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The article examines the peculiarities of the formation and development of our country's legislation on criminal responsibility for insulting a military serviceman. The application of the historical method in this case made it possible to investigate the historical conditioning of the criminalization of such a socially dangerous act as an insult to a person in general and an insult to a military serviceman in particular. The studied legal monuments of the following periods: princely period; the period when Ukrainian lands were part of the Austro-Hungarian and Russian empires; the period of the Ukrainian SSR; the period of the independent state of Ukraine before the adoption of the new Criminal Code of Ukraine and the modern period. It is emphasized that the responsibility for an insult accrues a long time in the history of the legislation of our country. It contained norms on responsibility for the insult of any person, as well as for the insult of specifically defined persons: a woman, a mother, a father, a nobleman, etc. The insult was possible both by word and by physical actions. It was determined that for the first time the responsibility for insulting a serviceman was established by the Military Ordinance of Peter the I. The mentioned ordinance recognized only an officer (a special subject) as the subject of an insult. In the future, insult of various persons were criminalized: priests; officials; policemen, military personnel and others. Article 435-1 of the Criminal Code of Ukraine of 2001 fixed the composition of the insult of a serviceman in this form for the first time. And although disposition of the article causes certain remarks from scientists, practical workers and representatives of civil society, it is an important step in the criminal legal protection of the right of military personnel to professional honor and dignity. The author emphasizes that the criminalization of the insult of a military serviceman meets the conditions of historical conditionality and is timely and necessary. The article also provides author's definitions of the concepts of professional honor and dignity; criminal offense and its forms.

The domain structure of a fluid ferroelectric nematic is dramatically different from the domain structure of solid ferroelectrics since it is not restricted by rectilinear crystallographic axes and planar surface facets. We demonstrate that thin films of a ferroelectric nematic seeded by colloidal inclusions produce domain walls (DWs) in the shape of conics such as a parabola. These conics reduce the bound charge within the domains and at the DWs. An adequate description of the domain structures requires one to analyze the electrostatic energy, which is a challenging task. Instead, we demonstrate that a good approximation to the experimentally observed polydomain textures is obtained when the divergence of spontaneous polarization—which causes the bound charge—is heavily penalized by assuming that the elastic constant of splay in the Oseen-Frank energy is much larger than those for twist and bend. The model takes advantage of the fact that the polarization vector is essentially parallel to the nematic director throughout the sample.

IntroductionPeriodontal diseases are known to be associated with polymicrobial biofilms and inflammasome activation. A deeper understanding of the subgingival cytological (micro) landscape, the role of extracellular DNA (eDNA) during periodontitis, and contribution of the host immune eDNA to inflammasome persistence, may improve our understanding of the mechanisms underlaying severe forms of periodontitis.MethodsIn this work, subgingival biolfilms developing on biologically neutral polyethylene terephthalate films placed in gingival cavities of patients with chronic periodontitis were investigated by confocal laser scanning microscopy (CLSM). This allowed examination of realistic cytological landscapes and visualization of extracellular polymeric substances (EPS) including amyloids, total proteins, carbohydrates and eDNA, as well as comparison with several single-strain in vitro model biofilms produced by oral pathogens such as Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus gordonii, S. sanguinis and S. mitis. Fluorescence in situ hybridization (FISH) analysis was also used to identify eDNA derived from eubacteria, streptococci and members of the Bacteroides–Porphyromonas–Prevotella (BPP) group associated with periodontitis.ResultsAnalysis of subgingival biofilm EPS revealed low levels of amyloids and high levels of eDNA which appears to be the main matrix component. However, bacterial eDNA contributed less than a third of the total eDNA observed, suggesting that host-derived eDNA released in neutrophil extracellular traps may be of more importance in the development of biofilms causing periodontitis.DiscussioneDNA derived from host immunocompetent cells activated at the onset of periodontitis may therefore be a major driver of bacterial persistence and pathogenesis.

Проблематика. Надмірне накопичення меланіну в шкірі призводить до низки захворювань і косметологічних проблем. Для зменшення біосинтезу пігменту використовують інгібітори тирозинази, однак більшість із них мають суттєві побічні ефекти. Відомо, що при сумісному застосуванні ліків можуть спостерігатися синергізм, адитивний ефект і антагонізм. Комбіноване лікування декількома інгібіторами тирозинази розглядається як перспективний підхід до зменшення побічних ефектів і підвищення терапевтичної ефективності. Мета. Дослідження сумісного використання інгібіторів тирозинази для визначення типу їх взаємодії: синергізм, адитивна дія. Методика реалізації. У роботі використовували тирозиназу, виділену з грибів Agaricus bisporus. Інгі­бування ензиму досліджуваними сполуками визначали, вимірюючи його активність за тирозином (30 хв у 0,05 M Na-фосфатному буферному розчині, рН 6,5, 25 °С). Для вивчення сумісного інгібування розчини сполук змішували попарно в декількох концентраціях. Взаємодію розраховували з використанням комбінаційного індексу та побудови ізоболограм. Результати. Для визначення впливу сумісної дії речовин на активність тирозинази були обрані як стандартні інгібітори ензиму (койєва кислота, арбутин, фенілтіосечовина), так і виявлений нами 3-(2-гідроксифеніламіно)-1,3-дигідро-індол-2-он. Розрахунок комбінаційного індексу та побудова ізоболограм для всіх досліджених сумішей стандартних інгібіторів тирозинази показали адитивний ефект при одночасному застосуванні в усіх вивчених випадках. Одночасне застосування койєвої кис­лоти чи арбутину із 3-(2-гідроксифеніламіно)-1,3-дигідро-індол-2-оном має синергетичний ефект, однак суміш фенілтіосечовини із похідним індолу продемонструвала адитивну дію. Висновки. Сумісне використання інгібіторів тирозинази в різних комбінаціях показало як адитивний, так і синергетичний ефекти. Синергетичний ефект при одночасному застосування двох інгібіторів відкриває широкі можливості для створення більш ефективних, економічних засобів лікування гіперпігментації в результаті зменшення концентрації кожного інгібітора.

This study analyzes the current situation of application of precision farming technologies and solutions by agricultural enterprises of the Republic of Kazakhstan. The main players and used solutions have been identified. The statistics of application, as well as the potential of use is examined. Within the framework of the analysis of the applied solutions the advantages and disadvantages of competitors in the market were determined. It was defined that the applied systems provide the possibility of remote management, but EGISTIC is more focused on the management of all processes of the farm, including the warehouse, while John Deere is focused on the management and analytics of agricultural machinery. EGISTIC offers features for warehousing and inventory planning, something not found in the base version of John Deere Operations Center. John Deere focuses on data sharing which can be important for large farms or groups of farmers. EGISTIC makes extensive use of satellite imagery to analyze field conditions which can be a great asset for identifying problem areas and planning interventions. Depending on the specific needs and priorities of an agribusiness, one system may be preferable to another. If machinery management is the main focus, John Deere might be the best choice. If in-depth analysis of field conditions and inventory control is important, EGISTIC may be more appropriate. By analyzing, the directions for research are highlighted. A conceptual model of information system for precision farming is developed. Hardware for realization of the conceptual model is possible on the basis of universal programmable logic controller of modular architecture being developed. Within the limits of the given research the conceptual model of the universal programmable logic controller of modular architecture and the structural model of the software of the universal programmable logic controller of modular architecture have been developed. The interaction with the conceptual adaptive model of information and communication system is also considered. This paper analyzes the key principles and functions of both the universal programmable logic controller and the information and communication system, as well as their possible integration within a single concept.

The primary objective of this article is to establish a set of fundamental criteria for the selection of scientific partners for collaborative research efforts. Achieving this objective entails addressing the challenge of identifying criteria that are both objective and universally applicable, capable of encompassing various fields of scientific research, such as natural sciences, technical sciences, and economic sciences, among others. One such criterion, applicable to scientists, may involve assessing their publication activity within specific research areas that align with the objectives of the relevant scientific research or international projects. In the contemporary landscape of scientific research, there is a growing urgency to enhance the effectiveness of research endeavors and to foster efficient collaboration within scientific communities. This is particularly vital for organizations oriented towards project-based research. In the formation of research project teams, a conventional approach is to select partners from the pool of scientists possessing the requisite qualifications and experience in the execution of such projects. A widely accepted yardstick for evaluating the outcomes of scientists' research endeavors is the citation metrics associated with their publications. Typically, these metrics take the form of scalar values. While this approach offers several advantages, it is not without its limitations. One notable drawback is the potential loss of information when converting raw data into scalar metrics, and the existence of certain edge cases where the parameter remains unchanged despite variations in the number of citations and publications. Hence, it is pertinent to explore the development of new methodologies or modifications to existing ones that can effectively evaluate the results of scientists' research activities while mitigating these limitations.Начало формы The article describes the criteria for the search and selection of partners for joint scientific research. This will make it possible to effectively form teams for narrowly focused scientific research or international collaboration projects in interdisciplinary scientific projects such as the European Horizon Program or educational projects such as the Erasmus plus program. Also, the proposed solution will allow the formation of small teams for joint scientific publications. It is imperative to acknowledge that the process of partner selection is predominantly driven by a consideration of the knowledge, whether it be novel or foundational, possessed by prospective partners who are entrusted with the execution of a project. It becomes crucial to delineate the specific criteria governing partner selection which can vary contingent upon factors such as the typology of partners, the nature of project tasks, the depth of knowledge possessed, and related contextual variables. A vital underpinning for the formation of project consortia is the mathematical conundrum of choice which furnishes a formal rationale for the judicious selection of a particular partner.

Patients with chronic kidney disease (CKD) have high cardiovascular risk (CVR), which is often underestimated by conventional tools. The coronary artery calcium score (CACS) significantly improves CVR stratification by conventional tools, but it is often not available in low-resources settings. Aldosterone may be a cheaper alternative to CACS for CVR assessment in CKD patients. The aim was to assess the ability of serum aldosterone level to predict CACS in patients with CKD in comparison to standard predictors. This single-center study included 57 patients aged 40 to 67 years with CKD (estimated glomerular filtration rate [eGFR] ≥45 ml/min) and arterial hypertension. Serum aldosterone, sex, age, body mass index, blood pressure, total cholesterol, eGFR, and proteinuria were used for prediction of CACS>0 Agatston units (AU) and CACS>100 AU. The area under the curve (AUC) with 95% confidence intervals (CI) and the mean Brier scores were examined for predictors of CACS. Aldosterone predicted a CACS>100 AU (AUC = 0.72, 95% CI: 0.56–0.88), but not a CACS>0 AU. Age predicted a CACS>100 AU (AUC = 0.80, 95% CI: 0.67–0.93) and a CACS>0 AU (AUC = 0.75, 95% CI: 0.62–0.89). The addition of aldosterone to age for prediction of a CACS>100 AU improved the mean Brier score, compared to the model with age alone, from 0.16 to 0.14, but not the AUC (0.83, 95% CI: 0.70–0.95). Aldosterone was a significant predictor of a CACS>100 AU in patients with CKD, but aldosterone was not a better predictor than age alone.

The article describes the solution to the problem of clustering scientists' publications, taking into account the finding of similarities in the annotations and texts of these publications based on n-grams of analysis and cross-references, as well as the tasks of identifying potential project groups for the implementation of research and educational projects based on the results of clustering. The selection of scientific partners in the world practice is done without a comprehensive assessment of their activities. Most of the well-known indexes for evaluating the research activities of scientists need to consider information about citations fully. The methods developed in the study for evaluating the scientific activities of scientists and universities, as well as methods for selecting scientific partners for the implementation of educational and scientific projects on a scientific basis, allow us to organize the influential work of universities qualitatively. In the article, a probabilistic thematic model is constructed that allows the clustering of scientists' publications in scientific fields, considering the citation network, which is an important step in solving the problem of identifying subject scientific spaces. As a result of constructing the model, the problem of increasing instability of clustering of the citation graph due to a decrease in the number of clusters has been solved. The main objective of this work is to address the challenge of selecting suitable partners for collaboration in scientific and educational projects. To achieve this, a method for choosing project executors has been developed, which employs fuzzy logical inference to harmonize expert opinions regarding candidate requirements. This approach helps facilitate the multi-criteria selection of potential partners for scientific and educational projects. In addition to the method, various software modules have been created as part of this research. These modules are designed for the automated collection of information on the publications and citation records of scientists through international scientometric databases. They also encompass a visualization module and a user interface that aids in evaluating the scientific activities of university teaching staff. Choosing partners for grants or strategic collaborations, especially in the context of a globalized and highly mobile scientific community, remains a pertinent issue. The approach described in this research involves clustering the scientific publications of potential project partners. Furthermore, it incorporates conducting comparative citation analyses of these publications and establishing proximity based on n-gram annotation analysis. These methods provide a scientific basis for making informed choices when selecting partners, which is crucial for initiating and advancing research projects. Consequently, the selection of partners for forming research project teams is an immediate and pressing task.

Мета статті полягає у введенні до наукового обігу та аналізу досі невідомих картографічних джерел, які зберігаються у різних музейних та архівних установах. Наукова новизна пов’язана з тим, що розглянуті чотири плани і карти 1821, 1851, 1863 рр., що стосуються Ольвії та її околиць, що досі ніколи не попадали до наукового вжитку дослідників. Наведено невідомі факти існування села Ольвія (Широке); два фрагменти аркуша «військової зйомки» Херсонської губернії 1851 р. (масштаб 1 : 42 000) з урочищем Сто Могил і ділянкою на північ від с. Парутине. Вперше розглянуто аркуш карти 1851 р. та план А.П. Чиркова 1863 р., на яких зображені Велике та Мале Аджигольські містечка (нині поселення Дніпровське ІІ), вперше описані академіком Е.Е. Келлером. Висновки. У рамках порівняльного аналізу планів було встановлено локалізацію кургану, в якому була знайдена золота маска (1842 р.). Також була локалізована на планах курганна група біля балки Широкої, які булі розкопані у 1844 і 1853 рр. Наводиться інформація про кам’яні склепи, відомі у трьох з них. У ході проведеного дослідження вдалося не тільки порівняти плани між собою, але й локалізувати раніше невідоме місцезнаходження «археологічного будинку», співвіднести місцезнаходження курганів, розкопаних у 1842, 1844 і 1853 рр. а також розібратися у заплутаній бібліографії стосовно місцезнаходження Аджигольського містечка.

The C60 fullerene effect (oral administration at a dose of 1 mg kg−1) on the selected biomechanical parameters of muscle gastrocnemius contraction, biochemical indicators of blood and muscle tissue as well as histological changes in rat muscle tissue after chronic alcoholization for 3, 6 and 9 months was studied in detail. Water-soluble C60 fullerenes were shown to reduce the pathological processes development in the muscle apparatus by an average of (35–40)%. In particular, they reduced the time occurrence of fatigue processes in muscle during the long-term development of alcoholic myopathy and inhibited oxidative processes in muscle, thereby preventing its degradation. These findings open up the possibility of using C60 fullerenes as potent antioxidants for the correction of the pathological conditions of the muscle system arising from alcohol intoxication.

The authors of the article offer their understanding of the actual meanings of interactive lectures as the important component of the cloud-oriented learning environment of the medical university. We use different research methods for data collection: analysis and generalization of scientific sources to substantiate the theoretical research platform; modeling and research teaching method to determine the components of a lecture and clarify the conditions for conducting interactive lectures; sociometric analysis of the effectiveness of interaction within a small group to assess learning outcomes in different lecture formats. Two lecture formats (with elements of interactive media and interactive) while teaching of clinical disciplines in Donetsk National Medical University is described. The organizational and didactic conditions for conducting interactive lectures on clinical disciplines have been determined and characterized. The organizational conditions include educational resources and active elements of the Moodle educational platform: flexible & functional design of an interactive lecture; cognitive and motivational criteria of the effectiveness of an interactive lecture. It is concluded, that didactic principles of teaching (scientificity, the continuity of obtaining scientific knowledge and the formation of clinical experience, students’ activity and cognitive creative independence, interactivity) ensure the effectiveness of interactive lectures. It has been proven that inquiry-based learning and evidence-based medicine principles enhance the conversion of passive presentation of educational material into communication practices aimed at the development of clinical thinking in students. The authors came to the conclusion that tutoring provides the creation of an individual educational trajectory, contributes to the formation of social skills and professional reflection in the future neurologist.

Multicomponent reactions effectively contribute to modern organic and medicinal chemistry. 4-Thiazolidinone core and cyclopropyl moiety are important structural motifs for design of potential biologically active molecules. In the present paper, the convenient step-economy and cost-effective synthesis of 2-(cyclopropylamino)-5-(4-methoxybenzylidene)thiazol-4(5H)-one (2) is described based on the application of the MCR methodology. The proposed approach includes direct one-pot interaction of 2-thioxothiazolidin-4-one (rhodanine), 4-methoxybenzaldehyde with cyclopropylamine which was used in 10% excess compare to other reagents. The structure of synthesized compound 2 was confirmed using 1H, 13C, 2D NMR, LC-MS, IR and UV spectra. The presence of prototropic amino/imino tautomerism for synthesized compound 2 was observed based on spectral analysis data. Screening of antimicrobial activity against 12 strains of Gram-positive and Gram-negative bacteria, as well as yeasts, was performed for synthesized derivative 2.

Abstract Background Tooth impaction is a common problem in orthodontic practice and in some cases accompanied by pain and pathological changes of surrounding teeth. Understanding the cellular and molecular mechanisms underlying tooth impaction allows finding the most effective orthodontic treatment for patients with impacted teeth (IT). RANK (receptor activator of NF-κB) / RANKL (RANK ligand) / OPG (osteoprotegerin) signaling pathway controls bone resorption and may be involved in the regulation of tooth eruption. The study aimed to evaluate bone remodeling based on the assessment of the RANKL/RANK/OPG status in patients with IT. Methods Bone samples from 18 patients (mean age 25.27 ± 3.34) were divided into 3 groups: 1 – bone tissue of healthy persons (control group); 2 – bone tissue, that was taken near the healthy tooth in patients with tooth impaction; 3 – bone tissue, that was collected near the IT. Levels of RANKL, RANK, OPG, osteocalcin (OC), NF-κB p65 subunit, NFATc1, and caspase-3 were determined by western blotting. The difference between groups was assessed using ANOVA followed by Tukey’s post-hoc test. P-value ≤0.05 was considered statistically significant. Results We established a 1.73-fold elevation of RANK level in the IT area vs. control, indicating the recruitment of preosteoclasts. An increase in RANKL, OPG, and OC content was demonstrated (1.46-, 1.48-, and 1.42-fold respectively), reflecting the high activity of osteoblasts near the IT. Despite the activation of the RANKL/RANK/OPG system in the impaction area, NF-κB and NFATc1 levels did not change compared vs. control, indicating a blocked/delayed process of osteoclastogenesis. We found a decrease in the content of procaspase-3 (1.28-fold), while the level of its active form p17 increased by 2.26 folds near the healthy tooth in patients with IT compared with control. In the area of ​​IT, we observed an increase in procaspase-3 and p17 levels (1.32 and 1.78 folds). This reflects impairments of caspase-3 activation and accumulation of its inactive form in the IT area that may contribute to the tooth eruption failure. Conclusions Tooth impaction may be associated with the disturbances in the caspase-3 cascade activation and the imbalance in the RANKL/RANK/OPG system, and as a result, blocked bone resorption.

The article examines the political views of Afghan students studying in the Ukrainian SSR and their attitude towards the Soviet intervention in Afghanistan and the withdrawal of Soviet troops from that country. The sources of the study were KGB analytical reports from the Branch Archive of the Ukrainian Security Service, documents of educational institutions in Kirovohrad where Afghans studied, from the State Archives of Kirovohrad region, texts of the Soviet-Afghan educational cooperation agreements, notices and diary records of the USSR ambassador in Afghanistan and other Soviet officials on meetings and conversation with Afghan politicians. It was proven that the studying of Afghans in the USSR was one of the means of the Soviet policy toward Afghanistan aimed at its forced socialist modernization. The studying of Afghans in the Soviet Union led to emergence of a large pro-Soviet stratum of the Afghan society. The factors that determined the different attitudes of Afghan students studying in the Ukrainian SSR to the armed Soviet intervention in the Afghan crisis in December 1979 were identified. Most Afghans endorsed the USSR's military intervention in the "Afghan crisis". They believed that this was necessary to protect the achievements of the "April Revolution" and to counter "world imperialism". Some of them expressed concern, fear, and even negative attitudes toward the USSR policies. These sentiments were influenced by a factional affiliation: supporters of the "Parcham" and the "Hulk" group associated with N. M. Taraki endorsed the Soviet intervention, while supporters of H. Amin condemned it. The Afghan students in the Ukrainian SSR largely rejected the withdrawal of the Soviet troops from Afghanistan in February 1989. Most of them viewed it as a betrayal by the Soviet Union. They were convinced that this would lead to the fall of M. Najibullah's regime and the defeat of the "April Revolution" in Afghanistan.

The article examines the documents of Jimmy Carter Administration (1977-1981) published in «Foreign Relations of the United States» series that represent the U.S. position on the Soviet intervention in the Democratic Republic of Afghanistan in December 1979. The author argues that the growing Soviet presence and finally a military intervention in Afghanistan was taken seriously in the United States and made Washington watch the developments in this country closely. The Soviet intervention in Afghanistan became one of the major themes in the U.S. foreign policy. It was presented in a large array of documents of various origins, such as the Department of State correspondence with the U.S. Embassies in Afghanistan and the Soviet Union; analytical reports of the Department of Defense, the Central Intelligence Agency, and Bureau of Intelligence and Research; exchanges of memorandums between National Security Council officers and other officials; memos from National Security Adviser Z. Brzezinski to J. Carter, and others. They represented the preconditions, preparations and implementation of Soviet intervention in Afghanistan. The authors of the documents discussed in details the possible motives of the Soviet leaders, and predicted the short-term consequences of the USSR’s intervention for the region and the whole world. Due to the clear understanding of the developments in Afghanistan in December 1979 by the J. Carter administration, it completely rejected the Soviet official version of them that adversely affected the bilateral Soviet-U.S. relations and international relations in general. Due to the lack of accessible Soviet sources on the USSR’s intervention in Afghanistan, the documents of Jimmy Carter’s administration fill this gap and constitute a valuable source for a researcher.

A 3-phenylpropanal and citral were studied in the multicomponent reaction with the isorhodanine and maleimides (EDDA catalyst) with the aim of the novel thiopyrano[2,3-d]thiazoles synthesis. 3-Phenylpropanal reacts with the selective formation of the thiopyrano[2,3-d]thiazoles whereas citral led to the mixture of two products and Michael adducts are major. The one-pot/two-steps protocol was proposed for citral transformation to the target thiopyrano[2,3-d]thiazoles. The structures and stereochemistry of newly synthesized compounds were studied by spectral and X-ray data.

Background. The problem of disposal of the fat-containing tannery waste can be solved by anaerobic fermentation. This raises the important question of the effect of inhibitor compounds on the process of methanogenesis and on the output of biogas. In particular, the effects of NaCl and NaHCO3 used in technology and antibiotics that accumulate in subcutaneous fat when used in animal husbandry for digestion of fat-containing raw materials have not yet been studied. Objective. The purpose of the paper is determination of possible influence of salts and antibiotics on the process of methanogenesis and on the output of biogas and methane. Methods. The study was conducted in laboratory reactors with a volume of 0.5 dm3 under anaerobic conditions at 38 ± 1 °С with the addition of different concentrations of salts and antibiotics (the sample was used without the addition of test compounds to control the process). The anaerobic association of microorganisms in the form of an inoculum served as the biological agent. Results. The effect of salt content on the destabilization of methanogenesis during digestion of fat-containing raw materials and the effect of the antibiotic content of tetracycline and norfloxacin on the yield of biogas from fatty raw materials were determined. Thus, with the use of NaCO3, the greatest inhibition occurs at a concentration of 11.4 g/dm3 (decrease in biogas output by 54%), with a further increase in the concentration to 22.8 g/dm3 an increase of 18.2% is observed compared to the concentration of 11.4 g/dm3. It is shown that the concentration of methane in biogas with the use of NaCO3 decreases with increasing concentration of the inhibitor, which confirms its negative impact on the process of methanogenesis. Conclusions. Biogas yield is increased by 17% at a NaCl concentration of 3.8 g/dm3, and biogas and methane production decreases even more at NaCl concentrations of 7.6 g/dm3. When using antibiotics, tetracycline and norfloxacin, the allowable rate in raw materials is 2.5 mg/dm3 for both antibiotics.

The COVID-19 pandemic caused by the coronavirus SARS-CoV-2 has become a serious challenge for medicine and science. Analysis of the molecular mechanisms associated with the clinical manifestations and severity of COVID-19 has identified several key points of immune dysregulation observed in SARS-CoV-2 infection. For diabetic patients, factors including higher binding affinity and virus penetration, decreased virus clearance and decreased T cell function, increased susceptibility to hyperinflammation, and cytokine storm may make these patients susceptible to a more severe course of COVID-19 disease. Metabolic changes induced by diabetes, especially hyperglycemia, can directly affect the immunometabolism of lymphocytes in part by affecting the activity of the mTOR protein kinase signaling pathway. High mTOR activity can enhance the progression of diabetes due to the activation of effector proinflammatory subpopulations of lymphocytes and, conversely, low activity promotes the differentiation of T-regulatory cells. Interestingly, metformin, an extensively used antidiabetic drug, inhibits mTOR by affecting the activity of AMPK. Therefore, activation of AMPK and/or inhibition of the mTOR-mediated signaling pathway may be an important new target for drug therapy in COVID-19 cases mostly by reducing the level of pro-inflammatory signaling and cytokine storm. These suggestions have been partially confirmed by several retrospective analyzes of patients with diabetes mellitus hospitalized for severe COVID-19.

A series of 11-substituted 3,5,10,11-tetrahydro-2H-benzo[6,7]thiochromeno[2,3-d][1,3]thiazole-2,5,10-triones were obtained via hetero-Diels-Alder reaction of 5-alkyl/arylallylidene/-4-thioxo-2-thiazolidinones and 1,4-naphthoquinones. The structures of newly synthesized compounds were established by spectral data and a single-crystal X-ray diffraction analysis. According to U.S. NCI protocols, compounds 3.5 and 3.6 were screened for their anticancer activity; 11-Phenethyl-3,11-dihydro-2H-benzo[6,7]thiochromeno[2,3-d]thiazole-2,5,10-trione (3.6) showed pronounced cytotoxic effect on leukemia (Jurkat, THP-1), epidermoid (KB3-1, KBC-1), and colon (HCT116wt, HCT116 p53-/-) cell lines. The cytotoxic action of 3.6 on p53-deficient colon carcinoma cells was two times weaker than on HCT116wt, and it may be an interesting feature of the mechanism action.

This paper analyses the definition of inverse and direct problems in engineering dimensional chains calculation based on discrete analogue data and the methodologies for solving these problems. It is shown that the direct dimensional chains calculation, which belongs to the class of inverse boundary value problems in a stochastic formulation, can be transformed into multi-criteria problems of stochastic optimization with mixed conditions. The new multi-step solutions search methodology for these problems is based on non-linear robust estimation methods. It can be achieved through hierarchical two-level decisions synthesis scheme development. At the first step, this scheme includes identification of surrogate models (in the form of regression equations). At the second step, the effective robust estimates are computed to determine unknown values; estimations of unknown quantities are carried out under a priori and parametric data uncertainties. Results of calculations of inverse and direct problems in engineering dimensional chains for two-stage axial compressors are presented. They were obtained using interactive computer systems for decision-making support “ROD&IDS”.

(1) Lung cancer (both small cell and non-small cell) is the leading cause of new deaths associated with cancers globally in men and women. Long noncoding RNAs (lncRNAs) are associated with tumorigenesis in different types of tumors, including lung cancer. Herein, we discuss: (1) An examination of the expression profile of lncCDH5-3:3 in non-small cell lung cancer (NSCLC), and an evaluation of its functional role in lung cancer development and progression using in vitro models; (2) A quantitative real-time polymerase chain reaction assay that confirms lncCDH5-3:3 expression in tumor samples resected from 20 NSCLC patients, and that shows its statistically higher expression levels at stage III NSCLC, compared to stages I and II. Moreover, knockout (KO) and overexpression, as well as molecular and biochemical techniques, were used to investigate the biological functions of lncCDH5-3:3 in NSCLC cells, with a focus on the cells’ proliferation and migration; (3) The finding that lncCDH5-3:3 silencing promotes apoptosis and probably regulates the cell cycle and E-cadherin expression in adenocarcinoma cell lines. In comparison, lncCDH5-3:3 overexpression increases the expression levels of proliferation and epithelial-to-mesenchymal transition markers, such as EpCAM, Akt, and ERK1/2; however, at the same time, it also stimulates the expression of E-cadherin, which conversely inhibits the mobility capabilities of lung cancer cells; (4) The results of this study, which provide important insights into the role of lncRNAs in lung cancer. Our study shows that lncCDH5-3:3 affects important features of lung cancer cells, such as their viability and motility. The results support the idea that lncCDH5-3:3 is probably involved in the oncogenesis of NSCLC through the regulation of apoptosis and tumor cell metastasis formation.

The article concerns issues of the genre of fictional biography. The study examined the peculiarities of the artistic transformation of the circumstances of the F. M. Dostoyevsky's creative biography in J. M. Coetzee's novel “The Master of Petersburg”. The author has investigated a lot of intertextual sources as factors of the fictionalization of Dostoyevsky's biography, such as essays Stavrogin by Nikolai Berdyaev, Dostoevsky and patricide by Sigmund Freud, Dostoevsky – but in moderation by Thomas Mann, academic biographies of F. M. Dostoevsky and especially Dostoevsky’s novel Devils. An attempt was made to find out the motives of the author's appeal to the “dark” side of the inner world of Dostoevsky. The culminating episode of the novel, when Dostoevsky begins to write the novel Devils, is considered on three levels of the artistic system of the novel: 1) plot motivation; 2) characterological aspects; 3) conceptual level, determined by the problem of creativity as the central problem of the novel. Writer's work is mainly an irrational and intuitive sphere, Dionysian phenomenon, fraught with unpredictable consequences. So the author of the article tries to identify the “positive program” of the Coetzee's novel as a work about “darkness of human heart”, that is cleared by the artist's genius, but it does not protect against moral losses.

Present work is devoted to the purposeful search of novel promising anti-inflammatory agents among the insufficiently known 3'-R-10'-R1-spiro[hetaryl-3(4),6'-[1,2,4]triazino[2,3-c]quinazolin]-2'(7'H)-ones. The virtual combinatorial library of previously unknown spiro-condensed derivatives of [1,2,4]triazino[2,3-c]quinazolines was formed and promising COX-2 inhibitors were identified by molecular docking method. Potential anti-inflammatory agents were synthesized by [5+1]-cyclocondensation of substituted 3-(2-aminophenyl)-6-R-1,2,4-triazin-5(2H)-ones with heterocyclic ketones. The structures of synthsized compounds were verified by complex of physicochemical methods and spectral characteristics features were discussed. Obtained compounds were studied for anti-inflammatory activity using formalin induced paw edema model and highly active compounds were identified. Conducted SAR-analysis showed that combination of triazino[2,3-c]quinazoline moiety with spiro-condensed fragments is a reasonable approach for creating novel anti-inflammatory agents.

A series of 5-methyl-7-phenyl-3H-thiazolo[4,5-b]pyridin-2-ones has been designed, synthesized, and characterized by spectral data. Target compounds were screened for their antimicrobial activity against some pathogenic bacteria and fungi, and most of them showed moderate activity, especially compound 3g, which displayed the potent inhibitory effect against Pseudomonas aeruginosa and Escherichia coli with MIC value of 0.21 μM. The active thiazolopyridine derivatives 3c, 3f, and 3g were screened for their cytotoxicity effects on HaCat, Balb/c 3T3 cells using MTT assay, which revealed promising results. In silico assessment for compounds 3c, 3f, and 3g also revealed suitable drug-like parameters and ADME properties. The binding interactions of the most active compound 3g were performed through molecular docking against MurD and DNA gyrase, with binding energies and an inhibitory constant compared to the reference drug ciprofloxacin. The tested thiazolo[4,5-b]pyridines constitute an exciting background for the further development of new synthetic antimicrobial agents.

Целью исследования было обнаружение маркеров психолингвистической экспликации вербальной агрессии в реакциях пользователей социальных сетей «Фейсбук», «ВКонтакте», «Твиттер» на журналистские публикации о результатах э-декларирования чиновниками Украины своих доходов в период с 23 августа по 7 ноября 2016 года. Методика исследования состояла в следовании таким процедурам: осуществление наблюдения за корреляцией между маркерами психолингвистической экспликации вербальной агрессии (далее – ВА) читателей и фактами про электронное декларирование (далее – ЭД), изложенными в журналистских материалах; установление фактов наличия/отсутствия корреляции между показателями уровня ВА читателей и фактами про ЭД, изложенными в журналистских материалах; идентификация по месяцам 2016 года (август, сентябрь, октябрь, ноябрь) сообщений-комментариев интернет-читателей по поводу э-деклараций чиновников и установление динамики изменений в показателях вербальной «агрессии» (раздражение, риторические вопросы с элементами сарказма, сарказм, презрение). Результаты анализа 52 текстов сообщений-комментариев, зафиксированных нами, позволили идентифицировать признаки агрессивных текстов сообщений-комментариев интернет-читателей в ответ на публикации журналистов об э-декларировании доходов чиновников в Украине (в период с 23 августа по 7 ноября 2016 года). Выводы. Исследованная нами группа интернет-читателей зафиксировала достаточно высокий уровень корреляции между их вербальной агрессией и данными электронного декларирования доходов чиновников Украины (в период с 23 августа по 7 ноября 2016 года), что отразило уровень социального напряжения в Украине. Также отмечено: после того, как высокий уровень вербальной агрессии достиг своего пика в комментариях интернет-читателей, на его смену «пришел» другой маркер вербальной агрессии – сарказм, сменившийся после окончания процесса э-декларирования презрением со стороны интернет-читателей.

У статті прорецензовано монографію, в якій досліджуються зміни у соціально-економічній, суспільно-політичній та культурно-духовній сферах суспільного життя радянської України в період горбачовської перебудови, аналізуються етапи кризи партійно-радянської системи, характеризуються основні закономірності та рушійні сили процесів, які призвели до відновлення державної незалежності українського народу.

Neuroinflammation is an integral part of epilepsy pathogenesis and other convulsive conditions, and non-steroidal anti-inflammatory drugs (NSAIDs) present a potent tool for the contemporary search and design of novel anticonvulsants. In the present paper, evaluation of the anticonvulsant activity of the potential NSAID dual COX-2/5-LOX inhibitor darbufelone methanesulfonate using an scPTZ model in mice in dose 100 mg/kg is reported. Darbufelone possesses anticonvulsant properties in the scPTZ model and presents interest for in-depth studies as a possible anticonvulsant multi-target agent with anti-inflammatory activity. The series of 4-thiazolidinone derivatives have been synthesized following the analogue-based drug design and hybrid-pharmacophore approach using a darbufelone matrix. The synthesized derivatives showed a significant protection level for animals in the scPTZ model and are promising compounds for the design of potential anticonvulsants with satisfactory drug-like parameters.

Zero-dimensional models based on the description of the thermo-gas-dynamic process are widely used in the design of engines and their control and diagnostic systems. The models are subjected to an identification procedure to bring their outputs as close as possible to experimental data and assess engine health. This paper aims to improve the stability of engine model identification when the number of measured parameters is small, and their measurement error is not negligible. The proposed method for the estimation of engine components’ parameters, based on multi-criteria identification, provides stable estimations and their confidence intervals within known measurement errors. A priori information about the engine, its parameters and performance is used directly in the regularized identification procedure. The mathematical basis for this approach is the fuzzy sets theory. Synthesis of objective functions and subsequent scalar convolutions of these functions are used to estimate gas-path components’ parameters. A comparison with traditional methods showed that the main advantage of the proposed approach is the high stability of estimation in the parametric uncertainty conditions. Regularization reduces scattering, excludes incorrect solutions that do not correspond to a priori assumptions and also helps to implement the gas path analysis with a limited number of measured parameters. The method can be used for matching thermodynamic models to experimental data, gas path analysis and adapting dynamic models to the needs of the engine control system.

4-(1H-[1,2,4]-Triazol-5-ylsulfanyl)-1,2-dihydropyrazol-3-one (4) was synthesized with a yield of 55% via ring-switching hydrazinolysis of 5-ethoxymethylidenethiazolo[3,2-b][1,2,4] triazol-6-one (3) in ethanol medium. The initial 1H-[1,2,4]-triazole-3-thiol (1) was modified via a two-step reaction: S-alkylation with chloroacetic acid under Williamson reaction conditions, and further one-pot cyclization–condensation with triethylorthoformate in the acetic anhydride medium, yielding compound 3. The structures of compounds 3 and 4 were confirmed by LC-MS, NMR spectra and a single X-ray diffraction analysis (for compound 4).

Background and objectives. Stroke-induced mortality is the third most common cause of death in developed countries. Intense interest has focused on the recurrent ischemic stroke, which rate makes up 30% during first 5 years after first-ever stroke. This work aims to develop criteria for the prediction of acute recurrent cerebral ischemic hemispheric stroke (RCIHS) outcome on the basis of comprehensive baseline clinical, laboratory, and neuroimaging examinations. Materials and Methods. One hundred thirty-six patients (71 males and 65 females, median age 74 (65; 78)) with acute RCIHS were enrolled in the study. All patients underwent a detailed clinical and neurological examination using National Institutes of Health Stroke Scale (NIHSS), computed tomography of the brain, hematological, and biochemical investigations. In order to detect the dependent and independent risk factors of the lethal outcome of the acute period of RCIHS, univariable and multivariable regression analysis were conducted. A receiver operating characteristic (ROC) analysis with the calculation of sensitivity and specificity was performed to determine the prediction variables. Results. Twenty-five patients died. The independent predictors of the lethal outcome of acute RCIHS were: Baseline NIHSS score (OR 95% CІ 1.33 (1.08−1.64), p = 0.0003), septum pellucidum displacement (OR 95% CI 1.53 (1.17−2.00), p = 0.0021), glucose serum level (OR 95% CI 1.28 (1.09−1.50), p = 0.0022), neutrophil-to-lymphocyte ratio (OR 95% CI 1.11 (1.00−1.21), p = 0.0303). The mathematical model, which included these variables was developed and it could determine the prognosis of lethal outcome of the acute RCIHS with an accuracy of 86.8% (AUC = 0.88 ± 0.04 (0.88−0.93), p < 0.0001).

Summary Inflammation is characterized by endothelium that highly expresses numerous adhesion molecules to trigger leukocyte extravasation. Central to this event is increased gene transcription. Small Rho-GTPases not only control the actin cytoskeleton, but are also implicated in gene regulation. However, in inflammation, it is not clear how this is regulated. Here, we show that the guanine-nucleotide exchange factor Trio expression is increased upon inflammatory stimuli in endothelium. Additionally, increased Trio expression was found in the vessel wall of rheumatoid arthritis patients. Trio silencing impaired VCAM-1 expression. Finally, we excluded that Trio-controlled VCAM-1 expression used the classical NFκB or MAP-kinase pathways, but rather acts on the transcriptional level by increasing phosphorylation and nuclear translocalization of Ets2. These data implicate Trio in regulating inflammation and provide novel targets for therapeutic purposes to treat inflammatory diseases such as rheumatoid arthritis.

This article investigates the creation and monitoring of the fundamental value of a company, the methods of its valuation, and capital market responses to changes of the fundamental value. The author uses the basic theory of discounted cash flows as his main theoretical model. This theory states that the investment value equals the net present value of future cash flows that is created as a result of this investment. Other theories referred to in the article are derived from the aforementioned model. The article contains an empirical analysis of correlation dependence between the fundamental value and the market capitalization. The figures obtained from international companies during a 5-year time period showed that the highest indices of fundamental value increase were used as output data. The article argues that the total business return has the highest correlation index with respect to a company’s market value. The reasons affecting the results of the empirical research have been analyzed. The author gives some recommendations on the appreciation of a company’s market value.

Commonly accepted point is that functional organization structure is a poor environment for project management. The scenario repository approach is designed especially to support project management in environment with great amount of operational activity taking into account, that in such cases, project tasks have their reflection in the tasks of business-processes. Creation of a special project and operation task management tools set allows to create a new approach in change management in enterprises with functional organization structure, optimize the processes, involved in project management activities, compile the knowledge base of project and operational task management using the project task - operational task mapping to reveal the bottle necks of both.

Introduction: The invasion of Ukraine by Russian troops on February 24, 2022, and the beginning of the full-scale war had huge humanitarian consequences. The major challenges facing the Ukrainian health care system included the disruption of medical infrastructure and logistics, the termination of the supply of expendable materials, significant migration, and a dramatic increase in high-velocity blast and gunshot injuries among combatants and civilians.The aim of the present study was to analyze the challenges and solutions in patient care faced by the Ukrainian system of maxillofacial surgery during the war in different regions of the country., Materials and Methods: A cross-sectional study was designed and implemented as an online survey to collect national data concerning maxillofacial surgeons' experiences and professional activities. The study was initiated and supported by Bogomolets National Medical University (Kyiv, Ukraine), the Ukrainian representative of AO CMF (Arbeitsgemeinschaft für Osteosynthesefragen Craniomaxillofacial Surgery) and the University of Helsinki (Finland).The questionnaire was developed by specialists in maxillofacial surgery and sociologists and contained 65 close-ended questions. Surgeons who had not worked in this specialty in inpatient departments of hospitals since at least the beginning of the full-scale war were excluded from the study. We received and analyzed 97 responses that met the abovementioned criteria. The geography of respondents covered all the regions and the main cities of Ukraine, expect for the occupied territories., Results: After a year of warfare, the percentage of surgeons who treated patients with blast and gunshot injuries increased from 43.4% to 86.6%. This percentage was higher in military hospitals and in regions located in the vicinity of the front line. We found that, during the war, 78.6% of respondents performed osteosynthesis in cases of high-velocity multifragmented facial bone fractures (in such cases, 58.3% of them strictly followed AO CMF recommendations, while 41.7% performed the fixation based on available hardware, existing technical possibilities and their own preferences). We found that 70.2% of respondents had the opportunity to apply Computer-Aided Design/Computer-Aided Manufacture technology and patient-specific implants for the treatment of gunshot injuries, 38.1% reported that their hospitals were able to perform microsurgical reconstructions for facial defects, 79.4% of respondents reported that their departments received humanitarian aid and support from volunteer organizations (either Ukrainian or international), which significantly facilitated the treatment process., Conclusions: According to this nationwide survey of Ukrainian maxillofacial surgeons during a year of the full-scale war, 86.6% of respondents were involved in the treatment of gunshot and ballistic injuries in civilians and combatants. The main problems reported by the respondents were (1) a lack of experience and knowledge related to the treatment of severe wounds, especially by secondary reconstruction, and (2) a deficit of resources (equipment, materials, and medications) under conditions of disrupted logistics and changes in the numbers and nosological distribution of patients. There were the opportunity to transfer the patients to European clinics (29.9%), online consultations (45.4%), collaboration with foreign surgeons who come to Ukraine asvolunteers (32%)., (© The Association of Military Surgeons of the United States 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)