Formation of Professional-Pedagogical Culture оf Future Specialists оf Physical Culture аnd Sports Specialties

The results of research showed the need to organize in the institution of higher education conditions and a set of measures aimed at the formation of professional-pedagogical culture of future specialists, which makes it possible to strengthen educational work with them based on the translation of the values of the cultural and sports heritage of the subject of the state, the effective formation of their professionalism and pedagogical culture. The proposed system of professional training of future specialists of physical education and sports on acme-culturological bases directs teachers to improve the quality of training graduates in their future professional activities

ПРИМЕНЕНИЕ ИПИЛИМУМАБА У БОЛЬНЫХ ДИССЕМИНИРОВАННОЙ МЕЛАНОМОЙ КОЖИ

Introduction: Application of ipilimumab (IPI) in the treatment of patients with disseminated melanoma, first demonstrated an increase in survival that was an important event in cancer immunotherapy. We present the results of treatment of patients within the framework of enhanced access to the drug (SA184-EAP).Materials and methods: from September 2012 to August 2014 71 patients with metastatic melanoma, with signs of tumor progression, received earlier from 1 to 6 lines of drug therapy were enrolled in protocol of treatment in Petrov Oncology Institute. Median age of patients was 51 years (range from 21 to 76 years). In 39 (60%) of patients IV stage was diagnosed, 25% of patients had metastases to the brain, 28% - had liver metastases, 19% - had bone metastases. All patients received IPI 3 mg/kg once every 3 weeks for total 4 administration.Results: A total there were 229 administrations of IPI in 71 patients (average number of administrations was 3.2). Thirty-nine patients (59%) had 4 administrations and 21 patients (35%) had 1-2 administrations. Most of the patients had at least one adverse event (AE) associated with the treatment. In 15 patients (21%) there were no adverse events. Three patients died due to adverse events possibly related to treatment: 1 – had kidney failure, 1 - had pulmonary embolism, 1 - had cerebral edema and the progression of cancer. Grade 3-4 adverse events were observed in 10 (14.1%) patients: grade 3 rash  - in 3 (4.2%) patients, grade 3 diarrhea - in 2 (2.8%) patients, grade 3 fatigue - in 2 (2 8%) patients, grade 3 dyspnea - in 1 (1.4%) patients, grade 4 of ALT and AST increasing - in 1 (1.4%) patient, grade 3 hypokalemia - in 1 (1.5%) patient. Efficacy of treatment was assessed in 54 patients, complete regression was detected in 3 (6%) patients, partial - in 6 (11%) patients. An objective response to treatment was observed in 28% of patients, the stabilization of process in 6 (11%) patients. Median follow-up was 144 days. The median time to progression was 81 days (95%; CI 73-105). The median overall survival was 411 days (95%; CI - 303-519).Conclusion: Treatment with IPI satisfactorily tolerated by most patients and has significant clinical efficacy as the second and subsequent lines of drug therapy in patients with disseminated melanoma.Введение: Применение ипилимумаба (ИПИ) для лечения больных диссеминированной  меланомой  кожи, впервые продемонстрировавшее увеличение выживаемости, явилось важным событием в иммунотерапии  злокачественных опухолей. Мы представляем  результаты лечения больных в рамках программы  расширенного  доступа к препарату (СА184-ЕАР).Материалы и методы: В ФГБУ «НИИ онкологии  им.  Н. Н. Петрова» Минздрава России в программу с сентября2012 г. по август2014 г. включен 71 больной диссеминированной меланомой, с признаками прогрессирования опухолевого процесса, получивших ранее  от 1 до 6 линий лекарственной терапии. Средний возраст составил 51 год (21–76 лет). У 39 (60%) больных установлена IV стадия M1c, 25% пациентов имели метастатическое поражение головного мозга, 28% – метастазы в печени, 19% – метастазы в костях. Все больные получали ИПИ в дозе 3 мг/кг 1 раз в 3 недели, всего 4 введения.Результаты: У  71 больного проведено 229 введений  ИПИ (в среднем-3,2).  Тридцать девять больных (59%) получили 4 введений, 21 (35%) – 1–2 введения.  Большинство пациентов имело хотя бы одно нежелательное явление (НЯ), связанное  с лечением. У  15 больных (21%) нежелательных явлений не наблюдалось. Трое больных умерло от нежелательных явлений, возможно связанных с проводимой терапией: 1 – от почечной недостаточности, 1 – от тромбоэмболии легочной артерии, 1 – от отека головного мозга на фоне прогрессирования  опухолевого процесса. НЯ 3–4 ст. наблюдались  у 10 (14,1%) больных: сыпь 3 ст.– у 3 (4,2%), диарея 3 ст. у 2 (2,8%), слабость 3 ст. у 2 (2,8%), одышка 3 ст. у 1 (1,4%), повышение уровня АЛТ и АСТ 4 ст. у 1 (1,4%), гипокалиемия 3 ст. у 1 (1,5%) больных. Эффективность лечения оценена у 54 больных, полный регресс  выявлен у 3 (6%) больных, частичный – у 6 (11%) больных. Объективный ответ на терапию наблюдался  у 28% пацинентов, стабилизация  процесса  у 6 (11%). Средняя длительность наблюдения составила 144 дня. Медиана времени до прогрессирования – 81 (95% ДИ 73–105)  дней. Медиана общей выживаемости составила 411 дней (95% ДИ – 303–519).Заключение: Терапия  ИПИ удовлетворительно переносится большинством больных и обладает значимой клинической эффективностью в качестве второй и последующих линий лекарственной  терапии у пациентов диссеминированной  меланомой  кожи

SEMANTIC TRANSFORMATIONS OF THE PARAGUAY LINGUISTIC SYSTEM COMPONENTS

Since the beginning of the conquest of the American continent the confrontation of indigenous and European cultures has been observed. Languages, as a part of any culture, an indispensable element of any society respond to the changes in social, political and economic life, respond to the revision of moral and religious values and concepts. This response is revealed in the changes of the structure of the language in general and in the changes of each component of the above-mentioned structure in particular, and it refers to different levels of the language: phonetics, grammar, syntax, vocabulary. Bartomeu Meliá, by analogy with biology, calls the relations between Сastellano (Castilian Spanish) and Guarani a “linguistic ecology”, because language interaction can cause either their flourishing or such changes that can lead to the contamination of the semantics of the words. Semantic transformations have a piecemeal character determined not only by temporal factors, but also by other circumstances among which, along with the geographical aspect, cultural aspect has essential value. The meaning of the words depends on the emotions of the speaker; “substitution of the words and creation of neologisms form speech”. This is in its turn an area of a particular incidence where in one way or another the process of loss of identity has been taking place, whether it is indigenous or Paraguayan language, but we can point it out according to certain features. Language interaction brings enormous potential capacity of future development and enrichment. Thus, for example, the Spanish language in due time was enriched with the Arabic language and later with Anglicisms (Americanisms), etc. We talk here about the borrowings that the recipient language adopts because of its relevant needs. For example, the conquerors brought to America the animals that the native people did not know. These animals were very useful for their everyday life activities. As the Guarani did not have lexical units in their language to name them, they adapted the notions of the Spanish language with certain phonological changes: vaka ‘vaca’(‘cow’), kabayú ‘caballo’ (‘horse’), kabara ‘cabra’ (‘goat’), ovechá ‘obeja’ (‘goat’), etc. In addition to new technologies in all spheres of economic and socio-political life, Europeans reversed the perception of cultural, moral and religious life. They introduced to the daily life the names of the numerals, the months of the year, the days of the week, etc., which the Guarani-speakers accepted as their own. They made them a part of the new system with which the Guarani world had come into contact. For example, to name the days of the week the Guarani have their own notions. Arakõi ‘lunes’(‘Monday’), araapy ‘martes’(‘Tuesday’), etc. Although in everyday life, together with the Guaraní words, Spanish words are used: Oky va’ekue lunes guive ‘it was raining since Monday’ / Haʼe heʼi: “Asẽvaʼerã lunes pyharevete ha aju jueves pyhare” “I was leaving on Monday morning early and coming back Thursday night,” he says. It is important to bear in mind that in the 20th-21st centuries the Guarani appealed to anglicisms to denote the novelties of the modern world: restaurante, güisqui, radio, celular, etc. At the time of initial contacts, the Indians also contributed their first three words to Сastellano (Castilian Spanish): guaraní, mandioca, avatí or, it is better to say, choclo ‘soft corn’. A notable area of semantic transformations comprises the words denoting relationships in Guarani. Contacts with colonizers caused almost no changes in this sphere. As a result, in their speech today we still hear this lexis almost intact, almost without semantic changes, especially in their religious songs, mystical stories. It is about the languages paĩ, mbyá, aché. The words related to the Guarani worldview, their religion in general are of a particular interest from the point of view of the semantic changes. For example, the word guahu ‘song of the Indians’ lost its ritual sense and acquired the rude meaning ‘howl’ or ‘barking of a dog’. However, in certain cases it continues to maintain its original meaning: aguahu papa ‘to sing a dirge; to cry telling things’. Another kotyhu7 ritual song is not even remembered today. Thus, as the result of the intercommunication of two religious cultures on the one hand we find that the Guaraní religious discourse and the poetics of its songs lost their face because of the colonial religious service proficiency. On the other hand, we observe the emergence of a new language: The Christian Guarani with notable differences in semantics compared to so called “classic” Guaraní. Spanish, as the language of the ruling class, privileged during the time of colonization underwent fewer changes at all levels of the system. In the semantic field, the appearance of new meanings or nuances of the discourse markers is distinguished: that is the class of words (homophones of adverbs, conjunctions, collocations, etc., such as: en fin, bueno, verdad, pues, etc. ‘at last, well, true, then or others’) who lost their original meaning due to the process of its dissolution, the function of which is the exhortation, smoothing, etc., of the speech. Un poco ‘a little’ after its adaptation into Guarani, along with its original equivalent, now also corresponds to the standard peninsular Spanish phrase ‘por favor’ (‘please’). Semantic changes of the languages, as a reflection of the changes in social life, caused the emergence of a unique linguistic continuum that characterizes a new society, not just a biological mixture of nations, but a cultural one that let us distinguish Paraguayans from their relatives living in the Rio de la Plata region, Argentina. As a result of the interaction of the two languages, Spanish and Guarani, today in Paraguay “the third language” Jopará exists and is used at all levels of social life

Quartz Whispering-Gallery-Mode Resonator With Microfluidic Chip as Sensor for Permittivity Measurement of Liquids

Studies of biological solutions require high measurement accuracy, the ability to detect low changes in substance concentration, and small amounts of the liquid under test. A microwave complex permittivity measurement technique based on a high-quality-factor whispering-gallery-mode resonator with a microfluidic chip allows small amounts of dielectric liquids to be investigated with high accuracy. An existing technique based on a sapphire resonator does not provide for a low-concentration detection limit for substances with low molecular weight. Here, we present an advanced technique based on a quartz dielectric resonator. The detection limit obtained for glucose in water solution was found to be about one order of magnitude lower for the quartz resonator cell than for the sapphire-resonator-based measurement cell. The limit is about or lower than the concentration of glucose in human blood. This fact means that the technique can be used as the sensor for investigations of biological solutions in the microwave range. A study of glucose, lactalbumin, and bovine serum albumin was successfully performed in the Ka -band using the developed sensor

Whispering-Gallery-Mode Resonator Technique With Microfluidic Channel for Permittivity Measurement of Liquids

Studies of biochemical liquids require precise determination of their complex permittivity. We developed a microwave characterization technique on the basis of a high-quality whispering-gallery mode (WGM) sapphire resonator with a microfluidic channel filled with the liquid under test. A novel approach allows obtaining the complex permittivity of biochemical liquids of sub-microliter/nanoliter volumes with high accuracy. The method is based on a special procedure of analysis of the interaction of electromagnetic field with liquid in a WGM microfluidic resonator and measurements of both the WGM resonance frequency shift and the change of the inverse quality factor. The approach is successfully applied to obtain the complex permittivity in the Ka-band of glucose, albumin bovine serum, lactalbumin, and cytochrome C aqueous solutions using the developed microwave technique

Microwave characterization of aqueous amino acid solutions using the multifrequency WGM resonator technique

Amino acids play essential role for humans. We studied the dielectric properties of the basic aliphatic amino acids and polar positive amino acids in solutions of different concentrations. The enhanced to a number of measurement frequencies high-Q single microwave whispering gallery-mode (WGM) quartz dielectric resonator based technique was applied. The technique allows liquids investigation of micro- to nano- liter volumes filled in microfluidic channel on six discrete frequencies in 30-40 GHz range. The dependencies of the complex permittivity on the molar mass show almost linear behavior for aliphatic amino acids for different concentrations. The investigation results are in good agreement with the calculated data obtained by Cole-Cole equation

Whispering-Gallery Mode Resonator Technique with Microfluidic Channel for Permittivity Measurement of Liquids

Studies of biochemical liquids require precise determination of their complex permittivity. We developed a microwave characterization technique on the basis of a high-quality whispering-gallery mode (WGM) sapphire resonator with a microfluidic channel filled with the liquid under test. A novel approach allows obtaining the complex permittivity of biochemical liquids of sub-microliter/nanoliter volumes with high accuracy. The method is based on special procedure of analysis of the interaction of electromagnetic field with liquid in WGM microfluidic resonator and measurements of both the WGM resonance frequency shift and the change of the inverse quality factor. The approach is successfully applied to obtain the complex permittivity in the Ka band of glucose, albumin bovine serum, lactalbumin and cytochrome C aqueous solutions using the developed microwave technique

Adaptation of gene loci to heterochromatin in the course of Drosophila evolution is associated with insulator proteins

Pericentromeric heterochromatin is generally composed of repetitive DNA forming a transcriptionally repressive environment. Dozens of genes were embedded into pericentromeric heterochromatin during evolution of Drosophilidae lineage while retaining activity. However, factors that contribute to insusceptibility of gene loci to transcriptional silencing remain unknown. Here, we find that the promoter region of genes that can be embedded in both euchromatin and heterochromatin exhibits a conserved structure throughout the Drosophila phylogeny and carries motifs for binding of certain chromatin remodeling factors, including insulator proteins. Using ChIP-seq data, we demonstrate that evolutionary gene relocation between euchromatin and pericentric heterochromatin occurred with preservation of sites of insulation of BEAF-32 in evolutionarily distant species, i.e. D. melanogaster and D. virilis. Moreover, promoters of virtually all protein-coding genes located in heterochromatin in D. melanogaster are enriched with insulator proteins BEAF-32, GAF and dCTCF. Applying RNA-seq of a BEAF-32 mutant, we show that the impairment of BEAF-32 function has a complex effect on gene expression in D. melanogaster, affecting even those genes that lack BEAF-32 association in their promoters. We propose that conserved intrinsic properties of genes, such as sites of insulation near the promoter regions, may contribute to adaptation of genes to the heterochromatic environment and, hence, facilitate the evolutionary relocation of genes loci between euchromatin and heterochromatin.peerReviewe