819 research outputs found

    SUBMERGED GRAVEL SCRUBBER DEMONSTRATION AS A PASSIVE AIR CLEANER FOR CONTAINMENT VENTING AND PURGING WITH SODIUM AEROSOLS -- CSTF TESTS AC7 - AC10

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    Four large-scale air cleaning tests (AC7 - AC10) were performed in the Containment Systems Test Facility (CS'lF) to demonstrate the performance of a Submerged Gravel Scrubber for cleaning the effluent gas from a vented and purged breeder reactor containment vessel. The test article, comprised of a Submerged Gravel Scrubber (SGS) followed by a high efficiency fiber demister, had a design gas flow rate of 0.47 m{sup 3}/s (1000 ft{sup 3}/min) at a pressure drop of 9.0 kPa (36 in. H{sub 2}O). The test aerosol was sodium oxide, sodium hydroxide, or sodium carbonate generated in the 850-m{sup 3} CSTF vessel by continuously spraying sodium into the air-filled vessel while adding steam or carbon dioxide. Approximately 4500 kg (10,000 lb) of sodium was sprayed over a total period of 100 h during the tests. The SGS/Demister system was shown to be highly efficient (removing ~99.98% of the entering sodium aerosol mass), had a high mass loading capacity, and operated in a passive manner, with no electrical requirement. Models for predicting aerosol capture, gas cooling, and pressure drop are developed and compared with experimental results

    The politics of playing along: radio and regulation in democratic Europe

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    The loss of localism has been a common trend in most radio markets in Europe and the United States. Deregulation of ownership led to a concentration phenomenon that has affected local radios in several western democracies. New forms of regulation have been considered as possible ways to stop the erosion of localism by applying rules to markets in the defense of diversity, pluralism, and the local dimension. This article analyses the local radio market in Portugal, by assessing the changes in the legislation and by examining the regulatory action that can, according to its remit, act preventively to avoid market forces to harm these principles.info:eu-repo/semantics/publishedVersio

    Genetic Variants of VEGFA and FLT4 Are Determinants of Survival in Renal Cell Carcinoma Patients Treated with Sorafenib

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    Molecular markers of sorafenib efficacy in patients with metastatic renal cell carcinoma (mRCC) are not available. The purpose of this study was to discover genetic markers of survival in patients with mRCC treated with sorafenib. Germline variants from 56 genes were genotyped in 295 patients with mRCC. Variant-overall survival (OS) associations were tested in multivariate regression models. Mechanistic studies were conducted to validate clinical associations. VEGFA rs1885657, ITGAV rs3816375, and WWOX rs8047917 (sorafenib arm), and FLT4 rs307826 and VEGFA rs3024987 (sorafenib and placebo arms combined) were associated with shorter OS. FLT4 rs307826 increased VEGFR-3 phosphorylation, membrane trafficking, and receptor activation. VEGFA rs1885657 and rs58159269 increased transcriptional activity of the constructs containing these variants in endothelial and RCC cell lines, and VEGFA rs58159269 increased endothelial cell proliferation and tube formation. FLT4 rs307826 and VEGFA rs58159269 led to reduced sorafenib cytotoxicity. Genetic variation in VEGFA and FLT4 could affect survival in sorafenib-treated patients with mRCC. These markers should be examined in additional malignancies treated with sorafenib and in other angiogenesis inhibitors used in mRCC. Significance: Clinical and mechanistic data identify germline genetic variants in VEGFA and FLT4 as markers of survival in patients with metastatic renal cell carcinoma.Peer reviewe

    Size-dependent spinodal and miscibility gaps for intercalation in nano-particles

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    Using a recently-proposed mathematical model for intercalation dynamics in phase-separating materials [Singh, Ceder, Bazant, Electrochimica Acta 53, 7599 (2008)], we show that the spinodal and miscibility gaps generally shrink as the host particle size decreases to the nano-scale. Our work is motivated by recent experiments on the high-rate Li-ion battery material LiFePO4; this serves as the basis for our examples, but our analysis and conclusions apply to any intercalation material. We describe two general mechanisms for the suppression of phase separation in nano-particles: (i) a classical bulk effect, predicted by the Cahn-Hilliard equation, in which the diffuse phase boundary becomes confined by the particle geometry; and (ii) a novel surface effect, predicted by chemical-potential-dependent reaction kinetics, in which insertion/extraction reactions stabilize composition gradients near surfaces in equilibrium with the local environment. Composition-dependent surface energy and (especially) elastic strain can contribute to these effects but are not required to predict decreased spinodal and miscibility gaps at the nano-scale

    Clozapine-induced agranulocytosis is associated with rare HLA-DQB1 and HLA-B alleles

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    Clozapine is a particularly effective antipsychotic medication but its use is curtailed by the risk of clozapine-induced agranulocytosis/granulocytopenia (CIAG), a severe adverse drug reaction occurring in up to 1% of treated individuals. Identifying genetic risk factors for CIAG could enable safer and more widespread use of clozapine. Here we perform the largest and most comprehensive genetic study of CIAG to date by interrogating 163 cases using genomewide genotyping and whole-exome sequencing. We find that two loci in the major histocompatibility complex are independently associated with CIAG: a single amino acid in HLA-DQB1 (126Q) (P = 4.7 x 10(-14), odds ratio (OR) = 0.19, 95% confidence interval (CI) = 0.12-0.29) and an amino acid change in the extracellular binding pocket of HLA-B (158T) (P = 6.4 x 10(-10), OR = 3.3, 95% CI = 2.3-4.9). These associations dovetail with the roles of these genes in immunogenetic phenotypes and adverse drug responses for other medications, and provide insight into the pathophysiology of CIAG

    Inhibition of GSK-3 induces differentiation and impaired glucose metabolism in renal cancer

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    Glycogen synthase kinase-3 (GSK-3), a constitutively active serine/threonine kinase, is a key regulator of numerous cellular processes ranging from glycogen metabolism to cell cycle regulation and proliferation. Consistent with its involvement in many pathways, it has also been implicated in the pathogenesis of various human diseases including Type II diabetes, Alzheimer's disease, bipolar disorder, inflammation and cancer. Consequently it is recognized as an attractive target for the development of new drugs. In the present study, we investigated the effect of both pharmacological and genetic inhibition of GSK-3 in two different renal cancer cell lines. We have shown potent anti-proliferative activity of 9-ING-41, a maleimide-based GSK-3 inhibitor. The anti-proliferative activity is most likely caused by G0-G1 and G2-M phase arrest as evident from cell cycle analysis. We have established that inhibition of GSK-3 imparted a differentiated phenotype in renal cancer cells. We have also shown that GSK-3 inhibition induced autophagy, likely as a result of imbalanced energy homeostasis caused by impaired glucose metabolism. Additionally, we have demonstrated the antitumor activity of 9-ING-41 in two different subcutaneous xenograft RCC tumor models. To our knowledge, this is the first report describing autophagy induction due to GSK-3 inhibition in renal cancer cells

    Spinodal Decomposition and Inflation: Dynamics and Metric Perturbations

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    We analyse the dynamics of spinodal decomposition in inflationary cosmology using the closed time path formalism of out of equilibrium quantum field theory combined with the non-perturbative Hartree approximation. In addition to a general analysis, we compute the detailed evolution of two inflationary models of particular importance: lambda Phi^4 new inflation and natural inflation. We compute the metric fluctuations resulting from inflationary phase transitions in the slow roll approximation, showing that there exists a regime for which quantum fluctuations of the inflaton field result in a significant deviation in the predictions of the spectrum of primordial density perturbations from standard results. We provide case examples for which a blue tilt to the power spectrum (i.e. n_s > 1) results from the evolution of a single inflaton field, and demonstrate that field fluctuations may result in a scalar amplitude of fluctuations significantly below standard predictions, resulting in a slight alleviation of the inflationary fine tuning problem. We show explicitly that the metric perturbation spectrum resulting from inflation depends upon the state at the outset of the inflationary phase.Comment: 26 pages, 19 figure
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