22,712 research outputs found

    Welcome and Opening Remarks

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    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

    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

    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

    Pseudomagnetic Fields in a Locally Strained Graphene Drumhead

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    Recent experiments reveal that a scanning tunneling microscopy (STM) probe tip can generate a highly localized strain field in a graphene drumhead, which in turn leads to pseudomagnetic fields in the graphene that can spatially confine graphene charge carriers in a way similar to a lithographically defined quantum dot (QD). While these experimental findings are intriguing, their further implementation in nanoelectronic devices hinges upon the knowledge of key underpinning parameters, which still remain elusive. In this paper, we first summarize the experimental measurements of the deformation of graphene membranes due to interactions with the STM probe tip and a back gate electrode. We then carry out systematic coarse grained, (CG), simulations to offer a mechanistic interpretation of STM tip-induced straining of the graphene drumhead. Our findings reveal the effect of (i) the position of the STM probe tip relative to the graphene drumhead center, (ii) the sizes of both the STM probe tip and graphene drumhead, as well as (iii) the applied back-gate voltage, on the induced strain field and corresponding pseudomagnetic field. These results can offer quantitative guidance for future design and implementation of reversible and on-demand formation of graphene QDs in nanoelectronics.Comment: 21 pages, 9 figure

    Crystal growth and magnetic structure of MnBi2Te4

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    Millimeter-sized MnBi2_2Te4_4 single crystals are grown out of Bi-Te flux and characterized by measuring magnetic and transport properties, scanning tunneling microscope (STM) and spectroscopy (STS). The magnetic structure of MnBi2_2Te4_4 below TN_N is determined by powder and single crystal neutron diffraction measurements. Below TN_N=24\,K, Mn2+^{2+} moments order ferromagnetically in the \textit{ab} plane but antiferromagnetically along the crystallographic \textit{c} axis. The ordered moment is 4.04(13) μB\mu_{B}/Mn at 10\,K and aligned along the crystallographic \textit{c}-axis. The electrical resistivity drops upon cooling across TN_N or when going across the metamagnetic transition in increasing fields below TN_N. A critical scattering effect was observed in the vicinity of TN_N in the temperature dependence of thermal conductivity. However, A linear temperature dependence was observed for thermopower in the temperature range 2K-300K without any anomaly around TN_N. These indicate that the magnetic order in Mn-Te layer has negligible effect on the electronic band structure, which makes possible the realization of proposed topological properties in MnBi2_2Te4_4 after fine tuning of the electronic band structure

    TOP2A and EZH2 Provide Early Detection of an Aggressive Prostate Cancer Subgroup.

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    Purpose: Current clinical parameters do not stratify indolent from aggressive prostate cancer. Aggressive prostate cancer, defined by the progression from localized disease to metastasis, is responsible for the majority of prostate cancer–associated mortality. Recent gene expression profiling has proven successful in predicting the outcome of prostate cancer patients; however, they have yet to provide targeted therapy approaches that could inhibit a patient\u27s progression to metastatic disease. Experimental Design: We have interrogated a total of seven primary prostate cancer cohorts (n = 1,900), two metastatic castration-resistant prostate cancer datasets (n = 293), and one prospective cohort (n = 1,385) to assess the impact of TOP2A and EZH2 expression on prostate cancer cellular program and patient outcomes. We also performed IHC staining for TOP2A and EZH2 in a cohort of primary prostate cancer patients (n = 89) with known outcome. Finally, we explored the therapeutic potential of a combination therapy targeting both TOP2A and EZH2 using novel prostate cancer–derived murine cell lines. Results: We demonstrate by genome-wide analysis of independent primary and metastatic prostate cancer datasets that concurrent TOP2A and EZH2 mRNA and protein upregulation selected for a subgroup of primary and metastatic patients with more aggressive disease and notable overlap of genes involved in mitotic regulation. Importantly, TOP2A and EZH2 in prostate cancer cells act as key driving oncogenes, a fact highlighted by sensitivity to combination-targeted therapy. Conclusions: Overall, our data support further assessment of TOP2A and EZH2 as biomarkers for early identification of patients with increased metastatic potential that may benefit from adjuvant or neoadjuvant targeted therapy approaches. ©2017 AACR
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