Arc/Arg3.1 mRNA Global Expression Patterns Elicited by Memory Recall in Cerebral Cortex Differ for Remote Versus Recent Spatial Memories

The neocortex plays a critical role in the gradual formation and storage of remote declarative memories. Because the circuitry mechanisms of systems-level consolidation are not well understood, the precise cortical sites for memory storage and the nature of enduring memory correlates (mnemonic plasticity) are largely unknown. Detailed maps of neuronal activity underlying recent and remote memory recall highlight brain regions that participate in systems consolidation and constitute putative storage sites, and thus may facilitate detection of mnemonic plasticity. To localize cortical regions involved in the recall of a spatial memory task, we trained rats in a water-maze and then mapped mRNA expression patterns of a neuronal activity marker Arc/Arg3.1 (Arc) upon recall of recent (24 h after training) or remote (1 month after training) memories and compared them with swimming and naive controls. Arc gene expression was significantly more robust 24 h after training compared to 1 month after training. Arc expression diminished in the parietal, cingulate and visual areas, but select segments in the prefrontal, retrosplenial, somatosensory and motor cortical showed similar robust increases in the Arc expression. When Arc expression was compared across select segments of sensory, motor and associative regions within recent and remote memory groups, the overall magnitude and cortical laminar patterns of task-specific Arc expression were similar (stereotypical). Arc mRNA fractions expressed in the upper cortical layers (2/3, 4) increased after both recent and remote recall, while layer 6 fractions decreased only after the recent recall. The data suggest that robust recall of remote memory requires an overall smaller increase in neuronal activity within fewer cortical segments. This activity trend highlights the difficulty in detecting the storage sites and plasticity underlying remote memory. Application of the Arc maps may ameliorate this difficulty

Three-Dimensional Geometric Morphometric Analysis of Fossil Canid Mandibles and Skulls

Acknowledgements We thank C.P. Klingenberg for critical discussion of methodology. A. Drake and R. Losey were supported by a grant from the Social Sciences and Humanities Research Council of Canada grant (#SSHRC IG 435-2014-0075) and a European Research Council Grant to D. Anderson (#295458). M. Sablin acknowledges participation of ZIN RAS (state assignment № АААА-А17-117022810195-3) to this research. Supplementary information accompanies this paper at doi:10.1038/s41598-017-10232-1Peer reviewedPublisher PD

Cosmological Production of Vector Bosons and Cosmic Microwave Background Radiation

The intensive cosmological creation of vector W, Z- bosons in the cosmological model with the relative units is considered. Field theoretical models are studied, which predict that the CMB radiation and the baryon matter in the universe can be products of decay and annihilation processes of these primordial bosons.Comment: 31 pages, 1 figur

Analytical Challenges and Metrological Approaches to Ensuring Dietary Supplement Quality: International Perspectives

The increased utilization of metrology resources and expanded application of its’ approaches in the development of internationally agreed upon measurements can lay the basis for regulatory harmonization, support reproducible research, and advance scientific understanding, especially of dietary supplements and herbal medicines. Yet, metrology is often underappreciated and underutilized in dealing with the many challenges presented by these chemically complex preparations. This article discusses the utility of applying rigorous analytical techniques and adopting metrological principles more widely in studying dietary supplement products and ingredients, particularly medicinal plants and other botanicals. An assessment of current and emerging dietary supplement characterization methods is provided, including targeted and non-targeted techniques, as well as data analysis and evaluation approaches, with a focus on chemometrics, toxicity, dosage form performance, and data management. Quality assessment, statistical methods, and optimized methods for data management are also discussed. Case studies provide examples of applying metrological principles in thorough analytical characterization of supplement composition to clarify their health effects. A new frontier for metrology in dietary supplement science is described, including opportunities to improve methods for analysis and data management, development of relevant standards and good practices, and communication of these developments to researchers and analysts, as well as to regulatory and policy decision makers in the public and private sectors. The promotion of closer interactions between analytical, clinical, and pharmaceutical scientists who are involved in research and product development with metrologists who develop standards and methodological guidelines is critical to advance research on dietary supplement characterization and health effects

Compact Source of Electron Beam for Facility of Electron-Beam Welding with the Location of the Electron Gun and the Source of High Voltage in a Single Monoblock. Concept and Bench Tests of the Monoblok Prototype

Представлен прототип компактного источника электронного пучка для установок электронно-лучевой сварки с расположением электронной пушки и источника высоковольтного напряжения в едином моноблоке. Размещение электронной пушки, источника высоковольтного напряжения, электроники управления пучком и питания накала катода источника электронного пучка для электронно-лучевой сварки в едином корпусе-моноблоке снижает вес и стоимость (за счёт уменьшения количества используемых материалов), объём и занимаемые производственные площади. Это существенно расширяет возможности применения представляемого типа источников электронного пучка в разнообразных областях деятельности человека, в том числе в космических технологиях в открытом пространстве космоса. Цель работы – показать целесообразность концепции компоновки источника электронного пучка в едином корпусе-моноблоке на примере стендовых испытаний прототипа источника-моноблока. Спроектирован и изготовлен прототип источника-моноблока. Проведены его предварительные стендовые испытания с лазерным подогревом катода. Обсуждаются возможные применения. Получен электронный ток источника до 70 мА с энергией 90 кэВ. Данный результат демонстрирует возможность практической реализации нового способа компоновки источника электронного пучкаA prototype of an electron beam compact source for electron-beam welding is presented. The electron gun and a high-voltage source are united in a single monoblock. The placement of the electron gun, the high-voltage source, the beam control electronics and the power supply of the cathode heating of the electron beam source for electron beam welding in a single monoblock housing reduces weight and cost by reducing the amount of materials used, volume and occupied production areas. This significantly expands the possibilities of using the presented type of electron beam sources in various fields of human activity, including space technologies in the open space of space. The purpose of the work is to show the expediency of the concept of arranging the electron beam source in the single monoblock housing as the example of bench tests of the source prototype. The prototype of the monoblock was designed and manufactured. Its preliminary bench tests with laser cathode heating were carried out. Its possible applications are discussed. An electron source current up to 70 mA with an energy of 90 keV was obtained. The result obtained demonstrates the possibility of practical implementation of a new method of arranging an electron beam sourc

Modeling of GERDA Phase II data

The GERmanium Detector Array (GERDA) experiment at the Gran Sasso underground laboratory (LNGS) of INFN is searching for neutrinoless double-beta ($0\nu\beta\beta$) decay of $^{76}$Ge. The technological challenge of GERDA is to operate in a "background-free" regime in the region of interest (ROI) after analysis cuts for the full 100$\,$kg$\cdot$yr target exposure of the experiment. A careful modeling and decomposition of the full-range energy spectrum is essential to predict the shape and composition of events in the ROI around $Q_{\beta\beta}$ for the $0\nu\beta\beta$ search, to extract a precise measurement of the half-life of the double-beta decay mode with neutrinos ($2\nu\beta\beta$) and in order to identify the location of residual impurities. The latter will permit future experiments to build strategies in order to further lower the background and achieve even better sensitivities. In this article the background decomposition prior to analysis cuts is presented for GERDA Phase II. The background model fit yields a flat spectrum in the ROI with a background index (BI) of $16.04^{+0.78}_{-0.85} \cdot 10^{-3}\,$cts/(kg$\cdot$keV$\cdot$yr) for the enriched BEGe data set and $14.68^{+0.47}_{-0.52} \cdot 10^{-3}\,$cts/(kg$\cdot$keV$\cdot$yr) for the enriched coaxial data set. These values are similar to the one of Gerda Phase I despite a much larger number of detectors and hence radioactive hardware components

Modeling of GERDA Phase II data

The GERmanium Detector Array (Gerda) experiment at the Gran Sasso underground laboratory (LNGS) of INFN is searching for neutrinoless double-beta (0νββ) decay of 76Ge. The technological challenge of Gerda is to operate in a “background-free” regime in the region of interest (ROI) after analysis cuts for the full 100 kg·yr target exposure of the experiment. A careful modeling and decomposition of the full-range energy spectrum is essential to predict the shape and composition of events in the ROI around Qββ for the 0νββ search, to extract a precise measurement of the half-life of the double-beta decay mode with neutrinos (2νββ) and in order to identify the location of residual impurities. The latter will permit future experiments to build strategies in order to further lower the background and achieve even better sensitivities. In this article the background decomposition prior to analysis cuts is presented for Gerda Phase II. The background model fit yields a flat spectrum in the ROI with a background index (BI) of 16.04+0.78−0.85⋅10−3 cts/(keV·kg·yr) for the enriched BEGe data set and 14.68+0.47−0.52⋅10−3 cts/(keV·kg·yr) for the enriched coaxial data set. These values are similar to the one of Phase I despite a much larger number of detectors and hence radioactive hardware components

A community effort in SARS-CoV-2 drug discovery.

peer reviewedThe COVID-19 pandemic continues to pose a substantial threat to human lives and is likely to do so for years to come. Despite the availability of vaccines, searching for efficient small-molecule drugs that are widely available, including in low- and middle-income countries, is an ongoing challenge. In this work, we report the results of an open science community effort, the "Billion molecules against Covid-19 challenge", to identify small-molecule inhibitors against SARS-CoV-2 or relevant human receptors. Participating teams used a wide variety of computational methods to screen a minimum of 1 billion virtual molecules against 6 protein targets. Overall, 31 teams participated, and they suggested a total of 639,024 molecules, which were subsequently ranked to find 'consensus compounds'. The organizing team coordinated with various contract research organizations (CROs) and collaborating institutions to synthesize and test 878 compounds for biological activity against proteases (Nsp5, Nsp3, TMPRSS2), nucleocapsid N, RdRP (only the Nsp12 domain), and (alpha) spike protein S. Overall, 27 compounds with weak inhibition/binding were experimentally identified by binding-, cleavage-, and/or viral suppression assays and are presented here. Open science approaches such as the one presented here contribute to the knowledge base of future drug discovery efforts in finding better SARS-CoV-2 treatments.R-AGR-3826 - COVID19-14715687-CovScreen (01/06/2020 - 31/01/2021) - GLAAB Enric