La valeur potentielle des agro-forêts tropicales comme modèle d'intensification écologique de l'agriculture est un sujet d'intérêt croissant. Les agro-forêts tropicales sont des agroécosystèmes caractérisés par une forte diversité végétale et une diversité d'organisation spatiale des individus. Les structures complexes de ces agroécosystèmes en font des systèmes « proches » des écosystèmes naturels. Cette complexité améliorerait la fourniture de nombreux services écosystémiques. Dans ce travail, nous nous sommes intéressés au service de régulation naturelle des bio-agresseurs des cultures. Notre hypothèse est que la complexité de structure (composition et structure spatiale) des agro-forêts influence la présence et l'intensité d'attaque des bio-agresseurs de la culture principale. En effet, l'augmentation de la diversité végétale à l'échelle de la parcelle diminuerait l'intensité d'attaque de bio-agresseurs spécialistes via la diminution de l'abondance de la ressource. Inversement, cette diversité amplifierait celle des bio-agresseurs généralistes via l'introduction potentielle d'hôtes alternatifs. Une diversité de structures spatiales d'individus associés est aussi susceptible d'influencer le microclimat et par son biais les bio-agresseurs des cultures. Pourtant, l'importance relative de l'effet de la composition (via la dilution ou l'amplification de la ressource) et de la structure spatiale (via l'altération du microclimat) du peuplement végétal sur l'intensité d'attaque de bio-agresseurs a rarement été étudiée. L'objectif de ce travail est de quantifier les interactions entre les caractéristiques de composition et de structure spatiale du peuplement végétal d'agroécosystèmes complexes et l'intensité d'attaque de bio-agresseurs de la culture principale à l'échelle de la parcelle. Ce travail est appliqué aux agro-forêts à cacaoyers du Costa Rica et du Cameroun. En effet, la culture du cacaoyer est l'une des rares encore réalisée traditionnellement au sein d'agro-forêts dans la majorité des pays producteurs. Nous nous intéresserons à trois bio-agresseurs du cacaoyer choisis pour leurs caractéristiques de dissémination et de développement contrastées : au Costa Rica, la moniliose sur un réseau de parcelles installées dans la région de Talamanca ; au Cameroun la pourriture brune et les mirides sur un réseau de parcelles installées dans la région Centre. Dans un premier temps nous avons construit des typologies descriptives des structures spatiales des agro-forêts à cacaoyers du Costa Rica et du Cameroun afin d'identifier la variabilité des structures spatiale des agro-forêts au sein d'une même région. Ces typologies ont permis d'identifier des structures spatiales horizontales variées allant de la régularité à l'agrégation significatives des arbres d'ombrage selon les pays étudiés. Dans un deuxième temps nous avons identifié et hiérarchisé les caractéristiques de composition et de structure spatiale à l'échelle de la parcelle agroforestière qui influencent l'intensité d'attaque de la moniliose au Costa Rica ; et de la pourriture brune et des mirides au Cameroun. La structure spatiale du peuplement végétal joue un rôle prépondérant dans l'ensemble de nos résultats. L'agrégation des arbres forestiers augmente l'intensité d'attaque de la moniliose au Costa Rica et la densité des mirides au Cameroun. La pourriture brune quant à elle augmente lorsque la densité des individus de la strate basse augmente à l'échelle de la parcelle. Pour finir, nous montrons que la quantité de tissus sensible plutôt que la composition en hôte explique l'intensité de la moniliose et la densité en miride. Ces résultats sont discutés en fonction des nombreux mécanismes qui relient la structure de la végétation aux bio-agresseurs et des caractéristiques de ces bio-agresseurs. Notre travail fournit une description précise de la structure d'agro-écosystèmes tropicaux complexes. / The potential value of tropical agroforests as a model for ecological intensification of agriculture is a subject of increasing interest. Tropical agroforests are agroecosystems characterized by high plant diversity and a complex spatial structure of individuals. With their forest-like structures, agroforests are close to natural ecosystems. The complex structure of agroforests would seem to improve the provision of numerous ecosystem services.This work concerned natural pest and disease regulation services in complex agroecosystems. Our hypothesis was that complex agroforest structures (composition and spatial structure) influence the pest and disease attack intensity on the main crop. Indeed, an increase in plant diversity in agroecosystems is known to reduce specialized pest and disease attack intensity due to a decrease in resource abundance and density on a plot scale. Conversely, plant diversity could increase the generalist pest and disease attack intensity due to the potential introduction of alternative hosts. Moreover, diversity in plant spatial structure has an impact on microclimatic conditions and, thereby, on the pest and disease attack intensity. However, the relative importance of host composition effects on pest and disease intensity, due to resource dilution or amplification, and plant spatial structure effects, due to microclimatic alteration, is still unknown.Our objective was to quantify interactions between the composition and spatial structure characteristics of agroforests and the pest and disease attack intensity on a plot scale.This work was applied to cacao agroforests in Costa Rica and Cameroon. Indeed, cacao is one of the last crops still to be grown in traditional agroforests in the majority of producing countries. The study was conducted on two cacao diseases and one pest chosen for their contrasting spread and development characteristics: in Costa Rica, Frosty Pod Rot (FPR) intensity was studied in cacao agroforests in the Talamanca region; in Cameroon, Black Pod (BP) intensity and mirid density were studied in cacao agroforests in the Centre region.Firstly, we established shade tree spatial structure typologies for cacao agroforests in Costa Rica and Cameroon, in order to identify spatial structure diversity in the same region. A diversity of spatial structures was identified ranging from significant regularity to significant aggregation, depending on the shade tree stand and country studied.Secondly, we identified and classified the host composition, amount of sensitive tissue and the spatial structure characteristics of the associated plants, according to their explanatory power in explaining FPR intensity, BP intensity and mirid density in cacao agroforests. The spatial structure of the associated plants was a crucial characteristic of agroforests in explaining FPR and BP intensity and mirid density. Indeed, forest tree regularity decreased FPR intensity in Costa Rica and mirid density in Cameroon. The BP intensity was reduced by a decrease in the density of individuals belonging to strata lower than or equal to the cacao tree stratum. Lastly, the amount of sensitive tissue rather than the host composition variables explained the increase in FPR intensity in Costa Rica and the mirid density in Cameroon. Our results are discussed in line with several mechanisms that explain plant diversity and pest and disease relationships.Our work provides a precise description of complex tropical agroecosystem structures. We quantified the relationship between observed plant structures and the pest and disease regulation ecosystem service. In the context of agroecology, this work opens up prospects for identifying and understanding ecological mechanisms involved in natural pest and disease regulation in cacao agroforests on a plot scale.

Les gyromètres laser He-Ne sont des senseurs inertiels dont la fiabilité et la précision sont reconnues depuis le milieu des années 1980. Leur grande sensibilité leur permet de mesurer des vitesses de rotation avec une précision qui atteint 10⁻³ °/ h dans le domaine aéronautique. Cependant, du fait d’un fonctionnement complexe basé sur une physique riche et variée, ses performances sont fortement dépendantes des conditions de fonctionnement et de toute modification du processus de fabrication. Dans ce cas, un travail de modélisation prend tout son sens, puisqu’il permet, outre une compréhension claire et précise des différents phénomènes physiques, un accès à des études paramétriques non envisageables expérimentalement. La modélisation globale du fonctionnement d’un gyrolaser He-Ne a ainsi été l’objectif principal de la collaboration entre la société Sagem (groupe Safran), un des leaders mondiaux dans le domaine des senseurs inertiels, et le Laboratoire de Physique des Gaz et des Plasmas (LPGP). Cette modélisation est « multiphysique » du fait de la diversité des domaines que couvre la physique du gyrolaser (Plasma, Physique Atomique, Lasers). C’est pourquoi nous avons développé trois modèles spécifiquement adaptés à chaque domaine. Le premier décrit la modélisation de la colonne positive du plasma de décharge dans une approche fluide. Ce modèle permet une description quantitative du plasma et l’accès aux grandeurs telles que la densité électronique et la fonction de distribution en énergie des électrons. Ces grandeurs sont les entrées nécessaires au second modèle qui traite la cinétique des états excités du plasma He-Ne. Un modèle collisionnel-radiatif à 1 dimension radiale (1D-CRM) a ainsi été développé. L’aspect 1D se justifie par l’importance des phénomènes de transport d’atomes et de rayonnement pouvant influer sur le profil radial de l’inversion de population du laser. Le transfert radiatif par auto-absorption des transitions radiatives résonantes a notamment été modélisé en résolvant l’équation de Holstein-Biberman à partir d’une méthode Monte-Carlo. Cet aspect constitue un élément majeur de ce travail de thèse. La diffusion des atomes excités du mélange He-Ne a également été prise en compte en résolvant l’équation de diffusion avec différentes conditions au bord à la surface du capillaire.A partir des populations et des taux cinétiques de peuplement et dépeuplement calculés par 1D-CRM, l’amplification laser dans la cavité a été modélisée dans le cadre d’une approche Maxwell-Bloch à 2 niveaux (NADIA) en incluant la saturation inhomogène du gain c’est-à-dire en tenant compte de la vitesse des atomes émetteurs dans la direction de propagation des faisceaux lasers. La cinétique de NADIA a été optimisée et les processus de transports dans l’espace des phases ont également été implémentés. Ce modèle a été utilisé pour étudier les performances du gyrolaser liées au milieu amplificateur et pour dériver les paramètres physiques nécessaires au développement d’un simulateur du gyrolaser.Dans ce simulateur, un modèle physique simplifié dérivé de NADIA, a été couplé à des modules « systèmes » dans le but de reproduire en sortie le signal opérationnel d’un gyrolaser. Ceci nous a permis de réaliser des études paramétriques sur les grandeurs caractérisant les performances d’un gyrolaser notamment le biais dynamique et le Random-Walk. Nous montrons en particulier que les performances de notre simulateur sont en bon accord avec celles observées en conditions opérationnelles. De plus, nos résultats montrent que ce simulateur est également un outil puissant pour l’analyse de données expérimentales. / Ring laser gyros (RLG) are inertial sensors whose reliability and accuracy have been recognised since the mid-1980s. Their high sensitivity enables them to measure angular velocity with an accuracy of 10⁻³ °/ h in aeronautics. However, because of a complex functioning based on a rich and varied physics, their performances are highly dependent on the working conditions and on any modification in the manufacturing process. In this case, a numerical modelling is pertinent since it allows both a clear understanding of the ring laser physics and parametric studies which are not experimentally feasible. The global modelling of a He-Ne RLG has been the main objective of the collaboration between Sagem (Safran group), which is one of the world leader in the inertial sensors field, and the Gas and Plasma Physics Laboratory (LPGP).This modelling is “multi-physics” since RLG physics involves several disciplines (plasma, atomic and laser physics). Therefore we have developed three models specifically adapted to each field. The first one describes the modelling of the positive column of the glow discharge following a fluid approach. This model allows a quantitative description of the plasma and gives access to fundamental quantities like the electron density or the electron energy distribution function. These quantities are the required inputs for the second model which treats the kinetics of the excited states inside the He-Ne plasma. For this, a collisional-radiative model in a radial geometry (1D-CRM) has been developed. The radial geometry is justified by the importance of the transport processes of atoms and radiations which can influence the radial profile of the population inversion. Notably, the radiative transfer by self-absorption of the resonant radiative transitions has been modelled by solving the Holstein-Biberman equation by a Monte-Carlo method. This aspect is a major component of this PhD work. Diffusion of excited atoms inside the plasma has also been taken into account by solving the diffusion equation with different boundary conditions at the capillary surface. From the populations and the kinetic rates computed by 1D-CRM, the laser amplification inside the cavity has been modelled using a two-level Maxwell-Bloch approach (NADIA) taking into account the inhomogeneous gain saturation, which means to consider the thermal speed of the atoms in the direction of propagation of the laser beams. The kinetics of NADIA has been optimized and transport processes in the phase space have also been implemented. This model has been used to study the performances of the RLG linked to the amplifying medium and to derive the physical parameters needed for the development of a simulator.Concerning this simulator, a simplified physical model from NADIA has been coupled to system modules in order to reproduce the operating signal of a RLG. This allows to conduct parametric studies on the quantities defining the RLG performance in particular the dynamic bias and the so-called “Random Walk”. We showed notably that the results of our simulator are in good agreement with experimental measurements in operating conditions. Moreover, our results show that this simulator is a powerful tool for analysing experimental data.

La chaîne laser Apollon 10PW est un projet de grande envergure visant à fournir des impulsions de 10 PW et atteindre des intensités sur cibles de 10^22 W/cm^2. Dans l’état de l'art actuel, les lasers à dérive de fréquence (CPA) de haute intensité à base de cristaux titane saphir (Ti:Sa), sont limités à des puissances de crête de 1,3 PW pour des impulsions de 30-fs, en raison du rétrécissement spectral par gain dans les amplificateurs. Pour accéder au régime multipetawatt, le rétrécissement de gain doit être évité. Pour cela une technique alternative d’amplification appelée amplification paramétrique optique d'impulsions à dérive de fréquence (OPCPA) est utilisée. Elle offre la possibilité d’amplifier sur des très larges bandes spectrales de gain et d’accéder à des durées d'impulsion aussi courtes que 10 fs. Le laser Appolon 10 PW exploite une technologie hybride d’OPCPA et de Ti:Sa-CPA pour atteindre in fine des impulsions de 15 fs avec une énergie de 150 J. L’OPCPA est réalisé essentiellement sur les étages d'amplification de basse énergie et de très fort gain (ou le rétrécissement par le gain se fait le plus ressentir), ceci pour obtenir des impulsions de 100 mJ, 10 fs. Deux étages OPCPA sont préus ; le premier en régime picoseconde, le second en régime nanoseconde, et subséquemment on utilisera le Ti:Sa pour l'amplification de très haute énergie pour atteindre le régime multi-Joule.Les travaux de cette thèse porte sur le pilote OPCPA du laser Apollon-10 PW et se concentre sur le développement d’une source d’impulsions ultra-courtes avec un contraste élevé. Pour atteindre l’objectif final de 15 fs, 150 J, le pilote doit permettre l’obtention d’impulsions dont le spectre supporte des durées de 10 fs, ceci avec un contraste temporel d'au moins 10^10. Dans cette thèse nous nous intéressons à la mise en œuvre des premiers étages du pilote. Ce travail concerne les étages de compression, de nettoyage d’impulsions et d’amplification OPCPA en régime picoseconde. Ainsi, en partant d'une source commerciale Ti:Sa délivrant des impulsions de 25-fs avec un contraste de 10^8, nous réalisons tout d’abord un élargissement spectral par auto-modulation de phase et une amélioration du contraste par génération de polarisation croisée (XPW). Ensuite, nous nous intéressons aux différents étireurs ps possibles incluant un filtre dispersif programmable (dazzler) en vue d’injecter l’OPCPA picoseconde de manière optimale. La solution directe utilisant un bloc de verre BK7 a été retenue et son association avec un compresseur compact pour le diagnostique de la compressibilité a été étudiée. Enfin, l’amplificateur OPCPA ps a été mis en œuvre dans des configurations à simple et double étages. / The Apollon-10 PW laser chain is a large-scale project aimed at delivering 10 PW pulses to reach intensities of 10^22 W/cm^2. State of the art, high intensity lasers based solely on chirped pulse amplification (CPA) and titanium sapphire (Ti:Sa) crystals are limited to peak powers reaching 1.3 PW with 30-fs pulses as a result of gain narrowing in the amplifiers. To access the multipetawatt regime, gain narrowing can be suppressed with an alternative amplification technique called optical parametric chirped pulse amplification (OPCPA), offering a broader gain bandwidth and pulse durations as short as 10 fs. The Apollon-10 PW laser will exploit a hybrid OPCPA-Ti:Sa-CPA strategy to attain 10-PW pulses with 150 J and 15 fs. It will have two high-gain, low-energy amplification stages (10 fs ,100 mJ range) based on OPCPA in the picosecond and nanosecond timescale and afterwards, and will use Ti:Sa for power amplification to the 100-Joule level.Work in this thesis involves the progression of the development on the Apollon-10 PW front end and is focused on the development of a high contrast, ultrashort seed source supporting 10-fs pulses, stretching these pulses prior to OPCPA and the implementation of the picosecond OPCPA stage with a target of achieving 10-mJ pulses and maintaining its bandwidth. To achieve the final goal of 15-fs, 150-J pulses, the seed source must have a bandwidth supporting 10-fs and a temporal contrast of at least 10^10. Thus from an initial commercial Ti:Sa source delivering 25-fs pulses with a contrast of 10^8, spectral broadening via self-phase modulation and contrast enhancement with cross polarized (XPW) generation was performed. Subsequently, the seed pulses were stretched to a few picoseconds to match the pump for picosecond OPCPA. Strecher designs using an acousto-optic programmable dispersive filter (dazzler) for phase control in this purpose are studied. A compact and straightforward compressor using BK7 glass is used and an associated compressor for pulse monitoring was also studied. Lastly, the picosecond OPCPA stage was implemented in single and dual stage configurations.

INTRODUÇÃO: A síndrome de Williams-Beuren (SWB) é uma doença genética causada por uma microdeleção na região 7q11.23 e caracterizada por dismorfismos faciais típicos, deficiência intelectual, comportamento hipersociável, cardiopatia congênita, principalmente a estenose aórtica supravalvar (EASV), e outras malformações variáveis. MÉTODOS: Foram avaliados 65 pacientes (40 do sexo masculino, 25 do sexo feminino), com idades entre 2 e 59 anos (mediana = 14 anos), com características clínicas sugestivas de SWB. Todos os pacientes eram filhos de pais normais. A técnica de Multiplex Ligation-dependent Probe Amplification® (MLPA®) foi usada com kit específico com sondas da região da SWB (MRC Holland). As sondas foram hibridadas ao DNA e os fragmentos ligados foram amplificados por PCR e analisados com software específico. RESULTADOS: A deleção de todas as sondas da região 7q11.23 testadas foi detectada por MLPA® em 55/65 pacientes. Um caso de deleção atípica, ou seja, menor que 1,5 Mb, foi observada em um paciente com quadro clínico parcial da síndrome. Os nove pacientes sem deleção tinham um diagnóstico clínico duvidoso da SWB. Dois pacientes tiveram MLPA® positivo para SWB embora apresentassem resultados de FISH negativos. Os achados clínicos dos pacientes com deleção típica foram: fácies típica (98,2%), atraso do desenvolvimento neuropsicomotor (98,2%), comportamento hipersociável (94,5%), hiperacusia (94,5%) e cardiopatia (81,8%). Dentre os pacientes com cardiopatia, 42,2% apresentavam EASV (isolada ou associada a outras anomalias cardíacas), 26,7% apresentavam estenose pulmonar e 31,1% apresentavam outras cardiopatias isoladas ou em associação. Outros achados dos pacientes com deleção foram: anormalidades geniturinárias (85,4%), escoliose (56,4%), baixa estatura (43,6%), hérnias inguinais e/ou umbilicais (36,4%), hipertensão arterial (36,4%, com 20% destes apresentando estenose de artérias renais), estrabismo (34,5%), microcefalia (30,9%), sinostose radioulnar (10,9%), hipotireoidismo (14,5%) e hipotireoidismo subclínico (7,3%). Hipercalcemia foi detectada em um paciente apenas. Outros dois pacientes apresentaram nefrocalcinose e um paciente apresentou hipercalciúria, com níveis de cálcio sérico normais. Três pacientes adolescentes foram a óbito por causas cardiovasculares, incluindo um caso de óbito após transplante cardíaco. CONCLUSÕES: A técnica de MLPA® foi eficaz na detecção da microdeleção na região 7q11.23 possibilitando a confirmação diagnóstica da SWB em 84,6% dos pacientes estudados. Além disso, foi possível detectar uma deleção menor atípica em um paciente com fenótipo parcial e confirmar o diagnóstico em dois pacientes com quadro clínico típico de SWB e resultados de FISH negativos. Portanto, o MLPA® constitui-se um método promissor na investigação diagnóstica da SWB. Por ser uma doença multissistêmica, a SWB exige cuidados multidisciplinares e acompanhamento específico a fim de se prevenir complicações / INTRODUCTION: Williams-Beuren syndrome (WBS) is a genetic disorder caused by a microdeletion in 7q11.23 region. It is characterized by typical facial dysmorphisms, mental retardation, hipersociable behavior, congenital heart disease, mainly supravalvular aortic stenosis (SVAS), and other variable congenital malformations. METHODS: 65 patients (40 males, 25 females), aged 2-59 years old (median = 14 years old), with clinical characteristics suggesting WBS, were evaluated. All patients had normal parents. Multiplex Ligation-dependent Probe Amplification® (MLPA®) was performed with a kit with probes in WBS region (MRC Holland). The probes were hybridized to the DNA and the ligated fragments were amplified by PCR and analyzed with specific software. RESULTS: The deletion for all tested probes in the 7q11.23 region was detected by MLPA® in 55/65 patients. One case of atypical deletion, smaller than 1.5 Mb, was observed in one patient with partial clinical picture of the syndrome. The nine patients without the deletion did not have a definitive clinical diagnosis of WBS. Two patients had positive MLPA® results even though they had negative FISH for WBS. The clinical characteristics of the patients with the typical deletion were: typical facies (98.2%), neuropsicomotor delay (98.2%), hypersociable behavior (94.5%), hyperacusis (94.5%) and congenital heart disease (81.8%). Among the patients with cardiac abnormalities, 42.2% had SVAS (isolated or not), 26.7% had pulmonary valve stenosis and 31.1% had other cardiac anomalies (isolated or grouped). Other findings in patients with deletion comprised: genitourinary abnormalities (85.4%), scoliosis (56.4%), short stature (43.6%), inguinal and/or umbilical hernias (36.4%), arterial hypertension (36.4%, with 20% of these presenting renal arteries stenosis), strabismus (34.5%), microcephaly (30.9%), radioulnar synostosis (10.9%), hypothyroidism (14.5%), and subclinical hypothyroidism (7.3%). Hypercalcaemia was detected in only one patient. Two other patients had nephrocalcinosis and one patient had hypercalciuria, with normal serum calcium levels. Three adolescents died due to cardiovascular problems, including one case that died after a cardiac transplantation. CONCLUSIONS: MLPA® was effective to detect the microdeletion in 7q11.23 region confirming the diagnosis of WBS in 84.6% of the patients. It was also possible to detect a small atypical deletion in one patient with partial phenotype and confirm the diagnosis in two patients with typical clinical characteristics of WBS and negative FISH results. Thus, MLPA® is a promising method in the diagnostic investigation of WBS. WBS is a multisystemic disorder and therefore requires multidisciplinary care and specific follow-up in order to prevent complications

O surgimento de novos serviços que requerem uma largura de banda cada vez maior, bem como o crescente número de usuários de tais serviços, têm introduzido desafios às empresas operadoras de telecomunicações em sua capacidade de atender a estas demandas sem perda apreciável da qualidade de serviço e mantendo, ainda assim, os custos num nível aceitável pelos usuários. Neste contexto, redes ópticas passivas (PONs) vêm atraindo grande interesse em anos recentes. Na sua variante de longo-alcance, as redes PON permitem uma consolidação do uso dos equipamentos e centrais de serviço requeridos, reduzindo custos operacionais e de instalação. Uma das formas de atingir este maior alcance dá-se por meio da inserção de amplificadores ópticos nas redes de acesso. Neste trabalho, portanto, estudaram-se alguns tipos de amplificadores ópticos e suas possíveis aplicações em redes de acesso, levando a topologias de longo alcance e alta capacidade. Foram realizadas avaliações experimentais de um extensor, baseado em amplificadores ópticos semicondutores (SOAs), na rede GPON do CPqD, sob a Meta 3 do Projeto GIGA, possibilitando a obtenção de uma topologia do tipo Fiber-to-the-Building (FTTB) com 80 km de extensão e 128 usuários atendidos por uma única central de serviço. Além dessas validações experimentais, foram simulados computacionalmente SOAs com características otimizadas bem como sistemas que utilizam fibras dopadas com érbio bombeadas remotamente, sendo que nestes últimos, atingiram-se distâncias superiores a 100 km. / The emergence of new services which require an increasing bandwidth, as well as the growing number of users of such services, have introduced challenges to the network operators in regard to their capacity of supporting these demands with no penalty on the required quality of service, while keeping the costs at an acceptable level for the users. In this context, passive optical networks (PONs) have attracted a great deal of interest in recent years. In the long-reach configuration, PON networks allow for a consolidation of equipament usage, reducing operational and installation costs. One way to achieve this longer reach is by the insertion of optical amplifiers in the access network. Therefore, in our work, we have investigated several optical amplifier configurations, as well as their application in access networks, leading to longreach and high capacity network topologies. Experimental evaluations of an extender, based on semiconductor optical amplifiers, were carried out in the CPqD GPON network, under Goal 3 of GIGA Project, allowing the achievement of a Fiber-to-the-Building (FTTB) topology with 80km of extension and 128 users served by a single central office. Besides these experimental validations, were simulated computationally SOAs with optimized characteristics as well as systems using remotely pumped erbium-doped fibers, whereas in the latter were reached distances exceeding 100 km.

Le tissu adipeux, longtemps considéré comme réservoir énergétique et tissu de soutien mécanique a été promu au rang d'organe endocrine car sécréteur d'hormones. Il est utilisé depuis une trentaine d'année en chirurgie plastique cosmétique et réparatrice comme agent de comblement dans le cadre de lipoatrophie, de reconstruction mammaire ou de liftings. Ses effets régénérateurs observés sont attribués à la présence de cellules souches mésenchymateuses (CSM), les ASC (adipose-derived stem/stromal cells) assimilables aux CSM de la moelle osseuse. Leur auto renouvèlement et multipotentialité sont exploités en médecine régénérative. Nous nous sommes intéressés à la cicatrisation des plaies difficiles. Le premier article porte sur la sélection de différents dispositifs de prélèvement et d'extraction des ASC humaines à partir de lipoaspirat. Par rapport à la méthode de référence et quel que soit le dispositif, les cellules extraites ne montrent pas de résultats significativement différents en terme de rendement d'extraction et viabilité cellulaire, de capacité proliférative (clonogénicité, doublement de population et temps de doublement), de phénotype (marqueurs CD90, CD73, HLA-ABC CD45, CD14 et HLA-DR par cytométrie en flux), de stabilité génétique (caryotype et expression du gène codant pour hTERT) et de multipotentialité (différenciation adipo-, ostéo- et chondrogénique). Dans nos mains, le dispositif GID-SVF1 s'est montré le plus pratique tant au niveau du prélèvement que de son utilisation. Le second article démontre biocompatibilité et la biodisponibilité du produit fini (ASC dans acide hyaluronique) in vitro et sa tolérance chez la souris nude. Le troisième article confirme sa tolérance et établit son efficacité chez la souris nude sur de large plaie excisionnelle utilisant le modèle de Galiano. En effet, la cicatrisation complète est plus rapide pour les souris traitées avec les ASC (14 jours contre 21 jours pour les souris non traitées, p<0.001) avec une meilleure vascularisation du tissu cicatriciel (immunomarquage CD31, iontophorèse couplée au laser Doppler). Ce travail complète les prérequis aux essais cliniques en validant le prélèvement grâce à des dispositifs permettant la digestion des lipoaspirats et l'obtention de la SVF. L'amélioration significative de la cicatrisation dans notre modèle de plaie valide non seulement l'efficacité des ASC mais aussi leur véhicule / Adipose tissue, for a while considered as an energy reservoir and a mechanical support tissue, is nowadays recognized as an endocrine organ. It is used for more than thirty years in cosmetic and reconstructive plastic surgery as filler for lipodystrophy, breast reconstruction or lifting. Its regenerative potential is attributed to mesenchymal stem cells (MSC), the so-called ASC (Adipose-derived stem/stromal cells) similar to MSC from bone marrow. Their self-renewing capacity and their multupotency are exploited in regenerative medicine. We are interested in chronic wound healing. The first article deals with several devices for the harvesting of fat and the isolation of human ASC from lipoaspirates. When compared to the reference method and whatever the device, the extracted cells do not show any statistical differences in terms of cell yield and viability, proliferative capacity (clonogenicity, population doubling and doubling time), phenotype (CD90, CD73, HLA-ABC CD45, CD14 et HLA-DR using flow cytometry), genetic stability (karyotype and hTERT gene expression) and multipotentiality (adipo-, osteo- et chondrogenic differentiation). In our hands, GID SVF-1TM device was the most easy to handle for the harvest and also for its use. The second article demonstrates the biocompatibility and bioavailability of our final product (ASC in hyaluronic acid) in vitro and its tolerance in nude mice. The third article reinforces its tolerance and establishes its effectiveness in nude mice on large excisional wounds using Galiano model. Indeed, complete wound healing is more rapid in ASC-treated mice (14 days versus 21 days in untreated mice, p<0.001) with a better healed tissue vascularization (CD31 immunostaining, Dopplercoupled iontophoresis). This work fulfills the requirements for clinical trials in validating the harvest of lipoaspirate using devices that allow fat digestion and SVF extraction. The significant improvement of wound healing in our model validates not only ASC effectiveness but also their vehicle

INTRODUÇÃO: A síndrome de Williams-Beuren (SWB) é uma doença genética causada por uma microdeleção na região 7q11.23 e caracterizada por dismorfismos faciais típicos, deficiência intelectual, comportamento hipersociável, cardiopatia congênita, principalmente a estenose aórtica supravalvar (EASV), e outras malformações variáveis. MÉTODOS: Foram avaliados 65 pacientes (40 do sexo masculino, 25 do sexo feminino), com idades entre 2 e 59 anos (mediana = 14 anos), com características clínicas sugestivas de SWB. Todos os pacientes eram filhos de pais normais. A técnica de Multiplex Ligation-dependent Probe Amplification® (MLPA®) foi usada com kit específico com sondas da região da SWB (MRC Holland). As sondas foram hibridadas ao DNA e os fragmentos ligados foram amplificados por PCR e analisados com software específico. RESULTADOS: A deleção de todas as sondas da região 7q11.23 testadas foi detectada por MLPA® em 55/65 pacientes. Um caso de deleção atípica, ou seja, menor que 1,5 Mb, foi observada em um paciente com quadro clínico parcial da síndrome. Os nove pacientes sem deleção tinham um diagnóstico clínico duvidoso da SWB. Dois pacientes tiveram MLPA® positivo para SWB embora apresentassem resultados de FISH negativos. Os achados clínicos dos pacientes com deleção típica foram: fácies típica (98,2%), atraso do desenvolvimento neuropsicomotor (98,2%), comportamento hipersociável (94,5%), hiperacusia (94,5%) e cardiopatia (81,8%). Dentre os pacientes com cardiopatia, 42,2% apresentavam EASV (isolada ou associada a outras anomalias cardíacas), 26,7% apresentavam estenose pulmonar e 31,1% apresentavam outras cardiopatias isoladas ou em associação. Outros achados dos pacientes com deleção foram: anormalidades geniturinárias (85,4%), escoliose (56,4%), baixa estatura (43,6%), hérnias inguinais e/ou umbilicais (36,4%), hipertensão arterial (36,4%, com 20% destes apresentando estenose de artérias renais), estrabismo (34,5%), microcefalia (30,9%), sinostose radioulnar (10,9%), hipotireoidismo (14,5%) e hipotireoidismo subclínico (7,3%). Hipercalcemia foi detectada em um paciente apenas. Outros dois pacientes apresentaram nefrocalcinose e um paciente apresentou hipercalciúria, com níveis de cálcio sérico normais. Três pacientes adolescentes foram a óbito por causas cardiovasculares, incluindo um caso de óbito após transplante cardíaco. CONCLUSÕES: A técnica de MLPA® foi eficaz na detecção da microdeleção na região 7q11.23 possibilitando a confirmação diagnóstica da SWB em 84,6% dos pacientes estudados. Além disso, foi possível detectar uma deleção menor atípica em um paciente com fenótipo parcial e confirmar o diagnóstico em dois pacientes com quadro clínico típico de SWB e resultados de FISH negativos. Portanto, o MLPA® constitui-se um método promissor na investigação diagnóstica da SWB. Por ser uma doença multissistêmica, a SWB exige cuidados multidisciplinares e acompanhamento específico a fim de se prevenir complicações / INTRODUCTION: Williams-Beuren syndrome (WBS) is a genetic disorder caused by a microdeletion in 7q11.23 region. It is characterized by typical facial dysmorphisms, mental retardation, hipersociable behavior, congenital heart disease, mainly supravalvular aortic stenosis (SVAS), and other variable congenital malformations. METHODS: 65 patients (40 males, 25 females), aged 2-59 years old (median = 14 years old), with clinical characteristics suggesting WBS, were evaluated. All patients had normal parents. Multiplex Ligation-dependent Probe Amplification® (MLPA®) was performed with a kit with probes in WBS region (MRC Holland). The probes were hybridized to the DNA and the ligated fragments were amplified by PCR and analyzed with specific software. RESULTS: The deletion for all tested probes in the 7q11.23 region was detected by MLPA® in 55/65 patients. One case of atypical deletion, smaller than 1.5 Mb, was observed in one patient with partial clinical picture of the syndrome. The nine patients without the deletion did not have a definitive clinical diagnosis of WBS. Two patients had positive MLPA® results even though they had negative FISH for WBS. The clinical characteristics of the patients with the typical deletion were: typical facies (98.2%), neuropsicomotor delay (98.2%), hypersociable behavior (94.5%), hyperacusis (94.5%) and congenital heart disease (81.8%). Among the patients with cardiac abnormalities, 42.2% had SVAS (isolated or not), 26.7% had pulmonary valve stenosis and 31.1% had other cardiac anomalies (isolated or grouped). Other findings in patients with deletion comprised: genitourinary abnormalities (85.4%), scoliosis (56.4%), short stature (43.6%), inguinal and/or umbilical hernias (36.4%), arterial hypertension (36.4%, with 20% of these presenting renal arteries stenosis), strabismus (34.5%), microcephaly (30.9%), radioulnar synostosis (10.9%), hypothyroidism (14.5%), and subclinical hypothyroidism (7.3%). Hypercalcaemia was detected in only one patient. Two other patients had nephrocalcinosis and one patient had hypercalciuria, with normal serum calcium levels. Three adolescents died due to cardiovascular problems, including one case that died after a cardiac transplantation. CONCLUSIONS: MLPA® was effective to detect the microdeletion in 7q11.23 region confirming the diagnosis of WBS in 84.6% of the patients. It was also possible to detect a small atypical deletion in one patient with partial phenotype and confirm the diagnosis in two patients with typical clinical characteristics of WBS and negative FISH results. Thus, MLPA® is a promising method in the diagnostic investigation of WBS. WBS is a multisystemic disorder and therefore requires multidisciplinary care and specific follow-up in order to prevent complications

Les microrésonateurs à mode de galerie passifs à base de cristal ou de verre fabriqués par la méthode de fusion possèdent un facteur de qualité limité à quelques 10E8. Ceci est généralement dû à la contamination de la surface du résonateur lors de sa fusion. Dans ces travaux, nous proposons de contourner cette limitation en utilisant des microrésonateurs actifs pour compenser les pertes. Afin de caractériser les microrésonateurs actifs de très haut facteur de qualité ainsi obtenu, nous nous appuyons sur la méthode CRDM (Cavity Ring Down Measurement). Cette méthode interférométrique est d'une part bien adaptée à la caractérisation de résonateurs de très haut facteur de qualité et d'autre part elle permet de remonter de manière univoque aux facteurs de qualité intrinsèque Qo et extrinsèque Qe du résonateur. Dans un régime de compensation de pertes, nous avons pu atteindre tous les régimes de couplage et obtenus des facteurs de qualité intrinsèques excédant les 10E10. En régime d'amplification sélective, nous avons démontré expérimentalement que l'on pouvait obtenir des gains élevés allant jusqu'à 33 dB et des retards de groupe excédant 2,3 µs dans ces microrésonateurs actifs. Ces microrésonateurs de très haut facteur de qualité et de très haute finesse peuvent présenter un couplage modal se manifestant par un doublet de résonances. Une confrontation théorie/expérience avec la méthode CRDM permet de mesurer un écart très faible entre les doublets. Par ailleurs, ces microrésonateurs présentant un fort confinement spatial et une forte surtension, sont propices à l'observation d'effets non-linéaires. Une modélisation intégrant l'effet thermique et l'effet Kerr a été réalisée. Une confrontation théorie/expérience nous a permis d'estimer la puissance réellement injectée dans le mode ainsi qu'à estimer le volume du mode. / Glass-based whispering gallery mode (WGM) microresonators are easy to produce by melting techniques. However, they suffer from surface contamination which limits their long term quality factor to only about 10E8. In this thesis, we show that an optical gain provided by erbium ions can compensate for residual losses. The optical characterization method is based on frequency-swept “Cavity-Ring-Down-Measurement”. This method can fully describe the linear properties of microcavities such as coupling regime and group delay. In compensation loss regime we demonstrate that it is possible to control the coupling regime of an ultrahigh Q-factor microresonator from undercoupling to spectral selective amplification. Under the selective amplification regime, we obtain an internal Q-factor exceding 10E10. In selective amplification, we experimentally show that it is possible to obtain high amplification up to 33 dB and a high group delay. The microresonators with high Q-factor and high finesse could give rise to a modal coupling which exhibits a splitting of the resonance in the transmission. A characterization of this phenomenon with the cavity ring down method was realized. Moreover, these microresonators, are conducive to the non-linear effect observation. A model incorporating the thermal effect and the Kerr effect has been achieved. Confrontation between theory and experiment allowed us to estimate the real optical power injected into the mode as well as estimating the mode volume.

In this thesis, we report the observations of optical squeezing from second harmonic generation (SHG), optical parametric oscillation (OPO) and optical parametric amplification (OPA). Demonstrations and proposals of applications involving the squeezed light and electro-optic control loops are presented. ¶ In our SHG setup, we report the observation of 2.1 dB of intensity squeezing on the second harmonic (SH) output. Investigations into the system show that the squeezing performance of a SHG system is critically affected by the pump noise and a modular theory of noise propagation is developed to describe and quantify this effect. Our experimental data has also shown that in a low-loss SHG system, intra-cavity nondegenerate OPO modes can simultaneously occur. This competition of nonlinear processes leads to the optical clamping of the SH output power and in general can degrade the SH squeezing. We model this competition and show that it imposes a limit to the observable SH squeezing. Proposals for minimizing the effect of competition are presented. ¶ In our OPO setup, we report the observation of 7.1 dB of vacuum squeezing and more than 4 dB of intensity squeezing when the OPO is operating as a parametric amplifier. We present the design criteria and discuss the limits to the observable squeezing from the OPO.We attribute the large amount of squeezing obtained in our experiment to the high escape efficiency of the OPO. The effect of phase jitter on the squeezing of the vacuum state is modeled. ¶ The quantum noise performance of an electro-optic feedforward control loop is investigated. With classical coherent inputs, we demonstrate that vacuum fluctuations introduced at the beam splitter of the control loop can be completely cancelled by an optimum amount of positive feedforward. The cancellation of vacuum fluctuations leads to the possibility of noiseless signal amplification with the feedforward loop. Comparison shows that the feedforward amplifier is superior or at least comparable in performance with other noiseless amplification schemes. When combined with an injection-locked non-planar ring Nd:YAG laser, we demonstrate that signal and power amplifications can both be noiseless and independently variable. ¶ Using squeezed inputs to the feedforward control loop, we demonstrate that information carrying squeezed states can be made robust to large downstream transmission losses via a noiseless signal amplification. We show that the combination of a squeezed vacuum meter input and a feedforward loop is a quantum nondemolition (QND) device, with the feedforward loop providing an additional improvement on the transfer of signal. In general, the use of a squeezed vacuum meter input and an electro-optic feedforward loop can provide pre- and post- enhancements to many existing QND schemes. ¶ Finally, we proposed that the quantum teleportation of a continuous-wave optical state can be achieved using a pair of phase and amplitude electro-optic feedforward loops with two orthogonal quadrature squeezed inputs. The signal transfer and quantum correlation of the teleported optical state are analysed. We show that a two dimensional diagram, similar to the QND figures of merits, can be used to quantify the performance of a teleporter.

Ce mémoire présente une étude théorique et expérimentale de l'amplification continue d'images à l'aide d'un oscillateur paramétrique optique (OPO).<br />Une première partie est consacrée aux propriétés classiques de cavités nécessaires à l'imagerie, dites "dégénérées en modes transverses". On étudie tout d'abord théoriquement le problème général de la transmission d'une image à travers une cavité quelconque.<br />Ensuite, deux exemples de cavités dégénérées sont abordés: la cavité hémi-confocale puis la cavité autoimageante. Ensuite les propriétés quantiques spatiales du vide émis par un oscillateur paramétrique optique sous le seuil d'oscillation sont abordées. On traite tout d'abord l'effet de la taille finie du milieu non-linéaire sur la compression de bruit locale en sortie d'un OPO en cavité confocale. Cette étude est étendue au cas de la cavité auto-imageante où l'on montre la possibilité de générer des faisceaux EPR locaux.<br />Une troisième partie est consacrée à l'amplification optique au niveau quantique. On construit un modèle théorique d'OPO monomode aussi proche que possible de notre expérience. Nous étudions ensuite le problème de l'optimisation des caractéristiques de l'OPO pour l'amplification sans bruit.<br />Enfin une partie expérimentale étudie l'amplification d'images à l'aide d'un OPO dégénéré en modes transverses sous le seuil d'oscillation. Cette étude est réalisée tout d'abord en cavité semi-confocale avec un cristal de type II puis en cavité confocale avec un cristal de type I. Nous prouvons le caractère quantique des images amplifiées. Le facteur de bruit du système est caractérisé, prouvant un régime d'amplification "sans bruit".