92 research outputs found

    Literary Travel Genre in M. Shaginyan's Creative Work

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    Рассматривается жанровое своеобразие книги М.Шагинян «Путешествие по Советской Армении». При опоре на исследования В.Гуминского, В.Михайлова, анализируются композиция, структура повествования, художественное время и пространство, различные формы воплощения авторской позиции.The author describes the genre peculiarities of M. Shaginyan's Journey through Soviet Armenia. With reference to works by V. Guminsky, and V. Mikhailov, the author analyzes the composition, and the structure of the narrative, literary time and space, along with the different types of the writer's attitude expression

    ВНЕДРЕНИЕ ТЕХНОЛОГИИ «ЦИФРОВОЙ ДВОЙНИК» НА ОСНОВЕ МЕТОДОВ ЦИФРОВОГО ПРОЕКТИРОВАНИЯ НА РОССИЙСКИХ ПРЕДПРИЯТИЯХ ВЫСОКОТЕХНОЛОГИЧНЫХ ОТРАСЛЕЙ

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    The article is devoted to the study of the effectiveness of the introduction of digital technology "digital double" at the enterprises of high-tech industries in Russia. This paper structurally lists the production and economic benefits of using a digital double for enterprises. A detailed analysis of the current level of digital design at Russian enterprises in high-tech industries. The author emphasizes that the “digital double” technology endows high-tech products of the future with breakthrough competitive advantages by improving its technical and economic characteristics. From which it follows that digital design and modeling of high-tech products is a powerful tool to reduce costs through which the leaders of world high-tech markets form a «guaranteed reserved development».Статья посвящена исследованию эффективности внедрения цифровой технологии «цифровой двойник» на предприятиях высокотехнологичных отраслей в России. В данной работе структурно перечислены производственные и экономические выгоды от использования цифрового двойника для предприятий. Проведен подробный анализ текущего уровня цифрового проектирования на российских предприятиях высокотехнологичных отраслей. Автор особо отмечает, что технология «цифровой двойник» наделяет высокотехнологичную продукцию будущего прорывными конкурентными преимуществами за счет улучшения ее технико-экономических характеристик. Из чего следует, что цифровое проектирование и моделирование высокотехнологичной продукции является мощным инструментом снижения затрат, посредством которого лидеры мировых высокотехнологичных рынков формируют «гарантированное зарезервированное развитие»

    The influence of soluble components and culture conditions on hepatic differentiation of human pluripotent stem cells

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    Investigation of the hepatotoxicity of therapeutic compounds in vitro before clinical studies requires a reliable human liver cell model. Due to the disadvantages of using primary cell lines, hepatocellular carcinoma cell lines, and animal models, stem cell-derived liver models represent a promising tool for drug testing. Existing stem cell-derived liver models have immature characteristics, causing a demand for deeper investigation and improvements in hepatic differentiation procedures. Hepatocytes, the most abundant cell population in the liver, are responsible for drug metabolism. This feature makes them the most desirable liver cell population for drug testing. Pluripotent stem cell (PSC) differentiation into hepatocytes occurs in a few stages, namely, definitive endoderm (DE), hepatic progenitors (hepatoblasts), fetal hepatocytes, and adult hepatocytes. Each stage is controlled by defined external biochemical signals and physical environmental features provided by the surrounding extracellular matrix (ECM). Successful hepatic differentiation in vitro depends on the ability of the chosen conditions to mimic natural development. The right approach should focus on the assessment of the cellular state at every step of the differentiation. This thesis aimed to develop an effective method for human PSC differentiation into functional hepatocyte-like cells (HLCs) in two-dimensional (2D) and three-dimensional (3D) environments via spatially and temporally controlled physical and biochemical cues. First, we compared six previously developed differentiation medium compositions for their effectiveness in PSC differentiation into DE. We conducted differentiation for human induced PSCs (hiPSCs) and human embryonic stem cells (hESCs). We assessed the dynamic effectiveness of the differentiation using different combinations of growth factors (activin A and Wnt-3a) and/or small molecules (sodium butyrate salt and IDE1). We demonstrated activin A to be an efficient and sufficient agent for DE induction, while sodium butyrate and Wnt-3a were dispensable and IDE1 was inefficient for this purpose. Second, we applied the protocol for generating DE cells in 2D culture to the differentiation of hiPSCs into DE in 3D. We investigated the influence of the formed spheroid size and the presence of scaffold on spheroid morphological characteristics as well as the success of DE formation. We demonstrated a reverse correlation between spheroid size and the efficacy of DE formation. A scaffold-based 3D environment can be beneficial for spheroid culture. However, it can negatively affect cell aggregation if the scaffold material possesses strong cell affinity. Moreover, the hydrogel-based scaffold can also impede mass transport and therefore slow down cell differentiation. Third, we investigated the effect of the thyroid hormone triiodothyronine (T3) in the hepatic differentiation of hiPSCs-derived hepatic cells. We found that T3 increased the expression of thyroid hormone responsive protein THRSP (or SPOT14) and decreased the expression of alpha-1-fetoprotein (AFP). To further investigate the role of AFP in thyroid hormone - mediated hepatic differentiation, we developed an effective protocol based on CRISPR/Cas9-mediated genome editing to create an AFP knockout (AFP-KO) cell line. The improved genome editing approach includes a staggered transfection and the use of a Cas-9-linked selection marker. By comparing wild type and AFP-KO cell lines, we found that AFP does not determine the action of T3 in hepatocyte differentiation. This study suggests an effective method for hPSCs differentiation into definitive endoderm cells which is necessary for further liver cell formation. It demonstrates the importance of the culture environment and control of spheroid size for spheroid formation and hiPSCs differentiation in 3D culture conditions. It shows that the thyroid hormone affects the expression of particular fetal and liver maturation genes, thereby participating in hepatic differentiation of hiPSCs. Furthermore, finally, this study suggests an improved methodology for RNA-based CRISPR-Cas9-mediated genome editing in hPSCs for the study of gene functions during the differentiation of hPSCs in vitro. Taken together, these findings are important for the further development of hPSC-derived liver cell models.Terapeuttisten yhdisteiden hepatotoksisuuden tutkiminen in vitro ennen kliinisiä tutkimuksia edellyttää luotettavaa ihmisen maksasolumallia. Primaaristen solulinjojen, hepatosellulaaristen karsinoomasolulinjojen ja eläinmallien puutteiden vuoksi kantasoluista johdetut maksamallit ovat lupaava työkalu lääkkeiden testaamiseen. Olemassa olevilla kantasoluista peräisin olevilla maksamalleilla on vajavaisuuksia, jotka edellyttävät maksan erilaistumismenetelmiä koskevia lisätutkimuksia ja parannuksia. Hepatosyytit, maksan runsain solupopulaatio, ovat vastuussa lääkkeiden metaboliasta. Tämä ominaisuus tekee niistä halutuimman maksasolutyypin lääkkeiden testaamiseen. Pluripotentit kantasolut (PSC) erilaistuvat hepatosyyteiksi muutamassa vaiheessa, definitiivisestä endodermistä (DE), maksan esisolujen (hepatoblastit) ja alkion hepatosyyttien kautta ja kypsiksi hepatosyyteiksi. Jokaista vaihetta kontrolloivat tietyt ulkoiset biokemialliset signaalit ja ympäröivään solunulkoiseen matriisiin (ECM) liittyvät fyysiset ympäristötekijät. Maksan onnistunut erilaistuminen in vitro riippuu valittujen olosuhteiden kyvystä jäljitellä maksan luonnollista kehitystä. Oikean lähestymistavan tulisi keskittyä solun erilaistustilan arviointiin erilaistamisen jokaisessa välivaiheessa. Tämän väitöskirjatyön tarkoituksena oli kehittää tehokas menetelmä ihmisen PSC:n erilaistumiseen toiminnallisiksi hepatosyyttien kaltaisiksi soluiksi (HLC) kaksiulotteisissa (2D) ja kolmiulotteisissa (3D) ympäristöissä spatiaalisesti ja ajallisesti ohjattujen fyysisten ja biokemiallisten vihjeiden avulla. Ensin työssä vertailtiin kuuden aiemmin käytetyn molekyylin tehokkuutta PSC:n erilaistamisessa DE:ksi. Suoritimme erilaistumisen ihmisen indusoiduille PSC:lle (hiPSC) ja ihmisen alkion kantasoluille (hESC). Arvioimme erilaistumisen dynaamista tehokkuutta käyttämällä erilaisia kasvutekijöiden (aktiviini A ja Wnt-3a) yhdistelmiä ja/tai pieniä molekyylejä (natriumbutyraattisuola ja IDE1). Osoitimme aktiviini A:n olevan tehokas ja riittävä lähtöaine DE-induktioon, kun taas natriumbutyraatti ja Wnt-3a olivat tarpeettomia ja IDE1 oli tehoton tähän tarkoitukseen. Toiseksi hyödynsimme 2D-viljelmän protokollaa hiPSC:n erilaistumiseen DE-soluiksi 3D:ssä. Tutkimme muodostuneen solusferoidin koon ja käytetyn matriksin vaikutusta sferoidin morfologisiin ominaisuuksiin sekä DE-erilaistuksen tehokkuuteen. Osoitimme negatiivisen korrelaation pallomaisen koon ja DE-muodostuksen tehokkuuden välillä. Viljelymatriksiin perustuva 3D-ympäristö voi olla hyödyllinen sferoidiviljelmälle. Se voi kuitenkin vaikuttaa myös negatiivisesti solujen aggregaatioon, jos materiaalilla on vahva soluaffiniteetti. Lisäksi hydrogeelipohjainen alusta voi estää massansiirtoa ja siten hidastaa solujen erilaistumista. Kolmanneksi tutkimme kilpirauhashormonin trijodityroniinin (T3) vaikutusta hiPSC:stä peräisin olevien epäkypsien maksasolujen maksaerilaistukseen. Havaitsimme, että T3 lisäsi kilpirauhashormoniin reagoivan THRSP (tai SPOT14) -proteiinin ilmentymistä ja vähensi alfa-1-fetoproteiinin (AFP) ilmentymistä. Tutkiaksemme tarkemmin AFP:n roolia kilpirauhashormonivälitteisessä maksan erilaistumisessa kehitimme tehokkaan protokollan, joka perustuu CRISPR/Cas9-välitteiseen genomieditointiin AFP-geeninpoisto (AFP-KO) -solulinjan luomiseksi. Tämä parannettu genomin muokkausmenetelmä sisältää vaiheittaisen transfektion ja Cas-9-linkitetyn valintamarkkerin käytön. Vertaamalla villityyppi- ja AFP-KO-solulinjoja havaitsimme, että AFP ei määritä T3:n toimintaa hepatosyyttien erilaistumisessa. Tämä tutkimus tuotti tietoa tehokkaasta menetelmästä hPSC:n erilaistumiseen lopullisiksi endodermisoluiksi, mikä on välttämätöntä maksasolujen muodostumisen jatkamiseksi. Tutkimus osoittaa kasvatusympäristön ja sferoidikoon hallinnan tärkeyden sferoidien muodostumisen ja hiPSC:n erilaistumisen kannalta 3D-viljelyolosuhteissa. Tutkimus osoittaa myös, että kilpirauhashormoni vaikuttaa tiettyjen sikiön ja maksan kypsymisgeenien ilmentymiseen ja osallistuu siten hiPSC:n maksan erilaistumiseen. Lopuksi tämä tutkimus tuotti tietoa parannellusta menetelmästä RNA-pohjaiseen CRISPR-Cas9-välitteiseen hPSC:n genomieditointiin geenitoimintojen tutkimiseksi hPSC:n erilaistumisen aikana in vitro. Yhdessä nämä havainnot ovat tärkeitä hPSC:stä johdettujen maksasolumallien jatkokehitykselle.ei saavutettav

    Сведения о клановых именах джаму манден в африканских, западных и арабских источниках

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    В работе предпринята попытка консолидации сведений о клановых именах (джаму) Западного Судана. В начале приведен краткий историографический обзор публикаций, касающихся данной темы от первых упоминаний о джаму до тенденций развития данного направления исследований последнего десятилетия. Конечным результатом явилось составление словаря, который содержит статьи о чуть менее, чем 400 именах, каждое из которых описано сообразно определенному шаблону – набору характеристик, таких как географическая дистрибуция, кастовая принадлежность etc. Кроме того словарь включает в себя тексты устной традиции, объясняющие происхождение имен и отношения между ними. Собранные воедино данные из публикаций европейских ученых составляют скелет словаря. Помимо этого, автором выполнен перевод с языка манинка на русский сочинения гвинейского ученого и просветителя, изобретателя письменности нко Сулемана Канте, труды которого ранее не переводились на европейские языки. Частично текст был внесен в словарь, полная версия в формате параллельного текста – на нко и русский перевод, снабженный необходимым комментарием, – приведена в приложении.This research attempts to consolidate data about clan names (jamu) used in Western Sudan. The study begins with a short historiographic review of publications related to this topic from the first mention of jamu to the trends in the development of this area of research in the last decade. The final result is the compilation of a dictionary, that contains slightly less than 400 names, each of which is described according to a certain pattern - a set of characteristics such as the geographical distribution, caste etc. In addition, the dictionary includes texts of oral tradition, explaining the origin of names and the relationship between them. The data collected from the publications of European scientists constitute the frame of the dictionary. The author made a translation from the Maninka language to Russian of works of Souleymane Kante, the Guinean scholar and enlightener, the inventor of the N'ko writing. His works had not previously been translated into European languages.The text was partly added to the dictionary, the full version in the parallel text format - N'ko and Russian translation, provided with the necessary comments is given in the Appendix

    Management mechanisms of the health oriented educational system development : by the example of Belgorod region schools

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    The article deals with the management mechanisms of the health oriented school educational system development: the structure of management at the public, administrative, pedagogical and pupils’ levels; the usage of motivational and reflexive methods of management. The relationship between school management functions and components of the health oriented school educational system (management, educational process, health service, school environment) is shown. By the example of Belgorod region schools the effectiveness of the presented management mechanism is prove

    Опыт формирования здорового образа жизни школьников в условиях региональной инновационной площадки Белгородской области

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    The article is devoted to an important problem of modern Russian education -saving the pupils’ health and forming a healthy lifestyle of children and teenagers. The authors examine the results of the regional innovation platforms which united six schools of the Belgorod regio

    The experience of formation of schoo-lchildren’s healthy lifestyle in the conditions of activities of the regional innovative platform in Belgorod region

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    The article is devoted to an important problem of modern Russian education -saving the pupils’ health and forming a healthy lifestyle of children and teenagers. The authors examine the results of the regional innovation platforms which united six schools of the Belgorod regio

    The Islamic Republic of Iran in Search of its Foreign Policy Identity: Revolutionary Innovation or Continuity?

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    Self-perception in the international arena plays a great role in the development of a country's foreign policy strategy. Not all states can answer the question «who are we in relation to others»? In particular, we can describe the past 20 century and the first decades of the 21st century as the time of Tehran's search for its foreign policy identity, which is not finished even today. Despite many discussion, the Iranian political elite has not only failed to find a single definition of its foreign policy selfhood, but has produced several more formulas of its own identity, which often contradict each other, although they coexist. The events of 1979, when the new leadership that came to power in the course of revolutionary upheavals announced the rejection of the traditions of the Shah's Iran and the building of a new "revolutionary" nation with its own special foreign policy identity, had a significant impact on the process of forming the Iranian selfhood. The article analyzes the main trends that exist in the Iranian foreign policy self-perception, in order to confirm the hypothesis that the «revolutionary experiment» did not lead to a break in the continuity in the issue of Iranian self-identification. On the contrary, there is an attempt by the country's leadership to combine Islamic, revolutionary and nationalist principles in determining the role of their country in the international arena, which let us speak about the multi-component foreign policy identity of modern Iran

    Management mechanisms of the health oriented educational system development : by the example of Belgorod region schools

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    The article deals with the management mechanisms of the health oriented school educational system development: the structure of management at the public, administrative, pedagogical and pupils’ levels; the usage of motivational and reflexive methods of management. The relationship between school management functions and components of the health oriented school educational system (management, educational process, health service, school environment) is shown. By the example of Belgorod region schools the effectiveness of the presented management mechanism is prove
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