МЕТОДОЛОГИЧЕСКИЕ АСПЕКТЫ РАЗВИТИЯ ДПО В УСЛОВИЯХ ПОСТИНДУСТРИАЛЬНОЙ ЭКОНОМИКИ

The paper considers the methodological aspects which characterize interrelation of cycles of economic activity and models of educational processes. The authors analyze influence of cycles of economic activity on educational processes including: cycles eras of E. Toffler, resource cycles of J. Forrester, century cycles of F. Brodel, formational cycles of M. Evans, big cycles of economic activity of N. D. Kondratyev, intermediateterm cycles of economic activity of S. Kuznets, minor cycles of economic activity of K. Zhuglyar, short business cycles of economic activity J. Kitchina, ultrashort cycles of economic activity of G. Moore. It is shown that in modern conditions of acceleration of scientific and technical progress when duration practically of all cycles of economic activity is reduced, load of the DPO system increases. First of all it concerns training in the technologies connected with short business cycles of J. Kitchina and ultrashort cycles of G. Moore as duration of other types of education in time exceeds life cycle of the specified technologies. It is also shown that in the conditions of saturated market, production personalisation level increases in the system of production (goods, works and services). In the conditions of change of mass and large-lot production by sredneseriyny, smallscale and individual production increases load of the DPO system, including growth of a share of training in small groups and individual training.Рассмотрены методологические аспекты, характеризующие взаимосвязь циклов экономической активности и моделей образовательных процессов. Проанализировано влияние на образовательные процессы циклов экономической активности, включая циклы-эпохи Э. Тоффлера, ресурсные циклы Дж. Форрестера, вековые циклы Ф. Броделя, формационные циклы М. Эванса, большие циклы экономической активности Н. Д. Кондратьева, средние циклы экономической активности С. Кузнеца, малые циклы экономической активности К. Жугляра, короткие бизнес-циклы экономической активности Дж. Китчина, ультракороткие циклы экономической активности Г. Мура. Показано, что в современных условиях ускорения научно-технического прогресса, когда сокращается продолжительность практически всех циклов экономической активности, возрастает нагрузка на систему ДПО. В первую очередь это касается обучения технологиям, связанным с короткими бизнес-циклами Дж. Китчина и ультракороткими циклами Г. Мура, поскольку продолжительность других видов образования превышает жизненный цикл указанных технологий. Также продемонстрировано, что в условиях насыщенного рынка в системе производства продукции (товаров, работ и услуг) возрастает уровень персонализации производства. Смена массового и крупносерийного производства на среднесерийное, мелкосерийное и индивидуальное увеличивает нагрузку на систему ДПО, включая рост доли обучения в малых группах и индивидуального обучения

Comprehensive mapping of tissue cell architecture via integrated single cell and spatial transcriptomics

elocation-id: 2020.11.15.378125elocation-id: 2020.11.15.378125The spatial organization of cell types in tissues fundamentally shapes cellular interactions and function, but the high-throughput spatial mapping of complex tissues remains a challenge. We present сell2location, a principled and versatile Bayesian model that integrates single-cell and spatial transcriptomics to map cell types in situ in a comprehensive manner. We show that сell2location outperforms existing tools in accuracy and comprehensiveness and we demonstrate its utility by mapping two complex tissues. In the mouse brain, we use a new paired single nucleus and spatial RNA-sequencing dataset to map dozens of cell types and identify tissue regions in an automated manner. We discover novel regional astrocyte subtypes including fine subpopulations in the thalamus and hypothalamus. In the human lymph node, we resolve spatially interlaced immune cell states and identify co-located groups of cells underlying tissue organisation. We spatially map a rare pre-germinal centre B-cell population and predict putative cellular interactions relevant to the interferon response. Collectively our results demonstrate how сell2location can serve as a versatile first-line analysis tool to map tissue architectures in a high-throughput manner.Competing Interest StatementThe authors have declared no competing interest

Mediators and biomarkers of inflammation in meningitis: Cytokine and peptidome profiling of cerebrospinal fluid

© 2016, Pleiades Publishing, Ltd.Differential diagnosis of bacterial and viral meningitis is an urgent problem of the modern clinical medicine. Early and accurate detection of meningitis etiology largely determines the strategy of its treatment and significantly increases the likelihood of a favorable outcome for the patient. In the present work, we analyzed the peptidome and cytokine profiles of cerebrospinal fluid (CSF) of 17 patients with meningitis of bacterial and viral etiology and of 20 neurologically healthy controls. In addition to the identified peptides (potential biomarkers), we found significant differences in the cytokine status of the CSF of the patients. We found that cut-off of 100 pg/ml of IL-1β, TNF, and GM-CSF levels discriminates bacterial and viral meningitis with 100% specificity and selectivity. We demonstrated for the first time the reduction in the level of two cytokines, IL-13 and GM-CSF, in the CSF of patients with viral meningitis in comparison with the controls. The decrease in GM-CSF level in the CSF of patients with viral meningitis can be explained by a disproportionate increase in the levels of cytokines IL-10, IFN-γ, and IL-4, which inhibit the GM-CSF expression, whereas IL-1, IL-6, and TNF activate it. These observations suggest an additional approach for differential diagnosis of bacterial and viral meningitis based on the normalized ratio IL-10/IL-1β and IL-10/TNF > 1, as well as on the ratio IFN-γ/IL-1β and IFN-γ/ TNF < 0.1. Our findings extend the panel of promising clinical and diagnostic biomarkers of viral and bacterial meningitis and reveal opposite changes in the cytokine expression in meningitis due to compensatory action of proand antiinflammatory factors

Non-monotonic variation with salt concentration of the second virial coefficient in protein solutions

The osmotic virial coefficient $B_2$ of globular protein solutions is calculated as a function of added salt concentration at fixed pH by computer simulations of the ``primitive model''. The salt and counter-ions as well as a discrete charge pattern on the protein surface are explicitly incorporated. For parameters roughly corresponding to lysozyme, we find that $B_2$ first decreases with added salt concentration up to a threshold concentration, then increases to a maximum, and then decreases again upon further raising the ionic strength. Our studies demonstrate that the existence of a discrete charge pattern on the protein surface profoundly influences the effective interactions and that non-linear Poisson Boltzmann and Derjaguin-Landau-Verwey-Overbeek (DLVO) theory fail for large ionic strength. The observed non-monotonicity of $B_2$ is compared to experiments. Implications for protein crystallization are discussed.Comment: 43 pages, including 17 figure

HCV IRES manipulates the ribosome to promote the switch from translation initiation to elongation.

The internal ribosome entry site (IRES) of the hepatitis C virus (HCV) drives noncanonical initiation of protein synthesis necessary for viral replication. Functional studies of the HCV IRES have focused on 80S ribosome formation but have not explored its role after the 80S ribosome is poised at the start codon. Here, we report that mutations of an IRES domain that docks in the 40S subunit's decoding groove cause only a local perturbation in IRES structure and result in conformational changes in the IRES-rabbit 40S subunit complex. Functionally, the mutations decrease IRES activity by inhibiting the first ribosomal translocation event, and modeling results suggest that this effect occurs through an interaction with a single ribosomal protein. The ability of the HCV IRES to manipulate the ribosome provides insight into how the ribosome's structure and function can be altered by bound RNAs, including those derived from cellular invaders

Ubiquitin-independent proteosomal degradation of myelin basic protein contributes to development of neurodegenerative autoimmunity

© The Author(s). Recent findings indicate that the ubiquitin-proteasome system is involved in the pathogenesis of cancer as well as autoimmune and several neurodegenerative diseases, and is thus a target for novel therapeutics. One disease that is related to aberrant protein degradation is multiple sclerosis, an autoimmune disorder involving the processing and presentation of myelin autoantigens that leads to the destruction of axons. Here, we show that brainderived proteasomes from SJL mice with experimental autoimmune encephalomyelitis (EAE) in an ubiquitinindependent manner generate significantly increased amounts of myelin basic protein peptides that induces cytotoxic lymphocytes to target mature oligodendrocytes ex vivo. Ten times enhanced release of immunogenic peptides by cerebral proteasomes from EAE-SJL mice is caused by a dramatic shift in the balance between constitutive and β1ihigh immunoproteasomes in the CNS of SJL mice with EAE. We found that during EAE, β1i is increased in resident CNS cells, whereas β5i is imported by infiltrating lymphocytes through the blood-brain barrier. Peptidyl epoxyketone specifically inhibits brain-derived β1ihigh immunoproteasomes in vitro (kobs/[I] = 240 M-1s-1), and at a dose of 0.5 mg/kg, it ameliorates ongoing EAE in vivo. Therefore, our findings provide novel insights into myelin metabolism in pathophysiologic conditions and reveal that the β1i subunit of the immunoproteasome is a potential target to treat autoimmune neurologic diseases

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 &gt; 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