The human heart has poor endogenous regeneration. If myocytes are lost due to injury, the myocardium is unable to restore its myocyte content and instead undergoes compensatory hypertrophy and remodeling. Cardiac tissue engineering aims to recreate and provide functional myocardium that replaces the injured myocardium. In this study, human engineered heart muscle (EHM) from cardiomyogenically differentiated human embryonic stem cells was generated. EHMs consisted of elongated, anisotropically organized cardiomyocyte bundles and responded “physiologically” to increasing calcium concentrations. To generate large myocardium capable of encompassing the ventricles, a novel process to systematically upscale the dimensions of engineered myocardium to a humanized Biological Ventricular Assisted Device (hBioVAD) was introduced. The hBioVADs formed a “pouch-like” myocardium at rabbit heart dimensions and were beating spontaneously. Further enhancement by biomimetic pulsatile loading generated “more mature” myocardium. Additional paracrine functionality was integrated by generating insulin-like growth factor-1 (IGF-1) secreting fibroblasts for tissue engineering applications. IGF-1 release induced higher levels of Akt phosphorylation and hypertrophy in cardiomyocytes resulting in increased force generation of EHM. Finally, feasibility of “paraBioVAD” (IGF-1 cell line and cardiomyocytes) implantation was demonstrated in a healthy rat model. Histological observations demonstrated engraftment on the heart and the presence of vascular structures. In conclusion, a humanized “paraBioVAD” technology for mechanic and paracrine heart support was developed. Future studies will assess its therapeutic utility in heart failure

Titanium (Ti) foams of different densities 1622-4100 Kgm-3 made by a powder sintering technique were studied as to their structural and mechanical properties. The foams were tested under static and dynamic loading. The material was tested quasi statically and dynamically under strain rates in the range of 0.001-2500 s-1 and under different loading modes. It was found that strain rate sensitivity is more pronounced in lower density foams. Experiments were complimented by virtual testing. Based on the Voronoi tessellations a computational method was developed to generate stochastic foam geometries. Statistical control was applied to produce geometries with the microstructural characteristics of the tested material. The generated structures were numerically tested under different loading modes and strain rates. Voronoi polyhedrals were used to form the porosity network of the open cell foams. The virtually generated foams replicated the geometrical features of the experimentally tested material. Meshes for finite element simulations were produced. Existing material models were used for the parent material behaviour (sintered Ti) and calibrated to experiments. The virtual foam geometries of different densities were numerically tested quasi statically under uniaxial, biaxial and triaxial loading modes in order to investigate their macroscopic behaviour. Dynamic loading was also applied for compression. Strain rate sensitive and insensitive models were used for the parent material model in order to examine the influence of geometry and material strain rate sensitivity under high rates of deformation. It was found that inertial effects can enhance the strain rate sensitivity for low density foams and numerical predictions for the generated foam geometries were in very good agreement with experimental results. Power laws were established in scaling material properties with density. The study includes: 1. Information on the material behaviour and data for macroscopically modelling this type of foams for a range of densities and under different strain rates. 2. A proposed method for virtually generating foam geometries at a microscopic scale and examine the effect of geometrical characteristics on the macroscopic behaviour of foams.

This thesis addresses the puzzle of variation in first-generation regulatory policies for controversial science and technology, as demonstrated in the cases of agricultural genetically modified organisms (GMOs) and human embryonic stem cell research in the United Kingdom and the United States. Why did policy outcomes vary in each technology case? This study answers this question by placing greater emphasis on institutional factors. Although works within institutional analysis, bureaucracy and regulation literatures make significant progress in revealing how existing institutions can shape outcomes, how far one can characterize bureaucratic behavior and whether interest groups capture regulation, they nevertheless create an opening for research that: describes a mechanism for path dependence to explain variation in policies; shows the degree to which bureaucratic behaviors can influence outcomes; and, highlights instances in which regulatory officials hold power. This thesis makes an original contribution by providing new historical details relating to these cases, and by providing an extensive elaboration of Pierson’s criteria for increasing returns and a so-called secondary test of path dependence to explain outcomes. The study recounts the biography of key policy documents in each case by tracing the process of decision-making through government and archival sources, secondary literature and more than 40 elite interviews. In doing so, it details the activities of key governmental bodies within the European Union, UK and US. Moreover, it shows how the Coordinated Framework (1986) and Human Fertilisation and Embryology Act 1990 framework represented decision-making structures which triggered changes in actors and interests and shaped permissive outcomes for GMOs and stem cell research in the US and UK, respectively. Furthermore, lack of comparable structures may help account for restrictive policies for GMOs in Europe and the UK, and for stem cell research in the US.

Engineered nanomaterials (ENMs) have become ubiquitous in consumer products and industrial applications, and consequently the environment. Much of the environmentally released ENMs are expected to enter terrestrial ecosystems via land application of nano-enriched biosolids to agricultural fields. Among the organisms most likely to encounter nano-enriched biosolids are the key soil bacteria known as plant growth promoting rhizobacteria (PGPR). I reviewed what is known concerning the toxicological effects of ENMs to PGPR and observed the need for high-throughput methods to evaluate lethal and sublethal toxic responses of aerobic microbes. I addressed this issue by developing high-throughput microplate assays which allowed me to normalize oxygen consumption responses to viable cell estimates. Oxygen consumption is a crucial step in cellular respiration which may be examined relatively easily along with viability and may provide insight into the metabolic/physiological response of bacteria to toxic substances. Because many of the most toxic nanomaterials (i.e. metal containing materials) exhibit some level of ionic dissolution, I first developed my methods by examining metal ion responses in the PGPR, Bacillus amyloliquefaciens GB03. I found this bacterium exhibits differential oxygen consumption responses to Ag+, Zn2+, and Ni2+. Exposure to Ag+ elicited pronounced increases in O2 consumption, particularly when few viable cells were observed. Also, while Ni2+ and Zn2+ are generally thought to induce similar toxic responses, I found O2 consumption per viable cell was much more variable during Ni2+ exposure and that Zn2+ induced increased O2 utilization to a lesser extent than Ag+. Additionally, I showed my method is useful for probing toxicity of traditional antibiotics by observing large increases in O2 utilization in response to streptomycin, which was used as a positive control due to its known effects on bacterial respiration. After showing the utility of my method for examining metal ion responses in a single species of PGPR, I investigated the toxicity of silver ENMs (AgENMs) and ions to three PGPR, B. amyloliquefaciens GB03, Sinorhizobium meliloti 2011, and Pseudomonas putida UW4. The ENM exposures consisted of untransformed, polyvinylpyrrolidone coated silver ENMs (PVP-AgENMs) and 100% sulfidized silver ENMs (sAgENMs), which are representative of environmentally transformed AgENMs. I observed species specific O2 consumption responses to silver ions and PVP-AgENMs. Specifically, P. putida exhibited increased O2 consumption across the observed range of viable cells, while B. amyloliquefaciens exhibited responses similar to those found in my first study. Additionally, S. meliloti exhibited more complex responses to Ag+ and PVP-AgENMs, with decreased O2 consumption when cell viability was ~50-75% of no metal controls and increased O2 consumption when cell viability was <50%. I also found the abiotically dissolved fraction of the PVP-AgENMs was likely responsible for most of the toxic response, while abiotic dissolution did not explain the toxicity of sAgENMs. My work has yielded a straightforward, cost-effective, and high-throughput method of evaluating viability and oxygen consumption in aerobic bacteria. I have used this method to test a broad range of toxic substances, including, metal ions, antibiotics, and untransformed and transformed ENMs. I observed species specific toxic responses to Ag+, PVP-AgENMs, and sAgENMs in PGPR. These results not only show the clear utility of the methodology, but also that it will be crucial to continue examining the responses of specific bacterial strains even as nanotoxicology, as a field, must move toward more complex and environmentally relevant systems.

Articular cartilage has a low propensity for self-repair, due to which 27 million people are affected by osteoarthritis every year in North America. The current repair techniques used for cartilage defects possess flaws that reduce long-term clinical success. Tissue engineering carries with it the promise of engineering hyaline-like cartilage with physical and biochemical properties, similar to that of native cartilage. This being said, the primary objective of my project was to engineer clinically relevant sized articular cartilage constructs. To achieve my objective, first, I investigated the effect of continuous culture on cartilaginous tissue growth. Constructs grown under continuous media flow significantly accumulated more collagen and glycosaminoglycan, and displayed a stratified morphology, similar to that found in native cartilage. The second goal was to further increase chondrocyte proliferation, and extracellular matrix (ECM) accumulation. To achieve this, constructs were grown in a bioreactor with media supplemented with 14 mM sodium bicarbonate (NaHCO3). Constructs cultivated in the bioreactor with NaHCO3 supplementation exhibited a significant (p<0.05) increase in ECM accumulation (a 98-fold increase in glycosaminoglycans and a 25-fold increase in collagen content), cell proliferation (a 13-fold increase), and thickness (a 28-fold increase) compared to all other conditions (static and reactor without NaHCO3 supplementation). The third goal was to engineer cartilage constructs with as little cells as possible, reducing donor site morbidity. From the results obtained, it was evident that the monolayer constructs outperformed all the other constructs (pellet, biopsy, and minced). The final goal was to understand the underlying reason for the increased proliferation. First, I investigated if there were any differences present in intracellular pH (pHi) and intracellular buffering capacity. Second, I determined the role of extracellular pH (pHe) on cell proliferation. In an effort to accurately achieve this, I, for the first time, have reported on measuring pHi of chondrocytes while still in culture (2D and 3D cultures) using a confocal microscope. This study demonstrated the importance of extracellular environments, such as pHe, extracellular buffering capacity, and the presence of carbon dioxide and bicarbonate ions for chondrocyte proliferation. / Thesis (Ph.D, Chemical Engineering) -- Queen's University, 2012-10-30 19:19:32.026

Superligas são materiais utilizados nas indústrias aeronáuticas, nucleares, metal-mecânicas, petroquímicas, automotivas e biomédicas, sendo considerados de difícil retificação (Difficult To Grind - DTG), devido às suas características peculiares. Para a retificação eficiente destes materiais, frequentemente utiliza-se rebolos superabrasivos com grãos de cBN (cubic boron nitride) e ligante vitrificado, devido a seu desempenho superior, quando comparado aos rebolos convencionais. Entretanto, é necessária a utilização de periféricos e sistemas auxiliares eficientes, elevando-se, assim, os custos. Visando a redução dos custos operacionais, os rebolos convencionais com grãos cerâmicos e ligantes com alta capacidade de retenção surgem como uma alternativa promissora. Neste cenário de comparação ferramental, torna-se necessário mensurar o desempenho das mesmas, que incluem requisitos técnicos e indicadores de sustentabilidade do processo. Assim, o objetivo desta dissertação é avaliar um rebolo convencional modificado tecnologicamente (grão cerâmico e ligante de alto desempenho), comparando-o com um rebolo de cBN vitrificado, buscando-se mensurar as diferenças de desempenho e critérios de sustentabilidade (econômicos, ambientais e sociais) do processo, quando da retificação de superligas, com diferentes graus de usinabilidade. A metodologia de análise comparativa do desempenho dos rebolos deu-se pela avaliação da influência de parâmetros de entrada (velocidade de corte, material e taxa específica de remoção utilizada) nas variáveis de saída, a serem monitoradas, relativas ao processo (potência; energia específica; desgaste - relação G e força tangencial por grão-; superfície do rebolo; e cavacos), à qualidade final da peça (rugosidade, circularidade e análise superficial - topografia, microestrutura e microdureza) e custos associados ao processo, além dos indicadores de sustentabilidade. Como resultados, em relação ao impacto da velocidade de corte, demonstrou-se que seu aumento é benéfico ao processo, devido à diminuição da espessura de corte e menores forças por grão, acarretando em menores desgastes do rebolo (maior relação G) e melhor qualidade superficial da peça retificada. Tal resultado é inversamente proporcional à taxa de remoção. No tocante aos materiais, comprovou-se que as superligas analisadas possuem diferentes capacidades de retificação, devido às diferentes microestruturas e propriedades químico-mecânicas, que impactam no desempenho da ferramenta abrasiva. O material Inc.751 apresentou a pior capacidade de retificação dentre os materiais analisados, devido, principalmente, à sua matriz austenítica e presença de Alumínio e Titânio na composição química. Pela análise dos cavacos, comprovou-se que os mesmos possuem formatos alongados, típico de materiais dúcteis e ratificou-se a eficiência da refrigeração na região de contato rebolo/peça. Com a curva característica dos rebolos, verificou-se que as ferramentas possuem comportamentos distintos, com superioridade ao rebolo de cBN, devido à maior capacidade de retenção dos grãos pelo ligante. Pela verificação superficial dos rebolos, não se observou empastamento evidente, constatando a eficiência do sistema de limpeza de alta pressão. Pela análise topográfica das peças, verificou-se que a retificação não induziu danos térmicos às mesmas. A avaliação dos indicadores de sustentabilidade proporcionou uma melhor análise da eficiência do processo, facilitando na tomada de decisão quanto ao desempenho do rebolo e/ou condição ideal. Como conclusão, a aplicabilidade do rebolo convencional em substituição ao rebolo de cBN foi confirmada para a retificação das superligas testadas. / Superalloys are materials used in aeronautical, nuclear, metal-mechanical, petrochemical, automotive, and biomedical industries, and they are considered Difficult To Grind (DTG) due to their peculiar characteristics. For efficient grinding of these materials, superabrasive grinding wheels with cBN (cubic boron nitride) grains and vitrified bond are often used because of their superior performance when compared to conventional grinding wheels. However, it is necessary to use efficient peripheral and auxiliary systems, thus raising costs. Aiming to reduce costs, conventional wheels with ceramic grains and binders with high retention capacity appear as a promising alternative. In this tool comparison scenario, it is necessary to measure their performance, which includes technical requirements and process sustainability indicators. Thus, the objective is to evaluate a engineered conventional grinding wheel, comparing it with a vitrified cBN wheel, aiming to measure performance differences and sustainability criteria (economic, environmental, and social) of the process, when grinding superalloys with different degrees of grindability. The methodology of comparative analysis of the performance of the grinding wheels was based on the evaluation of the influence of input parameters (cutting speed, material, and specific removal rate) in the output variables to be monitored related to the process (power, specific energy, roughness - ratio G and tangential force per grain, Ft1g, grinding wheel surface, and chips), to the final quality of the piece (roughness, roundness, and surface analysis - topography, microstructure, and microhardness) and costs, in addition to the sustainability indicators. As results, in relation to the impact of the cutting speed, it was demonstrated that its increase is beneficial to the process, due to the reduction of the cutting thickness and lower Ft1g, causing less wheel wear and better surface quality of the ground piece. This result is inversely proportional to the removal rate. Regarding the materials, it was verified that the analyzed superalloys have different grinding capacities due to the different microstructures and chemical-mechanical properties that impact the performance of the abrasive tool. The material Inc.751 presented the worst grinding capacity among the analyzed materials, mainly due to its austenitic matrix and the presence of Aluminum-Titanium in its composition. By the analysis of the chips, it was verified that they have elongated formats, typical of ductile materials, and it was ratified the efficiency of the cooling system. With the wheel characteristic curves, it was verified that the tools have different behaviors, superior to the cBN wheel, due to the greater capacity of retention of the grains by the binder. Through the investigation of the grinding wheels, no evident wheel loading was observed, noting the efficiency of the high-pressure cleaning system. By the analysis of the pieces, it was verified that the grinding did not induce thermal damages to them. The evaluation of the sustainability indicators provided a better analysis of the efficiency of the process, making easier the decision-making on the performance of the grinding wheel and/or ideal condition. Concluding, the feasibility of the conventional wheel in substitution of the cBN wheel was confirmed for the grinding of the tested superalloys.

L'ingénierie tissulaire, qui consiste à remplacer un tissu lésé par un biosubstitut constitué de cellules réparatrices ensemencées dans une matrice de support biodégradable, possède un potentiel prometteur pour la réparation du Ligament Croisé Antérieur (LCA). Or, aucune solution opérationnelle n'a encore été proposée à ce jour, notamment au vu du nombre de domaines scientifiques impliqués. Dans ce travail, nous avons dressé un cahier des charges pour la définition de cette matrice en nous appuyant sur l'état de l'art. Une matrice de support tressée multicouche constituée de fibres de P(LL85/CL15) a été imaginée, puis les outils nécessaires à sa fabrication à l'échelle du laboratoire ont été mis en place. Nous avons ensuite développé des outils numériques spécifiques permettant la modélisation de sa géométrie et de son comportement biomécanique multi-échelles, qui ont été mis à profit afin d?optimiser les caractéristiques de la matrice compte tenu du cahier des charges établi. De plus, des caractérisations biologiques ont montré que la matrice était compatible avec la culture de cellules souches, et était susceptible d?accueillir la formation d'un néo-tissu. Par ailleurs, nous avons mis en place un bioréacteur spécifique permettant d'imposer à la matrice de support des cycles de traction-torsion sous environnement contrôlé. L'utilisation des informations locales issues de la modélisation biomécanique, afin d'interpréter ou d'optimiser les résultats de culture cellulaire sous sollicitations cycliques, constitue une perspective majeure du présent travail. Notre investigation permet en outre de penser qu'un nouveau biosubstitut pour le LCA pourrait prochainement être proposé / Tissue engineering, which consists in replacing an injured tissue with a biodegradable scaffold seeded with cells, has the potential to overcome the limitations associated with current reconstructions strategies of the Anterior Cruciate Ligament (ACL). However, no relevant solution has been proposed yet, especially due to the variety of scientific fields involved in this approach. In the current study, the key requirements for the design of a new scaffold have been listed from the current state of art. A scaffold based on P(LL85/CL15) fibers arranged into a multilayer braided structure has been proposed, and the tools needed to process this scaffold have been developed. Dedicated numerical tools have been proposed in order to predict the morphological and multiscale biomechanical behavior of the scaffold. These simulation tools have enabled to optimize the scaffold geometry in order to match the selected key requirements for ACL tissue engineering. Moreover, preliminary biological assessments have shown that the scaffold was suited for the culture of stem cells and for tissue formation. In addition, a dedicated bioreactor has been developed in order to prescribe tension-torsion cycles within a controlled environment. The use of local information issued from the biomechanical simulations open large perspectives as far as the optimization of culture conditions and the understanding of mechanisms that govern the formation of a ligamentous tissue are concerned. As a conclusion, the present study is likely to enable a new solution for ACL tissue engineering to emerge in the next years

<p></p><p></p><p></p><p>In urbanized river basins, sanitary wastewater and urban runoff (non-sanitary water) from urban agglomerations drain to complex engineered networks, are treated at centralized wastewater treatment plants (WWTPs) and discharged to river networks. Discharge from multiple WWTPs distributed in urbanized river basins contributes to impairments of river water-quality and aquatic ecosystem integrity. The size and location of WWTPs are determined by spatial patterns of population in urban agglomerations within a river basin. Economic and engineering constraints determine the combination of wastewater treatment technologies used to meet required environmental regulatory standards for treated wastewater discharged to river networks. Thus, it is necessary to understand the natural-human-engineered networks as coupled systems, to characterize their interrelations, and to understand emergent spatiotemporal patterns and scaling of geochemical and ecological responses. </p><br><p></p><p></p><p>My PhD research involved data-model synthesis, using publicly available data and application of well-established network analysis/modeling synthesis approaches. I present the scope and specific subjects of my PhD project by employing the <i>Drivers-Pressures-Status-Impacts-Responses</i> (<i>DPSIR</i>) framework. The defined research scope is organized as three main themes: (1) River network and urban drainage networks (<i>Foundation</i>-<i>Pathway of Pressures</i>); (2) River network, human population, and WWTPs (<i>Foundation</i>-<i>Drivers</i>-<i>Pathway of Pressures</i>); and (3) Nutrient loads and their impacts at reach- and basin-scales (<i>Pressures</i>-<i>Impacts</i>).</p><br><p></p><p></p><p>Three inter-related research topics are: (1) the similarities and differences in scaling and topology of engineered urban drainage networks (UDNs) in two cities, and UDN evolution over decades; (2) the scaling and spatial organization of three attributes: human population (POP), population equivalents (PE; the aggregated population served by each WWTP), and the number/sizes of WWTPs using geo-referenced data for WWTPs in three large urbanized basins in Germany; and (3) the scaling of nutrient loads (P and N) discharged from ~845 WWTPs (five class-sizes) in urbanized Weser River basin in Germany, and likely water-quality impacts from point- and diffuse- nutrient sources. </p><br><p></p><p></p><p>I investigate the UDN scaling using two power-law scaling characteristics widely employed for river networks: (1) Hack’s law (length-area power-law relationship), and (2) exceedance probability distribution of upstream contributing area. For the smallest UDNs, length-area scales linearly, but power-law scaling emerges as the UDNs grow. While area-exceedance plots for river networks are abruptly truncated, those for UDNs display exponential tempering. The tempering parameter decreases as the UDNs grow, implying that the distribution evolves in time to resemble those for river networks. However, the power-law exponent for mature UDNs tends to be larger than the range reported for river networks. Differences in generative processes and engineering design constraints contribute to observed differences in the evolution of UDNs and river networks, including subnet heterogeneity and non-random branching.</p><br><p></p><p></p><p>In this study, I also examine the spatial patterns of POP, PE, and WWTPs from two perspectives by employing fractal river networks as structural platforms: spatial hierarchy (stream order) and patterns along longitudinal flow paths (width function). I propose three dimensionless scaling indices to quantify: (1) human settlement preferences by stream order, (2) non-sanitary flow contribution to total wastewater treated at WWTPs, and (3) degree of centralization in WWTPs locations. I select as case studies three large urbanized river basins (Weser, Elbe, and Rhine), home to about 70% of the population in Germany. Across the three river basins, the study shows scale-invariant distributions for each of the three attributes with stream order, quantified using extended Horton scaling ratios; a weak downstream clustering of POP in the three basins. Variations in PE clustering among different class-sizes of WWTPs reflect the size, number, and locations of urban agglomerations in these catchments. <b></b></p><br><p></p><p></p><p>WWTP effluents have impacts on hydrologic attributes and water quality of receiving river bodies at the reach- and basin-scales. I analyze the adverse impacts of WWTP discharges for the Weser River basin (Germany), at two steady river discharge conditions (median flow; low-flow). This study shows that significant variability in treated wastewater discharge within and among different five class-sizes WWTPs, and variability of river discharge within the stream order <3, contribute to large variations in capacity to dilute WWTP nutrient loads. For the median flow, reach-scale water quality impairment assessed by nutrient concentration is likely at 136 (~16%) locations for P and 15 locations (~2%) for N. About 90% of the impaired locations are the stream order < 3. At basin-scale analysis, considering in stream uptake resulted 225 (~27%) P-impaired streams, which was ~5% reduction from considering only dilution. This result suggests the dominant role of dilution in the Weser River basin. Under the low flow conditions, water quality impaired locations are likely double than the median flow status for the analyses. This study for the Weser River basin reveals that the role of in-stream uptake diminishes along the flow paths, while dilution in larger streams (4≤ stream order ≤7) minimizes the impact of WWTP loads. </p><br><p></p><p></p><p>Furthermore, I investigate eutrophication risk from spatially heterogeneous diffuse- and point-source P loads in the Weser River basin, using the basin-scale network model with in-stream losses (nutrient uptake).Considering long-term shifts in P loads for three representative periods, my analysis shows that P loads from diffuse-sources, mainly from agricultural areas, played a dominant role in contributing to eutrophication risk since 2000s, because of ~87% reduction of point-source P loads compared to 1980s through the implementation of the EU WFD. Nevertheless, point-sources discharged to smaller streams (stream order < 3) pose amplification effects on water quality impairment, consistent with the reach-scale analyses only for WWTPs effluents. Comparing to the long-term water quality monitoring data, I demonstrate that point-sources loads are the primary contributors for eutrophication in smaller streams, whereas diffuse-source loads mainly from agricultural areas address eutrophication in larger streams. The results are reflective of spatial patterns of WWTPs and land cover in the Weser River basin.</p><br><p></p><p></p><p>Through data-model synthesis, I identify the characteristics of the coupled natural (rivers) – humans – engineered (urban drainage infrastructure) systems (CNHES), inspired by analogy, coexistence, and causality across the coupled networks in urbanized river basins. The quantitative measures and the basin-scale network model presented in my PhD project could extend to other large urbanized basins for better understanding the spatial distribution patterns of the CNHES and the resultant impacts on river water-quality impairment.</p><p><br></p><p></p>

The deep geological repository concept is based on “engineered barriers systems (EBS)” that are constructed in the repository and “natural barriers” provided by the surrounding geological environment. The EBS comprises of variety of sub-systems or components, such as the waste form, canister, buffer, backfill, seals, and plugs. Geological disposal is based on the concept of multiple barriers that work together to provide containment. The buffer is made up of densely compacted bentonite or bentonite-sand mix. Bentonite has both mechanical and physico-chemical functions, to fulfill as a barrier material in DGR. The bentonite buffer should hold the containers in place and prevent collapse of the excavation. A plastic deformability of the bentonite is desired to redistribute the stresses that can result from creep in the rock, and prevent transfer of excessive stresses to the canisters. The bentonite buffer must create an impermeable zone around the containers to ensure that the radionuclide released from the vitrified waste is limited by diffusive transport rather than advective transport in groundwater. Another important property of the highly compacted bentonite is its swelling potential. Its swelling potential should be as high as possible, to guarantee the sealing of any cracks occurring in the buffer material or in the storage gallery and thus ensure good imperviousness. Besides its mechanical function, bentonite buffer must sorb escaping radionuclides and thus retard their migration to the geo-environment. The bentonite buffer must retain its mechanical and physico-chemical functions over a span of several hundred thousand years to fulfill its role as a containment barrier in DGR. The bentonite buffer should maintain its physico-chemical and hydro-mechanical integrity on exposure to groundwater. Nuclear power agencies of several countries have identified suitable bentonites for use as buffer in DGR through laboratory experiments and large scale underground testing facilities. Japan has identified Kunigel VI bentonite, South Korea-Kyungju bentonite, China-GMZ bentonite, Belgium-FoCa clay, Sweden-MX-80 bentonite, Spain-FEBEX bentonite and Canada-Avonseal bentonite as candidate bentonite buffer for deep geological repository program. Bentonite from Barmer (Rajasthan State) was identified as suitable buffer for use in Indian deep geological repositories. The influence of moisture and dissolved salt migration on the physico-chemical and hydro-mechanical properties of Barmer bentonite has not been examined. The study is important to understand the clay’s behaviour under deep geological repository conditions, where, the bentonite buffer would come in contact with groundwater. Infiltration of groundwater with variable chemical composition could alter the physico-chemical and hydro-mechanical properties of the clay. The objectives of the thesis are as follows: Examine the influence of permeation of distilled water (DW) and synthetic ground water (SGW) solutions under constant volume condition on suction, physico-chemical and moisture content/dry density characteristics of compacted Barmer bentonite specimens as function of permeation period (maximum permeation period– 30 days). Examine the influence of variation in dry density and gravimetric water content as consequence of DW and SGW solution permeation on swell pressure and unconfined compression strength of Barmer bentonite specimens. Compare experimental swell pressures of re-constituted bentonite specimens with swell pressures predicted by diffuse double layer models. Examine the influence of total dissolved solids (TDS) concentration of permeating solution on the unsaturated permeability of compacted Barmer bentonite specimens. Organization of thesis: After the first introductory chapter, a detailed review of literature is performed in Chapter 2 to review the physicochemical, mineralogical and hydro-mechanical properties of bentonites identified as buffer materials for deep geological repositories of various countries. Based on current understanding and need to perform similar studies with Barmer clay, the chapter develops the scope and objectives of the study. Chapter 3 presents a detailed experimental program of the study. Chapter 4 examines the influence of permeation of distilled water (DW) and synthetic groundwater (SGW) solutions (under constant volume conditions) on the total suction of compacted bentonite specimens at two locations in the clay. The influence of variation in dry density on the moisture migration-suction inter-relations of compacted bentonite specimens is also examined. The associated changes of DW and SGW solution migration under constant volume conditions on the physico-chemical properties, water content and dry density of compacted Barmer bentonite specimens are also examined. The experimental results brought out that matric suction mainly contributed (75 to 92 %) to total suction of the permeated specimens; the permeated specimens experienced reduction in matric suction with increase in gravimetric water content from increase in degree of saturation. Osmotic suction contributed to 10 to 25 % of the total suction of the permeated specimens and was observed to increase with gravimetric water content due to solubilization of salts contained in the voids of the compacted bentonite specimens. The total suction of compacted Barmer bentonite specimen was responsive to the total dissolved solids concentration of the permeating solutions as the specimen permeated with more saline solution (higher TDS value) exhibited lesser total suction. Upon permeation with DW and SGW solutions, the CEC of bentonite was unaltered, while, pH and TDS values were affected. Softening of the bentonite clay occurred from increase in water content and existence of compression zones (material used to seal 1mm gap in relative humidity probe aperture) that in turn facilitated dissipation of swelling stress leading to reduction in dry density values. Chapter 5 examines influence of reduction in dry density and increase in water content on the swell pressure and compression strength characteristics of compacted Barmer bentonite specimens upon DW and SGW solution migration as the results could provide insight into possible deviations from the design properties upon wetting of bentonite buffer by groundwater under deep geological repository conditions. The experimental swelling pressures are also compared with those predicted by Gouy-Chapman diffuse double layer theory. The dry density of 1.6 Mg/m specimens permeated with DW and SGW solutions reduced to 1.59 to 1.36 Mg/m and water contents increased to 18.9 to 27 % on permeation with distilled water and SGW solutions for 30 days. The reductions in dry density and increase in water content caused 30 to 70 % reductions in swell pressures and 31 to 74 % decrease in unconfined compression strength values. Specimens initially compacted to dry density of 1.8 Mg/m, experienced reduction in dry density ranging from 1.79 to 1.52 Mg/m and increase in water content from 18.6 to 24.2 % on permeation of DW and SGW solutions for 30 days. These reductions in dry density and increase in water caused the swell pressures to reduce from 4 to 55 % and unconfined compressive strengths to reduce by 31 to 67 %. Comparison of swell pressures gave -8 to 127 % variations between theoretical (from DDL theory) and experimental values due to errors associated with estimation of surface area and dissolved salt concentrations in pore water. Chapter 6 examines the influence of salinity of permeating solution on the unsaturated permeability of compacted Barmer bentonite specimens. The salinity of permeants was varied by permeating distilled water (DW) and synthetic ground water solutions under constant volume conditions over maximum period of 30 days. Experimental results showed that the saturated permeability coefficients (ksat) of specimens compacted to 1.6 Mg/m, responded to variations in TDS of the permeant. Comparatively, the ksat values of specimens compacted to 1.8 Mg/mwere unaffected by variation in TDS of the permeant. Permeation of DW and SGW solutions decreased the ksat values with time from cation hydration and growth of diffuse ion layers for both, 1.6 and 1.8 Mg/mseries specimens. Increase in gravimetric water content from DW and SGW permeation increased the kunsat values of 1.6 Mg/m specimens from reduction in total suction. Re-orientation of soil structure mobilized larger kunsat values for specimens permeated with SGW solutions than DW at similar total suction. Permeation of DW and SGW solutions had lesser impact on kunsat values of the 1.8 Mg/m specimens in comparison to the 1.6 Mg/m series specimens. Further at both densities, the influence of permeation was more evident at location closer to hydration surface. Chapter 7 summarizes the main findings of this study.