49 research outputs found

    Statistical evaluation of the equivalence scale based on joint accommodation for households of the Russian Federation

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    © 2015, Econjournals. All rights reserved. In this article an evaluation of equivalence scales for households of the Russian Federation is made using the data from “Russian monitoring of the economic situation and public health HSE” for the year 2013. Calculation of equivalence scales is done through a regression estimate of the Engel curve. Identified on the basis of the value of the resulting regression model scale are significantly different from the official scale of the Federal State Statistics Service of the Russian Federation. The authors have shown that it has significant implications for the evaluation of the relative poverty of certain vulnerable groups, in turn, has great significance for the implementation of targeted social policies

    Docking Server for the Identification of Heparin Binding Sites on Proteins

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    Many proteins of widely differing functionality and structure are capable of binding heparin and heparan sulfate. Since crystallizing protein–heparin complexes for structure determination is generally difficult, computational docking can be a useful approach for understanding specific interactions. Previous studies used programs originally developed for docking small molecules to well-defined pockets, rather than for docking polysaccharides to highly charged shallow crevices that usually bind heparin. We have extended the program PIPER and the automated protein–protein docking server ClusPro to heparin docking. Using a molecular mechanics energy function for scoring and the fast Fourier transform correlation approach, the method generates and evaluates close to a billion poses of a heparin tetrasaccharide probe. The docked structures are clustered using pairwise root-mean-square deviations as the distance measure. It was shown that clustering of heparin molecules close to each other but having different orientations and selecting the clusters with the highest protein–ligand contacts reliably predicts the heparin binding site. In addition, the centers of the five most populated clusters include structures close to the native orientation of the heparin. These structures can provide starting points for further refinement by methods that account for flexibility such as molecular dynamics. The heparin docking method is available as an advanced option of the ClusPro server at http://cluspro.bu.edu/

    A Novel Dimeric Inhibitor Targeting Beta2GPI in Beta2GPI/Antibody Complexes Implicated in Antiphospholipid Syndrome

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    Background: b2GPI is a major antigen for autoantibodies associated with antiphospholipid syndrome (APS), an autoimmune disease characterized by thrombosis and recurrent pregnancy loss. Only the dimeric form of b2GPI generated by anti-b2GPI antibodies is pathologically important, in contrast to monomeric b2GPI which is abundant in plasma. Principal Findings: We created a dimeric inhibitor, A1-A1, to selectively target b2GPI in b2GPI/antibody complexes. To make this inhibitor, we isolated the first ligand-binding module from ApoER2 (A1) and connected two A1 modules with a flexible linker. A1-A1 interferes with two pathologically important interactions in APS, the binding of b2GPI/antibody complexes with anionic phospholipids and ApoER2. We compared the efficiency of A1-A1 to monomeric A1 for inhibition of the binding of b2GPI/antibody complexes to anionic phospholipids. We tested the inhibition of b2GPI present in human serum, b2GPI purified from human plasma and the individual domain V of b2GPI. We demonstrated that when b2GPI/antibody complexes are formed, A1-A1 is much more effective than A1 in inhibition of the binding of b2GPI to cardiolipin, regardless of the source of b2GPI. Similarly, A1-A1 strongly inhibits the binding of dimerized domain V of b2GPI to cardiolipin compared to the monomeric A1 inhibitor. In the absence of anti-b2GPI antibodies, both A1-A1 and A1 only weakly inhibit the binding of pathologically inactive monomeric b2GPI to cardiolipin. Conclusions: Our results suggest that the approach of using a dimeric inhibitor to block b2GPI in the pathologica

    FRET Detection of Lymphocyte Function-Associated Antigen-1 Conformational Extension

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    Lymphocyte function-associated antigen 1 (LFA-1, CD11a/CD18, αLβ2-integrin) and its ligands are essential for adhesion between T-cells and antigen-presenting cells, formation of the immunological synapse, and other immune cell interactions. LFA-1 function is regulated through conformational changes that include the modulation of ligand binding affinity and molecular extension. However, the relationship between molecular conformation and function is unclear. Here fluorescence resonance energy transfer (FRET) with new LFA-1-specific fluorescent probes showed that triggering of the pathway used for T-cell activation induced rapid unquenching of the FRET signal consistent with extension of the molecule. Analysis of the FRET quenching at rest revealed an unexpected result that can be interpreted as a previously unknown LFA-1 conformation

    Uptake of the Necrotic Serpin in Drosophila melanogaster via the Lipophorin Receptor-1

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    The humoral response to fungal and Gram-positive infections is regulated by the serpin-family inhibitor, Necrotic. Following immune-challenge, a proteolytic cascade is activated which signals through the Toll receptor. Toll activation results in a range of antibiotic peptides being synthesised in the fat-body and exported to the haemolymph. As with mammalian serpins, Necrotic turnover in Drosophila is rapid. This serpin is synthesised in the fat-body, but its site of degradation has been unclear. By “freezing” endocytosis with a temperature sensitive Dynamin mutation, we demonstrate that Necrotic is removed from the haemolymph in two groups of giant cells: the garland and pericardial athrocytes. Necrotic uptake responds rapidly to infection, being visibly increased after 30 mins and peaking at 6–8 hours. Co-localisation of anti-Nec with anti-AP50, Rab5, and Rab7 antibodies establishes that the serpin is processed through multi-vesicular bodies and delivered to the lysosome, where it co-localises with the ubiquitin-binding protein, HRS. Nec does not co-localise with Rab11, indicating that the serpin is not re-exported from athrocytes. Instead, mutations which block late endosome/lysosome fusion (dor, hk, and car) cause accumulation of Necrotic-positive endosomes, even in the absence of infection. Knockdown of the 6 Drosophila orthologues of the mammalian LDL receptor family with dsRNA identifies LpR1 as an enhancer of the immune response. Uptake of Necrotic from the haemolymph is blocked by a chromosomal deletion of LpR1. In conclusion, we identify the cells and the receptor molecule responsible for the uptake and degradation of the Necrotic serpin in Drosophila melanogaster. The scavenging of serpin/proteinase complexes may be a critical step in the regulation of proteolytic cascades

    Wege des Viruseintritts: am Beispiel der Erkältungsviren

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    Stylistic figure of illusion and reality in the publicistic text of the 2010-th years

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    В статье рассматривается специфика употребления одной из фигур речи в заголовке публицистического текста 2010-х годов - оксюморона. Особое внимание уделяется продуктивной модели оксюморона и новизне его использования в заголовках современных публицистических текстов. Установлено, что по сравнению с известными функциями (эмоционально-оценочной, функцией интриги адресата), свойственными и художественному тексту, в современных публицистических текстах оксюморон выполняет смысловую функцию: через иллюзию, ирреальность отражает реальное, рациональное. Оксюморон анализируются как продукт лингвокреативной практики журналиста, а также в контексте стилистики и коммуникативной направленности текста. В ходе контекстуального анализа оксюморон рассматривается не только как стилистическая фигура, он признается особым приемом построения современного публицистического текста. Особое внимание уделено использованию оксюморона с целью отражения алогичности событий, явлений, которые отражаются в публицистическом тексте, а также его функциям в конкретных текстах. В статье отражается сопоставление функций оксюморона в художественном тексте и публицистическом тексте 2010-х годов. Отмечается, что оксюморон - редкая фигура речи в публицистическом тексте, которая используется главным образом в заголовках текстов, выполняя оценочную и особую смысловую функции.The specific of the use of one of the figures of speech - the oxymoron - in the headline of the publicistic text of the 2010s is considered. Particular attention is paid to the productive model of the oxymoron and the novelty of its use in the headlines of modern journalistic texts. It is determined that, in comparison with the known functions (emotionally-valued, the function of intrigue of the addressee), peculiar as well to the artistic text, in modern publicistic texts the oxymoron fulfills the semantic function: through illusion, unreal reflects real, rational. Oxymoron is analyzed as a product of the linguistic-creative practice of a journalist, as well as in the context of the stylistics and communicative orientation of the text. During the contextual analysis, the oxymoron is considered not only as a stylistic figure, but it is recognized as a special method of constructing a modern publicistic text. Particular attention is paid to the use of an oxymoron in order to reflect the illogicality of events, occurrences that are reflected in the publicistic text, as well as to its functions in specific texts. The article reflects the comparison of the functions of the oxymoron in the artistic text and the publicistic text of the 2010s. It is noted that an oxymoron is a rare figure of speech in a publicistic text, which is used mainly in the headings of texts, performing evaluative and special semantic functions

    Paronymyas a Source of Language Game and Generation of Creative Text

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    В статье анализируется роль паронимии в афоризме как малом речевом жанре; паронимия дифференцируется на слова-паронимы и слова-парономазы. Паронимы и парономазы, отражая языковую игру на уровне семантики и звукового состава слов, являются средством порождения афоризма как интеллектуального жанра, острый смысл которого усиливается паронимией. Афоризм рассматривается как малый речевой жанр, представляющий собой креативный текст, созданный конкретным автором, который обладает высоким уровнем языковой компетентности. Демонстрируется то, как созвучные по форме слова включаются в механизмы языковой игры на уровне семантики и общих фоновых знаний адресата и адресанта. Анализ афоризмов с точки зрения использования в них паронимов и парономазов показывает, что благодаря обыгрыванию их разных значений создается креативный текст с глубоким подтекстом иронической или комической тональности. В статье выявляются основные приемы использования в афоризмах паронимов и парономазов, при этом учитываются и авторские неологизмы.The article examines the role of paronymy in the aphorism as a small speech genre; paronymy is differentiated into words-paronyms and words-paronomas. Reflecting the language game at the level of semantics and sound structure of words, paronyms and paronomas serve asa meanof generating an aphorism as an intellectual genre, a keen sense of which is enhanced by paronymy.Aphorism is considered as a small speech genre - creative text written by specific author with a high level of language competence. It demonstrates how consonant forms of words become part of the mechanisms of language game at level of semantics and general background knowledge of the sender and the recipient. Analysis of aphorisms in terms of using paronyms and paronomas shows that thanks to the play with their different values within a small volume of text, the creative text with the deep implied sense of ironic or comic tone is created. The article identifies the main techniques for using paronymsand paronomas in aphorisms; the author neologismsare also taken into account

    Statistical evaluation of the equivalence scale based on joint accommodation for households of the Russian Federation

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    © 2015, Econjournals. All rights reserved. In this article an evaluation of equivalence scales for households of the Russian Federation is made using the data from “Russian monitoring of the economic situation and public health HSE” for the year 2013. Calculation of equivalence scales is done through a regression estimate of the Engel curve. Identified on the basis of the value of the resulting regression model scale are significantly different from the official scale of the Federal State Statistics Service of the Russian Federation. The authors have shown that it has significant implications for the evaluation of the relative poverty of certain vulnerable groups, in turn, has great significance for the implementation of targeted social policies
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