ARGO: a web system for the detection of degenerate motifs and large-scale recognition of eukaryotic promoters

Reliable recognition of the promoters in eukaryotic genomes remains an open issue. This is largely owing to the poor understanding of the features of the structural–functional organization of the eukaryotic promoters essential for their function and recognition. However, it was demonstrated that detection of ensembles of regulatory signals characteristic of specific promoter groups increases the accuracy of promoter recognition and prediction of specific expression features of the queried genes. The ARGO_Motifs package was developed for the detection of sets of region-specific degenerate oligonucleotide motifs in the regulatory regions of the eukaryotic genes. The ARGO_Viewer package was developed for the recognition of tissue-specific gene promoters based on the presence and distribution of oligonucleotide motifs obtained by the ARGO_Motifs program. Analysis and recognition of tissue-specific promoters in five gene samples demonstrated high quality of promoter recognition. The public version of the ARGO system is available at and

Regulated expression of matrix metalloproteinases, inflammatory mediators, and endometrial matrix remodeling by 17beta-estradiol in the immature rat uterus

<p>Abstract</p> <p>Background</p> <p>Administration of a single physiological dose of 17beta-estradiol (E2:40 microg/kg) to the ovariectomized immature rat rapidly induces uterine growth and remodeling. The response is characterized by changes in endometrial stromal architecture during an inflammatory-like response that likely involves activated matrix-metalloproteinases (MMPs). While estrogen is known as an inducer of endometrial growth, its role in specific expression of MMP family members in vivo is poorly characterized. E2-induced changes in MMP-2, -3, -7, and -9 mRNA and protein expression were analyzed to survey regulation along an extended time course 0-72 hours post-treatment. Because E2 effects inflammatory-like changes that may alter MMP expression, we assessed changes in tissue levels of TNF-alpha and MCP-1, and we utilized dexamethasone (600 microg/kg) to better understand the role of inflammation on matrix remodeling.</p> <p>Methods</p> <p>Ovariectomized 21 day-old female Sprague-Dawley rats were administered E2 and uterine tissues were extracted and prepared for transmission electron microscopy (TEM), mRNA extraction and real-time RT-PCR, protein extraction and Western blot, or gelatin zymography. In inhibitor studies, pretreatment compounds were administered prior to E2 and tissues were harvested at 4 hours post-hormone challenge.</p> <p>Results</p> <p>Using a novel TEM method to quantitatively assess changes in stromal collagen density, we show that E2-induced matrix remodeling is rapid in onset (< 1 hour) and leads to a 70% reduction in collagen density by 4 hours. Matrix remodeling is MMP-dependent, as pretreatment with batimastat ablates the hormone effect. MMP-3, -7, and -9 and inflammatory markers (TNF-alpha and MCP-1) are transiently upregulated with peak expression at 4 hours post-E2 treatment. MMP-2 expression is increased by E2 but highest expression and activity occur later in the response (48 hours). Dexamethasone inhibits E2-modulated changes in collagen density and expression of MMPs although these effects are variable. Dexamethasone upregulates MMP-3 mRNA but not protein levels, inhibiting E2-induced upregulation of MMP-7, and -9, and MCP-1 mRNA and protein but not inhibiting the hormone-induced increase in TNF-alpha mRNA.</p> <p>Conclusion</p> <p>The data demonstrate that E2-regulated endometrial remodeling is rapid in onset (<1 hour) and peak expression of MMPs and inflammatory mediators correlates temporally with the period of lowest stromal collagen density during uterine tissue hypertrophy.</p

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Modeling the linear wear intensity with consideration of hardness and average pressure to friction surface

Разработаны математические модели для определения интенсивности линейного износа материалов с учетом твердости и среднего давления на поверхность трения. Проанализирована корректность модели определения среднего давления на поверхность трения за время эксперимента и его влияние на результат абразивного износа. Выполнено построение графика зависимости интенсивности линейного износа от среднего давления на поверхность трения и твердости испытуемых материалов. Полученная поверхность интенсивности линейного износа является геометрической моделью, позволяющей прогнозировать величину абразивного износа материалов.Mathematical model for determining the linear wear intensity with consideration of hardness and average pressure to friction surface has been designed. The correctness of method for determining the average pressure to friction surface during the experiment and its influence on the abrasive wear was analyzed. Graph of the linear wear intensity dependence on the average pressure on the friction surface and tested material hardness was plotted. The obtained surface of the linear wear intensity is the geometrical model which allows predicting the material abrasive wear quantity

Determination of the amount of abrasive particles on the friction surfage in the test by Brinell-Howart method

Розглянуто моделювання зношування металів при випробуваннях методом Бринелля-Ховарта з метою визначення кількості абразивних частинок у зоні стикання гумового диску та абразиву в кожен момент часу в залежності від розмірів абразивних частинок та гумового диску. Отримані результати дозволяють здійснити зменшення кількості випробувань при збереженні необхідної точності випробувань.The paper considers the method of testing for abrasive wear according to the Brinell-Howarth scheme with an indication of the structural elements of the installation, which may differ in size, surface geometry and materials. The quantitative rather than qualitative nature of the results of the method is noted, which does not allow the test results to be transferred to conditions other than standard. The tasks are formulated aimed at eliminating the main drawback of research: the lack of models of the studied processes and methods for determining the parameters of these models. Elimination of these disadvantages will allow to extend the research results to natural conditions different from the model ones. In this regard, the task of developing a theory of modeling abrasive wear of metals during tests by the Brinell-Howarth method was established. A mathematical model has been built for determining the amount of abrasive particles in the zone of interaction of a rubber disk and an abrasive at a given time, depending on the size of abrasive particles and a rubber disk. An important component of this work is the real consideration of the interaction of each spherical abrasive particle with a metal sample. Boundary conditions for the application of these models during testing by the Brinell-Howarth method are identified. This modeling is considered in the context with the subsequent de-velopment of this modeling technique. The work considers real processes associated with abrasive wear of materials during test-ing. The paper also considers the basis for the further construction of mathematical modeling of the process of abrasive wear of metals when tested by the Brinell-Howarth method. It is not the average statistical wear of metals that is studied, but the wear of each spherical abrasive particle with further summation of the wear values by weight

Modeling of metal wear process is not fixet abrasive

Экспериментально реализован метод испытаний на износ цилиндрических образцов, выполняющих вращательные движения вокруг оси в абразивной смеси. Разработана методика определения основных величин, участвующих в процессе абразивного изнашивания.Simulated wear process of cylindrical specimens, performing rotational movements around a common axis in the abrasive mixture. A method of determining basic quantities involved in the process of abrasive wear

An unconventional methot for approximating experimental dependences of abrasive wear

Розглядаються експериментальні залежності абразивного зносу поверхонь мідних та сталевих мате-ріалів нежорстко закріпленими абразивними частинками та пропонується нетрадиційний вдосконалений спосіб їх апроксимації підвищеної точності. Запропонований алгоритм знаходження оптимальної апрокси-муючої функції для процесів тертя та зношування дає можливість на ранніх стадіях обґрунтовано і най-більш точно прогнозувати термін зношування деталей або їх покриттів, а також призначати періоди проведення регламентних робіт.Experimental dependences of abrasive wear of a surface of copper and steel materials are considered by nonrigidly fixed abrasive particles and the nonconventional advanced way of their approximation of the increased accuracy is offered. All types of average sizes are involved in this method: arithmetic average; geometrical average; square average; average harmonious and so on. Basic components of analytical dependence of size of wear in the form of the table of the main functions of which the approximating function is formed are considered. The basic rules of application of the algorithm on a concrete example of de-pendence of wear of a surface of steel and copper materials are specified by nonrigidly fixed abrasive particles. The offered algorithm of finding of the optimum approximating function allows automation of the search by means of com-puter programming and gives the chance at early stages is proved and most precisely to predict the term of wear of details or their coverings and also to appoint the periods of carrying out scheduled works. Forecasting of terms of wear of details of cars plays a key role in safety and efficiency of use of civil and military equip-ment. The considered technique will play an essential role in increase in production efficiency

Determining the components of Lagrange's equation which describes the cylinder and plane interaction

В роботі розроблена методика визначення компонент рівняння Лагранжа для процесів механічної взаємодії контактуючих тіл циліндричної та плоскої форми. Знайдений розподіл навантаження вздовж дуги нормального до осі перерізу циліндра площиною. Складене рівняння Лагранжа для розглянутої взаємодії з урахуванням неголономної в’язі.Method of determining Lagrange’s equation components for mechanical interaction of contacting bodies with cylindrical and plane shape. In this paper there was found the load distribution along the arc of section normal to axis and formed by cylinder and plane Lagrange’s equation for considered interaction was obtained taking into account nonholonomic connections