91 research outputs found

    Myosin-binding protein C displaces tropomyosin to activate cardiac thin filaments and governs their speed by an independent mechanism

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    Myosin-binding protein C (MyBP-C) is an accessory protein of striated muscle thick filaments and a modulator of cardiac muscle contraction. Defects in the cardiac isoform, cMyBP-C, cause heart disease. cMyBP-C includes 11 Ig- and fibronectin-like domains and a cMyBP-C-specific motif. In vitro studies show that in addition to binding to the thick filament via its C-terminal region, cMyBP-C can also interact with actin via its N-terminal domains, modulating thin filament motility. Structural observations of F-actin decorated with N-terminal fragments of cMyBP-C suggest that cMyBP-C binds to actin close to the low Ca(2+) binding site of tropomyosin. This suggests that cMyBP-C might modulate thin filament activity by interfering with tropomyosin regulatory movements on actin. To determine directly whether cMyBP-C binding affects tropomyosin position, we have used electron microscopy and in vitro motility assays to study the structural and functional effects of N-terminal fragments binding to thin filaments. 3D reconstructions suggest that under low Ca(2+) conditions, cMyBP-C displaces tropomyosin toward its high Ca(2+) position, and that this movement corresponds to thin filament activation in the motility assay. At high Ca(2+), cMyBP-C had little effect on tropomyosin position and caused slowing of thin filament sliding. Unexpectedly, a shorter N-terminal fragment did not displace tropomyosin or activate the thin filament at low Ca(2+) but slowed thin filament sliding as much as the larger fragments. These results suggest that cMyBP-C may both modulate thin filament activity, by physically displacing tropomyosin from its low Ca(2+) position on actin, and govern contractile speed by an independent molecular mechanism

    Science and Ideology in Economic, Political, and Social Thought

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    This paper has two sources: One is my own research in three broad areas: business cycles, economic measurement and social choice. In all of these fields I attempted to apply the basic precepts of the scientific method as it is understood in the natural sciences. I found that my effort at using natural science methods in economics was met with little understanding and often considerable hostility. I found economics to be driven less by common sense and empirical evidence, then by various ideologies that exhibited either a political or a methodological bias, or both. This brings me to the second source: Several books have appeared recently that describe in historical terms the ideological forces that have shaped either the direct areas in which I worked, or a broader background. These books taught me that the ideological forces in the social sciences are even stronger than I imagined on the basis of my own experiences. The scientific method is the antipode to ideology. I feel that the scientific work that I have done on specific, long standing and fundamental problems in economics and political science have given me additional insights into the destructive role of ideology beyond the history of thought orientation of the works I will be discussing

    Determinants of preventable readmissions in the United States: a systematic review

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    <p>Abstract</p> <p>Background</p> <p>Hospital readmissions are a leading topic of healthcare policy and practice reform because they are common, costly, and potentially avoidable events. Hospitals face the prospect of reduced or eliminated reimbursement for an increasing number of preventable readmissions under nationwide cost savings and quality improvement efforts. To meet the current changes and future expectations, organizations are looking for potential strategies to reduce readmissions. We undertook a systematic review of the literature to determine what factors are associated with preventable readmissions.</p> <p>Methods</p> <p>We conducted a review of the English language medicine, health, and health services research literature (2000 to 2009) for research studies dealing with unplanned, avoidable, preventable, or early readmissions. Each of these modifying terms was included in keyword searches of readmissions or rehospitalizations in Medline, ISI, CINAHL, The Cochrane Library, ProQuest Health Management, and PAIS International. Results were limited to US adult populations.</p> <p>Results</p> <p>The review included 37 studies with significant variation in index conditions, readmitting conditions, timeframe, and terminology. Studies of cardiovascular-related readmissions were most common, followed by all cause readmissions, other surgical procedures, and other specific-conditions. Patient-level indicators of general ill health or complexity were the commonly identified risk factors. While more than one study demonstrated preventable readmissions vary by hospital, identification of many specific organizational level characteristics was lacking.</p> <p>Conclusions</p> <p>The current literature on preventable readmissions in the US contains evidence from a variety of patient populations, geographical locations, healthcare settings, study designs, clinical and theoretical perspectives, and conditions. However, definitional variations, clear gaps, and methodological challenges limit translation of this literature into guidance for the operation and management of healthcare organizations. We recommend that those organizations that propose to reward reductions in preventable readmissions invest in additional research across multiple hospitals in order to fill this serious gap in knowledge of great potential value to payers, providers, and patients.</p

    American Gut: an Open Platform for Citizen Science Microbiome Research

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    McDonald D, Hyde E, Debelius JW, et al. American Gut: an Open Platform for Citizen Science Microbiome Research. mSystems. 2018;3(3):e00031-18

    Teoria do valor: bases para um método

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    O Brasil na nova cartografia global da religião

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    The business of writing and speaking : a managerial communication manual/ Robbins

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    ix, 233 hal.; ill.; 24 cm
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