Translational recoding: Canonical translation mechanisms reinterpreted.

During canonical translation, the ribosome moves along an mRNA from the start to the stop codon in exact steps of one codon at a time. The collinearity of the mRNA and the protein sequence is essential for the quality of the cellular proteome. Spontaneous errors in decoding or translocation are rare and result in a deficient protein. However, dedicated recoding signals in the mRNA can reprogram the ribosome to read the message in alternative ways. This review summarizes the recent advances in understanding the mechanisms of three types of recoding events: stop-codon readthrough, -1 ribosome frameshifting and translational bypassing. Recoding events provide insights into alternative modes of ribosome dynamics that are potentially applicable to other non-canonical modes of prokaryotic and eukaryotic translation

Technology Platforms as an Efficient Tool to Modernize Russia's Economy

There is an urgent need to consider the dynamic development of the global economy from the point of view of its positive impact on competitiveness improvement in national manufacturing industries, and the best ways to modernize the country economy. The purpose of the paper is to provide with perspectives for development of instruments related to technology platforms within the framework of innovation management and adapted to the conditions of Russia's economic reality. The major method in studying this issue is mathematical economic modeling which has made it possible to facilitate expediency in determining a technology platform as an effective innovation control instrument.  The paper considers European and Russian experience in deploying technology platforms, and identifies national features characteristic to the performance of the innovation management instrument.  A mathematical economic model is used for justifying the efficiency of introducing technology platforms into Russian institutional innovation system. The practical significance of results and conclusions is in its ability to improve the mechanisms of developing and implementing federal and regional innovation development programs, development of the innovation infrastructure, stimulation of the innovation activity, use of a set of technology platform instruments by public authorities.  Keywords: technology platforms, innovative development, modernization, triple helix. JEL Classifications: C02, C18, O2

Long-Term Monitoring of Liver Fibrosis and Steatosis in Patients with Chronic Hepatitis C after Achieving a Sustained Virologic Response to Antiviral Therapy

Aim: to analyze the dynamics of fibrosis and steatosis of the liver according to fibroelastometry in patients with chronic hep-atitis C (CHC) after ≥ 6 months from transient elastometry (TE) achieving a sustained virologic response (SVR) to antiviral therapy.Materials and methods. At baseline, a prospective observational study included 628 CHC patients with known stage of liver fibrosis (F) before AVT, some of whom were phased out due to non-compliance with the inclusion criteria. The final analysis included 297 patients who had transient elastometry (TE) data with CAP™ technology on the severity of liver fibrosis (± steatosis) before treatment and after ≥ 6 months after reaching SVR (67 % – interferonfree regimens of therapy). Median follow-up from the moment SVR was confirmed was 3 years [2; 6].Results. At the end of the study, the average age of patients was 49 ± 12 years, of which 53 % were men. In the long-term period after reaching SVR, regression of liver fibrosis was diagnosed in 80 % of cases (including in patients with cirrhosis), and the progression of fibrosis was in 3 % of patient. At the same time, regression of liver steatosis was detected only in 31 % of the patient, worsening of the results was in 23 % (26 % of them had the appearance of steatosis (S) of the liver of 1–3 degrees in persons with no fatty liver before the start of AVT). In the group of patients with liver steatosis, the proportion of men was significantly higher (p = 0.004). Clinically significant stages of fibrosis F3–F4 were significantly more often recorded in patients with hepatic steatosis, both before treatment (46 % S1–S3 and 22 % S0, p < 0.001) and after ≥ 6 months after reaching SVR (19 % S1–S3 and 9 % S0, p = 0.023).Conclusion. In patients with chronic hepatitis C with SVR achieved in the long term, despite a significant regression of liver fibrosis, a high prevalence of hepatic steatosis remains. The data obtained indicate the feasibility of routine diagnosis of both fibrosis and steatosis of the liver in the management of patients with chronic HCV infection before and after successful antiviral therapy

ВОЗМОЖНОСТИ ДИФФУЗИОННО-ВЗВЕШЕННЫХ ИЗОБРАЖЕНИЙ В ДИФФЕРЕНЦИАЛЬНОЙ ДИАГНОСТИКЕ ЗЛОКАЧЕСТВЕННОЙ И ДОБРОКАЧЕСТВЕННОЙ МЕДИАСТИНАЛЬНОЙ ЛИМФАДЕНОПАТИИ

Introduction. Mediastinal lymphadenopathy can be caused by a wide range of benign and malignant states. Determination of the genesis of lymphadenopathy is crucial for treatment planning and prognosis of the disease.The purpose of the study was to evaluate the diagnostic accuracy of diffusion weighted imaging (DWI) with apparent diffusion coefficient (ADC) measurements in differentiating malignant versus benign mediastinal lymphadenopathy. Material and Methods. 48 consecutive patients with at least one enlarged mediastinal lymph node revealed on CT-scans were examined on 1,5 T MR-machine with conventional images and respiratory-triggered DWI. In all patients one of the biggest solid lymph nodes was selected for ADC measurements and mean ADCs of each node were recorded. ADCs were correlated with the results of complete diagnostic work-up (including histopathological diagnosis in 41 patients) and follow-up CT. Statistics included Student’s t-test, Mann-Whitney U-test and ROC-curve analysis. Results. 27 lymph nodes were classified as malignant (metastases, lymphoma) and 21 lymph nodes were classified as benign (sarcoidosis, reactive hyperplasia, tuberculosis). Mean ADC of malignant lymph nodes (1,02 ± 0,29×10−3 mm2/s) was significantly lower than that of benign lymph nodes (1,57 ± 0,32×10−3 mm2/s), p<0,0001. The cut-off value of ≤1,3×10−3mm2/s for ADC indicated the malignancy with a sensitivity of 81,5 % and a specificity of 85,7%. The area under the ROC-curve was 0,89 (95 % confidence interval: 0,77, 0,96), p<0,0001. Conclusion. DWI is a promising technique in chest pathology. DWI with ADC measurements could be used as a good complementary tool in the diagnostic work-up of patients with mediastinal lymphadenopathy.Введение. Медиастинальная лимфаденопатия может быть обусловлена широким спектром доброкачественных и злокачественных заболеваний. Определение характера лимфаденопатии играет ключевую роль в выборе тактики лечения и оценке прогноза заболевания. Цель исследования – изучить возможности диффузионно-взвешенных изображений (ДВИ) с оценкой измеряемого коэффициента диффузии (ИКД) в дифференциальной диагностике злокачественных и доброкачественных форм медиастинальной лимфаденопатии. Материал и методы. В исследование включено 48 пациентов с наличием как минимум одного увеличенного медиастинального лимфоузла по результатам компьютерной томографии. Исследование проводилось на магнитно-резонансном томографе с напряженностью поля 1,5 Тл с получением традиционных изображений и синхронизированных с дыханием ДВИ. У каждого пациента выбирался один из наиболее крупных солидных лимфоузлов, в котором оценивалось среднее значение ИКД. Значения ИКД сравнивались с результатами гистологического исследования (у 41 пациента), комплексного клинико-лучевого обследования и динамического наблюдения. Для статистической обработки результатов исследования использовались t-критерий Стьюдента, U-критерий Манна – Уитни, ROC-анализ. Результаты. У 27 пациентов установлено злокачественное поражение лимфоузлов (метастазы, лимфома), у 21 – доброкачественные изменения (саркоидоз, реактивная гиперплазия, туберкулез). Среднее значение ИКД при злокачественной лимфаденопатии (1,02 ± 0,29×10−3 мм2/с) оказалось ниже, чем при доброкачественной (1,57 ± 0,32×10−3 мм2/с), отличия статистически значимы (p<0,0001). Пороговое значение ИКД, составившее ≤1,3×10−3 мм2/с (95 % доверительный интервал: 1,06; 1,64), позволило выявлять злокачественное поражение лимфоузлов с чувствительностью 81,5 % и специфичностью 85,7 %; площадь под ROC-кривой составила 0,89 (95 % доверительный интервал: 0,77; 0,96), р<0,0001. Заключение. ДВИ являются перспективным методом лучевой диагностики патологии органов грудной клетки. ДВИ с оценкой ИКД могут быть использованы в качестве дополнительной методики в комплексном обследовании пациентов с медиастинальной лимфаденопатией

ДИФФЕРЕНЦИАЛЬНАЯ ДИАГНОСТИКА МЕДИАСТИНАЛЬНОЙ ЛИМФАДЕНОПАТИИ ПРИ ЛИМФОМЕ И САРКОИДОЗЕ С ПОМОЩЬЮ ДИФФУЗИОННО-ВЗВЕШЕННОЙ МАГНИТНО-РЕЗОНАНСНОЙ ТОМОГРАФИИ

The aim of the study. Investigation of the potential of diffusion-weighted magnetic resonance imaging (DW-MRI) with apparent diffusion coefficient (ADC) evaluation for differential diagnosis of mediastinal lymphadenopathy in lymphoma and sarcoidosis.Materials and methods. The study included 15 patients with sarcoidosis and 7 patients with lymphoma. In each patient ADC values of 3 largest lymph nodes were measured.Results. Differences of mean ADC values in lymphoma (1,01±0,3×10-3mm2/s) and sarcoidosis (1,51±0,25×10-3mm2/s) were significant, p<0,0001. Optimal cut-point value for ADC of ≤1,1×10-3mm2/s differentiated lymphoma from sarcoidosis with sensitivity of 76,2%, specificity of 97,8% and accuracy of 90,9%, the area under the ROC-curve was 0,89.Conclusion. Preliminary results of the study have demonstrated the potential of DW-MRI in differential diagnosis of lymphoma and sarcoidosis and expediency of the further study.Цель. Изучение возможностей диффузионно-взвешенной магнитно-резонансной томографии (ДВ-МРТ) грудной клетки с оценкой измеряемого коэффициента диффузии (ИКД) в дифференциальной диагностике медиастинальной лимфаденопатии при лимфоме и  саркоидозе.Материалы и методы. В исследование включены 15 пациентов с саркоидозом и 7  пациентов с лимфомой. У каждого пациента значения ИКД измерены в трех наиболее  крупных лимфатических узлах.Результаты. Выявлены значимые отличия средних значений ИКД при лимфоме (1,01±0,3×10-3 мм2/с) и саркоидозе (1,51±0,25×10-3 мм2/с), p<0,0001. При использовании порогового значения ИКД ≤1,1×10-3 мм2/с чувствительность, специфичность и точность метода в дифференциальной диагностике лимфомы и саркоидоза составили 76,2; 97,8 и  90,9% соответственно, площадь под ROC-кривой — 0,89.Заключение. Предварительные результаты показали высокую информативность ДВ-МРТ в дифференциальной диагностике лимфомы и саркоидоза и целесообразность продолжения исследования

Clinical Practice Guidelines of the Russian Society for the Study of the Liver, the Russian Gastroenterological Association, the National Scientific Society of Infectious Disease Specialists for the Diagnosis and Treatment of Chronic Hepatitis C

Аim: diagnosis and treatment algorithms in the clinical recommendations intended for general practitioners, gastroenterologists, infectious disease specialists, hepatologists on the of chronic hepatitis C are presented.Summary. Chronic viral hepatitis C is a socially significant infection, the incidence of which in the Russian Federation remains significantly high. Over the past 10 years, great progress has been made in the treatment of hepatitis C — direct acting antiviral drugs have appeared. The spectrum of their effectiveness allows to achieve a sustained virological response in more than 90 % of cases, even in groups that were not previously considered even as candidates for therapy or were difficult to treat — patients receiving renal replacement therapy, after liver transplantation (or other organs), at the stage of decompensated liver cirrhosis, HIV co-infected, etc. Interferons are excluded from the recommendations due to their low effectiveness and a wide range of adverse events. The indications for the treatment have been expanded, namely, the fact of confirmation of viral replication. The terms of dispensary observation of patients without cirrhosis of the liver have been reduced (up to 12 weeks after the end of therapy). Also, these recommendations present approaches to active screening of hepatitis in risk groups, preventive and rehabilitation measures after the end of treatment.Conclusion. Great success has been achieved in the treatment of chronic hepatitis C. In most cases, eradication of viral HCV infection is a real task even in patients at the stage of cirrhosis of the liver, with impaired renal function, HIV co-infection, after solid organs transplantation

SIMULATION AND EXPERIMENTAL STUDY OF HYDRODYNAMIC CHARACTERISTICS OF SORBENTS FOR ION-SELECTIVE TREATMENT OF LRW

Given are the results of experimental study of hydrodynamic resistance of a layer of sorbents used for cesium removal LRW. Conducted is a simulation of water flow through the sorbent layer with SolidWorks Flow Simulation program. The simulation results are com-pared with the experiments data

Effective transcription factor binding site prediction using a combination of optimization, a genetic algorithm and discriminant analysis to capture distant interactions

<p>Abstract</p> <p>Background</p> <p>Reliable transcription factor binding site (TFBS) prediction methods are essential for computer annotation of large amount of genome sequence data. However, current methods to predict TFBSs are hampered by the high false-positive rates that occur when only sequence conservation at the core binding-sites is considered.</p> <p>Results</p> <p>To improve this situation, we have quantified the performance of several Position Weight Matrix (PWM) algorithms, using exhaustive approaches to find their optimal length and position. We applied these approaches to bio-medically important TFBSs involved in the regulation of cell growth and proliferation as well as in inflammatory, immune, and antiviral responses (NF-κB, ISGF3, IRF1, STAT1), obesity and lipid metabolism (PPAR, SREBP, HNF4), regulation of the steroidogenic (SF-1) and cell cycle (E2F) genes expression. We have also gained extra specificity using a method, entitled SiteGA, which takes into account structural interactions within TFBS core and flanking regions, using a genetic algorithm (GA) with a discriminant function of locally positioned dinucleotide (LPD) frequencies.</p> <p>To ensure a higher confidence in our approach, we applied resampling-jackknife and bootstrap tests for the comparison, it appears that, optimized PWM and SiteGA have shown similar recognition performances. Then we applied SiteGA and optimized PWMs (both separately and together) to sequences in the Eukaryotic Promoter Database (EPD). The resulting SiteGA recognition models can now be used to search sequences for BSs using the web tool, SiteGA.</p> <p>Analysis of dependencies between close and distant LPDs revealed by SiteGA models has shown that the most significant correlations are between close LPDs, and are generally located in the core (footprint) region. A greater number of less significant correlations are mainly between distant LPDs, which spanned both core and flanking regions. When SiteGA and optimized PWM models were applied together, this substantially reduced false positives at least at higher stringencies.</p> <p>Conclusion</p> <p>Based on this analysis, SiteGA adds substantial specificity even to optimized PWMs and may be considered for large-scale genome analysis. It adds to the range of techniques available for TFBS prediction, and EPD analysis has led to a list of genes which appear to be regulated by the above TFs.</p

Plasma–liquid interactions: a review and roadmap

Plasma–liquid interactions represent a growing interdisciplinary area of research involving plasma science, fluid dynamics, heat and mass transfer, photolysis, multiphase chemistry and aerosol science. This review provides an assessment of the state-of-the-art of this multidisciplinary area and identifies the key research challenges. The developments in diagnostics, modeling and further extensions of cross section and reaction rate databases that are necessary to address these challenges are discussed. The review focusses on non-equilibrium plasmas