Experimental studies of restoration of ball mill trunnion

The article deals with the analysis of experimental data on reconstruction of cement mill axles by the auxiliary machine at the place of operation. Based on the experimental research in repair the regression models of large-size equipment are developed, coefficients of equations of regression are defined. Importance of coefficients is estimated, and the adequacy of regression models is checke

Comprehensive assessment of specific antibodies on infectious activity of tick-borne encephalitis virus

Vaccines for prophylactic immunization provide the most reliable and effective protection against the vast majority of infectious diseases. Tick-borne encephalitis (TBE) represents a high-priority medical issue at the territory of the Eurasian continent. Of great importance is assessing a role of distinct antibody titers especially low titers, observed quite often in vaccinated individuals, sometimes posing obstacles in determining a threshold of seropositivity as well as the level of specific protection against TBE virus. We aimed at obtaining data to assess antiviral activity of virus-specific antibodies with distinct titer levels based on the in vitro, ex vivo and in vivo experimental studies with a highly virulent Far-Eastern strain of tick-borne encephalitis virus. The in vitro, ex vivo and in vivo comprehensive experimental studies with a highly virulent Far-Eastern strain of tick-borne encephalitis virus (TBEV) were conducted and the dynamics of antiviral activity of virus-specific antibodies at variable titers (1:100–1:3200) was measured (timeframe ranged within 1–96 hours p.i.) to provide a rationale for evaluating the antiviral immune response. It was found that the in vitro experiments demonstrated that the IgG at 1:100 titer exerted a weak anti-TBEV neutralizing effect at all time-points examined. The IgG 1:400 titer caused a 2 log PFU/mL decline in TBEV Dal strain yield at 72 h post-infection, whereas at 1:3200 titer it completely suppressed TBEV replication throughout the observation period. The ex vivo experiments with blood serum obtained from vaccinated subjects demonstrating a range of TBEV antibody titers (sera from vaccinated individuals with varying anti-TBEV antibody titers) and in vivo (outinbred white mice) experiments revealed a delayed virus elimination for antibody titers at 1:100 and 1:200 as well as rapid virus elimination (1–2 days p.i.) for antibody titers greater than 1:400. Thus, antibody titer at 1:400 may be considered as the universal anti-TBEV protection threshold. In order to properly conclude regarding the revaccination schedule it is advised to start with testing blood serum for durability of anti-TBEV immune response. Subjects with TBEV antibody titers at 1:100 and 1:200 should be strongly recommended to undergo a mandatory revaccination. Such an approach is believed to be the most effective way toward enhancing efficacy of vaccine-mediated protection against TBE

IMMUNOPATHOGENESIS OF HEART FAILURE IN PATIENTS WITH INFECTIVE-IMMUNE MYOCARDITIS

Aim. To study quantitative parameters, specifics of functional state of the main subpopulations of peripheral blood lymphocytes of the infective-immune myocarditis patients (IIM) and postmyocarditis cardiosclerosis (PMC), and specifics of cytokine profile.Material and methods. Totally, 35 IIM patients included, and 39 with PMC. In 17 patients with IIM there was significant heart failure (HF) — III functional class (FC) by New-York Heart Association (NYHA), in 18 patients with IIM there were no signs of HF, or mild signs (0-II FC by NYHA). In 18 patients with PMC there were no signs of HF, and in 21 — there was I FC by NYHA. The controls were 10 formally healthy persons. Study of population and subpopulation contents, and lymphocytes activation markers of peripheral blood, was done with four-color laser flow cytometry using FACSCalibur equipment and relevant monoclonal antibodies (Beckton Dickinson, USA). We studied the mean cytokines concentrations characterizing Th1-, Th2- and Th17- subpopulations of the helper lymphocytes. Measurement of serum cytokines was done with the method solid-phase immune-enzyme assay with LLC “Vectro-Best” (Russia) media. Statistics was done with software PASW Statistics 18.Results. Inflammatory diseases of myocardium show the deviations of native, as acquired immunity. In IIM and PMC there was significant decrease of NKTlymphocytes, not related to the severity of HF signs and durations of the disease. Immunity activation signs in IIM group showed the increase of the early activator marker CD25 expression activation, that was marked during the first 2 weeks from the disease onset. Following, by the end of the 1st month and on the 2nd month from the disease onset, the increase of T- and non-T-lymphocytes was found with the signs of delayed activation, revealed by HLA-DR antigen expression. The activator marker patterns were differ in patients with different grade of HF severity. Concentration of interferon-γ (IFN-γ) and interleukine (IL)-4 was more than 3 times higher in IIM patients comparing to controls. There was more than 7-times higher increase of IL-17A, and concentrations of effectory cytokines of Th17-subpopulation — IL-8 and granulocyte-macrophagal colony-stimulating factor (GM CSF). The level of IFN-γ reached maximal levels during the first 2 weeks from the disease onset. Later, IFN-γ concentration declined. Opposite, serum level of IL-4 was significantly increased by the end of the 1st and on the 2nd month from disease onset. Concentrations of IL-17A, IL-8 and GM CSF in blood serum were increased during the whole 2nd week, by the end of the 1st month and on the 2nd month. Th17-cytokines concentrations were significantly increased in PMC patients. Level of IL-17A was higher than in controls almost two times, IL8 — by 51%, GM CSF — by 50%. Serum levels of IL-4, and IL-17A, IL-8 and GM CSF were higher in subgroup of PMC patients with the disease duration less than 6 months. Conclusion. Disorders of anti-infection immunity and mechanisms of selfrestriction of immune reactions do play important role in development of myocardium damage of inflammatory origin

Роль IL-23 в развитии Th17-лимфоцитов у пациентов с туберкулезом легких

The objective: to evaluate the role of IL-23 in the development of Th17 lymphocytes in patients with different clinical and pathogenetic forms of pulmonary tuberculosis.Subjects and Methods. 165 pulmonary tuberculosis patients were examined. Venous blood was used for tests. Mononuclear leukocytes were isolated by centrifugation and monocytes were extracted and transformed into dendritic cells. The concentration of IL-23 in the supernatants of culture suspensions of dendritic cells was determined by ELISA. Immunophenotyping of Th17 lymphocytes (CD4+CD161+IL-17A+ cells) was performed by flow cytometry. Real-time PCR was used to determine the expression of the RORC2 transcription factor gene in lymphocytes.Results. In patients with infiltrative drug susceptible and drug resistant pulmonary tuberculosis against the background of normal production of IL-23 by dendritic cells, an increase in blood level of Th17 lymphocytes and the level of mRNA of the RORC2 transcription factor gene was registered. The course of disseminated pulmonary tuberculosis (regardless of drug susceptibility and resistance) is associated with pronounced decrease in the concentration of IL-23 in vitro and the absence of response from Th17 lymphocytes.Цель исследования: оценить роль IL-23 в развитии Th17-лимфоцитов у пациентов с различными клинико-патогенетическими вариантами туберкулеза легких.Материалы и методы. Обследовано 165 пациентов с туберкулезом легких (ТБЛ). Материалом для исследования являлась венозная кровь. Центрифугированием выделяли мононуклеарные лейкоциты и осуществляли экстракцию моноцитов и их трансформацию в дендритные клетки. Твердофазным иммуноферментным методом определяли концентрацию IL-23 в супернатантах культуральных суспензий дендритных клеток. Методом проточной цитофлуориметрии проводили иммунофенотипирование Th17-лимфоцитов (CD4+CD161+IL-17A+ клеток). Методом ПЦР в режиме реального времени определяли экспрессию гена транскрипционного фактора RORC2 в лимфоцитах.Результаты. У пациентов с инфильтративным лекарственно-чувствительным и лекарственно-устойчивым ТБЛ на фоне нормопродукции IL-23 дендритными клетками регистрируется повышение содержания Th17-лимфоцитов в крови и уровня мРНК гена транскрипционного фактора этих клеток – RORC2. Течение диссеминированного ТБЛ (вне зависимости от лекарственной чувствительности возбудителя) сопровождается выраженным снижением концентрации IL-23 in vitro и отсутствием реакции со стороны Th17-лимфоцитов

Electromagnons in multiferroic RMn2O5 compounds and their microscopic origin

We summarize the existing experimental data on electromagnons in multiferroic RMn2O5 compounds, where R denotes a rare earth ion, Y or Bi, and discuss a realistic microscopic model of these materials based on assumption that the microscopic mechanism of magnetically-induced ferroelectricity and electromagnon absorption relies entirely on the isotropic Heisenberg exchange and magnetostrictive coupling of spins to a polar lattice mode and does not involve relativistic effects. This model explains many magnetic and optical properties of RMn2O5 manganites, such as the spin re-orientation transition, magnetically-induced polarisation, appearance of the electromagnon peak in the non-collinear spin state and the polarisation of light for which this peak is observed. We compare experimental and theoretical results on electromagnons in RMn2O5 and RMnO3 compounds.Comment: 20 pages, 9 figures, to be published in J. Phys.: Condens. Matter, special issue on multiferroic

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation : Data From ROCKET AF

M. Kaste on työryhmän ROCKET AF Steering Comm jäsen.Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS(2) score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P= 75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, approximate to 7 in 10 deaths were cardiovascular, whereasPeer reviewe

Development of Spatial Thinking in Process of Studying Stereometry

The article examines the development of spatial thinking while studying solid geometry. The key note of the study is to examine the selected levels of spatial thinking: the creation and manipulation of spatial images in the course of solving stereometric problems

The significance of notch signaling in the regulation of Тreg-lymphocyte differentiation in patients with infiltrative pulmonary tuberculosis

Data on the role of regulatory T lymphocytes (Treg) in the immunopathogenesis of tuberculosis are actively accumulating in the current literature. The overwhelming effect of Treg cells on the proliferation, functional activity of Th1 lymphocytes and antigen-presenting cells allows to consider this population as a possible target of modulation of the immune response in patients with tuberculosis. The Notch signaling pathway participates in the regulation of FoxP3 transcription factor expression and, therefore, is capable of supporting suppressor activity of Treg lymphocytes. A key role in the functioning of the Notch signaling cascade belongs to the enzyme γ-secretase that cleaves the intracellular domain of the receptor (Notch ICD), with the subsequent formation of a complex that regulates cell differentiation. The actively studied inhibitor of γ-secretase is DAPT – N-[N-(3.5-difluorophenacetyl)-L-alanyl]-S-phenylglycine tert-butyl ester). Mononuclear leukocytes isolated from the blood of patients with drug-sensitive and drug-resistant pulmonary tuberculosis by gradient centrifugation before the start of anti-tuberculosis therapy were used as the material for the study. The cells were cultured under conditions of stimulation with Mycobacterium tuberculosis antigens CFP10-ESAT6 or with the addition of γ-secretase inhibitor (DAPT) at doses of 5 μM/L and 10 μM/L in combination with CFP10-ESAT6 at 37 °C and 5% CO2 for 72 h to the incubation medium. The number of Treg lymphocytes was assessed by flow cytofluorimetry by determining the expression of the CD4 surface receptor (FITC) and the intracellular transcription factor FoxP3 (PE). In intact cell cultures of pulmonary tuberculosis patients, the relative number of Treg lymphocytes was statistically significantly (p < 0.001) higher than that of healthy donors. Stimulation of cells with CFP10-ESAT6 antigens was accompanied by an increase in the proportion of CD4+FoxP3+ cells in both groups of tuberculosis patients. Addition of γ-secretase inhibitor at a concentration of 5 μM/L to the incubation medium did not lead to statistically significant changes in the number of Treg lymphocytes. The increase in DAPT concentration up to 10 μM/L was accompanied by a decrease in the number of Treg lymphocytes in comparison with the corresponding indices upon stimulation with CFP10-ESAT6 antigens in all groups of the subjects. Regardless of cultivation conditions, the number of CD4+FoxP3+ cells in patients with drug-resistant mycobacteria exceeded their number in patients with drug-sensitive pulmonary tuberculosis. Inhibition of the Notch signaling pathway by a γ-secretase inhibitor (DAPT) at a concentration of 10 μM/L contributed to a decrease in the number of Treg lymphocytes in patients with drug-sensitive and drug-resistant pulmonary tuberculosis. Reduction of Treg lymphocyte number by γ-secretase inhibitor confirms the importance of Notch signaling cascade as a potential target for correction of Treg lymphocytes immunosuppressive activity and pathogenetic therapy of tuberculosis