Regensburg, Univ., Diss., 2009.

In 1988, Galle Fort in Sri Lanka was declared a world heritage site by UNESCO. The new historic-preservation regulatory setup that came with this designation displaced its inhabitants in their own homes. This thesis examines on how these inhabitants negotiate preservation regulations and the government’s effort to maintain a “world heritage” status based on their view. It focuses on how people adapt to the newly regulated environment and create spaces for their own daily practices. This study identifies that there are people who follow the government rules and transform themselves into subjects, while others break government rules and create the lived spaces they want. In-between are the majority of people who both become subjects of the space and also negotiate with the government rules to create their (negotiated) living environments. Although the government has more power, the people with less power have been transforming the space to meet their own needs and create a sense of place. / Department of Urban Planning

The theme of the thesis is the influence of the urban development activities on the historic commercial areas. Hence, the thesis focuses on the evaluation of these factors which cause alterations and transformations within the area and aims to propose compatible solutions against the problems in order to achieve the sustainability of the historic texture within the commercial area. In this thesis, Yeni Galle Pazari Hani,, one of the 16th century Ottoman Hans in the Hanlar District of Bursa, is studied together with its immediate surrounding. In order to define necessities and requirements of a transformed historic commercial area, it is aimed to conduct research, analysis, and decision stages concerning the studied area. For this purpose, the values, the problems and the potentials of the study area are defined and alternative conservation solutions are proposed. It is also aimed to present the principles and decisions on the preservation and rehabilitation of the study area, called as &amp / #8216 / Yeni Galle Pazari Hani and its immediate surrounding&amp / #8217 / , in environmental scale. Therefore, the main aim of the thesis is to determine the principles and the tools of an urban conservation project within the context of environmental scale and to re-gain the unity of Yeni Galle Pazari Hani as much as possible by integrating it into the current atmosphere of Hanlar District in Bursa together with the traditional texture surrounding it. In this study, the insufficiency observed in preparatory stages of most of current restoration projects was emphasized. Hence, before intervention of such kind of traditional areas, it is aimed to take care of documentation, to make a comprehensive study on unobserved parts of traditional texture such as archeological excavation, and to form a worksheet containing principles and decisions for future studies that would be done under various disciplines. The proposal for the case of Yeni Galle Pazari Hani is significant as being composed of documentation, observation and decision parts of a proper intervention, although it can be accepted as an incomplete project, since being the first step of a comprehensive restoration project for the study area. In conclusion, this study exemplifies the documentation and the evaluation of the transformation in a historic commercial area and the suggestion to solve the general problems among the Historical Commercial Center of the cities by taking decisions on conservation and rehabilitation for the sustainability of the study area.

Seeking to widen the existing literature on postcolonial cities, this thesis conducts an inquiry into the multilocality of postcolonial space. Through ethnographic research in Sri Lanka’s Galle Fort, it investigates how different social groups differently use and interpret the city’s former colonial built environment. Specifically, it examines how the postcolonial city is socially produced and constructed as a place of home for local communities, a World Heritage Site, and a gentrifying neighborhood. Using interviews, observations, and spatial analyses, it teases out the local, national, and transnational socio-economic forces that drive these processes, as well as the power-dynamics and resistances that come into play. It finds that postcolonial uses of space often relate to, and sometimes recall, social struggles that characterized urban space under colonialism. Drawing on these findings, it highlights the importance of studying social relations, heritage management, and gentrification in postcolonial cities in conversation with literatures on colonial urbanisms.

Most medicines are taken orally. To enter the systemic circulation, they dissolve in the intestinal fluid, cross the epithelial barrier, and pass through the liver. Intestinal absorption is driven by the unique features of the gastrointestinal tract, including the bile colloids formed in the lumen and the mucus layer covering the intestinal epithelium. Neglecting this multifaceted environment can lead to poor drug development decisions, especially for poorly water-soluble drugs that interact with bile and mucus. However, there is a lack of a rationale nexus of molecular interactions between oral medicines and gastrointestinal components with drug bioavailability. Against this background, this thesis aims to develop biopharmaceutical strategies to optimize the presentation of oral therapeutics to the intestinal epithelial barrier. In Chapter 1, the dynamics of bile colloids upon solubilization of the poorly-water soluble drug Perphenazine was studied. Perphenazine impacted molecular arrangement, structure, binding thermodynamics, and induced a morphological transition from vesicles to worm-like micelles. Despite these dynamics, the bile colloids ensured stable relative amounts of free drug substance. The chapter was published in Langmuir. Chapter 2 examined the impact of pharmaceutical polymeric excipients on bile-mediated drug solubilization. Perphenazine and Imatinib were introduced as model compounds interacting with bile, whereas Metoprolol did not. Some polymers altered the arrangement and geometry of bile colloids, thereby affecting the molecularly soluble amount of those drugs interacting with bile. These insights into the bile-drug-excipient interplay provide a blueprint to optimizing formulations leveraging bile solubilization. The chapter was published in Journal of Controlled Release. Chapter 3 deals with the impact of bile on porcine intestinal mucus. Mucus exposed to bile solution changed transiently, it stiffened, and the overall diffusion rate increased. The bile-induced changes eased the transport of the bile-interacting drug substance Fluphenazine, whereas Metoprolol was unaffected. This dichotomous pattern was linked to bioavailability in rats and generalized based on two previously published data sets. The outcomes point to a bile-mucus interaction relevant to drug delivery. The chapter is submitted. The Appendix provides a guide for biopharmaceutical characterization of drug substances by nuclear magnetic resonance spectroscopy aiming at establishing a predictive algorithm. In summary, this thesis deciphers bile-driven mechanisms shaping intestinal drug absorption. Based on these molecular insights, pharmaceuticals can be developed along a biopharmaceutical optimization, ultimately leading to better oral drugs of tomorrow. / Die meisten Arzneimittel werden oral eingenommen. Um in den Blutkreislauf zu gelangen, liegen sie in der Darmflüssigkeit gelöst vor, überwinden die Epithelbarriere und passieren die Leber. Die intestinale Absorption wird durch die einzigartigen Eigenschaften des Magen-Darm-Trakts, einschließlich der im Lumen gebildeten Gallenkolloide und der Schleimschicht, die das Darmepithel bedeckt, bestimmt. Die Vernachlässigung dieser facettenreichen Umgebung kann zu schlechten Entscheidungen bei der Arzneimittelentwicklung führen, insbesondere bei schlecht wasserlöslich Wirkstoffen, die mit Galle und Schleim interagieren. Es fehlt jedoch eine rationale Verknüpfung der molekularen Wechselwirkungen zwischen oralen Arzneimitteln und gastrointestinalen Komponenten mit der Bioverfügbarkeit von Arzneimitteln. Vor diesem Hintergrund zielt diese Arbeit darauf ab, biopharmazeutische Strategien zur Optimierung der Präsentation von oralen Therapeutika an der intestinalen Epithelbarriere zu entwickeln. In Kapitel 1 wurde die Dynamik von Gallenkolloiden bei der Solubilisierung des schwer wasserlöslichen Wirkstoffes Perphenazin untersucht. Perphenazin beeinflusste die molekulare Anordnung, die Struktur sowie die Bindungsthermodynamik und führte zu einem morphologischen Übergang von Vesikeln hin zu wurmartigen Mizellen. Trotz dieser Dynamik sorgten die Gallenkolloide für stabile relative Mengen an freiem Arzneistoff. Dieses Kapitel wurde in Langmuir veröffentlicht. In Kapitel 2 wurde der Einfluss von pharmazeutischen polymeren Hilfsstoffen auf die Solubilisierung von Wirkstoffen durch Galle untersucht. Perphenazin und Imatinib wurden als Modellverbindungen eingeführt, die mit der Galle interagieren, während Metoprolol dies nicht tat. Einige Polymere veränderten die Anordnung und Geometrie der Gallenkolloide und beeinflussten somit die molekular lösliche Menge von solchen Wirkstoffen, die mit der Galle wechselwirken. Diese Einblicke in das Zusammenspiel von Galle und Arzneistoffen bieten einen Ansatz zur Optimierung von Formulierungen, die die Solubilisierung in der Galle nutzen. Dieses Kapitel wurde in Journal of Controlled Release veröffentlicht. Kapitel 3 befasst sich mit den Auswirkungen von Galle auf den Dünndarmschleim von Schweinen. Schleim, der Gallenlösung ausgesetzt war, veränderte sich vorübergehend, versteifte sich und die Gesamtdiffusionsrate nahm zu. Die durch die Galle hervorgerufenen Veränderungen erleichterten den Transport des mit der Galle interagierenden Wirkstoffs Fluphenazin, während Metoprolol unbeeinflusst blieb. Dieses dichotome Muster konnte mit der Bioverfügbarkeit bei Ratten verknüpft werden und durch zwei zuvor veröffentlichte Datensätze mit insgesamt 50 Verbindungen verallgemeinert werden. Die Ergebnisse deuten auf eine Wechselwirkung zwischen Galle und Schleim hin, die für die Verabreichung von Medikamenten relevant ist. Dieses Kapitel ist eingereicht. Der Anhang bietet einen Leitfaden für die biopharmazeutische Charakterisierung von Arzneimittelsubstanzen durch kernmagnetische Resonanzspektroskopie mit dem Ziel des Aufstellens von prädiktiven Algorithmen. Zusammenfassend entschlüsselt diese Arbeit die von der Galle gesteuerten Mechanismen, die die Aufnahme von Arzneimitteln im Darm beeinflussen. Auf der Grundlage dieser molekularen Erkenntnisse können Arzneimittel entlang einer biopharmazeutischen Optimierung entwickelt werden, was letztendlich zu besseren oralen Arzneimitteln führt.

La galle du collet, caractérisée par la formation d'une tumeur, représente la bactériose la plus répandue chez la vigne et entraine d'importantes pertes économiques à travers le monde. L'agent responsable de cette maladie est le plasmide Ti (pTi) qui confère à ces bactéries hôtes, telles que des Allorhizobium vitis, leur pouvoir pathogène. En plus du pTi, les A. vitis sont aussi les hôtes d'autres plasmides dont les fonctions et les modes de dissémination sont peu documentés. Afin d'étudier l'adaptation particulière des souches d'A. vitis à la vigne, nous nous sommes intéressés à la diversité de ces pathogènes ainsi qu'au rôle de ces plasmides et à la régulation de leur dissémination. Tout d'abord, nous avons analysé la diversité des isolats provenant de vignobles du Maroc atteints par la galle du collet. Nous avons pu mettre en évidence que l'ensemble des isolats pathogènes (e.g. porteur d'un pTi) forme 4 groupes génétiques se distinguant par le type d'opine produit. Nous nous sommes par la suite intéressés à la souche A. vitis S4 qui héberge 5 plasmides dont 3 possèdent un mécanisme de transfert pouvant être régulé par un système de communication bactérienne nommé quorum sensing (QS). Nous avons montré que le système QS du plasmide p130 (renommé pApi) contrôle non seulement le transfert conjugatif du pApi mais aussi d'autres fonctions plasmidiques non caractérisées. Ce système QS nécessite la synthèse d'une molécule signal de type N-acyl-homosérine lactone qui d'après nos travaux de caractérisation possède une structure atypique. De plus, des analyses génomiques couplées à des tests de résistance au cuivre nous ont permis d'identifier, sur le plasmide p79 d'A. vitis S4, un îlot de gènes potentiellement impliqués dans la résistance au cuivre de cette souche. Via des analyses de diversité ainsi que l'étude d'une souche modèle, nos travaux fournissent des connaissances sur l'adaptation d'Allorhizobium vitis à son unique plante hôte, la vigne / Crown gall disease, characterized by the formation of a tumor, represents the most widespread bacteriosis in the vineyard and causes significant economic losses throughout the world. The causing agent is the Ti plasmid (pTi) which confers pathogenicity to their bacterial hosts, such as Allorhizobium vitis. In addition to pTi, A. vitis harbours other plasmids whose functions and ways of dissemination are poorly documented. In order to study the peculiar adaptation of A. vitis strains to grapevine, we studied the diversity of these pathogens as well as the role of plasmids and the regulation of their dissemination.First, we analyzed the diversity of isolates from vineyards of Morocco affected by crown gall. We highlighted that all the pathogenic isolates (e.g. carrying a pTi) form 4 genetic groups that are distinguished by the type of opine produced and the ability to induce a hypersensitive response. We then focused on strain A. vitis S4, which contains 5 plasmids, including 3 possessing a transfer mechanism that can be regulated by a bacterial communication system called quorum sensing (QS). We demonstrated that the QS system of plasmid p130 (renamed pApi) controls not only the conjugative transfer of the pApi but also other uncharacterized plasmid-encoded functions. This QS system requires the synthesis of a N-acyl-homoserine lactone signal molecule with an atypical structure. In addition, genomic analyzes combined with copper resistance assays allowed us to identify, on plasmid p79 of A. vitis S4, a genomic island that is likely involved in copper resistance of this strain.Through analyzes of diversity and study of a model strain, our work provides insight into adaptation of Allorhizobium vitis to its unique host plant, grapevine

This study looks at the degree to which Emile Galle's theories of symbolic ornamentation are observed in contemporary landscape architecture design. Galle's theories consist of three components: the first relates to the functional aspects of design, and the last two relate to the aesthetic aspects. These three components are used to evaluate three case studies. In the case studies, Bicentennial Commons in Cincinnati and Canal Walk in Indianapolis show a partial though apparent utilization of Galle's theories, while Riverwalk in Milwaukee comes closest of the three to demonstrating the application of Galle's theories in Landscape Architecture. However, none fully exhibit Galle's theories. Nonetheless, the case studies, and in particular Riverwalk, exhibit the initial stages of a renewed interest in ornamentation in which culture is symbolically represented through nature. Landscape Architects, more than ever, are being called upon to embody the meaning of the land through a cultural synthesis in an expression of past/present and man/nature. / Department of Landscape Architecture

Phloeomyzus passerinii est un important ravageur des peupleraies en Europe. Ce puceron se développe sur les troncs de peuplier, avec un mode nutrition mal connu, et présente des performances variables selon les génotypes de peuplier. Dans une optique de gestion de cet insecte, il était nécessaire de clarifier la nature de ses interactions trophiques avec son hôte. En complément, nous avons étudié comment la résistance de l’hôte et des facteurs environnementaux, comme la fertilisation et une contrainte hydrique, pouvaient affecter ces interactions. Des approches histologiques et biochimiques ont permis de mettre en évidence l’induction par l’insecte d’un tissu organise dans l’écorce d’un génotype sensible (I-214), qualifiable de pseudo-galle, où les composés phénoliques solubles disparaissent mais ou des acides aminés s’accumulent. Des approches complémentaires ont montré que le comportement de nutrition du puceron était optimisé sur ces tissus modifiés, et son développement larvaire amélioré. Concernant les mécanismes de résistance, dans un génotype très résistant (Brenta), la formation de la pseudogalle était totalement inhibée, suite à une lignification intense et étendue des tissus, empêchant l’installation du puceron. Dans un génotype de résistance intermédiaire (I-45/51), la formation était seulement partiellement inhibée, diminuant les performances démographiques et comportementales de l’insecte, et la capacité du tissu modifié à accumuler des acides aminés. Pour étudier l’impact environnemental, nous avons considéré les effets de trois niveaux de fertilisation et de trois niveaux d’irrigation du sol. La fertilisation n’a pas modifié les performances du puceron, probablement à cause d’une accumulation d’acides aminés par la pseudogalle d’autant plus forte que la fertilisation était faible. Le déficit hydrique a affecté les interactions, notamment au travers d’un effet génotype dépendant, favorisant le développement de l’insecte lors d’une contrainte intermédiaire chez le génotype résistant seulement et affectant négativement le développement chez les génotypes sensible et résistant lors d’une contrainte élevée. / Phloeomyzus passerinii is an important pest of cultivated poplar stands in Europe. It develops onpoplar trunks, thanks to an undefined feeding mode, and exhibits variable performances depending on poplargenotypes. To develop efficient management strategies, we have investigated the trophic interactions betweenthis pest and its host. In addition, we have studied how host resistance and environmental factors, like fertilizationand water deficit, could affect these interactions. Histological and biochemical approaches highlighted theinduction by the aphid of an organized tissue in the bark of a susceptible poplar genotype (I-214), considered as apseudogall, where soluble phenolic compounds disappear but amino acids accumulate. Behavioral andphysiological approaches showed that the aphid nutrition behavior is optimized on these modified tissues, andthat its nymphal development is improved. Regarding resistance mechanisms, on a highly resistant genotype(Brenta), pseudogall formation was totally inhibited, due to an intense and extended lignification, preventing aphidsettlement. On a moderately resistant genotype (I-45/51), pseudogall formation was only partially inhibited,reducing demographic and behavioral performances of the insect, and the ability of the pseudogall to accumulateamino acids. To study environmental impacts, we considered the effects of three soil fertilization levels and threeirrigation levels. Fertilization did not modify aphid performances, probably due to an increase in amino acidsaccumulation by the pseudogall when fertilization decreased. Water deficit affected the interactions, through agenotype dependant effect, favoring insect development under an intermediate deficit on the resistant genotypeonly, and negatively affecting the development on both susceptible and resistant genotypes during a severe waterdeficit.