title: Karola Toth

contributor:
Waddington, J.M.
Bourbonniere, R.A.
Geography

subject: carbon, restored peatland, organic carbon, dissolved organic carbon, carbon dynamics

abstract:
ABSTRACT
The effects of restoration on dissolved organic carbon (DOC) dynamics
were examined at the Boi~-des-Bel peatland. This study included both laboratory
measurements of DOC production by different peatland vegetative components
and field measurements of DOC dynamics within a recently restored, a cutover
and a natural peatland.
Shrub and herbaceous plant material were found to be the most significant
producers of DOC in the short term. Moss, peat and straw samples had a high
potential to release DOC ;;ontinuously under warm, moist and aerobic conditions.
On a short timescale, all components have the potential to release the three
dissolved organic matter (DOM) fractions examined with humic acid (HA) most
prominently being produced by shrubs and herbaceous plants and hydrophilic
(HPI) and hydrophobic (HPO) fractions by mosses, peat and straw.
Comparison of growing season results over three study years at the
restored and cutover site indicated that DOC concentrations increased after
restoration while DOC export decreased due to lowered runoff caused by the
blockage of drainage ditches. Compared to the natural peatland, both the restored
and the cutover site had a more humic DOM character. No difference could be
found between the character of DOM released from the restored and cutover sites.
The most active layer of DOM production was the top 75 em where the water
iii
table fluctuated during the season. Water storage units such as pools and ditches
also play an important role in DOM export from the site.
Spring snowmelt was found to be the most significant DOC export event
of the study season in 2001, when export values were significantly larger than
those measured during the growing season. Solubility of the different DOM
fractions was the main controlling factor on the DOM character seen at the
outflows. Storm events contributed significantly to the summer DOC output.
DOC dynamics were affected by antecedent moisture conditions and differences
emerged between the restored and cutover site during this period.
The results of this study emphasize the importance of managing water
table fluctuations and the restoration (reestablishment) of Sphagnum species in
order to improve the retention of DOM within cutover peatlands.

abstract: Thesis

abstract: Master of Science (MS)


title: The Absolute Yields of Xenon and Krypton in U 238 Spontaneous Fission

contributor:
Thode, H. G.
Physics

subject:
absolute yields
xenon
krypton
spontaneous fission

abstract: The absolute abundances of fission-product xenon and krypton isotopes in six uranium minerals were determined mass spectrometrically using the isotope dilution technique. The fission products were resolved into a U spontaneous fission component, a U 235 neutron-induced fission component, and a U 238 neutron-induced fission component. The presence of U 238 of neutron-induced fission indicated that t he neutron energies in uranium minerals were higher than had been suspected. Internal consistency in the analysis was achieved only when the I 29 yield in u235 thermal neutron fission reported by Purkayastha and Martin was lowered by 20%. The number of U 238 spontaneous fissions was calculated from the lead age, U 238 content, and the U 238 pontaneous fission half life. A comparison of the number of fission products from U 238 spontaneous fission and the number of spontaneous fissions in each of the six minerals showed that five of the six minerals had lost large portions of their noble gases. A fractionation of krypton relative to xenon accompanied this loss. The results obtained for the sixth mineral indicated little or no loss of xenon and krypton. Absolute yields for  U 238 spontaneous fission were therefore determined from an analysis of this mineral.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Silver in freshwater and seawater fish: toxicity, bioaccumulation, and physiology

title: Silver in Fish

contributor:
Wood, C.M.
Biology

subject:
silver
fish
freshwater
seawater
bioaccumulation
physiology
toxicity
rainbow trout
freshwater teleosts
seawater teleosts
elasmobranchs

abstract:
Freshwater rainbow trout were exposed to 9.2 µg/L total Ag (as AgNO3, a level approximately equal to the 168 h LC50) for 144 h to clarify the toxic mechanism of silver in freshwater teleosts. It was found that silver inhibits active Na+ and Cl- uptake at the gills, resulting in a net loss of both ions from the fish and creating a metabolic acidosis. This leads to a classic stress response (mobilization of cortisol and glucose into the blood plasma), and hyperventilation as a respiratory response to decreased blood pH. Plasma ammonia levels rise without any decrease in ammonia excretion; ammonia excretion later increases. This suggests that the increased plasma levels are due to increased metabolic production. Increased [H+] (decreased pH) results in excess H+ ions in the internal fluids, which are either complexed with ammonia to form NH4+ or are buffered in muscle tissue. The latter results in increased movement of K+ ions into the plasma, which are then excreted at the gills, preventing hyperkalemia. In the end, freshwater teleosts probably die from iono-and osmo-regulatory failure and associated cardiovascular collapse.
Seawater teleosts (rainbow trout, tidepool sculpins, English sole, and plainfin midshipmen) and elasmobranchs (Pacific spiny dogfish and long nose skate) were exposed to constant concentrations on total Ag (as AgNO3) ranging from 1.5 to 50.0 µg/L for periods of up to 21 d at salinities of 18 ppt or 30 ppt. These exposure levels are well below those causing acute toxicity in seawater. Silver appears to enter marine teleosts and marine elasmobranchs differently. Seawater teleosts drink the seawater, so the intestines are a major site of silver uptake, along with the gills. Since marine elasmobranchs do not drink, the gills appear to be the sole site of silver uptake from the water. As in freshwater, the liver is the main site for silver accumulation in all marine fish studied. Despite similar terminal liver silver concentrations, marine elasmobranchs have a higher rate of silver accumulation since the livers in elasmobranchs are 10-20 fold larger than in teleosts.
Both environmental salinity and exposure concentration play direct roles in determining silver bioaccumulation in marine teleosts. Increasing salinity alters the speciation of silver in the water, which decreases the amount of silver able to enter the fish. Increased silver concentrations mean more silver is available to enter the fish and subsequently cause sublethal toxic effects. Oxygen consumption decreased during the first 7 d of chronic exposure to sublethal silver levels in marine teleosts, with the decrease being more pronounced at higher (still sublethal) silver levels. Ammonia excretion, unaltered during acute exposure (48 h) to high silver levels (250 µg/L), was decreased during the first 7 d of exposure to sublethal silver levels (14.5-50.0 µg/L). This suggests that silver interferes with energy demanding processes such as protein synthesis or iono-regulation. Activity levels of the main enzyme involved in iono-regulation, namely Na+/K+ -ATPase, was affected differently in different fish. In a marine teleost that lives solely in seawater (plainfin midshipmen), silver inhibited the gill ATPase activity after 7 d of exposure, with the inhibition being more effective at higher silver levels. In the tidepool sculpin, a truly euryhaline species, gill ATPase activity increased as the silver levels increased, the latter probably representing a compensatory strategy. Similarly, intestinal ATPase activity was unchanged in the midshipmen, but was increased in the sculpins. Drinking rate in tidepool sculpins, which is involved with both iono-and osmo-regulation, was unaffected by salinity, but was decreased in fish exposed to silver for 8 d.
Overall, Ag is far less toxic in seawater than in freshwater, but the mechanisms of toxicity are similar. In both waters, Ag interferes with iono- and osmo-regulation. In seawater, Ag exhibits a significant potential for bioaccumulation and interference with physiological processes during long term low level exposures of marine fish, especially at lower salinity levels.

abstract: Thesis

abstract: Master of Science (MSc)


title: Radiation induced graft copolymerization in wood

contributor:
Hodgins, J.W.
Chemical Engineering

subject:
radiation
graft copolymerization
wood
styrene
dioxane lignin
spruce periodate lignin
braun's "isolated native lignin"
radical concentration
free radicals

abstract:
1. Investigations of styrene polymerized in wood using ionizing radiation as the chain initiator indicate that property improvements are of the same order as for thermally initiated polymerization.
2. Free radicals have been detected in irradiated cellulose, Dioxane lignin, Spruce Periodate lignin and Beaun’s “Isolated Native Lignin” as well as in wood subjected to radiation. Consequently, wood radical identification is not possible.
3. Analysis of radical concentrations and decay suggest the presence of one or more decaying radical species in irradiated wood. The persistent maximum in radical concentration found corresponds to one or two unique radical sites per molecule; possibly the terminal hydroxyl group.
4. Results suggest that in the grafting reaction the initiation is a direct radical-monomer couple and does not involve decomposing peroxides.

abstract: Thesis

abstract: Master of Engineering (ME)


title: Fission Yield Studies and Closed Shell Effects in Atomic Nuclei

contributor:
Thode, H.G.
Physics

subject: Atomic nuclei, atomic, closed shell effects, fission yield studies, closed shell effects in atomic nuclei

abstract: The relative fission yields of the isotopes of krypton and xenon have been determined mass spectrometrically. Abnormal fission yields, resulting in fine structure in the mass fission yield curve, have been found in both mass ranges. A shift of the fine structure to lower masses has been observed in going from U^235 + n fission to U^238 + n fission. From this shift in fine structure, it has been possible to determine the proportion of U^235 and U^236 neutron fission that have occurred in the sample. Evidence is presented to show that the observed fine structure and the shift in this fine structure is the result of a combination of two effects involved the extra stability of closed neutron shells of 50 and 82 neutrons which fall in the Kr and Xe ranges respectively.                                                                                The capture of thermal neutrons by Xe^135, which modifies the fission yields in the 135 and 136 mass chains, has been studied so that the observed fission yields at these masses may be suitably corrected.                                                                                Finally, the branching ratio between the isomeric states of Kr^85 and the half-life of the long-lived isomer have been re-determined and found to be 0.29 and 10.27 ± 0.18 yrs. respectively.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: The neural basis of movement perception

contributor:
Heron, W.
Psychology

subject:
movement
perception
neural
neurology
striate cortex
velocity
direction of movement
apparent-movement

abstract: An investigation of the neurological basis of movement was carried out by studying the responses of single cells in the striate cortex of the unanesthetized cat. Three aspects of movement perception were studied: velocity, direction of movement, and apparent-movement. It was found that the relation between velocity of movement and rate of cell discharge was a power function, that the idea that cells respond to one direction of movement is true only in a statistical sense, and that the cortical mechanisms for real movement probably differ from those for apparent-movement. Several developments in methodology are also described.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Invertebrate Diversity: An Individualized Programme for Life Science

title: Invertebrate diversity: An individualized programme

title: Invertebrate diversity

contributor:
Humphreys, D.A.
Rollo, C.D.
Biology

subject:
invertebrate
diversity
life science
Hall-Dennis report
education
Ministry of Education Guidelines
grade nine
grade ten
science programmes
Personalized System of Instruction
self-paced learning

abstract:
Educational changes in Ontario, initiated by the Hall-Dennis Report, resulted in a public perception of declining educational standards in the 1970's. Ministry of Education Guidelines, which were implemented in an attempt to remedy this, created a major disruption in our grade nine and ten science programmes.
The grade ten Life Science course had become fragmented and the classes polarized between bright and slow students. Traditional teaching methods were no longer functioning well and, as a result, students were poorly motivated.
In this project, the Life Science curriculum is restructured to improve continuity of subject matter and student motivation. The major innovation is an individualized unit on invertebrate diversity. This modular unit is designed for self-paced mastery learning. The six modules of this unit are based on the Personalized System of Instruction (P.S.I.). Optional activities are incorporated into each module to challenge and motivate industrious students.
The means of evaluation of the new curriculum unit are outlined and various criteria for the success of the project are specified.

abstract: Master's of Science in Teaching (MST)


title: Dietary uptake of copper in freshwater rainbow trout (Oncorhynchus mykiss): A study of mechanisms

title: Dietary uptake of copper in rainbow trout: A study of mechanisms

subject:
diet
copper
freshwater
rainbow trout
Oncorhynchus mykiss
mechanisms
bioaccumulation
toxicity
stomach
anterior intestine

abstract:
In aquatic environments Cu is both a vital nutrient and an important toxicant. Consequently fish require Cu as a micronutrient and can obtain this metal from either water or their diet. Inadequate intake of Cu is associated with reduced growth and development, while decreased growth rates, mortality and reduced swimming capacity have been reported in fish when Cu accumulates in excess of cellular needs. Characterization of Cu uptake is therefore critical in understanding the dynamics that govern toxicity and the risks associated with exposure to an aquatic contaminant. While mechanisms of waterborne uptake and toxicity are well understood, far less is known about gastrointestinal Cu uptake in fish. In vivo and in vitro techniques were therefore used in this study to investigate dietary Cu uptake in freshwater rainbow trout.
The mid and posterior regions of the intestine emerged as important sites for Cu absorption in trout, while the role of the stomach and anterior intestine in Cu absorption requires further investigation. The intestinal uptake route was kinetically characterized as a low affinity absorption pathway as compared to the branchial route. Cu uptake appeared to occur via a hypoxia-resistant, carrier-mediated, saturable process which could be fueled by Cu(II)^2+ at concentrations typically found in the fluid phase of chyme in the trout intestine.
Experimental manipulation of mucosal NaCl levels stimulated Cu uptake, Na2SO4 had an identical effect, implicating Na rather than the anion. These responses were unrelated to solvent drag, osmotic pressure or changes in TEP. The presence of excess luminal Ag and L-histidine stimulated Cu and Na uptake indicating that a portion of Cu transport was mediated by a Na-Cu co-transport system. Partial inhibition of Cu and Na uptake by phenamil and hypercapnia stimulated Na and Cu transport suggest Cu entry could also occur via the apical Na channel. The Na-dependent mechanism thus either involves more than one component or a unique Na-Cu co-transport mechanism with these combined characteristics mediates part of Cu uptake.
Cu uptake was sensitive to pH and competed by Fe and Zn implicating DMT1 in the transport of Cu in the trout intestine. These factors had no effect on Na uptake, leading to the identification of a Na-independent mechanism for Cu uptake in the trout intestine. While the Na dependent nature of Cu uptake and Ag stimulated Cu transport argue against a role for Ctrl in this process, Cu transport characteristics identified in this study compare well with a recently identified Cu transporter in Ctr1 deficient mouse embryonic cells, indicating the existence of a similar transport mechanism in the trout intestine.

abstract: Thesis

abstract: Master of Science (MSc)


title: A mechanistic approach to acute lead toxicity in the rainbow trout: Investigations of lead-induced ionoregulatory disruption

title: Lead-induced ionoregulatory disruption in the rainbow trout

subject:
acute lead toxicity
rainbow trout
ionoregulation
biotic ligand model
Michaelis-menten kinetics

abstract:
Relative to other metals, little is known about lead toxicity in fish. The use of predictive models such as the biotic ligand model (BLM) has been limited, a situation that is at least partially due to the lack of understanding of lead's acute toxic mechanism and characterization of key binding sites involved in this toxicity.
Using the rainbow trout as a model species, the acute toxic mechanism for lead was found to be ionoregulatory disruption. While having no apparent respiratory or acid/base effects, Pb exposure resulted in significant ionoregulatory impacts that affected Ca2+ homeostasis, as well as Na+ and Cl- balance.
Active Ca2+ uptake by the gills obeyed typical Michaelis-Menten kinetics, and Pb interacted in a competitive fashion with the uptake process. Exposure to increasing waterborne Pb concentrations resulted in significant increases in Km value while Jmax showed little or no change. A slower, non-competitive interaction occurred after prolonged Pb-exposure, evidenced by a significant reduction of high-affinity Ca2+ -ATPase activity that correlated well with branchial Pb accumulation. Conversely, calcium had a protective effect against branchial Pb accumulation, this relationship being predominately competitive in nature. Voltage-independent calcium channel blockers La3+, Cd, and Zn significantly reduced gill Pb burden while the voltage-dependent, L-type calcium channel blockers, nifedipine and verapamil, did not, suggesting Pb enters fish by a similar mechanism to that of Ca2+. Stimulated stanniocalcin release by CaCl2 injection also significantly reduced branchial Pb accumulation.
Based on the evidence presented in this thesis, it is apparent that acute Pb toxicity occurs by ionoregulatory disruption. It is likely that Pb shares a similar uptake pathway as that for Ca2+ and that resulting accumulation results in disruption of Ca2+ influx as well as Na+ and Cl- balance. This study has provided data essential to the characterization of key binding sites involved in Pb toxicity, and ultimately, validates the development and application of predictive models such as the BLM.

abstract: Thesis

abstract: Master of Science (MSc)


title: A genetic analysis of the eastern timber wolf

contributor:
White, Bradley N.
Biology

subject:
genetic analysis
eastern timber wolf
Algonquin Provincial Park
red wolf
Canis rufus
Canis lycaon
Pukaskwa National Park
Frontenac Axis

abstract:
While studying packs of the eastern timber wolf in Algonquin Provincial Park in Ontario, DNA profiles at 8 microsatellite loci and the mitochondrial control region were found to be similar to those of the red wolf, C. rufus. Based on this it was suggested that both the red wolf and the eastern timber wolf have a common origin, evolving in North America, with the coyote diverging from them 150,000-300,000 years ago and with neither having any recent connection with the gray wolf that evolved in Eurasia. It was further proposed, that the eastern timber wolf retain its original species designation of C. lycaon instead of the present status of a subspecies of the gray wolf.
Four "types" or "races" of wolves have been previously described in Ontario. Using DNA profiles, assignment tests identified four groups, which were typified by animals in Algonquin Provincial Park, Pukaskwa National Park, Frontenac Axis and those north of Lake Superior. The tests indicate that Frontenac animals are hybrids between the western coyote and C. lycaon and represent the eastern coyote. Pukaskwa maintains a small wolf population, which is genetically closer to the gray wolves of the Northwest Territories than the surrounding C. lycaon. These may represent an isolated remnant population of the original "Ontario type" (C. lupus). Animals north of Lake Superior were identified as C. lycaon, but represent products of hybridization between C. lycaon and C. lupus.
Currently within Ontario, Algonquin Park contains the largest protected area of the eastern timber wolf. DNA profiles, including Y-linked microsatellite loci were used to establish maternity, paternity and kin relationships for 102 animals from 24 packs over a 12-year period. A complex pack structure was identified. A pack is not composed simply of an unrelated breeding pair and their offspring and subordinates appear to enter pack systems through adoption, pack splitting, dispersal and immigration. Relatively high genetic structuring was found between the Park animals and the "Tweed" wolves to the southeast suggesting introgression of coyote genetic material is not a present concern to the integrity of park animals. Evidence of gene flow with animals to the west, northeast and northwest coupled with the high genetic diversity, suggest that the Park animals are not an island population, but the southern part of a larger metapopulation of C. lycaon.
Increased interest in the relationship of the red and eastern wolves led to the investigation of a gene in the major histocompatibility complex. Allelic variation in the exon 2 region of the DLA-DQA1 locus was analysed for gray wolves, red wolves, the eastern timber wolf and the western coyote. Twelve alleles were identified, seven of which were previously characterized in dogs. Non-synonomous nucleotide substitutions was 3.0 times higher than the synonomous changes, indicative of strong positive selection. These data provide baselines for the determination of allele frequencies and their distribution across the geographical range of the four species in North America.
The results in this thesis have sparked numerous debates with respect to the protection of the wolves in Algonquin Provincial Park and reintroduction of wolves into Northeastern United States. The data support the idea that the C. lycaon population in Ontario is relatively large, numbering in the thousands rather than the hundreds. Concern for the conservation of wolves in Ontario should be directed at the declining numbers of gray wolves present in Ontario.

abstract: Thesis

abstract: Master of Science (MSc)


title: Simulation of the Equilibrium Operation of a Candu Reactor and Studies of the Collapsing Procedure in the Fuel Management Design Program

contributor:
Trojan, O. A.
Engineering Physics

subject:
equilibrium operation
collapsing procedure
fuel management
design program
simulation
CANDU reactor

abstract: Estimates of fuel management data for the equilibrium operation of a specific CANDU reactor have been obtained by simulating a period of the reactor's history using the Fuel Management Design Program (FMDP). The collapsing procedure in FMDP has been tested and improved. This procedure prepares a coarse mesh model of the reactor core from a detailed fine mesh calculation. The program calculates a set of coarse mesh parameters which, when used in the flux calculation, will regenerate exactly the same eigenvalue and flux distribution as the fine mesh model. These parameters can then be used with the coarse mesh, to calculate flux distributions for a series of perturbations from the reference calculation used in collapsing. Several coarse mesh models were generated and studied. It was found that coarse mesh calculations with collapsed parameters result in large savings in computing costs compared to the same calculations with fine mesh, but with very little loss in accuracy.

abstract: Thesis

abstract: Master of Engineering (ME)


title: The Fatigue Behavior of Dispersion Strengthened Nickel

contributor:
Ham, R. K.
Metallurgy

subject:
fatigue behavior
dispersion
strengthened nickel
nickel

abstract: Fatigue and dispersion strengthening are reviewed generally. Experiments are described in which thin film transmission electron microscopy, as well as optical and electron fractography were employed to elucidate the mechanism of fatigue failure in dispersion strengthened nickel. It was found that whereas fatigue crack initiation occurs as in conventional materials, the propagation of both fatigue and tensile cracks is abnormal. The material fails in shear wherever possible although this is prevented where triaxial tensile stresses exist. Particle-matrix detachment does not occur during either tensile or fatigue stressing.

abstract: Thesis

abstract: Master of Science (MS)


title: The Role of Stress Proteins in Cellular Resistance to Photodynamic Therapy in Bladder Cancer T24 Cells and Colon Cancer HT29 Cells

contributor:
Singh, G.
Biology

subject:
stress protein
cellular resistance
cellular
stress
photodynamic therapy
bladder cancer
cancer
colon cancer
bladder cancer T24 cells
colon cancer HT29 cells

abstract: As Photodynamic Therapy (PDT) becomes increasingly popular as a treatment modality for some solid tumours, the need for a better understanding of the mechanism(s) of action and resistance are paramount. To this end we have generated Photofrin® PDT-induced resistant variants to numerous cell lines including the colon cancer cell line HT29. There is significant evidence indicating that stress proteins play an important role in determining the outcome of PDT on a cell. In this thesis the roles of the mitochondrial Heat Shock Protein 60 (Hsp60) as well as the endoplasmic Glucose Related Protein 78 (GRP78) were examined in the HT29 cells and their Photofrin induced resistant variant HT29-P14. The expression and role of these two stress proteins were also examined in T24 Bladder carcinoma cells and their GRP 78 stable-overexpressing clones Hsp60 protein was expressed at slightly higher basal levels in the resistant HT29-P14 cells relative to the parental HT29 cells. After incubation alone or PDT action, a temporal and dose dependent induction of Hsp60 was observed and this too was found to be significantly greater in the resistant cells. In the T24 model, no Hsp60 induction was observed following drug incubation or PDT. GRP78 protein levels were increased by PDT action but not by Photofrin® incubation alone in all cell lines tested. In the T24 model, GRP78 transfection resulted in a stable 2-fold increase in protein levels and a 10-20-fold increase in cell survival after PDT at the highest dose tested. A temporal and dose dependent response was noted in all cells and induction of GRP78 protein was lower in the stable overexpresser such that all cell lines had similar post induction levels. In the HT29 and HT29-P14 resistant cells, GRP78 protein levels were similar at basal level, and, both cell lines exhibited the same temporal and dose dependent increases in expression post PDT. Finally, broad scale expression profiling using a "stress" microarray in the HT29 and HT29-P14 resistant variants revealed a very similar expression profile for the 168 of the 169 stress proteins tested with the exception of the small Heat Shock Protein 27 (Hsp27). As confirmed by northern and western blot analysis, Hsp27 is over 20 fold greater at the transcriptional level and 10-15 fold greater at the translational level in the HT29-P14 resistant variant. These findings implicate Hsp27, Hsp60 and GRP78 as possible mediators of cellular sensitivity to Photofrin-mediated PDT. Specifically, Hsp27 appears to play a role in the increased resistance of our induced resistant HT29-P14 cells.

abstract: Thesis

abstract: Master of Science (MS)


title: Health Practices and the Paleo Diet: Understanding Healthy Eating from Paleo Adopters' Perspectives

contributor:
Gillett, James
Sociology

subject:
Health Practices
Healthy Eating
Food
Diet
Paleo Diet
Symbolic Interaction
Qualitative

abstract:
In the context of expanding public concern about the healthfulness of food, this thesis examines how health is understood and taken up in individuals’ everyday activities of eating. Sociological frameworks emphasize the complex relations shaping health practices in context; however, a greater focus on the structured nature of practice has weakened appreciation of the agent. Food scholars investigating choice and constructions of healthy food and eating categories, highlight processes involving meaning, experience, action, and identity, at work in contexts of healthy eating. To better locate the agent of health practices, and to connect a health practices approach to healthy eating scholarship, this study draws on theory and methods from the symbolic interactionist tradition in an analysis of lived experiences of healthy eating. Using ethnographic data, including qualitative interviews with 18 adopters of the Paleo Diet, and analysis techniques from grounded theory, this study aims to add nuance to current sociological understandings of health practices. Findings reveal that subjective understandings of the relationship between food and health evolve through interpretive processes involving meaning. By connecting cultural understandings of health to personal, embodied experiences, adopters achieve multilayered understandings of healthy eating that legitimate and catalyze their commitment to their diet. Facing challenges to achieving a Paleo diet, adopters, as agents, engage in material and symbolic work to create “doable” and “livable” versions of Paleo better aligned with resources, preferences, and understandings. Adopters also construct and work to maintain valued identities surrounding their practice; however, Paleo identities are spoiled identities, as adopters sought to manage conflicting expectations of what constitutes healthy eating, and impressions of who eats a Paleo diet.
This thesis demonstrates how an interactionist perspective that appreciates the processual, subjective, and interactional elements of agents’ situated and contextual practices, can be usefully brought in to investigate and inform understandings of activities affecting health.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Diffraction of Microwaves Along the Axis of Propagation Behind Conducting and Dielectric Rods and A Plastic Prism

title: Diffraction of Microwaves

contributor:
McLay, A.B.
Physics

subject: Diffraction, Microwaves, Axis of propagation, dielectric rods, plastic prism, diffraction of microwaves

abstract: Scope and Contents: The first chapter of this thesis consists of a general introduction and a brief description of previous work done in this same laboratory. Also included is a preliminary description of the present experiment. This is followed, in Chapter 2, by a detailed description of the experimental apparatus. The third and last chapter contains a description of the procedure used in obtaining results, as well as the results themselves. Measurements were made of the diffraction patterns of a plastic prism, and five rods in a total of nine different cases. In all cases, the intensity measurements were made along the axis of propagation of the incident beam behind the diffracting object. A polarization normal to the axis of the rods was used. Theoretical calculations were made in three cases, and compared with the experimental results.

abstract: Thesis

abstract: Master of Science (MS)


title: Studies on the Molecular Nature of Keratinocyte-Derived Interleukin-1

title: The Molecular Nature of Keratinocyte-Derived Interleukin-1

contributor:
Harley, C. B.
Biochemistry

subject:
molecular nature
keratinocyte-derived
interleukin-1
molecular

abstract:
Interleukin-1 (IL-1), originally defined as a product of activated macrophages, has since been found to be produced by many cell types including keratinocytes. The nature of this IL-1 activity in keratinocytes, originally known as epidermal cell-derived thymocyte activating factor (ETAF) has been the subject of many studies. In the
course of this work it was found that the human keratinocyte cell line COLO 16 contains mRNA homologous to human monocyte-derived IL-1B. A 1.2 kbp cDNA was selected with a human IL-B probe from a lgt11 library constructed from COLO 16 mRNA. Sequence analysis revealed that this eDNA was nearly identical to the 3' 1.2 kb of human monocyte IL-1B. In addition, a partial cDNA (F8) was isolated from COLO 16 cells which has a distinct sequence from either IL-1a or B. There is evidence to suggest that the F8 message may be derived from differential splicing of a region of the human genome which also gives rise to the cGMP-gated ion channel in rod photoreceptor cells. The F8 cDNA hybridized on Northern blots of COLO 16 mRNA to a 1.6 kb message of low abundance. Antisera generated against a synthetic peptide based on inferred protein sequence from the cDNA reacted with a 20 and 30 kDa species in both COLO 16 cells and PMA-stimulated normal human keratinocytes. Expression of
the partial cDNA in COS-1 cells resulted in activity in the thymocyte co-stimulation and D10.G4.1 T-cell stimulation assays, suggesting that ETAF activity may be due to a combination of IL-1 and F8.

abstract: Thesis

abstract: Master of Science (MS)


title: Functional Studies of the Novel Nuclear Hormone Receptor LXR-alpha

contributor:
Capone, John P.
Biochemistry

subject:
functional study
novel nuclear hormone receptor
LXR-a

abstract:
The regulation of gene expression at the transcriptional level is one of the paramount
mechanisms for maintaining control of growth, development and metabolic homeostasis.
The Liver X Receptor (LXRa) is a novel member of the nuclear hormone receptor
superfamily of transcription factors, which was originally isolated in our laboratory.
Subsequent studies have revealed that LXRa is an essential transcriptional regulator of
cholesterol homeostasis and a number of potent LXRa activators, including the oxysterol
22(R)-hydroxycholesterol have also been identified. As other members of the
superfamily, LXRa exerts its regulatory control of target genes directly by binding to
LXRa-responsive enhancer elements (LXREs), located upstream of the target gene
promoter. Our laboratory initially demonstrated that LXRa heterodimerizes with the
Retinoid X Receptor (RXRa) and cooperatively binds to a synthetic LXRE (DR4-
LXRE), which consists of direct repeats of the hexad core consensus sequence spaced by
four nucleotides. Tc date, two naturally occurring LXREs have been identified,
including the LXRE--L\MTV element, located in the promoter region of the mouse
mammary tumor vims long terminal repeat and the CYP7 A-LXRE element, located in
the proximal promoter region of the rat cholesterol a-hydroxylase gene.
In order to delineate the mechanism by which LXRa mediates the transcriptional
regulation of target genes, a series of highly integrated characterization studies were
initiated. Our initial interest was identifying the transactivation properties ofLXRa.
Thus, a series of tramient transfection studies were performed, which investigated the
effect of various LXREs, ligands/activators and cell lines on LXRa.-mediated
transactivation. Ultimately, these studies revealed that the LXRa.-mediated
transcriptional response was highly varied and specifically dependent upon the response
element, ligand and cell line employed. Thus, these investigations indicate the specificity
and great diversity in the nuclear hormone receptor-mediated transcriptional regulation of
target genes. Furthermore, these studies resulted in the establishment of a viable and
efficient transient transfection assay for further LXRa. in vivo investigations.
Nuclear hormone receptors, including LXRa., are comprised of several modular
domains termed AlB, C, D and E. A number of recent studies have implicated the highly
divergent AlB domain of variety of nuclear receptors, and their isoforms, as a participant
in transactivation. Specifically, these nuclear receptors have been shown to posses,
within their respective AlB domains, an autonomous ligand-independent transactivation
function termed the AF-1 domain, which can either function independently or can
synergize with the E domain of the same receptor. Thus, determination of whether or not
the 97 amino acid AI B domain of LXRa. participated in LXRa.-mediated transactivation
became a main focus; in our investigation of LXRa.. In vitro EMSA analysis revealed
that deletion of up to 63 amino acids of the N-terminal region of the LXRa. AlB domain
did not effect either LXRa./ RXR.a. heterodimerization nor cooperative binding to
LXREs. In vivo transient transfection assays further illustrated that theN-terminal 63
amino acids of the LXR.a. AlB domain were dispensable for LXR.a./RXR.a.-mediated
transactivation. Therefore, as determined by the limitations of these assays, theNIV
terminal63 amino acids of the LXRa AlB domain do not participate in neither
transactivation nor heterodimerization and subsequent binding to LXR.Es.
Transcriptional regulation, mediated by members of the nuclear hormone receptor
superfamily, has been shown to involve multiple auxiliary co-factors, which modulate
receptor-mediated tnmsactivation. These co-factors can either serve to repress (corepressors)
or activate (co-activators) transcription not only through blocking or
facilitating interactio r1s, respectively, between receptors and the basal transcription
machinery but also through chromatin remodeling. Thus, the identification of LXRainteracting
co-facton and the subsequent investigation of their ability to modulate LXRamediated
transactiva1ion, were of particular interest. We demonstrated, via utilization of
in vitro GST-binding assays, that LXRa interacts with RIP 140, SRC-1a and SMRT cofactors
in a ligand-independent manner. Furthermore, these studies illustrate that the
LXRa AF-2 core domain is necessary for efficient RIP 140 and SRC-1a binding.
Surprisingly, this domain appears to impede, although not absolutely, the SMRTILXRa
interaction, which has also been observed for the Retinoic Acid Receptor (RAR)/SMRT
interaction. Functional studies ofLXRa, RXRa and RIP 140 indicate that RIP 140
antagonizes LXRa/RXR.a-mediated transactivation, which suggests that RIP 140 may
serve to attenuate the transcriptional response of nuclear receptors modulated by other,
more potent co-activators, as previously suggested in Peroxisome Proliferator-activated
receptor a (PPARa);RIP 140 studies. As well, it is apparent that neither'the RIP
140/LXRa interaction nor the RIP 140-mediated repression of LXRa activity is effected
upon deletion of the N-terminal 63 amino acids of the LXR.a. AlB domain. Interestingly,
functional studies of LXR.a., RXR.a. and the partial SRC-1a clone, which lacks the Nterminal
PAS-bHLH domain, indicate that this SRC-1a clone antagonized LXR.a.IRXR.a.mediated
transactivation. While this result may simply demonstrate the necessity for a
full length SRC-1a clone it may also indicate SRC-1 isoform-specific differences as
previously illustrated in Estrogen Receptor (ER)/SRC-1 studies. Lastly, preliminary
functional studies of LXR.a., RXR.a. and S:MR.T indicate that S:MR.T has no significant
effect on LXR.a./RXR-mediated transactivation. These tentative results indicate that
while LXR.a. and SMRT interaction in solution, S:MR.T may not be able to interact with
LXR.a. when bound to DNA, and is thus unable to modulate LXR.a.-mediated
transcriptional activation as previously demonstrated for the PP ARy and the orphan
receptor Rev Erb. Taken together, the investigations presented in this study of LXR.a., further our understanding of not only the mechanism by which LXR.a. mediates its transcriptional
response, but also hew nuclear receptors achieve specificity and diversity in the
activation of target gene expression.

abstract: Thesis

abstract: Master of Science (MS)


title: The Effects of Amino Acids and Mitogen Activated Protein Kinase (MAPK) Inhibitors on Fluid Secretion and Ion Transport by Isolated Malpighian Tubules of Rhodnius Prolixus and Drosophila Melanogaster

contributor:
O'Donnell, M.J.
Biology

subject:
amino acids
mitogen
kinase (mapk) inhibitors
fluid secretion
ion transport
isolated malpighian tubules
rhondnius prolixus
drosophila melanogaster

abstract:
Insect haemolynph typically contains very high levels of free amino acids 50 1 00 times that which is normal for mammalian plasma. This study examines the modulatory effects of amino acids on fluid secretion and ion transport by isolated MTs of Rhodnius prolixus and Drosophila melanogaster.
The results show that the secretion rates of isolated Malpighian tubules of both Rhodnius and Drosophila are modulated by the presence of specific amino acids in the bathing saline. Some amino acids are stimulatory, some are inhibitory and others have little or no effect. Glutamine appears to be particularly important as a stimulant of fluid secretion. As well, secreted fluid pH and Na +concentration increase and K+ concentration decreases in response to glutamine. Amino acids do not appear to be important as metabolite. in Rhodnius tubules, nor do they act to draw significant amounts of water into the lumen by osmosis. Significant stimulation of fluid secretion can be achieved by physiological levels of particular amino acids, whereas those amino acids that inhibit fluid secretion only do so at concentrations much above those at which they occur naturally in the haemolymph. Amino acids are known to be compatible osmolytes and may be acting to maintain cell homeostasis and thus to sustain fluid secretion. The passive movement of amino acids may result in cell volume changes, and some form of osmosensor is may be coupled to activation of specific kinases to produce the observed increases in fluid secretion. The effects of several kinase inhibitors were therefore examined.
The glutamine dependent increase in MT fluid secretion is blocked by two inhibitors of the stress activated protein kinase (SAPK) pathway, SP600125 and dicumoral. Inhibitors of other kinases (PKA, PKC, PKG, PI-3, p38, ERK and MEK), did not block glutamine's effects on fluid secretion rate. Alterations in cytoskeletal structure appear not to be required because cytoskeletal disrupting agents did not block the glutamine dependent inc~ease in fluid secretion, nor was the increase dependent upon protein synthesis. Results of this study are the first to suggest a role for the SAPK pathway in the control of fluid secretion rates by insect Malpighian tubules.

abstract: Thesis

abstract: Master of Science (MS)


title: Effects of Short-Term Lower Limb Immobilization on Skeleton Muscle Function and Morphology in Men and Women

contributor:
Tarnopolsky, Dr. Mark A.
Kinesiology

subject:
lower limb immobilization
skeletal muscle function
morphology

abstract:
The purpose of this study was to determine the effects of short-term (14d) unilateral leg immobilization using a simple knee brace (60° flexion)/crutchmediated model on muscle function and morphology in men (M, N=13) and women (W, N=14). Isometric and isokinetic (concentric SLOW, 0.52 rad•s-1 and FAST, 5.24 rad•s-1) knee extensor peak torque was determined at three time points (PRE, DAY -2, and DAY -14). At the same time points, magnetic resonance imaging was used to measure the cross-sectional area of the quadriceps femoris and DEXA scanning was used to calculate leg lean mass. Muscle biopsies were taken from vastus lateralis at PRE and DAY-14 for myosin ATPase and myosin heavy chain analysh Women showed greater decreases (PRE vs. DAY-14) compared to men in specific strength (N•cm-2) for isometric (M=3.1±13.3, W=17.1±15.9%; p= 0.055, [mean±SD]) and concentric SLOW (M=4.7±11.3, W=16.6±18.4%; p<0.05) contractions. There were no immobilization-induced sex-specific differences in the decrease in quadriceps femoris cross-sectional area (M=5.7±5.0, W=5.9±:5.2%) or leg lean mass (M=3.7±4.2, W=2.7±2.8%). There were no fiber type transformations, and the decrease in Type I (M=4.8±5.0, W=5.9±3.4%), IIa (M=7.9±9.9, W=8.8±8.0%) and Ilx (M=10.7±10.8, W=10.8±12.1 %) fiber areas was similar between sexes. These findings indicate that immobilization-indt: ced loss of knee extensor muscle strength is greater in women compared tc men in spite of a similar extent of atrophy at the myofiber and whole muscle levels after only 14d of unilateral leg immobilization. Furthermore, we have described an effective and safe method of knee
immobilization that results in significant reductions in quadriceps muscle strength and fiber size.

abstract: Thesis

abstract: Master of Science (MS)


title: Verbal-Motor Behaviour in Adults With and Without Down Syndrome

contributor:
Elliott, Digby
Human Biodynamics

subject:
verbal-motor
down syndrome

abstract: Previous research has indicated found that individuals with Down syndrome (DS) have difficulties in processing auditory information for the planning of movements relative to their peers with undifferentiated developmental handicaps. This modality-specific information-processing difficulty has been found for the preprogramming of goal-directed aiming movements (Le Clair & Elliott, 1995) and in simple reaction times (Davis, Sparrow, & Ward, 1991; Hermelin, 1964). The purpose of the present study was to assess whether or not a model of atypical cerebral specialization for the perception of speech sounds, proposed by Elliott and colleagues, could explain these findings. Thus, participants performed a choice reaction aiming task under three conditions. Colour-coded targets were cued by a visual cue at the target location, a visual cue remote from the target location, or a verbal cue identifying the target. Results revealed that while the reaction times did nCit differ between the two groups with handicaps, the participants with DS, unlike the two control groups, had significantly longer movement times in the verbal than in two visual conditions. These results support the model of biological dissociation.

abstract: Thesis

abstract: Master of Science (MS)


title: On The Decay of Br82

contributor:
Kennett, Dr. T. J.
Physics

subject: br82

subject: decay

abstract: Single-crystal, pair, and two-dimensional spectrometry methods have been applied to a study of the decay radiations from 36-hour br82. Two new gamma rays have been discovered and a new energy level in Kr82 has been established. Double and triple gamma summing is discussed. Also regression analysis techniques for coincidence data analysis have been studied. This has been applied to the case of Br82 to derive gamma ray intensities.

abstract: Thesis

abstract: Master of Science (MS)


title: Phosphoenolpyruvate Carboxykinase (PCK) Gene Regulation in Sinorhizobium Meliloti

title: PCK Gene Regulation in S. Meliloti

contributor:
Finan, T. M.
Biology

subject:
phosphoenolpyruvate carboxykinase
gene regulation
sinorhizobium meliloti

abstract: Phosphoenolpyruvate carboxykinase (Pck) catalyzes the first step of gluconeogenesis, and the gene which encodes this enzyme (pckA) is transcriptionally regulated. High pckA expression is observed in succinate-grown cells, while little expression is observed in glucose-grown cells. pckA regulatory mutants have previously been isolated (Osteras et al. 1997) and pckR, a gene encoding a Lacl-GaIR DNA-binding transcriptional regulator, has been implicated in the regulation of pckA transcription. Here we shew that pckR insertion mutations result in a dramatic decrease in pckA expression even in succinate-grown cells. We demonstrate that the previously identified rpk-9 mutation is tightly linked to pckR. The rpk-9 mutation results in constitutive pckA expression, and we show that plasmids carrying the pckR gene complement the rpk-9 mutation in glucose-grown cells. A putative Lacl-GaIR operator binding site has been identified in the pckA promoter, however no evidence of an interaction between this site and the pckR gene product could be found.

abstract: Thesis

abstract: Master of Science (MS)


title: Stress Corrosion Cracking of Bioglass^TM

contributor:
Nicholson, P. S.
Engineering

subject:
stress corrosion
bioglass

abstract: The objective of this study was to investigate the stress corrosion behaviour of BioglassTM 4555 in order to predict the lifetime of the glass in use as a load-bearing prosthetic device. As part of this study, the development of BioglassTM and the medical tests conducted to assess the glass's biocompatibility are reviewed. The results of implant tests in laboratory animals which indicate that stress corrosion cracking of the glass may be a prohibitive factor to its use are presented. The theories of glass corrosion and stress corrosion cracking of silica based glasses are discussed and an extensive review of the literature presented. The corrosion behaviour of the glass was analysed and found to be similar to that obtained by previous workers. The depths of the corrosion layers were found to be smaller. This was attributed to alumina contamination of the glass. The fatigue parameters of the glass were measured by slow crack-growth studies and strength measurements in a corrosive solution simulating the physiological environment. The values of A and n in the equation relating crack velocity (v) and stress intensity (K1) v=AK1n, were found to be 1x10-173 and 30 respectively. Lifetime predictions for the glass were performed. It was determined that the glass was suitable for use as a prosthetic device if the maximum tensile stress encountered in vivo did not exceed 15MPa.

abstract: Thesis

abstract: Master of Engineering (ME)


title: Development of an in vivo DNA Cloning Procedure for Bacteria

subject:
development
in vivo
DNA Cloning
DNA Cloning Procedure
bacteria

abstract: In this thesis, we describe the development of a method to delete and to clone specific large regions from the 1700 kilobase pExo megaplasmid of Rhizobium meliloti. In principal, the region to be cloned is flanked by FRT sites, which direct site specific recombination by the Flp recombinase. Targeting constructs were designed to include part of the IS50 from Tn5, the FRT site, an origin of transfer (oriT), and a replication origin from RK2 or the F plasmid. These constructs were directed to known Tn5-derivative insertion sites in the pExo megaplasmid. A plasmid which expresses the Flp recombinase constitutively in R. meliloti was made, and the transfer of this plasmid to FRT-flanked megaplasmid regions was shown to result in the deletion of the intervening DNA. We demonstrated that the pExo megaplasmid DNA regions could be captured in Escherichia coli, however in this case, the megaplasmid excision event appears to be directed by the oriT sites rather than the FRT sites. We present strong evidence that a specific 50 kb region contains the oriV of the pExo megaplasmid; R. meliloti strains deleted for this region could not be isolated, and this region was found to replicate autonomously in Agrobacterium tumefaciens. Preliminary sequence analysis has revealed strong homology within this region to genes encoding the RepABC replication proteins of several Rhizobium and Agrobacterium plasmids.

abstract: Thesis

abstract: Master of Science (MS)


title: Implications of Altering Signalling Pathways and Cell Morphology by Polyoma Middle-T at the Onset of Morphological Cell Changes

contributor:
Andrews, David
Biochemistry

subject:
signalling pathways
cell morphology
polyoma middle-t
morphological cell changes

abstract: Subcellular localization of polyoma mT was determined by immuno-fluorescence microscopy, using primary monoclonal/ polyclonal antibodies and secondary polyclonal antibodies conjugated with fluorescent dyes. Our results confirm and extend previous studies reporting the association of mT with an intracellular compartment. However, it is shown that the perinuclear compartment containing the bulk of mT expressed in MRC5 cells is both Brefeldin A resistant and distinct from the known compartments of the secretory pathway. The integrity of most subcellular compartments was not altered by mT expression. However, secondary lysosomes and late endosomes were reorganized in cells expressing mT. Early in cell transformation mT alters several members of the cytoskeletal array, with the most profound effects on actin. In cells coinfected with viruses encoding either mT or pp60csrc, the areas of subcellular localization of both proteins are largely overlapping. In addition, mT recruits She to this subcellular localization indicating that mitogenesis as well as morphological cell transformation may be regulated from this novel intracellular compartment.

abstract: Thesis

abstract: Master of Science (MS)


title: The Characterisation of Antibody Responses to Different Herpesvirus Vaccine Vector Strategies

contributor:
Rosenthal, Kenneth
Biology

subject:
antibody response
herpesvirus vaccine
vector strategies
different herpesvirus

abstract:
Herpes simplex virus is man's oldest viral enemy. Infections result in symptoms ranging from mild skin lesions to deadly herpes simplex encephalitis, making HSV one of the most costly of viral diseases to treat. Thus the development of a vaccine is imperative. To this end, several vaccine strategies have been utilized to generate immunity to HSV in rodents. These include the use of recombinant DNA, recombinant adenoviruses, and dendritic cells transduced with either of the former and re-introduced to the host to induce immunity. In this study, different aspects of these vaccine types were examined. Antibody and cytotoxic T-cell (CTL) responses to a DNA vaccine encoding gB of HSV-1 (gB-DNA) were evaluated. This resulted in variable long lived antibody responses to a wide range of dosages and CTL responses which followed dose-response relationships. An adenovirus expressing gB of HSV -1 (AdgB) which is able to generate IgA responses (Gallichan et al., 1993) was utilized to determine the best method of mucosal administration to optimize these responses. It was suggested in a previous report that nasal associated lymphoid tissue (NALT) was the desired target for inducing lgA responses (Heritage et al., 1997). Accordingly, the hypothesis was formulated that NALT can produce IgA responses similar to those produced from a combination of inductive sites. To test this hypothesis, mice were immunized either awake or asleep with AdgB assuming that awake delivery restricts induction to the NALT, whereas asleep administration disseminates AdgB throughout the respiratory system. The results demonstrate participation of lower airways in the induction of immunity is desirable for
generating IgA responses. Lastly, dendritic cells transduced with AdgB were assessed for their ability to generate systemic and mucosal antibody responses, resulting in the inability to generate IgA, but the ability to generate systemic antibody responses.

abstract: Thesis

abstract: Master of Science (MS)


title: The Integrity of the Randomization Process

contributor:
Goldsmith, C. H.
Statistics

subject:
randomization process
integrity

abstract:
Thesis
Master of Science (MS)


title: Glycopeptide Antibiotic Biosynthesis and Resistance in Streptomyces toyocaensis

contributor:
Wright, G.D.
Biochemistry

subject: glycopeptide, glycopeptide antibiotic biosynthesis, streptomyces, streptomyces toyocaensis, resistance

abstract:
Genetic and biochemical studies were conducted on S. toyocaensis NRRL 15009,
a gram-positive spomlating filamentous bacterium, and producer of the glycopeptide
antibiotic A47934. This compound is structurally similar to the clinically important
antibiotic vancomycin, and the recent spread of vancomycin-resistant enterococci (VRE)
in North American hospitals has driven the need for new glycopeptides with enhanced
activities. Studies were aimed at developing an understanding of the mechanism of
A47934 biosynthesis inS. toyocaensis NRRL 15009, as well as the mechanism of
resistance employed by this organism. Two cosmid clones, containing a partial A47934
biosynthesis gene cluster on a total of65 kilobases of S. toyocaensis NRRL 15009
chromosomal DNA, were isolated for study. Preliminary sequencing indicates the
presence of several genes predicted in glycopeptide assembly, such as peptide synthetases
and glycosyltransfe~ases. Furthermore, using a oligonucleotide probe designed to
identify D-alanine-D-alanine ligases, an 8.1 kilobase chromosomal fragment was isolated
from S. toyocaensis NRRL 15009 and found to contain genes very similar to VRE vanH,
vanA and vanX. Phylogenetic analysis of the predicted products of these genes showed
them to be more similar to the VRE enzymes than any other in each enzyme class. These
genes were also found in the vancomycin producer A. orienta/is C329.2 and several other
glycopeptide antibiotic producing organisms. Not only does this imply that these
organisms employ a mechanism of resistance similar to clinical VRE, it also suggests that
these organisms may have been the source of the VRE genes. The enzymes VanHst and
DdlN were studied in some detail and found to have biochemical properties similar to
their corresponding VRE enzymes VanH and VanA, respectively. Given that the latter
group of enzymes has physical properties that have impeded detailed analysis of enzyme
mechanism, these new enzymes could find use as model systems in drug development
programs.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Resistance Training-Induced Changes in Human Muscle Protein Synthesis and Fibre Morphology

contributor:
Phillips, Dr. Stuart M.
Kinesiology

subject:
training-induced changes
protein synthesis
fibre morphology

abstract:
Muscle proteins are in a continuous state of recycling. This process involves a balance between synthesis and breakdown. These opposing processes dictate muscle protein gains and losses. Muscle hypertrophy occurs when synthesis exceeds breakdown. In order for the accretion of new muscle proteins, a chronic state of net positive muscle protein balance (synthesis> breakdown) is required.
Resistance exercise is a potent stimulus of protein turnover and the combined effects of exercise and feeding have shown to be necessary for net protein anabolism. Resistance training has been reported to increase muscle strength and induce changes in skeletal muscle morphology. These positive strength adaptations include muscle fibre hypertrophy and a shift in fibre type from IJX to IIA.
Previous investigations of resistance training-induced changes in muscle protein synthesis and fibre morphology have utilized cross-sectional or longitudinal, bilateral training designs. Thus, the purpose of this study was to investigate the effects of a progressive eight week unilateral leg resistance training program on skeletal muscle morphology, and resting and exercise-stimulated mixed muscle protein fractional synthesis rate (FSR). Eight young men performed two training sessions each week, and each session consisted of four sets of knee extension (KE) and four sets of leg press (LP) at 80% 1 repetition maximum (1 RM). Needle biopsies from the vastus lateralis muscle of the trained (T) leg were taken before and after training and analyzed for fibre composition, cross-sectional area (CSA), and myosin heavy chain (MHC) content. Muscle protein FSR was determined using a primed constant stable isotope infusion of [13C6]-phenylalanine in both the T and untrained (UT) legs. Training induced type IIX and IIA fibre hypertrophy (P <0.05) with no change for 1ype I fibre CSA. There was no significant change in histochemically determined fibre composition or MHC content. After training, 1RM strength of the T leg significantly increased compared to baseline values (P < 0.01). At rest, FSR was significantly elevated in the T versus the UT leg (P < 0.01). Following an acute bout of resistance exercise, which was performed at the same relative intensity (80% 1 RM) for the T and UT legs, FSR was greater in the UT versus the T leg (P < 0.01). There was a lower exercise-induced increase in muscle FSR in the T versus the UT leg compared to their respective resting values <T: P = 0.08, UT: P < 0.01). These data show that resistance training resulted in significant muscle fibre hypertrophy and elevated rate of muscle protein synthesis at rest. In addition, the acute response to resistance exercise was characterized by an attenuated rise in muscle protein FSR in the T versus the UT leg. We conclude that resistance training markedly attenuates the acute muscle protein synthetic response following resistance exercise, even when loads are matched at the same relative intensity.

abstract: Thesis

abstract: Master of Science (MS)


title: The Fatigue of Ordered Cu3Au

contributor:
Ham, R.K.
Metallurgy

subject: Fatigue, Ordered Cu3Au

abstract:
Current theories to explain the st!'engthening caused by
ordering a.re reviewed. Localization of slip was observed to occur
during high strain reverse bending, and was associated with crack
initiation. A mechanism for the breakdown of order strengthening
mechanisms is suggested as an explanation for this localization.

abstract: Thesis

abstract: Master of Science (MS)


title: The Sustainability of the Term Index Plant Microfossil

contributor:
Radforth, N.W.
Biology

subject: index plant microfossil

abstract: Plant Microfossil have been extracted from separate thin layers of a sample of rock from the York River formation of the Gaspe region. These have been illustrated and described. An index plant microfossil assemblage for that particular facies has been illustrated.

abstract: Thesis

abstract: Master of Science (MS)


title: Peptide Modified PDMS: Surface Modification For Improved Vascular Cell Interactions

contributor:
Sheardown, H
Jones, K.S.
Chemical Engineering

subject: Peptide modified PDMS, PDMS, surface modification, vascular cell interactions, surface modification for improved vascular cell interactions

abstract:
Many of the materials used today for cardiovascular implants exhibit good bulk
mechanical properties but fail to provide desirable surface properties for reducing
thrombogenicity and promoting tissue integration. In fact, biological responses at the
blood-material interface, including non-specific protein adsorption, coagulation, and
platelet adhesion and activation significantly limit the use of currently available materials
in many blood contacting applications. As our understanding of the biological responses
to foreign materials has grown, so too has the potential for creating 'bioactive' materials
capable of inducing and directing beneficial cellular processes. One promising technique
for circumventing undesirable blood-biomaterial interactions involves seeding vascular
endothelial cells (ECs) onto synthetic vascular grafts as a means of exploiting the
physiological anticoagulant characteristics of the endothelium. Methods for improving
cell retention on these constructs include immobilization of cell recognition motifs on the
biomaterial surface in order to improve interactions between cells and the synthetic
substrate. However, there remains the need to better understand the interactions between
surface bound ligands and cells, and the role of linker molecule chemistry on ligand
bioactivity and cellular response. In the current work, a novel method was optimized for
modifying poly (dimethylsiloxane) (PDMS) with cell adhesion peptides tethered via a
heterobifunctional allyl-, NSC-terminated polyethylene oxide (PEO) linker molecule.
These novel surfaces combine the protein repellant property of PEO with the cell binding
property of cell adhesion peptides. It was found that surfaces modified in this manner
reduced protein adsorption to PDMS while increasing cell adhesion. Therefore the use of
a generic PEO linker molecule was shown to be a very promising method of reducing
non-specific protein interactions while maintaining ligand bioactivity.
Silicone surfaces were also modified with diaminobutane (DAB) dendrimers in an
attempt to increase the surface capacity for attachment of biomolecules and to compare
the effect of surface peptide density with ligand mobility. Grafting cell adhesion peptides
via surface bound dendrimers was found to increase the surface peptide density when
compared to peptides grafted via the PEO spacer alone. However, cell adhesion was not
significantly improved on the dendrimer-peptide modified surfaces compared to PDMS
controls. This observation provides evidence that the properties of the linker molecule
used for attachment of cell adhesion peptides to a biomaterial surface may be a critical
factor in determining peptide bioactivity. In this case the peptides bound to the surface
via the highly mobile linear PEO linker showed increased cell adhesion when compared
to peptides linked via the rigid, highly branched dendrimer. It is therefore hypothesized
that ligand mobility on a biomaterial surface may significantly influence ligand-cell
receptor interactions to an even greater extent than surface peptide density.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Minor Alkaloids of Lycopodium Flabelliforme

contributor:
Maclean, David B.
Chemistry

abstract: An examination of the alkaloids of L. flabelliform var. ambiguum was undertaken. By using chromatographic and counter-current distribution methods, the known alkaloids lycopodine, dihydrolycopodine and a-obscurine have been isolated. In addition two new minor alkaloids, fiabelliformine (C16H25O2N) and flabelline (C18H30ON2) have been isolated. The structure of flabelline has been established by infrared and nuclear magnetic resonance data, and chemical examination.

abstract: Thesis

abstract: Master of Science (MSc)


title: Development of a Thermostabilization Platform for Point-of-Care Diagnostics, Food Safety, and Vaccine Deployment

contributor:
Filipe, Carlos
Chemical Engineering

abstract:
Thermostabilization of labile biomolecules is crucial for the advancement of global health. The World Health Organization has identified accessible quality-assured diagnostics, prevention of antibiotic resistance, and universal access to vaccination as three of the most important issues for global health today. One major challenge is that many biomolecules, such as enzymes and vaccines, are thermally unstable and require refrigeration at all times. Maintaining refrigeration is a major logistical problem, since many developing countries and rural areas do not have access to reliable electricity. Moreover, the cost to maintain the cold chain infrastructure presents a substantial financial barrier. Therefore, there is a great need for the thermostabilization of labile biomolecules.
This work presents a simple thermostabilization method that uses pullulan and trehalose to encapsulate labile biomolecules within a sugar glass matrix. To address the problem of accessible quality-assured diagnostics, we thermally stabilized molecular biology reagents in ready-to-use mastermixes. Thermally stabilized polymerase chain reaction (PCR) and rolling circle amplification (RCA) mastermixes were shown to be stable for at least 12 weeks at room temperature. This can significantly improve the accessibility of diagnostic tools since, DNA amplification techniques such as PCR and RCA can be used as diagnostic tools to provide rapid detection of diseases with high specificity and sensitivity.
To address the problem of antibiotic resistance, this work demonstrated a method to stabilize bacteriophages as a coating on surfaces for food safety applications. Bacteriophages, are viruses that kill bacteria with high specificity while having a low risk of developing antibiotic resistance. The bacteriophages encapsulated in pullulan-trehalose films were able to retain infectivity for up to 3 months at ambient storage conditions. We further optimized the stability of bacteriophage in pullulan-trehalose films performing a four factor, two level design of experiment (DOE). It was shown that vacuum drying and storing the films in a closed container with low-humidity can increased the long-term viability of bacteriophage by over 1000-fold.
To address the need for universal immunization, we stabilized enveloped DNA and RNA viral vaccines by drying them in a pullulan and trehalose mixture. The thermally stabilized live-attenuated HSV-2 vaccine retained immunogenicity for at least 2 months when stored at 40 °C. Inactivated influenza vaccine stabilized in pullulan and trehalose retained immunogenicity for at least 3 months at 40 °C.
Overall, this thesis presents a versatile thermostabilization method using pullulan and trehalose as stabilizers. This method was used to thermally stabilize molecular biology reagents, bacteriophages, and vaccines. The achievements from this work have the potential to significantly improve global health by creating thermally stable molecular diagnostic kits that are accessible and reliable, by preventing antibiotic resistance with stabilized bacteriophage coatings, and by deploying thermally stable vaccine for universal immunization.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: An Examination of the Repair of Cisplatin-Damaged DNA in Human Cells Using Adenovirus as a Probe

title: The Repair of Cisplatin-Damaged DNA in Human Cells

contributor:
Rainbow, Dr. Andrew J.
Biology

subject:
cisplatin-damaged DNA
human cells
adenovirus
probe

abstract: The repair of DNA damage is vital to the health and survival of organisms and their cells. In humans, there exist several disorders that involve the inefficient processing or repair of DNA damage. Cellular sensitivity to DNA-damaging agents is a hallmark of repair-deficient syndromes which are often associated with an increased risk of cancer. In this work, I have investigated the repair of cisplatin-damaged DNA by utilizing host cell reactivation and cellular capacity assays that assess DNA repair using adenovirus (Ad) as a probe. Cisplatin is a widely used chemotherapeutic drug that induces both intrastrand and interstrand crosslinks in DNA. The host cell reactivation (HCR) assay examines the ability) of host cells to repair and hence, replicate cisplatin-damaged Ad DNA. This assay is believed to primarily be a measure of bulk nucleotide excision DNA repair. The cellular capacity assay examines the ability of cisplatin-damaged cells to support the replication of undamaged Ad DNA, and is thought to reflect the repair of the active cellular genes necessary for Ad replication. The repair of cisplatin-damaged DNA was studied in three human genetic syndromes -Roberts syndrome (RS), xeroderma pigmentosum (XP) and Li-Fraumeni syndrome (LFS). Fanconi's anemia (FA) cells were also used as a contml strain. RS is characterized by growth retardation, limb reductions and craniofacial abnormalities. Cell; from a subset of RS patients, termed RS+, are hypersensitive to several DNA-damaging agents, and it has been suggested that this hypersensitivity may result from a deficiency in the DNA repair capacity of these cells. (XP patients are sensitive to ultra violet light and are prone to the development of skin cancers. Cells from these patients are deficient in the nucleotide excision repair (NER) pathway responsible for repair of UV -induced lesions.) Patients with FA have a variety of congenital abnormalities, including a high susceptibility to leukemia. FA cells are sensitive to DNAcrosslinking agents such as mitomycin C (MMC) and cisplatin. Using the HCR and cellular capacity assays, deficiencies in DNA repair were detected in the XP and FA fibroblasts but not in the RS+ fibroblasts when compared to normal strains. The NERdeficient XP cells showed a significant reduction in both HCR of cisplatin-damaged Ad and in their capacity to support Ad replication following cellular cisplatin damage suggesting that cisplatin damage is repaired at least in part by the NER pathway. The normal HCR and capacity response of the RS+ cells compared to the XP cells suggests that the hypersensitivity of RS+ cells to DNA damage is not due to a deficiency in NER. The FA cells had normal HCR of cisplatin-damaged Ad but were significantly reduced in their capacity to support Ad replication following cisplatin treatment which was attributed to a defici,~ncy in the repair of DNA interstrand crosslinks. RS+ cells were not reduced in their capc.city to support Ad DNA replication, suggesting that the RS+ cellular hypersensitivity doe; not result from a deficiency in interstrand crosslink repair as seen with FA cells. LFS is a cancer prone syndrome that involves mutations in the p53 tumour suppressor gene. It was found that HCR of cisplatin-damaged Ad was normal in both p53-heterozygous and -hemizygous LFS cells, whereas the NER-deficient XP cells had significantly reduced HCR. The capacity of cisplatin-damaged, p53-heterozygous LFS fibroblasts was significantly reduced compared to normal cells. This suggests that although the LFS fibroblasts appear to have normal bulk NER, as shown by HCR, they appear to be deficier in the repair of the actively transcribed cellular genes necessary for viral replication. These results suggest a role for p53 in the repair of cisplatin damage of active genes.

abstract: Thesis

abstract: Master of Science (MS)


title: Quantitative Analyses of Candida Albicans Biofilm Formation

contributor:
Xu, Dr. Jianping
Biology

subject:
quantitative analyses
Candida albicans
biofilm formation

abstract: Strains of pathogens are typically described as virulent or non-virulent. However, in the majority of pathogens, strains often vary continuously and quantitatively in their virulence and pathogencity. Biofilm formation is one of the recently recognized virulence factors in many human pathogens and little is known about the variation and evolution of biofilms among natural strains. In this study, I examined quantitative variation of biofilms among natural strains of the human pathogenic yeast Candida albicans. A total of 115 natural strains of C. albicans from three sources (vaginal, oral and environmental) were quantified by two mebods: (i) the XTT tetrazolium reduction assay, and (ii) optical density following staining by crystal violet dye. Mature biofilm was confirmed by observation using confocal laser scanning microscopy. My analyses indicated that strains from each of the three scurces varied widely in biofilm formation abilities and that biofilm formation ability was positively correlated to cell surface hydrophobicity (CSH). For each strain, multilocus genotypes were determined by PCR-RFLP, my comparative genotype and biofilm analyses denonstrated that natural clones and clonal lineages of C. albicans exhibited extensive quantitative variation for biofilm formation. I also examined potential interactions among strains within C. albicans and between different Candida species. My preliminary results suggest significant variation and complex patterns of strains or species interaction during Candida biofilm development.

abstract: Thesis

abstract: Master of Science (MS)


title: Towards a Multiscale, Spatially Explicit Analysis of the Littoral Zone Macrobenthos Along the North Shore of Hamilton Harbour

title: Macrobenthos of Hamilton Harbour

contributor:
Kolasa, Dr. Jurek
Biology

subject:
multiscale study
littoral zone macrobenthos
north shore
hamilton
harbour

abstract: Macrobenthos and macrophytes of the north shore littoral zone of Hamilton Harbour were extensively sampled in late August 1994. Benthic community structure is described, including the presence of several oligochaete and chironomid genera previously unreported in the harbour. Community structure is scale dependent and identifying which spatial scales contribute important structure is a useful step in determining which environmental factors have the greatest impact on the benthic community. This information can be used to plan efficient benthos monitoring programs, and to construct spatially explicit models of the harbour ecosystem. Most of the variation in the data set (approx. 88%) is due to small scale patchiness, probably related to patchiness of the macrophyte community and sediment grain size, as well as biotic processes such as predation and competition. Large scale structure is related to a water depth gradient, probably involving changes in dissolved oxygen concentrations, light attenuation, and sediment grain size. Macrophytes also respond to this gradient. There is little important structuring of the benthos community at intermediate spatial scales. Models of benthic communities in the harbour must deal with spatial pattern effects such as autocorrelation. Additionally, spatial patterns provide information useful for understanding causes of community structure. A method is developed for the spatial pattern analysis of the benthic community data, which allows the simultaneous evaluation of patterns at various scales, with minimal mixing of information between scales.

abstract: Thesis

abstract: Master of Science (MS)


title: The role of the gut microbiome in Major Depressive Disorder

contributor:
Bercik, Premysl
Medical Sciences (Neurosciences)

subject:
depression
microbiome
MDD
microbiota
Major depressive disorder
bacteria
gut brain axis
nervous system
GABA
metabolites

abstract:
The aetiology of major depressive disorder (MDD) is poorly understood. Current evidence suggests immune activation and gut microbiota may play a role. Recent studies demonstrated that behavioural traits can be transferred through microbiota transplantation into germ-free (GF) mice. Here we study whether microbiota from patients with MDD can induce depressive-like behaviour.
Methods: GF NIH Swiss mice were colonized with stool microbiota from a patient with MDD with elevated faecal β-defensin 2, or a healthy donor (HC). After three weeks, behaviour was assessed using standard tests. Expression of neuroimmune markers was assessed in the gut and brain using gene expression profiling and immunohistochemistry. Microbiota composition was assessed by 16S rRNA sequencing.
Results: Microbiota profiles differed between the two groups of mice (p=0.001). Mice colonised with microbiota from a single characterised MDD patient (MDD1), exhibited lower preference for sucrose (p=0.002) and more emotionality (p=0.003) than mice with HC microbiota, however other MDD mice did not display abnormal behaviour. Abnormal MDD1 behaviour was associated with lower BDNF expression in the dentate gyrus of the hippocampus (p=0.02). Mice colonised with another characterised MDD patient (MDD4 mice) did not have differences in BDNF expression in the same region (p=0.20). MDD1 and MDD4 mice had altered hippocampal and gut gene expression for genes associated with the immune and nervous system. In summary, GF mice colonized with MDD1 microbiota exhibit depression-like behaviors. This appears to be accompanied by changes in intestinal permeability and neuroimmune function. These results suggest that gut microbiota has the capacity to influence the expression of MDD in some patients.

abstract: Thesis

abstract: Master of Science (MSc)


identifier: Feit, Harvey A. 1968. Mistassini Hunters of the Boreal Forest: Ecosystem Dynamics and Multiple Subsistence Patterns. M.A. Thesis, McGill University, Department of Anthropology. 193 pp.

subject:
Ecosystem analysis
Hunting Peoples
Hunting Territory debates
Boreal forest fires
Mistassini Cree
Subsistence

abstract:
Available online at McGill University at:
http://digitool.library.mcgill.ca/R/-?func=dbin-jump-full&object_id=147751&silo_library=GEN01

abstract: This thesis applies an ecosystem analysis in a hunting and gathering culture for the first time. It shows how ecosystem analysis makes possible the resolution of long standing debates unresolved by previous cultural ecological analyses over the aboriginality of the family hunting territory system, and over what were the primary bases of subsistence before contact with fur traders. On the basis of an extensive review of current biological knowledge on the boreal forest ecosystem an attempt is made to reconstruct the pre-contact strategy of adaptation of Mistassini Indians of the sub-arctic boreal forest of Quebec, with particular stress on mechanisms for maintaining human population density equilibrium.

abstract: Cree Developmental Change Project at McGill University, Canada Department of Forestry and Rural development, Centre d'études Nordiques de l'Université Laval


title: The Perceptual vs. Motoric Basis of Bimanual Coordination in Young Adults and Individual's with Parkinson's Disease

contributor:
Wishart, L.R.
Human Biodynamics

subject: parkinson's disease, young adults with parkinson's disease, perceptual vs motoric basis, bimanual coordination, individuals with Parkinson's disease

abstract:
The research presented in this thesis investigates the motoric versus perceptual
basis of bimanual coordination stability. A general introductory section provides an
overview of Parkinson's disease, upper limb coordination in healthy younger and healthy
older adults and individuals with Parkinson's disease, and the current views of the basis
of bimanual coordination stability. Following the general introductory section are two
manuscripts for the two experiments. Both experiments followed similar paradigms.
Healthy young adult~ participated in the first experiment and individuals with
Parkinson's disease and healthy older adults participated in the second experiment.
Following the presentation of the empirical work is a general discussion section.
This section is intended to summarize the two experiments, to discuss potential
methodological issues and to provide ideas for future experiments.

abstract: Thesis

abstract: Master of Science (MSc)


abstract:
The research presented in this thesis investigates the motoric versus perceptual
basis of bimanual coordination stability. A general introductory section provides an
overview of Parkinson's disease, upper limb coordination in healthy younger and healthy
older adults and individuals with Parkinson's disease, and the current views of the basis
of bimanual coordination stability. Following the general introductory section are two
manuscripts for the two experiments. Both experiments followed similar paradigms.
Healthy young adults participated in the first experiment and individuals with
Parkinson's disease and healthy older adults participated in the second experiment.
Following the presentation of the empirical work is a general discussion section.
This section is intended to summarize the two experiments, to discuss potential
methodological issues and to provide ideas for future experiments.

abstract: Thesis

abstract: Master of Science (MS)


title: Dose Limit Changes to the Lens of the Eye & Its Regulatory Implications

contributor:
Mcneill, Fiona
Chettle, David
Chambers, Douglas
Medical Physics

subject:
Ionizing Radiation
Lens Opacities
Cataractogenesis
ICRP
Radiation Cataracts
Lens of the Eye
Vision Impairment
Cataracts
Radiation
Medical Physics

abstract:
The commission on radiological protection through publication 118 decided to recommend a change to the eye dose limit in 2011. ICRP recommendations made in publications, especially ‘publication 60’ and its subsequent update ‘publication 103’ has served as standards for regulatory authorities worldwide in limiting ionizing radiation exposure both to workers and members of the public. For example in Canada, the Canadian Nuclear Safety Commission (CNSC) generally directly adopts recommendations from ICRP. The previous dose limit for the lens of the eye was 150 mSv year-1, based on Publication 60 and 103. Regulatory agencies worldwide have been using this value and subsequently nuclear facilities, hospitals and universities have designed their radiation protection program based on this dose limit for several decades. The new revised eye dose limit now being equivalent to the whole body dose limit will pose significant challenges for sectors where the eye exposure was not characterized as the limit was previously five times over the whole body exposure.

A two-step approach was used in conducting this study, firstly a through literature search was conducted on the effects of ionizing radiation to the eye, its radiobiology, fundamentals in established both dose limits was analyzed. Secondly, the authors spent time researching institutions that use ionizing radiation and interviewed engineers, medical physicists, radiation safety officers and regulators from a wide array of fields and industries. Based on the ICRP publications, the review of the literature and the interviews conducted with the nuclear industry, there is consensus in Canada and among IAEA member states that the dose limit for the lens of the eye should be reduced from the original proposed limit of 150 mSv per year.  However not to the recommendations suggested by ICRP 118, but, to a standard reasonable and an achievable limit that is 50 mSv per year.

abstract: Thesis

abstract: Master of Science (MSc)

abstract:
The International Commission on Radiological Protection (“ICRP”), the independent governing body responsible for radiation protection, since the early 1950s has been issuing recommendations that are widely used as radiological protection standards by regulatory agencies worldwide, primarily UN member states. Since its inception in 1928, the ICRP has served as the basis for radiation protection and value based judgements in protecting both human and non-human biota. In 2011, the commission published (ICRP Pub. 118) its review of epidemiological studies and decided to recommend a change to the previously established eye dose limit.

Based on the review of the literature and the research conducted within the academic, veterinary, nuclear and medical industry, there is general consensus in Canada and among IAEA members states that the dose limit for the lens of the eye should be reduced from the original proposed limit, but not to the recommendations suggested by ICRP 118.


title: MARGINAL LIKELIHOOD INFERENCE FOR FRAILTY AND MIXTURE CURE FRAILTY MODELS UNDER BIRNBAUM-SAUNDERS AND GENERALIZED BIRNBAUM-SAUNDERS DISTRIBUTIONS

contributor:
Balarishnan, Narayanaswamy
Mathematics and Statistics

subject: frailty model; mixture cure model; mixture cure frailty model; Birnbaum-Saunders distribution; generalized Birnbaum-Saunders distribution; cen- sored data; cluster time data; Monte Carlo simulation; piecewise constant hazards; model discrimination; maximum likelihood estimation; marginal likelihood approach; likelihood ratio test; Akaike information criterion; Bayesian information criterion.

abstract:
Survival analytic methods help to analyze lifetime data arising from medical and reliability experiments. The popular proportional hazards model, proposed by Cox (1972), is widely used in survival analysis to study the effect of risk factors on lifetimes. An important assumption in regression type analysis is that all relative risk factors should be included in the model. However, not all relative risk factors are observed due to measurement difficulty, inaccessibility, cost considerations, and so on. These unobservable risk factors can be modelled by the so-called frailty model, originally introduced by Vaupel et al. (1979). Furthermore, the frailty model is also applicable to clustered data. Cluster data possesses the feature that observations within the same cluster share similar conditions and environment, which are sometimes difficult to observe. For example, patients from the same family share similar genetics, and patients treated in the same hospital share the same group of profes- sionals and same environmental conditions. These factors are indeed hard to quantify or measure. In addition, this type of similarity introduces correlation among subjects within clusters. In this thesis, a semi-parametric frailty model is proposed to address aforementioned issues. The baseline hazards function is approximated by a piecewise constant function and the frailty distribution is assumed to be a Birnbaum-Saunders distribution.

Due to the advancement in modern medical sciences, many diseases are curable, which in turn leads to the need of incorporating cure proportion in the survival model. The frailty model discussed here is further extended to a mixture cure rate frailty model by integrating the frailty model into the mixture cure rate model proposed originally by Boag (1949) and Berkson and Gage (1952). By linking the covariates to the cure proportion through logistic/logit link function and linking observable covariates and unobservable covariates to the lifetime of the uncured population through the frailty model, we obtain a flexible model to study the effect of risk factors on lifetimes. The mixture cure frailty model can be reduced to a mixture cure model if the effect of frailty term is negligible (i.e., the variance of the frailty distribution is close to 0). On the other hand, it also reduces to the usual frailty model if the cure proportion is 0. Therefore, we can use a likelihood ratio test to test whether the reduced model is adequate to model the given data. We assume the baseline hazard to be that of Weibull distribution since Weibull distribution possesses increasing, constant or decreasing hazard rate, and the frailty distribution to be Birnbaum-Saunders distribution.
D ́ıaz-Garc ́ıa and Leiva-Sa ́nchez (2005) proposed a new family of life distributions, called generalized Birnbaum-Saunders distribution, including Birnbaum-Saunders distribution as a special case. It allows for various degrees of kurtosis and skewness, and also permits unimodality as well as bimodality. Therefore, integration of a generalized Birnbaum-Saunders distribution as the frailty distribution in the mixture cure frailty model results in a very flexible model. For this general model, parameter estimation is carried out using a marginal likelihood approach. One of the difficulties in the parameter estimation is that the likelihood function is intractable. The current technology in computation enables us to develop a numerical method through Monte Carlo simulation, and in this approach, the likelihood function is approximated by the Monte Carlo method and the maximum likelihood estimates and standard errors of the model parameters are then obtained numerically by maximizing this approximate likelihood function. An EM algorithm is also developed for the Birnbaum-Saunders mixture cure frailty model. The performance of this estimation method is then assessed by simulation studies for each proposed model. Model discriminations is also performed between the Birnbaum-Saunders frailty model and the generalized Birnbaum-Saunders mixture cure frailty model. Some illustrative real life examples are presented to illustrate the models and inferential methods developed here.

abstract: Thesis

abstract: Doctor of Science  (PhD)


title: The Process of Medical Referral

subject:
medical referral
process

abstract:
The purpose of this research was to develop a model of the complex process of medical referral, in
which a physician consults with or refers a patient to a specialist. Fifty cases of referral were investigated
by interviewing the referring physician, patient and specialist(s). Involved with the case at various points
before and after the referral. Referrals were followed first in a southern Ontario city and, for comparison,
in northwestern Ontario. Trust in the competence of specialist advisors was found to be the key component in understanding the process of referral. Referral in settings where there is mutual respect between referring physicians and consultants, particularly where they worked in close physical association, was contrasted with referral in settings where there is isolation of referring doctor from consultant, and a tendency towards breakdown in the process of the referral. Finally, when the activities and beliefs of patients as well as doctors were examined, patients were found to have a much greater influence on the initiation, process and outcome of referral than has been previously recognized.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Application of First Order Unimolecular Rate Kinetics to Interstitial Laser Photocoagulation

contributor:
Wyman, Douglas
Medical Physics

subject:
first order unimolecular
rate kinetics
interstitial laser coagulation
coagulation
laser
unimolecular rate kinetics
kinetics

abstract:
An investigation of the temperature response and corresponding lesion growth resulting from in vivo interstitial laser photocoagulation was performed in order to test the applicability of Arrhenius theory. The irradiations were performed in vivo in rabbit muscle for various exposures at 1.0W using an 805 nm diode laser source coupled to an optical fibre with a pre-charred tip, thereby forcing it to function as a point heat source. Temperature responses were measured using a five-microthermocouple array along a range of radial distances from the point heat source. Each temperature profile was fitted with a curve predicted by the Weinbaum-Jiji bioheat transfer equation. The lesions were resected 48 hours after irradiation and the
boundary of thermal damage resulting in necrosis was determined histologically. Numerical integration of the Arrhenius integral using temperature-time data at the lesion boundary produced corresponding activation energy and pre-exponential factor pairs (Ea , a) consistent with reported values for various other endpoints and tissue types. As well, theoretical predictions of the lesion growth from Arrhenius theory agreed well with experimental results. However, the thermal parameters, which are generally assumed to be constant when solving the bioheat transfer equation, were found to vary with radial distance from the source, presumably due to a dependence on temperature.

abstract: Thesis

abstract: Master of Science (MS)


title: The Role of Terminal Repeat Sequences in the Preservation of the Ends of the Adenovirus Genome

title: Role of ITRs in the Preservation of the Ends of Adenovirus

contributor:
Graham, Frank
Biology

subject:
terminal repeat sequences
preservation
adenovirus genome

abstract: The requirement for identical inverted terminal repeats (ITRs) for viral viability and the role of internal viral sequences in the specification of the sequences of the termini were investigated. The viral strains used in this study were a variant Ad2 strain Ad2 (mac) and the wild type Ad5 strain which was very similar to the former one in sequence except at the extreme end of the terminal repeat. A hybrid virus (sub54), obtained by recombination between Ad2 (mac) and Ad5, derived the left 41-51% of its genome from Ad2 (mac) and the right 59-49% from Ad5. The identity of the termini was determined by Southern blotting analysis using 32p end labeled oligocleoxynucleotides. Analysis of the sub54 isolate indicated that both Ad2 (mac) and Ad5 ITRs were present. Plaque purification of sub54 demonstrated that viruses with non identical terminal sequences were viable and allowed their characterization. This analysis also indicated that Ad5 ITRs are converted to Ad2 (mac) ITRs possibly as a result of repair of the ends to yield viruses with identical termini. A model involving replication and emphasizing the importance of panhandle formation as a replicative intermediate is proposed. These results also indicated a possible role of the internal sequences of adenovirus in the selection and maintenance of serotype specific ITRs. The preference for Ad2 (mac) termini observed during repair of the ends of sub54 may be related to the origin of the genes coding for the adenoviral polymerase and/or the terminal protein both of which were derived from Ad2 (mac). Further investigation would be required to determine whether these replicative proteins are actually involved in ITR conversion. Transformation of Escherichia coli with a DNA preparation from sub54 infected rat embryo cells resulted in the isolation of the plasmid pFG154. This plasmid contained the entire adenovirus genome with an Ad2 (mac) ITR at the "left" terminus covalently linked to an Ad5 ITR at the "right". Analysis of the viral progeny generated upon transfection of mammalian cells with pFG154 indicated that the Ad2 (mac) ITRs were very efficiently converted to Ad5 termini. These results, although apparently contradictory to those initially obtained from the plaque purification of sub54, may be explained by an ITR repair model which is specific for infectious circles.

abstract: Thesis

abstract: Master of Science (MS)


title: Genetic Analysis of Second Site Revertants of fix114 in Rhizobium Meliloti

title: Second Site Revertants of fix114 in R. meliloti

contributor:
Finan, T. M.
Biology

subject:
rhizobium meliloti
fix114
second site revertant
genetic analysis

abstract: R. meliloti carrying defined deletions that remove fix114 form Fix- nodules which are devoid of intracellular bacteria. Occasionally strains which carry these deletions form pink nodules which appear effective in contrast to the normal white ineffective nodules formed by strains carrying fix114 mutations. Bacteria isolated from these pink nodules retain the original deletion and form effective pink nodules when reinoculated onto alfalfa. It is hypothesized that these isolates carry second site mutations which enable the bacteria to overcome the symbiotic block associated with the fix114 mutation. In this work, five independent isolates were examined and were shown to carry second site mutations that suppress the symbiotic ineffectiveness completely on alfalfa and incompletely on sweet clover. The five independent second site revertants can be divided into two classes based on genetic data and on their sensitivity to detergents and both classes were localized to the chromosome of the wild type Rm1021. One such second site revertant allele, sfx-1, was cloned and localized to a large 18 kb BamHI fragment.

abstract: Thesis

abstract: Master of Science (MS)