Les travaux de cette thèse présentent la synthèse par une polymérisation RAFT en miniémulsion de nanoparticules fluorescentes (NPFs) polymères à coeur BODIPY copolymérisé au styrène et à couronne hydrophile biocompatible et fonctionnalisable à base de poly(oxyde d'éthylène) et de poly(acide acrylique). Les propriétés de fluorescence de ces NPFs ont été étudiées par spectroscopie de fluorescence stationnaire et résolue en temps. L'élaboration de la synthèse de ce type de NPFs, et la mise au point d'un procédé "one-pot" sont présentés dans un premier temps. Ensuite, les propriétés spectroscopiques de ces NPFs sont étudiées, notamment l'influence de la concentration en monomères de BODIPY au coeur des NPFs pouvant mener à la formation d'agrégats peu ou pas fluorescents. Les propriétés spectroscopiques (longueur d'onde d'émission de fluorescence et rendement quantique) du coeur des NPFs ont été modulées. Cela est rendu possible en réalisant la synthèse de monomères de BODIPY portant des groupements aromatiques encombrés, ou présentant différentes fonctions polymérisables. La couronne hydrophile des NPFs a également été modifiée afin d'obtenir différentes répartitions des unités acide acrylique et oxyde d'éthylène dans les chaînes de copolymères en surface. Ces nouvelles NPFs sont également synthétisées par un procédé "one-pot". Enfin, des molécules à fonctions amine (fluorophores, protéines) ont été introduites dans la couronne hydrophile de ces diverses NPFs par une chimie de couplage peptidique sur les fonctions acides carboxyliques. Des nano-senseurs de pH ratiométriques ont ainsi pu être élaborés.

La barrière hémato-encéphalique (BHE) protège le système nerveux central (SNC) en contrôlant le passage des substances sanguines et des cellules immunitaires. La BHE est formée de cellules endothéliales liées ensemble par des jonctions serrées et ses fonctions sont maintenues par des astrocytes, celles ci sécrétant un nombre de facteurs essentiels. Une analyse protéomique de radeaux lipidiques de cellules endothéliales de la BHE humaine a identifié la présence de la voie de signalisation Hedgehog (Hh), une voie souvent liées à des processus de développement embryologique ainsi qu’au niveau des tissus adultes. Suite à nos expériences, j’ai déterminé que les astrocytes produisent et secrètent le ligand Sonic Hh (Shh) et que les cellules endothéliales humaines en cultures primaires expriment le récepteur Patched (Ptch)-1, le co-récepteur Smoothened (Smo) et le facteur de transcription Gli-1. De plus, l’activation de la voie Hh augmente l’étanchéité des cellules endothéliales de la BHE in vitro. Le blocage de l’activation de la voie Hh en utilisant l’antagoniste cyclopamine ainsi qu’en utilisant des souris Shh déficientes (-/-) diminue l’expression des protéines de jonctions serrées, claudin-5, occcludin, et ZO-1. La voie de signalisation s’est aussi montrée comme étant immunomodulatoire, puisque l’activation de la voie dans les cellules endothéliales de la BHE diminue l’expression de surface des molécules d’adhésion ICAM-1 et VCAM-1, ainsi que la sécrétion des chimiokines pro-inflammatoires IL-8/CXCL8 et MCP-1/CCL2, créant une diminution de la migration des lymphocytes CD4+ à travers une monocouche de cellules endothéliales de la BHE. Des traitements avec des cytokines pro-inflammatoires TNF-α and IFN-γ in vitro, augmente la production de Shh par les astrocytes ainsi que l’expression de surface de Ptch-1 et de Smo. Dans des lésions actives de la sclérose en plaques (SEP), où la BHE est plus perméable, les astrocytes hypertrophiques augmentent leur expression de Shh. Par contre, les cellules endothéliales de la BHE n’augmentent pas leur expression de Ptch-1 ou Smo, suggérant une dysfonction dans la voie de signalisation Hh. Ces résultats montrent que la voie de signalisation Hh promeut les propriétés de la BHE, et qu’un environnement d’inflammation pourrait potentiellement dérégler la BHE en affectant la voie de signalisation Hh des cellules endothéliales. / The blood-brain barrier (BBB), composed of tightly bound endothelial cells (ECs), regulates the entry of blood-borne molecules and immune cells into the CNS. Recent studies indicate that the Hedgehog (Hh) signaling pathway in adult tissues plays an important role in vascular proliferation, differentiation and tissue repair. Using a lipid membrane raft-based proteomic approach, I have identified the Hedgehog (Hh) pathway as a signaling cascade involved in preserving and upkeeping BBB functions. My study shows that human astrocytes express and secrete Sonic Hh (Shh) and conversely, that human BBB-ECs bear the Hh receptor Patched-1 (Ptch-1), the signal transducer Smoothened (Smo) as well as transcription factors of the Gli family. Furthermore, activation of the Hh pathway in BBB-ECs restricts the passage of soluble tracers in vitro. By blocking the Hh signaling in vitro and by using Shh knock-out (-/-) embryonic mice, I demonstrate a reduced expression of TJ molecules claudin-5, occludin and ZO-1. Hh activation also decreases the surface expression of cell adhesion molecules ICAM-1 and VCAM-1, and decreases BBB-ECs secretion of pro-inflammatory chemokines IL-8/CXCL8 and monocytes chemoattractant protein 1 MCP-1/CCL2, resulting in a reduction of migrating CD4+ lymphocytes across human BBB-EC monolayers. In vitro treatment with inflammatory cytokines TNF-α and IFN-γ, upregulates the production of astrocytic Shh and the BBB-EC surface expression of Ptch-1 and Smo. In active Multiple Sclerosis (MS) lesions, in which the BBB is disrupted, Shh expression is drastically upregulated in hypertrophic astrocytes, while Ptch-1 and Smo expression is down-regulated or left unchanged, suggesting that a deregulation in the Hh signaling pathway may prevent the barrier stabilizing properties of Hh. Our data demonstrate an anti-inflammatory and BBB-promoting effect of astrocyte-secreted Hh and suggest that a pro-inflammatory environment disrupt the BBB by impacting, at least in part, on Hh signaling in brain ECs.

Gegenstand dieser Arbeit war die Synthese von thermisch schaltbaren Kammcopolymeren auf Basis von N-(Isopropylacrylamid) (NiPAAm) und Polyethylenglykolmakromonomeren (PEGMA). Die intensive Charakterisierung der aus diesen Copolymeren hergestellten Schichten und deren Anwendung als Zellkultursubstrate war ein weiteres Forschungsziel dieser Arbeit. Die mit Hilfe der neuartigen Schichten erhaltenen Zellkultursubstrate wurden anhand verschiedener adhärenter Zelllinien erfolgreich getestet. Alle getesten Zelltypen (Mausfibroblasten, humane Endothelzellen der Nabelschnurvene und humane korneale Endothelzellen) proliferierten auf den angebotenen Zellkultursubstraten bei 37°C und konnten durch senken der Temperatur geerntet werden.

本研究透過針對台東縣都蘭社群建造傳統竹筏所記載的民族誌，探索該社群在政府授權的美麗灣民間興建營運後轉移模式(BOT)發展案中的角色與互動。研究內容包括了(1)對民間興建營運後轉移之模式的總體回顧，以及美麗灣此個案的評估。(2)在地阿美族社群對發展計畫反對的詳細論述。(3)在替代發展方案上的建議。我的田野調查包含了在社群集會與示威抗議活動上的參與觀察，但調查的重心則立基於一條阿美竹筏建造與出海的過程。本文的結論提供了一套能夠兼顧在地居民互動及外來廠商利益的發展方案，旨在透過融合相關各方的觀點以圖能夠減少衝突並促進共同利益。 / This research explores the dimensions and interactions of the Amis community under the Miramar Resort (MR) Build-Operate-Transfer (BOT) development project authorized by the local county government through an ethnographic approach on the construction of a traditional bamboo raft in the township of Dulan, Taitung, Taiwan. The content of this study includes (1) A status review of the BOT policy in general and the MR development project in particular, (2) A detailed account of the local Amis community’s opposition to the project, and (3) Suggestion on alternative methods of land management. My fieldwork includes participant observation in the context of seminar meetings and activist demonstrations. However the centerpiece of the research at Dulan revolves around my personal participation in the construction of an Amis traditional bamboo raft and its launching into the ocean. Conclusions offer alternative ways for the development of an area that is interactive with indigenous peoples and outside commercial interests. The perspective taken is aimed at alleviating conflict through incorporating the views of stakeholders in the best interests of all parties involved.

CAPITULO 1 â Perfil dos carpinteiros artesanais de embarcaÃÃes a vela do litoral do estado do Cearà No contexto mundial, durante o sÃculo XV, a construÃÃo naval das embarcaÃÃes veleiras passaram por evoluÃÃes que propiciaram o empreendimento de grandes viagens. Chegando ao Brasil iniciou-se um longo processo de interaÃÃo construtiva das embarcaÃÃes locais com o conhecimento europeu. As jangadas inicialmente construÃdas sem velas evoluÃram e se propagaram por todo o nordeste e, principalmente no Cearà como embarcaÃÃo de pesca artesanal, evoluindo das jangadas de troncos Ãs atuais de tÃbuas, assim como ocorreu evoluÃÃo construtiva artesanal das canoas e botes. O litoral cearense foi percorrido no perÃodo de setembro de 2010 a maio de 2012, identificando-se in loco os tipos de embarcaÃÃes construÃdas, e localizando e entrevistando construtores artesanais de embarcaÃÃes a vela, foco principal deste trabalho. Foram entrevistados 36 carpinteiros de comprovado reconhecimento local, que responderam questionÃrio estruturado com perguntas direcionadas diretamente à identificaÃÃo do construtor artesanal, seu perfil profissional e da sua arte construtiva, permitindo registros fotogrÃficos, filmagens e gravaÃÃes. Os dados de cada questionÃrio foram transcritos para planilhas eletrÃnicas e analisadas, combinando com as gravaÃÃes de entrevistas transcritas e das filmagens. A pesquisa constatou a baixa escolaridade dos carpinteiros artesanais entrevistados, com 44% de alfabetizados e 42% de analfabetos; a inexistÃncia de qualquer registro construtivo empregado; mÃdia de idade; media de tempo de trabalho e frequÃncia da distribuiÃÃo do tempo de trabalho entre os carpinteiros entrevistados; influÃncia e origem do aprendizado e ausÃncia de enquadramento funcional destes jà que nÃo se aposentam como construtores artesanais. Resultados importantes foram obtidos sobre o perfil do carpinteiro artesanal cearense, considerados importantes para a manutenÃÃo da tradiÃÃo cultural de suas tÃcnicas aplicadas à construÃÃo de embarcaÃÃes a vela, e que compÃem o patrimÃnio histÃrico e socioeconÃmico do estado. CAPITULO 2 â A construÃÃo dos diferentes tipos de embarcaÃÃes a vela do litoral do estado do Cearà As embarcaÃÃes a vela sÃo usadas na pesca desde a Idade MÃdia e foram introduzidas no Brasil no inÃcio do descobrimento. No CearÃ, a frota veleira à constituÃda por jangadas, paquetes, canoas e botes, e este estudo objetivou descrever os aspectos e processo construtivos destas embarcaÃÃes, e verificar a existÃncia de diferenciaÃÃo entre localidades quanto aos custos, tempo de construÃÃo, materiais, ferramentas manuais, posicionamento dos mastros com os tipos e tamanhos de vela e elaboraÃÃo de planos de linhas. A metodologia constou de levantamentos de dados in loco, no perÃodo de maio 2010 a dezembro de 2012, com entrevistas com 36 carpinteiros artesanais em 25 localidades de praia de dezoito municÃpios, e aplicaÃÃo de questionÃrios e registros por gravaÃÃo, fotografia e filmagem. O mÃtodo construtivo adotado pelos construtores à o do âesqueleto primeiroâ, ao qual os diversos componentes sÃo acrescentados. O principio para a construÃÃo dos botes triÃngulo e bastardo à o mesmo adotado por toda a forÃa de trabalho, que sÃo idÃnticos no aspecto construtivo e de estrutura de casco, diferem no tipo de mastro e vela, tendo o bastardo um mastro fixo com vela latina bastarda e o bote triÃngulo vela latina triangular. Os custos de construÃÃo variam em ordem decrescente para botes, jangadas, canoas e paquetes, determinados pelo comprimento da embarcaÃÃo e tipo de madeira. Pontualmente, registrou-se em Bitupità a existÃncia da vela quadrangular latina, denominada de âvela quatro punhosâ, envergada em mastro bastardo nas canoas de curral. CAPITULO 3 â A navegaÃÃo praticada por mestres marcadores nas embarcaÃÃes a vela no estado do Cearà A orientaÃÃo praticada a bordo de embarcaÃÃes veleiras para navegaÃÃo e pesca utiliza referÃncias de terra para compor as linhas de posiÃÃo denominadas caminho e assento que, ao se cruzarem, determinam o local desejado. Esta atividade vem acontecendo desde a existÃncia da jangada de piÃba e se perpetua por transmissÃo entre geraÃÃes. O estudo foi desenvolvido com mestres marcadores de trÃs localidades, Baleia, Fortaleza e Redonda, onde predominam canoas, jangadas e botes, respectivamente. A prÃtica desta modalidade de navegaÃÃo à idÃntica para os diferentes tipos de embarcaÃÃo e diferem pouco entre as localidades estudadas. O exercÃcio da orientaÃÃo exige que o mestre marcador tenha boa visÃo e memÃria para encontrar caminho e assento, alÃm de sofrer restriÃÃes na ausÃncia da luz solar. Essa atividade à iniciada pelos marcadores ainda na juventude, e esses conhecimentos sÃo adquiridos independentes do grau de instruÃÃo e se consolidam tanto pelo exercÃcio da pesca quando pela experiÃncia adquirida. A observaÃÃo de estrelas e planetas revela a direÃÃo do caminho de volta ao porto de origem tendo a estrela do porto vÃrias denominaÃÃes no litoral cearense. A falta de visibilidade do litoral, ocasionada por chuva, cerraÃÃo ou outros fatores, interfere negativamente na identificaÃÃo de pontos de referÃncia existentes no litoral. A marcaÃÃo terrestre vem sendo gradativamente substituÃda pelo uso do GPS na localizaÃÃo dos pesqueiros mais produtivos, com grande aceitaÃÃo pelos mais jovens. O baixo preÃo e eficiÃncia comprovada desse equipamento tÃm justificado sua difusÃo ao longo de todo o litoral do CearÃ. CAPITULO 4 â EmbarcaÃÃes a vela do litoral do estado do CearÃ, distribuiÃÃo espacial da frota e da produÃÃo pesqueira O Cearà possui 573 km de litoral, distribuÃdo por 20 municÃpios costeiros e conta com 113 localidades de pesca estuarina e marinha. Este estudo se baseia nos seguintes dados estatÃsticos do Programa ESTATPESCA a- composiÃÃo da frota por tipo de barco e municÃpio; b- produÃÃo de pescado por tipo de barco e municÃpio; c- produÃÃo das principais espÃcies de peixe por tipo de embarcaÃÃo. Foi feita a descriÃÃo das caracterÃsticas das embarcaÃÃes a vela do Cearà de uma forma mais detalhada que as dividiu em jangadas ocada e de isopor; paquetes ocado e de isopor; canoa de Paracuru; canoa de Moitas-Baleia; canoa de Camocim (bianas); Canoa de Acarau-PreÃ-BitupitÃ; canoas de currais de BitupitÃ; canoa-paquete de Fleixeiras-Guagiru e botes triangulo e bastardo. Os resultados mostram que os paquetes sÃo maioria numÃrica e com maior distribuiÃÃo geogrÃfica, destacam-se pela versatilidade, por serem leves para encalhe e movimentaÃÃo na faixa de praia, pela necessidade de pequena tripulaÃÃo e baixo custo de construÃÃo e manutenÃÃo. Os botes tÃm a menor abrangÃncia territorial, com o bastardo bem concentrados em Camocim e o triÃngulo com maior concentraÃÃo em IcapuÃ. A canoa tem predominÃncia exclusiva no litoral oeste e a jangada, no litoral leste. Em termos relativos, as embarcaÃÃes participaram da captura nas seguintes proporÃÃes: canoas = 45,3 %; paquete = 22,3 %; botes = 22,4%, destacando-se os municÃpios de Camocim, Itarema, Icapuà e AcaraÃ. Estes tÃm produÃÃo mais seleta, capturando espÃcies de maior valor comercial, a saber guaiÃba, cavala, pargo, sirigado, carapitanga e dourado. As jangadas vÃm perdendo importÃncia relativa na captura do pescado, mas ainda com destaque para os municÃpios de Fortaleza, Aquiraz, Beberibe Cascavel e Aracati. / CHAPTER 1 â Profile of the artisanal carpenters of sail crafts in Cearà State In a worldwide scenario, during the XV Century, the naval building of sail craft underwent an evolutionary development that enabled the undertaking of long-length voyages across the oceans. By arriving at Brazil, an intensive interaction process between local sail boat construction and that of European-derived knowledge. The sail rafts, at first built without sail, were deployed over the whole Brazilian northeast, mainly in Cearà State, as artisanal crafts, evolving from simple dugouts to the actual wooden ones as well as canoes and rowboats. For this research work, the Cearà Stateâs coast was surveyed from September, 2010 to May, 2012, taking in situ stock of all types of constructed crafts, and pinpointing and interviewing artisanal builders of sailboats, who are than main target population of this survey. To this aim, 36 accomplished carpenters, locally recognized as such, were required to answer a number of questionnaires directed toward a full appraisal of the artisanal naval builders, its professional profile and handicraft, for which photographic records, pictures and sound recordings were obtained. The derived data were transferred to electronic spreadsheets and then analyzed by crosschecking the recorded interviews and the movie pictures. This survey led to the following results: occurrence of low reading ability by the artisanal carpenters so that 44 per cent were found to be illiterate; non-existence of any kind of professional registration by the competent public offices; mean age of 22.1 years; high mean working time and frequency of distribution among the sampled population; factors of influence and origin of learning techniques and absence of functional framing, since they to do not retire as naval builders. Significant results were got as to the artisanal carpentersâs profile in Cearà State, which were deemed quite relevant for the maintenance of the folklore of their techniques applied to the construction of sail crafts, and round up the historic and socioeconomic heritage of the Cearà Stateâs coastline . CHAPTER 2 â Construction of different types of sail craft along Cearà Stateâs coastline The sailboats are used in fisheries since the middle ages and were introduced in Brazil at the beginning of its discovery. The Cearà Stateâs fleet is made up of rafts, canoes and boats whose study was meant for describing aspects of the building process and for ascertaining the existence of differentiation among fishing communities as to costs, construction time, basic materials, hand tools and positioning of masts according to boat size, sail types and setting of lining patterns. The methodology consisted of data surveys carried out locally, in the period from May, 2010 through December, 2012, by means of interviews with 36 artisanal carpenters in 25 fishing sites of 18 costal counties, by applying questionnaires and data gathering by recording, photography and movie pictures. The constructive technique consists of mounting a âprimary skeletonâ to which all other component parts are attached. The building principle of the triangle and bastard boats is the same as adopted by the whole of the labor force, which are identical as to their constructive pattern and hull framework, but differ as to the types of masts ands sails, namely the bastard one having a fixed mast and a storm jib, and the triangle one having a triangular storm jib. The construction costs vary in a decreasing order for boats, rafts and canoes, as determined by the craft length and kind of timber. Somewhat exceptionally there was identified in BitupitÃ, Barroquinha county, the existence of a square storm jib named âfour-fist sailâ, bent up as a bastard mast in the fish-weir canoes. CHAPTER 3 â The navigation practiced by master position markers on board sail boats in Cearà State The orientation carried out on board sailboats for navigation and fishing makes use of landmarks in order to compose the position lines named pathway and outpost that, while intercrossing, determine the sought after site. This activity has been taking place since the very early existence of the sail raft and it endures itself from generation to generation. This study was undertaken by master markers in some fishing localities, namely Baleia, Fortaleza and Redonda where canoes, sail rafts and boats are respectively predominant. The practice of this kind of navigation is similar for the various types of boats and diverges from one another very little among the studied landing points. The exercise of orientation requires that the master marker has got good eyesight and memory in order to find out the pathway and the outpost, besides undergoing setbacks from the absence of sunlight. That activity is started when the fisherman is still young, and his long-lived expertise is acquired independently of the educational degree as it is derived from both the fishing chores and the accumulated experience. The observation of stars and planets reveals the way back to the home port whose identifying star receives many nominations along Cearà Stateâs coastline. The lack of visibility brought about by rain, clouding, and other factors meddle with the identification of conspicuous landmarks. This age- old technique has been gradually replaced by the use of GPS devices for pinpointing the most productive fishing grounds, with a high degree of acceptance by the young generation. The low purchase price and the proved efficiency of that equipment has accounted for the diffusion of their advantages among the fishing communities of Cearà State. CHAPTER 4 â Sail crafts in Cearà Stateâs coastline: fleet and fishing production spatial distribution The Cearà Stateâs coastline spreads over 573 km distributed by 20 coastal counties, and 113 estuarine and marine fishing communities. This study is based on the following statistical data gathered through the ESTATPESCA Program: fleet composition by types of boat and county; fish production by type of boat and county; catch composition of the main fish species by type of boat. A detailed description of the sailboats in Cearà was presented in order to provide information on a number of variants of their main types, namely hollow raft, styrofoam-fulled rafts, canoe from Paracuru, canoe from Moitas-Baleia; canoe from Camocim; canoe from AcaraÃ-PreÃ-BitupitÃ; canoe from Bitupità fish-weirs, canoe-raft from Fleixeiras-Guagiru, triangle boat and bastard boat. The results show the small raft holds a numeric majority and a wider geographic distribution, standing out by being lighter to anchor on the beach sand, requiring fewer crew, and entailing lower construction and maintenance costs. The boats show a narrower territorial range, with the bastard ones being concentrated in Camocim county and the triangle ones more frequent in Icapuà county. The canoe and the large-sized raft hold an outstanding predominance on the western and the eastern sides of Cearà Stateâs coastline, respectively. In relative terms, the main types of fishing craft took part in the caches according to the following proportions: canoes = 45.3 per cent; small raft = 22.3 per cent; boats = 22.4 per cent. Among their home counties stand out Camocim, Itarema, Icapuà and AcaraÃ, the ones that boast a more exclusive fish production made out of such species as yellowtail snapper, king mackerel, Caribbean red snapper, black grouper, dog snapper and dolphin. The large-sized rafts have shown of late a tendency for playing a lesser part in fish catching, but they are still relevant in such Cearà Stateâs counties as Fortaleza, Aquiraz, Beberibe Cascavel and Aracati.