225 research outputs found
Enhancement by postfiltering for speech and audio coding in ad-hoc sensor networks
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
Extreme Plasma Astrophysics
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
Analysis of the eukaryotic topoisomerase II DNA gate: a single-molecule FRET and structural perspective
Type II DNA topoisomerases (topos) are essential and ubiquitous enzymes that perform important intracellular roles in chromosome condensation and segregation, and in regulating DNA supercoiling. Eukaryotic topo II, a type II topoisomerase, is a homodimeric enzyme that solves topological entanglement problems by using the energy from ATP hydrolysis to pass one segment of DNA through another by way of a reversible, enzyme-bridged double-stranded break. This DNA break is linked to the protein by a phosphodiester bond between the active site tyrosine of each subunit and backbone phosphate of DNA. The opening and closing of the DNA gate, a critical step for strand passage during the catalytic cycle, is coupled to this enzymatic cleavage/religation of the backbone. This reversible DNA cleavage reaction is the target of a number of anticancer drugs, which can elicit DNA damage by affecting the cleavage/religation equilibrium. Because of its clinical importance, many studies have sought to determine the manner in which topo II interacts with DNA. Here we highlight recent single-molecule fluorescence resonance energy transfer and crystallographic studies that have provided new insight into the dynamics and structure of the topo II DNA gate
Observation of Photoion Backward Emission in Photoionization of He and N2
We experimentally investigate the effects of the linear photon momentum on
the momentum distributions of photoions and photoelectrons generated in
one-photon ionization in an energy range of 300 eV 40 keV.
Our results show that for each ionization event the photon momentum is imparted
onto the photoion, which is essentially the system's center of mass.
Nevertheless, the mean value of the ion momentum distribution along the light
propagation direction is backward-directed by times the photon momentum.
These results experimentally confirm a 90 year old prediction.Comment: 5 pages, 3 figure
Structural Insights into the Quinolone Resistance Mechanism of Mycobacterium tuberculosis DNA Gyrase
Mycobacterium tuberculosis DNA gyrase, an indispensable nanomachine involved in the regulation of DNA topology, is the only type II topoisomerase present in this organism and is hence the sole target for quinolone action, a crucial drug active against multidrug-resistant tuberculosis. To understand at an atomic level the quinolone resistance mechanism, which emerges in extensively drug resistant tuberculosis, we performed combined functional, biophysical and structural studies of the two individual domains constituting the catalytic DNA gyrase reaction core, namely the Toprim and the breakage-reunion domains. This allowed us to produce a model of the catalytic reaction core in complex with DNA and a quinolone molecule, identifying original mechanistic properties of quinolone binding and clarifying the relationships between amino acid mutations and resistance phenotype of M. tuberculosis DNA gyrase. These results are compatible with our previous studies on quinolone resistance. Interestingly, the structure of the entire breakage-reunion domain revealed a new interaction, in which the Quinolone-Binding Pocket (QBP) is blocked by the N-terminal helix of a symmetry-related molecule. This interaction provides useful starting points for designing peptide based inhibitors that target DNA gyrase to prevent its binding to DNA
Structural Elucidation and Functional Characterization of the Hyaloperonospora arabidopsidis Effector Protein ATR13
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
High Confidence Prediction of Essential Genes in Burkholderia Cenocepacia
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
Exploiting bacterial DNA gyrase as a drug target: current state and perspectives
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
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