Created-by-current states in long Josephson junctions

Critical curves "critical current - external magnetic field" of long Josephson junctions with inhomogeneity and variable width are studied. We demonstrate the existence of the regions of magnetic field where some fluxon states are stable only, if the external current through the junction is different from zero. Position and size of such regions depend on length of the junction, its geometry, parameters of inhomogeneity and form of the junction. The noncentral (left and right) pure fluxon states are appeared in the inhomogeneous Josephson junction with increase in the junction length. We demonstrate new bifurcation points with change in width of the inhomogeneity and amplitude of the Josephson current through the inhomogeneity.Comment: 7 pages, 8 figure

"Зелений" синтез етилових естерів 4-гідрокси-2-оксо-1,2-дигідрохінолін-3-карбонових кислот

One of the most convenient methods for obtaining ethyl of N-substituted 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylates and their tricyclic analogues at present is condensation of the corresponding anilines with triethyl methanetricarboxylate. In spite of the fact that there are many methods describing the successful performance of this reaction in conditions of laboratory, but unfortunately, all of them appeared to be completely unusable for large production for a variety of reasons. The study of quality of the esters of 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acids by HPLC has shown that all of them contain from 2.4 to 5.6% of specific admixtures of 4-hydroxy-1,2-dihydroquinolin- 2-ones. In laboratory conditions these amounts can be neglected, but for industrial manufacture they can turn into great losses. The source of admixtures of 4-hydroxy-1,2-dihydroquinolin-2-ones appearing in crude esters can be only the esters themselves. It is obvious that ester grouping is partially destroyed not in the process of separation of the final products, but during the course of the basic reaction. It has been experimentally proven that the cause of contamination of the target products with the admixtures of the corresponding 4-hydroxy-1,2-dihydroquinolin-2-ones is water, which is present in reagents. Applying the principles of «green chemistry» the alternative for carrying out the syntheses of ethyl 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylates adapted for industrial manufacture has been suggested on the basis of N-substituted anilines and triethyl methanetricarboxylate.Одним из наиболее удобных способов получения этиловых эфиров N-замещённых 4-гидрокси-2-оксо-1,2-дигидрохинолин-3-карбоновых кислот и их трициклических аналогов в настоящее время остаётся конденсация соответствующих анилинов с триэтилметантрикарбоксилатом. Несмотря на то, что методов успешного проведения этой реакции в лабораторных условиях описано достаточно много, все они, к сожалению, по разным причинам оказались совершенно непригодными для крупного производства. Изучение качества получаемых сложных эфиров 4-гидрокси-2-оксо-1,2-дигидрохинолин-3-карбоновых кислот методом ВЭЖХ показало, что все они содержат от 2,4 до 5,6% специфических примесей 4-гидрокси-1,2-дигидрохинолин-2-онов. В лабораторной практике этими количествами можно пренебречь, но для промышленного производства они могут обернуться значительными потерями. Источником появления в неочищенных эфирах примесей 4-гидрокси-1,2-дигидрохинолин-2-онов могут быть только сами эти эфиры. Очевидно сложноэфирная группировка частично разрушается не при выделении конечных продуктов, а ещё в процессе проведения основной реакции. Экспериментально доказано, что причиной загрязнения целевых продуктов примесями соответствующих 4-гидрокси-1,2-дигидрохинолин-2-онов является присутствующая в реагентах вода. Руководствуясь принципами «зелёной химии», мы предложили адаптированный под промышленное производство вариант проведения синтезов этиловых эфиров 4-гидрокси-2-оксо-1,2-дигидрохинолин-3-карбоновых кислот на основе N-замещённых анилинов и триэтилметантрикарбоксилата.Одним з найбільш зручних способів одержання етилових естерів N-заміщених 4-гідрокси-2-оксо-1,2-дигідрохінолін-3-карбонових кислот та їх трициклічних аналогів на теперішній час залишається конденсація відповідних анілінів з триетилметантрикарбоксилатом. Незважаючи на те, що методів успішного проведення цієї реакції в лабораторних умовах описано досить багато, всі вони, на жаль, з різних причин виявились зовсім непридатними для масштабного виробництва. Вивчення якості одержуваних естерів 4-гідрокси-2- оксо-1,2-дигідрохінолін-3-карбонових кислот методом ВЕРХ показало, що всі вони містять від 2,4 до 5,6% специфічних домішок 4-гідрокси-1,2-дигідрохінолін-2-онів. У лабораторній практиці такими кількостями можна знехтувати, але для промислового виробництва вони можуть обернутися значними втратами. Джерелом появи в неочищених естерах домішок 4-гідрокси-1,2-дигідрохінолін-2-онів можуть бути тільки самі ці естери. Очевидно естерне угрупування частково розкладається не при виділенні кінцевих продуктів, а ще в процесі проведення основної реакції. Експериментально доведено, що причиною забруднення цільових продуктів специфічними домішками відповідних 4-гідрокси-1,2-дигідрохінолін-2-онів є присутня в реагентах вода. Керуючись принципами «зеленої хімії», ми запропонували адаптований під промислове виробництво варіант проведення синтезів етилових естерів 4-гідрокси-2-оксо-1,2-дигідрохінолін-3-карбонових кислот на основі N-заміщених анілінів та триетилметантрикарбоксилату

Synthesis and Cytotoxic Effect of 1-Aryl-Substituted-6-Imino-2,7-Dioxabicyclo[3.2.1]Octane-4,4,5-Tricarbonitriles

The work was carried out within the framework of scholarship SP-127.2016.4 from the President of the Russian Federation for young scientists and graduate students

Effects of glyprolines on free-radical oxidation in the brain neocortex of white rats in mild traumatic brain injury

The aim of the study was to compare the effect of glyproline peptides RGRGP (Arg-Gly-Arg-Gly-Pro), RGP (Arg-GlyPro), PRPGP (Pro-Arg-Pro-Gly-Pro) and PGPL (Pro-Gly-Pro-Leu) peptide substances at various concentrations on the free radical oxidation intensity of the brain tissues of Wistar males after intraperitoneal administration of peptide solutions after traumatic brain injury.Material and methods. The brain tissue of Wistar males aged 2–3 months (n = 126) were used in the experiment. RGRGP, RGP, PRPGP, and PGPL peptides were provided by Academician N.F. Myasoyedov. Traumatic brain injury (TBI) was modeled by free fall of a load. From the second to the fifth day of the experiment, the animals were injected intraperitoneally with peptides. On the sixth day, the animals were taken out of the experiment. The activity of free radical oxidation was determined in freshly prepared homogenates of sections of the cerebral cortex by chemiluminescence (CL).Results. TBI significantly enhance free-radical oxidation intensity of the neocortex in brain tissue of Wistar rats, and the studied peptides affect it in different ways - from a decrease in CL intensity (the minimum value in TBI + RGP 0.1 group) to its increase (the maximum value in TBI + RGPGP 0.1 group). The effect depends on the dose of glyproline.Conclusions. The results obtained, based on the analysis of the free radical oxidation intensity of tissues, mainly indicate a different degree of correction of tissue homeostasis indicators. It can be assumed that Arg-Pro-Gly peptide can be the basis for the development of new drugs for post-stress rehabilitation after injuries of various levels and genesis

Hypertensive crisis as cerebrovascular disease risk factor

Objective. To assess main epidemiological indicators for hypertensive crises (HC) in the population of productive age and to study possible correlations of crisis associated arterial hypertension (AH) with clinical and instrumental phenomenon of chronic cerebrovascular diseases. Materials and methods. Data of several studies presented: cross-sectional studies of 726 people aged 35-64 and 415 people aged 40-59. Observational cohort study of 109 patients aged 57.4±5.8 with uncomplicated AH. For the detection of HC in anamnesis, there were used special criteria which widens standard HC definition for additional account of light and mild severity cases. Results. Overall AH prevalence was 45% (95% CI 41-51), in men - 48% (40.2-55.9), in women - 45% (38.4-51.6). History of HC in anamnesis was 11.8% (95% CI 9-15.2), in men 8.8% (5.4-14) and in women - 13.8% (10-18.7). Proportion of HC associated AH defined at the level of 25-30% of all AH cases. The most prevalence of HC associated AH was found in people with “high normal” (130-139/85-89) arterial pressure - 37%. Prevalence of the complaints on headaches, dizziness, poor memory and lower intellectual productivity was higher in people with HC. Chronic cerebrovascular disease was found 2-fold frequently in HC associated AH. But in generally analysis of possible correlations of HC with clinical and instrumental phenomenon of chronic cerebrovascular diseases didn’t revealed any statistically significant differences. Conclusion. HC burden for healthcare system is serious, because it is important risk factor for cerebrovascular diseases and associated with significant lowering of the quality of life. Prevalence of the HC cases with light and mild severity is underestimated. Despite that the study of the most prevalent forms of HC (rare, light and mild severity) didn’t find any associations with morphological or persistent clinical pathology, functional phenomenon were found statistically significant frequently

Феномен подавления ДНК-метилтрансферазы 3А при формировании резистентного фенотипа в клетках рака молочной железы

Introduction. Rearrangement of molecular pathways and activation of bypass signaling determine the progression of tumor cell resistance to various drugs. Study of the common features of resistant formation mechanisms is essential for breast and other cancer beneficial treatments.Materials and methods. The present work was performed on estrogen receptor α ERα-positive (ERα – estrogen receptor α) McF-7 breast cancer cells, established sublines resistant to the mTOR inhibitor rapamycin or antiestrogen tamoxifen, and ERα-negative MDA-MB-231 breast cancer cells. Methods used include MTT test, transient transfection, immunoblotting, real-time polymerase chain reaction and methylation analysis by bisulfite pyrosequencing.Results. We have shown that the resistance of breast cancer cells to targeted and hormonal drugs is associated with the suppression of DNA methyltransferase 3A (DNMT3A) and respective changes in DNA methylation; DNMT3A knockdown results in the partial resistance to both drugs demonstrating the pivotal role of DNMT3A suppression in the progression of cell resistance.Conclusion. Totally, the results obtained highlight the possible mechanism of tumor cell resistance to targeting/hormonal drugs based on the deregulation of DNMTs expression and demonstrate  direct connection between DNMT3A suppression and resistance progression.Введение. Переключение сигнальных путей и активация параллельных сигнальных каскадов относятся к ключевым факторам, определяющим развитие резистентности опухолевых клеток, и изучение механизмов подобной реаранжировки является одной из актуальных задач современной онкологии.Материалы и методы. Настоящая работа выполнена на ERα-положительных  (ERα – эстрогеновый рецептор α) клетках рака молочной железы MCF-7 и полученных из них сублиниях, устойчивых к ингибитору mTOR рапамицину или антиэстрогену тамоксифену, а также на ERα-отрицательных клетках рака молочной железы MDA-MB-231. Используемые методы включают тест МТТ, транзиторную трансфекцию, иммуноблоттинг, полимеразную цепную реакцию в реальном времени и анализ метилирования с помощью бисульфитного пиросеквенирования.Результаты. Мы показали, что резистентность клеток рака молочной железы к таргетным и гормональным препаратам связана с подавлением ДНК-метилтрансферазы 3А (DNMT3A) и соответствующими изменениями в метилировании ДНК. Нокдаун DNMT3A приводит к частичной резистентности к обоим препаратам, что демонстрирует ключевую роль подавления DNMT3A в развитии резистентности опухолевых клеток.Заключение. В целом, полученные результаты свидетельствуют о возможном механизме формирования устойчивости опухолевых клеток к таргетным/гормональным препаратам, основанном на дерегуляции экспрессии DNMT, и демонстрируют прямую связь между подавлением DNMT3A и развитием резистентности

State of rat colon microbiocenosis in chronic restraint stress treated with Selank

It is currently accepted that stress significantly affects composition of microbiocenosis due to changes in permeability of intestinal barrier and pro-inflammatory effects. This, in turn, changes behavioral reactions, anxiety and stress response. In this regard, it seems promising to use regulatory peptide-based neurotropic drugs including Selank to correct stress-induced dysbiosis. Our study was aimed at assessing state of rat colon microbiocenosis in modelled chronic restraint stress and treated with Selankby using 65 Wistar male rats divided into five groups (per 13 rats in each): group 1 — rats injected with saline; group 2 — injected with saline and induced chronic restraint stress; group 3–5 — administered with Selank at dose of 80 μg/kg, 250 μg/kg and 750 μg/kg body weight, respectively, and induced chronic restraint stress. Quantitative and qualitative study of animal colon microbiota was carried out according to the method by L.I. Kafarskaja and V.M. Korshunov. Identification of microorganisms was carried out by using a Maldi Biotyper Microflex mass spectrometer (Bruker, United States). Microbial species-specific composition was presented as lg CFU/g mass of examined sample. For each identified microbial genus, the relative mean and frequency of occurrence were calculated. Statistical significance of differences in mean values was determined by using Student’s t-test. Chronic restraint stress in the experiment did not result in affecting dominant microbiota species in rat colon nor reduce their frequency, however, it significantly influenced examined parameters for commensal microbiota disturbing pattern of pathogenic bacterial strains. Use of Selank led to the reversing changes in composition of colonic microbiocenosis caused by stress model. Moreover, magnitude of parameters examined in experiment after applying Selank at dose of 750 μg/kg reached those in non-stressed animals. Thus, effects related to Selank administration may presumably be mediated due to both central and peripheral effects including immunotropic and anti-inflammatory activities which contributed to restoring colon microbiocenosis composition in stress model

NKX2-3 Transcriptional Regulation of Endothelin-1 and VEGF Signaling in Human Intestinal Microvascular Endothelial Cells

BACKGROUND: NKX2-3 is associated with inflammatory bowel disease (IBD). NKX2-3 is expressed in microvascular endothelial cells and the muscularis mucosa of the gastrointestinal tract. Human intestinal microvascular endothelial cells (HIMECs) are actively involved in the pathogenesis of IBD and IBD-associated microvascular dysfunction. To understand the cellular function of NKX2-3 and its potential role underlying IBD pathogenesis, we investigated the genes regulated by NKX2-3 in HIMEC using cDNA microarray. METHODOLOGY/PRINCIPAL FINDINGS: NKX2-3 expression was suppressed by shRNA in two HIMEC lines and gene expression was profiled by cDNA microarray. Pathway Analysis was used to identify gene networks according to biological functions and associated pathways. Validation of microarray and genes expression in intestinal tissues was assessed by RT-PCR. NKX2-3 regulated genes are involved in immune and inflammatory response, cell proliferation and growth, metabolic process, and angiogenesis. Several inflammation and angiogenesis related signaling pathways that play important roles in IBD were regulated by NKX2-3, including endothelin-1 and VEGF-PI3K/AKT-eNOS. Expression levels of NKX2-3, VEGFA, PI3K, AKT, and eNOS are increased in intestinal tissues from IBD patients and expression levels of EDN1 are decreased in intestinal tissues from IBD patients. These results demonstrated the important roles of NKX2-3, VEGF, PI3K, AKT, eNOS, and EDN1 in IBD pathogenesis. Correlation analysis showed a positive correlation between mRNA expression of NKX2-3 and VEGFA and a negative correlation between mRNA expression of NKX2-3 and EDN1 in intestinal tissues from IBD patients. CONCLUSION/RELEVANCE: NKX2-3 may play an important role in IBD pathogenesis by regulating endothelin-1 and VEGF signaling in HIMECs

Challenges in QCD matter physics - The Compressed Baryonic Matter experiment at FAIR

Substantial experimental and theoretical efforts worldwide are devoted to explore the phase diagram of strongly interacting matter. At LHC and top RHIC energies, QCD matter is studied at very high temperatures and nearly vanishing net-baryon densities. There is evidence that a Quark-Gluon-Plasma (QGP) was created at experiments at RHIC and LHC. The transition from the QGP back to the hadron gas is found to be a smooth cross over. For larger net-baryon densities and lower temperatures, it is expected that the QCD phase diagram exhibits a rich structure, such as a first-order phase transition between hadronic and partonic matter which terminates in a critical point, or exotic phases like quarkyonic matter. The discovery of these landmarks would be a breakthrough in our understanding of the strong interaction and is therefore in the focus of various high-energy heavy-ion research programs. The Compressed Baryonic Matter (CBM) experiment at FAIR will play a unique role in the exploration of the QCD phase diagram in the region of high net-baryon densities, because it is designed to run at unprecedented interaction rates. High-rate operation is the key prerequisite for high-precision measurements of multi-differential observables and of rare diagnostic probes which are sensitive to the dense phase of the nuclear fireball. The goal of the CBM experiment at SIS100 (sqrt(s_NN) = 2.7 - 4.9 GeV) is to discover fundamental properties of QCD matter: the phase structure at large baryon-chemical potentials (mu_B > 500 MeV), effects of chiral symmetry, and the equation-of-state at high density as it is expected to occur in the core of neutron stars. In this article, we review the motivation for and the physics programme of CBM, including activities before the start of data taking in 2022, in the context of the worldwide efforts to explore high-density QCD matter.Comment: 15 pages, 11 figures. Published in European Physical Journal