ДОСЛІДЖЕННЯ ДИНАМІКИ СЕРИЄСНОГО ЕЛЕКТРОДВИГУНА З РІЗНИМИ ІМПУЛЬСНИМИ СХЕМАМИ РЕГУЛЮВАННЯ

The improved scheme of impulsive regulation of series excitation direct current motor was developed. Theimpulsive regulation models for offered and existent schemes were developed, the electro-mechanicalprocesses of electric drive were probed and comparative analysis was presented.Разработана усовершенствованная схема импульсного регулирования двигателя постоянноготока последовательного возбуждения. Для предложенной и существующей схем импульсного регулирования разработаны имитационные модели, с помощью которых исследованы электромеханические процессы тягового электропривода и выполнен их сравнительный анализ.Розроблена вдосконалена схема імпульсного регулювання двигуна постійного струму послідовногозбудження. Для запропонованої і існуючої схем імпульсного регулювання розроблені моделі, за допомогою яких досліджені електромеханічні процеси тягового електроприводу в цих схемах і виконаноїх порівняльний аналіз

A Systematic Analysis of Cell Cycle Regulators in Yeast Reveals That Most Factors Act Independently of Cell Size to Control Initiation of Division

Upstream events that trigger initiation of cell division, at a point called START in yeast, determine the overall rates of cell proliferation. The identity and complete sequence of those events remain unknown. Previous studies relied mainly on cell size changes to identify systematically genes required for the timely completion of START. Here, we evaluated panels of non-essential single gene deletion strains for altered DNA content by flow cytometry. This analysis revealed that most gene deletions that altered cell cycle progression did not change cell size. Our results highlight a strong requirement for ribosomal biogenesis and protein synthesis for initiation of cell division. We also identified numerous factors that have not been previously implicated in cell cycle control mechanisms. We found that CBS, which catalyzes the synthesis of cystathionine from serine and homocysteine, advances START in two ways: by promoting cell growth, which requires CBS's catalytic activity, and by a separate function, which does not require CBS's catalytic activity. CBS defects cause disease in humans, and in animals CBS has vital, non-catalytic, unknown roles. Hence, our results may be relevant for human biology. Taken together, these findings significantly expand the range of factors required for the timely initiation of cell division. The systematic identification of non-essential regulators of cell division we describe will be a valuable resource for analysis of cell cycle progression in yeast and other organisms

Персонализированная терапия при солидных опухолях: результаты ретроспективного многоцентрового исследования клинической применимости теста FoundationOne® Medicine

Background. The use of targeted sequencing panels makes it possible to optimize and personalize the treatment strategy for cancer patients. Given the lack of a clear «portrait of the patient», the role of large panels (200 or more genes) in the treatment of a patient has not yet been determined.Aim. Assessment of the relationship between the results of targeted sequencing of tumor tissue or ctDNA and the treatment carried out after obtaining these data in patients with various solid tumors.Materials and methods. We retrospectively evaluated the NGS results and the treatments, provided to the 184 patients after NGS testing between 06.2016 and 06.2021. For analysis, one of two methods is used: a histological sample or the patient’s blood plasma. Evaluation of the results and determination of treatment tactics were carried out within the framework of a multidisciplinary commission. The frequency of detection of molecular disorders, the number of mutations in each sample, and the frequency of detection of targets for targeted therapy were assessed.Results. Molecular disorders were detected in 88.5 % (n = 163). The average number of mutations in one sample was 6. The maximum was detected in colorectal cancer patients; their average value was 8. The minimum was determined in non-small cell lung cancer and ovarian cancer patients, the average number of mutations was 3 in each localization. The average time from the moment the material was received by the laboratory to the generation of the report was 11 days. Targeted targets were identified in 25 (13.6 %) patients and therapy was started. Therapy with tyrosine kinase inhibitors of the first – third generations were performed in 12 (48 %) patients, PARP inhibitors – in 3 (24 %), BRAF and MEK inhibitors – in 2 (8 %), anti-HER2 therapy – in 1 (4 %). Targeted therapy within international clinical trials was initiated in 4 (16 %) patients. Immunotherapy was recommended in 3 (12 %) patients. In multivariate analysis, the chance of prescribing therapy based on the results of FM1 analysis was influenced by: mRAS (odds ratio 0.08; 95 % confidence interval 0.01–0.65; p = 0.018) and mEGFR (odds ratio 4.8; 95 % confidence interval 1.4–16.3; p = 0.012).Conclusion. The effectiveness of the FM1 test in real clinical practice in the Russian Federation corresponds to international data. In the presence of a mutation in the RAS genes, an additional FM1 test determines a low chance of detecting clinically significant disorders for which personalized treatment can be prescribed. The high frequency of prescription of therapy based on the results of blood plasma tests is due to the cohort of patients with non-small cell lung cancer and the detection of a mutation in the EGFR gene.Введение. Применение панелей таргетного секвенирования дает возможность оптимизировать и персонализировать стратегию лечения онкологических пациентов. Учитывая отсутствие четкого «портрета пациента», на сегодняшний день не определена роль больших панелей (200 и более генов).Цель исследования – оценка связи результатов таргетного секвенирования ткани опухоли или циркулирующей опухолевой ДНК и проведенного после получения этих данных лечения у больных с различными солидными опухолями.Материалы и методы. На базе 6 российских центров за период с июня 2016 г. по июнь 2021 г. было выполнено таргетное секвенирование FoundationOne® Medicine 184 пациентам с солидными опухолями. Для проведения анализа использовали 1 из 2 методов: гистологический образец или плазма крови пациента. Оценка результатов и определение тактики лечения проводились в рамках мультидисциплинарной комиссии. Оценивали частоту выявления молекулярных нарушений, число мутаций в каждом образце, частоту выявления мишеней для таргетной терапии.Результаты. Молекулярные нарушения выявлены у 88,5 % (n = 163). Среднее число мутаций в 1 образце – 6. Максимальное число выявлено при колоректальном раке, их среднее значение составило 8. Минимальное же число определялось при немелкоклеточном раке легкого и раке яичников, среднее число мутаций составило по 3 в каждой локализации. Среднее время с момента поступления материала в лабораторию до формирования отчета составило 11 дней. У 25 (13,6 %) пациентов выявлены таргетные мишени и начато лечение. Терапия ингибиторами тирозинкиназы I–III поколений проведена 12 (48 %) пациентам, PARP-ингибиторами – 3 (24 %), BRAF- и MEK-ингибиторами – 2 (8 %), анти-HER2 терапия – 1 (4 %). Таргетная терапия в рамках международных клинических исследований начата у 4 (16 %) пациентов. Иммунотерапия рекомендована 3 (12 %) пациентам. При многофакторном анализе на шанс назначения терапии по результатам анализа FM1 влияли mRAS (отношение шансов 0,08; 95 % доверительный интервал 0,01–0,65; р = 0,018) и mEGFR (отношение шансов 4,8; 95 % доверительный интервал 1,4–16,3; р = 0,012).Выводы. Эффективность применения теста FM1 в реальной клинической практике в РФ соответствует международным данным. При наличии мутации в генах RAS дополнительное проведение теста FM1 определяет низкий шанс выявления клинически значимых нарушений, к которым можно будет назначить персонализированное лечение. Высокая частота назначения терапии по результатам анализа плазмы крови обусловлена когортой пациентов с немелкоклеточным раком легкого и выявлением мутации в гене EGFR

Micromechanical Properties of Injection-Molded Starch–Wood Particle Composites

The micromechanical properties of injection molded starch–wood particle composites were investigated as a function of particle content and humidity conditions. The composite materials were characterized by scanning electron microscopy and X-ray diffraction methods. The microhardness of the composites was shown to increase notably with the concentration of the wood particles. In addition,creep behavior under the indenter and temperature dependence were evaluated in terms of the independent contribution of the starch matrix and the wood microparticles to the hardness value. The influence of drying time on the density and weight uptake of the injection-molded composites was highlighted. The results revealed the role of the mechanism of water evaporation, showing that the dependence of water uptake and temperature was greater for the starch–wood composites than for the pure starch sample. Experiments performed during the drying process at 70°C indicated that the wood in the starch composites did not prevent water loss from the samples.Peer reviewe

Cancer Biomarker Discovery: The Entropic Hallmark

Background: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. Methodology/Principal Findings: Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. Conclusions/Significance: We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-throughput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases

Hypotensive episodes on program hemodialysis during dialysis procedure: modern approach for diagnostics, prophylaxis and correction

The study objective is to evaluate the effectiveness of different approaches to correction and prevention of arterial hypotension episodes in patients undergoing long-term hemodialysis (HD).Materials and methods. The study included 35patients undergoing long-term hemodialysis in the dialysis center. In all patients, automatic non-invasive measurement of arterial pressure (AP) was performed using a built-in option of the “artificial kidney” device. Prior to the study, all patients underwent clinical test with evaluation of “dry weight” and bioelectrical impedance analysis. Crossover design was used in the study: at the beginning, hypotensive episodes were corrected in all patients using the standard method (the first 4 hemodialysis procedures); then during the following 4 procedures in addition to standard methods a computer algorithm automatically controlling ultrafiltration rate using an automatic system of pressure control (ASPC) with constant AP monitoring (AP was measured prior to hemodialysis and after it and at least 1 time in the first 5 min of the procedure; from the 4h procedure onwards, intervals were determined by the algorithm automatically) was used. Values of mean AP during hemodialysis procedures for the whole monitoring period were analyzed. The duration of the study was 3 weeks for all patients.Results. Mean pre-dialysis systolic and diastolic AP in the patients for the standard approach was 124.6 ± 27.7 and 74.5 ± 21.1 mm Hg, post-dialysis AP was 114.4 ± 24.4 and 71.3 ± 16.3 mm Hg, respectively. For ASPC, pre-dialysis and post-dialysis AP was statistically significantly higher than for the standard approach: 133.2 ± 21.3 and 79.3 ± 15.8 mm Hg (p <0.001; p = 0.009), 125.7 ± 23.9 and 75.9 ± 18.3 mm Hg (p <0.001; p <0.001). Detailed analysis of intra-dialysis AP measured during the standard approach showed that it was 110.2 ± 17.3 and 68.3 ± 13.9 mm Hg. Using ASPC, intra-dialysis AP was significantly higher: 124 ± 20.5 and 75.9 ± 14.2 mm Hg (p = 0.03; p = 0.02). Mean AP was also higher: 82.5 ± 13.9 mm Hgfor the standard approach versus 91.5 ± 15.6 mm Hg (p = 0.01) for ASPC. The ultrafiltration rates were slightly higher without ASPC (8.2 ml/kg/hour vs. 7.9 ml/kg/hour). Therefore, it was shown that the use of ASPC in addition to standard methods of hypotension correction is effective and safe. There weren»t any significant differences in «hemodialysis-dose effectiveness» (Kt/V) in both groups; however, in the ASPC group target values of inorganic phosphorus in serum (for a dialysis patient) were reached which is one of the most important parameters of hemodialysis adequacy. Concentration of inorganic phosphorus for the ultrafiltration control algorithm was 1.5 mmol/l, for the standard dialysis program — 1.8 mmol/l which shows benefits of ASPC. This data didn»t reach statistical significance (p = 0.07) which likely can be attributed to a low number of observations.Conclusion. Intra-dialysis hypotension with high ultrafiltration rates is a frequent and potentially dangerous complication of hemodialysis which negatively affects patients» long-term prognosis mainly due to an increase in cardiovascular morbidity and mortality. A new method for prevention and correction of hypotension using ASPC allows to decrease ultrafiltration rate on time preventing a hypotensive episode, decreasing its rates and improving attainment of AP target values (both pre- and post-dialysis) as well as intra-dialysis variation during dialysis procedure

A new approach in prevention and correction of intradialysis hypotension in patients on maintenance hemodialysis

The aim of the study was to evaluate the efficacy of various approaches to correcting and preventing hypotension episodes in patients on maintenance hemodialysis (HD).Material and methods. The study included 35 patients on maintenance hemodialysis in the Dialysis Center "MCHTP No. 1", which is a part of "B. Braun Avitum" network centers in the Russian Federation. All patients underwent an automatic blood pressure (BP) measurement using a machine-inbuilt option device for noninvasive blood pressure measurement. Prior to the study, all patients underwent a clinical test with a "dry weight" assessment and a bio-impedance analysis. The study had a cross-over design: first, all patients were treated using the standard methods for correcting hypotension episodes (at 4 initial procedures). Then, in the following 4 procedures, in addition to standard methods, a computer algorithm was used to automatically regulate the ultrafiltration (UF) rate: the automatic pressure monitoring system (biologic rr comfort) with continuous monitoring of blood pressure throughout the procedure; BP was recorded before and after the HD procedure, as well as at least once every 5 minutes during 3 initial procedures; and starting from the 4th procedure, the intervals were determined by the algorithm automatically. The average blood pressure values were analyzed during the dialysis procedures for the entire observation period. The duration of the study was 3 weeks for each patient.Results. The average predialysis blood pressures in the group with the standard approach to hemodynamic correction were 124.6 ± 27.7 and 74.5 ± 21.1 mm Hg, the postdialysis blood pressures were 114.4 ± 24.4 and 71.3 ± 16.3 mm Hg. With the use of automatic pressure monitoring system, the predialysis and postdialysis blood pressures were significantly higher than those with the standard approach: 133.2 ± 21.3 and 79.3 ± 15.8 mm Hg (p < 0.001 and p = 0.009), vs. 125.7 ± 23.9 and 75.9 ± 18.3 mm Hg (p < 0.001 and p < 0.001), respectively. Upon closer examination of the intradialysis pressure variations, the intradialysis blood pressures were 110.2 ± 17.3 and 68.3 ± 13.9 mm Hg when measured by using the standard approach, and significantly higher: 124 ± 20.5 and 75.9 ± 14.2 mm Hg when the automatic pressure monitoring system was used (p = 0.03; p = 0.02). Also, higher mean arterial pressures were noted: 82.5 ± 13.9 with the standard approach vs.91.5 ± 15.6 mm Hg (p = 0.01) with the automatic pressure monitoring system. Studying UF rates, we found that the UF rate was slightly higher without using the automatic pressure monitoring system (8.0 ml/kg/h vs. 7.9 ml/kg/h). Thus, the new approach used in addition to the standard methods of correcting hypotension was effective and safe. No significant differences were seen in Kt/V values. However, when automatic pressure monitoring system was used in patients, the target phosphate levels were achieved: the inorganic phosphorus value was 1.5 mmol/L when using the UF control algorithm vs. 1.8 mmol/L with a standard dialysis program. However, these data did not reach the statistical significance (p = 0.07).Conclusion. Intradialysis hypotension and high UF rates remain frequent and potentially dangerous complications of HD procedure, which worsen the long-term prognosis of patients on HD, mainly due to the increase in cardiovascular morbidity and mortality. The new approach to the prevention and correction of hypotension by using the automatic pressure monitoring system allows one to reduce the UF rate in a timely manner, preventing the development of hypotension episodes, reducing their rates, and improving the achievement of target blood pressure values, both preand postdialysis, as well as intradialysis blood pressure variations

ДОСЛІДЖЕННЯ РЕЖИМІВ ГАЛЬМУВАННЯ В СИСТЕМІ ІМПУЛЬСНОГО РЕГУЛЮВАННЯ СЕРІЄСНОГО ЕЛЕКТРОДВИГУНА

With the help of the developed simulation model, the electromechanics processes of electro drive breakingmode are probed.С помощью разработанной имитационной модели исследованы электромеханические процессытягового электропривода с сериесным электродвигателем в режиме рекуперативного торможения.За допомогою імітаційної моделі, що була розроблена, досліджено електромеханічні процеси тягового електроприводу з серієсним електродвигуном в режимі рекуперативного гальмування

ДОСЛІДЖЕННЯ РЕЖИМІВ ГАЛЬМУВАННЯ В СИСТЕМІ ІМПУЛЬСНОГО РЕГУЛЮВАННЯ СЕРІЄСНОГО ЕЛЕКТРОДВИГУНА

With the help of the developed simulation model, the electromechanics processes of electro drive breakingmode are probed.С помощью разработанной имитационной модели исследованы электромеханические процессытягового электропривода с сериесным электродвигателем в режиме рекуперативного торможения.За допомогою імітаційної моделі, що була розроблена, досліджено електромеханічні процеси тягового електроприводу з серієсним електродвигуном в режимі рекуперативного гальмування

ИССЛЕДОВАНИЕ РЕЖИМОВ ТОРМОЖЕНИЯ В СИСТЕМЕ ИМПУЛЬСНОГО РЕГУЛИРОВАНИЯ СЕРИЕСНОГО ЭЛЕКТРОДВИГАТЕЛЯ

С помощью разработанной имитационной модели исследованы электромеханические процессы тягового электропривода с сериесным электродвигателем в режиме рекуперативного торможения