Quantifying the velocity field near the wall in microfluidic devices is important because surface effects become significant at micro- to nanometer scales. Recent studies have suggested that the "no-slip" boundary condition breaks down in microscale flows of Newtonian liquids, where the amount of slip is usually extrapolated from velocity components measured far from the wall. This doctoral thesis presents a new technique, multilayer nano-particle image velocimetry (MnPIV), for measuring the tangential velocity components at different distances from and within about 500 nm of the wall and its application to measuring slip. The feasibility of MnPIV was demonstrated using synthetic images of plane Couette flow incorporating Brownian diffusion and imaging noise. The errors in MnPIV data were then quantified with Brownian dynamics simulations. Calibration experiments were used to correlate the image intensity of the tracer to its distance from the wall z. Multilayer nPIV was then used to determine the z-positions and distribution of the particles for z < 500 nm in experimental studies of microscale Poiseuille flow. The tracers were divided into three distinct layers based on their image intensities, and the average velocity of each layer was placed at the average z-position sampled by the particles in that layer. The resultant velocity gradients were within 6% on average of analytical predictions for 2D Poiseuille flow. Finally, the results of MnPIV studies of aqueous solutions flowing through microchannels with hydrophilic and hydrophobically-coated fused silica surfaces suggest that if the slip lengths are nonzero for both of these surfaces, they are less than the uncertainty in these results, or 27 nm and 31 nm for the hydrophilic and hydrophobic channels, respectively.

Articular cartilage on weight-bearing joints experiences three main forces: fluid-induced shear across the surface, perfusion through the cartilage from the surrounding fluid, and compression during motion of the joint. A new bioreactor that employs two of these forces was developed in this lab to study their effect on tissue-engineered cartilage development. The focus of this research and overall hypothesis is that bioreactors that employ both perfusion and shear will improve chondrogenesis and preservation to produce functionally relevant cartilage by modulating shear stress and introducing exogenous preservation factors. Applying both a low shear stress across the surface of cell-seeded scaffolds and perfusion through them in a perfusion concentric cylinder (PCC) bioreactor may stimulate chondrocytes to undergo chondrogenesis. Experimental data showed that the PCC bioreactor stimulated cartilage growth over the course of four weeks, supported by the appearance of glycosaminoglycan (GAG) and collagen type II, which are markers for articular cartilage. Computational fluid dynamics modeling showed that shear stress across the face of the construct was heterogeneous, and that only the center experienced a relatively uniform shear stress of 0.4 dynes/cm^2 when the outer cup of the bioreactor rotated at 38 rpm. When compared to a concentric cylinder (CC) bioreactor that employed only shear stress, the PCC bioreactor caused a significant increase in cellular proliferation, which resulted in a 12-fold increase in cell number per construct compared to 7-fold increase within the CC bioreactor. However, the PCC bioreactor had a less pronounced effect on glycosaminoglycan and collagen content with 1.3 mg of GAG and 1.8 mg of collagen per construct within the CC bioreactor and 0.7 mg of GAG and 0.8 mg of collagen per construct within the PCC bioreactor after 28 days in culture (p < 0.05). Our results led to an important observation that the PCC bioreactor affected cellular proliferation significantly but not extracellular matrix synthesis. The next objective of this study focused on the PCC bioreactor to evaluate the direct role of perfusion and shear on chondrogenesis in vitro and in vivo.

Η παρούσα διατριβή ασχολείται με την καμπτική ενίσχυση δοκών οπλισμένου σκυροδέματος με στρώσεις σκυροδέματος στο εφελκυόμενο ή στο θλιβόμενο πέλμα τους. Ιδιαίτερα ασχολείται με τον προσδιορισμό της ολίσθησης στη διεπιφάνεια τους. Συγκεκριμένα στο 1ο Κεφάλαιο γίνεται βιβλιογραφική ανασκόπηση για τις διεπιφάνειες σκυροδέματος. Παρουσιάζονται όλα τα προσομοιώματα που προτείνονται είτε σε Κανονισμούς, είτε από διάφορους ερευνητές, για τον προσδιορισμό της διατμητικής αντοχής της διεπιφάνειας, καθώς και για τον προσδιορισμό της σχέσης διατμητικής τάσης – ολίσθησης στη διεπιφάνεια σκυροδέματος. Στο 2ο Κεφάλαιο, παρουσιάζεται βιβλιογραφική ανασκόπηση για τις διεπιφάνειες σκυροδέματος με χάλυβα ή σύνθετα υλικά, σε σύμμικτες κατασκευές και σε μέλη ενισχυμένα με ελάσματα χάλυβα ή από ινοπλισμένα πολυμερή (ΙΟΠ), καθώς και πειραματικά αποτελέσματα κατανομής ολίσθησης σε διεπιφάνεια δοκών οπλισμένου σκυροδέματος ενισχυμένες με στρώση σκυροδέματος. Στο 3ο Κεφάλαιο παρουσιάζεται η πειραματική διερεύνηση δοκών οπλισμένου σκυροδέματος (Ο.Σ.) ενισχυμένων με στρώσεις σκυροδέματος. Εξετάστηκαν δύο ομάδες δοκιμίων. Στην πρώτη ομάδα εξετάστηκαν τέσσερα πρισματικά δοκίμια σκυροδέματος που ενισχύθηκαν με στρώση σκυροδέματος και στη συνέχεια δοκιμάστηκαν με φόρτιση τριών σημείων. Η δεύτερη ομάδα αναφέρεται σε πέντε δοκούς Ο.Σ. ενισχυμένες επίσης με στρώση σκυροδέματος, καθώς και σε αντίστοιχες μονολιθικές δοκούς που όλες δοκιμάστηκαν με φόρτιση τεσσάρων σημείων. Σε όλα τα δοκίμια και των δύο ομάδων μετρήθηκε η αντοχή τους καθώς και η ολίσθηση στη διεπιφάνεια τους. Στο 4ο Κεφάλαιο προτείνεται αναλυτική διαδικασία για τον υπολογισμό της ολίσθησης στη διεπιφάνεια σκυροδέματος και η εφαρμογή της στα πειραματικά δοκίμια που παρουσιάστηκαν στο Κεφάλαιο 3 καθώς και σε κάποια άλλα δοκίμια της βιβλιογραφίας που παρουσιάστηκαν στο 1ο Κεφάλαιο. Το 5ο Κεφάλαιο της παρούσας διατριβής, εξετάζει την επιρροή της συστολής ξήρανσης στο μέγεθος της ολίσθησης. Στο κεφάλαιο αυτό, παρουσιάζονται πειραματικές μετρήσεις της παραμόρφωσης και ολίσθησης λόγω συστολής ξήρανσης στα δοκίμια και των δύο ομάδων πειραματικών δοκιμίων που παρουσιάζονται στο Κεφάλαιο 3 και προτείνεται αναλυτικός τρόπος υπολογισμού της ολίσθησης και της διατμητικής τάσης στη διεπιφάνεια, συνυπολογίζοντας την επιρροή της συστολής ξήρανσης. Τέλος, παρουσιάζονται τα συνολικά συμπεράσματα που προέκυψαν στα πλαίσια της παρούσας διατριβής, καθώς και προτάσεις για μελλοντική έρευνα. / The present thesis concerns the flexural strengthening of reinforced concrete (RC) beams by placing a new concrete layer on their compressive or tensile side. The main objective of the thesis is to evaluate interface slip. The first chapter is a literature review on concrete interfaces. Theoretical models, suggested by design codes or other researchers, for the calculation of the shear resistance and the relationship between the shear stress and the slip at the interface are presented. Moreover, experimental results for the shear stress against slip relationship at the concrete interface are given. The second chapter presents a literature review on the shear stress and slip distribution at concrete to steel or concrete to fibre reinforced polymer (FRP) interfaces. Theoretical and experimental results for the value of shear stress at the interface of concrete beams strengthened with steel or FRP plates and shear stress and slip distribution at the interface of composite steel and concrete beams are presented. The third chapter concerns an experimental investigation of RC beams strengthened with concrete layers. Two types of specimens are examined. The first group are prismatic RC specimens strengthened with a concrete layer and tested by three point bending. The second group contains 10 RC beams. Five are strengthened with a concrete layer on their compressive or tensile side, four are respective monolithic specimens and the final one is a control beam without any strengthening. These beams are tested under four point bending. In all tests, for both groups of specimens, load against deflection curves are determined and the slip along the interface is measured. An analytical evaluation of the slip at the interface of RC beams strengthened with concrete layers and the verification of the method comparing the analytical results with respective experimental results presented in Chapters one and three is presented in Chapter four. The shrinkage effect on interface slip and shear stress is examined in Chapter five. Experimental measurements of shrinkage strains and slip on specimens of both experimental groups presented in Chapter three are presented. An analytical evaluation of the extra slip and shear stress at the interface caused by shrinkage effect is also suggested. Finally, all results of the thesis and suggestions for future work are given.

Este trabalho apresenta a avaliação das tensões de cisalhamento nas interfaces verticais de paredes de alvenaria interconectadas em casos onde atuam simultaneamente carregamentos verticais e ações horizontais. Os valores obtidos para as máximas tensões de cisalhamento são comparados com as resistências estabelecidas na norma brasileira em vigor, NBR 10837 (ABNT, 1989), e no texto base para sua revisão. Os valores das referidas normas também são confrontados com valores experimentais, avaliando-se criticamente a aplicação dos limites normativos na prática de projetos de edifícios existentes. Adicionalmente, são avaliadas duas formas distintas de modelagem de edifícios de alvenaria estrutural, quando submetidos às ações horizontais. A primeira consiste em uma abordagem simplificada e bastante usual entre projetistas, a associação plana de paredes isoladas. Sua aferição é importante para fornecer ao projetista uma ferramenta que lhe permita obter resultados de maneira rápida e confiável. A segunda forma de modelagem é uma análise de pórtico tridimensional que permite uma análise mais completa das paredes de contraventamento, incluindo os efeitos das deformações por cisalhamento. Com o intuito de avaliar as diferenças observadas entre os dois modelos, foram empregados testes estatísticos, que permitem analisar se eles são estatisticamente iguais a um nível de significância de 5%. Para aquisição dos dados para as análises são feitos estudos de casos com quatro edifícios residenciais usuais, com diferentes arranjos arquitetônicos, variando-se o número de pavimentos em quatro, oito, doze e dezesseis, de modo a se obter maior representatividade dos resultados. Com os resultados obtidos nas avaliações, concluiu-se que os valores adotados como limites de resistência pelo texto base da revisão da NBR 10837 (ABNT, 1989) parecem ser rigorosos para realidade brasileira. Com relação à comparação dos modelos estudados, os testes estatísticos direcionam a uma conclusão importante, que é a de não haver diferença entre eles, para um nível de 5% de significância. / This work presents the evaluation of the shear stress at the vertical interfaces of interconnected masonry walls simultaneously subjected to vertical and horizontal loads. The obtained maximum shear stress values are compared to the shear strengths prescribed by the current Brazilian code, NBR 10837 (ABNT, 1989), and by its review base text. The prescribed values are also confronted with experimental values, critically evaluating the application of the regulatory limits in the practical design of existing buildings. Additionally, two different ways of modeling the structural masonry buildings when submitted by horizontal actions are evaluated. The first one is a simple approach, largely used by designers, that consists in the two dimensional association of isolated walls. Its evaluation is important to provide the designer with a quick and reliable analytical tool. The second way of modeling is a three dimensional frame analysis, which allows a more complete simulation of the shear walls, including the shear strain effects. In order to evaluate the differences between the two models, statistical tests were employed for examining whether they are statistically equal at a significance level of 5%. Case studies were performed taking into account four residential buildings with different architectural arrangements. The number of floors was also varied considering four, eight, twelve and sixteen, in order to obtain more meaningful results. The developed analysis showed that the strength limits prescribed by the review base text of the NBR 10837 (ABNT, 1989) seem to be very much strict according to the Brazilian common practice. Regarding the comparison of the studied analytical models, the statistical tests showed that there is no difference between them at a significance level of 5%.

O aprimoramento dos meios para obtenção do bioetanol a partir de diferentes tipos de biomassa traz novos problemas e desafios para a engenharia. O Brasil, devido a fatores climáticos e uma produção de etanol a partir da cana de açúcar já estabilizada, possui uma posição mundial vantajosa na produção sucroalcooleira. Otimizar os meios já existentes e os em desenvolvimento pode não somente aumentar a eficiência da produção, como também reduzir os impactos ambientais causados pelo modelo de produção atualmente utilizado. O processo de fermentação é utilizado tanto na produção de etanol de primeira como de segunda geração, portanto melhorias no desempenho dos fermentadores contribui de maneira significante para o melhor aproveitamento da matéria prima. Diversas tentativas de melhorias são apresentadas na literatura, principalmente por meio do estudo de parâmetros do escoamento que podem influenciar o processo fermentativo, como tensão de cisalhamento, perfis de velocidade e tempo de residência, assim como a influência da geometria do fermentador sobre esses parâmetros. Em alguns estudos, algoritmos de otimização são utilizados para determinar os melhores coeficientes das reações químicas, mas não há estudos, até o momento, que proporcionem otimização simultânea dos parâmetros da geometria e do escoamento em um fermentador contínuo, presentes em cerca de 30% das usinas brasileiras. O objetivo deste trabalho é obter os parâmetros geométricos ideais para um fermentador contínuo, de forma a minimizar a tensão de cisalhamento a variância da distribuição de tempos de residência (DTR) no fermentador. O Ansys CFX® foi utilizado como ferramenta na simulação computacional do escoamento. As geometrias dos fermentadores ideais para cada um dessas análises, obtidas utilizando Algoritmos Genéticos e otimização univariada, respectivamente, foram propostas neste estudo. / The enhancement of bioethanol production means from different types of biomass presents significant problems and engineering challenges. Due to climate and a well-established sugar-cane ethanol production, Brazil is in a privileged position in the global ethanol production scenario. Providing effective means to optimize existing production methods can both improve the efficiency and reduce the environmental impact of the currently used production model. Improvements on this process can have a significant effect in several stages of production, once the production process is used both for first and second-generation ethanol. Several attempts to improve the ethanol production process are presented in the literature. Most studies have investigated how to improve parameters such as shear stress, velocity profiles and residence time, and of the influence of the bioreactor geometry on the parameters. The use of genetic algorithms has been reported in some cases, but there have not been reports on studies combining the optimization of flow parameters and algorithms to choose ideal geometric parameters for continuous fermenters, used in 30% of Brazilian industries in the field. The main aim of this study is to obtain ideal geometric parameters for a continuous fermenter, in order to maximize or minimize flow parameters that can influence on the fermenting process. The aim of this study is obtain the ideal geometry parameters for a continuous fermenter, minimizing two of flow parameters which can influence the fermentation process, namely the shear stress and the variance of residence time distribution (RTD). The flow parameters was obtained by computational fluid dynamics. The ideal fermenter geometries was obtained by two different optimization methods: the genetic algorithms and univariate optimization. The ideal geometries was proposed in this study.

Orientador: Pilar Rodriguez de Massaguer / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos / Made available in DSpace on 2018-08-12T12:11:20Z (GMT). No. of bitstreams: 1 RodriguesJunior_Salatir_D.pdf: 5567332 bytes, checksum: 70d0366fec71ac0d7df65013c7939248 (MD5) Previous issue date: 2008 / Resumo: O presente trabalho teve por objetivo verificar o efeito da tensão de cisalhamento sobre os parâmetros cinéticos de inativação térmica (valores D e z) de Bacillus atrophaeus (antigo B. subtilis ATCC 9372), em suspensão aquosa pH 6,87. A fim de atingir esse objetivo, foi construído um reator de cisalhamento, capaz de aplicar tensões de cisalhamento de até 9,82Pa em temperaturas de pasteurização (90,5 a 96,2ºC ± 0,5ºC). Foi aplicado um Delineamento Composto Central Rotacional, com duas variáveis independentes ¿ Tensão de cisalhamento e Temperatura ¿ e valor D como variável resposta. Foram executados 12 experimentos, e o modelo obtido foi ¿Log (D) = 11,30 ¿ 1,104x10-1 T(ºC) ¿ 1,153x10-2 s(Pa)¿, com R² = 0,97, sendo os termos lineares das variáveis significativos a p < 0,1. Também foram determinados os valores D e z de B. atrophaeus na faixa de temperatura de pasteurização (92~97ºC), pelo método tradicional em tubos TDT (batelada), e usando dados cinéticos adquiridos de uma planta piloto HTST Microthermics (contínuo), em condições de tensão de cisalhamento similares àquelas aplicadas no reator. A fim de avaliar o processamento térmico contínuo aplicado na unidade HTST, foi usada a metodologia de determinação de processo equivalente conhecida como Paired Equivalent Isothermal Exposures ¿ PEIE (Welt et al., 1997). Os valores de z obtidos foram: 11,8ºC ± 1,56ºC pelo método TDT e 6,35ºC ± 0,35ºC no reator de cisalhamento e na primeira seção de retenção da unidade piloto HTST. Diversos autores reportaram mudanças nos parâmetros cinéticos de microrganismos, ao realizar a sua determinação por métodos em batelada (tubos TDT, ou capilar) e em processos contínuos. À semelhança desses autores, foi verificado que os valores D de B. subtilis foram significativamente (p<0.05) inferiores em todos os processos em que foi aplicado cisalhamento. A razão entre os valores D experimentais obtidos no reator de cisalhamento e os valores obtidos pelo modelo estimado pelo método TDT foi calculada, e variou entre 57% e 75%, indicando redução significativa na resistência térmica do microrganismo. Existe, portanto, potencial de aplicação industrial imediata deste tipo de sistema, a fim de causar a redução da resistência de esporos suspensos em líquidos sob processamento térmico, e levando a processos térmicos mais brandos / Abstract: This research aimed to determine the effect of temperature, and shear stress, on Bacillus atrophaeus (former B. subtilis ATCC 9372) spores suspended in sterile distilled water, pH 6.9. To achieve such objective, a Shear Reactor was developed to be capable of applying 9.82Pa shear stress, under pasteurization conditions (90,5 a 96,2ºC ± 0,5ºC). A Central Composite Design of experiments was used and it was composed by two independent variables ¿ Shear stress and Temperature ¿ and one response ¿ the D-value. Twelve experiments were performed, and the model obtained was ¿Log (D) = 11,30 ¿ 1,104x10-1 T(ºC) ¿ 1,153x10-2 s(Pa)¿, with R² = 0,97, and the linear terms statistically significant (p < 0,1). The D and z-values of B. atrophaeus were determined in the pasteurization range of temperature (92~97ºC), using the classical TDT tube method (batch method), and using kinetic data acquired in a Microthermics HTST pilot plant (continuous method), under shear stress conditions similar to shear reactor. The continuous thermal process was evaluated through the Paired Equivalent Isothermal Exposures ¿ PEIE ¿ method (Welt et al., 1997). The z-values obtained were: 11,8 ± 1,56ºC (TDT-method), and 6,35 ± 0,35ºC (Shear reactor and first retention section of the HTST pilot plant). Several authors reported changes in the kinetic parameters of microorganisms, when determining it through batch or continuous methods. Just like them, in this research it was verified that the D-values under shear stress process were statistically lower (p<0.05) than those in batch method (no shear). The ratio between experimental D values obtained in the shear reactor and those obtained from the TDT model was calculated and ranged between 57% and 75%, indicating a significant reduction of the microorganism¿s thermal resistance. Hence there is an immediate potential for industrial application of this kind of process since it causes the reduction of the resistance of spores in fluids under thermal process allowing for less aggressive thermal process / Doutorado / Doutor em Ciência de Alimentos

An investigation of the flow characteristics and sediment transport processes has been carried out in a two-stage meandering channel. Three phases of experiments have been conducted with various floodplain roughnesses. The dimensions of the flume are 13m long and 2.4m wide with a fixed valley slope of 11500. The meandering main channel has a sinuosity of 1.384 with top width of 0.4m. In each phase of the experiment, hydraulic data pertaining to stage-discharge, bed topography and sediment transport rate were measured at various overbank flow depths. Several flow depths were chosen to measure the three-dimensional velocities by means of Laser Doppler Anemometer and the morphological bedforms were recorded using the Photogrammetric technique. The boundary shear stresses were also measured by means of a Preston Tube and Vane Indicator. The experimental results showed that the presence of the energy losses due to momentum exchange and turbulence, bedforms roughness and floodplain roughness induced additional flow resistance to the main channel flow, particularly for shallow overbank flows. The combination of these losses affected a significant reduction in velocity and boundary shear stress in the main channel which, subsequently led to the reduction of sediment discharge at low relative depth for most tested cases. The reduction was more pronounced when the floodplain roughness increased. The examination of the three-dimensional velocity indicated that the formation of bedforms in the main channel is significantly affected by the flow structures, especially the secondary flow. A new method for predicting velocity and sediment transport rate has been introduced based on the two-dimensional equation (Spooner's) coupled with the self-calibrated empirical transport formula. The proposed method gave accurate prediction for depthaveraged velocity and sediment transport rate for two-stage meandering channel.

Dans le but de développer des matériaux à partir d’une ressource renouvelable de moindre coût que l’amidon, des matériaux à base de farine de maïs ont été élaborés par extrusion-injection. La caractérisation des propriétés physico-chimiques de ces matériaux a révélé que le taux de glycérol (ajouté à la farine de maïs en tant que plastifiant) et le profil des zones de cisaillement employé lors de l’extrusion influencent significativement le taux de déstructuration de l’amidon et des protéines de la farine de maïs. Ceci a pu être établi en croisant notamment les résultats de l’analyse par diffraction aux rayons X, par spectroscopie infra-rouge à transformée de Fourier, de l’analyse calorimétrique différentielle à balayage à des observations par microscopie confocale à balayage laser des matériaux. De plus, le suivi des cinétiques d’hydrolyse en sucres réducteurs de l’amidon par des enzymes amylolytiques en présence et en absence d’enzymes protéolytiques a pu être relié à la déstructuration des protéines. Les matériaux obtenus présentent cependant des inconvénients rédhibitoires pour certaines applications comme l’hygroscopie élevée et le vieillissement rapide dans le temps. L’ajout de polybutylène succinate (PBS) au mélange farine-glycérol a cependant permis de conduire à une amélioration des propriétés mécaniques et à une réduction de l’hygroscopie de ces matériaux. Les observations de la morphologie de ces matériaux par microscopie électronique à balayage ont montré que la farine de maïs et le PBS sont incompatibles et présentent une morphologie qui varie selon le taux de PBS dans le mélange (30, 50 ou 70%). L’étude de la cinétique d’hydrolyse de l’amidon de la farine de maïs par des enzymes amylolytiques a permis de mettre en évidence l’influence de plusieurs facteurs : (i) la cristallinité de l’amidon, (ii) l’aire spécifique, (iii) la porosité et (iv) la morphologie des matériaux. De plus, l’évaluation de la biodégradation par voie microbienne en milieu liquide et solide par voie aérobie ou anaérobie a montré les mêmes tendances globales que les résultats obtenus par voie enzymatique. Ainsi, les matériaux élaborés à partir des formulations présentant des proportions de PBS excédant 50 % ne sont pas biodégradables au sens de la norme ISO 14855/1999 et sont également faiblement hydrolysés par les enzymes amylolytiques. / In order to develop materials from a cheaper renewable resource than starch, materials based on corn flour were prepared by extrusion and injection. The physicochemical characterization of these materials revealed that the glycerol content (used as plasticizer) and the profiles of shear zones used during extrusion significantly influence the destructuration intensity of starch and proteins of that composed corn flour. This could be established by combining the results of X-ray diffraction analysis, Fourier transform infrared spectroscopy, differential scanning calorimetry, and laser scanning confocal microscopy observations. In addition, the kinetics of the hydrolysis of starch into reducing sugars by amylolytic enzymes in the presence and absence of proteolytic enzymes significantly differed only when the initial structuration of proteins in corn flour was preserved. The materials obtained presented limitations for some applications namely due to their high hygroscopicity and rapid aging over time. The addition of polybutylene succinate (PBS) to flour-glycerol mixture improved mechanical properties and reduced hygroscopicity of the materials. The observation of these materials by scanning electron microscopy showed that corn flour and PBS are incompatible and have a morphology that varies according to the PBS content in the mixture (30, 50 or 70%). The study of the hydrolysis kinetics of starch corn flour by amylolytic enzymes contributed to highlight the influence of several parameters : (i) starch crystallinity, (ii) specific area, (iii) porosity, and (iv) material morphology. In addition, the evaluation of the microbial biodegradation in liquid and solid media aerobically or anaerobically showed the same overall trends as the results obtained by enzymatic hydrolysis. Thus, materials produced from formulations having PBS ratios exceeding 50% are not biodegradable according to the ISO 14855/1999 and are weakly hydrolyzed by amylolytic enzymes.

Protéolyse du facteur von Willebrand et cardiopathies à forces de cisaillement élevées: nouvelles approches diagnostiques et thérapeutiques Dans la première partie de ce travail, nous mettons en évidence l’intérêt d’une immunothérapie spécifique à base d’anticorps monoclonal pour la prévention de la dégradation du facteur von Willebrand (VWF) sous assistance circulatoire mécanique à flux continu. Via un anticorps monoclonal murin ciblant le domaine D4 du VWF et inhibant partiellement l’interaction VWF-ADAMTS13, une inhibition partielle de la dégradation du VWF est observée sur sang total dans un modèle ex-vivo d’assistance circulatoire mécanique.Dans la seconde partie, nous avons étudié l’influence de soudaines variations de l’intensité des forces de cisaillement sur la multimérisation du VWF dans 3 modèles in-vivo: un modèle lapin de sténose de l’aorte ascendante, à l’initiation d’une assistance ventriculaire gauche par une pompe à flux continu chez des patients en insuffisance cardiaque terminale et lors d’un remplacement valvulaire aortique par voie percutané chez des patients avec un rétrécissement aortique sévère. Les variations observées du profil multimérique sont très dynamiques survenant quelques minutes après les modifications des conditions de flux. Notre étude met ainsi en évidence une nouvelle application potentielle du VWF comme biomarqueur d’anomalies de flux dans les cardiopathies à forces de cisaillement élevées. Un monitoring en temps réel du VWF pourrait notamment avoir un intérêt en cardiologie interventionnelle pour les techniques percutanées utilisées pour le traitement du rétrécissement aortique.La dernière partie de ce travail porte sur le développement d’un test ELISA pour le diagnostic des formes acquises ou constitutionnelles de maladie de Willebrand secondaire à une protéolyse excessive du VWF par l’ADAMTS13. Ce test pourrait constituer une alternative intéressante aux actuelles méthodes électrophorétiques pour le diagnostic et la prise en charge de ces pathologies hémorragiques. / In the first part of the thesis, we describe a novel approach based on antibody-based therapy to prevent the acquired von Willebrand factor (VWF) degradation observed in continuous-flow mechanical circulatory assist device therapy. Via a murine monoclonal antibody directed against VWF D4 domain and thus interfering with VWF-ADAMTS13 binding, a partial inhibition of VWF degradation is observed in whole blood using an ex vivo circulatory assist device model. In the second part of the thesis, we investigated the relationship between acute changes in shear stress and variations in VWF multimeric profile in three distincts models in vivo: in a rabbit aortic banding model, in end-stage heart failure patients at initiation of continuous-flow ventricular assist device therapy and in severe aortic stenosis patients undergoing percutaneous aortic valve procedures. Variations in VWF multimeric profile in those settings are highly dynamic occuring within minutes after changes in shear stress status. Our study highlights that VWF could be used as a biomarker of blood flow in high shear cardiovascular disorders. A bedside VWF-monitoring could be of clinical interest in interventional cardiology for percutaneous aortic valve procedures used in severe aortic stenosis.The last part of the thesis focused on the development of an ELISA-based diagnosis of constitutive or acquired VWF disorders associated with an increased ADAMTS13-mediated VWF proteolysis. Such assay might represent an attractive alternative to electrophoresis-based assays in the diagnosis and management of such bleeding disorders.

The aim of this study is to create CFD tools and models capable of simulating pulsatile blood flow in abdominal aortic aneurysm (AAA) and stent graft. It helps to increase the current physiological understanding of rupture risk of AAA and stent graft fixation or migration. Firstly, in order to build a general solver for the AAA modeling with reasonable accuracy, a third/fourth order modified OCI scheme is originally developed for general numerical simulation. The modified OCI scheme has a wider cell Reynolds number limitation. This high order scheme performs well with general rectangular mesh for incompressible fluid. Second, a velocity based finite volume method is originally developed to calculate the stress field for solid in order to capture the transient changes of the blood vessel since the artery is a rubber like material. All one, two and three dimensional classical cases for solid are tested and good results are obtained. The velocity based finite volume method show good potential to calculate the stress field for solid and easy to blend with the finite volume fluid solver. It has been recognized that fluid structure interaction (FSI) is very crucial in biomechanics. In this regard, the velocity based finite volume method is then further developed for FSI application. A well known one dimensional piston problem is studied to understand the feasibility of the fluid structure coupling. The numerical prediction matches the analytical solution very well. The velocity based method introduces less numerical damping compared with a stagger method and a monolithic method. Finally, the work focuses on practical pulsatile boundary conditions, non-Newtonian blood viscous properties and bifurcating geometry, and provides an overview of the hemodynamic within the AAA model. A modified Womersley inlet and imbalance pressure outlet boundary conditions are originally used in this study. The Womersley inlet boundary represents better approximation for pulsatile flow compared with the parabolic inlet condition. Numerical results are presented providing comparison between different boundary conditions using different viscous models in both 2D and 3D aneurysms. Good agreement between the numerical predictions and the experimental data is achieved for 2D case. 3D stent models with different bifurcation angles are also tested. The Womersley inlet boundary condition improves the existing inlet conditions significantly and it can reduce the Aneurysm neck computation domain. The influence of the non-Newtonian model to the wall shear stress (WSS) and strain-rate is also studied. The non-Newtonian model tends to produce higher WSS at both proximal and distal end of the aneurysm as compared with the Newtonian model (both 2D and 3D cases). The computed strain-rate distribution at the centre of the aneurysm is different between these two models. The influence of imbalance outlet pressure at the iliac arteries to the blood flow is originally investigated. The imbalance outlet pressure boundary conditions affect the computed wall shear stress significantly near the bifurcation point. All the pulsatile Womersley inlet, non-Newtonian viscosity properties and the imbalance pressure outlet need to be considered in blood flow simulation of AAA.