482 research outputs found
Stochastic model for nucleosome sliding in the presence of DNA ligands
Heat-induced mobility of nucleosomes along DNA is an experimentally
well-studied phenomenon. A recent experiment shows that the repositioning is
modified in the presence of minor-groove binding DNA ligands. We present here a
stochastic three-state model for the diffusion of a nucleosome along DNA in the
presence of such ligands. It allows us to describe the dynamics and the steady
state of such a motion analytically. The analytical results are in excellent
agreement with numerical simulations of this stochastic process.With this
model, we study the response of a nucleosome to an external force and how it is
affected by the presence of ligands.Comment: 10 pages, 8 figures, submitted to Eur. Phys. J.
Detection and imaging in a random medium: A matrix method to overcome multiple scattering and aberration
We present an imaging technique particularly suited to the detection of a
target embedded in a strongly scattering medium. Classical imaging techniques
based on the Born approximation fail in this kind of configuration because of
multiply scattered echoes and aberration distortions. The experimental set up
we consider uses an array of programmable transmitters/receivers. A target is
placed behind a scattering medium. The impulse responses between all array
elements are measured and form a matrix. The core of the method is to separate
the single-scattered echo of the target from the multiple scattering
background. This is possible because of a deterministic coherence along the
antidiagonals of the array response matrix, which is typical of single
scattering. Once this operation is performed, target detection is achieved by
applying the DORT method (French acronym for decomposition of the time reversal
operator). Experimental results are presented in the case of wide-band
ultrasonic waves around 3 MHz. A 125-element array is placed in front of a
collection of randomly distributed steel rods (diameter 0.8mm). The slab
thickness is three times the scattering mean free path. The target is a larger
steel cylinder (diameter 15 mm) that we try to detect and localize. The quality
of detection is assessed theoretically based on random matrix theory and is
shown to be significantly better than what is obtained with classical imaging
methods. Aside from multiple scattering, the technique is also shown to reduce
the aberrations induced by an heterogeneous layer.Comment: 48 pages, 18 figures, corrected typos, v
Capturing systematically users' experience of evaluation tools for integrated AMU and AMR surveillance
Tackling antimicrobial resistance (AMR) is a goal for many countries. Integrated surveillance of antimicrobial use (AMU) and resistance is a prerequisite for effective risk mitigation. Regular evaluation of any surveillance is needed to ensure its effectiveness and efficiency. The question is how to evaluate specifically integrated surveillance for AMU and AMR. In an international network called CoEvalAMR, we have developed guidelines for selection of the most appropriate tools for such an evaluation. Moreover, we have assessed different evaluation tools as examples using a country case format and a methodology with a focus on the user's experience. This paper describes the updated methodology, which consists of a brief introduction to the case and to the tool separately. Moreover, there are 12 functional aspects and nine content themes which should be scored using a 4-tiered scale. Additionally, four Strengths, Weaknesses, Opportunities, Threats (SWOT) questions should be addressed. Results are illustrated using radar diagrams. An example of application of the updated methodology is given using the ECoSur evaluation tool. No tool can cover all evaluation aspects comprehensively in a user-friendly manner, so the choice of tool must be based upon the specific evaluation purpose. Moreover, adequate resources, time and training are needed to obtain useful outputs from the evaluation. Our updated methodology can be used by tool users to share their experience with available tools, and hereby assist other users in identifying the most suited tool for their evaluation purpose. Additionally, tool developers can get valuable information for further improvements of their tool
In vivo antiviral efficacy of prenylation inhibitors against hepatitis delta virus
Hepatitis delta virus (HDV) can dramatically worsen liver disease in patients coinfected with hepatitis B virus (HBV). No effective medical therapy exists for HDV. The HDV envelope requires HBV surface antigen proteins provided by HBV. Once inside a cell, however, HDV can replicate its genome in the absence of any HBV gene products. In vitro, HDV virion assembly is critically dependent on prenyl lipid modification, or prenylation, of its nucleocapsid-like protein large delta antigen. To overcome limitations of current animal models and to test the hypothesis that pharmacologic prenylation inhibition can prevent the production of HDV virions in vivo, we established a convenient mouse-based model of HDV infection capable of yielding viremia. Such mice were then treated with the prenylation inhibitors FTI-277 and FTI-2153. Both agents were highly effective at clearing HDV viremia. As expected, HDV inhibition exhibited duration-of-treatment dependence. These results provide the first preclinical data supporting the in vivo efficacy of prenylation inhibition as a novel antiviral therapy with potential application to HDV and a wide variety of other viruses
QUBIC: The QU Bolometric Interferometer for Cosmology
One of the major challenges of modern cosmology is the detection of B-mode
polarization anisotropies in the CMB. These originate from tensor fluctuations
of the metric produced during the inflationary phase. Their detection would
therefore constitute a major step towards understanding the primordial
Universe. The expected level of these anisotropies is however so small that it
requires a new generation of instruments with high sensitivity and extremely
good control of systematic effects. We propose the QUBIC instrument based on
the novel concept of bolometric interferometry, bringing together the
sensitivity advantages of bolometric detectors with the systematics effects
advantages of interferometry. Methods: The instrument will directly observe the
sky through an array of entry horns whose signals will be combined together
using an optical combiner. The whole set-up is located inside a cryostat.
Polarization modulation will be achieved using a rotating half-wave plate and
interference fringes will be imaged on two focal planes (separated by a
polarizing grid) tiled with bolometers. We show that QUBIC can be considered as
a synthetic imager, exactly similar to a usual imager but with a synthesized
beam formed by the array of entry horns. Scanning the sky provides an
additional modulation of the signal and improve the sky coverage shape. The
usual techniques of map-making and power spectrum estimation can then be
applied. We show that the sensitivity of such an instrument is comparable with
that of an imager with the same number of horns. We anticipate a low level of
beam-related systematics thanks to the fact that the synthesized beam is
determined by the location of the primary horns. Other systematics should be
under good control thanks to an autocalibration technique, specific to our
concept, that will permit the accurate determination of most of the systematics
parameters.Comment: 12 pages, 10 figures, submitted to Astronomy and Astrophysic
Cholinesterase Inhibitors and Hospitalization for Bradycardia: A Population-Based Study
Laura Park-Wyllie and colleagues examined the health records of more than 1.4 million older adults and show that initiation of cholinesterase inhibitor therapy is associated with a more than doubling of the risk of hospitalization for bradycardia
Multiple Beneficial Health Effects of Natural Alkylglycerols from Shark Liver Oil
Alkylglycerols (alkyl-Gro) are ether lipids abundant in the liver of some elasmobranch fish species such as ratfishes and some sharks. Shark liver oil from Centrophorus squamosus (SLO), or alkyl-Gro mix from this source, have several in vivo biological activities including stimulation of hematopoiesis and immunological defences, sperm quality improvement, or anti-tumor and anti-metastasis activities. Several mechanisms are suggested for these multiple activities, resulting from incorporation of alkyl-Gro into membrane phospholipids, and lipid signaling interactions. Natural alkyl-Gro mix from SLO contains several alkyl-Gro, varying by chain length and unsaturation. Six prominent constituents of natural alkyl-Gro mix, namely 12:0, 14:0, 16:0, 18:0, 16:1 n-7, and 18:1 n-9 alkyl-Gro, were synthesized and tested for anti-tumor and anti-metastatic activities on a model of grafted tumor in mice (3LL cells). 16:1 and 18:1 alkyl-Gro showed strong activity in reducing lung metastasis number, while saturated alkyl- Gro had weaker (16:0) or no (12:0, 14:0, 18:0) effect. Multiple compounds and mechanisms are probably involved in the multiple activities of natural alkyl-Gro
QUBIC: The Q&U Bolometric Interferometer for Cosmology - A novel way to look at the polarized Cosmic Microwave Background
In this paper we describe QUBIC, an experiment that takes up the challenge posed by the detection of primordial gravitational waves with a novel approach, that combines the sensitivity of state-of-the art bolometric detectors with the systematic effects control typical of interferometers. The so-called "self-calibration" is a technique deeply rooted in the interferometric nature of the instrument and allows us to clean the measured data from instrumental effects. The first module of QUBIC is a dual band instrument (150 GHz and 220 GHz) that will be deployed in Argentina during the Fall 2018.Fil: Mennella, Aniello. University of Milan; ItaliaFil: Ade, P. A. R.. Cardiff University; Reino UnidoFil: Aumont, J.. Institut d'Astrophysique Spatiale; FranciaFil: Banfie, S.. Istituto Nazionale Di Fisica Nucleare; ItaliaFil: Battaglia, P.. Università degli Studi di Trieste; ItaliaFil: Battistelli, E. S.. Università degli Studi di Roma "La Sapienza"; ItaliaFil: Baùe, F.. Istituto Nazionale Di Fisica Nucleare; ItaliaFil: Buzi, D.. Università degli Studi di Roma "La Sapienza"; ItaliaFil: Columbro, F.. Università degli Studi di Roma "La Sapienza"; ItaliaFil: Bélie, B.. Institute of Fundamental Electronics; FranciaFil: Bennett, D.. Maynooth University; IrlandaFil: Bergé, L.. Centre de Sciences Nucléaires et de Sciences de la Matière; FranciaFil: Bernard, J. Ph.. Institut de Recherche en Astrophysique et Planétologie; FranciaFil: Bersanelli, M.. University of Milan; ItaliaFil: Bigot Sazy, M. A.. APC; FranciaFil: Bleurvacq, N.. APC; FranciaFil: Bordier, G.. APC; FranciaFil: Brossard, J.. APC; FranciaFil: Bunn, E. F.. Richmond University; Estados UnidosFil: Burke, D. P.. Maynooth University; IrlandaFil: Buzi, D.. Università degli Studi di Roma "La Sapienza"; ItaliaFil: Buzzelli, A.. Universita Tor Vergata; ItaliaFil: Cammilleri, D.. APC; FranciaFil: Cavaliere, F.. University of Milan; ItaliaFil: Chanial, P.. APC; FranciaFil: Etchegoyen, Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Harari, Diego Dario. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Medina, Maria Clementina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Romero, Gustavo Esteban. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Suarez, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaThe European Physical Society Conference on High Energy PhysicsVeneciaItaliaEuropean Physical Societ
Partitioning the Proteome: Phase Separation for Targeted Analysis of Membrane Proteins in Human Post-Mortem Brain
Neuroproteomics is a powerful platform for targeted and hypothesis driven research, providing comprehensive insights into cellular and sub-cellular disease states, Gene × Environmental effects, and cellular response to medication effects in human, animal, and cell culture models. Analysis of sub-proteomes is becoming increasingly important in clinical proteomics, enriching for otherwise undetectable proteins that are possible markers for disease. Membrane proteins are one such sub-proteome class that merit in-depth targeted analysis, particularly in psychiatric disorders. As membrane proteins are notoriously difficult to analyse using traditional proteomics methods, we evaluate a paradigm to enrich for and study membrane proteins from human post-mortem brain tissue. This is the first study to extensively characterise the integral trans-membrane spanning proteins present in human brain. Using Triton X-114 phase separation and LC-MS/MS analysis, we enriched for and identified 494 membrane proteins, with 194 trans-membrane helices present, ranging from 1 to 21 helices per protein. Isolated proteins included glutamate receptors, G proteins, voltage gated and calcium channels, synaptic proteins, and myelin proteins, all of which warrant quantitative proteomic investigation in psychiatric and neurological disorders. Overall, our sub-proteome analysis reduced sample complexity and enriched for integral membrane proteins by 2.3 fold, thus allowing for more manageable, reproducible, and targeted proteomics in case vs. control biomarker studies. This study provides a valuable reference for future neuroproteomic investigations of membrane proteins, and validates the use Triton X-114 detergent phase extraction on human post mortem brain
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