The main objective of this thesis is a fabrication drawings on the theme "Children's Home" by urban, architectural, design and construction-technical solution that meets and complies with applicable standards, regulations and laws.

This diploma thesis provides an overview of gene conversion, its role in the pathogenesis of human diseases and the use of methods based on next-generation sequencing (NGS) for detection rare variants of DNA sequence. Labeling of target DNA molecules by random nucleotides in primer and NGS were used for detection point mutations arising de novo in the β-glucocerebrosidase gene by gene conversion between it and its pseudogene in meiotic and mitotic cells of control subjects. Primers specific for the active gene were used to selectively amplify the ninth and tenth exon of the gene where "recombinant" variants occur most frequently. Sequences generated from 20 genomic DNA samples on Illumina MiSeq platform were quality filtered, sorted by unique labels and consensus sequences were created from alignments of sequences carrying the same DNA tag. The number of potential point mutations in the samples ranged between 12 and 48. The mutations were manually re-evaluated from the alignments. The number of alignments with unique labeling was in the range of 7-15 thousand per sample. Only three samples carried possible recombinant mutations, suggesting a lower frequency of conversion in the region than reported by other techniques. Analysis of unique sequences in primer indicated possible ways to improve the...

Abstract Heart failure (HF) is a complex pathological state, involving simultaneous alterations in several signalling pathways and changes in gene programming. In HF, activation of the neurohumoral factors and renin-angiotensin-aldosterone (RAA) system occurs as a compensatory mechanism to combat the abnormal ventricular function. Developments in cardiac gene delivery methods have exerted a significant impact to treat HF and to discover the novel molecular mechanisms associated with HF and other cardiac diseases. This study demonstrated that adenovirus–mediated gene delivery of B-type natriuretic peptide (BNP) into the anterior wall of the left ventricle decreased myocardial fibrosis and increased capillary density. Post-infarction BNP improved systolic function associated with normalization of cardiac sarcoplasmic reticulum Ca2+-ATPase (SERCA) 2 expression and phospholamban phosphorylation at Thr17. On the other hand, (Pro)renin receptor ([P]RR) gene delivery resulted deleterious effects on cardiac function and (P)RR activation induced distinct angiotensin II (Ang II)-independent extracellular matrix remodelling and worsening of cardiac function. (P)RR gene delivery resulted in Ang II-independent activation of extracellular-signal regulated (ERK1/2) phosphorylation and increased myocardial fibrosis. In conclusion, the present study indicates that myocardial BNP gene delivery can achieve pleiotropic, context-dependent, favourable effects on cardiac function and that BNP can act locally as a mechanical load–activated regulator of angiogenesis and fibrosis. These results also implicate that (P)RR blockers may display additional cardiac effects in addition to its ability to evoke effective RAA system blockade. Overall, the findings of this study provide a better understanding of the molecular mechanisms involved in the biological actions of BNP and (P)RR, and identify BNP and (P)RR as potential novel drug targets for the treatment of HF. / Tiivistelmä Neuroendokriinisellä aktivaatiolla, jonka seurauksena aiheutuu muun muassa verisuonten supistumista ja laajenemista sekä nesteen kertymistä elimistöön, on tärkeä merkitys sydämen vajaatoiminnan kehittymisessä. Neuroendokriininen aktivaatio kompensoi sydämen vajaatoiminnan seurauksena tapahtuvaa kammioiden poikkeavaa toimintaa. Yksi keskeisimmistä verisuonia supistavista tekijöistä on reniini-angiotensiini-aldosteroni (RAA) -järjestelmä, ja verisuonia laajentaviin tekijöihin kuuluvat muun muassa natriureettiset peptidit, kuten B-tyypin natriureettinen peptidi (BNP) ja A-tyypin natriureettinen peptidi. Geeninsiirtomenetelmillä on ollut merkittäviä vaikutuksia uusien hoitomenetelmien kehittämisessä, sydämen vajaatoiminnan syiden selvittämisessä ja uusien kohdegeenien tunnistamisessa sydämen vajaatoiminnan hoitoon. Väitöskirjan tutkimustulokset osoittivat, että suora adenovirusvälitteinen geeninsiirto rotan sydämen vasemman kammion etuseinään on toimiva menetelmä uusien kohdegeenien löytämiseksi sydämen vajaatoiminnan hoitoon. BNP:n geeninsiirto vähensi merkitsevästi fibroosin muodostumista ja lisäsi verisuonten uudismuodostumista sydämessä. Sydäninfarktin jälkeen BNP paransi sydämen systolista toimintaa, johon liittyi aktiivisen kalsiumpumpun, SERCA2:n ja fosfolambaani-proteiinin fosforylaation normalisoituminen. (Pro)reniini reseptorin ([P]RR) geeninsiirto aiheutti angiotensiini II:sta riippumatonta solunulkoisen matriksin uudelleenmuotoutumista ja sydämen toiminnan huonontumista sekä lisääntynyttä sydämen fibroosia. Väitöskirjatutkimus antaa uutta tietoa solunsisäisistä molekulaarisista mekanismeista sydänsoluissa. BNP geeninsiirto aiheutti sydämen tautitilasta riippuvia suotuisia tapahtumia, ja se toimi paikallisesti muun muassa fibroosia ehkäisevänä tekijänä. (P)RR geeninsiirtotulosten perusteella voidaan olettaa, että (P)RR:n salpaus saattaa olla uusi tehokas hoitokeino sydämen vajaatoiminnan hoitoon.

The purpose of this thesis is to cover the topic of the Czech catholic children's magazines within the period of 1945 - 1948. Firstly the thesis contextualizes the historical background in the terms of looking back to the period of the occupation and then turns to the consequences that the occupation brought to the catholic population. Further the thesis offers an insight to the situation after 1945 mainly from the catholic point of view and focuses on the catholic press within the given period. In the next section the thesis characterizes the trends of the children's and juvenile literature in the period of 1945 - 48 through literary pieces, which form an integral part of the analyzed magazines. This part also deals with the general overview of the Czech children's and juvenile periodicals output within the given period. The main part of the thesis then characterizes and analyzes two chosen periodicals: Anděl strážný (The Guardian Angel) a magazine for catholic children and Dorost (The Juvenils) a magazine for catholic juvenils. This part of the thesis analyses the contents, structures and partly also the visual appearances of the chosen periodicals and tracks any changes of these aspects in single volumes. Marginally the thesis also mentions the editors and authors of the texts and illustrations....

De nouveaux composants du système rénine angiotensine (SRA) continuent d'être découverts et leurs fonctions étudiées. Cette thèse présente de nouvelles relations entre enzyme de conversion de l’angiotensine (ECA), thrombose et maladies cardiovasculaires (MCV), d’une part, et d’autre part, un rôle pour le récepteur de la (pro)rénine dans le développement du système nerveux central (SNC). Tout d’abord, nous avons étudié l'association de la double mutation de l’ECA et l’inhibiteur de l’activateur du plasminogène-1 (PAI-1) sur l’incidence d’évènements cardiovasculaires chez les patients Libanais hypertendus et hypercholestérolémiques, par rapport à d'autres gènes cardiovasculaires polymorphes des cytokines pro-inflammatoires dans les cellules mononuclées circulantes. Les résultats ont montré que les patients exprimant une double mutation ECA/PAI-1, respectivement Del/4G, sont à haut risque d’apparition des MCV. Dans une deuxième partie, nous avons étudié la relation entre récepteur de la (pro)rénine dont le gène est appelé Atp6ap2, et la voie de signalisation Wnt/bêta-caténine dans les cellules souches/progénitrices neurales (CSPN). À cette fin, nous avons isolé des CSN à partir d’embryons de souris Atp6ap2-/Y, et étudié leur auto-renouvellement et leur différenciation en neurones, astrocytes et oligodendrocytes in vitro. Nos résultats suggèrent que Atp6ap2 est nécessaire à l’auto-renouvellement des CSN indépendamment de la voie de signalisation Wnt/bêta-caténine chez les mammifères. Enfin, nous avons montré qu’il existait une corrélation entre l’expression ATP6AP2 et le degré de différenciation neuronale des cellules souches mésenchymateuses humaines (CSMh) isolées à partir du tissu adipeux. / New components of the renin angiotensin system (RAS) continue to be discovered and their functions studied. This thesis provides new insights on the role of angiotensin converting enzyme (ACE) in thrombosis and cardiovascular diseases (CVD) and of the (pro)renin receptor in the development of the central nervous system (CNS). First, we studied the role of ACE in CVD by analyzing the impact and the association of a mutation in ACE and in plasminogen activator inhibitor-1 (PAI-1) genes compared to other polymorphic cardiovascular genes of proinflammatory cytokines in peripheral blood mononuclear cells in hypertensive hypercholesterolemic Lebanese patients. We showed that Lebanese patients expressing a double mutation (Del/4G) of ACE and PAI-1, respectively, are at high risk of developing CVD, suggesting that combined ACE/PAI-1 mutations may be considered as a potential marker of CVD onset. In the second part, we studied the relation between the (pro)renin receptor, whose gene is called Atp6ap2, and Wnt/beta-catenin signaling pathway, in neural stem/progenitor cells (NSPC) during development. To this end, we used an in vitro model of neural stem cells (NSC) isolated from Atp6ap2-/Y mice embryos and studied their self-renewal capacity and their differentiation into neurons, astrocytes and oligodendrocytes. Our results suggest that Atp6ap2 is necessary for self-renewal of NSC independently of the Wnt/beta-catenin signaling pathway in mammals. In addition, we showed that the expression of ATP6AP2 in human mesenchymal stem cells (hMSC) isolated from adipose tissue was correlated with their degree of neuronal differentiation.

Comment résoudre les problèmes de congestion liés au développement urbain ? Les investissements massifs dans les infrastructures et le traitement monétaire et coercitif des comportements ayant montré leurs limites, nous proposons d'explorer la possibilité de favoriser les comportements positifs (covoiturage, vélo, télétravail). Nous commençons par élargir le modèle comportemental de l'individu en posant comme préalable à l'étude des motivations la prise en compte du cadre dans lequel il se situe. Nous justifions théoriquement cet apport principalement par les travaux du psychologue Daniel Kahneman et du sociologue Ervin Goffman. Nous précisions ensuite notre démarche méthodologique : en montrant combien la démarche des expérimentations de laboratoire est reliée à l'hypothèse comportementale de l'homo œconomicus, nous montrons la cohérence de notre hypothèse de cadre avec celle des expériences de terrain. Nous décrivons ensuite trois expériences visant à montrer (i) comment le cadre correspond à une représentation confortée par un discours dominant (ii) l’importance de la mesure rétroactive de cette représentation et (iii) comment les motivations agissent à l’intérieur de ce cadre. Nous en déduisons plusieurs principes susceptibles de favoriser un changement de comportements de mobilité à même de traiter le problème de congestion : (i) la place de l’individu dans les schémas de transports, (ii) le temps ou le bien être comme indicateur de mesure et (iii) les représentations collectives comme support de coordination. / How to solve congestion problems related to urban development? As the massive investment in infrastructure and the monetary and coercive treatment of behaviors have shown their limits, we propose instead to explore the promotion of positive behavior (carpooling, biking, telecommuting). We start by expanding the behavioral model of the individual, by taking into account the context (frame) in which it happens. We justify this contribution primarily through the work of the psychologist Daniel Kahneman and the sociologist Ervin Goffman . Then we clarify our methodological approach: by showing how the process of laboratory experiments is connected to the behavioral factors of the homo oeconomicus, we show the consistency of our frame hypothesis with field experiments. We then describe three experiments to show (i) how the frame is underpinned by a dominant discourse (ii) the importance of the retroactive measure of this representation and (iii) how motivations acts within that frame. We derive several principles to promote a change of mobility behavior able to treat congestion: (i) the place of the individual in transport schemes, (ii) using time or well-being as a measurement indicator and (iii)collective representations as coordination enablers.

This work is a result of the current state of the art and the measurement of drivers' reactions and their behavior through the eyetracker during the passage through pedestrian crossings on which the pedestrian crossed. The subject of the measurement was the assessment of the design of the pedestrian crossing and its subsequent influence on the reactions of drivers and their behavior.

This diploma thesis presents the design of sidewalks in selected localities in Kyjov. This master's thesis deals with the three projects. The first one is a revitalisation of Vrchlickeho street, next one deals Svatoborska and Riegerova street. The last part is a design of sidewalks in these streets: Brandlova, U vodojemu, Moravanska and Netcicka. The redesign of horizontal and vertical solution is developed and proposed based on the obtained data. These projects are focused on the increase of comfort of the sidewalks, maximalisation of the number of parking lots and improves traffic safety. It was important to connect the designed parts as roads and sidewalks to the rest of the landscape, buildings and roads continuously. This proposal contains solution of the drainage, the traffic signs, the improvement of the safety and comfort of pedestrians and persons with disabilities. This redesign respects affected lands and their usage. It respects existing engineer networks and requirements of territorial plan of the town Kyjov.

This work is aimed at design and implementation of system for supporting metrics in software development projects. The procedure of design and application of measurement methods is described. Further metrics data analysis in three domains is described: frequency domain, time domain and relationship domain; together with forms of visualization. Finally, the requirements for system for supporting metrics are enlisted, along with design of architecture and details of implementation.

The thesis deals with SEO problems (Search Engine Optimization). The part of the thesis is creation of tool which analyzes web pages in multilanguage versions and results provides with appropriate educational effect for user. According the analyzing that can be also used in the regular interval it's possible to show optimization history. The tool uses Microsoft technologies, especially ASP.NET, SQL Server 2008 or Microsoft Server 2008 and is developed by Visual Studio 2010.