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Stress tests conducted by Czech National Bank and market risk modelling in big Czech banks
Fedynets, Yuriy ; Šedivý, Jan (advisor) ; Dvořák, Michal (referee)
This bachelor thesis deals with bank stress testing practices and risk modelling, risk measurement and risk management in banking sector. The theoretical part is focused on definition and description of different types of market risk, models and instruments used for their measurement, regulation, explanation of the nature of stress tests and their further classification. Output of the practical part includes analysis of stress tests conducted by Czech National Bank in recent years and their comparison with reality, replication of VaR calculation of the foreign exchange instruments of the real banking portfolio and measurement of the impact of the adverse market events on the banks financial situation.
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Assessing the Fiscal Sustainability of the Czech Republic
Ambriško, Róbert ; Dingová, Vilma ; Dvořák, Michal ; Hájková, Dana ; Hromádková, Eva ; Kulhavá, Kamila ; Štiková, Radka
We present a model of public finance for the Czech Republic that addresses the main sources of risks to long-term fiscal sustainability: ageing-related expenditures and revenues, and the corresponding evolution of government debt. The baseline model is based on recent demographic projections issued by the Czech Statistical Office that forecast a shrinking share of the working-age population. Along with regulations and microeconomic incentives embedded in the tax and expenditure systems, demographic developments will affect economic growth and government expenditure and revenues in the long run. Population ageing is found to have a significant impact on future government expenditure via spending on old-age pensions and health care, where the cost profiles are modelled to reflect technological progress in the treatment of ageing-related illnesses. The analysis shows that under the current policy settings, a compound demographic effect will cause the primary government balance to turn negative at the beginning of the 2030s. The growing primary deficits, along with interest payments, which react to debt dynamics, will lead to a rapid escalation of government debt. While the outcome of the model is dependent on the specific settings of macroeconomic trends and policy variables, our wide range of sensitivity analyses show that without a policy response, even the most optimistic population scenario delivers an unsustainable path for public finances.
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Molecular mechanisms of amoeboid invasion of cancer cells
Paňková, Daniela ; Brábek, Jan (advisor) ; Dvořák, Michal (referee) ; Vomastek, Tomáš (referee)
Tumour cell invasion is one of the most critical steps in malignant progression. It includes a broad spectrum of mechanisms, including both individual and collective cell migration, which enables them to spread towards adjacent tissue, and form new metastases. Understanding the mechanisms of cell spreading, and invasion, is crucial for effective anticancer therapy. Two modes of individual migration of tumour cells have been established in a three-dimensional environment. Mesenchymally migrating cells use proteases to cleave collagen bundles, and thus overcome the ECM barriers. Recently described protease-independent amoeboid mode of invasion has been discovered in studies of cancer cells with protease inhibitors. During my PhD study, I have focused on determining the molecular mechanisms involved in amoeboid invasion of tumour cells. We have examined invasive abilities in non-metastatic K2 and highly metastatic A3 rat sarcoma cell lines. We have shown that even though highly metastatic A3 rat sarcoma cells are of mesenchymal origin, they have upregulated Rho/ROCK signalling pathway. Moreover, A3 cells generate actomyosin-based mechanical forces at their leading edges to physically squeeze through the collagen fibrils by adopting an amoeboid phenotype. Amoeboid invasiveness is also less dependent on...
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DNA damage and signalling pathways in cellular senescence
Hubáčková, Soňa ; Hodný, Zdeněk (advisor) ; Dvořák, Michal (referee) ; Růžičková, Šárka (referee)
Organisms such as mammals need tissue renewal as an important process for maintenance of their viability. Because proliferation is essential also for tumourigenesis, cells need tumour-suppressor mechanisms to protect organism against cancer. Cellular senescence, the permanent state of cell-cycle arrest, features one of these intrinsic barriers against tumourigenesis after DNA damage and understanding of this process may lead to finding of novel therapeutic targets and to optimization of chemotherapy for patients with cancer. In the first part of the PhD thesis, we investigated activation of JAK/STAT signalling pathway in drug-induced senescence. We used genotoxic drugs like aphidicolin, camptothecine, 5-bromo- 2'-doexyuridin, etoposide or thymidine to induce premature senescence in normal and cancer cells. All this chemicals were able to persistently activate JAK/STAT signalling in monitored cells. Activation of STATs was accompanied with up-regulation of expression of interferon-stimulated genes (ISGs), such as MX1, IRF1, IRF7 and PML. Since IRF1 and IRF7 can be directly involved in stimulation of the IFN genes, we show activated expression as well as secretion of IFNbeta and IFNgamma, but not IFNalpha in drug-induced senescent cells. Furthermore, an inhibition of JAK1 as a major kinase of STAT...
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Non-economic neocolonialism and its conflicts
Dvořák, Michal ; Riegl, Martin (advisor) ; Soukup, Jaromír (referee)
The aim of the thesis is to analyze specific phenomenon of non-economic neocolonialism and its conflicts. I have done the analysis of two conflicts (in Western Sahara and in Namibia) in context of the Cold War, I was trying to discover the context between dynamics and domestic political development of metropolitan country and the conflict. The next aspect was a regional dimension of the conflicts, that is why I analyzed the influence of neighboring countries and their motivation in the conflicts. The main aspect was an international dimension of the conflicts, that is why I examined the approach of the Soviet Union, the United States of America, the United Nations and the Organization of African Unity to the conflicts. The main research question was: What types of processes and mechanisms have led Namibia to independence, while the Western Sahara was still under foreign control? The next questions were: What led the superpowers to affect the conflicts, which were in the periphery of world competition? How behaved the world organizations during the conflicts? Had any influence in these conflicts? And last: What kind of interest had the neighboring countries in these conflicts?
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Regulation of transcription by proteins of the Early growth response and Myb families
Čermák, Vladimír ; Dvořák, Michal (advisor) ; Vomastek, Tomáš (referee) ; Elleder, Daniel (referee)
The regulation of transcription of tens of thousands of genes in a vertebrate organism is an enormously complex phenomenon which entails the participation of thousands of various regulatory proteins. The largest functional category of these regulators is accounted for by sequence-specific DNA-binding proteins known as transcription factors. Proteins of the EGR and Myb families of transcription factors are long-studied regulators of a variety of physiological processes including cellular proliferation and differentiation. The structural and physical aspects of their function have been well characterized. Their cell-type specific participation in complex gene-regulatory networks, on the other hand, is still incompletely understood and represents a major challenge in the respective research areas. Preliminary analysis of gene expression data from metastasizing PR9692 and non- metastasizing PR9692-E9 chicken sarcoma cell lines revealed that the transcription factor EGR1 is expressed at a higher level in metastasizing cells and can thus take part in the regulatory processes that underlie the differences between the two cell lines. Further investigation demonstrated that the introduction of exogenous EGR1 into PR9692-E9 cells restored their metastatic potential to a level indistinguishable from PR9692...
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Molecular mechanisms of fibroblastoid cell phenotype transitions:dedifferentiation of myofibroblasts and influencing of invasiveness and metastasis of sarcoma
Kosla, Jan ; Dvořák, Michal (advisor) ; Peková, Soňa (referee) ; Reiniš, Milan (referee)
Fibroblasts are the principal cellular component of the connective tissue. They are a heterogeneous group of cells which contribute to the structure of connective tissue and wound healing by their ability to produce extracellular matrix (ECM). Fibroblasts and cells derived from them are involved in many pathological processes such as formation of malignant tumors and fibrosis. Tumor progression which finally leads to metastasis is a serious biomedical problem. There is a growing body of the recent evidence showing an important role of the tumor stroma and its interaction with cancer cells in cancer progression. Tumor stroma comprises mainly of myofibroblasts and their products, namely ECM, soluble factors, and enzymes. Myofibroblasts contribute more or less to all steps of cancer progression. Furthermore myofibroblasts play a key role in fibrosis, another serious human disease which is not efficiently treatable and which is associated with cancer progression. These facts made us to search for molecular means capable of eliminating the myofibroblastic phenotype. We succeeded to entirely dedifferentiate primary myofibroblasts by concomitant inhibition of TGFβ signaling and perturbation of MAPK signaling in a chick model that we have introduced. Malignant fibroblasts form sarcomas. ECM is the first...
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The use of CAM assay for characterization and study of cancer cell invasive properties
Vágnerová, Lenka ; Dvořák, Michal (advisor) ; Geryk, Josef (referee)
The chorioallantoic membrane (CAM) of chicken embryos belongs to the in vivo model systems frequently used for the study of angiogenesis and cell invasiveness. Using CAM assay we have tested selected chicken sarcoma cell lines characterized by different angiogenic properties and different ability to form metastasis. In addition to CAM assay, several other methods have been used to characterize the phenotype of these cell lines. We have selected a few proteins which could significantly influence the angiogenic and metastatic properties of investigated cell lines. We have established cell lines stably overexpressing these genes and compared their phenotypes with parental cell lines. We have shown that genes encoding ISL1, ARNT2, PROM1, HOXA11 proteins participate, in our experimental model, in activation of programes controlling angiogenesis and cell invasion.
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Study of extracellular nucleic acids in maternal circulation in the cases of pathological and physiological pregnancies
Žejšková, Lenka ; Hromadníková, Ilona (advisor) ; Černá, Marie (referee) ; Dvořák, Michal (referee)
In 1997, Prof. Dennis Lo discovered the presence of cell-free fetal DNA (cffDNA) in the maternal plasma and serum of pregnant women. This finding started the development of new non-invasive prenatal diagnosis methods, which are currently in the forefront of the advanced care of mother and fetus. Non-invasive genetic tests based on the detection of paternally inherited alleles, including determination of fetal sex in cases at risk of X-linked disorders or congenital adrenal hyperplasia and RHD or RHCE genotyping in alloimunized pregnancies, were quickly introduced into routine practice. This thesis focuses on the basic characteristics of cffDNA and fetal cells in maternal circulation and its usage for non-invasive prenatal diagnosis, especially in cases of placental insufficiency related complications, e.g. preeclampsia and IUGR. This severe disorder is characterized by placental dysfunction with an abnormal invasion of trophoblasts and a defect in the transformation of maternal spiral arteries, leading to placental ischemia followed by increased apoptosis of trophoblast associated with an elevated concentration of cell-free nucleic acids in maternal circulation. Until recently, cffDNA quantification studies were mostly done using amplification of SRY or DYS-14 genes localized on chromosome Y, and...
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Regulace pre-mRNA sestřihu v prostředí buněčného jádra
Hnilicová, Jarmila ; Staněk, David (advisor) ; Půta, František (referee) ; Dvořák, Michal (referee)
Eukaryotic genes contain non-coding sequences - introns that are removed during pre-mRNA splicing by the spliceosome. The spliceosome is composed of five snRNPs (U1, U2, U4/U6 and U5) which assemble on pre-mRNA in a step-wise manner and together with additional non-snRNP proteins catalyse splicing. Mutations in splicing factors can cause severe diseases, for example a point missense mutation (called AD29) in hPrp31 (U4/U6 snRNP specific protein) induces retinitis pigmentosa, disease often leading to complete blindness. In this PhD thesis we show that the hPrp31 AD29 mutant is unstable and is not properly incorporated into spliceosomal snRNPs. In addition, the expression of the mutant protein reduces cell proliferation, which indicates that it interferes with cellular metabolism (likely splicing) and could explain the induction of retinitis pigmentosa. Next, we focus on a role of nuclear environment in pre-mRNA splicing. It was shown that new U4/U6·U5 snRNPs are preferentially assembled in non-membrane nuclear structure - Cajal body. Here we expand this finding and provide evidence that Cajal bodies are also important for U4/U6·U5 snRNP recycling after splicing. In addition, we analyzed a role of chromatin and particularly histone acetylation modulates in splicing regulation. Using inhibitor of...
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