92 research outputs found

    Double Exchange Alone Does Not Explain the Resistivity of La1xSrxMnO3La_{1-x} Sr_x MnO_3

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    The La1xSrxMnO3La_{1-x} Sr_x MnO_3 system with 0.2x0.40.2 \lesssim x \lesssim 0.4 has traditionally been modelled with a ``double exchange'' Hamiltonian, in which it is assumed that the only relevant physics is the tendency of carrier hopping to line up neighboring spins. We present a solution of the double exchange model, show it is incompatible with many aspects of the resistivity data, and propose that a strong electron-phonon interaction arising from a Jahn-Teller splitting of the outer Mn d-level plays a crucial role.Comment: Figure available via concentional mail. Contact [email protected]

    Stochastic Model for Surface Erosion Via Ion-Sputtering: Dynamical Evolution from Ripple Morphology to Rough Morphology

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    Surfaces eroded by ion-sputtering are sometimes observed to develop morphologies which are either ripple (periodic), or rough (non-periodic). We introduce a discrete stochastic model that allows us to interpret these experimental observations within a unified framework. We find that a periodic ripple morphology characterizes the initial stages of the evolution, whereas the surface displays self-affine scaling in the later time regime. Further, we argue that the stochastic continuum equation describing the surface height is a noisy version of the Kuramoto-Sivashinsky equation.Comment: 4 pages, 7 postscript figs., Revtex, to appear in Phys. Rev. Let

    The Concussion Recognition Tool 5th Edition (CRT5): Background and rationale

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    The Concussion Recognition Tool 5 (CRT5) is the most recent revision of the Pocket Sport Concussion Assessment Tool 2 that was initially introduced by the Concussion in Sport Group in 2005. The CRT5 is designed to assist non-medically trained individuals to recognise the signs and symptoms of possible sport-related concussion and provides guidance for removing an athlete from play/sport and to seek medical attention. This paper presents the development of the CRT5 and highlights the differences between the CRT5 and prior versions of the instrument

    Multi-omics analyses reveal ClpP activators disrupt essential mitochondrial pathways in triple-negative breast cancer

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    ClpP activators ONC201 and related small molecules (TR compounds, Madera Therapeutics), have demonstrated significant anti-cancer potential in vitro and in vivo studies, including clinical trials for refractory solid tumors. Though progress has been made in identifying specific phenotypic outcomes following ClpP activation, the exact mechanism by which ClpP activation leads to broad anti-cancer activity has yet to be fully elucidated. In this study, we utilized a multi-omics approach to identify the ClpP-dependent proteomic, transcriptomic, and metabolomic changes resulting from ONC201 or the TR compound TR-57 in triple-negative breast cancer cells. Applying mass spectrometry-based methods of proteomics and metabolomics, we identified ∼8,000 proteins and 588 metabolites, respectively. From proteomics data, 113 (ONC201) and 191 (TR-57) proteins significantly increased and 572 (ONC201) and 686 (TR-57) proteins significantly decreased in this study. Gene ontological (GO) analysis revealed strong similarities between proteins up- or downregulated by ONC201 or TR-57 treatment. Notably, this included the downregulation of many mitochondrial processes and proteins, including mitochondrial translation and mitochondrial matrix proteins. We performed a large-scale transcriptomic analysis of WT SUM159 cells, identifying ∼7,700 transcripts (746 and 1,100 significantly increasing, 795 and 1,013 significantly decreasing in ONC201 and TR-57 treated cells, respectively). Less than 21% of these genes were affected by these compounds in ClpP null cells. GO analysis of these data demonstrated additional similarity of response to ONC201 and TR-57, including a decrease in transcripts related to the mitochondrial inner membrane and matrix, cell cycle, and nucleus, and increases in other nuclear transcripts and transcripts related to metal-ion binding. Comparison of response between both compounds demonstrated a highly similar response in all -omics datasets. Analysis of metabolites also revealed significant similarities between ONC201 and TR-57 with increases in α-ketoglutarate and 2-hydroxyglutaric acid and decreased ureidosuccinic acid, L-ascorbic acid, L-serine, and cytidine observed following ClpP activation in TNBC cells. Further analysis identified multiple pathways that were specifically impacted by ClpP activation, including ATF4 activation, heme biosynthesis, and the citrulline/urea cycle. In summary the results of our studies demonstrate that ONC201 and TR-57 induce highly similar and broad effects against multiple mitochondrial processes required for cell proliferation

    Phenotype Sequencing: Identifying the Genes That Cause a Phenotype Directly from Pooled Sequencing of Independent Mutants

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    Random mutagenesis and phenotype screening provide a powerful method for dissecting microbial functions, but their results can be laborious to analyze experimentally. Each mutant strain may contain 50–100 random mutations, necessitating extensive functional experiments to determine which one causes the selected phenotype. To solve this problem, we propose a “Phenotype Sequencing” approach in which genes causing the phenotype can be identified directly from sequencing of multiple independent mutants. We developed a new computational analysis method showing that 1. causal genes can be identified with high probability from even a modest number of mutant genomes; 2. costs can be cut many-fold compared with a conventional genome sequencing approach via an optimized strategy of library-pooling (multiple strains per library) and tag-pooling (multiple tagged libraries per sequencing lane). We have performed extensive validation experiments on a set of E. coli mutants with increased isobutanol biofuel tolerance. We generated a range of sequencing experiments varying from 3 to 32 mutant strains, with pooling on 1 to 3 sequencing lanes. Our statistical analysis of these data (4099 mutations from 32 mutant genomes) successfully identified 3 genes (acrB, marC, acrA) that have been independently validated as causing this experimental phenotype. It must be emphasized that our approach reduces mutant sequencing costs enormously. Whereas a conventional genome sequencing experiment would have cost 7,200inreagentsalone,ourPhenotypeSequencingdesignyieldedthesameinformationvalueforonly7,200 in reagents alone, our Phenotype Sequencing design yielded the same information value for only 1200. In fact, our smallest experiments reliably identified acrB and marC at a cost of only 110110–340

    Consensus statement on concussion in sport—the 5 th international conference on concussion in sport held in Berlin, October 2016

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    The 2017 Concussion in Sport Group (CISG) consensus statement is designed to build on the principles outlined in the previous statements1–4 and to develop further conceptual understanding of sport-related concussion (SRC) using an expert consensus-based approach. This document is developed for physicians and healthcare providers who are involved in athlete care, whether at a recreational, elite or professional level. While agreement exists on the principal messages conveyed by this document, the authors acknowledge that the science of SRC is evolving and therefore individual management and return-to-play decisions remain in the realm of clinical judgement. This consensus document reflects the current state of knowledge and will need to be modified as new knowledge develops. It provides an overview of issues that may be of importance to healthcare providers involved in the management of SRC. This paper should be read in conjunction with the systematic reviews and methodology paper that accompany it. First and foremost, this document is intended to guide clinical practice; however, the authors feel that it can also help form the agenda for future research relevant to SRC by identifying knowledge gaps

    Resilience of benthic deep-sea fauna to mining activities

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    With increasing demand for mineral resources, extraction of polymetallic sulphides at hydrothermal vents, cobalt-rich ferromanganese crusts at seamounts, and polymetallic nodules on abyssal plains may be imminent. Here, we shortly introduce ecosystem characteristics of mining areas, report on recent mining developments, and identify potential stress and disturbances created by mining. We analyze species' potential resistance to future mining and perform meta-analyses on population density and diversity recovery after disturbances most similar to mining: volcanic eruptions at vents, fisheries on seamounts, and experiments that mimic nodule mining on abyssal plains. We report wide variation in recovery rates among taxa, size, and mobility of fauna. While densities and diversities of some taxa can recover to or even exceed pre-disturbance levels, community composition remains affected after decades. The loss of hard substrata or alteration of substrata composition may cause substantial community shifts that persist over geological timescales at mined sites. (C) 2017 Elsevier Ltd. All rights reserved.European Union Seventh Framework Programme (FP7) under the MIDAS project; FCT [IF/00029/2014/CP1230/CT0002, SFRH/ BPD/110278/2015]; Spanish RTD project NUREIEV [CTM2013-44598-R]; Ministry of Economy and Competitiveness [SGR 1068]; Generalitat de Catalunya autonomous government; European Union Horizon research and innovation programme [689518]; Fundacao para a Ciencia e a Tecnologia [UID/MAR/04292/2013]; German Ministry of Research (BMBF) [03F0707A-G]; Program Investigador FCT [IF/01194/2013/CP1199/CT0002]info:eu-repo/semantics/publishedVersio

    International Olympic Committee consensus statement on pain management in elite athletes

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    Pain is a common problem among elite athletes and is frequently associated with sport injury. Both pain and injury interfere with the performance of elite athletes. There are currently no evidence-based or consensus-based guidelines for the management of pain in elite athletes. Typically, pain management consists of the provision of analgesics, rest and physical therapy. More appropriately, a treatment strategy should address all contributors to pain including underlying pathophysiology, biomechanical abnormalities and psychosocial issues, and should employ therapies providing optimal benefit and minimal harm. To advance the development of a more standardised, evidence-informed approach to pain management in elite athletes, an IOC Consensus Group critically evaluated the current state of the science and practice of pain management in sport and prepared recommendations for a more unified approach to this important topic
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