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

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