15,613 research outputs found

    Welcome and Opening Remarks

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    Transcriptional repression by ApiAP2 factors is central to chronic toxoplasmosis

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    Tachyzoite to bradyzoite development in Toxoplasma is marked by major changes in gene expression resulting in a parasite that expresses a new repertoire of surface antigens hidden inside a modified parasitophorous vacuole called the tissue cyst. The factors that control this important life cycle transition are not well understood. Here we describe an important transcriptional repressor mechanism controlling bradyzoite differentiation that operates in the tachyzoite stage. The ApiAP2 factor, AP2IV-4, is a nuclear factor dynamically expressed in late S phase through mitosis/cytokinesis of the tachyzoite cell cycle. Remarkably, deletion of the AP2IV-4 locus resulted in the expression of a subset of bradyzoite-specific proteins in replicating tachyzoites that included tissue cyst wall components BPK1, MCP4, CST1 and the surface antigen SRS9. In the murine animal model, the mis-timing of bradyzoite antigens in tachyzoites lacking AP2IV-4 caused a potent inflammatory monocyte immune response that effectively eliminated this parasite and prevented tissue cyst formation in mouse brain tissue. Altogether, these results indicate that suppression of bradyzoite antigens by AP2IV-4 during acute infection is required for Toxoplasma to successfully establish a chronic infection in the immune-competent host

    Normal sleep bouts are not essential for C. elegans survival and FoxO is important for compensatory changes in sleep

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    Additional file 6: Decreased lag-2 function does not slow vulval development. The progeny of wild type and lag-2(q420) animals raised at 25.5 °C were selected at the L4 stage, prior to lethargus entry. Vulval eversion was scored after 3 h; the percentage of animals completing vulval eversion was recorded. Significance was assessed by student’s two-tailed t-test p value < 0.5; error bars represents SEM from 3 trials. Total number of animals: wild type n = 45 and lag-2(q420) n = 42

    Audit Committee Accounting Expertise, Analyst Following, and Market Liquidity

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    We study the relation between audit committee accounting expertise, analyst following, and market liquidity. Our main results indicate that analyst following increases subsequent to the appointment of an accounting expert to the audit committee. We also provide evidence that accrual quality, as opposed to audit quality or management earnings forecasts, is the channel through which accounting expertise increases analyst following and improves analyst forecast properties. We also show that audit committee accounting expertise is related to higher trading volume and lower liquidity risk, supporting incentives for greater analyst following. Our study extends prior literature by providing evidence that audit committee accounting expertise enhances firms’ information environment beyond the effects it has on financial reporting quality or analysts’ forecast properties. Our study also complements the literature on determinants of analyst following and market liquidity, both of which are related to cost of capital. Results from our study should be useful to firms seeking to enhance analyst following and market liquidity

    Using state space differential geometry for nonlinear blind source separation

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    Given a time series of multicomponent measurements of an evolving stimulus, nonlinear blind source separation (BSS) seeks to find a "source" time series, comprised of statistically independent combinations of the measured components. In this paper, we seek a source time series with local velocity cross correlations that vanish everywhere in stimulus state space. However, in an earlier paper the local velocity correlation matrix was shown to constitute a metric on state space. Therefore, nonlinear BSS maps onto a problem of differential geometry: given the metric observed in the measurement coordinate system, find another coordinate system in which the metric is diagonal everywhere. We show how to determine if the observed data are separable in this way, and, if they are, we show how to construct the required transformation to the source coordinate system, which is essentially unique except for an unknown rotation that can be found by applying the methods of linear BSS. Thus, the proposed technique solves nonlinear BSS in many situations or, at least, reduces it to linear BSS, without the use of probabilistic, parametric, or iterative procedures. This paper also describes a generalization of this methodology that performs nonlinear independent subspace separation. In every case, the resulting decomposition of the observed data is an intrinsic property of the stimulus' evolution in the sense that it does not depend on the way the observer chooses to view it (e.g., the choice of the observing machine's sensors). In other words, the decomposition is a property of the evolution of the "real" stimulus that is "out there" broadcasting energy to the observer. The technique is illustrated with analytic and numerical examples.Comment: Contains 14 pages and 3 figures. For related papers, see http://www.geocities.com/dlevin2001/ . New version is identical to original version except for URL in the bylin

    Three-Dimensional Direct Simulation Monte Carlo Method for Slider Air Bearings

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    The direct simulation Monte Carlo (DSMC) method is used to solve the three-dimensional nano-scale gas film lubrication problem between a gas bearing slider and a rotating disk, and this solution is compared to the numerical solution of the compressible Reynolds equations with the slip flow correction based on the linearized Boltzmann equation as presented by Fukui and Kaneko [molecular gas film lubrication (MGL) method] [ASME J. Tribol. 110, 253 (1988)]. In the DSMC method, hundreds of thousands of simulated particles are used and their three velocity components and three spatial coordinates are calculated and recorded by using a hard-sphere collision model. Two-dimensional pressure profiles are obtained across the film thickness direction. The results obtained from the two methods agree well with each other for Knudsen numbers as large as 35 which corresponds to a minimum spacing of 2 nm. The result for contact slider is also obtained by the DSMC simulation and presented in this paper
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