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Improvement of quality, function and transplantation outcomes of pancreatic islets using RNA interference
Kosinová, Lucie
Transplantation of insulin producing tissue is the only therapeutic method so far allowing type 1 diabetic patients to achieve long-term independence of insulin administration. Transplantation of isolated pancreatic islets (PI) into liver represents a safer but less effective alternative to whole-organ transplantation. This is caused by a significant loss of transplanted islets within a short time after transplantation due to the instant blood-mediated inflammatory reaction (IBMIR). This reaction is triggered by molecules of tissue factor, abundantly expressed on the surface of PI cells. Tissue factor activates directly the coagulation pathway leading to platelet aggregation, complement activation, and infiltration of islet graft by leukocytes which results in a destruction of up to 60 % of transplanted tissue, and a formation of ischemic areas of downstream lying liver tissue. Tissue factor also stimulates angiogenesis which makes it necessary for revascularization of PI after transplantation. Inhibition of tissue factor gene in isolated PI using RNA interference provides an opportunity for short-term suppression of tissue factor expression, leading to protection of PI in the early post-transplantation period without hindering the connection of capillaries to the recipient vascular system later...
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Improvement of quality, function and transplantation outcomes of pancreatic islets using RNA interference
Kosinová, Lucie ; Kříž, Jan (advisor) ; Štechová, Kateřina (referee) ; Petrák, Ondřej (referee)
Transplantation of insulin producing tissue is the only therapeutic method so far allowing type 1 diabetic patients to achieve long-term independence of insulin administration. Transplantation of isolated pancreatic islets (PI) into liver represents a safer but less effective alternative to whole-organ transplantation. This is caused by a significant loss of transplanted islets within a short time after transplantation due to the instant blood-mediated inflammatory reaction (IBMIR). This reaction is triggered by molecules of tissue factor, abundantly expressed on the surface of PI cells. Tissue factor activates directly the coagulation pathway leading to platelet aggregation, complement activation, and infiltration of islet graft by leukocytes which results in a destruction of up to 60 % of transplanted tissue, and a formation of ischemic areas of downstream lying liver tissue. Tissue factor also stimulates angiogenesis which makes it necessary for revascularization of PI after transplantation. Inhibition of tissue factor gene in isolated PI using RNA interference provides an opportunity for short-term suppression of tissue factor expression, leading to protection of PI in the early post-transplantation period without hindering the connection of capillaries to the recipient vascular system later...
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Study of the role of the B-chain N-terminus conformation of insulin in binding to the insulin receptor
Kosinová, Lucie ; Žáková, Lenka (advisor) ; Obšil, Tomáš (referee)
According to the International Diabetes Federation (IDF), there were 371 million people in the age from 20 to 79 years worldwide affected by diabetes in 2012. This means diabetes has become a global epidemic disease and, therefore, the importace of insulin research still grows. Insulin is a protein hormone that plays a key role in regulating blood glucose level which has a widespread impact on whole metabolism. Insulin acts through binding of its monomeric form to the insulin receptor. It is clear that insulin monomer has to undergo structural changes upon binding to the insulin receptor as the residues which are crucial for the interaction are burried within the native form. According to studies of highly active hormone analogs and the new information about the insulin-insulin receptor complex, there is a strong evidence that the C-terminal part of the B-chain is a dynamic element in insulin activation and receptor binding. Probably, there is also a great importance of the B-chain N- terminus and the transition between T and R conformations of insulin. However, the exact significance of the T and R states of insulin still remains unclear. In this work, several new insulin analogs AibB3-insulin, AibB5-insulin, AibB8- insulin, N-MeAlaB8-insulin and D-ProB8-insulin were prepared for the purpose of...
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Synthesis and characterization of AibB8LysB28ProB29-insulin to study T a R conformations of insulin
Kosinová, Lucie ; Stiborová, Marie (advisor) ; Flegel, Martin (referee)
According to the International Diabetes Federation, there were 285 million people in the age from 20 to 79 years suffering from diabetes on the planet in 2010. This means diabetes has become a global epidemic so the importace of insulin research is still growing. Insulin is a protein hormone that plays a key role in regulating blood glucose level which has a widespread impact on the whole metabolism. Insulin acts through binding of its monomeric form to the insulin receptor. At present, however, the active monomeric structure of insulin is still unknown. It is clear that insulin monomer must undergo structural changes upon binding to the insulin receptor as the residues crucial for the interaction are burried within the native form. According to studies of highly active hormon analogs there is an ample evidence that the C-terminal part of the B-chain is a dynamic element in insulin activation and receptor binding. Probably, there is also great importance of the B-chain N- terminus and the transition between T and R conformation. However, the exact significance of the T and R states of insulin remains unclear. In this work, a new insulin analog AibB8LysB28ProB29-insulin was prepared for the purpose of studying significance of the T and R conformations of insulin and their relationship to the active...
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Study of free volumes in Nafion using positronium
Košinová, Lucie ; Čížek, Jakub (advisor) ; Vlach, Martin (referee)
Title: Study of free volumes in Nafion using positronium Author: Lucie Košinová Department: Department of Low-Temperature Physics Supervisor: doc. Mgr. Jakub Čížek, Ph.D., Department of Low-Temperature Physics Abstract: The object of this thesis is investigation of the absorption of water in Nafion and the influence of temperature on the absorption and desorption kinetics. Study of the absorption and desorption of water was carried out either measurement of changes in the macroscopic physical properties of Nafion (weighing, differential scanning calorimetry) either by microscopic characterization of the size distribution of free volume that arises as a consequence of an imperfect arrangement of polymer chains. For this purpose I used a non- destructive method used positron annihilation spectroscopy, which is currently the only technique capable of determination of the size distribution of free volumes having the free volume distribution by size of a few Å. The development of the size distribution and the concentration free volumes in the sample were determined on the based on the measurement of lifetime spectra of positrons annihilating in the sample of Nafion. The results obtained in this thesis can be further used in research of Nafion, which is widely used as a semipermeable membrane during industrial...
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Study of free volumes in Nafion using positronium
Košinová, Lucie ; Čížek, Jakub (advisor) ; Vlach, Martin (referee)
Title: Study of free volumes in Nafion using positronium Author: Lucie Košinová Department: Department of Low-Temperature Physics Supervisor: doc. Mgr. Jakub Čížek, Ph.D., Department of Low-Temperature Physics Abstract: The object of this thesis is investigation of the absorption of water in Nafion and the influence of temperature on the absorption and desorption kinetics. Study of the absorption and desorption of water was carried out either measurement of changes in the macroscopic physical properties of Nafion (weighing, differential scanning calorimetry) either by microscopic characterization of the size distribution of free volume that arises as a consequence of an imperfect arrangement of polymer chains. For this purpose I used a non- destructive method used positron annihilation spectroscopy, which is currently the only technique capable of determination of the size distribution of free volumes having the free volume distribution by size of a few Å. The development of the size distribution and the concentration free volumes in the sample were determined on the based on the measurement of lifetime spectra of positrons annihilating in the sample of Nafion. The results obtained in this thesis can be further used in research of Nafion, which is widely used as a semipermeable membrane during industrial...
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Study of the role of the B-chain N-terminus conformation of insulin in binding to the insulin receptor
Kosinová, Lucie ; Žáková, Lenka (advisor) ; Obšil, Tomáš (referee)
According to the International Diabetes Federation (IDF), there were 371 million people in the age from 20 to 79 years worldwide affected by diabetes in 2012. This means diabetes has become a global epidemic disease and, therefore, the importace of insulin research still grows. Insulin is a protein hormone that plays a key role in regulating blood glucose level which has a widespread impact on whole metabolism. Insulin acts through binding of its monomeric form to the insulin receptor. It is clear that insulin monomer has to undergo structural changes upon binding to the insulin receptor as the residues which are crucial for the interaction are burried within the native form. According to studies of highly active hormone analogs and the new information about the insulin-insulin receptor complex, there is a strong evidence that the C-terminal part of the B-chain is a dynamic element in insulin activation and receptor binding. Probably, there is also a great importance of the B-chain N- terminus and the transition between T and R conformations of insulin. However, the exact significance of the T and R states of insulin still remains unclear. In this work, several new insulin analogs AibB3-insulin, AibB5-insulin, AibB8- insulin, N-MeAlaB8-insulin and D-ProB8-insulin were prepared for the purpose of...
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Synthesis and characterization of AibB8LysB28ProB29-insulin to study T a R conformations of insulin
Kosinová, Lucie ; Stiborová, Marie (advisor) ; Flegel, Martin (referee)
According to the International Diabetes Federation, there were 285 million people in the age from 20 to 79 years suffering from diabetes on the planet in 2010. This means diabetes has become a global epidemic so the importace of insulin research is still growing. Insulin is a protein hormone that plays a key role in regulating blood glucose level which has a widespread impact on the whole metabolism. Insulin acts through binding of its monomeric form to the insulin receptor. At present, however, the active monomeric structure of insulin is still unknown. It is clear that insulin monomer must undergo structural changes upon binding to the insulin receptor as the residues crucial for the interaction are burried within the native form. According to studies of highly active hormon analogs there is an ample evidence that the C-terminal part of the B-chain is a dynamic element in insulin activation and receptor binding. Probably, there is also great importance of the B-chain N- terminus and the transition between T and R conformation. However, the exact significance of the T and R states of insulin remains unclear. In this work, a new insulin analog AibB8LysB28ProB29-insulin was prepared for the purpose of studying significance of the T and R conformations of insulin and their relationship to the active...
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Airlines' integration and its impact on the consumer behaviour of customers.
Kosinová, Lucie ; Valentová, Jana (advisor) ; Hovorka, Lukáš (referee)
This thesis describes the process of integration between airlines and its positive and negative impacts on customers. It deals with characteristic features of individual forms of integration with the greatest attention paid to alliances and mergers. With respect to the fact that the passenger's choice of airline is to a large extent influenced by the price of the ticket, an empirical model is introduced to explore the impact of the membership in one of the global alliances on the final price of the long-haul tickets. Besides, the attention is paid to the nature and diversification of services provided. In the next section the thesis deals with the upcoming merger between British Airways and Iberia, its preconditions, form of the new company and identification of the potential risk factors that could have a negative impact on the company.
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Současné trendy v letecké dopravě
Kosinová, Lucie ; Vaško, Martin (advisor) ; Bakos, Tomáš (referee)
Bakalářská práce popisuje současné nejdůležitější trendy v letecké dopravě. Pozornost je věnována především regulaci a následné deregulaci odvětví, spolupráci mezi leteckými dopravci, řízení vztahu se zákazníky a využívání informačních technologií. V jednotlivých kapitolách je posuzován dopad těchto trendů na cestující a to především z hlediska zvyšování dostupnosti létání a snaze dopravců přimět cestující, aby si pro svoji cestu vybrali právě jejich společnost.
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