579 research outputs found
Cyclonic vortex in a rotating layer with isolated heat source
No full textFormation of cyclonic vortex from isolated heat source in a rotating fluid layer was studied experimentally and numerically. It was shown that structure of the vortex strongly depends on main governing parameters such as Grasshof number and Rossby number. PIV measurements were carried out for fluids with different values of Prandtl number (from 40 to 250). Numerical simulations were done using CFD software FlowVision
Perspectives on intimate relationships and self-determination in young adults with Down syndrome
No full textIntimate relationships are significantly associated with quality of life for young people with Down syndrome (DS). These relationships are a facet of social participation within the scope of OT practice that is not often addressed in practice. This descriptive study explores self-determination and perceptions of intimate relationships from the perspective of young adults with DS (ages 18-30 years) and their caregivers. Implications of findings for OT practice are discussed. Primary Author and Speaker: Katherine Williams Contributing Authors: Evguenia Popova, Katie Fran
The challenges of machine translation of academic publications
No full textClear translation remains a major challenge to better communication and understanding of the international academic literature, despite advances in Machine Translation (MT). Automatic translation systems which captured the detail and the sense of any manuscript in any language for a reader from any other linguistic background would find global applications.In this article, we discuss the current opportunities and constraints to the wider use of machine translation and computer-assisted human translation (CAT). At the present stage of technology development, these instruments offer a number of advantages to specialists working with scientific texts. These include the facility to skim and scan large amounts of information in foreign languages, and to act as digital dictionaries, thesauri and encyclopedias. Word-to-word and phrase-to-phrase translation between many languages and scripts is now well advanced. The availability of modern machine translation has therefore changed the work of specialist scientific translators, placing greater emphasis on more advanced text and sense editing skills. However, machine translation is still challenged by the nuances of language and culture from one society to another, particularlyin the freestyle literature of the arts and humanities. Scientific papers are generally much more structured, but the quality of machine translation still largely depends on the quality of the source text. This varies considerably between different scientific disciplines and from one author to another. The most advanced translation systems are making steady progress. It is timely to revisit traditional training programmes in the field of written translation to focus on the development of higher-level research competencies, such as terminology search, and so to make best use of evolving machine translation technologies. More widely, we consider that there is a challenge across the higher education systems in all countries to develop a simple, clear and consistent “international” writing style to assist fast, reliable and low-cost machine translation and hence to advance mutual understanding across the global scientific literature
Maria Popova. Politicized Justice in Emerging Democracies: A Study of Courts in Russia and Ukraine
Get PDFA book on politicized justice in Russia and Ukraine has long been overdue— and not only because of the topicality and seriousness of the problem, which the author, Maria Popova, recognizes very well. Impartial and independent courts are crucial for Ukraine’s integration into the European Union, and we are only left to hope that sooner or later such courts will become an urgent issue for Russia as well. The problem is made graphic in this book through a photo on the front cover that depicts the 2011 hearing o f the case of Iuliia Tymoshenko, the former Prime Minister of Ukraine. Standing behind her in court is a special division of the militia
Image of Heavenly Jerusalem in the «Ladder» of John Climacus
No full textThe article contains a linguistic analysis of the lexemes Ἱερουσαλήμ, παράδεισος and ἄνω, representing the image of the Heavenly Jerusalem. The material for the analysis is the text of the first Slavic translation of the “Ladder” of John Climacus, preserved in the oldest Russian manuscript of the monument. The author's ideas about the ideal city — the ultimate goal of every Christian — are revealed. It is noted that this image determined the development of the iconographic scheme "Vision of the Ladder by St. John Climacus". Cases of atypical translations, scribe's errors and readings characterizing the supposed Byzantine original of the Preslav translation of the “Ladder” are indicated. Attention is focused on the skill of the author of the first Slavic translation of the Ladder and the inexperience of the scribe of the first surviving manuscript of this translation, which confirms the validity of the linguotextological method of L.P. Zhukovskaya, the essence of which lies in the need to involve in the analysis the maximum possible number of sources. Lexemes were discovered that were not recorded in the dictionaries of the ancient Greek language (2) and in the dictionaries of the Old Church Slavonic and Old Russian languages (4).</p
Dihydroorotate dehydrogenase : new insights into an old target
No full textPurine and pyrimidine nucleotides are important for both biosynthetic and regulatory pathways in cells. As constituents of the DNA and RNA molecules, the requirements for nucleotides in actively dividing cells are increased. Therefore, the enzymes from the purine and pyrimidine nucleotide synthesis pathways are considered attractive targets for treatment of diseases associated with deregulated cell proliferation, such as cancer. Dihydroorotate dehydrogenase (DHODH), an enzyme from the de novo pyrimidine ribonucleotide synthesis pathway located on the inner mitochondrial membrane, has been intensively studied in the past few years as a target for anti-cancer therapy. As a result, several inhibitors of DHODH are currently in clinical trials for treatment of myeloid malignancies.In a screen for p53 activators, we discovered a novel class of DHODH inhibitors with a tetrahydroindazole core structure (Paper I). The hit compound from the screen, the chiral compound named HZ00, increased p53 translation without increasing p53 mRNA levels or the stability of the protein. Furthermore, treatment with HZ00 accumulated cancer cells in the S-phase of the cell cycle while it led to cell cycle arrest in normal fibroblasts. After screening of commercially available HZ analogues, we discovered the more potent compound HZ05. The active enantiomer of the chiral HZ compound was the (R)-enantiomer, confirmed by the co-crystallization of DHODH with HZ05 where only (R)-HZ05 was bound to the quinone tunnel of DHODH (membrane binding domain). Additionally, both compounds acted synergistically with the MDM2 inhibitor nutlin-3 (which protects p53 from degradation) in different tumor cell lines and in a melanoma xenograft model.Following the discovery of the HZ compounds as inhibitors of DHODH, we investigated the structure and function of DHODH using mass spectrometry and molecular dynamics simulations (Paper II) and afterwards optimized the HZ compounds in a structure activity relationship study (SAR, Paper III). Using non-denaturing mass spectrometry, we established that the interactions between DHODH and its co-factor FMN, the lipids present in the mitochondrial membrane, as well as ligands such as the DHODH inhibitor brequinar, have stabilizing effect on the protein. Furthermore, molecular dynamic stimulations demonstrated the flexibility of the membrane binding domain and the transmembrane helix. We also illustrated that the lipid interactions that stabilize the membrane binding domain may affect the binding of longer ligands, which is important for the design of new inhibitors. The optimization of the HZ-compounds was based on a metabolic soft spot study and the crystal structure of DHODH with (R)-HZ05 obtained in Paper I. The activity of many of the new HZ inhibitors was improved in the in vitro enzymatic assay as well as in cellular assays using a melanoma cell line. Based on in vitro metabolic stability analysis we identified a lead compound in the series, which demonstrated high specificity towards DHODH. The new active HZ-analogues were also able to trigger p53 transcription factor function and affected the cell growth/viability of a melanoma cell line with only a small effect on a normal fibroblast, suggesting a reasonably wide therapeutic window. Supplementation with an excess of uridine ameliorated both, the activation of p53 by the HZ compounds and their effect on cell growth/viability. Under our experimental conditions, the new HZ analogues did not activate DNA damage markers. Additionally, we demonstrated that the ability of DHODH inhibitors to induce apoptosis related g-H2AX was prevented by co-treatment with the pan-caspase inhibitor Z-VAD-FMK.Due to the re-emerging interest in DHODH as a drug target, we investigated the early events triggered after inhibition of this enzyme (Paper IV). For that purpose, we performed RNA sequencing analysis of cells treated with two DHODH inhibitors for up to 4 h. One of the earliest significant changes was the fast downregulation of PNUTS mRNA. This event was observed at the protein level as well. The PNUTS decrease was accompanied by an increase of p53 protein, although the correlation between the two changes requires further investigation. Nevertheless, due to the early decrease in PNUTS we propose that the downregulation of PNUTS mRNA may be a marker for DHODH inhibition.List of scientific papersI. Ladds, M.J.G.W., van Leeuwen, I.M.M., Drummond, C.J., Chu, S., Healy A.R., Popova, G., Pastor-Fernández, A., Mollick, T., Darekar, S., Sedimbi, S.K., Nekulova, M., Sachweh, M.C.C., Campbell, J., Higgins, M., Tuck, C., Popa, M., Safont, M.M., Gelebart, P., Fandalyuk, Z., Thompson, A.M., Svensson, R., Gustavsson, A., Johansson, L., Färnegårdh, K., Yngve, U., Saleh, A., Haraldsson, M., D’Hollander, A.C.A., Franco, M., Zhao, Y., Håkansson, M., Walse, B., Larsson, K., Peat, E.M., Pelechano, V., Lunec, J., Vojtesek, B., Carmena, M., Earnshaw, W.C., McCarthy, A.R., Westwood, N., Arsenian Henriksson, M., Lane, D.P., Bhatia, R., McCormack, E., and Laín, S.A*. DHODH inhibitor increases p53 synthesis and enhances tumor cell killing by p53 degradation blockage. Nature Communications. 2018 Mar 16;9(1):1107. §These authors contributed equally, *Corresponding author. https://doi.org/10.1038/s41467-018-03441-3. II. Costeira-Paulo, J., Gault, J., Popova, G., Ladds, M.J.G.W., van Leeuwen, I.M.M., Sarr, M., Olsson, A., Lane, D.P.*, Laín, S.*, Marklund, E.G.*, and Landreh, M.* Lipids shape the electron acceptor-binding site of the peripheral membrane protein dihydroorotate dehydrogenase. Cell Chemical Biology. 2018 Mar 15;25(3):309-317.e4. *Corresponding author. https://doi.org/10.1016/j.chembiol.2017.12.012 III. Popova, G.*, Ladds, M.J.G.W., Johansson, L., Saleh, A., Larsson, J., Sandberg, L., Sahlberg, S. H., Qian, W., Gullberg, H., Garg, N., Gustavsson, A., Haraldsson, M., Lane, D.P., Yngve, U., and Laín, S. Optimization of tetrahydroindazoles as inhibitors of human dihydroorotate dehydrogenase and evaluation of their activity and in vitro metabolic stability. *Corresponding author. [Submitted]IV. Popova, G.§*, Sanchez, Y.P.§, Lane, D., Pelechano, V., Laín, S*. Protein phosphatase 1 nuclear targeting subunit, PNUTS, an early marker of DHODH inhibition. *Corresponding author. §These authors contributed equally, *Corresponding author. [Manuscript]</p
Phase nature of adaptation processes
No full textПопова Т.В., доктор биологических наук, профессор кафедры информационной безопасности Южно-Уральского государственного университета (Челябинск).
Popova T.V., a Dr.Sci.Biol., the professor of chair of information security of the South Ural state university (Chelyabinsk).Автор приводит результаты многолетних исследований адаптационных изменений в организме лиц разного возраста, пола и физического состояния при нагрузках физического и умственного характера. Приводятся данные о фазовом характере адаптационных процессов, который необходим для обеспечения оптимального психофизического состояния организма. The author cites the results of long-term studies of adaptive changes in the body of persons of different age, sex and physical condition with loads of physical and mental nature. The data on the nature of the phase
of adaptation processes, which is required for optimal mental and physical condition of the body
Законодательное регулирование деятельности международных коммерческих арбитражей Швейцарии. Общие положения
Get PDFThis article deals with the basic sources of law, which regulate International Commercial Arbitration in Switzerland, and specifies the conditions of their application.В статье рассматриваются основные источники права, регулирующие международный коммерческий арбитраж в Швейцарии, определяются условия их применения
Общие вопросы оспаривания решений международных коммерческих арбитражей в Швейцарии
Get PDFThis article investigates processual and legal aspects, which concern the possibility of contestation of decisions of International Commercial Arbitrations in Switzerland and permissibility of refusal from the contestation by agreement of the parties.В статье рассматриваются процессуально-правовые аспекты, касающиеся возможности оспаривания в Швейцарии решений международных коммерческих арбитражей, а также и допустимости отказа от оспаривания соглашением сторон
The notion of «identity»: to the problem of definition.
No full textThe article is devoted to systematization of the definitions of the notion «identity» in the
modern philosophical and sociological literature. The author describes the main types of such
definitions. The article also traced the dependence of these definitions on the discursive context of
use of the indicated term.Стаття присвячена систематизації дефініцій поняття «ідентичність» у сучасній
філософській та соціологічній літературі. Авторка виокремлює головні типи таких
визначень. У статті також простежується залежність цих дефініцій від дискурсивного
контексту використання зазначеного терміну.Макіївський економіко-гуманітарний інститу
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