Glaciation is considered one of the main natural processes that can have a significant impact on the long term performance of DGRs. The northern part of the American continent has been subjected to a series of strong glaciation and deglaciation events over the past million years. Glacial cycles cause loading and unloading, temperature changes and hydraulic head changes at the ground surface. These changes can be classified as transient boundary conditions. It is widely accepted that the periodic pattern of past glacial cycles during the Late Quaternary period are resultant of the Earth’s orbital geometry changes that is expected to continue in the future. Therefore, from the safety perspective of DGRs, such probable events need to be taken into account. The objective of this thesis is to develop a numerical model to investigate the thermo-hydro-mechanical-chemical (THMC) coupled processes that have resulted from long term past and future climate changes and glaciation cycles on a proposed DGR in sedimentary rocks in southern Ontario. The first application is done on a large geological cross section that includes the entire Michigan basin by using a hydro-mechanical (HM) coupled process. The results are compared with field data of anomalous pore water pressures from deep boreholes in sedimentary rocks of southern Ontario. In this work. The modeling results seem to support the hypothesis that at least the underpressures in the Ordovician formation could be partially attributed to past glaciation. The second application is made on site conditions by using the THMC model. The results for the pore water pressure, tracer profiles, permafrost depth and effective stress profile are compared with the available field data, the results show that the solute transport in the natural limestone and shale barrier formations is controlled by diffusion, which provide evidence that the main mechanism of transport at depth is diffusion-dominant. The third application is made on site conditions to determine the effect of underground changes in DGRs due to DGR construction. The results show that future glaciation loads will induce larger increases in effective stresses on the shaft. Furthermore, it is found that hypothetical nuclide transport in a failed shaft can be controlled by diffusion and advection. The simulation results show that the solute transported in a failed shaft can reach the shallow bedrock groundwater zone. These results might imply that a failed shaft will substantially lose its effectiveness as a barrier. The fourth application is proposed to investigate the geochemical evolution of sedimentary host rock in a near field scale. In this part, a new thermo-hydro-mechanical-geochemical simulator (COMSOL-PHREEQC) is developed. It is anticipated that there will be a geochemical reaction within the host rock that results from interaction with the water enriched with the CO2 generated by nuclear waste.

Animal chemosensation involves several families of G protein-coupled receptors (GPCRs) and, though some of these families are well characterized in vertebrates and nematode worms, receptors have not been identified for most metazoan lineages. In this dissertation, I use a combination of bioinformatics approaches to identify candidate chemosensory receptors in three invertebrates that occupy key positions in the metazoan phylogeny. In the sea urchin Strongylocentrotus purpuratus, I uncovered 192 candidate chemosensory receptors many of which are expressed in sensory structures including pedicellariae and tube feet. In the cephalochordate Branchiostoma floridae, my survey uncovered 50 full-length and 11 partial odorant receptors (OR). No ORs were identified in the urochordate Ciona intestinalis. By exposing conserved amino acid motifs and testing the ability of those motifs to discriminate between ORs and non-OR GPCRs, I identified three OR-specific amino acid motifs that are common in cephalochordate, fish and mammalian ORs and are found in less than 1% of non-ORs from the rhodopsin-like GPCR family. To further investigate the antiquity of vertebrate ORs, I used the OR-specific motifs as probes to search for orthologs among the protein predictions from 12 invertebrates. My search uncovered a novel group of genes in the cnidarian Nematostella vectensis. Phylogenetic analysis that included representatives from the major subgroups of rhodopsin-like GPCRs showed that the cnidarian genes, the cephalochordate and vertebrate ORs, and a subset of genes S. purpuratus from my initial survey, form a monophyletic clade. The taxonomic distribution of these genes indicates that the formation of this clade began at least 700 million years ago, prior to the divergence of cnidarians and bilaterians. Furthermore, my phylogenetic analyses show that three of the four major subgroups of rhodopsin-like GPCRs existed in the ancestor of cnidarians and bilaterians. The utility of the new genes I describe here is that they can be used to identify candidate olfactory cells and organs in cnidarians, echinoderms and cephalochordates that can be tested for function. These genes also provide the raw material for surveys of other metazoans as their genomes become available. My sequence level comparison between chordates, echinoderms and cnidarians exposed several conserved amino acid positions that may be useful for understanding receptor mediated signal transduction. ORs and other rhodopsin-like GPCRs have roles in cell migration, axon guidance and neurite growth; therefore duplication and divergence in the rhodopsin-like gene family may have played a key role in the evolution of cell type diversity (including the emergence of complex nervous systems) and in the evolution of metazoan body plan diversity. / Graduate

The Neolithic and late Iron Age pottery from the settlement site of Pool, Sanday, Orkney, was studied on two levels. Firstly, a morphological and technological study was carried out to establish a sequence for the site. Secondly an assessment was made of the usefulness of X-ray Fluorescence Analysis, Inductively Coupled Plasma Spectrometry and Petrological analysis to coarse ware studies, using the Pool assemblage as a case study. Recording of technological and typological attributes allowed three phases of Neolithic pottery to be identified. The earliest phase included sherds of Unstan Ware. This phase was followed by an assemblage characterised by pottery with incised decoration, which was stratified below a traditional Grooved Ware assemblage. The change in pottery styles and manufacturing methods with the Grooved Ware indicated that it evolved elsewhere. Grass tempered and burnished pottery characterised the Iron Age assemblage. Pottery samples from all phases of the site were analysed by XRF and ICPS. In addition, pottery from late Iron Age sites in the area was analysed for comparison with the Pool Iron Age pottery. XRF and ICPS analyses did not distinguish between either different phases at Pool or different Orcadian sites. This was attributed to the similarities in geological deposits over much of Orkney and the variations which can occur within a clay source. A clay survey was carried out in the vicinity of the site, and samples taken for comparison with the Pool pottery. Identification of rocks and minerals in thin section, and grain-size analysis, indicated that the Pool pottery was made locally to the site, and that both primary and secondary clays were used. It was concluded that petrological analysis is more suitable than elemental analysis in the study of coarse wares.

Ste2p and Ste3p are well-characterized yeast pheromone G-protein Coupled Receptors (GPCR) those are involved in the signaling of mating responses that lead to cell fusion. Their signaling–associated interactions with G-protein/MAPK signal transduction machinery are well established, homologous to those in mammalian systems, and serve as a simplified model system in GPCR research. While the arrestin- mediated biased signaling mechanism of mammalian GPCR has not been discovered for the pheromone receptors, a recent demonstration of α-arrestins being involved in the internalization of the pheromone GPCR, Ste2p was reported. The present study was designed to reevaluate and extend the alternate functionality for pheromone receptors and to determine the role of yeast arrestins in the yeast mating. Specific residues in the TM6 of Ste2p exhibiting strong mating and constitutive MAPK signaling were combined and investigated in terms of their effect on MAPK signal transduction leading to cell cycle arrest as well as their impact on downstream mating projection formation and zygote formation events. Our findings indicate that Ste2p possess as specific residues that govern its relative bias for mediating MAPK signaling or mating events. Relative dose response experiments accounting for systemic and observation bias for these mutations yielded evidence of mutational-derived functional biases for Ste2p and further validated the alternate pheromone dependent functionalities for Ste2p. Further, arrestin knockout and knock-in studies showed that Art1 (Ldb19) is selectively involved in the regulation of zygote formation but not MAPK signal transduction following the binding of ligand to Ste2p receptors. In addition, ligand stimulated selective localization of Art1 (Ldb19) to the mating projection, implicating it in the regulation of downstream mating functionalities. Overall, while leaving the full mechanism of alternate/biased Ste2p signaling to be elucidated, these results highlight the possibility of continued relevance of the yeast pheromone-mating pathway as a simplified model for GPCR research in the context of arrestin-mediated biased GPCR signaling.

UDP-sugars were identified as extracellular signaling molecules, assigning a new function to these compounds in addition to their well-defined role in intracellular substrate metabolism and storage. Previously regarded as an orphan receptor, the G protein-coupled receptor (GPCR) P2Y14 (GPR105) was found to bind extracellular UDP and UDP-sugars. Little is known about the physiological functions of this GPCR. To study its physiological role a gene-deficient (KO) mouse strain expressing the bacterial LacZ reporter gene was used to monitor the physiological expression pattern of P2Y14. P2Y14 is mainly expressed in pancreas and salivary glands and in subpopulations of smooth muscle cells of the gastrointestinal tract, bronchioles, blood vessels and uterus. Among other phenotypical differences KO mice showed a significantly impaired glucose tolerance following oral and intraperitoneal glucose application. An unchanged insulin tolerance points towards an altered pancreatic islet function. Transcriptome analysis of pancreatic islets showed that P2Y14 deficiency significantly changed expression of components involved in insulin secretion. Insulin secretion tests revealed a reduced insulin release from P2Y14-deficient islets highlighting P2Y14 as a previously unappreciated modulator of proper insulin secretion.

G protein-coupled receptors (GPCRs) are known to exist as oligomers, but there is much uncertainty over the oligomeric size, the number of interacting G proteins and the stability of that interaction. The present approach to these questions has been threefold. Monomers of the M2 muscarinic receptor were purified from Spodoptera frugiperda (Sf9) cells and reconstituted in phospholipid vesicles, where they spontaneously formed tetramers. The size of the reconstituted complex was determined from its electrophoretic mobility after cross-linking and inferred from a quantitative, model-based assessment of cooperative effects in the binding of two muscarinic antagonists: N-methylscopolamine and quinuclidinylbenzilate. Binding of the agonist oxotremorine-M to receptor reconstituted with purified G proteins revealed at least three classes of sites that interconverted from higher to lower affinity upon the addition of guanylylimidotriphosphate (GMP-PNP). The binding properties resemble those of muscarinic receptors in myocardial preparations, thereby implying the existence of tetramers in native tissues. G proteins that copurify with the M2 receptor from cardiac membranes also were found to exist as oligomers, some of which contain both alpha(o) and alpha(i2), and the purified complexes contained receptor and G protein in near-equal amounts. A tetrameric receptor implies a tetramer of G proteins, a conclusion that is supported by the distribution of sites between different states identified in the binding of [35S]GTPgammaS to the purified complex. Covalent adducts of a GPCR fused to a Galpha-subunit provide a model system in which the relationship between receptor and G protein complex is defined with respect to stability and composition. Such a fusion of the M2 receptor and Galpha(i1) underwent a cleavage near the amino terminus of the alpha-subunit, however, flagging the likelihood of similar effects in other such adducts. Truncation of the amino terminus prior to fusion generated a stable product that revealed GMP-PNP-sensitive, biphasic binding of oxotremorine-M and noncompetitive interactions between N-methylscopolamine and quinuclidinylbenzilate. A covalent RG complex therefore exhibits the functional properties of M2 receptors in native systems. These observations are consistent with the notion that signaling through the M2 receptor occurs via cooperative interactions within a stable complex that comprises four receptors and four G proteins.

Landfills are considered to be one of the major sources of anthropogenic methane (CH4) emissions in the environment. A landfill biocover system optimizes environmental conditions for biotic CH4 consumption that controls the fugitive and residual emissions from landfills. A compost material has more oxidation potential in comparison to any other material due to its high porosity, organic content, free flux for gases and water holding capacity. Thermal, hydraulic, bio – chemical and mechanical (THMCB) properties are important factors that can significantly affect the performance of biocover material with regards to CH4 oxidation potential as well as structural stability. Technical data on the thermal, hydraulic and mechanical (THM) properties of compost based biocover materials are quite limited. Hence, a detailed experimental program has been carried out at the University of Ottawa to study the THM properties and behaviour of compost biocover material by conducting experimental tests on small compost samples as well as by performing column experiments. The test results indicate that lower water content (dry of optimum for compaction curve) shows more free air space (FAS) in comparison to higher water content. The compost has almost the same shear strength for various initial water contents and dry unit weights; however, it settles and swells more at higher water content than lower water content per mechanical test results. The thermal and hydraulic properties of compost are a function of the compaction degree in addition to various other parameters. It is also found that the THM properties of compost are strongly coupled and the degree of saturation greatly affects the FAS.

The development and fabrication of silicon-based phononic band gap crystals has been gaining interest since phononic band gap crystals have implications in fundamental science and display the potential for application in engineering by providing a relatively new platform for the realization of sensors and signal processing elements. The seminal study of phononic band gap phenomenon for classical elastic wave localization in structures with periodicity in two- or three-physical dimensions occurred in the early 1990’s. Micro-integration of silicon devices that leverage this phenomenon followed from the mid-2000’s until the present. The reported micro-integration relies on exotic piezoelectric transduction, phononic band gap crystals that are etched into semi-infinite or finite-thickness slabs which support surface or slab waves, phononic band gap crystals of numerous lattice constants in dimension and phononic band gap crystal truncation by homogeneous mediums or piezoelectric transducers. The thesis reports, to the best of the author's knowledge, for the first time, the theory, design methodology and experiment of an electrostatically actuated silicon-plate phononic band gap quasi-crystal architecture, which may serve as a platform for the development of a new generation of silicon-integrated sensors, signal processing elements and improved mechanical systems. Electrostatic actuation mitigates the utilization of piezoelectric transducers and provides action at a distance type forces so that the phononic band gap quasi-crystal edges may be free standing for potentially reduced anchor and substrate mode loss and improved energy confinement compared with traditional surface and slab wave phononic band gap crystals. The proposed phononic band gap quasi-crystal architecture is physically scaled for fabrication as MEMS in a silicon-on-insulator process. Reasonable experimental verification of the model of the electrostatically actuated phononic band gap quasi-crystal architecture is obtained through extensive dynamic harmonic analysis and mode shape topography measurements utilizing optical non-destructive laser-Doppler velocimetry. We have utilized our devices to obtain fundamental information regarding novel transduction mechanisms and behavioral characteristics of the phononic band gap quasi-crystal architecture. Applicability of the phononic band gap quasi-crystal architecture to physical temperature sensors is demonstrated experimentally. Vibration stabilized resonators are demonstrated numerically.

Biomimetic peptides are autonomously folding secondary structural units designed to serve as models for examining processes that occur in proteins. Although de novo biomimetic peptides are not simply abbreviated versions of proteins already found in nature, designing biomimetic peptides does require an understanding of how native proteins are formed and stabilized. The discovery of autonomously folding fragments of ribonuclease A and tendamistat pioneered the use of biomimetic peptides for determining how the polypeptide sequence stabilizes formation of alpha helices and beta hairpins in aqueous and organic solutions. A set of rules for constructing stable alpha helices have now been established. There is no exact set of rules for designing beta hairpins; however, some factors that must be considered are the identity of the residues in the turn and non-covalent interactions between amino acid side chains. For example, glycine, proline, aspargine, and aspartic acid are favored in turns. Non-covalent interactions that stabilize hairpin formation include salt bridges, pi-stacked aromatic interactions, cation-pi interactions, and hydrophobic interactions. The optimal strand length for beta hairpins depends on the numbers of stabilizing non-covalent interactions and high hairpin propensity amino acids in the specific peptide being designed. Until now, de novo hairpins have not previously been used to examine biological processes aside from protein folding. This thesis uses de novo designed biomimetic peptides as tractable models to examine how non-covalent interactions control the redox properties of tyrosine in enzymes. The data in this study demonstrate that proton transfer to histidine, a hydrogen bond to arginine, and a pi-cation interaction create a peptide environment that lowers the midpoint potential of tyrosine in beta hairpins. Moreover, these interactions contribute equally to control the midpoint potential. The data also show that hydrogen bonding is not the sole determinant of the midpoint potential of tyrosine. Finally, the data suggest that the Tyr 160D2-Arg 272CP47 pi-cation interaction contributes to the differences in redox properties between Tyr 160 and Tyr 161 of photosystem II.

The increased interest in the offshore wind resource in both industry and academic and the extension of the wind field where offshore wind turbine can be deployed has stimulated quite a number of offshore wind turbines concepts. This thesis presents a design of mono-column platform supported for 5 MW baseline wind turbine developed by the National Renewable Energy Laboratory (NREL), with a single tether anchored to the seabed. The design, based on the pioneer concept SWAY, results from parametric optimized design processes which account for important design considerations in the static and dynamic view, such as the stability, natural frequency, performance requirements as well as the economic feasibility. Fully coupled aero-hydro-servo-elastic model is established in the time-domain simulation tool FAST (Fatigue, Aerodynamics, Structures, and Turbulence) with the hydrodynamic coefficients from HydroGen, an indoor program providing same outputs as the commercial software WAMIT. The optimized model is verified by imitating the frequency-domain approach in FAST and thus comparing the results with the frequency-domain calculations. A number of simulations with various wind and wave conditions are run to explore the effect of wind speed and wave significant height in various water depths. By modifying the optimized model to a downwind turbine with the nacelle rigidly mounted on the tower and the single tether connected to the platform by a subsea swivel, the modified models are more closed to the original SWAY-concept wind turbine. These models are compared based on the platform motion, tether tension, displacement, nacelle velocity and acceleration, resonant behavior as well as the damping of the coupled systems. The results of these comparisons prove the advantage of the modified model in performance. The modified model has also clarified itself a good candidate for deep water deployment.