525 research outputs found

    Method of determining the optimal settings of automatic excitation regulators of synchronous machines in EPS

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    The stability of the electric power system can be improved by forming of the correct settings of automatic exciting regulators. Currently, there is no unified methodology of automatic exciting regulators, so analysis of their impact is still an urgent task. The article describes the approach to solving above-mentioned problem, which combines several methods. Research based on Hybrid Real Time Simulator of EPS developed in Tomsk Polytechnic University

    Glycyrrhetinic acid and its derivatives as inhibitors of poly(ADP-ribose)polymerases 1 and 2, apurinic/apyrimidinic endonuclease 1 and DNA polymerase β

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    Aim. For strengthening the efficiency of monofunctional alkylating antineoplastic drugs it is important to lower the capacity of base excision repair (BER) system which corrects the majority of DNA damages caused by these reagents. The objective was to create inhibitors of the key BER enzymes (PARP1, PARP2, DNA polymerase β, and APE1) by the directed modification of glycyrrhetinic acid (GA). Methods. Amides of GA were produced from the GA acetate by formation of the corresponding acyl chloride, amidation with the appropriate amine and subsequent deacylation. Small library of 2-cyano substituted derivatives of GA methyl esters was obtained by the structural modification of GA framework and carboxylic acid group. The inhibitory capacity of the compounds was estimated by comparison of the enzyme activities in specific tests in the presence of compounds versus their absence. Results. None of tested compounds inhibits PARP1 significantly. Unmodified GA and its morpholinic derivative were shown to be weak inhibitors of PARP2. The derivatives of GA containing keto-group in 11 triterpene framework were shown to be moderate inhibitors of pol β. Compound 3, containing 12-oxo-9(11)-en moiety in the ring C, was shown to be a single inhibitor of APE1 among all compounds studied. Conclusions. The class of GA derivatives, selective pol β inhibitors, was found out. The selective inhibitor of APE1 and weak selective inhibitor of PARP2 were also revealed

    Foreign Direct Investments in Business Services: Transforming the Visegrád Four Region into a Knowledge-based Economy?

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    Foreign direct investments (FDIs) in the service sector are widely attributed an important role in bringing more skill-intensive activities into the Visegrad Four (V4). This region—comprising Poland, the Czech Republic, Hungary and Slovakia—relied heavily on FDIs in manufacturing, which was often found to generate activities with limited skill content. This contribution deconstructs the chaotic concept of “business services” by analysing the actual nature of service sector activities outsourced and offshored to the V4. Using the knowledge-based economy (KBE) as a benchmark, the paper assesses the potential of service sector outsourcing in contributing to regional competitiveness by increasing the innovative capacity. It also discusses the role of state policies towards service sector FDI (SFDI). The analysis combines data obtained from case studies undertaken in service sector outsourcing projects in V4 countries. Moreover, it draws on interviews with senior employees of investment promotion agencies and publicly available data and statistics on activities within the service sector in the region. It argues that the recent inward investments in business services in the V4 mainly utilize existing local human capital resources, and their contribution to the development of the KBE is limited to employment creation and demand for skilled labour

    Personalized targeted therapy of moderate and severe atopic asthma in Russia

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    Introduction. Taking into account the prevalence of asthma and especially severe atopic asthma which requires carefully selected and expensive therapy, the appearance of the domestic biosimilar omalizumab among biological therapy drugs makes the choice of treatment for this category more affordable. The article presents the results of an observational open prospective clinical trial of the omalizumab biosimilar in severe athopic asthma patients.The purpose of this study was to evaluate the efficacy and safety of the domestic production biosimilar in the real clinical practice.Materials and methods. The study involved 10 adult patients aged 19 to 55 years with a diagnosis of moderate to severe uncontrolled persistent asthma treated with mediun to high dose ICS and second&more controller (ACQ-5 ≥ 1,5, FEV1 < 80% of the predicted normal value). For 26 weeks all patients received the omalizumab. The evaluation of the efficacy was provided taking into account asthma symptoms improvement the results of ACQ-5, FEV1, PEF, asthma exacerbations and the use of health resources. Results. According to the results of data analysis due to omalizumab all patients demonstrated reducing daily asthma symptoms, nocturnal awakening and night time symptom, shortness of  breath and SABA using. An  asthma control improvement was observed after 1 month treatment (Δ ACQ-5 1.6 [1.2; 2.4], p = 0.0002 compared to the baseline data) with a continued tendency to further increase during 6 months of the study. A statistically significant increase in FEV1 was noted (initially, FEV1 56.7% [51.25; 61.8] of the predicted; after 1 month, FEV1 67.5% [63.45; 70.6] of the predicted, p = 0.00003; after 6 months, FEV1 80.6% [80.55; 84.05] of the predicted, p >< 0.001). Omalizumab biosimilar used allowed to reduce the background asthma therapy. No asthma exacerbation was registered due to 26 weeks omalizumab treatment. Conclusions. Based on the results of the study, it was shown that the administration of the omalizumab biosimilar to patients with severe atopic asthma improves control over the symptoms, lung function and reduces the amount of asthma exacerbations, and has a good safety>< 80% of the predicted normal value). For 26 weeks all patients received the omalizumab. The evaluation of the efficacy was provided taking into account asthma symptoms improvement the results of ACQ-5, FEV1, PEF, asthma exacerbations and the use of health resources.Results. According to the results of data analysis due to omalizumab all patients demonstrated reducing daily asthma symptoms, nocturnal awakening and night time symptom, shortness of  breath and SABA using. An  asthma control improvement was observed after 1 month treatment (Δ ACQ-5 1.6 [1.2; 2.4], p = 0.0002 compared to the baseline data) with a continued tendency to further increase during 6 months of the study. A statistically significant increase in FEV1 was noted (initially, FEV1 56.7% [51.25; 61.8] of the predicted; after 1 month, FEV1 67.5% [63.45; 70.6] of the predicted, p = 0.00003; after 6 months, FEV1 80.6% [80.55; 84.05] of the predicted, p < 0.001). Omalizumab biosimilar used allowed to reduce the background asthma therapy. No asthma exacerbation was registered due to 26 weeks omalizumab treatment.Conclusions. Based on the results of the study, it was shown that the administration of the omalizumab biosimilar to patients with severe atopic asthma improves control over the symptoms, lung function and reduces the amount of asthma exacerbations, and has a good safety

    Complex 99mTc-PDA-DTPA for myocardial imaging

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    The 123I-labeled fatty acids such as 123I-Iodophenylpentadecanoic acid and 123I-Beta-methyliodophenylpentadecanoic acid are the agents used clinically for myocardial imaging. Fatty acids are the major source of energy for the normal myocardium. However, under ischemic conditions the myocardial cells switch to glucose metabolism for their energy needs. Fatty acids undergo prolonged metabolic stunning in patients with reversible ischemia, thereby helping in early diagnosis of coronary artery disease in highrisk patients. High cost andlimited availability of cyclotron-produced 123I, makes 99mTc-labeled fatty acids more desirable for the purpose. In diagnosis the dominant radionuclide is 99mTc. It is estimated that it is involved in about 85% of all imaging procedures in nuclear medicine. The method for preparation of new 99mTc-fatty chemical systems based on modified diethylene triamine pentaacetic acid (DTPA) molecule has been elaborated in this work . The main advantage using DTPA as chelate agent for radioactive label, is the molecule or it's derivative ability to form sufficiently stable complexes with different radioactive metals including technetium-99. Moiety of pentadecanoic acid addition gave the ability to prepare modified complex of DTPA. In a labeling procedure, freshly eluted Na99mTcO4 (20mCi) was added to a mixture of cysteine, stannous chloride, PDK-DTPA and ethanol in a vial. On keeping the reaction mixture at 90 0C for 30 min, [99mTc-PDK-DTPA] radiopharmaceutical was formed. Thereafter, the reaction mixture was cooled over ice and characterized by HPLC. The result of dynamic scintigraphic research showed, that after being injected, the substance is actively acumulated into myocardium. Eventually one can say that modified DTPA-moleculs are functionally suitable for myocardial imaging

    Genetic environment of the blaKPC-2 gene in a Klebsiella pneumoniae isolate that may have been imported to Russia from Southeast Asia

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    The nucleotide sequence of a blaKPC-2-harboring plasmid (pKPCAPSS) from Klebsiella pneumoniae ST273 isolated in Saint Petersburg, Russia, from a patient with history of recent travel to Vietnam is presented. This 127,970-bp plasmid possessed both IncFII and IncR replicons. blaKPC-2 was localized on a hypothetical mobile element. This element was flanked by 38-bp inverted Tn3 repeats and included a Tn3-specific transposase gene, macrolide resistance operon (mphA-mrx-mphR), and a fragment of blaTEM with unique polymorphisms. © 2017 American Society for Microbiology. All Rights Reserved

    Sudden cardiac death in childhood RASopathy-associated hypertrophic cardiomyopathy: Validation of the HCM risk-kids model and predictors of events

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    Background: RASopathies account for nearly 20% of cases of childhood hypertrophic cardiomyopathy (HCM). Sudden cardiac death (SCD) occurs in patients with RASopathy-associated HCM, but the risk factors for SCD have not been systematically evaluated. Aim: To validate the HCM Risk-Kids SCD risk prediction model in children with RASopathy-associated HCM and investigate potential specific SCD predictors in this population. Methods: Validation of HCM Risk-Kids was performed in a retrospective cohort of 169 patients with a RASopathy-associated HCM from 15 international paediatric cardiology centres. Multiple imputation by chained equations was used for missing values related to the HCM Risk-Kids parameters. Results: Eleven patients (6.5%) experienced a SCD or equivalent event at a median age of 12.5 months (IQR 7.7–28.64). The calculated SCD/equivalent event incidence was 0.78 (95% CI 0.43–1.41) per 100 patient years. Six patients (54.54%) with an event were in the low-risk category according to the HCM Risk-Kids model. Harrell's C index was 0.60, with a sensitivity of 9.09%, specificity of 63.92%, positive predictive value of 1.72%, and negative predictive value of 91%; with a poor distinction between the different risk groups. Unexplained syncope (HR 42.17, 95% CI 10.49–169.56, p < 0.001) and non-sustained ventricular tachycardia (HR 5.48, 95% CI 1.58–19.03, p < 0.007) were predictors of SCD on univariate analysis. Conclusion: Unexplained syncope and the presence of NSVT emerge as predictors for SCD in children with RASopathy-associated HCM. The HCM Risk-Kids model may not be appropriate to use in this population, but larger multicentre collaborative studies are required to investigate this further

    Friedreich's ataxia-associated childhood hypertrophic cardiomyopathy: a national cohort study

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    OBJECTIVE: Hypertrophic cardiomyopathy (HCM) is an important predictor of long-term outcomes in Friedreich's ataxia (FA), but the clinical spectrum and survival in childhood is poorly described. This study aimed to describe the clinical characteristics of children with FA-HCM. DESIGN AND SETTING: Retrospective, longitudinal cohort study of children with FA-HCM from the UK. PATIENTS: 78 children (<18 years) with FA-HCM diagnosed over four decades. INTERVENTION: Anonymised retrospective demographic and clinical data were collected from baseline evaluation and follow-up. MAIN OUTCOME MEASURES: The primary study end-point was all-cause mortality (sudden cardiac death, atrial arrhythmia-related death, heart failure-related death, non-cardiac death) or cardiac transplantation. RESULTS: The mean age at diagnosis of FA-HCM was 10.9 (±3.1) years. Diagnosis was within 1 year of cardiac referral in 34 (65.0%) patients, but preceded the diagnosis of FA in 4 (5.3%). At baseline, 65 (90.3%) had concentric left ventricular hypertrophy and 6 (12.5%) had systolic impairment. Over a median follow-up of 5.1 years (IQR 2.4-7.3), 8 (10.5%) had documented supraventricular arrhythmias and 8 (10.5%) died (atrial arrhythmia-related n=2; heart failure-related n=1; non-cardiac n=2; or unknown cause n=3), but there were no sudden cardiac deaths. Freedom from death or transplantation at 10 years was 80.8% (95% CI 62.5 to 90.8). CONCLUSIONS: This is the largest cohort of childhood FA-HCM reported to date and describes a high prevalence of atrial arrhythmias and impaired systolic function in childhood, suggesting early progression to end-stage disease. Overall mortality is similar to that reported in non-syndromic childhood HCM, but no patients died suddenly
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