Study of the Stressed State Near the Crack That Initiates at the Inclusion Under Longitudinal Shift Wave Influence

The purpose of this paper is to study the stress state near the crack that initiates at the inclusion when subjected to a longitudinal shear wave. The formulated problem is reduced to a system of singular integro-differential equations with fixed singularities with respect to the unknown voltage surges and displacements on the surface of a defect. To solve this system, a similar collocation method is used. There have been shown dependences of the change in the dimensionless values of the stress intensity factors (SIF) on the dimensionless value of the wave number in the case of wave propagation at different angles.Метою цієї роботи є дослідження напруженого стану біля тріщини, що відходить від включення під впливом хвилі поздовжнього зсуву. Сформульована задача приведена до системи сингулярних інтегро-диференціальних рівнянь з нерухомими особливостями відносно невідомих стрибків напружень і переміщень на поверхні дефекту. Для розв’язання цієї системи використовується аналогічний колокаційний метод. Показано залежності зміни безрозмірних значень коефіцієнтів інтенсивності напружень (КІН) від безрозмірного значення хвильового числа у випадку поширення хвилі під різними кутами.Целью данной работы является исследование напряженного состояния возле трещины, которая отходит от включения при воздействии волной продольного сдвига. Сформулированная задача приведена к системе сингулярных интегро-дифференциальных уравнений с неподвижными особенностями относительно неизвестных скачков напряжений и перемещений на поверхности дефекта. Для решения этой системы используется аналогичный коллокационный метод. Показаны зависимости изменения безразмерных значений коэффициентов интенсивности напряжений (КИН) от безразмерного значения волнового числа в случае распространения волны под разными углами

Стероидные ингибиторы CYP17A1 – платформа для разработки новых противоопухолевых агентов

This review deals with studies of researches of novel CYP17A1 steroidal inhibitors and relative compounds published over the last ten years. The review contains six chapters in which novel targets of well-known CYP17A1 inhibirors (abiraterone and galeterone), anti-cancer and anti-proliferative activities of them major metabolites and new synthetic analogs, and in addition another nitrogen-containing androstane and pregnane derivatives are considered. In the review 354 structures of novel steroid derivatives and them anti-cancer efficiency data are considered. Analysis of the literature data allows us to consider steroidal inhibitors of CYP17A1 as multi-target anti-cancer agents with high pharmacological potential.Обзор посвящен результатам исследований новых стероидных ингибиторов CYP17A1 и структурно родственных соединений, опубликованным за последнее десятилетие. Он состоит из шести глав, в которых рассматриваются новые мишени для известных ингибиторов CYP17A1 – абиратерона и галетерона, противоопухолевая и антипролиферативная активность основных метаболитов и новых синтетических производных абиратерона и галетерона, а также других азотсодержащих производных андростана и прегнана. Приведены структуры 354 новых стероидных производных и данные об их влиянии на стероидогенез и пролиферацию клеток – процессы, вовлечённые в развитие опухоли и поддержание её роста. Анализ цитированной литературы позволяет рассматривать стероидные ингибиторы CYP17A1 как “мультитаргетные” агенты с высоким фармакологическим потенциалом

Embryonal Antigens in Maize Caryopses: The Temporal Order of Antigen Accumulation during Embryogenesis

The sequential appearance of a specific group of embryonal antigens (EA), presumably globulins, was demonstrated in developing maize (Zea mays L.) caryopses using a double immunodiffusion test with absorption of common antigens. Cross immunoelectrophoresis was employed to follow the differential pattern of EA accumulation in the growing scutellum and embryonic axis. The transient nature of two predominant EA seems to indicate their role as specific protein reserves of embryonal tissues. Another presumably organ-specific EA was maintained in callus obtained from a 28-day-old culture of scutellum isolated from the mature non-germinated caryopsis

Development of a new humanized mouse model to study acute inflammatory arthritis

BACKGROUND: Substantial advances have been generated in understanding the pathogenesis of rheumatoid arthritis (RA). Current murine models of RA-like disease have provided great insights into the molecular mechanism of inflammatory arthritis due to the use of genetically deficient or transgenic mice. However, these studies are limited by differences that exist between human and murine immune systems. Thus, the development of an animal model that utilizes human immune cells, will afford the opportunity to study their function in the initiation and propagation of inflammatory arthritis. METHODS: One to two-day old irradiated NOD-scid IL2rγ(null) (NSG) mice were reconstituted with human CD34+ cord blood stem cells. Leukocytes were analyzed by flow cytometry and circulating antibodies were determined by ELISA. Arthritis was induced by injecting complete Freund’s adjuvant into knee or ankle joints. Mice were also treated with the TNF inhibitor, Etanercept, or PBS and joints were analyzed histologically. RESULTS: Humanized mice were established with high reconstitution rates and were able to spontaneously produce human immunoglobulins as well as specific IgG in response to immunization. Intraperitoneal injection of thioglycolate or injection of complete Freund’s adjuvant into joints resulted in migration of human immune cells to the injected sites. Arthritic humanized mice treated with Etanercept had markedly less inflammation, which was associated with decreased total numbers of human CD45+ cells, including human lymphocytes and neutrophils. CONCLUSIONS: The humanized mouse model is a new model to study inflammatory arthritis disease using human leukocytes without rejection of engrafted tissue. Future studies may adapt this system to incorporate RA patient cord blood and develop a chimeric animal model of inflammatory arthritis using genetically predisposed immune cells

Distribution of exogenous 25-hydroxycholesterol in Hep G2 cells between two different pools

AbstractBinding of [26,27-3H]25-hydroxycholesterol (25HC) to human hepatoma Hep G2 cells was saturated within 120 min. Two intracellular pools of 25HC were identified in a pulse-chase experiment: (i) an exchangeable pool which was in dynamic equilibrium with 25HC in the medium (t1/2 of reversible exchange 15 min) and (ii) an unexchangeable pool which remained in cells during incubation in medium containing LPDS. 25HC from the exchangeable pool inhibits cholesterol biosynthesis, decreases the HMG CoA reductase mRNA level and stimulates cholesterol acylation. 25HC from the unexchangeable pool was partially bound to cytosolic proteins and apparently utilized for metabolic transformation. Incubation of Hep G2 cells with [26,27-3H]25HC in the presence of a 30-fold molar excess of 3β-hydroxy-5α-cholest-8(14)-en-15-one was found to cause (i) 2-fold decrease in the binding of [26,27-3H]25HC to cytosolic proteins (sedimentation constant of radioactive complex was 4–5 S) and (ii) the 35% inhibition of 25HC transformation to polar metabolites

Social work in psychiatry

The analysis of activity of a social service shows that the social experts participating in rendering of the mediko-social help to patients in establishments of public health services, realise the socially-psychological, socially-pedagogical and socially-legal activity directed on restoration, preservation and strengthening of their health.Анализ деятельности социальной службы показывает, что социальные специалисты, участвующие в оказании медико­социальной помощи пациентам в учреждениях здравоохранения, реализуют социально-психологическую, социально-педагогическую и социально-правовую деятельность, направленную на восстановление, сохранение и укрепление их здоровья

Исследование in silico взаимодействия производных 2’-{[(e)-андрост-5-ен-17-илиден]-метил}оксазолинов с андрогеновым рецептором

The ability of novel oxazolinyl derivatives of pregna-5,17(20)-diene to interact with the androgen receptor (AR) was investigated using molecular modelling methods. Six new derivatives differed in oxazolinyl radicals in 17 position were used. It was shown that all compounds were able to docked in the ligand-binding domain of AR only when the AR helix-12 was removed. It is suggested that these compounds have antagonistic properties. Results of docking and simulation of molecular dynamics with estimation of binding energy allow to predict that two compounds can be effective AR antagonists.Методами молекулярного моделирования оценена способность новых азотсодержащих стероидных производных 2’-{[(E)-андрост-5-ен-17-илиден]-метил}оксазолинов взаимодействовать с андрогенным рецептором. Исследованы 6 оксазолиновых производных 17(20)Е-прегна-5,17(20)-диена, различающихся структурой гетероцикла. Показано, что все соединения способны связываться с андрогенным рецептором только в случае, когда из структуры рецептора была удалена 12 спираль. Это позволяет предполагать, что данные лиганды должны проявлять антагонистические свойства. Результаты докинга и молекулярной динамики с оценкой энергии связывания лигандов позволили предположить, что два из исследованных соединений могут быть эффективными антагонистами андрогенного рецептора

The PYRIN Domain-only Protein POP1 Inhibits Inflammasome Assembly and Ameliorates Inflammatory Disease

SummaryIn response to infections and tissue damage, ASC-containing inflammasome protein complexes are assembled that promote caspase-1 activation, IL-1β and IL-18 processing and release, pyroptosis, and the release of ASC particles. However, excessive or persistent activation of the inflammasome causes inflammatory diseases. Therefore, a well-balanced inflammasome response is crucial for the maintenance of homeostasis. We show that the PYD-only protein POP1 inhibited ASC-dependent inflammasome assembly by preventing inflammasome nucleation, and consequently interfered with caspase-1 activation, IL-1β and IL-18 release, pyroptosis, and the release of ASC particles. There is no mouse ortholog for POP1, but transgenic expression of human POP1 in monocytes, macrophages, and dendritic cells protected mice from systemic inflammation triggered by molecular PAMPs, inflammasome component NLRP3 mutation, and ASC danger particles. POP1 expression was regulated by TLR and IL-1R signaling, and we propose that POP1 provides a regulatory feedback loop that shuts down excessive inflammatory responses and thereby prevents systemic inflammation

CD11b suppresses TLR activation of nonclassical monocytes to reduce primary graft dysfunction after lung transplantation

Primary graft dysfunction (PGD) is the leading cause of postoperative mortality in lung transplant recipients and the most important risk factor for development of chronic lung allograft dysfunction. The mechanistic basis for the variability in the incidence and severity of PGD between lung transplant recipients is not known. Using a murine orthotopic vascularized lung transplant model, we found that redundant activation of Toll-like receptors 2 and 4 (TLR2 and -4) on nonclassical monocytes activates MyD88, inducing the release of the neutrophil attractant chemokine CXCL2. Deletion of Itgam (encodes CD11b) in nonclassical monocytes enhanced their production of CXCL2 and worsened PGD, while a CD11b agonist, leukadherin-1, administered only to the donor lung prior to lung transplantation, abrogated CXCL2 production and PGD. The damage-associated molecular pattern molecule HMGB1 was increased in peripheral blood samples from patients undergoing lung transplantation after reperfusion and induced CXCL2 production in nonclassical monocytes via TLR4/MyD88. An inhibitor of HMGB1 administered to the donor and recipient prior to lung transplantation attenuated PGD. Our findings suggest that CD11b acts as a molecular brake to prevent neutrophil recruitment by nonclassical monocytes following lung transplantation, revealing an attractive therapeutic target in the donor lung to prevent PGD in lung transplant recipients