rAAV expressing recombinant antibody for emergency prevention and long-term prophylaxis of COVID-19

IntroductionNumerous agents for prophylaxis of SARS-CoV-2-induced diseases are currently registered for the clinical use. Formation of the immunity happens within several weeks following vaccine administration which is their key disadvantage. In contrast, drugs based on monoclonal antibodies, enable rapid passive immunization and therefore can be used for emergency pre- and post-exposure prophylaxis of COVID-19. However rapid elimination of antibody-based drugs from the circulation limits their usage for prolonged pre-exposure prophylaxis.MethodsIn current work we developed a recombinant adeno-associated viral vector (rAAV), expressing a SARS-CoV-2 spike receptor-binding domain (RBD)-specific antibody P2C5 fused with a human IgG1 Fc fragment (P2C5-Fc) using methods of molecular biotechnology and bioprocessing.Results and discussionsA P2C5-Fc antibody expressed by a proposed rAAV (rAAV-P2C5-Fc) was shown to circulate within more than 300 days in blood of transduced mice and protect animals from lethal SARS-CoV-2 virus (B.1.1.1 and Omicron BA.5 variants) lethal dose of 105 TCID50. In addition, rAAV-P2C5-Fc demonstrated 100% protective activity as emergency prevention and long-term prophylaxis, respectively. It was also demonstrated that high titers of neutralizing antibodies to the SARS-CoV-2 virus were detected in the blood serum of animals that received rAAV-P2C5-Fc for more than 10 months from the moment of administration.Our data therefore indicate applicability of an rAAV for passive immunization and induction of a rapid long-term protection against various SARS-CoV-2 variants

Efficiency of Finding Muon Track Trigger Primitives in CMS Cathode Strip Chambers

In the CMS Experiment, muon detection in the forward direction is accomplished by cathode strip chambers~(CSC). These detectors identify muons, provide a fast muon trigger, and give a precise measurement of the muon trajectory. There are 468 six-plane CSCs in the system. The efficiency of finding muon trigger primitives (muon track segments) was studied using~36 CMS CSCs and cosmic ray muons during the Magnet Test and Cosmic Challenge~(MTCC) exercise conducted by the~CMS experiment in~2006. In contrast to earlier studies that used muon beams to illuminate a very small chamber area ($< \! 0.01$~m$^2$), results presented in this paper were obtained by many installed CSCs operating {\em in situ} over an area of $\approx \! 23$~m$^2$ as a part of the~CMS experiment. The efficiency of finding 2-dimensional trigger primitives within 6-layer chambers was found to be~$99.93 \pm 0.03\%$. These segments, found by the CSC electronics within $800$~ns after the passing of a muon through the chambers, are the input information for the Level-1 muon trigger and, also, are a necessary condition for chambers to be read out by the Data Acquisition System

Gold Prospects in the Western Segment of the Russian Arctic: Regional Metallogeny and Distribution of Mineralization

Location of the deposits and occurrences of gold mineralization in metamorphic complexes of the Kola region is controlled by tectonic zones at the regional scale at the boundaries of major segments of the Fennoscandian Shield. Three zones are the most important: (1) the system of Neoarchean greenstone belts Kolmozero&#8315;Voron&#8217;ya&#8315;Ura-guba along the southern boundary of the Murmansk craton; (2) the suture, delineating the core of the Lapland&#8315;Kola orogeny in the north; and (3) the series of overthrusts and faults at the eastern flank of the Salla&#8315;Kuolajarvi belt. Gold deposits and occurrences are located within greenstone belts of Neoarchean and Paleoproterozoic age, and hosted by rocks of different primary compositions (mafic metavolcanics, diorite porphyry, and metasedimentary terrigenous rocks). The grade of metamorphism varies from greenschist to upper amphibolite facies, but the mineralized rocks are mainly lower amphibolite metamorphosed, close to the transition from greenschist to amphibolite facies. Gold deposits and occurrences in the northeastern part of the Fennoscandian Shield formed during two periods: the Neoarchean 2.7&#8315;2.6 Ga and the Paleoproterozoic 1.9&#8315;1.7 Ga. According to paleo-geodynamic reconstructions, these were the periods of collisional and accretionary orogeny in the region. Those Archean greenstone belts, which were reworked in the Paleoproterozoic (e.g., Strel&#8217;na and Tiksheozero belts), can contain gold deposits of Paleoproterozoic age

Gold and Arsenic in Pyrite and Marcasite: Hydrothermal Experiment and Implications to Natural Ore-Stage Sulfides

Hydrothermal synthesis experiments were performed in order to quantify the states of Au and As in pyrite and marcasite. The experiments were performed at 350 °C/500 bar and 490 °C/1000 bar (pyrite–pyrrhotite buffer, C(NaCl) = 15 and 35 wt.%). The synthesis products were studied by EPMA, LA-ICP-MS, and EBSD. The EPMA was applied for simultaneous determinations of Au, As, Fe, and S, with a Au detection limit of 45–48 ppm (3σ). The analyses were performed along profiles across zonal grains. The concentrations of As and Au up to 5 wt.% and 8000 ppm, respectively, were determined in pyrite and up to 6 wt.% and 1300 ppm in marcasite. In pyrite, the Au concentration decreases with fluid salinity and temperature increases. Strong positive Au–As correlation and strong negative Au–Fe and As–S correlation were identified in pyrite. Comparison of the correlations with theoretical lines implies Au–As clustering. The cluster stoichiometry is inferred to be [AuAs10]. Most probably, As in pyrite presents in the form of clusters and in the As→S solid solution. Incorporation of Au in As-rich pyrite can be controlled by the reductive deposition mechanism. In marcasite, the concentrations of Au are not correlated with the As content. The [AuAs10] clusters enrich the {210}, {113}, and {111} pyrite faces, where the former exhibits the highest affinity to Au and As. The affinity of {110} and {100} forms to Au and As is lower. Implication of the experimental results to data for natural auriferous pyrite shows that the increase of Au content at C(As) > 0.5–1 wt.% is caused by the incorporation of the Au-As clusters, but not because of the formation of Au→Fe solid solution. Therefore, the concentration of “invisible” gold in pyrite is dictated solely by the hydrothermal fluid chemistry and subsequent ore transformations

Nuclear astrophysics with radioactive ions at FAIR

The nucleosynthesis of elements beyond iron is dominated by neutron captures in the s and r processes. However, 32 stable, proton-rich isotopes cannot be formed during those processes, because they are shielded from the s-process flow and r-process β-decay chains. These nuclei are attributed to the p and rp process. For all those processes, current research in nuclear astrophysics addresses the need for more precise reaction data involving radioactive isotopes. Depending on the particular reaction, direct or inverse kinematics, forward or time-reversed direction are investigated to determine or at least to constrain the desired reaction cross sections. The Facility for Antiproton and Ion Research (FAIR) will offer unique, unprecedented opportunities to investigate many of the important reactions. The high yield of radioactive isotopes, even far away from the valley of stability, allows the investigation of isotopes involved in processes as exotic as the r or rp processes