Organization of innovative project management on the base of multimode modeling of probabilities mixture of labor processes

© 2014, Mediterranean Center of Social and Educational Research. All rights reserved. In this study we suggest an approach to the organization of innovative projects management based on multimode modeling of probabilities mixture of labor processes. The proposed model allows managers to optimize the control actions influence on separate labor processes for achieving the innovative project result in the minimum time. Organization of management on the basis of the proposed model minimizes the risks of management bureaucracy and labor processes uncontrollability

Mechanism of Oxygen Activation in Hydroxylation Reactions Involving Cytochrome P450

In the 20-37 °c range the kinetics of cyclohexene epoxidation, naphthalene and cyclohexane hydroxylation and oxidative demethylation of a group of amines in the presence of rat liver microsomes, NADPH and 0 2 has been studied

ПЕПТИДНЫЙ ФАГОВЫЙ ДИСПЛЕЙ В СКРИНИНГЕ ПЕПТИДОМИМЕТИКОВ ТРОМБОКСАН СИНТАЗЫ

In order to identify potential inhibitors and modulators of thromboxane synthase, its molecular cloning, heterologous expression, isolation, and purification have been carried out. The recombinant protein is isolated in the homogenous state and possesses the functional activity. Peptide with an amino acids sequence SGVYKVLYDWQHGGF is identified using the random dodecapeptides phage library. It is revealed that this peptide has a great similarity to thrombopoietin peptidomimetic. This allows one to suppose the role of this hormone in the thromboxane synthase regulation.С целью поиска ингибиторов и модуляторов активности тромбоксан синтазы проведена гетерологическая экспрессия, выделение и очистка тромбоксан синтазы человека. Рекомбинантный белок получен в гомогенном состоянии и обладает функциональной активностью. С использованием фаговой библиотеки рандомизированных додекапептидов идентифицирован пептид с аминокислотной последовательностью SGVYKVLYDWQHGGF, обладающий высоким сродством к белку. Показано высокое сходство его последовательности с последовательностью пептидомиметика тромбопоэтина, что позволяет предположить роль этого гормона в регуляции активности тромбоксан синтазы

ФАГОВЫЙ ДИСПЛЕЙ В КОНСТРУИРОВАНИИ АНТИТЕЛ С ЗАДАННЫМИ СВОЙСТВАМИ

Antibodies are an essential tool being a part of immunodiagnostics, therapeutics and life science research instruments. In this paper we analyze the recent developments in recombinant antibodies generation by means of phage display technology. We also provide our own results dedicated to antibodies development process. Analysis of antibody-antigen complexes with resolved structures allow to create synthetic phage display library of Fab antibody fragments with the diversity of 1010 independent clones. Utilizing a negative selection approach, we succeeded in generation and characterization of specific single-domain antibodies that has substantially different binding kinetics to CYP11B2 and CYP11B1 isoenzymes – proteins with 93% sequence identity. We also generated specific binders to a few high-molecular weight human antigens – erytropoetin, growth hormone and thyroperoxidase.Уникальная особенность моноклональных антител высокоспецифично взаимодействовать с молекулярными мишенями позволила им занять ведущее положение в терапии онкологических и аутоиммунных заболеваний, стать незаменимым инструментом протеомных исследований и компонентом диагностических систем. Представлен обзор новейших литературных данных по использованию метода фагового дисплея для получения рекомбинантных антител, которые другими методами получить невозможно, а также собственные оригинальные результаты в этой области. На основании бионформационного анализа структур депонированных комплексов антител с антигенами нами создана комбинаторная библиотеки Fab фрагментов антител человека, обладающая разнообразием более 1010 независимых клонов и способная служить источником рекомбинантных антител. С использованием негативной селекции нами получены и характеризованы высокоспецифичные однодоменные антитела к альдостерон-синтазе (цитохром Р45011В2, CYP11B2), не обладающие в ИФА кросс-реактивностью с ее гомологом CYP11B1 (93% идентичности последовательностей), а также антитела к таким высокомолекулярным мишеням, как эритропоэтин, соматотропный гормон и тиреопероксидаза человека.

Altermagnetic lifting of Kramers spin degeneracy

Lifted Kramers spin-degeneracy has been among the central topics of condensed-matter physics since the dawn of the band theory of solids. It underpins established practical applications as well as current frontier research, ranging from magnetic-memory technology to topological quantum matter. Traditionally, lifted Kramers spin-degeneracy has been considered to originate from two possible internal symmetry-breaking mechanisms. The first one refers to time-reversal symmetry breaking by magnetization of ferromagnets, and tends to be strong due to the non-relativistic exchange-coupling origin. The second mechanism applies to crystals with broken inversion symmetry, and tends to be comparatively weaker as it originates from the relativistic spin-orbit coupling. A recent theory work based on spin-symmetry classification has identified an unconventional magnetic phase, dubbed altermagnetic, that allows for lifting the Kramers spin degeneracy without net magnetization and inversion-symmetry breaking. Here we provide the confirmation using photoemission spectroscopy and ab initio calculations. We identify two distinct unconventional mechanisms of lifted Kramers spin degeneracy generated by the altermagnetic phase of centrosymmetric MnTe with vanishing net magnetization. Our observation of the altermagnetic lifting of the Kramers spin degeneracy can have broad consequences in magnetism. It motivates exploration and exploitation of the unconventional nature of this magnetic phase in an extended family of materials, ranging from insulators and semiconductors to metals and superconductors, that have been either identified recently or perceived for many decades as conventional antiferromagnets

Структура и функции ароматазы и ее нестероидные ингибиторы

The analysis of the structure and function of aromatase (SYP19) - enzyme from the family of cytochrome P-450 that catalyzes the aromatization of six-membered ring A of the steroidal skeleton, namely transformation of androgens into estrogens peripheral and tumor tissues in the body, has been performed, and data in its non-steroidal inhibitors have been summarized.Проведен анализ структуры и функции ароматазы (СYP19) - фермента семейства цитохромов Р-450, кодируемого расположенным на коротком плече 15-й хромосомы (локус 15q21) геном CYP19A1, катализирующего ароматизацию шестичленного цикла А стероидного скелета и обуславливающего метаболизм стероидных гормонов, а именно трансформацию андрогенов в эстрогены периферическими и опухолевыми тканями организма. Обобщены данные по ее нестероидным ингибиторам. Обсуждены особенности первичной и пространственной структуры СYP19, обуславливающие взаимодействие с мембраной клетки и субстратом, обеспечивающие транспорт последнего между липидным бислоем мембраны и активным центром фермента. Показано, что наиболее эффективными ингибиторами СYP19 в настоящее время являются соединения, содержащие в составе молекулы азольные и азиновые гетероциклические фрагменты

Разработка мультиплексной системы для определения 11 генетических маркеров предрасположенности к развитию ожирения

A system has been developed to identify 11 genetic markers associated with the risk of obesity: rs10852521, rs11075990, rs1121980, rs1421085, rs1477196, rs17817449, rs3751812, rs7206790, rs8047395, rs9940128 (FTO gene) and rs1137101 (LEPR gene) by minisequencing (SNaPshot analysis). The conditions for carrying out the amplification and minisequencing reactions, as well as the compositions of the reaction mixtures, were optimized so that the analysis was carried out for all 11 markers simultaneously. The resulting system was tested and showed a high degree of reproducibility and sensitivity required for the detection of these polymorphisms.С помощью метода минисеквенирования (SNaPshot анализ) разработана система для определения 11 генетических маркеров, связанных с риском развития ожирения: rs10852521, rs11075990, rs1121980, rs1421085, rs1477196, rs17817449, rs3751812, rs7206790, rs8047395, rs9940128 (ген FTO) и rs1137101 (ген LEPR). Условия проведения реакций амплификации и минисеквенирования, а также составы реакционных смесей оптимизированы так, чтобы проводить анализ по всем 11 маркерам одновременно. Полученная система апробирована и показала высокую степень воспроизводимости и чувствительности, необходимой для определения данных полиморфных вариантов

Altermagnetic lifting of Kramers spin degeneracy

Lifted Kramers spin degeneracy (LKSD) has been among the central topics of condensed-matter physics since the dawn of the band theory of solids1,2. It underpins established practical applications as well as current frontier research, ranging from magnetic-memory technology3–7 to topological quantum matter8–14. Traditionally, LKSD has been considered to originate from two possible internal symmetry-breaking mechanisms. The first refers to time-reversal symmetry breaking by magnetization of ferromagnets and tends to be strong because of the non-relativistic exchange origin15. The second applies to crystals with broken inversion symmetry and tends to be comparatively weaker, as it originates from the relativistic spin–orbit coupling (SOC)16–19. A recent theory work based on spin-symmetry classification has identified an unconventional magnetic phase, dubbed altermagnetic20,21, that allows for LKSD without net magnetization and inversion-symmetry breaking. Here we provide the confirmation using photoemission spectroscopy and ab initio calculations. We identify two distinct unconventional mechanisms of LKSD generated by the altermagnetic phase of centrosymmetric MnTe with vanishing net magnetization20–23. Our observation of the altermagnetic LKSD can have broad consequences in magnetism. It motivates exploration and exploitation of the unconventional nature of this magnetic phase in an extended family of materials, ranging from insulators and semiconductors to metals and superconductors20,21, that have been either identified recently or perceived for many decades as conventional antiferromagnets21,24,25

Endocrinologic, neurologic, and visual morbidity after treatment for craniopharyngioma

Craniopharyngiomas are locally aggressive tumors which typically are focused in the sellar and suprasellar region near a number of critical neural and vascular structures mediating endocrinologic, behavioral, and visual functions. The present study aims to summarize and compare the published literature regarding morbidity resulting from treatment of craniopharyngioma. We performed a comprehensive search of the published English language literature to identify studies publishing outcome data of patients undergoing surgery for craniopharyngioma. Comparisons of the rates of endocrine, vascular, neurological, and visual complications were performed using Pearson’s chi-squared test, and covariates of interest were fitted into a multivariate logistic regression model. In our data set, 540 patients underwent surgical resection of their tumor. 138 patients received biopsy alone followed by some form of radiotherapy. Mean overall follow-up for all patients in these studies was 54 ± 1.8 months. The overall rate of new endocrinopathy for all patients undergoing surgical resection of their mass was 37% (95% CI = 33–41). Patients receiving GTR had over 2.5 times the rate of developing at least one endocrinopathy compared to patients receiving STR alone or STR + XRT (52 vs. 19 vs. 20%, χ2P < 0.00001). On multivariate analysis, GTR conferred a significant increase in the risk of endocrinopathy compared to STR + XRT (OR = 3.45, 95% CI = 2.05–5.81, P < 0.00001), after controlling for study size and the presence of significant hypothalamic involvement. There was a statistical trend towards worse visual outcomes in patients receiving XRT after STR compared to GTR or STR alone (GTR = 3.5% vs. STR 2.1% vs. STR + XRT 6.4%, P = 0.11). Given the difficulty in obtaining class 1 data regarding the treatment of this tumor, this study can serve as an estimate of expected outcomes for these patients, and guide decision making until these data are available