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Introduction. The drug can be used in the treatment of one disease and for the prevention and treatment of another pathological process. This is possible due to the repurposing of medicines. Creating drugs from scratch takes a long time to develop and implement, which leads to large financial costs, and also has a high dropout rate of candidate substances and requires significant financial costs. The main advantage of repurposing instead of creating new drug is relatively low financial costs and a significant reduction in the first two phases of clinical trials.Text. Drug repurposing is based on pharmacology, pharmacokinetics, pharmacodynamics, pharmaceuticals and clinical trials, where the first two phases are significantly reduced compared to the creation of a completely new. There are examples of successful repurposing and negative side effects with off-label drug use, which is unsafe but the best solution for orphan diseases. A targeted search for the possibility of repurposing drugs using an automatic procedure is being carried out, where a large number of chemical compounds are tested for activity or affinity for receptors and enzymes – high-throughput screening. Computer design has become widespread, which or repurposing "in silico", where information about the drug is used: targets, chemical structures, metabolic pathways, side effects, followed by the construction of appropriate models. Machine learning (ML) algorithms: Bayes classifier, logistic regression, support vector machine, decision tree, random forest and others are successfully used in biochemical pharmaceutical, toxicological research. But the most promising development of reprofiling is associated with the use of deep neural networks (DNN). Using deep learning, DNN were found to outperform other algorithms for drug development and toxicity prediction.Conclusion. Currently, interest in drug repurposing has grown markedly. A search for the keywords «drug repurposing» showed 2,422 articles on the problem of new uses for drugs that already exist in medicine.

A validated method for the quantitative determination of venlafaxine, O-desmethylvenlafaxine in human plasma by tandem liquid chromatographymass spectrometry (HPLC/MS/MS) has been proposed. Sample preparation was carried out by liquid-phase extraction with support (SLE, from «supported liquid extraction») using HyperSEP cartridges and washing with 3-methylbutyl ether. The measure of the target analytes was carried on a triple quadrupole mass spectrometer under multiple-reaction monitoring (+MRM) mode with the electrospray ionization. The calibration curves were linear with regression coefficient r2 > 0.999. The method validation was showed high sensitivity, specificity, accuracy and reproducibility, as well as stability of analytes after freeze/thaw cycles and storage at –20 °C. The method is developed for using in therapeutic drug monitoring.

Aim. To study the functional state of the expiratory muscles in patients with type 2 diabetes mellitus on the basis of changes in their electrical activity when using a functional test with a static expiratory effort. Materials and methods. 47 patients with type 2 diabetes mellitus and 40 patients without disorders of carbohydrate metabolism were examined. To study the electrical activity of the expiratory muscles, surface electromyography (EMG) of the external oblique abdominal muscle (OAM), rectus abdominis muscle (RAM), and internal intercostal muscles (IIM) was performed using a functional test with a static expiratory effort. Results. When performing a functional test with a static expiratory effort in both groups, a decrease in the frequency and an increase in the amplitude of EMG was observed, however, in patients with type 2 diabetes mellitus, these changes were less pronounced. There were also differences in the dynamics of changes in EMG indicators. In patients with type 2 diabetes mellitus, the decrease in the frequency of EMG OAM began from 10 seconds of the test, IIM – from 15 seconds, in the comparison group – from 5 and 10 seconds, respectively. The OAM EMG amplitude in the main group did not change significantly, in the comparison group it increased from 5 seconds of expiratory effort. At the 10th second of the test, the amplitude index of the EMG OAM in patients with type 2 diabetes mellitus was 10.4% lower (p=0.027) than in the comparison group, and at the 15th second – by 10.5% (p=0.033). Conclusion: The change in the electrical activity of the expiratory muscles in patients with type 2 diabetes mellitus is due to the slowed down dynamics of the frequency-amplitude characteristics of the EMG OAM, uncompensated IIM fatigue, as well as lower values of the OAM EMG amplitude when performing a functional exercise test with a static expiratory effort.

The article attempts to structure the impact of the coronavirus pandemic on the sociopolitical organization of society and legal regulation. The authors offer their own vision of the most significant changes that have occurred in various spheres of society in this specific period. The pandemic has demonstrated the diverse effects of digitalization (both highly positive in terms of social progress and sustainable development, and extremely negative). In addition, during the period of antiviral regulation, certain trends and patterns of legal regulation were spontaneously laid down; they can lead to fundamental and critical changes in the legal system. The article features the trends outlined by the pandemic and formulates proposals, allowing to take into account the extreme experience of survival in the conditions of the viral threat and to enter the post-pandemic world with minimal losses.

The lack of sufficient legal regulation of relations associated with the use of artificial intelligence and robotics is associated with the conceptual lack of resolution of the basic issues underlying modern models of legal regulation for anything: about the concept and general status of the phenomenon to be settled. With regard to the research topic, this translates into questions about the concept and legal personality of artificial intelligence. These questions represent a kind of logical metaphor: in order to start modeling the legal personality of artificial intelligence, we must first define its concept; and the legal concept of artificial intelligence will be formulated differently depending on whether we consider it as a subject or an object of law. The authors investigate the technical, moral and legal aspects of the problem concerning the status and understanding artificial intelligence, and draw conclusions about the basic conditions for the legal regulation of this area.

The measurement data obtained at the GPS network in the southwestern part of the Baikal Rift System for the period from 1994 to 2020 were analyzed. The spatial relationship between seismic events and tectonic strain rates was estimated. The field of modern horizontal motions and deformations was calculated for the Tunka, South Baikal, and Khubsugul depressions. The rotation pole of the Siberian block was defined. The general geodynamic setting on the western flank of the Baikal Rift System is characterized by low horizontal velocities in the range of 0.5–1.4 mm yr–1. Based on calculation of the relative deformations, the contrast zones of dilatation with narrow zones with the “non-Baikal” type of directions of deformation processes against the background tectonic extension regimes have been determined for the first time in the Bystraya and Khubsugul tectonic depression. Tectonic stresses are accumulated in these narrow zones and released in earthquakes.

The research objective of the paper is to generalize the ethical problems associated with the development and implementation of autonomous robotic technologies (autonomous robotic devices, ARD) in the civil and military spheres. Unresolved ethical problems hinder the development of legal regulation of new technologies. The authors propose a typology of ethical problems of digitalization for the purpose of creating legal regulation concerning the use of artificial intelligence (AI) and other technologies. Depending on the scope of social relations covered and the forms of regulation proposed, the authors identified four groups of ethical problems of global digitalization, which are considered in the paper: philosophical, humanitarian, socio-ethical, and ethical-legal problems. It is concluded that the legitimacy of managerial decisions that endow robotic technologies with the potential to make decisions in the civil and military spheres should be determined in terms of ethical principles of regulating such relations.

The present work was aimed at the development of an analytical method with high sensitivity, selectivity, and rapidity for pharmacokinetic studies. The new method for quantitative determination of fludrocortisone in human blood plasma employs HPLC and mass spectrometric detection with electrospray ionization (ESI). The deuterium-labeled analog of fludrocortisone (fludrocortisone-D5) was used as the internal standard. The lower limit of quantitation (LLOQ) was 10 pg/mL. The calibration curve was linear in the range 10 – 1000 pg/mL. The coefficient of reliability was at least 0.99. Liquid extraction was used for sample preparation. The proposed technique was tested by studying the bioequivalence of a generic drug in a single administration to healthy volunteers at a dose of 0.1 mg.

З кожним днем відеоігри набувають все більшої популярності, зростає попит на нові креативні рішення як і у ігровому процесі, так і у графіці. Велику роль у вирішені даної проблеми відіграють фрактали. Вони знайшли багато варіантів використання: від зображення дерев та об’єктів у 3D просторі, побудови ландшафтів карт до інтеграції їх у гемплей на більш глибшому рівні, як наприклад побудови основної концепції гри, коли однакові невеликі частини гри є частинами більшої, але все ще подібною на них по концепції. З цього постає необхідність у пошуку нових способів використання фрактальних алгоритмів для покращення графічного та концептуального рівня гри. У даній роботі проведено аналіз способів використання фракталів для побудови ландшафтів карт та спрощення процесу реалізації ландшафтного заповнення локацій; генерації складних лабіринтів; алгоритми процедурної генерації 3D лабіринтів відеогри на основі кросплатформленого ігрового двигуна; організацію взаємодії гравця з грою за допомогою фракталів; можливість його використання у інших типах відеоігор. Наведено огляд ігрових застосунків в яких використовується фрактальна графіка, а саме: The Legend of Zelda, Link’s Awakening, Свідок, Пробудження Лінка, I Love Hue. Для спрощення використання фракталів при побудові лабіринтів наведено їх класифікацію в залежності від властивостей, якими вони володіють. До таких властивостей можна віднести розмірность, гіперрозмірність, топологію відтворення, тесселяцію, маршрутизацію, текстуру і пріоритет. Лабіринт може використовувати по одному елементу з кожного наведеного класу в будь-якому поєднанні. Використання фракталів в відеоіграх дозволяє значно зменшити об’єм оперативної пам’яті, необхідний для функціонування гри та збільшити її швидкодію за рахунок оптимізації алгоритму. Ключові слова: фрактал, фрактальний дизайном гри, Fractal Design, Link’s Awakening, фрактальна графіка, фрактальні лабіринти, фрактальне моделювання.

Purpose of the study. Educational methodological activity plays an important role in the life of the university, on the one hand, it determines the content of the educational process and sets the direction of development, on the other hand, it requires a significant amount of time from teachers, staff and managers. Continuing changes in the system of Russian higher education are reflected in educational methodological activities. When introducing and refining higher education standards and other normative documents, the means of describing the educational process in educational and methodological documentation change. The composition of educational methodological documents and the requirements for them are changing. Such concepts as “competence”, “type of activity”, “tasks of professional activity”, “labor functions”, etc. appear and then transform. The present work aims to track the dynamics of these changes and assess the increase in the complexity of educational methodological support. Materials and Methods. To assess the dynamics of development of educational and methodological support, we will carry out a retrospective substantive analysis of educational and methodological support for each stage of its development, starting with the first generation of state educational standards. The analysis results will be visualized with the Entity-Relationship" diagrams, which allow reflecting the main entities of the scope, their attributes and relationships. Examples of entities are: competence, professional standard, educational result (different forms of skills), topic, module, etc. Such diagrams can be interpreted as metamodels of educational and methodological support. Next, we will carry out a comparative analysis of the obtained sequence of metamodels, which will allow us to understand the dynamics of their development. Results. A set of metamodels of educational and methodological activities was built. The dynamics of the growth of the number of entities and relationships by year was found. We also studied changes in entities and details. A set of metamodels of educational and methodological activities was built, including metamodels for the following stages: state educational standards of the first generation, second generation, federal state educational standards or the third generation, generation 3+, generation 3 ++. If the first two models are characterized by relative simplicity, then the standards of the third generation required the development of a significant number of new entities associated with competencies, and another increase in complexity is observed for generation 3 ++, which is associated with the introduction of professional standards. The dynamics of growth in the number of entities, attributes and especially relationships has been established. Over the past two decades, the number of entities that are used in the creation of educational and methodological support has increased from 9 to 32, and the number of connections between them from 12 to 45. Changes in individual entities and details were also studied as the metamodels of educational and methodological support developed. Conclusion. Based on the results of the analysis, describing tools for the educational and methodological support tend to become considerably more sophisticated. This is reflected in the labor costs of the formation of documents, as well as the time that must be spent by teachers and staff on studying the language of description of educational and methodological documents. Thus, there are risks of the educational and methodological support quality reducing and the risk of a gap between educational and methodological documentation and the real educational process of the university.

The paper examines the doctrinal aspects of understanding cyber terrorism as an atypical manifestation (form) of traditional terrorism updated in light of the intensive development and widespread dissemination of information and communication technologies (ICT) in the modern world. The conclusion is substantiated that cyber terrorism is a conceptually relevant concept, which is perceived either as a method of committing a terrorist act (reduced understanding), or as any crimes of a terrorist nature that are committed using information and communication technologies (broad understanding). Analysis and generalization of scientific positions allowed us to define this phenomenon of social reality as the illegal use of information and communication technologies in relation to computer information, computer systems and networks in critical segments of the state and in the private sector, which pose a risk of death, causing significant property damage or the onset of other socially dangerous consequences, with the aim of whipping up fear and tension, as well as influencing the authorities for political or other motives characteristic of the ideology of terrorism.

The article deals with the problem of combating cybercrime in the Russian Federation in the context of its transition to the digital economy. Society and the state in the 90s and early 2000s did not recognize the danger behind cybercrimes. The concept of absolute freedom of dissemination of information, which existed at the time, and other factors have led to a high increase in cybercrime today. The authors concluded that the situation changed only in the last decade, when they began to fight against cybercrime in a comprehensive manner. The article also discusses the issue of delimiting cybercrimes from related criminal acts. The Russian Federation has recognized cybercrime as the main threat to state security and the stability of society. This is reflected both in the development of criminal-legal measures to combat cybercrimes and in preventive measures of an administrative nature. Objects of the so-called critical information infrastructure received special legal protection. The article also reviewed the social danger of some cybercrimes having been already liable to criminal responsibility.

This article examines the impact of digitalization processes on public relations, the legal culture of society, the transformation of public order, and the established value-normative regulators. The authors identify and analyze the key trends and problems of the modern transformation of society, state and law, discuss the main scenarios of interaction between the state-legal organization of society and the rapidly developing new "meta foundations" of social order. They critically assess the attitude according to which digital technologies and algorithmic solutions in the XXI century will ensure systemic control and safety of society. The content of the work also argues that the complete and final virtualization of the regulatory legal space is a rather lengthy and highly contradictory process. The final part of the research substantiates that the emergence of new digital spheres of legal regulation, in a situation where traditional elements of the state, public, and private life move somewhat into a digital virtual space, places the law before new challenges to be addressed based on traditional general legal approaches.

In the proposed article, the author tries to prove that the important reason for the existence of systemic errors in the interpretation of law is directly related to the problem of understanding the object of legal science. The research was conducted within the framework of a systematic approach by the method of logical analysis. The author’s understanding of the object of legal science is highlighted, its logical structure is revealed. The connections between the structural elements have been established and the dependence of the appearance of systemic errors in the interpretation of the law on one or another scientific interpretation of this connection has been clarified. It is emphasized that among all known ways of interpreting law in the paradigm of different types of legal understanding, the marker of the presence or absence of systemic errors in the interpretation of law is a special legal method of interpretation based on special legal factors: a) features of legal understanding; b) the dominance in the legal science of a particular society and in a particular historical time of certain legal doctrines, views, theories on the essence of law, its functional role in society; c) features of legal practice; d) levels of development of legal reality. A hypothetical judgment is made that the solution of the issue of avoiding systemic errors in the interpretation of law should be carried out within the framework of the problem of the main issue of jurisprudence. Accordingly, the notion of law enshrined at the level of official legal doctrine should be used, which would reflect the objective trends of legal development of mankind in accordance with the laws of natural law and universal legal values formed at the intersection of material and spiritual needs of society. The author’s definition of the following concept is proposed: law is an objectively determined, rationally substantiated through a slice of general interest system of principles, institutions, norms, rules of conduct verified by social practice (which in systematic interaction do not contradict the requirements of morality and actions of the laws of natural law), the functioning and implementation of which are associated with government institutions that have a recognized right (privilege) to exercise coercion. A special vector of consideration is devoted to doctrinal legal errors, examples of negative consequences for the state, society due to systemic errors in the interpretation of law are given. Keywords: error, legal error, system errors of interpretation of law, precautionary measures.

The article discusses the use of the Agile methodology in providing educational and methodological activities at university. The article presents the current results of the study carried out with the financial support of the Russian Foundation for Basic Research (RFBR) in the framework of the research project No. 19-013-00690 “Economics of educational and methodological activities in high school”. The article proposes the requirements that can be applied to the use of the Agile methodology in providing educational and methodological activities of the University. The possibility and expediency of using this methodology for the successful implementation of these processes has been substantiated. The principles and tools of Agile in adaptation to the educational process of the university are presented. The components of the proposed approach are considered, in particular: the basic principles of the Agile methodology and the possibility of their application in educational and methodological activities; the compatibility of Agile with the existing system of educational and methodological support; areas where Agile technologies and principles can be adapted immediately and without significant problems. The problems on the way of introducing flexible methodologies into the educational and methodological activities of the university are indicated.

Background — Recurrent upper airway obstruction during the sleep is a key feature of obstructive sleep apnea (OSA). In patients with OSA, an intermittent upper airway obstruction yields an increase in inspiratory effort and, consequently, an augmented impact on inspiratory muscles (IM). However, the issue of IM fatigue development in OSA patients is still controversial. Objective — to investigate the functional condition of IM in patients with OSA of various degrees of severity. Material and Methods — Were examined 82 men (30-65 years old), who were distributed among four groups depending on the OSA severity. Cardiorespiratory monitoring was performed to detect OSA. IM electrical activity was detected via surface electromyography (EMG) while holding the breath (during the inhalation). Results — In the course of our study, we detected a reduction in the frequency of EMG of accessory IM, specifically sternocleidomastoid muscle (SCMM) and external intercostal muscles (EIM), accompanied by a simultaneous increase in the amplitude of EMG of SCMM, EIM, and diaphragm (D), while holding the breath (during the inhalation), in the group of patients without OSA. In patients with mild OSA, when holding the breath during the inhalation, the frequency of EMG of SCMM and EIM decreased, while the amplitude of SCMM and EIM increased. In patients with moderate OSA, when holding the breath during the inhalation, a decrease in the frequency of SCMM EMG with a simultaneous increase in the amplitude of the EIM EMG were revealed. Same maneuver in the group of patients with severe OSA yielded no significant changes in the frequency and amplitude of EMG of respiratory muscles. Conclusion — Periodic obstruction of the upper airways with OSA leads to the development of fatigue resistance in accessory IM.

На підставі результатів раніше виконаних теоретичних та експериментальних досліджень визначено умови змін мікроструктури білих квазіевтектичних легованих чавунів шляхом їх термічної обробки, яка базується на принципах «регенерації» мікроструктури гетерофазних матеріалів із поліморфними матричними фазами. Показано формування, в процесі оптимальної термічної обробки дослідженого білого чавуну, дисперсних, однорідних за розмірами та характером свого розподілення в структурі кристалів легованого структурно вільного цементиту, замість пластинчастого, що входив до складу ледебуриту, а також наддисперсних ділянок матричної фази, що містять нанорозмірні частинки цементиту. Наголошено на спільних рисах процесів «регенерації» мікроструктури у гетерофазних матеріалах різного хімічного складу, що забезпечує надійне отримання високих показників механічних властивостей

According to seismological and geodetic data, the central part of the South Baikal basin is under an extension regime of the Earth’s crust. This study presents for the first time seismological evidence of a transtensive stress field in a local area adjacent to the eastern side of the Central Baikal subbasin. Two independent approaches to determining the orientation of the principal stress axes show a subhorizontal orientation of the axes of stresses of minimum and maximum compression, which results in a strike–slip component in the focal mechanisms of the earthquakes. The area under consideration is a part of the Ust’-Barguzin transfer zone, in which the transfer of deformations between South Baikal and the Barguzin basin takes place. The results obtained are in agreement with the geological and structural data and may indicate the contribution of horizontal displacements in the transfer of deformations between the segments of the rift zone.

Introduction: the authors discuss the topic of digitalization as potentially one of the most effective ways to fight against corruption in modern Russia. Various forms of information technology application are analyzed, including “egovernment”, “e-Parliament”, and “e-justice”. Pointing to the certainly positive side of this phenomenon, such as the impossibility of the use of private agreements in the decision-making process in favor of one side or another, etc., the authors note the shortcomings of the procedure of digitalization, such as, for example, the ability of a human judge to “let all the circumstances of the incident go through himself”, to very humanely evaluate the motives of the crime, the attitude of the perpetrator towards the offense, the possibility of socializing the specified person; and on this basis to determine a fair and reasonable form and amount of punishment. The purpose of the research: to reveal the importance of introducing modern information technologies in the work of all branches of government as one of the areas of anticorruption. Objectives: to reveal the content of the term “e-justice”, to consider the main trends in the research on the issues related to the proliferation of digital technologies in the administration of justice and to assess the adequacy of their magnitude to modern realities; to emphasize the question of practical implementation of information technology as an effective mechanism of the fight against corruption. Methods: system, structural and functional, analysis, synthesis, expert assessment. Results: the authors describe one of the trends of the modern interdisciplinary research, which is not sufficiently covered in the scientific literature, and is manifested in an attempt to see the novelty in the relations through the use of the latest technical means; the activities carried out in electronic form and/or through the use of digital technologies, dedicated to the digitalization of the judicial system, aimed at improving the quality of the work of the courts, ensuring maximum transparency of their decision-making and reducing corruption in the justice system. Conclusions: the digitalization of cases will reduce all document flow and ensure the safety of all available criminal cases and materials, allowing us to improve the quality of preliminary investigation or preparation for trials, reduce the risks of possible falsification of evidence, and the introduction of “electronic justice” will reduce the manifestation of any forms of corruption in the justice sector.

In a block of two articles, the authors discuss the effectiveness of digital democracy mechanisms in times of crisis in the development of society. In particular, the COVID-19 pandemic and the situation caused by become the object of analysis. It is assumed that in the so-called Eastern States, due to the peculiarities of the legal mentality and the presence of certain archetypes, critical situations are more easily stopped by public-power mechanisms. The authors believe that in certain conditions, the tools of digital democracy can play a negative role, in particular, it means that in Western societies, what the authors call the “mediavirus” — the result of excessive informatization and freedom of speech — may become even more dangerous than its biological founder.

In the second part of the study, the authors address the issue of the possibility of introducing censorship to reduce the level of “covidopanic”. The article analyzes the issues of digital control and restriction of human rights, as well as the attitude to such restrictions in Western and Eastern states. The authors propose an original concept of alternation: to replace freedom with consumption, or at least try to use it as a “smoke screen” in Western states during crisis periods. The author concludes that it is necessary to rethink the classical concept of Western democracy.

The first (preliminary) results of a systematic search for minor ground level enhancement (GLEs) in solar cosmic rays (SCRs) in the 24th solar activity cycle are presented. The search was conducted based on the data of the global network of neutron monitors with allowance for the results of direct satellite measurements. The initial assumption is that such increases point to the possible acceleration of solar particles in shock waves, which are generated by coronal mass ejections. The shape of the integral spectrum of the accelerated particles according to observations of neutron monitors and measurements from near-Earth space vehicles could serve as a determinant for checking that hypothesis. Studying the spectra manifests an informativity of our approach to a better understanding of SCR source properties.

Background The relationship between a daily dose of olanzapine, its serum concentration, and the genotype of young nonsmoking men treated for schizophrenia or schizophreniform disorder was investigated in day-to-day clinical practice. Pharmacogenetics was also examined for the selected patients. Methods A total of 49 participants were recruited as in-patients at the Mental Health Research Center (Moscow, Russia). Inclusion criteria were patients who had been diagnosed with schizophrenia or schizoaffective disorder (following DSM-IV guidelines) and were being treated with OLZ. A prospective, observational, open-study design was implemented. In line with the literature, patients were only included if they attained steady-state OLZ concentrations lasting for at least 8 days. A liquid chromatographic-tandem mass spectrometric method was developed for analyzing OLZ in human serum. The single cytochrome P450 polymorphisms were genotyped using an amplifier real-time polymerase chain reaction system following standard protocols. Results Evidence indicating that CYP2D6 polymorphism has a significant (P = 0.046) effect on the pharmacokinetics of olanzapine was obtained, confirming the beneficial effects of therapeutic drug monitoring (TDM) for olanzapine. Conclusions TDM should therefore be used as a standard care during olanzapine therapy. TDM is also useful in assessing adherence and may have a role in limiting olanzapine dosage geared at minimizing the risk of long-term toxicity.