The thesis analyses the female patients' data from Clinical hematology department in České Budějovice hospital from year 2014 to 2015 and tries to statistically confirm connection between D-dimer level and hypercoagulable states described in previous bachelor thesis. D-dimer assay is due to negative predictive value and high sensitivity an initial laboratory test to rule out tromboembolic disease. However, it has low specificity. The elevated level of D-dimer is observed in conditions like infection, trauma, acute cancer, recent surgery or pregnancy and last studies showed increased D-dimer level even in combination with inherited hypercoagulable states. Thus, it is necessary to analyse the level of D-dimer in pregnant women related to specific hypercoagulable states. Moreover, the thesis analyses the influence of other factors like anticoagulation therapy on D-dimer level and tries to find connection between D-dimer level and pregnancy associated complication, birth weight or a type of delivery.

This thesis was about the relationship of the Factor V Leiden mutation and activated protein C resistance. I looked up patients with Leiden mutation and activated protein C resistance. I monitored the frequency of thromboembolism and miscarriages in the personal and family case history of patients. Subsequently, I looked up if other risk factors which affect clinical manifestations in patients with this mutation can be found.

1. Abstract Pheochromocytoma/ paraganglioma (FEO/PGL) may be developed on the basis of an inherited genetic mutation of different genes. They are associated with a high risk of developing of secondary hypertension, organ damage and metastatic disease that can be fatal. The aim was to focus on the possibility of genetic testing in patients with FEO/PGL, especially in patients with malignant tumors. The issue FEO/PGL, however, concerns not only the examination and assessment of risks arising therefrom, as well as other therapies and monitoring, including appropriate recommendations for clinical practice. We demonstrated a 20% incidence of cardiovascular (CV) complications before determining the final diagnosis of FEO/PGL, mainly arrhythmic, followed by complications of myocardial ischemia and accentuate atherosclerosis. Elevated levels of vitamin C and decreased levels of malondialdehyde (MDA) following the successful removal of the tumor demonstrated reduction of oxidative stress postoperatively. We found that early postoperative testing of levels of plasma metanephrines to confirm the success of surgical removal of FEO/PGL is already possible, since there was no significant correlation between plasma levels of metanephrines and postoperative examination interval. Distribution of frequency of metastatic...

The diploma thesis is focused on the transmediality and adaptation phenomena and on the process of adaptation translation into the performative medium, a movie. The phenomena are grounded in the academical background, and their origin and historical development of their studies are contained in the theoretical part of the thesis. Furthermore, the different approaches to evaluation of the final product of the adaptation process are analyzed and it is explained that the evaluation of the adaptation is not bound by the fidelity criteria, but rather the overall transformation of the original message into the new media, in this case a movie. Due to these findings, the method of qualitative comparative analysis was used for the analytical part of the thesis. The qualitative research was focused mainly on the adaptation shifts as defined by Katerina Perdikaki, modulation, modification, mutation. Four biographical books of well- known personalities and their subsequent movie adaptations were analyzed. From these stories, four key moments were chosen to be used for the qualitative comparative analysis in order to research the adaptation shifts in the individual stories and their impact on the process of the creation of the adaptation and the final performative piece. The sample of the books was carefully...

In clinical practice, infections caused by persistent bacteria have become a worldwide problem. We are talking about a subpopulation of cells that are able to withstand lethal doses of antibiotics and after their elimination are capable of resuscitation and re-induction of the disease. The opportunistic pathogen Staphylococcus aureus is one of this bacteria and causes various serious chronic infections. During the long-term persistence in patients, persistent bacteria acquire adaptive mutations. The aim of this diploma thesis was to monitor the degree of persistence in selected clinical isolates, and at the same time to demonstrate the effect of adaptive mutations on the degree of persistence as well as to molecularly characterize the persistent state by gene expression. I had chronological isolates of S. aureus at my disposal, the initial one being the primoisolate, an isolate taken at the diagnostics of cystic fibrosis before the start of antibiotic treatment. Another was taken at a distance of one year and the last with a half-year interval from the previous one. Following whole genome sequencing, genes in which adaptive mutations occurred were identified. The first method determines the degree of persistence by calculating CFU (Colony Forming Units) after antibiotic treatment. I found that this...

Technique of pulsed field gel electrophoresis (PFGE) has found widespread use in the analysis of the genome of all life organisms. It is applied to the separation of the large DNA molecules above thousands base pairs up to millions of base pairs in size, where using conventional gel electrophoresis techniques are not possible (for instance large bacterial, yeast, fungal or mammalian chromosome). Presented work was realized as a comparative analysis of genome of several carotenogenic yeasts. The conditions of isolation and analysis of chromosomal yeast DNA were optimized. A lysis of yeast cells and deproteination of DNA within agarose chops was shown as the most appropriate method for DNA isolation. Cultivation to late exponential phase (50 hours) is the most suitable to obtaining intact DNA in sufficient amount and quality. Carotenogenic yeasts undergo the random mutagenesis using alkylation reagent ethyl methanesulfonate (EMS). Genome of pigment overproducing mutants was analyzed by pulsed field gel electrophoresis and amount of carotenoids by high pressure liquid chromatography (HPLC). However, overproduction of beta-carotene was analyzed in mutant strains Rhodotorula glutinis (10.6 g/l of biomass enriched 0,34 mg/g of beta-carotene) and Cystofilobasidium capitatum (8.5 g/l of biomass enriched 0,23 mg/g of beta-carotene). Selection of mutant strains overproducing carotenoid pigments was in presented experiment series successful in almost all analyzed strains except in the case of the strain Rhodotorula aurantiaca.

The work deals with genetic algorithms and their potential use in application software to optimize high voltage switching elements of distribution network. Theoretical part explains the basic concepts of genetic algorithms such as a gene, population and chromosome and basic principles of the development of genetic algorithms.. The main task of the thesis is to design the algorithm that will simulate the distribution of the sectionalizers by telecontrolled section switches or reclosers and analyze how to set the the parameters affecting the convergence speed of genetic algorithm. The basic parameters affecting the convergence of breeding, mutation probability, population size or using of elitism. The second goal is finding a suitable set of input parameters for the selected population sizes without and with using elitism. The results of the work determine the most appropriate settings for each generation and determining the approximate number of generations needed to find the best solution. The genetic algorithm applocation was tested on a less extensive distribution network with six switching elements

This thesis describes a new approach to the detection of protein stability change upon amino acid mutations. The main goal is to create a new meta-tool, which combines the outputs of eight well-established prediction tools and due to suitable method of consensus making, it is able to improve the overall prediction accuracy. The optimal strategy of combination of outputs of these tools is found by using a various number of machine learning methods. From all tested machine learning methods, KStar showed the highest prediction accuracy on the training dataset compiled from experimentally validated mutations originating from ProTherm database. Due to this reason, it is chosen as an optimal prediction technique. The general prediction abilities is validated on the testing dataset composed of multi-point amino acid mutations extracted also from ProTherm database. Since the multi-point mutations were not used for training any of integrated tools, we suppose that such comparison is objective. As a result, the developed meta-tool based on KStar technique improves the correlation coefficient about 0.130 on the training dataset and 0.239 on the testing dataset, respectively (the comparison is being made against the most succesful integrated tool). Based on the obtained results, it is possible to claim that machine learning methods are suitable technique for the problems from area of protein predictions.

Chronic myeloid leukemia is a clonal haematopoietic disease, with characteristic BCR-ABL1 fusion gene. Despite the significant improvement in patient treated with tyrosine kinase inhibitors (TKI), 20-30 % of patients develop resistance. One of the main causes of treatment failure are mutations in the BCR-ABL1 kinase domain (KD). The aim of this work was to elucidate the molecular mechanisms of resistance and mutagenesis development in CML using an in vitro CML model KCL-22. The main part of this work was focused on the identification of genes involved in DNA damage response and repair, that could play a role in the process of mutagenesis of BCR-ABL1. We used the RT2 Profiler PCR Arrays method for the group of selected genes regulating DNA damage response and repair. We identified the genes XRCC6 and PARP1 whose gene expression was significantly and specifically decreased during KD BCR-ABL1 mutagenesis. Products of these genes are involved in repairing DNA double-strand breaks through non-homologous end joining (NHEJ). During study of the KD BCR-ABL1 mutagenesis we also found that clones, which developed mutations, did not show the increased BCR-ABL1 expression in the beginning of the culture compared to the clones in which mutations have not evolved. Key words: myeloid leukemia, mutation,...

Osteogenesis imperfecta is an inherited disorder caused mainly by collagen type I genes mutations, COL1A1 and COL1A2. These mutations affect especially connective tissue. Disease is characterized by fragile bones, deformations and increased frequency of fractures. It's worldwide extensive disorder regardless of age, sex, nationality or races. The incidence is 1: 16 - 20 000 births. Currently, we described nine clinically distinct forms of Osteogenesis imperfecta. Only the first four types OI, type I-IV, are caused by collagen type I genes mutations . In these nine types there are distinguished mild and severe forms. Type II and III are lethal forms, death occur offen during prenatal period or in the first days of the life affected individuals. Characteristic clinical features of collagen forms OI are an increased incidence of fractures, deformations of bones, blue sclera, hearing loss, Dentinogenesis imperfecta small or subnormal growth (Marini, 2010). This study alignment is mainly the description of the clinical forms, exploring the molecular basis of disease and determine the relationship between the type and position of the mutation and the resulting phenotype of affected individuals. We have analysed exons 31-40, including associated non-coding regions, of the COL1A1 gene (so-called MLBR =...