La myopathie à agrégats tubulaire (MTA) est une maladie rare caractérisée par la présence, dans la biopsie musculaire, d’« agrégats tubulaires ». Nous avons retrouvé 15 cas de MTA parmi 13987 biopsies musculaires réalisées dans les 35 dernières années dans notre service. Parmi ces cas, se trouvait une famille de trois patients qui ne pouvaient être inclus dans aucun groupe clinique connu de myopathie à agrégats tubulaires, car ils étaient asymptomatiques avec une hyperCKémie isolée et un test de contracture positif.Nos travaux ont mis en évidence des mutations hétérozygotes du gène STIM1. Ces mutations localisées dans la partie du gène qui code le domaine intraluminal EF-hand, entrainent une activation constitutive de STIM1 avec exacerbation du mécanisme SOCE et en conséquence l’augmentation de l’influx de Ca2+, démontré dans des myoblastes transfectés. Nous avons également mis en évidence la mutation p.Arg304Trp du gène STIM1, comme cause du syndrome de Stormorken. Cela augmente le spectre phénotypique des mutations de ce gène.Nos résultats de l’analyse protéomique montrent que la protéostase dans la MTA est dérégulée, car le profil du protéome est différent chez les patients et dans les agrégats tubulaires microdisséqués par laser, en comparaison a des contrôles. Les protéines enrichies s’avèrent appartenir à des voies biologiques impliquées dans l’homéostase ionique, les systèmes de membranes de la triade et de l’exosome et dans le métabolisme mitochondrial.Nos travaux ouvrent des perspectives pour mieux comprendre la physiopathologie de la myopathie à agrégats tubulaires et ainsi pouvoir proposer des solutions thérapeutiques efficaces. / Myopathy with tubular aggregates (MTA) is a rare disease characterized by the presence of tubular aggregates in muscle biopsy. We found 15 cases of MAT in our registry including 13987 muscle biopsies performed over 35 years. Among them, there was a family of three patients that did not fit any of the previously described clinical groups of MTA, since they were asymptomatic with isolated hyperCKemia and positive contracture test. Our works revealed heterozygous mutations in the gene STIM1. These mutations localized in the gene portion that codes for the intraluminal EF-hand domain, leads to a constitutive activation of STIM1 with SOCE mecanism enhancement and consequent increase of the Ca2+ entry which was demonstrated using transfected myoblasts. We also revealed the mutation p.Arg304Trp in the coding sequencing of the CC1 domain of STIM1, as the cause of Stormorken syndrome. This fact increases the phenotypical spectra of the mutations for this gene.The results of our proteomic analysis show that the proteostasis in MTA is disturbed, because the proteome profile is different in total muscle of the patients and in their tubular aggregates when compared to controls. The enriched proteins belong to the biological pathways linked to ionic homeostasis, membrane systems of the triads and the exosome, and to the mitochondrial metabolism.Our works bring perspectives for the continuation of our studies, in order to better understand the physiopathology of the myopathy with tubular aggregates and propose efficacious therapeutic solutions.

Le traitement à la chaux est une technique qui améliore considérablement la maniabilité et le comportement mécanique des sols à problèmes. Cependant, la durabilité de ce traitement dans les ouvrages en terre sur le long terme représente un enjeu important pour leur stabilité. En outre, la procédure de mise en place, et par conséquent, la taille des agrégats qui en résulte, est un paramètre essentiel qui peut influencer le comportement des sols traités à la chaux utilisés dans le domaine de la construction d’ouvrages. Ce travail de thèse vise à étudier le comportement thermo-hydro-mécanique des sols traités à la chaux, et plus particulièrement les effets du temps de cure et de la taille des agrégats. Des échantillons de sols limoneux et argileux traités à la chaux ont été préparés avec des agrégats de différentes tailles puis soumis à des temps de cures plus ou moins longs. Ces matériaux ont ensuite été étudiés à travers des observations de la microstructure, des analyses minéralogiques, des mesures de la conductivité thermique, de la perméabilité à l’air et de la capacité de rétention d'eau, complétées par de la détermination de la compressibilité et des mesures des modules de cisaillement en petites déformations. Les résultats montrent que le traitement à la chaux modifie de manière significative le comportement thermo-hydro-mécanique des sols. De plus, le comportement des sols traités est fortement influencé par la taille des agrégats. Plus celle-ci est grande, plus la conductivité thermique et la perméabilité à l'air est importante. En revanche, la capacité de rétention en eau est diminuée de même que la compressibilité et la rigidité du sol / Lime treatment is a technique which greatly improves the workability and the mechanical behaviour of problematic soils. However, the sustainability of this treatment in the earthworks for the long term is an important issue for their stability. Besides, the aggregate size resulting from the construction procedure is an essential parameter that may influence the behaviour of treated soils in field construction. The present work deals with the thermo-hydro-mechanical properties of lime-treated soils, with an emphasis put on the curing time and the aggregate size effects. Lime-treated soil samples (both silt and clay) were prepared with different sizes of aggregates and cured during different periods. Afterwards, these soils were studied through microstructural observations, mineralogical analyses, thermal conductivity, air permeability and water retention capacity measurements, as well as the determinations of compressibility and small strain shear modulus. The results show that significant changes of thermo-hydro-mechanical behaviour of soils are induced by lime treatment after curing. Moreover, the aggregate size also plays an essential role in the behaviour of treated soils. Samples prepared with the large aggregates present higher thermal conductivity and air permeability, but with lower water retention capacity, poorer compression behaviour and smaller stiffness

No description available.

Performance evaluation of Luwex company between years 2003 and 2007. To make changes in optimisation recommendation for managing board. Optimisation of financial managing company based on financial analysis.

[pt] Os agregados são os bens minerais mais consumidos pela indústria de construção civil. Em pavimentos asfálticos, os agregados consistem em cerca de 85 por cento do volume total, e suas propriedades influenciam diretamente em seu comportamento. O presente trabalho refere-se ao estudo da viabilidade de agregados de rochas submetidas ao processo de metamorfismo em condições de alto grau para utilização em pavimentação asfáltica. Os agregados em questão são originados da Pedreira Itereré, localizada em Campos dos Goytacazes, região norte do Estado do Rio de Janeiro, Brasil. A rocha é um granulito félsico, composto majoritariamente por minerais félsicos (aproximadamente 88 por cento), fenocristais de plagioclásio e quartzo, e em menor quantidade pode se observar minerais máficos, piroxênio, biotita e minerais opacos. Sabe-se que rochas sãs com predominância de quartzo e feldspatos apresentam boa resistência mecânica, contudo tendem a ter problemas na adesividade ao ligante asfáltico. Para avaliar os agregados de granulito realizou-se a análise da rocha em lâmina petrográfica e na difração de raios – X, análise granulométrica, ensaios de massa específica e absorção, abrasão Los Angeles, perda ao choque no treton, análise da forma e da textura superficial no AIMS. Além desses, foram avaliadas propriedades do ligante asfáltico como a análise da composição química no FTIR, fracionamento em maltenos e asfaltenos, e sua interação com o agregado nos ensaios de adesividade e de adsorção. Os resultados mostraram uma moderada resistência a degradação mecânica com 30 por cento de abrasão Los Angeles e 12,6 por cento de perda ao choque no treton. A adesividade foi insatisfatória provavelmente devido ao baixo percentual de asfalteno no ligante, e a baixa capacidade de adsorção do agregado. A graduação e propriedades de massa específica, absorção, forma e textura superficial adequadas para revestimentos tipo camada porosa de atrito, mas para utilizar a rocha em pavimentos deve-se adicionar um aditivo devido à insatisfatória adesividade. / [en] Aggregates are the mineral goods most consumed by the construction industry. In asphalt pavements, the aggregates consist of about 85 percent of the total volume, and their properties directly influence their behavior. The present work refers to the study of the feasibility of aggregates of rocks submitted to the process of metamorphism under high-grade conditions for use in asphalt paving. The aggregates in question originate from the Itereré Quarry, located in Campos dos Goytacazes, northern region of the State of Rio de Janeiro, Brazil. Rock is a felsic granulite, composed mainly of felsic minerals (approximately 88 percent), phenocrysts of plagioclase and quartz, and to a lesser extent, can observe mafic minerals, pyroxene, biotite and opaque minerals. It is known that healthy rocks with predominance of quartz and feldspars and good mechanical resistance, however tend to have problems in the adhesiveness to the asphalt binder. In order to evaluate aggregates of granulates, analyze the analysis of the rock in petrographic scale and in the X - ray diffraction, granulometric analysis, mass and absorption tests, Los Angeles abrasion, treton shock loss, analysis of the surface texture in the AIMS. In addition, asphaltic binder properties were evaluated, such as the analysis of chemical composition in FTIR, fractionation in maltenes and asphaltenes, and their interaction with the aggregate in the adhesion and adsorption tests. The results showed a moderate resistance to mechanical degradation with 30 percent Los Angeles abrasion and 12.6 percent treton shock loss. The adhesiveness was unsatisfactory for the low percentage of asphaltene in the binder, and the low adsorption capacity of the aggregate. The graduation and specific mass properties, absorption, shape and surface texture suitable for porous layer coatings of friction, but to use the rock in pavements add an additive due to unsatisfactory adhesion.

京都大学 / 新制・課程博士 / 博士(工学) / 甲第23219号 / 工博第4863号 / 新制||工||1759(附属図書館) / 京都大学大学院工学研究科分子工学専攻 / (主査)教授 田中 庸裕, 教授 近藤 輝幸, 准教授 菅瀬 謙治, 教授 佐藤 啓文 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DGAM

La formation d'agrégats d'anticorps monoclonaux en solution est difficile à empêcher. Même si la présence de gros agrégats est assez rare, leur existence peut avoir des effets dramatiques dans les systèmes d'injection, en menant à des situations de colmatage partiel ou total de la restriction dans ce dernier. Cela entraîne une injection mal contrôlée ou même une obstruction totale du système d'injection. Très peu est connu sur le rôle de la taille des agrégats et de la pression appliquée sur de tels évènements de colmatage. Dans cette thèse, nous présentons un système microfluidique modèle, imitant les systèmes médicaux d'injection afin de comprendre fondamentalement le colmatage de restrictions d'une taille donnée. Des solutions très concentrées en anticorps monoclonaux nous permettent de créer des agrégats de protéines (plus grands que 50 micromètres) en utilisant un stress mécanique ou thermique. Nous montrerons que le colmatage a lieu quand les agrégats atteignent la taille de la restriction et peut dans certains cas être défait en augmentant la pression appliquée. La possibilité observée d'éjecter des agrégats de la restriction via une augmentation en pression indique le rôle important de la déformabilité des agrégats de protéines, à ce jour complètement inexplorée. Nous réalisons des expériences systématiques pour différentes tailles relatives d'agrégats et de pressions appliquées, et nous mesurons le débit en sortie. Malgré leurs formes et densités différentes, nous pouvons prédire le nombre d'évènements de colmatage pour une taille donnée de restriction par des mesures utilisant le Flow Imaging Microscopy (MFI). De plus, notre système peut détecter l'occurrence de très gros agrégats (très rares) souvent non détectés par d'autres techniques. Avec un modèle mécanique simple, nous pouvons estimer pour la première fois un ordre de grandeur du module d'Young et un diamètre effectif de pores pour des agrégats d'anticorps monoclonaux. Nous avons également développé une autre expérience modèle dans un canal hyperbolique couplé avec un flow focusing afin d'observer la déformation d'agrégats sous écoulement élongationnel. Nous décrirons leur comportement en analysant leurs trajectoires qui sont pour la plupart d'entre eux du tumble et de l'alignement avec l'écoulement. De plus, nous développerons un modèle mécanique qui tient compte de la force de friction dans une expérience modèle contrôlée avec une solution polymérique de PEGDA. Nous étudierons ainsi le rôle d'une différence de pression minimale à appliquer pour remettre la particule en mouvement dans la restriction, et ainsi relier cela aux agrégats de protéines. / The formation of aggregates in solutions of monoclonal antibodies is difficult to prevent. Even if the occurrence of large aggregates is rather rare, their existence can have dramatic effects in injection devices, as they can lead to partial or total clogging of constrictions in the latter. This leads to badly controlled injection or even total obstruction of the device. Little is know on the role of aggregate size and applied pressure on such clogging events. In this thesis, we present a microfluidic model system, mimicking medical injection devices to gain fundamental understanding of the clogging of constrictions of given size. Highly concentrated solutions of monoclonal antibodies allow us to create protein aggregates (bigger than 50 micrometers) using mechanical or heat stress. We show that clogging occurs when aggregates reach the size of the constriction and can in some cases be undone by increasing the applied pressure. The observed possibility to eject aggregates from constrictions via an increase in pressure indicates the important role of protein aggregate deformability, so far completely unexplored. We perform systematic experiments for different relative aggregate size and the applied pressure, and measure the flow-rate. Despite their different shapes and density, we can predict the number of clogging events for a given constriction size by Flow Imaging Microscopy (MFI) measurements. In addition our device can detect the occurrence of very rare big aggregates often overlooked by other detection techniques. With a simple mechanical model where we neglected the friction, we could estimate for the first time an order of magnitude for the Young modulus and a porous diameter for monoclonal antibodies aggregates. We also develop another model experiment with an hyperbolic channel coupled with a flow focusing to observe deformation of the aggregates under extensional flow. We describe their behavior by analyzing their trajectories which are for most of them tumbling and alignment with the flow. Moreover, we develop a mechanical model which took into account the friction force in a controlled model experiment with polymeric solution. We thus investigate the role of a minimal applied pressure to generate the particle movement into the constriction, and then link it with protein aggregates.

Harvesting only 4 % of light striking the Earth could possibly fulfill present energy demands of a mankind. Chlorosome of green sulfur bacteria is re- garded as suitable light-harvesting system for photosynthesis imitation. This work presents comparison of absorption and hole burning spectra of artificially prepared aggregates similar to chlorosomes with different compositions in order to verify the proposed role of quinones in excitation quenching and its redox de- pendence. Absorption spectra at room and helium temperature showed a resem- blance between artificial aggregates and chlorosomes. Hole burning experiments verified the role of quinones in excitation quenching under aerobic conditions. Even more pronounced excitation quenching was observed under anaerobic con- ditions. Significant improvements of the original experimental set-up provided better experimental data which raised many further question that are worth trying to answer in the future.

Amino acid phenylalanine plays a key role in numerous biological processes and is also involved in amyloid fibril diseases. The aim of the thesis is to deepen our understanding of its behavior and partitioning at interfaces, and to investigate its clustering. Classical atomistic molecular dynamics simulations were performed for phenylalanine and three other aromatic molecules which chemical structure is derived from it - phenylglycine, phenylacetic acid and tyrosine. Molecules are simulated at both water-air and at water-DPPC-air interfaces. Phenylalanine, phenylglycine and phenylacetic acid demonstrate surface activity at the water-air interface, whereas tyrosine is not surface active. All molecules interact with the lipid monolayer at the water-DPPC-air interface but only phenylalanine penetrates deep into the monolayer. Formation of transient clusters is observed in the interfacial regions, mostly for phenylalanine. Powered by TCPDF (www.tcpdf.org)

Transportation geotechnics associated with constructing and maintaining properly functioning transportation infrastructure is a very resource intensive activity. Large amounts of materials and natural resources are required, consuming proportionately large amounts of energy and fuel. Thus, the implementation of the principles of sustainability is important to reduce energy consumption, carbon footprint, greenhouse gas emissions, and to increase material reuse/recycling, for example. This paper focusses on some issues and activities relevant to sustainable earthwork construction aimed at minimising the use of energy and the production of CO2 while improving the in-situ ground to enable its use as a foundation without the consumption of large amounts of primary aggregate as additional foundation layers. The use of recycled materials is discussed, including steel slag and tyre bales, alongside a conceptual framework for evaluating the utility of applications for recycled materials in transportation infrastructure.