Формирование интегрированной системы менеджмента качества на предприятии

Объектом исследования является система менеджмента качества ООО "Томскводоканал". Цель: разработка рекомендаций по созданию и внедрению интегрированной системы менеджмента В процессе исследования проводились: ?Анализ литературных источников по теме ВКР. ?Изучение нормативно-методической базы для разработки документации. ?Анализ систем менеджмента ООО "Томскводоканал". ?Изучение специфики требований стандарта ISO 18000:2007. ?Изучение специфики требований стандарта ISO 14000:2015. -- Создание рекомендации по разработке и внедрению интегрированной системы менеджмента.Object of a research is the quality management system of LLC Tomskvodokanal. Purpose: development of recommendations about creation and introduction of the integrated system of management In the course of the research were carried out: ? The analysis of references on subject VKR. ? Studying of standard and methodical base for development of documentation. ? Analysis of systems of management of LLC Tomskvodokanal. ? Studying of specifics of requirements of ISO 18000:2007. ? Studying of specifics of requirements of ISO 14000:2015. - Creation of the recommendation about development and deployment of the integrated system of management

Инженерно-геологическое районирование промплощадки Эльгинского горно-обогатительного комбината в Якутии по несущей способности грунтов

Проведение инженерно-геологического районирования важно для перспективного планирования строительства на изучаемой территории в будущем. Огромную роль при этом играют опасные геологические процессы, распространенные на данной территории. Достаточно полную и достоверную картину состояния изучаемой территории по степени благоприятности ее к дальнейшему освоению может дать только комплексный анализ. Именно оценка наличия опасных инженерно-геологических процессов, данные о скорости их развития и распространения в пространстве и времени, а также учет их возможного негативного влияния на строительство и дальнейшую эксплуатацию позволит предотвратить экономический и социальный ущерб.Carrying out engineering and geological zoning is important for the future planning of construction in the study area in the future. A huge role in this is played by the dangerous geological processes common in this territory. Only a comprehensive analysis can give a sufficiently complete and reliable picture of the state of the studied territory by the degree of its favorableness for further development. It is an assessment of the presence of dangerous engineering and geological processes, data on the speed of their development and spread in space and time, as well as taking into account their possible negative impact on construction and further operation, will prevent economic and social damage

Life histories of the copepods Pseudocalanus minutus, P. acuspes (Calanoida) and Oithona similis (Cyclopoida) in the Arctic Kongsfjorden (Svalbard)

The year-round variation in abundance and stage-specific (vertical) distribution of Pseudocalanus minutus and Oithona similis was studied in the Arctic Kongsfjorden, Svalbard. Maxima of vertically integrated abundance were found in November with 111,297 ind m−2 for P. minutus and 704,633 ind m−2 for O. similis. Minimum abundances comprised 1,088 ind m−2 and 4,483 ind m−2 in June for P. minutus and O. similis, respectively. The congener P. acuspes only occurred in low numbers (15–213 ind m−2), and successful reproduction was debatable. Reproduction of P. minutus took place in May/June, and stage distribution revealed a 1-year life cycle with copepodids CIII, CIV, and CV as the overwintering stages. Oithona similis exhibited two main reproductive peaks in June and August/September, respectively. Moreover, it reproduced more or less continuously throughout the whole year with all stages occurring during the entire sampling period, suggesting two generations per year. Both species migrated towards greater depth in November, but O. similis preferred to stay longer in the upper 100 m as compared to Pseudocalanus. The reproduction of the two species in Kongsfjorden seemed to be linked to phytoplankton dynamics

Herstellung und Charakterisierung hochaffiner Inhibitoren für die Zytokine IL-6 und LIF basierend auf den Liganden-bindenden Domänen ihrer Rezeptor-Untereinheiten

Cytokines are small secreted proteins produced by different cell types in nearly all tissues. They are used as intercellular mediators being involved in the regulation of immunity and inflammation. Dysregulated cytokine production plays an important role in the development and progression of different diseases. Dysregulated IL-6 production can lead to chronic inflammatory diseases like rheumatoid arthritis or to different types of cancer. While the importance of fused cytokine receptors for the treatment of dysregulated cytokine production has already been noticed, their mode of action has not been studied in detail. This should be carried out in the present study for the IL-6 inhibitor IL-6 receptor fusion protein (IL-6-RFP) constructed in our group. The first part of this work presents a detailed biochemical characterization of the IL-6 inhibitor IL-6-RFP. This inhibitor comprises the ligand-binding domains of glycoprotein 130 (gp130) and interleukin-6 receptor alpha (IL-6R alpha), which were fused by a linker. In this work, it could be shown, that IL-6-RFP is a highly specific inhibitor which does not influence the bioactivities of the cognate IL-6-type cytokines OSM and LIF. Furthermore, a two-fold molar excess of IL-6-RFP over IL-6 is already sufficient to trap IL-6 completely in a binary IL-6/IL-6-RFP complex. The complex IL-6/IL-6-RFP is more stable and has a higher binding affinity than the complex of IL-6 and its soluble receptors sgp130 and sIL-6R alpha. Accordingly, IL-6 acts as an inhibitor by binding IL-6 in solution with a higher affinity than its soluble receptors and thereby neutralizing it. Because of its high affinity, IL-6-RFP resolves IL-6 from its receptor complex on the cell surface as could be shown by live cell imaging. Next, the stoichiometry of the complex IL-6/IL-6-RFP was analysed by blue native PAGE and gel filtration. It could be shown that the complex IL-6-/IL-6-RFP is built up in analogy to the hexameric IL-6 receptor complex, the structure of which was revealed by x-ray structure analysis in other studies. It was stated, that the IL-6 receptor complex is composed of two molecules of each IL-6, IL-6R alpha and gp130. The first part of the present study highlights that IL-6-RFP is a promising IL-6 inhibitor for the treatment of diseases caused by dysregulated IL-6 expression. IL-6-RFP is an inhibitor for a cytokine recruiting its receptors with all three receptor binding sites (sites I, II and III). But many cytokines bind to their receptors by using only their sites II and III. LIF, OSM, IL-27, IL-31 and other cytokines belong to this group. The aim of the second part of this work was to reveal how those cytokines can be blocked with the help of fused soluble receptors. As a prototype for such a new site II/III inhibitor an inhibitor for LIF should be constructed comprising the ligand-binding domains of the respective receptors. It was revealed that the first five domains of the murine LIFR [LIFR(D1-D5)] were sufficient for a potent binding of human LIF. For inhibition of human LIF the murine LIFR was used since it is known that the murine LIFR binds human LIF with an extraordinarily high affinity. For the precipitation of murine LIF the fusion protein mLIF-RFP was well suited. It is composed of the first N-terminal domains of the murine LIFR fused to the cytokine-binding module of murine gp130. In cell culture experiments it was demonstrated that a five-fold molar surplus of LIFR(D1-D5) or mLIF-RFP over human or murine LIF efficiently repressed the phosphorylation of STAT3. LIFR(D1-D5) and mLIF-RFP are specific inhibitors and do not inhibit the the bioactivity of IL-6. Furthermore, mLIF-RFP does not repress the bioactivity of the cognate cytokine OSM. For the complete inhibition of gene induction after stimulation of MEF cells with human or murine LIF an addition of LIFR(D1-D5) or mLIF-RFP in a molar ratio of 1:1 was already sufficient. The construction of the site II/III inhibitor mLIF-RFP is a strategy which can be applied for the development of other cytokine inhibitors based on the fusion of ligand binding receptor domains. These site II/III inhibitors could become useful tools for the investigation of the cytokines´ functions or for the treatment of diseases caused by dysregulated cytokine expression

Herstellung und Charakterisierung hochaffiner Inhibitoren für die Zytokine IL-6 und LIF basierend auf den Liganden-bindenden Domänen ihrer Rezeptor-Untereinheiten

Cytokines are small secreted proteins produced by different cell types in nearly all tissues. They are used as intercellular mediators being involved in the regulation of immunity and inflammation. Dysregulated cytokine production plays an important role in the development and progression of different diseases. Dysregulated IL-6 production can lead to chronic inflammatory diseases like rheumatoid arthritis or to different types of cancer. While the importance of fused cytokine receptors for the treatment of dysregulated cytokine production has already been noticed, their mode of action has not been studied in detail. This should be carried out in the present study for the IL-6 inhibitor IL-6 receptor fusion protein (IL-6-RFP) constructed in our group. The first part of this work presents a detailed biochemical characterization of the IL-6 inhibitor IL-6-RFP. This inhibitor comprises the ligand-binding domains of glycoprotein 130 (gp130) and interleukin-6 receptor alpha (IL-6R alpha), which were fused by a linker. In this work, it could be shown, that IL-6-RFP is a highly specific inhibitor which does not influence the bioactivities of the cognate IL-6-type cytokines OSM and LIF. Furthermore, a two-fold molar excess of IL-6-RFP over IL-6 is already sufficient to trap IL-6 completely in a binary IL-6/IL-6-RFP complex. The complex IL-6/IL-6-RFP is more stable and has a higher binding affinity than the complex of IL-6 and its soluble receptors sgp130 and sIL-6R alpha. Accordingly, IL-6 acts as an inhibitor by binding IL-6 in solution with a higher affinity than its soluble receptors and thereby neutralizing it. Because of its high affinity, IL-6-RFP resolves IL-6 from its receptor complex on the cell surface as could be shown by live cell imaging. Next, the stoichiometry of the complex IL-6/IL-6-RFP was analysed by blue native PAGE and gel filtration. It could be shown that the complex IL-6-/IL-6-RFP is built up in analogy to the hexameric IL-6 receptor complex, the structure of which was revealed by x-ray structure analysis in other studies. It was stated, that the IL-6 receptor complex is composed of two molecules of each IL-6, IL-6R alpha and gp130. The first part of the present study highlights that IL-6-RFP is a promising IL-6 inhibitor for the treatment of diseases caused by dysregulated IL-6 expression. IL-6-RFP is an inhibitor for a cytokine recruiting its receptors with all three receptor binding sites (sites I, II and III). But many cytokines bind to their receptors by using only their sites II and III. LIF, OSM, IL-27, IL-31 and other cytokines belong to this group. The aim of the second part of this work was to reveal how those cytokines can be blocked with the help of fused soluble receptors. As a prototype for such a new site II/III inhibitor an inhibitor for LIF should be constructed comprising the ligand-binding domains of the respective receptors. It was revealed that the first five domains of the murine LIFR [LIFR(D1-D5)] were sufficient for a potent binding of human LIF. For inhibition of human LIF the murine LIFR was used since it is known that the murine LIFR binds human LIF with an extraordinarily high affinity. For the precipitation of murine LIF the fusion protein mLIF-RFP was well suited. It is composed of the first N-terminal domains of the murine LIFR fused to the cytokine-binding module of murine gp130. In cell culture experiments it was demonstrated that a five-fold molar surplus of LIFR(D1-D5) or mLIF-RFP over human or murine LIF efficiently repressed the phosphorylation of STAT3. LIFR(D1-D5) and mLIF-RFP are specific inhibitors and do not inhibit the the bioactivity of IL-6. Furthermore, mLIF-RFP does not repress the bioactivity of the cognate cytokine OSM. For the complete inhibition of gene induction after stimulation of MEF cells with human or murine LIF an addition of LIFR(D1-D5) or mLIF-RFP in a molar ratio of 1:1 was already sufficient. The construction of the site II/III inhibitor mLIF-RFP is a strategy which can be applied for the development of other cytokine inhibitors based on the fusion of ligand binding receptor domains. These site II/III inhibitors could become useful tools for the investigation of the cytokines´ functions or for the treatment of diseases caused by dysregulated cytokine expression

Особенности эксплуатации компрессорной станции магистрального газопровода в условиях распространения многолетнемерзлых грунтов

Определение особенностей эксплуатации компрессорной станции с учетом снижения степени воздействия ряда негативных факторов и принятия решения для обеспечения безотказной работы оборудования.Determination of the features of explotation of the compressor station, taking into account the reduction in the degree of impact of a number of negative factors and the decision to ensure trouble-free operation of equipment

Characterization of the Interleukin (IL)-6 Inhibitor IL-6-RFP: fused receptor domains act as high affinity cytokine-binding proteins.

Although fusion proteins of the extracellular parts of receptor subunits termed cytokine traps turned out to be promising cytokine inhibitors for anti-cytokine therapies, their mode of action has not been analyzed. We developed a fusion protein consisting of the ligand binding domains of the IL-6 receptor subunits IL-6Ralpha and gp130 that acts as a highly potent IL-6 inhibitor. Gp130 is a shared cytokine receptor also used by the IL-6-related cytokines oncostatin M and leukemia inhibitory factor. In this study, we have shown that the IL-6 receptor fusion protein (IL-6-RFP) is a specific IL-6 inhibitor that does not block oncostatin M or leukemia inhibitory factor. We characterized the complex of IL-6-RFP and fluorescently labeled IL-6 (YFPIL-6) by blue native PAGE and gel filtration. A 2-fold molar excess of IL-6-RFP over IL-6 was sufficient to entirely bind IL-6 in a complex with IL-6-RFP. As shown by treatment with urea and binding competition experiments, the complex of IL-6 and IL-6-RFP is more stable than the complex of IL-6, soluble IL-6Ralpha, and soluble gp130. By live cell imaging, we have demonstrated that YFP-IL-6 bound to the surface of cells expressing gp130-CFP is removed from the plasma membrane upon the addition of IL-6-RFP. The apparent molecular mass of the IL-6.IL-6-RFP complex determined by blue native PAGE and gel filtration suggests that IL-6 is trapped in a structure analogous to the native hexameric IL-6 receptor complex. Thus, fusion of the ligand binding domains of heteromeric receptors leads to highly specific cytokine inhibitors with superior activity compared with the separate soluble receptors