The prevalence of cardiovascular disease (CVD) has increased dramatically due in part to the increased rates of obesity in North America. Atherosclerosis, the most prevalent type of CVD, is a progressive disease characterized by the build-up of plaque within the arteries. The plaque development leads to the narrowing of arteries, referred to as stenosis, and restricts crucial blood flow to the organs of the body. This condition is often treated by the implantation of a stent, a wire mesh scaffold device placed in the region of an atherosclerotic plaque after balloon angioplasty. The stent was developed to improve the clinical outcome of angioplasty procedures by mitigating the effects of elastic recoil by the vessel wall and maintaining vessel patency after angioplasty. Since the introduction of stents as a treatment option over a decade ago, in-stent restenosis (ISR) has been an iatrogenic outcome and remains an unsolved limitation of the interventional treatment device, resulting in stent failure and additional surgical procedures to restore blood flow. Many improvements have been made in stent design in order to reduce the likelihood of ISR, but none have eliminated the problem. Endothelial cells lining vessel walls transduce local hemodynamic loading in the stent vicinity, such as wall shear stress magnitude (WSS), into biochemical signals that lead to the progression of ISR. Hence, resolving the hemodynamics in the vicinity of the stent is crucial to reducing the rates of stent failure. The objective of the study is to address the problem of ISR by clearly elucidating the flow physics induced by stent implantation, accounting in particular for vessel curvature, by first considering idealized stent models, then progressing to an actual stent model. Stent designs are typically based upon data originating solely from studies of flow in straight vessels, which, once optimized for this configuration, may lead to suboptimal performance when placed in tortuous vessels. Previous stent studies have almost categorically neglected the effects of curvature on the flow physics, despite the fact that even extremely mild curvature changes the axial WSSM distribution within the vessel and induces the development of secondary flows, which alters the advection of chemicals released into the lumen. Using computational fluid dynamics (CFD) techniques, this study seeks to (i) determine the impact of stent strut amplitude and frequency on primary and secondary flow structures; (ii) determine the significance of the stent strut shape in the size of the stagnation zone; (iii) evaluate flow behavior in the transition region from smooth walled to stented vessel; and (iv) examine the collection of these effects in a full stent model geometry in a curved tube. This study takes a systematic approach, dissecting the impact of the stent first into simplified foundational components, then investigating each component and finally synthesizing the components into a full stent model with the long-term goal of optimizing stent design to reduce the rate of restenosis. As well, the study findings can aid in understanding the signal transduction mechanisms of the endothelial cells, which play a role in the development of ISR, and reduce the cardiovascular disease mortality rate by improving the clinical outcome of treatment procedures. Further, the study findings contribute to the fundamental understanding of flow in curved pipes with wall protrusions, the impact of the choice of the constitutive model of the fluid, and the hemodynamic environment in the vicinity of the stent.

O crescimento dos núcleos de recristalização em direção à matriz deformada geralmente não ocorre de forma isotrópica. Perturbações locais na velocidade de migração dos contornos levam ao surgimento de protrusões. Trata-se de um aspecto importante na recristalização, porém ainda pouco explorado na literatura, especialmente quanto ao entendimento de quais mecanismos microestruturais explicam sua formação. O objetivo desta Tese de Doutorado é estudar a formação das protrusões na recristalização do nióbio oligocristalino. Para tal, uma chapa de nióbio com grãos bastante grosseiros foi retirada da seção longitudinal de um lingote fundido por feixe eletrônico. Foram selecionados de forma aleatória cinco grãos (A, B, C, D e E) para se avaliar eventuais efeitos de orientação na formação de protrusões. A chapa foi laminada a frio com vários passes até 50% de redução de espessura. Na sequência, a chapa foi dividida em duas partes, sendo que na primeira foi dado prosseguimento na laminação até atingir 70% de redução de espessura, enquanto que a segunda sofreu rotação de 90° em relação à direção de laminação inicial. As amostras foram recozidas entre 800 e 1200°C por 60 min. O grão E LC recristalizou em todas temperaturas estudadas, e o LD nas temperaturas entre 1000 e 1200°C. O grão A LC recristalizou em todas temperaturas, exceto em 1000°C, e LD recristalizou apenas em 1200°C. O grão C LC recristalizou apenas em 1200°C. Os grãos B e D não recristalizaram em nenhuma temperatura. Não foi possível identificar e associar diferenças significativas quanto ao potencial termodinâmico para recristalização à frente dos contornos com a formação das protrusões. Medidas de EBSD em 3D obtidas por seccionamento serial mostraram diferenças importantes do ponto de vista energético entre o contorno formado entre a protrusão e a matriz recuperada e o contorno entre a lateral do grão recristalizado e a matriz recuperada. O primeiro par é mais móvel, o que explica a morfologia alongada das protrusões. / The growth of recrystallization nuclei towards the deformed matrix generally does not occur in an isotropic manner. Local disturbances in the migration along grain boundaries lead to the formation of protrusions. This is an important aspect in recrystallization, but still less explored in the literature, especially regarding the understanding of which microstructural mechanisms explain its formation. This Thesis aims at to study the formation of protrusions during recrystallization of a niobium oligocrystal. A coarse-grained niobium plate was cut out from the longitudinal section of an electron-beam cast ingot. Five coarse grains (A, B, C, D and E) were randomly selected for this study to evaluate possible orientation effects on protrusion formation. The plate was cold rolled with several passes up to 50% thickness reduction. The sheet was cut into two parts. The former was straight rolled until 70% thickness reduction while the latter was rotated 90° with respect to the initial rolling direction. The samples were annealed at 800 to 1200°C for 60 min. Grain E CR recrystallized at all temperatures studied, and SR at temperatures between 1000 and 1200°C. Grain A CR recrystallized at all temperatures except 1000°C, and SR recrystallized only at 1200°C. Grain C CR recrystallized only at 1200°C. Grains B and D did not recrystallize at any temperature. It was not possible to identify and to associate significant differences of the thermodynamic potential for recrystallization ahead of the boundaries with the formation of protrusions. 3D EBSD measurements obtained by serial sectioning showed important differences regarding grain boundary energy between the boundary formed between the protrusion and the recovered matrix and the boundary formed by the lateral part of the recrystallized grain and the recovered matrix. The first pair is more mobile, which explains the elongated morphology of the protrusions.

Controlling and predicting rupture and dewetting of quiescent thin water films, hundreds of microns thick, was studied experimentally. Wax, polycarbonate, steel and aluminium surfaces were immersed in water; the water level was lowered to form thin films above the surfaces. Spontaneous film rupture only occurred on wax, a low-energy surface. Films ruptured at the edges of the other—high-energy—surfaces. Increased surface roughness decreased chances of rupture and dewetting in the film. Introducing large wax or steel protrusions (on the order of millimetres) on smooth surfaces showed films rupturing above the protrusions and adhering to them; further thinning caused rupture and dewetting away from the protrusions. Entrapped air bubbles, injected through the surface and into the film, ruptured as they breached the film surface to form stable holes in the film if it was sufficiently thin. Entrapped air was the best means of rupturing films on all surfaces.

Controlling and predicting rupture and dewetting of quiescent thin water films, hundreds of microns thick, was studied experimentally. Wax, polycarbonate, steel and aluminium surfaces were immersed in water; the water level was lowered to form thin films above the surfaces. Spontaneous film rupture only occurred on wax, a low-energy surface. Films ruptured at the edges of the other—high-energy—surfaces. Increased surface roughness decreased chances of rupture and dewetting in the film. Introducing large wax or steel protrusions (on the order of millimetres) on smooth surfaces showed films rupturing above the protrusions and adhering to them; further thinning caused rupture and dewetting away from the protrusions. Entrapped air bubbles, injected through the surface and into the film, ruptured as they breached the film surface to form stable holes in the film if it was sufficiently thin. Entrapped air was the best means of rupturing films on all surfaces.

No description available.

L’endocytose est le processus qui permet l’entrée spécifique et active dans la cellule du milieu extracellulaire et des substances qu’il contient. Ces dernières années, plusieurs mécanismes d’endocytose ont été identifiés, mais seule la voie impliquant la clathrine a été bien caractérisée. Il a été montré que certains récepteurs de cytokines comme celui de l’interleukine-2 (IL-2) empruntent une voie d’endocytose indépendante de la clathrine. Précédemment, mon laboratoire a identifié huit facteurs impliqués dans cette voie d’entrée dont l’actine et la dynamine. Nous savons notamment que l’activation de la RhoGTPase Rac1 permet l’induction des kinases Pak1 et Pak2 régulant ainsi la cortactine, le recrutement de N-WASP et la polymérisation d’actine nécessaire à l’internalisation de l’IL-2R. Cependant, les facteurs en amont de cette cascade Rac-Pak étaient inconnus et le rôle du cytosquelette d’actine restait mal défini. Les travaux que j’ai effectué durant mon doctorat ont mis en évidence que la PI3K en interagissant avec l’IL-2R, permettait la production locale de PI(3,4,5)P3 qui induisait le recrutement de Vav2; un facteur conduisant à l’activation de Rac1. De plus, j’ai montré que Rac1 activé était ensuite recruté par la PI3K, permettant ainsi l’activation locale de la cascade Rac/Pak lors de l’entrée de l’IL-2R. Ces données, qui ont fait l’objet d’une publication, ont montré que la PI3K n’était pas seulement impliquée dans la signalisation de l’IL-2, mais également dans son endocytose. Par la suite, la réalisation d’un crible par ARNi portant sur l’étude du rôle de 324 protéines humaines lors de l’entrée de l’IL-2R, a permis l’identification de 65 nouveaux facteurs impliqués dans ce mécanisme. Parmi ces protéines, j’ai étudié plus particulièrement le rôle du complexe WAVE connu pour être induit à la membrane plasmique par Rac1 et la PI3K. J’ai confirmé l’implication de ce complexe lors de l’entrée de l’IL-2R et mis en évidence qu’il interagissait avec le récepteur. De plus, cette étude a montré que le complexe WAVE était impliqué précocement dans ce mécanisme, probablement en permettant le recrutement du récepteur aux pieds de protrusions membranaires que le complexe pourrait induire. Cette localisation spécifique du récepteur suggère ainsi un nouveau mécanisme de formation des vésicules d’endocytose dont le puits s’initierait à partir des invaginations existantes à la base des protrusions membranaires. / Endocytosis is a basic and essential process used by eukaryotic cells to internalize, actively and specifically, a wide range of molecules. To date, several endocytic routes have been characterized, but the only well studied pathway is clathrin-dependent. This study focuses on a poorly characterized mechanism, the clathrin-independent endocytosis, used by several cytokine receptors such as the interleukin 2 receptors (IL-2R). Previously, my lab identified 8 factors in this process, most of them are related to actin polymerization and dynamin. We now know that the activation of the RhoGTPase Rac1 is required to induce Paks that regulate cortactin, N-WASP recruitment and actin polymerization essential for IL-2R uptake. However, upstream factors involved in the Rac-Pak cascade were unknown and the actin cytoskeleton function poorly characterised. During my PhD, I showed that IL-2R and the phosphatidylinositol 3-kinase (PI3K) interact, leading to the local production of phosphatidylinositol (3,4,5)-triphosphate (PIP3) and the recruitment by this lipid of the RacGEF Vav2, an activator of Rac1. In addition, I showed that activated Rac1 was able to interact with PI3K allowing the local activation of the Rac-Pak cascade during IL-2R entry. These published data highlight the dual role of PI3K as a regulator of both IL-2R endocytosis and IL-2 signaling. In an attempt to identify new actors involved in the endocytosis of IL-2R, I then performed a small interfering RNA (siRNA) screening, targeting 324 proteins involved mainly in membrane deformation. From this screening we identified 65 proteins and among them we found the WAVE complex as a new factor implicated in IL-2R uptake. Interestingly, to be recruited and activated at the plasma membrane, the WAVE complex required Rac1 and PI3K, two proteins essentials during IL-2R entry. First, I confirmed the results obtained from the screening and found that IL-2R can interact with the WAVE complex. In addition, I observed an early involvement of this complex during IL-2R uptake, which could be needed for the localization of the receptor at the basis of plasma membrane protrusions. These results reveal a new model for the formation of endocytic vesicles: IL-2R is recruited at the basis of WAVE-induced membrane protrusions initiating the pit and vesicle.

En algorithmique et en complexité, la plus grande part de la recherche se base sur l’hypothèse que P ≠ NP (Polynomial time et Non deterministic Polynomial time), c'est-à-dire qu'il existe des problèmes dont la solution peut être vérifiée mais non construite en temps polynomial. Si cette hypothèse est admise, de nombreux problèmes naturels ne sont pas dans P (c'est-à-dire, n'admettent pas d'algorithme efficace), ce qui a conduit au développement de nombreuses branches de l'algorithmique. L'une d'elles est la complexité paramétrée. Elle propose des algorithmes exacts, dont l'analyse est faite en fonction de la taille de l'instance et d'un paramètre. Ce paramètre permet une granularité plus fine dans l'analyse de la complexité.Un algorithme sera alors considéré comme efficace s'il est à paramètre fixé, c'est-à-dire, lorsque sa complexité est exponentielle en fonction du paramètre et polynomiale en fonction de la taille de l'instance. Ces algorithmes résolvent les problèmes de la classe FPT (Fixed Parameter Tractable).L'extraction de noyaux est une technique qui permet, entre autre, d’élaborer des algorithmes à paramètre fixé. Elle peut être vue comme un pré-calcul de l'instance, avec une garantie sur la compression des données. Plus formellement, une extraction de noyau est une réduction polynomiale depuis un problème vers lui même, avec la contrainte supplémentaire que la taille du noyau (l'instance réduite) est bornée en fonction du paramètre. Pour obtenir l’algorithme à paramètre fixé, il suffit de résoudre le problème dans le noyau, par exemple par une recherche exhaustive (de complexité exponentielle, en fonction du paramètre). L’existence d'un noyau implique donc l'existence d'un algorithme à paramètre fixé, la réciproque est également vraie. Cependant, l’existence d'un algorithme à paramètre fixé efficace ne garantit pas un petit noyau, c'est a dire un noyau dont la taille est linéaire ou polynomiale. Sous certaines hypothèses, il existe des problèmes n’admettant pas de noyau (c'est-à-dire hors de FPT) et il existe des problèmes de FPT n’admettant pas de noyaux polynomiaux.Un résultat majeur dans le domaine des noyaux est la construction d'un noyau linéaire pour le problème Domination dans les graphes planaires, par Alber, Fellows et Niedermeier.Tout d'abord, la méthode de décomposition en régions proposée par Alber, Fellows et Niedermeier, a permis de construire de nombreux noyaux pour des variantes de Domination dans les graphes planaires. Cependant cette méthode comportait un certain nombre d’imprécisions, ce qui rendait les preuves invalides. Dans la première partie de notre thèse, nous présentons cette méthode sous une forme plus rigoureuse et nous l’illustrons par deux problèmes : Domination Rouge Bleue et Domination Totale.Ensuite, la méthode a été généralisée, d'une part, sur des classes de graphes plus larges (de genre borné, sans-mineur, sans-mineur-topologique), d'autre part, pour une plus grande variété de problèmes. Ces méta-résultats prouvent l’existence de noyaux linéaires ou polynomiaux pour tout problème vérifiant certaines conditions génériques, sur une classe de graphes peu denses. Cependant, pour atteindre une telle généralité, il a fallu sacrifier la constructivité des preuves : les preuves ne fournissent pas d'algorithme d'extraction constructif et la borne sur le noyau n'est pas explicite. Dans la seconde partie de notre thèse nous effectuons un premier pas vers des méta-résultats constructifs ; nous proposons un cadre général pour construire des noyaux linéaires en nous inspirant des principes de la programmation dynamique et d'un méta-résultat de Bodlaender, Fomin, Lokshtanov, Penninkx, Saurabh et Thilikos. / In the fields of Algorithmic and Complexity, a large area of research is based on the assumption that P ≠ NP(Polynomial time and Non deterministic Polynomial time), which means that there are problems for which a solution can be verified but not constructed in polynomial time. Many natural problems are not in P, which means, that they have no efficient algorithm. In order to tackle such problems, many different branches of Algorithmic have been developed. One of them is called Parametric Complexity. It consists in developing exact algorithms whose complexity is measured as a function of the size of the instance and of a parameter. Such a parameter allows a more precise analysis of the complexity. In this context, an algorithm will be considered to be efficient if it is fixed parameter tractable (fpt), that is, if it has a complexity which is exponential in the parameter and polynomial in the size of the instance. Problems that can be solved by such an algorithm form the FPT class.Kernelisation is a technical that produces fpt algorithms, among others. It can be viewed as a preprocessing of the instance, with a guarantee on the compression of the data. More formally, a kernelisation is a polynomial reduction from a problem to itself, with the additional constraint that the size of the kernel, the reduced instance, is bounded by a function of the parameter. In order to obtain an fpt algorithm, it is sufficient to solve the problem in the reduced instance, by brute-force for example (which has exponential complexity, in the parameter). Hence, the existence of a kernelisiation implies the existence of an fpt algorithm. It holds that the converse is true also. Nevertheless, the existence of an efficient fpt algorithm does not imply a small kernel, meaning a kernel with a linear or polynomial size. Under certain hypotheses, it can be proved that some problems can not have a kernel (that is, are not in FPT) and that some problems in FPT do not have a polynomial kernel.One of the main results in the field of Kernelisation is the construction of a linear kernel for the Dominating Set problem on planar graphs, by Alber, Fellows and Niedermeier.To begin with, the region decomposition method proposed by Alber, Fellows and Niedermeier has been reused many times to develop kernels for variants of Dominating Set on planar graphs. Nevertheless, this method had quite a few inaccuracies, which has invalidated the proofs. In the first part of our thesis, we present a more thorough version of this method and we illustrate it with two examples: Red Blue Dominating Set and Total Dominating Set.Next, the method has been generalised to larger classes of graphs (bounded genus, minor-free, topological-minor-free), and to larger families of problems. These meta-results prove the existence of a linear or polynomial kernel for all problems verifying some generic conditions, on a class of sparse graphs. As a price of generality, the proofs do not provide constructive algorithms and the bound on the size of the kernel is not explicit. In the second part of our thesis, we make a first step to constructive meta-results. We propose a framework to build linear kernels based on principles of dynamic programming and a meta-result of Bodlaender, Fomin, Lokshtanov, Penninkx, Saurabh and Thilikos.

In this project we studied the effect of different parameters on heat transfer in two-dimensional microchannels, microtubes and also tube-in-block heat exchangers for various engineering applications. These included the use of flow restrictions to enhance local heat or mass transfer rate, enhancement of conjugate heat transfer with discrete heating and magnetic coolers (or heaters) associated with magnetic refrigeration system. The results of this research will help in designing the heating or cooling systems and selection of their appropriate geometrical dimensions and materials for specific applications. Types of problems studied in this project are: steady state analysis of forced convection around a restricted flow passage in a micro channel, effect of protrusions in a microtube or microchannel for conjugate heat transfer with uniform or discrete heating and transient analysis of heat transfer in trapezoidal microchannels under time varying heat source. For each of these problems a numerical simulation model was developed. The mass, momentum, and energy conservation equations were solved in the fluid region and energy conservation in the sold region to arrive at the velocity and the temperature distributions. Detailed parametric study was carried out for each problem. The parameters were shape and size of the restriction/protrusion, number of restrictions/protrusions, wall thickness, Reynolds number, solid materials and working fluids. The results showed that in microtubes the local value of Nusselt number increases at the restriction/protrusion and the global value for the whole tube is somewhat lower. For a two-dimensional microchannel, both the local Nusselt number at the restriction/protrusion as well as the global Nusselt number for the entire channel is higher. In the trapezoidal channels the results showed that with the increase in Reynolds number, the outlet temperature decreased and the average heat transfer coefficient increased. With an increase in magnetic field there was an increase in the solid fluid interface temperature and in turn the average heat transfer coefficient increased. With a decrease in the channel height and width there was an increase in the average Nusselt number in the channel.

No description available.

Thesis (MScEng (Civil Engineering))--University of Stellenbosch, 2006. / Stepped spillways constructed of roller compacted concrete (RCC) is a hydraulic and cost effective measure to dissipate energy of large water flows over the spillway of a dam. Stepped spillways, like other spillway types, have its limitations and a measure to improve the energy dissipation effectiveness is proposed. Two hydraulic models were constructed at the hydraulics laboratory of the Department of Water Affairs and Forestry (DWAF) in Pretoria, South Africa. The scales of the models were 1:20 and 1:30. The study proposes the use of triangular protrusions applied over the spillway surface. The protrusions have the same height as the steps, with the width of the protrusions varying. The triangular protrusions deflect the water sideways resulting in higher energy losses. The results indicate that the protrusions reduce scouring at the toe of the dam, thus increasing the roughness of the steps. It also indicate that aeration occur earlier than with normal stepped spillways. An optimal spacing, lateral and across the steps, are proposed. The construction of the protrusions is also discussed, as well as the cost implications. It is concluded that the protrusions are effective at a unit discharge up to 35 m3/s.m. This value is however dependent on the configuration of the apron downstream of the toe of the dam. It is proposed that protrusions be added on the downstream face of the dam on every second step, with one protrusion and then no protrusion alternating in the flow path. It is recommended that the protrusions be cast in situ.