ИНДИВИДУАЛЬНЫЙ ПОДХОД К ПРИМЕНЕНИЮ АНТИТРОМБОЦИТАРНОЙ ТЕРАПИИ. НА ЧТО ОПЕРЕТЬСЯ В РЕШЕНИИ?

Use of antiplatelet therapy in the world indicates real difference in individual drug effect between patients, including the effect on prognosis. Problems of personification of individual approach, concerning antiplatelet therapy, are discussed.Опыт применения антиагрегантной терапии указывает на существенную разницу в реакции больных на антиагреганты, вызывающую различия в выраженности эффекта терапии по влиянию на исходы заболевания. Обсуждены проблемы индивидуального подхода в антиагрегантной терапии

Status of ART-XC/SRG Instrument

Spectrum Roentgen Gamma (SRG) is an X-ray astrophysical observatory, developed by Russia in collaboration with Germany. The mission will be launched in March 2016 from Baikonur, by a Zenit rocket with a Fregat booster and placed in a 6-month-period halo orbit around L2. The scientific payload consists of two independent telescopes - a soft-x-ray survey instrument, eROSITA, being provided by Germany and a medium-x-ray-energy survey instrument ART-XC being developed by Russia. ART-XC will consist of seven independent, but co-aligned, telescope modules. The NASA Marshall Space Flight Center (MSFC) is fabricating the flight mirror modules for the ART-XC/SRG. Each mirror module will be aligned with a focal plane CdTe double-sided strip detectors which will operate over the energy range of 6-30 keV, with an angular resolution of less than 1, a field of view of approximately 34 and an expected energy resolution of about 10 percent at 14 keV

Characterization of Oligomers of Heterogeneous Size as Precursors of Amyloid Fibril Nucleation of an SH3 Domain: An Experimental Kinetics Study

Correction: Characterization of Oligomers of Heterogeneous Size as Precursors of Amyloid Fibril Nucleation of an SH3 Domain: An Experimental Kinetics Study. PLoS ONE 9(1): 10.1371/annotation/dbb84118-9ada-43e4-8734-8f8322be1a59. doi: 10.1371/annotation/dbb84118-9ada-43e4-8734-8f8322be1a59Understanding the earliest molecular events during nucleation of the amyloid aggregation cascade is of fundamental significance to prevent amyloid related disorders. We report here an experimental kinetic analysis of the amyloid aggregation of the N47A mutant of the α-spectrin SH3 domain (N47A Spc-SH3) under mild acid conditions, where it is governed by rapid formation of amyloid nuclei. The initial rates of formation of amyloid structures, monitored by thioflavine T fluorescence at different protein concentrations, agree quantitatively with high-order kinetics, suggesting an oligomerization pre-equilibrium preceding the rate-limiting step of amyloid nucleation. The curves of native state depletion also follow high-order irreversible kinetics. The analysis is consistent with the existence of low-populated and heterogeneous oligomeric precursors of fibrillation that form by association of partially unfolded protein monomers. An increase in NaCl concentration accelerates fibrillation but reduces the apparent order of the nucleation kinetics; and a double mutant (K43A, N47A) Spc-SH3 domain, largely unfolded under native conditions and prone to oligomerize, fibrillates with apparent first order kinetics. On the light of these observations, we propose a simple kinetic model for the nucleation event, in which the monomer conformational unfolding and the oligomerization of an amyloidogenic intermediate are rapidly pre-equilibrated. A conformational change of the polypeptide chains within any of the oligomers, irrespective of their size, is the rate-limiting step leading to the amyloid nuclei. This model is able to explain quantitatively the initial rates of aggregation and the observed variations in the apparent order of the kinetics and, more importantly, provides crucial thermodynamic magnitudes of the processes preceding the nucleation. This kinetic approach is simple to use and may be of general applicability to characterize the amyloidogenic intermediates and oligomeric precursors of other disease-related proteins.This work was financed by the Andalucía Government (grant FQM-02838), the Spanish Ministry of Science and Innovation (grant BIO2009-07317), and the European Regional Development Fund of the European Union. D. Ruzafa is recipient of a research fellowship from the F.P.U. program of the Spanish Ministry of Education. L. Varela is financed by the G.R.E.I.B. program of the University of Granada

Hadron Energy Reconstruction for the ATLAS Calorimetry in the Framework of the Non-parametrical Method

This paper discusses hadron energy reconstruction for the ATLAS barrel prototype combined calorimeter (consisting of a lead-liquid argon electromagnetic part and an iron-scintillator hadronic part) in the framework of the non-parametrical method. The non-parametrical method utilizes only the known $e/h$ ratios and the electron calibration constants and does not require the determination of any parameters by a minimization technique. Thus, this technique lends itself to an easy use in a first level trigger. The reconstructed mean values of the hadron energies are within $\pm 1$ of the true values and the fractional energy resolution is $[(58\pm3)/\sqrt{E}+(2.5\pm0.3)$. The value of the $e/h$ ratio obtained for the electromagnetic compartment of the combined calorimeter is $1.74\pm0.04$ and agrees with the prediction that $e/h > 1.7$ for this electromagnetic calorimeter. Results of a study of the longitudinal hadronic shower development are also presented. The data have been taken in the H8 beam line of the CERN SPS using pions of energies from 10 to 300 GeV.Comment: 33 pages, 13 figures, Will be published in NIM

The Cryo-EM Structure of a Complete 30S Translation Initiation Complex from Escherichia coli

Formation of the 30S initiation complex (30S IC) is an important checkpoint in regulation of gene expression. The selection of mRNA, correct start codon, and the initiator fMet-tRNAfMet requires the presence of three initiation factors (IF1, IF2, IF3) of which IF3 and IF1 control the fidelity of the process, while IF2 recruits fMet-tRNAfMet. Here we present a cryo-EM reconstruction of the complete 30S IC, containing mRNA, fMet-tRNAfMet, IF1, IF2, and IF3. In the 30S IC, IF2 contacts IF1, the 30S subunit shoulder, and the CCA end of fMet-tRNAfMet, which occupies a novel P/I position (P/I1). The N-terminal domain of IF3 contacts the tRNA, whereas the C-terminal domain is bound to the platform of the 30S subunit. Binding of initiation factors and fMet-tRNAfMet induces a rotation of the head relative to the body of the 30S subunit, which is likely to prevail through 50S subunit joining until GTP hydrolysis and dissociation of IF2 take place. The structure provides insights into the mechanism of mRNA selection during translation initiation

The ART-XC telescope on board the SRG observatory

ART-XC (Astronomical Roentgen Telescope - X-ray Concentrator) is the hard X-ray instrument with grazing incidence imaging optics on board the Spektr-Roentgen-Gamma (SRG) observatory. The SRG observatory is the flagship astrophysical mission of the Russian Federal Space Program, which was successively launched into orbit around the second Lagrangian point (L2) of the Earth-Sun system with a Proton rocket from the Baikonur cosmodrome on 13 July 2019. The ART-XC telescope will provide the first ever true imaging all-sky survey performed with grazing incidence optics in the 4-30 keV energy band and will obtain the deepest and sharpest map of the sky in the energy range of 4-12 keV. Observations performed during the early calibration and performance verification phase as well as during the on-going all-sky survey that started on 12 Dec. 2019 have demonstrated that the in-flight characteristics of the ART-XC telescope are very close to expectations based on the results of ground calibrations. Upon completion of its 4-year all-sky survey, ART-XC is expected to detect ~5000 sources (~3000 active galactic nuclei, including heavily obscured ones, several hundred clusters of galaxies, ~1000 cataclysmic variables and other Galactic sources), and to provide a high-quality map of the Galactic background emission in the 4-12 keV energy band. ART-XC is also well suited for discovering transient X-ray sources. In this paper, we describe the telescope, results of its ground calibrations, major aspects of the mission, the in-flight performance of ART-XC and first scientific results.Comment: 19 pages, 30 figures, accepted for publication in Astronomy and Astrophysic

The eROSITA X-ray telescope on SRG

eROSITA (extended ROentgen Survey with an Imaging Telescope Array) is the primary instrument on the Spectrum-Roentgen-Gamma (SRG) mission, which was successfully launched on July 13, 2019, from the Baikonour cosmodrome. After the commissioning of the instrument and a subsequent calibration and performance verification phase, eROSITA started a survey of the entire sky on December 13, 2019. By the end of 2023, eight complete scans of the celestial sphere will have been performed, each lasting six months. At the end of this program, the eROSITA all-sky survey in the soft X-ray band (0.2-2.3 keV) will be about 25 times more sensitive than the ROSAT All-Sky Survey, while in the hard band (2.3-8 keV) it will provide the first ever true imaging survey of the sky. The eROSITA design driving science is the detection of large samples of galaxy clusters up to redshifts z > 1 in order to study the large-scale structure of the universe and test cosmological models including Dark Energy. In addition, eROSITA is expected to yield a sample of a few million AGNs, including obscured objects, revolutionizing our view of the evolution of supermassive black holes. The survey will also provide new insights into a wide range of astrophysical phenomena, including X-ray binaries, active stars, and diffuse emission within the Galaxy. Results from early observations, some of which are presented here, confirm that the performance of the instrument is able to fulfil its scientific promise. With this paper, we aim to give a concise description of the instrument, its performance as measured on ground, its operation in space, and also the first results from in-orbit measurements

The ART-XC Instrument on Board the SRG Mission

Spectrum Roentgen Gamma (SRG) is an X-ray astrophysical observatory, developed by Russia in collaboration with Germany. The mission will be launched in 2014 from Baikonur, by a Zenit rocket with a Fregat booster and placed in a 6-month-period halo orbit around L2. The scientific payload consists of two independent telescopes . a soft-x-ray survey instrument, eROSITA, being provided by Germany and a medium-x-ray-energy survey instrument ART-XC being developed by Russia. ART-XC will consist of seven independent, but co-aligned, telescope modules with seven corresponding cadmium-telluride focal plane detectors. Each will operate over the approximate energy range of 6- 30 keV, with an angular resolution of <1 ', a field of view of ~30 ' and an energy resolution about 10% at 14 keV. The NASA Marshall Space Flight Center (MSFC) will fabricate some of the mirror modules, to complement others fabricated by VNIIEF in Russia

Design, Construction and Installation of the ATLAS Hadronic Barrel Scintillator-Tile Calorimeter

The scintillator tile hadronic calorimeter is a sampling calorimeter using steel as the absorber structure and scintillator as the active medium. The scintillator is located in "pockets" in the steel structure and the wavelength-shifting fibers are contained in channels running radially within the absorber to photomultiplier tubes which are located in the outer support girders of the calorimeter structure. In addition, to its role as a detector for high energy particles, the tile calorimeter provides the direct support of the liquid argon electromagnetic calorimeter in the barrel region, and the liquid argon electromagnetic and hadronic calorimeters in the endcap region. Through these, it indirectly supports the inner tracking system and beam pipe. The steel absorber, and in particular the support girders, provide the flux return for the solenoidal field from the central solenoid. Finally, the end surfaces of the barrel calorimeter are used to mount services, power supplies and readout crates for the inner tracking systems and the liquid argon barrel electromagnetic calorimeter