295 research outputs found

    Characterization of radiolytically generated degradation products in the strip section of a TRUEX flowsheet

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    This report presents a summary of the work performed to meet the FCRD level 2 milestone M3FT-13IN0302053, “Identification of TRUEX Strip Degradation.” The INL radiolysis test loop has been used to identify radiolytically generated degradation products in the strip section of the TRUEX flowsheet. These data were used to evaluate impact of the formation of radiolytic degradation products in the strip section upon the efficacy of the TRUEX flowsheet for the recovery of trivalent actinides and lanthanides from acidic solution. The nominal composition of the TRUEX solvent used in this study is 0.2 M CMPO and 1.4 M TBP dissolved in n-dodecane and the nominal composition of the TRUEX strip solution is 1.5 M lactic acid and 0.050 M diethylenetriaminepentaacetic acid. Gamma irradiation of a mixture of TRUEX process solvent and stripping solution in the test loop does not adversely impact flowsheet performance as measured by stripping americium ratios. The observed increase in americium stripping distribution ratios with increasing absorbed dose indicates the radiolytic production of organic soluble degradation compounds

    Laboratory Simulation of Charge Exchange - Produced X-Ray Emission from Comets

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    In laboratory experiments using the engineering spare microcalorimeter detector from the ASTRO-E satellite mission, we recorded the x-ray emission of highly charged ions of carbon, nitrogen, and oxygen, which simulates charge exchange reactions between heavy ions in the solar wind and neutral gases in cometary comae. the spectra are complex and do not readily match predictions. We developed a charge exchange emission model that successfully reproduces the soft x-ray spectrum of comet Linear C/1999 S4, observed with the Chandra X-ray Observatory

    Oncogenic ras induces gastrin gene expression in colon cancer

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    AbstractBackground & Aims: The expression of gastrin, as a tumor growth factor, is significantly increased in some colon cancers compared with the low levels found in normal mucosa. The aim of this study was to elucidate the transcriptional mechanisms of gastrin induction in colon cancer. Methods: Gastrin messenger (mRNA) levels and K-ras genotype were determined in colon cancer cell lines and surgical specimens. Colon cancer cells were transfected with oncogenic ras expression vectors, and transcriptional activity was assayed with gastrin-luciferase reporter genes. Results: Colon cancer cell lines and tissues with K-ras mutations all had significantly higher gastrin mRNA levels than those that were ras wild type. Treatment of several ras mutant cell lines with PD98059, an inhibitor of mitogen-activated protein kinase kinase, resulted in a decrease in endogenous gastrin mRNA levels. The effects of ras on gastrin expression appeared to be mediated through the gastrin promoter because transfection of oncogenic ras and activated raf expression vectors both induced gastrin-promoter, luciferase-reporter genes. The inductive effects of oncogenic ras could be blocked by the coexpression of dominant negative forms of raf and extracellular regulated kinase. Conclusions: Oncogenic ras induces gastrin gene expression through activation of the Raf-MEK-ERK signal transduction pathway.GASTROENTEROLOGY 1998;115:1144-115

    The top 100 global water questions: Results of a scoping exercise

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    Global water security presents a complex problem for human societies and will become more acute as the impacts of climate change escalate. Water security connects the practical water and sanitation challenges of households to the dynamics of global hydroclimates and ecosystems in the Anthropocene. To ensure the successful deployment of attention and resources, it is necessary to identify the most pressing questions for water research. Here, we present the results of a scoping exercise conducted across the global water sector. More than 400 respondents submitted an excess of 4,000 potential questions. Drawing on expert analysis, we highlight 100 indicative research questions across six thematic domains: water and sanitation for human settlements; water and sanitation safety risk management; water security and scarcity; hydroclimate-ecosystem-Anthropocene dynamics; multi-level governance; and knowledge production. These questions offer an interdisciplinary and multi-scalar framework for guiding the nature and space of water research for the coming decades

    PI3K-ÎŽ and PI3K-Îł Inhibition by IPI-145 Abrogates Immune Responses and Suppresses Activity in Autoimmune and Inflammatory Disease Models

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    SummaryPhosphoinositide-3 kinase (PI3K)-Ύ and PI3K-γ are preferentially expressed in immune cells, and inhibitors targeting these isoforms are hypothesized to have anti-inflammatory activity by affecting the adaptive and innate immune response. We report on a potent oral PI3K-Ύ and PI3K-γ inhibitor (IPI-145) and characterize this compound in biochemical, cellular, and in vivo assays. These studies demonstrate that IPI-145 exerts profound effects on adaptive and innate immunity by inhibiting B and T cell proliferation, blocking neutrophil migration, and inhibiting basophil activation. We explored the therapeutic value of combined PI3K-Ύ and PI3K-γ blockade, and IPI-145 showed potent activity in collagen-induced arthritis, ovalbumin-induced asthma, and systemic lupus erythematosus rodent models. These findings support the hypothesis that inhibition of immune function can be achieved through PI3K-Ύ and PI3K-γ blockade, potentially leading to significant therapeutic effects in multiple inflammatory, autoimmune, and hematologic diseases
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