Bending oscillations of a cylinder, surrounded by an elastic medium and containing a viscous liquid and an oscillator

The article considers dynamic processes mathematical modeling in a mechanical system, consisting of an elastic hollow cylinder, surrounded by an elastic medium and containing viscous liquid and vibrating coaxial rigid cylinder. The amplitude frequency characteristic for investigating bending cylinder oscillations as one-mass system is defined. It is shown, that the constructed amplitude characteristic makes it possible to define the considered system resonance frequencies oscillations. The calculations demonstrated the significance of taking into account viscous liquid inertia and the surrounding elastic medium

Contribution of Northern European Universities to the Implementation of Research Policy in the Arctic

The Arctic region has long been at the center of world politics and economy. One of the reasons for the transformation of the global fringe into a center of attraction for the economic, geo-ecological and geopolitical interests of foreign countries is the Arctic is undergoing dynamic transformations. In the socio-political and scientific research agenda of the Arctic States, there are acute issues of accumulation and exchange of knowledge about changes taking place in the natural and socio-economic environment of a non-standard region from the point of view of management. The Arctic strategies of the Northern European States seek to fill the vacuum about the trends of environmental changes in the Arctic, the impact of natural transformations on the environment, socio-economic development, population security, and the use of natural resources by indigenous peoples. This task is planned to be solved through the development of research activities of universities located in the Far North and in the Arctic zone of Denmark, Norway, Finland and Sweden, as well as Iceland. The article describes the scientific interests of the Northern European States in the Arctic. Using analytical and comparative methods, the goal is achieved — to characterize universities as one of the parts of their scientific and educational space in the Nordic countries. An attempt is made to answer the question: how does educational and research activities contribute to the implementation of state program documents for the development of natural resources in the Arctic and the use of its spaces? The further direction of scientific research may be to compare the educational and research activities of universities in Northern Europe and universities in the Arctic zone of the Russian Federation

Четверта міжнародна наукова-практична конференція «Комп’ютерне моделювання в хімії і технологіях та системах сталого розвитку»

Розроблена імітаційна комп'ютерна модель стаціонарного процесу безперервного адіабатичного нітрування ароматичних сполук, що супроводжується відгонкою частини реакційної маси. Досліджено закономірності адіабатичного нітрування бензолу і толуолу.A simulation computer model of the stationary process of continuous adiabatic nitration of aromatic compounds, accompanied by distillation of the reaction mass were developed. Regularities of the adiabatic nitration of benzene and toluene were studied.Разработана имитационная компьютерная модель стационарного процесса непрерывного адиабатического нитрования ароматических соединений, сопровождающегося отгонкой части реакционной массы. Исследованы закономерности адиабатического нитрования бензола и толуола

Препаративний метод синтезу 4-(трифлуорометокси)піперидину та 4-(трифлуорометоксиметил)піперидину

Aim. To develop a convenient synthetic approach for the preparation of multigram amounts of 4-(trifluoromethoxy)-piperidine and 4-(trifluoromethoxymethyl)piperidine – promising building blocks for medicinal chemistry.Results and discussion. 4-(Trifluoromethoxy)piperidine (8.4 g) and 4-(trifluoromethoxymethyl)piperidine (12.9 g) were synthesized in 5 stages starting from 4-hydroxypiperidine (the overall yield 40 %) and 4-(hydroxymethyl)piperidine (the overall yield 13.5 %), respectively.Experimental part. The first stage of the synthetic strategy was acylation of 4-hydroxypiperidine with benzoyl chloride. N-benzoyl-4-hydroxypiperidine obtained was transformed to N-benzoyl-4-(trifluoromethoxy)piperidine in two stages using the Hiyama method (the synthesis of the corresponding S-methyl xanthate with the subsequent desulfurization/fluorination using N-bromosuccinimide and Olah’s reagent). Then the N-benzoyl group was reduced to benzyl one, which was removed using 1-chloroethyl chloroformate. The similar approach was applied to the synthesis of 4-(trifluoromethoxymethyl)piperidine starting from 4-(hydroxymethyl)piperidine. The structure and composition of the compounds synthesized were confrmed by 1Н, 13C and 19F NMR spectroscopy,mass-spectrometry and elemental analysis.Conclusions. The synthetic approach developed is a convenient method for the multigram preparation of4-(trifluoromethoxy)piperidine and 4-(trifluoromethoxymethyl)piperidine and can be used for the synthesis of other secondary amines containing the CF3O-group.Key words: fluorination; trifluoromethoxy group; xanthate; piperidine; protection groupМета. Розробити зручний синтетичний метод для одержання мультиграмових кількостей 4-(трифлуорометокси)піперидину та 4-(трифлуорометоксиметил)піперидину – перспективних будівельних блоків для медичної хімії.Результати та їх обговорення. Синтезовано 4-(трифлуорометокси)піперидин (8,4 г) та 4-(трифлуорометоксиметил)піперидин (12,9 г) у п’ять стадій, виходячи з 4-гідроксипіперидину (сумарний вихід – 40%) та 4-(гідроксиметил)піперидину (сумарний вихід – 13,5%) відповідно.Експериментальна частина. Першою стадією синтетичної стратегії було ацилювання 4-гідроксипіперидину бензоїлхлоридом. Одержаний N-бензоїл-4-гідроксипіперидин було перетворено на N-бензоїл-4-трифлуорометоксипіперидин у дві стадії з використанням методу Хіями (синтез відповідного S-метилксантату і наступні десульфуризація та флуорування з використанням N-бромосункциніміду та реагенту Ола). Далі N-бензоїльну групу було відновлено до бензильної, зняття якої проводили з використанням 1-хлороетилхлороформіату. Аналогічну схему було використано для синтезу 4-(трифлуорометоксиметил)піперидину, виходячи з 4-(гідроксиметил)піперидину. Структуру і склад синтезованих сполук доведено даними 1Н, 13C і 19F ЯМР-спектроскопії, мас-спектрометрії та елементного аналізу.Висновки. Розроблений метод є зручним підходом до синтезу мультиграмових кількостей 4-(трифлуорометокси)піперидину та 4-(трифлуорометоксиметил)піперидину та може бути використаний для синтезу інших вторинних амінів, що містять CF3O-групу.Ключові слова: флуорування; трифлуорометоксигрупа; ксантат; піперидин; захисна груп

Organizational Mechanisms for Implementing Russia's Arctic Strategy in the 21st Century

The Arctic in the 21st century remains a popular topic in the natural-scientific, economic, socio-humanitarian, and political spheres. The relevance of studying the Arctic is determined by the fact that in recent decades, deep and irreversible transformations have taken place in this region, and a full under-standing of the causes and consequences of which for the economy and environmental management has not yet developed. As a result of climate change and globalization, there is a growing interest in the Arctic macro-region on the part of many foreign countries that developed strategies and programs for the development of national Arctic zones at the beginning of the XXI century. Against the background of global competition for resources and transport communications, it seems relevant to analyze the features of the development of Russia's state policy for managing the Arctic zone of the Russian Federation in the XXI century. The article analyzes the mechanisms of implementation of Russian state policy in the Arctic based on the strategic planning system and reveals the bottlenecks in the system of state management of the Arctic region. It is concluded that the core of Russia's policy in the Arctic is innovative modernization that can ensure sustainable socio-economic development, infrastructure development, rational use of natural resources, protection of local ecosystems and development of indigenous communities

Препаративний метод синтезу α,α-дифлуоро-γ-аміномасляної кислоти

Aim. To develop a convenient synthetic approach for the preparation of multigram amounts of 2,2-difluoro-γ-aminobutyric acid, which is pharmacologically promising analog of γ-aminobutyric acid (GABA).Results and discussion. α,α-Difluoro-γ-aminobutyric acid (2,2-difluoro-GABA, 53 g) has been synthesized using the reaction of ethyl bromodifluoroacetate (EBDFA) addition to benzyl acrylate in the presence of copper as a key stage.Experimental part. The reaction of EBDFA with benzyl acrylate in the presence of copper and tetramethylethylenediamine (TMEDA) was carried out; the resulting product was transformed to the target α,α-difluoro-γ-aminobutyric acid (in the form of hydrochloride) by consecutive debenzylation, Curtius rearrangement and treatment with hydrochloric acid to remove protecting groups. The synthesis was scaled up for the preparation of 53 g of α,α-difluoro-γ-aminobutyric acid. The ethyl ester of α,α-difluoro-γ-aminobutyric acid was also prepared and further transformed to 3,3-difluoropyrrolidine-2-one. The structure of the compounds synthesized was confirmed by 1Н, 13C and 19F NMR spectroscopy, mass spectrometry and elemental analysis.Conclusions. It has been shown that the synthetic approach developed can be used for the preparation of α,α-difluoro-γ-aminobutyric acid in multigram amounts. The pathway is much more convenient, cheaper and safer compared to the method earlier described.Received: 30.07.2020 Revised: 19.08.2020 Accepted: 27.08.2020Мета. Розробити зручний синтетичний метод для одержання мультиграмових кількостей α,α-дифлуоро-γ-аміномасляної кислоти – фармакологічно перспективного аналога γ-аміномасляної кислоти (ГАМК).Результати та їх обговорення. Синтезовано 53 г α,α-дифлуоро-γ-аміномасляної кислоти (2,2-дифлуоро-ГАМК), використовуючи приєднання етилбромодифлуороацетату (ЕБДФА) до бензилакрилату в присутності міді як ключову реакцію.Експериментальна частина. Проведено реакцію ЕБДФА з бензилакрилатом у присутності міді та тетраметилетилендіаміну (ТМЕДА); одержаний продукт було перетворено на цільову α,α-дифлуоро-γ-аміномасляну кислоту (у вигляді гідрохлориду) шляхом послідовних реакцій дебензилювання, перегрупування Курціуса та обробки хлоридною кислотою для зняття захисних груп. Синтез було масштабовано для приготування 53 г α,α-дифлуоро-γ-аміномасляної кислоти. Одержано етиловий естер α,α-дифлуоро-γ-аміномасляної кислоти, який було перетворено на 3,3-дифлуоропіролідин-2-oн. Структуру і склад синтезованих речовин доведено даними 1Н, 13C і 19F ЯМР-спектроскопії, мас-спектрометрії та елементного аналізу.Висновки. Показано, що розроблений синтетичний шлях дозволяє одержати мультиграмові кількості α,α-дифлуоро-γ-аміномасляної кислоти та є набагато зручнішим, дешевшим і безпечнішим порівняно із раніше описаним методом.Received: 30.07.2020Revised: 19.08.2020Accepted: 27.08.202

Scalable Production and Purification of Adeno-Associated Viral Vectors (AAV).

Here we describe methods for the production of adeno-associated viral (AAV) vectors by transient transfection of HEK293 cells grown in serum-free medium in orbital shaken bioreactors and the subsequent purification of vector particles. The protocol for expression of AAV components is based on polyethyleneimine (PEI) mediated transfection of a 2-plasmid system and is specified for production in milliliter to liter scales. After PEI and plasmid DNA (pDNA) complex formation the diluted cell culture is transfected without a prior concentration step or medium exchange. Following a 3-day batch process, cell cultures are further processed using different methods for lysis and recovery. Methods for the purification of viral particles are described, including iodixanol gradient purification, immunoaffinity chromatography, and ultrafiltration, as well as quantitative PCR to quantify vector titer

How accurately can we predict the melting points of drug-like compounds?

© 2014 American Chemical Society. This article contributes a highly accurate model for predicting the melting points (MPs) of medicinal chemistry compounds. The model was developed using the largest published data set, comprising more than 47k compounds. The distributions of MPs in drug-like and drug lead sets showed that >90% of molecules melt within [50,250]°C. The final model calculated an RMSE of less than 33 °C for molecules from this temperature interval, which is the most important for medicinal chemistry users. This performance was achieved using a consensus model that performed calculations to a significantly higher accuracy than the individual models. We found that compounds with reactive and unstable groups were overrepresented among outlying compounds. These compounds could decompose during storage or measurement, thus introducing experimental errors. While filtering the data by removing outliers generally increased the accuracy of individual models, it did not significantly affect the results of the consensus models. Three analyzed distance to models did not allow us to flag molecules, which had MP values fell outside the applicability domain of the model. We believe that this negative result and the public availability of data from this article will encourage future studies to develop better approaches to define the applicability domain of models. The final model, MP data, and identified reactive groups are available online at http://ochem.eu/article/55638

Aberrant expression of selenium-containing glutathione peroxidases in clear cell renal cell carcinomas

Aim: To find putative diagnostic markers for clear cell renal cell carcinomas (ccRCC). Material and methods: Quantitative polymerase chain reaction (Q-PCR), bisulfite treatment, methylation-specific PCR, analysis on cBioPortal for Cancer Genomics. Results: We have found that expression of GPX 1, GPX3, and GPX4 genes was decreased in ccRCC. We have shown that the number of alanine (GCG) repeats at the amino terminus of the GPX1 protein is variable. It was reported earlier that an allele that possess 5 alanine repeats is associated with the increased cancer risk. According to the obtained data, the allele with the 5 alanine repeats was also present in a group of healthy donors. Moreover, the frequency of alleles with repeats was similar among ccRCC patients and healthy individuals. We found that decreased expression of GPXs genes was not associated with promoter methylation. To provide other explanation, an analysis on the gene copy number was performed. We have found the heterozygous deletions for GPX1 gene, amplification for GPX3 gene, and no change in gene copy number for GPX4. Conclusions: Our data support the hypothesis that GPX1, GPX3, and GPX4 genes may play a role in ccRCC cancerogenesis and therefore they might be considered as putative diagnostic markers for ccRCC. Key Words: clear cell renal cell carcinomas, selenium-containing GPXs, genetic and epigenetic regulation

Scenarios for the development of the Arctic region (2020–2035)

The importance of selecting the development of the Arctic seems to be relevant since rapid and irreversible changes are taking place there. Climate change and globalization are their prominent examples. A complex of factors has both positive and negative impacts on the use of natural resources and the positioning of states located not only within the Arctic but also outside it. The questions arise: what is the significance of these changes for geography, politics, and the management system? How should the comprehension of these processes be built? The relevance of the topic is enhanced by the fact that Russia has the most significant Arctic sector among the states with access to the Arctic Ocean. Therefore, our country has a leading role in working out strategies for the development of the Arctic. The comprehensive approach (considering the economic and political-geographical positions) is central in the article to analyze the directions of development of the Arctic territories. The method reveals the possibilities of sustainable development, which will provide Russia with strategic benefits within the Arctic and globally. The article discusses scenarios for the development of the Arctic, including the Arctic zone of the Russian Federation, in the long-term perspective (until 2035). Substantiation of the long-term prospects for the development of the Arctic, despite Russian and foreign research, seems to be unrealistic due to lack of knowledge about the nature and consequences of climatic changes currently observed in this region and affecting global environmental management. The authors concluded that the priority directions of the Arctic development should be the ones based on positive and innovative trends