1,729 research outputs found

    Tauroursodeoxycholic acid exerts anticholestatic effects by a cooperative cPKC alpha-/PKA-dependent mechanism in rat liver.

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    Objective: Ursodeoxycholic acid (UDCA) exerts anticholestatic effects in part by protein kinase C (PKC)-dependent mechanisms. Its taurine conjugate, TUDCA, is a cPKCa agonist. We tested whether protein kinase A (PKA) might contribute to the anticholestatic action of TUDCA via cooperative cPKCa-/PKA-dependent mechanisms in taurolithocholic acid (TLCA)-induced cholestasis. Methods: In perfused rat liver, bile flow was determined gravimetrically, organic anion secretion spectrophotometrically, lactate dehydrogenase (LDH) release enzymatically, cAMP response-element binding protein (CREB) phosphorylation by immunoblotting, and cAMP by immunoassay. PKC/PKA inhibitors were tested radiochemically. In vitro phosphorylation of the conjugate export pump, Mrp2/Abcc2, was studied in rat hepatocytes and human Hep-G2 hepatoma cells. Results: In livers treated with TLCA (10 mmol/l)+TUDCA (25 mmol/l), combined inhibition of cPKC by the cPKCselective inhibitor Go¨6976 (100 nmol/l) or the nonselective PKC inhibitor staurosporine (10 nmol/l) and of PKA by H89 (100 nmol/l) reduced bile flow by 36% (p,0.05) and 48% (p,0.01), and secretion of the Mrp2/ Abcc2 substrate, 2,4-dinitrophenyl-S-glutathione, by 31% (p,0.05) and 41% (p,0.01), respectively; bile flow was unaffected in control livers or livers treated with TUDCA only or TLCA+taurocholic acid. Inhibition of cPKC or PKA alone did not affect the anticholestatic action of TUDCA. Hepatic cAMP levels and CREB phosphorylation as readout of PKA activity were unaffected by the bile acids tested, suggesting a permissive effect of PKA for the anticholestatic action of TUDCA. Rat and human hepatocellular Mrp2 were phosphorylated by phorbol ester pretreatment and recombinant cPKCa, nPKCe, and PKA, respectively, in a staurosporine-sensitive manner. Conclusion: UDCA conjugates exert their anticholestatic action in bile acid-induced cholestasis in part via cooperative post-translational cPKCa-/PKA-dependent mechanisms. Hepatocellular Mrp2 may be one target of bile acid-induced kinase activation

    Control of Silica Dust in Slate Milling Operations

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    The Mine Safety and Health Administration (MSHA) conducted a study to assess the present state of technology used for controlling employees\u27 respirable silica-bearing dust exposures during dimension slate milling operations. For this study, twelve slate milling operations were visited and various measurements were taken and observations made. These measurements and observations included exhaust and room airflow, types of enclosures, water usage, and building volumes for each of the milling processes. These mills usually employed between five and twenty people. From the study, general guidelines were developed from the best practices observed and can be used at the various sawing, splitting, trimming, and drilling operations throughout the industry

    Applications of Information Theory to Analysis of Neural Data

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    Information theory is a practical and theoretical framework developed for the study of communication over noisy channels. Its probabilistic basis and capacity to relate statistical structure to function make it ideally suited for studying information flow in the nervous system. It has a number of useful properties: it is a general measure sensitive to any relationship, not only linear effects; it has meaningful units which in many cases allow direct comparison between different experiments; and it can be used to study how much information can be gained by observing neural responses in single trials, rather than in averages over multiple trials. A variety of information theoretic quantities are commonly used in neuroscience - (see entry "Definitions of Information-Theoretic Quantities"). In this entry we review some applications of information theory in neuroscience to study encoding of information in both single neurons and neuronal populations.Comment: 8 pages, 2 figure

    Identifikasi Pengaruh Penggunaan Heatsink Terhadap Keluaran Modul Surya

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    Panas matahari yang diserap oleh modul surya dapat menaikkan suhu dan menurunkan tegangan keluarannya. Upaya penurunan suhu modul surya agar dalam kondisi standar diperlukan untuk menjaga agar kinerjanya tetap optimal. Pemasangan bahan penyerap panas seperti heatsink merupakan salah satu metode yang dapat digunakan sebagai upaya mendinginkan modul surya. Heatsink mampu mengurangi suhu rata-rata modul surya hingga 2,43°C dan meningkatkan tegangan keluaran rata-rata modul surya hingga 2,23 Volt. Kondisi ini dapat dilihat dari rata-rata tegangan output Voc modul surya yang ditambahkan heatsink dapat mencapai tegangan rata- rata 20,76 Volt dibandingkan dengan modul tanpa penambahan heatsink 18,52 Volt. Disimpulkan bahwa penambahan bahan penyerap panas berupa heatsink lebih efektif menurunkan suhu modul surya dari pada tanpa menggunakan heatsink

    Lebesgue regularity for differential difference equations with fractional damping

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    We provide necessary and sufficient conditions for the existence and unique-ness of solutions belonging to the vector-valued space of sequences �(Z, X) forequations that can be modeled in the formΔu(n)+Δu(n)=Au(n)+G(u)(n)+ (n), n ∈ Z,,>0,≥0,where X is a Banach space, ∈ �(Z, X), A is a closed linear operatorwith domain D(A) defined on X,andG is a nonlinear function. The oper-ator Δdenotes the fractional difference operator of order >0inthesense of Grünwald-Letnikov. Our class of models includes the discrete timeKlein-Gordon, telegraph, and Basset equations, among other differential differ-ence equations of interest. We prove a simple criterion that shows the existenceof solutions assuming that f is small and that G is a nonlinear term

    Perturbation theory of the space-time non-commutative real scalar field theories

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    The perturbative framework of the space-time non-commutative real scalar field theory is formulated, based on the unitary S-matrix. Unitarity of the S-matrix is explicitly checked order by order using the Heisenberg picture of Lagrangian formalism of the second quantized operators, with the emphasis of the so-called minimal realization of the time-ordering step function and of the importance of the ⋆\star-time ordering. The Feynman rule is established and is presented using ϕ4\phi^4 scalar field theory. It is shown that the divergence structure of space-time non-commutative theory is the same as the one of space-space non-commutative theory, while there is no UV-IR mixing problem in this space-time non-commutative theory.Comment: Latex 26 pages, notations modified, add reference

    Optimum Small Optical Beam Displacement Measurement

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    We derive the quantum noise limit for the optical beam displacement of a TEM00 mode. Using a multimodal analysis, we show that the conventional split detection scheme for measuring beam displacement is non-optimal with 80% efficiency. We propose a new displacement measurement scheme that is optimal for small beam displacement. This scheme utilises a homodyne detection setup that has a TEM10 mode local oscillator. We show that although the quantum noise limit to displacement measurement can be surpassed using squeezed light in appropriate spatial modes for both schemes, the TEM10 homodyning scheme out-performs split detection for all values of squeezing.Comment: 13 pages, 7 figure

    How to understand Pakistan’s hybrid regime: the importance of a multidimensional continuum

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    Pakistan has had a chequered democratic history but elections in 2013 marked a second turnover in power, and the first transition in Pakistan’s history from one freely elected government to another. How do we best categorize (and therefore understand) political developments in Pakistan? Is it now safe to categorize it as an electoral democracy or is it still a hybrid case of democracy? Using the Pakistani case as an example, this article argues that hybrid regimes deserve consideration as a separate case (rather than as a diminished sub type of democracy or authoritarianism), but must be categorised along a multidimensional continuum to understand the dynamics of power within the political system

    Improving the value of public RNA-seq expression data by phenotype prediction.

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    Publicly available genomic data are a valuable resource for studying normal human variation and disease, but these data are often not well labeled or annotated. The lack of phenotype information for public genomic data severely limits their utility for addressing targeted biological questions. We develop an in silico phenotyping approach for predicting critical missing annotation directly from genomic measurements using well-annotated genomic and phenotypic data produced by consortia like TCGA and GTEx as training data. We apply in silico phenotyping to a set of 70 000 RNA-seq samples we recently processed on a common pipeline as part of the recount2 project. We use gene expression data to build and evaluate predictors for both biological phenotypes (sex, tissue, sample source) and experimental conditions (sequencing strategy). We demonstrate how these predictions can be used to study cross-sample properties of public genomic data, select genomic projects with specific characteristics, and perform downstream analyses using predicted phenotypes. The methods to perform phenotype prediction are available in the phenopredict R package and the predictions for recount2 are available from the recount R package. With data and phenotype information available for 70,000 human samples, expression data is available for use on a scale that was not previously feasible

    First imaging results from the Iapetus B/C flyby of the Cassini spacecraft

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    Cassini had a relatively close flyby at Iapetus on New Year's Eve 2005. The 288 ISS images set various constraints on the origin theories of the dark/bright dichotomy, as revealed multiple surface structures at up to 740 m/pxl size
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