1,504 research outputs found

    Dynamics and calcium association to the N-terminal regulatory domain of human cardiac troponin C: a multiscale computational study.

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    Troponin C (TnC) is an important regulatory molecule in cardiomyocytes. Calcium binding to site II in TnC initiates a series of molecular events that result in muscle contraction. The most direct change upon Ca(2+) binding is an opening motion of the molecule that exposes a hydrophobic patch on the surface allowing for Troponin I to bind. Molecular dynamics simulations were used to elucidate the dynamics of this crucial protein in three different states: apo, Ca(2+)-bound, and Ca(2+)-TnI-bound. Dynamics between the states are compared, and the Ca(2+)-bound system is investigated for opening motions. On the basis of the simulations, NMR chemical shifts and order parameters are calculated and compared with experimental observables. Agreement indicates that the simulations sample the relevant dynamics of the system. Brownian dynamics simulations are used to investigate the calcium association of TnC. We find that calcium binding gives rise to correlative motions involving the EF hand and collective motions conducive of formation of the TnI-binding interface. We furthermore indicate the essential role of electrostatic steering in facilitating diffusion-limited binding of Ca(2+)

    Description of an 8 MW reference wind turbine

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    An 8 MW wind turbine is described in terms of mass distribution, dimensions, power curve, thrust curve, maximum design load and tower configuration. This turbine has been described as part of the EU FP7 project LEANWIND in order to facilitate research into logistics and naval architecture efficiencies for future offshore wind installations. The design of this 8 MW reference wind turbine has been checked and validated by the design consultancy DNV-GL. This turbine description is intended to bridge the gap between the NREL 5 MW and DTU 10 MW reference turbines and thus contribute to the standardisation of research and development activities in the offshore wind energy industry

    NLO QCD+EW predictions for 2\ell2v diboson signatures at the LHC

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    We present next-to-leading order (NLO) calculations including QCD and electroweak (EW) corrections for 2\ell2ν diboson signatures with two opposite-charge leptons and two neutrinos. Specifically, we study the processes ppe+μνeνμpp \to e^+\mu^-\nu_e\overline{\nu}_{\mu} and ppe+eννpp \to e^+e^-\nu\overline{\nu}, including all relevant off-shell diboson channels, W+W,ZZ,γZW^+W^-, ZZ, \gamma Z, as well as non-resonant contributions. Photon-induced processes are computed at NLO EW, and we discuss subtle differences related to the definition and the renormalisation of the coupling α for processes with initial- and final-state photons. All calculations are performed within the automated Munich/Sherpa+OpenLoops frameworks, and we provide numerical predictions for the LHC at 13 TeV. The behaviour of the corrections is investigated with emphasis on the high-energy regime, where NLO EW effects can amount to tens of percent due to large Sudakov logarithms. The interplay between WW WW and ZZZZ contributions to the same-flavour channel, ppe+eννpp \to e^+e^-\nu\overline{\nu}, is discussed in detail, and a quantitative analysis of photon-induced contributions is presented. Finally, we consider approximations that account for all sources of large logarithms, at high and low energy, by combining virtual EW corrections with a YFS soft-photon resummation or a QED parton shower

    Uncovering Shakespeare\u27s Sisters in Special Collections and College Archives, Musselman Library

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    Foreword by Professor Suzanne J. Flynn I have taught the first-year seminar, Shakespeare’s Sisters, several times, and over the years I have brought the seminar’s students to the Folger Shakespeare Library in Washington, D.C. There, the wonderful librarians have treated the students to a special exhibit of early women’s manuscripts and first editions, beginning with letters written by Elizabeth I and proceeding through important works by seventeen and eighteenth-century women authors such as Aemelia Lanyer, Anne Finch, Aphra Behn, and Mary Wollstonecraft. This year I worked with Carolyn Sautter, the Director of Special Collections and College Archives, to give my 2018 seminar students the opportunity to produce a sequel to the Folger exhibit of early modern women writers. Special Collections houses an impressive array of first editions from the nineteenth and twentieth centuries, many of them acquired from Thomas Y. Cooper, the former editor of the Hanover Evening Sun newspaper, who donated over 1600 items to Musselman Library in 1965. Working with Kerri Odess-Harnish, we chose first editions of eight significant works of literature written by American and British women from the mid-nineteenth through the mid-twentieth centuries. The students worked in pairs, researching a single book and producing a report that outlines important biographical facts about the author, the book’s publication and reception history, and finally the significance of the book in the years since its publication. We hope that our project will draw attention to the wealth of literary treasures housed in Special Collections at Musselman Library, but especially to these works by eight of “Shakespeare’s Sisters.

    Enhancing the emotional and social skills of the youth to promote their wellbeing and positive development: a systematic review of universal school-based randomized controlled trials

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    Background: The acquisition of social and emotional skills is associated with positive youth development, character education, healthy lifestyle behaviours, reduction in depression and anxiety, conduct disorders, violence, bullying, conflict, and anger. School-based interventions aimed to enhance these skills go beyond a problem-focused approach to embrace a more positive view of health; they could also improve the youth's wellbeing. Aim: To describe the main features and to establish the effectiveness of universal school-based RCTs for children and the youth, aimed to promote their psychosocial wellbeing, positive development, healthy lifestyle behaviours and/or academic performance by improving their emotional and social skills. Methods: Systematic review by searching for relevant papers in PubMed/Medline with the following key words: "mental health" OR "wellbeing" OR "health promotion" OR "emotional learning" OR "social learning" OR "emotional and social learning" OR "positive youth development" OR "life skills" OR "life skills training" AND "school". Interval was set from January 2000 to April 2014. Results: 1,984 papers were identified through the search. Out of them 22 RCTs were included. While most interventions were characterized by a whole-school approach and SAFE practices, few studies only used standardized measures to assess outcomes, or had collected follow-up data after ≥ 6 months. The results of all these trials were examined and discussed. Conclusion: Universal school-based RCTs to enhance emotional and social skills showed controversial findings, due to some methodological issues mainly. Nevertheless they show promising outcomes that are relatively far-reaching for children and youth wellbeing and therefore are important in the real worl

    Warfare, Fiscal Capacity, and Performance

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    We exploit differences in casualties sustained in pre-modern wars to estimate the impact of fiscal capacity on economic performance. In the past, states fought different amounts of external conflicts, of various lengths and magnitudes. To raise the revenues to wage wars, states made fiscal innovations, which persisted and helped to shape current fiscal institutions. Economic historians claim that greater fiscal capacity was the key long-run institutional change brought about by historical conflicts. Using casualties sustained in pre-modern wars to instrument for current fiscal institutions, we estimate substantial impacts of fiscal capacity on GDP per worker. The results are robust to a broad range of specifications, controls, and sub-samples

    SUSY parameter determination at the LHC using cross sections and kinematic edges

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    We study the determination of supersymmetric parameters at the LHC from a global fit including cross sections and edges of kinematic distributions. For illustration, we focus on a minimal supergravity scenario and discuss how well it can be constrained at the LHC operating at 7 and 14 TeV collision energy, respectively. We find that the inclusion of cross sections greatly improves the accuracy of the SUSY parameter determination, and allows to reliably extract model parameters even in the initial phase of LHC data taking with 7 TeV collision energy and 1/fb integrated luminosity. Moreover, cross section information may be essential to study more general scenarios, such as those with non-universal gaugino masses, and distinguish them from minimal, universal, models.Comment: 22 pages, 8 figure
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