Direct Ascription of Missing Categorical Values in Survey Research Data

The complete datasets are a prerequisite for sustainable analyses, robust an- alytics and unbiased interpretation of results. Missing values in a survey occur when no data value is stored for the variable in an observation. Missing data can have a significant effect on the conclusions that can be drawn from the data. Direct ascription is the process of replacing missing data with predicted values. The aim of this work is to describe an approach to direct ascription of missing categorical values in survey research data based both on the assumption that values in a data set are missing at random and on the implementation of the correspondence analysis

MicroRNA-1-Mediated Inhibition of Cardiac Fibroblast Proliferation Through Targeting Cyclin D2 and CDK6

MicroRNA-1 (miRNA-1) has been long viewed as a muscle-specific miRNA and plays a critical role in myocardium and cardiomyocytes by controlling myocyte growth and rhythm. We identified that miRNA-1 is expressed in cardiac fibroblasts, which are one of the major non-muscle cell types in myocardium and are responsible for cardiac fibrosis in pathological conditions. In this study, we aimed to investigate the effect and mechanism of action of miRNA-1 on cardiac fibroblast proliferation. Subcutaneous angiotensin II (Ang II) infusion via osmotic minipumps for 4 weeks was used to induce myocardial interstitial fibrosis in male Sprague-Dawley rats. MiRNA-1 expression was significantly down-regulated by 68% in freshly isolated ventricular fibroblasts from Ang II-infused rats than that from control rats. Similar results were obtained in adult rat ventricular fibroblasts that were stimulated in culture by Ang II or TGFβ for 48 h. Functionally, overexpression of miRNA-1 inhibited fibroblast proliferation, whereas knockdown of endogenous miRNA-1 increased fibroblast proliferation. We then identified and validated cyclin D2 and cyclin-dependent kinase 6 (CDK6) as direct targets of miRNA-1 in cardiac fibroblasts using biochemical assays. Moreover, we showed that the inhibitory effects of miRNA-1 on cardiac fibroblast proliferation can be blunted by overexpression of its target, cyclin D2. In conclusion, our findings demonstrate miRNA-1 expression and regulation in adult ventricular fibroblasts, where it acts as a novel negative regulator of adult cardiac fibroblast proliferation that is at least partially mediated by direct targeting of two cell cycle regulators. Our results expand the understanding of the regulatory roles of miRNA-1 in cardiac cells (i.e., from myocytes to a major non-muscle cells in the heart)

Numerical Analysis of Fluid Particles Motion in Curved Ducts

The developed mathematical model allows determining the fields of speeds and pressure, when viscous incompressible fluid flows in 2-dimensional variable cross-section ducts at laminar flow mode. The dynamics of the condensed moisture is determined by the differential equation of the motion amount for the particle. Solving the equation the trajectories of the moisture drops motion and its speed in continuous medium flow

Balancing Specificity and Promiscuity in Enzyme Evolution: Multidimensional Activity Transitions in the Alkaline Phosphatase Superfamily

Highly proficient, promiscuous enzymes can be springboards for functional evolution, able to avoid loss of function during adaptation by their capacity to promote multiple reactions. We employ systematic comparative study of structure, sequence and substrate specificity to track the evolution of specificity and reactivity between promiscuous members of clades of the alkaline phosphatase (AP) superfamily. Construction of a phylogenetic tree of protein sequences maps out the likely transition zone between arylsulfatases (ASs) and phosphonate monoester hydrolases (PMHs). Kinetic analysis shows that all enzymes characterized have four chemically distinct phospho- and sulfoesterase activities, with rate accelerations ranging from 1011-1017-fold for their primary and 109-1012-fold for their promiscuous reactions, suggesting that catalytic promiscuity is widespread in the AP-superfamily. This functional characterization and crystallography reveal a novel class of ASs that is so similar in sequence to known PMHs that it had not been recognized as having diverged in function. Based on analysis of snapshots of catalytic promiscuity ‘in transition’ we develop possible models that would allow functional evolution and determine scenarios for trade-off between multiple activities. For the new ASs we observe largely invariant substrate specificity that would facilitate the transition from ASs to PMHs via trade-off-free molecular exaptation, i.e. evolution without initial loss of primary activity and specificity toward the original substrate. This ability to bypass low activity generalists provides a molecular solution to avoid adaptive conflict.BBSR

Magnetic and quadrupolar order in a one-dimensional ferromagnet with cubic crystal-field anisotropy

The zero temperature phase diagram of a one-dimensional S=2 Heisenberg ferromagnet with single-ion cubic anisotropy is studied numerically using the density-matrix renormalization group method. Evidence is found that although the model does not involve quadrupolar couplings, there is a purely quadrupolar phase for large values of the anisotropy. The phase transition between the magnetic and quadrupolar phases is continuous and it seems to be characterized by Ising critical exponents.Comment: 11 pages, 7 figures, REVTeX, accepted in Phys. Rev. B (scheduled on June 99

ФАКТОРЫ ЭФФЕКТИВНОСТИ ЛЕЧЕНИЯ НЕОПЕРАБЕЛЬНОГО НЕМЕЛКОКЛЕТОЧНОГО РАКА ЛЕГКОГО III СТАДИИ (ОБЗОР ЛИТЕРАТУРЫ)

In this review, the latest data on factors influencing efficiency of the treatment of locally advanced inoperable stage III non-small cell lung cancer (NSCLC) are analyzed. Concomitant chemoradiotherapy (CRT) is a current standard of treatment with the 5-year overall survival rate of 20–30 % and median survival time of 17–28 months. However, only a small proportion of patients (13–35 % by the data from population-based studies) can receive CRT. Radiotherapy is currently progressing towards new approaches, including IMRT and IGRT, showing promising results, however, these approaches are still experimental. Accelerated repopulation of clonogens is biological factor necessitating intensification of both RT and chemotherapy. For RT, accelerated hyperfractionation is an optimal way for that. There is some data evidencing negative role of delays in the radiation treatment to overall efficacy and even survival. Therefore, the optimal approach to the treatment of Stage III NSCLC seems to be early beginning of RT and short overall time for both RT and chemotherapy.В обзоре представлены современные данные об эффективности консервативного лечения неоперабельного местнораспространенного немелкоклеточного рака легкого и факторах, способных на нее влиять. Совместное использование ЛТ и ХТ в настоящее время является общепризнанным подходом с пятилетней выживаемостью 20–30 % и медианой выживаемости от 17 до 28 мес, при этом, по данным метаанализов, только одновременная ХЛТ дает преимущество в выживаемости перед ЛТ. Однако в практике значительная часть больных не получает химиотерапию даже в последовательном режиме. По данным популяционных исследований, радикальное химиолучевое лечение получают 13–35 % больных. Лучевая терапия совершенствуется, опубликованы перспективные данные о результатах использования методов IMRT, IGRT, изотоксической эскалации дозы, но эти подходы остаются экспериментальными. Риск ускоренной репопуляции клоногенов при НМРЛ диктует необходимость интенсификации лечения, сокращение его общего времени. Схемы ускоренного гиперфракционирования представляются наиболее оптимальным путем к достижению этой цели. Данные ряда экспериментальных и клинических исследований также свидетельствуют о негативной роли задержек во времени начала любого лечения, а особенно лучевого. Оптимальной тактикой лечения НМРЛ III стадии представляется раннее начало ЛТ и короткая ее продолжительность

4EHP and GIGYF1/2 mediate translation-coupled messenger RNA decay

Current models of mRNA turnover indicate that cytoplasmic degradation is coupled with translation. However, our understanding of the molecular events that coordinate ribosome transit with the mRNA decay machinery is still limited. Here, we show that 4EHP-GIGYF1/2 complexes trigger co-translational mRNA decay. Human cells lacking these proteins accumulate mRNAs with prominent ribosome pausing. They include, among others, transcripts encoding secretory and membrane-bound proteins or tubulin subunits. In addition, 4EHP-GIGYF1/2 complexes fail to reduce mRNA levels in the absence of ribosome stalling or upon disruption of their interaction with the cap structure, DDX6, and ZNF598. We further find that co-translational binding of GIGYF1/2 to the mRNA marks transcripts with perturbed elongation to decay. Our studies reveal how a repressor complex linked to neurological disorders minimizes the protein output of a subset of mRNAs

Quantum phase transitions and thermodynamic properties in highly anisotropic magnets

The systems exhibiting quantum phase transitions (QPT) are investigated within the Ising model in the transverse field and Heisenberg model with easy-plane single-site anisotropy. Near QPT a correspondence between parameters of these models and of quantum phi^4 model is established. A scaling analysis is performed for the ground-state properties. The influence of the external longitudinal magnetic field on the ground-state properties is investigated, and the corresponding magnetic susceptibility is calculated. Finite-temperature properties are considered with the use of the scaling analysis for the effective classical model proposed by Sachdev. Analytical results for the ordering temperature and temperature dependences of the magnetization and energy gap are obtained in the case of a small ground-state moment. The forms of dependences of observable quantities on the bare splitting (or magnetic field) and renormalized splitting turn out to be different. A comparison with numerical calculations and experimental data on systems demonstrating magnetic and structural transitions (e.g., into singlet state) is performed.Comment: 46 pages, RevTeX, 6 figure

RNF219 attenuates global mRNA decay through inhibition of CCR4-NOT complex-mediated deadenylation

The CCR4-NOT complex acts as a central player in the control of mRNA turnover and mediates accelerated mRNA degradation upon HDAC inhibition. Here, we explored acetylation-induced changes in the composition of the CCR4-NOT complex by purification of the endogenously tagged scaffold subunit NOT1 and identified RNF219 as an acetylation-regulated cofactor. We demonstrate that RNF219 is an active RING-type E3 ligase which stably associates with CCR4-NOT via NOT9 through a short linear motif (SLiM) embedded within the C-terminal low-complexity region of RNF219. By using a reconstituted six-subunit human CCR4-NOT complex, we demonstrate that RNF219 inhibits deadenylation through the direct interaction of the α-helical SLiM with the NOT9 module. Transcriptome-wide mRNA half-life measurements reveal that RNF219 attenuates global mRNA turnover in cells, with differential requirement of its RING domain. Our results establish RNF219 as an inhibitor of CCR4-NOT-mediated deadenylation, whose loss upon HDAC inhibition contributes to accelerated mRNA turnover

Выживаемость больных раком ободочной кишки после радикальных операций, выполненных в медицинских организациях Архангельской области: популяционный анализ по данным регистра рака

Background. surgery is the main method of treatment of colon cancer (cc). Radical surgery performed in non-specialized hospitals can lead to the adverse outcomes.The aim of this study was to assess CC survival after radical surgery performed in state hospitals of the arkhangelsk region (North-West Russia) in 2010–21.Material and Methods. data on all the 2142 cases of radical surgery of CC were obtained from the arkhangelsk regional cancer registry (ARCR). One- and five-year cancer-specific survival rates were estimated by the survival tables; cumulative survival function was calculated by the Kaplan–meier method. Univariate and multiple cox regression analysis was carried out to identify independent predictors associated with CC death risk after radical surgery in state hospitals (incl. sex, age at the time of diagnosis, topography, morphology and stage of CC).Results. less than half (42.8 %) of patients underwent surgery at the arkhangelsk clinical cancer center (accc), a single specialized hospital. one- and five-year survival rates of all patients were 86.5 % (95 % CI: 84.9–87.9 %) and 65.1 % (95 % ci: 62.7–67.4 %), respectively. The 5-year survival rate of patients who underwent surgery in the accc was significantly higher than that in patients who underwent surgery in other state non-specialized hospitals (76.0 % (95 % ci: 72.5–79.0 % versus 49.3–73.8 %, p<0.0001). The relative risk of death of CC patients depended on the state hospital where radical surgery was performed and the stage of CC; it did not depend on patients’ sex, morphology and topography of CC.Conclusion. our results demonstrate the need to search for specific reasons for the relatively low survival in patients after radical surgery performed in non-specialized hospitals.Актуальность. Хирургическое вмешательство является основным методом радикального лечения больных раком ободочной кишки (РОК). Выполнение радикальных хирургических операций в неспециализированных государственных медицинских организациях (ГМО) может оказывать неблагоприятное влияние на исход.Цель исследования – по данным Архангельского областного канцер-регистра (АОКР) оценить выживаемость больных РОК после радикального хирургического лечения в ГМО Архангельской области в 2010–21 гг.Материал и методы. Из базы данных АОКР извлечены записи о 2142 случаях радикального хирургического лечения РОК. Одно- и пятилетняя опухолеспецифическая выживаемость (ОСВ) пациентов оценена по таблицам дожития; кумулятивная функция выживаемости (КФВ) рассчитана методом Каплана–Мейера. В серии процедур одно- и многофакторного регрессионного анализа Кокса рассчитаны значения коэффициента относительного риска (ОР) смерти пациентов от РОК, оперированных в ГМО региона, в зависимости от величин факторов прогноза (пол, возраст на момент постановки диагноза, топография, морфология, стадия).Результаты. Менее половины (42,8 %) пациентов получили хирургическое лечение РОК в Архангельском клиническом онкологическом диспансере (АКОД) – профильной медицинской организации. Одно- и 5-летняя ОСВ всех пациентов составила 86,5 % (95 % ДИ: 84,9–87,9 %) и 65,1 % (95 % ДИ: 62,7–67,4 %) соответственно. Уровень пятилетней ОСВ пациентов, оперированных в АКОД, составил 76,0 % (95 % ДИ: 72,5–79,0 %), а оперированных в иных медицинских организациях варьировал в диапазоне 49,3–73,8 % и был значимо ниже, чем в АКОД (р<0,0001). В многофакторной модели риск смерти зависел от ГМО, где было выполнено хирургическое вмешательство, и стадии заболевания; не зависело от пола больных, морфологии и топографии новообразования.Заключение. Результаты исследования определяют необходимость поиска специфических причин относительно низкой ОСВ пациентов после хирургического лечения РОК, выполненного в непрофильных ГМО