THE PROCEDURE FOR THE PARTICIPATION OF SMALL BUSINESS ENTITIES-AGRICULTURAL PRODUCERS IN THE PUBLIC PROCUREMENT PROCESS

Background. Currently, agro-industrial holdings occupy a dominant position in Russia, which creates certain imbalances both in the agricultural and processing industries of the agro-industrial sector of the economy. In this connection, it is necessary to create conditions for the full functioning of SMP-agricultural producers. For this purpose, cooperation, conclusion of contracts or participation in state and municipal procurement can be used. Purpose. Determination of the algorithm of participation of SMP-agricultural producers in the procurement process at the state and municipal levels. The work is theoretical in nature and is aimed at developing methodological approaches to the implementation of state and municipal purchases from agricultural producers. Materials and methods. The study is based on legislative and regulatory acts and, at the same time, on the opinions of various authors on the problem of the participation of SMEs in the contract system of state and municipal procurement. Results. In the course of the study, legislative and regulatory acts were considered in relation to procurement of various levels; an assessment of the participation of small businesses-agricultural producers in the field of public procurement was given; algorithms for the participation of this kind of entities in the procurement process were formed. Conclusion. As a result, various aspects and features of the participation of small businesses in public procurement were identified

AD51B in Familial Breast Cancer

Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11–1.19, P = 8.88 x 10−16) and among familial cases (OR: 1.24, 95% CI: 1.16–1.32, P = 6.19 x 10−11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk

Centrality evolution of the charged-particle pseudorapidity density over a broad pseudorapidity range in Pb-Pb collisions at root s(NN)=2.76TeV

Peer reviewe

Fixation of Administrative Offenses in Russia and Foreign Countries: the Legal and Social Aspects

We analyze the experience in fixing administrative offenses. The article also raises the problems of using automatic fixation as a source of evidence in cases of administrative offenses. We gave an examples of the positive impact of automatic fixation of administrative offenses on road safety, in particular we proved that the use of administrative fixation tools should also be the preventive measure that helps to regulate traffic. The problem of using the means of fixing administrative offenses on cars with foreign state marks, which are increasingly appearing on roads, is becoming more relevant. We also considered the sociological aspect in order to understand how the society relates to this activity and correct its direction

The Role of Continuing Education in the Formation of Professional Skills in the Process of Individual Driving Training

This article presents solutions that are defined as a paradigm shift in driving schools, which will allow restructuring the process of driver training and reducing the risk of accidents. Thus, the study discusses ways to reduce the accident rate of drivers who have recently received a license to drive a car. To achieve the goal, accident statistics were analysed depending on driving experience and driver age. The influence of the Internet and computer games on the psychology of novice drivers was also studied. Finally, the process of driving skills formation in the entrepreneurial educational process of driving schools is described. We suggested that novice drivers should demand the proper driving school and consider the criteria by which they can choose a suitable and effective driving school to obtain complete and in-depth knowledge

Enhanced Adsorption Selectivity of Carbon Dioxide and Ethane on Porous Metal–Organic Framework Functionalized by a Sulfur-Rich Heterocycle

Porous metal–organic framework [Zn2(ttdc)2(bpy)] (1) based on thieno [3,2-b]thiophenedicarboxylate (ttdc) was synthesized and characterized. The structure contains intersected zig-zag channels with an average aperture of 4 × 6 Å and a 49% (v/v) guest-accessible pore volume. Gas adsorption studies confirmed the microporous nature of 1 with a specific surface area (BET model) of 952 m2·g–1 and a pore volume of 0.37 cm3·g–1. Extensive CO2, N2, O2, CO, CH4, C2H2, C2H4 and C2H6 gas adsorption experiments at 273 K and 298 K were carried out, which revealed the great adsorption selectivity of C2H6 over CH4 (IAST selectivity factor 14.8 at 298 K). The sulfur-rich ligands and double framework interpenetration in 1 result in a dense decoration of the inner surface by thiophene heterocyclic moieties, which are known to be effective secondary adsorption sites for carbon dioxide. As a result, remarkable CO2 adsorption selectivities were obtained for CO2/CH4 (11.7) and CO2/N2 (27.2 for CO2:N2 = 1:1, 56.4 for CO2:N2 = 15:85 gas mixtures). The computational DFT calculations revealed the decisive role of the sulfur-containing heterocycle moieties in the adsorption of CO2 and C2H6. High CO2 adsorption selectivity values and a relatively low isosteric heat of CO2 adsorption (31.4 kJ·mol–1) make the porous material 1 a promising candidate for practical separation of biogas as well as for CO2 sequestration from flue gas or natural gas

Theoretical Justification of A Purposeful Search of Potential Neurotropic Drugs

A targeted search for potential drugs of neurotropic action involves the choice of a basic “pharmacophore”, which is advisable to carry out on the basis of the achieved principle among the classes of chemical compounds where active pharmaceutical substances with high targeted activity have already been identified. Therefore, the pyrrolidine core, which is the basic fragment of nootropics of the racetam group, is promising for the rational design of biologically active compounds of nootropic action. Its combination with other heterocyclic fragments, in particular, the 1,2,4-triazole ring, allows for these “hybrid” molecules to expect a permanent change in the magnitude of the pharmacological effects. Creation of a virtual library of compounds, 3D-pharmacophore screening and molecular docking is a promising way to optimize a targeted search for substances with a given pharmacological activity.The aim. To optimize targeted search for new nootropic compounds.Materials and methods. The base generation for the virtual screening was carried out using the Marvin Sketch 20.5 software. For receptor-oriented flexible docking, the Autodock 4.2 software package was used.Results. New derivatives of 1-benzyl-4-pyrrolidin-2-one were selected as the object of the study. Based on the results of the 3D pharmacophore screening and molecular docking to nootropic targets of the virtual base compounds, scoring functions were calculated. A detailed analysis of the geometrical arrangement of “hit compounds” at the active sites of nootropic receptors (PDB ID: 5UOW, 5CXV, 6PV7) made it possible to formulate hypotheses regarding possible ways of interaction of “hybrid” compounds with biotargets.The activity of promising molecules with respect to the studied receptors can be realized by creating complexes between them, the stability of which is ensured mainly due to the energetically favourable geometric arrangement of ligands in the active center of these acceptors, the formation of hydrogen bonds between them, and intermolecular electrostatic and donor-acceptor interactions.Conclusions. Structural modification of the pyrrolidine ring by combining with 1,2,4-triazole scaffold containing substituents of various electronic nature has been proposed. Using 3D-pharmacophore screening, the virtual base of 1-benzyl-4-pyrrolidin-2-one derivatives was analyzed in order to search among them for new molecules of nootropic action. Docking studies have identified a promising group of derivatives of 1-benzyl-4 (4-R-5-sulfanylidene-4,5 dihydro-1H-1,2,4-triazol-3-yl) pyrrolidin-2-one, which have affinity for nootropic biotargets and are promising for further synthetic and pharmacological studie

Fibrin Glue Implants Seeded with Dental Pulp and Periodontal Ligament Stem Cells for the Repair of Periodontal Bone Defects: A Preclinical Study

A technology to create a cell-seeded fibrin-based implant matching the size and shape of bone defect is required to create an anatomical implant. The aim of the study was to develop a technology of cell-seeded fibrin gel implant creation that has the same shape and size as the bone defect at the site of implantation. Using computed tomography (CT) images, molds representing bone defects were created by 3D printing. The form was filled with fibrin glue and human dental pulp stem cells (DPSC). The viability, set of surface markers and osteogenic differentiation of DPSC grown in fibrin gel along with the clot retraction time were evaluated. In mice, an alveolar bone defect was created. The defect was filled with fibrin gel seeded with mouse DPSC. After 28 days, the bone repair was analyzed with cone beam CT and by histological examination. The proliferation rate, set of surface antigens and osteogenic potential of cells grown inside the scaffold and in 2D conditions did not differ. In mice, both cell-free and mouse DPSC-seeded implants increased the bone tissue volume and vascularization. In mice with cell-seeded gel implants, the bone remodeling process was more prominent than in animals with a cell-free implant. The technology of 3D-printed forms for molding implants can be used to prepare implants using components that are not suitable for 3D printing

Safety and Immunogenicity of Betuvax-CoV-2, an RBD-Fc-Based SARS-CoV-2 Recombinant Vaccine: Preliminary Results of the First-in-Human, Randomized, Double-Blind, Placebo-Controlled Phase I/II Clinical Trial

COVID-19, being a life-threatening infection that evolves rapidly, remains a major public health concern calling for the development of vaccines with broad protection against different pathogenic strains and high immunogenicity. Aside from this, other concerns in mass immunization settings are also the scalability of production and relative affordability of the technology. In that regard, adjuvanted protein vaccines with particles mimicking the virus stand out among known vaccine technologies. The “Betuvax-CoV-2” vaccine, developed on the basis of a recombinant protein and an adjuvant, has already been tested in preclinical studies and has advanced to clinical evaluation. Open, double-blinded, placebo-controlled, randomized phase I/II clinical trial of the “Betuvax-CoV-2,” recombinant protein subunit vaccine based on the S-protein RBD fused with the Fc-fragment of IgG, was conducted to evaluate safety and immunogenicity in response to the vaccination. Methods: In the phase I/II clinical trial, 116 healthy adult men and women, ages 18–58, were enrolled: 20 in Stage I, and 96 in Stage II. In Stage I, 20 µg of the vaccine was administered intramuscularly on day 2, and either 5 µg (group 1) or 20 µg (group 2) on day 30. In Stage II, 20 µg of the vaccine was administered intramuscularly on day 2, and either 5 µg (group 3) or 20 µg (group 4) on day 30. In group 5, both injections were replaced with placebo. The primary outcome measures were safety (number of participants with adverse events throughout the study) and antigen-specific humoral immunity (SARS-CoV-2-specific antibodies measured by ELISA and CMIA). Antigen-specific cell-mediated immunity and changes in neutralizing antibodies (detected with a SARS-CoV-2 neutralization assay) were measured as a secondary outcome. The trial is registered with ClinicalTrials.gov (Study Identifier: NCT05270954). Findings: Both vaccine formulations (20 µg + 5 µg and 20 µg + 20 µg) were safe and well tolerated. Most adverse events were mild, and no serious adverse events were detected. On day 51,anti-SARS-CoV-2 total and IgG antibody titers and anti-SARS-CoV-2 neutralizing antibodies were significantly higher in the vaccine groups (both formulations) than in the placebo. A more pronounced CD4+-mediated immune response was observed in the group of volunteers administered with the 20 + 20 μg vaccine formulation. Interpretations: RBD-Fc-based COVID-19 “Betuvax-CoV-2” vaccine in doses (20 + 5 µg and 20 + 20 µg) demonstrated an excellent safety profile and induced a strong humoral response. Further research on the protective effectiveness of the “Betuvax-CoV-2” vaccine for the prevention of COVID-19 is on its way