Study of the effectiveness of various cannabinoid receptor 1 (CB1) agonists using molecular docking and molecular dynamics modeling

The binding of a series of small organic molecules, acting as agonists of the cannabinoid receptor CB1, was investigated by means of three methods of computational chemistry. Binding modes were predicted by means of molecular docking, and binding free energy was estimated via docking, molecular-mechanics Poisson-Boltzmann surface area method, and multistate Bennett acceptance ratio. No evident correlation was observed for the molecules between the experimental characteristics of affinity and three computed binding free energy estimates. The reasons for the discrepancy were discussed

Bounded and Almost Periodic Solvability of Nonautonomous Quasilinear Hyperbolic Systems

The paper concerns boundary value problems for general nonautonomous first order quasilinear hyperbolic systems in a strip. We construct small global classical solutions, assuming that the right hand side is small. For the nonhomogeneous version of a linearized problem, we provide stable dissipativity conditions ensuring a unique bounded continuous solution for any smooth right-hand side. In the autonomous case, this solution is two times continuously differentiable. In the nonautonomous case, the continuous solution is differentiable under additional dissipativity conditions, which are essential. A crucial ingredient of our approach is a perturbation theorem for general linear hyperbolic systems. In the case that all data of the quasilinear problem are almost periodic, we prove that the bounded solution is also almost periodic.Comment: 42 pages. The main result is generalized to cover more general first order quasilinear hyperbolic systems; improved presentation, a correction in Example in Subsection 3.

Intellectual potential as a means of reproduction and renewal of the unity of productive forces and industrial relations

The conceptual view on the unity of productive forces and industrial relations in modern social structures of production expressing the active relation of people to the accumulation of material goods as an indicator of the spiritual development of the social structure has been presented in the work. It is proved that the technological basis of society is a state priority of structural changes in the economy, which determines the rates of economic growth regardless of the level of development. The new paradigm, which was called "technological method of production" as a dynamic system of not only production forces, but also of technological production relations, due to the optimization of internal production processes transformed into a system of technological relations, the nature of which is determined by the nature of the operation or transition in the technological process, has been conceptually substantiated

Research of future masters of pedagogy’s socio-professional activity

The purpose was to conduct an empirical study of the content parameters of future masters of pedagogy’s socio-professional activity. Valid psychodiagnostic methods, purposeful observation, and statistical data processing methods were used to display relevant content parameters of socio-professional activity. With the clarification of reliable correlations, an ascertaining strategy was developed. It was revealed that respondents’ general activity (GA) had reliable connections with all parameters of motivation: internal (rs=.208; p<.01), external negative (rs=.099; p<.05), and external positive (rs=.128; p<.05), as opposed to creative activity (CA), which was only reliably associated with internal motivation (rs=.198; p<.01). It was discovered that creative activity had the most reliable correlations with the individual’s self-regulation parameters – four in total: modeling (rs=.088; p<.05), programming (rs=.112; p<.05), flexibility (rs=.228; p<.01) and independence (rs=.245; p<.01). It has been established that creative activity is essential in the development of the social and professional activity. It is concluded that it is preferential to operationalize received scientific facts into educational and professional training and professional development of future masters of pedagogy

Unusual in Water Multicomponent Reaction of 3-Amino-5-methylpyrazole, Acetylacetone and Aldehyde

Multicomponent reaction of 3-amino-5-methylpyrazole, aliphatic aldehyde (paraformaldehyde or acetaldehyde) and acetylacetone in water by conventional heating, microwave or ultrasound activation undergoes on molar amounts of reagents 2:1:2, respectively, leads bis(2,5,7-trimethylpyrazolo[1,5-a]pyrimidin-6-yl)-substituted methane or to corresponding 1,1-bis-substituted ethane

PEDAGOGIC DIAGNOSTIC METHODS OF JUVENILE CONVICTS SOCIAL HEALTH: EXPERIMENTAL STUDY

Convicts social health is regarded by the authors of the article as the state of social welfare including the ability to support the socially healthy relationships in the society.  To diagnose this state of ability among the juvenile convicts serving sentences in the correctional colonies is of special importance.  According to the experimental study there is not enough work done to develop social health among juvenile convicts in the places where the imprisoned are stayed.  The hypothesis of the investigation is the assumption that to form the social health among convicted male minors in the juvenile correctional facility will be more successful if they participate in the project “Book is the source of new life and the way to rehabilitation.”  To diagnose the state of social health of juvenile convicts the following methods and techniques have been used, they are watching, talking, summative assessment, formative assessment, testing, The Test of Viability  by D.A. Leontyev, The Questionnaire: Health, Activity, Mood (by V.A. Doskin, N.A. Lavrentyeva, V.B. Sharay, M.P. Miroshnikov); Success Stimuli and Failure Fear methods by A.A. Rean.  The summative assessment procedure was held in March 2019, the formative assessment experiment had been conducted for 3 months (from April till June 2019).  The summative assessment has shown that juvenile convicts have weak viability, reduced level of well-being, and activity, and mood as well; there is a low level of success stimuli and high level of failure fear.  The results of formative assessment have shown that the participation in the Project helps to form viability, activity, cheering up, decreasing of failure fear, increasing of success motivation; and it assists conforming social health of juvenile convicts as a whole.

The Assessment of the Level of Pollution of Slime Pits with Heavy Metals

In drilling and running oil and gas wells the great amount of toxic waste is formed and in the surface of the lithosphere and hydrosphere the great amount of different chemical elements and compounds access, they are needed to be isolated from the environment. The most useful way of isolation is their utilization in the slime pits on the wells territory. Heavy metals are dangerous waste in the drilling slime; they accumulate in soil and under some conditions they in form water-soluble parts and migrate in to the soil. The aim of this paper is to organize the chemical and analytical research of the amount of heavy metals in the drilling slime, and research the mechanism of their spreading on different depth and square in the slime pits typical for the oil site placed in KHANTY-Ugra

Structural photoactivation of a full-length bacterial phytochrome

Phytochromes are light sensor proteins found in plants, bacteria, and fungi. They function by converting a photon absorption event into a conformational signal that propagates from the chromophore through the entire protein. However, the structure of the photoactivated state and the conformational changes that lead to it are not known. We report time-resolved x-ray scattering of the full-length phytochrome from Deinococcus radiodurans on micro- and millisecond time scales. We identify a twist of the histidine kinase output domains with respect to the chromophore-binding domains as the dominant change between the photoactivated and resting states. The time-resolved data further show that the structural changes up to the microsecond time scales are small and localized in the chromophore-binding domains. The global structural change occurs within a few milliseconds, coinciding with the formation of the spectroscopic meta-Rc state. Our findings establish key elements of the signaling mechanism of full-length bacterial phytochromes

Первичный серологический статус и иммунологическая эффективность вакцинации против Streptococcus pneumoniae и Haemophilus influenzae типа b у детей с бронхолегочной дисплазией: когортное исследование

Background. The primary serological status of children with bronchopulmonary dysplasia (BPD) with respect to respiratory significant pathogens remains unstudied. Wherein, the efficacy of vaccination of children with BPD against Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) has been studied in a small number of studies which results are contradictory.Objective. Our aim was to study the pre-vaccinal serological status with regard to S. pneumoniae and Hib and the immunological efficacy of vaccination against these infections in children with BPD.Methods. The study included children with BPD without exacerbation. The immunological efficacy of conjugate vaccines — pneumococcal 13-valent and against Haemophilus influenza type b — was assessed by the level of IgG against S. pneumoniae and Hib using the ELISA method. The level of antibodies was determined before vaccination and 1 or 3–6 months afterwards.Results. The study included 32 children with BPD, mean age at the time of determining primary serological status was 13.3±1.3 months, at the time of vaccination — 15.2±1.5 months. The mean gestational age was 28.7±0.8 weeks, the body weight at birth was 1225±180 g. Before vaccination, all children with BPD had no protective antibody titre against S. pneumoniae and Hib averaging 0.2±0.034 and 0.13±0.0106 mg/L, respectively. One month after vaccination, the level of antibodies to S. pneumoniae reached 12.9±2.34 mg/L to Hib — 3.34±0.769 mg/L.Conclusion. After immunization with a pneumococcal 13-valent conjugate vaccine and a conjugate vaccine against Haemophilus influenzae type b, the concentration of IgG against S. pneumoniae exceeded the protective level in all examined patients (100%), the concentration to Hib — in 29 (90.6%).Обоснование. Первичный серологический статус детей с бронхолегочной дисплазией (БЛД) в отношении респираторно значимых патогенов остается неизученным. При этом эффективность вакцинации детей с БЛД против Streptococcus pneumoniae и Haemophilus influenzae типа b (Hib) изучалась в небольшом числе исследований, результаты которых противоречивы. Цель исследования — изучить довакцинальный серологический статус в отношении S. pneumoniae и Hib и иммунологическую эффективность вакцинации против этих инфекций у детей с БЛД.Методы. В исследование включали детей с БЛД, вне обострения. Иммунологическую эффективность конъюгированных вакцин — 13-валентной пневмококковой и против гемофильной инфекции типа b — оценивали по уровню IgG к S. pneumoniae и Hib методом ELISA. Уровень антител определяли до вакцинации и спустя 1 и 3–6 мес.Результаты. Включено 32 ребенка с БЛД средний возраст которых на момент определения первичного серологического статуса составил 13,3±1,3 мес, на момент вакцинации — 15,2±1,5 мес. Средний гестационный возраст — 28,7±0,8 нед, масса тела при рождении — 1225±180 г. У всех детей с БЛД до вакцинации отсутствовал защитный титр антител к S. pneumoniae и Hib, составив в среднем 0,2±0,034 и 0,13±0,0106 мг/л соответственно. Через 1 мес после вакцинации уровень антител к S. pneumoniae достигал 12,9±2,34 мг/л, к Hib — 3,34±0,769 мг/л.Заключение. После иммунизации 13-валентной пневмококковой конъюгированной вакциной и конъюгированной вакциной против гемофильной инфекции типа b концентрация IgG к S. pneumoniae превышала защитный уровень у всех обследованных пациентов (100%), концентрация к Hib — у 29 (90,6%).Конфликт интересовЛ.С. Намазова-Баранова — получение исследовательских грантов от фармацевтических компаний Пьер Фабр, Genzyme Europe B.V., ООО «Астра зенека Фармасьютикалз», Gilead / PRA «Фармасьютикал Рисерч Ассошиэйтс СиАйЭс», Teva Branded Pharma ceuti cal products R&D, Inc. / ООО «ППД Девелопмент (Смоленск)», «Сталлержен С.А.» / «Квинтайлс ГезмбХ» (Австрия). М.В. Федосеенко — получение гонораров от компании Sanofi, Pfizer за чтение лекций

Опыт вакцинации 13-валентной конъюгированной пневмококковой вакциной пациентки с ювенильным идиопатическим артритом с частыми респираторными инфекциями на фоне терапии метотрексатом

The article presents the experience of vaccination with a pneumococcal 13-valent conjugate vaccine (PCV13) of a patient aged 5 years with oligoarticular juvenile idiopathic arthritis (JIA) receiving methotrexate at a dose of 15 mg/m2 per week subcutaneously. Treatment with methotrexate provided a remission of JIA, but was accompanied by frequent respiratory infections — up to 8 times a year. During infection progression, methotrexate injections were omitted. Gaps in the treatment with methotrexate were accompanied by an exacerbation of the underlying condition. Vaccination of the patient with PCV13 reduced the frequency of respiratory infections to 2 times a year, which was accompanied by the development of persistent remission of the disease. Adverse events and exacerbation of JIA in a child after vaccination with PCV13 were not registered.Представлен опыт вакцинации 13-валентной конъюгированной пневмококковой вакциной (13ПКВ) пациентки в возрасте 5 лет с олигоартикулярным ювенильным идиопатическим артритом (ЮИА), получавшей метотрексат в дозе 15 мг/м2 в неделю подкожно. Лечение метотрексатом обеспечило ремиссию ЮИА, но сопровождалось частыми респираторными инфекциями — до 8 раз в год. При развитии инфекций инъекции метотрексата пропускались. Перерывы в лечении метотрексатом сопровождались обострением основного заболевания. Вакцинация пациентки 13ПКВ обеспечила снижение частоты респираторных инфекций до 2 раз в год, что сопровождалось развитием стойкой ремиссии заболевания. Нежелательных явлений и обострения ЮИА у ребенка на фоне вакцинации 13ПКВ не зарегистрировано