L’AE1 (SLC4A1) est un échangeur chlorure/bicarbonate. Cette protéine est la protéine membranaire la plus abondante à la surface des globules rouges des vertébrés. Elle est participe au transport du CO2 et à l’ancrage du cytosquelette à la membrane plasmique. Des mutations ponctuelles dans la partie membranaire de l’AE1, liées à des pathologies humaines, convertissent l’échange électroneutre en voie de conductance pour le sodium et le potassium ou induisent une fuite de cations dans un échangeur d’anions toujours fonctionnel. Les déterminants moléculaires qui induisent les mouvements d’ions au travers de cet échangeur sont encore inconnus. Le travail présenté a eu pour but d’identifier et de cartographier le site de transport de la protéine normale ou « pathologique ». Nous avons adapté à l’AE1 des outils basés sur la chimie des sulfhydriles capable de donner des informations sur le rôle d’acides aminés dans le site de transport de la protéine. Cette stratégie combinée à l’élaboration d’un modèle tridimensionnel de la protéine in silico basé sur le symporteur uracile/proton nous a permis de définir le site de transport de l’AE1. Nos résultats démontrent qu’un site de transport unique dans l’AE1 peut basculer entre 3 conformations différentes : échange chlorure/bicarbonate, fuite de cation et échange anionique ou fuite de cation uniquement. Ce site met en jeu les segments transmembranaires (TM) 3, 5 et 8 ainsi qu’une boucle intracellulaire très conservée située entre les TM 8 et 9. Le site de transport se structure autour des acides aminés L468, F471, L530, I533 et L673 se terminant au niveau du E681. La boucle intracellulaire 690 à 705 agissant comme un filtre à cations. / AE1 (SLC4A1, band 3) is a member of the SLC4 bicarbonate transporter family. This protein is the most abundant membrane protein on the surface of vertebrate red blood cells. The AE1 exchanges chloride and bicarbonate ions in physiological conditions. In red blood cells, it is essential to many tasks including CO2 transport and cytoskeleton anchoring in the plasma membrane. Point mutations in the membrane spanning domain of AE1 convert the electroneutral exchange into a conductance for sodium and potassium cations or induce a cation leak in a still functional anionic exchanger.The molecular determinants that induce the movement of ions through the exchanger are still unknown. This work aims at identifying and mapping the transport site of AE1 protein in normal and pathological conditions. We modified a sulfhydryl-based chemistry to AE1. This provided information on the role of amino acids in the transport site of the protein. This strategy combined with the development of a three-dimensional model of the protein in silico, based on the uracil/proton symporter, allowed us to define the transport site of AE1. Analysis of our results showed that a single transport site in AE1 can switch between three different conformations depending on protein mutation: classical chloride/bicarbonate exchange, cation leak and anion exchange, cation leak only. The transport site involves the transmembrane segments 3, 5 and 8 and a highly conserved intracellular loop between transmembrane segments 8 and 9. The transport site is centered around the amino acids L468, F471, L530, L673, I533 and ends at glutamic acid 681. The intracellular loop 690-705 acts as a cation filter.

Submitted by Jos? Henrique Henrique (jose.neves@ufvjm.edu.br) on 2018-04-19T18:44:37Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) luis_henrique_goncalves_aguiar.pdf: 1963486 bytes, checksum: ce8ee9274d520386492773d2e289f109 (MD5) / Approved for entry into archive by Rodrigo Martins Cruz (rodrigo.cruz@ufvjm.edu.br) on 2018-04-23T16:27:14Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) luis_henrique_goncalves_aguiar.pdf: 1963486 bytes, checksum: ce8ee9274d520386492773d2e289f109 (MD5) / Made available in DSpace on 2018-04-23T16:27:14Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) luis_henrique_goncalves_aguiar.pdf: 1963486 bytes, checksum: ce8ee9274d520386492773d2e289f109 (MD5) Previous issue date: 2017 / Considerando a grande quantidade de informa??es textuais dispon?veis atualmente, principalmente na web, est? se tronando cada vez mais dif?cil o acesso e a assimila??o desse conte?do para o usu?rio. Nesse contexto, torna-se necess?rio buscar tarefas capazes de transformar essa grande quantidade de dados em conhecimento ?til e organizado. Uma alternativa para amenizar esse problema, ? reduzir o volume de informa??es dispon?veis a partir da produ??o de resumos dos textos originais, por meio da sumariza??o autom?tica (SA) de textos. A sumariza??o autom?tica de textos consiste na produ??o autom?tica de resumos a partir de um ou mais textos-fonte, de modo que o sum?rio contenha as informa??es mais relevantes deste. A avalia??o de resumos ? uma tarefa importante no campo da sumariza??o autom?tica de texto, a abordagem mais intuitiva ? a avalia??o humana, por?m ? onerosa e improdutiva. Outra alternativa ? a avalia??o autom?tica, alguns avaliadores foram propostos, sendo a mais conhecida e amplamente usada ? a medida ROUGE (Recall-Oriented Understudy for Gisting Evaluation). Um fator limitante na avalia??o da ROUGE ? a utiliza??o do sum?rio humano de refer?ncia, o que implica em uma restri??o do idioma e dom?nio, al?m de requerer um trabalho humano demorado e oneroso. Diante das dificuldades encontradas na avalia??o de sum?rios autom?ticos, o presente trabalho apresenta o modelo Cassiopeia como um novo m?todo de avalia??o. O modelo ? um agrupador de textos hier?rquico, o qual consiste no uso da sumariza??o na etapa do pr?-processamento, onde a qualidade do agrupamento ? influenciada positivamente conforme a qualidade da sumariza??o. As simula??es realizadas neste trabalho mostraram que a avalia??o realizada pelo modelo Cassiopeia ? semelhante a avalia??o realizada pela ferramenta ROUGE. Por outro lado, a utiliza??o do modelo Cassiopeia como avaliador de sum?rios autom?ticos evidenciou algumas vantagens, sendo as principais; a n?o utiliza??o do sum?rio humano no processo de avalia??o, e a independ?ncia do dom?nio e do idioma. / Disserta??o (Mestrado Profissional) ? Programa de P?s-Gradua??o em Educa??o, Universidade Federal dos Vales do Jequitinhonha e Mucuri, 2017. / Considering the large amount of textual information currently available, especially on the web, it is becoming increasingly difficult to access and assimilate this content to the user. In this context, it becomes necessary to search for tasks that can transform this large amount of information into useful and organized knowledge. The solution, or at least an alternative, to moderate this problem is to reduce the volume of information available, from the production of abstracts of the original texts, through automatic summarization (SA) of texts. The Automatic Summarization of texts consists of the automatic production of abstracts from one or more source texts, which the summary must contain the most relevant information of the source text. The evaluation of abstracts is an important task in the field of automatic text summarization, the most intuitive approach is human evaluation, but it is costly and unproductive. Another alternative is the automatic evaluation, some evaluators have been proposed, and the most widely used is the ROUGE (Recall-Oriented Understudy for Gisting Evaluation). A limiting factor in ROUGE's evaluation is the use of the human reference summary, which implies a restriction of language and domain, as well as requiring time-consuming and expensive human work. In view of the difficulties encountered in the evaluation of automatic summaries, this paper presents the Cassiopeia model as a new evaluation method. The model is a hierarchical text grouper, which consists of the use of the summarization in the stage of the pre-processing, where the quality of the grouping is influenced positively according to the quality of the summarization. The simulations performed in this work showed that the evaluations performed by Cassiopeia in comparison to the ROUGE tool are similar. On the other hand, the use of the Cassiopeia model as an automatic summarization evaluator showed some advantages, the main ones are; being the non-use of the human abstract in the evaluation process, and the independent of the domain and the language.

Pre-vegetation alluvium is unique; at the present day, plants affect multiple aspects of river functioning and deposition and so those rivers that operated before the evolution of land plants largely lack modern sedimentological analogue. However, such rivers were the norm for the first 90% of Earth history and so a better understanding of their sedimentary product enables insight into both the fundamental underlying mechanisms of river behaviour and the ways in which fluvial processes operated on ancient Earth and other rocky planets. This study presents five original fieldwork based case studies and an analysis of a holistic database of all of Earth’s pre-vegetation alluvium. Together these research strands offer perspectives on the sedimentological characteristics and stratigraphic trends of pre-vegetation alluvium and the behaviour and functioning of pre-vegetation rivers. Results show that, in pre-vegetation alluvial settings: 1) a variety of fluvial styles are represented, but diminished in comparison with syn-vegetation alluvium; 2) ‘sheet-braided’ architectures are common but may record a variety of fluvial planforms; 3) meandering planforms were less frequent, particularly in small- to moderate-sized river systems; 4) mudrock is on average 1.4 orders of magnitude less common than it is in syn-vegetation alluvium; and 5) microbial matgrounds were present, but had negligible effect on preserved architecture and facies. This thesis demonstrates that whilst the physical laws governing fluvial fluid-sediment interaction have not changed, the theatre in which they operated irrevocably evolved with the greening of the continents.

Submitted by RAQUEL LUNEDO (bln.raquel@yahoo.com.br) on 2016-03-01T19:55:22Z No. of bitstreams: 1 TESE_Raquel_Lunedo_repositorio.pdf: 2945618 bytes, checksum: a9cae139d1f67fb1f8ba4fa91aef40eb (MD5) / Approved for entry into archive by Juliano Benedito Ferreira (julianoferreira@reitoria.unesp.br) on 2016-03-03T19:46:23Z (GMT) No. of bitstreams: 1 lunedo_r_dr_jabo.pdf: 2945618 bytes, checksum: a9cae139d1f67fb1f8ba4fa91aef40eb (MD5) / Made available in DSpace on 2016-03-03T19:46:23Z (GMT). No. of bitstreams: 1 lunedo_r_dr_jabo.pdf: 2945618 bytes, checksum: a9cae139d1f67fb1f8ba4fa91aef40eb (MD5) Previous issue date: 2016-02-16 / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / A hipótese testada neste projeto é que a restrição alimentar altera a composição da microbiota intestinal e a expressão gênica hepática em frangos de corte, e estas alterações podem influenciar a deposição tecidual das aves. Outra hipótese, é que a genética do frango influencia estas variáveis, e pode alterar a sua resposta frente a restrição alimentar. Os objetivos específicos foram analisar a resposta de duas linhagens de frangos de corte (crescimento rápido – Cobb – ou lento – Label Rouge) a dois programas de restrição alimentar (quantitativa ou energética) sobre: 1) o desempenho zootécnico; 2) a deposição tecidual; 3) a microbiota de íleo e ceco; 4) a expressão de genes relacionados ao metabolismo hepático. Para tal, dois experimentos foram conduzidos, sendo que no experimento I foram utilizados 480 frangos de corte, machos, da linhagem comercial Cobb500TM e no experimento II foram utilizados 480 frangos de corte, machos, da linhagem Label Rouge. Até os 21 dias as aves receberam mesma dieta e foram criadas em temperatura termoneutra. Aos 22 dias, oito grupos de 20 aves foram distribuídos dentro de cada um dos três tratamentos experimentais: 1. Controle (ad libitum – 3,176 Mcal/kg de EM e 19% PB); 2. Restrição energética (2,224 Mcal/kg EM e 19% PB) até os 43 dias de idade, com consumo equiparado ao controle; 3. Restrição quantitativa (restrição de 70%, ou seja, as aves restritas ingeriram apenas 30% da quantidade de ração consumida pelo grupo controle – 3,176 Mcal/kg EM e 19% PB) durante 7 dias, seguido de realimentação ad libitum até os 43 dias de idade. A restrição alimentar energética diminuiu o ganho de peso e o peso da carcaça e piorou a conversão alimentar em ambas as linhagens; diminuiu as contagens do grupo Lactobacillus e aumentou as contagens de Enterococcus e Enterobacteriaceae nas aves de crescimento rápido; favoreceu a proliferação de Lactobacillus, e diminuiu as populações de Enterococcus e Enterobacteriaceae nos cecos dos frangos de crescimento lento; induziu a expressão gênica das enzimas ACACA e FASN nas aves de crescimento lento e da enzima CPT1-A nas aves de crescimento rápido; e reduziu a massa de gordura corporal nas aves de crescimento rápido. Durante a semana de restrição alimentar quantitativa, não foi verificado ganho de peso em ambas as linhagens. A restrição levou a: diminuição das contagens do grupo Lactobacillus e aumento de Enterococcus e Enterobacteriaceae nas aves de crescimento rápido; indução da expressão gênica de ACACA, FASN e SREBP- 1 e repressão da expressão de CPT1-A nas duas linhagens. No período de realimentação, foi observado comportamento hiperfágico, melhor ganho de peso e melhor conversão alimentar nas aves restritas. O ganho compensatório não foi suficiente para alcançar o mesmo peso vivo. Nos frangos de crescimento rápido, a deposição tecidual foi semelhante ao controle, porém nas aves de crescimento lento ocorreu maior deposição de gordura e menor deposição de proteína corporal nas aves restritas. Em conclusão, apesar da resposta das variáveis ganho de peso e conversão alimentar aos programas de restrição alimentar ter sido semelhante nos dois grupos genéticos, a composição e a estabilidade da microbiota intestinal de frangos de corte foram dependentes da linhagem. Adicionalmente, encontramos evidências sobre a relação entre expressão de genes lipogênicos hepáticos e a deposição de lipídeos na carcaça de frangos de corte, além de demonstrar modificações no padrão de deposição tecidual em função da velocidade de crescimento da linhagem. / The hypothesis of this project is that feed restriction alters the composition of gut microbiota and hepatic gene expression in broilers, and these changes can influence the tissue deposition of birds. The second hypothesis is that the broiler genetics influence on these variables, and can change the response in front of feed restriction. The specific objectives were investigated the response of broilers (fast – Cobb – or slow-growing – Label Rouge – strains), in front of two feed restriction programs (energetic or quantitative), on: 1) growth performance; 2) tissue deposition; 3) ileal and cecal microbiota; 4) expression of genes related to hepatic metabolism. For this, two experiments were conducted. In the experiment I, were used 480 male Cobb500TM broilers, and in the experiment II, were used 480 male Label Rouge broilers. Up to 21 days of age, the birds received the same diet and were created in thermoneutral temperature. At 22 days of age, birds were divided into 3 experimental treatments (8 replicates of 20 birds): T1. Control (ad libitum – 3.176 Mcal/kg ME and 19% CP); T2. Energetic restriction (2.224 Mcal/kg ME and 19% CP) up to 42 days with consumption equivalent to control; T3. Quantitative restriction (70% restriction, i. e., restricted broilers ingested only 30% of the quantity consumed by the control group – 3.176 Mcal/kg ME and 19% CP) for 7 days, followed by refeeding ad libitum until 42 days. Energetic restriction reduces body weight gain and carcass weight and increased feed conversion ratio in both strains; reduced the Lactobacillus and increased the Enterococcus and Enterobacteriaceae copies in fast-growing broilers; promoted the Lactobacillus proliferation and reduced Enterococcus and Enterobacteriaceae populations in ceca of slow-growing broilers; induced the gene expression of ACACA and FASN in slow-growing, and CPT1-A in fast-growing broilers; and reduced the fat mass in fast-growing broilers. During the quantitative feed restriction period, was not verified body weight gain, independently of strain. The restriction leads to: reduction in Lactobacillus and increase in Enterococcus and Enterobacteriaceae copies in fast-growing broilers; induction of ACACA, FASN and SREBP-1 and reduction in CPT1-A gene expression in both strains. During the refeeding period, was observed hyperphagic behavior, better body weight gain and lower feed conversion ratio in restricted birds. The compensatory growth was not sufficient to achieve the same 42d body weight than the control treatment. For slowgrowing broilers, there was greater fat deposition and lower protein deposition after refeeding, whereas for fast-growing broilers, no difference between control and restricted birds were found. In conclusion, although the body weight gain and feed conversion ratio response of two genetic groups in front of feed restriction programs is similar, the composition and stability of the intestinal microbiota are strongly dependent on host. Additionally, the present data provide evidence on the relationship between hepatic lipogenic gene expression and lipids deposition in broilers carcass, and demonstrated that changes in the tissue deposition is directly related to growth rate in broilers. / CNPq: 141453/2012-5 / FAPESP: 2013/05924-6

Ce travail avait pour objectif principal l’étude par spectroscopie vibrationnelle Raman et IR, couplée à l’analyse statistique de type ACP, la détection des changements moléculaires induits par différentesclasses d’antibiotiques (ampicilline, céfotaxime,tétracycline et ciprofloxacine) vis-à-vis de deux bactéries modèles (E. coli et V. parahaemolyticus). Dans le cas d’E. coli, l’ampicilline et le céfotaxime ont provoqué une baisse des bandes protéiques en Raman et IR, une augmentation des carbohydrates en IR.L’addition de la tétracycline a entraîné une augmentation des acides nucléiques, une forte baisse de la phénylalanine en Raman, une diminution des bandes protéiques et une augmentation de l’ADN en Raman et IR. Concernant la ciprofloxacine, une augmentation des acides nucléiques en Raman, une augmentation des bandes protéiques et de l’ADN en IR ont été observées. Chez V. parahaemolyticus, le céfotaxime a provoqué une baisse des protéines en Raman et Infra-rouge, une augmentation des polysaccharides en Infra-rouge. L’addition de la tétracycline a entraîné une baisse de la phénylalanine en Raman, une baisse des protéines en Raman et Infra-rouge, une augmentation des polysaccharides en Infra-rouge. Concernant la ciprofloxacine, une augmentation des polysaccharides et une diminution des bandes protéiques en Raman et IR ont été détectées. Une nette discrimination entre les échantillons traités aux antibiotiques et le témoin a été enregistrée chez E. coli et V. parahaemolyticus. Pour cette dernière, le profil de résistance à l’ampicilline a aussi été observé. Ce travail jette les bases d’une compréhension des mécanismes d’antibio-résistance dans les systèmes bactériens. / The present study aimed to explore Raman and IR in combination with PCA to detect molecularchanges induced by different classes of antibiotics(ampicillin, cefotaxime, tetracycline and ciprofloxacin) against two bacterial models (E.coli and V. parahaemolyticus) In E. coli,ampicillin and cefotaxime treatments led to a decrease of protein bands in both Raman and IR,an increase of carbohydrates in IR. Tetracycline addition caused an increase of nucleic acids, a sharp decrease of phenylalanine in Raman, a decrease of protein bands and an increase of DNA in both Raman and IR. For ciprofloxacin, an increase of nuleic acids in Raman, an increase of protein bands and DNA in IR were observed. In V. parahaemolyticus, cefotaxime resulted in a decrease of protein bands in both Raman and IR,an increase of polysaccharides in IR. Tetracycline increase of polysaccharides and a decrease of proteins in both Raman and Infra-red were noticed. Clear discrimination of antibiotic-treated samples compared to the control was recorded for the three antibiotic classes in both E. coli and V. parahaemolyticus. For the latter, resistance pattern has also been observed for ampicillin. This work lays the foundations for an understanding of the mechanisms of antibiotic resistance in the bacterial systems.

A la fin du XIXe siècle, trois sociétés françaises de la Croix-Rouge apparaissent. Ces associations humanitaires sont auxiliaires du Service de Santé des armées. Les hommes et les femmes bénévoles soignent les soldats français blessés. Les femmes bénévoles sont infirmières, conductrices automobiles, etc. Peu à peu, elles s'imposent et deviennent essentielle dans le fonctionnement général des Croix-Rouges. Aux yeux des hauts gradés militaires, des médecins et des hommes des Croix-Rouges, elles se rendent indispensables par leurs zèles, leurs dévouements, leurs sacrifices notamment lors de la guerre entre la France de Napoléon III et la Prusse (1870-1871), pour la première fois véritablement pendant la Grande Guerre (1914-1918) et la Seconde Guerre mondiale (1939-1945). En temps de paix, les femmes sont polyvalentes. Elles collectent des fonds, tissent des réseaux avec les populations locales, les milieux économiques et politiques. Elles recrutent de nouvelles bénévoles pour les former ensuite au métier d'infirmière. Ces femmes appartiennent aux milieux aisés de la noblesse et de la bourgeoisie. Elles remplacent leurs homologues masculins quand ils sont en sous-effectifs à certaines fonctions et selon les périodes. Elles permettent aux Croix-Rouges de continuer à assurer leurs missions en faveur des combattants blessés, des victimes d'épidémies et catastrophes naturelles. Les femmes engagées dans les Croix-Rouges ont un destin extraordinaire. / At the end of the nineteenth century, three French companies of the Red Cross appear. These humanitarian organizations are auxiliaries of the Health Service of the Armed. Men and women volunteers care for the wounded French soldiers. Volunteers are women nurses, auto conductive, etc. Gradually they become necessary and essential in the overall functioning of the Red Cross. In the eyes of senior military officers, doctors and men of the Red Cross, they make themselves indispensable by their zeals, their devotion, their sacrifices particularly during the war between France and Napoleon III of Prussia (1870-1871), for the first time really in the Great War (1914-1918) and World War II (1939-1945). In peacetime, women are versatile. They raise funds, weave networks with local populations, economic and political circles. They recruit new volunteers for the next train as a nurse. These women belong to the upper classes of the nobility and bourgeoisie. They replace their male counterparts when they are understaffed in certain functions and over time. They allow the Red Cross to continue to assurer their missions for the wounded fighters, victims of natural disasters and epidemics. Women involved in the Red Cross have an extraordinary destiny.

Cette thèse de poïétique explore selon une double approche, théorique et pratique, les questions de l'origine et du métissage dans l'art. Elle s'appuie sur les œuvres d'artistes contemporains ainsi que sur des productions personnelles. Nous émettons l'hypothèse selon laquelle une réflexion sur l'origine, sur le métissage inscrit dans son corps propre mais aussi sur le métissage dans l'art, peut mettre en évidence l'altérité qui nous traverse jusque dans notre intériorité la plus intime. Dans un premier chapitre nous analysons le rouge-généalogique transmis par les générations de femmes au sein de ma famille. Puis nous explorons le rouge-blessure qui irrigue le passage du corps d'enfant à celui de femme. Enfin dans un dernier temps, nous abordons le rouge-exilique qui questionne directement le corps d'artiste. Lié à une recherche généalogique et personnelle, notre travail traite du déplacement physique, de la rupture vécue lorsque nous quittons notre pays natal jusqu'à la prise de conscience de notre corps-exilique sur le lieu d'accueil. Cette réflexion ne serait peut-être jamais née sans la question : « quelles sont vos origines ? », qui m'a un jour été posée face à mes œuvres. La question a résonné et fait écho en moi jusqu'à ce que je décide d'entreprendre un voyage à rebours parmi les souvenirs exhumés d'une collection d'objets personnels. Nous en concluons que l'artiste est toujours, de quelque manière que ce soit, un migrant et un exilé. L'artiste est celui qui, de ce flot de vie mais aussi d 'impermanence, de mélanges et de métissages, va chercher la continuité, mettre en évidence les transformations créatrices. Tous les rouges de mon œuvre, rouge-­généalogique, rouge-blessure, rouge-exilique, rouge de vie et de mort sont ainsi à l'image du plasma sanguin qui circule nous, qui nous fait vivre et dont je tire la matière transformatrice, métissée, créatrice de mon œuvre: ces rouges sont le plasma-créateur qui circule en l'artiste et préside à toute création. / This poietic thesis explores the question of origins and metissage in art using a dual approach - theoretical and practical. It is based on works of contemporary artists as well as persona! production. We forward a hypothesis, according to which, a reflection on the origin and also the metissage in art inscribed on the body, which could highlight the alterity that traverse us even in our innermost interiority. In the first chapter, we analyse the red genealogy transmitted by generations of women within my family. Later, we explore the red wound that irrigates the passage of child's body to that of a woman. And finally, in the last step we approach the exilic-red which directly questions the body of the artist. Our work is related to genealogical and persona! research deals with physical displacement, the disruption experienced when we leave our native land until the awareness about exilic body in the host land. This reflection might never arise without the following question "What is your origin?, which was once posed to me about my works. The question echoed within me until I decided to undertake a journey back to the exhumed souvenirs of a collection of persona! items. We conclude that the artist is always, in any way a migrant and an exile. The artist is the one who, in this stream of life and also in ephemeral state, in mixtures and metissage, seeks continuity and creative transformations. All the reds of my work, genealogical, wounded, exilic, red of life and death, are images of the blood plasma which circulates in us, which makes us live and from which I ex tract the transforming material -mixed and creative of my work. The reds are the creator plasma that circulates in the artist's body and presides over all creation.

Les cellules photoacoustiques sont des capteurs optiques qui utilisent l'absorption des photons par des molécules de gaz pour générer une onde de pression proportionnelle à leur concentration. Le signal photoacoustique est également inversement proportionnel au volume de la cellule. La miniaturisation de la cuve permet donc l’amélioration des performances du capteur. Le travail de cette thèse consiste en la conception, la réalisation et la caractérisation de cellules photoacoustiques résonantes différentielles d’Helmholtz (DHR) miniaturisées. Dans un premier temps, des simulations par la méthode des éléments finis de cellules à l'échelle millimétrique ont permis de montrer que la miniaturisation de ce type de résonateur est une voie prometteuse. Aussi, la réalisation ambitieuse d’une cellule DHR sur silicium a été engagée en utilisant les techniques de la microélectronique. Cependant, cette voie de miniaturisation extrême s'est heurtée à des difficultés de réalisation, qui n'ont pas permis d'obtenir des dispositifs fonctionnels. Une alternative de miniaturisation, à l'échelle centimétrique, utilisant des microphones MEMS du commerce, a donc été engagée. Trois cellules fabriquées par différentes méthodes ont été réalisées et testées pour la détection de méthane. La dernière génération a permis la détection d'environ 100 ppb de méthane avec un laser à cascade interbande commercial à 3,357 µm de longueur d’onde. Pour préparer la prochaine génération de cellules, l'optimisation de la géométrie a été effectuée par simulation. Cette optimisation permet d'envisager une augmentation de 43 % du signal par rapport à la cellule la plus performante. / Photoacoustic cells are optical sensors based on the absorption of photons by gas molecules. The pressure wave created by gas relaxation is proportional to the trace gas concentration. Furthermore the photoacoustic signal is inversely proportional to the cell volume. Thus cell miniaturization enables performances improvements. This work consists in designing, realizing and characterizing miniaturized photoacoustic cells, based on the differential Helmholtz resonator (DHR) principle. In a first phase, modeling by the finite element method of millimeter scale cells has shown that the miniaturization of this type of resonator should effectively improve the detection limit. Thus, the ambitious realization of a DHR cell on silicon by the use of microelectronic techniques has been attempted. However, this extreme miniaturization direction encountered design and fabrication difficulties which made the produced devices unusable. To overcome these difficulties, a miniaturization alternative, at the centimeter scale, using commercial MEMS microphones, has been carried out. Three cells have been built by different methods and have been tested for methane detection. The last cell generation can detect around 100 ppb of methane with a commercial interband cascade laser at 3.357 µm of wavelength. Finally, to anticipate the next cell generation fabrication, a geometry optimization has been performed by simulation. This optimization shows that a 43 % signal improvement, compared to the most performant cell already built.

La forte prévalence des hémoglobinopathies, notamment l'HbAS, l'HbC et l'α-thalassémie dans des zones d'endémie palustre est considérée comme la conséquence de la protection qu'elles procurent contre les formes létales du paludisme. De nombreux mécanismes ont été évoqués pour expliquer cette protection, ne sont pas cohérentes avec toutes les observations épidémio-cliniques disponibles. La première partie de ces travaux de thèse a abordé la réduction de la cytoadhérence des globules rouges (GR) parasités comme mécanisme potentiel commun aux trois hémoglobinopathies. Pour explorer plus en profondeur ce mécanisme, nous avons mené une étude comparative des phénotypes de cytoadhérence des isolats primaires de P. falciparum obtenus chez des patients HbAS et HbAC et HbAA. Cela avait pour but de déterminer si l'HbAS et l'HbAC jouaient un rôle dans la sélection et le maintien des souches virulentes de P. falciparum dans la nature. La deuxième partie de la thèse a concerné l'influence du trait drépanocytaire (HbAS) sur la déformabilité des GR non parasités d'une part et sur la rétention splénique des GR non parasités et parasités par les formes jeunes de P. falciparum d'autre part. Nous avons observé que l'adhésion des GR parasités aux cellules endothéliales micro-vasculaires humaines ainsi qu'aux monocytes était réduite avec les GR α-thalassémiques par rapport aux GR HbAA. Aucune différence statistiquement significative n’a en revanche été observée entre les profils de cytoadhérence des isolats primaires de P. falciparum issus de sujets HbAA, HbAS ou HbAC. L’étude de la déformabilité des GR a montré que les GR HbAS sont légèrement mais significativement moins déformables que les GR HbAA. En revanche, les GR HbAS parasités par les jeunes parasites de P. falciparum (anneaux) n’étaient pas plus retenus que leurs homologues HbAA dans la rate humaine isolé perfusée ex vivo, ou en microsphiltration, quelles que soient les conditions d’oxygénation. Nous n’avons observé aucune différence au niveau du taux de falciformation entre les GR parasités et non parasités que ce soit avec les GR HbAS ou avec les GR HbSS. En conclusion, nous proposons que la réduction de la cythoadhérence et la rétention splénique des GR contenant les formes matures de P. falciparum constituent un mécanisme commun à la protection des sujets HbAS, HbC et α-thalassémiques contre le paludisme. Ces deux phénomènes interconnectés peuvent rendre compte de l’ensemble des observations épidemio-cliniques disponibles sur la protection conférée par ces hémoglobinopathies. / The high prevalence of several inherited hemoglobin disorders, namely sickle cell trait (HbAS), HbAC and α-thalassemia, in malaria endemic areas is thought to be the consequence of their protective effects against malaria life-threatening manifestations. Numerous potential mechanisms have been proposed to explain this protective effect although many of them are not fully consistent with all available epidemiologic and clinical data. The first part of this thesis work explored the reduction of cytoadherence of infected RBC as a potential common mechanism for α-thalassemia-, HbAS- and HbAC-induced protection against malaria. To further explore this mechanism, and determine whether HbAS and HbAC select and maintain virulent P. falciparum parasite in nature, we compared the cytoadherence phenotype of P. falciparum isolates obtained from HbAS/HbAC and controls HbAA patients. The second part of the thesis work addressed the influence of HbAS on the deformability of uninfected RBC as well as the splenic retention of both uninfected RBCs and ring-infected RBCs. We observed a reduced adherence of α-thalassemic infected RBCs to human micro-vascular endothelial cells and monocytes compared to controls HbAA infected RBCs. The reduction was correlated to the number of non functional α- gene. Expression of PfEMP-1 on the surface of α- thalassemic infected RBCs was lower than on the surface of HbAA infected RBCs. There was no statistically significant difference between the cytoadherence of P. falciparum isolates obtained either from HbAS/HbAC or control HbAA malaria patients. The deformability of uninfected HbAS RBCs was slightly but significant lower than that of control uninfected HbAA RBCs. Retention rates of ring-infected HbAS and HbAA RBCs were similar either in human isolated spleen perfusion ex vivo and in microsphilters in vitro regardless of the oxygenation level. We did not observe any enhanced sickling of ring-infected RBCs compared to non infected RBCs, both in HbAS and HbSS samples. Based on these results along with available epidemiologic and previous experimental data, we propose a common malaria-protective mechanism of HbAS, HbAC and α-thalassemia whereby these hemoglobin disorders reduce the cytoadherence of mature P. falciparum-infected RBCs that stay in circulation where they are exposed to an enhanced splenic retention. These 2 mechanisms would act in conjunction to slower the rise of parasites loads in infected patients and protect them from sequestration-related complications of malaria.

The paper delas with the political development in Cambodia since it gained its independence until today. It introduces four authoritative regimes, which occured in the country until the end of the Cold war: Sihanouk's rule, Lon Nol's republic, Khmer Rouge revolution and the period of Vietnamese occupation and the government supported by the vietnamese communists. In the next part it deals with the UN mission called UNTAC, the aim of which was to settle down the conflict in the country and to accomplish the free and fair election. It countinues with the development in the 90-ties and in the new century. The paper finishes with the present situation and with the possible future development.