DNA double strand breaks (DSBs) are primarily repaired in eukaryotic cells by two different mechanisms – non-homologous end joining (NHEJ) or homologous recombination (HR). In mammalian somatic cells the balance between the two highly favours NHEJ. Gene targeting is a technique that exploits HR repair to alter a defined gene locus. While it holds potential to be implemented as a treatment option for several diseases, the outlook for using it in a clinical setting has been obstructed by a low gene targeting efficiency. This has been coupled to the low frequency of HR in mammalian cells. With the intention of shifting the repair balance, antibodies against DSB repair proteins will be introduced into mammalian cells. It is predicted that by targeting key repair proteins with antibodies, a compensatory increase in the frequency of HR can be fostered, ultimately resulting in improved gene targeting. / xv, 168 leaves : ill. ; 29 cm

Atherosclerosis occurs preferentially at branches and curves in arteries exposed to disturbed flow while sparing straight portions of arteries exposed to undisturbed flow. In vivo and in vitro studies have implicated NADPH oxidases in atherosclerosis and hypertension. Shear stress can induce reactive oxygen species production in endothelial cells from a variety of sources, including NADPH oxidases. Here, we examined the hypothesis that unidirectional laminar shear (LS) and oscillatory shear (OS) would differentially regulate gene expression profiles in NADPH oxidase-dependent and -independent manners, and that these genes would provide novel molecular targets in understanding endothelial cell biology and vascular disease. The p47phox subunit of the NADPH oxidase can be an important regulator of certain Nox isoforms, including Nox1 and Nox2 which may be responsible for shear-induced superoxide production. In order to isolate p47phox-dependent shear responses, we took advantage of the p47phox-/- transgenic mouse model which lacks a functional p47phox subunit. We developed a method to isolate murine aortic endothelial cells using an enzymatic digestion technique. These cells expressed characteristic endothelial markers, including VE-cadherin, PECAM1, and eNOS, and aligned in the direction of flow. We successfully isolated primary murine aortic endothelial cells from both wild-type C57BL/6 mice (MAE-WT) and p47phox-/- mice (MAE-p47). Furthermore, we established an immortalized cell line from each of these cell types, iMAE-WT and iMAE-p47. We carried out microarray studies using Affymetrix Mouse Genome 430 2.0 Arrays (39,000+ transcripts) on MAE-WT and MAE-p47 that were exposed to atheroprotective LS or atherogenic OS for 24 hours. In comparison to LS, OS significantly changed the expression of 187 and 298 genes in MAE-WT and MAE-p47, respectively. Of those, 23 genes showed similar gene expression patterns in both cell types while 462 genes showed different gene expression patterns in the two cell types, demonstrating a considerable role for p47phox-based NADPH oxidases in shear-dependent gene expression. Changes in expression of several genes, including Kruppel-like factor 2 (Klf2), endothelial nitric oxide synthase (eNOS), angiopoietin 2 (Ang2), junctional adhesion molecule 2 (Jam2), bone morphogenic receptor type II (Bmpr2), and bone morphogenic protein 4 (Bmp4) were confirmed by quantitative PCR and/or immunoblotting using both primary cells and immortalized cells. Of these genes, our data suggest that Jam2, Bmpr2, and Bmp4 may be shear-sensitive in a p47phox-dependent manner. Taken together, our studies have identified a set of shear- and p47phox-sensitive genes, including unexpected and novel targets, which may play critical roles in vascular cell biology and pathobiology.

Konstanz, Univ., Diss., 2008.

Thesis (Ph.D. in Toxicology) -- University of Colorado Denver, 2007. / Typescript. Includes bibliographical references (leaves 158-180). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;

Zugl.: Zittau, Internat. Hochsch.-Inst., Diss., 2009 u.d.T.: Odziemczyk, Angelika Joanna: Netzwerkkultur - eine kulturtheoretische Analyse in der deutsch-polnisch-tschechischen Zusammenarbeit

This diploma thesis deals with the technical and natural-close flood controls and their rate of usage in Světlá upon Sázava's Land Register Office. The work survey analysed the current flood controls and floods in the recent history of the area. In the assessment were included concrete activities of subjects working in the landscape (agriculturists, woodsmen and water-right office). The proposal of the communication strategy is the work output. The strategy should improve awareness of the local habitants and the subjects working in the landscape about usage of naturel-closed flood controls.

This diploma thesis deals with the issue of quality of life, especially in terms of the satisfaction of the city's population Zdar nad Sazavou. Quality of life is examined in terms of economic, social and environmental. In the literature review are defined thebasic concepts of quality of life, its history, approaches, models, methods of measurement and indicators . It also deals with the concept of sustainable development, quality of life is closely related. The main goal of this work is to evaluate the quality of life in the study area and subsequent proposals for measures to improve the quality of life.It also analyzes the current situation of the town of Zdar nad Sazavou and evaluates survey of citizens of the city.

This thesis has a case study deals with the development of local government in the municipality of Poříčí nad Sázavou district Benešov. The aim is to identify factors that affect the character of the political decisions made by local authorities in that municipality. The first part is devoted to the definition of basic terms concepts and characteristics of the local political system in the Czech republic based on a study of the literature. The second part is based on knowledge theoretical a part deal with socioeconomic analysis also identifies actors of the local political process and their interaction. The work includes comparison of the results of the municipal elections. Attention is focused on the development of the local political system, political participation and the formation of a municipal coalition.

This thesis deals with the issue of the formation of local authotrities in the municipality of Libčice nad Vltavou. The thesis is divided into theoretical and analytical parts and it is conceived as a case study. The theoretical part focuses on explaining the basic concepts of local politics and election. Further explanation of the terms used in the analytical part. The analytical part focuses on the city Libčice nad Vltavou. First is describes the history of the city, defined territory and population demographics and amenities. Furthermore the thesis deals with a various political actors in Libčice nad Vltavou, the election results from the year 1994 - 2014 and electoral support in individual election districts in the last two election. Attention is also paid to the creation of local party system and the continuity of candidacy. A detailed research of the election results from the years 1994 - 2014 characterized by the development of the local party system and voting behavior. Using semi-standardized interviews with representatives of local political parties, former actor of political life in the city and employees of the municipal office then is identified and formed a local cleavages that have Influence on the formation of local government, and then based on these interviews identified factors influencing the compilation of coalitions.

This thesis deals with design of a new trees exposure in the arboretum in Kostelec nad Černými lesy, where model of wetland habitats will be created. Emphasis is placed on the supplement autochthonous species especially willow - Salix. A literature review provides information about Arboretum Kostelec nad Černými lesy and compositional principles. It is focused on wetlands, floodplain forest and it is willow communities. Thesis includes the characteristic of the area and it's natural conditions. Inventory of area were made in the practical part. Botanical survey detect current vegetation cover. The area of interest was evaluated from the botanical point of view. Evaluation of the health condition of trees was done to improve the condition of existing vegetation and habitat model layout. Treatment and the existing vegetation felling, was proposed. Map outputs of the research were processed in ArcGIS 10.1. Exposure design was drawn in AutoCAD 2016. List of recommended trees that is based on analysis of Czech and foreign sources was created. Pathway and information system for visitors that use the QR code was designed. The results of this thesis can be applied in practice in Arboretum Kostelec. Model of wetland habitats can be used for research and educational purposes.