Search

Intranasal treatments, combined with vaccination, has the potential to slow mutational evolution of virusues by reducing transmission and replication. Here we illustrate the development of a SARS-CoV-2 receptor binding domain (RBD) nanoCLAMP and demonstrate its potential as an intranasally administered therapeutic. A multi-epitope nanoCLAMP was made by fusing a pM affinity single-domain nanoCLAMP (P2710) to alternate epitope binding nanoCLAMP, P2609. The resulting multimerised nanoCLAMP P2712 had sub-pM affinity for the Wuhan and South African (B.1.351) RBD (KD< 1 pM), and decreasing affinity for the Delta (B.1.617.2) and Omicron (B.1.1.529) variants (86 pM and 19.7 nM, respectively). P2712 potently inhibited ACE2:RBD interaction, suggesting its utility as a therapeutic. With an IC50= 0.4 ± 0.1 nM obtained from neutralization experiments using pseudoviral particles as well as patient cultured SARS-CoV-2 samples, nanoCLAMP P2712 protected K18-hACE2 mice from SARS-CoV-2 infection, reduced viral loads in the lungs and brains, and reduced associated upregulation of inflammatory cytokines and chemokines. Together, our findings warrant further investigation into the development of nanoCLAMPs as effective intranasally delivered COVID19 therapeutics.

Nanoemulsion technique based on Ouzo effect was applied for the fast and simple synthesis of Ag3PO4 at room temperature. X-ray powder diffraction analysis and Raman spectroscopy reviled that synthesized powder was single-phase. Using scanning electron microscopy analysis, it was found that the synthesized Ag3PO4 particles were near-spherical shape with an average diameter of 100 nm. The high value for the specific surface area of obtained powder was measured by Brunauer?Emmet?Teller method. Finally, the Ag3PO4 product was used as a photocatalyst for the photodegradation of crystal violet dye in an aqueous solution. Nanoemulsion strategy procedure provides a simple pathway to obtain a highly efficient single-phase Ag3PO4 photocatalyst.

In this paper, the authors investigate the needs and reasons for securing notaries when performing notary activities. The paper should investigate and answer, what is the interest of the state, notaries and parties, in connection with performing notarial activity, legal basis and manner of conducting professional liability insurance of notaries, determining the amount of the insured case, the occurrence of the insured case, comparative legal solutions rights. The paper deals with persons who are participants in insurance (insured, insurer, injured party and other persons covered by insurance), the concept and subject of insurance, in this case professional liability insurance, the risk it carries, protection of the injured party and protection of property.

The interfacial charge transfer (ICT) complex formation between zirconium dioxide (ZrO2), the material absorbing below 250 nm, and 5-aminosalicylic acid (5-ASA) leads to the formation of visible-light-absorbing inorganic–organic hybrids. The free amino groups, present on the hybrid's surface after the ICT complex formation, were used to reduce silver ions and link silver particles to ZrO2. The prepared samples were characterized by using transmission electron microscopy, X-ray diffraction analysis, and nitrogen adsorption–desorption isotherms. Density functional theory (DFT) calculations using a cluster model are applied to explain optical changes in hybrids, i.e., absorption redshift induced by the ICT complex formation. Decolorization of an organic dye crystal violet (CV), under ultraviolet-C or visible light, was used to compare the photocatalytic ability of the prepared samples. The ICT complex formation transformed ZrO2 into a hybrid material able to induce photocatalytic reactions under exclusive visible light excitation.

Recent studies of TiO2/TiS2 nanostructures with various morphologies have been reported, usually showing improved properties with applications from electronics and catalysis to solar cells and medicine. However, there is a limited number of studies on the crystal structures of TiO2/TiS2 compounds with corresponding properties. In this research, relevant crystal structures of TiO1–x S x (x = 0, 0.25, 0.5, 0.75 and 1) solid solutions were investigated using an ab initio method. For each composition, crystal structures adopting anatase, rutile and CdI2 structure type were calculated on LDA-PZ and GGA-PBE levels of theory. Novel phase transitions and predicted structures are presented, and apart from several interesting metastable structures, a very interesting pressure-induced phase transition is found in the TiOS compound. Furthermore, electronic properties were studied through the dependence of semiconducting properties on dopant concentration. The first description of the electronic properties of the mixed TiO1–x S x compounds in crystal form has been presented, followed by a detailed study of the structure–property relationship, which will possibly have numerous industrial and technological applications.

International audience; Due to the vital importance of the Central Nervous System (CNS), its potential infection and inflammation have to be tightly controlled. The surface of the CNS is connected to the periphery by a rich and complex tissue, the meninges. They contain a vast network of macrophages subdivided in at least two subpopulations endowed with elusive functions: a neonatal, MHC-II negative macrophage population, and an age-dependent population expressing MHC-II. Using in situ-histocytometry, flow cytometry, and single-cell RNA sequencing approaches, we showed that those populations have opposite dynamic behaviors in response to in vivo peripheral challenges such as LPS, SARS-CoV2 and lymphocytic choriomeningitis virus (LCMV), with an apparent contraction of the MHC-II+ population. Focusing on LCMV infection in experimental mouse models and using innovative pharmacological and genetic depletion strategies, we show that meningeal macrophages (MM) represent an early line of protection against this neuroinvasive pathogen. In their absence, specific areas in the meninges became highly infected, leading to fatal brain disease. While their intrinsic sensing of viral replication through the Mitochondrial antiviral-signaling protein (MAVS) was dispensable, sensing of IFNs through the STAT1 pathway played an important role in controlling viral spread. Unexpectedly, the age-dependent MHC-II+ macrophage population had an important role in controlling neuroinfection, by shutting down biosynthesis pathways and efficiently blocking viral replication. This work helps understanding the spatial organization of the brain defense system and the cellular and molecular mechanisms involved in CNS protection.

The surface of the central nervous system (CNS) is protected by the meninges, which contain a dense network of meningeal macrophages (MMs). Here, we examined the role of tissue-resident MM in viral infection. MHC-II� MM were abundant neonatally, whereas MHC-II+ MM appeared over time. These barrier macrophages differentially responded to in vivo peripheral challenges such as LPS, SARS-CoV-2, and lymphocytic choriomeningitis virus (LCMV). Peripheral LCMV infection, which was asymptomatic, led to a transient infection and activation of the meninges. Mice lacking macrophages but conserving brain microglia, or mice bearing macrophage-specific deletion of Stat1 or Ifnar, exhibited extensive viral spread into the CNS. Transcranial pharmacological depletion strategies targeting MM locally resulted in several areas of the meninges becoming infected and fatal meningitis. Low numbers of MHC-II+ MM, which is seen upon LPS challenge or in neonates, corelated with higher viral load upon infection. Thus, MMs protect against viral infection and may present targets for therapeutic manipulation., Authors affiliations: (1) Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, Inserm, CNRS, Marseille, France (2) Ecole Normale Supérieure de Lyon, Université Claude Bernard – Lyon I, Université de Lyon, Lyon, France (3)Centre d'Immunophénomique, Aix Marseille Université , Inserm, CNRS, Marseille, France (4) TERI (Tumor Escape, Resistance and Immunity) Department, Centre de Recherche en Cancérologie de Lyon, Centre Léon Bérard, Université Claude Bernard – Lyon 1, Université de Lyon, Inserm, CNRS, Lyon, France (5) Viral Immunology and Intravital Imaging Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA (6) Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China (7) University Paris-Saclay, Inserm U1015, Gustave Roussy Cancer Center, Villejuif, France (8) Singapore Immunology Network, A*STAR, Singapore, Singapore (9) Centre for Inflammation Biology and Cancer Immunology, Cancer Research UK King's Health Partners Centre, School of Immunology and Microbial Sciences, King's College London, London SE1 1UL, UK (10) Lead contact

Current deep convolutional networks are fixed in their topology. We explore the possibilites of making the convolutional topology a parameter itself by combining NeuroEvolution of Augmenting Topologies (NEAT) with Convolutional Neural Networks (CNNs) and propose such a system using blocks of Residual Networks (ResNets). We then explain how our suggested system can only be built once additional optimizations have been made, as genetic algorithms are way more demanding than training per backpropagation. On the way there we explain most of those buzzwords and offer a gentle and brief introduction to the most important modern areas of machine learning, Unpublished

This paper presents the improvements implemented at the University of Montenegro Information System in the Distance Learning (DL) segment during the COVID-19 pandemic. A comparative view of old and new DL system was made. The integration of all parts of DL is presented, with a description of the digital services, their technical characteristics, and the method of implementation. Comparative statistics on the use of the DL platform before and during the pandemic were also presented.

New binary catalytic systems based on sulphated zirconia-alumina were synthesized by controlled hydrolysis of alkoxides using relative molar ratios of constituents 1:1, 1:2 and 1:3 in favour of zirconia. The obtained differences in the final catalytic material’s properties may be related to organic precursor memory effect, the applied calcinations temperatures and used alumina contents. The addition of alumina to zirconia affected the structural and surface properties stabilizing bare zirconia by means of slower phase transformation of tetragonal zirconia crystal phase into monoclinic one, further resulting in smaller crystallites sizes and higher surface density of acidic function (sulphates). The best alumina impact on physico-chemical properties was achieved when the highest amount of alumina (e.g. 50%) and lower calcination temperature (500°C) were used, causing relatively high steady-state activity in isomerization of n-hexane at reaction temperature 250 °C. On the other hand, higher calcination temperature (600 °C) played a role in the genesis of greater sulphate density. Catalytic activity and selectivity are expressed as a complex synergistic function of relative density of acid sites together with positive status of other optimized physico-chemical properties of the catalytic material (by activation and calcination temperatures).

It is well-known that modern organizations stand out as leaders in their industries have one common factor that brings them together around the fact they are successful: they are all principally committed to innovation. This fact also applies to sports. Empirical research was conducted to determine a research analysis of attitudes of sport organization officials toward links between the sports sector, sports industry, and knowledge organizations with innovations in Montenegrin sport. Seventy-five subject representatives of sports organizations were ran- domly assigned as a sample, while the questionnaire used is based on the Community Innovation Survey (CIS). Descriptive statistics were employed to test the hypothesis. This study confirmed that there is significant potential for improving innovation in sports in Montenegro. Policymakers and other stakeholders, including sports admin- istrators and other sports leaders, should increase the ability of sports organizations to innovate in sports.

Using e-learning and social media has become a common part of students' academic lives in many sciences, including sport sciences. The purpose of this research study was to identify attitudes and preferences of students in sports science concerning the use of e-learning and social media at the University of Novi Sad. The present study was included respondents (N=297) from the Faculty of Sport and Physical Education at the University of Novi Sad from all levels of studies. The attitudes and preferences of the use of e-learning and social media were measured with three separate parts: (1) General information (8 items);(2) use of different genres of social media in teaching (28 items);(3) e-learning in the field of sports studies (13 items), and descriptive statistics (frequencies) were used to describe the basic features of the data. The results showed that participants mostly use Facebook (44.4% of students), Viber (66%), and WhatsApp (56.6%) to contact peer students for study in the context of learning purposes. In comparison, they do not use LinkedIn (1.3%), Twitter (0.3%) or Skype (4%). From another side, the students mostly share their messages via Viber and WhatsApp in the form of various questions (67% via Viber;62.6% via WhatsApp), video messages (20.5%;25.3%), screenshots of their screen (21.2%;27.6%), various links (23.2%;25.3%), comments on a current topic (22.2%;22.2%). In the participants' opinion (81.5%), the teaching process has been set back by the coronavirus pandemic. In contrast, the students experienced the pandemic's positive effect as an improvement in e-learning (51.2% of students). They shared the opinion that virtual teaching is not as effective as traditional teaching (85.2%). The theoretical and practical applications of these results are discussed. © 2021 Montenegrin Sports Academy. All rights reserved.

International audience; Lung-resident memory B cells (MBCs) provide localized protection against reinfection in respiratory airways. Currently, the biology of these cells remains largely unexplored. Here, we combined influenza and SARS-CoV-2 infection with fluorescent-reporter mice to identify MBCs regardless of antigen specificity. We found that two main transcriptionally distinct subsets of MBCs colonized the lung peribronchial niche after infection. These subsets arose from different progenitors and were both class switched, somatically mutated, and intrinsically biased in their differentiation fate toward plasma cells. Combined analysis of antigen specificity and B cell receptor repertoire segregated these subsets into “bona fide” virus-specific MBCs and “bystander” MBCs with no apparent specificity for eliciting viruses generated through an alternative permissive process. Thus, diverse transcriptional programs in MBCs are not linked to specific effector fates but rather to divergent strategies of the immune system to simultaneously provide rapid protection from reinfection while diversifying the initial B cell repertoire.

International audience; BackgroundThere is an urgent need of a new generation of vaccine that are able to enhance protection against SARS-CoV-2 and related variants of concern (VOC) and emerging coronaviruses.MethodsWe identified conserved T- and B-cell epitopes from Spike (S) and Nucleocapsid (N) highly homologous to 38 sarbecoviruses, including SARS-CoV-2 VOCs, to design a protein subunit vaccine targeting antigens to Dendritic Cells (DC) via CD40 surface receptor (CD40.CoV2).FindingsCD40.CoV2 immunization elicited high levels of cross-neutralizing antibodies against SARS-CoV-2, VOCs, and SARS-CoV-1 in K18-hACE2 transgenic mice, associated with viral control and survival after SARS-CoV-2 challenge. A direct comparison of CD40.CoV2 with the mRNA BNT162b2 vaccine showed that the two vaccines were equally immunogenic in mice. We demonstrated the potency of CD40.CoV2 to recall in vitro human multi-epitope, functional, and cytotoxic SARS-CoV-2 S- and N-specific T-cell responses that are unaffected by VOC mutations and cross-reactive with SARS-CoV-1 and, to a lesser extent, MERS epitopes.InterpretationWe report the immunogenicity and antiviral efficacy of the CD40.CoV2 vaccine in a preclinical model providing a framework for a pan-sarbecovirus vaccine.FundingsThis work was supported by INSERM and the Investissements d'Avenir program, Vaccine Research Institute (VRI), managed by the ANR and the CARE project funded from the Innovative Medicines Initiative 2 Joint Undertaking (JU).