162,045 research outputs found

    Theoretical predictions of gating behavior for mutants of Shaker-type Kv channels from inter-domain energetics

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    A multiscale physical model of Shaker-type Kv channels is used to span from atomic-scale interactions to macroscopic experimental measures such as charge/voltage (QV) and conductance/voltage (GV) relations. The model [1] comprises the experimentally well-characterized voltage sensor (VS) domains described by four replications of an independent continuum electrostatic model under voltage clamp conditions [2, 3] and a hydrophobic gate controlling the flow of ions by a vapor lock mechanism [4], connected by a simple coupling principle derived from known experimental results and trial-and-error. The total Hamiltonian of the system is calculated from the computed configurational energy for each components as a function of applied voltage, VS positions andg ate radius, allowing us to produce statistical-mechanical expectation values for macroscopic laboratory observables over the full range of physiological membrane potentials (|V| ≤ 100 mV, in 1 mV steps). The Shaker QV and GV relations seen in Seoh et al. [5] are predicted by this model. With this approach, functional energetic relations can be decomposed in terms of physical components, and thus the effects of modifications in those elements can be quantified. We find that the total work required to operate the gate is an order of magnitude larger than the work available to the VS, and that the the experimentally observed bistable gating is due to the VS slide-and-interlock behavior. The same model was systematically applied to VS charge mutants (Seoh et al. [5]). The QV and GV relations can be qualitatively predicted and the associated effects on functional domains determined. Additional features such as surface charges become significant for the pathological cases. Our engineering approach clearly elucidates that both normal function and mutant changes are electrostatic in nature.[1] Alexander Peyser, Dirk Gillespie, Roland Roth, and Wolfgang Nonner. Domain and inter-domain energetics underlying gating in Shaker-type Kv channels. Accepted: Biophys J,2014. doi:10.1016/j.bpj.2014.08.015.[2] Alexander Peyser and Wolfgang Nonner. Voltage sensing in ion channels: Mesoscale simulations of biological devices. Phys Rev E StatNonlin Soft Matter Phys, 86: 011910, Jul 2012. doi:10.1103/PhysRevE.86.011910.[3] Alexander Peyser and Wolfgang Nonner. The sliding-helix voltage sensor: mesoscale views of a robust structure-function relationship. Eur Biophys J, 41:705–721,2012. doi:10.1007/s00249-012-0847-z.[4] Roland Roth, Dirk Gillespie, Wolfgang Nonner, and Robert E. Eisenberg. Bubbles, gating, and anesthetics in ion channels. Biophys J, 94(11):4282–4298,2008. doi:10.1529/biophysj.107.120493.[5] Sang-Ah Seoh, Daniel Sigg, Diane M. Papazian, and Francisco Bezanilla. Voltage-sensing residues in the S2 and S4 segments of the Shaker K+ channel. Neuron, 16 (6):1159–1167, 1 June1996. doi:10.1016/S0896-6273(00)80142-7.[6] Stephen B. Long, Xiao Tao, Ernest B. Campbell, and Roderick MacKinnon. Atomic structure of a voltage-dependent K+ channel in a lipid membrane-like environment. Nature, 450(7168):376–382,2007. doi:10.1038/nature06265

    [Report to Chief J. E. Curry, by an unknown author #1]

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    Report to Chief J. E. Curry, by an unknown author. The report contains a list of officers who gave depositions to the United States Attorney

    [Report to Chief J. E. Curry, by an unknown author #2]

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    Report to Chief J. E. Curry, by an unknown author. The report contains a list of officers who gave depositions to the United States Attorney

    Murder on the mountain: author talk with Peter J. Wosh

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    Author talk by Peter J. Wosh on May 5th, 2022, on his book, "Murder on the Mountain: crime, passion, and punishment in gilded age New Jersey.

    Mr. Melvin J. Collier, RWWL AUC, June 2011

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    This video is a conversation with Mr. Melvin J. Collier. Mr. Collier talks about his book, "From Mississippi to Africa: A Journey of Discovery". Daniel Le, AUC Woodruff Library, is the interviewer

    A Tripartite Post-Recession Rebalancing

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    In this latest Advance & Rutgers Report, entitled “A Tripartite Post-Recession Rebalancing,” Dean James W. Hughes and Professor Joseph J. Seneca deliver an incisive assessment of the current market conditions and obstacles in the path of our economic recovery. They offer a statistical cautionary tale that the private and public sector need to hear and acknowledge in order for the economy to make continued progress.This report was published as Issue Paper Number 7, November 2011, in Advance & Rutgers Report

    Evidence for the decay B0→J/ψω and measurement of the relative branching fractions of meson decays to J/ψη and J/ψη′

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    First evidence of the B 0 → J / ψ ω decay is found and the B s 0 → J / ψ η and B s 0 → J / ψ η ′ decays are studied using a dataset corresponding to an integrated luminosity of 1.0 fb -1 collected by the LHCb experiment in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV. The branching fractions of these decays are measured relative to that of the B 0 → J / ψ ρ 0 decay:frac(B (B 0 → J / ψ ω), B (B 0 → J / ψ ρ 0)) = 0.89 ± 0.19 (stat) - 0.13 + 0.07 (syst),frac(B (B s 0 → J / ψ η), B (B 0 → J / ψ ρ 0)) = 14.0 ± 1.2 (stat) - 1.5 + 1.1 (syst) - 1.0 + 1.1 (frac(f d, f s)),frac(B (B s 0 → J / ψ η ′), B (B 0 → J / ψ ρ 0)) = 12.7 ± 1.1 (stat) - 1.3 + 0.5 (syst) - 0.9 + 1.0 (frac(f d, f s)), where the last uncertainty is due to the knowledge of f d / f s, the ratio of b-quark hadronization factors that accounts for the different production rate of B 0 and B s 0 mesons. The ratio of the branching fractions of B s 0 → J / ψ η ′ and B s 0 → J / ψ η decays is measured to befrac(B (B s 0 → J / ψ η ′), B (B s 0 → J / ψ η)) = 0.90 ± 0.09 (stat) - 0.02 + 0.06 (syst)

    The vanishing author in computer-generated works: a critical analysis of recent Australian case law

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    Abstract The use of software is ubiquitous in the creation of many copyright works, yet the requirement in copyright law that every work have a human author who engages in independent intellectual effort means that its use may prevent copyright subsistence. Several recent Australian cases have refocused attention on authorship as an essential criterion of copyright subsistence, and these cases suggest that much computer-produced output may be authorless and thus lack copyright protection. This article, the first in a two-part series, analyses how each case deals with the question of authorship of computer-produced works and why the use of software diminishes copyright protection for a significant number of computer-generated works. The article critiques the application of conventional notions of human authorship developed in the pre-computer age to modern productions and suggests alternative approaches to authorship that satisfy both the major objectives of copyright policy and the need to adapt to the computer age. The article argues that, without a broader judicial approach to authorship of computer-generated works, Parliament must remedy the lacuna in protection for these ‘authorless’ works. Possible solutions for reform are suggested. In a forthcoming article, the author comprehensively examines those reform proposals

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    [Newspaper Clipping: Author Claims Evidence of Second JFK Assassin #1]

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    Newspaper article titled "Author Claims Evidence of Second JFK Assassin." The article states that author Richard J. Whalen concluded "that there is circumstantial evidence to support the theory of a second assassin in the shooting of President John F. Kennedy.
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