Management decisions in organization management model

This article focuses on the problem of improving management decision-making in the modern organization. Despite the existence of a large number of publications devoted to this subject, the relevance of the problem of managerial decision-making in modern management is very important. The article contains an analysis of classifications management decisions and proposes decomposition method to a better understanding of management decision, to expand the scope of its application, to define the degree of responsibility for decision-making, to improve efficiency of management decisions. And thus, the decomposition of management decisions acts as one of the foundations development of methodological approaches to the formation of an information for management solutions.Данная статья посвящена проблеме совершенствования процесса принятия управленческих решений в современных условиях на предприятии. Несмотря на существование большого количества публикаций, затрагивающих данную тему, вопрос об актуальности проблемы принятия управленческих решений в современном менеджменте остается весьма значимым. В статье автором проводится анализ классификационных признаков управленческих решений, раскрывается сам процесс принятия управленческих решений в организации, и предлагается метод декомпозиции, который позволит лучше понять сущность управленческого решения, расширить область его применения, обозначить степень ответственности за принятие решений, повысить эффективность принимаемых управленческих решений. И таким образом, декомпозиция управленческих решений выступает в роли одной из основ разработки методологических подходов к формированию информационной обеспечивающей управленческих решений

Establishing the interaction between the CC chemokine ligand 5 and the receptors CCR1 and CCR5

Chemokines are important mediators and regulators of leukocyte trafficking, therefore, they play a crucial role in the development of inflammatory diseases. CCL5 or RANTES (regulated upon activation, normal T cell expressed and secreted) is a chemokine of relevance to many diseases. Moreover, CCL5-induced monocyte adhesion to inflamed endothelium was shown to be improved in the presence of CXCL4 (Platelet Factor 4). Since this synergy could be attributed to heterodimer formation, the first section of the present study surveys the structural interaction of CCL5 with CXCL4. The interaction was monitored employing the 15N-1H heteronuclear single quantum coherence (HSQC) nuclear magnetic resonance (NMR) technique. For this purpose, 15N-enriched CCL5 was recombinantly expressed in E. coli and subsequently purified. In HSQC spectroscopy, chemical shift changes were mainly observed in the N-terminal residues, which pointed toward a CC-type rather than a CXC-type interaction. Furthermore, small peptide antagonists, inhibiting the CXCL4/CCL5 dimerization, were designed (CKEY2 and the mouse orthologue MKEY). To investigate their pharmacological potential, the influence of MKEY on leukocyte adhesion to activated endothelium was monitored using intravital microscopy. As a control Met-CCT5, a strong antagonist for CCR1 and CCR5, was cloned, expressed and purified employing FPLC and HPLC techniques. Leukocyte recruitment was severely impaired in the presence of MKEY, compared to a control peptide (sMKEY) and in a similar range of Met-CCL5 which encourages the assumption that the synergy is mediated via the receptors CCR1 and/or CCR5. Despite all similarities, CCR1 and CCR5 were shown to mediate distinct functions when bound to CCL5, CCR1 rather mediates arrest and CCR5 appears to be more responsible for transendothelial migration. To establish which domains are important for this functional selectivity, we constructed different CCR5 variants with the distinct extracellular regions of CCR1. These chimeras were stably expressed in L1.2 and HEK293 cells and we investigated their function in response to CCL5, different CCL5 mutants, or together with CXCL4 using chemotaxis and cell arrest assays under laminar flow. First of all, CCL5, CCL5 40s and CCL5-E66A were recombinantly expressed and purified employing FPLC and HPLC techniques. By implementing CCL5 mutants (e.g. CCL5-E66A) with oligomerization defects in laminar flow assays, we were able to show that all receptor variants require oligomerization of CCL5 in order to function properly. In addition, our results reveal that the 40S loop of CCL5 is important for both the CCR1- and CCR5-mediated cell arrest. The 50s loop of CCL5, however, appeared to have a strong preference for CCR5 in inducing cell arrest, since CCR1 responded normal towards CCL5 50s and CCR5 being non-responsive. When the N-terminal domain of CCR5 was exchanged for that of CCR1, the resulting chimera was fully responsive towards CCL5 50s, suggesting that the N-terminal region of CCR1 interacts with the 50s domain of CCR5. The synergistic effect of CXCL4 on CCL5 induced cell arrest was observed in cells exclusively expressing CCR1 when compared to cells expressing CCR5. When the third extracellular loop of CCR1 was engineered into CCR5, the resulting chimeric receptor showed a significant response to the CXCL4/CCL5 heterocomplex, compared to CCL5 alone. These results were confirmed by constructing CCR1-based reverse chimeras for the N-terminal domain and the third extracellular loop. Furthermore we could show the heterodimerization of CCR1 and CCR5 and the synergy of the CXCL4/CCL5 complex is in THP-1 cells mediated via Gαi. In conclusion these results indicate that the extracellular regions of CCR1 and CCR5 have distinct and defined functions in leukocyte recruitment in response to CCL5. In the third section of this thesis the role of the sialyltransferase ST3Gal-IV on CCL5 receptor interaction was investigated, by using neutrophils and monocytes isolated from ST3Gal-IV deficient and from control mice in functional assays in vitro. The results indicate that the addition of sialic acids to the terminal portions of the N- or O-linked sugar chains of the corresponding receptors of CCL5 is of a minor importance for receptor binding and activation, since the cells similarly mobilize calcium upon stimulation with CCL5. Whereas, the adhesion of neutrophils and monocytes from ST3Gal-IV-/- was significant diminished. Taken together the results obtained here rather support the importance of ST3Gal-IV on the generation of functional selectins, which is in line with previous publications

Genetic dissection of a stem cell niche: the case of the Drosophila ovary

11 páginas, 6 figuras, 2 tablas.-- El material suplementario referido en este artículo puede verse en www.interscience.wiley.com/jpages/1058-8388/suppmatIn this work, we demonstrate a powerful new tool for the manipulation of the stromal component of a well-established Drosophila stem cell niche. We have generated a bric-a-brac 1 (bab1)-Gal4 line that drives UAS expression in many somatic ovary cell types from early larval stages. Using this Gal4 line, we could effectively induce FLP/FRT-mediated recombination in the stromal cells of the ovarian germline stem cell niche. Mutant clones were observed in the developing ovary of larvae and pupae, including in somatic cell types that do not divide in the adult, such as the cap cells and the terminal filament cells. Exploiting the ability of bab1-Gal4 to generate large clones, we demonstrate that bab1-Gal4 is an effective tool for analyzing stem cell niche morphogenesis and cyst formation in the germarium. We have identified a novel requirement for engrailed in the correct organization of the terminal filaments. We also demonstrate an involvement for integrins in cyst formation and follicle cell encapsulation. Finally using bab1-Gal4 in conjunction with the Gal80 system, we show that while ectopic dpp expression from stromal cells is sufficient to induce hyperplastic stem cell growth, neither activation nor inactivation of the BMP pathway within stromal cells affects germline stem cell maintenance.Grant sponsor: Spanish Ministerio de Ciencia y Tecnología; Grant number: BMC2003-01512; Grant sponsor: Junta de Andalucía; Grant number: CVI-280.Peer reviewe

Controlled intramyocardial release of engineered chemokines by biodegradable hydrogels as a treatment approach of myocardial infarction

Myocardial infarction (MI) induces a complex inflammatory immune response, followed by the remodelling of the heart muscle and scar formation. The rapid regeneration of the blood vessel network system by the attraction of hematopoietic stem cells is beneficial for heart function. Despite the important role of chemokines in these processes, their use in clinical practice has so far been limited by their limited availability over a long time-span in vivo. Here, a method is presented to increase physiological availability of chemokines at the site of injury over a defined time-span and simultaneously control their release using biodegradable hydrogels. Two different biodegradable hydrogels were implemented, a fast degradable hydrogel (FDH) for delivering Met-CCL5 over 24hrs and a slow degradable hydrogel (SDH) for a gradual release of protease-resistant CXCL12 (S4V) over 4weeks. We demonstrate that the time-controlled release using Met-CCL5-FDH and CXCL12 (S4V)-SDH suppressed initial neutrophil infiltration, promoted neovascularization and reduced apoptosis in the infarcted myocardium. Thus, we were able to significantly preserve the cardiac function after MI. This study demonstrates that time-controlled, biopolymer-mediated delivery of chemokines represents a novel and feasible strategy to support the endogenous reparatory mechanisms after MI and may compliment cell-based therapies

Учет расчетов с поставщиками в бюджетном учреждении

Выпускная квалификационная работа включает: 82 с. (без учета приложений), 25 таблиц, 8 рисунков, 39 источников и 13 приложений. Ключевые слова: казенное учреждение, бюджетный учет, учет расчетов с поставщиками, виды бюджетных учреждений, способы определения поставщиков. Объект исследования – Межмуниципальный отдел Министерства внутренних дел Российской Федерации «Асиновский» Управления Министерства внутренних дел Российской Федерации по Томской области. Цель работы – изучение особенностей организации учета расчетов с поставщиками в бюджетных учреждениях на примере МО МВД России «Асиновский».Final qualifying work include: 82. (excluding attachments), 25 tables, 8 figures, 39 13 sources and applications. Keywords: state institution, budgetary accounting, accounts payable, the types of budgetary institutions, methods of determination of suppliers. The object of study – Intermunicipal Department of the Ministry of internal Affairs of Russia "Asinovsky" of the Ministry of internal Affairs of the Russian Federation for Tomsk region. Purpose – to study the peculiarities of organization of accounting of calculations with suppliers in budgetary institutions on the example of MO the Ministry of internal Affairs of Russia "Asinovsky"