Genome-wide significant association with seven novel multiple sclerosis risk loci

Objective: A recent large-scale study in multiple sclerosis (MS) using the ImmunoChip platform reported on 11 loci that showed suggestive genetic association with MS. Additional data in sufficiently sized and independent data sets are needed to assess whether these loci represent genuine MS risk factors. Methods: The lead SNPs of all 11 loci were genotyped in 10 796 MS cases and 10 793 controls from Germany, Spain, France, the Netherlands, Austria and Russia, that were independent from the previously reported cohorts. Association analyses were performed using logistic regression based on an additive model. Summary effect size estimates were calculated using fixed-effect meta-analysis. Results: Seven of the 11 tested SNPs showed significant association with MS susceptibility in the 21 589 individuals analysed here. Meta-analysis across our and previously published MS case-control data (total sample size n=101 683) revealed novel genome-wide significant association with MS susceptibility (p<5×10−8) for all seven variants. This included SNPs in or near LOC100506457 (rs1534422, p=4.03×10−12), CD28 (rs6435203, p=1.35×10−9), LPP (rs4686953, p=3.35×10−8), ETS1 (rs3809006, p=7.74×10−9), DLEU1 (rs806349, p=8.14×10−12), LPIN3 (rs6072343, p=7.16×10−12) and IFNGR2 (rs9808753, p=4.40×10−10). Cis expression quantitative locus effects were observed in silico for rs6435203 on CD28 and for rs9808753 on several immunologically relevant genes in the IFNGR2 locus. Conclusions: This study adds seven loci to the list of genuine MS genetic risk factors and further extends the list of established loci shared across autoimmune diseases

Genome-wide significant association with seven novel multiple sclerosis risk loci

Objective: A recent large-scale study in multiple sclerosis (MS) using the ImmunoChip platform reported on 11 loci that showed suggestive genetic association with MS. Additional data in sufficiently sized and independent data sets are needed to assess whether these loci represent genuine MS risk factors. Methods: The lead SNPs of all 11 loci were genotyped in 10 796 MS cases and 10 793 controls from Germany, Spain, France, the Netherlands, Austria and Russia, that were independent from the previously reported cohorts. Association analyses were performed using logistic regression based on an additive model. Summary effect size estimates were calculated using fixed-effect meta-analysis. Results: Seven of the 11 tested SNPs showed significant association with MS susceptibility in the 21 589 individuals analysed here. Meta-analysis across our and previously published MS case-control data (total sample size n=101 683) revealed novel genome-wide significant association with MS susceptibility (p<5×10−8) for all seven variants. This included SNPs in or near LOC100506457 (rs1534422, p=4.03×10−12), CD28 (rs6435203, p=1.35×10−9), LPP (rs4686953, p=3.35×10−8), ETS1 (rs3809006, p=7.74×10−9), DLEU1 (rs806349, p=8.14×10−12), LPIN3 (rs6072343, p=7.16×10−12) and IFNGR2 (rs9808753, p=4.40×10−10). Cis expression quantitative locus effects were observed in silico for rs6435203 on CD28 and for rs9808753 on several immunologically relevant genes in the IFNGR2 locus. Conclusions: This study adds seven loci to the list of genuine MS genetic risk factors and further extends the list of established loci shared across autoimmune diseases

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase

Combined String Searching Algorithm

Проблема поиска образа в строке является классической задачей обработки данных. Несмо- тря на ряд существующих алгоритмов решения задачи, работа в этом направлении продол- жается. Предложенный алгоритм развивает теоретические основы задачи поиска образа в строке, комбинируя алгоритмы двух разных классов с прямым и обратным проходом образа, а именно алгоритмы Кнута-Морриса-Пратта и Боуера-Мура. В статье приведен анализ ра- боты предложенного комбинированного алгоритма и сравнение результатов его работы с базовыми алгоритмами, подтверждающее эффективность комбинированного алгоритма по- иска образа в строкеThe string search problem is a classical problem of data processing. Despite a number of existing algorithms for solving this problem, the work in this direction continues. The algorithm proposed in the article develops the theoretical basis of the string search problem by combining the algorithms of two different classes, i.e. forward and backward string searching algorithms, namely, Knuth- Morris-Pratt algorithm and Bower-Moore algorithm. The paper provides the analysis of the proposed combined algorithm and comparison of its results with the basic algorithms, confirming the efficacy of the combined string search algorith

Assessing the Effective Use of State Property: Accounting and Analytical Support and Analysis Methodology

The effective use of state property is one of the topical issues of economic policy affecting the interests of all segments of society. The need to comply with the principle of the effective use of budgetary funds is enshrined in Article 34 of the Budget Code of the Russian Federation. However, while studying the existing system of financial management in Russian practice, it was revealed that the current methodological approaches do not fully solve the tasks enshrined in the budget legislation. This is primarily due to the lack of proper accounting and analytical and methodological support for the relevant management procedures. Thus, the Federal State Information and Analytical System of the Federal Property Management Agency “Unified System of State Property Management” was used as the information base. However, this information system has some significant shortcomings, such as (1) the lack of a single regulatory act on the register at all levels of government; (2) the duplicated information about the property; and (3) there are no indicators and criteria in the register that would reflect effective property use, etc. Secondly, the approaches used to assess effective state property use are based on industry standards (health, education, etc.) in relation to the property and specific equipment necessary for the provision of public services. In this regard, the purpose of this study is to improve the concept and methodology for analyzing effective state (municipal) property use. The main areas for improving the methodology are (1) to develop a unified register of state property as the main source of accounting and analytical information; (2) to assess the property which state bodies and state institutions need to perform their functions and powers in full and of appropriate quality; and (3) to develop unified approaches for assessing the effective state (municipal) property use. As a result, the authors developed proposals introducing a unified register of the state (municipal) property, which includes indicators characterizing the physical state, recognition in accounting, and forms of the property disposal and use, which can be the basis for information and analytical support for assessing the effective state (municipal) property use at all levels. The study represents a system of indicators for assessing the effective state (municipal) property use, which consists of (1) indicators of the property disposal and use that make up the state treasury and (2) indicators of the property disposal and use of economic entities in the public sector. The results of the study are confirmed by empirical studies using the example of public institutions in the field of higher education and executive authorities

Combined String Searching Algorithm

Проблема поиска образа в строке является классической задачей обработки данных. Несмо- тря на ряд существующих алгоритмов решения задачи, работа в этом направлении продол- жается. Предложенный алгоритм развивает теоретические основы задачи поиска образа в строке, комбинируя алгоритмы двух разных классов с прямым и обратным проходом образа, а именно алгоритмы Кнута-Морриса-Пратта и Боуера-Мура. В статье приведен анализ ра- боты предложенного комбинированного алгоритма и сравнение результатов его работы с базовыми алгоритмами, подтверждающее эффективность комбинированного алгоритма по- иска образа в строкеThe string search problem is a classical problem of data processing. Despite a number of existing algorithms for solving this problem, the work in this direction continues. The algorithm proposed in the article develops the theoretical basis of the string search problem by combining the algorithms of two different classes, i.e. forward and backward string searching algorithms, namely, Knuth- Morris-Pratt algorithm and Bower-Moore algorithm. The paper provides the analysis of the proposed combined algorithm and comparison of its results with the basic algorithms, confirming the efficacy of the combined string search algorith

Quality assessment method for design solutions of automobile service station

The continuous growth of the motorization level of the society and the dynamically changing vehicle and automobile service markets require appropriate development of the transport and automobile service infrastructure. The drastic changes in the vehicle design produce additional or new requirements to the infrastructure intended for the maintenance, service, repair and parking of vehicles. In accordance with these requirements the existing structures are retrofitted and new ones are designed and built in line with the already developed and approved designs. Due to requirements to the infrastructure and numbers of factors to be taken into consideration, the design, as a rule, have different solutions. Decision making involves several steps: formulation of a set of variants, search and selection of the preferable variant among the variants set. But this search is limited by time and computers capacities so the chosen variant is not always the optimal or rational one. The search procedure has become more complicated by parameters and requirements expressed qualitatively. The quality assessment method for the design solutions allows to reduce the search area, and thus to scan considerably greater numbers of variants and to find the best solution. This paper represents a multi-attribute method that allows to assess the quality of design solutions for automobile service station layout and to choose the best solution out of the suggested set

Quality assessment method for design solutions of automobile service station

The continuous growth of the motorization level of the society and the dynamically changing vehicle and automobile service markets require appropriate development of the transport and automobile service infrastructure. The drastic changes in the vehicle design produce additional or new requirements to the infrastructure intended for the maintenance, service, repair and parking of vehicles. In accordance with these requirements the existing structures are retrofitted and new ones are designed and built in line with the already developed and approved designs. Due to requirements to the infrastructure and numbers of factors to be taken into consideration, the design, as a rule, have different solutions. Decision making involves several steps: formulation of a set of variants, search and selection of the preferable variant among the variants set. But this search is limited by time and computers capacities so the chosen variant is not always the optimal or rational one. The search procedure has become more complicated by parameters and requirements expressed qualitatively. The quality assessment method for the design solutions allows to reduce the search area, and thus to scan considerably greater numbers of variants and to find the best solution. This paper represents a multi-attribute method that allows to assess the quality of design solutions for automobile service station layout and to choose the best solution out of the suggested set

Tuning linkage isomerism and magnetic properties of bi- and tri-metallic cage silsesquioxanes by cation and solvent effects

International audienc