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[pt] A Mata Atlântica representa uma das regiões mais biodiversas e únicas do planeta e atualmente restam menos de 25 por cento de sua cobertura original. O Caminho da Mata Atlântica (CMA) é uma iniciativa de conservação que tem como missão engajar a sociedade na conservação e recuperação do bioma, por meio de atividades ao ar livre e da conexão de áreas naturais ao longo de uma trilha de longo curso (TLC). As TLC s, por sua vez, têm sido mundialmente reconhecidas como importantes ferramentas de conservação da biodiversidade e dos ecossistemas, uma vez que formam grandes corredores ecológicos. As rodovias são uma das principais causas de fragmentação de habitats naturais em todo o mundo e pioram ainda mais a situação de isolamento de áreas no bioma. Para mitigar os impactos negativos das estradas, algumas medidas compensatórias podem ser implementadas. O objetivo deste estudo foi analisar a legislação ambiental existente no âmbito federal e estadual do Rio de Janeiro relativa à restauração florestal, ao licenciamento ambiental e à concessão de rodovias, com o intuito de trabalhar estratégias para reduzir os impactos causados pela existência dessas estradas nas proximidades do traçado do CMA. Como resultado, podemos dizer que são poucos os contratos que trazem inovações nesse sentido. Considerando as graves consequências causadas pela fragmentação de habitats para a biodiversidade, é de extrema importância que seja dada mais atenção à construção das condicionantes de licença e das medidas compensatórias presentes nos contratos de concessão. O CMA pode ser uma solução, de forma a aumentar a conectividade entre os fragmentos e consolidar a trilha como um grande corredor funcional para a conservação da biodiversidade. / [en] The Atlantic Forest represents one of the most biodiverse and unique regions on planet Earth and less than 25 percent of its original coverage currently remains. The Atlantic Forest Trail (CMA) is a conservation initiative whose mission is to engage society in the conservation and recovery of the biome, through outdoor activities and the connection of natural areas along a long-distance trail. These, in turn, have been recognized worldwide as important tools for conserving biodiversity and ecosystems, as they form large ecological corridors. Highways are one of the main causes of fragmentation of natural habitats around the world and further worsen the situation of isolated areas in the biome. To mitigate the negative impacts of roads, some compensatory measures can be implemented, such as the creation of ecological corridors, based on forest restoration. The objective of this study was to analyze the existing environmental legislation at the federal and Rio de Janeiro state levels regarding forest restoration, environmental licensing and highway concessions, with the aim of working on strategies to reduce the impacts caused by the existence of these roads nearby the CMA route. As a result, we can say that few agreements bring innovations in this sense. Considering the serious consequences for biodiversity caused by habitats fragmentation, it is extremely important to give more attention to the construction of license conditions and compensatory measures present in concession agreements. CMA can be a solution, in order to increase connectivity between the fragments and consolidate the trail as a large functional corridor for biodiversity conservation.

This is a project about reconciling the rational world of architecture with the empirical world of nature. A small retreat on the Appalachian Trail near Dragon's Tooth, this project employs two elements belonging to each of those entities. The retreat is composed of a double envelope. The exterior envelope is a wooden screen and dry stacked stone wall relating to the natural world. In contrast, the second envelope is a glass and steel box, analogous to the rationality of man. Dimensional 2x4 lumber models are employed to study the light conditions, patterns, and construction of the wooden screen. / Master of Architecture

Bei Autoimmunkrankheiten wie der Multiplen Sklerose (MS) kommt es zu einer fehlgesteuerten Immunantwort mit Aktivierung und Persistenz autoreaktiver T-Zellen. Apoptose-regulierende Mechanismen wie das CD95-Rezeptor/CD95-Ligand- und TRAIL-Rezeptor/TRAIL-System könnten dabei eine wichtige Rolle spielen. Die lösliche Form des CD95-Rezeptor (sCD95) kann an CD95L binden und so die Apoptose aktivierter T-Zellen verhindern. Die systemische Blockade von TRAIL führt zur Exazerbation von Autoimmunerkrankungen in Tierversuchen. In der vorliegenden Arbeit wurden deshalb die Expression, Regulation und Bedeutung sowohl von sCD95 als auch von löslichem TRAIL (sTRAIL) und membranständigem TRAIL bei gesunden Probanden und Patienten mit schubförmig remittierender MS (RRMS) untersucht. Zytokine wurden mit ELISAs, Zelloberflächenproteine sowie Apoptose im Durchflusszytometer gemessen. Die Untersuchungen mit magnetisch gereinigten humanen Leukozytensubpopulationen und Zelllinien zeigten, dass sCD95 lediglich von zelltyp-spezifisch aktivierten humanen T-Zellen, sezerniert wird. TRAIL wurde vor allem von Monozyten, die mit IFN-beta stimuliert waren, sezerniert und auf der Zelloberfläche exprimiert. Zellkulturüberstände, die sTRAIL enthielten, lösten Apoptose in suszeptiblen Tumorzellen aus. TRAIL führte zu einer signifikanten Inhibition der Proliferation und der Produktion von Th1- und Th2-spezifischen Zytokinen bei humanen (auto)antigenspezifischen T-Zellen. Weder für die sCD95- noch für die TRAIL-Expression wurden Unterschiede zwischen RRMS-Patienten und gesunden Probanden nachgewiesen. Die Ergebnisse dieser Arbeit zeigen ein komplexes Regulations- und Expressionsmuster von sCD95 und TRAIL, ohne jedoch Anhaltspunkte für Unterschiede zwischen MS-Patienten und Gesunden zu liefern. Es ergaben sich wichtige Hinweise darauf, dass der protektive immunomodulatorische Effekt einer systemischen IFN-beta-Therapie bei MS durch TRAIL vermittelt werden könnte. / Autoimmune disorders such as Multiple Sclerosis (MS) are characterized by an aberrant immune response with activation and persistence of autoreactive T-cells. Apoptosis-regulating mechanism such as the CD95-Rezeptor/CD95-Ligand- and the TRAIL-Rezeptor/TRAIL-System may play a major role in this process. The soluble CD95 receptor (sCD95) can bind to CD95L and subsequently inhibit apoptosis of activated T-cells. The systemic blockade of TRAIL leads to the exacerbation of autoimmune disease in animal experiments. In this work I investigated the expression, regulation and significance of sCD95, soluble TRAIL (sTRAIL) and membrane-bound TRAIL in patients with remitting-relapsing MS (RRMS), and in healthy controls. Cytokines were measured by ELISA, membrane bound proteins and apoptosis were measured by flow cytometry. The experiments with magnetically sorted human leucocyte subpopulations and cell lines showed, that only cell-type specific activated human T-cells secrete sCD95. Both forms of TRAIL were expressed by monocytes stimulated with IFN-beta. Cell supernatants containing sTRAIL induced apoptosis in susceptible tumour cells. Furthermore TRAIL inhibited proliferation of (auto)antigen-specific T cells and the production of Th-1 and Th-2 specific cytokines. There were no differences in the expression of sCD95 and TRAIL between RRMS patients and healthy controls. This work shows a complex regulation pattern of sCD95 and TRAIL without being able to detect differences between MS patients and healthy controls. However, results point out that TRAIL could be an important mediator of the immunomodulatory effects of systemic IFN-beta therapy in MS.

TRAIL (TNF-related apoptosis inducing ligand) est une protéine anti-tumorale capable de se lier spécifiquement aux récepteurs agonistes de mort (TRAIL-Rl ou DR4 et TRAIL-R2 ou DR5) des cellules cancéreuses et d'induire leur apoptose sans être toxique pour les cellules saines. Grâce à leurs propriétés exceptionnelles, notamment leur biocompatibilité, les nanotubes de carbone et surtout les SWCNTSs sont utilisés dans un large éventail d'applications et sont considérés très prometteurs pour révolutionner la thérapie anticancéreuse en nanomédecine. Les SWCNTSs sont connus par leur diffusion rapide dans un milieu aqueux tel que le sang, ouvrant la voie de développement de nouveaux nanovecteurs de médicaments. L'objectif principal de nos travaux de thèse a consisté à fonctionnaliser TRAIL sur des SWCNTSs pour mimer sa fonction membranaire en induisant une forte agrégation des récepteurs et déclencher l'apoptose (mort cellulaire programmée). Dans un premier temps, la fonctionnalisation des SWCNTSs avec TRAIL a été réalisée: adsorption non covalente des molécules de PSE sur les nanotubes via 1t-1t stacking, puis greffage du TRAIL au complexe SWCNTS-PSE pour former le nanovecteur (nommé NPT). Ensuite, nous avons caractérisé notre NPT par différentes méthodes (RAMAN, XPS, IR, MET, STEM ... ) afin d'estimer le taux de greffage du TRAIL sur le NPT, qui était environ de 80%. Dans un deuxième temps, nous avons étudié les paramètres thermodynamiques tels que le pH et la température du NPT en comparaison avec TRAIL seul par une approche chromatographique d'affinité (CHLP). Les résultats obtenus montrent une meilleure affinité du nanovecteur par rapport à TRAIL seul avec le récepteur TRAIL-R2 immobilisé sur la colonne chromatographique. En outre, des calculs de docking ont montré également que le complexe NPT couplé aux homotrimères de TRAIL est le plus stable une fois docké au récepteur TRAIL-R2. Ainsi, nous avons montré que les interactions de type Van der Waals et des liaisons hydrogène régissent l'association NPT-DR5 pour un pH supérieur à 7,4 (comme pour TRAIL seul). Enfin, notre nanovecteur s'est avéré plus efficace que TRAIL seul dans des différents tests menés in vitro sur des plusieurs types de lignées tumorales. Le NPT a permis une augmentation du potentiel pro­apoptotique de TRAIL avec un gain de fonction apoptotique estimé entre 10-20 fois par rapport à celui obtenu avec TRAIL seul. Dans ce travail, nous fournissons ainsi une preuve de concept que les nanovecteurs basés sur la fonctionnalisation du TRAIL avec les SWCNTSs peuvent être utiles pour les futurs traitements anti-cancéreux en nanomédecine. / TRAIL (TNF-related apoptosis inducing ligand) is a protein involved in immune anti-tumor surveillance. This cytokine is able to bound specifically to agonist death receptors (TRAIL-Rl or DR4 and TRAIL-R2 or DR5) of cancer cells, inducing apoptosis without being taxie to healthy cells. Thanks to their exceptional properties such as biocompatibility, carbon nanotubes and especially single-walled carbon nanotubes (SWCNTSs) are used in a wide range of applications and are considered to be very promising for cancer therapy in nanomedicine. The SWCNTSs are known to rapidly diffuse in aqueous media such as blood, opening the way for the development of new drug nanovectors or nanocarriers. The main purpose of this work is to functionalize SWCNTSs with TRAIL to mimic the membrane function of TRAIL by inducing a strong aggregation of death receptors and then induce apoptosis. First of all, the choice of SWCNTS functionalization with TRAIL was considered the first key in this thesis: non-covalent adsorption of PSE molecules on the nanotubes via 1t-1t stacking and TRAIL was next attached to a SWCNTS-PSE to form our nanovector, called NPT. Then, the NPT was characterized by various methods (Raman, XPS, IR, TEM, STEM, ... ) in order to estimate the grafted degree of TRAIL on the NPT surface (about 80%). Secondly, we investigated the ef:fects of the thermodynamic parameters such as pH and temperature on NPT versus TRAIL by a chromatographie approach (HPLC). The results showed a better affinity for NPT compared to TRAIL alone with the TRAIL-R2 receptor immobilized on the chromatographie colurnn. In addition, docking calculations have also shown that the NPT complex coupled to TRAIL homotrimers is the most stable when docked to DR5. Thus, we have demonstrated that Van der Waals interactions and hydrogen bonds govem the NPT-DR5 association for pH > 7.4 (as for TRAIL). Finally, our TRAIL-based SWCNTSs nanovectors (NPT) proved to be more efficient than TRAIL alone towards death receptors in triggering cancer cell killing in vitro. These NPTs increased the pro-apoptotic potential of TRAIL by nearly 10 to 20-fold in different Human tumor cell lines tested including colorectal, non-small cell lung cancer, or hepatocarcinomas. We provide in this work a proof of concept that nanovectors based on SWCNTS functionalization with TRAIL may be useful for future cancer treatments in nanomedicine.

The role of executive functioning in substance dependence and addiction has received increased attention in recent years; however, the findings of empirical studies are at times contradictory and difficult to compare at face value. To address the current state of fragmentation and to delineate the current body of knowledge a systematic review of existing studies was conducted. The synthesis of the findings from these studies confirmed that lower neuropsychological performance scores of executive functioning are observed in substance dependent populations. Furthermore, the synthesis of the components of these studies provided a comprehensive overview and revealed a number of critical gaps in the current body of knowledge. The gaps include limitations concerning specific demographics of the samples studied (under-representation of females, adolescents, the elderly, individuals with limited education, and individuals from Africa, Oceania, Asia, Latin America and the Caribbean), as well as the scarce number of studies investigating specific substances; insufficient longitudinal studies; and the fragmentation of executive functioning as a theoretical construct. / Psychology / M.A. (Psychology)

This master thesis is the groundwork for realization of an educational nature trail in the Natural monument Milíčovský Forest and Ponds. The theoretical part deals with the nature protection in the Czech Republic, as a part of the European Union. Moreover, the characteristics of the given area are elaborated in detail with a focus on geology, flora and fauna in this part. In the practical part, I utilised the basic information as a basis for individual panels of the educational nature trail,. The graphical layout of individual panels is attached as an apendix of the thesis. The purpose of this study is to contribute to the protection of natureal values in Natural Natural monument Milíčovský Forest and Ponds. The information provided in this study should have wider impact in the way that they improve general understanding of nature. Furthermore they should extend general knowledge about Milíčovský Forest of its visitors and simultaneously they should reinforce their positive attitude toward nature as a whole.