170 research outputs found

    Poly(ADP-ribose)glycohydrolase is an upstream regulator of Ca2+ fluxes in oxidative cell death

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    Oxidative DNA damage to cells activates poly(ADP-ribose)polymerase-1 (PARP-1) and the poly(ADP-ribose) formed is rapidly degraded to ADP-ribose by poly(ADP-ribose)glycohydrolase (PARG). Here we show that PARP-1 and PARG control extracellular Ca2+ fluxes through melastatin-like transient receptor potential 2 channels (TRPM2) in a cell death signaling pathway. TRPM2 activation accounts for essentially the entire Ca2+ influx into the cytosol, activating caspases and causing the translocation of apoptosis inducing factor (AIF) from the inner mitochondrial membrane to the nucleus followed by cell death. Abrogation of PARP-1 or PARG function disrupts these signals and reduces cell death. ADP-ribose-loading of cells induces Ca2+ fluxes in the absence of oxidative damage, suggesting that ADP-ribose is the key metabolite of the PARP-1/PARG system regulating TRPM2. We conclude that PARP-1/PARG control a cell death signal pathway that operates between five different cell compartments and communicates via three types of chemical messengers: a nucleotide, a cation, and protein

    Complete Sequences of Multiple-Drug Resistant IncHI2 ST3 Plasmids in Escherichia coli of Porcine Origin in Australia

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    © Copyright © 2019 Wyrsch, Reid, DeMaere, Liu, Chapman, Roy Chowdhury and Djordjevic. IncHI2 ST3 plasmids are known carriers of multiple antimicrobial resistance genes. Complete plasmid sequences from multiple drug resistant Escherichia coli circulating in Australian swine is however limited. Here we sequenced two related IncHI2 ST3 plasmids, pSDE-SvHI2, and pSDC-F2_12BHI2, from phylogenetically unrelated multiple-drug resistant Escherichia coli strains SvETEC (CC23:O157:H19) and F2_12B (ST93:O7:H4) from geographically disparate pig production operations in New South Wales, Australia. Unicycler was used to co-assemble short read (Illumina) and long read (PacBio SMRT) nucleotide sequence data. The plasmids encoded three drug-resistance loci, two of which carried class 1 integrons. One integron, hosting drfA12-orfF-aadA2, was within a hybrid Tn1721/Tn21, with the second residing within a copper/silver resistance transposon, comprising part of an atypical sul3-associated structure. The third resistance locus was flanked by IS15DI and encoded neomycin resistance (neoR). An oqx-encoding transposon (quinolone resistance), similar in structure to Tn6010, was identified only in pSDC-F2_12BHI2. Both plasmids showed high sequence identity to plasmid pSTM6-275, recently described in Salmonella enterica serotype 1,4,[5],12:i:- that has risen to prominence and become endemic in Australia. IncHI2 ST3 plasmids circulating in commensal and pathogenic E. coli from Australian swine belong to a lineage of plasmids often in association with sul3 and host multiple complex antibiotic and metal resistance structures, formed in part by IS26

    An amorphous silicon photodiode array for glass-based optical MEMS application

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    A highly sensitive photo-detector array deposited on a glass substrate with an optional integrated optical filter have been presented. The active element is a vertically integrated hydrogenated amorphous silicon photodiode featuring a dark current of less than 1e-10 A/cm2 for -3V polarization and a maximal quantum efficiency of 80% near 580 nm. The prototype was encapsulated and successfully tested optically. It has a fill factor of only 44% which, however, can be easily increased to 90% using flip-chip bonding to an integrated electronic circuit for signal conditioning. The sensor is biocompatible and can be integrated with other glass-based and glass compatible micro-fabricated devices such as optical, microfluidic, lab-on-a-chip, chemical and biological devices in which photo-detection is a desired feature. ©2009 IEEE

    Modelling wind-driven rain on buildings in urbanized area using 3-D GIS and LiDAR datasets

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    This study investigated the distribution of the fraction of rainfall intercepted by the facades of buildings located in an urbanized area. We used the frequently used semi-empirical standard ISO-15927-3 to simulate Wind-Driven Rain on facades. The implementation of the Norm on a neighbourhood scale required a list of parameters, including building geometry and terrain characteristics. For the first time, we proposed the use of combined 3-D GIS and LiDAR data to retrieve all the information necessary to apply the Norm on a large set of buildings. The proposed methodology was tested on a dense urban area of 242 buildings with a wide range of original features. The distributions of simulated catch ratios per facade were exponentially distributed between 0 and 9%. Results obtained were smaller than those usually identified in the literature. This was in large part explained by two points: (i) the buildings considered are located in a dense urban area where surrounding buildings create an obstruction factor that limits WDR on facades and, (ii) not only are windward facades considered, but also facades located in the dominant wind direction which received almost no rain. Facade orientation is a clear factor that influenced the amount of rainfall in contact with it. Modern GIS techniques are sufficiently advanced to provide the necessary information to assess WDR. However, the accuracy of our conclusion was limited by the inherent simplicity of the Norm, which has potential for improvement in terms of the definition of the obstruction factor and the range of building geometry which it takes into consideration. (c) 2012 Elsevier Ltd. All rights reserved

    Des ennemis héréditaires aux alliés, rapprochement franco-allemand après la Seconde Guerre mondiale

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    法德两国同属欧洲大陆的核心国家,更是当今世界格局中颇具影响力的大国。历史上,两国在不同时期都曾一度称雄欧洲,展现强国风范。当今法国人强烈的民族自豪感源自于他们骄傲的光荣历史。宣称“朕即天下”的路易十四曾大扩法国的疆域,使其成为17世纪欧洲最强大的国家。而拿破仑更是雄心勃勃地继续为法国开疆辟土,其帝国在鼎盛时期一度囊括了整个欧洲大陆。当时的法国比历史上任何国家都更接近于控制整个欧洲。德意志国家一向是推动欧洲历史发展的强大力量。神圣罗马帝国也曾经称霸西欧,而18世纪中后期的普鲁士也被视为欧洲强国。因此法德两国的一举一动都可能对欧洲的未来发展产生深刻影响。与此同时,作为邻国,两国因领土的接壤而被紧密...Comme les pays les plus importants sur le continent européen, la France et l’Allemagne sont tous les grandes puissances à l’échelle mondiale. Elles se disputaient l’hégémonie de l’Europe dans les différentes périodes de l’histoire européenne. La grande fierté nationale actuelle des Français dérive de l’histoire glorieuse de la France. A l’époque de Louis XIV, le territoire français e...学位:文学硕士院系专业:外文学院欧洲语言文学系_法语语言文学学号:1212006115035

    Thin-film silicon detectors for particle detection

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    Integrated particle sensors have been developed using thin-film on ASIC technology. For this purpose, hydrogenated amorphous silicon diodes, in various configurations, have been optimized for particle detection. These devices were first deposited on glass substrates to optimize the material properties and the dark current of very thick diodes (with thickness up to 50 μm). Corresponding diodes were later directly deposited on CMOS readout chips. These integrated particle sensors have been characterized using light pulse illumination and beta particle irradiation from 63Ni and 90Sr sources. Direct detection of single low- and high-energy beta particles have been demonstrated. The application of this new integrated particle sensor concept for medical imaging is also discussed
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