La découverte en 2008 de supraconductivité à relativement haute température (Tc,max = 56K) dans les pnictures de Fer a ravivé les questions fondamentales sur l’origine et la nature de la supraconductivité posés par les supraconducteurs non conventionnels. En particulier, la présence d’une phase antiferromagnétique à proximité de celle supraconductrice dans leur diagramme de phase pose la question du lien entre magnétisme et supraconductivité. Ces supraconducteurs à base de Fe présentent un diagramme de phase générique, mais quelques exceptions remettent en question une description qui se voudrait universelle. Nous avons choisi d’étudier ces cas particuliers grâce à une sonde locale, la résonance magnétique nucléaire (RMN). Nos observations nous ont non seulement permis de comprendre la raison de ces exceptions, mais aussi de s’en servir pour mieux sonder les corrélations magnétiques dans ces matériaux, un ingrédient clé pour la compréhension de la supraconductivité. Premier sujet, la coexistence de supraconductivité et de magnétisme : celle-ci a été observée dans la plupart des supraconducteurs à base de Fer de façon homogène ou inhomogène, mais toujours pour des états magnétiques à faible TN et faibles moments en accord avec des descriptions itinérantes à faibles corrélations. Pourtant un nouveau composé au Sélénium est venu remettre en cause ces conclusions en présentant une apparente coexistence homogène entre une forte supraconductivité macroscopique (Tc ≈ 30K) et un très fort antiferromagnétisme (TN ≈ 600K, moments magnétiques de valeur élevée de 3.3µB). Cette observation suggère donc une description ici plutôt en terme d’isolants de Mott contrairement aux autres supraconducteurs à base de Fer. Nos mesures RMN permettent de montrer en fait l’existence d’une séparation de phase et de statuer sur la stœchiométrie et les propriétés électroniques des différentes phases, pour finalement réconcilier ce composé et les autres familles. Deuxième exception : dans la famille archétype BaFe₂As₂, tous les dopages sur site Fer ou Arsenic ou même l’application de pression mènent à la supraconductivité, sauf dans le cas du dopage au Manganèse ou au Chrome en site Fer, qui ne provoquent pas l’apparition de la supraconductivité. Nos mesures RMN nous ont permis de sonder la nature de la transition magnétique, mais aussi l’état métallique de ces composés substitués. Nous montrons en particulier que le trou supplémentaire du Manganèse substitué à la place du Fer reste en fait localisé sur son site et se manifeste alors par un moment magnétique localisé. Cette étude du dopage par le Manganèse ouvre la voie à l’idée d’utiliser le Manganèse en faible concentration comme source de moments localisés qui polarisent magnétiquement leur environnement. Cette polarisation permet en effet de caractériser la nature même des corrélations de spin. Nous avons donc utilisé la RMN ainsi que la magnétométrie-SQUID pour mesurer cette polarisation dans des composés supraconducteurs pour sonder les corrélations de spins de ces systèmes. Nous concluons que ces corrélations sont plutôt faibles et indépendantes de la température dans les composés dopés en électrons. / The discovery in 2008 of superconductivity at a rather high temperature in the iron pnictides (Tc,max = 56K) has revived the fundamental questions about the existence and the nature of the superconducting phase raised by the unconventional superconductors. In particular, the existence of an antiferromagnetic phase that is in vicinity of the superconducting phase in the phase diagram raises questions about the link between magnetism and superconductivity. These Iron based superconductors have a generic phase diagram, but some exceptions are questioning a description that would be universal. We chose to study these cases through a local probe, nuclear magnetic resonance (NMR). Our observations have not only allowed us to understand the reasons for these exceptions, but also be used to better probe the magnetic correlations in these materials, a key ingredient for the understanding of superconductivity. First subject, the coexistence of superconductivity and magnetism: it was observed in most superconductors based on iron homogeneously or inhomogeneously, but always for magnetic states at low TN and low magnetic moments in accordance with nesting descriptions with low correlations. Yet a new compound Selenium came to question these conclusions with an apparent homogeneous coexistence between a strong macroscopic superconductivity (Tc ≈ 30K) and a very strong antiferromagnetism (TN ≈ 600K, magnetic moments of high value of 3.3μB). This observation suggests a description rather in terms of Mott insulators, unlike other iron-based superconductors. Our NMR measurements show the existence of an effective phase separation and determine the stoichiometry and the electronic properties of the different phases, eventually reconciling this compound and other families. Second exception : in the archetype family BaFe₂As₂, all iron or arsenic on-site doping or even application of pressure leads to superconductivity, except in the case of Chrome or Manganese doping in Iron site, which does not cause the onset of superconductivity. Our NMR measurements have allowed us to probe the nature of the magnetic transition, but also the metallic state of the substituted compounds. We show in particular that the extra hole Manganese substituted in place of the iron is actually located on its atom and then manifested by a localized magnetic moment. This study of Manganese doping opens up the idea of using Manganese in low concentrations as a source of localized moments which magnetically polarize their environment. This polarization makes it possible to characterize the nature of the spin correlations. We used NMR and SQUID magnetometry, to measure the polarization in superconducting compounds to probe the spin correlations of these systems. We conclude that these correlations are rather low and independent of temperature in electrons doped compounds.

Ce travail de thèse porte sur la conception, la réalisation et l’évaluation expérimentale d’ un microsystème d’analyse dont l’originalité repose sur l’intégration d’une micro antenne planaire de spectroscopie par résonance magnétique nucléaire (SRMN) sur un système micro fluidique à base d’un polymère, le Cyclique Oléfine Copolymère (COC). La détermination des caractéristiques géométriques optimales du microsystème afin d’optimiser le couplage électromagnétique entre la micro antenne de détection et l’échantillon est effectuée à l’aide d’un modèle de calcul numérique, ce qui permet l’optimisation du rapport signal sur bruit (RSB). La réalisation du microsystème avec des procédés de micro fabrication développés au laboratoire ont permis de valides son fonctionnement dans un spectromètre dont le champ magnétique statique atteint 11.74 Tesla (fréquence de Larmor du proton égale à 500MHz). Travailler dans un champ aussi intense permet d’améliorer la sensibilité de détection mais nécessite de porter une attention particulière à l’homogénéité du champ magnétique qui, dans notre cas, peut être dégradée en raison de l’introduction du microsystème dans le spectromètre. En effet, les distorsions du champ magnétique, dues aux différentes susceptibilités magnétiques des matériaux constituant la microsonde, ont un impact direct sur la résolution spectrale. C’est pourquoi, une modélisation 3D par éléments finis est proposée afin de prévoir l’influence du microsystème sur la forme des raies spectrales et donc d’en déduire la résolution spectrale pouvant être espérée. La comparaison des résultats expérimentaux et ceux issus des simulations permet de valider le modèle de calcul numérique. Il apparait cependant nécessaire d’inclure le phénomène d’amortissement radiatif afin de pouvoir rendre compte des résultats expérimentaux relatifs à la résolution spectrale effectivement observée. / The work presented in this thesis involves the design, the development and the experimental evaluation of an analysis micro system. The originality of the work lies in the integration of a planar micro coil of spectroscopy by nuclear magnetic resonance (SNMR) on a micro fluidic system based on a polymer, cyclo olefin copolymer (COC). The determination of the optimum geometric characteristics of the micro system to improve electromagnetic coupling between the detection micro coil and the sample is performed with the aid of a numerical model that ensures the optimization of the signal to noise ratio (SNR). Using micro fabrication techniques developed in the laboratory, the micro system was developed and its behaviour was validated in spectrometer producing a static magnetic field off 11.74 Tesla (Larmor frequency of the proton equal to 500MHz). Working in such an intense field results in improved sensitivity of detection but requires paying close attention to the homogeneity of magnetic field. In this case the homogeneity can be degraded due to the introduction of the micro system in the spectrometer. Indeed, the distortions of the magnetic field, due to the different magnetic susceptibilities of the materials constituting the microprobe, have a direct impact on the spectral resolution. As such, 3D modelling by finite elements is proposed to predict the influence of the micro system on the shape of the spectral lines and to determine the best expected spectral resolution. The comparison of the experimental results to those obtained from simulation allows the validation of the numerical model. However, it appears necessary to include the effect of the radiation damping in the model to be able to justify the experimental results relative to the spectral resolution that was observed.

Phosphorus (P) one of the essential elements to plants and animals, is a non-renewable resource and accuatlly high demanded in agriculture. The World\'s population growth and future estimatives on food demands raises the question about the sustainability of the current agriculture systems, speccially concerns about the low P use efficiency in agroecosystems. Brazilian agriculture requires high P inputs and many researches has been developed to increase the crops yield and, consequently, food production efficiency. However, this development was achieved at the high costs of mineral fertilisers (specially P) and long-term perspectives about the costs of the intensification in the tropical agriculture is accuattly in debate. In this conxtext, in the present thesis chapter two we evaluated the evolution of the Brazilian cropland basis and P demands, quantifying the Brazil P Legacy and, based on scenarios involving the cropland area and yield expansion, we estimated the future (up to 2050) Legacy P and P fertilisers demand. We also estimated the potential aleviation that could be achieved in the mineral fertilizers consumption by utilisation and improvements on manure P recycling. Alternatively, considering the systems intensification and its effects on P availability, we proposed alternative scenarios to promote the Legacy P utilisation in Brazil\'s improved agriculture systems to grant the agriculture expansion without huge increments on the national P fertilisers consumption. A worldwide recognized advance in Brazilian agriculture is the Cerrado, where large cropland areas accually are cultivated twice a year, improving the food and fiber production without any additional disturbance of natural ecossystems. In this context, no-tillage (NT) agriculture has been widely used and, as consequence, soil fertility has been improved, which could be also farorable to the P availability, when rotation with crop species with P mobilization mechanisms are introduced, such as cover crops utilisation. However, the effects of these improved rotated systems on P bioavailability in long-term in tropical soils remains uncert in the literature and was our objective in the chapter three, where is described a study envolving the evaluation of long-term changes on P fractions in tropical Oxisols, from two long-term field trials involving tillage systems (NT and conventional tillage, CT) and cover crops (millet, brachiaria, maize and control, fallow). The long-term cultivation generated large amounts of legacy P in the soil and with the brachiaria introduction as cover crop, more P was recycled in the topsoil and labile P and all the organic P fractions increased. Based on the cover crop effects, we proposed that the bioavailability of the legacy P could be represented by the P extracted by the labile fractions + moderately labile P fractions. In the chapter four, we used other techniques actually widely applied to P speciation, and we applied in tropical soils affected by the native Cerrado conversion into NT and CT agriculture. A multiple approach to identify and quantify the P forms in tropical soils were proposed by the utilisation of Hedley\'s fractionation togheter with P K-edge XANES for P-bindings into inorganic soil matrix and liquid 31P-NMR spectroscopy to complement the organic P species in tropical soils. / Fósforo (P), um dos elementos essenciais às plantas e animais, é um recurso não-renovável e altamente demandado na agricultura atualmente. O crescimento da população mundial e as estimativas futuras da demanda de alimentos aumentam os questionamentos sobre a sustentabilidade dos sistemas agrícolas atuais, especialmente no que se refere a baixa eficiência no uso do P na agricultura. A agricultura brasileira requer altas quantidades de P e muitas pesquisas tem sido desenvolvidas para aumentar a produtividades das culturas e, conseequentemente, a eficiencia da produção de alimentos. Entretanto, este desenvolvimento tem sido alcançado a altos custos com uso de fertilizantes minerais (sobretudo P) e as perspectivas de longo prazo sobre os custos da intensificação da agricultura tropical estão atualmente em debate. Nesse contexto, no capítulo dois da presente tese avaliamos a evolução da área cultivada no Brasil e das demandas de P, quantificando o legado do P no Brasil e, baseado em cenários envolvendo a expansão da área cultivada e da produtividade, estimamos o futuro (até 2050) legado de P e as demandas por fertilizantes fosfatados. Ainda estimamos a potencial redução no consumo de fertilizantes fosfatados que pode ser alcançada pela utilização e melhorias na reciclagem do P oriundo de dejetos. Alternativamente, considerando a intensificação dos sistemas e seus efeitos na disponibilidade de P, propusemos cenários alternativos visando a utilização do \"Legacy P\" em sistemas agrícolas melhorados para garantir a expansão agrícola sem drásticos incrementos no consumo nacional de fertilizantes fosfatados. Um avanço internacionalmente reconhecido na agricultura Brasileira é o Cerrado, onde extensas áreas agrícolas são cultivadas duas vezes ao ano, incrementando assim a produção de alimentos e fibras sem qualquer custo aos ecossistemas naturais. Nesse contexto, a agricultura sob plantio direto (PD) tem sido amplamente difundida e, como consequencia, a fertilidade dos solos tem-se elevado, o que pode também favorecer a disponibilidade de P, quando são introduzidas rotações com espécies de plantas que apresentam mecanismos de mobilização do P, como o uso de plantas de cobertura. Entretanto, os efeitos desses sistemas melhorados de rotação na biodisponibilidade de P em solos tropicais no longo prazo permanecem incertos na literatura e foram objeto de estudo no capítulo três, onde está descrito um estudo envolvendo a avaliação das mudanças de longo-prazo nas frações de P em Latossolos, oriundos de dois experimentos de campo de longa duração no Cerrado, envolvendo a avaliação de sistemas de preparo (PD e preparo convencional, PC) e plantas de cobertura (milheto, braquiária milho e um controle, apenas pousio). O cultivo por longo tempo resultou em grandes quantididades de \"Legacy P\" acumulado no solo e, com o uso de braquiária como cultura de cobertura, maior quantidade de P foi reciclado para as camadas superiores do solo e as frações de P lábil e todas as frações organicas aumentaram. Baseado nos efeitos das plantas de cobertura, sugerimos que a biodisponibilidade do \"Legacy P\" pode ser representada pelo P extraído nas frações lábeis + o P de frações moderadamente lábeis. No capítulo quatro, utilizamos outras técincas atualmente difundidas para a especiação de P, aplicando-as em solos tropicais influenciados pela conversão do Cerrado nativo em agricultura sob PD e PC. Uma abordagem múltipla para identificação e quantificação de formas de P em solos tropicais foi proposta através da utilização do fracionamento de P proposto por Hedley em conjunto com a especiação de P por XANES da borda K do P para identificação de ligação do P a matrix inorgânica do solo, e espectroscopia de ressonância magnética nuclear (NMR) para complementação da identificação de espécies orgânicas de P em solos tropicais.

L’imagerie et la spectroscopie par résonance magnétique nucléaire (IRM et SRM) sont des méthodes non-invasives qui ont le potentiel d’estimer in vivo la quantité et la qualité des adiposités abdominales. Le contexte scientifique et clinique de ce manuscrit s’articule autour de l’étude de surnutrition « Poly-Nut » dont l’un des objectifs est d’analyser les évolutions des tissus adipeux (TA) dans une phase rapide de prise de poids. L’originalité et la complexité de cette thèse résident dans le développement, l’adaptation et la comparaison de plusieurs méthodes quantitatives d’IRM et de SRM, pour l’étude du signal lipidique dans un contexte clinique à 3T. La fiabilité et la validation des mesures obtenues in vivo par ces techniques font ici l’objet d’une étude approfondie. Pour l’analyse quantitative du signal de spectroscopie, différentes méthodes existantes ont été comparées à celle développée spécifiquement pour notre étude clinique. L’estimation paramétrique par moindres carrés non linéaires appliquée aux spectres RMN des lipides peut conduire, selon la fonction modèle utilisée, à un problème non linéaire mal posé. Nous montrons alors que l’utilisation d’un modèle simplifié se fondant sur la structure d’une chaine de triglycéride, comme utilisé récemment en imagerie quantitative, constitue une solution valide au regard de l’état de l’art. Ensuite différentes méthodes (IRM, SRM, Dual Energy X-ray absorptiometry, chromatographie en phase gazeuse) ont été utilisées pour caractériser les TA sous-cutanés et viscéraux. Le suivi par IRM du contenu lipidique du foie ainsi que du volume et de la composition en acide gras des TA à partir d’une unique acquisition en multi-écho de gradient est démontré. Enfin des développements expérimentaux menés parallèlement à l’étude clinique sur un imageur préclinique à 4,7T, comparent différentes stratégies d’encodage du déplacement chimique par imagerie et caractérisent des méthodes SRM pour estimer in vivo la proportion d’omégas-3 dans les chaînes d’acides gras. / Magnetic resonance imaging and spectroscopy (MRI and MRS) are non-invasive methods that have the potential to estimate in vivo the quantity and the quality of abdominal adipose tissues (AT). The scientific and clinical context of this thesis is based on an overfeeding study entitled "Poly-Nut". One of the main objectives of this study is to analyze changes in adipose tissues in a rapid phase of weight gain. The originality and complexity of this thesis rely in the development, adaptation and comparison of several quantitative methods of MRI and MRS, for the study of lipid signal, in a clinical context, at 3T. The reliability and the validation of the measurements obtained in vivo using these techniques are the main subject of this PhD thesis. For the quantitative analysis of the spectroscopy signal, different existing methods have been compared to those developed specifically for our clinical study. According to the model function used, the nonlinear-least-squares parametric estimation applied to the lipid spectra can lead to an ill-posed nonlinear problem. We demonstrated that the use of a simplified model based on the structure of a triglyceride chain, as recently used in quantitative imaging, was a valid solution regarding the state of the art. Then different methods (MRI, MRS, Dual Energy X-ray absorptiometry, gas chromatography) were used to characterize the subcutaneous and visceral AT. We demonstrated the feasibility of MRI to follow the lipid content in the liver as well as the volume and the fatty acid composition of AT using a single multiple gradient-echo acquisition. Finally, experimental developments were carried out in parallel with the clinical study, on a 4.7T preclinical system, first, to compare different strategies for encoding the chemical shift using imaging and, secondly, to characterize MRS methods for in vivo estimation of the relative proportion of omega-3 among all fatty acids.

Phosphorus (P) one of the essential elements to plants and animals, is a non-renewable resource and accuatlly high demanded in agriculture. The World\'s population growth and future estimatives on food demands raises the question about the sustainability of the current agriculture systems, speccially concerns about the low P use efficiency in agroecosystems. Brazilian agriculture requires high P inputs and many researches has been developed to increase the crops yield and, consequently, food production efficiency. However, this development was achieved at the high costs of mineral fertilisers (specially P) and long-term perspectives about the costs of the intensification in the tropical agriculture is accuattly in debate. In this conxtext, in the present thesis chapter two we evaluated the evolution of the Brazilian cropland basis and P demands, quantifying the Brazil P Legacy and, based on scenarios involving the cropland area and yield expansion, we estimated the future (up to 2050) Legacy P and P fertilisers demand. We also estimated the potential aleviation that could be achieved in the mineral fertilizers consumption by utilisation and improvements on manure P recycling. Alternatively, considering the systems intensification and its effects on P availability, we proposed alternative scenarios to promote the Legacy P utilisation in Brazil\'s improved agriculture systems to grant the agriculture expansion without huge increments on the national P fertilisers consumption. A worldwide recognized advance in Brazilian agriculture is the Cerrado, where large cropland areas accually are cultivated twice a year, improving the food and fiber production without any additional disturbance of natural ecossystems. In this context, no-tillage (NT) agriculture has been widely used and, as consequence, soil fertility has been improved, which could be also farorable to the P availability, when rotation with crop species with P mobilization mechanisms are introduced, such as cover crops utilisation. However, the effects of these improved rotated systems on P bioavailability in long-term in tropical soils remains uncert in the literature and was our objective in the chapter three, where is described a study envolving the evaluation of long-term changes on P fractions in tropical Oxisols, from two long-term field trials involving tillage systems (NT and conventional tillage, CT) and cover crops (millet, brachiaria, maize and control, fallow). The long-term cultivation generated large amounts of legacy P in the soil and with the brachiaria introduction as cover crop, more P was recycled in the topsoil and labile P and all the organic P fractions increased. Based on the cover crop effects, we proposed that the bioavailability of the legacy P could be represented by the P extracted by the labile fractions + moderately labile P fractions. In the chapter four, we used other techniques actually widely applied to P speciation, and we applied in tropical soils affected by the native Cerrado conversion into NT and CT agriculture. A multiple approach to identify and quantify the P forms in tropical soils were proposed by the utilisation of Hedley\'s fractionation togheter with P K-edge XANES for P-bindings into inorganic soil matrix and liquid 31P-NMR spectroscopy to complement the organic P species in tropical soils. / Fósforo (P), um dos elementos essenciais às plantas e animais, é um recurso não-renovável e altamente demandado na agricultura atualmente. O crescimento da população mundial e as estimativas futuras da demanda de alimentos aumentam os questionamentos sobre a sustentabilidade dos sistemas agrícolas atuais, especialmente no que se refere a baixa eficiência no uso do P na agricultura. A agricultura brasileira requer altas quantidades de P e muitas pesquisas tem sido desenvolvidas para aumentar a produtividades das culturas e, conseequentemente, a eficiencia da produção de alimentos. Entretanto, este desenvolvimento tem sido alcançado a altos custos com uso de fertilizantes minerais (sobretudo P) e as perspectivas de longo prazo sobre os custos da intensificação da agricultura tropical estão atualmente em debate. Nesse contexto, no capítulo dois da presente tese avaliamos a evolução da área cultivada no Brasil e das demandas de P, quantificando o legado do P no Brasil e, baseado em cenários envolvendo a expansão da área cultivada e da produtividade, estimamos o futuro (até 2050) legado de P e as demandas por fertilizantes fosfatados. Ainda estimamos a potencial redução no consumo de fertilizantes fosfatados que pode ser alcançada pela utilização e melhorias na reciclagem do P oriundo de dejetos. Alternativamente, considerando a intensificação dos sistemas e seus efeitos na disponibilidade de P, propusemos cenários alternativos visando a utilização do \"Legacy P\" em sistemas agrícolas melhorados para garantir a expansão agrícola sem drásticos incrementos no consumo nacional de fertilizantes fosfatados. Um avanço internacionalmente reconhecido na agricultura Brasileira é o Cerrado, onde extensas áreas agrícolas são cultivadas duas vezes ao ano, incrementando assim a produção de alimentos e fibras sem qualquer custo aos ecossistemas naturais. Nesse contexto, a agricultura sob plantio direto (PD) tem sido amplamente difundida e, como consequencia, a fertilidade dos solos tem-se elevado, o que pode também favorecer a disponibilidade de P, quando são introduzidas rotações com espécies de plantas que apresentam mecanismos de mobilização do P, como o uso de plantas de cobertura. Entretanto, os efeitos desses sistemas melhorados de rotação na biodisponibilidade de P em solos tropicais no longo prazo permanecem incertos na literatura e foram objeto de estudo no capítulo três, onde está descrito um estudo envolvendo a avaliação das mudanças de longo-prazo nas frações de P em Latossolos, oriundos de dois experimentos de campo de longa duração no Cerrado, envolvendo a avaliação de sistemas de preparo (PD e preparo convencional, PC) e plantas de cobertura (milheto, braquiária milho e um controle, apenas pousio). O cultivo por longo tempo resultou em grandes quantididades de \"Legacy P\" acumulado no solo e, com o uso de braquiária como cultura de cobertura, maior quantidade de P foi reciclado para as camadas superiores do solo e as frações de P lábil e todas as frações organicas aumentaram. Baseado nos efeitos das plantas de cobertura, sugerimos que a biodisponibilidade do \"Legacy P\" pode ser representada pelo P extraído nas frações lábeis + o P de frações moderadamente lábeis. No capítulo quatro, utilizamos outras técincas atualmente difundidas para a especiação de P, aplicando-as em solos tropicais influenciados pela conversão do Cerrado nativo em agricultura sob PD e PC. Uma abordagem múltipla para identificação e quantificação de formas de P em solos tropicais foi proposta através da utilização do fracionamento de P proposto por Hedley em conjunto com a especiação de P por XANES da borda K do P para identificação de ligação do P a matrix inorgânica do solo, e espectroscopia de ressonância magnética nuclear (NMR) para complementação da identificação de espécies orgânicas de P em solos tropicais.

Considérons un vecteur gaussien Y de loi N (m,sigma²Idn) et X une matrice de dimension n x p avec Y observé, m inconnu, Sigma et X connus. Dans le cadre du modèle linéaire, m est supposé être une combinaison linéaire des colonnes de X. En petite dimension, lorsque n ≥ p et que ker (X) = 0, il existe alors un unique paramètre Beta* tel que m = X Beta* ; on peut alors réécrire Y sous la forme Y = X Beta* + Epsilon. Dans le cadre du modèle linéaire gaussien en petite dimension, nous construisons une nouvelle procédure de tests multiples contrôlant le FWER pour tester les hypothèses nulles Beta*i = 0 pour i appartient à [[1,p]]. Cette procédure est appliquée en métabolomique au travers du programme ASICS qui est disponible en ligne. ASICS permet d'identifier et de quantifier les métabolites via l'analyse des spectres RMN. En grande dimension, lorsque n < p on a ker (X) ≠ 0, ainsi le paramètre Beta* décrit précédemment n'est pas unique. Dans le cas non bruité lorsque Sigma = 0, impliquant que Y = m, nous montrons que les solutions du système linéaire d'équations Y = X Beta avant un nombre de composantes non nulles minimales s'obtiennent via la minimisation de la "norme" lAlpha avec Alpha suffisamment petit. / Let Y be a Gaussian vector distributed according to N (m,sigma²Idn) and X a matrix of dimension n x p with Y observed, m unknown, sigma and X known. In the linear model, m is assumed to be a linear combination of the columns of X In small dimension, when n ≥ p and ker (X) = 0, there exists a unique parameter Beta* such that m = X Beta*; then we can rewrite Y = Beta* + Epsilon. In the small-dimensional linear Gaussian model framework, we construct a new multiple testing procedure controlling the FWER to test the null hypotheses Beta*i = 0 for i belongs to [[1,p]]. This procedure is applied in metabolomics through the freeware ASICS available online. ASICS allows to identify and to qualify metabolites via the analyse of RMN spectra. In high dimension, when n < p we have ker (X) ≠ 0 consequently the parameter Beta* described above is no longer unique. In the noiseless case when Sigma = 0, implying thus Y = m, we show that the solutions of the linear system of equation Y = X Beta having a minimal number of non-zero components are obtained via the lalpha with alpha small enough.

En raison de la diffusion incontrôlée sur le e-commerce, la sécurité et l’alternative légale aux stupéfiants habituels, les nouvelles substances psychoactives (NPS), d’apparition récente (2008), sont au cœur des phénomènes récents d’addiction et de décès mal expliqués. Au-delà des différents défis dans nos sociétés (prévention, législation), la capacité d’identifier les NPS dans des échantillons biologiques pour caractériser leur utilisation, présente de nombreux challenges analytiques. L’objectif principal de cette thèse a été de collecter des échantillons biologiques (sang, urine, cheveux) provenant de cas d’exposition à des NPS et d’y caractériser les substances présentes à l’aide de méthodes analytiques originales, dans le but d’enrichir les librairies de spectres de masse et d’améliorer, en conséquence, la détection de la consommation de NPS. En particulier, il s’agissait d’augmenter la fenêtre de détection de la prise de NPS en se focalisant sur les métabolites qui sont, le plus souvent, les produits majeurs d’élimination. Le développement analytique, par chromatographie liquide ultra haute performance couplée à la spectrométrie de masse en tandem (UHPLC-MS/MS), a demandé plusieurs mois d’optimisation afin d’obtenir une méthode robuste, exhaustive et sensible. Actuellement, la librairie de spectres MS comporte 114 NPS et est mise à jour régulièrement. A la suite de ce développement, ma thèse a porté sur l’étude de cas d’intoxication vus au service des urgences du CHU de Strasbourg, mais aussi en médecine légale, avec des situations de décès et d’identification de produits inconnus provenant de saisies (poudres et cristaux). Il a également été nécessaire de développer des outils analytiques complémentaires, tels que la caractérisation de métabolite(s) par étude sur microsomes hépatiques humains (HLMs), et l’utilisation de la spectroscopie par résonance magnétique nucléaire (RMN) afin d’identifier avec certitude certains composés et de déterminer leur degré de pureté. Les outils analytiques développés et la stratégie mise en place ont permis la rédaction de 18 publications, ainsi que l’agencement de nombreuses collaborations. / Due to the uncontrolled spread on the Internet and their legal alternative to usual drugs, the new psychoactive substances (NPS), recently appeared (2008), are at the center of recent phenomena of addiction and badly explained deaths. Beyond different challenges in our societies (prevention, legislation), the ability to identify NPS in biological samples, in order to characterize their use, presents many analytical challenges. The main objective of this thesis was to collect biological samples (blood, urine, hair) from cases of exposure to NPS and to characterize the substances present using original analytical methods, in order to enlarge the libraries of mass spectra and improve, as a result, the detection of NPS consumption. In particular, it was intended to increase the detection sensitivity of NPS intake by focusing on the metabolites that are often the major products of elimination. This analytical development, by ultra-high liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS), required several months of optimization in order to obtain a robust, exhaustive and sensitive method. At present, the mass spectra database has 114 NPS and is regularly updated. Thereafter, ma thesis focused on the study of cases of intoxication observed in the emergency department of Strasbourg, but also in legal medicine with situations of deaths and identification of unknown products collected from seizures (powders and crystals). It has also been necessary to implement complementary analytical tools, such as the characterization of metabolites by human liver microsomes (HLMs), and the use of nuclear magnetic resonance (NMR) spectroscopy to accurately identify the compounds and establish their purity degrees. The analytical tools developed, and the strategy adopted, allowed the writing of 18 publications, as well as the setting up of numerous collaborations.

Nous avons réalisé des couches minces de Co sur un substrat semi-conducteur (Si(111)) par voix électrochimique, en mode potentiostatique et en mode galvanostatique, et étudié leurs propriétés topographiques (AFM, MEB) et magnétique (RMN, effet Kerr, SQUID), afin de relier ces propriétés aux modes de croissance et aux conditions de dépôt à priori identiques conduisent à des morphologies et donc des propriétés magnétiques très différentes. Nous avons développé une approche rigoureuse avec un contrôle systématique de la qualité du substrat de départ pour clarifier les modes de nucléation et de croissance en fonction du potentiel appliqué en chronoampérométrie. Une transition d’un mode de nucléation instantanée vers un mode de nucléation progressive en fonction du potentiel appliqué est mise en évidence. La modélisation à l’aide du modèle de Scharifker-Hills des modes de nucléation et de croissance est cohérente avec les images de topographie AFM. La croissance est tridimensionnelle du type Volmer-Weber et l’aimantation est orientée dans le plan. Par RMN et également X-Ray Photoemission Spectroscopy (XPS), nous montrons qu’une couche d’hydroxyde de cobalt magnétiquement morte se forme à l’interface avec le Si. En mode galvanostatique, des grains avec des facettes parfaitement cristallisés présentent des domaines magnétiques localisés dans la plupart des ilots. Nous avons également effectué une étude très critique des techniques de dépôt/arrachage employées dans la littérature montrant que celle-ci sont inadaptées aux substrats semi-conducteur, un dépôt subsistant sur la surface quel que soit la technique d’arrachage choisie. / We have deposited thin layers of Co on a semiconductor substrate Si(111), by electrochemical method, in potentiostatic and galvanostatic mode, and we have studied their topographic properties (AFM, MEB) and magnetic (RMN, effet Kerr, SQUID). Thanks to these different techniques, we could relate these properties to the growth modes and to the a priori identical deposition conditions, which lead to different morphologies and therefore different magnetic properties. We have developed a rigorous approach with a systematic control of the quality of the substrate in order to clarify the nucleation and growth modes as a function of the potential applied in chronoamperometry. A transition from an instantaneous nucleation mode to a progressive nucleation mode as a function of the applied potential is highlighted. Modeling with Scharifker-Hills model of nucleation and growth modes is consistent with AFM topography images. The growth is three-dimensional of a Volmer-Weber type and the magnetization is oriented in the plane. By NMR and also X-Ray Photoemission Spectroscopy (XPS), we could show that a layer of magnetically dead cobalt hydroxide layer forms at the interface with Si. In galvanostatic mode, grains with perfectly crystallized facets have magnetic domains located in most of the islands. We have also carried out a very critical study of the deposition / tearing techniques used in the literature showing that they are unsuitable for semiconductor substrates, a deposit remaining on the surface whatever the tearing technique chosen.

La métabolomique par résonance magnétique nucléaire (RMN) permet d’étudier laréponse métabolique globale d’un système biologique à un stimulus ou un événementphysiopathologique (maladie, manipulation génétique, etc.). Cette discipline connaît un essorimportant dans la recherche clinique et biologique, et constitue ainsi un outil à fort potentielpour la découverte de biomarqueurs de maladies, et l’étude de la fonction des gènes.Cette thèse est dédiée à l’application de la métabolomique par RMN à hauts champspour l’étude des pathologies associées à la signalisation thyroïdienne chez la souris. L’objectifglobal est d’identifier des biomarqueurs spécifiques liés aux différentes maladies hormonales :l’hypothyroïdie et la maladie génétique émergente résistance à l’hormone thyroïdienne due àune mutation au niveau du récepteur TRα1 (RTHα). Cette dernière est particulièrementdifficile à diagnostiquer à cause du manque de marqueurs biochimiques et de symptômesspécifiques à cette maladie. De plus, elle présente des similitudes avec l’hypothyroïdie auniveau symptomatique. Des modèles murins de RTHα et de l’hypothyroïdie ont été analysés,et l’investigation a été menée sur l’urine et le plasma sanguin dans le but de différenciermétaboliquement ces maladies et d’identifier des biomarqueurs spécifiques à RTHα. Dessignatures métaboliques liées à chaque maladie ont été identifiées dans l’urine et le plasmasanguin. Cinq métabolites qui varient de façon significative ont été identifiés dans l’urinecomme étant liés à la maladie RTHα : trimethylamine, dimethylamine, isovalerylglycine, Nacetylglucosamineet la choline. Dans le sang, ce sont les lipides insaturés qui varient de façonsignificative chez les souris mimant la maladie RTHα. / Metabolomics by nuclear magnetic resonance (NMR) allows studying the metabolicresponse of a global biological system to a stimuli or a physiopathological even (diseases,genetic modifications, etc.). This discipline is growing especially in the clinical and biologicalfields, and represents a strong potential tool to identify biomarkers related to diseases, andstudy the function of genes.This thesis is dedicated to the application of metabolomics by high field NMR to studythyroid signalisation pathologies in mice. The main goal is to identify biomarkers related tothe emerging genetic disease called resistance to thyroid hormone due to a mutation in thyroidhormone receptor TRα1 (RTHα). This disease is particularly difficult to diagnose because ofthe lack of biochemical markers and specific symptoms. In addition, it presents commonfeatures with hypothyroidism in term of symptoms. Mice models of RTHα andhypothyroidism were analysed, and the investigation were driven on urine and blood plasmain order to differentiate metabolically theses diseases and identify biomarkers related toRTHα. Metabolic fingerprints related to each disease were identified in both urine and bloodplasma. Five metabolites vary significantly in the urine of RTHα mice: trimethylamine,dimethylamine, isovalerylglycine, N-acetylglucosamine and choline. Unsaturated lipids varysignificantly in the blood plasma of RTHα mice.The impact of thyroid hormones (TH) and the thyroid hormone receptor TRβ on theliver metabolism were also studied in the present manuscript through NMR-basedmetabolomics. A mouse model, with a specific knock-out of TRβ gene in hepatocytes (LTRβ-KO), were used to study this question. To understand the function of TH mediated by TRβ,the liver metabolic response to TH, obtained from liver aqueous extracts and intact livertissues, TRβKO and wild-type mice were compared. The results suggest the presence ofdirect and indirect effects of thyroid hormones on the liver metabolism.

Conducting and semiconducting polymers, consisting of delocalized π-electrons, have been studied for the past three decades. These materials have shown novel physical properties with interesting applications in batteries, detectors, light emitting diodes, field effect transistors, solar cells, biosensors etc. Nevertheless the charge transport properties are yet to be understood in detail due to the complexity of the system, especially due to the interplay of quasi-one dimensionality (q-1D), disorder, localization and electron-electron interactions(EEI). A combined investigation of both conductivity and spin lattice relaxation time, especially at very low temperatures and high magnetic fields, is really lacking in conducting polymers. In this thesis a set of experiments – dc conductivity, magnetoresistance (MR), Nuclear Magnetic Resonance (NMR) spin lattice relaxation time (T1) measurements, magnetic susceptibility amd ac conductivity have been carried out in conducting polymers. NMR being a local probe it is possible to get the nanoscopic scale charge transport mechanism. Further, this helps to develop a consistent understanding among a wide range of the physical properties in conducting polymers. In this thesis author has reported the results of experiments at ultra low temperature (mk) and ultra high magnetic field which give more insight about the roles of electron-electron interaction(EEI) and disorderin charge transport properties. This thesis describes a detailed study of charge transport and NMR relaxation in three representative conducting polymers namely polypyrrole(PPy)., poly-3-methylthiophene(P3MT) and poly3-hexylthiophene(P3HT). The emphasis is to understand the charge transport phenomena and NMR relaxation, especially at ultra low temperatures (down to 20 mk) and high magnetic field (up to 23.4 T). The NMR T1 relaxation mechanisms are discussed in terms of (i) Korringa relaxation, (ii) relaxation due to spin diffusion to paramagnetic centers (SDPC) amd (iii) reorientation of symmetric groups, depending upon the temperature range.