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Oleg Balanovsky,1– 3 Valeria Petrushenko,1,4 Karin Mirzaev,2,5 Sherzod Abdullaev,5 Igor Gorin,1,4 Denis Chernevskiy,2 Anastasiya Agdzhoyan,1,2 Elena Balanovska,2,3 Alexander Kryukov,5 Ilyas Temirbulatov,2,5 Dmitriy Sychev5 1Laboratory of Genome Geography, Vavilov Institute of General Genetics, Moscow, Russia; 2Laboratory of Human Population Genetics, Research Centre for Medical Genetics, Moscow, Russia; 3Biobank of North Eurasia, Moscow, Russia; 4Department of Bioinformatics Moscow Institute of Physics and Technology, Moscow, Russia; 5Department of Clinical Pharmacology and Therapeutics, Russian Medical Academy of Continuous Professional Education, Moscow, RussiaCorrespondence: Elena BalanovskaLaboratory of Human Population Genetics, Research Centre for Medical Genetics, Moscow, RussiaTel +7 499 612-81-79Email balanovska@mail.ruDmitriy SychevDepartment of Clinical Pharmacology and Therapeutics, Russian Medical Academy of Continuous Professional Education, Moscow, RussiaTel +7 495 680-05-99Email dmitry.alex.sychev@gmail.comBackground: Information about the distribution of clinically significant genetic markers in different populations may be helpful in elaborating personalized approaches to the clinical management of COVID-19 in the absence of consensus guidelines.Aim: Analyze frequencies and distribution patterns of two markers associated with severe COVID-19 (rs11385942 and rs657152) and look for potential correlations between these markers and deaths from COVID-19 among populations in Russia and across the world.Methods: We genotyped 1883 samples from 91 ethnic groups pooled into 28 populations representing Russia and its neighbor states. We also compiled a dataset on 32 populations from other regions using genotypes extracted or imputed from the available databases. Geographic maps showing the frequency distribution of the analyzed markers were constructed using the obtained data.Results: The cartographic analysis revealed that rs11385942 distribution follows the West Eurasian pattern: the marker is frequent among the populations of Europe, West Asia and South Asia but rare or absent in all other parts of the globe. Notably, the transition from high to low rs11385942 frequencies across Eurasia is not abrupt but follows the clinal variation pattern instead. The distribution of rs657152 is more homogeneous. The analysis of correlations between the frequencies of the studied markers and the epidemiological characteristics of COVID-19 in a population revealed that higher frequencies of both risk alleles correlated positively with mortality from this disease. For rs657152, the correlation was especially strong (r = 0.59, p = 0.02). These reasonable correlations were observed for the “Russian” dataset only: no such correlations were established for the “world” dataset. This could be attributed to the differences in methodology used to collect COVID-19 statistics in different countries.Conclusion: Our findings suggest that genetic differences between populations make a small yet tangible contribution to the heterogeneity of the pandemic worldwide.Keywords: severe COVID-19, genetic markers, AB0, rs11385942, rs657152, gene geography

Alexander Valerevich Kryukov,1 Dmitry Alekseevich Sychev,1 Denis Anatolevich Andreev,2 Kristina Anatolievna Ryzhikova,1 Elena Anatolievna Grishina,1 Anastasia Vladislavovna Ryabova,1 Mark Alekseevich Loskutnikov,3 Valeriy Valerevich Smirnov,4 Olga Dmitrievna Konova,1 Irina Andreevna Matsneva,2 Pavel Olegovich Bochkov1 1Russian Medical Academy of Continuous Professional Education, Moscow, Russia; 2Department of General Medicine, Sechenov First Moscow State Medical University, Moscow, Russia; 3L.A. Vorohobov City Clinical Hospital, Moscow, Russia; 4NRC Institute of Immunology FMBA of Russia, Moscow, Russia Introduction: Difficulties in non-vitamin K anticoagulant (NOAC) administration in acute stroke can be associated with changes in pharmacokinetic parameters of NOAC such as biotransformation, distribution, and excretion. Therefore, obtaining data on pharmacokinetics of NOAC and factors that affect it may help develop algorithms for personalized use of this drug class in patients with acute cardioembolic stroke. Patients and methods: Pharmacokinetics of apixaban in patients with acute stroke was studied earlier by Kryukov et al. The present study enrolled 17 patients with cardioembolic stroke, who received 5 mg of apixaban. In order to evaluate the pharmacokinetic parameters of apixaban, venous blood samples were collected before taking 5 mg of apixaban (point 0) and 1, 2, 3, 4, 10, and 12 hours after drug intake. Blood samples were centrifuged at 3000 rpm for 15 minutes. Separate plasma was aliquoted in Eppendorf tubes and frozen at -70°C until analysis. High-performance liquid chromatography mass spectrometry analysis was used to determine apixaban plasma concentration. Genotyping was performed by real-time polymerase chain reaction. CYP3A isoenzyme group activity was evaluated by determining urinary concentration of endogenous substrate of the enzyme and its metabolite (6-β-hydroxycortisol to cortisol ratio). Statistical analysis was performed using SPSS Statistics version 20.0. The protocol of this study was reviewed and approved by the ethics committee; patients or their representatives signed an informed consent. Results: ABCB1 (rs1045642 and rs4148738) gene polymorphisms do not affect the pharmacokinetics of apixaban as well as CYP3A5 (rs776746) gene polymorphisms. Apixaban pharmacokinetics in groups with different genotypes did not differ statistically significantly. Correlation analysis showed no statistically significant relationship between pharmacokinetic parameters of apixaban and the metabolic activity of CYP3A. Conclusion: Questions such as depending on genotyping results for apixaban dosing and implementation of express genotyping in clinical practice remain open for NOACs. Large population studies are required to clarify the clinical significance of genotyping for this drug class. Keywords: cardioembolic stroke, atrial fibrillation, non-vitamin K anticoagulants, apixaban, pharmacokinetics, pharmacogenetics

Writing his History of the Russian State N. M. Karamzin used the Russian chronicles, embassy documents, and diplomatic correspondence. He was among the first historians to turn to foreign sources, and to that end had to obtain copies of the documents shedding light on the relations between the Moscow State and the Teutonic Order in the first quarter of the 16th century. In the following years and up to the present time, however, both Russian and German researchers have been paying little attention to the analytical aspect of the Russian historiographer’s work. The article deals with the the attitude to Karamzin’s research activity, accentuating the significance of his work for assessing the events of 500 years ago and of today.

The aim of the study was to investigate the species diversity of AM fungi in different parts of the North Caucasus, biodiversity hotspot, the center of the world’s biological diversity. Samples were taken from 5 locations (stationary trial plots, STPs) in different ecosystems and at various altitudes. Identification was performed using sequencing for ITS1 and ITS2 regions, amplified with universal primers, Illumina MiSeq was employed. 19 genera of AM fungi were found on all STPs. The work did not reveal a correlation between the altitude and the species composition of AM fungi. At the same time, it should be assumed that a correlation could be found between the biodiversity of AM fungi and the type of ecosystem, which should be done in the future. The study shows it is necessary to use an analysis for both ITS regions, since the data obtained for each ITS region differ and complement each other. Analysis for the ITS2 region revealed 1.3 times more virtual taxa than for the ITS1, while the number of OTUs identified per species was similar for both regions. The highest biodiversity of AM fungi was found in STP #3 (with meadow flora). Only 4 species (Rhizophagus irregularis, R. intraradices, Paraglomus laccatum, and Claroideoglomus claroideum) were found on all five analyzed STPs. We found unexpectedly that with such a high biodiversity among the identified fungi, no different species were found in the Paraglomus genus, all the sequences of Paraglomus belonged to Paraglomus laccatum, whereas at least 9 species are distinguished in the genus by morphology. Further research will allow us to identify new strains of AM fungi, the efficiency of which may be higher than already studied ones. In the future this will make it possible to create more effective microbial biofertilizers for agriculture.

Energy storage units (ESU) and distributed generation (DG) plants including those using renewable energy sources can be used to develop isolated power supply systems (IPSS) and enhance their reliability. Operation of DG plants in the IPSS requires to consider restrictions for consumers maximum load, as well as effects of abrupt load increase or load shedding on the generating plants. These problems can be resolved using ESU and intelligent technologies for DG plants control. The paper considers IPSS of an industrial facility with turbogenerator plants (TGP), wind power plant (WPP) and high-capacity ESU for which fuzzy control systems and prognostic controllers were used. The simulation was performed in the MATLAB system using the Simulink and SimPowerSystems software packages. Normal and emergency modes were studied in IPSS with TGP, WPP, and high-capacity ESU. The simulation results indicated that combined use of high-capacity ESU and prognostic controller of TGP generator rotor speed allows to ensure stability and survivability of IPSS enhancing its damping properties. The auto-prognostic controller of the TGP generator, which does not require special adjustment, provides high quality indicators of the IPSS control in all considered modes.

The objective reality of social interaction demonstrates the further development of social relations in various aspects of human existence, which gives rise to new contradictions that require resolution, including legal regulation by the norms of various law branches. There is a need to establish the limits for the subject’s legally acceptable behaviour, upon reaching which the area of deviations begins. Sexual harassment is one of such problems emerged at the end of the 20th century. Many foreign countries faced with this social phenomenon have recognized the criminality of sexual harassment in continuation of the chosen political trend towards liberalization of sexual relations. Similar trends are also observed in Russian society. They are practiced both at the level of discussions within the doctrinal environment and at the legislative level. Concerned about the seriousness of the problem and armed with the results of sociological research, Russian forensic scientists are engaged in developing a concept for the criminalization of harassment. The purpose of this work is to study the criminological grounds for recognizing the wrongfulness of sexual harassment and to consider the current criminal law powers against harassment in order to confirm the need to criminalize this phenomenon or to deny it. To achieve this purpose, the opinions of domestic and foreign researchers were studied, a rather-legal analysis of the domestic policy tendencies in Russia and foreign states regarding the liberalization of sexual relations was carried out. The conditions of the modern Russian legislation in combating sexual harassment were studied. Applied are such general scientific research methods as analysis, synthesis, generalization, as well as such specific scientific methods as statistical method, content analysis, formal logical method, and rather-legal method. As a result, the authors come to the conclusion that there is a recognized unlawfulness of sexual harassment in the norms of the current Russian legislation and that it is inexpedient to criminalize this phenomenon as an independent crime in view of the sufficiency of powers available within the framework of the modern criminal law.

The purpose of the study is to identify the main trends and factors influencing the development of the theoretical concept of the legal system and possible categories derived from it. The methodological basis of the research is represented by such scientific methods as dialectical, logical, historical, predictive, systemic analysis and content analysis. This made it possible, in view of achievement of the said objective, to analyse the works of Russian and foreign comparativists, both the founders of modern comparative jurisprudence and novice researchers, as well as the materials of scientific conferences on the problem under investigation. The result of the study was the conclusion that the complex nature of the category “legal system” makes it possible to form a holistic picture of legal reality. At the same time, the result of the research depends on the criterion laid as a basis for this concept. The paper also substantiates the fact that presently one may observe a tendency towards a comprehensive understanding of the legal system, towards rejection of the formational approach in favour of the socio-cultural one, with regard for a number of other internal and external factors affecting the formation and functioning of the legal system. The novelty of the study was the conclusion that the concept of the legal system, as well as the categories derived from it, so far represent the basic theoretical function in formulating hypotheses, setting goals and objectives of comparative legal research. At the same time, the authors note that a unified approach to comprehending the essence, typology and classification of legal systems is objectively not possible in the conditions of multiple legal cultures and traditions of legal consciousness, which, ultimately, should be assessed as a positive stimulus for further research.

The paper considers specific features of formation and development of organizational structures in the Russian economy, aimed both at achieving economic and technological sovereignty and at developing cooperation and interaction of complementary industries and spheres of economic activity. The most important features of the proposed approach include the consideration and development of interaction through the lens of spatial characteristics of the domestic economy. According to the authors, the Russian economy is characterized by an increasingly important role of the spatial factor in solving all the main tasks of socio-economic development. This is associated with significant distances of delivery and provision of goods and services, as well as with a high degree of spatial dispersion of individual stages and redistribution within the value chain (added value). Failure to take this circumstance into account in the process of ‘radical’ economic reforms over the past 30–35 years has led to the degradation of many industries and spheres of economic activity – the rupture or elimination of fragments of value chains (added value) created in the process of industrialization. The authors of the paper develop and detail the approach to the formation of sustainable value chains (added value), called ‘pulse projects’, developed by the IEIE. It is proposed to develop these projects on the basis of a combination of vertical integration processes of complementary stages and redistribution (located in different regions of the country). Such development is closely related to the building of horizontal interactions at individual stages of economic processes and technological redistribution. This approach allows, according to the authors, to ensure the formation and development of horizontal interactions in the context of implementing both the tasks of spatial development and achieving the priorities of scientific and technological policy

In the process of the smart grids formation a special attention is started to be paid to the issues of power engineering facilities safe functioning and reduction in their negative impact on personnel and environment. One of the important factors of such an impact is the generation of significant levels of strength of electromagnetic fields (EMF) by high-voltage overhead power transmission lines (OPL). In the context of the electric power industry digitalization, in order to improve the electromagnetic safety of service personnel, development of methods and means for digital modeling of EMF created by power lines of various designs is required, including traction networks of electrified railways. Computer models providing an adequate determination of the OPL EMF can be implemented on the basis of methods and tools designed for determining the parameters of the modes of electric energy systems in phase coordinates, developed at the Irkutsk State University for Railroads Communications. As an example of using these methods, the solution to the problem of constructing pictures of the distribution of EMF in the space surrounding the intersection of a flexible symmetrical conductor and a 25 kV traction network is given.

Traction networks (TN) 25 kV generate higher electromagnetic fields (EMF) with frequency 50 Hz, whose strengths at a standardized height of 1.8 m, as a rule, do not exceed the permissible norms for electrical personnel. In places where railroads routes intersect with high voltage overhead power supply lines (OPL), interference of fields, generated by the traction network and OPL, occurs. This can lead to an increase in strengths and a complication of the EMF spatial structures. The article presents simulation results performed for a complex intersection, while 25 or 2 х 25 kV TN is crossed by a three-circuit 110-220 kV overhead power line at 90 degrees angle. Fazonord software application was used for simulating EMF strengths in points of traction networks and OPL intersection. Based on modeling results the following conclusions have been made: at intersection points of 1х25 kV traction network with a three-chain 110 - 220 kV power transmission line, the electrical field strength does not exceed the value acceptable for electrical personnel and reaches 4.2 kV/m; at the intersection with 2 х 25 kV traction network, this parameter decreases to 2.7 kV/m; the maximum amplitude of the magnetic field at the intersection points increases slightly.

Application of asynchronized generators (ASG) in distributed generation plants allows to obtain the following positive results: increase stability margins; expand reactive power adjustment ranges; simplify processes of synchronization to line due to possibility of frequency and EMF phase control; ensure the unit’s operation in synchronous mode when one of excitation windings is damaged. The work provides description of the developed ASG computer model and the system of excitation automatic control. The studies are conducted in the MATLAB system using the Simulink and SimPowerSystems software packages. Emergency modes were simulated for the mains with ASG-based distributed generation plants in conditions of inferior power quality. ASG influence on emergency modes and levels of harmonic distortions in the mains were determined.

The use of distributed generation (DG) plants in power supply systems is a rapid development line. However, the impact of DG on power quality is multivalued. On the one hand, the presence of DG allows to reduce voltage losses. On the other hand, a phenomenon called flicker and associated with rapid voltage fluctuations is possible. This effect is usually manifested at an abrupt voltage drop in the DG generator connection unit. The processes taking place in the network when flicker occurs in networks with DG have not been sufficiently studied. The article presents results of the flicker modeling in a network equipped with DG plants, implemented on the basis of synchronous generators. The results obtained indicated that with sharp disturbances caused by switching on and off an additional load, flicker is observed in networks with unregulated generators, accompanied by voltage and frequency fluctuations. Based on the wavelet transformation and spectral analysis methods, it was found that the power spectral density of the generated flicker-noise is inversely proportional to the frequency. The use of look-ahead control algorithms to control the excitation and rotors rotational speed of the DG plants generators, as well as concordant adjustment of their controllers, increases stability and removes flicker completely.

The wide use of distributed generation (DG) technologies in electrical energy systems (EES) requires development of new control algorithms in normal, emergency and postemergency modes. The issues of determining the static aperiodic stability (SAS) margin in EES equipped with DG plants are of particular relevance. These plants can be removed from the consumption centers, which can lead to SAS reserves depletion. The article presents the results of studies aimed at the developing SAS reserves express calculation methods in EES equipped with DG plants. An effective technique to determine stability margins was proposed based on one of the modifications of limiting modes equations. The results of determining SAS for an electrical network with distributed generation plants are presented. Additionally, the simulation of transient processes in the studied EES for various points in the space of the mode’s controlled parameters has been carried out in the Matlab system.

The objective of our research was to analyze the efficiency of identification of arbuscular mycorrhizal fungi (AMF) for 2 regions: ITS1 and ITS2 regions of AMF DNA isolated from the soils of the North Caucasus (Karachay-Cherkessia). For the first time the necessity of different AMF species identification using both ITS regions was revealed, but not one region. The research demonstrated: 1) the set of taxa is different using ITS1- and ITS2-based identification; 2) analysis of the ITS1 region reveals a greater number of operational taxonomic units; 3) ITS2 allows identification of AMF at the species level more often. Sample preparation for Illumina MiSeq analysis was optimized. Obligatory stages in the sample preparation were the purification of DNA in the agarose gel in Silica after isolation, as well as separate amplification of ITS1 and ITS2 followed by combining and joint sequencing for each sample. The results showed the highest AMF biodiversity for the 176Te sample from the ecosystem of the subalpine meadow of the southeastern slope of Malaya Hatipara mountain (43°25′48.0″N 41°42′31.0″E; 2401 m above sea level), in which 8 species of AMF were identified (Archaeospora spainiae, Claroideoglomus claroideum, Diversispora versiformis, Entrophpora infrequens, Funneliformis mosseae, Glomus indicum, Paraglomus laccatum, Rhizophagus irregularis).

The article presents modern approaches to the diagnosis and therapy of patients with allergic rhinitis. The document was developed by the professional association of pediatric specialists — the Union of Pediatricians of Russia — together with leading specialists of the Russian Association of Allergologists and Clinical Immunologists, the National Medical Association of Otorhinolaryngologists and is regularly updated taking into account the latest data on the effectiveness and safety of various medical interventions. The article provides information about the epidemiology of allergic rhinitis, provides characteristic diagnostic signs of the disease, allowing for establishment as timely as possible of a correct diagnosis and, taking into account a personalized approach, prescribe effective therapy.