Pore water pressure in a silt slope in Sollefteå, Sweden, was measured from 2009-2016. The results from2009-2012 were presented and evaluated in a publication by Westerberg et al. (2014) and this report is an extension of that project.In a silt slope the pore water pressures are generally negative, contributing to the stability of theslope. In this report the pore water pressure variations are analyzed using basic statistics and a connection between the pore water pressure variations, the geology and parameters such as temperature, precipitation and soil moisture are discussed.The soils in the slope at Nipuddsvägen consists of sandy silt, silt, clayey silt and silty clay. The main findings were that at 2, 4 and 6 m depth there are significant increases and decreases in the pore water pressure that can be linked with the changing of the seasons, for example there is a significant increase in the spring when the ground frost melts. As the seasons change, so do the temperature and amount and type of precipitation. Other factors that vary with the season are the amount of net radiation, wind speed and relative humidity, all of which affect the amount of evapotranspiration. At greater depths the pore water pressue is most likely affected by a factor/factors that varies from year to year, possibly the total amount of rainfall. Therefore, the anticipated increase in precipitation in Scandinavia due to climate change could be an important factor influencing slope stability.What precipitation, temperature and evapotranspiration have in common is that they affect the amount of water infiltrating the soil, and thereby the soil moisture content. How the soil moisture is distributed and flows through the soil (sub-surface flow) is governed by the different soil types and their mutual order in the slope, as well as by factors affecting the structure of the soil, e.g. animal burrows and aggregation. The formation of ground frost also affects the way in which the water present in the soil is redistributed.At c. 14 m depth in the slope, there is a saturated layer with positive pore water pressures, which could be one of several such layers. The overall groundwater situation in a silt slope is complex; several different bodies of water can develop, and to get a complete picture of the ground water situation (andthereby also the pore water pressure variations) thorough hydrological surveys are needed. / Under  2009-2016  mättes  porvattentrycket  i  en  siltslänt  i  Sollefteå.  Resultaten  från  2009-2012presenterades och utvärderades i en publikation av Westerberg et al. (2014) och detta examensarbete är en förlängning av det projektet.I en siltslänt är porvattentrycket vanligtvis negativt vilket bidrar till stabiliteten i slänten. I den härrapporten är variationerna av porvattentrycket analyserade med hjälp av enkel statistik och en koppling mellan variationerna och geologin samt parametrar så som temperatur, nederbörd och fukthalt i marken diskuteras.Jordarterna i slänten vid Nipuddsvägen består av sandig silt, silt, lerig silt och siltig lera. Slutsatsen var att på 2, 4 och 6 m djup ökade och minskade porvattentrycket med årstiderna, till exempel ökade porvattentrycket signifikant vid tjällossningen. När årstiderna skiftar ändras även temperaturen och mängden, och typen, av nederbörd. Andra faktorer som varierar över året är netto-instrålningen, vindhastigheten och den relativa fuktigheten och dessa faktorer påverkar i sin tur evapotranspirationen. På större djup beror antagligen portrycksvariationerna på någon eller några faktorer som skiljer sig åt från år till år, möjligtvis den totala mängden nederbörd. Därmed skulle den ökade nederbörd som förväntas i Skandinavien på grund av klimatförändringarna kunna påverka släntstabiliteten.Vad nederbörd, temeperatur och evapotranspiration har gemensamt är att de påverkar mängden vatten som infiltrerar marken, det vill säga de påverkar markens fukthalt. Hur vattnet är födelat i marken beror på de olika jordarterna och deras inbördes ordning i slänten, men också av faktorer som påverkar markens struktur så som aggregation och uppluckring av jorden på grund av marklevande djurs aktivitet. Även formationen av tjäle på vintern har troligtvis en viss inverkan på hur vattnet i marken omfördelas.På 14 m djup finns ett vattenmättat lager med positiva porvattentryck vilket skulle kunna vara ett av flera sådana lager. I en siltslänt är grundvattensituationen mycket komplex, flera magasin av vatten kan bildas. För att få en bra bild av grundvattensituationen (och där med också porvattentrycksvariationerna)behöver noggranna hydrologiska undersökningar genomföras.

Accurate prediction of colloid deposition rates in porous media is essential in several applications. These include natural filtration of pathogenic microorganisms such as bacteria, viruses, and protozoa, transport and fate of colloid-associated transport of contaminants, deep bed and river bank filtration for water treatment, fate and transport of engineered nanoparticles released into the environment, and bioremediation of contaminated sites. Colloid transport in porous media is a multi-scale problem, with length scales spanning from the sub-pore scale, where the particle-soil interaction forces control the deposition, up to the Darcy scale, where the macroscopic equations governing particle transport are formulated. Colloid retention at the Darcy scale is due to the lumped effect of processes occurring at the pore scale. This requires the incorporation of the micro-scale physics into macroscopic models for a better understanding of colloid deposition in porous media. That can be achieved through pore-scale modeling and the subsequent upscaling to the Darcy scale. Colloid Filtration Theory (CFT), the most commonly used approach to describe colloid attachment onto the soil grains in the subsurface, is found to accurately predict the deposition rates of micron-sized particles under favorable conditions for deposition. But, CFT has been found to over predict particle deposition rates at low flow velocity conditions, typical of groundwater flow, and for nanoscale particles. Also, CFT is found to be inapplicable at typical environmental conditions, where conditions become unfavorable for deposition, due to factors not considered in CFT such as deposition in the secondary minimum of the interaction energy profile, grain surface roughness, surface charge heterogeneity of grains and colloids, and deposition at grain-to-grain contacts. To the best of our knowledge, mechanistic-based models for predicting colloid deposition rates under unfavorable conditions do not exist. Currently, fitting the colloid breakthrough curve (BTC), obtained from the laboratory column-or field-scale experiments, to the advection-dispersion-deposition model is used to estimate the values of deposition rate coefficients. Because of their small size (less than 100 nm), nanoparticles, a sub-class of colloids, may interact with the porous medium in a different way as compared to the larger colloids, resulting in different retention mechanisms for nanoparticles and micron-sized particles. This emphasizes the need to study nanoparticles separately from larger, micrometer-sized colloids to better understand nanoparticle retention mechanisms. The work reported in this thesis contributes towards developing mathematical models to predict nanoparticle movement in porous media. A comprehensive mechanistic approach is employed by integrating pore-scale processes into Darcy-scale models through pore-network modeling to upscale nanoparticle transport in saturated porous media to the Darcy scale, and to develop correlation equations for the Darcy-scale deposition parameters in terms of various measurable parameters at Darcy scale. Further, a one-dimensional mathematical model to simulate the co-transport of viruses and colloids in partially saturated porous media is developed to understand the relative importance of various interactions on virus transport in porous media. Pore-network modeling offers a valuable upscaling tool to express the macroscopic behavior by accounting for the relevant physics at the underlying pore scale. This is done by idealizing the pore space as an interconnected network of pore elements of different sizes and variably connected to each other, and simulating flow and transport through the network of pores, with the relevant physics implemented on a pore to pore basis (Raoof, 2011). By comparing the results of pore-network modeling with an appropriate mathematical model describing the macro-scale behavior, a relationship between the properties at the macro scale and those at the pore scale can be obtained. A three dimensional multi-directional pore-network model, PoreFlow, developed by Raoof et al. (2010, 2013) is employed in this thesis, which represents the porous medium as an interconnected network of cylindrical pore throats and spherical pore bodies, to upscale nanoparticle transport from pore scale to the Darcy scale. The first step in this procedure is to obtain relationships between adsorbed mass and aqueous mass for a single pore. A mathematical model is developed to simulate nanoparticle transport in a saturated cylindrical pore by solving the full transport equation, considering various processes such as advection, diffusion, hydrodynamic wall effects, and nanoparticle-collector surface interactions. The pore space is divided into three different regions: bulk, diffusion and potential regions, based on the dominant processes acting in each of these regions. In both bulk and diffusion regions, nanoparticle transport is governed by advection and diffusion. However, in the diffusion region, the diffusion is significantly reduced due to hydrodynamic wall effects. Nanoparticle-collector interaction forces dominate the transport in the potential region where deposition occurs. A sensitivity analysis of the model indicates that nanoparticle transport and deposition in a pore is significantly affected by various pore-scale parameters such as the nanoparticle and collector surface potentials, ionic strength of the solution, flow velocity, pore radius, and nanoparticle radius. The model is found to be more sensitive to all parameters under favorable conditions. It is found that the secondary minimum plays an important role in the deposition of small as well as large nanoparticles, and its contribution is found to increase as the favorability of the surface for adsorption decreases. Correlation equations for average deposition rate coefficients of nanoparticles in a saturated cylindrical pore under unfavorable conditions are developed as a function of nine pore-scale parameters: the pore radius, nanoparticle radius, mean flow velocity, solution ionic strength, viscosity, temperature, solution dielectric constant, and nanoparticle and collector surface potentials. Advection-diffusion equations for nanoparticle transport are prescribed for the bulk and diffusion regions, while the interaction between the diffusion and potential regions is included as a boundary condition. This interaction is modeled as a first-order reversible kinetic adsorption. The expressions for the mass transfer rate coefficients between the diffusion and the potential regions are derived in terms of the interaction energy profile between the nanoparticle and the collector. The resulting equations are solved numerically for a range of values of pore-scale parameters. The nanoparticle concentration profile obtained for the cylindrical pore is averaged over a moving averaging volume within the pore in order to get the 1-D concentration field. The latter is fitted to the 1-D advection-dispersion equation with an equilibrium or kinetic adsorption model to determine the values of the average deposition rate coefficients. Pore-scale simulations are performed for three values of Péclet number, Pe = 0.05, 5 and 50. It is found that under unfavorable conditions, the nanoparticle deposition at pore scale is best described by an equilibrium model at low Péclet numbers (Pe = 0.05), and by a kinetic model at high Péclet numbers (Pe = 50). But, at an intermediate Pe (e.g., near Pe = 5), both equilibrium and kinetic models fit the 1-D concentration field. Correlation equations for the pore-averaged nanoparticle deposition rate coefficients under unfavorable conditions are derived by performing a multiple-linear regression analysis between the estimated deposition rate coefficients for a single pore and various pore-scale parameters. The correlation equations, which follow a power law relationship with nine pore-scale parameters, are found to be consistent with the column-scale and pore-scale experimental results, and qualitatively agree with CFT. Nanoparticle transport is upscaled from pore to the Darcy scale in saturated porous media by incorporating the correlations equations for the pore-averaged deposition rate coefficients of nanoparticles in a cylindrical pore into a multi-directional pore-network model, PoreFlow (Raoof et al., 2013). Pore-network model simulations are performed for a range of parameter values, and nanoparticle BTCs are obtained from the pore-network model. Those curves are then modeled using 1-D advection-dispersion equation with a two-site first-order reversible deposition, with terms accounting for both equilibrium and kinetic sorption. Kinetic sorption is found to become important as the favorability of the surface for deposition decreases. Correlation equations for the Darcy¬scale deposition rate coefficients under unfavorable conditions are developed as a function of various measurable Darcy-scale parameters, including: porosity, mean pore throat radius, mean pore water velocity, nanoparticle radius, ionic strength, dielectric constant, viscosity, temperature, and surface potentials on the nanoparticle and grain surface. The correlation equations are found to be consistent with the observed trends from the column experiments available in the literature, and are in agreement with CFT for all parameters, except for the mean pore water velocity and nanoparticle radius. The Darcy-scale correlation equations contain multipliers whose values for a given set of experimental conditions need to be determined by comparing the values of the deposition rate coefficients predicted by the correlation equations against the estimated values of Darcy-scale deposition parameters obtained by fitting the BTCs from column or field experiments with 1-D advection-dispersion-deposition model. They account for the effect of factors not considered in this study, such as the physical and chemical heterogeneity of the grain surface and nanoparticles, flow stagnation points, grain-to-grain contacts, etc. Colloids are abundant in the subsurface and have been observed to interact with a variety of contaminants, including viruses, thereby significantly influencing their transport. A mathematical model is developed to simulate the co-transport of viruses and colloids in partially saturated porous media under steady state flow conditions. The virus attachment to the mobile and immobile colloids is described using a linear reversible kinetic model. It is assumed that colloid transport is not affected by the presence of attached viruses on its surface, and hence, colloid transport is decoupled from virus transport. The governing equations are solved numerically using an alternating three-step operator splitting approach. The model is verified by fitting three sets of experimental data published in the literature: (1) Syngouna and Chrysikopoulos (2013) and (2) Walshe et al. (2010), both on the co-transport of viruses and clay colloids under saturated conditions, and (3) Syngouna and Chrysikopoulos (2015) for the co-transport of viruses and clay colloids under unsaturated conditions. The model results are found to be in good agreement with the observed BTCs under both saturated and unsaturated conditions. Then, the developed model was used to simulate the co-transport of viruses and colloids in porous media under unsaturated conditions, with the aim of understanding the relative importance of various processes on the co-transport of viruses and colloids. The virus retention in porous media in the presence of colloids is greater under unsaturated conditions as compared to the saturated conditions due to: (1) virus attachment to the air-water interface (AWI), and (2) co-deposition of colloids with attached viruses on its surface to the AWI. A sensitivity analysis of the model to various parameters showed that virus attachment to AWI is the most sensitive parameter affecting the BTCs of both free viruses and total mobile viruses, and has a significant effect on all parts of the BTC. The free and the total mobile virus BTCs are mainly influenced by parameters describing virus attachment to the AWI, virus interactions with mobile and immobile colloids, virus attachment to solid-water interface (SWI), and colloid interactions with SWI and AWI. The virus BTC is relatively insensitive to parameters describing the maximum adsorption capacity of the AWI for colloids, inlet colloid concentration, virus detachment rate coefficient from the SWI, maximum adsorption capacity of the AWI for viruses, and inlet virus concentration.

The production of membranous vesicles is observed to occur among organisms from all domains of the tree of life spanning prokaryotes (bacteria, archaea) and eukaryotes (plants, animals and fungi). Bacterial release of membrane-derived vesicles (MVs) has been studied most extensively in cases of Gram-negative species and implicating their outer membrane in formation of extracellular MVs. However, recent studies focusing on Gram-positive bacteria have established that they also undergo MV formation. Membrane vesicles are released during normal bacterial growth, they are derived from the bacterial membrane(s) and may function as transporters of different proteins, DNA and RNA to the neighbouring bacteria or to the cells of a mammalian host. The transport of virulence factors in a condensed manner via MVs to the host cells presumably protects these proteins from degradation and, thereby, targets the host cells in a specific manner. The aim of my thesis is to investigate secretion of MV-associated virulence factors and to study interactions of MVs produced by two selected Gram-negative and Gram-positive bacteria, i.e. Vibrio cholerae and Listeria monocytogenes, with eukaryotic host cells. Depending on whether the bacterium acts as an extracellular or intracellular pathogen, MVs may be considered to have specific functions, which may lead to the different outcomes of MV-host interactions. V. cholerae transport systems for virulence factors include the Type VI secretion system and MVs (also referred to as the “Type 0” secretion system). We have identified that the biologically active form of PrtV protease in different V. cholerae serogroups is transported via MVs. PrtV protease is essential for V. cholerae environmental survival and protection from natural predator grazing. We demonstrated that PrtV is primarily translocated via the inner membrane to the periplasmic space, where it undergoes autoproteolysis, and the truncated version of PrtV protein is packaged inside the MVs and released from the surface of bacteria. MV-associated PrtV protease showed a contribution to bacterial resistance towards the antimicrobial peptide LL-37, thereby, enhancing bacterial survival by avoiding this innate immune defense of the host. We also studied another virulence factor of V. cholerae, the pore-forming toxin VCC, which was found to be transported by MVs. MV-associated VCC is biologically active and triggers an autophagic response in the target cells. We suggested that autophagy serves as a cellular defense mechanism against the MV-associated bacterial virulence factor of V. cholerae. Listeria monocytogenes is a Gram-positive intracellular and facultative anaerobic food-borne pathogen causing listeriosis. It causes only sporadic outbreaks in healthy individuals, however, it is dangerous for a fetus or newborn child, and for pregnant and immunocompromised people, leading to a deadly infection in one third of the cases. We have analyzed MVs produced by L. monocytogenes and their interaction with eukaryotic cells. Confocal microscopy analysis showed that MVs are internalized into HeLa and HEK293 cells and are accumulated in lysosomes. Moreover, L. monocytogenes produces MVs inside the host cells and even inside the phagosomes. We found that the major virulence factor of L. monocytogenes, the cholesterol-dependent pore-forming protein listeriolysin O (LLO), is entrapped inside the MVs and resides there in an oxidized inactive state. LLO is known to induce autophagy by making pores in the phagosomal membrane of targeted eukaryotic cells. In our studies, we have shown that MVs effectively abrogated autophagy induced by Torin1, by purified LLO or by another pore-forming toxin from V. cholerae. We also found that MVs promote bacterial intracellular survival inside mouse embryonic fibroblasts. In addition, MVs have been shown to have a strong protective activity against host cell necrosis initiated by pore-forming toxin. Taken together, these findings suggested that in vivo MVs production from L. monocytogenes might be a relevant strategy of bacteria to manipulate host responses and to promote bacterial survival inside the host cells.

Afin de mieux comprendre les spécificités de l'écoulement des fluides en seuil en géométries confinées, nous avons opté pour une approche multi-échelle expérimentale et/ou numérique dans des milieux poreux complexes et modèles. Nous montrons qu'il est possible d'utiliser la RMN pour visualiser des écoulements de fluides à seuil en géométrie complexe. Dans un milieu poreux, il est également possible de mesurer la distribution statistique des vitesses, ceci sans problème de résolution spatiale, grâce à la méthodologie de réglage d'une expérience d'injection sous IRM que nous avons mise en place. A l'aide de ces techniques, nous montrons que l'écoulement d'un fluide à seuil dans un pore modèle (une expansion-contraction axisymétrique) se localise dans la partie centrale du pore, dans le prolongement du tube d'entrée, tandis que les régions extérieures restent dans le régime solide. Des simulations numériques confirment ces résultats et montrent que la localisation de l'écoulement provient du confinement engendré par la géométrie. A l'inverse, nous montrons que pour un fluide à seuil s'écoulant dans un milieu poreux réel (en trois dimensions), il n'existe pas de zones au repos. De plus, la distribution de vitesse est identique à celle d'un fluide newtonien. Une analyse de ces résultats nous permet de prédire la forme de la loi de Darcy pour les fluides à seuil et de comprendre l'origine physique des paramètres déterminés par des expériences d'injection « macroscopiques » / To better understand the specifics of the flow of yield stress fluids in confined geometries, we opted for a multi-scale experimental and / or numerical approach in complex and model porous media. We show the usefulness of NMR for the study of yield stress fluid's flows in complex geometry. In a porous medium, we can also measure the true probability density function of fluid velocities without spatial resolution problem thanks to a complete optimisation of the design process of a NMR-PGSE experiment. Using these measurement technics, we find that the flow of a yield stress fluid in a model pore (an axisymetric expansion-contraction) is localised in the central part of the pore, i.e. in the continuity of the entry duct, and the external region stay at rest in the solid regime. Numerical simulations confirm those results and point out that the flow localisation is due to the confinement caused by the geometry. On the contrary, no region at rest exists for a yield stress fluid flowing through a real porous media (in 3D). Furthermore, the velocity distribution is the same as a newtonian fluid. The analysis of the results makes it possible to deduce the form of the Darcy's law for yield stress fluids and provides an insight in the physical origin of the coefficients found by “macroscopical” injection experiments

Dans ce travail des électrodes macro- et mesoporeuses hautement organisées ont été fabriquées grâce à l' électrodéposition dans différents types de template. Des cristaux colloïdaux obtenus par la technique de Langmuir-Blodgett ont été infiltrés par des métaux ou des polymères conducteurs en utilisant l'électrodéposition potentiostatique suivi par la dissolution du template. La taille des pores, ainsi que l'épaisseur du film macroporeux pouvaient être contrôlée respectivement par le diamètre des billes de silice et par des oscillations temporelles du courant. Différentes superstructures colloïdales ont également été produites menant à des électrodes avec des défauts artificiels ou des gradients bien définis en termes de taille des pores. Des couches alternantes de différents métaux ont été déposées avec grande précision dans une monocouche de particules entrainant une modification des propriétés optiques du matériau. La miniaturisation a pu être démontrée par l'élaboration des microcylindres d'or macroporeux qui disposent non seulement d'une plus grande surface active mais aussi d'une plus grande activité catalytique envers la réduction de l'oxygène en comparaison avec leurs homologues non poreux. Dans ce même contexte une cellule électrochimique miniaturisée composé de deux électrodes macroporeuses a été proposée. Par ailleurs du platine mesoporeux a été électrodéposé en présence d`un template de type cristaux liquides lyotropes sur des réseaux de microélectrodes. Grâce à une plus grande surface active par rapport à leurs homologues non poreux des microélectrodes mesoporeuses ont montré une meilleure performance dans l'enregistrement de l' activité neuronale due à un niveau de bruit plus faible. / In the present work template-assisted electrodeposition was used to produce highly ordered macro- and mesoporous electrodes. Colloidal crystals obtained by the Langmuir-Blodgett (LB) technique were infiltrated using potentiostatic electrodeposition of metals and conducting polymers followed by removal of the inorganic template. In the resulting macroporous electrodes, the pore diameter was controlled by the size of the silica spheres, while the thickness could be controlled by temporal current oscillations caused by a periodic change of the electroactive area in the template. Various colloidal superstructures were produced in this way leading to electrodes with on purpose integrated planar defects or well-defined gradients in terms of pore size. Furthermore we showed that alternating multilayers of different metals could be deposited with high accuracy into a colloidal monolayer altering the optical properties of the material. Successful miniaturization of the process was demonstrated by elaborating macroporous gold microcylinders showing besides higher active surface areas also increased catalytic activity towards the reduction of oxygen compared to their flat homologues. In this context a miniaturized electrochemical cell composed of two macroporous gold electrodes was also proposed. Finally, mesoporous platinum films were deposited on microelectrode arrays (MEAs) using lyotropic liquid crystals as templates. The increased surface area of mesoporous compared to smooth electrodes led to improved performance in the recording of neuronal activity with MEAs owing to a reduced noise level.

Au sein des cellules, les ARNms sont liés par de nombreuses protéines, générant ainsi des particules appelées mRNPs (Ribonucléoparticules de messagers). Leur formation est cotranscriptionnelle, et leur composition va réguler l’ensemble des étapes du métabolisme des ARNms : stabilité, maturation, export, localisation et traduction. Au vu de l’importance de ces mécanismes dans la physiologie cellulaire, le contenu protéique des mRNPs est finement régulé dans le temps et l’espace et fait l’objet de nombreux remodelages. Ces changements de composition dépendent notamment des hélicases, ainsi que des modifications post-traductionnelles ; cependant, ces mécanismes demeurent à caractériser de façon plus approfondie. Une modification post-traductionnelle susceptible de moduler ces remaniements depuis la levure S. cerevisiae jusqu’aux métazoaires est la sumoylation. En effet, la SUMO-protéase Ulp1/SENP2, une enzyme clé de la machinerie de sumoylation, est localisée au panier des pores nucléaires, à proximité d’une plateforme d’ancrage des mRNPs destinées à l’export. Par ailleurs, il a été rapporté chez la levure que des mutants affectant la localisation et la stabilité d’Ulp1 présentent des défauts d’export et de localisation des mRNPs. Au vu de ces données, le laboratoire s’est intéressé aux rôles potentiels de la sumoylation dans le métabolisme de ces particules d’ARNm. Dans ce but, un crible protéomique a été réalisé chez la levure S. cerevisiae afin de comparer la composition des mRNPs entre des cellules sauvages ou mutantes pour Ulp1. Ce crible a mis en évidence un rôle d’Ulp1 dans le recrutement de deux composants des mRNPs, le complexe THO et l’hnRNP Hek2. Le complexe THO est un facteur multiprotéique qui participe à la prévention de l’instabilité génique et contribue à la transcription des ARNms, à l’assemblage des mRNPs et à leur export. L’hnRNP Hek2 est une protéine aux rôles multiples, dont l’association à un ARNm est susceptible de moduler sa stabilité, sa traduction et/ou sa localisation. Des analyses biochimiques nous ont permis de mettre en évidence l’existence de formes sumoylées de la sous-unité Hpr1 du complexe THO ainsi que de l’hnRNP Hek2. Toutes deux sont Ulp1-dépendantes, et interviennent sur la partie C-terminale de ces protéines. Nous avons également mis en évidence que chacune de ces sumoylations contrôle le recrutement de son substrat au sein des mRNPs. L’analyse fonctionnelle d’un mutant affectant la sumoylation d’Hpr1 a identifié cette modification comme nécessaire au recrutement du complexe THO sur une population d’ARNms impliqués dans la résistance au stress acide, autrement dégradés par l’exosome. Ainsi, l’absence de sumoylation d’Hpr1 diminue fortement la viabilité cellulaire en conditions de stress, un phénotype supprimé par l’inactivation de l’exosome. L’étude des effets de la sumoylation d’Hek2 suggère une modulation par SUMO de certaines de ses fonctions, notamment dans la localisation cellulaire des ARNms. L’ensemble de ces données fournit donc les deux premiers exemples de régulation du métabolisme des mRNPs par des événements de sumoylation intervenant au niveau du pore nucléaire. / Within the cells, mRNAs are associated to proteins, thereby generating particles called mRNPs (messenger ribonucleoproteins). mRNPs form in a cotranscriptional manner and their composition defines the fate of mRNAs by modulating the different steps of their metabolism, including their stability, their processing, their export, their localisation and their translation. In view of the importance of such mechanisms for cell physiology, several mechanisms ensure a tight spatio-temporal control of mRNPs composition through multiple mRNP remodelling events. These changes in the protein content of mRNPs depend on helicases and post-translational modifications, but remain to be further investigated. Sumoylation is one of the modifications that could contribute to mRNPs remodelling from yeast (S. cerevisiae) to metazoans. Indeed, it has been reported that the SUMO-protease Ulp1/SENP2, a key enzyme of the sumoylation machinery, is localized at the basket of nuclear pore complexes, in close vicinity with mRNPs committed for export. This particular localization, together with the reported defects in mRNPs export and localisation of yeast mutants affecting Ulp1, prompted the lab to ask whether sumoylation could contribute to mRNP biogenesis. In order to investigate this hypothesis, our lab compared mRNPs composition between wild-type and ulp1 mutant S. cerevisiae yeast strains using a proteomic approach. This screen identified two mRNP components that depend on Ulp1 for their recruitment onto these particles: the THO complex and the hnRNP Hek2. The THO complex is a multi-subunit factor that prevents genome instability and contributes to transcription, mRNP assembly and export. Hek2 has multiple functions in mRNA stability, translation and/or localization. Using biochemical approaches, we have been able to visualize sumoylated versions of the Hpr1 subunit of the THO complex and of the hnRNP Hek2. In both cases, this modification depends on Ulp1 activity and occurs on the C-terminal part of the protein. We further showed that these sumoylation events control THO and Hek2 recruitment onto mRNPs. Functional analysis of a mutant impairing Hpr1 sumoylation revealed that this modification is required for proper recruitment of the THO complex onto a subset of mRNAs involved in acidic stress resistance, which are otherwise degraded by the exosome. Decreased Hpr1 sumoylation results in a strong reduction of viability in acid stress conditions, a phenotype that is rescued by inactivation of the exosome. The investigation of the role of Hek2 sumoylation in mRNPs metabolism suggests that this modification regulates some of Hek2 functions, especially in mRNA localisation. All together, these results provide the two first examples of mRNPs components whose functions are regulated by sumoylation events occurring at the level of nuclear pores.

Mesoporous γ-Al2O3 is one of the most widely used catalyst supports for commercial catalytic applications. The performance of a catalyst strongly depends on the combination of textural, chemical and physical properties of the support. Pore size is essential since each catalytic system requires a unique pore size for optimal catalyst loading, diffusion and selectivity. In addition, high surface area and large pore volume usually result in higher catalyst loading, which increases the number of catalytic reaction sites and decreases reaction time. Therefore, determination of surface area and porosity of porous supports is critical for the successful design and optimization of a catalyst support. Moreover, it is important to produce supports with good thermal stability since pore collapsing due to sintering at high temperatures often results in catalyst deactivation. In addition, the ability to control the acidity of the catalyst enables us to design desirable acid sites to optimize product selectivity, activity, and stability in different catalytic applications. This dissertation presents a simple, one-pot, solvent-deficient method to synthesize thermally stable silica-doped alumina (SDA) without using templates. The XRD (X-ray diffraction), HTXRD (high temperature X-ray diffraction), SS NMR (solid state nuclear magnetic resonance), TEM (transmission electron microscopy), TGA(thermogravimetric analysis), and N2 adosorption techniques are used to characterize the structures of the synthesized SDAs and understand the origin of increased thermal stability. The obtained SDAs have a surface area of 160 m2/g, pore volume of 0.99 cm3/g, and a bimodal pore size distribution of 23 and 52 nm after calcination at 1100◦C. Compared to a commercial SDA, the surface area, pore volume, and pore diameter of synthesized SDAs are higher by 46%, 155%, and 94%, respectively. A split-plot fractional-factorial experimental design is also used to obtain a useful mathematical model for the control of textural properties of SDAs with a reduced cost and number of experiments. The proposed quantitative models can predict optimal conditions to produce SDAs with high surface areas greater than 250 m2/g, large pore volume greater than 1 cm3/g, and large (40-60 nm) or medium (16-19 nm) pore diameters. In my approach, I control acid sites formation by altering preparation variables in the synthesis method such as Si/Al ratio and calcination temperatures. The total acidity concentration (Brønsted and Lewis) of the synthesized SDAs are determined using ammonia temperatured program, pyridine fourier transform infrared spectroscopy (FTIR), and MAS NMR. The total acidity concentration is increased by introducing a higher mole ratio of Si to Al. In addition, the total acidity concentration is decreased by increasing calcination temperature while maintaining high surface area, large porosity, and thermal stability of γ-alumina support. I also present an optimized synthesis of various aluminum alkoxides (aluminum n-hexyloxide (AH), aluminum phenoxide (APh) and aluminum isopropoxide (AIP)) with high yields (90-95%). One mole of aluminum is reacted with excess alcohol in the presence of 0.1 mole % mercuric chloride catalyst. The synthesized aluminum alkoxides are used as starting materials to produce high surface area alumina catalyst supports. Aluminum alkoxides and nano aluminas are analyzed by 1H NMR, 13C NMR, 27Al NMR, gCOSY (2D nuclear magnetic resonance spectroscopy), IR (infrared spectroscopy), XRD, ICP (induced coupled plasma), and elemental analysis.

Les mécanismes responsables du transport hydrodynamique anormal (non-Fickéen) peuvent être rattachés à la complexité de la géométrie du milieu à l'échelle des pores. Dans cette thèse, nous étudions la dynamique des vitesses de particules à l'échelle des pores. À l'aide de simulations de suivi de particules effectuées sur un échantillon numérisé de grès de Berea, nous présentons une analyse détaillée de l'évolution Lagrangienne et Eulérienne et de leur dépendance aux conditions initiales. Le long de leur ligne de courant, la vitesse des particules montre un signal intermittent complexe, alors que leur sériede vitesses spatiales présente des fluctuations régulières. La distribution spatiale des vitesses des particules converge rapidementvers l'état stationnaire. Ces résultats dénotent un processus Markovienqui permet de prédire les fluctuations de vitesse dans le réseau poral.Ces processus, associés à la tortuosité et à la distance de corrélation de vitesse permettent de paramétrer un modèle de marche aléatoire dans le temps (CTRW) et de réaliser le changement d’échelle pour simuler le transport à l’échelle de Darcy. Le modèle, comme tout modèle issu d’un changement d'échelle, repose sur la définition d'un volume élémentaire représentatif (VER). Nous montrons qu’un VER basé sur les statistiques de vitesse permet de définir un support pertinent pour la modélisation du transport hydrodynamique pré-asymptotique à asymptotique, et ainsi d’éviter les limitations associées à l’équation d’advection-dispersionFickéenne. Cette approche est utilisée pour étudier l’impact de l’hétérogénéité du réseau poral sur le volume de mélange et la masse du produit d’une réaction bimoléculaire. / The mechanisms responsible for anomalous (non-Fickian) hydrodynamictransport can be traced back to the complexity of the medium geometry atthe pore-scale. In this thesis, we investigate the dynamics of pore-scaleparticle velocities. Using particle tracking simulations performed on adigitized Berea sandstone sample, we present a detailed analysis of theevolution of the Lagrangian and Eulerian evolution and their dependenceon the initial conditions. The particles experience a complexintermittent temporal velocity signal along their streamline while theirspatial velocity series exhibit regular fluctuations. The spatialvelocity distribution of the particles converges quickly to thesteady-state. These results lead naturally to Markov processes for theprediction of these velocity series.These processes, together with the tortuosity and the velocitycorrelation distance that are properties of the medium, allow theparameterization of a continuous time random walk (CTRW) for theupscaling of the transport. The model, like any upscaled model, relieson the definition of a representative elementary volume (REV). We showthat an REV based on the velocity statistics allows defining a pertinentsupport for modeling pre-asymptotic to asymptotic hydrodynamictransport at Darcy scale using, for instance, CTRW, thus overcomingthe limitations associated with the Fickian advection dispersionequation. Finally, we investigate the impact of pore-scale heterogeneityon a bimolecular reaction and explore a methodology for the predictionof the mixing volume and the chemical mass produced.

The diffusion behavior of guest molecules introduced in porous materials has been studied. Diffusion studies in such porous materials may help for elucidating the structural properties, transport mechanism and/or surface barriers of the zeolite structure. The focus of this work is on diffusion in nanoporous materials with complex pore spaces. First a short introduction in the basics of diffusion and the PFG NMR technique (Pulsed Field Gradient Nuclear Magnetic Resonance) is described. In the following two chapters the diffusion in hierarchical pore spaces or, to be more precise, zeolites with generated mesopores, which traverse the microporous bulk phase, are investigated. The hierarchical pore spaces consists in the first case of micro- and mesopores and in the second case of micro-, meso- and macropores. The diffusion behavior in these materials has been investigated revealing diffusion acceleration in the mesoporous samples, as compared to the purely microporous material. In the next chapter the diffusion behavior in glass samples with different porosity and their complementary pore space is investigated. Diffusion with full loaded pore spaces and surface diffusion, where the molecules were only able to diffuse along the pore walls, has been explored. The aim was to find out to what extent the diffusion in two complementary pore spaces is correlated. In the last chapter, the effect of an inorganic binder on the transport in zeolite pellets has been studied. First the diffusion behavior in binderless zeolite beads in comparison with the zeolite powder employed for their production has been explored. The particular interest was to find out up to which extent the diffusion patterns observed with the powder samples could again be recognized in the beads. In a second study the transport characteristics within binderless molecular sieves have been investigated, with the purpose to reveal differences in the diffusion behavior in comparison with their binder-containing counterparts.

Characterization of the pore structure is a crucial part in themanufacturing of porous media used for purification of biologicalpharmaceuticals. This project took place at Cytiva in Uppsala and aimedat optimizing a newly developed method in pore structurecharacterization called size-exclusion quantification NMR (SEQ-NMR). Bymeasuring with diffusion NMR on a polymer solution before and afterequilibration with a material of interest the pore structure of thematerial can be determined. This project aimed at reducing the durationof a SEQ-NMR experiment while examining the performance of the methodduring different conditions with the goal of making the methodapplicable for quality control procedures. The method was optimizedboth by simulations and by experimental diffusion NMR measurements. Itwas discovered that the performance of the method could be improved byhaving an optimal mixture of the polymer solution and duringexperiments distributing ten measurement points with linear spacing.With these parameters optimized the duration of the method could bereduced with 22 hours landing on a total duration of 8 hours. Theduration combined with the complexity of the method still makes themethod unsuitable for use in quality control of porous media. Despitethe small possibility of SEQ-NMR being a quality control method thisproject has proven the method to be both reproducible and sensitive.