Dissertations / Theses on the topic 'LCTM'

Ce travail de thèse vise à évaluer la faisabilité des calculs de transition dans le cadre des codes industriels. Les points forts ainsi que les faiblesses des modèles de transition basés sur des corrélations locales, γ et γ-Re_θ, sont analysés sur des configurations bi et tridimensionnelles, en se concentrant sur la modélisation physique et les aspects numériques. L'objectif est d'analyser le potentiel de ces modèles RANS en tant qu'outils prédictifs, capables de gérer automatiquement et de manière autonome la transition d'un écoulement du régime laminaire au régime turbulent. Nous évaluons les performances des modèles de transition sur un grand nombre de cas de test, couvrant un large éventail de mécanismes de transition. Dans le cas des configurations 3D, un point crucial est la modélisation de la transition due aux modes transversaux et stationnaires, qui sont les principaux mécanismes de transition tridimensionnel dans un environnement à faible turbulence. A cet effet, nous présentons dans cette thèse un recalibrage original du critère transversal Tc1, proposé à l'origine par Menter et Smirnov en 2014 et basé sur une formulation locale du célèbre critère transversal C1 de Daniel Arnal. Ce critère recalibré étend notamment le modèle γ existant pour la prédiction de la transition transversale autour des géométries complexes
This research work aims at assessing transition calculations feasibility in the context of the industrial codes. We discuss the strengths and weaknesses of the Local Correlation Based Transition Models (LCTM) γ and γ-Re_θ for two- and three-dimensional configurations, focusing on both modeling and numerical aspects. The purpose is to analyze the potential of these RANS-based models as predictive tools, that can handle automatically and autonomously laminar-to-turbulence transition. We evaluate the transition models performance on an extensive number of test cases, covering a wide range of transition mechanisms. In the case of 3D configurations, a crucial point is the modeling of transition due to stationary crossflow modes, which are the main threedimensional transition mechanism in a low free-stream turbulence environment. For this purpose, we present in this dissertation an original re-calibration of the Tc1 crossflow criterion, proposed by Menter and Smirnov in 2014 and based on a local formulation of the renowned empirical C1 criterion of Daniel Arnal. This re-calibrated criterion notably extends the existing γ model for stationary crossflow transition prediction around threedimensional non-wing-like geometries

Composite flow simulation tools for LCM processing can be expensive and time-consuming but necessary to design a mold system with proper placement of resin inlets and vacuum outlets. Composites manufacturing engineers would benefit from data regarding the impact of mold curvature radius on resin flow. This could help determine whether or not a particular part and mold would require expensive simulation software designed to handle complex flow paths through curved fabric architectures exhibiting variable permeability over the curvature, or if simple flow modeling would provide accurate enough simulations for sound tooling setup decision making. Four molds, with double curvature having equal radii, were fabricated with radii ranging from 3.2 to 25.4 mm to characterize the permeability of two different fiber reinforcements 1) a carbon biaxial NCF and 2) a fiberglass CSM over the mold curvatures. Three infusions of each material type were conducted on each of the 4 molds for a total of 24 test infusions. Flow front position vs. time data was captured during each experimental infusion. The permeability in the bend regions, KB, was first estimated by the integrated form of Darcy's Law to evaluate the permeability for average flow across the entire bend region. This was done for both the convex and concave regions using a geometric estimate for the increased compaction in the bend regions. The permeability increases as the tool radius increases, and the rate of increase diminishes as the tool radius increases and the permeability approaches the flat region permeability. An estimate of KB for VI was then made by applying a ratio calculated from the resulting permeability from the rigid- and VI-based models in the flat regions. Generic power law fits are reported that could be used in LCM process simulation, to give a model to estimate the permeability for any bend in the reinforcement part geometry. The results suggest that any curve with a radius higher than 25 mm requires no adjustment to the flat permeability.

Les composants passifs, représentent actuellement une butée importante en terme de volume occupé, de pertes et de faisabilité de l'intégration. De nouvelles structures électromagnétiques proposent de marier les trois composants habituellement rencontrés dans les convertisseurs sous la forme d'un seul composant baptisé LCT, assurant simultanément trois fonctionnalités : inductance-condensateur-transformateur. Nous avons dimensionné deux structures intégrées de prototypes LCT (bobiné & planar), employant, tous deux, une nouvelle topologie de circuit magnétique. En nous basant sur ces réalisations de composants passifs intégrées ainsi que sur une réalisation discrète, diverses approches sont proposées pour mieux estimer les pertes dans ces composants afin de pouvoir réaliser une étude comparative sur chacun des dispositifs. En particulier, la caractérisation fine du LCT en vue d'obtenir les éléments d'un schéma équivalent constitue un moyen d'atteindre ce résultat.

Thesis (Ph. D.)--Ohio State University, 2004.
Title from first page of PDF file. Document formatted into pages; contains xix, 245 p.; also includes graphics. Includes bibliographical references (p. 233-245).

Nematodes of the genus Meloidogyne are known as “root-knot” nematodes due to the characteristic knots or galls found on the roots of infected plants. Root-knot nematodes attack over 2000 species of plants and cause over 80 billion dollars lost annually. Giant cells are feeding sites of root-knot nematodes and are enlarged multinuclear cells induced by the nematodes in susceptible host roots and that function to provide nutrients to the nematode. This thesis presents data on two techniques of studying the nuclear condition in giant cells. Colchicine was used to arrest mitosis in giant cells in a previous study. Here we test the effect of colchicine on nematode activity. The results showed that colchicine did not affect nematode egg hatch, juvenile activity, or hatch of eggs produced by treated juveniles. These results confirm that colchicine can be used to arrest mitosis in giant cells without affecting the nematode parasite. A major obstacle to the study of giant cells is collecting tissue samples that are specific to giant cells. Laser capture microdissection (LCM) is a technique that allows one to sample a single giant cell. A focused laser beam was used to collect samples of giant cell cytoplasm from fixed and sectioned tissues. RNA was then extracted from those isolated samples. Using three tomato genes as test samples, specific primers were designed to measure expression level of Rb7, LHA4, and HXK1 gene by Real-Time PCR. Expression of LHA4 and Rb7 increased with time after inoculation, and immature giant cells reached levels that were 3 and 6 times, respectively, that of cortical cells, but which were not different from root meristem cells. Expression of HXK1 did not change with time after inoculation and has the same level of that in root tip and cortical tissues. These data confirmed that the techniques of LCM coupled with RT-real-time PCR can be used to quantitate expression of genes at different stages of giant cell development without contamination from surrounding cells.

En el transcurs de l'evolució de la humanitat l'alimentació ha ocupat un lloc predominant. La història de l'alimentació, de fet, ha corregut paral·lela a la història de la humanitat, o, com refereix García Almansa, «la història de l'alimentació és tan antiga com la humanitat mateixa».
L'ésser humà constitueix un sistema termodinàmic obert, a través del qual ha d'existir un fluxe ininterromput de matèria i energia per a mantenir la vida. La nutrició és un procés indispensable per a aquest fet. Per mitjà d'ella, l'organisme obté totes les substàncies necessàries per a l'obtenció d'energia adequada per al manteniment de les seves funcions vitals i per al creixement, desenvolupament i recanvi de les seves pròpies estructures
Una nutrició correcta és, doncs, una condició indispensable per a mantenir l'estat de salut en l'ésser humà. En l'organisme emmalalteixo la nutrició cobra un especial relleu, considerant-se fins i tot com un tipus de tractament (dietoterapia, terapeutica dietètica, etc.)
En el transcurso de la evolución de la humanidad la alimentación ha ocupado un lugar predominante. La historia de la alimentación, de hecho, ha corrido paralela a la historia de la humnidad, ó, como refiere García Almansa, «la historia de la alimentación es tan antigua como la humanidad misma».
El ser humano constituye un sistema termodinámico abierto, a través del cual debe existir un flujo ininterrumpido de materia y energía para mantener la vida. La nutrición es un proceso indispensable para este hecho. Por medio de ella, el organismo obtiene todas las sustancias necesarias para la obtención de energía adecuada para el mantenimiento de sus funciones vitales y para el crecimiento, desarrollo y recambio de sus propias estructuras
Una nutrición correcta es, pues, una condición indispensable para mantener el estado de salud en el ser humano. En el organismo enfermo la nutrición cobra un especial relieve, considerándose incluso como un tipo de tratamiento (dietoterapia, terapeútica dietética, etc.)

La France, à l'instar de nombreux pays européens, connaît un recul assez net de sa population paysanne et par la même occasion de son potentiel agricole. Cette baisse sensible, enregistrée sur les trente dernières années est la conséquence directe de l'exode massif des populations vers les grandes agglomérations. Cette mutation s'est accompagnée de la fermeture progressive des paysages, marqués le plus souvent par une colonisation rapide par des espèces forestières. Ces évolutions sont également dues au changement climatique qui favorise certaines espèces par rapport à d'autres. Du point de vue de la gestion du bassin versant, il est très important de savoir comment ces changements pourraient affecter les ressources en eau. La mise en œuvre de la directive-cadre sur l'eau du 24 octobre 2012, définit des structures de gestion de l'eau sur des unités hydrologiques (bassin versant, nappe d'eau souterraine) pour un bon état des eaux en 2015, et le respect des objectifs pour 2027 dans le cadre d'une nouvelle directive-cadre sur l'eau (DCE). Cette mise en œuvre nécessite de prendre en compte la diversité spatiale et thématique des données sur l'unité hydrologique considérée. La télédétection et les Systèmes d'Information Géographiques (SIG) sont des outils utiles permettant de représenter cette diversité. Ils servent à la fois à l'organisation, à l'actualisation et à l'analyse des données spatiales. Ils sont utiles également pour le paramétrage de modèles hydrogéochimiques afin de modéliser la variabilité spatio-temporelle des ressources en eau. L'intérêt de la télédétection et des SIG couplés au modèle hydrogéochimique WARMF, est mis en évidence dans l'étude du cas d'un grand bassin versant du Massif Jura : l'Ain (4780 km²). Une telle étude répond aux problèmes qui se posent lors d'une DCE : estimation des quantités des eaux sur des secteurs non-mesurés, prévision des quantités en fonction de scénarii de l'occupation des sols et de scénarii météorologiques, vulnérabilité des ressources en eau superficielles, effet de la matière organique sur la qualité des eaux. Cette étude fournit une base scientifique pour la formulation de stratégies pour la gestion de la ressource en eau. Le couplage de la télédétection et des SIG au modèle hydrogéochimique est une nouvelle approche offrant de grands avantages en matière de disponibilité des données, de construction des scénarii, et d'interprétation des résultats. Cette approche sera un outil efficace d'aide à la décision pour la gestion intégrée de la ressource en eau des lacs et plus largement du bassin versant (oxygène, pH, etc.)
France, as well as other European countries, experiences a sharp decline in rural population and at the same time its agricultural potential. This significant decline recorded over the past thirty years is the direct result of the mass exodus of the population to big cities. This change was accompanied by the gradual closure of landscapes usually marked by a rapid colonization of forest species. These changes also felt under the direct impact of climate change, which favors certain species than others. From the point of view of watershed management, it is very important to know how these changes might affect water resources. The implementation of the framework directive on water, 24 October 2012, defines the structures of water management on hydrological units (watershed, groundwater, etc.) for a good water status by 2015 and compliance goals for 2027 under a new water framework directive (WFD). This implementation requires taking into account the spatial and thematic diversity data on hydrologic unit considered. Remote Sensing (RS) and Geographic Information Systems (GIS) are useful tools to represent this diversity. They serve both the organization, updating and analysis of spatial data. They are also useful for setting the hydrogeochemical models in order to simulate the spatio-temporal variability of water resources. The value of RS and GIS coupled in the hydrogeochemical model WARMF is highlighted in the case study of a large watershed of the Massif Jura: Ain watershed (4780 km ²). This study addresses the problems that arise when a WFD: estimating quantities of water on non-measured sectors, forecasting quantities according to land-use and climate scenarios, vulnerability of water resources, the effect of organic matter on water quality. This study provides a scientific basis for the formulation of strategies for the management of water resources. The coupling of remote sensing and GIS in the hydrogeochemical models is a new approach offering great benefits in terms of data availability, the construction of scenarios, and interpretation of results. This approach will be an effective tool for decision support for integrated management of water resources of lakes and wider catchment (oxygen, pH, etc.)

Dans le contexte de l'amélioration de la compacité des alimentations d'électronique de puissance, l'intégration des composants passifs constitue l'un des principaux leviers pour atteindre des niveaux de miniaturisation conséquents. Dans ce cadre, différents travaux ont déjà été engagés de part le monde. Les travaux présentés dans ce mémoire concernent la réduction des volumes des composants passifs, inductance - transformateur – condensateur, indispensables à toute structure d'électronique de puissance, en mariant ces trois éléments en un seul et unique appelé composant « LCT ». L'adaptabilité de cette association dépend en grande partie des performances des diélectriques utilisables dans cette réalisation permettant l'intégration de capacités élevées pour ainsi insérer ce dispositif LCT dans tout type de structure. Actuellement, le développement des matériaux ne permettant pas d'envisager toutes les applications classiquement rencontrées en électronique de puissance, nous avons étudié une nouvelle structure de convertisseur à transfert d'énergie mixte (MET) adaptée au LCT pouvant offrir un intérêt industriel dans un futur proche compte tenu de sa similitude avec une alimentation à découpage classique Forward. Outre les matériaux diélectriques en cours d’évolution, l'expansion de ce concept passe par un travail de modélisation conséquent, ainsi que par des technologies de mise en œuvre performantes comme les circuits multicouches. A l’issu de ce travail, un prototype a été réalisé dont les performances sont présentées, comprenant un composant LCT au sein de cette structure MET
In the context of improving of the compactness of supplies power electronics, integration of passive components is the major keypoints to reach a high level of reduction. In order to achieve this, different works have already begun in the world. The works presented in this report include the reduction of volumes of passive components, transformer - inductor-capacitor, which are essential to any structure of power electronics, combining these three elements in a single component called "LCT". The adaptability of this association principally depends on the performance of dielectric used in this achievement allowing the integration of high capacity to insert the device LCT in any type of structure. Currently, the development of materials don’t permit to consider all applications typically used in power electronics. Therefore we studied a new converter with a mixed energy transfer (MET) adapted at the LCT which could provide industrial interest in the future. It presents similarity with the conventional converter Forward. In addition to the dielectric material actually in evolution, the expansion of this concept requires a consequence modelling work, and news technologies of implementation with high performance such as multilayer circuits. At the end of this work, a prototype was produced whose performances are presented, including a component LCT within this structure MET

As the green movement begins to sweep through the construction industry, decision-makers are beginning to include a sustainable aspect to their purchase decisions. Selecting a product solely based on its sustainability, however, is not enough to drive product selection in the construction industry. Cost still dominates the selection of building products. The level of sustainability of a product and its cost are not interconnected as market prices do not reflect the cost of environmental impacts, such as the cost of global warming or fossil fuel depletion. Having two distinct aspects to consider adds complexity in the product selection process. Typically, it constrains decision-makers to perform a trade-off analysis that does not necessarily guarantee the most environmentally preferable purchase decision. This study proposes a life-cycle management (LCM) system that reinforces the choices made by decision-makers by providing a scientific justification for those decisions. The proposed system analyses the environmental and economic performance of building product through life-cycle analysis and purchase price analysis. It operates on tools publicly available in the market and state-of-the-art analysis, assessment, and interpretation methods. The LCM system combines two distinct product attributes into a single performance score that can be easily interpreted. It allows decision-makers to compare product scores and ultimately make the most environmentally responsible and financially viable selection. A comprehensive approach is used to refine and test the LCM system using case studies comprised of an environmental and economic performance evaluation of flooring products. The contribution of this research includes the consideration of a holistic approach to product selection based on environmental and cost performance. Pre-construction estimators and construction managers could improve their estimating and product selection practices using the proposed system. Material suppliers can also benefit from this approach, as they can use it to enhance their pricing strategies, marketing plans, and overall product competitiveness.

A hipolactasia do tipo adulto é o fenótipo determinado pela diminuição da expressão da lactase após o período de lactação. Ela ocorre em um grande número de adultos em todo o mundo. A lactase é produzida pelos enterócitos e sua função principal é hidrolisar a lactose, que é o carboidrato do leite. Os indivíduos intolerantes à lactose irão apresentar sintomas como inchaço, flatulência, náusea e diarreia causados pela fermentação da lactose. A persistência da lactase (PL) é o fenótipo no qual a expressão da lactase se mantém elevada durante toda a vida. Na Europa, a PL foi relacionada a um polimorfismo de base única (SNP) localizado a aproximadamente 14 Kb do sítio de início da transcrição do LCT (gene da lactase), dentro de um íntron do gene MCM6, sendo este SNP uma troca de C para T na posição -13910 (rs4988235). Na África e Oriente Médio os seguintes SNPs foram relacionados a PL: - 13907C>G (rs41525747), -13915T>G (rs41380347), -14010G>C (rs145946881). O gene LCT também possui SNPs na região codificadora e na região promotora que não estão envolvidos com a PL. Estes SNPs apresentam alto desequilíbrio de ligação formando haplótipos, sendo que os haplótipos A, B, C e U são os mais frequentes na maioria das populações. No Brasil, dados sobre os alelos relacionados com a persistência da lactase são escassos. Além disso, dados populacionais relacionados à diversidade do gene LCT ainda não foram descritos para nossas populações. Portanto, o objetivo deste trabalho foi estudar a diversidade do gene LCT, da região codificadora do gene, da região promotora proximal e da região enhancer população brasileira. Um total de 1297 indivíduos foram analisados. As populações estudadas foram nativos brasileiros (Kaingang N=72, Xavante N=101, Guarani-Kaiowá N=84 e Guarani-Ñandeva N=59), eurodescendentes de Porto Alegre (Rio Grande do Sul, N=337), afrodescendentes de Porto Alegre (N=182), miscigenados de Belém (Pará, N=200) e de Recife (Pernambuco, N=262). Doze SNPs foram analisados, 10 nas regiões codificadora e promotora do LCT e 2 na região enhancer. As metodologias utilizadas na genotipagem destes SNPs foram PCR-RFLP, discriminação alélica pelo sistema TaqMan e sequenciamento. O sequenciamento também foi utilizado na busca de novos alelos da região enhancer. Com relação à população nativa, o único alelo de PL encontrado foi o -13910*T, variando de 0,5% em Xavante a 7,6% nos GuaraniÑandeva. O gene LCT foi altamente polimórfico apresentando 15 haplótipos com distribuição heterogênea nas populações nativas. Na população brasileira em geral, a frequência do alelo -13910*T foi maior (0,295) nos eurodescendentes de Porto Alegre e menor (0,175) na população de Belém. Nos grupos de afrodescendentes de Porto Alegre, Belém e Recife, 4 outras variantes, previamente descritas, da região enhancer foram encontradas: - 13779G>C, -13937G>A, -14010G>C, -14011C>T. Vinte e seis haplótipos previamente descritos foram identificados. O estudo de associação da presença do alelo -13910*T com a presença da síndrome metabólica nos eurodescendentes de Porto Alegre demonstrou que os indivíduos persistentes apresentam menor risco do que os não persistente de ter síndrome metabólica (OR=0,47; p=0,023). Na tentativa de auxiliar no entendimento das causas da PL foi realizado um estudo funcional da variante -13937G>A. Os resultados demonstraram que o alelo derivado não direciona maior expressão do gene repórter em células em cultura. Considerando os dados obtidos no presente trabalho e os disponíveis na literatura, ressaltamos a importância dos estudos que buscam compreender a PL pela busca de novos alelos, por estudos de correlação fenótipo-genótipo e também pelos estudos funcionais para a caracterização das variantes encontradas em relação ao fenótipo da lactase.
Adult-type hypolactasia is the phenotype determined by the decreased lactase expression after weaning. It occurs in a high number of adults in the world. Lactase is produced by the enterocytes and its major function is to hydrolyze lactose, the milk carbohydrate. The lactose intolerant individuals will have symptoms like bloating, flatulence, nausea and diarrhea caused by the lactose fermentation. Lactase persistence (LP) is the high lactase expression during adulthood. In Europe, the LP was related to a single nucleotide polymorphism (SNP) located approximately 14 Kb from the LCT (lactase gene) transcription initiation site, within a MCM6 gene intron, and this SNP is a C to T mutation in the -13910 position (rs4988235). In Africa and Middle East, the following SNPs were related to LP: - 13907C>G (rs41525747), -13915T>G (rs41380347), -14010G>C (rs145946881). LCT gene also has SNPs in the coding and promoter region that are not involved in the LP. These SNPs have high linkage disequilibrium forming haplotypes, with the A, B, C and U being the most frequent haplotypes in the majority of the populations. In Brazil, data about the LP related alleles are rare. Moreover, population data related to LCT gene diversity was not described for our population. Hence, the aim of this work was to study the LCT gene diversity in the coding region, in the proximal promoter region, and in the enhancer region in the Brazilian population. In total, 1297 individuals were investigated. The populations studied were Brazilian natives (Kaingang N=72, Xavante N=101, Guarani-Kaiowá N=84 and Guarani-Ñandeva N=59), Eurodescendants from Porto Alegre (Rio Grande do Sul state N=337), Afrodescendants from Porto Alegre (N=182), admixed individuals from Belém (Pará state, N=200) and from Recife (Pernambuco state, N=262). We analyzed 12 SNPs, 10 in the coding and promoter region of the LCT gene and 2 in the enhancer region. The genotyping methodologies applied were PCRRFLP, allelic discrimination by TaqMan system and sequencing. Sequencing was also employed for new alleles identification in the enhancer region. In relation to the native population, the only LP allele found was -13910*T, and the frequency ranged from 0.5% in Xavante to 7.6% in Guarani-Ñandeva. The LCT gene was highly polymorphic showing 15 haplotypes with heterogeneous distribution in the native populations. In the general population, the frequency of the -13910*T was higher (0.295) in Eurodescendants from Porto Alegre and lower (0.175) in the Belém population. In the groups of Afrodescendants from Porto Alegre, Belém and Recife, 4 other previously described variants in the enhancer region were found: -13779G>C, - 13937G>A, -14010G>C, -14011C>T. Twenty-six haplotypes previously described were found in the Brazilian population. The association study of the -13910*T allele and of the presence of the metabolic syndrome in the Eurodescendants from Porto Alegre showed that the persistent individuals have lower risk than the non-persistent of developing metabolic syndrome (OR=0.47, p=0.023). In an attempt to disclose LP causality, a functional study of the -13937G>A variant was performed. The results showed that the derived allele does not drive a higher expression of the reporter gene in cells in culture. Considering the results of this study and the data available in the literature, we emphasize the importance of the studies that try to determine the LP looking for new alleles, phenotype-genotype studies, and functional studies to characterize the variants found related to the lactase phenotype.

It generally takes 10 to 12 years for a new drug to hit the market. The pharmaceutical industry invests huge sums in these early stages of research and development. In spite of the rapidly rising research and development expenditures fewer and fewer blockbuster drugs are being developed. Longer lead times and aggressive generic post-patent competition have narrowed the timeframe for the pharmaceutical companies to profit on their investments.

In the face of these threats the pharmaceutical industry has developed a battery of strategies to prolong market exclusivity and to maximize return on investment. These emerging strategies are commonly known as Life cycle management (LCM), which actually is more of a concept than a method. A life cycle is a sequence that stretches all the way from early research and development, through marketing to finally end when the product is withdrawn from the market. By managing the product through these different stages the company can improve the commercial lifespan.

This thesis analyzes how Life cycle management is implemented in the Swedish pharmaceutical industry. The data is based on interviews from people who are active in the pharmaceutical business. Further, the thesis studies the strategies that AstraZeneca used for their gastrointestinal drugs Losec and Nexium.

Based on the collected data from the interviews a clear view of the role and involvement of LCM strategies appears. The value and importance of LCM have steadily increased during the last 10 years. LCM is heavily embedded in the decision processes of drugs today. Several strategies such as OTC switching and patent prolongation through pediatric indication application are common practice. The Swedish pharmaceutical industry has a prominent position in the advancement of LCM.

Idag lanseras mindre innovativa nya läkemedel än under 80- och 90-talet. Kostnaderna för att utveckla ett läkemedel har ökat och det tar dessutom längre tid från upptäckt till lansering. Läkemedel har endast en begränsad marknadsexklusivitet som styrs av patentskyddet. Vid patentutgång så utsätts läkemedlet för stenhård konkurrens från aggressiva generika tillverkare. De ställs hårdare krav på forskande farmaceutiska företag för att vara lönsamma i detta klimat.

Det finns en tydlig trend att läkemedelsföretag har blivit mer beroende av sina storsäljande läkemedel. Ett flertal offensiva strategier har utvecklats för att förlänga lönsamheten hos de mest framgångsrika läkemedlen, t.ex. genom att minska utvecklingstiden, utveckla nya formuleringar och expandera indikationerna. ”Life cycle management” (LCM) är ett samlingsbegrepp på dessa strategier, som används under en produkts livscykel för att förbättra den kommersiella livslängden. Försäljning och marknadsföring för innovativa läkemedel passerar distinkta faser och olika strategier krävs beroende på vilka fas en produkt befinner sig i.

I denna uppsats analyserar jag hur LCM är implementerat i den svenska läkemedelssektorn. Slutsatserna bygger på data från intervjuer av personer som är sysselsatta inom läkemedelsbranschen. Uppsatsen studerar dessutom de strategier som AstraZeneca har använt för sina två magtarmläkemedel Losec och Nexium.

Baserat på insamlad intervjudata så framkommer tydligt att LCM är starkt involverat i beslutsprocesserna runt ett läkemedel. Betydelsen av LCM har successivt ökat under de senaste 10 åren. Flera strategier för t.ex. patentförlängning är idag vanligt förekommande. Den svenska läkemedelsbranschen ligger relativt långt fram i denna utveckling.

A crescente presença de fármacos em efluentes tratados obriga ao desenvolvimento de metodologias eficientes, a custos reduzidos para a sua redução/remoção. Os processos de tratamento convencionais das ETARs não são geralmente eficazes na remoção de fármacos. A remoção destes compostos com carvões ativados (CA), ou por leitos construídos de macrófitas (LCM), individualmente, também apresentam limitações. Este trabalho teve como principal objetivo a avaliação da remoção do sulfametoxazol, usando um microcosmo de LCM, seguido de um processo de adsorção em três CA. Nos LCM, inicialmente, a cinética de remoção do sulfametoxazol foi muito rápida, pois durante a primeira meia hora, no leito plantado e no não plantado, a remoção foi de 75,3% e 39,4%, respetivamente. O CA em pó apresentou uma cinética de remoção muito rápida e a capacidade máxima de remoção nas condições de trabalho chegou aos 177 mg g-1. A sequência dos dois processos mostra-se promissora para a remoção do sulfametoxazol em particular em situações de derrames/emergências; Abstract: Evaluation of pharmaceuticals removal by hybrid constructed wetland systems followed by activated carbon adsorption The increasing presence of pharmaceuticals in treated wastewaters calls for the development of new efficient methodologies for their mitigation/removal, but which are also low cost. The conventional wastewater treatment processes of WWTPs are not generally effective in removing pharmaceuticals. The removal of these compounds using activated carbon (AC), or by constructed wetlands systems (CWS) also present limitations, each by itself alone. This work had as the main goal the evaluation of sulfamethoxazole removal from the liquid phase, using a microcosm of CWS, followed by adsorption to three ACs. In the CWS, initially, sulfamethoxazole removal kinetics was very fast, as during the first half-hour both in the planted bed an in the unplanted one the removal was of 75.3% and 39.4%, respectively. Powdered AC presented a very fast kinetics and sulfamethoxazole removal capacity of 177 mg g-1. The sequence of the two processes seems promising for the removal of sulfamethoxazole, in particular in spilling/emergency situations.

ALes travaux présentés sont une contribution à l’élaboration de composites à matrices thermoplastiques (TP) par un procédé de type Liquid Composite Molding non réactif pour l’industrie automobile. La thèse a été effectuée dans le cadre du projet ANR TAPAS (ThermoplAstic Process for Automotive composite Structure) et s’est focalisée sur la mise en œuvre de plaques composites en renfort continu injectées avec des matrices polyamides 6,6 (PA 6,6) de hautes fluidités par Resin Transfer Molding. Le premier objectif est porté sur l’optimisation des cadences d’injection à travers l’étude de la perméabilité de préformes unidirectionnelles (UD) en fibres de verre et à hauts modules mécaniques. L’architecture de ces UD a ainsi été modifiée de manière à faciliter les écoulements. La perméabilité des différents tissus a pu être évaluée par un couplage entre des mesures expérimentales et une modélisation analytique basée sur un raisonnement à deux échelles de pores : l’écoulement intra et inter-torons. Le deuxième objectif sur lequel les travaux de thèse se sont concentrés s’est reposé sur la maitrise de l’état d’imprégnation par le bais d’une étude complète sur les phénomènes qui se déroulent à l’interface entre la fibre et la matrice à haute température. Plusieurs viscosités et formulations du PA 6,6 ainsi qu’un traitement appliqué sur le verre ont pu être caractérisés et discutés en termes de mouillabilité et d’adhésion. Enfin, la dernière partie du manuscrit présente les résultats obtenus sur les plaques mises en œuvre par RTM-TP en injection in-plane. Les conditions optimales de fonctionnement ainsi que les aspects de saturation, de santé matière et des propriétés mécaniques sont ensuite présentés et discutés
The present work is a contribution to the thermoplastic composites manufacturing by a non-reactive Liquid Composite Molding process for the automotive industry. The thesis was carried out by the « ANR TAPAS » project (Thermoplastic Process for Automotive Composite Structure) and was focused on the elaboration of continious-fiber reinforced composites plates injected with a high-fluidity polyamide 6,6 (PA 6,6) by the Resin Transfer Molding process. The first goal was focused on increasing injection rates through the study of the in-plane permeability of unidirectional (UD) glass fiber fabrics with high mechanical modulus (HM). Experiments and modelling results showed that the permeability of these UD has been enhanced by modifying specific structural parameters of their architecture. The analytical model developped and used is based on a flow distribution according two differents scales of porosity : in and inter-yarns. The second part of the work was focused on the understanding of phenomenas that take place at the interface created between glass fiber and the matrix during the impregnation step. The wettability and adhesion of molten PA 6,6 dropped on a glass substrate is studied at different processing temperature. The last part introduce the thermoplastic composite plates elaborated by RTM-TP process. The optimum operating conditions as well as preforms saturation and mechanical properties are also studied and discussed

Bakgrund och problemdiskussion: Lyxvarumärkesföretag har börjat undersöka implementering av en strategi som erbjuder livslångt kundvärde. De har även visat intresse som tyder på att de vill tillämpa CRM-policys men är osäkra till hur stor del den går att tillämpa inom lyxindustrin. Vi har med inspiration från artikeln ”Is CRM for Luxury brands?” Cailleux, Mignot & Kapferer (2009) konstaterat att det existerar ett problem med den traditionella CRM som inte förstår ”luxury management” och de exakta implikationerna. Då begreppet CRM anses vara otillräcklig samt bristande vid tillämpning på lyxvarumärken anser vi att CRM inte är en optimal affärsstrategi för den sortens företag. Syfte: Vårt syfte med studien är att förstärka och komplettera CRM ur ett lyxperspektiv. Ambitionen är att utveckla existerande teori samt skapa en modell som är anpassad för lyxvarumärkesföretag. Vidare vill vi även tydliggöra de skillnader som existerar mellan klassisk CRM och LCRM. Metod: Uppsatsen har en teoretisk utgångspunkt och behandlas ur en kvalitativ metod tillsammans med respondenter från fallföretaget som besitter gedigen erfarenhet och ansvarspositioner inom lyxindustrin. Slutsats: CRM är inte en tillräcklig strategi att applicera mot lyxvarumärkesföretag då den inte är justerad för att tillgodose lyxvarumärkesföretagens plattform. Den utvecklade teorin LCRM har testats genom en empirisk studie och verifierats till att vara en lämplig strategi för lyxvarumärkesföretag. Genom en tillämpning av LCRM kan lyxvarumärkesföretag nå en ökad kundlojalitet ur ett långsiktigt  perspektiv.
Background and problem discussion: Luxury brands have begun to explore the benefits of an approach to create lifelong customer value. They have also shown interest in implementing CRM policies but are unsure how suitable it is for their market. The article “Is CRM for luxury brands?” Cailleux, Mignot & Kapferer (2009) has been used as an inspiration in this study as the article has found that the existing traditional CRM does not understand "luxury management" and the precise implications, i.e., how luxury brands want to expand while maintaining their prestige. Since the concept of CRM is considered to be insufficient and inadequate for the purposes of luxury brands, we believe that CRM is not an optimal business strategy for the type of business. Purpose: The purpose with this study is to enhance and supplement the strategy CRM to meet the luxury industry needs. The ambition is to develop existing theory and create a model that is suitable for luxury brands. Further, the purpose is to clarify the differences between CRM and LCRM. Method: The paper is theoretically based with a qualitative approach with respondents in leader positions and extensive experience within the luxury industry. Conclusion: CRM is an insufficient strategy to apply for businesses within the luxury industry because it does not understand the platform of a luxury brand. The developed theory LCRM has been tested through an empiric study and has been verified as a suitable strategy to apply for luxury brands. Through an implementation of LCRM luxury brands can achieve a higher customer loyalty in the long run.

Com este trabalho pretendeu-se avaliar a eficiência de remoção do diclofenac e furosemida, de uma solução aquosa contendo quatro fármacos, usando microcosmos de leitos construídos de macrófitas (LCM) com uma matriz de suporte de LECA+vermiculite, e plantado com Typha spp.. Foi avaliada a capacidade de remoção dos fármacos pela matriz, verificando-se que esta contribuiu com uma percentagem de remoção dos fármacos entre 53-54%, ao fim de 120h. Globalmente, o microcosmos atingiu elevadas eficiências de remoção de ambos os fármacos (70-78%). A presença de plantas contribuiu para uma remoção adicional dos dois fármacos entre 32-37%. Como otimização do microcosmos adicionou-se à matriz carvão ativado em pó, conseguindo-se um aumento significativo da eficiência de remoção dos fármacos (92- 99,5%). Este estudo, apesar do seu caráter preliminar, aponta para que LCMs construídos e operados analogamente aos deste trabalho serão potencialmente uma opção para o tratamento de águas contaminadas com estes dois fármacos; Role of the matrix composed of clay materials and activated carbon in the removal of pharmaceuticals by CWS Abstract: The aim of the present work was to assess the efficiency of a Constructed Wetlands Systems (CWS) microcosms in removing diclofenac and furosemide from an aqueous solution containing four pharmaceuticals. The CWS was constructed with LECA+vermiculite as support matrix and planted with Typha spp.. The contribution of the support matrix for the pharmaceuticals removal was evaluated in 53-54% after 120h. Overall, the microcosms attained high removal efficiencies for both pharmaceuticals (70-78%). The presence of plants contributed with additional removal of the two pharmaceuticals in between 32-37%. As an optimization of the microcosms, powdered activated carbon was added to the support matrix, which provided for a significant increase in the pharmaceuticals removal efficiencies (92-99.5%). This study, in spite of its still preliminary nature, suggests that CWS constructed and operated according to the guidelines reported in this work may potentially be an option for treating wastewater contaminated with these two pharmaceuticals.

Keloid disease (KD) is a cutaneous fibroproliferative tumour characterised by heterogeneity, locally aggressive invasion and therapeutic resistance. Clinical, histological and molecular differences between the keloid scar centre and margin as well as recent evidence of the importance of epithelial-mesenchymal interactions (EMI) in KD pathobiology contribute to the complexity and diversity of KD, which coupled with the lack of a validated animal model have hindered research and effective management. Despite significant progress in the field of KD research, reliance on conventional monolayer cell culture and whole tissue analysis methods have failed to fully reflect the natural architecture, pathology and complexity of KD in vivo. In order to address these challenges, a site-specific in situ approach was therefore employed here for the first time in KD research. The first aim of this work was to compare the value of this contemporary approach with traditional methods of tissue dissection. The second aim was to compare the genomic expression between well-defined, distinct keloid sites and normal skin (NS). The third aim was to develop and explore hypotheses arising from this site-specific gene expression profiling approach, so as to enhance understanding of KD pathobiology as a basis for improved diagnostic and therapeutic strategies in future KD management. The fourth aim was to probe these hypotheses with relevant functional in vitro studies. The current site-specific in situ approach was achieved through a combination of laser capture microdissection and whole genome microarray, allowing separation of epidermis from dermis for keloid centre, margin and extralesional sites compared with NS. This in situ approach yielded selective, accurate and sensitive data, exposing genes that were overlooked with alternative methods of dissection. Identification of significant upregulation of the aldo-keto reductase enzyme AKR1B10 in all three sites of the keloid epidermis (KE) in situ, implicated dysregulation of the retinoic acid (RA) pathway in KD pathogenesis. This hypothesis was supported by showing that induced AKR1B10 overexpression in NS keratinocytes reproduced the keloid RA pathway expression pattern. Moreover, co-transfection with a luciferase reporter plasmid revealed reduced RA response element activity. Paracrine signals released by AKR1B10-overexpressing keratinocytes into conditioned medium resulted in TGFβ1 and collagen upregulation in keloid fibroblasts, suggesting the disturbed RA metabolism exerts a pro-fibrotic effect through pathological EMI, thus further supporting the hypothesis of RA deficiency in KE. Gene expression profiling further revealed an upregulation of NRG1 and ErbB2 in keloid margin dermis. Exogenous NRG1 led to enhanced keloid fibroblast migration with increased Src and PTK2 expression, which were attenuated with ErbB2 siRNA studies. Together with the observed failure to recover this expression with NRG1 treatment, suggested the novel KD pathobiology hypothesis that NRG1/ErbB2/Src/PTK2 signaling plays a role in migration at the keloid margin. In addition to these hypotheses, LCM methodology with comprehensive analysis of the data permitted the development of additional novel working hypotheses that will inform future KD research, including inflammatory gene dysregulation and cancer-like stem cells that may contribute to the therapeutic resistance characteristic of KD.

Le fond diffus cosmologique (CMB), relique du Big-Bang chaud, porte les traces à la fois de la formation des structures des époques récentes et des premières phases énergétiques de l'Univers.Le satellite Planck, en service de 2009 à 2013, a fourni des mesures de haute qualité des anisotropies du CMB. Celles-ci sont utilisés dans cette thèse pour déterminer les paramètres du modèle cosmologique standard et autour du secteur des neutrinos.Ce travail décrit la construction d'un fonction de vraisemblance pour les hauts-l de Planck. Cela implique une stratégie de masquage pour l'émission thermique de la Galaxie ainsi que pour les sources ponctuelles. Les avant-plans résiduels sont traités directement au niveau du spectre de puissance en utilisant des templates physiques bases sur des études de Planck.Les méthodes statistiques nécessaires pour extraire les paramètres cosmologiques dans la comparaison entre les modèles et les données sont décrites, à la fois la méthode bayésienne de Monte-Carlo par chaînes de Markov et la technique fréquentiste du profil de la fonction de vraisemblance.Les résultats sur les paramètres cosmologiques sont présentés en utilisant les données de Planck seul et en combinaison avec les données à petites échelles des expériences de CMB basées au sol (ACT et SPT), avec les contraintes provenant des mesures des oscillations acoustiques des baryons (BAO) et des supernovae. Les contraintes sur l'échelle absolue de la masse des neutrinos et sur le nombre effectif de neutrinos sont également discutées
The cosmic microwave background (CMB), relic of the hot Big-Bang, carries the traces of both the rich structure formation of the late time epochs and the energetic early phases of the universe.The Planck satellite provided, from 2009 to 2013, high-quality measurements of the anisotropies of the CMB. These are used in this thesis to determine the parameters of the standard cosmological model and of the extension concerning the neutrino sector. The construction of an high-l Planck likelihood is detailed. This involves a masking strategy that deals in particular with the contamination from thermal emission of the Galaxy. The residual foregrounds are treated directly at the power spectrum level relying on physically motivated templates based on Planck studies.The statistical methods needed to extract the cosmological parameters in the comparison between models and data are described, both the Bayesian Monte Carlo Markov Chain techniques and the frequentist profile likelihood. Results on cosmological parameters are presented using Planck data alone and in combination with the small scale data from the ground based CMB experiment ACT and SPT, the Baryon Acoustic Oscillation and the Supernovae. Constraints on the absolute scale of neutrino masses and of the number of effective neutrino are also discussed

Les industries du transport, en particulier les industries automobile et aéronautique, font face plus que jamais à une problématique d’économie d’énergie, qui passe nécessairement par un allègement des structures. Dans ce contexte, les matériaux composites semblent être des candidats idéaux, en raison de l’exceptionnel compromis masse/performance qu’ils présentent. Les procédés LCM (Liquid Composite Molding) et plus particulièrement RTM (Resin Transfer Molding) sont très utilisés pour produire des pièces structurelles complexes de hautes performances. La qualité des pièces ainsi produites dépend fortement de la phase d’imprégnation des renforts fibreux, durant laquelle l’écoulement de la résine induit la création d’une zone non-saturée, provoquant par conséquent la formation de porosités qui affectent les propriétés mécaniques. Les travaux présentés dans cette thèse s’attachent à détecter et à quantifier la saturation du renfort par le biais d’une analyse des transferts de chaleur. Dans un premier temps, le tenseur de conductivité thermique d’un matériau modèle a été caractérisé à l’aide d’un large panel de dispositifs expérimentaux. Une méthode d’homogénéisation a été mise en place afin de prédire les propriétés thermiques du composite en fonction de la nature des vides rencontrés. Par la suite, un banc expérimental doté d’une métrologie thermique adaptée est conçu, permettant l’imprégnation d’un renfort par un fluide modèle. L’identification de la saturation est rendue possible par un modèle simplifié d’écoulement. Enfin, une approche par modélisation diphasique est proposée, démontrant la faisabilité de l’identification des perméabilités relatives de chacune des phases par la thermique
Transportation industries, especially aeronautics and automotive industries, are facing more than ever energy-saving issues, which imply weight reduction of structures. Within this context, composite materials appear to be appropriate candidates, due to their outstanding “strength to weight” ratio. Liquid Composite Molding (LCM) and particularly Resin Transfer Molding (RTM) are becoming increasingly important for a wide range of industrial applications involving complex structural parts. The quality of LCM products strongly depends on the impregnation of the fiber preform during the mold-filling stage. During this step, a partially saturated zone emerges in the flow, and induces consequently the formation of porosities, which drastically affect mechanical performances. This study presents an original approach in which heat transfers are used to quantify the saturation profile. In a first step, the effective thermal conductivity of a model composite material have been measured by several methods. A homogenization methodology based on asymptotic expansion has been performed at dual-scale in order to predict the thermal properties of the composite as a function of saturation. Several heat flux sensors and thermocouples were integrated in an experimental bench, which allows the injection of a model fluid into a textile preform. Finally, an alternative numerical approach is proposed by modeling a multi-phase flow, proving the feasibility of identifying the relative permeabilities of each phase through thermal analysis

Hos vuxna individer förekommer två fenotyper gällande produktionen av laktas, vilka kallas laktostolerans och laktosintolerans. Vid laktosintolerans produceras otillräckliga mängder laktas vilket framkallar symptom som magsmärtor och flatulens vid intagandet av mjölkprodukter. En enbaspolymorfism (LCT-13910C>T) har kopplats till laktostolerans hos nordvästeuropéer och kan genotypas med smältkurveanalys i realtids-PCR. På Laboratoriemedicin vid Länssjukhuset Ryhov används idag en metod vid genotypning av LCT-13910C>T där extraktion av DNA från blod krävs innan analys. Anledningen till detta är att DNA-polymeraset som ingår enzymmixen LightCycler® FastStart DNA Master HybProbe endast fungerar med rent DNA-templat. Med en annan enzymmix, Kapa Probe Force, ska analys kunna göras direkt på blod. För att utvärdera enzymmixen jämfördes resultat från befintlig metod och resultat från metod med Kapa Probe Force, gällande förmågan att identifiera genotyperna LCT-13910C/C, C/T och T/T samt med avseende på imprecision. Vid jämförelse mellan metoderna samstämde resultatet i avseende på genotyp till 100 % utifrån specificerade smälttemperaturer (Tm) för respektive genotyp angivna i kitet för primer/prober. Däremot syntes lägre fluorescensnivå på smältopparna i metod med Kapa Probe Force, men påverkade inte tolkning av smältkurvorna. En lägre prov-till-prov-variation sågs även i resultatet från metod med Kapa Probe Force gentemot befintlig metod.
Among adults two phenotypes are found with regards to production of lactase, these are termed lactase persistence and lactose intolerance. Lactose intolerance is characterized by a low production of lactase, which leads to symptoms such as stomach ache and flatulence after the consumption of dairy products. A single nucleotide polymorphism (LCT-13910C>T) has been correlated with the occurrence of lactase persistence in northwestern Europeans. Genotyping of LCT-13910C>T is possible with melting curve analysis in real time PCR. The currently used method for genotyping of LCT-13910C>T at Ryhov County Hospital requires the extraction of DNA template from blood, due to the fact that the DNA-polymerase in the kit LightCycler® FastStart DNA Master HybProbe requires pure DNA template for analysis. With another DNA-polymerase, included in the kit Kapa Probe Force, analysis on crude samples such as pure blood should be possible. Evaluation of Kapa Probe Force included comparison of the results from both methods with regards to identification of genotypes LCT-13910C/C, C/T and T/T and with regard to imprecision. The results from Kapa Probe Force were 100 % consistent with the results from existing method and acquired melting temperatures (Tm) were all within the accepted ranges specified in the kit of primers and probes. The fluorescence of melting curves acquired with Kapa Probe Force was significantly lower, however this had no effect when it came to interpreting the results. A lower variation could also be seen between samples with Kapa Probe Force compared to existing method.

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O presente trabalho discorre sobre uma alternativa para mitigar o problema do Lodo de Esgoto Sanitário – LES. Esse resíduo influencia negativamente de várias formas o meio ambiente, destacando-se a poluição das águas superficiais e subterrâneas. Teve como objetivo utilizar a biomassa presente no LES para a produção de combustíveis (Bio-óleo e Carvão). Tratou-se de um estudo experimental com a biomassa obtida na Estação Experimental de Tratamento Biológico de Esgotos Sanitários – EXTRABES, localizada na cidade de Campina Grande – PB. O experimento foi realizado em duas etapas: a primeira correspondente ao estudo termogravimétrico e cinético do LES; a segunda, a obtenção do bio-óleo e carvão oriundo da pirólise do LES, realizado no LABCON, instalado na Universidade Federal Fluminense – UFF. Os resultados obtidos do estudo termogravimétrico nas três razões de aquecimento 5,10 e 15ºC.min-1, constatam uma estabilidade térmica a 30ºC sobre atmosferas de ar sintético e N2. No estudo cinético determinaram-se os seguintes parâmetros: Energia de Ativação (Ea), Fator de frequência (A-1), Desvio padrão (sd) e o Coeficiente linear (r), que foram calculados por termogravimetria pelos métodos Coats-Redfern (CR); Madhusudanan (MD); Van Krevelen (VK) e Horowitz-Metzger (HM). Os espectros de FTIR da amostra do LES apresentaram bandas referentes à água, matéria orgânica e óxidos de silício. O bio-óleo foi obtido através do processo da conversão à baixa temperatura, em atmosfera de nitrogênio, atingindo 380°C com tempo de detenção de 2h. O proc esso de pirólise do LES resultou em 9% de bio-óleo, 57% de carvão e 34% de água de pirólise. Observou-se que o bio-óleo obtido é uma mistura complexa de hidrocarbonetos alifáticos, aromáticos, esteróides, compostos oxigenados e nitrogenados, que foi identificada pelas técnicas FTIR, RMN 1H, CG-EM. O carvão apresentou baixa área superficial, não sendo considerado potencialmente bom suporte catalítico, tanto pela metodologia de Langmuir, SLANG 0,748 m2.g-1 quanto por BET, SBET = 0,695m2.g-1. Os resultados confirmam que à Conversão à Baixa Temperatura é uma técnica promissora, tanto para o destino do LES, quanto para obtenção de biocombustíveis.
The present study discusses an alternative to mitigate Sewage Sludge – SS problem. This residue adversely affects the environment in various ways, highlighting pollution of surface and groundwater. It aimed to use the biomass present in the SS for fuel production (Biooil and coal). It was an experimental study with biomass obtained from the Estação Experimental de Tratamento Biológico de Esgotos Sanitários – EXTRABES, located in the city of Campina Grande – PB. The experiment was conducted in two stages: first corresponding to thermogravimetric and kinetic study of the SS; second, obtainment of biooil and coal originated from the pyrolysis of SS, conducted at LABCOM, installed at the Fluminense Federal University – FFU. The results obtained from the thermogravimetric study in the three heating rates 5, 10 and 15oC min-1, found a thermal stability at 30°C on atmospheres of synthetic air and N2. In the kinetic study the following parameters were determined: Activation Energy (Ea), frequency factor (A-1), standard deviation (sd) and linear coefficient (r), that were calculated by thermogravimetry by the Coats-Redern (CR); Madhusudanan (MD); Van Krevelen (VK) and Horowitz-Metzger (HM) methods. The FTIR spectrums from the SS sample presented bands related to water, organic matter and silicon oxides. The biooil was obtained through the conversion at low temperature process, in nitrogen atmosphere, reaching 380oC with holding time of 2h. The pyrolysis process of the SS resulted in 9% of biooil, 57% of coal and 34% of pyrolysis water. It was observed that the biooil obtained is a complex mixture of aliphatic hydrocarbons, aromatics, steroids, nitrogenous and oxygenated compounds, which was identified by the FTIR, RMN 1H, CG-EM techniques. The coal presented low superficial area, not being considered a potentially good catalytic support, by the Langmuir methodology, SLANG 0,748 m2.g-1 as well as the BET, SBET = 0,695m2.g-1. The results confirm that the Conversion at Low Temperature is a promising technique, for both the destination of the SS as well as for the obtainment of biofuels.

Les pegmatites à éléments rares de type LCT sont depuis longtemps étudiées et exploitées pour leurs gemmes et les métaux rares qu’elles contiennent. Malgré de nombreuses études réalisées sur les processus d’enrichissement en éléments rares, ou les mécanismes à l’origine de leurs textures, très peu d’études ont été dédiées aux mécanismes de mise en place des pegmatites et à leur répartition spatiale à l’échelle du champ. Afin de déterminer les mécanismes moteurs à l’origine de l’ascension de ces magmas, une étude multidisciplinaire a été menée sur 3 champs de pegmatites à éléments rares, répartis à l’échelle de la chaîne Varisque. Les résultats démontrent la proximité entre la localisation des pegmatites minéralisées et l’intensité de la déformation encaissante. De plus, la mise en place de ces magmas semble facilitée par un certain mode de fracturation. La modélisation numérique de la mise en place des magmas dans ces zones crustales fragilisées indique que l’ascension est facilitée par leurs faibles viscosité et densité, mais aussi par des perméabilités crustales très élevées (> 10⁻¹² m²), à des profondeurs de l’ordre de 10 km. Enfin, d’après les signatures isotopiques du Li mesurées sur des micas pegmatitiques, le lithium ne fractionne pas depuis le granite voisin, jusqu’aux pegmatites les plus différenciées, puisque les valeurs δ⁷Li (‰) sont toutes comprises dans une gamme de - 2 à + 2 ‰, similaire à celle rencontrée dans les granites orogéniques. Nous suggérons donc que la genèse des magmas pegmatitiques est commune à celle des granites hyperalumineux. Les mécanismes de fracturation et d’attraction (« magma-pumping ») sont envisagés pour avoir favorisé l’ascension de ces magmas résiduels, enrichis en éléments rares, de faibles volumes, au cours de transitions brutales et de courtes durées (~ 10³ ans), de la perméabilité. L’ensemble de ces résultats permet de remettre en question le modèle du granite parent classiquement utilisé pour la prospection de ces gisements, et de proposer un modèle revisité couplant la genèse et la mise en place de ces magmas
LCT-type rare-element pegmatites have long been studied and exploited for their gems and rare metals they contain. Despite many studies about the rare-element enrichment, or about the mechanisms leading their exotic textures, very few studies have been dedicated to the mechanisms controlling their emplacement and their spatial distribution at the scale of the pegmatite field. To better investigate the origin of ascent-driving mechanisms of these magmas, a multidisciplinary study was conducted on 3 rare-element pegmatite fields across the Variscan belt. The results demonstrate the spatial proximity of the rare-metals-rich pegmatites with the intensity of deformation of the hosting rocks. In addition, spatial statistical analyses suggest that the emplacement of such magmas has been facilitated by fracture-controlled model. According to numerical models, the rise of these pegmatite-forming melts along weakened crustal zones would be facilitated by their peculiar physico-chemical properties (low viscosity and density), but also by very high crustal permeability (> 10⁻¹² m²) at depths around 10 km. Finally, accordingly to Li isotope signatures measured on pegmatitic micas, lithium does not fractionate from neighbouring granite up to the more differentiated pegmatites, since all δ⁷Li (‰) fall within a range of - 2 to + 2 ‰, as for orogenic granites. Therefore, we suggest that the genesis these pegmatite-forming melts is common to that of peraluminous granites. Mechanisms of fracturation and magma-pumping may have favoured the rise of these low volumes of residual melts, enriched in rare-elements, during short periods (~ 10³ yrs) of strong permeability increase. These results question the granitic model commonly used for the exploration of this type of mineral deposits. We suggest a revisited model accounting for both genesis and emplacement controlling mechanisms of the pegmatite-forming melts

El Laboratorio de Creación Teatral (LCT) presenta un Modelo Didáctico para la enseñanza de Español como Lengua Extranjera basado en la Dramatización. Desde esta óptica nos planteamos el objetivo principal: Desarrollar un modelo didáctico basado en la dramatización que facilite un progreso efectivo en el desarrollo de la competencia comunicativa. Nuestro modelo estableció su metodología en la incorporación de la voz de los participantes, sus experiencias, actitudes, creencias, pensamientos y reflexiones, a fin de mejorar la calidad del proceso formativo y ayudar a los aprendientes en la reflexión sobre su proceso de aprendizaje, coincidiendo con la reforma a nivel europeo de la formación lingüística, en base a los principios metodológicos, los objetivos, los contenidos y el tipo de actividades recogidos en el Marco de referencia europeo para la enseñanza, aprendizaje y evaluación de las lenguas (2001). El estudio directo se realizó con estudiantes divididos en dos grupos, sobre los que se efectuó la observación participante y la recogida de datos (diarios o correos, cuestionarios y entrevistas informales). Esta micro-etnografía, o etnografía particularista, focalizó la observación e interpretación del fenómeno en una sola institución social (el Instituto Cervantes), un solo centro (el de Milán) y un solo nivel formativo (alumnos que han superado el nivel A2 de Español como Lengua Extranjera). Su carácter fue inductivo, basado en la experiencia y la exploración de primera mano sobre el escenario social, a través de la observación participante, la integración y adaptación progresiva del estudio a los sujetos participantes. Al finalizar el trabajo de campo, los participantes expresaron su percepción positiva del empleo de la dramatización para la formación personal, en el desarrollo de sus habilidades sociales, para la mejora de la relación profesor-alumno, para el crecimiento personal, y para potenciar las estrategias que favorecen la progresión de su competencia comunicativa. Ello, junto al alcance de los objetivos planteados, nos llevó a la conclusión que confirma nuestra tesis de partida: el empleo de técnicas de dramatización adaptadas a la enseñanza de ELE supone, además de incrementar la motivación del aprendiente, el desarrollo de sus habilidades comunicativas, de su creatividad y de sus valores humanos y sociales. Mediante el LCT potenciamos el aprendizaje significativo en ELE, una experiencia de adquisición que repercute directamente en el desarrollo de la competencia comunicativa, tanto en L2, como en la propia L1 del aprendiente.
The Laboratory of Theatrical Creation presents a didactic model for the teaching of Spanish as a Foreign Language, based upon dramatic performance. From this perspective, we lay out the principal objective: to develop a didactic model, based upon drama, that facilitates an effective progress in the development of communicative competence. Our model established its methodology through the incorporation of participants' voices, their experiences, attitudes, beliefs, thoughts and reflections, as a means of improving teaching quality and assisting the students to reflect upon their learning process. This model ties in with the reforms in European language standards, on the basis of its methodological principles, goals, contents and the type of activities gathered from the Common European Framework of Reference for Languages: Learning, Teaching, Assessment (2001). The direct study was performed with students divided into two groups, upon whom observation and data collection (journals or mail, questionnaires and informal interviews) were carried out. This micro-ethnography focussed the observation and interpretation on a single social institution (the Cervantes Institute), a single center (Milan) and a single level (students that have passed level A2 of Spanish as a Foreign Language.) Its character was inductive, based upon firsthand experience and exploration upon a social stage, through participant observation, integration, and progressive adaptation of the study to its participating subjects. Upon completion of fieldwork, the participants expressed a positive perception of the utilization of drama for personal training, development of social abilities, improvement of the teacher-student relationship, personal growth, and the strengthening of strategies that assist in the progression of their communicative competence. This, along with the scope of the established objectives, led us to a conclusion that confirms our thesis: the usage of dramatic techniques adapted to the teaching of ELE, in addition to increasing learner motivation, leads to the development of their communicative abilities, creativity, and human and social values. Through LCT we strengthen meaningful learning in ELE, an acquisition experience that has direct repercussions upon the development of communicative competence, as much in the learner’s L2, as in his own L1.

Recent developments in powder metal oxide processing have enabled co-extrusion of a honeycomb structure with alternating layers of metal and ceramic. Such a structure is envisioned for use as a Solid Oxide Fuel Cell (SOFC) if defects can be minimized during the manufacturing process. The two dissimilar materials tend to shrink at different rates during hydrogen reduction and sintering, inducing internal stresses that lead to structural defects such as cracks, or high residual stresses. The objective of this thesis is to characterize the shrinkage and relaxation mechanisms inherent in both the metal and ceramic so that internal stresses developed during manufacturing can be estimated and ultimately minimized. Constitutive models are adapted from the literature to simulate the sintering and viscoelastic behaviors of the ceramic. Likewise, existing models in the literature are used to characterize the viscoplastic relaxation of the porous powder metal phase and its sintering behavior. Empirical models are developed for the reduction behavior of the metal oxides, based on a series of experiments conducted that measure water vapor (hygrometry) and dimensional change (dilatometry) during reduction and sintering. Similarly, the necessary parameters for the sintering model and viscoplastic model were determined through a series of experiments. The constructed system of constitutive equations appears to have the essential elements for modeling dimensional change, porosity/strength and development of internal (residual) stresses in co-extruded SOFC structures.

The diploma thesis is related to the preparation of hydroxyapatite complex structures by additive manufacturing known as Lithography based ceramics manufacturing – LCM. A photosensitive suspension containing hydroxyapatite particles was used for 3D printing of ceramic complex structures. The influence of printing parameters on the resulting macrostructure, microstructure, density, and dimensional accuracy was evaluated. The aim was to obtain ceramic components without delamination of the layers and optimise following post-processing steps (cleaning and thermal treatment). It was found that the exposure time has a significant effect on the dimensional accuracy of printed parts. During observation microstructure of printed parts, a microporosity at the interface of printed layers, which can cause delamination of several layers was identified. High-temperature dilatometry showed different temperature of beginning densification process in the longitudinal and perpendicular directions to the layers. That could be an initiation mechanism for delamination of the layers. X-ray diffraction analysis determined a single-phase composition of powder in photosensitive suspension and sintered parts. A commercial product LithaSol 20 was suggested as a suitable cleaning agent and efficiency of the ultrasound field for cleaning was demonstrated. Based on the thermogravimetric analysis an optimized cycle of heat treatment was designed. The optimisation led to time saving (49 hours), while maintaining density, dimensional accuracy and macrostructure of the 3D printed structures.

The anterior cingulate cortex (ACC) is part of the cognitive and emotional brain circuitry that mediates social interaction. Imbalances between inhibitory, GABAergic neurons, and excitatory, glutamatergic neurons, in this region are essential to brain circuity during social responses and are thought to be involved with behaviors associated with autism spectrum disorder (ASD). Enriched cell populations of glutamatergic neurons, obtained through laser capture microdissection, were used for gene expression studies of GABAergic receptors (GABRA1, GABRA4, and GABBR1). Additionally, proteins that impact GABAergic synapses (Spinophilin, CPLX1, mTOR, IGF1R, PSD95, PARP1) were investigated using Western Blotting with punchdissected homogenate brain tissue from ACC and frontal cortical brain regions. No significant differences in gene expression nor protein were identified between ASD and control brain donors. Evidence of GABAergic synaptic pathology was not found; however, future studies of alternative GABAergic markers and increased study numbers are needed to confirm these findings in ASD human tissue.

The usage of navigation meshes for path planning in games and otherdomains is a common approach. One type of navigation mesh that recently has beendeveloped is the Local Clearance Triangulation (LCT). The overall aim of the LCT isto construct a triangulation in such a way that a property called theLocal Clearancecan be used to calculate a path in a more efficient and cheap way. At the time ofwriting the thesis there only exists one solution that creates an LCT, this solution isonly using the CPU. Since the process of creating an LCT involves the insertion ofmany points and edge flips which only affects a local area it would be interesting toinvestigate the potential performance gain of using the GPU. The objective of the thesis is to develop a GPU version based on thecurrent CPU LCT solution and to investigate in which cases the proposed GPU al-gorithm performs better. A GPU version and a CPU version of the proposed algorithm has beendeveloped to measure the performance gain of using the GPU, there are no algorith-mic differences between these versions. To measure the performance of the algorithmtwo tests have been constructed, the first test is called the Object Insertion test andmeasures the time it takes to build an LCT using generated test maps. The sec-ond test is called the Internal test and measures the internal performance of thealgorithm. A comparison between the GPU algorithm with an LCT library called Triplanner was also done. The proposed algorithm performed better on larger maps when imple-mented on a GPU compared to a CPU implementation of the algorithm. The GPU performance compared to the Triplanner was faster in some of the larger maps. An algorithm that builds an LCT from scratch is presented. Theresults show that using the proposed algorithm on the GPU substantially increasesthe performance of the algorithm compared to when implementing it on a CPU.

El linfoma de células del manto (LCM) es una entidad heterogénea tanto en sus aspectos biológicos como en su comportamiento clínico. La existencia de pacientes con mala respuesta al tratamiento sugiere que, de manera análoga a otros síndromes linfoproliferativos crónicos, existen alteraciones en los mecanismos de citotoxicidad inducida por fármacos. La heterogeneidad clínica del LCM queda reflejada, entre otros, por la variabilidad en la presentación de expresión hemoperiférica e infiltración del sistema nervioso central (SNC), dos complicaciones controvertidas y no suficientemente estudiadas.

La hipótesis planteada en la presente tesis fue que la heterogeneidad observada en el LCM podría ser debida a la existencia de alteraciones en los mecanismos de apoptosis en un subgrupo de pacientes y se relacionaría con el pronóstico de éstos. Por otro lado, el análisis exhaustivo de los pacientes con expresión hemoperiférica o infiltración del SNC permitiría establecer cuáles son las características clínicas y biológicas que determinan la aparición de estas complicaciones en determinados enfermos. Para confirmar esta hipótesis nos planteamos los siguientes objetivos: 1) estudiar las bases moleculares de la regulación de la apoptosis en el LCM, tanto en líneas celulares como en células primarias de pacientes afectos; 2) analizar la incidencia y el impacto pronóstico de la expresión hemoperiférica en los enfermos con LCM mediante citología y citometría de flujo y 3) estudiar la incidencia y los factores determinantes de la infiltración del SNC en pacientes afectos de esta hemopatía.

Para el estudio de las bases moleculares de la apoptosis en el LCM se analizaron cuatro líneas celulares portadoras de la t(11;14)(q13;q32), característica de esta entidad, y células primarias de 10 pacientes con LCM. El análisis de la viabilidad celular mediante marcaje con anexina V y yoduro de propidio, la detección de la pérdida de potencial de membrana y la producción de ROS, la determinación de caspasa 3 activa y de los cambios de conformación de BAX y BAK se llevaron a cabo mediante citometría de flujo (CMF). El análisis de diversas proteínas de la familia de BCL-2 se realizó mediante "Western blot". El estudio del ciclo celular se efectuó asimismo mediante CMF. El análisis de las alteraciones cromosómicas existentes en los LCM leucemizados se realizó mediante hibridación genómica comparada (CGH). Las diferencias entre subgrupos de pacientes se analizaron mediante la prueba exacta de Fisher y la t de Student. El análisis de supervivencia se llevó a cabo mediante el método de Kaplan y Meier y las diferencias observadas en términos de supervivencia se analizaron con el "log-rank test". El análisis de variables dependientes del tiempo se efectuó mediante el método de Mantel y Byar.

Los resultados obtenidos en el primer trabajo demuestran que la citotoxicidad inducida por mitoxantrona en las células del LCM fue debida a la activación de la vía mitocondrial de apoptosis, y tiene lugar, probablemente, de manera dependiente de la integridad de los sensores de daño al ADN. Los resultados del segundo trabajo permiten concluir que la expresión hemoperiférica detectada mediante CMF se observa en la mayoría de los pacientes con LCM, incluso en aquellos con recuentos linfocitarios normales. Aunque la leucemización morfológica no se asoció en nuestro estudio con ninguna alteración citogenética específica detectable mediante CGH, los casos con linfocitosis >/5 x 10(9)/L presentaron anomalías citogenéticas diferenciales y un peor pronóstico. Los resultados del tercer trabajo demuestran que la infiltración del SNC se presenta fundamentalmente en pacientes con LCM blastoide, índice proliferativo elevado, niveles de LDH sérica elevados e IPI de riesgo intermedio/alto o alto, en general en el contexto de recidivas o progresiones sistémicas.
"BIOLOGICAL AND CLINICAL PROGNOSTIC FACTORS IN MANTLE CELL LYMPHOMA"

TEXT:

Mantle cell lymphoma (MCL) is characterized by the presence of translocation t(11;14)(q13;q32), an aggressive clinical course and poor response to chemotherapy. Few data concerning drug-induced apoptosis in MCL have been reported. The aim of the first study that constitutes the present thesis was to analyze the mechanisms of drug-induced apoptosis in MCL. Four cell lines carrying the t(11;14) and primary cells of 10 patients with MCL were incubated in vitro with several drugs currently used in the treatment of lymphoproliferative disorders and drug-induced cell death was characterized. Our results support that MCL cells have functional apoptotic machinery but require the integrity of functional DNA-damage response genes for its activation.

From a clinical standpoint, extranodal involvement is a well-known feature in patients with MCL. Relatively few studies to date have focused on the peripheral blood (PB) involvement and the incidence of leukemic expression in MCL varies highly in different studies. The objective of our second study was to analyze the incidence, and the biological and clinical significance of leukemic involvement in patients with MCL. We investigated the incidence of PB involvement by both morphologic and flow cytometry (FC) analyses. Clinical features, genetic abnormalities detected by comparative genomic hybridization (CGH) and patient outcome were also determined. Leukemic expression at diagnosis detected by FC was a highly common feature, even in patients with a normal lymphocyte count. Although morphologically apparent leukemic expression was not associated with specific chromosomal alterations detected by CGH, a lymphocyte count >/ 5 x 10(9)/L was correlated with particular genetic abnormalities and a poor outcome.

The incidence of central nervous system (CNS) involvement in patients with MCL is also highly variable in different studies, and predicting factors and outcome of CNS infiltration in these patients have not been thoroughly investigated. The aim of our study was to assess the incidence and factors for CNS involvement in MCL. In addition, we analyzed the clinical features, therapy and outcome of patients with MCL once CNS infiltration was detected. Our results suggest that, in most cases, CNS involvement occur late in the course of the disease, as part of a generalized relapse or progression. Blastoid histology, high proliferative index, high serum LDH and high-risk IPI are the variables associated with a higher risk to develop this complication.

The Dumper Dew is a newly discovered pegmatite located on the eastfacing slope of Uncle Tom Mountain in Oxford County, Maine. It is a geochemically evolved LCT-type pegmatite petrogenetically linked to the middle Paleozoic Sebago batholith. Shallow emplacement of the Dumper Dew is evidenced by abundant miarolitic cavities found in the pegmatite. The sheet-like structure of the pegmatite coupled with its intrusion in lowmetamorphic grade country rock suggests rapid crystallization. Northern portions of the wall zone and intermediate zones have undergone hydrothermal alteration by the migration of late-stage fluids. The pegmatite hosts a diverse assemblage of rare-element mineral phases due to its high degree of geochemical fractionation. Trends of geochemical fractionation of individual mineral phases such as K-feldspar, muscovite, garnet, apatite, beryl, spodumene, triphylite-lithiophilite, tourmaline, cassiterite, and columbite-tantalite were attained via instrumentation assay. These trends illustrate an enhanced degree of magmatic differentiation relative to other pegmatites in the area.

Lithium Cesium Tantalum (LCT) pegmatites are important resources for rare metals like Cesium, Lithium or Tantalum, whose demand increased markedly during the past decade. At present, Cs is known to occur in economic quantities only from the two LCT pegmatite deposits at Bikita located in Zimbabwe and Tanco in Canada. Host for this Cs mineralisation is the extreme rare zeolite group mineral pollucite. However, at Bikita and Tanco, pollucite forms huge massive, lensoid shaped and almost monomineralic pollucite mineralisations that occur within the upper portions of the pegmatite. In addition, both pegmatite deposits have a comparable regional geological background as they are hosted within greenstone belts and yield a Neoarchean age of about 2,600 Ma. Furthermore, at present the genesis of these massive pollucite mineralisations was not yet investigated in detail. Major portions of Western Australia consist of Meso- to Neoarchean crustal units (e.g., Yilgarn Craton, Pilbara Craton) that are known to host a large number of LCT pegmatite systems. Among them are the LCT pegmatite deposits Greenbushes (Li, Ta) and Wodgina (Ta, Sn). In addition, small amounts of pollucite were recovered from one single diamond drill core at the Londonderry pegmatite field. Despite that, no systematic investigations and/or exploration studies were conducted for the mode of occurrence of Cs and especially that of pollucite in Western Australia. In the course of the present study nineteen individual pegmatites and pegmatite fields located on the Yilgarn Craton, Pilbara Craton and Kimberley province have been visited and inspected for the occurrence of the Cs mineral pollucite. However, no pollucite could be detected in any of the investigated pegmatites. Four of the inspected LCT-pegmatite systems, namely the Londonderry pegmatite field, the Mount Deans pegmatite field, the Cattlin Creek LCT pegmatite deposit (Yilgarn Craton) and the Wodgina LCT pegmatite deposit (Pilbara Craton) was sampled and investigated in detail. In addition, samples from the Bikita pegmatite field (Zimbabwe Craton) were included into the present study in order to compare the Western Australian pegmatites with a massive pollucite mineralisation bearing LCT pegmatite system. This thesis presents new petrographical, mineralogical, mineralchemical, geochemical, geochronological, fluid inclusion and stable and radiogenic isotope data. The careful interpretation of this data enhances the understanding of the LCT pegmatite systems in Western Australia and Zimbabwe. All of the four investigated LCT pegmatite systems in Western Australia, crop out in similar geological settings, exhibit comparable internal structures, geochemistry and mineralogy to that of the Bikita pegmatite field in Zimbabwe. Furthermore, in all LCT pegmatite systems evidences for late stage hydrothermal processes (e.g., replacement of feldspars) and associated Cs enrichment (e.g., Cs enriched rims on mica, beryl and tourmaline) is documented. With the exception of the Wodgina LCT pegmatite deposit, that yield a Mesoarchean crystallisation age (approx. 2,850 Ma), all other LCT pegmatite systems gave comparable Neoarchean ages of 2,630 Ma to 2,600 Ma. The almost identical ages of the LCT pegmatite systems of the Yilgarn and Zimbabwe cratons suggests, that the process of LCT pegmatite formation at the end of the Neoarchean was active worldwide. Nevertheless, essential distinguishing feature of the Bikita pegmatite field is the presence of massive pollucite mineralisations that resulted from a process that is not part of the general development of LCT pegmatites and is associated with the extreme enrichment of Cs. The new findings of the present study obtained from the Bikita pegmatite field and the Western Australian LCT pegmatite systems significantly improve the knowledge of Cs behaviour in LCT pegmatite systems. Therefore, it is now possible to suggest a genetical model for the formation of massive pollucite mineralisations within LCT pegmatite systems. LCT pegmatites are generally granitic in composition and are interpreted to represent highly fractionated and geochemically specialised derivates from granitic melts. Massive pollucite mineralisation bearing LCT pegmatites evolve from large and voluminous pegmatite melts that intrude as single body along structures within an extensional tectonic setting. After emplacement, initial crystallisation will develop the border and wall zone of the pegmatites, while due to fractionated crystallisation immobile elements (i.e., Cs, Rb) become enriched within the remaining melt and associated hydrothermal fluids. Following this initial crystallisation, a relatively small portion (0.5–1 vol.%) of immiscible melt or fluid will separate during cooling. This immiscible partial melt/fluid is enriched in Al2O3 and Na2O, as well as depleted in SiO2 and will crystallise as analcime. In addition, this melt might allready contains up to 1–2 wt.% Cs2O. However, due to the effects of fluxing components (e.g., H2O, F, B) this analcime melt becomes undercooled which prevents crystallisation of the analcime as intergranular grains. Since this analcime melt exhibits a lower relative gravity when compared to the remaining pegmatite melt the less dense analcime melt will start to ascent gravitationally and accumulate within the upper portion of the pegmatite sheet. At the same time, the remaining melt will start to crystallise separately and form the inner portions of the pegmatite. This crystallisation is characterised by still ongoing fractionation and enrichment of incompatible elements (i.e., Cs, Rb) within the last crystallising minerals (e.g., lepidolite) or concentration of these incompatible elements within exsolving hydrothermal fluids. As analcime and pollucite form a continuous solid solution series, the analcime melt is able to incorporate any available Cs from the melt and/or associated hydrothermal fluids and crystallise as Cs-analcime in the upper portion of the pegmatite sheet. Continuing hydrothermal activity and ongoing substitution of Cs will then start to shift the composition from Cs-analcime composition towards Na-pollucite composition. In addition, if analcime is cooled below 400 °C it is subjected to a negative thermal expansion of about 1 vol.%. This contraction results in the formation of a prominent network of cracks that is filled by late stage minerals (e.g., lepidolite, quartz, feldspar and petalite). Certainly, prior to filling, this network of cracks enhances the available conduits for late stage hydrothermal fluids and the Cs substitution mechanism within the massive pollucite mineralisation. Furthermore, during cooling of the pegmatite, prominent late stage mineral replacement reactions (e.g., replacement of K-feldspar by lepidolite, cleavelandite, and quartz) as well as subsolidus self organisation processes in feldspars take place. These processes are suggested to release additional incompatible elements (e.g., Cs, Rb) into late stage hydrothermal fluids. As feldspar forms large portions of pegmatite a considerable amount of Cs is released and transported via the hydrothermal fluids towards the massive pollucite mineralisation in the upper portion of the pegmatite. Consequently, the initial analcime can accumulate enough Cs in order to shift its composition from the Cs-analcime member (>2 wt.% Cs2O) towards the Na-pollucite member (23–43 wt.% Cs2O) of the solid solution series. The timing of this late stage Cs enrichment is interpreted to be quasi contemporaneous or immediately after the complete crystallisation of the pegmatite melt. However, much younger hydrothermal events that overprint the pegmatite are also interpreted to cause similar results. Hence, it has been demonstrated that the combination of this magmatic and hydrothermal processes is capable to generate an extreme enrichment in Cs in order to explain the formation of massive pollucite mineralisations within LCT pegmatite systems. This genetic model can now be applied to evaluate the potential for occurrences of massive pollucite mineralisations within LCT pegmatite systems in Western Australia and worldwide
Lithium-Caesium-Tantal-(LCT) Pegmatite repräsentieren eine bedeutende Quelle für seltene Metalle, deren Bedarf im letzten Jahrzehnt beträchtlich angestiegen ist. Im Falle von Caesium sind zurzeit weltweit nur zwei LCT-Pegmatitlagerstätten bekannt, die abbauwürdige Vorräte an Cs enthalten. Dies sind die LCT-Pegmatitlagerstätten Bikita in Simbabwe und Tanco in Kanada. Das Wirtsmineral für diese Cs-Mineralisation ist das extrem selten auftretende Zeolith-Gruppen-Mineral Pollucit. In den Lagerstätten Bikita und Tanco bildet Pollucit dagegen massive, linsenförmige und fast monomineralische Pollucitmineralisationen, die in den oberen Bereichen der Pegmatitkörper anstehen. Zusätzlich befinden sich beide Lagerstätten in geologisch vergleichbaren Einheiten. Die Nebengesteine sind Grünsteingürtel die ein neoarchaisches Alter von ca. 2,600 Ma aufweisen. Die Bildung derartiger massiver Pollucitmineralisationen ist bis jetzt noch nicht detailliert untersucht worden. Große Bereiche von Westaustralien werden von meso- bis neoarchaischen Krusteneinheiten (z.B. Yilgarn Kraton, Pilbara Kraton) aufgebaut, von denen auch eine große Anzahl an LCT-Pegmatitsystemen bekannt sind. Darunter befinden sich unter anderem die LCT-Pegmatitlagerstätten Greenbushes (Li, Ta) und Wodgina (Ta, Sn). Zusätzlich wurden kleine Mengen an Pollucit in einer einzigen Kernbohrung im Londonderry Pegmatitfeld angetroffen. Ungeachtet dessen, wurden in Westaustralien bis jetzt keine systematischen Untersuchungen und/oder Explorationskampagnen auf Vorkommen von Cs und speziell der von Pollucit durchgeführt. Im Verlauf dieser Studie wurden insgesamt neunzehn verschiedene Pegmatitvorkommen und Pegmatitfelder des Yilgarn Kratons, Pilbara Kratons und der Kimberley Provinz auf das Vorkommen des Minerals Pollucit untersucht. Allerdings konnte in keinem der untersuchten LCT-Pegmatitsystemen Pollucit nachgewiesen werden. Von vier der untersuchten LCT-Pegmatitsystemen, dem Londonderry Pegmatitfeld, dem Mount Deans Pegmatitfeld, der Cattlin Creek LCT-Pegmatitlagerstätte (Yilgarn Kraton) und der Wodgina LCT-Pegmatitlagerstätte (Pilbara Kraton) wurden detailliert Proben entnommen und weitergehend untersucht. Zusätzlich wurden die massiven Pollucitmineralisationen im Bikita Pegmatitfeld beprobt und in die detailierten Untersuchungen einbezogen. Der Probensatz aus dem Bikita Pegmatitfeld dient als Referenzmaterial mit dem die Pegmatitproben aus Westaustralien verglichen werden. Die vorliegende Arbeit fasst die wesentlichen Ergebnisse der petrographischen, mineralogischen, mineralchemischen, geochemischen und geochronologischen Untersuchungen sowie der Flüssigkeitseinschlussuntersuchungen und stabilen und radiogenen Isotopenzusammensetzungen zusammen. Alle vier der in Westaustralien untersuchten LCT-Pegmatitsysteme kommen in geologisch ähnlichen Rahmengesteinen vor, weisen einen vergleichbaren internen Aufbau, geochemische Zusammensetzung und Mineralogie zu dem des Bikita Pegmatitfeldes in Simbabwe auf. Weiterhin konnten in allen LCT-Pegmatitsystemen Hinweise für späte hydrothermale Prozesse (z.B. Verdrängung von Feldspat) nachgewiesen werden, die einhergehend mit einer Anreicherung von Cs verbunden sind (z.B. Cs-angereicherte Säume um Glimmer, Beryll und Turmalin). Mit der Ausnahme der Wodgina LCT-Pegmatitlagerstätte, in der ein mesoarchaisches Kristallisationsalter (ca. 2,850 Ma) nachgewiesen wurde, lieferten die Altersdatierungen in den anderen LCT-Pegmatitsystemen übereinstimmende neoarchaische Alter von 2,630 Ma bis 2,600 Ma. Diese fast identischen Alter der LCT-Pegmatitsysteme des Yilgarn und Zimbabwe Kratons suggerieren, dass die Prozesse, die zur LCT-Pegmatitbildung am Ende des Neoarchaikums führten, weltweit aktiv waren. Ungeachtet dessen stellt das Vorhandensein von massiver Pollucitmineralisation das Alleinstellungsmerkmal des Bikita Pegmatitfeldes dar, welche sich infolge eines Prozesses gebildet haben der nicht Bestandteil der üblichen LCT-Pegmatitentwicklung ist und sich durch eine extreme Anreicherung an Cs unterscheidet. Die neuen Ergebnisse die in dieser Studie von den Bikita Pegmatitfeld und den Westaustralischen LCT-Pegmatitsystemen gewonnen wurden, verbessern das Verständnis des Verhaltens von Cs in LCT-Pegmatitsystemen deutlich. Somit ist es nun möglich, ein genetisches Modell für die Bildung von massiven Pollucitmineralisationen in LCT-Pegmatitsystemen vorzustellen. LCT-Pegmatite weisen im Allgemeinen eine granitische Zusammensetzung auf und werden als Kristallisat von hoch fraktionierten und geochemisch spezialisierten granitischen Restschmelzen interpretiert. Die Bildung von massiven Pollucitmineralisationen ist nur aus großen und voluminösen Pegmatitschmelzen, die als einzelner Körper entlang von Störungen in extensionalen Stressregimen intrudieren möglich. Nach Platznahme der Schmelze bildet die beginnende Kristallisation zunächst die Kontakt- und Randzone des Pegmatits, wobei infolge von fraktionierter Kristallisation die immobilen Elemente (v.a. Cs, Rb) in der verbleibenden Restschmelze angereichert werden. Im Anschluss an diese erste Kristallisation entmischt sich nach Abkühlung eine sehr kleine Menge (0.5–1 vol.%) Schmelze und/oder Fluid von der Restschmelze. Diese nicht mischbare Teilschmelze/-fluid ist angereichert an Al2O3 und Na2O sowie verarmt an SiO2 und kristallisiert als Analcim. Zusätzlich kann diese Schmelze bereits mit 1–2 wt.% Cs2O angereichert sein. Aufgrund der Auswirkung von Flussmitteln (z.B. H2O, F, B) wird allerdings der Schmelzpunkt dieser Analcimschmelze herabgesetzt und so die Kristallisation des Analcims als intergranulare Körner verhindert. Da diese Analcimschmelze im Vergleich zu der restlichen Schmelze eine geringere relative Dichte besitzt, beginnt sie gravitativ aufzusteigen und sich in den oberen Bereichen des Pegmatitkörpers zu akkumulieren. Währenddessen beginnt die restliche Schmelze separat zu kristallisieren und die inneren Bereiche des Pegmatits zu bilden. Diese Kristallisation ist einhergehend mit fortschreitender Fraktionierung und der Anreicherung von inkompatiblen Elementen (v.a. Cs, Rb) in den sich als letztes bildenden Mineralphasen (z.B. Lepidolit) oder der Konzentration der inkompatiblen Element in die sich entmischenden hydrothermalen Fluiden. Da Analcim und Pollucit eine lückenlose Mischungsreihe bilden, ist die Analcimschmelze in der Lage, alles verfügbare Cs von der Restschmelze und/oder assoziierten hydrothermalen Fluiden an sich zu binden und als Cs-Analcim im oberen Bereich des Pegmatitkörpers zu kristallisieren. Fortschreitende hydrothermale Aktivität und Substitution von Cs verschiebt dann die Zusammensetzung des Analcims von der Cs-Analcim- zu Na-Pollucitzusammensetzung. Zusätzlich erfährt der Analcim bei Abkühlung unter 400 °C eine negative thermische Expansion von ca. 1 vol.%. Diese Kontraktion führt zu der Bildung des markanten Rissnetzwerkes das durch späte Mineralphasen (z.B. Lepidolit, Quarz, Feldspat und Petalit) gefüllt wird. Vor der Mineralisation allerdings, erhöht dieses Netzwerk an Rissen die verfügbaren Wegsamkeiten für die späten hydrothermalen Fluide und begünstigt somit den Cs-Substitutionsmechanismus in der massiven Pollucitmineralisation. Weiterhin kommt es bei der Abkühlung des Pegmatits zu späten Mineralverdrängungsreaktionen (z.B. Verdrängung von K-Feldspat durch Lepidolit, Cleavelandit und Quarz), sowie zu Subsolidus-Selbstordnungsprozessen in Feldspäten. Diese Prozesse werden weiterhin interpretiert inkompatible Elemente (z.B. Cs, Rb) in die späten hydrothermalen Fluide freizusetzen. Da Feldspäte große Teile der Pegmatite bilden, kann somit eine beträchtliche Menge an Cs freigeben werden und durch die späten hydrothermalen Fluide in die massive Pollucitmineralisation in den oberen Bereichen des Pegmatitkörpers transportiert werden. Infolgedessen ist es möglich, dass genügend Cs frei gesetzt werden kann, um die Zusammensetzung innerhalb der Mischkristallreihe von Cs-Analcim (>2 wt.% Cs2O) zu Na-Pollucit (23–43 wt.% Cs2O) zu verschieben. Die zeitliche Einordnung dieser späten Cs-Anreicherung wird als quasi zeitgleich oder im direkten Anschluss an die vollständige Kristallisation der Pegmatitschmelze interpretiert. Es kann allerdings nicht vernachlässigt werden, dass auch jüngere hydrothermale Ereignisse, die den Pegmatitkörper nachträglich überprägen, ähnliche hydrothermale Prozesse hervorrufen können. Somit konnte gezeigt werden, dass es durch Kombination dieser magmatischen und hydrothermalen Prozessen möglich ist, genügend Cs anzureichern, um die Bildung von massiven Pollucitmineralisationen in LCT-Pegmatitsystemen zu ermöglichen. Dieses genetische Modell kann nun dazu genutzt werden, um das Potential von Vorkommen von massiven Pollucitmineralisationen in LCT-Pegmatitsystemen in Westaustralien und weltweit besser einzuschätzen

A great effort has been carried out over the recent years in the understanding of the flow field and heat transfer in the internal cooling channels present in turbine blades. Indeed, advanced cooling schemes have not only lead to the increase of the gas turbine efficiency by increasing the Turbine Inlet Temperature above the material melting temperature, but also the increase of the turbine lifespan. To allow such progresses, modern experimental and numerical techniques have been widely applied in order to interpret and optimize the aerodynamics and heat transfer in internal cooling channels. However, the available data is limited in the case of internal cooling channels in turbine rotor blades. Rotation and temperature gradients introduce Coriolis and centripetal buoyancy forces in the rotating frame of reference, modifying significantly the aerothermodynamics from that of the stationary passages. In the case of turbine rotor blades, most of the investigations are either based on point-wise measurements or are constraint to low rotational regimes. The main objective of this work is to study the detailed flow and heat transfer of an internal cooling channel at representative engine dimensionless operating conditions. This work introduces a laboratory test section that operates ribbed channels over a wide range of Reynolds, Rotation and Buoyancy numbers. In the present work, the Reynolds number ranges from 15,000 to 55,000, the maximum Rotation number is equal to 0.77, and the maximum Buoyancy number is equal to 0.77. The new experimental facility consists in a versatile design that allows the interchangeability of the tested geometry, so that channels of different aspect ratios and rib geometries can be easily fitted. Particle Image Velocimetry and Liquid Crystal Thermography are performed to provide accurate velocity and heat transfer measurements under the same operating conditions, which lead to a unique experimental data set. Moreover, Large Eddy Simulations are carried out to give a picture of the entire flow field and complement the experimental observations. Additionally, the numerical approach intends to provide a robust methodology that is able to provide high fidelity predictions of the performance of internal cooling channels.

Les antennes microruban et en particulier l’antenne microruban rectangulaire sont étudiées et utilisées depuis plusieurs dizaines d’années.

Comme pour toute antenne, il est important de disposer pour ces antennes d’un modèle analytique qui permette une bonne compréhension du fonctionnement et fournisse de manière rapide des valeurs pour les principaux paramètres (fréquence de travail, impédance, gain, rendement et bande passante).

Au fil des ans, deux modèles, chacun comprenant de nombreuses variantes, ont été développés :le modèle dit « de la ligne de transmission » et le modèle dit « de la cavité ». Ces modèles sont soit peu rigoureux, soit complexes et donnent souvent des résultats assez éloignés de la réalité.

L’objectif de ce travail est double :définir un modèle qui soit d’une part aussi simple et direct que possible et d’autre part aussi précis que possible.

Le premier objectif est atteint dans la mesure où on n’utilise que la loi fondamentale du rayonnement des courants réels (électriques) en excluant tout recours à des courants virtuels (magnétiques).

Concernant l’objectif de précision, des comparaisons nombreuses avec des résultats d’un simulateur purement numérique et des mesures indiquent une amélioration pour tous les paramètres mais en particulier pour l’impédance qui est le point faible de tous les modèles existants.

Microstrip antennas and the rectangular microstrip antenna in particular have been studied and used for several decades.

As every antenna, the microstrip antenna requires a good analytical model that provides physical insight and an easy prediction of the antenna parameters (resonance frequency, impedance, gain, efficiency and bandwidth).

Over the years, two families of models have been developed, each involving many variants: the “transmission line” and the “cavity” models. These models either lack accuracy or are very complex and produce results that may be far away from reality.

The objective of this work is double: defining a model as simple and direct as possible and on the other hand as accurate as possible.

The first objective has been reached as all our calculations rest on the fundamental radiation formula by real (electrical) currents excluding any virtual (magnetic) currents.

Regarding accuracy, comparisons to numerical simulations and measurements show an improvement, in particular with regard to the prediction of the impedance parameters, which is the weak point of all existing models.

Doctorat en Sciences de l'ingénieur
info:eu-repo/semantics/nonPublished

Dans cette étude, une nouvelle approche numérique intitulée modèle de fuite multicouche a été développée permettant la simulation efficace par des éléments coques 2D multicouches de la nature tridimensionnelle de l’écoulement dans des préformes multicouches pourvues ou non d’un drainant et caractérisées par un fort gradient d’anisotropie le long de l’épaisseur. La convergence de l’approche développée a été démontrée via une comparaison avec un modèle 2D dans le plan xz. L’efficacité du modèle de fuite vis-à-vis du modèle 3D a été quantifiée. L’intérêt de la nouvelle approche numérique a été révélé via des problèmes à échelle industriel à savoir l’optimisation de la stratégie de dépôt de drainant dans un raidisseur en Hi-Tape, la simulation de remplissage d’une coque de bateau pendant le procédé VARTM et l’étude de l’écoulement dans un stratifié NCF
In this study, a new numerical approach called « Multilayer Leakage Model » has been developed for the efficient numerical simulation of the 3D flow by 2D multilayered shell elements in anisotropic multilayer preform with or without a distribution medium. The convergence of the developed approach has been demonstrated by a comparison with a 2D model in the xz plan. The efficiency of the multilayer leakage model versus the 3D model has been quantified. The advantage of the new numerical approach has been verified through industrial part simulations such as the optimization of distribution medium position in a Hi-Tape stiffener, the flow simulation of a boat in VARTM process and the flow analysis of a NCF laminate

Cette étude porte sur la mise en œuvre par infusion d'une nouvelle génération de renfort spécialement dédiée aux procédés LCM (Liquid Composite Molding) pour la réalisation de pièces composites. Par l’expérimentation et la simulation numérique, l’objectif de ces travaux est de comprendre et maîtriser les paramètres de fabrication afin de définir des outils de modélisation et de simulation représentatifs voir prédictifs du procédé. La caractérisation des paramètres du procédé et de la santé matière finale des pièces ont ainsi permis de définir l'échelle de modélisation et les phénomènes physiques devant être simulés. La stratégie numérique adoptée repose sur un couplage fort entre les équations de Stokes et de Darcy dans un cadre de grandes transformations et où les interfaces sont représentées par des Level-Set. Ce couplage modélise l'écoulement dans la préforme fibreuse assimilée à un milieu poreux homogène équivalent (modèle de Darcy) et l'écoulement dans les drainants (modèle de Stokes). Un modèle de Terzaghi réalise le couplage fluide-solide en représentant l'action du fluide sur le renfort via sa pression hydrostatique. L’évolution du taux volumique de fibres et de la perméabilité du milieu sont ainsi actualisés dans les différents problèmes. La confrontation des simulations numériques aux caractérisations expérimentales mettent en évidence qu'un effort important doit être réalisé dans la compréhension, la définition et la caractérisation de la perméabilité. Sur les renforts de l'étude, la question même de la représentation et de l'homogénéisation d'écoulements locaux complexes à travers la seule notion de perméabilité est à poser
This study deals with the manufacturing by infusion of a new high performance fibrous reinforcement solution developed for LCM (Liquid Composite Molding) composite materials manufacturing processes. Combining simulations with experimentations, the aim of this work is to understand and control the process parameters in order to develop accurate simulation tools. Involving specific experimental plan and protocols combined with in-situ monitoring technologies this study points out the physics and length scales challenging the process simulation. The numerical strategy considered in this works is based on a strong coupling between a Stokes and Darcy model undergoing large strains and where interfaces are represented and managed by a Level-Set method. At the process scale, the fluid mechanics problem describes the resin flow through the distribution medium and then through fibrous preforms assimilated to porous medium. A key feature of our approach is the fluid-solid interaction leading to couple a fluid/porous flow with a non-linear solid mechanic problem. The interaction phenomenon due to the resin flow in the orthotropic highly compressible preform is based on both Terzaghi’s law and explicit relations expressing permeability as function of porosity. Some numerical simulations are presented and compared to the experimental characterizations. The results point out the the first necessity to work on the permeability comprehension, definition and characterization. Applied to the specific reinforcements of the study, the representation of the complex local flows and their homogenization through this single permeability notion can also be questionable

Le maïs, l'une des plantes les plus cultivées au monde, sert de base dans l'alimentation humaine et des ruminants et pour la production d'agrocarburant. Sa valeur agronomique est principalement liée à la digestibilité des constituants de la paroi cellulaire (sucres, lignines,. . . ). De nombreuses études ont été menées afin d'améliorer la digestibilité de cette paroi, notamment sur la voie de biosynthèse des lignines. Au cours de ma thèse, nous avons démontré, chez le maïs, que la mutation du gène ZmCCR1 (Cinnamoyl-CoA reductase), codant pour une enzyme clé de la voie de biosynthèse des lignines, conduisait à une diminution des unités H associée à une meilleure digestibilité. La deuxième partie de mes recherches a porté sur l'identification des paramètres influençant la digestibilité à l'échelle cellulaire. En effet, il existe chez le maïs une très grande diversité de types cellulaires à paroi lignifiée non seulement entre différents organes, mais également au sein de chaque organe (sclérenchyme, parenchyme, vaisseaux de xylème. . . ). Dans ce but, une étude combinant de multiples techniques biochimique, histologique et transcriptomique, a été réalisée sur deux lignées de digestibilité contrastée. Ainsi, nous avons mis en évidence l'importance de la proportion de tissus lignifiés, plus particulièrement du sclérenchyme périvasculaire. Au-delà, le développement de la microdissection laser (LCM) a permis de souligner la différence de composition des tissus lignifiés
Maize is one of the most widely grown crops in the world and is grown for grain for human consumption, feedstock for cattle and more recently biofuel. When used as fuel, the most important agronomic trait is digestibility which is dictated by cell wall composition and structure. Many studies have been undertaken in order to improve cell wall digestibility and have essentially focused on the lignin biosynthetic pathway. During my PhD research, we have shown that a mutation in ZmCCR1 (Cinnamoyl-CoA reductase 1), key enzyme in lignin biosynthesis, modified lignin structure which in turn resulted in an increase in digestibility. Beyond lignification per se, my studies focused on the identification of other potential parameters influencing digestibility at the cellular level. This is especially pertinent in maize since its stem biomass is made up of different several lignified tissues and cell types. By combining cell wall biochemistry on laser microdissected (LMD) lignified tissues, with histological studies, we have been able to show that in highly contrasting lines (Cm484 and F98902) the lignified cell types patterning and in particular, the amount and cell wall composition are critical factors in determining maize digestibility

Philosophiae Doctor - PhD
Framed by the South African imperative of widening epistemological access to undergraduate science studies, this research takes the form of a case study to investigate the educational affordances of an extended introductory physics course. Using theoretical tools from Legitimation Code Theory (LCT) (Maton, 2014a) – in particular, semantic gravity and semantic density – the study characterizes the pedagogical practices and student learning in this Extended course, in relation to a Mainstream course in the same Physics Department. Data was collected through classroom observations, observations of student groups working on Mechanics physics tasks, and interviews with students. Two external languages of description were developed in order to translate between the LCT concepts of semantic gravity and semantic density and the empirical data from the physics context. The first language of description was used to characterize the semantic shifts in pedagogical practices, using a Concrete-Linking-Abstract continuum. The second language of description drew on physics education research on representations (Knight, 2007; Van Heuvelen, 1991a) tasks. Semantic profiles (Maton, 2013) were then constructed to show the semantic shifts in the pedagogical practices and in lecturers’ and students’ approaches to physics tasks. The study has shown that the extra curriculum time enabled different pedagogical practices. The Extended course showed a steady progression in pacing, initially with a less compressed semantic profile, while the Mainstream course showed a consistent compression. The Extended course showed a greater prevalence of the Linking level, with more time spent at the Concrete level and greater semantic flow. The courses also exhibited different communicative approaches, with students in the Extended course more engaged in making the semantic shifts together with the lecturer. The Extended course used more real-life illustrations as a starting point, whereas the Mainstream course tended to use verbal problem statements. Looking particularly at how problem tasks were dealt with, the study suggested that the lecturers’ pedagogical practices in dealing with physics tasks influenced the way in which the students tackled these tasks. The semantic profiles showed a more rapid shift up the semantic continuum in the Mainstream pedagogy and student work, while in the Extended pedagogy and student work, the semantic profiles indicated that more time was spent initially unpacking the concrete problem situation and explicitly shifting up and down the semantic continuum. In terms of methodological contribution, this study has demonstrated the usefulness of LCT tools for characterizing pedagogical practices and student learning in a physics context. Furthermore, the study has linked LCT to physics education literature and to research on epistemological access and academic literacies in a novel way. It has modified Maton’s form of semantic profiling, through introducing the following: a more detailed time scale, gradations of semantic strength on the semantic continuum, and coding for interactive engagement in pedagogical practices. The study thus has important implications for how curriculum and pedagogical practices might better support epistemological access to disciplinary knowledge in the field of physics, not only at the Extended course level but for introductory physics courses more generally.

Dissertação para obtenção do Grau de Mestre em Genética Molecular e Biomedicina
MicroRNAs (miRNAs) are emerging as a primary mediator of gene regulation in many different cell types. There is increasing evidence that specific subsets of miRNA play a prominent role in the nervous system, both in development and in specific neurodegenerative diseases. This study aims to elucidate the role of microRNA in selective motor neuron death that is the hallmark of amyotrophic Lateral sclerosis (ALS). Pre-symptomatic time-point was chosen since the levels of miRNAs are highly likely to be altered as a secondary consequence of cell injury and death in ALS. Laser capture microdissection (LCM) was used to study miRNA profiles in motor neurons of spinal cord tissue from SOD1G93A mice, the best characterized model of ALS. In preliminary work, using miRNA specific chips we have identified 2 miRNAs which are dramatically upregulated before disease onset. In this study, high RNA quality was achieved from laser captured cells, which consist in a major advance towards obtaining meaningful results of these miRNAs expression in downstream applications. Despite LCM technology has become increasingly sophisticated; rapidly obtaining enough amount of starting material for downstream applications is still extremely challenging. The combination of this optimized technique with microarrays, followed by RT-qPCR may provide insights into potential contribution of microRNAs to progression of neurodegeneration of motor neurons in ALS.

La fabrication de pièces composites à matrice organique chargée de particules par un procédé de type LCM (Liquid Composite Molding) soulève le problème de l'écoulement du mélange de la résine avec les charges à travers le renfort fibreux. L'augmentation de la viscosité due aux particules, d'une part, et la filtration éventuelle des charges par le réseau fibreux, d'autre part, sont deux phénomènes à considérer car ils peuvent engendrer d'importants défauts de fabrication. Cette étude, volontairement limitée à une géométrie 1D, comporte une phase expérimentale et une phase de modélisation à l'échelle macroscopique, complémentaires l'une de l'autre, et menées en parallèle. Un moyen simple de mesure de la quantité de charges présentes dans la pièce en fin d'injection a d'abord été mis au point. Des essais d'injection de pièces, menés dans différentes conditions expérimentales, ont mis en évidence l'existence de deux comportements de filtration distincts. La modélisation est basée sur une équation de conservation de la masse et trois équations constitutives. Le modèle de filtration proposé dépend de deux paramètres physiques et d'un seul paramètre numérique, qui ont été identifiés par méthode inverse à partir des résultats expérimentaux. Enfin, la résolution du modèle développé est couplée à celle de l'écoulement d'un fluide à travers un renfort fibreux. Les résultats de la simulation, tant pour le profil de concentration de charges dans la pièce que pour le temps d'injection, sont très satisfaisants et viennent valider la démarche générale de cette étude.

碩士
國立清華大學
資訊工程學系
102
This thesis presents the Life Cycle Prediction Model (LCPM), a probabilistic model that models the time when a context of a smartphone will remain the same as a life cycle. A correct prediction allows the corresponding sensors on the smartphone to be turned off during the life time of the context. Thus, it is possible to eliminate periodic and redundant sampling of the sensors, resulting in energy saving. Different ways of building the probabilistic LCPM for a given context are discussed, which try to trade off between miss predictions and energy consumption. We also address the issues resulting from miss predictions by identifying possible causes and proposing feasible solutions. Our experiments using data collected from real users on various contexts show that LCPM can adapts to different kinds of contexts and results in significant power saving.