physics

    International Nuclear Information System (INIS)

    Hayes-Sterbenz, Anna Catherine

    2017-01-01

    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. Lastly, 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.

  17. Structural Characterization of LRRK2 Inhibitors

    NARCIS (Netherlands)

    Gilsbach, Bernd K; Messias, Ana C; Ito, Genta; Sattler, Michael; Alessi, Dario R; Wittinghofer, Alfred; Kortholt, Arjan

    2015-01-01

    Kinase inhibition is considered to be an important therapeutic target for LRRK2 mediated Parkinson's disease (PD). Many LRRK2 kinase inhibitors have been reported but have yet to be optimized in order to qualify as drug candidates for the treatment of the disease. In order to start a

  18. Rational Design of Rho Protein Inhibitors

    National Research Council Canada - National Science Library

    Rojas, Rafael J

    2006-01-01

    ... nucleotide exchange factors (RhoGEFs). We have developed a high throughput screening strategy identify novel inhibitors of Rho activation are currently following up on several compounds which appear to selectively inhibit Rho activation. These compounds may form the basis of future drug development strategies for the treatment of metastatic breast cancer.

  19. Rational Design of Rho Protein Inhibitors

    National Research Council Canada - National Science Library

    Rojas, Rafael J

    2005-01-01

    ... nucleotide exchange factors (RhoGEFs). We have developed a high throughput screening strategy identify novel inhibitors of Rho activation are currently following up on several compounds which appear to selectively inhibit Rho activation. These compounds may form the basis of future drug development strategies for the treatment of metastatic breast cancer.

  20. [Mechanisms and efficacy of SGLT2 inhibitors].

    Science.gov (United States)

    Shiba, Teruo

    2015-03-01

    SGLT2 is a low affinity, high capacity glucose co-transporter, almost exclusively expressed in the kidney cortex. Inhibition of SGLT2 has been shown to increase the daily 50g or more urinary glucose excretion, as compared to placebo, leading to a reduction in blood glucose levels and indicated only for the treatment of type 2 diabetes. In Japan 6 species of SGLT2 inhibitors have already been sold and reported to results in a decrease of FPG by 14.4 to 45.8 (mg/dL), in a reduction of HbA1c by 0.35 to 1.24% and in loss of body weight by 1.29 to 2.50(kg). There is less effect of the SGLT2 inhibitor in diabetic subjects with renal impairment and the reduction in HbA1c and FPG will be approximately half of the average in those with 30 ≤ eGFR ≤ 59. The position of SGLT2 inhibitors would be considered as the drug administered in combination or add-on therapy when the young obese type 2 diabetics without renal impairment has not yet reached to the glycemic target with other drugs although in AACE consensus statement of 2013, it has been shelved for inexperienced use with respect to the positioning of the SGLT2 inhibitors.

  1. Th17 Inhibitors in Active Psoriatic Arthritis

    DEFF Research Database (Denmark)

    Naik, Girish S; Ming, Wai K; Magodoro, Itai M

    2018-01-01

    BACKGROUND: Several biologics targeting the Th17 pathway have been developed for the treatment of psoriatic arthritis (PsA), a disabling disease with moderate response and an increased incidence of serious infections to first-line biologics (TNF-α antagonists). Th17 inhibitors could replace TNF-α...

  2. Vildagliptin: the first innovative DDP-4 inhibitor

    Directory of Open Access Journals (Sweden)

    Edvin Villkhauer

    2010-09-01

    Full Text Available A review of the main stages of investigation undertaken by Novartis Pharmaceuticals in search of a new molecule for the treatment of type 2 diabetesmellitus, dipeptidyl peptidase-4 (DPP-4 inhibitor (Vildaglyptin. The data on specificity and selectivity of the action of this molecule are presentedalong with the results of its comparison with another agent of this group (sitagliptin.

  3. Curcumin derivatives as HIV-1 protease inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Sui, Z.; Li, J.; Craik, C.S.; Ortiz de Montellano, P.R. [Univ. of California, San Francisco, CA (United States)

    1993-12-31

    Curcumin, a non-toxic natural compound from Curcuma longa, has been found to be an HIV-1 protease inhibitor. Some of its derivatives were synthesized and their inhibitory activity against the HIV-1 protease was tested. Curcumin analogues containing boron enhanced the inhibitory activity. At least of the the synthesized compounds irreversibly inhibits the HIV-1 protease.

  4. Dissolution properties of cerium dibutylphosphate corrosion inhibitors

    NARCIS (Netherlands)

    Soestbergen, van M.; Erich, S.J.F.; Huinink, H.P.; Adan, O.C.G.

    2013-01-01

    The corrosion inhibitor cerium dibutylphosphate, Ce(dbp)3, prevents corrosion by cerium and dbp deposition at the alkaline cathode and acidic anode respectively. The pH dependent Ce(dbp)3 solubility seems to play an essential role in the inhibition degree. We found that Ce(dbp)3 scarcely dissolves

  5. SEARCH OF NEW SYNTHETIC INHIBITORS OF TYROSINASE

    Directory of Open Access Journals (Sweden)

    Yu. Shesterenko

    2017-11-01

    Full Text Available Melanin pigmentation of skin plays the most important role in the protection of organism against UV-irradiation, but the excessive accumulation of melanin brings to toxic melanodermia, melasma, lentigo and other skin lesions. Tyrosinase is the key enzyme of skin melanin pigment biosynthesis. In spite of certain progress in investigation of natural and synthetic tyrosinase inhibitors, actuality of such studies is of a high level, because the existing inhibitors are in some cases unstable, expensive, toxic, requires complex methods of synthesis or isolation from natural sources. The aim of the work is screening of new tyrosinase inhibitors, using the enzyme, isolated from Agaricus bisporus. Tyrosinase was isolated from Agaricus bisporus mushrooms by a modified method. It was found, that the introduction of polyethylene glycol 4000 in the extraction process promotes 3-fold reduction of polyphenol content, which leads to increase purity of enzyme with an increase in its activity by 25%. A search for new tyrosinase inhibitors among a wide range of compounds, including derivatives of 3-chloro-1,4-naphthoquinone, isatin, 3-hydroxy-2-naphthoic acid, etc was conducted. The studied substances did not displayed inhibitory effect at concentration of 0,1-0,5 mmol/dm3.

  6. Peptide aldehyde inhibitors of bacterial peptide deformylases.

    Science.gov (United States)

    Durand, D J; Gordon Green, B; O'Connell, J F; Grant, S K

    1999-07-15

    Bacterial peptide deformylases (PDF, EC 3.5.1.27) are metalloenzymes that cleave the N-formyl groups from N-blocked methionine polypeptides. Peptide aldehydes containing a methional or norleucinal inhibited recombinant peptide deformylase from gram-negative Escherichia coli and gram-positive Bacillus subtilis. The most potent inhibitor was calpeptin, N-CBZ-Leu-norleucinal, which was a competitive inhibitor of the zinc-containing metalloenzymes, E. coli and B. subtilis PDF with Ki values of 26.0 and 55.6 microM, respectively. Cobalt-substituted E. coli and B. subtilis deformylases were also inhibited by these aldehydes with Ki values for calpeptin of 9.5 and 12.4 microM, respectively. Distinct spectral changes were observed upon binding of calpeptin to the Co(II)-deformylases, consistent with the noncovalent binding of the inhibitor rather than the formation of a covalent complex. In contrast, the chelator 1,10-phenanthroline caused the time-dependent inhibition of B. subtilis Co(II)-PDF activity with the loss of the active site metal. The fact that calpeptin was nearly equipotent against deformylases from both gram-negative and gram-positive bacterial sources lends further support to the idea that a single deformylase inhibitor might have broad-spectrum antibacterial activity. Copyright 1999 Academic Press.

  7. Immune checkpoint inhibitors for metastatic bladder cancer.

    Science.gov (United States)

    Massari, Francesco; Di Nunno, Vincenzo; Cubelli, Marta; Santoni, Matteo; Fiorentino, Michelangelo; Montironi, Rodolfo; Cheng, Liang; Lopez-Beltran, Anto; Battelli, Nicola; Ardizzoni, Andrea

    2018-03-01

    Chemotherapy has represented the standard therapy for unresectable or metastatic urothelial carcinoma for more than 20 years. The growing knowledge of the interaction between tumour and immune system has led to the advent of new classes of drugs, the immune-checkpoints inhibitors, which are intended to change the current scenario. To date, immunotherapy is able to improve the overall responses and survival. Moreover, thanks to its safety profile immune-checkpoint inhibitors could be proposed also to patients unfit for standard chemotherapy. No doubts that these agents have started a revolution expected for years, but despite this encouraging results it appears clear that not all subjects respond to these agents and requiring the development of reliable predictive response factors able to isolate patients who can more benefit from these treatments as well as new strategies aimed to improve immunotherapy clinical outcome. In this review we describe the active or ongoing clinical trials involving Programmed Death Ligand 1 (PD-L1), Programmed Death receptor 1 (PD-1) and Cytotoxic-T Lymphocyte Antigen 4 (CTLA 4) inhibitors in urothelial carcinoma focusing our attention on the developing new immune-agents and combination strategies with immune-checkpoint inhibitors. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Current and Novel Inhibitors of HIV Protease

    Czech Academy of Sciences Publication Activity Database

    Pokorná, Jana; Machala, L.; Řezáčová, Pavlína; Konvalinka, Jan

    2009-01-01

    Roč. 1, č. 3 (2009), s. 1209-1239 ISSN 1999-4915 R&D Projects: GA MŠk 1M0508 Grant - others:GA AV ČR(CZ) IAAX00320901 Program:IA Institutional research plan: CEZ:AV0Z40550506 Keywords : HIV protease * protease inhibitor * HAART Subject RIV: CE - Biochemistry

  9. Proton pump inhibitors affect the gut microbiome

    NARCIS (Netherlands)

    Imhann, Floris; Bonder, Marc Jan; Vich Vila, Arnau; Fu, Jingyuan; Mujagic, Zlatan; Vork, Lisa; Feenstra, Ettje T.; Jankipersadsing, Soesma A; Cenit, Maria Carmen; Harmsen, Hermie J M; Dijkstra, Gerard; Franke, Lude; Xavier, Ramnik J; Jonkers, Daisy; Wijmenga, Cisca; Weersma, Rinse K; Zhernakova, Alexandra

    BACKGROUND AND AIMS: Proton pump inhibitors (PPIs) are among the top 10 most widely used drugs in the world. PPI use has been associated with an increased risk of enteric infections, most notably Clostridium difficile. The gut microbiome plays an important role in enteric infections, by resisting or

  10. Pharmacological caspase inhibitors: Research towards therapeutic perspectives

    Czech Academy of Sciences Publication Activity Database

    Kudělová, J.; Fleischmannová, J.; Adamová, E.; Matalová, Eva

    2015-01-01

    Roč. 66, č. 4 (2015), s. 473-482 ISSN 0867-5910 R&D Projects: GA ČR(CZ) GA14-28254S Institutional support: RVO:68081715 Keywords : caspase * caspase inhibitor * apoptosis Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 2.804, year: 2015

  11. Pharmacological caspase inhibitors: Research towards therapeutic perspectives

    Czech Academy of Sciences Publication Activity Database

    Kudělová, J.; Fleischmannová, Jana; Adamová, Eva; Matalová, Eva

    2015-01-01

    Roč. 66, č. 4 (2015), s. 473-482 ISSN 0867-5910 R&D Projects: GA ČR GB14-37368G Institutional support: RVO:67985904 Keywords : caspase * caspase inhibitor * apoptosis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.804, year: 2015

  12. Discovery of inhibitors of bacterial histidine kinases

    NARCIS (Netherlands)

    Velikova, N.R.

    2014-01-01

    Discovery of Inhibitors of Bacterial Histidine Kinases Summary

    The thesis is on novel antibacterial drug discovery (http://youtu.be/NRMWOGgeysM). Using structure-based and fragment-based drug discovery approach, we have identified small-molecule histidine-kinase

  13. Novel peptide-based protease inhibitors

    DEFF Research Database (Denmark)

    Roodbeen, Renée

    of novel peptide-based protease inhibitors, efforts were made towards improved methods for peptide synthesis. The coupling of Fmoc-amino acids onto N-methylated peptidyl resins was investigated. These couplings can be low yielding and the effect of the use of microwave heating combined with the coupling...

  14. Oestrogen, testosterone, cytotoxin and cholinesterase inhibitor ...

    African Journals Online (AJOL)

    Oestrogen, testosterone, cytotoxin and cholinesterase inhibitor removal during reclamation of sewage to drinking water. ... Risks associated with sewage effluent and reclaimed sewage should be closely monitored; therefore water at the Gammams Sewage Treatment Plant (GSTP) inlet and outlet, as well as reclaimed water ...

  15. Computational analysis of calculated physicochemical and ADMET properties of protein-protein interaction inhibitors

    Science.gov (United States)

    Lagorce, David; Douguet, Dominique; Miteva, Maria A.; Villoutreix, Bruno O.

    2017-04-01

    The modulation of PPIs by low molecular weight chemical compounds, particularly by orally bioavailable molecules, would be very valuable in numerous disease indications. However, it is known that PPI inhibitors (iPPIs) tend to have properties that are linked to poor Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) and in some cases to poor clinical outcomes. Previously reported in silico analyses of iPPIs have essentially focused on physicochemical properties but several other ADMET parameters would be important to assess. In order to gain new insights into the ADMET properties of iPPIs, computations were carried out on eight datasets collected from several databases. These datasets involve compounds targeting enzymes, GPCRs, ion channels, nuclear receptors, allosteric modulators, oral marketed drugs, oral natural product-derived marketed drugs and iPPIs. Several trends are reported that should assist the design and optimization of future PPI inhibitors, either for drug discovery endeavors or for chemical biology projects.

  16. Two-dimensional NMR studies of squash family inhibitors. Sequence-specific proton assignments and secondary structure of reactive-site hydrolyzed Cucurbita maxima trypsin inhibitor III

    Energy Technology Data Exchange (ETDEWEB)

    Krisnamoorthi, R.; Yuxi Gong; Chanlan Sun Lin (Kansas State Univ., Manhattan (United States)); VanderVelde, D. (Univ. of Kansas, Lawrence (United States))

    1992-01-28

    The solution structure of reactive-site hydrolyzed Cucurbita maxima trypsin inhibitor III (CMTI-III*) was investigated by two-dimensional proton nuclear magnetic resonance (2D NMR) spectroscopy. CMTI-III*, prepared by reacting CMTI-III with trypsin which cleaved the Arg5-Ile6 peptide bond, had the two fragments held together by a disulfide linkage. Sequence-specific {sup 1}H NMR resonance assignments were made for all the 29 amino acid residues of the protein. The secondary structure of CMTI-III*, as deduced from NOESY cross peaks and identification of slowly exchanging hydrogens, contains two turns, a 3{sub 10}-helix, and a triple-stranded {beta}-sheet. Sequential proton assignments were also made for the virgin inhibitor, CMTI-III, at pH 4.71, 30C. Comparison of backbone hydrogen chemical shifts of CMTI-III and CMTI-III* revealed significant changes for residues located far away from the reactive-site region as well as for those located near it, indicating tertiary structural changes that are transmitted through most of the 29 residues of the inhibitor protein. These chemical shift changes were relatively small compared to changes that occurred upon hydrolysis of the reactive-site peptide bond between Arg 5 and Ile6 in CMTI-III.

  17. Glossary of nuclear energy

    International Nuclear Information System (INIS)

    Seo, Du Hwan

    1987-01-01

    This book gives descriptions of explanations of terminologies concerning to nuclear energy such as analysis of financial safety of nuclear energy, radwaste disposal, fast breeder reactor, nuclear reactor and device, nuclear fuel and technique for concentration, using of nuclear energy radiation and measurement, plan for development of nuclear energy and international institution. This book includes 160 terms on nuclear energy and arranges in Korean alphabetical order.

  18. Nuclear energy - some aspects

    International Nuclear Information System (INIS)

    Bandeira, Fausto de Paula Menezes

    2005-05-01

    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

  19. Nuclear Installations Act 1965

    International Nuclear Information System (INIS)

    1965-01-01

    This Act governs all activities related to nuclear installations in the United Kingdom. It provides for the licensing procedure for nuclear installations, the duties of licensees, the competent authorities and carriers of nuclear material in respect of nuclear occurrences, as well as for the system of third party liability and compensation for nuclear damage. The Act repeals the Nuclear Installations (Licensing and Insurance) Act 1959 and the Nuclear Installations (Amendment Act) 1965 except for its Section 17(2). (NEA) [fr

  20. Applications of Nuclear Physics

    OpenAIRE

    Hayes, Anna C.

    2017-01-01

    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 und...

  1. Nuclear emergencies

    International Nuclear Information System (INIS)

    1991-01-01

    This leaflet, which is in the form of a fold-up chart, has panels of text which summarize the emergencies that could arise and the countermeasures and emergency plans that have been prepared should nuclear accident occur or affect the United Kingdom. The levels of radiation doses at which various measures would be introduced are outlined. The detection and monitoring programmes that would operate is illustrated. The role of NRPB and the responsible government departments are set out together with an explanation of how the National Arrangements for Incidents involving Radioactivity would be coordinated. (UK)

  2. Nuclear reactor

    International Nuclear Information System (INIS)

    Scholz, M.

    1976-01-01

    An improvement of the accessibility of that part of a nuclear reactor serving for biological shield is proposed. It is intended to provide within the biological shield, distributed around the circumference of the reactor pressure vessel, several shielding chambers filled with shielding material, which are isolated gastight from the outside by means of glass panes with a given bursting strength. It is advantageous that, on the one hand, inspection and maintenance will be possible without great effort and, on the other, a large relief cross section will be at desposal if required. (UWI) [de

  3. Nuclear recycling

    International Nuclear Information System (INIS)

    Spinrad, B.I.

    1985-01-01

    This paper discusses two aspects of the economics of recycling nuclear fuel: the actual costs and savings of the recycling operation in terms of money spent, made, and saved; and the impact of the recycling on the future cost of uranium. The authors review the relevant physical and chemical processes involved in the recycling process. Recovery of uranium and plutonium is discussed. Fuel recycling in LWRs is examined and a table presents the costs of reprocessing and not reprocessing. The subject of plutonium in fast reactors is addressed. Safeguards and weapons proliferation are discussed

  4. Nuclear power

    International Nuclear Information System (INIS)

    Anon.

    1993-01-01

    The Single Channel Trip System for the Dungeness B AGRs in the United Kingdom has enabled Nuclear Electric to enhance the performance of each of the twin reactors progressively towards the design figure of 660MW. The unique self-testing dynamic nature of the microprocessor-based ISAT system was one of the key factors in satisfying the UK Regulator that the system met the demanding requirements of the Dungeness B application, and current operational and maintenance experience is very encouraging. Systems based on the ISAT principle have application in reactor protection systems throughout the world. (Author)

  5. Nuclear stethoscope

    Energy Technology Data Exchange (ETDEWEB)

    Inagaki, Yoshiaki; Saito, Toshihiro; Shimizu, Masahiko (Chiba Univ. (Japan). School of Medicine)

    1983-06-01

    The nuclear stethoscope consisting of radiocardiography and data processing by a microcomputer was introduced with respect to its outline, reliability and clinical application. Ejection fractions (EF) obtained by this device showed a satisfactory correlation with values obtained by the cardiac pool multigate (MUGA) method using a scinticamera and minicomputer, with a slight tendency to overestimation. They showed a good correlation with left ventriculography, accompanied by a slight tendency to underestimation. The reproducibility of this device was also satisfactory. Clinically, EF values during exercise in ischemic heart disease were well correlated with those obtained by the MUGA method. This device permitted real time evaluation of left ventricular function and was highly reliable.

  6. Nuclear stethoscope

    International Nuclear Information System (INIS)

    Inagaki, Yoshiaki; Saito, Toshihiro; Shimizu, Masahiko

    1983-01-01

    The nuclear stethoscope consisting of radiocardiography and data processing by a microcomputer was introduced with respect to its outline, reliability and clinical application. Ejection fractions (EF) obtained by this device showed a satisfactory correlation with values obtained by the cardiac pool multigate (MUGA) method using a scinticamera and minicomputer, with a slight tendency to overestimation. They showed a good correlation with left ventriculography, accompanied by a slight tendency to underestimation. The reproducibility of this device was also satisfactory. Clinically, EF values during exercise in ischemic heart disease were well correlated with those obtained by the MUGA method. This device permitted real time evaluation of left ventricular function and was highly reliable. (Chiba, N.)

  7. Nuclear reactor

    International Nuclear Information System (INIS)

    Rau, P.

    1980-01-01

    The reactor core of nuclear reactors usually is composed of individual elongated fuel elements that may be vertically arranged and through which coolant flows in axial direction, preferably from bottom to top. With their lower end the fuel elements gear in an opening of a lower support grid forming part of the core structure. According to the invention a locking is provided there, part of which is a control element that is movable along the fuel element axis. The corresponding locking element is engaged behind a lateral projection in the opening of the support grid. The invention is particularly suitable for breeder or converter reactors. (orig.) [de

  8. Nuclear sound

    International Nuclear Information System (INIS)

    Wambach, J.

    1991-01-01

    Nuclei, like more familiar mechanical systems, undergo simple vibrational motion. Among these vibrations, sound modes are of particular interest since they reveal important information on the effective interactions among the constituents and, through extrapolation, on the bulk behaviour of nuclear and neutron matter. Sound wave propagation in nuclei shows strong quantum effects familiar from other quantum systems. Microscopic theory suggests that the restoring forces are caused by the complex structure of the many-Fermion wavefunction and, in some cases, have no classical analogue. The damping of the vibrational amplitude is strongly influenced by phase coherence among the particles participating in the motion. (author)

  9. Nuclear decommissioning

    International Nuclear Information System (INIS)

    Lawton, H.

    1987-01-01

    Sufficient work has now been done, on a world-wide basis, to justify confidence that full decommissioning of nuclear installations, both plant and reactors, can be carried out safely and efficiently. Projects in several countries should confirm this in the next few years. In the United Kingdom, good progress has been made with the Windscale Advanced Gas-cooled Reactor and supporting development work is finding solutions to resolve uncertainties. Estimates from several sources suggest that decommissioning costs can be kept to an acceptable level. (author)

  10. Nuclear dualism.

    Science.gov (United States)

    Karrer, Kathleen M

    2012-01-01

    Nuclear dualism is a characteristic feature of the ciliated protozoa. Tetrahymena have two different nuclei in each cell. The larger, polyploid, somatic macronucleus (MAC) is the site of transcriptional activity in the vegetatively growing cell. The smaller, diploid micronucleus (MIC) is transcriptionally inactive in vegetative cells, but is transcriptionally active in mating cells and responsible for the genetic continuity during sexual reproduction. Although the MICs and MACs develop from mitotic products of a common progenitor and reside in a common cytoplasm, they are different from one another in almost every respect. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Nuclear waste

    International Nuclear Information System (INIS)

    England-Joseph, J.

    1991-03-01

    This paper discusses the Department of Energy's (DOE) procedures for annually assessing the adequacy of the fee that utilities pay for disposal of spent (used) nuclear fuel. In a June 1990 report, it was recommended, among other things, that the Congress authorize DOE to automatically adjust the fee each year on the basis of an inflation index. At that time, DOE also favored fee indexing; however, it subsequently reversed its position. Because of this change, it is now believe that Congress should require DOE to index the fee to the rate of inflation

  12. Nuclear reactor

    International Nuclear Information System (INIS)

    Anthony, A.J.; Gruber, E.A.

    1979-01-01

    A nuclear reactor with control rods in channels between fuel assemblies wherein the fuel assemblies incorporate guide rods which protrude outwardly into the control rod channels to prevent the control rods from engaging the fuel elements. The guide rods also extend back into the fuel assembly such that they are relatively rigid members. The guide rods are tied to the fuel assembly end or support plates and serve as structural members which are supported independently of the fuel element. Fuel element spacing and support means may be attached to the guide rods. 9 claims

  13. Dry eye syndrome in aromatase inhibitor users.

    Science.gov (United States)

    Turaka, Kiran; Nottage, Jennifer M; Hammersmith, Kristin M; Nagra, Parveen K; Rapuano, Christopher J

    2013-04-01

    Aromatase inhibitors are frequently used as an adjuvant therapy in the treatment of breast cancer. We observed that several patients taking aromatase inhibitors presented with severe dry eye symptoms, and we investigated whether there is a relationship between aromatase inhibitors and dry eyes in these patients. Retrospective chart review. Forty-one women. A computerized search of health records was performed to identify patients using anastrazole, letrozole and exemestane seen by the Cornea Service from August 2008 to March 2011. The results were compared with age-matched controls. Ocular surface changes among aromatase inhibitors users. Of the 41 women, 39 were Caucasians. Thirty-nine patients had breast cancer (95%), one patient had ovarian cancer (2.5%) and one had an unknown primary cancer. Mean age was 68 ± 11.3 years (range 47-95). Most common presenting symptoms were blurred vision in 28 (68%) patients, irritation/foreign body sensation in 12 (29%) patients, redness in 9 (22%) patients, tearing in 6 (22%) patients and photosensitivity in 2 (5%) patients. Mean Schirmer's test measurement was 11 ± 5.8 mm (range 0.5-20 mm). Blepharitis was noted in 68 of 82 eyes (73%), decreased or poor tear function in 24 eyes (29%), conjunctival injection in 18 eyes (22%) and superficial punctate keratitis in 12 eyes (29%). Among an age-matched population (45-95 years), dry eye syndrome was found in only 9.5% of patients. Because the prevalence of ocular surface disease signs and symptoms appears to be higher in study group than control patients, aromatase inhibitors might be a contributing factor to the dry eye symptoms. © 2012 The Authors. Clinical and Experimental Ophthalmology © 2012 Royal Australian and New Zealand College of Ophthalmologists.

  14. RENAL SAFETY OF PROTON PUMP INHIBITORS

    Directory of Open Access Journals (Sweden)

    A. I. Dyadyk

    2017-01-01

    Full Text Available Proton pump inhibitors are a widely used in clinical practice, and are taken by millions of patients around the world for a long time. While proton pump inhibitors are well-tolerated class of drugs, the number of publications has been raised about adverse renal effects, specially their association with acute tubulointerstitial nephritis. It is one of the leading causes of acute renal injury and have catastrophic long-term consequences called chronic kidney disease. In this review, we consider epidemiology, pathogenesis, diagnostic criteria (including biopsy and morphological pattern, clinical manifestations and treatment of proton pump inhibitors-induced acute tubulointerstitial nephritis. A subclinical course without classical manifestations of a cell-mediated hypersensitivity reaction (fever, skin rash, eosinophilia, arthralgia is characteristic of acute tubulointerstitial nephritis. Increased serum creatinine, decreased glomerular filtration rate, electrolyte disorders, pathological changes in urine tests are not highly specific indicators, but allow to suspect the development of acute tubulointerstitial nephritis. The “gold” standard of diagnosis is the intravital morphological examination of the kidney tissue. Timely diagnosis and immediate discontinuation of the potentially causative drug is the mainstay of therapy and the first necessary step in the early management of suspected or biopsy-proven drug-induced acute tubulointerstitial nephritis. The usage of proton pump inhibitors should be performed only on strict indications with optimal duration of treatment and careful monitoring of kidney function. Multiple comorbidities (older age, heart failure, diabetes, cirrhosis, chronic kidney disease, hypovolemia increase potential nephrotoxicity. Awareness of this iatrogenic complication will improve diagnosis of proton pump inhibitors-induced acute tubulointerstitial nephritis by multidisciplinary specialists and increase the possibility

  15. Cost of care of haemophilia with inhibitors.

    Science.gov (United States)

    Di Minno, M N D; Di Minno, G; Di Capua, M; Cerbone, A M; Coppola, A

    2010-01-01

    In Western countries, the treatment of patients with inhibitors is presently the most challenging and serious issue in haemophilia management, direct costs of clotting factor concentrates accounting for >98% of the highest economic burden absorbed for the healthcare of patients in this setting. Being designed to address questions of resource allocation and effectiveness, decision models are the golden standard to reliably assess the overall economic implications of haemophilia with inhibitors in terms of mortality, bleeding-related morbidity, and severity of arthropathy. However, presently, most data analyses stem from retrospective short-term evaluations, that only allow for the analysis of direct health costs. In the setting of chronic diseases, the cost-utility analysis, that takes into account the beneficial effects of a given treatment/healthcare intervention in terms of health-related quality of life, is likely to be the most appropriate approach. To calculate net benefits, the quality adjusted life year, that significantly reflects such health gain, has to be compared with specific economic impacts. Differences in data sources, in medical practice and/or in healthcare systems and costs, imply that most current pharmacoeconomic analyses are confined to a narrow healthcare payer perspective. Long-term/lifetime prospective or observational studies, devoted to a careful definition of when to start a treatment; of regimens (dose and type of product) to employ, and of inhibitor population (children/adults, low-responding/high responding inhibitors) to study, are thus urgently needed to allow for newer insights, based on reliable data sources into resource allocation, effectiveness and cost-utility analysis in the treatment of haemophiliacs with inhibitors.

  16. ROS inhibitor N-acetyl-L-cysteine antagonizes the activity of proteasome inhibitors.

    Science.gov (United States)

    Halasi, Marianna; Wang, Ming; Chavan, Tanmay S; Gaponenko, Vadim; Hay, Nissim; Gartel, Andrei L

    2013-09-01

    NAC (N-acetyl-L-cysteine) is commonly used to identify and test ROS (reactive oxygen species) inducers, and to inhibit ROS. In the present study, we identified inhibition of proteasome inhibitors as a novel activity of NAC. Both NAC and catalase, another known scavenger of ROS, similarly inhibited ROS levels and apoptosis associated with H₂O₂. However, only NAC, and not catalase or another ROS scavenger Trolox, was able to prevent effects linked to proteasome inhibition, such as protein stabilization, apoptosis and accumulation of ubiquitin conjugates. These observations suggest that NAC has a dual activity as an inhibitor of ROS and proteasome inhibitors. Recently, NAC was used as a ROS inhibitor to functionally characterize a novel anticancer compound, piperlongumine, leading to its description as a ROS inducer. In contrast, our own experiments showed that this compound depicts features of proteasome inhibitors including suppression of FOXM1 (Forkhead box protein M1), stabilization of cellular proteins, induction of ROS-independent apoptosis and enhanced accumulation of ubiquitin conjugates. In addition, NAC, but not catalase or Trolox, interfered with the activity of piperlongumine, further supporting that piperlongumine is a proteasome inhibitor. Most importantly, we showed that NAC, but not other ROS scavengers, directly binds to proteasome inhibitors. To our knowledge, NAC is the first known compound that directly interacts with and antagonizes the activity of proteasome inhibitors. Taken together, the findings of the present study suggest that, as a result of the dual nature of NAC, data interpretation might not be straightforward when NAC is utilized as an antioxidant to demonstrate ROS involvement in drug-induced apoptosis.

  17. Cytogenetic study of Ascaris trypsin inhibitor in cultured human ...

    Indian Academy of Sciences (India)

    2009-04-01

    Apr 1, 2009 ... Although the physical and chemical properties of Ascaris trypsin inhibitors ... male of Ascaris suum according to the method of Pudles and. Rola (1967). ..... inhibitor isolated from Ascaris resulted in the appearance of dominant ...

  18. SGLT2 inhibitors: molecular design and potential differences in effect.

    Science.gov (United States)

    Isaji, Masayuki

    2011-03-01

    The physiological and pathological handling of glucose via sodium-glucose cotransporter-2 (SGLT2) in the kidneys has been evolving, and SGLT2 inhibitors have been focused upon as a novel drug for treating diabetes. SGLT2 inhibitors enhance renal glucose excretion by inhibiting renal glucose reabsorption. Consequently, SGLT2 inhibitors reduce plasma glucose insulin independently and improve insulin resistance in diabetes. To date, various SGLT2 inhibitors have been developed and evaluated in clinical studies. The potency and positioning of SGLT2 inhibitors as an antidiabetic drug are dependent on their characteristic profile, which induces selectivity, efficacy, pharmacokinetics, and safety. This profile decides which SGLT2 inhibitors can be expected for application of the theoretical concept of reducing renal glucose reabsorption for the treatment of diabetes. I review the structure and advancing profile of various SGLT2 inhibitors, comparing their similarities and differences, and discuss the expected SGLT2 inhibitors for an emerging category of antidiabetic drugs.

  19. Environmental life cycle analysis of potato sprout inhibitors

    NARCIS (Netherlands)

    Kerstholt, R.P.V.; Ree, C.M.; Moll, H.C.

    Potato sprout inhibitors are generally applied to suppress sprouting during winter storage. This study presents the compared environmental profiles of the two sprout inhibitors available on the Dutch market: A traditional chemical product with isopropyl-3-chlorophenylcarbamate (CIPC) and

  20. [Inhibitors of proteolytic enzymes under abiotic stresses in plants (review)].

    Science.gov (United States)

    Mosolov, V V; Valueva, T A

    2011-01-01

    Data on the role of proteolytic enzyme inhibitors in plant adaptation to various unfavorable environmental abiotic factors--water deficiency, salinization of soil, extreme temperatures, etc.--and also probable functions of proteinases inhibitors in natural plant senescense are considered.

  1. Nuclear cardiology

    International Nuclear Information System (INIS)

    Vos, P.H.

    1982-01-01

    This thesis deals with two topics in nuclear cardiology. In the first, left ventricular wall motion assessment using Fourier transform of local left ventricular time-activity curves in gated blood pool studies is evaluated. In the second, the interpretation of myocardial perfusion scintigrams is assessed which are obtained with thallium-201 or with another radiopharmaceutical with different physical, but identical biological properties. In all these investigations data acquisition and analysis by computer played an essential role. In chapter 1 the desirable properties of a nuclear medicine computer system are given and the computer system used for this work is described. Wall motion analysis of the left ventricle using Fourier transform of local time-activity curves in the left ventricular region in gated blood pool studies is described in chapter 2. In chapter 3 detection of non-perfused lesions in myocardial perfusion scintigraphy with thallium-201 is described. Detection of partly perfused lesions and the influence of scatter and photon energy on myocardial perfusion scintigraphy is described in chapter 4. (Auth.)

  2. Nuclear reactors

    International Nuclear Information System (INIS)

    Pearson, K.G.

    1977-01-01

    Reference is made to auxiliary means of cooling the nuclear fuel clusters used in light or heavy water cooled nuclear reactors. One method is to provide one or more spray cooling tubes. From holes in the side walls of those tubes coolant water may be sprayed laterally into the cluster against the rods. The flow of main coolant may thus be supplemented or even replaced by the auxiliary coolant. A difficulty, however, is that only those fuel rods close to a spray cooling tube can readily be reached by the auxiliary coolant. In the arrangement described, where the fuel rods are spaced apart by transverse grids, at least one of the interspaces between the grids is provided with an axially extending auxiliary coolant conduit having lateral holes through which an auxiliary coolant is sprayed into the cluster. A deflector is provided that extends from a transverse grid into a position in front of the holes and deflects auxiliary coolant on to parts of the fuel rods otherwise inaccessible to the auxiliary coolant. The construction of the deflector is described. (U.K.)

  3. Nuclear reactors

    International Nuclear Information System (INIS)

    Matheson, J.E.

    1983-01-01

    A nuclear reactor has an upper and a lower grid plate. Protrusions project from the upper grid plate. Fuel assemblies having end fittings fit between the grid plates. An arrangement is provided for accepting axial forces generated during the operation of the nuclear reactor by the flow of the cooling medium and thermal expansion and irradiation-induced growth of the fuel assembly, which comprises rods. Each fuel assembly rests on the lower grid plate and its upper end is elastically supported against the upper grid plate by the above-mentioned arrangement. The arrangement comprises four (for example) torsion springs each having a torsion tube and a torsion bar nested within the torsion tube and connected at one end thereto. The other end of the torsion bar is connected to an associated one of four lever arms. The torsion tube is rigidly connected to the other end fitting and the springs are disposed such that the lever arms are biassed against the protrusions. (author)

  4. Efficacy of nuclear forensics

    International Nuclear Information System (INIS)

    Kazi, Reshmi

    2011-01-01

    In a strange turn of history, the threat of global nuclear war has gone down, but the risk of a nuclear attack has gone up. The danger of nuclear terrorism and ways to thwart it, tackle it and manage it in the event of an attack is increasingly gaining the attention of nuclear analysts all over the world. There is rising awareness among nuclear experts to develop mechanisms to prevent, deter and deal with the threat of nuclear terrorism. Nuclear specialists are seeking to develop and improve the science of nuclear forensics so as to provide faster analysis during a crisis. Nuclear forensics can play an important role in detecting illicit nuclear materials to counter trafficking in nuclear and radiological materials. An effective nuclear forensic and attribution strategy can enable policy makers, decision makers and technical managers to respond to situations involving interception of special nuclear materials

  5. On China's Nuclear Doctrine

    Directory of Open Access Journals (Sweden)

    Xia Liping

    2015-12-01

    Full Text Available Nuclear weapons have played an important role in China's national strategy. China’s nuclear doctrine has a very strong continuity. Nevertheless, China has made readjustments in its nuclear doctrine according to the changes of its internal and external situation and its general strategic threat perception. China’s nuclear doctrine has experienced a process of evolution from anti-nuclear blackmail to minimum deterrence. There are five major parts in China's nuclear doctrine: policy of declaration, nuclear development, nuclear deployment, nuclear employment, and nuclear disarmament. Because China is faced with a different situation from other nuclear powers and has its own strategic culture, China has a nuclear doctrine with its own characteristics. China’s nuclear doctrine has been affiliated with and has served the national development strategy, national security strategy, national defense policy and military strategy of China.

  6. Reconversion of nuclear weapons

    CERN Document Server

    Kapitza, Sergei P

    1992-01-01

    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?

  7. Nuclear power in Asia

    Energy Technology Data Exchange (ETDEWEB)

    Hagen, Ronald E.

    1998-08-01

    Contains Executive Summary and Chapters on: Nuclear Energy in the Asian context; Types of nuclear power reactors used in Asia; A survey of nuclear power by country; The economics of nuclear power; Fuels, fuel cycles and reprocessing; Environmental issues and waste disposal; The weapons issues and nuclear power; Conclusions. (Author)

  8. Fundamentals of nuclear physics

    International Nuclear Information System (INIS)

    Jelley, N.A.

    1990-01-01

    The book is aimed at undergraduates in their final year, to give the student a thorough understanding of the principal features of nuclei, nuclear decays and nuclear reactions. Several models are described and used to explain nuclear properties with many illustrative examples. Sections follow on α-, β- and γ-decay, fission, thermonuclear fusion, reactions, nuclear forces and nuclear collective motion. (author)

  9. Nuclear energy basic knowledge

    International Nuclear Information System (INIS)

    Volkmer, Martin

    2013-11-01

    The following topics are dealt with: Atoms, nuclear decays and radioactivity, energy, nuclear fission and the chain reaction, controlled nuclear fission, nuclear power plants, safety installations in nuclear power plants, fuel supply and disposal, radiation measurement and radiation exposition of man. (HSI)

  10. The nuclear dilemma

    International Nuclear Information System (INIS)

    Mason, Colin.

    1983-01-01

    This paper discusses nuclear war, disarmament and national defence policies. The author argues that in spite of the obvious advantages of nuclear power in many parts of the world, the world cannot afford the risk of continuing with it because of the demonstrated close and deadly association of nuclear power and nuclear reactors with nuclear weapons

  11. Nuclear energy data

    International Nuclear Information System (INIS)

    1990-01-01

    Nuclear Energy Data is the OECD Nuclear Energy Agency's annual compilation of basic statistics on electricity generation and nuclear power in OECD countries. The reader will find quick and easy reference to the present status of and projected trends in total electricity generating capacity, nuclear generating capacity, and actual electricity production as well as on supply and demand for nuclear fuel cycle services [fr

  12. The validation of corrosion inhibitors for ancillary cooling systems at Sizewell B PWR

    International Nuclear Information System (INIS)

    Allan, S.J.; Garnsey, R.; Lawson, W.F.

    1994-01-01

    Sizewell B has several low temperature ancillary cooling circuits for removing low grade heat. One of the principal circuits is the Component Cooling Water System (CCWS) primarily constructed from carbon steel pipework but also containing stainless steel, titanium, copper and cupronickel components. Linked to the CCWS is another carbon steel system namely the Reserve Ultimate Heat Sink (RUHS) a system unique to Sizewell B providing an independent heat removal capability for the CCWS as a safety back-up. Both systems utilize demineralized water with the addition of an inhibitor to prevent corrosion. The vendor recommended inhibitor namely potassium chromate is highly toxic to marine life and initial discussions with the regulatory authorities indicated that it would be extremely difficult to obtain a discharge consent to cover leakage or potential system purges and dumps associated with maintenance operations. Thus an alternative was sought. Sodium nitrite (anhydrous NaN0 2 )/borax (Na 2 B 4 0 7 1OH 2 0) inhibitor solutions have been used for many years in the power industry for preservation of carbon steel plant and several proprietary formulations are based on this mixture. There has been extensive test work in the UK on this inhibitor for secondary side boiler storage on gas reactors and therefore it was considered a prime candidate for use at Sizewell B. Starting in 1985 a programme of work sponsored by Nuclear Electric plc has been completed by NNC Ltd to compare nitrite/borax with other suitable inhibitors and validate its use for Sizewell B. (authors). 5 figs., 1 tab

  13. Nuclear safety and nuclear insurance

    International Nuclear Information System (INIS)

    Abramovitz, A.

    1983-01-01

    To an extent, public opinion is against Koeberg, inspite of the fact that Escom, Koeberg's prospective licensee, are liable for damages caused in the event of an accident, that they carry public liability insurance bought in the market place to the maximum of ten million rand, and if that is not enough the government will take over responsibility for the rest. A question is put that if this kind of protection carries on, won't there always be a minority of the public who will find nuclear power socially, psychologically and politically unacceptable

  14. Dipeptidyl peptidase-4 inhibitor ameliorates early renal injury through its anti-inflammatory action in a rat model of type 1 diabetes

    Energy Technology Data Exchange (ETDEWEB)

    Kodera, Ryo, E-mail: kodera@cc.okayama-u.ac.jp [Center for Innovative Clinical Medicine, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 (Japan); Shikata, Kenichi [Center for Innovative Clinical Medicine, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 (Japan); Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 (Japan); Takatsuka, Tetsuharu; Oda, Kaori; Miyamoto, Satoshi; Kajitani, Nobuo; Hirota, Daisho; Ono, Tetsuichiro [Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 (Japan); Usui, Hitomi Kataoka [Department of Primary Care and Medical Education, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 (Japan); Makino, Hirofumi [Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 (Japan)

    2014-01-17

    Highlights: •DPP-4 inhibitor decreased urinary albumin excretion in a rat of type 1 diabetes. •DPP-4 inhibitor ameliorated histlogical changes of diabetic nephropathy. •DPP-4 inhibitor has reno-protective effects through anti-inflammatory action. •DPP-4 inhibitor is beneficial on diabetic nephropathy besides lowering blood glucose. -- Abstract: Introduction: Dipeptidyl peptidase-4 (DPP-4) inhibitors are incretin-based drugs in patients with type 2 diabetes. In our previous study, we showed that glucagon-like peptide-1 (GLP-1) receptor agonist has reno-protective effects through anti-inflammatory action. The mechanism of action of DPP-4 inhibitor is different from that of GLP-1 receptor agonists. It is not obvious whether DPP-4 inhibitor prevents the exacerbation of diabetic nephropathy through anti-inflammatory effects besides lowering blood glucose or not. The purpose of this study is to clarify the reno-protective effects of DPP-4 inhibitor through anti-inflammatory actions in the early diabetic nephropathy. Materials and methods: Five-week-old male Sprague–Dawley (SD) rats were divided into three groups; non-diabetes, diabetes and diabetes treated with DPP-4 inhibitor (PKF275-055; 3 mg/kg/day). PKF275-055 was administered orally for 8 weeks. Results: PKF275-055 increased the serum active GLP-1 concentration and the production of urinary cyclic AMP. PKF275-055 decreased urinary albumin excretion and ameliorated histological change of diabetic nephropathy. Macrophage infiltration was inhibited, and inflammatory molecules were down-regulated by PKF275-055 in the glomeruli. In addition, nuclear factor-κB (NF-κB) activity was suppressed in the kidney. Conclusions: These results indicate that DPP-4 inhibitor, PKF275-055, have reno-protective effects through anti-inflammatory action in the early stage of diabetic nephropathy. The endogenous biological active GLP-1 might be beneficial on diabetic nephropathy besides lowering blood glucose.

  15. Dipeptidyl peptidase-4 inhibitor ameliorates early renal injury through its anti-inflammatory action in a rat model of type 1 diabetes

    International Nuclear Information System (INIS)

    Kodera, Ryo; Shikata, Kenichi; Takatsuka, Tetsuharu; Oda, Kaori; Miyamoto, Satoshi; Kajitani, Nobuo; Hirota, Daisho; Ono, Tetsuichiro; Usui, Hitomi Kataoka; Makino, Hirofumi

    2014-01-01

    Highlights: •DPP-4 inhibitor decreased urinary albumin excretion in a rat of type 1 diabetes. •DPP-4 inhibitor ameliorated histlogical changes of diabetic nephropathy. •DPP-4 inhibitor has reno-protective effects through anti-inflammatory action. •DPP-4 inhibitor is beneficial on diabetic nephropathy besides lowering blood glucose. -- Abstract: Introduction: Dipeptidyl peptidase-4 (DPP-4) inhibitors are incretin-based drugs in patients with type 2 diabetes. In our previous study, we showed that glucagon-like peptide-1 (GLP-1) receptor agonist has reno-protective effects through anti-inflammatory action. The mechanism of action of DPP-4 inhibitor is different from that of GLP-1 receptor agonists. It is not obvious whether DPP-4 inhibitor prevents the exacerbation of diabetic nephropathy through anti-inflammatory effects besides lowering blood glucose or not. The purpose of this study is to clarify the reno-protective effects of DPP-4 inhibitor through anti-inflammatory actions in the early diabetic nephropathy. Materials and methods: Five-week-old male Sprague–Dawley (SD) rats were divided into three groups; non-diabetes, diabetes and diabetes treated with DPP-4 inhibitor (PKF275-055; 3 mg/kg/day). PKF275-055 was administered orally for 8 weeks. Results: PKF275-055 increased the serum active GLP-1 concentration and the production of urinary cyclic AMP. PKF275-055 decreased urinary albumin excretion and ameliorated histological change of diabetic nephropathy. Macrophage infiltration was inhibited, and inflammatory molecules were down-regulated by PKF275-055 in the glomeruli. In addition, nuclear factor-κB (NF-κB) activity was suppressed in the kidney. Conclusions: These results indicate that DPP-4 inhibitor, PKF275-055, have reno-protective effects through anti-inflammatory action in the early stage of diabetic nephropathy. The endogenous biological active GLP-1 might be beneficial on diabetic nephropathy besides lowering blood glucose

  16. Two-dimensional NMR studies of squash family inhibitors. Sequence-specific proton assignments and secondary structure of reactive-site hydrolyzed Cucurbita maxima trypsin inhibitor III.

    Science.gov (United States)

    Krishnamoorthi, R; Gong, Y X; Lin, C L; VanderVelde, D

    1992-01-28

    The solution structure of reactive-site hydrolyzed Cucurbita maxima trypsin inhibitor III (CMTI-III*) was investigated by two-dimensional proton nuclear magnetic resonance (2D NMR) spectroscopy. CMTI-III*, prepared by reacting CMTI-III with trypsin which cleaved the Arg5-Ile6 peptide bond, had the two fragments held together by a disulfide linkage. Sequence-specific 1H NMR resonance assignments were made for all the 29 amino acid residues of the protein. The secondary structure of CMTI-III*, as deduced from NOESY cross peaks and identification of slowly exchanging hydrogens, contains two turns (residues 8-12 and 24-27), a 3(10)-helix (residues 13-16), and a triple-stranded beta-sheet (residues 8-10, 29-27, and 21-25). This secondary structure is similar to that of CMTI-I [Holak, T. A., Gondol, D., Otlewski, J., & Wilusz, T. (1989) J. Mol. Biol. 210, 635-648], which has a Glu instead of a Lys at position 9. Sequential proton assignments were also made for the virgin inhibitor, CMTI-III, at pH 4.71, 30 degrees C. Comparison of backbone hydrogen chemical shifts of CMTI-III and CMTI-III* revealed significant changes for residues located far away from the reactive-site region as well as for those located near it, indicating tertiary structural changes that are transmitted through most of the 29 residues of the inhibitor protein. Many of these residues are functionally important in that they make contact with atoms of the enzyme in the trypsin-inhibitor complex, as revealed by X-ray crystallography [Bode, W., Greyling, H. J., Huber, R., Otlewski, J., & Wilusz, T. (1989) FEBS Lett. 242, 285-292].(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Cellular growth kinetics distinguish a cyclophilin inhibitor from an HSP90 inhibitor as a selective inhibitor of hepatitis C virus.

    Directory of Open Access Journals (Sweden)

    Rudolf K F Beran

    Full Text Available During antiviral drug discovery, it is critical to distinguish molecules that selectively interrupt viral replication from those that reduce virus replication by adversely affecting host cell viability. In this report we investigate the selectivity of inhibitors of the host chaperone proteins cyclophilin A (CypA and heat-shock protein 90 (HSP90 which have each been reported to inhibit replication of hepatitis C virus (HCV. By comparing the toxicity of the HSP90 inhibitor, 17-(Allylamino-17-demethoxygeldanamycin (17-AAG to two known cytostatic compounds, colchicine and gemcitabine, we provide evidence that 17-AAG exerts its antiviral effects indirectly through slowing cell growth. In contrast, a cyclophilin inhibitor, cyclosporin A (CsA, exhibited selective antiviral activity without slowing cell proliferation. Furthermore, we observed that 17-AAG had little antiviral effect in a non-dividing cell-culture model of HCV replication, while CsA reduced HCV titer by more than two orders of magnitude in the same model. The assays we describe here are useful for discriminating selective antivirals from compounds that indirectly affect virus replication by reducing host cell viability or slowing cell growth.

  18. Nuclear war nuclear proliferation and their consequences

    International Nuclear Information System (INIS)

    Aga Khan, Sadruddin

    1986-01-01

    The paper concerns the proceedings of a conference hosted by the Groupe de Bellerive to explore and discuss the implications for humanity of nuclear war, nuclear proliferation and their consequences, Geneva 1985. The conference was divided into five sessions, headed by the subject titles: the nuclear non-proliferation treaty (NPT) and its future, the spread of nuclear weapons among nations, global effects of a nuclear war, the nuclear arms race and arms control, the NPT and its future. Twenty eight papers were presented in the five sessions. (UK)

  19. Screening for Selective Protein Inhibitors by Using the IANUS Peptide Array.

    Science.gov (United States)

    Erdmann, Frank; Prell, Erik; Jahreis, Günther; Fischer, Gunter; Malešević, Miroslav

    2018-04-16

    Finding new road blacks: A peptidic inhibitor of calcineurin (CaN)-mediated nuclear factor of activated T cells (NFAT) dephosphorylation, which is developed through a template-assisted IANUS (Induced orgANisation of strUcture by matrix-assisted togethernesS) peptide array, is cell permeable and able to block the translocation of green fluorescent protein-NFAT fusion protein (GFP-NFAT) into the nucleus after stimulation. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Nuclear dewatering

    International Nuclear Information System (INIS)

    Anon.

    1989-01-01

    The Sizewell 'B' Nuclear Power Station, the first in a new family of PWR (Pressurised Water Reactor) stations in the UK, is currently under construction on the Suffolk coast. One of the first civil engineering tasks associated with the power station construction was the necessity to lower the water table by 17-18 m over an area of approximately 8 hectares to allow the excavation for the foundations to be carried out in the dry. The way chosen to do this was to construct a diaphragm wall around the site area. This had the least effect on surrounding sites -the Sizewell-A station and various nature reserves and wetlands. The reasons for the choice of method are discussed. Following the construction of the wall the water was pumped out from within the diaphragm wall in January 1988. (author)

  1. Nuclear prophecy

    International Nuclear Information System (INIS)

    Michaelis, A.R.

    1981-01-01

    It is shown that there are at least four instances known of reasonably accurate forecasts of the benefits and dangers of nuclear energy. H.G. Wells' atomic bomb of 1914, A.W. Stewart's chain reaction of 1923, Olaf Stapeldon's mushroom cloud of 1930 and Hans Dominik's tactical atomic weapon of 1927 are briefly reviewed as well as a forecast of the Three Mile island accident. These examples show that although the trained imagination of writers can approach the truth none can claim accuracy in predicting the facts. Where they do approach the truth is in the prediction of the consequences of the discoveries, social as well as military, of unlimited energy and of unlimited disasters. (U.K.)

  2. Nuclear waste

    International Nuclear Information System (INIS)

    1989-10-01

    The Department of Energy is awarding grants to the state of Nevada for the state's participation in DOE's program to investigate Yucca Mountain as a possible site for the disposal of civilian nuclear waste. This report has found that DOE's financial assistance budget request of $15 million for Nevada's fiscal year 1990 was not based on the amount the state requested but rather was derived by increasing Nevada's grant funds from the previous year in proportion to the increase that DOE requested for its own activities at the Nevada site. DOE's evaluations of Nevada's requests are performed too late to be used in DOE's budget formulation process because Nevada has been applying for financial assistance at about the same time that DOE submits its budget request to Congress

  3. Nuclear reactors

    International Nuclear Information System (INIS)

    Prescott, R.F.

    1976-01-01

    A nuclear reactor containment vessel faced internally with a metal liner is provided with thermal insulation for the liner, comprising one or more layers of compressible material such as ceramic fiber, such as would be conventional in an advanced gas-cooled reactor and also a superposed layer of ceramic bricks or tiles in combination with retention means therefor, the retention means (comprising studs projecting from the liner, and bolts or nuts in threaded engagement with the studs) being themselves insulated from the vessel interior so that the coolant temperatures achieved in a High-Temperature Reactor or a Fast Reactor can be tolerated with the vessel. The layer(s) of compressible material is held under a degree of compression either by the ceramic bricks or tiles themselves or by cover plates held on the studs, in which case the bricks or tiles are preferably bedded on a yielding layer (for example of carbon fibers) rather than directly on the cover plates

  4. Nuclear reactors

    Energy Technology Data Exchange (ETDEWEB)

    Prescott, R F; George, B V; Baglin, C J

    1978-05-10

    Reference is made to thermal insulation on the inner surfaces of containment vessels of fluid cooled nuclear reactors and particularly in situations where the thermal insulation must also serve a structural function and transmit substantial load forces to the surface which it covers. An arrangement is described that meets this requirement and also provides for core support means that favourably influences the flow of hot coolant from the lower end of the core into a plenum space in the hearth of the reactor. The arrangement comprises a course of thermally insulating bricks arranged as a mosaic covering a wall of the reactor and a course of thermally insulating tiles arranged as a mosaic covering the course of bricks. Full constructional details are given.

  5. Nuclear energy

    International Nuclear Information System (INIS)

    Anon.

    1994-01-01

    The Administrative Court of Braunschweig judges the Ordinance on Advance Funding of Repositories (EndlagervorausleistungsVO) to be void. The Hannover Regional Court passes a basic judgment concerning the Gorleben salt mine (repository) and an action for damages. The Federal Administrative Court dismisses actions against part-permits for the Hanau fuel element fabrication plant. The Koblenz Higher Administrative Court dismisses actions against a part-permit for the Muelheim-Kaerlich reactor. 31st Amendment of the German Criminal Code passed, involving amendments in environmental criminal code, defined in the 2nd amendment to the Act on Unlowful Practices Causing Damage to the Environment (UKG); here: Amendments to the law relating to the criminal code and penal provisions governing unlawful conduct in the operation of nuclear installations. (orig.) [de

  6. Nuclear waste

    International Nuclear Information System (INIS)

    1989-01-01

    This paper reviews the Department of Energy's management of underground single-shell waste storage tanks at its Hanford, Washington, site. The tanks contain highly radioactive and nonradioactive hazardous liquid and solid wastes from nuclear materials production. Hundreds of thousands of gallons of these wastes have leaked, contaminating the soil, and a small amount of leaked waste has reached the groundwater. DOE does not collect sufficient data to adequately trace the migration of the leaks through the soil, and studies predicting the eventual environmental impact of tank leaks do not provide convincing support for DOE's conclusion that the impact will be low or nonexistent. DOE can do more to minimize the environmental risks associated with leaks. To reduce the environmental impact of past leaks, DOE may be able to install better ground covering over the tanks to reduce the volume of precipitation that drains through the soil and carries contaminants toward groundwater

  7. Nuclear facilities

    International Nuclear Information System (INIS)

    Anon.

    2000-01-01

    Here is given the decree (2000-1065) of the 25. of October 2000 reporting the publication of the convention between the Government of the French Republic and the CERN concerning the safety of the LHC (Large Hadron Collider) and the SPS (Proton Supersynchrotron) facilities, signed in Geneva on July 11, 2000. By this convention, the CERN undertakes to ensure the safety of the LHC and SPS facilities and those of the operations of the LEP decommissioning. The French legislation and regulations on basic nuclear facilities (concerning more particularly the protection against ionizing radiations, the protection of the environment and the safety of facilities) and those which could be decided later on apply to the LHC, SPS and auxiliary facilities. (O.M.)

  8. Nuclear reactors

    International Nuclear Information System (INIS)

    Prescott, R.F.; George, B.V.; Baglin, C.J.

    1978-01-01

    Reference is made to thermal insulation on the inner surfaces of containment vessels of fluid cooled nuclear reactors and particularly in situations where the thermal insulation must also serve a structural function and transmit substantial load forces to the surface which it covers. An arrangement is described that meets this requirement and also provides for core support means that favourably influences the flow of hot coolant from the lower end of the core into a plenum space in the hearth of the reactor. The arrangement comprises a course of thermally insulating bricks arranged as a mosaic covering a wall of the reactor and a course of thermally insulating tiles arranged as a mosaic covering the course of bricks. Full constructional details are given. (UK)

  9. Nuclear reactor

    International Nuclear Information System (INIS)

    Gibbons, J.F.; McLaughlin, D.J.

    1978-01-01

    In the pressure vessel of the water-cooled nuclear reactor there is provided an internal flange on which the one- or two-part core barrel is hanging by means of an external flange. A cylinder is extending from the reactor vessel closure downwards to a seat on the core cupport structure and serves as compression element for the transmission of the clamping load from the closure head to the core barrel (upper guide structure). With the core barrel, subject to tensile stress, between the vessel internal flange and its seat on one hand and the compression of the cylinder resp. hold-down element between the closure head and the seat on the other a very strong, elastic sprung structure is obtained. (DG) [de

  10. Nuclear reactor

    International Nuclear Information System (INIS)

    Miyashita, Akio.

    1981-01-01

    Purpose: To facilitate and accelerate a leakage test of valves of a main steam pipe by adding a leakage test partition valve thereto. Constitution: A leakage testing partition valve is provided between a pressure vessel for a nuclear reactor and the most upstream side valve of a plurality of valves to be tested for leakage, a testing branch pipe is communicated with the downstream side of the partition valve, and the testing water for preventing leakage is introduced thereto through the branch pipe. Since main steam pipe can be simply isolated by closing the partition valve in the leakage test, the leakage test can be conducted without raising or lowering the water level in the pressure vessel, and since interference with other work in the reactor can be eliminated, the leakage test can be readily conducted parallel with other work in the reactor in a short time. Clean water can be used without using reactor water as the test water. (Yoshihara, H.)

  11. Nuclear reactor

    International Nuclear Information System (INIS)

    Aleite, W.; Bock, H.W.; Struensee, S.

    1976-01-01

    The invention concerns the use of burnable poisons in a nuclear reactor, especially in PWRs, in order to improve the controllability of the reactor. An unsymmetrical arrangement in the lattice is provided, if necessary also by insertion of special rods for these additions. It is proposed to arrange the burnable poisons in fuel elements taken over from a previous burn-up cycle and to distribute them, going out from the side facing the control rods, over not more than 20% of the lenth of the fuel elements. It seems sufficient, for the burnable poisons to bind an initial reactivity of only 0.1% and to become ineffective after normal operation of 3 to 4 months. (ORU) [de

  12. Nuclear reactor

    International Nuclear Information System (INIS)

    Schweiger, F.; Glahe, E.

    1976-01-01

    In a nuclear reactor of the kind which is charged with spherical reaction elements and in which control rods are arranged to be thrust directly into the charge, each control rod has at least one screw thread on its external surface so that as the rod is thrust into the charge it is caused to rotate and thus make penetration easier. The length of each control rod may have two distinct portions, a latter portion which carries a screw thread and a lead-in portion which is shorter than the latter portion and which may carry a thread of greater pitch than that on the latter portion or may have a number of axially extending ribs instead of a thread

  13. Nuclear cardiology

    Energy Technology Data Exchange (ETDEWEB)

    Cuaron, A

    1993-12-31

    Today, nuclear medicine techniques are routinely used in cardiological practice. They include procedures for the atraumatic investigation of different physiological processes in the various structures included in the central circulation: pericardium, myocardium, myocardial adrenergic innervation, cardiac chambers and valves, coronary microcirculation, and great vessels. Beside these in-Vivo procedures, they also comprise of in-Vitro methods for the detection and measurement in blood of various biological molecules of significance in the management of cardiac diseases. A common feature in this collection of in-Vivo and in-Vitro techniques is their ability to provide helpful clinical information for the diagnosis, prognosis and management of cardiac diseases. Their simplicity and safety for the patient allow their repeated use in the follow up of the progress of disease and in the assessment of the efficacy of the therapeutic measures 15 figs, 14 tabs

  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 cardiology

    International Nuclear Information System (INIS)

    Cuaron, A.

    1992-01-01

    Today, nuclear medicine techniques are routinely used in cardiological practice. They include procedures for the atraumatic investigation of different physiological processes in the various structures included in the central circulation: pericardium, myocardium, myocardial adrenergic innervation, cardiac chambers and valves, coronary microcirculation, and great vessels. Beside these in-Vivo procedures, they also comprise of in-Vitro methods for the detection and measurement in blood of various biological molecules of significance in the management of cardiac diseases. A common feature in this collection of in-Vivo and in-Vitro techniques is their ability to provide helpful clinical information for the diagnosis, prognosis and management of cardiac diseases. Their simplicity and safety for the patient allow their repeated use in the follow up of the progress of disease and in the assessment of the efficacy of the therapeutic measures

  16. Nuclear waste

    International Nuclear Information System (INIS)

    1988-01-01

    As required by the Nuclear Waste Policy Act of 1982, the Department of Energy is to annually determine whether the waste disposal fee will produce sufficient revenues to offset the total estimated costs of the waste disposal program. In its June 1987 assessment, DOE recommended that the fee remain unchanged even though its analysis showed that at an inflation rate of 4 percent the current fee would result in end-of-program deficits ranging from $21 billion to $76 billion in 2085. The 1988 assessment calls for reduced total costs because of program changes. Thus, DOE may be able to begin using a realistic inflation rate in determining fee adequacy in 1988 without proposing a major fee increase

  17. Nuclear reactor

    International Nuclear Information System (INIS)

    Tilliette, Z.

    1975-01-01

    A description is given of a nuclear reactor and especially a high-temperature reactor in which provision is made within a pressure vessel for a main cavity containing the reactor core and a series of vertical cylindrical pods arranged in spaced relation around the main cavity and each adapted to communicate with the cavity through two collector ducts or headers for the primary fluid which flows downwards through the reactor core. Each pod contains two superposed steam-generator and circulator sets disposed in substantially symmetrical relation on each side of the hot primary-fluid header which conveys the primary fluid from the reactor cavity to the pod, the circulators of both sets being mounted respectively at the bottom and top ends of the pod

  18. Nuclear waste

    International Nuclear Information System (INIS)

    1990-01-01

    Each year, nuclear power plants, businesses, hospitals, and universities generate more than 1 million cubic feet of hardware, rags, paper, liquid waste, and protective clothing that have been contaminated with radioactivity. While most of this waste has been disposed of in facilities in Nevada, South Carolina, and Washington state, recent legislation made the states responsible - either individually, or through groups of states called compacts - for developing new disposal facilities. This paper discusses the states' progress and problems in meeting facility development milestones in the law, federal and state efforts to resolve issues related to mixed waste (low-level waste that also contains hazardous chemicals) and waste with very low levels of radioactivity, and the Department of Energy's progress in discharging the federal government's responsibility under the law to manage the most hazardous low-level waste

  19. Nuclear insurance

    International Nuclear Information System (INIS)

    Anon.

    1993-01-01

    The German Nuclear Power Plant Insurance (DKVG) Association was able to increase its net capacity in property insurance to 637 million marks in 1993 (1992: 589 million). The reinsurance capacity of the other pools included, the total amount covered now amounts to 2 billion marks in property incurance and 200 million marks in liability incurance. As in the year before the pool can reckon with a stable gross premium yield around 175 million marks. The revival of the US dollar has played a decisive role in this development. In 1993 in the domestic market, the DKVG offered policies for 22 types of property risk and 43 types to third-party risk, operating with a gross target premium of 65 million marks and 16 million marks, respectively. The DKVG also participated in 540 foreign insurance contracts. (orig./HSCH) [de

  20. Improved Histone Deacetylase Inhibitors as Therapeutics for the Neurodegenerative Disease Friedreich’s Ataxia: A New Synthetic Route

    Directory of Open Access Journals (Sweden)

    Joel M. Gottesfeld

    2011-12-01

    Full Text Available Friedreich’s ataxia (FRDA is caused by transcriptional repression of the nuclear FXN gene encoding the essential mitochondrial protein frataxin. Based on the hypothesis that the acetylation state of the histone proteins is responsible for gene silencing in FRDA, previous work in our lab identified a first generation of HDAC inhibitors (pimelic o-aminobenzamides, which increase FXN mRNA in lymphocytes from FRDA patients. Importantly, these compounds also function in a FRDA mouse model to increase FXN mRNA levels in the brain and heart. While the first generation of HDAC inhibitors hold promise as potential therapeutics for FRDA, they have two potential problems: less than optimal brain penetration and metabolic instability in acidic conditions. Extensive optimization focusing on modifying the left benzene ring, linker and the right benzene ring lead to a novel class of HDAC inhibitors that have optimized pharmacological properties (increased brain penetration and acid stability compared to the previous HDAC inhibitors. This article will describe the chemical synthesis and pharmacological properties of these new HDAC inhibitors.

  1. Nuclear fuels

    International Nuclear Information System (INIS)

    Beauvy, M.; Berthoud, G.; Defranceschi, M.; Ducros, G.; Guerin, Y.; Limoge, Y.; Madic, Ch.; Santarini, G.; Seiler, J.M.; Sollogoub, P.; Vernaz, E.; Guillet, J.L.; Ballagny, A.; Bechade, J.L.; Bonin, B.; Brachet, J.Ch.; Delpech, M.; Dubois, S.; Ferry, C.; Freyss, M.; Gilbon, D.; Grouiller, J.P.; Iracane, D.; Lansiart, S.; Lemoine, P.; Lenain, R.; Marsault, Ph.; Michel, B.; Noirot, J.; Parrat, D.; Pelletier, M.; Perrais, Ch.; Phelip, M.; Pillon, S.; Poinssot, Ch.; Vallory, J.; Valot, C.; Pradel, Ph.; Bonin, B.; Bouquin, B.; Dozol, M.; Lecomte, M.; Vallee, A.; Bazile, F.; Parisot, J.F.; Finot, P.; Roberts, J.F.

    2009-01-01

    Fuel is one of the essential components in a reactor. It is within that fuel that nuclear reactions take place, i.e. fission of heavy atoms, uranium and plutonium. Fuel is at the core of the reactor, but equally at the core of the nuclear system as a whole. Fuel design and properties influence reactor behavior, performance, and safety. Even though it only accounts for a small part of the cost per kilowatt-hour of power provided by current nuclear power plants, good utilization of fuel is a major economic issue. Major advances have yet to be achieved, to ensure longer in-reactor dwell-time, thus enabling fuel to yield more energy; and improve ruggedness. Aside from economics, and safety, such strategic issues as use of plutonium, conservation of resources, and nuclear waste management have to be addressed, and true technological challenges arise. This Monograph surveys current knowledge regarding in-reactor behavior, operating limits, and avenues for R and D. It also provides illustrations of ongoing research work, setting out a few noteworthy results recently achieved. Content: 1 - Introduction; 2 - Water reactor fuel: What are the features of water reactor fuel? 9 (What is the purpose of a nuclear fuel?, Ceramic fuel, Fuel rods, PWR fuel assemblies, BWR fuel assemblies); Fabrication of water reactor fuels (Fabrication of UO 2 pellets, Fabrication of MOX (mixed uranium-plutonium oxide) pellets, Fabrication of claddings); In-reactor behavior of UO 2 and MOX fuels (Irradiation conditions during nominal operation, Heat generation, and removal, The processes involved at the start of irradiation, Fission gas behavior, Microstructural changes); Water reactor fuel behavior in loss of tightness conditions (Cladding, the first containment barrier, Causes of failure, Consequences of a failure); Microscopic morphology of fuel ceramic and its evolution under irradiation; Migration and localization of fission products in UOX and MOX matrices (The ceramic under irradiation

  2. Nuclear fuels

    Energy Technology Data Exchange (ETDEWEB)

    Beauvy, M.; Berthoud, G.; Defranceschi, M.; Ducros, G.; Guerin, Y.; Limoge, Y.; Madic, Ch.; Santarini, G.; Seiler, J.M.; Sollogoub, P.; Vernaz, E.; Guillet, J.L.; Ballagny, A.; Bechade, J.L.; Bonin, B.; Brachet, J.Ch.; Delpech, M.; Dubois, S.; Ferry, C.; Freyss, M.; Gilbon, D.; Grouiller, J.P.; Iracane, D.; Lansiart, S.; Lemoine, P.; Lenain, R.; Marsault, Ph.; Michel, B.; Noirot, J.; Parrat, D.; Pelletier, M.; Perrais, Ch.; Phelip, M.; Pillon, S.; Poinssot, Ch.; Vallory, J.; Valot, C.; Pradel, Ph.; Bonin, B.; Bouquin, B.; Dozol, M.; Lecomte, M.; Vallee, A.; Bazile, F.; Parisot, J.F.; Finot, P.; Roberts, J.F

    2009-07-01

    Fuel is one of the essential components in a reactor. It is within that fuel that nuclear reactions take place, i.e. fission of heavy atoms, uranium and plutonium. Fuel is at the core of the reactor, but equally at the core of the nuclear system as a whole. Fuel design and properties influence reactor behavior, performance, and safety. Even though it only accounts for a small part of the cost per kilowatt-hour of power provided by current nuclear power plants, good utilization of fuel is a major economic issue. Major advances have yet to be achieved, to ensure longer in-reactor dwell-time, thus enabling fuel to yield more energy; and improve ruggedness. Aside from economics, and safety, such strategic issues as use of plutonium, conservation of resources, and nuclear waste management have to be addressed, and true technological challenges arise. This Monograph surveys current knowledge regarding in-reactor behavior, operating limits, and avenues for R and D. It also provides illustrations of ongoing research work, setting out a few noteworthy results recently achieved. Content: 1 - Introduction; 2 - Water reactor fuel: What are the features of water reactor fuel? 9 (What is the purpose of a nuclear fuel?, Ceramic fuel, Fuel rods, PWR fuel assemblies, BWR fuel assemblies); Fabrication of water reactor fuels (Fabrication of UO{sub 2} pellets, Fabrication of MOX (mixed uranium-plutonium oxide) pellets, Fabrication of claddings); In-reactor behavior of UO{sub 2} and MOX fuels (Irradiation conditions during nominal operation, Heat generation, and removal, The processes involved at the start of irradiation, Fission gas behavior, Microstructural changes); Water reactor fuel behavior in loss of tightness conditions (Cladding, the first containment barrier, Causes of failure, Consequences of a failure); Microscopic morphology of fuel ceramic and its evolution under irradiation; Migration and localization of fission products in UOX and MOX matrices (The ceramic under

  3. SGLT2 Inhibitors: Benefit/Risk Balance.

    Science.gov (United States)

    Scheen, André J

    2016-10-01

    Inhibitors of sodium-glucose cotransporters type 2 (SGLT2) reduce hyperglycemia by increasing urinary glucose excretion. They have been evaluated in patients with type 2 diabetes treated with diet/exercise, metformin, dual oral therapy or insulin. Three agents are available in Europe and the USA (canagliflozin, dapagliflozin, empagliflozin) and others are commercialized in Japan or in clinical development. SGLT2 inhibitors reduce glycated hemoglobin, with a minimal risk of hypoglycemia. They exert favorable effects beyond glucose control with consistent body weight, blood pressure, and serum uric acid reductions. Empagliflozin showed remarkable reductions in cardiovascular/all-cause mortality and in hospitalization for heart failure in patients with previous cardiovascular disease. Positive renal outcomes were also shown with empagliflozin. Mostly reported adverse events are genital mycotic infections, while urinary tract infections and events linked to volume depletion are rather rare. Concern about a risk of ketoacidosis and bone fractures has been recently raised, which deserves caution and further evaluation.

  4. Serine protease inhibitors of parasitic helminths.

    Science.gov (United States)

    Molehin, Adebayo J; Gobert, Geoffrey N; McManus, Donald P

    2012-05-01

    Serine protease inhibitors (serpins) are a superfamily of structurally conserved proteins that inhibit serine proteases and play key physiological roles in numerous biological systems such as blood coagulation, complement activation and inflammation. A number of serpins have now been identified in parasitic helminths with putative involvement in immune regulation and in parasite survival through interference with the host immune response. This review describes the serpins and smapins (small serine protease inhibitors) that have been identified in Ascaris spp., Brugia malayi, Ancylostoma caninum Onchocerca volvulus, Haemonchus contortus, Trichinella spiralis, Trichostrongylus vitrinus, Anisakis simplex, Trichuris suis, Schistosoma spp., Clonorchis sinensis, Paragonimus westermani and Echinococcus spp. and discusses their possible biological functions, including roles in host-parasite interplay and their evolutionary relationships.

  5. Secreted and Transmembrane Wnt Inhibitors and Activators

    Science.gov (United States)

    Cruciat, Cristina-Maria; Niehrs, Christof

    2013-01-01

    Signaling by the Wnt family of secreted glycoproteins plays important roles in embryonic development and adult homeostasis. Wnt signaling is modulated by a number of evolutionarily conserved inhibitors and activators. Wnt inhibitors belong to small protein families, including sFRP, Dkk, WIF, Wise/SOST, Cerberus, IGFBP, Shisa, Waif1, APCDD1, and Tiki1. Their common feature is to antagonize Wnt signaling by preventing ligand–receptor interactions or Wnt receptor maturation. Conversely, the Wnt activators, R-spondin and Norrin, promote Wnt signaling by binding to Wnt receptors or releasing a Wnt-inhibitory step. With few exceptions, these antagonists and agonists are not pure Wnt modulators, but also affect additional signaling pathways, such as TGF-β and FGF signaling. Here we discuss their interactions with Wnt ligands and Wnt receptors, their role in developmental processes, as well as their implication in disease. PMID:23085770

  6. Raltegravir: first in class HIV integrase inhibitor

    Directory of Open Access Journals (Sweden)

    Zelalem Temesgen

    2008-06-01

    Full Text Available Zelalem Temesgen1, Dawd S Siraj21Mayo Clinic, Rochester, MN, USA; 2East Carolina University Greenville, NC, USAAbstract: On October 16, 2007, the US Food and Drug Administration (FDA approved raltegravir for treatment of human immunodeficiency virus (HIV-1 infection in combination with other antiretroviral agents in treatment-experienced adult patients who have evidence of viral replication and HIV-1 strains resistant to multiple antiretroviral agents. Raltegravir is first in a novel class of antiretroviral drugs known as integrase inhibitors. It has demonstrated potent anti HIV activity in both antiretroviral treatment-naïve and experienced patients. The most common adverse events reported with raltegravir during phase 2 and 3 clinical trials were diarrhea, nausea, and headache. Laboratory abnormalities include mild elevations in liver transaminases and creatine phosphokinase.Keywords: raltegravir, HIV, antiretroviral agents, integrase inhibitors

  7. Small molecule inhibitors of anthrax edema factor.

    Science.gov (United States)

    Jiao, Guan-Sheng; Kim, Seongjin; Moayeri, Mahtab; Thai, April; Cregar-Hernandez, Lynne; McKasson, Linda; O'Malley, Sean; Leppla, Stephen H; Johnson, Alan T

    2018-01-15

    Anthrax is a highly lethal disease caused by the Gram-(+) bacteria Bacillus anthracis. Edema toxin (ET) is a major contributor to the pathogenesis of disease in humans exposed to B. anthracis. ET is a bipartite toxin composed of two proteins secreted by the vegetative bacteria, edema factor (EF) and protective antigen (PA). Our work towards identifying a small molecule inhibitor of anthrax edema factor is the subject of this letter. First we demonstrate that the small molecule probe 5'-Fluorosulfonylbenzoyl 5'-adenosine (FSBA) reacts irreversibly with EF and blocks enzymatic activity. We then show that the adenosine portion of FSBA can be replaced to provide more drug-like molecules which are up to 1000-fold more potent against EF relative to FSBA, display low cross reactivity when tested against a panel of kinases, and are nanomolar inhibitors of EF in a cell-based assay of cAMP production. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Novel nonpeptidic inhibitors of peptide deformylase.

    Science.gov (United States)

    Jayasekera, M M; Kendall, A; Shammas, R; Dermyer, M; Tomala, M; Shapiro, M A; Holler, T P

    2000-09-15

    A novel series of nonpeptidic compounds structurally related to the known anticholesteremic thyropropic acid were found to inhibit Escherichia coli peptide deformylase (PDF), with IC50 values in the low-micromolar range. Kinetic analysis of [4-(4-hydroxyphenoxy)-3,5-diiodophenyl]acetic acid reveals competitive inhibition, with a Ki value of 0.66 +/- 0.007 microM. A structure-activity relationship study demonstrates that the carboxylate is required for activity, while the distal phenolic function can be methylated without significant effect. Either decreasing the number of iodine atoms on the molecule to one or increasing the number of iodine atoms to four results in the loss of an order of magnitude in potency. These compounds are the first nonpeptidic inhibitors disclosed and represent a template from which better inhibitors might be designed.

  9. Potent peptidic fusion inhibitors of influenza virus

    Energy Technology Data Exchange (ETDEWEB)

    Kadam, Rameshwar U.; Juraszek, Jarek; Brandenburg, Boerries; Buyck, Christophe; Schepens, Wim B. G.; Kesteleyn, Bart; Stoops, Bart; Vreeken, Rob J.; Vermond, Jan; Goutier, Wouter; Tang, Chan; Vogels, Ronald; Friesen, Robert H. E.; Goudsmit, Jaap; van Dongen, Maria J. P.; Wilson, Ian A.

    2017-09-28

    Influenza therapeutics with new targets and mechanisms of action are urgently needed to combat potential pandemics, emerging viruses, and constantly mutating strains in circulation. We report here on the design and structural characterization of potent peptidic inhibitors of influenza hemagglutinin. The peptide design was based on complementarity-determining region loops of human broadly neutralizing antibodies against the hemagglutinin (FI6v3 and CR9114). The optimized peptides exhibit nanomolar affinity and neutralization against influenza A group 1 viruses, including the 2009 H1N1 pandemic and avian H5N1 strains. The peptide inhibitors bind to the highly conserved stem epitope and block the low pH–induced conformational rearrangements associated with membrane fusion. These peptidic compounds and their advantageous biological properties should accelerate the development of new small molecule– and peptide-based therapeutics against influenza virus.

  10. [Immunoexpression and clinical significance of interleukin-21 and receptor activator of nuclear factor κB ligand in human periapical granulomas and radicular cysts].

    Science.gov (United States)

    Hu, Juhua; Li, Qian; Wang, Yanqing; Li, Song

    2015-06-01

    This study aimed to detect the immunoexpression of interleukin-21 (IL-21) and receptor activator. of nuclear factor KB ligand (RANKL) in periapical granulomas (PGs) and radicular cysts (RCs). The interaction of IL-21 with RANKL and its role in periapical pathogenesis were also speculated. A total of 32 PGs and 23 RCs were selected as experimental samples. Lesion size and occurrence of tenderness were recorded. Up to 10 healthy gingival tissues were collected as normal control samples. All tissues were subjected to immunohistocheincal analysis with anti-human IL-21 and RANKL polyclonal antibodies. The correlations of IL-21 with RANKL, lesion size, and the occurrence of tenderness of the PGs and RCs were evaluated. IL-21-positive cells were detected in all periapical lesion tissues but not in normal tissues. In the cyst group and granuloma group, the corresponding expression levels of IL-21 were 59.92±6.57 and 36.80± 6.81, whereas those of RANKL were 68.81±18.59 and 36.12±14.87, respectively. Moreover, t-test revealed a significantly higher expression of IL-21 and RANKL in RCs than in PGs (P<0.05). IL-21 and RANKL were positively correlated in both PGs and RCs (P<0.05). Furthermore, IL-21 was correlated with lesion size (P<0.05). This study demonstrated that IL-21 is potentially involved in the pathogenesis of apical periodontitis lesions. A role in the exacerbation of chronic inflammation, as well as in bone resorption, is suspected. Further studies are required to elucidate the specific functions of IL-21 in periradicular inflammatory processes.

  11. 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...

  12. 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.

  13. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... interventions. Children's (pediatric) nuclear medicine refers to imaging examinations done in babies, young children and teenagers. Nuclear ... nuclear medicine procedure work? With ordinary x-ray examinations, an image is made by passing x-rays ...

  14. NATO's Nuclear Glue

    National Research Council Canada - National Science Library

    Horton, Scott T

    2007-01-01

    .... nuclear weapons prepositioned in Europe? This paper reviews the past and current role of US nuclear forces in NATO, considers future nuclear policy options, and discusses potential consequences of those decisions...

  15. Nuclear Heart Scan

    Science.gov (United States)

    ... Home / Nuclear Heart Scan Nuclear Heart Scan Also known as Nuclear Stress Test , ... Learn More Connect With Us Contact Us Directly Policies Privacy Policy Freedom of Information Act (FOIA) Accessibility ...

  16. Nuclear analytical chemistry

    International Nuclear Information System (INIS)

    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

  17. Nuclear energy in Japan

    International Nuclear Information System (INIS)

    Guillemard, B.

    1978-01-01

    After having described the nuclear partners in Japan, the author analyzes the main aspects of Japan's nuclear energy: nuclear power plants construction program; developping of light water reactors; fuel cycle politics [fr

  18. Themes in nuclear law

    International Nuclear Information System (INIS)

    2003-01-01

    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

  19. Essay about nuclear right

    International Nuclear Information System (INIS)

    Puig, D.

    1994-01-01

    The present essay treat about all Uruguaian Nuclear Energy legislation. Nuclear energy history, international treaties, agreements, national programs, nuclear government politics, radiation protection regulations, wastes, radioactive materials transport, environment and safeguards has been given in this compilation

  20. Corrosion protection with eco-friendly inhibitors

    Science.gov (United States)

    Shahid, Muhammad

    2011-12-01

    Corrosion occurs as a result of the interaction of a metal with its environment. The extent of corrosion depends on the type of metal, the existing conditions in the environment and the type of aggressive ions present in the medium. For example, CO3-2 and NO-3 produce an insoluble deposit on the surface of iron, resulting in the isolation of metal and consequent decrease of corrosion. On the other hand, halide ions are adsorbed selectively on the metal surface and prevent formation of the oxide phase on the metal surface, resulting in continuous corrosion. Iron, aluminum and their alloys are widely used, both domestically and industrially. Linear alkylbenzene and linear alkylbenzene sulfonate are commonly used as detergents. They have also been found together in waste water. It is claimed that these chemicals act as inhibitors for stainless steel and aluminum. Release of toxic gases as a result of corrosion in pipelines may lead in certain cases to air pollution and possible health hazards. Therefore, there are two ways to look at the relationship between corrosion and pollution: (i) corrosion of metals and alloys due to environmental pollution and (ii) environmental pollution as a result of corrosion protection. This paper encompasses the two scenarios and possible remedies for various cases, using 'green' inhibitors obtained either from plant extracts or from pharmaceutical compounds. In the present study, the effect of piperacillin sodium as a corrosion inhibitor for mild steel was investigated using a weight-loss method as well as a three-electrode dc electrochemical technique. It was found that the corrosion rate decreased as the concentration of the inhibitor increased up to 9×10-4 M 93% efficiency was exhibited at this concentration.

  1. Acrosin inhibitor detecting along the boar epididymis

    Czech Academy of Sciences Publication Activity Database

    Maňásková-Postlerová, Pavla; Cozlová, Nina; Dorosh, Andriy; Šulc, Miroslav; Guyonet, B.; Jonáková, Věra

    2016-01-01

    Roč. 82, Jan 2016 (2016), s. 733-739 ISSN 0141-8130 R&D Projects: GA ČR(CZ) GAP503/12/1834; GA MŠk(CZ) ED1.1.00/02.0109; GA ČR GA14-05547S Institutional support: RVO:86652036 ; RVO:61388971 Keywords : Acrosin inhibitor * Boar epididymis * Spermatozoa Subject RIV: CE - Biochemistry Impact factor: 3.671, year: 2016

  2. Cyclooxygenase-2 inhibitors and knee prosthesis surgery

    OpenAIRE

    Meunier, Andreas

    2008-01-01

    Adverse effects of cyclooxygenase (COX) inhibitors on bone healing have previously been demonstrated in diaphyseal fracture models in animals. In spite of that, they are widely used as postoperative analgesics in orthopaedic surgery. After joint replacement, a bone repair process starts at the interface between bone and cement. If this process is disturbed, the prosthesis may never become rigidly fixed to the bone, leading to migration and with time loosening. This thesis investigates the eff...

  3. Aurora kinase inhibitors: Progress towards the clinic

    Czech Academy of Sciences Publication Activity Database

    Kollareddy, M.; Zheleva, D.; Dzubak, P.; Brahmkshatriya, Pathik; Lepšík, Martin; Hajduch, M.

    2012-01-01

    Roč. 30, č. 6 (2012), s. 2411-2432 ISSN 0167-6997 Grant - others:GA ČR(CZ) GA301/08/1649; GA ČR(CZ) GD303/09/H048 Program:GA; GD Institutional research plan: CEZ:AV0Z40550506 Keywords : Aurora kinases * cancer * inhibitors Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.498, year: 2012

  4. GSK-3 inhibitors induce chromosome instability

    Directory of Open Access Journals (Sweden)

    Staples Oliver D

    2007-08-01

    Full Text Available Abstract Background Several mechanisms operate during mitosis to ensure accurate chromosome segregation. However, during tumour evolution these mechanisms go awry resulting in chromosome instability. While several lines of evidence suggest that mutations in adenomatous polyposis coli (APC may promote chromosome instability, at least in colon cancer, the underlying mechanisms remain unclear. Here, we turn our attention to GSK-3 – a protein kinase, which in concert with APC, targets β-catenin for proteolysis – and ask whether GSK-3 is required for accurate chromosome segregation. Results To probe the role of GSK-3 in mitosis, we inhibited GSK-3 kinase activity in cells using a panel of small molecule inhibitors, including SB-415286, AR-A014418, 1-Azakenpaullone and CHIR99021. Analysis of synchronised HeLa cells shows that GSK-3 inhibitors do not prevent G1/S progression or cell division. They do, however, significantly delay mitotic exit, largely because inhibitor-treated cells have difficulty aligning all their chromosomes. Although bipolar spindles form and the majority of chromosomes biorient, one or more chromosomes often remain mono-oriented near the spindle poles. Despite a prolonged mitotic delay, anaphase frequently initiates without the last chromosome aligning, resulting in chromosome non-disjunction. To rule out the possibility of "off-target" effects, we also used RNA interference to selectively repress GSK-3β. Cells deficient for GSK-3β exhibit a similar chromosome alignment defect, with chromosomes clustered near the spindle poles. GSK-3β repression also results in cells accumulating micronuclei, a hallmark of chromosome missegregation. Conclusion Thus, not only do our observations indicate a role for GSK-3 in accurate chromosome segregation, but they also raise the possibility that, if used as therapeutic agents, GSK-3 inhibitors may induce unwanted side effects by inducing chromosome instability.

  5. FAITH - Fast Assembly Inhibitor Test for HIV

    Czech Academy of Sciences Publication Activity Database

    Hadravová, Romana; Rumlová, Michaela; Ruml, T.

    2015-01-01

    Roč. 486, Dec (2015), s. 78-87 ISSN 0042-6822 R&D Projects: GA ČR(CZ) GA14-15326S; GA MŠk LO1302; GA MŠk(CZ) LO1304 Institutional support: RVO:61388963 Keywords : retrovirus * HIV * assembly * assay * inhibitor Subject RIV: EE - Microbiology, Virology Impact factor: 3.200, year: 2015 http://www.sciencedirect.com/science/article/pii/S0042682215003864

  6. Monoamine oxidase inhibitors from Gentiana lutea.

    Science.gov (United States)

    Haraguchi, Hiroyuki; Tanaka, Yasumasa; Kabbash, Amal; Fujioka, Toshihiro; Ishizu, Takashi; Yagi, Akira

    2004-08-01

    Three monoamine oxidase (MAO) inhibitors were isolated from Gentiana lutea. Their structures were elucidated to be 3-3''linked-(2'-hydroxy-4-O-isoprenylchalcone)-(2'''-hydroxy-4''-O-isoprenyldihydrochalcone) (1), 2-methoxy-3-(1,1'-dimethylallyl)-6a,10a-dihydrobenzo(1,2-c)chroman-6-one and 5-hydroxyflavanone. These compounds, and the hydrolysis product of 1, displayed competitive inhibitory properties against MAO-B which was more effective than MAO-A.

  7. Trial Watch: Proteasomal inhibitors for anticancer therapy.

    Science.gov (United States)

    Obrist, Florine; Manic, Gwenola; Kroemer, Guido; Vitale, Ilio; Galluzzi, Lorenzo

    2015-01-01

    The so-called "ubiquitin-proteasome system" (UPS) is a multicomponent molecular apparatus that catalyzes the covalent attachment of several copies of the small protein ubiquitin to other proteins that are generally (but not always) destined to proteasomal degradation. This enzymatic cascade is crucial for the maintenance of intracellular protein homeostasis (both in physiological conditions and in the course of adaptive stress responses), and regulates a wide array of signaling pathways. In line with this notion, defects in the UPS have been associated with aging as well as with several pathological conditions including cardiac, neurodegenerative, and neoplastic disorders. As transformed cells often experience a constant state of stress (as a result of the hyperactivation of oncogenic signaling pathways and/or adverse microenvironmental conditions), their survival and proliferation are highly dependent on the integrity of the UPS. This rationale has driven an intense wave of preclinical and clinical investigation culminating in 2003 with the approval of the proteasomal inhibitor bortezomib by the US Food and Drug Administration for use in multiple myeloma patients. Another proteasomal inhibitor, carfilzomib, is now licensed by international regulatory agencies for use in multiple myeloma patients, and the approved indications for bortezomib have been extended to mantle cell lymphoma. This said, the clinical activity of bortezomib and carfilzomib is often limited by off-target effects, innate/acquired resistance, and the absence of validated predictive biomarkers. Moreover, the antineoplastic activity of proteasome inhibitors against solid tumors is poor. In this Trial Watch we discuss the contribution of the UPS to oncogenesis and tumor progression and summarize the design and/or results of recent clinical studies evaluating the therapeutic profile of proteasome inhibitors in cancer patients.

  8. Adverse Effects of COX-2 Inhibitors

    Directory of Open Access Journals (Sweden)

    Jagdish N. Sharma

    2005-01-01

    Full Text Available Cyclooxygenase-2 selective inhibitors (COXIBs were developed with the prime object of minimizing gastrointestinal adverse effects, which are seen with the use of traditional nonsteroidal anti-inflammatory drugs (NSAIDs. Their long-term use is limited by the development of hypertension, edema, and congestive heart failure in a significant proportion of patients. NSAIDs block the activity of both COX isozymes, COX-1 and COX-2, which mediate the enzymatic conversion of arachidonate to prostaglandin H2 (PGH2 and other prostaglandin (PG metabolites. It is well established that the cardiovascular profile of COX-2 inhibitors can be accounted for by inhibition of COX-dependent PG synthesis. Following the COX-mediated synthesis of PGH2 from arachidonate, PGH2 is metabolized to one of at least five bioactive PGs, including PGE2, PGI2, PGF2, PGD2, or thromboxane A2 (TXA2. These prostanoids have pleiotropic cardiovascular effects, altering platelet function and renal function, and they are acting either as vasodilators or vasoconstrictors. Although COX-1 and COX-2 exhibit similar biochemical activity in converting arachidonate to PGH2in vitro, the ultimate prostanoids they produce in vivo may be different due to differential regulation of COX-1 and COX-2, tissue distribution, and availability of the prostanoid synthases. PGs have been established as being critically involved in mitigating hypertension, helping to maintain medullary blood flow (MBF, promoting urinary salt excretion, and preserving the normal homeostasis of thrombosis, and the researchers found that the use of COX-2 inhibitors caused many serious complications in altering the normal body homeostasis. The purpose of the present research is to explain briefly the side effects of COX-2 inhibitors on the renal and cardiovascular system.

  9. Rust Inhibitor And Fungicide For Cooling Systems

    Science.gov (United States)

    Adams, James F.; Greer, D. Clay

    1988-01-01

    Mixture of benzotriazole, benzoic acid, and fungicide prevents growth of rust and fungus. Water-based cooling mixture made from readily available materials prevents formation of metallic oxides and growth of fungi in metallic pipes. Coolant remains clear and does not develop thick sludge tending to collect in low points in cooling systems with many commercial rust inhibitors. Coolant compatible with iron, copper, aluminum, and stainless steel. Cannot be used with cadmium or cadmium-plated pipes.

  10. Luminometric method for screening retroviral protease inhibitors

    Czech Academy of Sciences Publication Activity Database

    Horáková, D.; Rumlová, Michaela; Pichová, Iva; Ruml, Tomáš

    2005-01-01

    Roč. 345, č. 1 (2005), s. 96-101 ISSN 0003-2697 R&D Projects: GA AV ČR(CZ) IAA4055304; GA MŠk(CZ) 1M0508; GA MŠk(CZ) 1M0520 Institutional research plan: CEZ:AV0Z40550506 Keywords : retroviral protease * inhibitors * luminescent assay Subject RIV: CE - Biochemistry Impact factor: 2.670, year: 2005

  11. Serine proteinases and their inhibitors in fertilization

    Czech Academy of Sciences Publication Activity Database

    Jonáková, Věra

    2000-01-01

    Roč. 3, 3,4 (2000), s. 23 [ Proteolytic enzymes and their inhibitors in physiology and pathogenesis. 14.09.2000, Plzen] R&D Projects: GA ČR GV524/96/K162; GA ČR GA303/99/0357; GA MŠk VS96141 Grant - others:GA UK(CZ) 12/1998 Institutional research plan: CEZ:AV0Z5052915 Subject RIV: EB - Genetics ; Molecular Biology

  12. Curcumin – A Potent Inhibitor of Galectin-3 Expression

    Directory of Open Access Journals (Sweden)

    Jerka Dumić

    2002-01-01

    Full Text Available The expression of galectin-3, a b-galactoside binding lectin, was found to be affected by different kinds of stressors, and is strongly modified in numerous physiological and pathophysiological conditions. Although no precise regulatory mechanisms of galectin-3 expression are unraveled, transcription factors AP-1 (activator protein 1 and NF-kB (nuclear factor kappa B play an important role in these processes. Activities of both transcription factors are affected by curcumin, a biologically active compound extracted from rhizomes of Curcuma species. We have analyzed the impact of curcumin on the expression of galectin-3 in glioblastoma cells under basal conditions and under stress invoked by the cell exposure to alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG and ultraviolet C (UV-C light. Galectin-3 level was measured by western-blot technique using M3/38 monoclonal antibody. Curcumin has decreased the basal level of galectin-3, while the pretreatment of cells with curcumin has considerably reduced the inducible effect of UV-C radiation and abolished the inducible effect of alkylating agent. Thus, curcumin has been identified as a potent inhibitor of galectin-3 expression.

  13. Nuclear experts and nuclear weapons proliferation

    International Nuclear Information System (INIS)

    Mueller, H.

    1979-01-01

    In Germany the issue of nuclear weapons proliferation has attracted scant attention. Most potential nuclear weapon states are important trade partners of the FRG and, since further proliferation of nuclear weapons could worsen conflicts involving these, it should be in the FRG's interest to limit proliferation. The security of the FRG is also dependent on the common interest of the great powers to avoid nuclear war. The contradictory positions of Usa and the USSR on nuclear weapons policy regarding themselves and non-nuclear weapon states encourages less developed countries to see nuclear weaponry as useful. The NPT and IAEA safeguards have only limited inhibiting effect. The nuclear export policy of the FRG has been dominated by short term economic advantage, neglecting the negative long term effects of decreased political stability. The FRG should formulate a policy based on self-restraint, positive stimuli and extension of controls, using its economic strength to deter proliferation. (JIW)

  14. Nuclear reaction data and nuclear reactors

    Energy Technology Data Exchange (ETDEWEB)

    Paver, N [University of Trieste (Italy); Herman, M [International Atomic Energy Agency, Vienna (Austria); Gandini, A [ENEA, Rome (Italy)

    2001-12-15

    These two volumes contain the lecture notes of the workshop 'Nuclear Reaction Data and Nuclear Reactors: Physics, Design and Safety', which was held at the Abdus Salam ICTP in the Spring of 2000. The workshop consisted of five weeks of lecture courses followed by practical computer exercises on nuclear data treatment and design of nuclear power systems. The spectrum of topics is wide enough to timely cover the state-of-the-art and the perspectives of this broad field. The first two weeks were devoted to nuclear reaction models and nuclear data evaluation. Nuclear data processing for applications to reactor calculations was the subject of the third week. On the last two weeks reactor physics and on-going projects in nuclear power generation, waste disposal and safety were presented.

  15. 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.

  16. 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.

  17. The Iranian nuclear diplomacy

    International Nuclear Information System (INIS)

    Tabatabaei, Seyed Mohammad

    2008-01-01

    While assuming that civil nuclear means progress, and that military nuclear means danger, the author explains why Iran had decided to perform nuclear research and to implement electro-nuclear science, why Iran emphasises its willingness to develop uranium enrichment, what is the Iranian policy in terms of civil nuclear industry, why Iran does not want any shift of its nuclear programme towards military purposes

  18. Modelling of potentially promising SARS protease inhibitors

    International Nuclear Information System (INIS)

    Plewczynski, Dariusz; Hoffmann, Marcin; Grotthuss, Marcin von; Knizewski, Lukasz; Rychewski, Leszek; Eitner, Krystian; Ginalski, Krzysztof

    2007-01-01

    In many cases, at the beginning of a high throughput screening experiment some information about active molecules is already available. Active compounds (such as substrate analogues, natural products and inhibitors of related proteins) are often identified in low throughput validation studies on a biochemical target. Sometimes the additional structural information is also available from crystallographic studies on protein and ligand complexes. In addition, the structural or sequence similarity of various protein targets yields a novel possibility for drug discovery. Co-crystallized compounds from homologous proteins can be used to design leads for a new target without co-crystallized ligands. In this paper we evaluate how far such an approach can be used in a real drug campaign, with severe acute respiratory syndrome (SARS) coronavirus providing an example. Our method is able to construct small molecules as plausible inhibitors solely on the basis of the set of ligands from crystallized complexes of a protein target, and other proteins from its structurally homologous family. The accuracy and sensitivity of the method are estimated here by the subsequent use of an electronic high throughput screening flexible docking algorithm. The best performing ligands are then used for a very restrictive similarity search for potential inhibitors of the SARS protease within the million compounds from the Ligand.Info small molecule meta-database. The selected molecules can be passed on for further experimental validation

  19. Inhibitors of polyamine metabolism: review article.

    Science.gov (United States)

    Wallace, H M; Fraser, A V

    2004-07-01

    The identification of increased polyamine concentrations in a variety of diseases from cancer and psoriasis to parasitic infections has led to the hypothesis that manipulation of polyamine metabolism is a realistic target for therapeutic or preventative intervention in the treatment of certain diseases. The early development of polyamine biosynthetic single enzyme inhibitors such as alpha-difluoromethylornithine (DFMO) and methylglyoxal bis(guanylhydrazone) showed some interesting early promise as anticancer drugs, but ultimately failed in vivo. Despite this, DFMO is currently in use as an effective anti-parasitic agent and has recently also been shown to have further potential as a chemopreventative agent in colorectal cancer. The initial promise in vitro led to the development and testing of other potential inhibitors of the pathway namely the polyamine analogues. The analogues have met with greater success than the single enzyme inhibitors possibly due to their multiple targets. These include down regulation of polyamine biosynthesis through inhibition of ornithine decarboxylase and S-adenosylmethionine decarboxylase and decreased polyamine uptake. This coupled with increased activity of the catabolic enzymes, polyamine oxidase and spermidine/spermine N1-acetyltransferase, and increased polyamine export has made the analogues more effective in depleting polyamine pools. Recently, the identification of a new oxidase (PAO-h1/SMO) in polyamine catabolism and evidence of induction of both PAO and PAO-h1/SMO in response to polyamine analogue treatment, suggests the analogues may become an important part of future chemotherapeutic and/or chemopreventative regimens.

  20. Recent advances in botulinum neurotoxin inhibitor development.

    Science.gov (United States)

    Kiris, Erkan; Burnett, James C; Kane, Christopher D; Bavari, Sina

    2014-01-01

    Botulinum neurotoxins (BoNTs) are endopeptidases that target motor neurons and block acetylcholine neurotransmitter release. This action results in the muscle paralysis that defines the disease botulism. To date, there are no FDA-approved therapeutics to treat BoNT-mediated paralysis after intoxication of the motor neuron. Importantly, the rationale for pursuing treatments to counter these toxins is driven by their potential misuse. Current drug discovery efforts have mainly focused on small molecules, peptides, and peptidomimetics that can directly and competitively inhibit BoNT light chain proteolytic activity. Although this is a rational approach, direct inhibition of the Zn(2+) metalloprotease activity has been elusive as demonstrated by the dearth of candidates undergoing clinical evaluation. Therefore, broadening the scope of viable targets beyond that of active site protease inhibitors represents an additional strategy that could move the field closer to the clinic. Here we review the rationale, and discuss the outcomes of earlier approaches and highlight potential new targets for BoNT inhibition. These include BoNT uptake and processing inhibitors, enzymatic inhibitors, and modulators of neuronal processes associated with toxin clearance, neurotransmitter potentiation, and other pathways geared towards neuronal recovery and repair.