87 research outputs found
Approaches of Russian oil companies to optimal capital structure
Oil companies play a vital role in Russian economy. Demand for hydrocarbon products will be increasing for the nearest decades simultaneously with the population growth and social needs. Change of raw-material orientation of Russian economy and the transition to the innovative way of the development do not exclude the development of oil industry in future. Moreover, society believes that this sector must bring the Russian economy on to the road of innovative development due to neo-industrialization. To achieve this, the government power as well as capital management of companies are required. To make their optimal capital structure, it is necessary to minimize the capital cost, decrease definite risks under existing limits, and maximize profitability. The capital structure analysis of Russian and foreign oil companies shows different approaches, reasons, as well as conditions and, consequently, equity capital and debt capital relationship and their cost, which demands the effective capital management strategy
Жизненный и творческий путь академика М. М. Павлюченко
The article is devoted to the 110 anniversary of the birth of the Belarusian scientist, the founder of the section of chemical science – Chemistry of solids, the organizer and the first director of Institute of the General and Inorganic Chemistry of the National Academy of Sciences of Belarus, academician of the Academy of Sciences of Belarus – Mikhail Mikhaylovich Pavlyuchenko. In the article, the career devoted to search of the implication and chemical mechanism of the processes proceeding with participation of solids is described. Identification of the defining stages (limiting stages) and regularities of thermal dissociation reactions and synthesis of different classes and various structure of substances, as well as the definition of ways to operate these processes are described in this paper. His pedagogical and practical activities were purposeful, he looked for and found the young people interested in scientific research, excited them with his ideas, prepared 40 candidates and 3 Doctors of Chemistry. Together with the academician N. F. Ermolenko and the engineering structure of the institute, he prepared, proved the ways and possibilities of use and enrichment of sylvinites of the Starobinsky field, and repeatedly reported for the government and wide audience on importance of chemical industry development in Belarus. His course of life is a service to science and the Homeland.Статья посвящена 110-летию со дня рождения белорусского ученого, основателя раздела химической науки – химия твердого тела, организатора и первого директора Института общей и неорганической химии НАН Беларуси, академика Академии наук БССР Михаила Михайловича Павлюченко. Приводится описание его жизненного и творческого пути, показан поиск глубинного смысла химического механизма процессов, протекающих с участием твердых тел, выявлены определяющие этапы (лимитирующие стадии) и закономерности реакций термической диссоциации и синтеза разных классов и различной структуры веществ, а также определены пути и способы управления этими процессами. Его педагогическая и практическая деятельность были целенаправленными, он искал и находил заинтересованных в научных исследованиях молодых людей, увлекал их своими идеями и вел за собой. Им подготовлено 40 кандидатов и 3 доктора химических наук. Совместно с академиком Н. Ф. Ермоленко, инженерным составом Института подготовил, обосновал пути и возможности использования и обогащения сильвинитов Старобинского месторождения. Неоднократно докладывал перед правительством и широкой аудиторией о важности развития химической промышленности в Беларуси. Его жизненный путь – это служение науке и Родине
Group B <em>Streptococcus </em>engages an inhibitory siglec through sialic acid mimicry to blunt innate immune and inflammatory responses <em>in vivo</em>
Group B Streptococcus (GBS) is a common agent of bacterial sepsis and meningitis in newborns. The GBS surface capsule contains sialic acids (Sia) that engage Sia-binding immunoglobulin-like lectins (Siglecs) on leukocytes. Here we use mice lacking Siglec-E, an inhibitory Siglec of myelomonocytic cells, to study the significance of GBS Siglec engagement during in vivo infection. We found GBS bound to Siglec-E in a Sia-specific fashion to blunt NF-κB and MAPK activation. As a consequence, Siglec-E-deficient macrophages had enhanced pro-inflammatory cytokine secretion, phagocytosis and bactericidal activity against the pathogen. Following pulmonary or low-dose intravenous GBS challenge, Siglec-E KO mice produced more pro-inflammatory cytokines and exhibited reduced GBS invasion of the central nervous system. In contrast, upon high dose lethal challenges, cytokine storm in Siglec-E KO mice was associated with accelerated mortality. We conclude that GBS Sia mimicry influences host innate immune and inflammatory responses in vivo through engagement of an inhibitory Siglec, with the ultimate outcome of the host response varying depending upon the site, stage and magnitude of infection
Life-threatening hypersplenism due to idiopathic portal hypertension in early childhood: case report and review of the literature
<p>Abstract</p> <p>Background</p> <p>Idiopathic portal hypertension (IPH) is a disorder of unknown etiology and is characterized clinically by portal hypertension, splenomegaly, and hypersplenism accompanied by pancytopenia. This study evaluates the pathogenic concept of the disease by a systematic review of the literature and illustrates novel pathologic and laboratory findings.</p> <p>Case Presentation</p> <p>We report the first case of uncontrolled splenic hyperperfusion and enlargement with subsequent hypersplenism leading to life-threatening complications of IPH in infancy and emergent splenectomy.</p> <p>Conclusions</p> <p>Our results suggest that splenic NO and VCAM-1, rather than ET-1, have a significant impact on the development of IPH, even at a very early stage of disease. The success of surgical interventions targeting the splenic hyperperfusion suggests that the primary defect in the regulation of splenic blood flow seems to be crucial for the development of IPH. Thus, beside other treatment options splenectomy needs to be considered as a prime therapeutic option for IPH.</p
Defining the molecular role of gp91phox in the immune manifestation of acute allergic asthma using a preclinical murine model
<p>Abstract</p> <p>Objective</p> <p>The phenomena manifested during inflammation require interplay between circulating effector cells, local resident cells, soluble mediators and genetic host factors to establish, develop and maintain itself. Of the molecues involed in the initiation and perpetuation of acute allergic inflammation in asthma, the involvement of effector cells in redox reactions for producing O<sub>2</sub><sup>- </sup>(superoxide anion) through the mediation of NADPH oxidase is a critical step. Prior data suggest that reactive oxygen species (ROS) produced by NADPH oxidase homologues in non-phagocytic cells play an important role in the regulation of signal transduction, while macrophages use a membrane-associated NADPH oxidase to generate an array of oxidizing intermediates which inactivate MMPs on or near them.</p> <p>Materials and Methods and Treatment</p> <p>To clarify the role of gp91phox subunit of NADPH oxidase in the development and progression of an acute allergic asthma phenotype, we induced allergen dependent inflammation in a gp91<it><sup>phox</sup></it>-/- single knockout and a gp91phox-/-MMP-12-/- double knockout mouse models.</p> <p>Results</p> <p>In the knockout mice, both inflammation and airway hyperreactivity were more extensive than in wildtype mice post-OVA. Although OVA-specific IgE in plasma were comparable in wildtype and knockout mice, enhanced inflammatory cell recruitment from circulation and cytokine release in lung and BALf, accompanied by higher airway resistance as well as Penh in response to methacholine, indicate a regulatory role for NADPH oxidase in development of allergic asthma. While T cell mediated functions like Th2 cytokine secretion, and proliferation to OVA were upregulated synchronous with the overall robustness of the asthma phenotype, macrophage upregulation in functions such as proliferation, and mixed lymphocyte reaction indicate a regulatory role for gp91phox and an overall non-involvement or synergistic involvement of MMP12 in the response pathway (comparing data from gp91phox-/- and gp91phox-/-MMP-12-/- mice).</p
PREPARATION AND PROPERTIES OF MURINE ANTI-IDIOTYPIC MONOCLONAL ANTIBODIES RECOGNIZING PRIMARY RABBIT POLYCLONAL ANTIBODIES AGAINST MORPHINE DERIVATIVES
Anti-idiotypic antibodies (Ab2), according to the network theory of Jerne, are second-generation immunoglobulins that are produced against the idiotype of an antibody to a specific antigen. Despite the large number of works devoted to the study of the properties of these proteins, their role in the regulation of the immune system is not fully known. It may consist in maintaining or blocking a minimal immune response to the antigen. The study of Ab2 is of great practical and scientific importance. The special properties of Ab2, namely, the ability to partially reproduce the structure of the primary antigen and, upon immunization, induce the appearance of tertiary antibodies, which, like first-generation antibodies, can bind to the antigen, have found application in the development of Ab2-based vaccines, in particular, for the treatment of tumors. In view of the presence of a number of limitations on research related to psychoactive substances, the development of Ab2- based vaccines against drug addiction also seems promising. To example, anti-idiotypic antibodies obtained for this purpose possessing a cocaine-like structure are described in the literature. In this work, murine monoclonal anti-idiotypic antibodies (mAb2) mimicking the structure of various morphine derivatives were obtained. Rabbit polyclonal antibodies to the 6-hemisuccinyl derivative of morphine conjugated with bovine serum albumin isolated by affinity chromatography were used as primary antibodies for immunization. Four hybridoma clones were obtained as a result of the fusion of immunized mice lymphocytes with mouse Sp2/0 mouse myeloma cells by the Milstein-Köhler method. After growth in animals, mAb2 produced by hybridoma cells were affinity purified. We investigated the physicochemical and antigenic properties of the isolated antibodies. It was shown that the obtained mAb2 differ in immunological specificity, competing in different degree with morphine derivatives for binding to first-generation antibodies. We tested the possibility of using the obtained mAb2 as antigen analogues in the solid-phase enzyme-linked immunosorbent assay to determine the titer of primary antibodies against morphine in the blood serum of laboratory animals immunized with morphine derivatives. Based on the obtained anti-idiotypic antibodies, it is proposed to develop test systems to determine the serum opiate-specific antibodies in people after specific vaccination for therapeutic or prophylactic purposes to avoid the use of drugs as antigens immobilized on the solid phase in the analysis
Preparation of polyclonal and monoclonal anti-idiotypic antibodies against morphine-specific immunoglobulins
The preparation and study of anti-idiotypic (secondary) antibodies (Ab2) against monoclonal primary antibodies (Ab1) specific to biologically active molecules with a known structure is of great scientific and practical importance. Due to partial antigenic similarity of Ab2 and the initial antigen structures, these antibodies can be the basis of the vaccine, if the antigen usage is not possible, or is limited by law. In particular, one may create Ab2-based preparations, designed for immunization, in order to prevent and treat the drug addiction. The value of Ab2 properties increases even more if Ab1, used to obtain them, recognize different parts of the antigen molecule, which makes it possible to obtain second-generation antibodies with a wide range of specificity. In this work, the morphine-like polyclonal and monoclonal Ab2 were obtained. In each case, as the first-generation immunoglobulins for immunization, we used two murine monoclonal antibodies (mAbs) specific to different morphine derivatives: 3K11 antibodies to 3-0-carboxymethyl (CMM) and 2-p-carboxyphenylazomethyl (FAM) derivatives, as well as 6G1 antibodies to 6-hemisuccinyl derivative (GSM). After immunization of the horse with Ab1 and development of immune response, three pools of specific polyclonal antibodies were isolated from the animal blood serum: horse anti-species antibodies to the total mouse immunoglobulins (HAM); horse anti-idiotypic antibodies against 3K11 antibodies (HAM-K11), and against 6G1 antibodies (HAM-G1). In parallel, immunization of mice with 3K11 and 6G1 antibodies and fusion of obtained lymphocytes with Sp2/0 mouse myeloma cells by the Milstein-Köhler method resulted in three producers of anti-idiotypic antibodies: a clone producing mouse monoclonal Ab2 specific for mAb-6G1 (AIG1), as well as clones producing anti-mAb-3K11 antibodies (AI-K11A and AI-K11B). The physico-chemical and antigenic properties of all the Ab2 obtained were characterized. It was shown that the horse anti-idiotypic immunoglobulins not only belong to different classes, but are also polyvalent, while all monoclonal Ab2 obtained are represented by IgM immunoglobulins, being also strictly specific to the corresponding first-generation antibodies. Subsequently, the morphine-like properties of the first domestic polyclonal and monoclonal Ab2 obtained in the work will be investigated in a cellular model. Likewise, we shall study their ability to induce Ab3 as well as morphine-specific Ab1
Improved monitoring of clinical response in Systemic Lupus Erythematosus by longitudinal trend in soluble vascular cell adhesion molecule-1
This work was funded by Arthritis Research UK. MJL holds an Arthritis Research UK Clinician Scientist Fellowship (19631), and was previously supported by the St Thomas’ Lupus Trust. The study received support from the National Institute for Health Research (NIHR)-funded Flow Cytometry Core Facility and the Biomedical Research Centre based at Guy’s & St. Thomas’ National Health Service (NHS) Foundation Trust, in partnership with King’s College London
Роль наноструктурных модификаторов при получении композиционной корундовой керамики
Influence of highly disperse nanostructured modifiers of alumina – magnesia, partially stabilized zirconia – on the consolidation processes of composite ceramics of industrial corundum powders annealed at 1600–1700 °C, changes of its microstructure and physico-mechanical properties is investigated. It is established, that due to processes of self-diffusion of active modifiers there is a distribution of their nanograins on the borders of miсroparticles of corundum powder. In addition, nanostructured modifiers fill a pore space that causes sliding of particles under mechanical and thermal loads of material and transfers the mechanism of fragile destruction to pseudo-plastic. The entered nanostructured modifiers promote the process of lamellar zones formation throughout the material that also strengthens its mechanical properties. The correlation of composite ceramics structure and their physico-mechanical characteristics are developed.Исследовано влияние высокодисперсных наноструктурных модификаторов оксидов алюминия – магния, частично стабилизированного диоксида циркония на процессы консолидации композиционной керамики из промышленных порошков корунда, термообработанной при температуре 1600–1700 оС, изменения ее микроструктуры и физико-механических свойств. Установлено, что за счет процессов самодиффузии активных модификаторов происходит распределение их нанозерен по границам микрочастиц порошка корунда, а также заполнение порового пространства, что вызывает скольжение частиц при механических и тепловых нагрузках материала и переводит механизм хрупкого разрушения в псевдопластичный. Введенные наноструктурные модификаторы промотируют процесс образования пластинчатых зон в объеме материала, что также упрочняет его механические свойства. Разработаны составы композиционной керамики с повышенными физико-механическими характеристиками
Региональная адаптация федеральной модели оплаты медицинской помощи по клинико-статистическим группам на примере случаев госпитализации пациентов, требующих назначения генно-инженерных биологических препаратов
The existing model of financial support of medical assistance for clinical-statistical groups (CSGs) in 2018 provides for the reimbursement for hospital stay expenses by the compulsory medical insurance fund in patients claiming the need for genetically engineered biological products (GiBP) during their stay in a day-care or 24-hour inpatient facility. The payment is made to CSG no. 121 in a day care and to CSG no. 316 in a 24-hour inpatient facility. The heterogeneity of the expenses for therapy with GiBP necessitates further division of the Federal CSGs into subgroups located in the constituent parts of the Russian Federation. This process has been initiated in some parts of the country, and it is seen as a way of regional adaptation of the Federal Medical insurance model. The proposed subdivision of the Federal CSGs allows for setting the tariffs reflecting the real expenses incurred by a local medical organization due to the therapeutic use of GiBP. The models of such specific CSGs proposed by RF subjects (after an expert evaluation) can be taken as a basis for updating the Federal CSG model, taking into account the differences in the costs of different drug therapy regimens.Модель финансирования медицинской помощи по клинико-статистическим группам (КСГ) в 2018 г. предусматривает оплату случаев госпитализации пациентов, требующих назначение генно-инженерных биологических препаратов (ГИБП) в условиях дневного и круглосуточного стационара за счет средств системы общего медицинского страхования (ОМС). Оплата осуществляется в рамках КСГ №121 в дневном стационаре и КСГ №316 в круглосуточном стационаре. Стоимостная разнородность лекарственной терапии ГИБП обуславливает начатое в части субъектов РФ выделение подгрупп в составе федеральных КСГ, представляющее собой один из способов региональной адаптации модели, предложенный на федеральном уровне. Разукрупнение федеральных КСГ позволяет устанавливать тарифы в зависимости от фактически понесенных медицинской организацией затрат на лекарственную терапию ГИБП. Предложенные в субъектах РФ модели разукрупнения КСГ для назначения ГИБП после экспертной проработки могут быть взяты за основу актуализации федеральной модели КСГ, учитывающей различия в стоимости схем лекарственной терапии
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