169 research outputs found

    Extreme Plasma Astrophysics

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    This is a science white paper submitted to the Astro-2020 and Plasma-2020 Decadal Surveys. The paper describes the present status and emerging opportunities in Extreme Plasma Astrophysics -- a study of astrophysically-relevant plasma processes taking place under extreme conditions that necessitate taking into account relativistic, radiation, and QED effects.Comment: A science white paper submitted to the Astro-2020 and Plasma-2020 Decadal Surveys. 7 pages including cover page and references. Paper updated in late March 2019 to include a several additional co-authors and references, and a few small change

    Enhancement by postfiltering for speech and audio coding in ad-hoc sensor networks

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    Enhancement algorithms for wireless acoustics sensor networks~(WASNs) are indispensable with the increasing availability and usage of connected devices with microphones. Conventional spatial filtering approaches for enhancement in WASNs approximate quantization noise with an additive Gaussian distribution, which limits performance due to the non-linear nature of quantization noise at lower bitrates. In this work, we propose a postfilter for enhancement based on Bayesian statistics to obtain a multidevice signal estimate, which explicitly models the quantization noise. Our experiments using PSNR, PESQ and MUSHRA scores demonstrate that the proposed postfilter can be used to enhance signal quality in ad-hoc sensor networks

    Structural Elucidation and Functional Characterization of the Hyaloperonospora arabidopsidis Effector Protein ATR13

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    The oomycete Hyaloperonospora arabidopsidis (Hpa) is the causal agent of downy mildew on the model plant Arabidopsis thaliana and has been adapted as a model system to investigate pathogen virulence strategies and plant disease resistance mechanisms. Recognition of Hpa infection occurs when plant resistance proteins (R-genes) detect the presence or activity of pathogen-derived protein effectors delivered to the plant host. This study examines the Hpa effector ATR13 Emco5 and its recognition by RPP13-Nd, the cognate R-gene that triggers programmed cell death (HR) in the presence of recognized ATR13 variants. Herein, we use NMR to solve the backbone structure of ATR13 Emco5, revealing both a helical domain and a disordered internal loop. Additionally, we use site-directed and random mutagenesis to identify several amino acid residues involved in the recognition response conferred by RPP13-Nd. Using our structure as a scaffold, we map these residues to one of two surface-exposed patches of residues under diversifying selection. Exploring possible roles of the disordered region within the ATR13 structure, we perform domain swapping experiments and identify a peptide sequence involved in nucleolar localization. We conclude that ATR13 is a highly dynamic protein with no clear structural homologues that contains two surface-exposed patches of polymorphism, only one of which is involved in RPP13-Nd recognition specificity

    Exploiting bacterial DNA gyrase as a drug target: current state and perspectives

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    DNA gyrase is a type II topoisomerase that can introduce negative supercoils into DNA at the expense of ATP hydrolysis. It is essential in all bacteria but absent from higher eukaryotes, making it an attractive target for antibacterials. The fluoroquinolones are examples of very successful gyrase-targeted drugs, but the rise in bacterial resistance to these agents means that we not only need to seek new compounds, but also new modes of inhibition of this enzyme. We review known gyrase-specific drugs and toxins and assess the prospects for developing new antibacterials targeted to this enzyme

    High Confidence Prediction of Essential Genes in Burkholderia Cenocepacia

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    BACKGROUND: Essential genes are absolutely required for the survival of an organism. The identification of essential genes, besides being one of the most fundamental questions in biology, is also of interest for the emerging science of synthetic biology and for the development of novel antimicrobials. New antimicrobial therapies are desperately needed to treat multidrug-resistant pathogens, such as members of the Burkholderia cepacia complex. METHODOLOGY/PRINCIPAL FINDINGS: We hypothesize that essential genes may be highly conserved within a group of evolutionary closely related organisms. Using a bioinformatics approach we determined that the core genome of the order Burkholderiales consists of 649 genes. All but two of these identified genes were located on chromosome 1 of Burkholderia cenocepacia. Although many of the 649 core genes of Burkholderiales have been shown to be essential in other bacteria, we were also able to identify a number of novel essential genes present mainly, or exclusively, within this order. The essentiality of some of the core genes, including the known essential genes infB, gyrB, ubiB, and valS, as well as the so far uncharacterized genes BCAL1882, BCAL2769, BCAL3142 and BCAL3369 has been confirmed experimentally in B. cenocepacia. CONCLUSIONS/SIGNIFICANCE: We report on the identification of essential genes using a novel bioinformatics strategy and provide bioinformatics and experimental evidence that the large majority of the identified genes are indeed essential. The essential genes identified here may represent valuable targets for the development of novel antimicrobials and their detailed study may shed new light on the functions required to support life

    Effects of Terminal Dimethylation and Metal Coordination of Proline-2-formylpyridine Thiosemicarbazone Hybrids on Lipophilicity, Antiproliferative Activity, and hR2 RNR Inhibition

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