LHC Transverse Feedback System: First Results of Commissionning

A powerful transverse feedback system ("Damper") has been installed in LHC. It will stabilise the high intensity beam against coupled bunch transverse instabilities in a frequency range from 3 kHz to 20 MHz and at the same time damp injection oscillations originating from steering errors and injection kicker ripple. The LHC Damper can also be used as means of exciting transverse oscillations for the purposes of abort gap cleaning and tune measurement. The LHC Damper includes 4 feedback systems on 2 circulating beams (in other words one feedback system per beam and plane). Every feedback system consists of 4 electrostatic kickers, 4 push-pull wide band power amplifiers, 8 preamplifiers, two digital processing units and 2 beam position monitors with low-level electronics. The power and low-level subsystem layout is described along with first results from the commissioning of 16 power amplifiers and 16 electrostatic kickers located in the LHC tunnel. The achieved performance is compared with earlier predictions and requirements for injection damping and instability control. Requirements and first measurements of the performance of the power and low-level subsystems are summarized

SNP genes of immune response mediators and predisposition to development of socially significant diseases

Allele typing of single-nucleotide polymorphisms (SNPs) may be used in predictive medicine and to determine targets for the most effective treatment strategies for various diseases. The purpose of the present work was to investigate the association between the SNPs of inflammatory genes, e.g., IL10 (C819T; rs1800871; C592A; rs1800872); IL4 (C589T; rs2243250); fibrosis-related factors - TGFβ1 (G915C; rs1800471); MMP1 (1607insG; rs1799750); apoptosis-regulators (TNFRSF11B G1181C; rs2073618); vasoconstricting factors (CRP C3872T; rs1205); CYP1A1 (A2454G; rs1048943), endothelial dysfunction (EDN1 G925T; rs5370); (NOS3 C786T; rs2070744) and development of coronary heart disorders, breast cancer, bronchial asthma (BA) and threatened miscarriage in early pregnancy among population of the Republic of Adygea.DNA samples of unrelated donors and patients (n = 74) with verified diagnoses of bronchial asthma (n = 13), coronary heart disease (n = 10), breast cancer (n = 10) and threatened miscarriage in the first trimester of pregnancy (n = 8) were isolated from peripheral blood leukocytes and typed by allele-specific polymerase chain reaction with electrophoretic detection of results using commercial tests-systems of NPF “Litech”, Moscow.The study in a group of Adygea residents has revealed the statistical significance for the “normal” Arg25-allelic variant of the TGFβ1 gene (p < 0.05; F = 0.038; OR = 3.231; 95% CI = 1.081-9.656) in the development of bronchial asthma. There were no significant differences in SNP rs1800471 of the TGFβ1 gene in the groups with cardiovascular, oncological diseases and gestational disorders (p > 0.05). The frequency distribution of allelic variants NOS3 C786T; TNFRSF11B G1181C; 1607insG of the MMP1 gene; G925T of the EDN1 gene, and CYP1A1 2454G in the examined patients with cardiovascular disease and breast cancer did not significantly differ from the control group (p > 0.05). The statistical significance for the frequency of allelic variants rs1799750 (MMP1 gene) in cases of threatened early miscarriage and in women with a physiological course of pregnancy (F = 0.096; p < 0.05%: OR = 6.0) was close to reliable, but with a confidence interval > 1.0 (95% CI = 0,98036,716), thus requiring further research.The obtained data could be sufficient in order to suggest predisposition for bronchial asthma, as well as to develop a set of preventive measures taking into account the individual characteristics of each patient

Gene polymorphisms of IL-1β (C511T), IL-17A (G197A), IL-12B (A1188C), TNFα (G308A) and IL-4 (C589T) associated with threat of early reproductive losses

Prevalence of threatened miscarriage is 16-25% of all pregnancies. The symptomatics of the threatened miscarriage in the first trimester may develop due to conversion of initial inflammatory reaction that disturbs the intersystemic and local interactions in the endometrium, followed by placental insufficiency, intrauterine fetal affection and spontaneous abortion. The aim of our work was to study the association between single nucleotide polymorphisms (SNPs) of some cytokine genes, e.g., IL-1β (C511T, rs16944), IL-17A (G197A, rs2275913), IL-12B (A1188C, rs3212227), TNFα (G308A, rs1800629), and IL-4 (C589T, rs2243250) and the risk of early reproductive losses among residents of Adyghe Republic (RA). The work was carried out at the Immunogenetic Laboratory of our Research Institute of Complex Problems. The allelic variants of cytokine genes were detected by SNP-method in 106 samples of genomic DNA in women with the threatened abortion in 1st trimester (n = 58) and the uncomplicated gestation (n = 48). SNP-typing of polymorphic variants of cytokine genes IL-1β, IL-17A, IL-12B, TNFα and IL-4 was carried out by PCR (polymerase chain reaction) with allele-specific primers and electrophoretic detection of results on test systems of (Litech, Moscow). Statistical analysis of experimental data was carried out by SPSS Statistical program 17.0. The correspondence of SNP distributions to expected values at Hardy—Weinberg equilibrium and comparison of allelic variants/ genotypes frequencies were performed using the χ2 criterion (Chi-square with Yates correction), odd ratios (OR) detected at significance level p < 0.05 and 95% confidence interval (95% CI). Reliability of the differences for the SNP frequencies for small samples was evaluated using the Fisher’s exact criterion. Heterozygous variant (C511T; OR = 3.46; 95% Cl: 1.04-11.54) and homozygous “mutant” genotypes (T511T; OR = 5.71; 95% Cl: 1.12-29.09) of the main proinflammatory IL-1β was significantly associated (p < 0.05) with the risk of developing threatening miscarriage in the Adygea residents. The -511Т allele of IL-1β gene, and -1188C variant of IL-12B gene increase the risk of the early termination of pregnancy, respectively, 5.8-fold (95% Cl: 2.4213.92; p = 0.00004), and 2.97-fold (95% Cl: 1.23-7.19; p = 0.01). The “mutant” -511T allelic variant of the IL-1 p gene is associated with the risk of developing a symptome complex of threatening miscarriage in Russian ethnic group (p = 0.0001; OR = 14.09), and in Adygea ethnic group (p = 0.02; OR = 8.17), which is almost undetectable in women with normal pregnancy in the first trimester. Thus, only С511Т (rs16944) in IL-1β gene and A1188C (rs3212227) in IL-12B gene of the five typed cytokine genes may be used as marker polymorphisms of gestational distress for the women in Adygea

Imbalance of NK cell subpopulations and polymorphisms of proinflammatory cytokine genes in the pathogenesis of atherosclerosis

Understanding the pathogenetic mechanism of development and identifying trigger markers of the disease will significantly increase the efficiency of pre-nosological diagnosis and medical follow-up of patients. In this case, one should take into account the role of mutations in cytokine genes, which affect their biochemical activity and production level. The objective of the study was to investigate the role of mediators of acute and chronic inflammation (IL-17A, IL-1â, TNFá and IL-4), the ratio of natural killer cell subpopulations (CD56hiCD16-/CD56loCD16+) in pathogenesis of coronary atherosclerosis resulting into coronary heart disease.To analyze the results, an integrated approach was used, including molecular genetic methods such as polymerase chain reaction, typing of single-nucleotide substitutions in cytokine genes, isolation and cultivation of peripheral blood mononuclear cells, assessment of spontaneous and in vitro-induced production of immune system mediators, enzyme-linked immunosorbent assay, cytotoxic test, flow cytometry with monoclonal antibodies (Beckman Coulter, USA) to CD16, CD56 NK markers.The study included 130 residents of the North Caucasus, including the patients (n = 62) treated at the Cardiology Department of the Adyghe Republican Clinical Hospital (ARCB) with a verified diagnosis of ischemic heart disease (IHD), and a control group (n = 68), represented by unrelated healthy donors.Overexpression of cytokines in IHD patients was associated with distinct single nucleotide substitutions in certain genes. Studying a group of residents from the Republic of Adygeya, the authors experimentally established that harboring the 511C allele of the IL-1â gene (p < 0.0004; OR = 4.67), A197A of the IL-17A gene genotype (p < 0.04; OR = 3.88), G308 SNP of TNFá gene (p < 0.01; OR = 3.41), and 589T variant of IL-4 gene (p < 0.04; OR = 2.45) are associated with hyperproduction of the first-wave inflammatory mediators that increase the risk of developing ischemic heart disease. In atherosclerosis and associated cardiovascular diseases, we have noted a significant decrease in spontaneous and induced activity of natural killer cells involved in the utilization of “foamy cells”. The NK activity of peripheral blood mononuclear cell in patients with coronary heart disease is significantly reduced. In the IHD patients, an imbalance of phenotypically and functionally different CD56hiCD16-/CD56loCD16+ NK subpopulations with a predominance of CD56hiCD16- phenotype were revealed. Conclusions: Immuno-inflammatory mechanisms of evolving coronary atherosclerosis are associated with single-nucleotide substitutions, i.e., polymorphisms in the promoter regions of the IL-17A (G197A), IL-1 â (T511C), and TNFá (G308A), the known mediators of acute and chronic inflammation.Genetically determined overexpression of IL-17A, IL-1â, and TNFá, confirmed in experiments on evaluation of spontaneous and stimulated cytokine production in patients with CHD, together with reduced NK activity of РВМС, due to predominance of CD56hiCD16-, a subpopulation with high cytokine production, manifested by an increased pro-inflammatory component that triggers and provides long-term support to pathophysiological processes of atherosclerosis

PROGNOSTIC SIGNIFICANCE OF MET235/235THR POLYMORPHISMS OF GENE AGT FOR DEVELOPMENT OF CARDIOVASCULAR DISORDERS IN PROFESSIONAL SPORTSMEN

Aim. Assessment of Met235Thr polymorphisms of gene AGT, related to cardiovascular diseases (CVD), as early genetic predictors of occupational diseases in professional sportsmen in Adyghea Republic (AR).Material and methods. Dispersion of Met235/235Thr polymorphic variants of AGT gene studied via SNP-method (single nucleotide polymorphism) with allele-specific primers and electrophoretic detection of results (NPF “Litech”). С704Т polymorphisms of gene AGT (rs699) with replacements of cytosine by thymine at 704 position of gene, and methionine by threonine (Met>Thr) at 235 aminoacid consequence of angiotensine, were typed in the specimens of genomic DNA of professional sportsmen (n=40), donors (n=120) and CVD patients (n=64) aged 23-65 y. o., from two ethnicities — Adyges and Russians. Experimental findings were analized with relevant statistical software (SPSS Statistics 17.0).Results. Prevalence of 235Thr allele and Thr235Thr genotype of AGT is significantly higher in the group of patients comparing to healthy controls (р=0,05, χ2=5,84; р=0,01, χ2=6,2) and sportsmen (р=0,05, χ2 =6,15; р=0,02, χ2=5,04). High risk of CVD development in carriers of allele 235Thr variant (OR=4,34) as Thr235Thr mutation genotype (OR=3,89), caused by the increase of agiotensine level in blood plasma, confirms its association with the diseases of cardiovascular continuum (DCC) in AR inhabitants. Under conditions of intensive physical exertion the Thr235Thr genotype of qualified sportsmen is an adverse factor leading to cardiovascular pathology.Conclusion. The new data obtained, on the increased incidence of prognostically adverse Met235/235Thr polymorhpism of the gene AGT for CVD in professional sportsmen, can be applied for early molecular and genetic predictors of cardiovascular disorders at individual level, as for defining of risk groups with further correction of training schedule

PROGNOSTIC ROLE OF A1166C POLYMORPHISMS OF THE ANGIOTENSINE II RECEPTOR GENE (AGT2R1) IN CORONARY ATHEROSCLEROSIS AMONG ADYGHEA REPUBLIC INHABITANTS

Aim. The investigation of A1166/166C polymorphisms of the vascular receptor 1 type of angiotensine II gene (AGT2R1) association with the development of coronary and peripheral atherosclerosis in ethnic groups ofAdygheaRepublicinhabitants.Material and methods. The spread of A1166/166C polymorphic variants of the gene AGT2R1 was studied via the “single nucleotide polymorphism” (SNP) — method with allele-specific primers and electrophoretic results detection (by SPF “Litech”). Gene polymorphisms AGT2R1 (rs5186) with nucleotide replacement of adenine by cytosine (А>C) in the 1166th position of gene AGT2R1 were typified in the samples of donors genomic DNA (n=143) and of those with cardiovascular diseases (n=39) at the age 23-65 y. o. from two ethnic subgroups — Adyghes and Russians. The data was processed via software SPSS Statistics 17.0.Results. In the group of those with complicated coronary and peripheral atherosclerosis there was statistically significant increase of the prevalence of mutant1166Callele and of pathological monozygous genotype C1166C. The risk of cardiovascular diseases in the carriers of1166Callele increases 3,77 times (c2 =26,07; р=0,00003), and in the case with homozygous “mutant” CC genotype — 10,36 times (c2 =31,20; р=0,00002), that makes it to use the1166Callele and С1166С genotype AGT2R1 as genetic predictors of coronary atherosclerosis and markers of prenosological diagnostics of ischemic heart disease (c2 =42,96; р=0,0000005; OR (95%)=17,37).Conclusion. The results of this study, together with additional instrumental investigations of cardiovascular system functioning will help to improve the precision of diagnostics of atherosclerosis and its possible complications at earlier stages, that will help to decrease disability rate and mortality in economically active citizens