Les récepteurs AMPA (rAMPA) sont les récepteurs ionotropiques du glutamate responsables de la majeure partie des courants excitateurs rapides dans la transmission synaptique rapide. Lors de la libération de glutamate, le rAMPA passe par 3 états conformationnels majoritaires : pore fermé/agoniste non lié, pore ouvert/agoniste lié et pore fermé/agoniste lié. Le contrôle du nombre et de l’organisation dans la synapse des rAMPA, via une combinaison de diffusion latérale et d’endo/exocytose, est essentiel à la régulation de l’intensité de la transmission synaptique. Les interactions existant entre les protéines de la densité post-synaptique et les protéines partenaires des récepteurs régulent la diffusion des récepteurs, contrôlant leur nombre et leur organisation à la post-synapse. Mon travail de thèse a consisté à étudier l’impact de l’activation des rAMPA sur leur mobilité et leur organisation à la post-synapse. En effet, la fixation de glutamate sur les récepteurs ainsi que leur désensibilisation entraînent des modifications structurales majeures affectant leurs interactions avec les protéines d’échafaudage et les protéines accessoires. L’impact de telles modifications sur les propriétés de diffusion et sur l’organisation sub-synaptique de ces rAMPA était jusqu’à présent inconnu. Mes travaux démontrent une mobilisation des rAMPA synaptiques consécutivement à leur activation par le glutamate. A l’échelle moléculaire, je propose que le passage de l’état activé à l’état désensibilisé des rAMPA entraîne un changement d’affinité de ces derniers pour une de leur protéine partenaire : la Stargazin. Cette régulation glutamate dépendante de la diffusion des rAMPA participe au maintien de la fidélité de la transmission synaptique rapide. / AMPA receptors (AMPAR) are ionotropic glutamate receptors which are responsible for the vast majority of fast excitatory synaptic currents in fast transmission. Upon release of glutamate, AMPAR undergo three main conformational states: pore closed/agonist unbound, pore open/agonist bound and pore closed/agonist bound. Controlling the number of AMPAR and their organization in the synapse, through a combination of lateral diffusion and endo/exocytosis, is essential to regulate the intensity of synaptic transmission. The interactions between proteins of the post-synaptic density and accessory receptor proteins regulate the distribution of receptors, controlling their number and organization in the post-synapse. During my PhD, I studied the impact of AMPAR activation on their mobility and organization in the post-synapse. Indeed, the binding of glutamate to AMPAR and their following desensitization lead to major structural changes on the receptor which impacts on their interactions with scaffolding proteins and accessory proteins. The impact of such modifications on the lateral diffusion and sub-synaptic organization of AMPAR was not known yet. My findings show a mobilization of synaptic AMPAR following their activation by glutamate. At the molecular level, I suggest that the transition from the activated state to the desensitized state of AMPAR leads to a change in affinity of the receptor for their partner protein: Stargazin. This glutamate dependent regulation of AMPAR diffusion participates in maintaining the fidelity of fast synaptic transmission.

Particle-laden turbulent flow through a straight square duct at Reτ = 300 is studied using direct numerical simulation (DNS) and Lagrangian particle tracking. A parallelized 3-D particle tracking direct numerical simulation code has been developed to perform the large-scale turbulent particle transport computations reported in this thesis. The DNS code is validated after demonstrating good agreement with the published DNS results for the same flow and Reynolds number. Lagrangian particle transport computations are carried out using a large ensemble of passive tracers and finite-inertia particles and the assumption of one-way fluid-particle coupling. Using four different types of initial particle distributions, Lagrangian particle dispersion, concentration and deposition are studied in the turbulent straight square duct. Particles are released in a uniform distribution on a cross-sectional plane at the duct inlet, released as particle pairs in the core region of the duct, distributed randomly in the domain or distributed uniformly in planes at certain heights above the walls. One- and two-particle dispersion statistics are computed and discussed for the low Reynolds number inhomogeneous turbulence present in a straight square duct. New detailed statistics on particle number concentration and deposition are also obtained and discussed.

Transport of solid particles in a slit virtual impactor has been analyzed using visualization techniques. Particle trajectories were observed using laser-induced fluorescence of monodisperse particles seeded in the virtual impactor flow. It was observed from these trajectories that for smaller inertia particles essentially followed the flow streamlines, whereas higher inertia particles tend to deflect from their initial streamlines. These transport characteristics were used to determine particle collection efficiency curves, and the percentage of defect particle transmission, particles transmitted to the major flow that are well beyond the experimentally determined 50% cutoff. Defect percentages were found to be in good agreement with those based on a local stokes number approach, an analytical model using a converging flow velocity profile. It was hypothesized that these defects occur by virtue of larger particles passing through the near wall flow region and consequently transported to the major flow. The trajectories of such defect occurrences clearly show that these particles originated in the near wall region. Performance at higher mass loadings was evaluated using a background dust matrix generated by a turntable aerosol generator. At high mass loadings, clogging of the slit led to the deterioration of the impactor's performance. The time taken to clog the silt was estimated by modeling the slit edge as a single filter fiber of rectangular cross section with the primary mechanism of filtration being interception and was found to be in good agreement with the experimental data. Elimination of defect transmission and clogging would be possible by the provision of a sheath airflow, which ensures that the near wall regions are free of particles.

The advective motion of seawater governs the transport of almost everything, animate or inanimate, present in the ocean and those lacking the ability to outswim the currents have to follow the flow. This makes modelling of advective ocean transports a powerful tool in various fields of science where a displacement of something over time is studied. The present thesis comprises four different applications of ocean-transport modelling, ranging from large-scale heat transports to the dispersion of juvenile marine organisms. The aim has been to adapt the method not only to the object of study, but also to the available model-data sets and in situ-observations. The first application in the thesis is a study of the oceanic heat transport. It illustrates the importance of wind forcing for not only the heat transport from the Indian to the Atlantic Ocean, but also for the net northward transport of heat in the Atlantic. In the next study focus is on the particle-transport differences between an open and a semi-enclosed coastal area on the Swedish coast of the Baltic Sea. The modelled patterns of sedimentation and residence times in the two basins are examined after particles having been released from a number of prescribed point sources. In the two final studies the transport-modelling framework is applied within a marine-ecology context and the transported entities are larvae of some Scandinavian sessile and sedentary species and non-commercial fishes (e.g. the bay barnacle, the blue mussel, the shore crab and the gobies). The effects of depth distribution of dispersing larvae on the efficiency of the Marine Protected Areas in the Baltic Sea are examined. Further, the diversity in dispersal and connectivity depending on vertical behaviour is modelled for regions with different tidal regimes in the North Sea, the Skagerrak and the Kattegat. The spatial scales dealt with in the studies varied from global to a highly resolved 182-metres grid. The model results, excepting those from the global study, are based on or compared with in situ-data. / <p>At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Submitted. Paper 3: Submitted. 4: Manuscript.</p>

Transport of solid particles in a slit virtual impactor has been analyzed using visualization techniques. Particle trajectories were observed using laser-induced fluorescence of monodisperse particles seeded in the virtual impactor flow. It was observed from these trajectories that for smaller inertia particles essentially followed the flow streamlines, whereas higher inertia particles tend to deflect from their initial streamlines. These transport characteristics were used to determine particle collection efficiency curves, and the percentage of defect particle transmission, particles transmitted to the major flow that are well beyond the experimentally determined 50% cutoff. Defect percentages were found to be in good agreement with those based on a local stokes number approach, an analytical model using a converging flow velocity profile. It was hypothesized that these defects occur by virtue of larger particles passing through the near wall flow region and consequently transported to the major flow. The trajectories of such defect occurrences clearly show that these particles originated in the near wall region. Performance at higher mass loadings was evaluated using a background dust matrix generated by a turntable aerosol generator. At high mass loadings, clogging of the slit led to the deterioration of the impactor's performance. The time taken to clog the silt was estimated by modeling the slit edge as a single filter fiber of rectangular cross section with the primary mechanism of filtration being interception and was found to be in good agreement with the experimental data. Elimination of defect transmission and clogging would be possible by the provision of a sheath airflow, which ensures that the near wall regions are free of particles.

Models of the fate and transport of river plumes and the bacteria they carry into lakes are developed. They are needed to enable informed decisions about beach closures to avoid economic losses, and to help design water intakes and operate combined sewer overflow schemes to obviate exposure of the public to potential pathogens. This study advances our understanding of river plumes dynamics in coastal waters by means of field studies and numerical techniques. Extensive field measurements were carried out in the swimming seasons of 2006 and 2007 on the Grand River plume as it enters Lake Michigan. They included simultaneous aerial photography, measurements of lake physical properties, the addition of artificial tracers to track the plume, and bacterial sampling. Our observed results show more flow classes than included in previous studies (e.g. CORMIX). Onshore wind can have a significant effect on the plume and whether it impacts the shoreline. A new classification scheme based on the relative magnitude of plume-crossflow length scale and Richardson number based on the wind speed is devised. Previous studies on lateral spreading are complemented with a new relationship in the near field. The plume thickness decreased rapidly with distance from the river mouth and a new non-dimensional relationship to predict thickness is developed. Empirical near field models for surface buoyant plumes are reviewed and a near field trajectory and dilution model for large aspect ratio surface discharge channels is devised. Bacterial reductions due to dilution were generally small (less than 10:1) up to 4.5 km from the river mouth. E. coli decay rates were significantly affected by solar radiation and ranged from 0.2 to 2.2 day-1 which were within the range of previous studies in Lake Michigan. Total coliform survived longer than E. coli suggesting different die-off mechanisms. Mathematical models of the bacterial transport are developed that employ a nested modeling scheme to represent the 3D hydrodynamic processes of surface river discharges in the Great Lakes. A particle tracking model is used that provides the capability to track a decaying tracer and better quantify mixing due to turbulent diffusion. Particle tracking models have considerable advantages over gradient diffusion models in simulating bacterial behavior nearshore that results in an improved representation of bacteria diffusion, decay and transport. Due to the complexity and wide variation of the time and length scale of the hydrodynamic and turbulent processes in the near field (where plume mixing is dominated by initial momentum and buoyancy) and far field (where plume mixing is dominated by ambient turbulence), a coupling technique is adapted. The far field random walk particle tracking model incorporates the empirical near field model. It simulates the transport, diffusion and decay of bacteria as discrete particles and employs the near field output as the source and transports the particles based on ambient currents predicted by the 3D hydrodynamic model. The coupled model improves dilution predictions in the near field. The new techniques advance our knowledge of the nearshore fate and transport of bacteria in the Great Lakes and can be ultimately applied to the NOAA Great Lakes Coastal Forecasting System to provide a reliable prediction tool for bacterial transport in recreational waters.

Particle-laden turbulent flow through a straight square duct at Reτ = 300 is studied using direct numerical simulation (DNS) and Lagrangian particle tracking. A parallelized 3-D particle tracking direct numerical simulation code has been developed to perform the large-scale turbulent particle transport computations reported in this thesis. The DNS code is validated after demonstrating good agreement with the published DNS results for the same flow and Reynolds number. Lagrangian particle transport computations are carried out using a large ensemble of passive tracers and finite-inertia particles and the assumption of one-way fluid-particle coupling. Using four different types of initial particle distributions, Lagrangian particle dispersion, concentration and deposition are studied in the turbulent straight square duct. Particles are released in a uniform distribution on a cross-sectional plane at the duct inlet, released as particle pairs in the core region of the duct, distributed randomly in the domain or distributed uniformly in planes at certain heights above the walls. One- and two-particle dispersion statistics are computed and discussed for the low Reynolds number inhomogeneous turbulence present in a straight square duct. New detailed statistics on particle number concentration and deposition are also obtained and discussed.

No description available.

Tsunami are a fascinating but potentially devastating natural phenomena that have occurred regularly throughout history along New Zealand's shorelines, and around the world. With increasing population and the construction of infrastructure in coastal zones, the effect of these large waves has become a major concern. Many natural phenomena are capable of creating tsunami. Of particular concern is the underwater landslide-induced tsunami, due to the potentially short warning before waves reach the shore. The aims of this research are to generate a quality benchmark dataset suitable for comprehensive comparisons with numerical model results and to increase our understanding of the physical processes involved in tsunami generation. The two-dimensional experimental configuration is based on a benchmark configuration described in the scientific literature, consisting of a semi-elliptical prism sliding down a submerged 15° slope. A unique feature of these experiments is the method developed to measure water surface variation continuously in both space and time. Water levels are obtained using an optical technique based on laser induced fluorescence, which is shown to be comparable in accuracy and resolution to traditional electrical point wave gauges. In the experiments, the landslide density and initial submergence are varied and detailed measurements of wave heights, lengths, propagation speeds, and shore run-up are made. Particle tracking velocimetry is used to record the landslide kinematics and sub-surface water velocities. Particular attention is paid to maintaining a high level of test repeatability throughout the experimental process. The experimental results show that a region of high pressure ahead of the landslide forces up the water over the front half of the landslide to form the leading wave crest, which propagates ahead of the landslide. The accelerating fluid above, and the turbulent wake behind, the moving landslide create a region of low pressure, which draws down the water surface above the rear half of the landslide to form the leading trough. Differences in the phase and group velocities of the components in the wave packet cause waves to be continually generated on the trailing end of the wave train. The downstream position that these waves form continually moves downstream with time and the wave packet is found to be highly dispersive. The interaction of the landslide pressure field with the free surface wave pressure field is important, as the location of the low pressure around the landslide relative to the wave field acts to reinforce or suppress the waves above. This has a substantial effect on the increase or decrease in wave potential energy. When the low pressure acts to draw down a wave trough, the wave potential energy increases. When the low pressure is below a wave crest, it acts to suppress the crest amplitude, leading to an overall decrease in wave potential energy. Measurements of the efficiency of energy transfer from the landslide to the wave field show that the ratio of maximum wave potential energy to maximum landslide kinetic energy is between 0.028 and 0.138, and tends to increase for shallower initial landslide submergences and heavier specific gravities. The ratio of maximum wave potential energy to maximum landslide potential energy ranges between 0.011 and 0.059 and tends to be greater for shallower initial submergences. For two experimental configurations the ratio of maximum wave potential energy to maximum fluid kinetic energy is estimated to be 0.435 and 0.588. The wave trough initially generated above the rear end of the landslide propagates in both onshore and offshore directions. The onshore-propagating trough causes a large initial draw-down at the shore. The magnitude of the maximum draw-down is related to the maximum amplitude of the offshore-propagating first wave trough. A wave crest generated by the landslide as it decelerates at the bottom of the slope causes the maximum wave run-up observed at the shore. A semi-analytical model, based on inviscid and irrotational theory, is used to investigate the wave generation process of a moving submerged object in a constant depth channel. The simplified geometry allows a variety of phenomena, observed during the experimental tests, to be investigated further in a more controlled setting. The variations in the growth, magnitude, and decay of energy as a function of time is due the interaction of the pressure distribution surrounding the moving slider with the wave field, in particular, the leading crest and trough. The largest energy transfer between slider kinetic energy and wave potential energy occurs when there is prolonged interaction between the slider's low pressure region and the leading wave trough. The generation of onshore propagating waves by a decelerating landslide is confirmed, and the magnitude of the maximum wave run-up is found to be dependent on the magnitude of the slider deceleration. The model also shows that slides with Froude number close to unity convert substantial amounts of energy into offshore propagating waves. The onshore propagating wave potential energy is not as sensitive to Froude number. A further result from the model simulations is that the specific shape of the slider has only a minor influence on the wave response, provided the slider's length and area are known. A boundary element model, based on inviscid and irrotational theory, is used to simulate the laboratory experiments. Model predictions of the wave field are generally accurate, particularly the magnitude and range of wave amplitudes within the wave packet, the arrival time of the wave group, the amplitude of the run-up and run-down at the shore, the time the maximum run-down occurs, and the form and magnitude of the wave potential energy time history. The ratios of maximum wave potential energy to maximum slider kinetic energy are predicted to within ± 29%. The model predictions of the crest arrival times are within 3.6% of the measured times. The inability of the inviscid and irrotational model to simulate the flow separation and wake motions lead to a 45% under prediction of the maximum fluid kinetic energy. Both the semi-analytical and BEM models highlight the need for the correct specification of initial slider accelerations in numerical simulations in order to accurately predict the wave energy.

Single-particle tracking (SPT) is a method used to study the diffusion of various molecules within the cell. SPT involves tagging proteins with optical labels and observing their individual two-dimensional trajectories with a microscope. The analysis of this data provides important information about protein movement and mechanism, and is used to create multistate biological models. One of the challenges in SPT analysis is the variety of complex environments that contribute to heterogeneity within movement paths. In this thesis, we explore the limitations of current methods used to analyze molecular movement, and adapt analytical methods used in animal movement analysis, such as correlated random walks and first-passage time variance, to SPT data of leukocyte function-associated antigen-1 (LFA-1) integral membrane proteins. We discuss the consequences of these methods in understanding different types of heterogeneity in protein movement behaviour, and provide support to results from current experimental work. / Applied Mathematics