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Bonded hybrid joints in the automotive industry
Ševčík, Jan ; Hanáčková, Pavla (referee) ; Kubíček, Jaroslav (advisor)
This diploma thesis deals with bonded hybrid joints which are used for connecting parts of modern coachwork. Firstly, the thesis describes in general the process of production of the whole coachwork, from cutting of the blanks to the surface treatment including the analysis of the used materials. Subsequently, the problem of joining body parts through adhesives, but also by welding, soldering or other methods is discussed. Another part of this thesis is dedicated to an experiment in which the qualities of bonded hybrid joints were determined. Different ways of realizing the joint have been made which differed in the size of the glued surface, in the welding methods and in the process of their creation. The produced joints were tested for their strength and quality.
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Heidegger's Concept of Experience
Ševčík, Jan ; Benyovszky, Ladislav (advisor) ; Němec, Václav (referee)
Heidegger's Concept of Experience Abstract The paper aims to explore one of the central concepts of Heidegger's late philosophy. The experience here, compared to the concept in the early period of his thinking, takes on new forms of relation to the world and to the concealment and shows some basic features that the work will follow. These features of experience are: totality, immediacy, passivity, and the transformation of whoever experiences. A proper understanding of Heidegger's concept of experience should provide an important clue to understanding his late philosophy and the way of thinking that promotes it. But it also has wider implications for today's thinking and for grasping not only prominent experiences, such as religious experience.
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Využití zemědělského půdního fondu v katastrálním území Orlovice
Ševčík, Jan
This bachelor thesis deals with an evolution and use of an agricultural land fund in a cadastre unit of Orlovice, based on studies of historical and present map bases analyses. The work focuses on comparison of historical and present states of the agricultural land fund, general information of the agricultural land fund and an evolution of land ownership relations. In the thesis, I suggested provisions which would contribute to land protection and helped to general improvement of the landscape character in the area.
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Study of population specific alterations of breast cancer predisposition genes in Czech Republic.
Judasová, Kristýna ; Ševčík, Jan (advisor) ; Holá, Dana (referee)
Breast cancer is the most frequent malignant disease in the female population worldvide. About 10 % of all cases are of hereditary origin. The inactivation of tumor suppressor gene BRCA1 is the main genetic predisposing factor in breast cancer in the Czech Republic. Primarily, BRCA1 participates in DNA double strand break repair. Depending on cell cycle phase, the damage is repaired by homologous recombination or non-homologous end joining. Alternative splicing variants of BRCA1 are frequently detected during the genetic screening of high risk patients. The clinical significance of these variants is unknown. Understanding of the nature of breast cancer genetics is the critical factor for early diagnosis. Based on earlier studies from the Institute of Biochemistry and Experimental Oncology 1st Faculty of Medicine Charles University, two alternative splicing variants which were repeatedly detected in patients, were chosen for functional analysis. The aim of this work is to investigate the impact of alternative splicing variants BRCA1Δ5 and BRCA1Δ10 on DNA double strand breaks repair. Particular variants were over- expressed in the cells of model system. Activity of homologous recombination (HR) and non-homologous end joining (NHEJ) was scored by in vitro DNA repair assay. The cellular localization of...
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The functional in vitro analysis of the BRCA1alternative splicing variants
Ševčík, Jan ; Kleibl, Zdeněk (advisor) ; Stopka, Tomáš (referee) ; Macůrek, Libor (referee)
BACKGROUND: The inactivation of the tumor suppressor gene BRCA1 is a predisposing factor for a breast/ovarian cancer development. Formation of cancer-specific alternative splicing variants with aberrant biological properties can represent additional mechanism decreasing the overall BRCA1 activity in DNA double strand break (DDSB) repair. In this study, we analyzed BRCA1 alternative splicing variants BRCA114-15 and 17-19 ascertained previously during the screening of high-risk breast cancer individuals. METHODS: We established a stable MCF-7 cell line-based model system for an in vitro analysis of BRCA1 variants. Using this system, we analyzed the impact of BRCA114-15 and 17-19 variants on DNA repair kinetics using comet assay and confocal immunomicroscopy. The capacity of DNA repair was assessed directly by an in vitro NHEJ assay and indirectly by a mitomycin C sensitivity test. The proliferation activities were determined by a clonogenic assay and growth curves. RESULTS: Overexpression of BRCA114-15 and 17-19 increases the endogenous level of DNA damage, slows down the DDSB repair, and decelerates the initial phase of radiation-induced foci formation and prolongs their persistence. Moreover, BRCA114-15 and 17-19 differentially influence the activity of HR and NHEJ and sensitivity of MCF-7 cells to ionizing...
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A DNA double-strand break repair and it's disorders with a relationship to the cancerogenesis
Komžák, Josef ; Ševčík, Jan (advisor) ; Vopálenský, Václav (referee)
The DNA-double strand break (DSB) repair has an essential importance for the genomic integrity maintenance. The main DSB repair pathways are homologous recombination (HR), non-homologous end joining (NHEJ) and single-strand annealing (SSA). The most important protein factors contributing to the maintenance of genomic integrity by direct participation in DSB repair are MRN, ATM, Rad51, BRCA1/2 and PALB2 in the case of HR; Ku70/80 DNA-PKcs, XRCC4 and DNA ligase IV in the case of NHEJ and Msh2-Msh3 and Rad1- Rad10 in the case of SSA. If mutated, these proteins can cause the inability to repair DNA lesions leading to a malignant transformation. The predominant phenotype manifestation of BRCA1/2 inactivation is the hereditary breast and/or ovarian cancer (HBOC). Mutations in ATM have been described as a cause of ataxia telangiectasia and inactivation of NBN gene (Nbs1 protein) causes the Nijmegen breakage syndrome. Other syndromes connected with defects in a DSB repair pathways are Fanconi anemia and Werner syndrome. Detail knowledge of DSB repair process is a mandatory for diagnostics and effective therapy of a number of malignances. An example of practical and clinically relevant utilization of current knowledge about the DSB repair process is the concept of a synthetic lethality as a specific therapy. This...
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The role of proto-oncogene crk in invasiveness
Tomášová, Lea ; Rösel, Daniel (advisor) ; Ševčík, Jan (referee)
Proto-oncogene Crk was identified as an oncogenic product of an avian retrovirus in 1988. It is an adaptor protein containing SH2 and SH3 binding domains. Thanks to these domains Crk facilitates protein-protein interactions and therefore plays a crucial role in signal transduction. Crk forms signal complexes with several proteins and hence impacts many cellular processes, among them cell migration, tumorigenezis and invasion of the surrounding tissues. The increased invasiveness allows the tumour cells to detach from the primary tumour and form metastasis which is very problematic feature of cancer. Overexpression of Crk was observed in several tumour tissues, it correlates with an aggressive and metastatic phenotype of the tumours. The subject of this thesis is to describe the mechanisms of how Crk can regulate cellular motility and invasiveness.
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