Tesi sul tema "RMN en flux"

Ce travail porte sur l'etude des profils de vitesse d'ecoulement des fluides (newtoniens, non-newtoniens) et le calcul de la contrainte de cisaillement a partir des profils de vitesse mesures par la resonance magnetique nucleaire (rmn) a l'echelle macroscopique et a l'echelle microscopique. Ce travail comporte deux volets, le premier volet concerne l'analyse theorique du phenomene de la rmn et les principes de l'imagerie de flux a deux echelles. Le deuxieme volet concerne l'analyse experimentale, il comporte trois series d'experiences effectuees sur un spectro-imageur de 2. 35 tesla, afin de mesurer les profils de vitesse d'ecoulement d'un fluide newtonien (eau), d'un fluide non-newtonien, et d'ecoulement sanguin (in-vivo). Les resultats de ces experiences montrent une bonne concordance avec ce qui est predit par la theorie

Deux techniques sont presentees: les images a contraste de phase (reelles, imaginaires et de phase) qui permettent d'etudier les mouvements des parois cardiaques et l'angiographie irm obtenue par soustraction de deux images dans lesquelles les fluides en ecoulement donnent une intensite de signal differente. Trois methodes sont comparees. Une technique de "cine" irm basee sur la sequence echo de gradient ainsi que ses applications pour caracteriser les pathologies valvulaires est presentee

L'influence des facteurs génétiques et environnementaux sur l'utilisation des substrats au cours de la fermentation par les bactéries lactiques a été étudiée par le biais des méthodes isotopiques quantitatives. L'étude a été menée sur trois plans. Dans la première partie, on a fait varier de façon systématique les concentrations en glucose et en citrate. Dans la deuxième partie, deux souches génétiquement manipulées, dont les gènes codant pour deux enzymes clés ont été successivement modifiés, ont été choisis comme modèle d'étude. Il a pu être établi, grâce aux études isotopiques menées par SMRI en abondance naturelle, que ces modifications engendrent de considérables changements du flux métabolique. Ces études ont également montré clairement le rôle clé du pyruvate dans le métabolisme énergétique des bactéries lactiques. Dans la troisième partie, les coefficients de transfert du deutérium entre les hydrogènes du glucose (substrat) et ceux de l'acide lactique (produit principal) ont été déterminés par RMN 2H-en abondance naturelle. Il a été démontré que ce transfert dépendait à la fois de la voie métabolique empruntée et du type génétique
The way in which genetic and environmental factors influence the utilisation of substrates during fermentation by lactic acid bacteria has been examined using quantitative isotopic techniques. Three approaches have been used. Firstly, the concentrations of citrate and glucose and their ratio were systematically varied. Secondly, a genetically manipulated model was studied in which two key genes were altered sequentially. These deletions cause a major shift in the metabolic flux. The associated changes in substrate partitioning were determined by IRMS at natural abundance. These studies clearly show the key role of pyruvate in the energy metabolism of lactic acid bacteria. In the third part, the transfer coefficients of deuterium between glucose as substrate and lactic acid as product were measured by NMR at natural abundance. It was shown that these depend both on the pathway being used to metabolise glucose and on the genetic composition of the bacterial strain used

Nous étudions les propriétés cinétiques in vivo de l’énergétique dans le muscle squelettique actif. Le métabolisme énergétique est abordé comme un système de transfert d’énergie via des intermédiaires métaboliques : un système à deux modules (Producteur et Consommateur) connectés par un intermédiaire énergétique commun (PCr). L’analyse MoCA associée à la mesure de PCr par SRM 31P permet d’obtenir in vivo les coefficients d’élasticité et de contrôle pour une large gamme d’activité. Notre première étude montre un déplacement du contrôle sur le flux, de la demande vers la production, à mesure que l’activité contractile augmente; ce changement est principalement dû à un changement de sensibilité du Producteur vis-à-vis des intermédiaires énergétiques. L’analyse top-down d’élasticité est utilisée pour identifier les cibles de l’hypoxie chronique (6 semaines, 10,5%O2), de l’hypothyroïdisme et de l’activité physique chronique, décrits comme des stress pouvant modifier des réactions du Producteur et/ou du Consommateur. Les propriétés internes du système ne sont pas affectées par les changements de masse mitochondriale et/ou du type de fibres musculaires. La détermination expérimentale des propriétés internes du système permet de quantifier l’effet direct de l’hypoxie aiguë. Dans nos conditions, la principale adaptation du métabolisme énergétique à l’hypoxie chronique est une baisse de la sensibilité du Producteur vis-à-vis d’une diminution de l’O2 ambiant. La mise au point de notre approche permet d’étudier de manière intégrée le métabolisme énergétique du muscle squelettique et d’identifier les altérations fonctionnelles suite à des stimuli physiologiques ou pathologiques
We attempted to describe quantitatively the main kinetic properties of energy metabolism of contracting skeletal muscles of rats in vivo. For that, energy metabolism was defined as a two-module system (supply-demand) connected by energetic intermediate (PCr as representative) assessed in vivo by 31P MRS; such a simplification allowed application of top-down (modular) control analysis to obtain elasticity and control coefficients over a broad spectrum of muscle activities. The main finding of our first study was the shift of control over the contraction from demand at low workloads to supply at high workloads. This was mainly due to the change in sensitivity of supply toward energetic intermediates. Top-down elasticity analysis was used to identify the targets (supply and/or demand) of hypoxic conditioning (6 weeks at 10. 5% O2), hypothyroïdism and chronic physical activity, described as stress generating muscle remodelling. No change in the elasticity of neither supply nor demand toward intermediates were observed: internal properties of the system were unaffected by reported changes in mitochondrial content and/or change in fibre type composition. Once internal properties experimentally obtained, the direct effect of acute hypoxia by measuring the contraction energy flux change was quantified. The main response of energy metabolism to chronic hypoxia was the decrease in sensitivity of supply toward acute decrease in ambient O2. As demonstrated by these applications, the design and set up of our experimental modular approach has the potential to detect a number of physiological effects on energy metabolism of skeletal muscle at a system level of integration

Au cours des dernières décennies, des techniques de neuroimagerie atraumatiques et non invasives visant à évaluer les flux métaboliques cérébraux ont été développées. Parmi elles, la spectroscopie par résonance magnétique (SRM) du 31P présente l'avantage de permettre la mesure directe du flux cérébral de synthèse d'ATP, mais apparaît encore à ce jour un défi méthodologique. Dans une première étude de neuroimagerie multimodale, la consommation régionale de glucose CMRglc, la vitesse du cycle de Krebs (Vtca) et la vitesse de synthèse d'ATP (Vatp) ont été mesurées dans le cerveau de primate sain respectivement par TEP (tomographie par émission de positrons) 18F-FDG, SRM du 13C et transfert de saturation par SRM du 31P. La cohérence de ces trois flux a permis de valider la méthode de transfert de saturation par SRM du 31P pour la mesure directe de Vatp cérébrale. L'intérêt de la SRM du 31P a ensuite été évalué sur des patients atteints de la maladie de Huntington (MH). Un maintien de l’homéostasie métabolique, une diminution non significative de Vatp, et une augmentation significative du pH ont été mis en évidence dans le cerveau de ces patients. L'alcalinisation cérébrale, pour la première fois mesurée dans la MH, présentait de plus une corrélation avec les scores cliniques moteurs. Au vu de ce résultat, une étude visant à évaluer la précocité des variations de pH associées à la MH a été réalisée sur un modèle rongeur au cours d'une intoxication chronique à l'acide 3-nitropropionique (3NP). Une augmentation significative du pH précédant l'apparition de lésions striatales a été mise en évidence, démontrant la potentialité du pH comme biomarqueur précoce de la MH
Neuroimaging methods have considerably developed over the last decades and offer various non-invasive approaches for measuring cerebral metabolic fluxes. Among these methods, 31P magnetic resonance spectroscopy (MRS) has the particularity to directly measure cerebral ATP synthesis, but is still methodologically challenging. In this context, a multimodal neuroimaging study was performed in order to validate the saturation transfer 31P MRS method as a quantitative measurement of brain ATP synthesis. Glucose consumption (CMRglc), TCA cycle flux (Vtca ) and rate of ATP synthesis (Vatp) were measured in primate monkeys using 18F-FDG PET scan, indirect 13C MRS and saturation transfer 31P MRS, respectively. The consistency of these three fluxes with literature and, more interestingly, one with each other, demonstrated the robustness of saturation transfer 31 P MRS for directly evaluating ATP synthesis in the living brain. The potential of 31P MRS was then evaluated on Huntington's disease patients. Stability of metabolic homeostasis, non-significant decrease in Vatp, and significant increase in cerebral pH were shown in HD patient's brain. The increase in cerebral pH, detected for the first time in MH, was correlated with motor scores. Given these results, in order to assess the precocity of pH variations associated with MH, a study was performed on a rodent chronic model of MH. A significant increase in cerebral pH was detected before any lesions evidence, showing the potentiality of pH measurement as early biomarker of MH

Cette thèse présente une étude du métabolisme énergétique du spermatozoïde d’huître creuse, Crassostrea gigas. Les principaux objectifs sont (1) d’établir la dynamique des caractéristiques cellulaires et biochimiques du spermatozoïde de cette espèce durant la phase de mouvement, (2) d’identifier les voies de synthèse d’ATP et leurs substrats et (3) de déterminer l’implication du métabolisme énergétique dans le succès à la fécondation du spermatozoïde de cette espèce. Les résultats de ce travail montrent la longue durée du mouvement (de 24 à 72h) du spermatozoïde d’huître creuse et le maintien d’une concentration élevée en ATP intracellulaire, jusqu'à la fin du mouvement. Le rôle de la phosphorylation oxydative (OXPHOS) dans la synthèse d’ATP a été mis en évidence. Le spermatozoïde d’huître creuse montre une grande plasticité dans l’utilisation de ses voies de production d’énergie, assurant la synthèse d’ATP par d’autres voies qu’OXPHOS lorsque la mitochondrie est inhibée. L’accumulation de phosphoarginine en fin de mouvement montre une capacité de stockage de l’ATP synthétisé. La nature des substrats endogènes utilisés pour la synthèse d’ATP reste cependant à déterminer. La forte capacité de régulation du métabolisme énergétique du spermatozoïde d’huître creuse, associée à la possibilité de synthétiser de l’énergie au cours de sa longue phase de nage, contribuent probablement au succès du peuplement observé chez cette espèce. Ce travail apporte une première description du métabolisme énergétique du spermatozoïde d’huître creuse, améliorant la connaissance fine de cette cellule
The present study aims at describing the energy metabolism of Pacific oyster, Crassostrea gigas, spermatozoon. The main objectives are: (1) describing the kinetic of cellular and biochemical characteristics of Pacific oyster spermatozoon during its movement phase, (2) identifying the metabolic pathways to produce energy and their substrates, (3) determining the involvement of energy metabolism in fertilization success. The results showed the long duration (ranging 24 to 72h) of the movement of Pacific oyster spermatozoon and the maintenance of a high intracellular ATP content until the end of the movement phase. The role of oxidative phosphorylation (OXPHOS) in ATP production was highlighted. Alternative ATP producing pathways might contribute to sustain energy production when OXPHOS is impaired, showing the high adaptation capacity of Pacific oyster spermatozoa. An increase of phosphoarginine content observed at the end of the movement phase suggests energy storage capacity. Endogenous substrates involved in ATP synthesis must be determined. Both the high regulation capacity of the energy metabolism of Pacific oyster spermatozoa and their ability to restore energy stores catabolized during movement likely contribute to the successful settlement observed in the wild. In conclusion, this work provided a fine description of energetic metabolism of Pacific oyster spermatozoon

Ce travail est centre sur les developpements methodologiques en imagerie par resonance magnetique des fonctions du cerveau. Une nouvelle methode d'irm fonctionnelle quantitative basee sur la mesure du debit sanguin est tout d'abord decrite. Des images angiographiques ont permis de mesurer le debit dans une veine drainant le cortex moteur. Des variations significatives du debit sanguin entre des periodes de repos, de simulation mentale et d'execution d'un acte moteur ont ete mises en evidence. Ces informations fonctionnelles ne permettent pas de localiser precisement les regions corticales activees. Cette localisation a ete effectuee en appliquant un traitement approprie sur des images sensibles aux variations du taux d'oxygenation sanguine. Des cartes d'activation cerebrale de bonne resolution spatiale ( 3 mm) sont ainsi obtenues. Nous avons alors demontre que l'aire motrice primaire est activee lors de la simulation mentale d'un acte moteur. Les mouvements de la tete survenant pendant un examen fonctionnel induisent des erreurs sur les cartes d'activation. Un nouvel algorithme de correction des deplacements dans le plan des images est presente. Cet algorithme utilise les proprietes de la transformation de fourier concernant les rotations et les translations afin de determiner rapidement les parametres du deplacement. Des tests sur des images simulees ont permis de montrer la fiabilite et la precision de l'algorithme.

A seqüência de pulsos RMN-CWFP (Ressonância Magnética Nuclear - Precessão Livre de Onda Contínua) tem encontrado diversas aplicações na ciência. O presente trabalho analisa a grande sensibilidade dessa seqüência em relação a variações de seus parâmetros espectrais, exclusivamente em uma caracterização teórico-experimental da RMN-CWFP em fluxos do tipo plug-flow, exemplificados por medidas online através do transporte de sementes por uma esteira sob um campo magnético constante no tempo. Foram feitas simulações e medições em várias condições, variando os fatores que influenciam as medidas, como ângulo de nutação (?), ângulo de offset (?), tempo entre pulsos (Tp), gradiente (G), velocidade (v) e tempos de relaxação longitudinal (T1) e transversal (T2). Em determinadas condições fixas de ângulo de nutação, precessão, tempo entre pulsos, gradiente e velocidade, foi observado que poderia existir um ponto nulo com dependência entre T1 e T2. Esse fenômeno foi estudado e algumas aplicações foram sugeridas. O trabalho também validou a seqüência de pulsos CWFP em fluxo como ferramenta para análises quantitativas da massa de óleo em sementes.
The NMR-CWFP pulse sequence (Nuclear Magnetic Resonance - Continuous Wave Free Precession) has met several applications in the science. The present work analyses the high sensibility of this sequence to its spectral parameters variation, exclusively in a theoretical and experimental characterization of the flow NMR-CWFP of the kind plug-flow, exemplified by online measures by seeds transport through a mat under a magnetic field constant in time. Simulations and measurements were made on several conditions, varying the factors that have measurement influence, like flip angle (??, offset angle (??, time between pulses (Tp), gradient (G), velocity (v) and longitudinal and transversal relaxation times (T1 and T2). Under certain conditions of flip angle, precession, time between pulses, gradient and velocity, it was noticed that there might be a null point with T1 and T2 dependence. This phenomenon was studied and some applications have been suggested. The work has also validated the CWFP pulse sequence as a quantitative tool to quantitative analysis of seeds oil mass.

DØ est l'une des 2 expériences du collisionneur pp ̃du Fermi National Accelerator Laboratory près de Chicago. Après 5 années d'arrêt, le Run II a débuté en mars 2001. Il permettra d'explorer de nouveaux domaines de masses de squarks et de gluinos, particules supersymétriques dont la signature en jets et énergie tranverse manquante est l'objet de ce travail. Mais, avant le démarrage, j'ai travaillé sur des améliorations hardware et software de la mesure de l'énergie, essentielle pour les jets et l'énergie transverse manquante. Une simulation des chaînes de lecture et de calibration de chaque voie du calorimètre a été réalisée. Son résultat dépend de 8 grandeurs caractéristiques qui ont été extraites par traitement du signal de mesures de réflectométrie temporelle. Elle permettra de définir une stratégie de calibration du calorimètre. Une clusterisation des dépôts d'énergie calorimétrique a été réalisée (cellNN) basée sur la cellule et non la tour et exploitant au maximum la granularité du calorimètre notamment en débutant dans le 3ème compartiment électromagnétique, 4 fois plus granulaire que les autres. L'information longitudinale permet de séparer les particules électromagnétiques et hadroniques superposées. Ainsi, tous les éléments indispensables à la reconstruction individuelle des gerbes sont mis en œuvre. Puis, l'energy flow combine les clusters cellNN et les traces reconstruites dans la cavité centrale pour conserver la meilleure mesure de l'énergie et améliorer ainsi la reconstruction du flux d'énergie de chaque événement. L'efficacité des déclenchements calorimétriques actuels a été déterminée et utilisée pour une recherche de squarks et gluinos utilisant des événements Monte Carlo dans le cadre de mSUGRA. Une limite inférieure sur les masses des squarks et des gluinos qu'atteindra DØ avec 100 pb^(-1) de luminosité est prédite à partir d'outils de reconstruction standard; elle pourra être améliorée grâce à l'utilisation de l'energy flow
The DØ experiment is located at the Fermi National Accelerator Laboratory on the TeVatron proton-antiproton collider. The Run II has started in march 2001 after 5 years of shutdown and will allow DØ extend its reach in squarks and gluinos searches, particles predicted by supersymmetry. In this work, I focussed on their decays that lead to signature with jets and missing transverse energy. But before the data taking started, I studied bath software and hardware ways to improve the energy measurement which is crutial for jets and for missing transverse energy. For each calorimeter channel, the physics and the calibration signal has been simulated based on a database of the 8 parameters that describe each channel. The parameters have been extracted from time reflectometry measurements. The calibration strategy can be defined using this simulation. Energy deposits in the calorimeter has been clustered with celINN, at the cellievei instead of the tower level. Efforts have been made to take advantage of the calorimeter granularity to aim at individual particles showers reconstruction. CellNN starts from the third floor which has a quadruple granulariry compared to the other floors. The longitudinal information has been used to detect electromagnetic and hadronic showers overlaps. Then, clusters and reconstructed tracks from the central detectors are combined and their energies compared. The better measurement is kept. Using this procedure allows to improve the reconstruction of each event energy flow. The efficiency of the current calorimeter triggers has been determined. They has been used to perform a Monte Carlo search analysis of squarks and gluinos in the mSUGRA framework. The lower bound that DO will be able to put on squarks and gluinos masses with a 100 pb^(-1) integrated luminosity has been predicted. The use of the energy flow instead of standard reconstruction tools will be able to improve this lower limit

Ce travail porte sur le compose kappa-(et)2cun(cn)2br, supraconducteur organique a caractere bidimensionnel. La technique d'investigation utilisee est la resonance magnetique nucleaire (rmn). Les mesures ont ete menees sur deux types de noyaux, les protons et les carbones du centre de la molecule et. Ceci nous a permis d'avoir acces a des informations tres complementaires sur le systeme. Les conclusions essentielles de cette these sont les suivantes. La phase metallique ne peut pas etre decrite comme un liquide de fermi traditionnel. La rmn revele l'existence de fortes correlations antiferromagnetiques bien au-dessus de la transition supraconductrice qui sont sans doute les vestiges d'une phase antiferromagnetique. L'application d'une pression hydrostatique tend a ramener le systeme vers un comportement plus normal. Les proprietes de la phase mixte de l'etat supraconducteur sont tres anisotropes. En champ perpendiculaire, la contribution des curs de vortex domine la relaxation nucleaire du carbone qui depend donc fortement du champ. En champ parallele au contraire, les lignes de flux sont bloquees et cette contribution disparait. En revanche, sur le proton la relaxation est dominee par les effets lies aux mouvements des lignes de flux. Les excitations de basse energie revelees par la relaxation nucleaire du carbone montrent que le gap supraconducteur presente des lignes de zeros au niveau de fermi ou est tout au moins fortement anisotrope

Les recherches présentées dans ce manuscrit de thèse se divisent en deux parties. Dans la première partie, nous avons étudié la dégradation photocatalysée du N-méthoxy-N-(triméthylsilylméthyl)benzaldéhyde en présence de rose bengale dans l’acétonitrile. Les expériences de RMN 1D, la RMN 1H photo-CIDNP, ainsi que les analyses 2D 1H-13C HSQC et HMBC, combinées à une illumination in situ et ex situ, ont permis d'élucider la structure de plusieurs intermédiaires et produits formés durant cette réaction. L'illumination ex situ, réalisée à l'aide d'un système de flux continu, a été particulièrement utile pour compléter les résultats obtenus in situ et pour établir des comparaisons avec ceux obtenus par synthèse, soulignant ainsi l'importance de l'illumination ex situ dans l'étude des réactions en photochimie. Par ailleurs, les expériences de RMN 1H photo-CIDNP ont clairement démontré que la dégradation de l'éther de l’hémiaminal en présence de rose bengale passe par la formation d'un radical cation, sans engendrer de formation de 1,3-dipôle.Dans la seconde partie, nous nous sommes intéressés à la mécanistique de la réaction d’alkylation photo-induite via un complexe EDA (sel de Katritzky/DIPEA), en utilisant la RMN couplée à l’illumination in situ. Grâce aux expériences de RMN 1H photo-CIDNP, nous avons mis en évidence la présence de deux complexes EDA distincts dans le milieu réactionnel : un complexe 1:1 et un complexe 1:2 (sel de Katritzky : DIPEA), absorbant respectivement à λ = 450 nm et à λ = 520 nm. Les études de RMN 1D 1H et 1H photo-CIDNP ont révélé l'absence de diffusion du groupe partant du sel de Katritzky, prouvant ainsi que la réaction d’alkylation s'effectue dans la sphère de solvatation du complexe EDA. Ces observations, combinées aux données extraites des expériences de RMN 1H DOSY, ont permis d'identifier la nature des agrégats (complexe EDA/substrat) impliqués dans la réactivité aux deux longueurs d'onde, démontrant clairement le lien étroit entre la proportion de ces agrégats dans le milieu réactionnel et le rendement de la réaction d’alkylation photo-induite
The research presented in this thesis manuscript is organized into two main sections. The first section investigates the photocatalytic degradation of N-methoxy-N-(trimethylsilylmethyl)benzaldehyde in the presence of rose Bengal in acetonitrile. We utilized various techniques, including 1D NMR experiments, 1H photo-CIDNP, and 2D 1H-13C HSQC and HMBC analyses, alongside both in situ and ex situ illumination. These methods enabled us to elucidate the structures of several intermediates and products formed during the reaction. Notably, ex situ illumination, executed through a continuous flow system, proved particularly beneficial for complementing our in situ results and making comparisons with synthesized products, underscoring the significant role of ex situ illumination in the study of photochemical reactions. Moreover, the 1H photo-CIDNP experiments clearly indicated that the degradation of the hemiaminal ether in the presence of rose Bengal occurs via the formation of a cation radical, without the generation of any 1,3-dipole intermediates.In the second section, we shifted our focus to the mechanism of the photo-induced alkylation reaction via an EDA complex (Katritzky salt/DIPEA), employing NMR in conjunction with in situ illumination. 1H photo-CIDNP experiments revealed the presence of two distinct EDA complexes in the reaction medium: a 1:1 complex and a 1:2 complex (Katritzky salt: DIPEA), which absorb at λ = 450 nm and λ = 520 nm, respectively. Additional 1D 1H NMR and 1H photo-CIDNP studies demonstrated the absence of leaving group diffusion from the Katritzky salt, confirming that the alkylation reaction occurs within the solvation sphere of the EDA complex. These findings, along with data obtained from 1H DOSY NMR experiments, allowed us to ascertain the nature of the aggregates (EDA complex/substrate) participating in reactivity at both wavelengths. This clearly illustrates the close relationship between the proportion of these aggregates in the reaction medium and the yield of the photo-induced alkylation reaction

Nous presentons un ensemble de spectres obtenus par resonance magnetique nucleaire (rmn) du proton dans la phase supraconductrice de deux supraconducteurs organiques de structure voisine : -(bedt-ttf)#2cu(ncs)#2 et -(bedt-ttf)#2cun(cn)#2br. Dans le compose -(bedt-ttf)#2cu(ncs)#2 pour un champ applique perpendiculairement aux couches conductrices nous obtenons, dans la phase mixte, des formes de raie inattendues, tres differentes de celles prevues pour un reseau de vortex abrikosov triangulaire. En particulier, au-dessous d'une temperature t* qui depend de l'intensite du champ, nous observons une raie secondaire qui traduit un ecrantage diamagnetique bien plus important que celui attendu pour un reseau de vortex triangulaire. Nous montrons que ce sont les impulsions de champ radiofrequence qui, en perturbant violemment le reseau de vortex, conduisent a des conditions d'ecrantage particulieres. Une etude de ce phenomene pour des valeurs du champ comprises entre 0. 5 et 1 t montre qu'autour de 0. 82 t l'effet des impulsions de champ radiofrequence est maximal. Nous suggerons que cette valeur correspond a celle du champ de crossover dimensionnel du reseau de vortex. Nous estimons alors l'anisotropie #c/#a#b du compose entre 145 et 160. Le comportement aux basses temperatures de la nouvelle phase suggere, a l'instar des variations de la profondeur de penetration avec la temperature, que le gap supraconducteur de -(bedt-ttf)#2cu(ncs)#2 est anisotrope avec d'eventuelles lignes de nuds. Des mesures complementaires, notamment une etude du comportement de la phase secondaire en fonction de la duree des impulsions de champ radiofrequence, sont necessaires pour une meilleure comprehension de ce phenomene, inedit a notre connaissance. Une etude systematique des formes de raie du proton pour des temperatures inferieures a 4. 2 k dans le compose voisin -(bedt-ttf)#2cun(cn)#2br, dans un champ de 0. 8 t applique perpendiculairement aux plans conducteurs, nous a permis de determiner la profondeur de penetration #a#b(0) a 4920 100 a. Les variations lineaires de #a#b(t) aux basses temperatures indiquent que l'etat fondamental de ce compose ne peut etre decrit par un couplage bcs conventionnel isotrope.

DO est l'une des 2 expériences du collisionneur p-pbar du Fermi National Accelerator Laboratory près de Chicago. Après 5 années d'arrêt, le Run II a débuté en mars 2001. Il permettra d'explorer de nouveaux domaines de masses de squarks et de gluinos, particules supersymétriques dont la signature en jets et énergie transverse manquante est l'objet de ce travail. Mais, avant le démarrage, j'ai travaillé sur des améliorations hardware et software de la mesure de l'énergie, essentielle pour les jets et l'énergie transverse manquante.
Une simulation des chaînes de lecture et de calibration de chaque voie du calorimètre a été réalisée. Son résultat dépend de 8 grandeurs caractéristiques qui ont été extraites par traitement du signal de mesures de réflectométrie temporelle. Elle permettra de définir une stratégie de calibration du calorimètre.
Une clusterisation des dépôts d'énergie calorimétrique a été réalisée (cel1NN) basée sur la cellule et non la tour et exploitant au maximum la granularité du calorimètre notamment en débutant dans le Sème compartiment électromagnétique, 4 fois plus granulaire que les autres. L'information longitudinale permet de séparer les particules électromagnétiques et hadroniques superposées. Ainsi, tous les éléments indispensables â la reconstruction individuelle des gerbes sont mis en oeuvre.
Puis, l'energy flow combine les clusters ce11NN et les traces reconstruites dans la cavité centrale pour conserver la meilleure mesure de l'énergie et améliorer ainsi la reconstruction du flux d'énergie de chaque événement.
L'efficacité des déclenchements calorimétriques actuels a été déterminée et utilisée pour une recherche de squarks et gluinos utilisant des événements Monte Carlo dans le cadre de mSUGRA. Une limite inférieure sur les masses des squarks et des gluinos qu'atteindra DO avec 100 pb-1 de luminosité est prédite â partir d'outils de reconstruction standards; elle pourra être améliorée grâce à l'utilisation de l'energy flow.

Mestrado em Finanças
Avaliação extensa da REN-Redes Energéticas Nacionais SGPS SA, com uma ênfase especial na sua política de dividendos e características de instrumento obrigacionista ,seguindo o formato recomendado pelo CFA Institute sendo considerada informação pública até 9 de fevereiro de 2018. Para determinar o valor intrínseco dos segmentos operacionais da REN, Transmissão de Eletricidade, Transmissão de Gás Natural e Distribuição de Gás Natural, avaliou-se a empresa utilizando o modelo da soma das partes dos fluxos de caixa descontados (DCF) como principal método tendo em consideração diferentes custos de capital. Adicionalmente, avaliou-se a posição acionista na Electrogas utilizando o modelo dos dividendos descontados (DDM). Com um preço alvo de €2.76 por cada ação da REN em 2018FA, emite-se uma recomendação de COMPRA com baixo risco, representando um potencial de crescimento de 15% em relação ao preço de fecho (€2.43) a 9 de fevereiro de 2018. Adicionalmente, a política de dividendos da empresa foi analisada e comparada com as dos seus pares usando uma perspetiva de liquidação das empresas. O preço-alvo obtido pelo DDM é de €2.53.Foi levada a cabo uma análise de instrumento de renda fixa à ação da empresa para aferir da elasticidade do preço em relação ao seu custo dos capitais próprios. Conclui-se que um aumento de 1% neste parâmetro leva a uma descida do preço-alvo num cenário de liquidação das concessões (€2.49) para €2.20. A duração tem um efeito negativo de €0.32 enquanto que o ganho de convexidade é de €0.03.
This project is an extensive valuation of REN-Redes Energéticas Nacionais SGPS SA, with a special emphasis on its dividend policy and bond features. This equity research follows the CFA Institute format and only public information until 9th February 2018 was considered. To determine the intrinsic value of REN's three operational segments, Electricity Transmission, Natural Gas Transmission and Natural Gas Distribution, the company was valued using a Discounted Cash Flow (DCF) Sum of the parts approach as our main valuation method and considered different costs of capital to reflect the risk profile of each regulated activity. Additionally, to value the equity stake in Electrogas, it was used the Dividend Discount Model (DDM). With an estimated price target of €2.76 per REN's common share for 2018YE, a BUY recommendation is issued with low risk, representing a 15% upside potential from the 9th February closing price of €2.43. The price target obtained from the (DDM) is €2.53, representing a slightly 5% upside potential from the 9th February closing price. A fixed income instrument analysis approach was applied to REN's stock in a concession liquidation scenario to evaluate the elasticity of the stock price to its cost of equity. The results show that a 1% increase in the cost of equity would decrease the price target in a concession liquidation scenario (€2.49) to €2,20, with a negative duration effect of €0,32 and a gain of €0.03 from convexity.
info:eu-repo/semantics/publishedVersion

Mestrado em Finanças
Este projeto consiste num relatório de avaliação da REN - Redes Energéticas Nacionais, S.G.P.S., S.A. O relatório contém uma extensiva análise financeira à empresa, com foco na sua estratégia de gestão da dívida, e um entendimento geral do mercado energético em Portugal, na Europa e na América Latina (LATAM). Esta analise resultou num preço alvo de €2.76, representando um potencial de crescimento de 15% face ao preço fecho de €2.43, a 9 de fevereiro de 2018. Adicionalmente, a REN paga aos seus acionistas um dividendo de €0.171 por ação, o que representa uma dividend yield de 6.89%. A avaliação foi obtida com recurso ao método da soma das partes, na qual os negócios em Portugal foram avaliados utilizando o modelo dos free cash flows descontados e a participação da Electrogás do Chile com o modelo dos dividendos descontados e um múltiplo. Como suporte à avaliação, foram utilizados modelos de complementares. O modelo de regulação providencia à empresa uma espécie de natural hedge, tendo em conta que as suas vendas aumentam quando há um aumento da taxa de juro das obrigações portuguesas a 10 anos, compensando a empresa pelo aumento causado nos custos de financiamento. Com uma perspicaz gestão da dívida, a REN melhorou esse hedge, aumentando a proporção de dívida à taxa fixa para mais de 60% protegendo ainda mais o resultado líquido contra o espectável aumento das taxas de juro, criando desse modo o Yields Double Hedge. O relatório é apresentado segundo o formato do CFA Institute.
This project consists of an Equity Research Report on REN - Redes Energéticas Nacionais, S.G.P.S., S.A. It contains a comprehensive financial analysis of the company, with focus on its debt management strategy, and a brief understanding of the energy market in Portugal, Europe and Latin America (LATAM). This analysis resulted in a price target of €2.76, representing a 15% upside potential to the €2.43 closing price at February 9th, 2018. On top of that, REN pays a €0.171 dividend per share, translated in a 6.89% dividend yield. This valuation was obtained using a Sum of the parts approach, in which the businesses in Portugal where valued with the discounted free cash flow model, and the Electrogás share with the dividend discount model and a multiple. Additionally, some complementary approaches were used to support the base case valuation. The regulatory scheme provides to the company a natural hedge, in the sense that its revenues will increase when the 10Y Portuguese Yields increase, compensating the company for the losses due to the increase of the cost of debt. With crucial debt management, REN was able to improve that hedge, by increasing the share of fixed rate debt to above 60% protecting the net income, even more, against the expected increases in Yields, creating in that way the Yields Double Hedge. The report is presented under the CFA Institute Format.
info:eu-repo/semantics/publishedVersion

Mestrado em Finanças
Este projeto é uma avaliação extensa da REN-Redes Energéticas Nacionais SGPS SA, com uma ênfase especial nas oportunidades de investimento na região da América Latina. Esta avaliação de empresa segue o formato recomendado pelo CFA Institute e apenas foi considerada informação pública até 9 de fevereiro de 2018
This project is an extensive valuation of REN-Redes Energéticas Nacionais SGPS SA, with a special emphasis on growth opportunities in the Latin America region. This equity research follows the CFA Institute format and only public information until 9th February 2018 was considered.
info:eu-repo/semantics/publishedVersion

Mestrado em Finanças
Este projeto contém uma avaliação extensa da REN - Redes Energéticas Nacionais S.G.P.S, S.A. Este relatório segue as recomendações do Instituto CFA e considera apenas a informação pública disponível até 9 de fevereiro de 2018. O preço alvo foi obtido através de um método de avaliação absoluto, mais concretamente o método dos Fluxos de Caixa Descontados (DCF) para determinar o valor intrínseco de cada segmento operacional da REN (Transmissão de Eletricidade, Transmissão de Gás Natural, Distribuição de Gás Natural e Outros) e foi usado o Método dos Dividendos Descontados (DDM) para avaliar as operações chilenas e a soma das partes para determinar o valor total da empresa. Foi obtido um preço alvo de €2.76 por cada ação em 2018FA, representando um potencial de crescimento de 15% em relação ao preço de €2.43 a 9 de fevereiro de 2018, suportando a nossa recomendação de COMPRA para a REN, com baixo risco. Para suportar a nossa recomendação, foram também usados métodos complementares de avaliação, como o Fluxo de Caixa Livre para os Acionistas (FCFE), o Modelo dos Dividendos Descontados (DDM) e uma Avaliação de Múltiplos. Foi feita uma análise extra que considera a possibilidade de liquidação do negócio da REN e uma mudança para uma estrutura de regulamentação baseada nos custos totais (TOTEX). Ambas as análises representam um preço alvo mais baixo para a REN: €2.49 para o cenário de liquidação e €2.55 para uma mudança para uma estrutura de regulação baseada no TOTEX, embora ainda modestamente acima do preço atual.
This project contains an extensive valuation of REN - Redes Energéticas Nacionais S.G.P.S, S.A..This equity research report follows the guidelines and recommendations of the CFA Institute and only considers the public information available as at February 9th, 2018. The price target was achieved through an absolute valuation method in a form of a Discounted Cash Flow (DCF) Approach to derive the Enterprise Value of each REN's operational segments (Electricity, NG Transmission, NG Distribution, and Others) and used the Dividend Discount Model (DDM) to value Chilean operations, and then the Sum of the Parts Approach to determine the value of the entire company. A 2018YE price target of €2.76 per common share was reached, implying a 15% upside potential from the February 9th closing price of €2.43, supporting our BUY recommendation for REN, with low risk. To further support our recommendation, complementary valuation methods such as Free Cash Flow to Equity (FCFE), the DDM and a Multiples Valuation were applied. Additional analysis takes into consideration the possibility of a liquidation approach and a switch to a TOTEX regulatory framework. Both analysis account for a lower price target for REN: €2.49 for a liquidation approach and €2.55 as for a move to a TOTEX Framework, though still modestly above the €2.43 closing price.
info:eu-repo/semantics/publishedVersion

Les composites de type Cf/C sont utilisés en tant que pièces structurales dans les propulseurs spatiaux du fait de leurs excellentes propriétés mécaniques dans le domaine des très hautes températures. Néanmoins, l’atmosphère oxydante et corrosive créée lors du décollage des lanceurs et les hauts flux gazeux dégradent ces matériaux. Afin d’améliorer les performances de ces matériaux vis-à-vis de l’oxydation/corrosion, une protection composée de céramiques ultra-réfractaires (dites UHTC) peut être appliquée. Pour une efficacité de protection optimale, des phases UHTC ont été introduites en tant que constituants de la matrice. Dans ces travaux de thèse, la matrice a été réalisée par l’intermédiaire d’un procédé d’élaboration en phase liquide combinant : (i) l’introduction de poudres et (ii) la densification par infiltration réactive d’un métal fondu. La composition de la matrice appartient au système (B;C;Si;Zr). La caractérisation des matériaux après élaboration a permis de comprendre les mécanismes d’infiltration et les réactions permettant de mieux contrôler la composition chimique et la répartition des phases. Des essais sous torche oxyacétylénique ont été utilisés pour se placer dans des conditions proches de l’application visée. La caractérisation post-test des matériaux a permis d’évaluer l’efficacité de la protection dans le cas d’une utilisation unique et également d’une possible réutilisation. Les résultats en oxydation/corrosion ont permis de classer les matériaux en fonction de leur efficacité de protection
Since many decades, Carbon/Carbon composites are used as structural parts in rocket engines due to their excellent thermomechanical properties. However, under highly oxidizing/corrosive atmosphere and high gas flow rates, carbon suffers from severe oxidation. To improve oxidation resistance of these composites, Ultra High Temperature Ceramics (UHTC) can be used as a protection. To protect the whole composite, the introduction of UHTC as a matrix has been done using a liquid phase process combining: (i) slurry infiltration process and (ii) reactive melt infiltration. Matrix constituents belong to the (B;C;Si;Zr) system. Material characterisation allowed a better understanding of the infiltration mechanisms and of the phase distribution and composition in respect to the processing conditions. To select the best composition, oxyacetylene torch testing has been done to recreate spacecraft launch environmental conditions. Post-test characterisation has been done to evaluate protection efficiency of each matrix composition for single use and possible reuse. Finally, advantages and drawbacks assessment of each composition allowed to highlight the most protective composition and phase distribution

Data-flow (DF) testing was introduced more than thirty years ago aiming at verifying a program by extensively exploring its structure. It requires tests that traverse paths in which the assignment of a value to a variable (a definition) and its subsequent reference (a use) is verified. This relationship is called definition-use association (dua). While control-flow (CF) testing tools have being able to tackle systems composed of large and long running programs, DF testing tools have failed to do so. This situation is in part due to the costs associated with tracking duas at run-time. Recently, an algorithm, called Bitwise Algorithm (BA), which uses bit vectors and bitwise operations for tracking intra-procedural duas at run-time, was proposed. This research presents the implementation of BA for programs compiled into Java bytecodes. Previous DF approaches were able to deal with small to medium size programs with high penalties in terms of execution and memory. Our experimental results show that by using BA we are able to tackle large systems with more than 250 KLOCs and 300K required duas. Furthermore, for several programs the execution penalty was comparable with that imposed by a popular CF testing tool.
Teste de fluxo de dados (TFD) foi introduzido há mais de trinta anos com o objetivo de criar uma avaliação mais abrangente da estrutura dos programas. TFD exige testes que percorrem caminhos nos quais a atribuição de valor a uma variável (definição) e a subsequente referência a esse valor (uso) são verificados. Essa relação é denominada associação definição-uso. Enquanto as ferramentas de teste de fluxo de controle são capazes de lidar com sistemas compostos de programas grandes e que executam durante bastante tempo, as ferramentas de TFD não têm obtido o mesmo sucesso. Esta situação é, em parte, devida aos custos associados ao rastreamento de associações definição-uso em tempo de execução. Recentemente, foi proposto um algoritmo --- chamado \\textit (BA) --- que usa vetores de bits e operações bit a bit para monitorar associações definição-uso em tempo de execução. Esta pesquisa apresenta a implementação de BA para programas compilados em Java. Abordagens anteriores são capazes de lidar com programas pequenos e de médio porte com altas penalidades em termos de execução e memória. Os resultados experimentais mostram que, usando BA, é possível utilizar TFD para verificar sistemas com mais de 250 mil linhas de código e 300 mil associações definição-uso. Além disso, para vários programas, a penalidade de execução imposta por BA é comparável àquela imposta por uma popular ferramenta de teste de fluxo de controle.

L’objectif de cette thèse est de caractériser les Rejets Urbains par Temps de Pluie (RUTP) et leur flux au niveau des exutoires d’eaux pluviales de trois sous-bassins majeurs de l'agglomération orléanaise. Pour cela des prélèvements ponctuels d’eau ont été effectués et un modèle conceptuel a été utilisé. Les trois sous-bassins : La Corne (463 ha), l'Egoutier (2080 ha) et Ormes (2256 ha) ont des occupations du sol différentes.D’une manière générale, la conductivité, la demande chimique en oxygène (DCO), la demande biochimique en oxygène (DBO5 et la DBO28), le carbone organique dissout (COD), l'azote total(NT), et les concentrations en anions et cations majeurs étaient plus élevés par temps sec que par temps de pluie indiquant un effet de dilution par les précipitations. Il a été mis en évidence un mélange des eaux pluviales avec des eaux usées dans le sous bassin d’Ormes. L’occupation des sols et les activités anthropiques influencent de manière significative la qualité du ruissellement. Par exemple, dans le sous-bassin de l’Egoutier, la présence d’une zone imperméable (industries et habitations) importante (40% de la surface) est responsable d’une augmentation des paramètresDBO5, DBO28, COD et NT.Les flux aux exutoires des différents paramètres de qualité de l’eau ont été évalués et comparés à ceux issus des quatre principales stations d’épuration (STEP) et à ceux de la Loire. La charge destrois sous-bassins urbains représente environ 166,61% de la charge des quatre STEP. Les trois sous bassins ont un faible impact sur la Loire en termes de flux annuels (environ 1,62% pour les MES par temps de pluie).Deux versions d’un modèle conceptuel dit d'accumulation/lavage-transport ont été évaluées pour estimer les flux de ruissellement des polluants ; la version classique et une version modifiée dans laquelle le paramètre accumulation des polluants a une forme logarithmique. Les performances des modèles étaient acceptables pour les MES et la DCO. Les coefficients de corrélation étaient supérieurs à 90% pour le sous bassin de l’Egoutier, par exemple. Pour les éléments traces métalliques en phase particulaire, la corrélation avec l’expérience était bonne également. D’une manière générale, lorsqu'un flux mesuré était inférieur à 1 kg.ha-1, les modèles n’étaient plus applicables.Des premiers essais de simulation de la qualité et la quantité de RUTP ont été effectués à partir de MIKE URBAN, qui équipe les deux logiciels de modélisation MOUSE et SWMM. Les hydrogrammes ont indiqué que le débit maximum obtenu avec SWMM était toujours inférieur à celui obtenu avec MOUSE. La qualité de l’eau (masse de MES) était toujours plus fortement impactée par le lessivage des MES dans le modèle MOUSE que dans SWMM.Ce travail constitue la première étape du travail d'évaluation de RUTP pour l'Agglomération orléanaise. Il constitue une base solide pour un futur programme de surveillance continue
The objective of this thesis was to characterize urban runoff water at the level of stormwater outletson three major urban sub-basins of the Orléans agglomeration, covering land areas ranging in size from463 to 2257 ha and with contrasted land use. 11 individual rain events were sampled at runoff outletsbetween April 2015 and June 2017 and 10 campaigns were also carried out in dry weather.In general, it was observed that the conductivity, chemical oxygen demand (COD), biochemicaloxygen demand (BOD5 and BOD28), dissolved organic carbon (DOC), total nitrogen (NT), anions andmajor cations were found to be higher in dry weather conditions than in rainy weather. These resultsindicate a dilution effect due to precipitation.A mixture of rainwater and wastewater was also identified in the sub-basin of Ormes. Land use andhuman activities in the sub-basin studied were found to significantly influence the quality of the resultedrunoff from rainfall events. For example, in the Egouttier sub-basin 2, the presence of a large imperviouszone (industrial and residential, 40% of the surface area) was responsible for an increase in the parametersBOD5, BOD28, COD and NT.The flows at the outlets of the different water quality parameters were evaluated and compared withthose from the four main wastewater treatment plants (WWTP) and those from the Loire. The estimatedloads of the three sub-urban basins accounts for approximately 166.61% of the load of the four WWTP.The three sub-basins have a small impact on the Loire in terms of annual flows (about 1.62% for wetweather case).Two versions of a conceptual model of accumulation / washoff were evaluated to estimate pollutantrunoff; the classical version and a modified version in which the pollutant accumulation parameter has alogarithmic form. The performances of the models were found acceptable for the MES and the COD. TheNash-Sutcliffe (NS) coefficients were found as 0.84 and 0.85 for the two versions at the Egouttier subbasin.For trace elements in particulate phase, the correlation with the experimental measured value wasfound good as well. In general, when a measured flow was less than 1 kg.ha-1, the modified model was nolonger applicable.The first simulation tests of the quality and quantity of urban runoff were carried out with MIKEURBAN, which equips both MOUSE and SWMM modeling software. For water quantity, the hydrographsindicated that the maximum flow obtained with SWMM was always lower than that obtained with MOUSE.For water quality, TSS mass was still more strongly impacted by the leaching of TSS in the MOUSE modelthan in the SWMM model.This work can be considered as the first step of the evaluation work of RUTP for the Orléansagglomeration. It provides a solid foundation for a future monitoring program

Erosion et transferts de matières (i.e. matières en suspension-MES, associées avec le carbone et les éléments traces métalliques - ETM) par les fleuves et rivières sont contrôlés par des facteurs naturels (ex. géologie, climat) et peuvent être significativement modifiés par les pressions anthropiques et/ou, le changement climatique. En se basant sur une banque de données de concentrations en MES et de débits, à hautes résolutions temporelles (journalières) sur le long terme (1960-2008) à l’exutoire du bassin versant du Fleuve Rouge (Chine/Vietnam), les taux d’érosion ont été estimés en moyenne à 600 t/km²/an avec des valeurs variant de 160 à 1330 t/km²/an selon les années. Cette large gamme de taux d’érosion est liée fortement aux conditions hydrologiques interannualles, mais aussi à la présence de réservoir de HoaBinh en 1989. En effet, à partir 1989, chaque année, 50% de matières transportées par le Fleuve Rouge sont piégées dans ce réservoir, correspondant à un taux de sédimentation dans le réservoir de 52 à 200 cm/an. La variabilité spatiale des flux de MES du bassin versant du Fleuve Rouge au Vietnam suggère que les MES du Fleuve Rouge viennent principalement de l’érosion en amont du bassin versant (~80%), contrairement à ce que l’on observe pour le flux liquide (~21%). De plus, l’échange des processus érosion-transport-sédimentation dans la partie médiane du bassin versant dépend fortement des conditions hydrologiques ; à l’inverse, une forte sédimentation a été observée à l’entrée du Fleuve Rouge dans le delta, quelle que soit la condition hydrologique. De même, dans la partie vietnamienne du Fleuve Rouge, les facteurs majeurs influant sur le taux d’érosion seraient les maximas d’élévation et la pente moyenne du bassin. Un suivi hebdomadaire à bimestriel en 2008-2009 des paramètres biogéochimiques (carbone et ETM) ont permis de caractériser la qualité des eaux et des particules sur l’ensemble du bassin versant du Fleuve Rouge. Les concentrations en carbone organique (particulaire et dissous) dans les eaux du Fleuve Rouge sont relativement faibles et majoritairement d’origine allochtone. Les concentrations en carbone inorganique dissous (CID) sont très importantes, en faisant le composé majoritaire (60-90%) des eaux du Fleuve Rouge, en relation avec la présence de roches carbonatées dans le bassin versant. En terme de concentrations en ETM, la qualité des eaux et des particules transportées dans le bassin versant du Fleuve Rouge au Vietnam peut être qualifiée de mauvaise dans la partie amont et de médiocre en aval. L’étude de la répartition entre phase dissoute et phase particulaire a montré que l’essentiel des transferts se fait sous forme particulaire pour plupart des ETM (excepté Mo), dû aux forts taux d’érosion mécanique. De plus, l’étude à haute résolution spatiale (40 points) réalisée sur l’ensemble bassin versant du Fleuve Rouge au Vietnam des concentrations en ETM et de leur spéciation (dissous et particulaire) a mis en évidence de fortes anomalies géochimiques dans la partie amont. Enfin, l’identification des signatures géochimiques des particules érodées a révélé des signatures similaires entre les particules de l’amont et de l’aval du Fleuve Rouge, démontrant une contribution quasi-exclusive de la partie chinoise aux flux de matière (80-95% au flux total)
Erosion and transfer of suspended particulate matter (SPM), and associated elements (e.g. carbon, trace metal elements-ETM) by river are attributed to a combination of natural parameters related to geology and climatic influences and affected by human disturbance. Based on an extensive dataset of daily water discharge and SPM concentrations between 1960 and 2008 at the outlet of the Red River system, the annual SPM yield of the Red River is estimated at 600 t/km²/yr (ranged between 160 and 1330 t/km²/yr). This large range of sediment yield is strongly related to the inter-annual hydrological conditions and the operation of the HoaBinh Reservoir in 1989. In fact, the HoaBinh Reservoir reduces annual SPM delivery to the delta by half after 1989, i.e. the mean sedimentation rate of 52-200 cm/yr. The spatial variability of SPM fluxes in the Red River watershed suggests that most SPM were eroded from the upstream catchment located in China (80%), contrasting the water discharge with only 21%. In addition, the complex processes of erosion/sedimentation occurring in the middle Red River basin strongly depend on hydrological conditions; in contrast, an important sedimentation was observed at the entry point to the Red River Delta whatever the hydrological conditions. The major factors controlling the spatial variation of the sediment yields of the Vietnamese Red River watershed are maximum elevation and mean surface.During 2008-2009, high resolution sampling (weekly to bimestrial) of biogeochemical parameters (carbon and ETM) were performed at five key sites along the Red River system. The organic carbon (particulate and dissolved) concentrations in the Red River are relatively low and mainly allochtonous; in contrast, the dissolved inorganic carbon are very important and is the major carbon form (60 -90%) in relation to the abundance of carbonate rocks in the Red River watershed. In terms of ETM concentrations, the quality of water and SPM transported in the Vietnamese Red River watershed can be classified as poor upstream and as mediocre downstream. The study of the partition between the dissolved and particulate phases showed that most ETM transported in the Red River are in particulate phase (except Mo), due to the high mechanical erosion rate. In addition, high spatial resolution study (40 sites) performed in the Vietnamese Red River watershed of ETM concentrations and their speciation (dissolved and particulate) has highlighted strong geochemical anomalies in the upstream Red River. Finally, the identification of geochemical signals showed a similarity in the geochemical signal of particulate metal transport between upstream and downstream of the Red River, suggesting a contribution quasi-exclusively from the upstream part (in China) in the ETM fluxes of the Red River (80 -95%)
Quá trình xói mòn và vận chuyển vật chất (chất rắn lơ lửng, các-bon và kim loại nặng) bởi các dòng sông, suối chịu ảnh hưởng tổng hợp từ các quá trình tự nhiên (địa chất, khí hậu) và các hoạt động của con người. Dựa trên các bảng số liệu ngày về hàm lượng chất rắn lơ lửng và lưu lượng nước trong giai đoạn từ năm 1960 đến năm 2008 trên trục chính của sông Hồng tại trạm Sơn Tây (hạ nguồn của hệ thông sông Hồng trước khi chảy vào vùng đồng bằng), mục tiêu đầu tiên của luận án là nghiên cứu sự biến đổi theo thời gian tải lượng trung bình chất rắn lơ lửng của sông Hồng. Các kết quả cho thấy trong giai đoạn quan trắc, hàng năm sông Hồng chuyển tải ra biển khoảng 24×106 đến 200×106 tấn/năm (trung bình các năm là 90×106 tấn /năm), tương đương với hệ số xâm thực từ 160 đến 1330 tấn/km²/năm. Chính sự phụ thuộc mạnh mẽ của hàm lượng chất rắn lơ lửng vào các điều kiện thuỷ văn khác nhau đã tạo ra sự đa dạng về tải lượng chất rắn chuyển tải hàng năm của hệ thống sông Hồng. Tuy nhiên, trong những năm 1989-1990, khi hồ chứa Hoà Bình đi vào hoạt động, tải lượng chất rắn lơ lửng chuyển tải ra biển của hệ thống sông Hồng đã giảm sút còn khoảng 50×106 tấn, tức là đã giảm khoảng 50%. Dựa trên chiều cao và thể tích của hồ Hoà Bình, hệ số lắng đọng chất rắn lơ lửng trong lòng hồ được xác định vào khoảng 52-200 cm/năm. Như vậy, sau 20 năm đi vào hoạt động, độ dầy lớp bùn đất lắng đọng trong hồ Hoà Bình khoảng 10.4-40m, làm giảm đáng kể thể tích của hồ Hoà Bình.Mục tiêu tiếp theo của luận án là thiết lập cân bằng hàm lượng chất rắn lơ lửng trong các đoạn sông từ thượng nguồn sông Hồng (trạm Lào Cai), tại các hạ nguồn của 3 nhánh sông chính (sông Hồng tại Phú Thọ, sông Đà và sông Lô tại Việt Trì) và tại Sơn Tây trong thời kỳ 2003-2008. Diễn biến của các quá trình xói mòn, chuyển tải và lắng đọng diễn ra trên các đoạn sông một cách phức tạp, đan xen lẫn nhau và phụ thuộc chặt chẽ vào các điều kiện thuỷ văn. Tuy vậy, hiện tượng lắng đọng mạnh mẽ các chất rắn lơ lửng trong vùng hạ nguồn của hệ thống sông Hồng (từ Phú Thọ đến Sơn Tây) đã được ghi nhận trong tất cả các năm quan trắc, không phụ thuộc vào điều kiện thuỷ văn. Ngoài ra, dựa vào các số liệu thu thập được, chúng tôi đã lập bản đồ xói mòn cho toàn bộ lưu vực sông Hồng tại Việt Nam. Hơn thế, các kết quả còn chỉ ra rằng độ cao và độ dốc trung bình lưu vực là hai yếu tố chính ảnh hưởng đến hệ số xâm thực của lưu vực sông Hồng.Đánh giá chất lượng nước và chất lượng chất rắn lơ lửng chuyển tải trong hệ thống sông Hồng là mục tiêu thứ 3 của luận án. Để đạt được mục tiêu trên, chúng tôi đã tiến hành lấy các mẫu nước và chất rắn lơ lủng trên trục chính cũng như trên các nhánh sông chính của sông Hồng để phân tích hàm lượng các-bon hữu cơ và vô cơ cũng như hàm lượng kim loại nặng trong hai năm 2008-2009, với chu kì lấy mẫu hàng tuần đến hàng tháng. Hàm lượng các-bon hữu cơ (dạng hoà tan và lơ lửng) trong nước sông Hồng tương đối thấp tại tất cả các điểm lấy mẫu và nguồn gốc chính của các-bon hữu cơ là allochtone. Ngược lại, hàm lượng các-bon vô cơ hoà tan rất cao, chiếm khoảng 60-90% hàm lượng các-bon tổng và được giải thích bằng sự có mặt phong phú của núi đá vôi trên toàn lưu vực. Đối với kim loại nặng, dựa trên các kết quả phân tích về hàm lượng kim loại nặng trong nước và trong chất rắn lơ lửng và các tiêu chuẩn đánh giá chất lượng nước QCVN 08, chúng tôi đã đánh giá chất lượng nước cho toàn bộ hệ thống sông Hồng từ Lào Cai đến Sơn Tây. Nếu nước sông Hồng trên vùng thượng nguồn (tại Lào Cai và Phú Thọ) không đảm bảo chất lượng để có thể sử dụng làm nguồn nước sinh hoạt thì tại các vùng hạ lưu của sông Hồng, sông Đà và sông Lô, nhìn chung nước của 3 nhánh sông có thể dùng để cung cấp nước sinh hoạt nhưng phải qua các quá trình xử lí tách cặn lơ lửng. Hơn nữa, trong năm 2008, chúng tôi đã thực hiện hai chương trình lấy mẫu nước, chất rắn lơ lửng và trầm tích trên 40 điểm phân bố đều trên toàn bộ lưu vực sông Hồng tại Việt Nam trong mùa cạn và mùa mưa

La pertinence du plan de gestion d’un aquifère dépend de la connaissance que l’on a de ce milieu, et donc des informations utilisées pour le caractériser. Cette caractérisation est classiquement réalisée à partir d’études géologiques, piézométriques et de pompages d’essai. Ces études présentent toutefois certaines limitations, qui peuvent néanmoins être réduites par l’utilisation de méthodes complémentaires comme les méthodes géophysiques. L’objectif de cette thèse est de quantifier l’amélioration apportée par les informations géophysiques dans la caractérisation hydrogéologique des aquifères. Deux contextes géologiques sont sélectionnés pour les difficultés qu’ils posent à la caractérisation hydrogéologique, et l’importance des questions sociétales qui s’y posent : les aquifères de socle cristallin et les lentilles d’eau douce des cordons sableux côtiers. Les résultats de l’étude numérique et sa validation sur deux sites expérimentaux en Inde montrent que les informations complémentaires apportées par la tomographie de résistivité électrique et la méthode de sondage par résonance magnétique des protons (RMP) permettent de préciser l’interprétation de pompages d’essai en contexte de socle. L’incertitude sur la transmissivité est réduite en moyenne de 39 % et celle sur le coefficient d’emmagasinement de34 %. Cette approche hydrogéophysique permet ainsi de mieux décrire le milieu souterrain, et de proposer des modèles conceptuels plus complets. En milieu côtier sableux dans le Sud de l’Inde, l’utilisation combinée d’observations piézométriques, de la loi d’Archie et des méthodes de sondage lectromagnétiques en domaine temporel (TDEM) et RMP permet de quantifier un volume d’eau douce disponible de 510 litres en moyenne par mètre carré de surface au sol avant la mousson dans la partie inhabitée (contre 420 L/m2 dans la partie habitée), et 670 L/m2 après la mousson (contre 450 L/m2 dans la partie habitée). Ces volumes auraient été surestimés de 23 % si une approche plusclassique avait été utilisée. Le suivi temporel des mesures géophysiques permet également d’estimer la recharge nette de l’année hydrologique 2008 à 142 mm sur ce cordon (pour 2030 mm de précipitations). De plus, ce cordon sableux présente un champ géomagnétique hétérogène, qui ne permet pas la réalisation de mesures de signaux de Free induction decay, (FID) classiquement enregistrés en sondage RMP. Une nouvelle procédure de mesure et d’interprétation basée sur des signaux d’écho de spin a donc été testée et validée expérimentalement. La caractérisation du milieu avec ce nouveau protocole permet de préciser la teneur en eau du milieu, sous-estimée de 29 % par le protocole FID. Ce résultat ouvre de nouvelles perspectives dans la recherche d’une relation quantifiée entre la teneur en eau RMP et les différentes porosités hydrogéologiques
The pertinence of any aquifer management plan relies o nthe knowledge of this system, and therefore on the information used to chearacterize it. The aim of this thesis is to quantify the improvement of this characterization when geophysical methods are used complementary to hydrogeological techniques. Two hydrogeological contexts have been selected for the study, as their characterization is often difficult while they gather important populations : cristalline hard rock aquifers, and the freshwater lens of sandy coastal aquifers. The results of a numerical study and its validation on two study site located in India reveal that the information brought by electrical resistivity tomography (ERT) and magnetic resonance soundings (MRS) enable to precise the interpretation of pumping tests in hard rock areas. The uncertainly on transmissivity is reduced by an average of 39 % and by an average of 34 % for storativity. In a sandy coastal area, the combined use of water level measurements, Archie's law, time domain electromagnetism (TDEM) and MRS soundings enable to quantify the available freshwater volume. This volume would have been overstimated by 23 % with a more classical approach. Time lapse geophysics also enable to quantify the net recharge of the aquifer for 2008, as 142 mm (for a total rainfall of 2030 mm). As the site present an important geomagnetic field heterogeneity, a new protocol for the acquisition and the interpretation of MRS data has been tested and validated. It is based on the measurements of spin echo signals. It enables to constrain the estimation of water content on this site, which under-estimate by 29 % by the classicla protocol

Ultraluminous X-ray sources (ULXs) are a class of extragalactic, off nuclear and point-like sources with isotropic X-ray luminosities higher than 1e39 erg/s. They are supposed to be accreting Black Hole binaries systems but the accretion mechanisms at the basis of their extremely high X-ray luminosity are still matter of debate. We carried out a detailed spectral analysis of all the available XMM-Newton observations of two ULXs in NGC 1313, adopting a common model based on a multicolor disc plus a comptonizing component. We were able to describe the spectral evolution of the two sources within such a common framework. Furthermore, we investigated the chemical abundances of their local environments making use of both EPIC and RGS data. The results appear to indicate sub-solar metallicity for both sources. The possible existence of two spectral states in NGC 1313 X-1 and X-2 suggested to look for similar behaviours also in other ULXs. We then studied a larger sample of sources, including IC 342 X-1, NGC 5204 X-1, NGC 5408 X-1, Holmberg IX X-1, Holmberg II X-1, NGC 55 ULX1 and NGC 253 X-1. These sources were selected because they have a luminosity higher than 2e39 erg/s, are nearby, have one long observation and at least three other observations. The high quality observations provide at least 10000 counts in the EPIC instruments allowing us to constrain the curvature at high energy and to perform an analysis of the abundances of the material along the line of sight. We found that, in most of the spectra of the sources of our sample, the high energy component has a low temperature and is optically thick. However, because of the poor quality of some observations, the spectral fits are sometimes affected by a degeneracy between the spectral parameters and the roll-over of the spectrum at high energy is not easy to detect. For these reasons, similarly to what has been done for low counting statistics spectra of Galactic X-ray binaries (XRBs), we adopted the method of the hardness ratios that has also the advantage to allow us to study the spectral variability in a way completely independent of the spectral models. This analysis suggests the existence of possible characteristic evolutionary patterns on the color-color and intensity-color diagrams linking at least two different spectral states. This behaviour can be explained in terms of a non-standard accretion disc in which the increment of the accretion rate produces outflows that become more and more important at the highest luminosities. We tested the scenario of the ejection of a wind jointly analyzing the spectral and timing properties of the source NGC 55 ULX1 which shows a puzzling flux variability. In fact, fast drops in the flux are observed on time scales of minutes to hours that may be produced by optically thick blobs of matter that from time to time encounter our line of sight. We compared its variability properties with those of a Galactic accreting systems, EXO 0748-676, which is powered by a neutron star and is a known dipping source. We characterised the nature of the variability observed in the power density spectrum and, in particular, we checked the presence of a linear relation between the Root Mean Square (RMS) variability and the flux in several energy bands. We found that, in EXO 0748-676, the predominance of an (ionised) absorber strongly affects the RMS-flux relation which may anticorrelate when the absorption lines are unsaturated. On the other hand, no further variability is introduced when they are saturated and the variability is dominated by the accretion flow. In this case the source shows a positive correlation between RMS and flux. Since we found an anticorrelation in NGC ULX1, we suggest that at the highest flux levels, massive and unsaturated turbulent outflows are ejected. Finally, persistent ULXs, as those discussed above, do not allow us an easy comparison with the behaviour of Galactic XRBs. Transient ULXs are much more promising in this respect as they span different accretion regimes. Till now, only a handful of transient ULXs has been discovered and the link between them and the persistent sources is still unclear. We monitored the evolution of a new ULX (XMMU J004243.6+41251) discovered in January, 2012 in M31 by XMM-Newton. Its outburst showed that, at maximum luminosity, it entered in the ULX regime. It was then extensively followed by Swift during the flux decay. The source has experienced a fast rise in flux after discovery during which the XMM-Newton spectra changed from a powerlaw-like to a disk-like shape in the Swift spectra, suggesting a transition between the canonical low/hard and high/soft states. Its luminosity remained fairly constant for at least 40 days and then it faded below 1e38 erg/s. During the decay the disc emission softened and the temperature decreased from ~0.9 keV to ~0.5 keV. An optical follow-up and the UVOT images failed to provide evidence of a counterpart down to 22 mag in the optical band and to 23-24 mag in the near Ultraviolet. We compared the properties of XMMU J004243.6+412519 with those of other known ULXs and Galactic black hole transients, finding more similarities with the latter.
Le Ultraluminous X-ray sources (ULXs) sono una classe di sorgenti extragalattiche, lontane dal nucleo della galassia ospite e puntiformi, con una luminosità isotropica maggiore di 1e39 erg/s. Si pensa siano buchi neri in accrescimento in sistemi binari ma i meccanismi di accrescimento alla base della loro estrema luminosità X sono ancora lontani dall'essere totalmente compresi. In questo lavoro è stata svolta una dettagliata analisi spettrale di tutte le osservazioni disponibili di XMM-Newton di due ULXs in NGC 1313, adottando un modello comune basato su un disco multicolore più una componente di comptonizzazione. Noi siamo stati capaci di descrivere l'evoluzione spettrale delle due sorgenti all'interno di tale scenario. Inoltre, è stato possibile determinare le abbondanze chimiche dei loro ambienti locali facendo uso sia di dati EPIC che di dati RGS. I risultati sembrano indicare metallicità sub-solare per entrambe le sorgenti. La possibile esistenza di due stati spettrali in NGC 1313 X-1 e X-1 hanno suggerito di cercare comportamenti simili anche in altre ULXs. Per questo motivo, un campione più vasto di sorgenti, il quale include IC 342 X-1, NGC 5204 X-1, NGC 5408 X-1, Holmberg IX X-1, Holmberg II X-1, NGC 55 ULX1 e NGC 253 X-1, è stato studiato. Queste sorgenti sono state selezionate poichè la loro luminosità è maggiore di 2e39 erg/s, sono sorgenti vicine e posseggono un'osservazione lunga e almeno altre tre ulteriori osservazioni. L'alta qualità delle osservazioni fornisce almeno 10000 conteggi nello strumento EPIC, consentendoci di determinare con più precisione la curvatura ad alta energia e di svolgere un'analisi delle abbondanze del materiale presente lungo la linea di vista. E' stato trovato che, nella maggior parte degli spettri delle sorgenti del nostro campione, la componente ad alta energia mostra una bassa temperatura ed è otticamente spessa. Ad ogni modo, a causa della bassa qualità di alcune osservazioni, i fit spettrali sono a volte influenzati da una degenerazione fra i parametri spettrali e la curvatura ad alta energia dello spettro non è facilmente individuata. Per queste ragioni, in modo simile a ciò che è stato ampiamente fatto per gli spettri di sorgenti binarie Galattiche di raggi X, abbiamo adottato il metodo degli hardness ratios che hanno anche il vantaggio di consentirci di studiare la variabilità spettrale in un modo completamente indipendente dal modello spettrale. Questa analisi suggerisce l'esistenza di un possibile caratteristico cammino evolutivo sui diagrammi colore-colore and intensità-colore collegando almeno due differenti stati spettrali. Questo comportamento può essere spiegato in termini di un disco di accrescimento non standard in cui l'aumento del tasso di accrescimento produce fuoriuscite di materiale che diventano via via più importanti alle più alte luminosità. Lo scenario di emissione di vento è stato ulteriormente studiato analizzando le proprietà spettrali e temporali della sorgente NGC 55 ULX1 che mostra un'enigmatica variabilità nel flusso. Infatti, rapide diminuzioni del flusso emesso sono osservate su tempi scala di minuti od ore che potrebbero essere prodotti da nuvole di materiale otticamente spesso che di tanto in tanto entrano all'interno della nostra linea di vista, oscurando le regioni centrali della sorgente. E' stata fatta un'analisi comparativa fra le proprietà della sua variabilità con quelle di un sistema Galattico in accrescimento, EXO 0748-676, conosciuto per ospitare una stella di neutroni e per essere una sorgente con “dips". Abbiamo caratterizzato la natura della variabilità osservata negli spettri di potenza e, in particolare, abbiamo testato la presenza di una relazione lineare tra la variabilità quadratica media (RMS) e il flusso in diverse bande di energia. E' stato trovato che, in EXO 0748-676, la predominanza di un mezzo assorbente (ionizzato) influenza fortemente la relazione fra RMS e flusso che potrebbero anti-correlare qualora le linee in assorbimento fossero non sature. D'altra parte, nessuna variabilità ulteriore è introdotta quando esse sono sature e la variabilità è dominata dal flusso d'accrescimento. In questo caso la sorgente mostra una correlazione positiva tra flusso ed RMS. Poichè noi abbiamo individuato un'anti-correlazione in NGC 55 ULX1, proponiamo che ai livelli di flusso più alti, imponenti venti, non saturi e turbolenti, siano eiettati. Infine, ULX persistenti come quelle discusse sopra, non consentono una facile comparazione con il comportameno delle sorgenti binarie Galattiche. ULX transienti sono molto più promettenti sotto questo punto di vista poichè esse attraversano differenti regimi di accrescimento. Fino ad ora, solo una manciata di ULX transienti sono state scoperte e la connessione tra loro e le sorgenti persistenti è ancora poco chiara. Noi abbiamo monitorato l'evoluzione di una nuova ULX (XMMU J004243.6+41251) scoperta nel Gennaio 2012 nella galassia M31 da XMM-Newton. La sua accensione ha mostrato che, alla luminosità di picco, la sorgente è entrata nel regime ULX. E' stata poi ampiamente seguita da Swift durante la sua fase di decadimento in flusso. La sorgente ha sperimentato un veloce incremento del flusso dopo la sua scoperta, durante il quale gli spettri ottenuti da XMM-Newton si sono evoluti da un semplice andamento a legge di potenza fino ad una forma tipica per un disco d'accrescimento in tutti gli spettri Swift, suggerendo una transizione tra gli stati canonici low/hard and high/soft. La sua luminosità è rimasta abbastanza costante per almeno 40 giorni, per poi scendere al di sotto di 1e38 erg/s. Durante il decadimento, l'emissione del disco è diventata più soft e la temperatura è diminuita da ~0.9 keV fino a ~0.5 keV. Un follow-up ottico e immagini UVOT non sono riuscite a fornire evidenze di una controparte fino a 22 mag in banda ottica e fino a 23-24 mag nel vicino Ultravioletto. Noi abbiamo comparato le proprietà di XMMU J004243.6+41251 con quelle di altre ULX transienti e buchi neri Galattici, trovando più similitudini con le ultime.

Tese de doutoramento em Biociências, especialização em Bioquímica, apresentada à Faculdade de Ciências e Tecnologia da Universidade de Coimbra
Cancer therapies have significantly improved over the last decades. However, some cancers, such as lung cancer, still have very poor outcomes and high mortality rates, even when proper treatment is applied. New treatment strategies must be adopted, which will require better understanding of cancer mechanisms. For that purpose, three human lung cell lines were used in this study, MRC-5, a human lung fibroblast cell line and A549, H1299, two human non-small lung cancer cells. The metabolic remodeling occurring in carcinogenesis cells is firmly established. However, to understand the connection between the cellular metabolic profile and carcinogenesis, an accurate measurement of metabolic fluxes is required. In order to quantify the fluxes in these metabolic pathways, stable isotopes tracers and nuclear magnetic resonance techniques were employed. For the quantification of carbon intermediary metabolism cells were grown in 13C labelled glucose while for de novo lipogenesis (DNL) assessment 2H2O was supplemented to the culture media. To better understand and characterize cellular bioenergetics, mitochondrial membrane potential, oxygen consumption, and energy charge were also assessed. Also, recent reports describe a reductive carboxylation operated by isocitrate dehydrogenase (IDH), which may provide acetyl-coenzyme A to DNL, favoring carcinogenesis. To evaluate the impact of this reaction in the overall metabolism, IDH isoforms 1 and 2 were genetically silenced and metabolism was assessed by stable isotopes tracers. Finally, to establish a bridge between metabolic fluxes and cancer proliferation, substrate dependency studies were performed. Several metabolic inhibitors were also tested, targeting glycolysis, TCA cycle, pentose phosphate pathway (PPP) and transaminases. In this work we were able to quantify the glycolytic, TCA cycle and DNL fluxes. All cell lines exhibited heterogeneous metabolic profiles, with two distinct cancer cell lines. A549 cell line exhibited a more glycolytic phenotype while the H1299 cell line showed relatively active TCA cycle. However, both cell lines exhibited an increased DNL rate relatively to MRC-5 cell line. The overall mitochondrial bioenergetic parameters were in agreement with the metabolic profiles. The mitochondrial network was polarized and active in all cell lines, although H1299 cell line exhibited higher basal oxygen consumption and spare respiratory capacity. The reductive carboxylation operated by IDH did not contributed significantly to DNL. However, IDH silencing altered the redox homeostasis and IDH1 silencing in the A549 cell line increased the 13C enrichment of glutamine pools. Relatively to substrate dependency, all cell lines exhibited a reduced proliferation under glutamine deprivation. Finally, metabolic inhibition studies revealed an increased sensitivity in cancer cell lines to the inhibition of glucose-6-phosphate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase and transaminases, all reactions able to supply anabolic precursors or reducing equivalents. This work revealed that A549 and H1299 cancer cell lines exhibited different metabolic profiles even though they are both derived from non-small lung cancer. Both cancer cell lines have increased DNL but the reductive carboxylation by IDH did not contributed significantly. Nevertheless, IDH is involved in redox homeostasis and IDH1 may have a regulatory effect on glutamine pools. We were able to establish a connection between the metabolic profile and potential therapeutic targets, such as DNL or PPP.
As terapias anticancerígenas evoluíram significativamente nas últimas décadas. No entanto, os tratamentos nalguns tipos de cancros, como o do pulmão, continuam a ter baixas taxas de sucesso e elevadas taxas de mortalidade. Novas estratégias de tratamento terão de ser adotadas, as quais irão requerer uma aprofundada investigação acerca dos mecanismos do cancro. Para esse propósito, utilizámos neste estudo três linhas humanas de pulmão, MRC-5, uma linha celular de fibroblastos de pulmão e a A549 e H1299, ambas de adenocarcinoma de pulmão. A reestruturação metabólica que ocorre durante o processo carcinogénico está firmemente estabelecida. No entanto, para entender a conexão entre o perfil metabólico celular e a carcinogénese, é necessária uma quantificação precisa dos fluxos metabólicos. De forma a quantificar esses fluxos, utilizámos marcação por isótopos estáveis e técnicas de ressonância magnética nuclear. Para a quantificação e caracterização do metabolismo intermediário de carbono, as células foram cultivadas em meio de cultura contendo glucose marcada com 13C enquanto para a quantificação da lipogénese o meio de cultura foi suplementado com 2H2O. De forma a compreender melhor o metabolismo destas células, foram também avaliados parâmetros bioenergéticos, nomeadamente o potencial de membrana mitocondrial, o consumo de oxigénio e a carga energética. Descobertas recentes descrevem uma carboxilação redutiva operada pela isocitrato desidrogenase (IDH), a qual poderá abastecer acetilcoenzima A para a síntese lipídica, favorecendo o processo cancerígeno. Para avaliar o impacto desta reação no metabolismo, as isoformas 1 e 2 da IDH foram geneticamente silenciadas e o metabolismo foi analisado através de marcação por isótopos estáveis. Finalmente, para estabelecer uma ponte entre os fluxos metabólicos e a proliferação celular, realizaram-se estudos de dependência de substratos. Foram ainda utilizados vários inibidores metabólicos, dirigidos à glicólise, ciclo de Krebs, via das pentoses fosfato e transaminases. Neste estudo conseguimos quantificar os fluxos da glicólise, do ciclo de Krebs e da lipogénese. Todas as linhas celulares exibiram perfis metabólicos heterogéneos, sendo as duas linhas de cancro distintas. A linha celular A549 exibiu um fenótipo mais glicolítico enquanto a linha celular H1299 demonstrou uma atividade razoável do ciclo de Krebs. Contudo, ambas as linhas celulares de cancro exibiram uma elevada lipogénese relativamente à linha celular MRC-5. Os parâmetros bioenergéticos demostraram estar de acordo com os perfis metabólicos. A rede mitocondrial estava ativa e polarizada em todas as linhas celulares, mas no entanto, a linha H1299 exibiu um consumo basal de oxigénio e uma reserva respiratória máxima mais elevados. A carboxilação redutiva realizada pela IDH não contribuiu de forma significativa para a lipogénese. No entanto, o silenciamento da IDH causou distúrbios no redox intracelular e o silenciamento da IDH1 na linha celular A549 aumentou o enriquecimento de 13C na pool de glutamina. Relativamente à dependência de substrato, todas as linhas celulares revelaram uma redução da proliferação em condições de privação de glutamina. As linhas celulares cancerígenas exibiram uma sensibilidade aumentada relativamente à linha MRC-5, na inibição da glucose-6-fostato desidrogenase, gliceraldeído-3-fosfato desidrogenase e transaminases. Este trabalho revelou que as linhas celulares A549 e H1299 possuem diferentes perfis metabólicos apesar de serem ambas derivadas de adenocarcinoma do pulmão. As duas linhas cancerígenas possuem uma lipogénese aumentada mas a carboxilação redutiva através da IDH não contribui de forma significativa. No entanto, a IDH está envolvida no redox intracelular e a IDH1 poderá estar a exercer funções regulatórias nas pools de glutamina. Conseguimos ainda estabelecer uma relação entre o perfil metabólico e potenciais alvos terapêuticos, nomeadamente a lipogénese ou a via das pentoses fosfato.
FCT - SFRH/BD/66600/2009 e PTDC/EBB-EBI/115810/2009

Edge localized modes (ELMs) are a concern for future magnetic fusion devices, such as ITER, due to the large transient heat loads they generate on the plasma facing components. A very promising method of ELM suppression is an application of resonant magnetic perturbations (RMP); however, such application leads to localized places of higher heat fluxes called footprints. Both ELMs and RMP could limit the operational lifetime of the device. In this thesis, we analyze the temporal and spatial distribution of footprints using the tangle distance method in the aim to prevent a transient overheating. We also analyze quasi-double-null configuration of the ITER plasma which can be expected to be the most susceptible to overheating of the upper wall. Based on the modelling, the potentially dangerous configurations of the RMP have been shown. Using the ELM filament model included in the LOCUST GPU code, we study temporal and spatial distribution of the heat fluxes caused by ELMs in the axially symmetric and the asymmetric magnetic field. The results are compared with published experimental observations. Powered by TCPDF (www.tcpdf.org)

La caractérisation d'un aquifère est classiquement réalisée à partir d'études géologiques, piézométriques, géochimiques et de pompages d'essai. Ces techniques d'étude présentent certaines limites, qui peuvent néanmoins être réduites par l'utilisation de méthodes complémentaires comme certaines méthodes géophysiques. L'objectif de cette thèse est de quantifier l'amélioration apportée par les informations géophysiques dans la caractérisation hydrogéologique des aquifères. Deux contextes géologiquessont sélectionnés pour les difficultés qu'ils posent à la caractérisation hydrogéologique, l'importance des questions sociétales qui s'y posent et leur pertinence dans le cadre des interventions humanitaires : les aquifères de socle cristallin et les lentilles d'eau douce des cordons sableux côtiers. Les résultats d'une étude numérique et leur validation sur deux sites expérimentaux en Inde montrent que les informations complémentaires apportées par la technique de panneau électrique et la méthode de sondage par résonance magnétique des protons (RMP) permettent de préciser l'interprétation de pompages d'essai en contexte de socle. L'incertitude sur la transmissivité est réduite en moyenne de 39 % et celle sur le coefficient d'emmagasinement de 34 %. Cette approche hydrogéophysique permet ainsi de mieux décrire le milieu souterrain, et de proposer des modèles conceptuels plus complets. En milieu côtier sableux dans le Sud de l'Inde, l'utilisation combinée d'observations piézométriques, de la loi d'Archie et des méthodes de sondage électromagnétiques en domaine temporel (TDEM) et RMP permet de quantifier un volume d'eau douce disponible de 510 litres en moyenne par mètre carré de surface au sol avant la mousson dans la partie inhabitée (contre 420 L/m2 dans la partie habitée), et 670 L/m2 après la mousson (contre 450 L/m2 dans la partie habitée). Ces volumes auraient été surestimés de près de 40 % si une approche basée uniquement sur le TDEM et la loi d'Archie avait été utilisée. Le suivi temporel des mesures géophysiques permet également d'estimer la recharge nette de l'année hydrologique 2008 à 140 mm sur ce cordon (pour 2030 mm de précipitations). De plus, ce cordon sableux présente un champ géomagnétique hétérogène, qui rend la mesure de signaux de Free induction decay, (FID, classiquement enregistrés en sondage RMP) difficile. Une nouvelle procédure de mesure et d'interprétation basée sur des signaux d'écho de spin a donc été testée et validée expérimentalement. La caractérisation du milieu avec ce nouveau protocole permet de préciser la teneur en eau du milieu, sous-estimée de 26 % par le protocole FID. Ce résultat ouvre de nouvelles perspectives dans la recherche d'une relation quantifiée entre la teneur en eau RMP et les différentes porosités hydrogéologiques.