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Modeling the Heterogeneous Brain Tumor Microenvironment to Analyze Mechanisms of Vascular Development and ChemoresistanceCox, Megan Christine 13 June 2018 (has links)
Regulation of cancer cell phenotype by the tumor microenvironment has motivated further investigation into how microenvironmental factors could contribute to tumor initiation, development, and therapeutic resistance. Analyzing how the microenvironment drives tumor development and cancer cell heterogeneity is particularly important in cancers such as glioblastoma multiforme (GBM) that have no known risk factors and are characterized by a high degree of heterogeneity. GBM patients have a median survival of 15 months and therefore are in great need of more effective therapeutic options. The goal of this research is to generate in vitro models of the heterogeneous brain tumor microenvironment, with a focus on vascular dynamics, to probe the impact of microenvironmental cues on tumor progression and to integrate the tumor models with highly sensitive analytical tools to characterize the epigenome of discrete phenotypic subpopulations that contribute to intratumoral cellular heterogeneity. As GBM tumors are characterized by a dense vasculature, we delved into microenvironmental factors that may be promoting angiogenesis. The correlations emerging between inflammation and cancer led to analysis of the inflammatory molecule lipopolysaccharide (LPS). We utilized 3D micro-tissue models to simulate vascular exposure to ultra-low chronic inflammatory levels of LPS and observed an increase in vascular formation when brain endothelial cells were exposed to ultra-low doses of LPS. We also utilized our micro-tissue models to analyze histone methylation changes across the epigenome in response to microenvironmental cues, namely culture dimensionality and oxygen status. The H3K4me3 modification we analyzed is associated with increased gene transcription, therefore the alterations we observed in H3K4me3 binding across the genome could be a mechanism by which the tumor microenvironment is regulating cancer cell phenotype. Lastly, we developed a microfluidic platform in which vascular dynamics along with microenvironmental heterogeneities can be modeled in a more physiologically relevant context. We believe the studies presented in this dissertation provide insight into how vasculature primed by chronic inflammation and epigenetic alterations in tumor cells could both contribute to enhanced tumor development. Modeling these biological processes in our advanced microfluidic platform further enables us to better understand microenvironmental regulation of tumor progression, uncovering new potential therapeutic targets. / PHD / Regulation of cancer cell behavior by the tumor microenvironment, which includes the surrounding extracellular matrix, native healthy cells, and signaling molecules, has motivated further investigation into how microenvironmental factors could contribute to tumor initiation, development, and therapeutic resistance. Analyzing how the microenvironment drives tumor development and heterogeneity in cancer cell behavior is particularly important in cancers such as glioblastoma multiforme (GBM) that have no known risk factors and are characterized by a high degree of heterogeneity. GBM patients have a median survival of 15 months and therefore are in great need of more effective therapeutic options. The goal of this research is to generate models of the heterogeneous brain tumor microenvironment with a focus on how microenvironmental cues impact blood vessel development, which facilitates tumor progression. We will also use these tumor models, along with sensitive analytical tools, to characterize epigenetic modifications that potentially contribute to tumor cell heterogeneity. As GBM tumors are characterized by a dense vasculature, we delved into microenvironmental factors that may promote blood vessel growth. The correlations emerging between inflammation and cancer led to analysis of the inflammatory molecule lipopolysaccharide (LPS). We utilized 3D tumor models to simulate blood vessel exposure to ultra-low chronic inflammatory levels of LPS and observed an increase in blood vessel formation when brain endothelial cells were exposed to ultra-low doses of LPS. We also utilized our tissue models to analyze histone methylation changes across the epigenome in response to microenvironmental cues, namely culture dimensionality and oxygen status. The histone methylation changes we observed across the genome could be a mechanism by which the tumor microenvironment is regulating cancer cell v behavior. Lastly, we developed a microfluidic platform in which blood vessel development along with microenvironmental heterogeneities can be modeled in a more physiologically relevant context. We believe the studies presented in this dissertation provide insight into how blood vessel exposure to chronic inflammatory factors and epigenetic alterations in tumor cells could both contribute to enhanced tumor development. Modeling these biological processes in our advanced microfluidic platform further enables us to better understand microenvironmental regulation of tumor progression, uncovering new potential therapeutic targets.
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Food Democracy and The Construction of Risk in The Canadian and U.K. MediaChénier, Lynn A. 11 December 2009 (has links)
Using a critical discourse analysis (CDA), this thesis examines how risks and food security, in relation to Genetically Modified (GM) foods, are constructed within the media context. The project analyzes
news articles that appeared in two Canadian newspapers, The Globe and Mail and The Toronto Star, and two British newspapers, The London Times and the Guardian, during three particular time periods between 1997 and 2005. I evaluate whether or not the selected articles contribute to the public’s
understanding of science, and how journalism constructs risk and uncertainty. I also evaluate the use of expert knowledge by journalists. Using the theory of Risk Society, as proposed by sociologist Ulrich Beck, the project explores the connections between political, social, and economic issues connected to globalization. This thesis concludes that journalism in both Canada and Britain does not appear to adequately inform their citizens on matters of food security and the risks of GMOs.
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FRACTIONATION AND CHARACTERIZATION OF LIGNIN STREAMS FROM GENETICALLY ENGINEERED SWITCHGRASSLiu, Enshi 01 January 2017 (has links)
Development of biomass feedstocks with desirable traits for cost-effective conversion is one of the main focus areas in biofuels research. As suggested by techno-economic analyses, the success of a lignocellulose-based biorefinery largely relies on the utilization of lignin to generate value-added products, i.e. fuels and chemicals. The fate of lignin and its structural/compositional changes during pretreatment have received increasing attention; however, the effect of genetic modification on the fractionation, depolymerization and catalytic upgrading of lignin from genetically engineered plants is not well understood. This study aims to fractionate and characterize the lignin streams from a wild-type and two genetically engineered switchgrass (Panicum virgatum) species (low lignin content with high S/G ratio and high lignin content) using three different pretreatment methods, i.e. dilute sulfuric acid, ammonia hydroxide, and aqueous ionic liquid (cholinium lysinate). The structural and compositional features and impact of lignin modification on lignin-carbohydrate complex characteristics and the deconstruction of cell-wall compounds were investigated. Moreover, a potential way to upgrade low molecular weight lignin to lipids by Rhodococcus opacus was evaluated. Results from this study provide a better understanding of how lignin engineering of switchgrass influences lignin fractionation and upgrading during conversion processes based on different pretreatment technologies.
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Processo construtivo de edifícios de alvenaria estrutural sílico-calcária. / Calcium silicate bricks engineered masonry building process.Sabbatini, Fernando Henrique 05 June 1984 (has links)
O emprego de processos construtivos inovadores sem o domínio da tecnologia apropriada e sem a observância de requisitos mínimos de desempenho, conduz de maneira geral, a edifícios com sérios problemas patológicos. Por estas razões, a Alvenaria Estrutural, que tem sido empregada com prioridade na construção de edifícios habitacionais, nos últimos anos no Brasil, tem apresentado aqueles problemas com indesejável extensão e gravidade. Este trabalho procura estabelecer a tecnologia mais adequada para a construção de edifícios em Alvenaria Estrutural Não Armada, em especial, para a que utiliza o bloco sílico-calcário. Procura-se também salientar os aspectos ainda não suficientemente conhecidos e que necessitam, por isto, ser pesquisados. São apresentadas as principais características dos materiais empregados. O elemento construtivo essencial do processo - a parede resistente - é sistemicamente analisado sob diferentes abordagens. Como complemento, a análise é extendida para o edifício. No estudo, é enfatizado o mais comum e menos compreendido problema patológico da alvenaria sílico-calcária: as fissuras por retração na secagem. A tecnologia construtiva apropriada é estritamente condicionada pela necessidade de que seja evitada a ocorrência destas fissuras. Em resumo, este trabalho objetiva colaborar para o projeto e a construção de edifícios competentes e duráveis, o que, infelizmente, não tem sido a regra, quando processos inovadores são empregados. / Pathological buildings problems certainly occur when innovative constructive processes are employed without knowing their own technology and without getting to minimum performance requirements. Based on these reasons, the engineered masonry which has been mainly employed on housing constructions in Brazil during the last years, shows up severs pathological problems. This study aims to describe the most appropriate known technology for unreinforced engineered brickworks, mainly for that one employing calcium silicate bricks. Therefore, the important parameters which are not yet suitably known are pointed out, thus requiring further research. The materials main characteristics are introduced. The bearing wall which is the most important constructing element is systemically analised under different approaches. Coming at the end the concepts are extended to the whole building itself. Emphasis is given in this study to drying shrinkage cracking as the most usual problem in calcium silicate brickworks and to its mechanisms not yet fully understood. The correct building technology avoids the cracking problems by using the mentioned materials and processes. Summarising , this study intends to cooperate for the correct and durable housing buildings which unfortunately are not usual nowadays when innovative constructive processes are applied.
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Painéis compósitos híbridos de alta densidade fabricados a partir de partícula de madeira e de película de polipropileno biorientado: avaliação de propriedades para empregabilidade como piso / High density hybrid composite panels manufactured from wood and bioriented polypropylene film particles: properties evaluation for employability as a flooringMacedo, Laurenn Borges de 26 September 2018 (has links)
O modo de vida consumista, presente na sociedade moderna, está diretamente relacionado ao problema dos resíduos gerados pela atividade do setor econômico, tanto na produção quanto no pós-consumo desses bens. Neste contexto, é possível considerar o setor alimentício como responsável por grande produção de resíduos poliméricos (plásticos), bastantes utilizados na produção de embalagens. A reciclagem destes polímeros constitui umas das principais soluções para o reaproveitamento desse material, porém, nem todo tipo de polímero possui reciclagem em grande escala no Brasil. Como o caso da película de polipropileno biorientado (BOPP), que apesar de muito empregado, é exemplo de material polimérico não priorizado pelas cooperativas de catadores e sucateiros por não ser de interesse da indústria de reciclagem nacional, dadas as características de sua composição. Uma possibilidade para o reaproveitamento do BOPP constitui a produção de painéis aglomerados de partículas de madeira em consórcio com tal material. Assim, este trabalho tem como objetivo avaliar a potencialidade de painéis híbridos produzidos a partir de partículas de resíduos de madeiras e de BOPP e resina poliuretana à base de óleo de mamona para uso como piso em edificações, por intermédio de ensaios laboratoriais de desempenho físico e mecânico dos mesmos. Foram encontrados os resultados: 768 kg/m³ para densidade; 1,63% para inchamento em espessura 2h e 4,03% para 24h; 8,3% para absorção de água em 2h e 19,95% para 24h; porosidade de 41,01%; 0,48 MPa de resistência à tração perpendicular; 716,88 N de resistência ao arranchamento de parafuso para face e 950,81 N para topo; 2,96 μm de rugosidade superficial; 0,2145 mm em perda de espessura por abrasão; 0,28 mm de endentação por queda de esfera; 0,057 mm de endentação para cargas em pequenas áreas; 0,319 mm de endentação por carga rolante; coeficiente de atrito estático de 0,372 e dinâmico de 0,231. Os resultados alcançados para os ensaios realizados demonstram a alta potencialidade dos painéis de partículas híbridos de madeira e BOPP desenvolvidos neste trabalho. / Consumerist way of life, present in modern society, is directly related to residues problem generated by economic sector activity, both in production and in post-consumption of these goods. In this context, it is possible to consider food sector as responsible for large polymer waste (plastics) production, quite used in packaging production. These recycling polymers constitutes one of the main solutions for this material reutilization, however, not every polymer type has large-scale recycling in Brazil. As in the case of biaxially oriented polypropylene film (BOPP), which although very employed, is an example of polymeric material not prioritized by scavengers cooperatives and scrappers because it is not yet of interest to national recycling industry, given its composition characteristics. One possibility for BOPP reuse is agglomerated panels production of wood particles in consortium with such material. Thus, this work aims to evaluate the potentiality of hybrid panels produced from wood waste and BOPP particles and polyurethane resin based on castor oil for use as flooring in buildings, by means of laboratory tests of their physical and mechanical performance. Results found were: 768 kg/m³ for density; 1.63% for swelling in thickness (2h) and 4.03% (24h); 8.3% for water absorption (2h) and 19.95% (24h); porosity 41.01%; 0.48 MPa of internal bond; 716.88 N of resistance to screw pullout to face and 950.81 N of top; 2.96 μm of surface roughness; 0.2145 mm in thickness loss by abrasion; 0.28 mm in indentation by ball drop; 0.057 mm of indentations for loads in small areas; 0.319 mm of indentation by rolling load; coefficient of static friction 0.372 and dynamic 0.231. Results achieved for tests carried out demonstrate that hybrid wood and BOPP particle panels developed in this work high potentiality.
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Effect of Electronic Water Treatment System on Calcium Carbonate ScalingUnknown Date (has links)
Calcium carbonate precipitation and formation of clog particles inside the leachate
collection pipe can cause catastrophic failures in landfill operation. This study focuses on
quantifying the effectiveness of electronic scale control to reduce the clog formation within
the pipe network. A field scale model (40ft × 20ft) was constructed, featuring side-by-side
flow of electronically treated and untreated composite leachate. Data obtained in the first
phase of this study indicate that electronic scale control system does not have any
statistically significant effect on water quality parameters. The second phase of this study
identified calcite (CaCO3) to be the predominant phase present in the precipitates using
XRD/XRF diffraction pattern analyzed through a search match calculation program
(MATCH! Version 3.2.0) which concur with the previous studies. Furthermore, Rietveld
refinement using FullProf Suite confirms that there were no differences between the treated
and untreated precipitate based on the phases identified in the respective samples. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2016. / FAU Electronic Theses and Dissertations Collection
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Thermo-hydro-mechanically modified cross-laminated Guadua-bamboo panelsArchila Santos, Hector Fabio January 2015 (has links)
Guadua angustifolia Kunth (Guadua) is a bamboo species native to South and Central America that has been widely used for structural applications in small and large-scale buildings, bridges and temporary structures. Currently, its structural use is regulated within seismic resistant building codes in countries such as Peru and Colombia. Nevertheless, Guadua remains a material for vernacular construction associated with high levels of manual labour and structural unpredictability. Guadua buildings are limited to two storeys due to the overall flexibility of the slender and hollow culms and its connection systems. Its axial specific stiffness is comparable to that of steel and hardwoods, but unlike wood, Guadua’s hollow structure and lack of ray cells render it prone to buckling along the grain and to transverse crushing. As a result, Guadua’s mainstream use in construction and transformation into standard sizes or engineered Guadua products is scarce. Therefore, this work focussed on the development of standardised flat industrial structural products from Guadua devising replicable manufacturing technologies and engineering methods to measure and predict their mechanical behaviour. Cross-laminated Guadua panels were developed using thermohydro-mechanically modified and laminated flat Guadua strips glued with a high performance resin. Guadua was subjected to thermo-hydro-mechanical (THM) treatments that modified its microstructure and mechanical properties. THM treatment was applied to Guadua with the aim of tackling the difficulties in the fabrication of standardised construction materials and to gain a uniform fibre content profile that facilitated prediction of mechanical properties for structural design. Densified homogenous flat Guadua strips (FGS) were obtained. Elastic properties of FGS were determined in tension, compression and shear using small-clear specimens. These properties were used to predict the structural behaviour of G-XLam panels comprised of three and five layers (G-XLam3 and G-XLam5) by numerical methods. The panels were assumed as multi-layered systems composed of contiguous lamellas with orthotropic axes orientated at 0º and 90º. A finite element (FE) model was developed, and successfully simulated the response of G-XLam3 & 5 panels virtually loaded with the same boundary conditions as the following experimental tests on full-scale panels. G-XLam3 and G-XLam5 were manufactured and their mechanical properties evaluated by testing large specimens in compression, shear and bending. Results from numerical, FE predictions and mechanical testing demonstrated comparable results. Finally, design and manufacturing aspects of the G-XLam panels were discussed and examples of their architectural and structural use in construction applications such as mid-rise buildings, grid shells and vaults are presented. Overall, this research studies THM treatments applied to Guadua in order to produce standardised engineered Guadua products (EGP), and provides guidelines for manufacturing, testing, and for the structural analysis and design with G-XLam panels. These factors are of key importance for the use of Guadua as a mainstream material in construction.
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Process Models for Laser Engineered Net ShapingKummailil, John 29 April 2004 (has links)
The goal of this dissertation is to develop a model relating LENSâ„¢ process parameters to deposited thickness, incorporating the effect of substrate heating. A design review was carried out, adapting the technique of functional decomposition borrowed from axiomatic design. The review revealed that coupling between the laser path and laser power caused substrate heating. The material delivery mechanism was modeled and verified using experimental data. It was used in the derivation of the average deposition model which predicted deposition based on build parameters, but did not incorporate substrate heating. The average deposition model appeared capable of predicting deposited thickness for single line, 1- layer and 2-layer builds, performing best for the 1- layer builds which were built under essentially isothermal conditions. This model was extended to incorporate the effect of substrate heating, estimated using an energy partition approach. The energy used for substrate heating was modeled as a series of timed heating events from an instantaneous point heat source along the path of the laser. The result was called the spatial deposition model, and was verified using the same set of experimental data. The model appeared capable of predicting deposited thickness for single line, 1- layer and 2- layer builds and was able to predict the characteristic temperature rise near the borders as the laser reversed direction.
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Site-directed nucleases as tools for genome editing in fish / Les nucléases ciblées comme outil d’édition du génome du poissonRadev, Zlatko 19 December 2014 (has links)
L'application des techniques de séquençage à haut débit dans les dernières années a conduit à l'obtention de la séquence de génomes complets de plusieurs organismes. Le développement de nouveaux outils de génétique inverse était donc souhaitable afin de faire un usage optimal des données accumulées. Les nucléases hautement spécifiques représentent un outil unique pour induire des modifications ciblées du génome in vivo. L'induction d'une cassure double brin dans l'ADN est réparée soit par la voie de jonction d’extrémités nonhomologues soit par la voie très fidèle de la recombinaison homologue. Le ciblage d'un locus précis avec une nucléase spécifique stimule fortement la réparation de l'ADN, qui peut être utilisé pour induire des modifications ciblées dans le génome. Dans ma thèse, je vise à fournir une preuve de prinicipe pour l'utilisation des méganucléases et des transcription activator like effector nucléases (TALENs), deux classes communes de nucléases très spécifiques, comme nouveaux outils d'édition du génome chez le medaka, Oryzias latipes, et le poisson zèbre, Danio rerio. J'ai d’abord trouvé les conditions optimales d'utilisation de ces nucléases dans nos modèles de poissons. J'ai à cette occasion également développé une méthode très sensible et rapide pour la détection de modifications génomiques ciblées. J'ai ensuite induit des mutations au sein de trois gènes différents chez le poisson zèbre avec des TALENs. Les mutations dans le gène col6a1 ont conduit à la mise en évidence pour la première fois d’une technique de modification d’un site d’épissage d’un gène de poisson zèbre à l’aide d’une nucléase ciblée. Ce travail nous a permis d’établir une lignée de poisson avec une mutation dans le collagène VI alpha 1 qui est similaire à une mutation fréquemment trouvée chez les patients humains atteints de myopathie de Bethlem. De même, j’ai pu induire des mutations dans le gène nle1 du poisson zèbre qui vont permettre la mise en place de lignées de poissons mutants de ce gène. En outre, j'ai pu montrer qu’un nouveau type de nucléase, une TALEN Compact, était actif sur une cible chromosomique chez le poisson zèbre. En conclusion, les études que j'ai effectuées ont apporté la preuve de principe pour l'activité de TALENs et Compact TALENs ainsi que la première démonstration de modification de l'épissage à l’aide d’une TALEN chez le poisson zèbre et ont abouti à la mise en place d'une lignée de poisson dont le phénotype est proche d’un syndrome humain ouvrant la voie à la création de modèles pour d’autres mutations de ce type. Pour finir, je discute dans cette thèse des conditions permettant un usage le plus efficace des nucléases ciblées pour la génération de mutants et l’édition du génome. / The application of high throughput sequencing techniques in the recent years has led to obtaining the full genome sequences of many organisms. The development of novel tools for reverse genetics was thus desirable to make optimal use of the accumulated data. Site directed nucleases represent a unique platform to induce targeted genome modifications in vivo. Targeting a precise locus with a highly specific nuclease stimulates DNA repair, which can be harnessed for genome editing. Induction of a double strand break in DNA is repaired by either the error prone pathway of nonhomologous end joining or the high fidelity pathway of homologous recombination in the cell. Both mechanisms can be used to insert foreign DNA into the genome of the host. In my thesis, I aimed to provide proof of principle for the use of meganucleases and transcription activator like effector nucleases (TALENs), two common classes of site directed nucleases, as novel tools for genome editing in medaka, Oryzias latipes, and zebrafish, Danio rerio. During the first years of my thesis, I found the optimal conditions to use these nucleases in our fish models. I also developed a very sensitive and rapid method for detection of targeted genome modifications. I then induced mutations at three different endogenous loci in zebrafish with TALENs. The mutations in the col6a1 gene led to the first demonstration of splicing site modification in zebrafish using a TALE nuclease. This allowed the establishment of a fish line with a mutation in type VI collagen alpha 1 chain homologous to one mutation frequently found in human patients with Bethlem myopathy. Then I generated mutations in the nle1 gene which are heritable and from which establishment of mutant fish lines is in progress. In addition, by using the method for detection of targeted genome modifications I developed, I showed that a novel type of nuclease, a Compact TALEN, was active on a chromosomal target in zebrafish. In conclusion, the studies I performed provided proof of principle for the activity of TALENs and Compact TALENs as well as the first demonstration of TALEN-Mediated modification of splicing in zebrafish and resulted in the establishment of a fish line with mutated collagen VI. Induction of heritable mutations in the nle1 gene in zebrafish was also confirmed. Additionally, I proved that the choice of expression vector is crucial for the synthesis of active site directed nucleases for use in fish and established a novel efficient method for detection of targeted genomic mutations.
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Comportement hydromécanique différé des barrières ouvragées argileuses gonflantes / Hydro-mechanical behaviour of bentonite-sand mixture used as sealing materials in radioactive waste disposal galleriesSaba, Simona 09 December 2013 (has links)
Dans le but de vérifier l'efficacité des dispositifs de scellement ou des barrières ouvragées dans le stockage géologique des déchets radioactifs, l'Institut de Radioprotection et de Sûreté Nucléaire (IRSN) a mis en œuvre le projet expérimental SEALEX (SEALing performance EXperiments) auquel ce travail est étroitement lié. Dans le cadre de ce projet, des essais in-situ sont effectués à l'échelle représentative et dans des conditions naturelles sur un mélange compacté de bentonite et de sable. Ce matériau de mélange a été choisi pour sa faible perméabilité et surtout pour sa capacité de gonflement qui permet de colmater les vides existant dans le système, notamment le vide technologique correspondant au vide radial entre le noyau de scellement et la roche hôte et qui est inévitable au cours de l'installation du noyau dans le forage. Une fois les vides scellés, le gonflement à volume constant engendre une pression de gonflement aussi bien sur la roche hôte (radiale) que sur les structures de confinement en béton (axiale). Le comportement de ce matériau dans ces conditions de couplages hydromécaniques est alors étudié dans ce travail. La microstructure du matériau à son état initial a été premièrement examinée par micro-tomographie rayons-X. Ceci a permis de voir la distribution des grains de bentonite et de sable ainsi que le réseau de pores dans l'échantillon. Des macro-pores se sont retrouvés concentrés à la périphérie de l'échantillon ainsi qu'entre les grains de sable, ce qui pourra affecter à court terme la perméabilité. L'hydratation du même matériau en condition de gonflement limité a été ensuite observée par une photographie 2D et par la micro-tomographie aux rayons-X. Le mécanisme de gonflement par production de gel de bentonite, la cinétique de gonflement, la diminution de densité et l'homogénéisation du matériau final on été analysés. L'hydratation en conditions de gonflement empêché a été aussi étudiée par des essais où la pression de gonflement a été mesurée dans deux directions : radialement et axialement. La différence retrouvée entre les pressions de gonflement axiales et radiales a évoqué la présence d'une anisotropie de microstructure qui a été analysée en fonction de la masse volumique sèche de bentonite dans le mélange. Des essais en modèle réduit reproduisant à une échelle 1/10ème les essais in situ (SEALEX) ont été également effectués afin d'étudier le comportement du noyau compacté après la reprise des vides au cas d'un accident détruisant les éléments de confinement. Des mesures locales de pression de gonflement le long des échantillons ont permis de mettre en évidence l'évolution du gradient de densité durant le gonflement axial. Finalement une comparaison entre les résultats obtenus dans ce travail et ceux d'un essai in situ (SEALEX) a été faite. Une bonne correspondance entre les valeurs d'humidités relatives a été retrouvée pour les mêmes longueurs d'hydratation tout en prenant en compte la saturation par le vide technologique radial. Par contre, la comparaison des évolutions et des valeurs de pressions de gonflement était plus compliquée vu les différences de configurations des essais / In order to verify the effectiveness of the geological high-level radioactive waste disposal, the French Institution of Radiation protection and Nuclear Safety (IRSN) has implemented the SEALEX project to control the long-term performance of swelling clay-based sealing systems, and to which this work is closely related. Within this project, In-situ tests are carried out on compacted bentonite-sand mixture in natural conditions and in a representative scale. This material is one of the most appropriate sealing materials because of its low permeability and good swelling capacity. Once installed, this material will be hydrated by water from the host-rock and start swelling to close all gaps in the system, in particular the internal pores, rock fractures and technological voids. Afterwards, swelling pressure will develop. In the present work, laboratory experiments were performed to investigate the sealing properties under this complex hydro-mechanical conditions taking into consideration the effect of technological voids. The microstructure of the material in its initial state was first examined by microfocus X-ray computed tomography (µCT). This allowed identification of the distribution of grains of sand and bentonite as well as the pores in the sample. Macro-pores are found concentrated at the periphery of the sample and between the grains of sand, which could affect in the short term the permeability. The hydration of the same material in limited swelling conditions was then observed by 2D photography and 3D µCT. The swelling mechanism with bentonite gel production, the swelling kinetics, the density decrease and the homogenisation of the material were analyzed. The hydration in the conditions of prevented swelling was also studied by swelling pressure tests with radial and axial measurements of swelling pressure. The difference found between the axial and radial swelling pressures suggested the presence of an anisotropic microstructure. Mock-up tests at a 1/10 scale of the in situ SEALEX tests were carried out for the study of the recovery capacity of the mixture in case of an accident causing the failure of the confining structures. Local measurements of swelling pressures along the sample allowed analysis of the density gradient evolution during axial swelling. Finally, a comparison between the laboratory results and those from an in-situ test was done, showing a good fitting in the relative humidity curves for the same infiltration length while considering the saturation effect from the technological void. The swelling pressure comparison was more complex because of the different configurations of the tests (existence of technological void in-situ that could affect the kinetics)
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