Synthesis of nitroxyl radical by direct nucleophilic functionalization of a C-H bond in the azadiene systems

Cyclic dinitrones underwent nucleophilic substitution of the hydrogen atom in the reaction with a paramagnetic carbanion, the lithium derivative of 4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazol-1-oxyl 3-oxide, to give polyfunctional nitronyl nitroxyls. © 2012 Springer Science+Business Media New York

Genome-wide de Novo Prediction of Proximal and Distal Tissue-Specific Enhancers

Determining how transcriptional regulatory networks are encoded in the human genome is essential for understanding how cellular processes are directed. Here, we present a novel approach for systematically predicting tissue specific regulatory elements (REs) that blends genome-wide expression profiling, vertebrate genome comparisons, and pattern analysis of transcription factor binding sites. This analysis yields 4,670 candidate REs in the human genome with distinct tissue specificities, the majority of which reside far away from transcription start sites. We identify key transcription factors (TFs) for 34 distinct tissues and demonstrate that tissue-specific gene expression relies on multiple regulatory pathways employing similar, but different cohorts of interacting TFs. The methods and results we describe provide a global view of tissue specific gene regulation in humans, and propose a strategy for deciphering the transcriptional regulatory code in eukaryotes

New approach to synthesis of nitronyl and imino nitroxides based on SNH methodology

It is shown that SN H approach opens new possibilities in the synthesis of polyfunctional nitronyl and imino nitroxides. It is found that the interaction of 4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazol-3-oxide-1- oxyl lithium salt Li1 with 3,6-diaryl-1,2,4-triazines leads to formation of the corresponding triazines bearing nitronyl nitroxide or imino nitroxide substituent at position 5 of the heterocycle. The reaction of Li1 with pyridazine-N-oxide gives rise to nitroxide with buten-3-ynyl substituent 5. Spin-labeled 5 could be readily transformed by the use of 1,3-dipolar and nucleophilic addition reactions, as well as oxidative coupling, that gives a large group of new paramagnets: 2-(1H-pyrazol-5-yl)vinyl-, 2-ethynylcyclopropyl- , 2-(3-(ethoxycarbonyl) isoxazol-5-yl)vinyl-, 1-(pyrrolidin-1-yl)but-3-ynyl- substituted nitronyl nitroxide and a diradical - 2,2′-((1E,7E)-octa-1,7- dien-3,5-diyne-1,8-diyl)bis(4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazol-3-oxide- 1-oxyl). The new nitroxides were characterized by X-ray single crystal data, ESR and static magnetic susceptibility measurements. © ARKAT USA, Inc

SILICON MONOCRYSTALS FOR ALTERNATIVE ENERGY

This paper considers features of the formation and microstructure revealing of profound n- and p-type silicon monocrystals. Influence of hole and electron conductivity in semiconductors on the pattern of anodic etching is determined. Correlation among silicon microstructure, dislocation density and minority carriers’ lifetime has been studied. Influence of impurity diffusion from the surface into the space of the crystal on electrical properties’ changes of the semiconductor is shown

Роль факультетской терапевтической клиники Московской медицинской академии им. И.М.Сеченова в развитии отечественной пульмонологии

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WHAT RESULTS IN TENDON AND MUSCLE TISSUES OF THE ROTATOR CUFF FROM FULL-THICKNESS TEARS: DATA OF MRI, ARTHROSCOPY AND HISTOLOGY

Full-thickness rotator cuff tears - is abundant injury which leads to the expressed pain syndrome and functional violation of the top extremity. At making decision about necessary of surgery, MRI is the important source of information about the injury The purpose: to determine the qualitative and quantitative indicators of degenerative-dystrophic changes in muscular and tendinous parts of the rotator cuff. based on a combined MRI, arthroscopic and histological diagnostics of full-thickness rupture of shoulder cuff Methods: We have examined 28 patients with full-thickness rotator cuff tears. MRI of damaged joint to all patients before an operation was performed. Thereafter an arthroscopy was performed and intraoperative biopsy of the muscular and tendinous parts of the rotator cuff, with following histological examination. Results: It was found that at small full-thickness rotator cuff tears the intensity of degenerative changes in muscular and tendinous tissue was lower, so these tears are the most promising for all kinds of treatment. At medium and big tears intensity of degenerative changes in the tissues begins to prevail over productive inflammation and it limits to the ability of conservative treatment and increases the risk of unsuccessful outcomes of arthroscopic reconstruction. Conclusions: In this regard, it is necessary to search biological decisions, which complement the stage of arthroscopic reconstruction of the rotator cuff

Phase field modelling voids nucleation and growth in binary systems

We present a comprehensive study of voids formation, nucleation and growth in a prototype model of binary alloys subjected to irradiation by using a combined approach based on phase field and rate theories. It is shown that voids formation is caused by interaction of irradiation-produced vacancies through elastic deformation of a lattice and vacancy coupling with composition field of the alloy. Phase diagrams illustrating the formation of states related to solid solution, phase decomposition, and patterning are obtained. Formation of voids from supersaturated ensemble of vacancies is accompanied by composition rearrangement of alloy components. It was found that elastic inhomogeneity leading to the formation of anisotropic precipitates in an initially prepared binary alloy results in the formation of a void super-lattice under irradiation. It was shown that voids nucleate and grow with dose according to diffusion controlled precipitation processes, where universal dynamics of voids growth is revealed. Estimations of main quantitative and statistical characteristics of voids by using material parameters relevant to most of alloys and steels give good agreement with experimental observations.Comment: 21 pages, 10 figure

Селективные β-адреноблокаторы (небиволол и метопролола сукцинат) в терапии больных артериальной гипертонией и / или ишемической болезнью сердца в сочетании с бронхообструктивным синдромом: оценка эффективности и безопасности

The aim of study was to assess safety and efficacy of cardioselective beta-blockers (nebivolol and metoprolol succinate) in patients with hypertension (H) and/or ischaemic heart disease (IHD) and concomitant bronchoobstructive syndrome. The study involved 50 patients with H and/or IHD and concomitant bronchoobstructive syndrome (as a sign of stable COPD and/or asthma of any severity) and a need in β-blockers. Safety of the treatment was evaluated using respiratory symptoms and bronchial obstruction. Antihypertensive effect of β-blockers was assessed by 24-h blood pressure monitoring, antianginal effect was assessed by clinical signs, dose of nitrates, exercise tolerance (6-minute walking test), and Holter ECGmonitoring. Antiarrhythmic effect of β-blockers was evaluated by ECG monitoring. In patients with COPD or asthma, no deterioration in bronchial obstruction was found during treatment with nebivolol (FEV1 , 71.12 ± 19.95 % at the baseline and 73.19 ± 21.70 % at the end of the study) or metoprolol succinate (FEV1 , 81.08 ± 22.57 % and 84.58 ± 23.72 %, respectively). High antihypertensive efficacy of β-blockers was seen during the therapy while being a part of combined antihypertensive therapy or as a single-drug therapy. Both drugs significantly decreased systolic and diastolic blood pressure and reduced frequency and severity of angina attacks. Need in nitrates greatly decreased and exercise tolerance significantly increased in the patients. Antiarrhythmic effect of β-blockers was good. Both nebivolol and metoprolol succinate significantly decreased the heart rate. Thus, the study demonstrated safety of nebivolol and metoprolol succinate in patients with H and/or IHD and concomitant bronchoobstructive syndrome needed in administration of β-blockers. The drugs were also safe in patients with severe COPD or asthma and in exacerbations of the diseases not caused by β-blockers.Проведено исследование безопасности и эффективности применения селективных β-адреноблокаторов (небиволола и метопролола сукцината) у больных с артериальной гипертонией (АГ) и / или ишемической болезнью сердца (ИБС) в сочетании с бронхообструктивным синдромом. В исследовании участвовали 50 пациентов, страдающих АГ и / или ИБС и сопутствующим бронхообструктивным синдромом на фоне хронической обструктивной болезни легких (ХОБЛ) и / или бронхиальной астмы (БА) любой степени тяжести в состоянии ремиссии и нуждающихся в применении β-адреноблокаторов. Безопасность применения β-адреноблокаторов оценивалась по динамике респираторных симптомов и изменению бронхиальной проходимости (данные клинического и инструментального обследования), антигипертензивный эффект β-адреноблокаторов – по данным суточного мониторирования артериального давления (СМАД), антиангинальный – по динамике клинических проявлений, количеству принимаемых нитратов и толерантности к физической нагрузке (тест с 6-минутной ходьбой), ЭКГ-мониторированию по Холтеру (по его результатам оценивался также антиаритмический эффект β-адреноблокаторов). В результате проведенного исследования не отмечено ухудшение бронхиальной проходимости вследствие приема небиволола (исходно объем форсированного выдоха за 1-ю с (ОФВ1 ) – 71,12 ± 19,95 %, в конце периода наблюдения ОФВ1 – 73,19 ± 21,70 %) и метопролола сукцината (исходно ОФВ1 – 81,08 ± 22,57 %, в конце периода наблюдения ОФВ1 – 84,58 ± 23,72 %) у пациентов с ХОБЛ и / или БА. Отмечена хорошая антигипертензивная эффективность небиволола и метопролола сукцината в составе комплексной антигипертензивной терапии и в качестве монотерапии: препараты достоверно снижали систолическое и диастолическое АД. Существенно снизились частота и выраженность приступов стенокардии, потребность в приеме нитратов. Достоверно увеличилась переносимость физической нагрузки. Отмечена хорошая урежающая и антиаритмическая эффективность небиволола и метопролола сукцината. Таким образом, проведенное исследование показало безопасность применения небиволола и метопролола сукцината у пациентов с бронхообструктивным синдромом и АГ и / или ИБС при наличии показаний со стороны сердечно-сосудистой системы, а также возможность применения этих препаратов у пациентов с тяжелыми формами ХОБЛ и БА и в период обострения данных заболеваний, не связанный с применением β-адреноблокатора