A probe for measuring the specific heat of superconductors at low temperatures and in high magnetic fields has been built and commissioned. The probe has been tested using the relaxation method on samples of copper and the accuracy of the data is 1.3 % between 5 K and 30 K, data taken using the long range pulse method has a resolution of 10 mK. Specific heat measurements have been performed on members of the series (Pb(_1)-(_x))Cu(_1.8x)Mo(_6)S(_8), (Sn(_1-x))Eu(_x)Mo(_6)S(_8) and (Pb(_1-x)M(_x))Mo(_6)S(_8) where M = Gd and Eu, from 3 K up to 30 K and in magnetic fields up to 15 T. Additional results from resistivity, susceptibility, magnetisation. X-ray diffraction, transmission electron microscopy and electron dispersive-ray measurements are also presented. These data have been compared to results from other authors and are analysed in terms of the BCS and GLAG theories of superconductivity and the magnetic properties of these materials. The mean field model has been used to calculate numerically the magnetic contribution to the specific heat (cm) of both ferromagnetic and antiferromagnetic systems as a function of temperature and applied field both above and below the ordering temperature. In addition an approximate analytic form for the magnetisation has been used to calculate Cm above the ordering temperature. Expressions have been derived for the saturation value of the peak in C(_m): C(^sat)(_m) = 1.1245n(_cell)RJI(J+1) and the temperature dependence of the peak with applied field ȡ(μ(_o)H(_ext))/ȡT(_peak)=6.540/g(_J)(J+1). They allow the simple calculation of the values of J and g(_J)(J + 1) from specific heat data. The magnetic contribution to the specific heat of the samples (Sn(_0.65)Eu(0.35)Mo(_6)S(_8)) and (Sn(0.50)Eu(_0.50)Mo(_6)S(_8)) have been modelled using these calculations and excellent agreement is found by considering the magnetic ions as free ions. The sample is accurately modelled by including an additional minority phase (Gd(_2)S(_3)). The approximate expressions have also been used to analyse data on high temperature superconductors producing values of J and g(_J)}{J + 1) consistent with a doublet ground state. The properties of Chevrel phase materials have been determined as a function of doping level. The critical temperature is degraded by doping but an increase in the critical current density is observed in the series (Pb(_1-x)Cu(_1-8x)Mo(_6)S(_8) for very low levels of doping. Increases of up to 28 % in the upper critical field, that are probably due to the compensation effect and an increase in the normal state resistivity, are also observed in the series (Sn(_1-x)Eu(_x)Mo(_6)S(_8)) at high levels of doping and in the series (Pb(_1-x)Gd(_x)Mo(_6)s(_8) for low levels of doping.

The recent availability of X-ray Free Electron Lasers (XFELs) has opened a completely new and unexplored regime for the study of light-matter interactions. The extremely bright intensities delivered by XFELs can couple many photons into the target, turning well known interactions such as photoionization and scattering into new, non-linear, complex many-body phenomena. This thesis reports theoretical investigations aiming to improve the understanding of the fundamental processes and dynamics triggered by intense X-ray pulses, with a special focus in finite systems such as molecules and clusters. Sequential multiple photoionization in atomic clusters was investigated, where previous observations were extended for higher charge states where direct photoionization is frustrated. Through a rate equation study and subsequent molecular dynamics simulations, it was found that frustrated ionization is partially responsible for the low-energy peak observed in the electron energy spectrum. The influence of plasma evaporation over the formation of the sequential low-energy peak was also investigated, identifying the effects of the system size and photon energy. Multiple channel ionization was also investigated for the case of fullerenes. This is done through a series of studies, starting from a simplified rate equation scheme, and culminating with full molecular dynamics simulations. From these results, a good insight was obtained over the origin, physical meaning, and relevant parameters that give rise to the complicated features observed in the electronic spectra. The mechanisms responsible of all these features are expected to be present in other systems, making these results quite general. Diffractive imaging of biomolecules was studied in a final step, with a particular focus on the influence of intramolecular charge transfer mechanisms. To this end a conformer of T4 Lysozyme was used, a representative enzyme with well known structure. Charge migration is found to allow for additional processes such as proton ejection, a mechanism which enables an efficient release of energy from the system. This mechanism considerably suppresses structural damage for heavy ions, improving the quality of the measured diffraction patterns.

No description available.

Le travail de recherche mené au cours de cette thèse a été effectué dans le cadre d’une collaboration industrielle et a porté sur l’étude des caractéristiques physico-chimiques d’une matrice lipidique à libération prolongée. L’originalité de cette dernière tient à sa forme galénique, des microsphères calibrées d’environ 400 µm de diamètre, fabriquées par procédé de prilling puis conditionnées en sachets.Les caractérisations entreprises au cours de cette thèse ont été menées progressivement en partant de l’étude du comportement thermique individuel des constituants (excipients lipidiques et principe actif), puis de leurs mélanges pour définir les conditions d’existence et les caractéristiques structurales des phases solides qu’ils engendrent, notamment lors du prilling. Plusieurs diagrammes d’état partiels ont été construits pour permettre de cerner l’organisation de la matrice formant le produit fini et disposer de leviers fiables pour corriger d’éventuelles déviations du procédé de fabrication. Cette analyse était également indispensable pour décrire précisément le processus de libération du principe actif et en déterminer les paramètres cinétiques. / The research conducted in this thesis, during an industrial collaboration, is focused on the study of physicochemical characteristics of a sustained release lipid matrix. The originality of this matrix is its dosage form, microspheres of 400 microns in diameter, manufactured by a prilling process and packaged in stick-packs.The characterizations conducted during this thesis have been carried out gradually starting from the study of the thermal behavior of individual components (lipidic excipients and drug) and their mixtures to define the phase formation conditions and the structural characteristics of the solid phases generated, especially during the prilling process. Partial phase diagrams were constructed to understand the final product matrix organization and to identify actions to correct any deviations in the process. This analysis was also needed to accurately describe the drug release mechanism and to determine the kinetic parameters.

O câncer de mama é o tipo de câncer mais frequente entre as mulheres, sendo a mamografia a técnica mais utilizada para sua detecção. No entanto, essa técnica possui algumas limitações, como o baixo contraste, o qual pode ser associado, dentre outros fatores, a radiação espalhada. Apesar desse fato, novas técnicas baseadas na detecção do espalhamento vêm sendo empregadas em um vasto campo de aplicação, como na caracterização de materiais e tecidos biológicos. Há na literatura diversos estudos sobre perfil de espalhamento para a caracterização de tecidos mamários, porém ainda são poucos os estudos sobre imagem por espalhamento de mama e de otimização de contraste. Além disso, essas imagens são realizadas apenas em pequenas amostras de mama. Uma das possibilidades para o estudo de mamas de dimensões reais é a aplicação do método Monte Carlo (MC). Neste trabalho, foi estudado e otimizado um sistema de difração de raios X dispersivo em energia (SDRXDE) para medidas de perfis de espalhamento e um sistema para formação de imagens por espalhamento utilizando estas informações. O SDRXDE foi caracterizado experimentalmente, analiticamente e por simulação Monte Carlo, enquanto que o segundo sistema foi caracterizado analiticamente e por simulação Monte Carlo. Os resultados obtidos mostraram que as principais correções para o SDRXDE foram auto-atenuação, o espectro incidente, eficiência de detecção e múltiplo espalhamento. Outro fator importante que afeta o perfil de espalhamento resultante é a resolução de momento do sistema, o qual depende dos parâmetros geométricos (abertura dos colimadores, distâncias, ângulo de espalhamento e espessura da amostra) e da resolução de energia do detector. Os resultados para o sistema de imagem mostram claramente a capacidade dessas imagens na detecção de um nódulo no interior da mama. A respeito da otimização das condições de irradiação da mama e detecção da radiação espalhada, os resultados alcançados demostram a viabilidade experimental da geração destas imagens num ambiente clínico. / Breast cancer is the most frequent type of cancer among women, being mammography the technique more used for its detection. However, this technique presents some limitations, such as low contrast, which may be associated with scattered radiation. Thus, new scatterinng detection techniques have been employed in different fields such as characterization of biological materials and tissues, such as characterization of scattering profile for breast tissue, although there are still few studies on breast image and contrast optimization. Moreover, the images are originated from small breast samples. In this context, one of the possibilities for the study of actual breast dimensions is the application of the Monte Carlo method. Thus, this work studied optimized an energy X ray diffraction system (EDXRD) for measures of scattering profile and developed a system for imaging using this information. The EDXRD system was studied and optimized by experimentally, analytically and Monte Carlo simulation, while the image system was studied analytically and simulated by Monte Carlo. The results showed that the main corrections for the EDXRD system are self-attenuation, incident spectrum, detection eficiency and multiple scattering. Another important factor that affects scattering profile is the system momentum resolution, which depends on geometric parameters (collimator aperture, distances, scattering angle and sample thickness) and detector energy resolution. The results for the imaging system showed that a nodule could be detected within the breast. Finaly the optimizations of breast radiation conditions and radiation detection showed the viability of generating experimental scattering images in clinical environment.

Le traitement thermochimique de carbonitruration suivi d’une trempe est couramment utilisé pour améliorer la résistance à l’usure et à la fatigue de pièces mécaniques. Mais les origines de ce gain de propriétés mécaniques ne sont pas bien connues. La thèse a pour objectif de caractériser et modéliser, pour un acier faiblement allié 23MnCrMo5, l’influence de la concentration en carbone et en azote de l’austénite sur les cinétiques de transformations de phases au refroidissement, les microstructures résultantes et les duretés. Dans un premier temps, la démarche expérimentale repose sur l’élaboration d’éprouvettes enrichies de manière homogène par voie thermochimique en carbone, azote et carbone+azote, grâce à un nouveau procédé. Ensuite, les cinétiques de transformation et les évolutions microstructurales sont étudiées par dilatométrie, par diffraction des rayons-X haute énergie in situ (rayonnement synchrotron) et par MET. L’introduction d’azote induit une forte accélération des cinétiques de transformation et des microstructures plus fines notamment dans le domaine haute température (500_C - 700_C), que nous attribuons à la germination de la ferrite sur des nitrures CrN qui précipitent dans l’austénite pendant l’enrichissement. Les duretés sont par ailleurs beaucoup plus élevées que dans des échantillons enrichis en carbone. La DRX in situ a aussi permis d’identifier l’évolution des différentes phases (austénite, ferrite, cémentite, CrN) et leur chronologie pendant la transformation bainitique. Enfin, un modèle de prédiction des cinétiques de transformations de phases est construit pour simuler les profils de microstructures et de duretés dans des couches enrichies en carbone et/ou azote, conduisant à un relativement bon accord entre simulation et expérience / Carbonitriding thermochemical treatments followed by quench are commonly employed to improve wear and fatigue resistance of mechanical parts. However, the origin of this gain of mechanical properties is not well known. The objective of this PhD thesis is to characterize and to model, for a low-alloyed 23MnCrMo5 steel, the influence of austenite carbon and nitrogen concentrations on phase transformations kinetics during cooling. As a first step, the experimental procedure is based on the elaboration of specimens homogeneously enriched in carbon, nitrogen or carbon+nitrogen, thanks to a specifically designed process. Then, phase transformation kinetics and microstructural evolutions are studied by dilatometry, by high-energy synchrotron X-ray diffraction and by TEM. The introduction of nitrogen induces a strong acceleration of the phase transformation kinetics and much finer microstructures, in particular in high temperature range (500_C - 700_C). We attribute these effects to the nucleation of ferrite on CrN nitrides, which precipitated in austenite during the enrichment. In addition, the hardnesses are much higher than in specimens enriched in carbon. In situ XRD also allowed identifying the evolutions of the different phases (austenite, ferrite, cementite, CrN) and their chronology during the bainitic transformation. Finally, a model to predict the phase transformation kinetics is developed inorder to simulate the microstructure and hardness profiles inside layers enriched in carbon and/or nitrogen, leading to satisfactory agreement between simulation and experiments

Cette thèse concerne le développement de complexes de lanthanide et leur utilisation pour résoudre les structures de macromolécules biologiques par diffraction des rayons X, en particulier celles de protéines membranaires et de complexes protéiques de grande taille. Les complexes de lanthanide sont formés d’un atome de lanthanide et d’un ligand chimique qui assure une liaison non-covalente avec les surfaces protéiques. Introduits dans les cristaux de protéine, ces derniers constituent une sous-structure qui, déterminée par les méthodes de phasage de novo courantes, permet de résoudre la structure de la macromolécule d’intérêt. La première partie de ce travail de thèse est une étude menée sur la grande famille des complexes picolinates de lanthanide, complexes luminescents dont la fixation au sein des cristaux est aisément décelable. En premier lieu, nous avons défini les conditions dans lesquelles le complexe tris-dipicolinate de lanthanide peut être utilisé ainsi que ses éventuelles capacités à promouvoir la cristallisation (effet supramoléculaire). En second lieu, un nouveau complexe, dérivé du précédent, a été développé au cours de cette thèse : le tris-hydroxymethyltriazoledipicolinate de lanthanide (« [Ln(TDPA)3]3- »). Il nous a permis de réaliser un phasage de novo très précis conduisant à la détermination des structures du lysozyme de blanc d’œuf de poule et de la thaumatine de Thaumatococcus daniellii à haute résolution. Par ailleurs, différents ligands pour ce nouveau complexe ont été synthétisés par chimie-click, nous permettant de créer une panoplie de complexes uniques et des complexes hybrides. Nous avons montré que cette nouvelle famille de complexes présente une meilleure affinité pour les protéines permettant leur utilisation à de faibles concentrations. Les essais menés avec ces LnTDPA ont aussi permis d’entrevoir l’importance de la charge globale pour expliquer l’effet supramoléculaire. En troisième lieu, un tripicolinate cagé, le LnTNTPA, a également été évalué. Constitué d’une cage chimique de charge globale nulle, nous avons montré que ce nouveau complexe luminescent est le seul de cette famille picolinate qui puisse être utilisé en présence d’ions divalents. Dans la seconde partie de cette thèse, nous décrivons l’utilisation des complexes de lanthanide pour le phasage de protéines multimériques de grandes tailles par les méthodes de phasage de novo. Premièrement, la structure de l’aminopeptidase dodécamérique PhTET1-12s de 480 kDa a été déterminée à 4 Å de résolution à l’aide du tris-dipicolinate d’europium. Ceci nous a permis de démontrer que les complexes de lanthanide peuvent être utilisés pour obtenir un phasage précis, même à basse résolution. Deuxièmement, les complexes de lanthanide issus de l'imagerie médicale ont aussi permis de déterminer la structure de trois nouvelles enzymes homotétramériques de la famille des malate déshydrogénases. Ces structures permettent d’apporter de nouveaux éclaircissements sur l'adaptation halophile. Enfin, en utilisant ces enzymes en tant que bibliothèque de fonctions chimiques, nous avons pu mettre en place une nouvelle approche méthodologique pour comprendre finement les modes d'interaction des complexes de lanthanide. / This thesis aims to develop lanthanide complexes for solving biological macromolecular structures, especially membrane proteins and large protein complexes. Lanthanide complexes are composed of a lanthanide atom and a chemical ligand, which provides non-covalent binding to protein surfaces. Incorporated in protein crystals, they make up the substructure, determined by the widely-used de novo phasing methods, needed for solving the whole protein structure. The first part of the present work shows a study of the luminescent lanthanide picolinate complexes family, easily detectable in protein crystals. First, we defined the conditions in which the known lanthanide tris-dipicolinate can be used and we examined its possible ability to promote protein crystallization (supramolecular effect). Secondly, a newly developed lanthanide tris hydroxymethyltriazoledipicolinate complex "[Ln(TDPA)3]3-", derived from this previous complex, allowed us to obtain a very precise de novo phasing for solving the high-resolution structure of the hen egg white lysozyme and the thaumatin from Thaumatococcus daniellii. Besides, various ligands for these new complexes were synthetized by click chemistry, enabling us to create both unique complexes outfit and hybrid complexes. We have shown that this new complexes family presents a better affinity for proteins allowing their use at very low concentrations. Tests conducted with those LnTDPA have also evidenced the importance of complex global charge to explain the supramolecular effect. Third, a caged tripicolinate, the LnTNTPA, was evaluated. Characterized by a neutrally charged chemical cage, we have shown that this new luminescent complex is the only one of the picolinate complexes family that can be used in the presence of divalent ions. In the second part of this thesis, we describe the use of lanthanide complexes for phasing large multimeric proteins by de novo phasing methods. First, the structure of the 480 kDa dodecameric aminopeptidase PhTET1-12s was solved at 4 Å resolution by using the europium tris-dipicolinate which demonstrates that the lanthanide complexes can be used to obtain an accurate phasing, even at low resolution. Secondly, the lanthanide complexes from medical imaging also helped to solve the structures of three new homotetrameric enzymes from the malate dehydrogenases family. Those structures provide new insights into halophilic adaptation. Finally, by using these enzymes as a library of chemical functions, we developed a new methodological approach for a better understanding of the precise binding modes of those lanthanide complexes.

Estruturas da glândula pineal humana foram estudadas empregando os métodos de microscopia de luz, microscopia eletrônica de varredura, microscopia de varredura por espectrometria de raio-x e difração de raio-x. As peças para microscopia de luz foram fixadas em solução de formalina a 10% durante 48h e incluídas em parafina. Para a microscopia eletrônica de varredura, as peças foram fixadas em solução de Karnovsky modificada, sendo que parte das peças foram fraturadas em nitrogênio líquido para o exame das características internas do corpo píneal. Os resultados evidenciaram que o corpo píneal apresenta formações calcáreas distribuídas no interior do tecido conjuntivo. As formações calcáreas possuem tamanhos e formas diferentes. As estruturas calcáreas apresentam uma cápsula constituída pelo tecido conjuntivo. Na porção interna, a estrutura calcárea é constituída por uma série de !ameias concêntricas, com porosidade de aspecto amorfo. Evidenciou-se pela análise de difração de raio-x, a estrutura cristalina formada pelos átomos de vários elementos que compõem a formação calc área . / The structure of human pineal gland was studied by optic microscopy, scanning eletromicroscopy, spectrometer x-ray scanning eletron microscopy with energy dispersion (EDS). The tissues to analysis by optic microscopy were fixed in formalin at 1O % during 48 h and put in parffin. For S.E.M., the tissues were fixed in modified Kamovsky solution, and a part of the material was fracturated in liquid nitrogen to analysis of internal characteristic of the pineal body. The results showed that the pineal body has calcareon concretion distributed in the connective tissue. In the internai position, the calcareon structure was made of concentrics lamelae with amorf aspect. The x-ray difractor showed the cristalin structure of the atom arrangement of the elements that compose the calcarean concretions.

O objetivo deste trabalho é analisar a distribuição das tensões residuais que resultam da combinação das variações volumétricas resultantes dos gradientes térmicos e das transformações de fase que ocorrem durante a têmpera de cilindros de aço AISI/SAE 1045, 4140 e 4340. O modelo matemático usado para este objetivo utiliza o programa AC3 de modelagem de tratamentos térmicos (curvas de transformação, curvas de resfriamento, microestrutura e a dureza do material), para alimentar um modelo de elementos finitos, considerando acoplamento termo-mecânico e comportamento não linear elasto-plástico, para previsão de tensões residuais em cilindros de aço AISI/SAE 1045, 4140 e 4340 temperados em água. São apresentados, também, os resultados de observações metalográficas e perfis de dureza que confirmam qualitativamente as previsões do programa AC3. A verificação do modelo numérico por elementos finitos foi efetuada através da medição das tensões residuais nos cilindros de aço com o emprego da técnica de difração de raios X. A simulação numérica, através do método dos elementos finitos comprova, nos três casos estudados, a existência de tensões residuais de compressão na região superficial após o processo de têmpera e indica de maneira quantitativa e qualitativa que as tensões mais significativas são as tangenciais. Os resultados obtidos a partir do modelo numérico mostraram uma aderência significativa em comparação com os resultados experimentais. / The aim of this work is to analyze the distribution of residual stresses resulting from combination of volumetric changes due to heat gradients and phase changes occurring during the quenching process of AISI/SAE 1045, 4140 and 4340 steel cylinders. The mathematical model used for this objective uses the AC3 program for modeling thermal treatments (transformation curves, cooling curves, microstructure and material hardness), whose results were fed into a finite element model, considering thermal-mechanical coupling and non-linear elastic-plastic behavior for forecasting of residual stresses in AISI/SAE 1045, 4140 and 4340 steel cylinders quenched in water. The observed microstructures and measured hardness confirmed qualitatively the previsions of the AC3 program. The results of finite element modeling were compared to experimental measurements of residual stresses measured at the surface, using X-Ray diffraction techniques. The finite element numerical simulation shows, for the three studied cases, the presence of compressive residual stresses in the surface region after a quenching process and indicates qualitatively and quantitatively that the most significant stresses are the tangential ones. The results obtained from the numerical model showed a significant adherence in comparison with the experimental results.

As propriedades das ligações do complexo com metal de transição Cu(II)-L-alanil-L-valina e do composto orgânico Taurina foram determinadas por difração de raios-X a alta resolução. A análise da densidade de carga foi feita com o modelo multipolar de Hansen-Coppens para o estudo topológico da densidade de carga e determinação de populações dos orbitais d do metal. Radiação síncrotron (0.394 Å) e temperatura de hélio vaporizado foram utilizados na coleta de dados de difração de raios-X do complexo metálico. Para o orbital dx2-y2, a população reduzida é descrita pelas zonas de fuga de carga com eixo de simetria 4 nos mapas de deformação estática da densidade e do Laplaciano. Os valores da densidade de carga e das curvaturas nos pontos críticos localizados nas ligações Cu-N e Cu-O, indicam o caráter não iônico dessas ligações. Foi desenvolvido um algoritmo para obter as orientações preferenciais dos orbitais d de metais de transição da primeira linha coordenados em sítios assimétricos. As cargas atômicas foram determinadas por integração da densidade no esquema de partição de átomos topológicos (basins). O estudo de densidade de carga da Taurina foi realizado com dados coletados no difratômetro KappaCCD, usando radiação K\'alfa\' -Mo à temperatura de N2 vaporizado e dados de nêutrons obtidas na literatura. Propriedades topológicas de \'rô\' (\'VET.r\') foram calculadas do modelo. Os valores dos monopólos são comparados com cargas calculadas pela integração de \'rô\' (\'VET.r\') dentro de basins e determinadas por cálculos ab initio. / The bonding properties of the transition metal complex Cu(I1)-L-alanyl-L-valine and the Taurine compound have been determined by high resolution x-ray diffraction. The charge density analysis is performed using the Hansen-Coppens multipole model for both, the topological study of the electron density p(f) and the orbital population\'s analysis of the transition metal. Short wavelength synchrotron radiation (0.394 \'angstrom\') and vaporized helium temperature were used in the x-ray diffraction data collection of the metal complex. For the dx2-y2 orbital, the half population obtained is shown by the 4-fold depletion region in the static deformation and negative Laplacian maps. Values of the charge density and its curvature in the critica1 points located at the Cu-N and Cu-O bonds show the non-ionic character of these interactions. We have derived an algorithm to perform preferencial orientation search for the first row transition metal d-orbitals in non-symmetric sites. Atomic charge integration was carried out applying topological atoms partitioning (basins). The charge density of Taurine has been studied with data collected with a KappaCCD diffractometer using K\'alfa\'-Mo radiation at vaporized N2 temperature and neutron diffraction data obtained from the literature. Topological properties of \'rô\' (\'VET.r\') were calculated from the fitted model. Atomic charges given by the monopole parameters have been compared with those obtained by integration of the atomic basins and theoretical molecular calculations.