Die Verschmutzung von Süßgewässern mit organischen Mikroschadstoffen ist ein Problem, das sich weltweit zunehmend verschärft. Die vorliegende Doktorarbeit soll zu einem besseren Verständnis des Verhaltens einzelner Mikroschadstoffe und deren Transformationsprodukten in Flüssen beitragen, sowie die Rolle relevanter Einflussfaktoren untersuchen. Verhalten verschiedener Stoffe wurde im Oberflächenwasser eines urbanen Flusses analysiert. Es zeigte sich, dass die Sonneneinstrahlung für einige Verbindungen der wichtigste Einflussfaktor ist, während andere eher biologisch abgebaut wurden. Die Mahd von Makrophyten hatte ebenfalls stoffspezifische Folgen auf den Abbau. Um langfristige Variabilität von Stofftransport besser zu verstehen wurde eine neue Methode zur Schätzung des Stofftransports anhand von Schwankungen der elektrischen Leitfähigkeit getestet. Einige Stofftransportparameter änderten sich über die Jahreszeiten hinweg und transiente Speicherung unterschied sich zwischen den Flussabschnitten. Um im Besonderen den Einfluss von mikrobieller Diversität und von hyporheischem Austausch zu bewerten, wurde ein Meskosmenexperiment mit 20 rezirkulierenden Fließrinnen entwickelt. Es konnte festgestellt werden, dass vor allem mikrobielle Diversität einen starken Einfluss hat. Der neue Versuchsaufbau kann zukünftig für die Untersuchung weiterer Variablen Verwendung finden. Schließlich wurden Mikroschadstoffe und Transformationsprodukte in der hyporheischen Zone der Fließrinnen analysiert. Das Verhalten war sowohl stoffspezifisch als auch fließwegspezifisch. Die Ergebnisse unterstreichen die Bedeutung des oberflächennahen, hyporheischen Austauschs auf den Stoffabbau. Im Allgemeinen konnte die hohe Variabilität des Abbaus von Mikroschadstoffen mit besonderer Relevanz der hyporheischen Zone und der mikrobiellen Diversität nachgewiesen werden. Diese Faktoren sollten in zukünftigen Forschungsvorhaben besonders berücksichtigt werden. / Contamination of freshwaters with organic micropollutants is a worldwide emerging problem. The present thesis aims to contribute to a better understanding of the variability of the behaviour of individual micropollutants, the formation of transformation products in rivers and the specific role of relevant influencing factors. The behaviour of several substances was investigated in the surface water of an urban river by accounting for spatial and temporal dynamics. Solar radiation was identified to be the major driver for some compounds, while others were more susceptible to biodegradation. The response to macrophyte removal was also compound-specific. To better understand long-term variability of solute transport on a reach-scale a new method to estimate solute transport by use of electrical conductivity fluctuations was proposed and tested. Some solute transport metrics changed over the seasons and transient storage differed between river sections. To specifically assess the influence of microbial diversity and hyporheic exchange, a mesocosm experiment with 20 recirculating flumes was developed. It was found that microbial diversity in particular had a strong impact and the novel setup was suggested to be a useful method to test other variables in the future. Finally, the behaviour of micropollutants and transformation products in the hyporheic zone of the flumes was investigated on a centimeter-scale. The behaviour was found to be compound-specific as well as flowpath-specific. But several compounds were degraded most on the shortest, most oxic flowpath. The findings highlight the importance of shallow, small-scale hyporheic exchange for turnover of micropollutants. Generally, the high variability of micropollutant degradation depending on relevant influencing factors, specifically hyporheic exchange and microbial diversity, has been demonstrated. These factors are of great importance and need to be addressed and considered in future research.

Récemment, des études menées chez des patients atteints de la maladie d’Alzheimer (MA) suggèrent un rôle important de la clairance cérébrale des peptides bêta-amyloïde (Abeta) dans la physiopathologie de la MA. Les échanges de peptide Abeta entre le cerveau et le sang peuvent se faire à travers la barrière hémato-encéphalique (BHE). De nombreux transporteurs sont exprimés au niveau de la BHE, telles les protéines ABC (ATP-Binding Casette) et SLC (Solute Carriers). Il a été montré que l’influx du peptide Abeta à travers la BHE était partiellement médié par le récepteur RAGE (Receptor for Advanced Glycation End products) et son efflux par le récepteur LRP-1 (Low density lipoprotein receptor-related protein 1). De plus, l’implication de transporteurs ABC/SLC dans le passage cérébral du peptide Abeta a été suggérée. Il paraît donc important de caractériser les transporteurs ABC et/ou SLC impliqués dans le transport du peptide Abeta à travers la BHE. D’autre part, l’on peut se demander si, dans le cadre de la MA, la BHE subit des modifications, en termes d’étanchéité, d’expression de transporteurs, de mécanismes de transport, et si, dans ce cas, il y a une modification du transport du peptide Abeta à travers la BHE altérée. Nous avons d’abord montré que des transporteurs ABC et SLC étaient respectivement impliqués dans l’efflux et l’influx des peptides Abeta à travers la BHE. Concernant l’efflux, outre l’Abcb1, nous avons montré qu’Abcg2 et Abcg4 étaient impliquées dans la clairance cérébrale des peptides Abeta. Concernant l’influx, nous avons montré qu’Oatp1a4 pourrait jouer un rôle important dans la pénétration cérébrale des peptides Abeta. De plus, Abca1, principal transporteur ABC impliqué dans le transport du cholestérol, régule indirectement les taux cérébraux d’Abeta. En particulier, nous avons identifié la L-thyroxine et la rosuvastatine comme de puissants inhibiteurs respectifs de l’efflux et de l’influx cérébral d’Abeta. L’ensemble de ces transporteurs d’influx et d’efflux fixe ainsi la clairance cérébrale des peptides Abeta à travers la BHE. Or ces transporteurs sont régulés chez les souris 3xTg-AD (modèle de souris triple transgénique pour la MA exprimant à la fois les pathologies amyloïde et tau), dans des phases précoces et/ou tardives de la MA. Précocement, l’expression de Rage et d’Abca1 sont fortement augmentées au niveau de la BHE chez les souris 3xTg-AD. L’augmentation de Rage dès l’âge de 3 mois laisse supposer une augmentation très précoce de l’influx du peptide Abeta à travers la BHE. Mais cet influx semble être contre-balancé par l’augmentation concomitante d’Abcg4. Quant à Abca1, ne transportant pas directement le peptide Abeta, le rôle de son augmentation graduelle au cours du développement de la MA reste à déterminer. L’ensemble de ces régulations n’étant pas suffisantes pour empêcher l’accumulation cérébrale d’Abeta, des régulations plus tardives semblent se mettre en place, avec notamment l’augmentation de l’expression d’Abcb1 et d’Abcg2, et la diminution d’Oatp1a4. Ces mécanismes semblent donc correspondre à des phénomènes compensatoires ayant pour objectif d’augmenter la clairance cérébrale d’Abeta. Enfin, nous avons montré que l’intégrité physique de la BHE n’était pas altérée chez ces souris 3xTg-AD âgées de 3 à 18 mois. De plus, nos résultats ont montré que le volume vasculaire était diminué de manière précoce, notamment au niveau de l’hippocampe, chez les souris 3xTg-AD par rapport à leurs contrôles. Ce phénomène n’a pas été retrouvé chez les souris APP/PS1 n’exprimant que la pathologie amyloïde. Ces résultats suggèrent un rôle causal et précoce de la protéine tau hyperphosphorylée dans la pathologie de la MA. En conclusion, nos résultats soulignent l’importance de la BHE dans la physiopathologie de la MA. Ce travail de thèse ouvre des perspectives thérapeutiques, mais aussi des pistes pour la compréhension des mécanismes conduisant à une régulation de ces systèmes de transport dans la MA. / Recent studies in Alzheimer's disease (AD) patients have suggested an important role of cerebral clearance of Abeta peptide in the pathogenesis of AD. The blood-brain barrier (BBB) represents a major pathway for exchanges of Abeta between the brain and the peripheral circulation. Many transporters are expressed at the BBB, such as the ABC (ATP-Binding Casette) and SLC (Solute Carriers) proteins. It has been shown that the influx of Abeta peptide across the BBB was partially mediated by the receptor RAGE (Receptor for Advanced Glycation End products) and its efflux by the LRP-1 receptor (low density lipoprotein receptor-related protein 1). On the other hand, the involvement of ABC/SLC transporters in the brain efflux/influx of Abeta peptide has been suggested. It was therefore important to characterize the ABC/SLC transporters involved in the transport of Abeta peptide across the BBB. In addition, the disorders of the BBB have always been suggested in neurodegenerative diseases. The question is whether, in the context of AD, the BBB undergoes changes in terms of integrity, expression of transporters, transport mechanisms, and if, in this case, there is a change in the transport of Abeta peptide across the impaired BBB. We first showed that the BBB regulated the exchange of blood-brain Abeta peptides. Thus, the involvement of efflux (ABCG2 and ABCG4) and influx (Oatp1a4) transporters allows this equilibrium of Abeta peptides between the blood and the brain parenchyma. In addition, ABCA1, the main ABC transporter involved in cholesterol transport, regulates indirectly the brain levels of Abeta. We also identified the L-thyroxine and rosuvastatin as potent inhibitors of the efflux and influx transport of brain Abeta, respectively. All these influx and efflux transporters could control the transport of Abeta peptide across the BBB. However, these transporters are regulated in 3xTg-AD mice (triple transgenic mouse model for AD expressing both amyloid and tau pathologies) in the early and/or late stages of AD. Early, the expression of Abca1 and Rage are strongly increased at the BBB in 3xTg-AD mice. The high expression levels of Rage at the age of 3 months suggest an early increase in the influx transport of Abeta peptide across the BBB. But this increase seems to be compensated by the concomitant increase of Abcg4. As Abca1 does not directly mediate the transport of Abeta peptide, the role of its gradual increase in the development of AD remains to be determined. As all these regulations are not sufficient to prevent the accumulation of cerebral Abeta, the late regulations seem to develop, including increased expression of Abcb1 and Abcg2, and decreased expression of Oatp1a4. These mechanisms seem to correspond to compensatory phenomena with the objective to increase the cerebral clearance of Abeta. Finally, we have shown that the physical integrity of the BBB was not altered in 3xTg-AD mice aging from 3 to18 months. In addition, our results showed that the cerebral vascular volume was reduced early, especially in the hippocampus of 3xTg-AD mice compared to their age-matched controls. This phenomenon was not found in APP/PS1 mice expressing only the amyloid pathology. These results suggest a causal and early role of hyperphosphorylated tau in AD pathology.In conclusion, our results show the importance of the BBB and particularly of Abcg2, Abcg4 and Oatp1a4 transporters in the pathophysiology of AD. Knowledge of these transporters not only opens up therapeutic or prophylactic purposes, but also leads to the further understanding of the regulation mechanisms of these transport systems in AD.

No description available.

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / nÃo hà / Nas regiÃes Ãridas e semi-Ãridas à comum a acumulaÃÃo de sais no solo em quantidades prejudiciais ao crescimento e rendimento das plantas. Neste contexto, os fungos micorrÃzicos arbusculares (FMA) vÃm sendo estudados nos Ãltimos anos, havendo resultados que indicam que as associaÃÃes micorrÃzicas com as plantas minimizam alguns efeitos do estresse salino. O presente trabalho teve por objetivo avaliar, mediante parÃmetros fisiolÃgicos e bioquÃmicos, os efeitos da inoculaÃÃo dos fungos micorrÃzicos arbusculares na cultura do meloeiro sob estresse salino. Portanto foi instalado um experimento em casa-de-vegetaÃÃo do Departamento de CiÃncias do Solo da Universidade Federal do CearÃ, no Campus do Pici em Fortaleza. O delineamento experimental utilizado foi o inteiramente ao acaso, em arranjo fatorial 2 (plantas nÃo inoculadas e plantas inoculadas) x 4 (nÃveis de salinidade 0,5; 1,5; 3,0 e 4,5 dS m-1) com 4 repetiÃÃes, totalizando 32 unidades experimentais. No decorrer do experimento foram realizadas mediÃÃes de condutÃncia estomÃtica, taxa de transpiraÃÃo e taxa fotossÃntese. Ao fim de 37 dias apÃs a germinaÃÃo das plantas foi coletado o experimento, quando, entÃo, foram determinados os fatores de crescimento (matÃria seca e Ãrea foliar), as variÃveis microbiolÃgicas (dependÃncia micorrÃzica e colonizaÃÃo), os teores minerais (N, P, K, Ca, Mg, Na e Cl) e os solutos orgÃnicos (carboidratos solÃveis, NaminossolÃveis e prolina). A associaÃÃo com os FMA proporcionou um incremento no desenvolvimento da cultura do meloeiro, proporcionando um aumento na matÃria seca da parte aÃrea e na Ãrea foliar dessa cultura, principalmente no tratamento a 0,5 dS m-1; esse efeito benÃfico, entretanto, decresceu com o incremento da salinidade. A condutÃncia estomÃtica, taxa de transpiraÃÃo e taxa fotossintÃtica foram influenciadas de forma positiva pela associaÃÃo com os FMA, apresentando maiores valores nas plantas inoculadas em diferentes estÃdios de desenvolvimento dessa cultura. Os solutos orgÃnicos, prolina, N-aminossolÃveis e carboidratos solÃveis, nÃo contribuÃram diretamente para o ajuste osmÃtico dos tecidos foliares. A associaÃÃo simbiÃtica entre os FMA e as plantas de meloeiro nÃo proporcionou um aumento na tolerÃncia dessa cultura ao estresse salino, entretanto auxiliou na menor absorÃÃo dos Ãons potencialmente tÃxicos (Na e Cl) a partir da salinidade da Ãgua de irrigaÃÃo de 3 dS m-1. / Nas regiÃes Ãridas e semi-Ãridas à comum a acumulaÃÃo de sais no solo em quantidades prejudiciais ao crescimento e rendimento das plantas. Neste contexto, os fungos micorrÃzicos arbusculares (FMA) vÃm sendo estudados nos Ãltimos anos, havendo resultados que indicam que as associaÃÃes micorrÃzicas com as plantas minimizam alguns efeitos do estresse salino. O presente trabalho teve por objetivo avaliar, mediante parÃmetros fisiolÃgicos e bioquÃmicos, os efeitos da inoculaÃÃo dos fungos micorrÃzicos arbusculares na cultura do meloeiro sob estresse salino. Portanto foi instalado um experimento em casa-de-vegetaÃÃo do Departamento de CiÃncias do Solo da Universidade Federal do CearÃ, no Campus do Pici em Fortaleza. O delineamento experimental utilizado foi o inteiramente ao acaso, em arranjo fatorial 2 (plantas nÃo inoculadas e plantas inoculadas) x 4 (nÃveis de salinidade 0,5; 1,5; 3,0 e 4,5 dS m-1) com 4 repetiÃÃes, totalizando 32 unidades experimentais. No decorrer do experimento foram realizadas mediÃÃes de condutÃncia estomÃtica, taxa de transpiraÃÃo e taxa fotossÃntese. Ao fim de 37 dias apÃs a germinaÃÃo das plantas foi coletado o experimento, quando, entÃo, foram determinados os fatores de crescimento (matÃria seca e Ãrea foliar), as variÃveis microbiolÃgicas (dependÃncia micorrÃzica e colonizaÃÃo), os teores minerais (N, P, K, Ca, Mg, Na e Cl) e os solutos orgÃnicos (carboidratos solÃveis, NaminossolÃveis e prolina). A associaÃÃo com os FMA proporcionou um incremento no desenvolvimento da cultura do meloeiro, proporcionando um aumento na matÃria seca da parte aÃrea e na Ãrea foliar dessa cultura, principalmente no tratamento a 0,5 dS m-1; esse efeito benÃfico, entretanto, decresceu com o incremento da salinidade. A condutÃncia estomÃtica, taxa de transpiraÃÃo e taxa fotossintÃtica foram influenciadas de forma positiva pela associaÃÃo com os FMA, apresentando maiores valores nas plantas inoculadas em diferentes estÃdios de desenvolvimento dessa cultura. Os solutos orgÃnicos, prolina, N-aminossolÃveis e carboidratos solÃveis, nÃo contribuÃram diretamente para o ajuste osmÃtico dos tecidos foliares. A associaÃÃo simbiÃtica entre os FMA e as plantas de meloeiro nÃo proporcionou um aumento na tolerÃncia dessa cultura ao estresse salino, entretanto auxiliou na menor absorÃÃo dos Ãons potencialmente tÃxicos (Na e Cl) a partir da salinidade da Ãgua de irrigaÃÃo de 3 dS m-1. / Nas regiÃes Ãridas e semi-Ãridas à comum a acumulaÃÃo de sais no solo em quantidades prejudiciais ao crescimento e rendimento das plantas. Neste contexto, os fungos micorrÃzicos arbusculares (FMA) vÃm sendo estudados nos Ãltimos anos, havendo resultados que indicam que as associaÃÃes micorrÃzicas com as plantas minimizam alguns efeitos do estresse salino. O presente trabalho teve por objetivo avaliar, mediante parÃmetros fisiolÃgicos e bioquÃmicos, os efeitos da inoculaÃÃo dos fungos micorrÃzicos arbusculares na cultura do meloeiro sob estresse salino. Portanto foi instalado um experimento em casa-de-vegetaÃÃo do Departamento de CiÃncias do Solo da Universidade Federal do CearÃ, no Campus do Pici em Fortaleza. O delineamento experimental utilizado foi o inteiramente ao acaso, em arranjo fatorial 2 (plantas nÃo inoculadas e plantas inoculadas) x 4 (nÃveis de salinidade 0,5; 1,5; 3,0 e 4,5 dS m-1) com 4 repetiÃÃes, totalizando 32 unidades experimentais. No decorrer do experimento foram realizadas mediÃÃes de condutÃncia estomÃtica, taxa de transpiraÃÃo e taxa fotossÃntese. Ao fim de 37 dias apÃs a germinaÃÃo das plantas foi coletado o experimento, quando, entÃo, foram determinados os fatores de crescimento (matÃria seca e Ãrea foliar), as variÃveis microbiolÃgicas (dependÃncia micorrÃzica e colonizaÃÃo), os teores minerais (N, P, K, Ca, Mg, Na e Cl) e os solutos orgÃnicos (carboidratos solÃveis, NaminossolÃveis e prolina). A associaÃÃo com os FMA proporcionou um incremento no desenvolvimento da cultura do meloeiro, proporcionando um aumento na matÃria seca da parte aÃrea e na Ãrea foliar dessa cultura, principalmente no tratamento a 0,5 dS m-1; esse efeito benÃfico, entretanto, decresceu com o incremento da salinidade. A condutÃncia estomÃtica, taxa de transpiraÃÃo e taxa fotossintÃtica foram influenciadas de forma positiva pela associaÃÃo com os FMA, apresentando maiores valores nas plantas inoculadas em diferentes estÃdios de desenvolvimento dessa cultura. Os solutos orgÃnicos, prolina, N-aminossolÃveis e carboidratos solÃveis, nÃo contribuÃram diretamente para o ajuste osmÃtico dos tecidos foliares. A associaÃÃo simbiÃtica entre os FMA e as plantas de meloeiro nÃo proporcionou um aumento na tolerÃncia dessa cultura ao estresse salino, entretanto auxiliou na menor absorÃÃo dos Ãons potencialmente tÃxicos (Na e Cl) a partir da salinidade da Ãgua de irrigaÃÃo de 3 dS m-1. / The accumulation of salts in the soil is a common problems of arid and semi-arid regions, that cause reduction in plant growth and yield. In this context, the arbuscular mycorrhizal fungi (AMF) have been studied in recent years, with results indicating that their associations with the plants roots minimize some effects of salt stress. The objective of this work was to evaluate the influence of increasing levels of salinity of the irrigation water in the melon plants mycorrhized with AMF. The experiment was carried out at the greenhouse of the Departamento de CiÃncias dos Solo da Universidade Federal do CearÃ, in Fortlaeza, CearÃ. The experiment design was completely randomized with treatments outlined following a 2 x 4 factorial design, comprised of two mycorrhiza treatments (inoculated and not inoculated plants) x 4 levels of salinity (CEa = 0.5; 1.5; 3.0 and 4.5 dS m-1), with 4 repetitions. During the experiment were conducted measurements of stomatal conductance, transpiration and photosynthesis rates. The plants were collected thirty-seven days after germination, when growth (dry and leaf area), microbiological traits (dependency and mycorrhizal colonization), mineral content (N, P, K, Ca, Mg, Na, Cl) and the organic solutes concentrations (soluble carbohydrates, N-aminossolÃveis and proline) were measured. The mycorrhized plants showed higher production of shoot dry matter and leaf area, in relation to non-inoculated plants, mainly in the treatment of 0.5 dS m-1. However, this beneficial effect decreased in the higher levels of salinity. The stomatal conductance, transpiration rate and photosynthetic rate were influenced by AMF, being the values higher in mycorrhized plants. The organic solutes, proline, N-aminossolÃveis carbohydrates soluble, did not contribute directly to the osmotic adjustment of leaf tissue. The symbiotic association between the AMF, and the melon has not provided an increase in tolerance of this culture to salt stress, however helped in lower absorption of potentially toxic ions (Na, Cl) from the salinity of irrigation water 3.0 dS m - 1. / The accumulation of salts in the soil is a common problems of arid and semi-arid regions, that cause reduction in plant growth and yield. In this context, the arbuscular mycorrhizal fungi (AMF) have been studied in recent years, with results indicating that their associations with the plants roots minimize some effects of salt stress. The objective of this work was to evaluate the influence of increasing levels of salinity of the irrigation water in the melon plants mycorrhized with AMF. The experiment was carried out at the greenhouse of the Departamento de CiÃncias dos Solo da Universidade Federal do CearÃ, in Fortlaeza, CearÃ. The experiment design was completely randomized with treatments outlined following a 2 x 4 factorial design, comprised of two mycorrhiza treatments (inoculated and not inoculated plants) x 4 levels of salinity (CEa = 0.5; 1.5; 3.0 and 4.5 dS m-1), with 4 repetitions. During the experiment were conducted measurements of stomatal conductance, transpiration and photosynthesis rates. The plants were collected thirty-seven days after germination, when growth (dry and leaf area), microbiological traits (dependency and mycorrhizal colonization), mineral content (N, P, K, Ca, Mg, Na, Cl) and the organic solutes concentrations (soluble carbohydrates, N-aminossolÃveis and proline) were measured. The mycorrhized plants showed higher production of shoot dry matter and leaf area, in relation to non-inoculated plants, mainly in the treatment of 0.5 dS m-1. However, this beneficial effect decreased in the higher levels of salinity. The stomatal conductance, transpiration rate and photosynthetic rate were influenced by AMF, being the values higher in mycorrhized plants. The organic solutes, proline, N-aminossolÃveis carbohydrates soluble, did not contribute directly to the osmotic adjustment of leaf tissue. The symbiotic association between the AMF, and the melon has not provided an increase in tolerance of this culture to salt stress, however helped in lower absorption of potentially toxic ions (Na, Cl) from the salinity of irrigation water 3.0 dS m - 1. / The accumulation of salts in the soil is a common problems of arid and semi-arid regions, that cause reduction in plant growth and yield. In this context, the arbuscular mycorrhizal fungi (AMF) have been studied in recent years, with results indicating that their associations with the plants roots minimize some effects of salt stress. The objective of this work was to evaluate the influence of increasing levels of salinity of the irrigation water in the melon plants mycorrhized with AMF. The experiment was carried out at the greenhouse of the Departamento de CiÃncias dos Solo da Universidade Federal do CearÃ, in Fortlaeza, CearÃ. The experiment design was completely randomized with treatments outlined following a 2 x 4 factorial design, comprised of two mycorrhiza treatments (inoculated and not inoculated plants) x 4 levels of salinity (CEa = 0.5; 1.5; 3.0 and 4.5 dS m-1), with 4 repetitions. During the experiment were conducted measurements of stomatal conductance, transpiration and photosynthesis rates. The plants were collected thirty-seven days after germination, when growth (dry and leaf area), microbiological traits (dependency and mycorrhizal colonization), mineral content (N, P, K, Ca, Mg, Na, Cl) and the organic solutes concentrations (soluble carbohydrates, N-aminossolÃveis and proline) were measured. The mycorrhized plants showed higher production of shoot dry matter and leaf area, in relation to non-inoculated plants, mainly in the treatment of 0.5 dS m-1. However, this beneficial effect decreased in the higher levels of salinity. The stomatal conductance, transpiration rate and photosynthetic rate were influenced by AMF, being the values higher in mycorrhized plants. The organic solutes, proline, N-aminossolÃveis carbohydrates soluble, did not contribute directly to the osmotic adjustment of leaf tissue. The symbiotic association between the AMF, and the melon has not provided an increase in tolerance of this culture to salt stress, however helped in lower absorption of potentially toxic ions (Na, Cl) from the salinity of irrigation water 3.0 dS m - 1.

Ce travail contribue à l'acquisition des connaissances sur les mécanismes et les facteurs contrôlant le transfert des éléments traces dans le système sol-nappes d'eaux souterraines. Le nombre de plus en plus important de sols contaminés par les éléments traces potentiellement toxiques suite aux activités industries a reçu beaucoup d'attention au cours des deux dernières décennies. Les polluants accumulés dans ces sols peuvent alors être transférés dans différents compartiments de l'environnement en fonction de leur origine, leur spéciation et les conditions physico-chimiques et biologiques du milieu. Ainsi, une des problématiques est la pollution des nappes d'eau souterraine par ces éléments traces. Les flux massiques d'éléments traces dans les sols vers les nappes d'eau souterraines sont un paramètre d'entrée important pour prévoir le devenir des pollutions des aquifères et donc à évaluer le potentiel de la contamination des ressources en eau potable. L’objectif de cette thèse a été de proposer une méthode de mesure des flux en laboratoire qui permette de simuler au mieux les conditions naturelles des transferts des éléments traces vers les nappes. Pour cela, nous avons mis au point une colonne de laboratoire non-saturée. Cette colonne a été testée dans différentes conditions de lixiviation, comparée aux méthodes de lixiviations normées et testée en condition d’immobilisation des éléments traces lors de l’apport d’amendements. Dans un premier temps, la colonne de laboratoire permet de diminuer l’erreur sur l’estimation des flux. Elle permet des mettre en évidence des phénomènes de sorption, désorption et complexation des éléments traces sur les substrats, contrôlant ainsi les transferts verticaux.Dans un deuxième temps nous avons évaluer l’effet d’amendements minéraux sur la mobilité des éléments traces sur deux sols contaminés par des extractions chimiques. Nous avons ensuite étudié la lixiviation de ces éléments suite à l’apport d’amendements: de l’hydroxyapatite et de la Grenaille d’acier dans ces deux sols en utilisant les colonnes de sol développés précédemment. L'étude de la localisation des éléments traces sur les minéraux nouvellement formés suite à l'apport de ces amendements minéraux et leur interaction avec les constituants minéraux d'origine des sols (microscopie couplé à des spectromètres de fluorescence X) nous a permis de comprendre et de déterminer les réactions mis en jeu au cours de la lixiviation de ces éléments. Ainsi, l’apport d’hydroxyapatite (HA) et de Grenaille d’acier (GA) ont permis de diminuer significativement les concentrations en Cd, Zn dans les lixiviats. En revanche, l’apport de HA et GA aux sols augmente significativement la libération de As (dans le cas de HA) et Pb suite a l’apport de GA et HA. Les phases minérales porteuses de ces éléments traces, ont pu être caractériser et ainsi les mécanismes responsables de l’immobilisation ou du relargage ont pu être identifiés. / This work contributes to the knowledge of the mechanisms and factors controlling the transfer of trace elements, particularly in the soil- groundwater pathway. Extensive soil contamination with potentially toxic traces elements from various industries has in many industrialized countries received significant attention over the last two decades. Mass fluxes of trace elements in soils to groundwater are important input parameter for predicting the fate of pollution of aquifers and thus to assess the potential for contamination of drinking water resources. The objective of this study was to propose a method for measuring the fluxes in laboratory to simulate the natural conditions. For this, we have developed an unsaturated soil column. This column was then tested in various leaching conditions (compared to standardized leaching methods and tested under conditions of immobilization of trace elements). At first, the laboratory column reduces the error in the estimation of flux. And allows to highlight sorption, desorption and complexation of trace elements on the substrates. In a second step we evaluate the effect of mineral amendments on the mobility of trace elements in two contaminated soils (extraction), the study their location on the newly formed minerals (microscopy coupled with X-ray fluorescence spectrometers) and finally the leaching of these. The addition of hydroxyapatite (HA) and Steel Shot (GA) have significantly reduced the concentrations of Cd, Zn and As (in the case of the contribution of GA). In contrast, the addition of HA and GA in soils significantly increases the release of As (in the case of HA) and Pb following the addition of GA and HA). Mineral phases carrying these trace elements have been well characterized and the mechanisms responsible for the retention or release have been identified.

La tomographie de résistivité électrique (ERT) est une méthode courante géophysique de terrain, souvent utilisée pour détecter et l’évolution suivre les panaches de polluants en zone saturée. L’ERT est cependant une méthode intégratrice dont la fiabilité des modèles est confronte aux problèmes de non unicité des solutions du problème inverse. Ces contraintes limitent l’interprétation des modèles a un aspect qualitatif de la distribution des contrastes de résistivité modélises en 2D ou 3D, résultant du choix des paramètres d’inversion et de l’association de paramètres du milieu non identifiables a l’échelle du volume poreux.Cette thèse propose de tester la faisabilité de la méthode pour quantifier les paramètres de transport de polluants et de solutés miscibles au contact des eaux souterraines, ainsi que la sensibilité des paramètres d’inversion les plus influents sur la modélisation.Les tests expérimentaux sont réalisés en laboratoire sur des empilements 2D de billes de verre sphériques (de l’ordre de la 100èn de μm) dans un réservoir en plexiglas transparent. Deux réseaux verticaux de 21 électrodes sont disposes sur les bords latéraux du réservoir pour effectuer le suivi ERT du traceur sale (NaCl dissout) a partir de 210 points de mesures en dipôle-dipôle transverse acquis toutes les 5 minutes afin d’optimiser la résolution temporelle. Le dispositif est également dispose face a un panneau lumineux permettant de réalise un suivi vidéo simultané du colorant.L’analyse vidéo révèle une propagation plus rapide du colorant sur les bords latéraux qui reste somme toute négligeable pour les débits a la pompe les plus faibles. En revanche les mesures ERT sont fortement perturbées par les effets résistant de la cellule plexiglas qui se répercutent sur les modèles. La normalisation des mesures de résistivité apparente à partir d’une série acquise à l’état initial permet de les atténuer fortement.La modélisation est particulièrement sensible au choix du maillage, aux normes appliques (L1 ou L2) sur les données et les paramètres, et au facteur d’amortissement _. Des valeurs trop élevées de _ et du facteur d’acceptance tendent à lisser les contrastes au niveau du front de dispersion et augmentent l’impact des effets des bords horizontaux sur D et _. A l’inverse, une modélisation contrainte par de faibles valeurs de α et du facteur d’acceptante donne des résultats plus proches l’analyse vidéo, mais produit des effets de bosses à l’avant et à l’arrière du front.La vitesse interstitiel u est indépendante du choix des paramètres d’inversion pour l’ERT. Pour les deux méthodes u est toujours inférieure au débit impose par la pompe, dont le décalage est exprimé par le facteur retard Rf . Les effets de retard résultent de l’adsorption du Na+ sur les surfaces des billes de verre chargées négativement qui retarde le front de dispersion du suivi ERT. Pour le suivi vidéo, la taille importante de la molécule du colorant favorise son piégeage dans les zones ou la perméabilité est plus faible, en plus d’une éventuelle affinité avec la surface solide. Les contrastes de conductivité et la stabilité de l’interface créent par la différence de densité entre les fluides testes ici n’ont pas d’influences significatives sur la dispersion qui est dominée par le débit impose a la pompe. Les estimations du coefficient de dispersion D en fonction du nombre de Péclet sont cohérentes avec la courbe théorique de Bachmat (1968). Cependant la dispersivité α augmente pour les vitesses d’écoulement les plus élevées. Les premières expérimentations de terrain réalises en 2D sur des sables de Fontainebleau présentent l’avantage de s’affranchir des effets de bords inhérents au laboratoire. En revanche la recalibration des données normalisées par la loi de Archie est plus complexe puisqu’il est nécessaire de tenir compte de l’état de saturation de la résistivité des fluides initialement présents. De plus l’erreur importante sur les modèles ne permet pas de déduire une estimation fiable des paramètres de transport u, α (ou D), et Rf . / Electrical resistivity tomography is a common geophysical method often used to detect and follow plumepollutants in aquifers. However ERT is an integrative method whose reliability of the models is faced tothe non-unicity of the inverse problem solutions. These constraints limit the interpretation to a qualitativeview of the resistivity contrasts modelled in 2D or 3D, resulting of the chosen inverse parameters and thecombination of several hydrodynamic paramaters related to the poral network.The purpose of this thesis was to test the abilities of the ERT imaging to quantify solute transport parametersin miscible displacement occurred in groundwater and the sensitivity of inverse parameters most affectingthe modelled dispersion front.Laboratory experiments are conducted on glass beads poured into a transparent plexiglas container. Twovertical lines of 21 stainless steel electrodes are fixed on the lateral sides of the container to perform the ERTmonitoring, of the NaCl dissolved in the tracer, from a sequence of 210 quadripole measurements acquiredin transverse dipole-dipole each 5 minutes. A light panel is placed behind the experimental device and avideo follow up of the dyed part of the tracer is acquired from the other side.Video analysis reveal a faster propagation of the dye in contact of the vertical edge, which is negligible forthe lowest flow rates imposed by the pump. In contrast, ERT mesurements are strongly disturbed by theresistant edges of the plexiglas container which affect the resulting models. Normalisation of the apparentresisitivity measurements acquired at the experimental stage and by the Archie’s law strongly tones downthese resistive artefacts.ERT modelling is here particularly sensitive to the grid mesh, the norm (L1 or L2 ) applied on data andparameters, and the damping factor λ. High values of λ and the cutoff factor tend to smooth the resistivityconstrasts in the area of the mixing front and increase the weight of the horizontal edge effects on D andα. While results from inverse modelling constraint by low λ and cutoff factors are much closer to the videoanalysis but with enhanced side slope effects at the rear and the front of the mixing area.The interstitial velocity u is independant of the chosen inverse parameters. For both methods u is alwaysinferior to the flow rate provided by the pump, whose the gap is expressed as a retardation factor Rf . Thisretardation is due to adsorption of Na+ on the beads surfaces, which contributes to delay the dispersionfront followed by ERT. The retardation expressed by the video analysis can be due to the important sizeof the molecule of the dye which is easily slowed down in lower permeability areas, added to an eventualaffinity to the solid surface.The ranges of fluid conductivity contrasts and stability of the interfaces tested here have no influences onthe dispersion which is dominated by the flow velocity u. Estimations of the dispersion coefficient D asfunction of the Péclet is consistent with the theoretical curve of Bachmat (1968) and Bijeljic & al (2004).Field experiments are first conducted in 2D on homogeneous unsaturated sand which is considered as aninfinite half-space. However, data normalisation is much more complicated since the saturation state andthe initial fluid conductivities need to be estimated to calibrate the Archie’s law. Because of the 3D tracerinflitration, the RMS error of 2D-ERT models highlights that the inversion process is not enough constraintby data which does not allow to quantify the transport parameters. 3D experiments were then adaptedto detect and follow plumes of saline tracers injected in the centre of the electrode device. From 3D ERTmeasurements we are able to produce reliable models in order to estimate such transport parameters as themean flow velocity, and transverse and longitudinal dispersivities.

La compréhension et la maîtrise des mécanismes qui pilotent le vieillissement des aciers en présence d’une sursaturation de lacunes est un défi dans de nombreux domaines industriels, et particulièrement dans le cas des réacteurs nucléaires. Ces aciers contiennent invariablement des solutés interstitiels en tant qu’éléments d’alliage ou impuretés, et des lacunes (V) qui sont des défauts structuraux d’équilibre. Nous avons choisi le système Fe-V –X (X = C, N ou O) comme matériau modèle d’un acier ferritique. Au sein de ce système, des amas lacunes-solutés interstitiels sont susceptibles de se former car, malgré les concentrations très faibles de leurs constituants, ces amas présentent une énergie de liaison importante. Dans cette étude, nous avons tout d’abord cherché à calculer les propriétés intrinsèques d’équilibre de ces amas traités individuellement, à la fois leur propriétés thermodynamiques (énergie libre de liaison) et cinétiques (mobilité, taux de dissociation, ainsi que leur lien avec une description continue de la diffusion). Cette caractérisation effectuée à l’échelle atomique a ensuite permis de mettre en évidence différents effets de ces amas sur un système macroscopique contenant simultanément différents types d’amas : augmentation des limites de solubilité des solutés et de la concentration totale des lacunes en solution solide, couplage de flux entre lacunes et solutés, accélération des cinétiques de précipitation des solutés et dissolution des précipités par une stabilisation de la solution solide par les lacunes. Ces résultats ont été obtenus grâce au développement et/ou à l’extension de méthodes analytiques de physique statistique qui décrivent les constituants de ces amas et leurs interactions à l’échelle atomique. Enfin, nous nous sommes également intéressés aux cavités dans le fer-α, dont l’étude nécessite une approche différente de celle des petits amas. Entre autres, nous avons étudié les effets d’un réseau discret sur la forme d’équilibre d’une cavité, et décrit différents mécanismes d’évolution de ces objets à l’échelle atomique. / Understanding and monitoring the aging of steels under vacancy supersaturation is a challenge of great practical interest for many industrial groups, and most of all for those related to nuclear energy. These steels always contain interstitial solutes, either as alloying elements or as impurities, and vacancies (V) that are equilibrium structural defects of materials. We have chosen the Fe-V -X system (X = C, N or O) as a model system for ferritic steels. Vacancy-solute clusters are likely to form in such systems because, despite the very low concentrations of their components, these cluster show very high attractive bonding. First of all, we have been working on the computation of intrinsic equilibrium properties of individual clusters, both thermodynamic (free binding energies) and kinetic (mobilities, dissociation coefficients, and their relationship with continuum diffusion) properties. Thanks to this atomic-scale characterization procedure, we have been able to highlight various effects of these clusters on a macroscopic system containing different cluster types : increase of solute solubility limits and total vacancy concentrations, flux couplings between interstitial solutes and vacancies, acceleration of solute precipitation kinetics and precipitate dissolution by solid solution stabilization due to vacancies. These results would not have been obtained without the development and/or extension of analytical methods in statistical physics which are able to describe cluster’s components and their interactions at the atomic scale. Finally, we have also been working on cavities in α-iron, the study of which requires a different approach. Our study highlights the impact of the atomic discrete lattice on the equilibrium shape of cavities, and describes various kinetic mechanisms of these objects at the atomic scale.

Pevaporation is a method for separating volatile components from liquid mixtures at ambient temperatures. The paint processing industry uses Hansen solubility parameters (HSP) to indicate polymer solubility. The potential of this method to predict solvent-polymer affinity was investigated for screening potential membrane materials for the pervaporation of a model solution containing linalool and linalyl acetate (major components of lavender essential oil), in ethanol. Published HSP values were collated for various polymers, and statistically analysed to determine variations in HSP values for polymer species. An investigation of published research into pervaporation of organic/organic binary solutions separated by homogeneous membranes indicated that the solvent whose HSP value was closest to that of the polymer would preferentially permeate. This relationship did not always hold for halogenated solvents or aqueous/organic solutions. Conflicting literature regarding the relationship between solvent uptake by polymers and HSP relative energy differences was resolved using a logarithmic relationship between these two parameters. The following membranes were selected, using their HSP to indicate their potential to interact with lavender oil components: Polyamide (PA: 26.9 micro;m), Polycarbonate (PC: 20.5 micro;m), Poly(ether imide) (PEI: 29.2 micro;m), Poly(ether sulphone) (PES: 27.6 micro;m), Polyethylene (HDPE: 10 micro;m, LDPE: 13-30 micro;m), Polyimide (PI: 30.0 micro;m), Poly(methyl methacrylate) (PMMA: 50 micro;m), Polypropylene (PP: 15.9 micro;m), and Poly(tetrafluoro ethylene) (PTFE: 26.7 micro;m). The HSP (dispersive, polar hydrogen bonding components) for each membrane were calculated using the mean value obtained from swelling experiments, group contribution (calculated using Hoftyzer-Van Krevelen, Hoy and Beerbower methods), refractive indices (dispersive component), dielectric constants (polar component), and published HSP values. Pervaporation experiments investigated the effect of membrane thickness, process temperature, permeate pressure, impinging jet heights, feed flow rates and concentrations, and pre-soaking the membrane; on flow rate and selectivity in a polyethylene membrane. Membrane thickness was the dominant factor in membrane selectivity; the thinnest membranes (11.3-14.8 micro;m) had much poorer selectivity than membranes gt;24.7 micro;m. Temperatures between 22-34ordm;C, permeate pressure lt;10 kPa, impinging jet heights between 0.36-3.36 mm, feed flow rates between 541-1328 mL/min and concentrations between 1.78-6.01 % v/v of linalool and linalyl acetate in ethanol did not significantly affect selectivity. Flow rates increased with operating temperature, permeate pressure, and impinging jet heights. However, feed flow rate and concentration had no effect on membrane flux rate. Pre-soaking the membrane reduced the time to reach steady-state. Selected membranes were further investigated under standard operating conditions (permeate temperature 30ordm;C, permeate pressure lt;10 kPa, impinging jet height 1.36 mm, feed flow rate 804 mL/min and feed concentration of 5% v/v of linalool and linalyl acetate in ethanol). PMMA completely disintegrated in feed solution, and PC was too brittle to make an effective homogeneous membrane. PA, PC, PEI and PTFE had the highest efficiency (selectivity x flow rate) in their homogeneous form. However, PEI, PI and PTFE had the greatest selectivity, thus further trials should be done to improve stability and flow rates through these membranes. Pervaporation selectivity did not always follow trends predicted by HSP. Although polymers such as PA, PEI, PES, and PI preferentially permeated linalool as predicted, PC, PP and PTFE did not preferentially permeate linalyl acetate. This may have been due to the difference in size and diffusivity of these molecules (linalyl acetate, the larger molecule, did not follow the sorption selectivity predictions), or reliability of literature HSP values and those calculated by group contribution. This research shows that HSP is a good screening method for pervaporation membranes, especially where the molecules being separated are of comparable size. Polymers that have HSP close to the desired component and not to other components tend to have the best selectivity and flux characteristics. However, diffusion is an important factor, and is not completely accounted for by HSP. Recommendations for further research include: carrying out pervaporation analyses of selected polymers using pure lavender essential oil; modifying polymers to form asymmetric or composite membranes with improved permeation characteristics; and potential use of thin channel inverse gas chromatography to determine a more accurate HSP which includes diffusivity.

Drug transport across cells and cell membranes in the human body is crucial for the pharmacological effect of drugs. Active transport governed by transport proteins plays an important role in this process. A vast number of transport proteins with a wide tissue distribution have been identified during the last 15 years. Several important examples of their role in drug disposition and drug-drug interactions have been described to date. Investigation of drug-drug interactions at the transport protein level are therefore of increasing interest to the academic, industrial and regulatory research communities. The gene expression of transport proteins involved in drug transport was investigated in the jejunum, liver, kidney and colon to better understand their influence on the ADMET properties of drugs. In addition, the gene and protein expression of transport proteins in cell lines, widely used for predictions of drug transport and metabolism, was examined. The substrate and inhibitor heterogeneity of many transport proteins makes it difficult to foresee whether the transport proteins will cause drug-drug interactions. Therefore, in vitro assays for OCT1 and OATP1B1, among the highest expressed transport proteins in human liver, were developed to allow investigation of the inhibitory patterns of these proteins. These assays were used to investigate two data sets, consisting of 191 and 135 registered drugs and drug-like molecules for the inhibition of OCT1 and OATP1B1, respectively. Numerous new inhibitors of the transport proteins were identified in the data sets and the properties governing inhibition were determined. Further, antidepressant drugs and statins displayed strong inhibition of OCT1 and OATP1B1, respectively. The inhibition data was used to develop predictive in silico models for each of the two transport proteins. The highly polymorphic nature of some transport proteins has been shown to affect drug response and may lead to an increased risk of drug-drug interactions, and therefore, the OCT1 in vitro assay was used to study the effect of common genetic variants of OCT1 on drug inhibition and drug-drug interactions. The results indicated that OCT1 variants with reduced function were more susceptible to inhibition. Further, a drug-drug interaction of potential clinical significance in the genetic OCT1 variant M420del was proposed. In summary, gene expression of transport proteins was investigated in human tissues and cell lines. In vitro assays for two of the highest expressed liver transport proteins were used to identify previously unknown SLC transport protein inhibitors and to develop predictive in silico models, which may detect previously known drug-drug interactions and enable new ones to be identified at the transport protein level. In addition, the effect of genetic variation on inhibition of the OCT1 was investigated.

Transport across the membrane of a cell is of crucial importance for cellular functions. The solute carrier family,SLC38 is a family of membrane proteins that transports various substances through the membrane and thusperforms many physiologically important functions, for example, transport of glutamine from astrocyte toneurons in the central nervous system. In this paper, we demonstrate that one of the transporters in this familynamed SLC38A6 forms several protein complexes with a variety of proteins in the membrane and in synapticvesicles, suggesting that SLC38A6 is involved in the synaptic release of neurotransmitters in synapses. Weperformed sensitive protein interaction analysis between the protein of interest and a variety of proteinsexpressed at different sites in the neuronal cell. We showed that SLC38A6 interacts with proteins in the cellmembrane as well as in the membrane of synaptic vesicles. The current theory is that SLC38A6 interact withthese proteins when the synaptic vesicles are in close proximity with the cell membrane during the release of theneurotransmitters.