title: Azapropazone and derivatized EDTA and DTPA complexes as MRI contrast agents

contributor:
Lyne, Colin James
Chemistry

subject: Chemistry Chemistry

abstract: Azapropazone is a non-steroidal anti-inflammatory drug (NSAID), that had not been structurally characterized before this work began. The X-ray crystal structure of azapropazone is presented here. The synthesis of several derivatives of azapropazone is outlined. The X-ray crystal structures of the derivatives are presented and described and compared to the structure of azapropazone. The discrepancies in the literature on the previously proposed structures of azapropazone and its derivatives are also discussed. Contrast agents for MRI are necessary for site-specific image enhancement. Potential new agents are presented in this work. The synthesis and characterization of amino acid derivatives of ethylenediaminetetracetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA) is described. The amino acids used are the benzyl esters of glycine, phenylalanine, and tyrosine. The relaxivities of the ligands with Gd(III) were determined and compared to the relaxivities of similar complexes in the current literature. The synthesis and characterization of azapropazone derivatives of EDTA and DTPA is described. The possibility of inflammation-site imaging is discussed. The relaxivities of these ligands with Gd(III) was determined and compared to the relaxivities of similar complexes in the current literature. The results of biodistribution studies and single photon emitted computed tomography (SPECT) images of rats injected with the glycine or azapropazone DTPA derivative complexed with ¹¹¹In(III) are described.

abstract: Doctor of Philosophy (PhD)


title: Fault Detection and Diagnosis in Dynamic Multivariable Chemical Processes Using Speech Recognition Methods

contributor:
MacGregor, J.F.
Taylor, P.A.
Chemical Engineering

subject:
Chemical Engineering
Chemical Engineering

abstract:
Fault Detection and Diagnosis have become important topics in the process industries. The off-line diagnosis of past transient upsets can lead to important process or operation modifications that can improve the future behavior of the process. The rapid on-line diagnosis of faults is even more important since it can anticipate and minimize the impact of otherwise costly effects.

The first part of this thesis addressed the problem of fault diagnosis in multivariate, dynamic, continuous chemical processes. Two types of faults were considered: deterministic (whose root cause is a randomly occurring deterministic event) and stochastic (caused by an underlying stochastic process). A realistic simulation of a chemical plant was used as a test bed for the proposed methods. Due to the lack of accurate dynamic models for this type of process, a Pattern Recognition approach was followed. Within this framework, several methods were designed for the on-line and offline diagnosis of both types of faults. All methods consisted of: I) a feature extraction step, where magnitude invariant features are extracted from both the reference patterns and the pattern of the new unknown fault, and II) a similarity assessment step where the distance between the new pattern and each of the reference patterns is estimated using Dynamic Time Warping.

Due to the use of magnitude invariant features and the ability of Dynamic Time Warping to synchronize similar patterns with distorted temporal correlations, the results were satisfactory in diagnosing deterministic faults. In the case of stochastic faults, the results were inconclusive. The correlation pattern between the variables was used as the feature for the diagnosis of stochastic faults. However, the slow dynamics and the effect of the recycle in the simulated chemical plant meant that unrealistically long records of data are required for an accurate estimate of this feature.

The second part of the thesis investigated the problem of fault detection in batch processes, and in particular the problem of batch trajectories of unequal duration and poor synchronization. A new method, based on Dynamic Time Warping, was proposed for the synchronization of batch trajectories of this type; the method is multivariate and requires minimal process knowledge. It was also shown how to use Dynamic Time Warping to synchronize a new batch trajectory with the reference trajectories so that batch monitoring methods based on Multivariate Statistical Methods could be used. Finally, a new on-line monitoring method was presented, based on the concept of instantaneous quadratic distance, which does not require prediction of the future behavior of the batch trajectory.

abstract: Doctor of Philosophy (PhD)


title: Dopamine-glutamate interactions in the striatum

contributor:
Mazurek, Michael F.
Neurosciences

subject:
Neuroscience and behavioral Sciences
Neuroscience and Neurobiology
Social and Behavioral Sciences
Neuroscience and Neurobiology

abstract: The striatum is part of a neural feedback network that modifies the functioning of the cerebral cortex. The importance of the striatum is underlined by the clinical consequences of striatal dysfunction: disordered signaling in the striatum gives rise to the clinical syndrome of Parkinson's disease, while degeneration of striatal output neurons produces the clinical manifestations of Huntington's disease. The striatum is a complex structure comprised of two major populations of neurons: the spiny projection neurons that carry the striatal output to other nuclei in the basal ganglia; and several subtypes of aspiny cells that project locally within the striatum to modify striatal output. The two major inputs to the striatum are the glutamatergic pathway from the cerebral cortex and the dopaminergic pathway from the substantia nigra. The goal of my research is to explore the nature and functional significance of dopamine-glutamate signaling and its role in the striatum and basal ganglia. My first series of studies in vivo demonstrated that altering dopaminergic tone in the striatum by D2-dopamine receptor blockade or by 6-hydroxy-dopamine lesion of the nigrostriatal dopamine projection in the rat could modify the pathological, neurochemical and behavioural consequences of glutamate-receptor-mediated-stimulation. In order to investigate the details of this interaction, I developed an in vitro tissue culture system. I showed initially that the growth of striatal neurons in serum free culture parallels their in vivo development. I then went on to use this in vitro system to demonstrate the differential effects of selective glutamate receptor agonists on transmitter release from subpopulations of the two major classes of striatal neurons: (i) those in which somatostatin and neuropeptide Y are colocalised with nitric oxide and (ii) the substance P-containing spiny projection neurons. This series of studies demonstrated that substance P release was selectively stimulated through the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor while somatostatin and neuropeptide Y release were selectively provoked by stimulation of the kainate receptor. Stimulation of the metabotropic glutamate receptor had little effect on the release of any of the three peptides. My final series of experiments examined the differential effects of selective dopamine receptor stimulation on glutamate-receptor-induced release of substance P, somatostatin and neuropeptide Y. The D1 agonist SKF 38393, and to a significantly lesser extent the D2 agonist quinpirole, attenuated glutamatergic release of substance P from the spiny neurons. In contrast, the D2 agonist quinpirole potentiated the release of neuropeptide Y and somatostatin from aspiny neurons. The D1 agonist SKF 38393 attenuated glutamate receptor stimulated release of neuropeptide Y, without significantly affecting the release of somatostatin from the same cultures. This latter result indicates that dopamine can differentially regulate transmitter release not only from separate populations of striatal neurons but also differentially control release of transmitter that are colocalised within a single population of neurons. To my knowledge these studies are the first to demonstrate this differential regulation in the striatum, and implies that the delicate balance required for both normal cognition and movement may be intimately related to the balance of signaling between the intrinsic (somatostatin-neuropeptide Y-containing) and extrinsic (substance P-containing) neuronal populations in the striatum.

abstract: Doctor of Philosophy (PhD)


title: Geographies of oppression and resistance: Contesting the reproduction of the heterosexual regime

contributor:
Chouinard, Vera
Geography

subject: Geography Geography

abstract: In this thesis I offer a specifically lesbian and geographic analysis of particular struggles for social change in Hamilton, Canada. Through an investigation of the deployment of the political regime of heterosexuality in the regulation and containment of local anti-violence activism in the 1990s, I build on emerging work in feminist, and lesbian and gay geographies on the institution of heterosexuality as regulatory. Through an exploration of both the struggles over the development of spaces of political resistance, and the importance of gender, sexuality, and "difference" in local urban politics, I suggest that "unnaturalizing" categories such as Woman/Man can offer insights to the processes of identity formation in place. Through employing a politically engaged methodology and constructing this research as part of local struggles for social change, I offer local activists critical analyses of political strategies and processes of institutionalization in Hamilton, as well as challenging the ongoing invisibility of lesbians in geography and beyond.

abstract: Doctor of Philosophy (PhD)


title: Characterization and modeling of strained layers grown on V-grooved substrates

contributor:
Weatherly, George C.
Materials Science and Engineering

subject:
Materials Science and Engineering
Materials Science and Engineering

abstract: Growth of superlattices on V-grooved substrates has become a popular method of producing quantum wires. The success of this technique to date has been limited to the lattice-matched AlGaAs/GaAs system. The unpredictability of the morphology and defects found in lattice-mismatched systems has been a major hindrance in their development. Additionally, the misfit stresses in lattice mismatched systems may play an important role in determining the properties of the laser. In V-grooves, the singular points at the corners of the groove produce a stress distribution completely different from the case of layers grown on a planar substrate. Accurate knowledge of the stress distribution is hence necessary because a stress can affect the optoelectronic properties and lead to defects, limiting the life of the laser. The aim of the project was two fold: first to characterize the InGaAs/InP growth on (211)A and (111)B grooves using molecular beam epitaxy in terms of faceting, thickness variation, and composition variation; second to obtain an analytical and numerical stress distribution for the case of a layer with uniform composition and thickness grown on a sharp V-groove. The characterization was performed using transmission electron microscope and degree of polarization methods. Composition analysis was done with a high resolution scanning transmission electron microscope. Numerical simulation was done using a commercial finite element program, 'ABAQUS'. The results showed a clearly distinct morphology for layers grown on faceted (211)A and (111)B substrates. The differences observed in faceting, thickness variations, and composition variations in the (211)A and (111)B grooves suggest that the lower incorporation rate of group III atoms on (111)B surfaces leads to increased interfacet diffusion compared to (211)A grooves, where a higher incorporation rate produces layers with uniform composition and thickness. Furthermore, the 46.5% increase in In content found at the bottom of (111)B grooves indicates that the mean diffusion length of In is much higher than Ga for the growth conditions used in this study. The large variation in composition in (111)B grooves produced extensive defects at the bottom of the groove and at certain locations of the sidewall where the misfit exceeds the critical limit. The analytical and numerical solution of the stress distribution were in good agreement with experimental results. The stress fields obtained by these methods would be useful in helping to predict the optoelectronic properties of the quantum wire. Furthermore these models are useful in determining the composition and thickness of the layers which need to be grown to obtain specific optical properties.

abstract: Doctor of Philosophy (PhD)


title: Russell on Truth

contributor:
Griffin, Nicholas
Philosophy

subject: Philosophy Philosophy

abstract:
Before June 1905, Russell does not treat the problem of truth at length; but in the five subsequent years he devotes a number of important papers to the question: What is Truth? In his attempt to find the answer to this question in the following few years, he criticises and rejects all other prevalant theories of the time. In consequence Russell is able to establish his own view on the nature of truth in 1910.

The aim of this thesis is to present a unified view of the whole period, with its different aspects and their evaluation. This unified view will represent a transition from the initial indecision of 1905 to a definite formulation of the notion of 'truth' in 1910. In the controversies of this transitional period, certain defects of the then prevalant views have been pointed out, apart from those of Russell. Certain defects in Russell's criticisms have also been pointed out. Finally it has been shown that Russell's own positive notion of 'truth' is also not an adequate one.

abstract: Master of Arts (MA)


title: Pb isotope systematics in cenozoic igneous rocks from the Rio Grande Rift region, United States of America

contributor:
Dickin, A. P.
Geology

subject: Geology Geology

abstract: The Rio Grande Rift is a major tectonomagmatic feature of the North American craton. Physiographically, the present rift is recognized as a series of grabens and half-grabens which extend for over 1000 km from south-central Colorado into Chihuahua, Mexico. Rift structures, however, are recognized as far north as the Colorado-Wyoming border. Basaltic magmatism within the rift began by 30 Ma in southern New Mexico, and by 25 Ma in northern New Mexico and Colorado. Within-rift magmatism is low in volume in comparison to rift-related activity on the rift shoulders and flanks. Petrologic studies of Rio Grande Rift-related volcanics are numerous, yet focus primarily on suites erupted in north-central New Mexico and Colorado. However, recently published abstracts suggest areas of southern New Mexico are receiving much needed attention. Initial attempts at characterizing the petrologic diversity and mantle sources of rift-related volcanics have concentrated on major and trace element data, as well as the application of Sr and Nd isotopes. Only minor attention has been given to Pb isotope variations. This thesis contains the most recent compilation of Pb isotope data for volcanic rocks erupted within the Rio Grande Rift region. The oldest rocks included in this work are monzonite stocks erupted c. 60 Ma within the Colorado Mineral Ben. Using Pb isotope data in combination with trace element variations and Sr-Nd isotopes, a model is developed which suggests the stocks were initially derived from mantle sources with geochemical properties similar to those which produced rift-related basaltic volcanics in northwest Colorado beginning at 25 Ma. Two chapters of the thesis are devoted to exploring the utility of Pb isotopes as tracers of crustal influence in continental basaltic volcanism. One deals specifically with documenting Pb isotope variations in the northwest Colorado region, whereas the second focuses on variations in the Espanola Basin of north-central New Mexico. Major results of the northwest Colorado study (1) suggest that the asthenosphere contributed to early rift (25 Ma volcanism), (2) better characterize the geochemical signature of lithospheric and asthenospheric sources during periods of active volcanism, and (3) confirm earlier suspicions regarding the effects of crustal contamination in several rock suites. Work on basaltic components of volcanism in the Espaanola Basin indicate that crustal contamination was also an important process in producing the observed Pb and Sr isotopic variations in both early and later rift lavas. The remaining chapter of the thesis is a synthesis of all available rift data, from northern Colorado to southern New Mexico. An analysis of changes in the Pb isotopic composition of the lithosphere with latitude is presented, as well as a cross-rift transect of the central rift region. Further, a model which combines previously published ideas on the tectonomagmatic development of the Rio Grande Rift and the Basin and Range province is proposed. The most important results of the combined model are the proposition that rifting began earlier than previously thought, and that the timing of extension and magmatism in the Rio Grande Rift is very similar to that of the Basin and Range province. Additional data from the rift, particularly the southern region, will help to confirm or deny this model.

abstract: Doctor of Philosophy (PhD)


title: Stable isotope analyses in otoliths of cod (Gadus morhua L., 1758): Implication for long-term environmental changes in the Canadian Atlantic

contributor:
Schwarcz, Henry P.
Brand, Uwe
Geology

subject: Geology Geology

abstract:
Stable isotopic analysis has been widely used in study of proxy materials with concentric layers. such as fossil shells. corals. and tree rings. and has recently begun to blossom in fish otoliths. This study describes some new developments of stable isotopic analyses in otoliths of cod (Gadus morhua) from the northeast Scotian Shelf, Nova Scotia, and demonstrates how powerful those analyses are in study of marine environmental changes.

It is known that the relationship between oxygen isotope (δ¹⁸Ow) and salinity is very useful in study of coastal settings, especially for study of the dynamic processes, water currents and possible sources of mixing, and the estimation of isotopic composition in paleo-oceans. In this study, I found that the best equation for describing this relationship in the 4Vs area is: δ¹⁸Ow = 0.524S -18.38. I also found that this relationship varies vertically with water depth, especially at depths greater than 200 m. The oxygen isotopic records in 4 V s over the last 20 years show that the variation trend for surface water was steadily more negative in δ¹⁸Ow and lower in salinity. However, at depths greater than 200 m, a warmer water mass appeared around 1985, indicating that some distinct environmental events happened during that period.

Sagittal otoliths of cod were analyzed based on seasonal translucent (winter) and opaque (summer) aragonite zones, by a newly-established micromilling technique (DM 2800). The δ¹⁸Ow values range from 0 to +3.0 %0, with minor isotopic variations between seasons. However. there were significant differences in the growth of the first-year, indicating that juvenile cod are more active than adults at the early stage of their life history. Comparing opaque otolith zones of the 4-5 year group from different years of capture, the secular isotopic variation gradually increased by about 1 % over the period of 1984-94, corresponding to a temperature decrease in the surrounding seawater of about 5⁰C. This result is in agreement with the data from summer groundfish trawling survey and with other independent investigations. Based on the δ¹⁸O values in otoliths (greater or less than 0.75 %), two types of cod in 4Vs were recognized. It suggests that about 20 % of the total cod were recruited from the Gulf of St. Lawrence (migratory) where the δ¹⁸O was relatively lower, whereas the other 80 % were indigenous to the 4Vs area. Such a classification may have the potential for using δ¹⁸Ow signals from different water masses to study recruitment and migration of cod. and possibly other fish species.

The life-long δ¹⁸C variation in otoliths of cod shows a consistent increase during the first 4 to 6 years, from the minimum values between -5 and -2.5 % to a maximum near 0%. The early rise in δ¹⁸C is partly due to the fraction of metabolic HCO₃⁻ in the cod's blood, and partly due to a dietary shift or trophic effect. The maximum in δ¹⁸C is attained at an age (4-5 y) close to that of the age of maturity, and used to determine the age of sexual maturity of the 4Vs cod. Furthermore, the maximum δ¹⁸C variation attained by otoliths is in synchrony with the coeval temperature decrease in seawater from 1984 to 1994, during which the cod stocks experienced a drastic decline in the Canadian Atlantic.

In this study, I also analyzed otoliths of known-history Norwegian cod from experiments. These cod were reared in ocean-pens for as long as 6 years, and provide a unique opportunity to examine their isotopic variations and environmental influences. Comparing these to otoliths from the 4 V s field cod, there are distinct differences in the range of isotopic composition, the life-long variations in δ¹⁸O and δ¹⁸C, and the degree of correlation between δ¹⁸O and δ¹⁸C. These differences probably arise from the living environmental constraints and food supply in the two different settings. The isotopic temperature estimation was very close to the records during rearing, suggesting that temperature is a controlling factor in the forming of seasonal otolith zones.

abstract: Doctor of Philosophy (PhD)


title: Glycoprotein K of herpes simplex virus (HSV): Role in viral egress and HSV-induced cell-cell fusion

contributor:
Johnson, David C.
Medical Sciences

subject:
Medical Sciences
Medical Sciences

abstract: The fusion of cellular and viral membranes induced by herpes simplex virus type 1 (HSV-l) is essential for many stages of the replication cycle including virus penetration into host cells, nucleocapsid envelopment, virus egress and transmission of virus from infected to uninfected cells. Wild-type infections also induce low levels of cell-cell fusion, and syncytial mutants of HSV cause cells to fuse extensively. Previous studies have demonstrated that a large fraction of syncytial viruses contain mutations in the HSV-l UL53 gene, indicating that UL53 likely plays a central role in HSV -induced membrane fusion. Consequently, the objectives of this thesis are as follows: 1) Identify and characterize the UL53 gene product produced by wild-type and syncytial strains of HSV -I, and 2) Investigate the role of this protein in HSV -induced membrane fusion and in HSV-l replication. A single 40-kDa protein containing unprocessed, high-mannose N-linked oligosaccharides was detected in cells infected with wild-type and syncytial strains of HSV -I. This protein was designated gK, the ninth HSV -l glycoprotein to be described. gK is unique among HSV -1 glycoproteins since all other HSV glycoproteins examined to date exist as two proteins species; an immature protein with unprocessed oligosaccharides and a mature fonn containing complex N-linked oligosaccharides and O-linked oligosaccharides acquired during post-translational processing in the Golgi apparatus. The gK protein also exhibited signs of heat induced aggregation, an attribute which is commonly observed in proteins spanning the membrane multiple times. Low levels of gK were expressed in HSV -infected cells relative to HSV glycoproteins with a direct role in membrane fusion. which is more consistent with a regulatory role for gK in the membrane fusion process. Wild-type gK. but not other HSV glycoproteins. inhibited cell-cell fusion induced by HSV -1 strains encoding a mutant form of gK (gKˢʸⁿ). As such. the recessive phenotype displayed by gKˢʸⁿ may be symptomatic of a loss-of-function mutation, which disrupts a regulatory function governing membrane fusion. Glycoprotein K was not detected in HSV-l virions and immunofluorescence microscopy demonstrated that gK is not transported to the surfaces of cells infected with either wild-type or syncytial HSV. Instead, gK accumulates in the perinuclear and nuclear membranes of cells, and is unlikely to reach the Goigi apparatus because gK oligosaccharides remained sensitive to endoglycosidase H, These findings are in contrast to the behaviour of all other HSV glycoproteins described to date, which are expressed on the cell surface and incorporated into the virion envelope. Therefore gK must influence membrane fusion indirectly. since the protein is absent from the virion and does not reach the plasma membrane. Furthermore, these results imply that syn mutations in gK induce fusion between the surface membranes of HSV -infected cells by deregulating some aspect of virus replication. Resident proteins are maintained within intracellular compartments (eg. Goigi membranes) by one of three mechanisms: retrieval signals. retention through oligomerization, or retention through membrane thickness. Increasing gK protein synthesis by 10-20 fold did not overcome the block in cell surface transport, and this property is typical of membrane proteins maintained within intracellular compartments by retention signals. Furthermore, gK expressed in the absence of other HSV proteins by using a recombinant adenovirus vector, exhibited the traits and subcellular distribution of gK expressed in HSV -infected cells. These observations indicate that gK contains the targeting signals responsible for gK retention in the endoplasmic reticulum (ER) and nuclear envelope. Although the process controlling gK retention is still uncertain, gK oligomeric structures were observed in cells overexpressing the gK protein, suggesting that the fonnation of oligomeric assemblies may contribute to gK retention in the ER. In addition, sequence analysis identified a tyrosine-based motif (YTK[FILM]) conserved by the gK homologs of eight different alphaherpesviruses, which may have the potential to act as an ER retrieval signal. To further investigate the role of gK in membrane fusion and HSV replication, a gK-negative mutant (F-gKβ) was constructed. Since gK was found to be essential for virus replication, F-gKβ was propagated on complementing cells which can express gK. F-gKβ produced normal plaques characterized by rounded cells when plated on complementing cells, and F-gKβ produced syncytia on cells expressing low levels of gK. In contrast, F-gKβ formed microscopic plaques (consisting of 3-6 infected cells) on gK-negative cell lines and these plaques were reduced by 10² to 10⁶ in number. In the absence of gK, large quantities of unenveloped caps ids accumulated in the cytoplasm of HSV-infected cells and virus panicles did not reach the cell surface. The few enveloped panicles that were assembled displayed a reduced capacity to enter cells and initiate infection. Overexpression of gK also caused defects in virus egress, although virions accumulated in the perinuclear space, and large multilamellar membranous structures juxtaposed with the nuclear envelope were observed. Together these results demonstrate that gK regulates or facilitates HSV egress from cells. In addition, these findings raise the possibility that defects in gK may influence cell-cell fusion by altering the cell surface transport of viral particles, or other viral andlor cellular components which govern the fusion process.

abstract: Doctor of Philosophy (PhD)


title: Oxygen sensing, plasticity and catecholaminergic functions in cultured chromaffin cells of rat carotid body and adrenal medulla: Modulation by chronic hypoxia and acetylcholine receptors

contributor:
Nurse, Colin A.
Biology

subject: Biology Biology

abstract: The mammalian carotid body is a chemosensory organ, located at the bifurcation of the common carotid artery. It senses blood levels of oxygen, carbon dioxide, and acidity and maintains homeostasis via the control of breathing. Type I or glomus cells of the carotid body are the putative chemoreceptors which transduce blood-borne chemical stimuli into electrical signals carried by the carotid sinus nerve, which projects to the respiratory control center in the brainstem. It is likely that oxygen chemoreception in the carotid body involves the concerted actions of multiple neurotransmitters or neuromodulators, e.g. dopamine, acetylcholine and substance P, released from glomus cells onto apposed sensory terminals of the carotid sinus nerve. Further, carotid body catecholamines have been implicated in the resetting of chemoreceptor sensitivity after birth, ventilatory acclimatization to chronic hypoxia, and "blunting" of the ventilatory response in high-altitude dwellers. Catecholamine release is also critical for the animal's ability to survive the hypoxic stress associated with delivery and the transition to extrauterine life, though in this case, the origin is from a different source, the adrenomedullary chromaffin cells. The primary goal of this thesis was to elucidate the cellular and molecular mechanisms underlying oxygen chemoreception and the adaptive responses of chemoreceptors to chronic hypoxia. The use of dispersed cell cultures of the rat carotid body and adrenal medulla permitted the direct exposure of putative oxygen chemoreceptors to low oxygen. In addition, high performance liquid chromatography, immunocytochemistry, and pharmacological tools were used to delineate the cellular and molecular mechanisms which underlie oxygen sensing and adaptation of the isolated chemoreceptors to chronic hypoxia in vitro. In normoxic carotid body cultures, acute hypoxia stimulated dopamine release in a dose- and Ca²⁻dependent manner, possibly via closure of Ca²⁻-dependent K⁻ channels. Exposure of glomus cells to chronic hypoxia in vitro triggered a wide array of adaptive responses with the potential to modify the level of released neurotransmitter. These "plastic" responses include: (1) an apparent down-regulation of functional oxygen-sensitive, Ca²⁻-dependent K⁻ channels; (2) up-regulation of GAP-43 immunoreactivity; and (3) enhanced basal extracellular dopamine, which appears to be set by positive and negative feedback regulation via nicotinic and muscarinic acetylcholine receptors, respectively, and inhibition of dopamine transporters. In chronic hypoxia, acetylcholine appears to be an important autocrine/paracrine modulator of dopaminergic function in carotid body cultures. These cellular adaptations may relate to changes in carotid body chemosensitivity during chronic hypoxia in vivo. Similar to carotid body glomus cells, neonatal adrenomedullary chromaffin cells express oxygen-chemoreceptive properties. Exposure of neonatal chromaffin cultures to acute hypoxia or a specific blocker of Ca²⁻-dependent K⁻ channels stimulated catecholamine (predominantly epinephrine) release in vitro. These findings in glomus and adrenomedullary chromaffin cells suggest that hypoxia may close Ca²⁻-dependent K⁻ channels, leading to membrane depolarization, entry of extracellular Ca²⁻ and catecholamine release. However, unlike glomus cells, adrenomedullary chromaffin cells possess a developmentally regulated oxygen-sensing mechanism, since hypoxia had no significant effect on catecholamine release in juvenile adrenomedullary chromaffin cells.

abstract: Doctor of Philosophy (PhD)


title: Roles of nerve growth factor in developing and mature dorsal root ganglion neurons

contributor:
Diamond, Jack
Medical Sciences

subject:
Medical Sciences
Medical Sciences

abstract: This thesis examines the roles of nerve growth factor (NGF) in developing and mature dorsal root ganglion neurons, especially in the context of reparative nerve growth mechanisms in the adult peripheral nervous system (PNS). Peripheral nerve injury evokes two types of growths in the periphery, regeneration and/or collateral sprouting. However, these growth processes differ in a number of respects. Axonal regeneration is triggered by the injury and occurs independently of NGF whereas collateral sprouting is evoked and sustained by an increase in a target-derived signal, NGF. Indeed, cutaneous denervation is shown to result in a significant and prolonged increase in the level of NGF mRNA compared to the level in innervated skin. In addition, NGF mRNA is demonstrated to be expressed in not only the distal nerve pathways but also in non-nerve associated epidermally- and dermally-located cells. These findings indicate that an increase in NGF synthesis is associated with the increased availability of NGF in denervated skin, and that cutaneous nerves play a role in regulating NGF synthesis. Other findings in this thesis serve to strengthen the distinction between the injury-induced nerve growth responses. mRNA expression of the two NGF receptors, p75ᴺᴳᶠᴿ and trkA, are shown to increase in undamaged DRG neurons whose axons are sprouting into denervated skin, a proposed response that is most-likely related to the increased availability of target-derived NGF based on the findings that (i) NGF mRNA is increased in denervated skin, and (ii) polyclonal anti-NGF antiserum blocks the increase in the mRNA level of at least p75ᴺᴳᶠᴿ. In contrast to these findings, there was little or no change in receptor mRNA levels in regenerating neurons, consistent with the observations that NGF does not play a role in this process. Finally, here it is demonstrated that the NGF-driven collateral sprouting is severely impaired in adult rats that had received daily injections of anti-NGF serum during the first 2 weeks of postnatal life. However, after nerve crush the same nociceptive axons regenerated normally. Since NGF expression levels was found to be normal in innervated and denervated skin, NGF insufficiency was not responsible for the impairment in sprouting. Moreover, the possibility of a permanently defective axoplasmic transport was eliminated since sensory thresholds and axon calibers were also normal. Lastly, the finding that systemically-injected NGF promoted nociceptive sprouting, implies that the neurons had not become NGF-insensitive, nor had they reached a sprouting "ceiling". Indeed, the difference between the effects of exogenous and endogenous NGF is understandable if the latter accesses only the nerve terminals, and if the terminals' ability to take up NGF is defective. Thus, the exogenous NGF may work entirely through regions of the neuron that are outside this functional "compartment". To this end, although NGF uptake must have been adequate to account for the healthy state of the neurons, the terminals apparently failed to take up enough of the increased NGF produced in the collateral sprouting paradigm either to evoke sprouting, or to cause the usual upregulation of p75ᴺᴳᶠᴿ in the neurons of the dorsal root ganglion (DRG); there was, however, enough increased uptake to bring about the usual upregulation of trkA. This last finding suggests that neurotrophin deficiencies induced by adverse conditions during development might permanently compromise the organism's ability to mount neurotrophin-based reparative nerve growth in response to neuronal loss or peripheral nerve injury.

abstract: Doctor of Philosophy (PhD)


title: Lapped transforms based on DLS and DLC basis functions and applications

contributor:
Yip, P.
Electrical and Computer Engineering

abstract:
During the past decade, discrete block transforms have evoked considerable interest in the signal processing area. Discrete block transform is realized by first dividing the sample sequence of a signal to be processed into a series of blocks. The transform operation is then carried out by taking the inner products between the finite-length signal and a set of basis functions. This produces a set of coefficients which may then be further processed in compression, quantization, and encoding. Generally, block transforms can be divided into two types. One is called "nonlapped transform"; the other, "lapped transform". In the first system, the blocks are contiguous and no overlap (conjunction) is involved. The second system has overlapped operations: i.e., the data blocks may be overlapped.

In signal or image compression, it is well known that the non-lapped transforms produce an artifact called the "blocking effect" in the reconstructed signal or image. The blocking effect is partially due to the sharp cutoff of the data block. In lapped transforms where the data blocks overlap, the gradual decay of the basis functions in the overlapped region helps to reduce this blocking effect.

In this dissertation, we use a bell function to establish the discrete local sine (DLS) transform and the discrete local cosine (DLC) transform. The basis functions of this general type have a smooth cutoff and are shown to have orthogonality properties. The orthonormality and lapped orthogonality of DLS/DLC transforms indicate that DLS and DLC belong to the family of the lapped block transform system. We derive sufficient and necessary conditions for perfect reconstruction for lapped block transforms based on DLS/DLC basis functions, although, in general, lapped transform matrices are not unitary. These conditions are useful for designing optimum lapped block transforms in special applications. For example, in image and speech coding, we can design an optimal lapped transform system with the perfect signal reconstruction property.

Other properties of the transforms are also discussed. These include scaling-in-time, shifting-in-time, difference-in-time, the uniqueness property, and the convolution property. Fast algorithms for implementing DLS and DLC are developed. Based on Given's rotations and butterfly operations, we decompose an Mth-order DLS or DLC with length M + L⁻ into a set of sparse matrices, where L is the length of the overlapped region. Because of the partially recursive nature of the structure, DLS and DLC fast algorithms can be implemented with parallel processors.

As examples, we consider two applications using lapped transforms. The first application is in acoustic echo cancellation. We use block transforms to implement a subband acoustic echo canceller. However, due to the frequency aliasing problem in a filter bank system [36], the direct application of block transforms in an echo canceller does not function very well. We propose an improved method. By changing the subsampling rate in block transforms, echo residuals can be reduced significantly. Moreover, we develop an optimum lapped transform using a criterion of maximum energy concentration. With the optimum designed lapped transform, an obvious performance improvement can be observed from echo suppression. Image compression [65], a tool for efficiently encoding a picture (two dimensional data), is the second application of lapped orthogonal transforms discussed in this thesis. We develop a new sub-optimal lapped transform based on DLS and DLC for image coding. The results are compared with those obtained from using the lapped orthogonal transform (LOT) and modulated lapped transform (MLT). Computer simulation results show significant improvement in the reduction of block effects.

abstract: Doctor of Philosophy (PhD)


title: Response of rainbow trout (Oncorhynchus mykiss) to simulated climate warming and sublethal ammonia

contributor:
Wood, Chris M.
Biology

subject: Biology Biology

abstract:
The earth's temperature is predicted to increase roughly 1-5°C over the next 50 years, against a backdrop of increasing environmental pollution. This is expected to have a profound effect on fish, organisms whose life processes are intimately linked to their environmental temperature. The present investigation quantified, in the laboratory, the basic bioenergetic, physiological, and toxicological responses of juvenile rainbow trout (Oncorhynchus mykiss) to a naturally fluctuating water temperature cycle (characteristic of inshore Lake Ontario), and to this cycle +2°C (simulated warming scenario) in the presence or absence of 70μM total ammonia (a common environmental pollutant).

This thesis provides concrete evidence that small temperature increase and low-level environmental pollution substantially alter the growth, feeding, physiology, and metabolism of juvenile rainbow trout, especially at the temperature extremes: positively during minimum winter temperatures (≈42% increase in growth rate and energy conversion efficiency), and negatively during summer maximum temperatures (≈38% decrease in growth rate and 11% decrease in conversion efficiency). Their responses to sublethal ammonia can be quite different based on seasonal temperature, but within the optimal temperature for growth (16-20°C), +70 μM ammonia appears to stimulate nitrogen retention and metabolism. Significant decreases during late summer in the activity of some of the enzymes involved in nitrogen metabolism indicated that protein systems of juvenile trout are potentially sensitive to the combination of chronic temperature increase in combination with sublethal ammonia pollution. An important factor influencing the responses of trout to a warmer, more polluted environment is nutritional status (i.e., 5-7 fold increase in oxygen consumption per unit protein growth). It is apparent from this investigation that juvenile trout in a better nutritional state will exhibit at least some adaptation to chronic temperature increase. However, this adaptation, either alone or in the face of sublethal ammonia pollution, may require a significant increase in the overall cost of living (10-17%).

abstract: Doctor of Philosophy (PhD)


title: Star formation in molecular clouds and globular clusters

contributor:
Pudritz, Ralph E.
Physics and Astronomy

subject:
Astrophysics
Astrophysics and Astronomy
Astrophysics and Astronomy

abstract:
Giant molecular clouds (GMCs) and cores, which are the sites of star formation in the Galaxy today, are supported against their own gravity and an external pressure by a combination of thermal and magnetic pressures, and by an internal turbulence which is characterized by gas velocity dispersions that increase outwards within a given cloud. Until now, however, models of isothermal spheres (in which velocity dispersion is independent of radius) have been used as the starting point for theories of star formation. Thus, this thesis presents a generalization of the classic Bonnor-Ebert stability analysis of pressure-bounded, self-gravitating spheres of isothermal gas, to include clouds with arbitrary equations of state (EOS). The results are applied to GMCs and cores in order to model their internal structure. It is found that the simplest EOS which is consistent with all the salient features of these clouds is a "pure logotrope," in which P/Pⅽ=1+A ln(ρ/ρc). Detailed comparisons with data are made to estimate the value of A, and an excellent fit to the observed dependence of velocity dispersion on radius in cores is obtained with A≃0.2. This phenomenological model is then used to construct a new theory for gravitational collapse and star formation in turbulent molecular gas. Points of similarity and contrast between this and the collapse of an isothermal sphere are discussed. In particular, it is found that the rate of mass accretion onto a protostar in a logotrope increases with time (as M∝ t³), rather than remaining constant as in an isothermal sphere. Low-mass stars therefore take longer to form than previously suspected, while high-mass stars form more rapidly. This result has implications for the interpretation of observations of young stellar objects (the so-called "Class 0" protostars are discussed explicitly), for the origin and form of the stellar initial mass function, and for the process of star formation in clusters.

GMCs and cores are further characterized by a mass spectrum, N(m)=dN/dm, which scales roughly as m⁻¹⋅⁵ and is reminiscent of the distribution of globular cluster masses in the globular cluster systems (GCSs) observed around most galaxies. This suggests that star formation in protogalaxies may have followed the same basic pattern that it does today, i.e., that globular clusters formed in clumps of gas embedded in much larger (∼10⁸-10⁹M⨀) protogalactic fragments. Within this framework, the first theory of the GCS N(m) (which is directly related to the more frequently discussed globular cluster luminosity function, dN/dMᵥ) is developed here. A kinetic equation is formulated to statistically follow the collisional build-up and subsequent disruption (by the side-effects of internal massive-star formation) of protocluster clumps within a parent fragment, and solved for the mass spectrum which gives a detailed balance between the rates of these processes. This N(m) agrees well with observations of the Milky Way, M31, and M87 GCSs, for cluster masses in excess of ∼10⁵M⨀. In addition, the theory naturally accounts for observations which suggest that, at least at these high masses, N(m) is largely independent of galactocentric radius within any one GCS. The model makes specific predictions, regarding the lifetimes of cluster-forming cores, that should be applicable to present-day Galactic GMCs and cores as well.

abstract: Doctor of Philosophy (PhD)


title: Schottky contacts to indium phosphide and their applications

contributor:
Mascher, Peter
Simmons, John G.
Engineering Physics

subject:
Engineering Physics
Other Engineering
Other Engineering

abstract: InP and related materials have become important materials for applications in many electronic and photonic devices because of their high electron mobilities and high saturation electron drift velocities. InGaAs and InGaAsP, grown lattice matched to InP, are the materials of choice for making light sources and detectors in the wavelength range of 1.3-1.6 μm for the present day high data rate, long haul, fibre-optic communication systems. InGaAs metal-semiconductor-metal (MSM) photodetectors, InGaAs high-electron mobility transistors (HEMTs) and their monolithic integration as photoreceivers are promising devices for opto-electronic integrated circuits (OEICs). In the fabrication of the InGaAs MSM-PDs and HEMTs, good Schottky contacts are critical to achieve high performance, such as low dark current and high breakdown voltage, of the devices. However, the Schottky barrier height of metal/InGaAs contacts is only about 0.2-0.3 eV, which is not high enough for device applications. InP was chosen as the contact material in our fabrications of InGaAs MSM-PDs and HEMTs because of its compatibility in growth and lattice matched to In₀₅₃Ga₀₄₇As. In this research, the following investigations were carried out to understand the physics of the InP Schottky barrier, to obtain good Schottky contacts to InP, and to improve the performance of the InP/InGaAs MSM-PDs. (1) It was found that the current-voltage characteristics of metal(s)-InP Schottky contacts depart from the behavior predicted for the thermionic emission model. To explain these barrier anomalies. a modified current-voltage relationship was developed based on the inhomogeneous Schottky barrier. (2) A systematic investigation on metallization schemes shows that the Schottky barrier height of metal(s)-InP ranges from 0.38 to 0.5 eV, depending on the metal(s) and deposition techniques and the surface conditions of the InP. Among them, Au/Ti/Pt produces the highest barrier height while Au/Ni/Pt has the best uniformity in metal(s)-InP Schottky contacts. To further increase the Schottky barrier height, a thin In1-xGxP (x ranges from 0.1 to 0.3) layer of 100-200 Å grown on top of InP was employed. The barrier height obtained is found between 0.56 to 0.65 eV. The dark current is significantly reduced while the reverse breakdown voltage is increased from about 15 V to 20 V. (3) High-performance InGaAs MSM-PDs with InP as the barrier layer was fabricated. The MSM-PDs with a finger width of 2μm, finger spacing of 2μm, and an active area of 50 x 50 μm², have a dark current of about 200 nA at a bias of 10 V, a low capacitance of 0.2 pF, and breakdown voltages of about 15 V. A fairly high responsivity of 0.75±0.05 A/W at λ=1.3 μm was obtained. The temporal response is characterized by a rise time of about 4.0±0.2 ps, fall time of 8.0±0.2 ps, and FWHM of 8.5±0.2 ps which corresponds to a 3-dB frequency (unit current gain cut-off frequency), f3dB, of 20 GHz. The performance is comparable to the best of those InGaAs MSM-PDs with InAlAs as the contact layer. (4) Because of the lateral conduction in MSM-PDs and the Fermi-level pinning in InP due to surface states, the surface conditions play an important role in device performance. Surface passivation using (NH₄)₂Sx solution was successfully implemented to improve the performance of InGaAs/InP MSM-PDs.

abstract: Doctor of Philosophy (PhD)


title: Thin Film Coplanar Transmission Lines

contributor:
Campbell, C.K.
Electrical Engineering

subject:
Electrical and Computer Engineering
Electrical and Computer Engineering

abstract:
The theoretical aspects of coplanar waveguides were studied with special emphasis on the attainment of precise characteristic impedances and low losses in the 1-2 Ghz frequency range. To this end, a literature survey was performed, and characteristic impedance design curves were reproduced exactly by means of a digital computer. An exact tolerance analysis method was then performed in order to determine geometrical tolerances which would enable a characteristic impedance of 50 Ω +/- 10% to be attained for a given relative dielectric constant of 9.2 +/- 10%. A loss theory which neglected dielectric losses and assumed thin films of conducting metal less than 1 skin depth thick was also presented. Two similar fabrication techniques were studied and 43 coplanar waveguide samples were fabricated. Of these 43 samples, 32 were tested by swept frequency techniques and time domain reflectometer techniques.

The theory for characteristic impedance was found to be accurate to within +/- 2 Ω providing a few simple design guidelines were followed. The transmission loss theory corresponded very well with experimental measurements, which were estimated to be accurate to within 22%. Furthermore, fixtures for mounting the samples quickly and repetitively were designed and fabricated.

abstract: Master of Engineering (ME)


title: Syntheses and reactions of aminooxycarbenes from thermolysis of Δ³-1,3,4-oxadiazolines

contributor:
Warkentin, John
Chemistry

subject: Chemistry Chemistry

abstract: Δ³-1,3,4-Oxadiazolines, spiro-fused at C2 to C2 to oxazolidines (33a,b) or to C2 of tetrahydro-1,3-oxazines (106a-c), were synthesized by oxidation of semicarbazones 103 with PhI(OAc)₂. Oxadiazoline 33a was reacted with acylating agents and with benzenesulfonyl chloride to give 33c-j and 33k, respectively. Oxadiazolines 106d and 106e were prepared by reacting 106a and 106b, respectively, with benzoyl chloride. Thermolysis of oxadiazolines 33 and 106 in benzene at 90⁰C (k⁹⁰∼1-50x10⁻⁵s⁻¹) generated oxazolidin-2-ylidenes 28 and tetrahydro-1,3-oxazin-2-ylidenes 113, respectively, as major fragmentation intermediates. Specifically, 33c-j and 106d,e (N-carbonyl) gave essentially quantitative yields of the corresponding aminooxycarbenes, while thermolysis of 3b (N-methyl) produced ca. 70% of 28b; for 106c (N-methyl), an upper limit of ca. 20% was determined for the formation of 113c. Experiments on the thermolysis of 2,2-dioxy oxadiazolines 86 at 110⁰C in benzene led to the detection (and isolation, in one case) of ketene acetals 87 as minor products; compounds tentatively identified as oxiranes 94 were also observed. Formation of these and other products was rationalized in terms of a thermolytic scheme involving the intermediacy of carbonyl ylides 91 which predominantly fragment to dioxycarbenes 92 and acetone. Aminooxycarbenes 28b-g,j and 113d,e were intercepted with phenols to give OH insertion products 119/124; an activation energy of 20.4 kcal/mol was measured for nitrogen inversion in oxazolidines 119. Carbenes 28b,d-f and 113d reacted with two equivalents of methyl or phenyl isocyanate to give hydantoins 120; in contrast, 4(5H)-oxazolones 125 formed when 28d,f or dimethoxycarbene () were generated in the presence of benzoyl isocyanate. The major products in the reaction of 28d-f with dimethyl acetylenedicarboxylate or with methyl propiolate, oxazolines 157, resulted from apparent acyl transfers from N to C in the proposed dipolar intermediates. Carbene 28f inserted into the activated CH bond of 1,3-diones to produce 170; the minor products of these reactions (e.g. 173) provided evidence for the involvement of ion pairs. β-Lactam-4-ylidene 194, generated from thermolysis of β-lactam oxadiazoline 193, underwent intramolecular OH insertion to give 2,3-benzooxapenam 195 in 53% yield.

abstract: Doctor of Philosophy (PhD)


title: Synthesis, structure and properties of selected lithiated transition metal oxides

contributor:
Greedan, John E.
Chemistry

subject: Chemistry Chemistry

abstract: This thesis discloses a newly discovered series of compounds, Li₂CryMn₂-yO₄, wherein 0.1≤y≤1.9. This series consists of two solid solutions regions with a cross-over occurring at a composition near y = 1.4. The chemical structure of these phases was identified by x-ray powder diffraction. Phases with y≥1.4 have an ordered rock salt structure in which the lithium and transition metal cations form alternating layers between the sheets of oxygen atoms. The phases with y<1.4 have a different rock salt related structure in which the lithium ions and transition metal ions are arranged in interleaving chains within the cubic-close-packed oxygen framework. The resulting structures are distorted from cubic symmetry by the presence of the Jahn-Teller ion, Mn³⁺. The compositions with y< 1.65 were found to be particularly useful as cathodes in lithium ion type, electrochemical cells. The chemical and ordered magnetic structure of three materials, orthorhombic LiMnO₂, 1T-Li₂NiO₂ and a low temperature form of LiFeO₂ were determined from neutron diffraction data. LT-LiFeO₂ and 1T-Li₂NiO₂ are metastable phases prepared by chimie douce synthetic methods. A detailed study of the magnetic properties of 1T-Li₂NiO₂ and orthorhombic LiMnO₂ revealed complex behaviour involving a competition between two- and three-dimensional ordering. Neutron diffraction was also employed to identify the chemical structure of Li₂NiMnO₄. The electrochemical behaviour of orthorhombic LiMnO₂, LT-LiFeO₂. Li₂NiMnO₄ and Li₂Ni₁.₅Mn₀.₅O₄ was investigated in lithium ion cells. Orthorhombic LiMnO₂ proved to be particularly useful as a cathode material as it undergoes a phase transition in situ to the lithiated spinel phase λ-Li₂Mn₂O₄. Consequently, orthorhombic LiMnO₂ provides a convenient, air stable precursor to the electrochemically useful, but not air stable, λ-Li₂Mn₂O₄ phase.

abstract: Doctor of Philosophy (PhD)


title: Study of the mechanical properties of magnesium-8.5wt% aluminum by in-situ neutron diffraction

contributor:
Embury, J.D.
Weatherly, G.C.
Materials Science and Engineering

abstract: The mechanical behaviour in uniaxial tension and compression of extruded and aged Mg-8.5wt%Al was studied. In-situ neutron diffraction was used to follow the elastic lattice strains under load in the matrix and the precipitates. The internal stresses determined from these measurements are highest in grains unfavourably oriented for both basal slip and {10Τ2} twinning, lowest in grains oriented favourably for both, and in between for grains oriented favourably for {10Τ2} twinning only. Most variations in scattered peak intensity are due to the lattice reorientation produced by {10Τ2} twinning. A critical resolved shear stress criterion is shown to apply for twinning. Intensity variations which cannot be explained by {10Τ2} twinning occurred in some grains during tensile loading. They are likely due to {10Τ1} twinning which produces c-axis compression, unlike {10Τ2} twinning. Transmission electron microscopy revealed the presence of c- and non-basal a-dislocations in the undeformed alloy. Basal slip is the most common slip system, though non-basal a-slip also occurs. Only {10Τ2} twinning was observed by TEM. Twins often traversed grains completely, despite the presence of the precipitates. Schmid factor considerations show that pure magnesium yields first by basal slip. The early portion of the stress-strain curve should thus be considered a region of rapid strain hardening due to basal dislocation pile-ups at grain boundaries. In compression {10Τ2} twinning can also occur at very low applied stress. Strengthening in the alloy before yield is explained using a Brown and Clarke mean-stress hardening model. Beyond yield, relaxation mechanisms reduce the mean stress contribution essentially to zero in tension. The mechanical and physical properties of the intermetallic were obtained from experiments on a single crystal. Property correlations have been used to estimate the fracture toughness and yield stress, assuming its behaviour is similar to that of a ceramic.

abstract: Doctor of Philosophy (PhD)


title: Interactions of class A and class L amphipathic helical peptides with model membranes

contributor:
Epand, Richard M
Biochemistry

subject: Biochemistry Biochemistry

abstract: Amphipathic α-helix, that is an α-helix with opposing hydrophilic and hydrophobic faces oriented along the long axis of the helix, is an often encountered secondary structural motif in biologically active peptides and protein. In this thesis, there were systematically studied membrane interactions of two amphipathic α-helical peptides: the 18L peptide, which belongs to the class L (lytic peptides), and the Ac-18A-NH₂ peptide of the class A (apolipoprotein) according to classification of Segrest et al. (1990). It was found previously [Tytler et al., 1993] that class A and class L peptides have opposing effects on some properties of biological and model membranes. In order to elucidate the molecular mechanism responsible for this so-called reciprocal effect in biological membranes, we studied a number of aspects of membrane interactions of 18L and Ac-18A-NH₂ peptides including equilibrium and kinetics membrane binding, permeabiIization, fusion and conductance. These functionally different peptides also displayed a number of similarities in membrane interactions and thus parallel studies of these two peptides provide an insight into the general features of amphipathic peptide membrane interactions. It was found that membrane binding equilibrium and kinetics for both peptides can be described as monomer partitioning with saturation at high peptide/lipid ratios. The rate of peptide-membrane association is relatively close to the diffusion limit Increase in membrane affinity correlates with a decrease in dissociation rate, i.e. with slower peptide exchange. Both for cationic 18L and zwitterionic Ac-18A-NH₂, the presence of acidic lipids increased membrane binding constants by two orders of magnitude. We have shown that the dynamic character of the peptide membrane equilibrium can be used for selective peptide targeting and disruption of membranes with specific lipid composition. Titration calorimetry experiments show that the free energy of binding results from an entropic contribution. The free energy of peptide-membrane association is in the range of 8. 5-12. 8 kcal/mol. In regards to effects on membrane domain organization, 18L and Ac-18A-NH₂ peptides displayed more similarities than differences. While binding with high affinity to fluid membranes, peptides were unable to penetrate into the lipid membrane in the gel state. If trapped kinetically by cooling from the fluid phase, peptides dissociated from the gel membrane on the time scale of several hours. Charge-charge interaction were capable of inducing lateral domain formation in fluid membranes. Both peptides had affinity for anonic lipids which resulted in about 30 percent enrichment of acidic lipids within several nanometers of the peptide's tryptophan, but there was no long-range order in peptide-induced lipid demixing. Peptide insertion in fluid acidic membranes was accompanied by only a small increase in bilayer surface and a decrease in polarity in the membrane core. Peptide-lipid charge-charge interactions were also capable of modulating existing domain composition in the course of the main phase transition in mixtures of anionic phosphatidylglycerol with zwitterionic phosphatidylcholine. We were unable to observe any peptide-induced lateral phase separation in fluid zwitterionic membranes with nonbilayer phase propensity. Peptides actually improved lipid mixing within the temperature range of the main phase transition of the DMPC:DMPE binary system. Peptide-membrane permeabilizing activity was significantly affected by the presence of acidic lipids and, in zwitterionic membranes, the presence of nonbilayer forming lipids. In anionic membranes (DOPC:DOPG, DOPG) both peptides caused leakage in the range of bound peptide/lipid ratios of 1: 100 to 1: 1 0 and on the time scale of seconds. In zwitterionic vesicles in the range of bound peptide/lipid ratios 1 :50 to 1: 10, 18L caused both leakage and fusion on the time scale of hundreds of seconds. At the same peptide/lipid ratios. higher lipid concentrations favoured more fusion and less leakage. Ac-18A-NH₂ caused vesicle leakage, but not fusion. The lytic activity of 18L increased and that of Ac-18A-NH₂ decreased with an increase in the content of an inverted phase forming lipid. A reciprocal effect of 18L and Ac-18A-NH₂ was observed in both the vesicle leakage and vesicle fusion assays with zwitterionic lipids. Reciprocal effects of 18L and Ac-18A-NH₂, were restricted only to membranes with a high propensity for nonbilayer phase formation (DOPE, Me-DOPE, DOPC:DOPE,DOPC:Me-DOPE). The decrease in the content of nonbilayer phase forming lipid or addition of acidic lipids reduces or eliminates the reciprocal effects. This suggests that nonbilayer phase propensity is the physical property responsible for observation of reciprocal effects of A- and L-class peptides in biological membranes. Analysis of the mechanism of 18L induced permeabilization of zwitterionic membranes have shown that 18L peptide destabilises membranes. leading to a transient formation of large defects (diameter> 3 om) which generally results in contents leakage. but in the presence of bilayer-bilayer contact can lead to vesicle fusion. This defect formation is accompanied by phospholipid flip-flop and or peptide translocation. Peptide insertion into the membrane also significantly reduces membrane stability to mechanical tension making it susceptible to osmotic lysis. This mechanism may be general for the action of class L peptides.

abstract: Doctor of Philosophy (PhD)


title: Beowulf: The Concept of the Hero

contributor:
Lee, M. A.
English

subject:
Arts and Humanities
English Language and Literature
Arts and Humanities

abstract: This thesis deals with the Old English poem Beowulf. Through a detailed study of it and of other literature of a heroic and tragic nature, it explores the character, attributes, and achievements of a hero of this kind of fiction and draws some conclusions about the significance which may be found in the hero's nature and accomplishments. In the process, other literary works, not necessarily epic or Anglo-Saxon, are referred to, enabling the hero to be studied from a number of illuminating angles. Each of the first three chapters puts Beowulf in a particular context; the last two chapters combine the different threads of development and present a conclusion.

abstract: Master of Arts (MA)


title: Jet to jet impingement in a confined space

contributor:
Wood, P. E.
Hrymak, A.N.
Chemical Engineering

abstract:
Reaction injection moulding (RIM) is commercially used in industry for making polymer parts. In this process, two or more jets produce impingement mixing of low viscosity monomers or oligomers in a mixhead. In order to better understand an impingement mixer, it is essential to understand the flow field created by the opposed laminar jets in a similar configuration. In this thesis, an experimental investigation and analysis of the flow field created by the two equal and opposed cylindrical laminar jets impinging near the closed end of a confined space (mixhead) has been conducted. Three important flow and geometrical parameters which influence the flow field are considered. These are (i) jet Reynolds numbers (Re), (ii) H/D, a ratio of the position (H) (the distance in - Z direction from the impingement point to the closed end) to mixhead diameter (D), and (iii) viscosity of the fluid used. Both qualitative and quantitative studies have been performed using an experimental model of the mixhead which simulates a RIM type configuration. For qualitative analysis, two flow visualization methods, namely, dye injection and particle tracing methods have been used. For quantitative analysis, the laser Doppler anemometer (LDA) technique has been used to quantify the velocity fields (only U and V components).

It has been found that Re shows a significant effect on the flow field. For Re< 50, flow remains in a statically stable mode and rotating vortices are formed near the impingement plane. At slightly higher Re (≥50), the flow pattern changes to dynamically stable mode and the impingement plane oscillates. At Re≥90, the flow attains an unstable mode. In fact, the vortices gradually grow with increasing Re and at a critical value of Re they dynamically interact with each other causing oscillations about the impingement plane. For both static and dynamic stable zones, the length of circulating region increases as a function of Re (l/D = a - be⁻ᶜᴿᵉ) between 50 to 90. For Re > 90, the recirculating region shrinks before breaking into an unstable zone at a Re of approximately 125.

The piston position (H/D) plays an important role in the stability of the flow pattern. An unstable flow pattern transforms to a steady flow pattern when the piston is moved down from H/D = -0.5 to -0.75 at Re = 150. Furthermore, it appears that the flow patterns are always unstable at very high Re values since no stable patterns could be obtained up to HID = -1.0 at Re = 200. In stable modes, flow fields of both side of impingement plane are like a mirror image of each other. It appears that viscosity of the fluid has no significant influence on the flow patterns at constant Re. The vector and streamline plots obtained by LDA for Re = 50, and 150 agree with the flow pattern obtained with flow visualization methods. Also, the experimental measurements confirm that the flow in the vortex regions is 3-dimensional.

Vigorous fluctuations are evident up to one-half mixhead diameter above the impingement point. The axial velocity (V) along the mixhead axis reaches a velocity profile of a developed one dimensional steady flow within 1 to 1.5 mixhead diameters. However, the radial velocity (U) along the mixhead axis reduces to an insignificant value at a distance equal to approximately two jet-diameters above the impingement point. The frequency analysis of the time series of velocity components showed higher harmonics as the Re increases from Re = 50 to 150. The periodic structure completely vanishes at Re = 200. The periodic nature of time series which vanishes at Re = 200 for H/D = 0, vanishes at Re = 150 when H/D = -0.5. This shows that H/D ratio also influences the breakdown of any periodic nature in the flow field.

abstract: Doctor of Philosophy (PhD)


title: The Effect of General Cognitive Ability, Teamwork KSA's, and The "Big Five" Personality Factors on the Performance of Engineering Design Teams: Implications for the Selection of Teams

contributor:
Wiesner, Willi H.
Business Administration

subject: Business Business

abstract:
General cognitive ability, Teamwork KSA's, and the "Big Five" personality factors (Conscientiousness, Extraversion, Neuroticism, Agreeableness, and Openness to Experience) were examined as potential selection measures for three-person Engineering design teams. This study used objective product evaluations as the performance criteria for the teams rather than measures of satisfaction and self-reported performance which had been used as proxies for performance in past studies. Self-reports of satisfaction and performance were measured in order to test the validity of using these measures as proxies for objective performance.

In the short period of time over which this study took place, it was apparent that some teams were able to perform at a minimally acceptable level, and some were not. Successful teams were characterized by higher composite levels of general cognitive ability, Extraversion, Agreeableness, Emotional Stability, and Teamwork KSA scores than their unsuccessful counterparts. However, from a selection standpoint, only general cognitive ability and Neuroticism provided unique variance in differentiating successful from unsuccessful teams. The heterogeneity of Conscientiousness was negatively related to the performance of successful teams.

Team member self-reports of satisfaction and performance were moderately related to the team's product performance, although the relationships were not sufficiently large to suggest that a proxy relationship exists.

abstract: Doctor of Philosophy (PhD)


title: Biobehavioural Determinants of Colitis-induced Anorexia

contributor:
Weingarten, H.P.
Psychology

subject: Psychology Psychology

abstract: Although acute inflammation of the colon (colitis) results in a large suppression of eating, the mechanisms underlying this anorexia remain unknown. Since interleukin-1 (IL-1) receptors are implicated in colitis-induced anorexia and since IL-1 stimulates the release of oxytocin (OT), a neuropeptide implicated in the control of eating, I evaluated the role of OT in the rat model of colitis induced by intrarectal infusion of 2,4,6-trinitrobenzene sulfonic acid (TNB). Antagonism of central OT by a specific OT receptor antagonist did not diminish the magnitude or time course of colitis-induced anorexia. Similarly, no elevations in plasma OT levels correlated with the colitis-induced anorexia, which has been interpreted to mean that malaise was not associated with the anorexia. Subsequently, I examined whether the suppression of food intake could be explained by an exaggerated satiety response to the post-ingestive consequences of food intake that normally signal meal termination. To obtain experimental control over post-ingestive consequences, intragastric preloads were delivered prior to a meal. The various preloads used did not result in a greater suppression of food intake in TNB-treated rats. However, these experiments did reveal significant suppression in the rate of intake for rats with colitis, which suggests a possible shift in response to taste. "Taste Reactivity" measures were taken to assess this possibility. Colitis resulted in a specific change in behaviour and movements that are interpreted to indicate that the food was perceived as less positive. Together, these studies suggest that neither central OT, malaise, nor exaggerated response to post-ingestive consequences are mediators of the colitis-induced anorexia. The shift in Taste Reactivity measures suggests the anorexia may be mediated by a change in taste hedonic perception.

abstract: Doctor of Philosophy (PhD)


title: Thiol Complexes of Gold(I): Structure and Chemistry of the Gold Based Anti-Arthritis Drugs

contributor:
Lyne, Colin James
Chemistry

subject: Chemistry Chemistry

abstract:
The chemistry of gold is briefly reviewed, with emphasis on its oxidation states, unique properties and structures of its complexes. The chemistry relevant to the use of gold thiol complexes in medicine is discussed and related to the questions posed in this work.

The preparation of 1:1 gold to thiomalate complexes, as both sodium and ammonium salts, is described, as well as the preparation of highly optically pure thiomalic acid and gold complexes thereof. The use of electrospray ionization mass spectrometry for the characterization of gold thiol complexes is described and its structural implications are discussed and compared with results from other studies.

The preparation and characterization of 1:2 gold to thiomalate complexes, as ammonium salts, are described. The crystal structures of both racemic and optically pure samples are described and compared. These complexes are the first gold thiomalate complexes for which crystal structures have been determined. The preparation and characterization of an analogous complex of D-penicillamine is described. The crystal structure of this complex is presented and discussed.

The gold complex of 2,4,6-tri-(isopropyl) thiophenol was confirmed, by X-ray crystallography, to have a cyclic hexameric structure. A 1:2 complex of gold with the triphenylphosphinesulfide ligand was prepared as a difluorodioxophosphate salt and its structure was determined by X-ray crystallography.

abstract: Doctor of Philosophy (PhD)


title: 'Placing' Lay Perceptions of Health and Illness

contributor:
Eyles, J.
Geography

subject: Geography Geography

abstract: This thesis contributes to a little researched topic in health geography, that of lay perceptions of health and illness and their relationship to space. Informed by a symbolic interactionist perspective, the qualitative method of in depth interviewing is used to access and explore how 53 informants, living in relatively remote towns in Ontario, conceptualize health and illness. In this study, two notions of place are used. Place is used in both its geographic and experiential senses. Place-in-life, defined in the study largely by age, appears to have an influences on how people perceive health and illness. It is speculated that the differences found between the sites are linked to the presence of a papermill as well as the large number of Native Canadians living in Papermill Town. This study used the theory of symbolic interactionism to uncover the meanings that people held about health and illness. Although a relatively new theory to health geography, it was particularly useful for exploring how these meanings impact upon the physical and social bodies interaction with the world and how they contribute to and maintain a person's place-in-the-world.

abstract: Doctor of Philosophy (PhD)


title: A limnological and paleolimnological investigation of lakes in Wood Buffalo National Park, northern Alberta and the Northwest Territories, Canada

contributor:
MacDonald, G.M.
Smol, J.P.
Geography

subject: Geography Geography

abstract:
Physical, chemical and biological variables were measured in 35 lakes from Wood Buffalo National Park, northern Alberta and the Northwest Territories, Canada. Of these lakes, 22 were sinkholes, situated on limestone and gypsum, five were situated on the Canadian Shield and eight were shallow, "muskeg" lakes located on calcareous shales. For each of the 35 lakes, 37 environmental variables were measured, and diatoms from the surface 1-cm of deep water sediments (i.e. a surface sediment calibration or training set) were identified and enumerated. Two hundred and seventy-six diatom taxa were identified in the 35 lakes; 199 of these taxa were in relative abundances of ≥ 1%. Principal component analyses (PCA) and canonical correspondence analysis (CCA) revealed that underlying geology strongly influenced limnic properties, and therefore diatom community composition. Shield lakes were characterized by higher concentrations of AI and Fe, and lower pH values, specific conductivities and concentrations of ions associated with calcareous rocks (e.g. Ca, SO₄, Li, Mg, Na, etc.) than either the sinkhole or the muskeg lakes. The muskeg lakes were differentiated from the sinkhole lakes by higher concentrations of nitrogen and organic carbon (i.e. NH₃, particulate nitrogen and dissolved organic carbon), which was reflected in proxies of higher productivity (particulate organic carbon and chlorophyll a) and lower secchi depths.

Diatom distributions were strongly influenced by the environmental variables distinguishing the three lake types. The 22 sinkhole lakes were further classified by the type of surrounding vegetation. Six vegetation groups were recognized: 1) spruce; 2) pine; 3) mixed; 4) shrubs/poplar; 5) recently burned; and 6) rocky. These vegetation groups, in part, reflect fire history. Unlike geology, surrounding vegetation, and therefore fire, generally had little influence on limnic properties or diatom community composition. PCA and CCA showed that, based on water chemistry and diatom assemblages, of the six vegetation groups, only the spruce group was distinct. Spruce sites were characterized by high levels of dissolved inorganic carbon, and therefore unique diatom assemblages.

The results from the analyses of modern limnic properties and surface sediment diatoms are corroborated by high-resolution analyses of fossil diatom and chrysophyte assemblages from a Rainbow Lake A (RLA) sediment core. RLA contains annually-laminated sediments which were sampled at 5-year continuous intervals in order to study the impacts of known fire events, long-term vegetation change and recent climatic change. Park records and dendrochronological techniques were used to determine that at least three fires (circa 1860, 1880 and 1894), and to a limited extent a fourth fire (circa 1943), burned the catchment area of RLA. Paleolimnological evidence, including biogenic silica, diatom and chrysophyte analyses, suggests that RLA did not respond markedly to fire occurrence, and therefore short-term (10's of years) vegetation change.

Similarly, high-resolution diatom analyses (one sample for every 5 years) from RLA for the last 800 years revealed no change in diatom community composition coincident with a long-term (100's of years) vegetation change circa 1536. The lack of Iimnic response to this vegetation change may be related to the lake's relatively small catchment area or the calcareous bedrock that underlies the drainage area.

Although there was no change in diatom community composition coincident with the circa 1536 vegetation change, there was a dramatic change in diatom community composition circa 1836, that persisted to the present time. This change most likely reflects an increase in the internal loading of phosphorus, possibly as a result of a breakdown in meromixis, due to variations in ice out and spring circulation, or an increase in the duration of summer stratification, as a result of warmer summer conditions. The timing of this event is coincident with the marked changes in diatom community composition noted in sediment cores from ponds on Ellesmere Island The results of this thesis, coupled with the work of others, suggest that recent environmental changes, most likely climate related, have been having widespread impacts on remote lacustrine environments since the early part of the nineteenth century. Unlike past, long-term vegetation shifts, neither underlying geology or catchment area, are mitigating limnic response to this recent change.

abstract: Doctor of Philosophy (PhD)


title: Density Matrix Renormalization Group Study of the Enhanced Hole-Hopping Model of High Temperature Superconductivity

contributor:
Marsiglio, Frank
Physics

subject: Physics Physics

abstract: The thermodynamic behaviour of the enhanced hole-hopping model of high temperature superconductivity is investigated using the numerical Density Renormalization Group (DMRG) technique. The enhanced hole-hopping or Δt model is a Hubbard-like lattice model that has been proposed to account for superconductivity in the high temperature superconducting materials. Extensive results for this model have been obtained by others within the BCS approximation. This thesis does not attempt to motivate the use of the Δt model but rather it is the goal of this work to characterize the accuracy of two techniques used to study this model. In particular, the ground state energy and binding energy for a pair of particles as calculated within the DMRG are compared to similar results obtained from BCS and Exact Diagonalization studies. The DMRG is a relatively new numerical technique and consequently a detailed discussion of its implementation is given. Application of the DMRG necessarily confines investigation to one dimension. Analysis of finite size effects is also presented where warranted.

abstract: Doctor of Philosophy (PhD)


title: IDENTIFICATION AND CHARACTERIZATION OF GENES THAT PROTECT ESCHERICHIA COLI FROM HYDROGE PEROXIDE MEDIATED OXIDATIVE STRESS

contributor:
Schellhorn, H.E.
Biology

subject: Biology Biology

abstract:
Reactive oxygen species are major agents responsible for degenerative disease, ageing, mutagenesis and carcinogenesis. Enteric bacteria, such as Escherichia coli and Salmonella typhimurium, can serve as model cellular systems for understanding the physiological and genetic responses to oxidative stress in higher eukaryotes due to the similarity in the nature of response. The smaller size of the bacterial genome, simpler and well understood bacterial metabolic pathways and relative ease of manipulation of bacteria makes them a preferred tool for certain applications.

Enteropathogenic bacteria encounter endogenous toxic oxygen species during aerobic respiration and exogenously during phagocytosis by neutrophils and macrophages. Survival of bacteria under these circumstances depends on a multigene response to oxidative stress. For rapid adaptation, the cell elevates the synthesis of several known antioxidant enzymes such as catalase, superoxide dismutase and also a variety of stress proteins of unknown function. The adaptation and resistance to oxidative stress are thought to be crucial aspects of bacterial pathogenesis.

The genes encoding many of the antioxidant response proteins remain unidentified. We have used chromosomal mutagenesis to identify genes that play a protective function during H20 2 generated oxidative stress. The present work reports isolation and characterization of genes that are regulated by OxyR, a member of the LysR family of transcriptional regulators, involved in the regulation of a subset of the oxidative stress induced genes and other OxyR independent genes. One of the genes characterized in this work encodes a putative signal transducer protein (also implicated in iron regulation), known as BarA. Another gene identified in the oxidative stress response is rna, encoding an endoribonucleosidase RNase I.

Escherichia coli has two hydroperoxidases that breakdown hydrogen peroxide. The present study shows that the transcription of katG gene, encoding hydroperoxidase I (HPI), regulated by OxyR during peroxidative stress, is also regulated by stationary phase specific sigma factor RpoS during normal growth and during stress generated by weak acids.

abstract: Doctor of Philosophy (PhD)


title: Major histocompatibility complex class II sequence variation in cetaceans: DQβ and DRβ variation in beluga (Delphinapterus leucas) and DQβ variation in North Atlantic right whales (Eubalaena glacialis)

contributor:
White, B.N.
Biology

subject: Biology Biology

abstract:
Allelic variation at the Major Histocompatibility Complex (Mhc) class II loci DQβ and DRβ was assessed in a large sample (~300) of beluga (Delphinapterus leucas) and a sample (~12) of narwhal (Monodon monoceros) in order to study the evolutionary significance of the Mhc in cetaceans and to compare levels of variation among beluga populations. Mhc class II DQβ allelic variation was also analysed in a preliminary survey of right (Eubalaena glacialis) and bowhead (Balaena mysticetus) whales. In each survey variation was assessed by analysis of class II loci Bchain exon 2 nucleotide sequences. Exon 2 encodes for the peptide binding region of the class II molecules. These sequences were amplified via the polymerase chain reaction, followed by either cloning and DNA sequencing or single-stranded conformation polymorphism analysis.

A low amount of variation was observed at the beluga DQβ locus while a low to moderate amount of variation was observed at the beluga DQβ1 locus and the right whale DQβ loci when compared with terrestrial mammals. Two DRβ loci in beluga and two DQβ loci in right and bowhead whales were detected. Comparison among beluga DQβ, among beluga DRβ1, and among right whale DQβ sequences show, at each locus, a high ratio of nonsynonymous to synonymous substitutions per site. Further, in each case, the majority of substitutions did not maintain the physio-chemical properties of the residue and were found at sites implicated as being important in the selective binding of foreign antigen. This evidence of positive selection is similar to that found at functional Mhc loci and is consistent with the functional significance of Mhc class II loci in the immune response of cetaceans. Comparison of beluga and right whale DQβ sequences shows a reduced rate of synonymous substitutions in cetaceans. This may explain the low to moderate levels of variation found in the order.

No significant differences in Mhc allelic or genotypic frequencies were observed among beluga summering populations which are believed to share a common overwintering area in either the Hudson Strait or the Bering Sea Significant differences (p ≤ 0.0001) were found among sampling locations of the High Arctic/Baffin Bay beluga population. This suggests a recurrent role of Arctic polynyas as overwintering locations for some groups of High Arctic beluga, i.e. beluga sampled from Cunningham Inlet. DRβ1 allele and genotype frequencies were also significantly different (p ≤ 0.0001) among the overwintering locations, Hudson Strait, Bering Sea, Baffin Bay, Cunningham Inlet, and the St. Lawrence. DQβ allele frequencies were only significantly different (p ≤ 0.005) between the High Arctic/Baffin Bay beluga and all other sampling locations.

Comparison of DQβ and DRβ1 allele and genotype frequencies within the St. Lawrence population between dead beached beluga and live biopsy darted whales shows no evidence of a sample collection bias, however, a larger sample size is needed to detect non-trivial small effects. No reduction in the number of DQβ alleles was found in the St. Lawrence beluga population. A slight reduction in the number of DRβ1 alleles was observed (six vs. eight), however, these five alleles each represent one of the five genetically distinct allelic lineages found in beluga This indicates that the evolutionary potential of this population at these class II molecules remains, despite a recent population bottleneck. The effects of the historic bottleneck are observed upon examination of DRβ1-DQβ haplotypes. Evidence for linkage disequilibrium between these loci is noted in the St. Lawrence. Comparison of possible haplotypes shows the St. Lawrence has about half the haplotypes found in Arctic populations. The short term effects of this reduction are unknown and further investigation of Mhc variation within this population is warranted.

abstract: Doctor of Philosophy (PhD)


title: Numerical Analysis of the Behaviour of Fluid Infiltrated Soils

contributor:
Pietruszczak, S.
Civil Engineering

subject:
Civil Engineering
Civil Engineering

abstract:
This thesis deals with numerical modelling of the behaviour of soils infiltrated with fluids. The main objectives are to study the effect of viscosity of the fluid on the response of particulate media under static and dynamic loadings, and to examine the influence of partial saturation on the behaviour under undrained conditions. The latter study is relevant to low as well as high degrees of saturation.

In the formulation incorporating the effect of viscous fluid, the effective stress principle is modified by including the shear stress developed in the fluid phase. As this shear stress depends on the rate of shear strains the overall response is rate dependent. The formulation is implemented in a finite element algorithm and a number of numerical examples, including dynamic creep at low and high stress levels, are provided.

In the next part of this thesis, the liquefaction of saturated soils is investigated. In these studies the effect of viscosity of liquefied material on the stability of the soil-foundation systems under earthquake excitation is examined. Furthermore, the stability theory is reviewed and a simplified stability criterion is introduced. The problems of stability of a strip foundation and a soil column are analyzed.

In the last pan, a mathematical formulation for the behaviour of partially saturated soils is implemented in the finite element algorithm and some boundary-value problems are solved. In order to examine the performance of the constitutive model, a series of experimental tests are carried out. Subsequently, the effect of partial saturation on the stability of soil-foundation systems is examined. The liquefaction phenomenon under earthquake loading is studied for the case of high degrees of saturation, while the bearing capacity of fine grained soils is analyzed for the case of low degrees of saturation.

abstract: Doctor of Philosophy (PhD)


title: The Doping Dependence of the Optical Properties of High-Temperature Super-Conductors

contributor:
Timusk, T.
Physics

subject: Physics Physics

abstract:
The phenomenon of high-temperature superconductivity (HTSC) is one of the most intensively studied ones in the modern condensed matter physics. The initial drive to produce a room-temperature superconductor led to the discovery of completely new physics, that can not be explained by the existing theories. This includes not only the properties of HTSC materials in the superconducting state but in the normal state as well. I fact, much of the current research effort is aimed at the understanding of the unconventional normal-state properties of HTSC materials, in a hope that this understanding will unlock the mystery of the superconductivity phenomenon.

The superconducting transition temperature of a HTSC material can be changed by chemical doping. While at the initial stages of the HTSC research the research effort was focused on the so-called "optimal" doping regime, the one with a highest superconducting transition temperature, recently attention has begun shifting towards the whole doping range.

The work, results of which are presented in this thesis, is aimed at the understanding of the doping dependence of the optical properties of the high-temperature superconducting materials. In particular, we are interested in the infrared energy range since it provides a wealth of information about the low-energy electronic excitations. Mostly the normal-state properties were studied. Several materials studied in this work allowed us to cover the whole metallic doping range of HTSC. The main emphasis of the work presented in this thesis is, however, the "overdoped" regime, where the transition temperature decreases as the material becomes a better metal. This part of the HTSC phase diagram was largely ignored before. We believe therefore, that the new results, presented in this thesis, are an important contribution to the general effort in the field of high-temperature superconductivity research.

abstract: Doctor of Philosophy (PhD)


title: Moment Analyzer: Microprocessor Based

contributor:
Kitai, R.
Electrical Engineering

subject:
Electrical and Electronics
Electrical and Electronics

abstract: A microprocessor based moment analyzer for the measurement of the first four statistical moments of a random or periodic signal has been developed and implemented. The processing circuitry uses the current state-of-the-art semiconductor components to produce an instrument that is cheaper and more compact then all previous implementations. It also provides more flexibility and demonstrates the current design philosophy of employing programmable LSIs as major building blocks. The instrument consists of two custom designed boards and utilizes the microprocessor as well as other facilities in an existing INTEL Prompt 80 microcomputer development system.

abstract: Master of Engineering (ME)


title: SISYPHUS DREAMS - THE PREPOSITIONAL POETICS OF ERIN MOURÉ

contributor:
Coldwell, Joan
English

abstract:
Like many of Canada's contemporary poets, Erin Mouré is concerned with what she calls "both the trap and the way out: worlds/language ("Changes" 43)." What she seeks to resist is the seduction of the comfortable in language which perpetuates the status quo and enables "anaesthesia," the pull of the dominant order with its claims to truth and common sense.

While Mouré has received a great deal of critical attention, no intensive study of her work as a whole has been attempted. This thesis presents an analysis of her poetic practice as it is informed by her understanding of the relationship between language and our social and bodily existence. In both her theoretical and poetic work, Mouré challenges the binary nature of thought and language, proposing a relational system based on the preposition that eludes the emphasis on the primacy of the opposition of "I" and "Other." Michel Foucault's concept of the transgression and Gilles Deleuze's articulation of the "nuptial" provide important models for the discussion of Moure's prepositional poetics, as does Judith Butler's critique of gender discourses based on the concept of an extra-discursive space.

This discussion begins with an analysis of Moure's transgressive strategies that enable her to elude the moment of interpretation and the assignation of 'meaning' to her work. Chapter Two turns to the body/language binary with a critique of the oppositional stances created for the body by discourses that seek to 'recuperate' the body as an emancipated female space. Instead, Mouré's poetic practice suggests a gestalt structure of 'being in the world' that does not depend on an opposition of discursive and bodily experience. In Chapter Three, I will discuss the civic context of the body, what Moure calls "the Polis," and address the notion of the poet as responsible agent. Part of this responsibility involves a critique of the 'comfort' of accessibility, the individual and of authority. Each chapter includes a brief survey of the critical debate and a close reading of the poetry, focussing largely on the later texts, Furious and Sheepish Beauty, Civilian Love.

abstract: Master of Arts (MA)


title: Electrophysiology and transmitter sensitivities of isolated rat petrosal neurons: Synapse formation and hypoxic signaling in co-culture with carotid body chemoreceptors

contributor:
Nurse, Colin A.
Biology

subject: Biology Biology

abstract: The mammalian carotid body (CB), located at the carotid bifurcation, is a peripheral chemosensory organ which senses arterial Po₂, Pco₂ and pH, and controls breathing via reflex responses. Chemoreceptor (glomus) cells in the CB contain various neurotransmitters which are released in response to chemosensory stimuli onto petrosal sensory nerve endings, but the underlying synaptic mechanisms are unclear. In this study, a combination of electrophysiological and pharmacological techniques were used to characterize membrane currents and sensitivity of cultured rat petrosal neurons (PN) to putative CB neurotransmitters. Further, co-cultures of PN and glomus cells were used to test for de novo functional synapse formation, and to elucidate the neurotransmitter mechanisms that mediate hypoxic signaling. Conventional whole-cell and perforated patch recordings revealed that many PN contained, in addition to previously-characterized voltage-gated Na⁺, K⁺, and Ca⁺ currents, a cation non-selective inward rectifier (Ih) which was activated at hyperpolarized membrane potentials, and appears to regulate spike frequency during chemosensory signaling. A subpopulation of PN contained a fast inactivating outward current (I), which also regulates spike frequency in neurons. The membrane properties of PN were largely unaffected by the natural CB stimulus, hypoxia (Po$\sb2$ = $\sim$25 mm Hg). Acetylcholine (ACh), a putative CB neurotransmitter, was excitatory and depolarized $\sim$68% of petrosal neurons (n = 109) via hexamethonium-sensitive, nicotinic ACh receptors (nAChR). 5-HT, another putative CB neurotransmitter, was also excitatory and depolarized $\sim$43% of PN (n = 123), in association with a conductance increase; this response was mediated by MDL72222-sensitive 5-HT$\sb3$ receptors. More than one-half of CB glomus cells (n = 20) were also excited by 5-HT, but in contrast, this response was associated with a conductance decrease, and mediated by 5-HT$\sb2$ receptors. Dopamine depolarized approximately 30% PN (n = 69), but inhibited spike activity triggered by depolarizing stimuli (n = 4). Similarly, GABA also caused depolarization in $\sim$84% of PN (n = 90), but inhibited spike activity via GABA$\rm\sb{A}$ receptors. In co-cultures of dissociated rat PN and CB cells, synaptic-like activity was recorded from some neurons that were juxtaposed to glomus cell clusters. This activity, absent in PN cultured alone (n = 104), was observed in 77 out of 170 co-cultured neurons, and comprised spikes and subthreshold potentials (SSP) that resembled postsynaptic potentials seen at chemical synapses. Moreover, and especially in HCO$\sp-\sb3$/CO$\sb2$-buffered medium, many chemosensory complexes were functional, since a hypoxic stimulus (Po$\sb2$ = $\sim$25 mm Hg) was transduced and relayed (as a depolarization and/or increased spike discharge) to $\sim$30% 'juxtaposed' neurons (n = 140). These spike discharges and SSP were reversibly inhibited by 200 $\mu$M hexamethonium (n = 12), suggesting that functional chemical synapses can develop de novo in co-culture and that ACh is likely an important excitatory neurotansmitter in CB chemoreception. Substance P (SP) increased spontaneous spike activity in co-cultured PN (21/36) via SP NK-1 receptors, and this may be related to its ability to modulate the transient I$\rm\sb{A}$ current in these neurons. Thus, these co-cultures have provided new insights into the synaptic and neurotransmitter mechanisms underlying CB chemoreception during hypoxia.

abstract: Doctor of Philosophy (PhD)