title: Two-Phase Flow Regime Transitions Under a D.C. Electric Field

contributor:
Chang, J.S.
Girard, R.
Montgomery, J.
Engineering Physics

subject: air-water flow regime, electric field, model,

abstract: The air-water flow reqime transitions in a horizontal pipe under the influence of a stronq electric field perpendicular to the interface are studied. The separated flow model to predict flow regime transitions has been developed. The present version of the model is a modification of Taitel and Dukler's separated flow model. This assumes that all flow reqimes are perturbations from stratified smooth flow. Expressions for the electrical force are derived and added to the conservation and constitutive equations to obtain new transition criteria. The theoretical results are compared with observations of air-water flow in a 1.27 cm. and 1.9 cm. internal diameter pipe. Good agreement was found when no electric field was applied, however, the experimentally observed effect of the electric field was not as pronounced as predicted by theory. Further experiments to refine the theoretical model are presented.

abstract: Thesis

abstract: Master of Engineering (ME)


title: Multivariate Data Analysis for Process Evaluation, Prediction and Monitoring at INCO's Copper Cliff Smelting and Refining Operations

contributor:
MacGregor, J.F.
Kourti, Theodora
Chemical Engineering

subject: Industrial, univariate fashion, variables,  INCO's, Copper Cliff, nickel carbonyl,

abstract:
Industrial processes generate large quantities of process and product quality data. Most of this data is stored and is analyzed in a univariate fashion. However important information may be lost through the implementation of univariate analysis methods. This information is contained in the correlation structure amongst the process and product quality variables and between these two types of variables. Through multivariate analysis this information is retained. As a result process evaluation, prediction and monitoring are more effectively performed.
Multivariate data analysis techniques were therefore applied to data sets that summarized three of INCO's Copper Cliff smelting and refining processes. In the first instance the analysis of historical data pertaining to a batch leaching process was undertaken and the time required for leaching was predicted. In the second a multivariate soft sensor was developed in order to predict the concentration of nitric oxide contained in the feed gas to the smelter acid plant. The final project involved the analysis and monitoring of a continuous nickel carbonyl process.
The resulting models were evaluated and significant variables with respect to the variation in the process and product quality data and the correlation between them were identified. The product quality data was also well predicted using new process data only that was input to the models. Finally new data was input to the models and the process was monitored using a reduced number of latent variables. Contribution plots were used to identify the original variables that contributed most to the observations that exceeded the established control limits.

abstract: Thesis

abstract: Master of Science (MSc)


title: Three Essays on Labour and Health Economics

contributor:
Sweetman, Arthur
Magee, Lonnie
Hurley, Jeremiah
Economics

abstract:
This thesis comprises three essays in labour economics, econometrics and health economics. The first essay uses educational quality outcomes in immigrants’ home countries to explain the variation of immigrants’ rates of return to education in Canada. The second essay explores an econometrics technique (i.e., generalized method of moments) that combines macro level data and micro survey data to reduce the bias and/or variance of estimates. The goal of this essay is to address nonresponse and attrition issues that are commonly encountered in surveys in health services and health economics. The last chapter is an empirical investigation on the association between diabetic patients’ hospitalizations and their family doctor’s payment model.
The first chapter uses international test scores as a proxy for the quality of immigrants’ source country educational outcomes to explain differences in the rate of return to schooling among immigrants in Canada. The average quality of educational outcomes in an immigrant’s source country and the rate of return to schooling in the host country labour market are found to have a strong and positive association. However, in contrast to those who completed their education pre-immigration, immigrants who arrived at a young age are not influenced by this educational quality measure. Also, the results are not much affected when the source country’s GDP per capita and other nation-level characteristics are used as control variables. Together, these findings reinforce the argument that the quality of educational outcomes has explanatory power for labour market outcomes. The effects are strongest for males and for females without children.
The second chapter explores a technique that combines macro and micro level data. Administrative data in the health sector normally provide censuses of relevant populations but the scope of the variables is often limited and frequently only aggregate summary statistics are publically available. In contrast, survey datasets have a broader set of variables but commonly suffer from nonresponse, attrition and small sample sizes. This paper explores a technique that combines complementary population and survey data using a method of moments technique that matches auxiliary moments of the two data sources in estimating micro-econometric models. We provide Monte Carlo evidence showing that the approach can give appreciable reductions in both bias and variance. We show an example looking at midwife training and another looking at an optometrist’s location of work, to illustrate its use in a health human resource context. This approach could have wide applicability in health economics and health services.
The third chapter investigates the impact of a blended capitation model (Family Health Organizations -- FHOs) compared to an enhanced fee-for-service model (Family Health Groups - FHGs) on diabetic patients in Ontario, Canada. Using comprehensive administrative data and primary care reform as a quasi-natural experiment, we construct a panel for diabetic patients and employ a difference-in-differences approach to identify the impact of a change in the general practitioner’s (GP’s) remuneration model on patients’ hospital admissions. We find that on both the intensive and extensive margins, the hospital admissions for senior female patients statistically significantly increased after their GP’s remuneration model changed from FHG to FHO. In contrast, the impacts on male patients and younger female patients were small and not statistically significant. The results provide a cautionary message regarding the differences in practice patterns towards senior diabetic patients between GPs as a function of their payment model.

abstract: Thesis

abstract: Candidate in Philosophy


title: On the Dynamics of Imperfect Crystals

contributor:
Taylor, D.W.
Physics

subject:
physics
crystals
algebraic prodcedure

abstract: In part (a) of the abstract, the decimal points should be subscript.

abstract:
An algebraic procedure for considering the general n-tuple problem for a random defect lattice is developed in this thesis. When specialized to pairs {n=2) the deviations from randomicity have also been considered. The low concentration defect theory (n=l) is used to calculate: a) the frequencies and widths of phonons in disordered Cu₀.₉₇ Au₀.₃₃
b) the frequency shift of singular points in the defect-induced (Na⁺ , Sm⁺⁺) far infrared spectrum of RBr as a function of defect concentration
c) the one phouon side bands of H₂, D₂, and N₂ in solid Ar. In order to take into account the "long range" behaviour of random substitutional defects, an effective lattice theory is formulated. This theory proves essential to the discussion of the Cu/Au dispersion curves and the one phonon side band of the vibrational spectrum of a H₂, (D₂) molecule in solid Ar.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Energy Dispersive X-ray Fluorescence Spectrometry and Kinetic Modeling of Elemental Strontium in Human Bone

contributor:
Chettle, David
Pejovic-Milic, Ana
Medical Physics

abstract:
For the first time in the available literature, this work presents data based on long term in-vivo human bone strontium measurements performed with an in-house custom developed I-125 based X-ray fluorescence system (IVXRF). Its negligible radiation risk and non-invasive nature allowed for frequent measurements at the ankle and finger sites, obtaining information about trabecular and cortical bone, respectively. While the phantom standards used to calibrate the system cannot be used to extract absolute bone strontium concentration, analysis of phantom consistency indicated excellent reproducibility, reporting a mean normalized strontium signal ± SD of 1.1198 ± 0.02171. This work comprises two important contributions besides system analysis; (i) the continued measurements of osteoporotic individuals self-administering with strontium supplements in order to acquire long term data and (ii) kinetic modeling.
     A total of 21 individuals (18 females, 3 males) were measured throughout the study, 10 are baseline individuals (no prior history of strontium intake and for whom natural bone strontium readings were acquired). Although similar patterns of strontium uptake were observed for all individuals, a wide variation of the strontium signal between individuals was observed, raising the question of physiological influences. Power and exponential functions were tested on 8 baseline individuals based on one and two compartmental configurations. Parameters represented the mean baseline strontium signal,

half-life and strontium uptake. Ankle and finger values showed correlation of 0.804, which is significant at the 95% level. Half-lives (300 ± 163) days and (2200 ± 1661) days (p=0.000711 and p=0.0147) for the ankle and finger, respectively, indicated statistically significant different times, suggesting one compartment has a quicker turnover than the other. However, while the exponential model best describes the data set, the models were inconclusive which points to the need for a more controlled study, eliminating variable factors between individuals such as dosage, health and dietary consumption.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Characterizing the impact of maternal obesity on offspring ovarian development in rats

contributor:
Deborah, Sloboda
Biochemistry and Biomedical Sciences

abstract: Maternal obesity predisposes offspring to non-communicable disease and reproductive dysfunction. Previous work has shown that female rat offspring born to mothers fed a high fat (HF) diet throughout pregnancy and lactation enter puberty early and display aberrant reproductive cyclicity. It is currently unknown what mechanisms are driving this reproductive phenotype, however, the ovary is likely involved. The present study shows that offspring born to HF-fed mothers have impaired ovarian function likely stemming from altered ovarian development early in life. Neonates born to HF fed mothers have reduced AMH signaling that appears to result in more primordial follicles assembled. During the prepubertal period, excess primordial follicles are removed from the primordial follicle pool likely due to increased primordial follicle demise or an increase in the number of growing follicles undergoing atresia. This study shows that as adults, offspring born to HF fed mothers also have more atretic follicles, appearing to be due to decreased FSH responsiveness that could be induced by both low expression levels of the oocyte-secreted factor, GDF9, and high expression levels in antral follicles of the granulosa-cell derived factor, AMH. Changes in ovarian follicle dynamics was not associated with increased oxidative stress or the induction of inflammation. Interestingly, the addition of a postweaning high fat diet appears to spare offspring born to HF fed mothers from an increase in follicular atresia. This study demonstrates that maternal HF diet induced obesity has long lasting effects on ovarian development and function in female offspring. Given the high rates of obesity in female populations worldwide and the growing concern over trans-generational inheritance of disease risk, future studies are needed to fully delineate the molecular mechanisms mediating ovarian dysfunction induced by a maternal obesogenic diet. This will allow the design of targeted interventions that will hopefully improve the health of future generations.

abstract: Thesis

abstract: Master of Science (MSc)


title: An Agent-Semantical Theory of Reference

contributor:
Simpson, Evan
Philosophy

subject:
singular reference
philosophy
semantics
pragmatics

abstract:
This work provides a theory of singular reference based on the idea that the function of a referring expression is to get an audience to think of some particular item. Although this obvious fact has not escaped anyone's notice, many believe that the considerations associated with this communicatory function do not belong to "semantics" but to "pragmatics". Others regard such considerations as relating to "perlocutionary", as opposed to "illocutionary", effects. By contrast the framework presented, which can be described as "Gricean", puts forward the theory of communication as the primary arena of semantics. I take the view (derived from Wittgenstein) that representation is to be explained in terms of agency.

 Starting from a simple condition for paradigm acts of reference, the theory is developed by considering three areas of contemporary concern: names, definite descriptions and intentional contexts. While the "cluster" theory is upheld as an insight into the problem of determining the conventional bearer of a name, it is conceded that names function semantically in a manner postulated by Mill. Donnellan's distinction between referential and attributive uses of definite descriptions is redrawn; unlike recent accounts of this distinction, the account proposed represents the distinction as a sharp one The account of intentional contexts introduces an approac which exploits the Gricean model for analyzing a speaker' strategy. This approach differs significantly from other published accounts of intentional contexts.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


contributor:
York, Lorraine
English and Cultural Studies

subject:
celebrity
memoir
women's writing
Canada
twentieth-century
autobiography

abstract: “Women’s Celebrity in Canada: Contexts and Memoirs, 1908-2011” is equal parts cultural history and literary analysis. It examines the cultural contexts and conditions that shaped the emergence and development of modern celebrity in English Canada, focusing in particular on the role of mass media and bureaucratic policy in the production, dissemination, and consumption of celebrity by Canadians across the twentieth century. Reading celebrity as a function or mode of being and moving in the public sphere, this project historicizes women’s access to that sphere: it examines how ideological constructions of gender and fame have shaped how women in Canada have been able to access and use the tools and technologies of celebrity, and it argues that these conditions have had an impact on how women represent themselves in public life-writing texts. These celebrity autobiographies, this project demonstrates, not only narrate gendered experiences of celebrity but, in their rhetorical strategies and publication conditions, reveal the cultural climate of being and speaking as a famous woman at different historical junctures. In tracing the trends, tactics, and experiments in self-representation over the century, this project is able to uncover and examine the ideological and cultural pressures exerted on public women to perform particular identities and how these women attempted to manage, contest, and negotiate these conditions.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)

abstract: "Women's Celebrity in Canada: Contexts and Memoirs, 1908-2011" examines the autobiographies produced by famous Canadian women across the twentieth century. It contextualizes the production of these texts by documenting the conditions under which women cultivated fame in Canada. The autobiographies of these women are read as tools for managing celebrity and their form and content is examined for what they can tell us about the condition of being and speaking as a famous woman at different historical junctures.


title: The Design and Testing of a Waterwaste Treatment Process suitable for Arctic Application

contributor:
Benedek, Andrew
Civil Engineering

subject: design, test, potential package sewage treatment, Arctic environment

abstract:
The purpose of the project was to design and test the components of a potential package sewage treatment plant suitable for the Arctic environment. The designed treatment plant was simplistic in concept while utilizing the advantages of both biological and physical-chemical treatment.
The system was tested over a ten-week period. The emphasis of the testing was on treatment of high-strength wastes. In addition the effects of temperatures and system start-up-shutdown conditions were assessed. The results indicated that the system operated well under most of the conditions tested. Both the physical-chemical and biological processes complemented each other with the former providing the necessary treatment at start-up and the latter providing low cost treatment once the system had been in. operation for a month.
With the high degree of treatment performance achieved, it was felt the process was feasible for Arctic application. However, further testing was recommended to develop the complete package unit.

abstract: Thesis

abstract: Master of Engineering (ME)


title: Archeometry of Five Pleistocene Sites as Inferred from Uranium and Thorium Isotopic Abundances in Travertine

contributor:
Schwarcz, H. P.
Geology

subject:
archaeology
Uranium
Thorium
Pleistocene
Neanderthal
Mousterian culture

abstract:
The U/Th dating method has been applied to five archeological sites in France. The U/Th method relies upon the co-precipitation of uranium with calcium carbonate in speleothems formed in caves. Because 230Th forms in the calcite from the decay of 234U a radiometric clock is begun in the newly deposited calcite. Dates are derived from measuring the isotopic abundances of the uranium and thorium in the calcite. For many archeological samples, preroasting of the sample before analysis is necessary to improve the yields. Normally, relative dates for archeological sites are derived from the comparison of paleoclimatic interpretations determined from sedimentological, faunal, and palynological studies of the cave sediments with global climatic records. These methods have established that the Mousterian culture and Neanderthals appeared in Europe at the beginning of the Würm, 80 Ka BP. Absolute dates determined for samples from Lachaise, Montgaudier,
Pech de l'Aze, Abri Vaufrey, and Grotte 13, where archeological or faunal material is associated stratigraphically with speleothems sampled, have established that there were several regional climatic phenomena experienced in southern France. These events are dated at 80 to 120 Ka BP, interpreted to be the Riss/ Würm interglacial, and at 38 to 50 Ka, interpreted to be the Würm I/II interstadial. Furthermore, archeological materials and human skeletal remains associated with these sites and the speleothems therein, have proven that the Nean~erthals must have evolved prior to 150 Ka BP, but that they did not develop their Mousterian culture until about 125 Ka BP.

abstract: Thesis

abstract: Master of Science (MSc)


title: Controlled Solidification of Eutectic Cast Iron

contributor:
Kirkaldy, J.S.
Purdy, G.R.
Metallurgy

subject: Eutectic, alloys, electron-beam, iron-graphite

abstract:
Eutectic Fe-C, Ni-C and Fe-C-Si alloys have been solidified
directionally in an electron-beam floating zone apparatus under carefully
controlled conditions and the resulting morphologies in these alloy
systems have been studied as a function of rate. In addition, the
transition from the stable iron-graphite (grey iron) to the metastable
iron-iron carbide (white iron) mode has been observed and has been
related to the iron-carbon/iron-iron carbide double phase diagram by
means of undercooling measurements. Interlamellar spacing measurements
carried out on both the graphitic and carbidic modes using material of
the same composition and purity under identical experimental conditions
showed a λaR-1/2 and a λaR-1/3 relationship in the iron-graphite and
iron-iron carbide eutectic systems, respectively.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: A Perturbed Angular Correlation Study of Hafnium

contributor:
Cameron, J.A.
Physics

subject: Lutetium 177 ions, iron, nickel, impurity

abstract:
Lutetium 177 ions were implanted in iron and nickel foils using a mass separator. The rotations of the angular correlation pattern caused by the hyperfine fields acting on the implanted nuclei were measured for the 71-250 keV and the 208-113 keV cascades in the beta-decay product Hafnium 177. Using measured data, the g-factor for the 250 keV spin 11/2, second excited state in Hf177 was determined, as were the internal fields acting on the Hf177 impurity in iron and nickel.
The results are as follows:
g11/2 = 0.277 ± 0.080 HFe(int) = -133 ± 7 k0e HNi(int) = -58.6 ± 8 k0e

abstract: Thesis

abstract: Master of Science (MSc)


title: The Crystal Structures of CsCH₃SO₃, LiN₂H₅SO₄, and K₂Cr₂O₇

contributor:
Brown, I.D.
Physics

subject:
X ray diffraction
cesium methylsulfonate
lithium hydrazinium sulfate
triclinic potassium dichromate
structures

abstract: X-ray diffraction experiments have been used to determine the structure of cesium methylsulfonate (CsCH₃SO₃), lithium hydrazinium sulfate (LiN₂H₅SO₄), above 160ºC and triclinic potassium dichromate (K₂Cr₂O₇). The solved CsCH₃SO₃ structure is compared with BaSO₄ and the CsCH₃SO₃⁻¹ ion stereochemistry is dicussed in terms of a current theory of bonding for such groups. The previously known structure of room temperature ferroelectric LiN₂H₅SO₄ has recieved additional refinement and a comparison is made with the structure determined above 160ºC. The symmetry and structure  found for K₂Cr₂O₇ are compared with similar compounds and predictions are given for the yet unsolved structures of other K₂Cr₂O₇ phases. The first accurate data for the Cr₂O₇⁻² ion stereochemistry is presented. This ion is compared to similar ones, and the possibility of extending a bonding theory to such ions involving chromium is discussed.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: An Examination of Aristotle's Concept of Matter in the Context of Change

contributor:
Georgiadis, C.
Philosophy

subject: philosophy Aristotle causality change

abstract: The concept of matter is discussed by Aristotle in the context of investigations dealing with the issues of causality, substance, and change. The following inquiry focusses (sic) on the discussion of matter in the context of change by analysing the two accounts of change that Aristotle gives in the first book of the Physics and the ninth book of the Metaphysics, respectively. The two schemas of change are outlined and the development of the concept of matter is followed from the hypokeimenon of accidental change, to the primary matter of elemental change, to the matter that underlies substantial change and finally to the potential of the second model of change.

abstract: Thesis

abstract: Master of Arts (MA)


title: Interferon-gamma Mediated Host Responses to Enteric Pathogen, Citrobacter rodentium

contributor:
Coombes, Brian K.
Biochemistry and Biomedical Sciences

subject: A/E pathogen, EPEC, Citrobacter rodentium, host response, microbiology, enteric pathogen, natural killer cell, interferon-gamma

abstract: Diarrheal disease caused by attaching and effacing pathogens, such as enteropathogenic E. coli (EPEC), is a worldwide health concern. As the second leading cause of diarrheal-related death in young children, new investigations into host defense against EPEC, as well as future therapeutics, is greatly needed. To elucidate the host immune responses to these enteric pathogens, the attaching and effacing (A/E) murine pathogen, Citrobacter rodentium, has been widely used. It is well understood that C. rodentium infection induces a robust Th1 response within the host. Yet how these pleiotropic IFNγ immune responses are initiated, propagated, and the accessory immune cell types involved remains poorly understood. In this thesis, I investigated how innate immune cell types such as natural killer cells, which are significant producers of IFNγ, mediate these Th1 directed responses. This work identified that both NK and NK-like innate lymphoid type 1 cells (ILC1s) are capable of producing IFNγ in response to C. rodentium, and NK cells rapidly increase in numbers within the colon during the early stages of infection. Depletion of these cell types causes a delayed Th1 CD4+ T cell response within the colon, resulting in increased bacterial load, and greater degree of colonic pathology at later time points. Additionally, depletion of these cells results in decreased CXCL9 chemokine expression in mice. I later determined that CXCL9 exhibited direct antimicrobial action against Citrobacter in vitro. Depletion of this chemokine in vivo, in the absence of adaptive immune responses, or its receptor CXCR3, results in increased mortality rates, elevated bacterial loads, greater degree of pathology, and deeper penetration of bacteria within the colonic crypts. These data indicate a potential direct antimicrobial role for this IFNγ-induced chemokine, independent of its known properties for the homing of T cells to the site of infection. These findings demonstrate the importance of accessory IFNγ-producing immune cells in not only mediating Th1 CD4+ T cells responses, but also other innate host defense mechanisms against A/E pathogens.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: HEAR THIS, READ THAT; AUDIOVISUAL INTEGRATION EFFECTS ON RECOGNITION MEMORY

contributor:
Shore, David I.
Psychology

subject:
Multisensory Integration
Audiovisual
Recognition Memory

abstract: Our experience with the world depends on how we integrate sensory information. Multisensory integration generates contextually rich experiences, which are more distinct and more easily retrievable than their unisensory counterparts. Here, we report a series of experiments examining the impact semantic audiovisual (AV) congruency has on recognition memory. Participants were presented with AV word pairs which could either be the same or different (i.e., hear “ring”, see “phone”) followed by a recognition test. Recognition memory was found to be improved for words following incongruent presentations. Results suggest higher cognitive processes may be recruited to resolve sensory conflicts, leading to superior recognition for incongruent words. Integration may help in easing the processing of multisensory events, but does not promote the processing needed to make them distinctive.

abstract: Thesis

abstract: Master of Science (MSc)


title: Neutron Scattering of the Frustrated Magnets Ba2YOsO6 and Yb2Ti2O7

contributor:
Gaulin, Bruce D.
Physics and Astronomy

subject:
magnetism
frustration
neutron scattering

abstract: First we shall consider the rare-earth titanate Yb2Ti2O7 which has been extensively studied within the past two decades but is still not very well understood. There has been much debate over the nature of the magnetic ground state of this system with studies reporting the development of long-range order below 250mK to the absence of long-range order below 250mK. One culprit suspected of generating these differences in behaviour of the ground state is the effect of crystal growth on sample quality.  In order to address this discrepancy, measurements of the crystal-field levels of Yb2Ti2O7 were conducted on two powder samples of different composition since the exact ground state selection depends on size and anisotropy of the magnetic moment. The second focus of this thesis concerns the family of rock-salt ordered double perovskites of the form Ba2YXO6 in which X is either a 4d or 5d magnetic ion. The interplay between the strong spin orbit coupling expected for such heavy magnetic ions and frustration has been theoretically predicted to exhibit a variety of exotic phenomena. Neutron scattering is utilized to investigate the low temperature dynamics of the system Ba2YOsO6 to compare with that observed in the 4d analog, Ba2YRuO6.

abstract: Thesis

abstract: Master of Science (MSc)


title: A Conductometric and Spectroscopic Investigation of Some Solutes in Anhydrous HF

contributor:
Gillespie, R.J.
Chemistry

subject:
conductivity
hydrogen fluoride
ionization
electrolytes

abstract:
 Conductivity measurements on liquid hydrogen fluoride solutions of some simple bases and fluoroanion salts were carried out, and a set of equivalent ionic conductivities have been determined. The conductivities of electrolytes in hydrogen fluoride have been compared to those of analogous electrolytes in water and strong acid solvents. A method for the investigation of more complex electrolytes was developed.

 The mode of ionization of adducts of sulfur tetrafluoride, thionyl tetrafluoride and selenium tetrafluoride with fluoride acceptors in hydrogen fluoride has been investigated by conductivity and nmr spectroscopy. The structures of the solid adducts have also been investigated by Raman spectroscopy. The structure and stability of other sulfur-oxide-fluoride adducts have been investigated and found to differ from adducts of thionyl tetrafluoride.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: INVESTIGATING THE ROLE OF LEPTIN AND GSK-3 IN THE OSTEOGENIC  DIFFERENTIATION OF VASCULAR  SMOOTH MUSCLE CELLS

title: MECHANISM(S) OF VASCULAR CALCIFICATION

contributor: Medical Sciences (Thrombosis & Haemostasis & Atherosclerosis)

subject:
leptin
vascular calcification
vascular smooth muscle cells

abstract:
Obesity is a major risk factor for insulin resistance, type 2 diabetes, cardiovascular disease (CVD), and vascular calcification. Vascular calcification is correlated with advanced CVD and a significant predictor of cardiovascular events. Obese individuals tend to have increased levels of circulating leptin, an adipocytokine that is a significant independent predictor of cardiovascular disease.
   We have shown that daily intraperitoneal injections of exogenous leptin (125 μg/mouse/d) can promote vascular calcification in an ApoE-/- mouse model of atherosclerosis. This increase in calcification is associated with an increase in the expression of several osteoblast-specific markers and is independent of any affect on atherosclerotic lesion size. Our studies suggest that leptin mediates the osteogenic differentiation of vascular smooth muscle cells (VSMCs) to promote vascular calcification via a pathway involving the inhibition of glycogen synthase kinase (GSK)-3 activity.
   Other studies have suggested that endoplasmic reticulum (ER) stress-induced GSK-3 activity promotes the development of atherosclerosis. Therefore, we hypothesized that during the progression of vascular disease, GSK-3 functions as a checkpoint for VSMCs at which cells can commit to: i) de-differentiation, thereby contributing to atherosclerosis, or ii) osteogenic differentiation, thereby contributing to vascular calcification. We investigated the effects of modulating GSK-3 activity on the differentiation of VSMCs in vitro. We found that many of the molecular tools that are typically used to modulate ER stress can promote the expression of osteoblast-specific markers and the osteogenic differentiation of MOVAS cells. However, because many of these interventions affect multiple pathways in MOVAS cells, the specific role of the ER stress – GSK-3 pathway is difficult to discern. Future studies are required to determine the effects of direct modulation of GSK-3 on vascular calcification and to delineate the mechanisms/effects of various ER stressors in the osteogenic differentiation of VSMCs.

abstract: Thesis

abstract: Doctor of Philosophy (Medical Science)


title: Determination of Ion Exchange Parameters for Binary Systems and Application to Ternary Systems

contributor:
Baird, Malcolm H.I.
Chemical Engineering

subject:
ion exchange
equilibrium data
mathematical model
binary system
kinetic effect

abstract:
Ion exchange equilibrium data can be used to predict the viability of a proposed process. Ion exchange equilibria have been studied considerably since the 1950's but the complexity of the basic research has tended to reduce its direct usefulness to the practising engineer. This research has been undertaken to determine if a moderately simple method of experimentation and analysis could be applied to predict ion exchange equilibria to within limits of accuracy acceptable to engineers.

 The first step in the research was to develop a simple mathematical model for a binary system to calculate the selectivity coefficient and resin capacity from batch experiments. The model was successfully applied for the exchange of Na+ with five heavy metal ions: Ni²⁺; Cu²⁺; Cd²⁺; Pb²⁺ and Zn²⁺ on a typical commercial resin (Dowex HCR-W2). The binary parameters were then used to predict the equilibrium values for several ternary systems. From these ternary experiments, it was determined that binary data can be used to predict ternary systems if the selectivity coefficients of the two ions involved are either almost equal or differed by at least a factor of five. A kinetic effect was proposed to explain the discrepancies observed between the predicted and experimental values for the intermediate ratios of selectivity coefficients of the involved ions, although further work is required to confirm this hypothesis.

 Several packed bed experiments were performed to check some of the results from the binary and ternary system experiments and as exploratory work for future research. These experiments confirmed the capacity data calculated from the binary system experiments and were consistent with the trends observed in the ternary system experiments.

abstract: Thesis

abstract: Master of Engineering (ME)


title: Assessing Structure-Function Relationships in a Mouse Model of Emphysema using Ventilation and Perfusion (V/Q) SPECT/CT

contributor: Medical Sciences (Division of Physiology/Pharmacology)

subject: Pre-clinical Imaging, SPECT/CT, Emphysema, Ventilation/Perfusion Ratio

abstract:
Emphysema is a condition of the lung characterized by abnormal, permanent enlargement of the airspaces distal to the terminal bronchiole, accompanied by a destruction of their walls. The primary pathogenesis of emphysema is poorly understood. One of the major issues of COPD is that no diagnostic tests are sensitive enough to detect early disease. Standard pulmonary function tests (PFTs) do not explain the underlying pathophysiology of airflow limitation, nor do they provide information on how COPD may be affecting pulmonary blood flow. Functional imaging, specifically ventilation and perfusion (V/Q) Single Photon Emission Computed Tomography (SPECT), is a sensitive tool that can provide information on pulmonary function in different lung regions. When V/Q images are co-registered to CT, regional analysis can be coupled to structural information. The objective of this study was to examine how emphysematous change identified and localized by CT density based thresholds affects lung function as measured by V/Q SPECT in a mouse model of the disease.
A dose response study was conducted where Female BALB/c mice were exposed intranasally to 0.0, 0.5, 2.5 and 5.0 units (U) of porcine pancreatic elastase (PPE). V/Q SPECT/CT scanning was performed 45 days post exposure, followed by measurement of lung compliance using the Flexivent® rodent ventilator 46 days post exposure. Whole lung slice analysis software was used to quantify airspace enlargement and alveolar capillary density from histological sections of the lung. CT pulmonary angiography (CTPA) was also performed on controls and mice exposed to 5 U PPE to examine vascular density.
In this mouse model of emphysema, V/Q SPECT was useful in quantitatively examining how ventilation and perfusion is affected in mild and severe emphysema while providing evidence of low log(V/Q) ratio in otherwise normal lung densities. This could be caused by airflow obstruction as a result of widespread narrowing or loss of small conducting airways. Low log(V/Q) ratio is caused by mild emphysema indicating airflow obstruction or dysfunctional hypoxic vasoconstriction in underventilated regions of the lung. The majority of severely emphysematous regions of the lung have matched but equally reduced log(V/Q), although low log(V/Q) is also present. Pulmonary hypertension in response to chronic hypoxia may explain our finding of reduced perfusion activity and vascular density in emphysematous lung, but further research is required to investigate the presence of this pathology.
V/Q SPECT was also shown to be superior in the detection of emphysema compared to CT and Flexivent measured lung compliance providing evidence towards shifting the current assessment and monitoring paradigms. Due to the widespread availability of this imaging technique, it could be used to screen asymptomatic smokers for early disease and identify and locate pathology so therapies targeting the appropriate disease pathway can be prescribed. This will inevitably improve patient care.

abstract: Thesis

abstract: Master of Science (MSc)


title: B.O.F. Control

contributor:
Kay, D.A.R.
Chemical Engineering

subject:
Basic Oxygen Furnace
carbon evaluation rate

abstract:
A production Basic Oxygen Furnace installation at Dominion Foundries
and Steel Ltd., Hamilton, Ontario is used to develop a method of dynamically predicting the time during steelmaking at which a specified bathcarbon content will be reached.

The carbon evolution rate is calculated from continuous stack gas analysis and flow data. This information, combined with a known bath carbon content measured shortly before the end of the blow, is used to perform carbon mass balances. Bath carbon contents, calculated from these mass balances can be expressed as a function of time by a simple updated-mathematical model which is then used to predict the end point time.

A new technique for determining stack gas flow rates by utilizing an injected chemical tracer is evaluated.

abstract: Thesis

abstract: Master of Engineering (ME)


title: BURNOUT AMONG ACADEMIC CLINICIANS AS IT CORRELATES WITH WORKLOAD AND DEMOGRAPHIC VARIABLES

contributor:
McConnell, Meghan
Education

subject:
Burnout
Academic clinicians
Work stress
Administration

abstract:
Background & Rationale: Burnout syndrome (BOS) is a psychological state resulting
from prolonged exposure to job stressors. It is commonly observed in occupations with
human interaction. The most visible impact of burnout is a decrease in work performance
and the overall quality of service, and within healthcare professionals, BOS correlates
with reported medical errors. Academic healthcare workers are particularly predisposed
to experience BOS given the high level of work-related stress that characterizes their jobs.
There is a scarcity of studies investigating burnout in academic clinicians.
Objective: The goal of this study is to identify the prevalence of burnout in academic
clinicians in the Faculty of Health Sciences at McMaster University and investigate
potential demographic and workload variables that contribute to self-reported measures of
burnout.
Methods: A novel modification to the MBI (Maslach Burnout Inventory) scale was
distributed to all academic clinicians at McMaster University through an internet-based
survey. The MBI scale was modified to reflect three hypothesized sources of burnout for
academic clinicians: interactions with students/trainees, interactions with patients and
interactions with administration. The scale comprised of three dimensions of burnout:
Emotional Exhaustion (EE), Depersonalization (DP) and Personal accomplishment (PA).
Demographic and workload data were also collected.
Results: Factor analysis and internal consistency showed that the modified MBI scale
was associated with valid and reliable scores, respectively, within this population. Results
showed that academic clinicians experienced high levels of burnout due to administration interactions relative to that attributed to patients and students. The prevalence of burnout
for the EE subscale are: administration = 51.8%;, patients = 26.4%, students = 11.7%);
for the DP subscale: administration = 44.8%, patients, = 24.5%, students, = 9.8%); and
the PA subscale: administration =16.3%, patients = 33.4%, students =33.7%). Regression
analyses suggested that young age, surgical specialty, low academic rank, academic main
practice, female gender, numerous night shifts and living alone contribute to EE and DP
subscales. Meanwhile, high number of patients under their care was shown to contribute
to increasing PA.
Conclusion: Burnout Syndrome is prevalent among academic clinicians at McMaster
University. The major source of burnout was attributed to interactions with administration.
Surgical specialties and young faculty staff members correlated with burnout. Further
studies are needed to further characterize the nature of administrative interactions that
contribute to burnout and to solidify other contributing variables.

abstract: Thesis

abstract: Master of Health Sciences (MSc)

abstract: Burnout syndrome (BOS), is a syndrome characterized by depleted energy resources, dealing with  people as if they were impersonal objects and with decreased personal accomplishment. Physicians and educators are at risk of the syndrome. BOS has been linked to providing suboptimal care and medical errors. Our study investigated the prevalence of BOS in academic clinicians (physicians who work in a teaching hospitals) since they have two roles; physicians and educators. We also investigated any demographic variables related to BOS. We have created a novel modifications to Maslach Burnout Inventory ( one of the main scales used to measure BOS). We have established its validity and reliability. Our study showed that almost 50% of academic clinicians have burnout. Major source is due to their interaction with administration, followed by interaction with patients and lastly interaction with studens. Surgeons, females, young age, single, increased night on-call and low academic rank were predictors for burnout. A larger scale study is needed to pinpoint the kind if administrative interaction that is related to BOS. The ultimate goal is to make our teaching hospital work environment more friendly and transpiring to better patient care.


title: MODULATION OF CORTICOPSINAL OUTPUT TO THE HAND VIA SOMATOSENSORY AFFERENT INPUT

contributor:
Nelson, Aimee
Kinesiology

subject: Sensorimotor Neurophysiology

abstract: The primary somatosensory cortex (SI) and primary motor cortex (M1) receive somatosensory afferent input to influence motor hand circuitry and control. Much of the literature has investigated this relationship extensively using animal models.  In contrast, much of these relationships and neural mechanisms are still not well understood in humans. The present work investigated homosynaptic and hetersynaptic protocol’s modulatory effects on SI and M1 sensorimotor circuitry. Experiment 1 used the homosynaptic protocol continuous theta-burst stimulation (cTBS) over SI and M1 and measured motor evoked potentials (MEP) and short-latency afferent inhibition (SAI). CTBS over M1 suppressed MEPs and did not alter SAI.  In contrast, cTBS over SI facilitated MEPs and decreased median and digital nerve evoked SAI. Experiment 2 used the heterosynaptic protocol rapid-rate paired associative stimulation (rPAS) on SI and M1. SAI and MEPs were measured to investigate the sensorimotor changes following rPAS.  Results indicated minimal decreases in SAI but increases in MEPs following SI rPAS. However, M1 rPAS lead to significant reductions in SAI and increased MEPs. The findings from this thesis highlight the selective modulation of sensorimotor circuitry through the use of various stimulation protocols.

abstract: Thesis

abstract: Master of Science in Kinesiology


title: Inhibition of Influenza A Replication Using Cell Penetrating Protein Mimetics

contributor: Medical Sciences (Molecular Virology and Immunology Program)

subject:
Influenza virus
mimetics
peptide
microbiology
molecular modeling
virology
polymerase
ZMM

abstract: The Influenza virus is a major human respiratory pathogen responsible for seasonal ‘flu’ outbreaks and sporadic global pandemics. The Influenza polymerase complex is necessary for viral RNA synthesis and full virulence and requires the assembly of three conserved subunits: PA, PB1 and PB2. A recombinant chimeric protein mimetic consisting of the N-terminus (20 amino acids) of PB1 fused to Maltose Binding Protein (MBP) and Tat Nuclear Localization Signal (NLS) was designed and purified with the aim of inhibiting the assembly of the polymerase by mimicking PB1. The cell-penetrating protein mimetic was shown to efficiently enter the cell nucleus and prevent assembly of the Influenza polymerase, thus inhibiting viral replication. When MDCK cells were incubated with the mimetic and subsequently challenged with Influenza A virus, viral replication decreased up to 98% at 50 µM. Using a nuclear extraction assay, the mimetic was shown to efficiently penetrate the plasma membrane and enter the host nucleus. GST pull-down assays showed that the mimetic interacts with PA. Molecular modeling was then employed to predict the improved hypothetical free energy of binding between PB1 and PA and determined two significant substitutions for PB1 threonine at position six: glutamic acid (T6E) and arginine (T6R). These mutations increased potency of the mimetic at 25 µM (71% for T6E and 77% for T6R compared to 36% for the native construct) and 12.5 µM (27% for T6E and 70% for T6R compared to 16% for the native construct), suggesting a more stable interaction with PA consistent with molecular modeling. Using various in vitro assays, the mimetic was shown to be non-toxic to host cells. Targeting critical protein-protein interactions using a peptide fused to a cell-penetrating carrier protein presents a novel and intriguing approach in designing anti-viral therapeutics.

abstract: Thesis

abstract: Master of Science in Medical Sciences (MSMS)


title: Geomorphic and Hydrologic Information from High Altitude Aerial Photography

contributor:
Howarth, P.J.
Geography

subject: high, altitude, photography, surficial deposits, aerial, pattern geometry, hydrology

abstract:
High altitude photography represents a new, potentially valuable,
but largely untested information source for the interpretation of surficial
deposits. It differs significantly in sensitivity and perspective from
conventional aerial photography. It posesses different values and
limitations which must be evaluated in their own right.
The photography examined is shown to provide an excellent and
reliable record of stream pattern geometry, and of stream flow regularity
characteristics which are related to deposit slope form and material characteristics.
The important image density component of the photographic
record must be corrected for distortion but shows a consistent relationship
with characteristics of near surface deposit hydrology.
Photography and imagery from high or orbital altitudes will soon
be a widely if not universally available information source. It is evident
that such information can make a valid and useful contribution in geomorphic
studies. This information is complimentary to existing techniques
of data collection, and likely to realize substantial savings in time and
efficiency while permitting wider application of findings.

abstract: Thesis

abstract: Master of Science (MSc)


title: Clarifying the nature of face processing deficits in adults with autism spectrum disorder

contributor:
Rutherford, M. D.
Psychology

subject:
face processing
autism spectrum disorder
norm-based coding
face aftereffects

abstract: Individuals with autism spectrum disorder (ASD) have difficulties in many areas of social cognition including face perception. Decades of research examining face processing abilities in ASD populations have yielded equivocal results. The current thesis includes a series of experiments intended to clarify the nature of the face processing deficits seen in ASD. In Study 1 I examined norm-based coding of facial identity in adults with ASD. I measured identity aftereffects in adults with and without ASD and found no significant group differences. In Study 2 I examined simple (Experiment 1) and opposing (Experiment 2) figural aftereffects for male and female faces and found no significant group differences as adults with ASD. In Study 3 I examined perceptual strategies employed by adults with ASD when processing emotional facial expressions and found that adults with ASD employ a rule-based strategy. Finally, in Study 4 I examined what drives face processing deficits in adults with ASD; deficits in processing emotional information in faces or a deficit in processing socially complex information in faces. I found that adults with ASD had a deficit in discriminating basic and complex emotional facial expressions, suggesting that emotion-perception demands are associated with poor face processing in ASD. The results of the studies demonstrate that adult with ASD show typical perceptual mechanisms underlying face perception, use an atypical perceptual strategies when processing facial expressions, and have a specific deficit in processing emotional expressions.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: TRANSIENT ELECTRO-THERMAL ANALYSIS OF TRACTION INVERTERS

contributor:
Emadi, Ali
Mechanical Engineering

subject:
Electro-Thermal Analysis
Power Electronics
Reliability
Junction Temperature Estimation

abstract:
The thermal design constraint of power electronic converters under the specific power loss and heat sink is mainly determined by the maximum permissible junction temperature of the power devices. As the power density and switching frequency increase, transient electro-thermal models become more and more important for the thermal management system design of the power electronic converters. In traction inverters, the junction temperature has huge variation because the fundamental frequency and phase currents vary significantly during the load cycles. Thus, the junction temperature estimation becomes extremely important for the reliability of traction inverters.
In this thesis, the transient electro-thermal analysis of a traction inverter considering the inter-dependency of the power losses and junction temperature in an iterative process is implemented. Considering the impact of circuit stray parameters on the switching loss, the temperature dependent power loss model is built based on the datasheet values and the measured switching losses. A state-of-the-art thermal model of the entire inverter including the power modules and the heat sink is developed considering the thermal coupling effects of multiple power devices. By using transient thermal simulation, the linearity of the heat transfer process of the entire traction inverter is verified. The impact of the material thermal properties on the thermal impedance is also presented. In addition, the accuracy of the combination of the thermal subsystem models is verified with simulation. The developed transient electro-thermal model is then used to simulate the junction temperature profiles of the inverter under different operating conditions. Finally, the developed model is experimentally verified. By considering the thermal impedance of the thermal grease layer, the simulation results match with the experimental results very well.
The proposed electro-thermal model can provide important information for the thermal management system design, package optimization, long-term reliability analysis, and maximum rating characterization of the traction inverters.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Muscle Contributions to Knee Loads in Healthy Young Women

contributor:
Maly, Monica
Rehabilitation Science

abstract:
Lower extremity muscles are primary contributors to knee loading during static and dynamic activities. The underlying philosophy of this thesis contends that a more robust understanding of the relationships between muscle function and the loading environment in the healthy knee is needed for clinicians to prescribe effective lower extremity muscle training programs. The primary objectives were to (i) identify changes in knee mechanics and muscle function during gait, static squats and lunges after lower extremity neuromuscular fatigue, (ii) explore relationships between knee loading, and peak knee extensor and flexor strength and power, and (iii) identify isometric standing muscle training postures which elicit minimal medial knee loads.
In the studies addressing objective (i), isotonic lower extremity fatigue reduced the peak knee extension moment during gait, decreased vastus lateralis activation, and decreased mean knee moments during static lunging. These findings indicated that fatigue altered muscle recruitment strategies and may have concurrently altered the knee loading environment during these submaximal tasks. However, these biomechanical alterations are not consistent with those in knee osteoarthritis or ligament injury. In the studies addressing objective (ii), peak knee extension torque and power were important in describing healthy knee loading during the early and late stance phases of gait, respectively. Finally in the studies addressing objective (iii), isometric muscle training postures were identified which targeted quadriceps and hamstrings muscle activation without overloading the medial compartment of the knee. Muscle activation levels required to increase lower limb torque production capacity can be achieved by performing squats and lunges and these postures elicit lower knee moments than those experienced during gait.
This work expands the understanding of healthy knee function and the relationships between muscle function and mechanical knee loading. These insights will contribute toward the future creation of muscle training programs and guidelines for knee OA or ACL injury.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: THE MINI MILESTONES ASSESSMENT (MINI-MAS), A DIRECT OBSERVATIONAL TOOL TO ASSESS CLINICAL MILESTONES IN THE ERA OF COMPETENCY-BASED EDUCATION

contributor:
Dore, Kelly
Health Sciences

subject: Competency Milestones Assessment

abstract:
Background: Competency based medical education will move training programs away from a time based standard to a model of competence and milestones. Assessment, observation and feedback are key ingredients to successful implementation. Work based assessment tools will be an important part of a multi-modal programmatic assessment for learners.
Purpose: The purpose of the study was: 1) to facilitate the development and implement a pilot competency-based curriculum into the general pediatric component of the PGY 1 year at McMaster University, pediatric residency program, 2) to develop a tool, the Mini Milestones Assessment (Mini-MAS) to assess six medical competencies and progression through milestones using the Dreyfus Developmental Model and to pilot the tool in the general pediatric rotations for the PGY 1 and 4 residents and 3) to test the reliability, validity, acceptability and feasibility of the Mini-MAS tool.
Method: Twelve PGY 1 residents at McMaster Children’s Hospital were required to complete 40 observations (10 history taking, 10 physical exam, 5 clinical reasoning, 5 communication with families, 5 communication with staff and 5 collaboration) during their general pediatric component of the 2013-2014 academic year.  These same competencies were also observed for 9 PGY 4 residents over the same competencies over the same time period although this group was required to complete only 15-20 encounters. Following the study period, a survey was administered to the residents and faculty to assess acceptability and feasibility of the Mini-MAS tool. Kane’s validity framework, which is divided into four components (scoring, generalization, extrapolation and decision), was used to evaluate the Mini-MAS tool.
Results: PGY 1 and PGY 4 residents had an average of 36 and 16 observations completed, respectively, across a wide variety of settings and clinical problems with multiple assessors.  The scale of the Mini-MAS tool was used appropriately. The tool was able to differentiate between the PGY 1 and PGY 4 learners and showed progress of the PGY 1 learners through the academic year. The G coefficient overall for the Mini-MAS tool was 0.8 for the PGY1 residents and 0.5 for the PGY 4 residents. Correlation between the six competencies assessed was low, achieved by only one competency being observed and having grounded anchors. Learners and faculty were satisfied with the tool. The tool allowed learners to be observed more frequently and receive timely valuable feedback.
Conclusion:  A pilot competency based curriculum for PGY 1 residents was successfully implemented. The Mini-MAS tool added, as a formative assessment mode to a multi-modal assessment program will benefit the trainee, by increasing their observations and providing residents with valuable feedback. The assessment will inform residents where they stand with respect to their level of training, what competencies they can improve on and how they can make such improvements.

abstract: Thesis

abstract: Master of Science (MSc)


title: EXPERIMENTAL METHODS TO ELUCIDATE LUNG EXTRACELLULAR MATRIX EFFECTS ON FIBROBLAST/MYOFIBROBLAST PHENOTYPE

contributor:
Janssen, Luke
Kolb, Martin
Medical Sciences

abstract:
Introduction
	Idiopathic pulmonary fibrosis (IPF) is a debilitating restrictive lung disease with no curative treatments. Accumulation of lung extracellular matrix (ECM) and myofibroblasts are two hallmarks of this disease. Previous studies have demonstrated that an increase in lung ECM in the formation of scar tissue promotes further myofibroblast accumulation exacerbating IPF disease progression. Lung ECM influence on myofibroblast phenotype is not fully understood. Methods to elucidate lung ECM effects on myofibroblast phenotype were developed in this thesis.
Aim
	This study sought to determine whether lung ECM could modulate fibroblast/myofibroblast phenotype.
Methods
	Histological and western blot analyses were used to evaluate lung ECM isolation through manual decellularization of whole rat lungs with sodium deoxycholate (SDC). To evaluate the effects decellularization has on lung ECM, histological analyses were conducted to compare sodium dodecyl sulfate (SDS) and SDC ability to retain collagen and elastic fibers following decellularization. Histological examination of drop-wise and whole lung reseeding techniques of decellularized lung ECM were assessed.  To further mimic in vivo conditions, a novel lung bioreactor incorporating physiological lung respiration and vascular perfusion was developed. The effects of stiff cell culture plastic on alpha smooth muscle actin (α-SMA) phenotype of control and IPF-derived myofibroblasts were evaluated. Western blot, immunohistochemisty, immunocytochemistry, and immunofluorescent analyses were used to evaluate whether normal lung ECM could reverse the α-SMA positive phenotype of lung myofibroblasts.
Results
	Manual decellularization with SDC was effective at decellularizing whole rat lung. Histological examination showed that SDC was more effective at retaining collagen and elastic fibers than SDS following decellularization. Whole lung reseeding technique was far superior compared to the drop-wise technique at consistently reseeding lung ECM. Lung bioreactor maintained A549 cells within decellularized whole lung for 3 days. Furthermore, normal lung ECM was capable of reversing α-SMA positive phenotype of both control and IPF-derived myofibroblasts.
Conclusions
	Methods developed in this thesis advances the understanding of decellularization and reseeding techniques required to study lung ECM on cell phenotype. Interestingly, and contrary to previous work, it appears that α-SMA phenotype of myofibroblasts was reversible when cultured on normal lung ECM.

abstract: Thesis

abstract: Master of Health Sciences (MSc)


title: ROLE OF MYOCARDIN RELATED TRANSCRIPTION FACTOR-A IN TRANSCRIPTION GROWTH FACTOR BETA-INDUCED EPITHELIAL TO MESENCHYMAL TRANSITION OF LENS EPITHELIAL CELLS

title: ROLE OF MRTF-A IN EPITHELIAL TO MESENCHYMAL TRANSITION IN THE LENS

contributor:
West-Mays, Judith
Biomedical Engineering

subject: Lens, PCO, EMT, MRTF-A, TGFβ, MMP, αSMA

abstract:
Transcription growth factor beta (TGFβ) mediated epithelial to mesenchymal transition (EMT) of lens epithelial cells (LEC) is known to cause posterior capsular opacification (PCO). In this work, I have focused on the TGFβ-induced EMT pathway governed by the cellular actin cytoskeleton dynamics.
	This study is the first to report the involvement of transcription co-factor myocardin related transcription factor-A (MRTF-A) in TGFβ-induced EMT in the lens. Using rat lens epithelial explants, I have conclusively established that in LECs, TGFβ induces nuclear migration of MRTF-A leading to induction of αSMA expression. Furthermore, I have manipulated the intracellular translocation of MRTF-A indirectly using actin binding drugs and established that inhibiting nuclear migration of MRTF-A reduces αSMA production by the cells. In addition, direct manipulation of MRTF-A using adenoviral vectors carrying modified gene constructs show that presence of functional MRTF-A construct in the nucleus is necessary to trigger αSMA expression by causing EMT.
	In order to understand the involvement of matrix metalloproteinase -9 (MMP-9) in this specific pathway, explants were treated with an MMP2/9 inhibitor and rhMMP9. I have established that rhMMP-9 does not significantly affect the intracellular migration of MRTF-A. Nevertheless, gene expression studies showed that MMP-9 induces the expression of MRTF-A. Taken together, I believe MMP-9 functions through a feedback mechanism controlling MRTF-A expression in the cell. However, the presence of MMP-9 is necessary but not sufficient for induction in MRTF-A nuclear translocation.
	Overall, the work presented in this thesis demonstrates for the first time the presence of MRTF-A in LECs and successfully shows that the intracellular translocation of MRTF-A as an integral part of TGFβ induced EMT. Therefore, in the future, MRTF-A may be used as a successful target molecule to inhibit in order to prevent EMT leading to PCO.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Obsidian Circulation Networks in Southwest Asia and Anatolia (12,000 - 5700 B.P.): A Comparative Approach

contributor:
Carter, Tristan
Anthropology

subject:
Network analysis
Obsidian circulation

abstract:
This Master’s thesis documents and interrogates networks of regional interaction
in southwest Asia and Anatolia during the Neolithic and Chalcolithic periods (12,000 -
5700 B.P.) by comparing the variable use of obsidian raw material variants at 151 sites.
This represents an effort to bring together all of the obsidian sourcing data produced for
this broad archaeological setting, and evaluate it from a heterarchical approach that
highlights the distributed nature of regional interaction. Heterarchical perspectives are
applied here through the use of network analysis in order to highlight clusters of sites that
are more connected to each other than they are to others in the system, and to determine
the roles of each site in the system’s overall structure. As such, order is highlighted as a
result of the organization of data-driven ties among sites, which are unrestricted by
presumptions relating to geographical position or of pre-defined rank. The results are
compared with more established models of regional interaction in the settings of interest,
and heterarchical perspectives through network analysis are shown to complement
common understandings of broad-scale connectivity at various points in time.

abstract: Thesis

abstract: Master of Arts (MA)


title: Assessment of Various Thermoplastic Masks Used for Radiation Therapy Immobilization in Terms of Shrinkage and Pressure

contributor:
Ostapiak, Orest
Medical Physics

abstract:
The aims of this study are first, to assess and compare the amount of
deformation for seven thermoplastic masks from three different manufacturers
[Aquaplast RT-1889YS (Aqua variable perf), Fiberplast RT-1889KYS (Fiber variable
perf), Embrace RT-8320 (Embrace), AccuPerf IMRT head mask RG461-4SHT
(AccuPerf), Fiberplast RT-1889KS (Fiberplast), Aquaplast RT-1989S (Aqua thick), and
Aquaplast RT-1889S( Aquaplast)] using time lapse photography, and second, to
measure the amount of pressure exerted by each mask on a rigid head phantom
using pressure sensitive film.
For the first aim, all masks were marked with fiducial points located near
forehead, nose, and chin. The masks were fabricated on a rigid head phantom
following manufacturer instructions. Each mask was mounted on a plastic mounting
tray, and photographed in a sagittal view over the span of one week. The fiducial
coordinates were determined by a center of mass algorithm. A scale factor was
determined by photographing a graph sheet mounted in place of the mask.
For the second aim, the pressure exerted by each mask was evaluated by
mounting the mask on the head phantom after sandwiching a strip of pressure
sensitive film between the two at three anatomical locations: the forehead, nose,
and chin.
Measurement of translation in the posterior direction did not give
reproducible results as direct caliper measurements did not agree with those from
the time-lapse photography technique.
In the superior/inferior direction, the Embrace mask showed the greatest
deformation at forehead and nose areas (1.069±0.017mm (inferiorly), and
0.432±0.010mm (inferiorly) respectively), while the Aqua thick mask showed the
greatest deformation at chin area (0.970±0.016mm (superiorly)). The averaged median pressure of the masks at the forehead location were
not significantly different except for the Fiber variable perf which showed the
greatest averaged median pressure ( 0.118 MPa). At the nose location, no mask
showed a significantly different averaged median pressure. At the chin location, the
Aqua thick mask showed a significantly higher averaged median pressure compared
to the others (0.180 MPa).

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: The Historical Geography of the City of Ottawa

subject:
Ottawa
geography
Ottawa Valley
historical geography

abstract:
An abstract is unavailable.
Thesis
Bachelor of Arts (BA)


title: DIGITAL COMPENSATION OF FIBER POLARIZATION MODE DISPERSION AND INTRACHANNEL NONLINEAR IMPAIRMENTS IN COHERENT FIBER OPTIC SYSTEMS

contributor:
Kumar, Shiva
Electrical and Computer Engineering

subject:
Phase noise
PMD
Chromatic dispersion
Nonlinearity
DSP
Adaptive equalizer
DBP

abstract:
The presence of various impairments in fiber channel has forced researchers to uncover solutions to minimize those effects. With the advancement of technology, optical solutions were finally easier to implement in the system. To this day, optical compensation methods are still found to be as the best way to minimize fiber impairments. With the development of digital signal processing (DSP) and FIR techniques, coherent detection with digital signal processing (DSP) is developed, analyzed theoretically and numerically and experimentally demonstrated in long-haul high speed fiber‐optic transmission system. The use of DSP in conjunction with coherent detection unleashes the benefits of coherent detection which rely on the preservation of full information of the transmitted field. These benefits include high receiver sensitivity, the ability to achieve high spectral‐efficiency and the use of advanced modulation formats. The local oscillator (LO) of coherent receiver alleviates the need for hardware phase‐locking and polarization tracking, which can now be achieved in the digital domain. The computational complexity previously associated with coherent detection is hence significantly diminished and coherent detection is once again considered a feasible detection alternative.
In this thesis, an optical fiber communication scheme using the coherent detection method is simulated. Firstly, at the beginning of each chapter, we introduce the various compensation methods for certain optical fiber impairments which is developed by the pioneers. However, such technique does introduce enormous complexity to the system, in addition to a large cost. For that reason, the main focus had to shift to an alternative method. DSP techniques has enabled simple techniques to mitigate various impairments in fiber-optical systems.
In this thesis, the background knowledge about the structure of fiber-optical transmission system is provided. After the mathematical analysis of the various impairments (laser noise, chromatic dispersion, polarization mode dispersion and nonlinearity) in fiber-optical links, the compensation methods by using DSP techniques are provided. By the methods of fourth-power carrier recovery algorithm and feedforward carrier recovery algorithm, the phase rotation in constellation due to laser noise is compensated in QPSK systems and QAM systems, respectively. The feedforward carrier recovery algorithm has a high tolerance for laser linewidth in high-order QAM system. As for PMD compensation, on the basis of adaptive equalizers in both time domain and frequency domain achiever by the pioneers, a novel LMS algorithm is proposed in this thesis.  It has a fair comparative and steady computational complexity with the increase in the number of training blocks. The last part is the nonlinearity compensation. The DBP compensation is a popular method for nonlinearity compensation but its computational complexity is fair high (Shao J, Kumar S and Liang X., 2013). We adopt two kinds of fold-DBP which are distance-folded DBP and dispersion-folded DBP to compensate the joint impairments of chromatic dispersion and nonlinearity in dispersion-managed system. The distance-folded DBP works well in the full compensation dispersion-managed system but in the presence of RDPS, only the dispersion-folded DBP is efficient.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Development and characterization of a mouse model of HSV-2 infection during pregnancy

subject:
HSV-2
Pregnancy
Intrauterine Infection

abstract: Problem: Primary HSV-2 infection during pregnancy is associated with adverse pregnancy outcomes. However the mechanisms underlying these outcomes remain largely unknown. In this study we developed and characterized a mouse model of primary HSV-2 infection during early pregnancy and examined its effects on pregnancy and fetal outcomes. Methods of Study: C57BL/6 female mice positive for vaginal plugs were infected intravaginally (IVAG) with 10^3/10^4/10^5 PFU/mouse of HSV-2 (333) or saline (control) on gestational day (GD) 5. For comparison, female mice in diestrus stage were infected with HSV-2 at the same doses. Survival, pathology scores and vaginal viral shedding were measured post-infection. Systemic viral dissemination was examined by real-time PCR. Vaginal tissue, implantation sites, placenta and fetuses were examined by histology. Maternal serum (GD 13) and amniotic fluid (GD 8) was collected for multiplex cytokine analysis. Results: The minimum viral inoculation dose for infection in pregnant mice was 10^3 PFU of HSV-2, compared to 100-fold higher dose required to infect diestrus mice (10^5 PFU). There was a dose-dependent increase in implantation failure and number of resorptions with increasing dose of viral inoculum in pregnant mice at GD 8. In the 10^3 PFU group, although vaginal viral shedding was observed in all mice, 75% survived the infection, while all the mice in 10^4 and 10^5 PFU groups succumbed to infection by GD 13-15. There was evidence of abnormal placental morphology and necrotic fetal tissues in HSV-2 infected, pregnant mice compared to controls. Presence of HSV-2 DNA was measured in the vaginal tract, uterus (mated non-pregnant mice), and implantations of infected mated mice. HSV-2 DNA was also present in the spleen of the GD 13 time point group. Conclusions: These results indicate a 100-fold increase in susceptibility to HSV-2 infection during early pregnancy. At higher inoculation doses, IVAG HSV-2 infection spread systemically resulting in poor pregnancy outcomes and maternal mortality, especially in later gestation. At lower inoculation dose, the infection was localized in the reproductive tract and implantation sites, resulting in increased inflammation and adverse outcomes. This model will help to understand pathological mechanisms underlying adverse outcomes following primary HSV-2 infection in pregnancy.

abstract: Thesis

abstract: Master of Science (MSc)


contributor:
Weaver, John
History

subject: Disability; First World War; Rehabilitation; Pensions; Social Welfare; Canada

abstract: The following dissertation examines the little-known history of Canada’s Great War disabled. During the Great War Canada mobilized 620,000 soldiers, most of them volunteers. Nearly 120,000 would one day receive compensation for a disability incurred on, or aggravated by military service. Thousands more suffered from related injuries, diseases, or traumas but lacked the documentary evidence necessary to garner material support from the state. The core objective of this dissertation is to explore how policy-makers responded to these challenges, and how their efforts shaped the daily experiences of veterans from all walks of life. By fusing an analysis of policy with a social history of disability, this study uncovers the multiple paths disabled veterans embarked upon during their civil re-establishment. Few followed unfirom trajectories. The affects of disability on a veteran’s wellbeing varied widely based on numerous factors including pre-war social standing, support networks, material resources, age, and overall health. While most studies of disability and the Great War have focued on the cultural, medical, or political impact of disability, few adequately explain how both government policy and extraneous forces affected the lives of disabled veterans. Utilizing a wealth of statistical data and a large sample group of case files, “State, Service, and Survival: Canada’s Great War Disabled, 1914-44” is the first Canadian study to address this gap in our collective understanding of the war’s legacy.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)


title: Experimental Study of Single Phase Turbulent Pipe Flow with Variable Obstructions

contributor: Engineering Physics and Nuclear Engineering

abstract:
A considerable amount of effort is expended to better characterize and avoid the critical heat flux (CHF) phenomena in nuclear reactor systems. Most fuel assemblies used in power reactors possess small structures to maintain them in place as well as maintain the physical integrity of the assembly and element to element clearances. These structures act as local flow obstructions that modify the turbulent flow characteristics and in general improve the heat transfer. In CANDU reactors, a series of bearing pads are used to maintain clearances between the fuel and the pressure tube while spacer pads maintain element to element clearances. This thesis experimentally investigates the impact of bearing pads on the downstream flow and turbulence characteristics under room temperature and pressure conditions.
The test section is fabricated from a 30 cm long and 2.54 X 2.54 cm squared transparent cast acrylic piece. Machined through the center is a cylindrical flow channel with inner diameter of approximately 11 cm. CANDU fuel bundle bearing pad simulators have been designed and constructed at McMaster University to allow for the study of the local flow characteristics downstream of these obstructions. Measurements are taken with unobstructed flow and a variety of obstruction heights to examine the turbulence features generated. Each bearing pad is removable and is secured in place using high strength magnets. The test section connects to an existing room temperature fluid loop capable of delivering accurate flows up to a Reynolds number of 100000.
In order to validate the test section and measurement methods, a series of experiments were performed without obstructions. These measured velocity and turbulence data were compared to literature values to ensure similarity. After this validation study, experiments were carried out using room temperature water as fluid at three different turbulent Reynolds numbers of 30700, 61400 and 99000 with and without obstructions, using Laser Doppler Velocimetry. Results in the streamwise direction were as expected, with velocity perturbations that in general decreased with increasing Reynolds number. Some evidence of local recirculation in the wake of the obstruction was also measured. In the azimuthal direction, velocity and turbulence measurements were largely isotropic downstream of the obstruction for low Reynolds numbers and small obstructions. At higher Reynolds number and/or larger obstructions, the components in the azimuthal direction were systematic and exhibited coherent like structures (i.e., rotating flow or swirl). Of particular importance was the decay of turbulence with downstream length which was significant in cases where no coherent structures were present. With coherent structures, the turbulence levels remained high for much further distances. The source of the structures at high Reynolds number is not clear as all physical geometries were verified to ensure no systematic biases were present.

abstract: Thesis

abstract: Master of Science (MSc)


title: Numerical Analysis of Thermal Stratification in Large Horizontal Thermal Energy Storage Tanks

contributor:
Lightstone, Marilyn
Mechanical Engineering

subject:
Thermal Stratification
Thermal Storage
Horizontal Tank
Drake Landing Solar Community
Thermal System
Storage Tank

abstract:
In order to enhance the performance of a large horizontal thermal energy storage, a numerical model was generated and validated using measurements obtained from Drake Landing Solar Community (DLSC).  A total of nine different baffle configurations were tested in order to  enhance the thermal stratification.  The designs were tested for a total of six different cases of charging, discharging and simultaneous charging and discharging in an attempt to better identify key features that mix the tank under realistic conditions.  Characterization of the tank performance was done by monitoring the tank outlet temperature and computing Huhn's efficiency Second Law characterization index).

Results show that the current tanks at DLSC experience excessive mixing due to plume entrainment that occurs during the spreading of the inlet jet.  The introduction of a  baffle into the middle of the tank was found to have no impact on the level of stratification.   In addition, most designs tested have a relatively high level of stratification during charging, discharging and simultaneous charging and discharging, but fail to sustain the level of stratification when a positive buoyant jet is introduced.

It was demonstrated that the inlets and outlets should be moved to the top and bottom of the tank to eliminate stagnant fluid that is not easily discharged.  Horizontal baffles are effective in allowing the inlet jet to spread horizontally but not vertically, thus reducing the mixing.  Alternatively, a simple solution would be to increase the size of the inlet, which has a comparable performance to the best baffle configurations.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Cyberbullying impacts on users’ satisfaction with information and communication technologies: the role of Perceived Cyberbullying Severity

contributor:
Hassanein, Khaled
Business Administration

subject: cyberbullying satisfaction technology severity

abstract:
Cyberbullying is a term that encompasses aggressive behaviours performed through different information and communication technologies (ICT), with the intention to harm or cause discomfort to others. Cyberbullying has gained prominence due to reported cases of teenage suicides linked to cyberbullying. Researchers have studied the prevalence and outcomes of cyberbullying (e.g. truancy) and strategies used by victims to deal with cyberbullying (e.g. email address change). However, researchers have not taken into account victims’ perceptions of the severity of the cyberbullying they experience and how those perceptions affect them at a personal level and their experience with ICT.
This study combines Transactional Theory of Stress and Coping with the Expectation-Confirmation Theory and proposes two research models that will aid in understanding (i) the contextual factors that affect victims’ perceptions of cyberbullying, and (ii) the consequences of those perceptions on victims’ satisfaction with the ICT through which cyberbullying occurs. In addition, this study proposes two secondary objectives aimed at (i) developing and validating a scale to measure victims’ perception of cyberbullying severity and (ii) exploring its impact on victims’ use of different coping mechanisms.
A survey-based study involving 229 cyberbullying victims is employed to empirically validate the proposed theoretical models, using structural equation modeling techniques. Results indicate that victims’ perception of the severity of a cyberbullying episode affects her/him at a personal level and negatively impacts her/his ICT beliefs,  which in turn, impact her/his satisfaction with ICT. The analysis of different contextual factors indicates that the harshness of the message(s) the victim receives, the importance of the ICT through which cyberbullying occurred to her/him, her/his self-esteem, and knowing who the bully is affect a victim’s evaluation of the severity of a cyberbullying episode. Implications of these results for academics and practitioners, as well as limitations of this study, are discussed.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)


title: The Effect of Subsurface Hydrology on DDT Degradation in Soils at Point Pelee National Park, Ontario, Canada

contributor:
Smith, James E.
Geology

subject:
DDT
Subsurface Hydrology
soil
Point Pelee National Park

abstract:
 Systematic soil sampling and analyses provided DDT, DDE and DDD, organic and mineral matter concentrations, as well as various soil physical and hydraulic properties from three study sites at Point Pelee National Park. A soil's physical properties, soil and water management practices, and DDT application history, can affect DDT degradation and change the relative amount of its metabolites. DDD is the principal product of the dechlorination of DDT in high moisture content, reducing
anaerobic soil environments. The main degradation product in soils under aerobic conditions is DDE. %DDT, %DDE and %DDD abundances used in conjunction with soil environment characterization data, can be used to indicate not only whether DDT is degrading, but what environmental factors are controlling its degradation. At the Park,
DDT is primarily lost from the soil by microbial degradation to DDE and DDD. %DDT, %DDE and %DDD ratios from each study site indicated that wetter more organic-rich soil environments degraded DDT to its metabolites at a faster rate than drier less organicrich soils. Moreover, historical water level data was used to illustrate that this wetter
study site was flooded for part of the year when adjacent marsh water levels were high. These conditions resulted in the accumulation of organic matter over time and the creation of alternating anaerobic/aerobic conditions in the soils resulting in an increased
rate of degradation of DDT in these areas. Based on the relative %DDT in the soils at each study site, relative half-life estimates for the first order decay of DDT to its metabolites DDE and DDD were calculated. Half-life estimates for DDT at the wettest and most organic-rich study site range from 6 to 8 years; significantly lower than the two other study sites, which range from 15 to 30 years and are on the high end of the range reported in the literature.

abstract: Thesis

abstract: Master of Science (MSc)


title: Remediation of DDT Contaminated Soil: A Field Study

contributor:
Smith, James E.
Environmental Science

subject:
Point Pelee Nation Park
DDT, DDe, DDD
soil

abstract:
 Point Pelee National Park in Leamington, Ontario, Canada contained a large component of private farming and recreation until the 1960's. DDT was applied at the park as pest control in the orchards and recreational areas between 1948 and 1960. Recent studies have shown that the compounds DDT, DDE and DDD are highly persistent in the shallow soils of Point Pelee National Park. A laboratory treatability
experiment has been effective in the removal of DDT, DDE and DDD from columns packed with soil collected from Point Pelee National Park, using hydroxypropyl-ß-cyclodextrin. Cyclodextrins are microbially produced cyclic oligosaccharides which have a unique hydrophilic shell and a hydrophobic cavity. They are able to form inclusion complexes and aid in the transport of relatively insoluble compounds. A pilotscale
field remediation experiment involving the application of hydroxypropyl-ß-cyclodextrin to a Random Latin-Squares design was completed at Point Pelee National Park over the course of five months. Systematic soil sampling and analyses provided DDT, DDE and DDD concentrations throughout the remediation experiment in order to assess the removal efficiency of hydroxypropyl-ß-cyclodextrin. In-Situ volumetric moisture content was monitored throughout the study with a TDR based system.
Systematic soil sampling and analyses at the conclusion of the study provided water content, organic matter content, bulk density, porosity, hydraulic conductivity as well as sampling with depth. The application of a hydroxypropyl-ß-cyclodextrin solution did result in a substantial decrease of the concentrations of DDT, DDE and DDD from the
surface soil at Point Pelee National Park. By the end of the experiment, the concentration of DDD was consistently below the regulatory limits set by the Ontario Ministry of Environment and Energy for Parkland/Recreational Land-Use. In addition to the observed decrease in concentration, there was a decrease in the degree of variation
between the measured concentrations, transport of the mass of DDT, DDE and DDD to depth and an observed tailing effect at late-times. There were also fundamental changes to the system due to the application of the cyclodextrin (HPCD) solution including an increase in moisture content and organic matter, a decrease in infiltration and a
corresponding decrease in field saturated hydraulic conductivity. There was no appreciable benefit of the application of a high concentration solution over a low concentration solution due to an observed "clogging" -effect. The results of this study indicates that further research is necessary to determine the extent of vertical mobilization
of DDT, DDE and DDD to groundwater and the role of biological matter in the observed fundamental changes responsible for the "clogging" -effect.

abstract: Thesis

abstract: Master of Science (MSc)


title: Understanding the Role of Competition in Video Gameplay Satisfaction

contributor:
Head, Milena
Business

subject:
Games
Video Gaming
Competition
Flow
Information Systems
Teaching

abstract: Considerable amount of time is spent playing video games in today’s society. There are various elements in video games that make them entertaining and satisfying, which can be leveraged to provide engaging and satisfying experiences in educational and workplace contexts. One of the key elements in many video games is competition. Based on Self-Determination Theory (SDT) and the Theory of Flow, this dissertation explores the process through which competition makes a video game satisfying. A structural model is proposed that examines the impacts of Situational Competitiveness (manipulated via different modes of competition) and Dispositional Competitiveness (as a personality trait) on gameplay experience.  The proposed model is validated through an experimental design study with 104 university students. The results show that the perception of video game competitiveness has a strong direct and indirect (mediated through Challenge and Arousal) effect on Flow experience and Satisfaction. While an individual’s personality impacts the perception of a game’s competitiveness, this perception can also be influenced by the mode of competition (playing against a computer, stranger or friend). Additionally, Social Presence is found to play a role by mediating the relationship between the mode of competition and Situational Competitiveness.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)


title: Investigating the roles of co-infection and female sex hormones on HIV-1 infection and replication in the female genital tract.

contributor: Medical Sciences (Molecular Virology and Immunology Program)

subject: HIV

subject: Female Sex Hormones/Hormonal Contraceptives

subject: Epithelial Cells

abstract:
Although women constitute more than half of the estimated 34-40 million people living with HIV/AIDS worldwide, little is known about the early events of HIV-1 infection in the female genital tract (FGT). Genital epithelial cells (GECs) line the FGT and act as intrinsic barriers providing mechanical protection against foreign microbes. GECs are also sentient and are capable of sensing and immunologically responding to various types of pathogens including sexually transmitted infections (STIs). These responses play a central role in preventing disease and also help mobilize both innate and adaptive immune cells against invading threats. While it is well understood that GECs exert important physical and immunological protective roles in the FGT, little is known regarding the role of GECs and GEC inflammatory responses in HIV infection.
It is estimated that 40% of all new HIV infections are established each year in the FGT. Our understanding of the early events following HIV transmission in the FGT remains particularly elusive in the context of endogenous or exogenous factors found in the genital microenvironment that may influence susceptibility to HIV-1. Inflammation is known to play a critical role in increasing HIV susceptibility, replication as well as initiating and maintaining chronic immune activation, a hallmark of disease progression. Among the key factors in the FGT that are known to or that could influence inflammation are sexually transmitted co-infections and female sex hormones.
The work summarized in this thesis examines how GEC innate immune responses to co-infecting microbes or female sex hormones impact HIV infection and replication in the FGT. Our results show that GEC innate immune response against herpes simplex virus type 2 (HSV-2), a common HIV co-infecting agent, consists of elevated proinflammatory cytokines and chemokines in addition to biologically active interferon-β. Furthermore, our results show that these responses require potent viral HSV-2 replication and that proinflammatory cytokine and chemokine responses are enhanced in the absence of the HSV-2 virus host shutoff protein. Based on this work, we decided to investigate whether GEC inflammatory responses to common STIs played a role in regulating HIV replication in T-cells. We found that HIV co-infecting microbes, specifically HSV-1, HSV-2 and Neisseria gonorrhoeae, directly induced HIV replication in T-cells, and caused primary GECs to upregulate inflammatory responses that indirectly increased HIV replication in T-cells.
Next we examined a translational aspect of the aforementioned studies by examining whether blocking inflammatory pathways, using the broad anti-inflammatory compound curcumin, could provide prophylactic or therapeutic protection against HIV. We found that curcumin pre-treatment a) protected the genital epithelial barrier against HIV-1-mediated disruption and inflammation, b) prevented the gp120-mediated upregulation of chemokines by GECs that recruit HIV target cells to the FGT, c) blocked GEC innate inflammatory responses to co-infecting microbes and indirect activation of the HIV promoter in T-cells, d) decreased HIV amplification in chronically infected T-cells and e) blocked HSV-2 viral replication in GECs by a mechanism that likely involves NFκB.
Lastly, it has long been speculated that female sex hormones can regulate inflammatory responses, and numerous lines of evidence suggest that they may also regulate susceptibility to HIV-1. Thus, we investigated how female sex hormones and the hormonal contraceptive medroxyprogesterone acetate (MPA), used by more than 100 million women worldwide, regulated HIV infection and replication in GECs and whether inflammation played an important role in this regulation. Our results showed that progesterone and in particular MPA increased uptake of HIV-1 and transcytosis, but not replication, across GECs – in the absence of a proinflammatory milieu - and that this enhanced transcytosis resulted in increased infection of HIV target cells.
These results demonstrate that sex hormones and co-infection both play an important role in regulating HIV-1 infection and replication in the FGT. Furthermore, our results suggest that anti-inflammatory compounds such as curcumin may offer paradigm shifting prophylactic or therapeutic strategies against HIV-1 infection and future research should investigate its potential benefit in vivo.

abstract: Thesis

abstract: Doctor of Philosophy (Medical Science)


title: Upper Devonian Plant Microfossils from Eastern and Arctic Canada: Their Taxonomy and Palaeoecological Significance

contributor:
Radforth, N.W.
Biology

subject:
microfossils
taxonomy
paleoecological significance
Canada

abstract:
Plant microfossils are extracted from strata of Upper Devonian
age occurring at two previously uninvestigated localities in Eastern
Canada and in the Canadian Arctic. The extraction procedure includes
a new permanent palynological mounting technique using corn syrup and Permount, a synthetic resin. In addition, a method of eliminating by-product in residues after hydrofluoric acid, is also described. A number of miospore and acritarch form species are described
and figured; nine new form species of miospores are proposed. The
miospore species recovered from both localities indicate a geological
age of early Upper Devonian (Frasnian) for the enclosing strata. A new way of assessing qualitative, regional palaeofloristic
changes is provided by tabulation of morphological characteristics of
individual miospores. The use of miospore species in defining Upper
Devonian microfloral provinces and Upper Devonian-Lower Carboniferous migration of parent forms is demonstrated.

abstract: Thesis

abstract: Master of Science (MSc)


title: Regulation of xCT by NRF-2 in Breast Cancer Cells

contributor: Medical Sciences (Division of Physiology/Pharmacology)

subject:
Breast Cancer
Reactive Oxygen Species
System X
xCT
NRF-2
Glutamate

abstract:
Cancer cells adapt to high levels of oxidative stress in order to survive and proliferate, making the transcription factors involved in antioxidant defence regulation targets of interest. The transcription factor NF E2 Related Factor 2 (NRF-2) regulates cellular defence genes including those encoding intracellular redox-balancing proteins such as enzymes involved in glutathione metabolism. Glutathione in particular is an important intracellular antioxidant molecule. NRF-2 binds to the Antioxidant Response Element (ARE) in the promoter of its target genes. Under basal conditions, Kelch-like ECH-associated protein 1 (KEAP1) acts as an inhibitor that targets NRF-2 for ubiquitination. During oxidative stress, NRF-2 dissociates from KEAP1 and enters the nucleus to bind to the ARE sequence.
	It is hypothesized that the elevated Reactive Oxygen Species may be depleting the glutathione levels within the cancer cell. System xc- is a cystine/glutamate antiporter that exports glutamate while importing cystine to synthesize glutathione. In response to oxidative stress, the cells increase system xc- activity in order to provide cystine for glutathione synthesis. There is evidence that expression of xCT, the specific subunit of system xc-,is regulated by NRF-2. However this has not yet been demonstrated in human breast cancer cells, which is the focus of this project.
Basal expression of NRF-2, KEAP1 and xCT was characterized in three breast cancer cell lines (MDA-MB-231, MCF-7 and T47D) and compared to two non-cancer cell lines (184B5 and MCF10A). Basal protein levels of NRF-2 and KEAP1 showed no differences between cell lines. Basal protein levels of xCT were increased in MCF10A cells than T47D cells. MCF-7 cells were treated with hydrogen peroxide (H2O2) resulting in NRF-2 protein accumulation in the nucleus. With H2O2 treatment, xCT mRNA levels increased in MCF-7 cells. Additionally, transient overexpression of NRF-2 increased extracellular glutamate levels in MCF-7 cells. These data support a model that under oxidative stress, NRF-2 is localized to the nucleus and transcriptionally upregulates xCT. This is the first study in which the regulation of xCT has been linked to oxidative stress via NRF-2 in human breast cancer cells.

abstract: Thesis

abstract: Master of Science (MSc)