Введение полных расстояний и мер недостоверности для формул логик Лукасевича для автоматической кластеризации множеств логических высказываний из базы знаний

В статье рассмотрены логические высказывания экспертов, которые можно представить в виде логических формул n-значной логики Лукасевича. Используя теоретико-модельный подход, введены полные расстояния между формулами и меры недостоверности формул. Изучены свойства введенных величин. Также показаны вычисления и применения величин для кластеризации групп формул n-значной логики Лукасевича из базы знаний (экспертной системы)

FEATURES OF THE USE OF INTRODUCTORY COMPONENTS IN L.N. TOLSTOY’S NOVEL «WAR AND PEACE» IN THE LESSONS OF RUSSIAN LANGUAGE AS A FOREIGN

В данной статье рассмотрены сложности, возникающие при употреблении вводных конструкций у студентов, изучающих русский язык как иностранный. Источником рассмотрения примеров таких конструкций будет роман Л.Н. Толстого «Война и мир».=This article is discusses the difficulties that arise from the use of introductory constructions among students studying Russian as a foreign language. The source of consideration of examples of such constructions is the novel of Leo Tolstoy «War and Peace»

FEATURES OF THE USE OF INTRODUCTORY COMPONENTS IN L.N. TOLSTOY’S NOVEL «WAR AND PEACE» IN THE LESSONS OF RUSSIAN LANGUAGE AS A FOREIGN

В данной статье рассмотрены сложности, возникающие при употреблении вводных конструкций у студентов, изучающих русский язык как иностранный. Источником рассмотрения примеров таких конструкций будет роман Л.Н. Толстого «Война и мир».=This article is discusses the difficulties that arise from the use of introductory constructions among students studying Russian as a foreign language. The source of consideration of examples of such constructions is the novel of Leo Tolstoy «War and Peace»

Emotional Intelligence as a Factor in Adolescent Hardiness

The article discusses the possibilities of developing emotional intelligence among teachers in order to increase the hardiness of children and adolescents.В статье рассматриваются возможности развития эмоционального интеллекта у педагогов с целью повышении жизнестойкости детей и подростков

Repression of interrupted and intact rDNA by the SUMO pathway in Drosophila melanogaster

Ribosomal RNAs (rRNAs) are essential components of the ribosome and are among the most abundant macromolecules in the cell. To ensure high rRNA level, eukaryotic genomes contain dozens to hundreds of rDNA genes, however, only a fraction of the rRNA genes seems to be active, while others are transcriptionally silent. We found that individual rDNA genes have high level of cell-to-cell heterogeneity in their expression in Drosophila melanogaster. Insertion of heterologous sequences into rDNA leads to repression associated with reduced expression in individual cells and decreased number of cells expressing rDNA with insertions. We found that SUMO (Small Ubiquitin-like Modifier) and SUMO ligase Ubc9 are required for efficient repression of interrupted rDNA units and variable expression of intact rDNA. Disruption of the SUMO pathway abolishes discrimination of interrupted and intact rDNAs and removes cell-to-cell heterogeneity leading to uniformly high expression of individual rDNA in single cells. Our results suggest that the SUMO pathway is responsible for both repression of interrupted units and control of intact rDNA expression

Меланома кожи: от системной биологии к персонифицированной терапии

Systematic biology is a new field of biomedicine based on the integrative approach to molecular mechanisms of the operation of living systems including in case of the development of pathological processes. In this connection, up-to-date therapeutic approaches to skin melanoma treatment can be considered on the basis of key changes in intermolecular interactions taking place during tumor development.Системная биология является новой областью биомедицины, в основе которой лежит интегративный подход к рассмотрению молекулярных механизмов функционирования живых систем, в том числе при развитии патологических процессов. В этой связи современные терапевтические подходы в отношении меланомы кожи могут быть рассмотрены на основании ключевых изменений межмолекулярных взаимодействий, происходящих при формировании данной опухоли

Dynamics of the chemokine ENA-78/CXCL5 levels in blood serum and skin exudate in patients with atopic dermatitis

Currently, there are only scarce data on dynamics of biologically active substances in the lesions associated with atopic dermatitis. Persistence of microorganisms in atopic dermatitis is high on the skin surface. However, pathophysiological significance of ENA-78/CXCL5 for development of atopic dermatitis was not studied so far. The ENA-78/CXCL5 is known to be produced by endotheliocytes, keratinocytes, eosinophils, fibroblasts to activate neutrophil migration, especially under the influence of LPS-containing microorganisms. The aim of this study was to evaluate the dynamics of ENA-78/CXCL5 chemokine levels in blood serum and skin exudates in the patients with atopic dermatitis, as well as to determine pathophysiological role of the chemokine in pathogenesis of dermatosis. 80 patients with limited and widespread forms of atopic dermatitis and 15 volunteers were under observation. The dynamics of ENA-78/CXCL5 levels was studied in blood sera and skin exudates. Blood samples for the study were drawn at the time periods of exacerbation and remission. Skin exudates were taken from the patients during the exacerbation period using disposable insulin syringes and 20-G disposable needles. In healthy volunteers, the skin exudate was obtained by the “skin window” technique as described by V.V. Klimov and coauthors “A method for assessing minimal inflammatory activity of skin in atopic dermatitis in remission”. The cell analysis was conducted by flow cytofluorimetry using the LEGEND plex TM Human Proinflammatory Chemokine Panel (USA) according to the manufacturer’s protocol. Serum concentrations of chemokine ENA-78/CXCL5 in adolescents with atopic dermatitis, exceeded the range for healthy volunteers. During remission of dermatitis, the chemokine level did not reach the indices in the control group. In adults, the ENA-78/CXCL5 concentration, both at the onset of symptoms and upon their resolution, was below the control levels. Maximal concentrations of ENA-78/CXCL5 chemokine were detected in the skin exudates. As based on our data on the dynamics of ENA-78/CXCL5 chemokine levels, it could be assumed that this substance may represent a sufficient link in pathogenesis of atopic dermatitis, by causing migration of neutrophils and monocytes to the affected area. The ENA-78/CXCL5 chemokine may be a marker of microbial pathogenesis and cellular damage in atopic dermatitis

Potential Arrhythmogenic Role of TRPC Channels and Store-Operated Calcium Entry Mechanism in Mouse Ventricular Myocytes

Background and Purpose: Store-operated calcium entry (SOCE) is an important physiological phenomenon that extensively mediates intracellular calcium ion (Ca2+) load. It has been previously found in myocytes isolated from neonatal or diseased hearts. We aimed to determine its existence, molecular nature in undiseased hearts and its potential arrhythmogenic implications under hyperactive conditions.Experimental Approach: Ventricular myocytes isolated from adult FVB mice were studied by using Ca2+ imaging and whole-cell perforated patch-clamp recording. In addition, lead II ECGs were recorded in isolated Langendorff-perfused mice hearts. Functional TRPC channel antibodies and inhibitors, and TRPC6 activator hyperforin were used.Key Results: In this study, we demonstrate the existence and contribution of SOCE in normal adult mouse cardiac myocytes. For an apparent SOCE activation, complete depletion of sarcoplasmic reticulum (SR) Ca2+ by employing both caffeine (10 mM) and thapsigargin (1 μM) or cyclopiazonic acid (10 μM) was required. Consistent with the notion that SOCE may be mediated by heteromultimeric TRPC channels, SOCEs observed from those myocytes were significantly reduced by the pretreatment with anti-TRPC1, 3, and 6 antibodies as well as by gadolinium, a non-selective TRPC channel blocker. In addition, we showed that SOCE may regulate spontaneous SR Ca2+ release, Ca2+ waves, and triggered activities which may manifest cardiac arrhythmias. Since the spontaneous depolarization in membrane potential preceded the elevation of intracellular Ca2+, an inward membrane current presumably via TRPC channels was considered as the predominant cause of cellular arrhythmias. The selective TRPC6 activator hyperforin (0.1–10 μM) significantly facilitated the SOCE, SOCE-mediated inward current, and calcium load in the ventricular myocytes. ECG recording further demonstrated the proarrhythmic effects of hyperforin in ex vivo mouse hearts.Conclusion and Implications: We suggest that SOCE, which is at least partially mediated by TRPC channels, exists in adult mouse ventricular myocytes. TRPC channels and SOCE mechanism may be involved in cardiac arrhythmogenesis via promotion of spontaneous Ca2+ waves and triggered activities under hyperactivated conditions

Time course of autoantibodies to collagen type I and III in blood serum and skin exudate in atopic dermatitis

In accordance with Clinical Guidelines of the Russian Society of Dermatovenerologists and Cosmetologists, atopic dermatitis is a chronic allergic genetically determined dermatosis of a multifactorial nature. There are, however, some aspects that challenge the allergic nature of dermatosis. For example, according to literature data, not all the patients have increased synthesis of immunoglobulin E, some of them are torpid to antihistamine treatment, and, when examining the skin of some patients with atopic dermatitis, an absolute polymorphism of rashes is revealed, thus being not typical to the reagin-type allergic reactions. According to modern data, autoimmune theory is assumed for the mechanisms of atopic dermatitis. However, objective proofs of this theory have not been presented, thus drawing our attention to the studies of this issue. The aim of this study was to identify autoimmune pathogenetic mechanisms of atopic dermatitis. The study included 40 adolescents and 40 adult patients with limited and extended forms of atopic dermatitis. The patients were evaluated during the period of exacerbation and remission of the disease. Blood and skin exudates samples were taken from all the patients. The control group consisted of 30 practically healthy volunteers in whom skin exudate was obtained by the “skin window” technique as proposed by Klimov V.V. et al. “A method for assessing minimal inflammatory activity of skin in atopic dermatitis in remission”. Concentrations of IgG autoantibodies to collagen types I and III were determined in blood serum and skin exudate samples applying ELISA techniques with ready-made panels AEA571Hu ELISA Kit for Anti-Collagen Type I Antibody (USA), AEA176Hu ELISA Kit for Anti-Collagen Type III Antibody (USA), according to the manufacturer’s protocols. For the first time, the contents of autoantibodies to skin collagen types I and III in the patients with atopic dermatitis we studied in parallel, i.e., at systemic level and in affected skin. If compared to the group of healthy volunteers, the concentration of autoantibodies to collagen types I and III was found to be increased in all the patients with atopic dermatitis, both during exacerbation and in remission of the disease. The maximal values of autoantibodies to collagen types I and III were recorded in blood serum upon development of clinical symptoms of dermatosis, along with low contents of these antibodies detectable in their skin exudates. Permanently high concentrations of autoantibodies to collagen types I and III in blood serum at exacerbation and remission of atopic dermatitis, and their low level in their skin exudate suggest emergence of circulating and precipitating immune complexes, thus allowing us to consider atopic dermatitis as an autoimmune process