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Pathogenesis of Huntington's disease in peripheral tissues
Vachútová, Dominika ; Motlík, Jan (advisor) ; Fiala, Ondřej (referee)
Huntington's disease (HD) is an autosomal dominant inherited disorder with manifest of symptoms around the age of 40. This disorder is caused by an expansion of CAG repeats in huntingtin gene, Huntingtin (Htt) is a protein expressed in almost all tissues. HD is mainly characterized by neurodegeneration in the basal ganglia and cerebral cortex, but mutation in huntingtin have also serious influence on peripheral tissues. Many studies show serious heart dysfunction, weight loss, altered glucose homeostasis, impairment of energetic metabolism and muscular atrophy in HD patients and animal models. Till now, mechanism of these changes has not been sufficiently described and there is nor an adequate treatment yet. Key words: Huntington's disease, mutated huntingtin, CAG repeat, peripheral tissue
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Crime prevention through environmental design strategy and its use in selected Prague's localities
Fiala, Ondřej ; Šiftová, Jana (advisor) ; Šilhánková, Vladimíra (referee)
In this thesis I focus on the preventive strategy called Crime prevention through environmental design (CPTED). The aim of this strategy is to act preventively against crime and to reduce fear of crime by means of modification of the physical setting in public spaces. CPTED is theoretically based mainly on findings of crime geography, environmental criminology and architecture. After presenting this concept at the theoretical level I focus on six concrete locations in Prague. On the basis of my field research I investigate if the principles of CPTED are applied in these locations. I also refer to differences between locations, where the preventive principles were applied and locations without use of the CPTED standards. Through the use of questionnaires I try to verify if people really feel safer in places where the principles of CPTED were used. Then I observe the types of activites and the structure of people in those six examined locations. Semistructured interviews with the employees of the Prague municipal police were realised to complete the characteristics of these places. In the last part of the thesis I consider the possibilities of design adjustments in the unsuitable locations according to the CPTED principles.
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Runoff Changes in the Šumava/Bohemian Forest Region
Fiala, Ondřej ; Kliment, Zdeněk (advisor) ; Královec, Václav (referee)
RUNOFF CHANGES IN THE ŠUMAVA / BOHEMIAN FOREST REGION Abstract: The goal of this thesis is to the evaluation of possible causes of changes in runoff regime in the Šumava region from time and spacial point of view. The thesis includes research and applied part. The research part is dedicated to methods of evaluation of runoff changes and their possible causes in teh Šumava region such as anthropogenic factors (changes in the river network, dams, drainage, land - use changes), natural factors (climate changes, peatbogs influence) and disturbances (wind calamities and bark beetle outbreaks, floods). In the applied part there is an analysis of precipitaion - runoff regime for long-term time series of average annual, monthly and minimal daily discharges and monthly precipitations for selected gauging stations in upper Otava, Ostružná, Volyňka, upper Blanice and Teplá Vltava basins using simple and double mass curves and Mann - Kendall test. In conclusion the achieved results were evaluated, discussed and compared with subject publications. Key words: disturbance, Mann - Kendall test, runoff, discharge, mass curves, precipitation, Šumava, changes
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Object selection in raster image
Fiala, Ondřej ; Pelikán, Josef (advisor) ; Kolomazník, Jan (referee)
A common task solved during a work with raster images is a object selection. Results obtained from this task are used in a number of applications - from analysis of the growth of human settlements to automatic medical diagnosis. This work describes in detail the object selection in raster images and focuses on active contours models. This work also consider extending the graphic program GIMP, bringing a new plug-in for object selection in raster images. The solution is based on the original classic model of active contours, the extended model using a gradient vector field (GVF) and proposed improvements. The work presents results obtained by this tool and brings recommendations for future development of active contours models.
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Prognostic and Predictive Factors in Patients with Metastatic Colorectal Cancer Treated with Targeted Therapy
Šorejs, Ondřej ; Fiala, Ondřej (advisor) ; Pešta, Martin (referee) ; Poprach, Alexandr (referee)
Introduction: In recent years, significant progress has been made in the treatment of metastatic colorectal cancer (mCRC) due to the use of targeted therapy. Bevacizumab is a monoclonal antibody (mAb) against vascular endothelial growth factor (VEGF) and cetuximab and panitumumab are monoclonal antibodies against epidermal growth factor receptor (EGFR). MicroRNAs (miRs) are single-stranded non-coding RNA chains of 18-25 nucleotides in length that are involved in the regulation of gene expression and thus significantly influence the biological behaviour of cancer cells. Dysregulations at the miR level are considered promising candidates for prognostic and predictive biomarkers. Aims: The aim of this work, divided into two parts, was to evaluate the association of dysregulation of selected miRs with the effect of targeted therapy in patients with mCRC. Methods: The first study included 63 mCRC patients treated with chemotherapy and bevacizumab. The second study included 46 mCRC patients treated with chemotherapy and cetuximab or panitumumab. Assessment of treatment effect included progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and disease control rate (DCR). Samples of frozen tumor and adjacent non- tumor tissue obtained during primary tumor surgery were used...
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Prediction of Treatment Effect in Solid Tumors
Houfková, Kateřina ; Pešta, Martin (advisor) ; Fiala, Ondřej (referee) ; Šána, Jiří (referee)
Current research of treatment of oncological diseases is focused on the identification of changes that occur in the process of carcinogenesis and on the search for therapeutics that would make it possible to eliminate the manifestation of these changes. Early diagnosis, estimating prognosis, monitoring of the course of the disease and prediction of the effect of treatment are increasingly associated with the determination of appropriate biomarkers. The assessment of predictive biomarkers should become an integral part of treatment decisions and, as a result, help patients to prolong life and improve quality of life. The aim of my thesis was to find prognostic and predictive biomarkers for more effective treatment of cancer patients. In cooperation with a number of clinical departments of the University Hospital in Pilsen, I focused on the research of these biomarkers at the Department of Biology, especially in non-small cell lung cancer, endometrial cancer, colorectal cancer, liver metastases of colorectal cancer, clear cell renal cell carcinoma and sarcomas. We focused on the research of molecules that are involved in the process of carcinogenesis and whose levels in body fluids or directly in tumor tissue would be able to predict further disease development or therapeutic response. Using molecular...
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Options for prediction of treatment efficacy of EGFR tyrozine kinase inhibitors in patient with advanced non-small cell lung cancer
Fiala, Ondřej ; Pešek, Miloš (advisor) ; Salajka, František (referee) ; Skřičková, Jana (referee)
Introduction: Targeted therapy with low molecular-weight tyrosine kinase inhibitors (TKI) directed at inhibition of epidermal growth factor receptor (EGFR) is a novel effective option for systemic treatment of locally-advanced or metastatic non-small cell lung cancer (NSCLC). Finding biomarkers that predict the efficacy of targeted treatment may increase the treatment efficacy and also prolong survival of patients. Aims: To assess the frequency of activating EGFR mutations and KRAS mutations in our patients and their role for prediction of EGFR-TKI treatment efficacy. To compare the efficacy and safety of EGFR-TKI and chemotherapy in the first-line treatment of patients harboring activating EGFR mutations. Methods: 613 patients with cytologically or histologically confirmed NSCLC were tested for activating EGFR mutation, of which 448 patients were also tested for KRAS mutation. First-line therapy was evaluated in 54 patients harboring activating EGFR mutations. Mutations were detected using denaturing capillary electrophoresis, and verified by direct DNA sequencing. Survival of patients was assessed using the methodology of Kaplan-Meier, the comparison was calculated using log-rank test. Results: Activating EGFR mutations were detected in 73 (11.9%) patients, more frequently in patients with...
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Genetics and phenotypic characteristics of early-onset Parkinson's disease
Fiala, Ondřej ; Růžička, Evžen (advisor) ; Seeman, Pavel (referee) ; Bojar, Martin (referee)
Objective: Mutations in the parkin (PARK2) gene have been associated with autosomal recessive early-onset Parkinson's disease (EOPD) with various frequencies in different populations. The aim of the study is to describe phenotypic characteristics of Czech EOPD patients, to evaluate the influence of environmental risk factors, and to determine the frequency of parkin allelic variants in patients and healthy controls. Methods: A total of 70 EOPD patients (age at onset ≤ 40 years) and 75 controls were phenotyped and screened for the sequence variants and exon rearrangements in the parkin gene. Results: The main features in the phenotype of the patients' sample were: the absence of cognitive deficit, high occurrence of dystonia, depression, hyperhidrosis, an excellent response to dopaminergic therapy, early onset of dyskinesia and motor fluctuation. Patients with mutations in the parkin gene had significantly lower age at onset. The agricultural occupation and work with chemicals increased the risk of EOPD, however the coffee drinking appeared to be a protective factor. Parkin mutations were identified in five patients (7.1%): the p.R334C point mutation was present in one patient, four patients had exon deletions. The detected mutations were observed in the heterozygous state except one homozygous...
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Molecular biomarkers of solid tumors and their use in prognosis and prevention of cancer
Elsnerová, Kateřina ; Václavíková, Radka (advisor) ; Fiala, Ondřej (referee) ; Vymetálková, Veronika (referee)
Molecular biomarkers of solid tumors and their use in prognosis and prevention of cancer Molekulární biomarkery solidních nádorů a jejich využití v prognóze a prevenci nádorových onemocnění Mgr. Kateřina Elsnerová Summary Malignant tumors of ovary and breast are among the most widespread cancers in women. Despite improvements in diagnostics and in therapy, mortality is still very high. An important tool for early cancer detection, as well as for monitoring prognosis and preventing progression, are molecular biomarkers; biomarkers were the topic of this work. The aim of this work was to find out (i) whether there are differences in gene expression between tumor and non-tumor tissues, and among controls (C), primary tumors (pT) and intraperitoneal metastases (iM), respectively; (ii) whether gene expression or genetic variants (single nucleotide polymorphisms, DNA methylation, germline mutations) associate with clinical data of patients, thus being potentially relevant for prognosis. In epithelial ovarian cancer (EOC), 50 of 94 genes were deregulated in controls compared to tumors. Fifteen of 66 genes were deregulated in intraperitoneal metastases compared to primary tumors. Gene expression of ABCA7, ABCB2, ABCC3, ESR2, NH1H4 and NR1I1 was deregulated either in comparison of primary tumors and metastases, or...
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Slaměný rodinný dům v obci Benešov u Semil
Fiala, Ondřej
The bachelor thesis is focused on design of construction of family house using natural materials, especially straw. First, the reader learns both general and technical information about the material used, and gets some reason why the natural building material has just been used. The main part of the work is devoted to designing the documentation of a straw family single-storey house with an attic on a particular plot. An object visualization can be considered as an add-on. This work is gently shed on the idea of a journey through a construction that reflects the environment as a gift of man, this gift should be passed on to the next generations in the best condition.
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