This thesis documents an inquiry into the architecture of contemplative spaces and the process and evolution of the design of such a place. Man has often sought a place of solitude, a shelter, where the diversities diminish and differences become insignificant. In the recent decades many non-denominational temples and chapels, such as the MIT peace chapel, were built around the world by seekers of unity in diversity. This study explores the design of such a place and inquires into how the subtle architectural aspects contribute to the quality of solitude and tranquility of that place. These aspects are further explored in the design of a rotunda which becomes the heart of the thesis. / Master of Architecture

The solved site is located in the historic town of Znojmo, on the site of the former castle. Its unique position not only adds significant urban areas, but are an integral part of the city skyline. There is one of the most important monuments in the country, Rotunda of St. Catherine (annually visited by tourists to 20000) and former brewery Hostan. The operation ended here and the city bought the land with buildings. There is now the question of what to do with the place and where to get funds for its cultivation. The main idea is to expand the urban areas and the structure of the brewery premises. The spatial concept is based on a pedestrian street leading from the entry of the city to the rotunda, lined with town houses and buildings with shops, housing and services. The aim is to maintain the existing street brewery trail as part of the development and create space for a typical town of Znojmo. South route would remain in its original state, would continue to serve as a lookout trail flowing into the area around the rotunda, accompanied only by peaceful summer terrace offering views of the surrounding area. Around the rotunda is created a cultivated park area used for recreation and offering beautiful views of the surrounding area. Thanks to the closed square and the location of the rotunda it becomes the dominant area. Northern route would be connected with the area by the stairs from the panoramic terrace. It could thus become a valuable space that would serve to stay and rest. It is important to the influx of new services also solve the parking, which will be located in the parking house. There are parking stacker designed to minimize space requirements. This will ensure the required parking space without negatively affecting the street spaces. Panorama of small buildings will be revived by integrating with the surrounding with the recovery of its original landmark - the tower. It will be part of the former Northern Justice, which will be used as a park area designated for sport and recreation. The tower would serve the prospect of an observatory on top of offering the prospect of the surrounding area during the day and evening look at the night sky. The square will be closed by parking house, which will conclude the street Přemyslovců composition. All necessary utilities will be held in Castle Street.

La mise au point et la validation d’une méthode de dosage par CLHP des alcaloïdes majoritaires (cépharanthine,xylopinine, tétrahydropalmatine) de Stephania rotunda sont réalisées. La méthode est appliquée au dosage des alcaloïdesdans différentes parties de la plante. Le tubercule est la drogue végétale la plus riche en alcaloïdes majoritaires, enparticulier en cépharanthine (1%). Le dosage des alcaloïdes majoritaires des tubercules d’origine différente est effectué.La cépharanthine est beaucoup plus concentrée dans le tubercule de Pailin (1,9%). La comparaison de la compositionchimique du tubercule cultivé et sauvage montre des résultats proches. L’isolement de huit alcaloïdes est effectué parChromatographie Flash. Leur structure est déterminée par SM et RMN. La cépharanthine, la xylopinine, latétrahydropalmatine, la palmatine et la roémérine précédemment décrites sont réisolées. La pseudopalmatine, lastéphanine et la vireakine, alcaloïde nouveau, sont décrites pour la première fois dans la plante. L’étude pharmacologiquede S. rotunda montre que la majorité des extraits testés (76%) présentent in vitro une activité antiplasmodiale intéressantesur la souche W2 de Plasmodium falciparum avec une CI50 < 5 μg/ml. La cépharanthine et la pseudopalmatine sont lesalcaloïdes les plus actifs avec une CI50 de 0,7 et 1 μg/ml, respectivement. Les effets sur la croissance in vitro de la soucheW2, des associations alcaloïdes/alcaloïdes et alcaloïdes/molécules antimalariques de référence sont testés. L’étude in vitrodu métabolisme hépatique de la cépharanthine montre la présence d’un métabolite principal M1 cytochrome dépendant.Une importante variabilité inter-individuelle de la formation de M1 est observée. L’étude de la variabilité inter-sexemontre qu’il n’y a pas de différence significative entre homme et femme. Les études in vitro de différentes espècesanimales indiquent une variabilité inter-espèces. L’enzyme responsable de la formation du métabolite M1 est déterminée.Le CYP3A4 est très fortement impliqué dans la métabolisation de la cépharanthine. Enfin, la détermination structurale dumétabolite majoritaire M1 a été réalisée par CDI-SM/SM. Cette étude nous a permis de conclure que la structure dumétabolite M1 correspond à un composé N-déméthylé. / An HPLC method is developed and validated for the simultaneous determination of major alkaloids: cepharanthine,xylopinine, tetrahydropalmatine in tuber of Stephania rotunda Lour. The validated method was successfully applied toquantify the three alkaloids in various parts of the plant. The higher content of major alkaloids, in particularcepharanthine (1%), is found in the tuber of this plant. The major alkaloids of tubers from different regions aredetermined. The cepharanthine is concentrated in tuber of Pailin (1.9%). The comparison of the chemical composition ofcultivated and wild tubers shows similar results. Eight alkaloids were isolated from S. rotunda using FlashChromatography. Their structures are elucidated by MS and NMR. Cepharanthine, xylopinine, tetrahydropalmatine,palmatine and roemerine previously described are reisolated. Pseudopalmatine, stephanine, and vireakine (newaporphine alkaloid) are described for the first time in the plant. Pharmacological study of S. rotunda shows that themajority of extracts (76%) exert in vitro antiplasmodial activity against a chloroquine resistant strain of Plasmodiumfalciparum (W2) with IC50 < 5 μg/ml. Cepharanthine and pseudopalmatine display significative activity with IC50 valuesof 0.7 and 1 μg/ml, respectively. Isobol experiments are performed with W2 strain by combination of alkaloids/alkaloidsand alkaloids/antimalarial reference molecules. In vitro metabolism study of cepharanthine using human liver microsomesshows the cytochrome-dependant formation of a major metabolite M1. Enzymatic kinetics were investigated with pooledhuman liver microsomes to determine Michaelis-Menten constants. Important inter-individual variability of cepharanthinemetabolism is observed. In vitro studies indicate an important inter-species variability. The enzyme responsible for theformation of M1 metabolite is investigated. This study shows that CYP3A4 is involved in the metabolism of thecepharanthine. The structure of M1 metabolite, identified by CDI-MS/MS, corresponds to a N-desmethyle derivative ofcepharanthine.

Ce doctorat porte sur l’étude de l’activité antipaludique de la cépharanthine. Deux méthodes écologiques d’extraction, utilisant des micro-ondes et ultrasons, ont été proposées. L'activité antiplasmodiale a été évaluée par le calcul de la concentration qui inhibe 50 % de la croissance parasitaire. Les cibles potentielles ont été évaluées par l’étude de la variation d’expression des gènes. Au niveau microscopique, la cépharanthine a semblé inhiber le développement parasitaire et bloquer les parasites au stade anneau. Au niveau transcriptomique, la cépharanthine semble avoir un impact sur le transport de protéines plasmodiales à la surface du globule rouge ; sur des organelles nécessaires à la survie du parasite, et sur les interactions entre le globule rouge parasité et l’endothélium ou les globules rouges sains. Des études de combinaisons thérapeutiques ont montré que la cépharanthine semble potentialiser certains antipaludiques. Une analyse quantitative de la cépharathine plasmatique a permis d’effectuer une étude pharmacocinétique. La cépharanthine pourrait être un chef de file intéressant pour le développement de nouveaux antipaludiques. / This PhD focuses on the study of the antimalarial activity of cepharanthine. Two green extraction methods, using microwave and ultrasound, have been proposed. The antiplasmodial activity was evaluated by calculating the concentration inhibiting 50 % of parasite growth. Potential targets were evaluated by studying the variation of gene expression. At the microscopic level, cepharanthine seemed to inhibit the parasite growth and to block parasite at the ring stages. The transcriptomic assay showed that cepharanthine seems to have an impact on the transport of Plasmodium proteins to the red blood cell surface, on organellar functions necessary for the survival of the parasite, and on the interactions between infected red blood cells and the endothelium or healthy red blood cells. The study of combination therapies showed that cepharanthine appears to potentiate some antimalarial compounds. A quantitative analysis of cepharathine in mouse plasma allowed performing a pharmacokinetic study. Cepharanthine could be an interesting lead to the development of new antimalarial drugs.

The dissertation is focused on the National Cultural Monument - the Romanesque Rotunda of Saint Catherine in Znojmo, in particular on the way the interior influences an integral medieval mural fresco decoration. An impact of the interior on the fresco decoration of a fresco-secco type is judged by available information sources, which draw from long-time, mainly foreign professional experience. The rotunda interior analysis is based on long-term measurement of temperature and humidity parameters and evaluated by a statistical approach. An impact of variable input boundary conditions on the interior is parametrically tested in a dynamic numerical simulation. Obtained results show a positive effect of the installed floor heating in the rotunda and on the other hand a negative impact of visitors on the state of the integral mural painting in the object. A final part of the dissertation includes practical recommendations resulting from a postulate of the preventive heritage preservation of the National Cultural Monument.

Tese de mestrado integrado. Engenharia Civil. Especialização em Vias de Comunicação. Universidade do Porto. Faculdade de Engenharia. 2012

The first part of the thesis deals with Romanesque rotundas. These are introduced and set in historical and cultural context of the early Middle Ages to understand the cause of their origin. A substantial part is devoted to formal analysis of individual rotundas located in Prague and its close surroundings, their function in various interpretations of Czech researchers. The next part of the thesis is dedicated to the work itself where the original parts of the individual rotundas are drawn. The theoretical principles are applied in the last part of the thesis, where they are united with a/r/tography research. It is described and used for subsequent methodical series of art education, which were taught at the first grade of primary school.

Diploma project “Chronicle House” is representing the creation of fictional historiographical interpretation of “the spirit of the place”. Rotunda is the columbarium The existence of object inside of the object, in this context, automatically creates a feeling of layeringness. The columbarium is oval shaped and the base level all the way by the perimeter consists of old windows from the panel houses, which were going through the process of modernization, particularly – change of windows. It serves now as a commemoration space. On the inside of the rotunda has been placed a museum of the ceased houses, where in the columbarium niches are placed models of these houses with the dates of birth and death, as well as with short epiphanies.

Draft spa in the Swiss city of Yverdon. CONTAINS part of the public baths, spas, health spas and hotel.

Urbanistic and architectural study of future development of castle area in Znojmo. Main focus will be on creation of sustainable and vital part of the city with connections to landscape, townscape, castle, old brewery and romanesque rotunda of st. Catherine. Adaptation of historic buildings of castle and brewery for cultural and social center of town. Reconstruction and conversion will be based on theoretical work from previous semester. Urbanistic goal is creation and redefinition of public spaces of castle garden, rotunda hill and Hradni street and its integration with historic town center of Znojmo and valley of river Dyje.