title: THE MOVEMENT PATTERNS AND HOME RANGES OF BLANDING’S TURTLES (EMYDOIDEA BLANDINGII) IN TWO PROTECTED AREAS IN ONTARIO CANADA

contributor:
Chow-Fraser, Patricia
McClelland, Grant
Biology

subject:
Blanding's turtle
conservation
Emydoidea blandingii
GPS logger
habitat
home range
movement patterns
radio telemetry
Ecology and Evolutionary Biology
Terrestrial and Aquatic Ecology
Zoology
Ecology and Evolutionary Biology

abstract: The distribution of Blanding’s turtles in North America is centered on the Great Lakes region, where the impacts from high levels of development have reduced and isolated populations. They are particularly sensitive to habitat loss and fragmentation because of their broad habitat requirements, migratory behaviour, and relatively large seasonal movements and home ranges. Consequently, Blanding’s turtles have been designated a species at-risk throughout the majority of their geographic range. In 2011 we conducted a radio-tracking program to compare the home ranges and movement patterns of Blanding’s turtles in two eco-regions of Ontario that have contrasting habitat and landscape characteristics: Georgian Bay Islands National Park and Rondeau Provincial Park. We also used GPS loggers to supplement data collection by radio-tracking and to evaluate the effectiveness of GPS loggers in tracking the movements of a semi-aquatic species. We found differences in home range between our two study populations that may be linked to landscape features and seasonal differences in movement within the population in Georgian Bay Islands National Park. We also determined that GPS loggers, when used in combination with radio-tracking, can effectively track the movements of Blanding’s turtles with a higher temporal and spatial resolution than by radio-tracking alone. This study highlights the importance of developing management strategies that are tailored to the spatial requirements of distinct populations, and the need for conservation measures that protect aquatic and terrestrial habitat surrounding the main activity centres of Blanding’s turtles.

abstract: Master of Science (MSc)


title: DOES FOLIC ACID SUPPLEMENTATION PREVENT NICOTINE-INDUCED BETA CELL DYSFUNCTION

contributor: Medical Sciences (Division of Physiology/Pharmacology)

subject:
Diabetes
Beta cell
Beta cell dysfunction
nicotine
Folic acid
Chemical and Pharmacologic Phenomena
Medical Pharmacology
Medical Physiology
Chemical and Pharmacologic Phenomena

abstract:
Previous studies suggest that nicotine impairs pancreatic function, which may explain the increased risk of T2DM in smokers. We have previously shown that nicotine exposure results in decreased beta cell function, an effect which appears to be mediated via increased beta cell oxidative stress. The goal of this study is to determine whether folic acid, an antioxidant, can prevent nicotine-induced beta cell dysfunction in the beta cell.

INS 1E cells, a rat pancreatic beta cell line, were treated with nicotine or vehicle ± 10µM folic acid for 48 hours. Nicotine treatment decreased both basal and glucose stimulated insulin secretion, but had no effect on insulin content, mitochondrial function or markers of apoptosis. Expression of oxidative stress/damage markers (HSP70 and 4-HNE), antioxidant enzymes (Cu/ZnSOD, MnSOD and CAT), insulin gene transcription factor PDX1 and KATP channel subunit kir6.2 were determined by western blot analysis. Expression of HSP70, 4-HNE and MnSOD were significantly increased with nicotine treatment (p=0.002, 0.05 and 0.03 respectively). Cu/ZnSOD and CAT expression remained unchanged with nicotine treatment. The addition of folic acid significantly reduced HSP70 expression, 4-HNE expression, CAT expression, but did not alter the expression of MnSOD. There was a significant (p6.2expression (p=0.019) which showed a trend toward reduced expression following treatment with folic acid (p=0.067).

Nicotine treatment significantly increases markers of oxidative stress and oxidative damage in pancreatic beta cells; an effect which was reversed by folic acid administration. Nicotine and folic acid treatment increased insulin content, likely mediated through an increase in the insulin gene transcription factor, PDX1. Furthermore, nicotine treatment increased expression of kir6.2, suggesting a defect in the insulin secretory mechanism. This effect was reversed with folic acid treatment.Although many studies suggest that Canadians are meeting or exceeding recommended folate levels, this is not true in smokers. Our data suggest that additional folate supplementation in smokers may prevent nicotine-induced damage to the pancreas and thus reduce the risk of type 2 diabetes.

abstract: Master of Science (MSc)


title: Repeated Selfish Routing with Incomplete Information

contributor:
Karakostas, George
Ryan Leduc, Douglas Down
Computing and Software

subject:
Selfish Routing
Repeated Game
Toll
Digital Communications and Networking
Other Computer Engineering
Digital Communications and Networking

abstract:
Selﬁsh routing is frequently discussed. The general framework of a system of non-cooperative users can be used to model many diﬀerent optimization problems such as network routing, traﬃc or transportation problems.

It is well known that the Wardrop user equilibria (i.e. the user optima) generally do not optimize the overall system cost in a traﬃc routing problem.

In order to induce the equilibrium ﬂow to be as close to the optimal ﬂow as possible, the term “toll” is introduced. With the addition of tolls, a traﬃc system does not show the actual cost to the users but the displayed cost of users, which is the summation of the actual cost and the toll. A common behavioral assumption in traﬃc network modeling is that every user chooses a path which is perceived as the shortest path, then the whole system achieves the equilibrium of the displayed cost. It is proved that there exists an optimal toll which can induce the equilibrium ﬂow under displayed cost to be the optimal ﬂow in reality.

However, this conclusion holds only if the selﬁsh routing executes only once. If the game is played repeatedly, the users will detect the diﬀerence between the actual and displayed costs. Then, they will not completely trust the information given by the system and calculate the cost. The purpose of this thesis is to ﬁnd out the optimal strategy given by the system–how to set tolls in order to maintain the ﬂow as close to the optimal ﬂow as possible.

abstract: Master of Science (MSc)


title: Experimental and Numerical Investigation of Solar Thermal Buffer Zone

contributor:
Hamed, Mohamed S.
Razaqpur, Ghani
Mechanical Engineering

subject:
Passive Solar Heating
Renewable Energy
Solar Energy
Green Buildings
Energy Systems
Heat Transfer, Combustion
Mechanical Engineering
Energy Systems

abstract:
Solar thermosiphons integrated into the thermal envelop of buildings has been studied for their potential to take advantage of solar energy in heating buildings. The annual performance of the Solar Thermal Buffer Zone cannot currently be predicted with the correlations from previous research. Also, no work has been done on using the thermal buffer zone with a natural convection for energy savings in a building even though it has the potential to provide heating. The goal of this project was to design, analyze and determine the feasibility of a thermal buffer zone in a building. A thermal buffer zone can be defined as a fluid filled cavity which envelopes a building. This cavity provides a building with additional insulation but also allows for collection of solar energy and to be distributed throughout the structure in order to heat the interior. To show the physical aspect, the flow visualization in the project, computational fluid dynamic (CFD) software was used which was experimentally not possible. A physical prototype was then designed and constructed in order to test the effectiveness of the TBZ.

This experiment included radiation as the heat source and the ability to vary geometric lengths. The performance parameters of mass flow rate were comparable between the numerical predictions and experimental results. However, due to uncertainties in the current experimental setup, full validation of the numerical model was not possible. These uncertainties would have to be addressed before the numerical model that was developed can be fully validated and used for generating correlations.

abstract: Master of Applied Science (MASc)


title: Understanding Determinants of Active Travel

contributor:
Scott, Darren
Geography

subject:
Physical Activity
Built Environment
Active Travel
Walking
Social Environment
Barriers
Human Geography
Urban Studies and Planning
Human Geography

abstract:
Lack of physical activity participation is one of the greatest challenges facing health care providers and policy makers in Canada. Increases in health problems linked to inactive lifestyles, such as obesity, heart disease, and asthma, have led health promotion experts to engage Canadians to become more active. Despite these efforts, many Canadians remain inactive and at risk. Active travel (AT), defined in this study as walking for travel, is a key form of physical activity that continues to decline. This dissertation examines the decline of AT and role the individual, physical, and social environment have on AT.

The individual environment is examined by providing evidence of how perceived barriers to walking influence the AT of population sub-groups by modeling each barrier comparing agreement versus disagreement. Results find females, senior citizens, and those with a higher body mass index identify the most barriers, while young adults, parents, those owning a driver’s license, and those owning a bus pass identify the fewest barriers.

The physical environment is examined by providing an improved conceptualization of the built environment (BE). First, the BE-AT relationship is examined by comparing the relationship when measuring the BE using an aggregate method with a disaggregate approach of measurement. As a result, both aggregate and disaggregate BE variables are significant, but the aggregate approach hides the fact that only two of the five BE variables are significant when using the disaggregate approach. Second, the influence the modifiable areal unit problem (MAUP) has on the relationship between AT and the BE is investigated. The results find that the relationship between AT and the BE are influenced by scale zone effect of MAUP.

The social environment is examined through the adoption of a conceptual framework from the physical activity literature that combines the social environment with individual and physical environments. A series of linear regression models evaluating the different components of the social environment find that only role models and neighborhood social cohesion influence AT, despite the fact that the social environment is significantly related to walking for exercise in the literature.

abstract: Doctor of Philosophy (PhD)


title: A New Pool Boiling Facility for the Study of Nanofluids

contributor:
Novog, D. R.
Engineering Physics

subject: nanofluids; pool boiling; high speed video; experiment design

subject: Heat Transfer, Combustion

subject: Heat Transfer, Combustion

abstract:
Nanofluids are engineered colloidal dispersions of nanoparticles in a liquid. The field of nanofluids has seen much interest due to reported heat transfer enhancements over the corresponding pure fluids at low particle concentrations. Particularly, a large increase in critical heat flux (CHF) has been widely reported along with modification of the boiling interface. Inconsistencies in reported impact on nucleate boiling heat transfer and the degree of CHF enhancement illustrate the need for further study.

A pool boiling experiment has been designed and constructed at McMaster University to allow for the study the boiling of water-based nanofluids. The facility has been commissioned with saturated distilled water tests at atmospheric pressure, heat flux levels up to 1200 kW·m-2, and at wall superheat levels up to 19.5oC. Wall superheat and heat flux uncertainties were estimated to be ±0.6oC and ±20 kW∙m-2, respectively. For the installed test section, heat flux is limited to 2.62 ± 0.06 MW·m-2. A high speed video system for the analysis of bubble dynamics was tested and used for qualitative comparisons between experimental runs. This system was tested at 2500 FPS and an imaging resolution of 39 pixels per mm, but is capable of up to 10 000 FPS at the same spatial resolution. Heat flux versus wall superheat data was compared to the Rohsenow correlation and found to qualitatively agree using surface factor Csf = 0.011. Results were found to have a high degree of repeatability at heat flux levels higher than 600 kW·m-2.

The new facility will be used to conduct studies into the pool boiling of saturated water-based nanofluids at atmospheric pressure. Additional work will involve the control and characterization of heater surface conditions before and after boiling. Quantitative analysis of bubble dynamics will be possible using high speed video and particle image velocimetry.

abstract: Master of Applied Science (MASc)


title: Examining the Consequences of Employee Perceptions of the Employee-Organization Relationship

contributor:
Hackett, Rick D.
Wiesner, Willi
Luchak, Andrew
Business Administration

subject:
side bets
social exchange
economic exchange
organizational commitment
employee-organization relationships
organizational citizenship behaviour
task performance
Human Resources Management
Human Resources Management

abstract: Using a social exchange perspective I develop a relationship typology based upon an organizational member’s psychological investments, or “side bets,” in his or her organization. This study thus examines, for the first time in the employee-organization exchange relationship (EOR) literature, the combined impact of perceptions that organizational members have with respect to their perceived social and economic investments in their organization. Specifically, outcomes of four unique EOR profiles are examined: “loyalist” (high social, high economic); “altruist” (high social, low economic); “captive” (low social, high economic); “mercenary” (low social, low economic). In a matched sample of 334 working professionals (167 employees matched with their corresponding supervisors), the hypotheses of this study are largely supported. Altruists are highest in their perceptions of organizational support, followed in descending order by the loyalists, mercenaries, and captives. Also as predicted, altruists are highest in affective commitment, followed in descending order by the loyalists, captives, and mercenaries. In terms of continuance commitment, contrary to prediction, loyalists have the highest levels of continuance commitment; however, as predicted, captives have higher levels than altruists and mercenaries. Altruists, as predicted, have the highest level of OCB, followed in descending order by loyalists, mercenaries, and captives. Finally, as predicted, mercenaries have the highest level of task performance followed in descending order by altruists, loyalists, and captives. Theoretical and practical considerations of these findings are discussed.

abstract: Doctor of Philosophy (PhD)


title: Structural Analysis of Ginsenosides and Sugars: An Electrospray and Tandem Mass Spectrometry Study

contributor:
McCarry, Brian E.
Terlouw, Johan K.
Chemistry

subject: Chemistry Chemistry

abstract:
Carbohydrates are an abundant class of biological molecules. This thesis presents methodologies for structure characterization of a class of triterpene glycosides, the ginsenosides, sugars and polyols. The sugars included simple monosaccharides, as well as complex saccharides such as the carrageenans, a family of sulfated polysaccharides. The methodologies employed positive and negative ion electrospray ionization (ESI) mass spectrometry and tandem mass spectrometry (MS/MS).

Positive ion electrospray mass spectrometry (ESMS) of solutions containing a ginsenoside and any alkali metal ion produced the [M+metal]+ ion. By contrast, when the transition metal ions, Ni++, Co++ and Zn++, are used, the [M+Metal-H]+ ion was observed. Collision-induced dissociation (CID) of the metal attachment ions accommodated their structure characterization. The relative intensity ratio of the product ions provided information on the point of attachment of the sugars to the core, as well as whether they are monosaccharides or disaccharides.

Negative ion ESMS of basic solutions of ginsenosides showed a peak corresponding to the [M-H]- ion whose CID spectrum provided the identity of the core, the sugars comprised in the ginsenoside and their order of attachment to the ginsenoside. Both positive and negative ion CID experiments provided information that can be used to propose a structure for ginsenosides. In line with this, these methodologies were used to develop a liquid chromatography mass spectrometry (LC/MS) and LC/MS/MS method for separation and structural characterization of new ginsenosides from root extracts. The structure proposals for ten new ginsenosides are provided.

The carrageenans are a family of partially sulfated polysaccharides of which there are three major types, kappa (k), iota (i) and lamda (l). These types are different because each has a disaccharide subunit containing a specific number of sulfate groups with Na+ counterions. Both matrix-assisted laser/desorption ionization time-of-flight mass spectrometry and negative ion ESMS proved to be useful structure probes for these compounds. Dilute solutions of carrageenans undergo H+ exchange and subsequent expulsion of SO3 thus generating a carrageenan with lower sulfate content.

Ginsenosides differing only in the presence of geometric isomeric sugars are not differentiated by CID experiments. This observation raised the question of differentiating geometric and (stereo) isomeric polyols using ESMS and MS/MS experiments. Two approaches were investigated to address this question; the first employing negative ion, and the other positive ion mode.

The structures of polyols and sugars were analyzed as their boric acid complexes by negative ion infusion ESMS and MS/MS experiments. The positive ion approach employed complexation to oxovanadium(IV), VO++. In both systems, ethylene glycol the simplest polyol was employed as the internal standard. Full scan ESMS experiments provided information on the ease of complexation of the analyte relative to ethylene glycol by comparing the intensity ratio of ions corresponding to their complexes with boric acid and VO++. CID experiments probed the structures of these complexes. Both methodologies were valuable for differentiating geometric and stereoisomeric diols, and isomeric methyl glycosides.

Both ESI and MALDI involve solution- and gas-phase processes. A small chemical ionization mass spectrometry project involving alkylation reactions of N-ethyl- and N-methylaniline, and o-, m- and p-ethyl- and o-, m- and p-methylaniline with iodomethane and iodoethane was undertaken. It was observed that the N-site is the primary site for alkylation.

abstract: Doctor of Philosophy (PhD)


title: Attenuation and Photodetection of Sub-Bandgap Slow Light in Silicon-on-Insulator Photonic Crystal Waveguides

contributor:
Knights, Andrew P.
Jessop, Paul E.
Cassidy, D.T.
Engineering Physics

subject: absorption

subject: photodetectors

subject: silicon photonics

subject: silicon-on-insulator

subject: photonic crystals

subject: slow light

subject: Electromagnetics and photonics

subject: Electronic Devices and Semiconductor Manufacturing

subject: Engineering Physics

subject: Electromagnetics and photonics

abstract: A glass-clad, slow-light photonic-crystal waveguide is proposed as a solution to sub-bandgap light detection in silicon photonic circuits. Such detection in silicon is perceived as a challenge owing to silicon's indirect band gap and transparency to 1550nm wavelengths, yet is essential for achieving low-cost, high-yield integration with today's microelectronics industry. Photonic crystals can be engineered in such a way as to enhance light-matter interaction over a specific bandwidth via the reduction of the group velocity of the propagating wave (i.e. the slowing of light). The interaction enhanced for light detection in the present work is electron-hole pair generation at defect sites. The intrinsic electric field of a p-i-n junction enables light detection by separating the electron-hole pairs as a form of measurable current. The photonic-crystal waveguides are designed to have bandwidths in the proximity of a wavelength of 1550nm. Refractive indices of over 80 near the photonic-crystal waveguide's Brillouin zone boundary are measured using Fourier transform spectral interferometry and are found to correspond to numerical simulations. Defect-induced propagation loss was seen to scale with group index, from 400dB/cm at a group index of 8 to 1200dB/cm at a group index of 88. Scaling was sublinear, which is believed to be due to the spreading of modal volume at large group index values. Photodetectors were measured to have responsivities as high as 34mA/W near the photonic-crystal waveguide's Brillouin zone boundary for a reverse bias of 20V and a remarkably short detector length of 80um. The fabrication of each device is fully CMOS-compatible for the sake of cost-effective integration with silicon microelectronics.

abstract: Master of Applied Science (MASc)


title: SEISMIC PERFORMANCE QUANTIFICATION OF CONCRETE BLOCK MASONRY STRUCTURAL WALLS WITH CONFINED BOUNDARY ELEMENTS AND DEVELOPMENT OF THE NORMAL STRAIN-ADJUSTED SHEAR STRENGTH EXPRESSION (NSSSE)

contributor:
El-Dakhakhni, Wael
Civil Engineering

subject:
masonry
seismic design
design codes
shear strength
shear walls
Structural Engineering
Structural Engineering

abstract: The masonry construction industry represents a historically significant and substantial portion of both existing and new residential, commercial and institutional low- to medium-rise structures across Canada. Although commonly chosen for its aesthetic qualities by architects, structural masonry walls constructed with concrete block units are also an effective lateral force (wind or seismic) resisting system. The purpose of this dissertation is to address what are perceived to be overly conservative and outdated practices within masonry construction and design by adopting analysis and design practices which have had success with similar reinforced concrete wall systems. The results from a test program reporting on the behavior of nine fully-grouted reinforced masonry (RM) structural walls containing confined boundary elements are analyzed and presented according to force-, displacement- and performance-based seismic design considerations. The boundary element containing four vertical bars with lateral confinement stirrups selected represents a readily codified and practically achievable means of achieving seismic performance enhancement. The design and detailing of the specimens represented a range of parameters that would be anticipated to vary within low- to medium-rise RM buildings. In addition, an analytical study is carried out to derive, from first principles of stress equilibrium and strain compatibility, the necessary constitutive material and mechanics-based equations needed to solve for the state of shear stress and strain in an idealized cracked masonry macro-element. The algorithm proposed is validated by comparing the proposed model to existing test data and is further developed towards predicting the design shear strength of RM structural walls. The results from these experimental and analytical research programs are subsequently used to provide a set of proposed code clauses at the end of the thesis. Prescriptive design requirements are proposed for a new category of Special Ductile Masonry Shear Wall containing boundary elements including integration of a new shear strength expression. These clauses have been written with the intention of adoption within the CSA S304.1 and the MSJC North American masonry designs standards.

abstract: Doctor of Philosophy (PhD)


title: STUDY OF GREEN SOLID STATE LASERS BASED ON MGO:PPLN CRYSTALS FOR LASER DISPLAY APPLICATIONS

contributor:
Xu, Chang-qing
Engineering Physics

subject:
Nonlinear Optics
Lasers
Second Harmonic Generation
Laser Display
Other Engineering
Other Engineering

abstract:
Laser-based displays have been under active development over the past 50 years. Visible lasers are considered as the “ultimate” light sources for display applications due to their high brightness, high directionality and high color saturation. Unlike commercially available red and blue laser diodes, semiconductor laser diodes that can directly emit green light with sufficient power and efficiency required in laser display are still not ready yet. Significant effort has been paid around the world to overcome this “green bottleneck”.

The aim of this thesis is to investigate a practical solution to build a compact green laser to satisfy the cost/performance requirement for laser display applications. Frequency doubling based on MgO doped periodically poled lithium niobate (MgO:PPLN) is the main research direction of this thesis work.

The thesis focuses on several engineering issues, mainly related to practical applications. Two different approaches have been explored: single-pass frequency doubling and intra-cavity frequency doubling. In the single-pass configuration, an all-fiber Q-switched fiber laser was used as the fundamental laser source because the high peak pump power can increase the conversion efficiency. 3.1%/W/cm nonlinear conversion efficiency was achieved which show good agreements with the theoretical simulations. The single-pass frequency doubling of a novel annealing proton exchanged (APE) MgO:PPLN ridge waveguide was also investigated. Over 120 mW green laser with a 53.2% conversion efficiency was achieved. The results have shown remarkable improvements comparing with the reported waveguide devices.

On the other hand, in the intra-cavity frequency doubling, Nd:YVO4/MgO:PPLN microchips for low power (300 mW CW green power and 530 mW modulated green power) applications have been demonstrated experimentally and investigated theoretically. It has been shown that although the plane-parallel cavity structure with discrete components can provide 2.9 W green laser with 29.6% conversion efficiency, it is complex for mass production. One of the important research achievements of this thesis is to study and optimization of a novel monolithically integrated Nd:YVO4/MgO:PPLN module (namely mGreen module) which combines the advantages of the microchip structure and the discrete plane-parallel cavity structure. 1.28 Watt output green laser has been achieved through a compact configuration based on the optimized mGreen module. Power scaling based on this monolithic green laser module by employing an array concept has also been investigated. The dependence of output power on pump beam gap has been studied both theoretically and experimentally.

abstract: Doctor of Philosophy (PhD)


title: COMPREHENSIVE METABOLOMICS ANALYSIS OF PEANUT ALLERGY AND PEANUT-INDUCED ANAPHYLAXIS

contributor:
McCarry, Brian
Chemistry

subject:
Metabolomics
Allergy
Anaphylaxis
Analytical Chemistry
Analytical Chemistry

abstract:
The work in this thesis encompasses (a) the development of a robust analytical method suitable for the comprehensive analysis of polar and non-polar metabolites in a single analysis and (b) the application of this method to the study of the metabolites involved in peanut allergy. During the course of this work the methods for the analysis of large metabolite data sets evolved significantly and the approaches used in this work evolved in parallel to the literature. This work constitutes the first comprehensive metabolomic investigation of an allergy response.

Hypersensitivity or allergy to peanuts is an increasingly problematic health concern around the world involving approximately 1-2% of children in North America. There are no useful clinical biomarkers for this allergy. Comprehensive metabolomics holds vast potential for the discovery of metabolites and metabolite pathways that may be involved during the development of peanut allergy and during peanut-induced anaphylaxis. The comprehensive study of metabolites involved in peanut allergy presented a significant challenge since no single analytical technique is capable of analysis of all metabolites within a single analytical run.

The thesis begins with development of a tandem column liquid chromatography-electrospray ionization-mass spectrometry method which allowed the separation and analysis of both polar and non-polar metabolites in a single analysis. This tandem column technique was also shown to significantly reduce the amount of ion suppression observed compared to the ion suppression observed when using either column independently.

This methodology was applied to the comprehensive metabolomics analysis of blood serum samples obtained from mice which were (a) being sensitized to peanuts and (b) undergoing anaphylaxis. This analysis discovered a profound impact on metabolites involved with purine metabolism, resulting in an elevation of uric acid levels. This discovery led to further investigations which confirmed that uric acid is essential for peanut sensitization in mice. This discovery was only possible due to the use of a comprehensive metabolomics approach.

The analytical methodology was then applied to the study of metabolomic changes in sensitized mice as they experienced peanut-induced anaphylaxis. A number of metabolomic changes including taurine level elevation were correlated with peanut-induced anaphylaxis. Finally, a serendipitous opportunity arose to analyze blood serum samples from peanut allergic children that had undergone an oral peanut challenge. The comprehensive metabolomic study of these samples revealed massive changes in their serum metabolomes as a result of peanut exposure. A number of lipids and lysophospho-lipids were shown to have increased dramatically and may represent novel biomarker candidates for peanut-induced anaphylaxis in humans.

In summary, this thesis had demonstrated that comprehensive metabolomic analyses can be successfully applied to complex syndromes such as peanut allergy and yield useful mechanistic and clinical insights to this disorder.

abstract: Doctor of Philosophy (PhD)


title: Pulsed Laser Heteroepitaxy of High Quality CdTe Thin Films on Sapphire Substrates

contributor:
Preston, J.S.
Engineering Physics

subject:
Cadmium Telluride
Pulsed Laser Deposition
Heteroepitaxy
Semiconductor and Optical Materials
Semiconductor and Optical Materials

abstract:
The growth of CdTe thin films on Al2O3 (0001) substrates by pulsed laser deposition from undoped pressed powder targets was studied. Thin film crystal structure was investigated by x-ray texture analysis as a function of plume flux, growth temperature and film thickness. Crystal texture increased for a decrease in plume flux. Single crystal CdTe (111) films were obtained by optimizing the plume flux. Increasing the growth temperature demonstrated a reduction in twin density. An optimum temperature of 300°C minimized the twin density without adverse desorption effects. The twin density decreased as an inverse squared function of film thickness. Single crystal CdTe films with comparable structural quality to Bridgeman single crystal wafers were grown under optimal conditions.

The optoelectronic properties of CdTe films were investigated by photoluminescence and photoreflectance spectroscopy. The room temperature bandgap energy of 1.51 eV was consistent between spectroscopic measurements. Broadening parameters for spectra were consistent with reference high quality material. Low temperature photoluminescence spectra had a dominant emission consistent with bound excitons found in bulk CdTe. Emissions consistent with self-compensation or doping were not found. Hall effect and conductivity measurements at 300 K demonstrated high resistivity for undoped material and electron mobilities comparable to bulk CdTe for lightly doped films. Spectroscopic and electrical measurements of high structural quality CdTe films were consistent with high optoelectronic quality.

An as-grown ability of the films to detach from their substrate was discovered. X-ray texture analysis and photoluminescence spectroscopy of films released onto rigid secondary carriers demonstrated that they maintained their structural and optoelectronic quality proceeding lift-off. Substrates having films released from them were found to be suitable for repeated growth. The technological relevance of this discovery is likely to drive further study into the lift-off phenomena and controlled doping of CdTe thin films.

abstract: Master of Applied Science (MASc)


title: Event-Related Potentials Reflect the Affective Priming Capacity of Music on Speech

contributor:
Connolly, John
Choy, Tsee Leng
Humanities

subject:
Event-Related Potentials
ERPs
Music
Language
Speech
Priming
Affect
Emotion
Semantics
Cognition and Perception
Cognitive Psychology
Modern Languages
Musicology
Other Music
Cognition and Perception

abstract: Music, like language, is a universal means of communication unique to humans, and the overlap of music and linguistic cognitive and neurological processes is well established. Performers and listeners alike are drawn to music as an avenue of emotional expression, as music is recognized for its rich emotional content. The study of affective priming indicates the communication of emotion-based concepts: stimuli that are related by affect give rise to response facilitation, an effect not observed to stimuli that are unrelated by affect. The measure of event-related brain potentials (ERPs) reveal, with exquisite temporal accuracy, that music clearly conveys emotion concepts in a manner commensurate to written language and prosody. To date, ERP studies of affective priming with music have involved written language and prosody, and have focused on the N400, an indication of semantic cognitive integration. The current study is the first to measure ERP responses in an affective priming paradigm of music and speech. In addition to the N400, the current study is the first of its kind to measure the N300, indicating cognitive categorization and the P300, reflecting recognition. Three sets of analyses – based on categorically correct responses, behaviourally correct responses and subjective responses – reveal N300 and N400 affective priming effects, corresponding to deliberate cognitive categorization and conceptual integration, respectively.

abstract: Master of Science (MSc)


title: β-catenin overexpression within the metanephric mesenchyme causes renal dysplasia via upregulation of the Gdnf signalling axis

contributor:
Bridgewater, Darren
Medical Sciences

subject:
Kidney development
branching morphogenesis
Developmental Biology
Genetic Processes
Medical Sciences
Developmental Biology

abstract: Renal dysplasia, a developmental disorder characterized by defective nephrogenesis and branching morphogenesis, ranks as one of the major causes of renal failure among the pediatric population. The molecular mechanisms underlying the pathogenesis of renal dysplasia are not well understood; however, changes in gene expression are a major contributing factor. In this study, we demonstrate that the levels of activated β-catenin, a transcriptional co-regulator, are elevated in the nuclei of ureteric, stromal, and mesenchymal cells within dysplastic human kidney tissue. To determine the mechanisms by which mesenchymal β-catenin over-expression leads to renal dysplasia, we generated a conditional mouse model in which β-catenin was stabilized exclusively in the metanephric mesenchyme. Kidneys from these mutant mice are remarkably similar to dysplastic human kidneys. In addition, these mutant mice also demonstrate the formation of 4 to 6 ectopic kidneys. While nephrogenesis appeared normal, investigation of ureteric branch pattern revealed ectopic ureteric budding off the Wolffian duct, ectopic branching off the initial ureteric bud stalk and a disorganization of branch patterning. In-situ hybridization of mutant kidneys revealed increased expression of Gdnf, Cret, and Wnt11, key factors that regulate ureteric branch patterning. We further demonstrate that β-catenin directly binds to TCF consensus binding sites within the Gdnf promoter region located 4.9kb, 2.25kb and 2.1kb upstream of the Gdnf transcriptional start site. Molecular cloning of the 4.9kb fragment upstream of a luciferase gene revealed that ß-catenin regulates gene transcription from the 4.9kb consensus site. Consistent with these findings, genetic deletion of β-catenin from the metanephric mesenchyme cell lineage lead to decreased Gdnf expression and a reduction in ureteric branching morphogenesis resulting in renal hypoplasia. Taken together, our findings establish that β-catenin is an essential regulator of Gdnf expression within the metanephric mesenchyme. Furthermore, we have identified a novel disrupted signalling pathway that contributes to the pathogenesis of renal dysplasia. In this pathway, an over-expression of β-catenin directly leads to an over-expression of Gdnf, causing ectopic and disorganized branching morphogenesis and, consequently, renal dysplasia.

abstract: Master of Health Sciences (MSc)


title: The Nature of Certainty in Wittgenstein's On Certainty

contributor:
Arthur, Richard
Griffin, Nick
Lapointe, Sandra
Philosophy

subject:
Wittgenstein
Certainty
Hinges
Norms
Agreement
Knowledge
Foundationalism
Learning
Arts and Humanities
Arts and Humanities

abstract: In this thesis I examine the concept of certainty in the work of Ludwig Wittgenstein, with a focus on the collection of remarks entitled On Certainty. In the first part I examine two essays of G.E. Moore that initiated Wittgenstein’s discussion of certainty and critique of Moore’s two essays. As I show, Wittgenstein believes that Moore misunderstood the use of the expression of I know in relation to the propositions of common sense. Instead, Wittgenstein believes that the common sense propositions stand for a certainty that belongs to the language-game itself, a certainty that stands fast for everyone who participates in the language-game, like hinges on which the rest of our knowledge and doubt turn. The rest of my thesis is spent examining three different interpretations of this notion of hinge certainty. The first is hinges as presuppositions to combat skeptical arguments, offered by the philosophers Crispin Wright and H.J. Glock. The second is that hinges are Wittgenstein’s version of foundationalism, serving as the foundational framework of human language, a notion primarily advocated by the philosophers Avrum Stroll and Danièle Moyal-Sharrock. I then examine the interpretation of hinges as learned norms of judging and acting that we must display certainty in if we are to learn a language. This is the interpretation of Rush Rhees and Meredith Williams, and is the position that I support. Finally, I show that contrary to some the remarks in On Certainty express a unified theme, rather than a series of disjointed and contradictory ideas.

abstract: Master of Philosophy (MA)


title: ISSUES REGARDING COMPLEX COMMUNITY-BASED CARDIOVASCULAR HEALTH INTERVENTIONS

contributor:
Dolovich, Lisa
Kaczorowski, Janusz
Thabane, Lehana
Health Research Methodology

subject: Cardiovascular Health Awareness Program

subject: Complex Interventions

subject: Theoretical Framework

subject: Intervention Fidelity

subject: Multilevel Analysis

subject: Partnership Strength

subject: Community Health and Preventive Medicine

subject: Health Services Research

subject: Knowledge Translation

subject: Other Social and Behavioral Sciences

abstract:
The thesis presents three papers discussing some of the methodological issues regarding studies investigating complex community-based cardiovascular health interventions. All three studies involved the Cardiovascular Health Awareness Program (CHAP), a standardised blood pressure and risk factor assessment and educational sessions held in pharmacies or other locally accessible areas in small to mid-sized communities in Ontario, Canada.

The first paper reviews the literature and proposes a guide on how to develop a theoretical framework for complex community-based interventions using CHAP as an example. The paper describes a stepwise process of developing a theoretical framework including challenges encountered and strategies employed to overcome them.

The second paper presents how recently published randomized controlled trials evaluating complex community-based cardiovascular health interventions monitored and reported implementation fidelity based on a structured review of the published articles and a survey of their primary authors. The results showed that fidelity reporting of included studies was better than those described in previous reviews. Fidelity was verified through self-reports by implementers and supervision by researchers. Strategies described to standardize intervention delivery were through training of implementers and use of implementation guides. The authors’ survey results were consistent with the review results though there were some gaps which could be improved to strengthen fidelity reporting.

A data analysis issue with studies investigating complex community-based interventions is that outcomes can be affected by factors from multiple levels. The third paper explores the association of individual, partnership, and community-related factors with CHAP participants’ use of health-related community resources and cardiovascular risk behaviours. This was a cross-sectional analysis of an on-going cohort study. The results showed that individual factors (age and self-efficacy) had the most consistent association with the outcomes. Community and partnership level variables showed less consistent association with the outcome. Methodological and analytical challenges were presented.

abstract: Doctor of Philosophy (PhD)


title: Lung Immunopathology Following Influenza And Pneumococcus Infection: Mechanisms Of Disease And Therapeutic Approaches

contributor:
Xing, Zhou
Medical Sciences

subject:
lung
immunopathology
influenza
pneumococcus
superinfection
immunity
Immunology of Infectious Disease
Immunopathology
Immunology of Infectious Disease

abstract: Influenza is a highly contagious respiratory disease. Yearly epidemics and pandemics account for high morbidity and mortality worldwide. Lung immunopathology is a major factor causing death following influenza. In addition, secondary bacterial superinfections that occur after influenza further complicate the lung immunopathology and contribute to higher morbidity and mortality. The research presented in this thesis addressed important, understudied questions in the complicated field of tissue immunopathogenesis and host defense to influenza and pneumococcal infections. Firstly, in a model of acute respiratory influenza infection, we found that the classically proinflammatory cytokine TNF plays a dual and biphasic role at different times post-infection. While it does have pro-immune roles in the beginning stages, TNF acts as a negative type 1 immune regulator at later points of infection. TNF controls the level of immune activation and has a key role in preventing lung immunopathology and aberrant tissue remodeling. Secondly, to further investigate mechanisms of lung pathology, we elucidated the role of bacterial replication and over activated host immune responses during bacterial superinfection following influenza. In our model of pulmonary Streptococcus pneumoniae infection after influenza, we found that dual infected animals experience rapid weight loss and succumb to infection. Bacterial outgrowth, dysregulated cytokine and chemokine expression, and severe lung neutrophilia and immunopathology are linked to the poor clinical outcome. Combined treatment with both an antibiotic azithromycin and corticosteroid dexamethasone best improves clinical outcome, bacterial clearance, cellular and cytokine responses, and immunopathology. Thirdly, in our continuing interest for improved therapies during pulmonary infections, we tested the transgenic expression of type I IFN as a treatment during S. pneumoniae infection. We found that IFN-a controls bacterial outgrowth and improves clinical outcome. Together, our findings provide novel insights into the mechanisms of lung immunopathology and treatment protocols for pulmonary influenza and pneumococcal infections.

abstract: Doctor of Philosophy (Medical Science)


title: Syntheses of Fluorine-18 Labelled Compounds and Radiopharmaceuticals by Electrophilic Fluorination

contributor:
Chirakal, R. V.
Schrobilgen, G. J.
Chemistry

subject: Chemistry Chemistry

abstract:
Previously, the fate of 5-fluoro-L-DOPA in the human brian was unknown because an efficient method for the synthesis of [18F]5-fluoro-L-DOPA in mCi quantities was not available. In the present work, a method for the synthesis of [18F]5-fluoro-L-DOPA in mCi quantities was developed by studying the reactivity and selectivity of fluorine during the electrophilic fluorination of L-DOPA in acidic solvents. As a result of this work, the present study has reported the first clinical study, using positron emission tomography (PET), that compared the in vivo behaviour of [18F]2-, [18F]5- and [18F]6-fluoro-L-DOPA, in the living human brain.

The site-specific fluorination method developed in the present work was extended to develop a high-yield synthesis of [18F]3-fluoro-L-α-methyltyrosine, which is a tumour imaging agent. Direct fluorination of L-α-methyltyrosine with [18F]F2 in HF solvent produced the 3-fluoro isomer as the major product in 30% radiochemical yield (RCY) with respect to [18F]F2, the highest RCY to date. These studies also revealed that a previous report had incorrectly characterized [18F]3,5-difluoro-L-α-methyltyrosine as [18F]2-fluoro-L-α-methyltyrosine. This methodology was further extended to develop a new PET tracer, [18F]5-fluoro-3-nitro-L-tyrosine, in order to trace "reactive nitrogen species", which are responsible for tissue damage in vivo.

A recent study has claimed that XeF2 exchanges with [2,2,2-crypt-M][18F] (M = K or Cs) to produce [18F]XeF2 at room temperature in CH2Cl2 solvent and that exchange between F and XeF2 cannot occur in CH3CN solvent. Contrary to previous work, the present study showed that both XeF2 and F react with CH2Cl2 at room temperature and that XeF2 fluorinates 2,2,2-crypt under rigorously anhydrous conditions. The major products resulting from these reactions include several hydrochlorofluorocarbons and large amounts of HF and HF2. Thus, the exchange between XeF2 and 18F reported in the prior work arises from exchange between XeF2 and HF/HF2, and does not involve fluoride ion. Furthermore, two-dimensional EXSY and single selective inversion NMR spectroscopic studies in the present work have shown that anhydrous [N(CH3)4][F] exchanges with XeF2 in CH3CN solvent. The exchange between XeF2 and F is postulated to proceed by the formation of the trifluoroxenate(II) anion, XeF3, a novel VSEPR system (i.e., the first AX3E3 arrangement), as the exchange intermediate.

abstract: Doctor of Philosophy (PhD)


title: MODELING AND MECHANISTIC INSIGHTS INTO THE DEVELOPMENT OF ALLERGIC AIRWAY RESPONSES TO HOUSE DUST MITE

contributor: Martin R. Stämpfli, Paul M. O’Byrne, Anthony J. Coyle

contributor: Medical Sciences (Molecular Virology and Immunology Program)

subject: allergic asthma

subject: house dust mite allergens

subject: mouse model

subject: airway inflammation

subject: allergic sensitization

subject: Th2 immunity

subject: Biological Phenomena, Cell Phenomena, and Immunity

abstract: Allergic asthma is a chronic and complex disease of the airways characterized by dysregulated immune-inflammatory responses to aeroallergens and reversible airflow obstruction. The prevalence and economic burden of allergic asthma have increased substantially over the last five decades. Despite remarkable progress in our understanding of the immunobiology and pathophysiology of asthma, the ontogeny of the disease remains elusive. As a result, there is a lack of effective preventative strategies. Here, we used a murine model of allergic asthma to house dust mite (HDM), the most pervasive indoor aeroallergen worldwide to address issues pertaining to the development of allergic asthma. First, we provided a comprehensive computational view of the impact of dose and length of HDM exposure on both local and systemic allergic outcomes (Chapter 2). Parameters, such as thresholds of responsiveness, and non-linear relationships between allergen exposure, allergic sensitization and airway inflammation were identified. We, then, investigated molecular signatures implicated in the onset of allergic responses (Chapter 3). HDM exposure was associated with production of the epithelial-associated cytokines TSLP, IL-25 and IL-33. However, only IL-33 signaling was necessary for intact Th2 immunity to HDM, likely because of its superior ability to induce the critical co-stimulatory molecule OX40L on dendritic cells and expand innate lymphoid cells. Lastly, as individuals are most likely exposed to allergens concomitantly to other environmental immunogenic agents, we studied the impact of an initial immune perturbation on allergic responses to sub-threshold amounts of HDM (Chapter 4). We showed that transient expression of GM-CSF in the airway substantially lowers the threshold of allergen required to generate robust, HDM-specific Th2 immunity, likely through increasing IL-33 production from alveolar type II cells. These studies favor a paradigm whereby distinct molecular pathways can elicit type 2 immunity, intimating the need to classify asthma into distinct clinical subsets.

abstract: Doctor of Philosophy (PhD)


title: DIFFERENTIAL PLURIPOTENT REGULATION DEPENDENT UPON DEFINED FACTORS IN HUMAN INDUCED PLURIPOTENT STEM CELLS

contributor:
Bhatia, Mick
Draper, Jon
Bedard, Andre
Biochemistry

subject:
Human pluripotent stem cells
self-renewal
differentiation
Biochemistry
Biochemistry

abstract: Human pluripotent stem cells (hPSCs) exist as a heterogeneous population within a dynamic niche, which governs their ability to self-renew and differentiate. Evidence modeled after mouse embryonic stem cells (mESCs) reveals the existence of a developmentally primitive, or homogeneous, state through chemically defined culture methods that is modulated by NANOG, a core pluripotent regulator. However, the differentiation potential and transcription factor control of the homogeneous state in human pluripotent stem cells remains elusive. Previous work suggests that bFGF/ACTIVIN extrinsic regulation provides the heterogeneous nature of hiPSCs with ability to differentiate into several multilineage lineage progenitors. Here, we illustrate that altering the extrinsic environment of hiPSCs with LIF and inhibitors of GSK3b and MAPK/ERK1/2 pathways (LIF/2i), rewires the intrinsic pluripotent regulation of OCT4 and NANOG, which ultimately prevents the in vitro hematopoietic differentiation potential. Upon conversion of hiPSCs to a primitive state of pluripotency with LIF/2i, this study reveals that prolonged culture of hiPSCs with LIF/2i erases the hematopoietic differentiation potential through retained expression of the POU domain pluripotent transcription factor, OCT4. Interestingly, shRNA mediated knockdown of OCT4 recovers the restricted differentiation potential in LIF/2i cultured hiPSCs, while knockdown of NANOG, does not. This study identifies a distorted differentiation potential of hPSCs cultured in mouse ESC conditions, despite comparable gene expression profiles and signaling pathway dependence. In efforts to simplify culture methods of human pluripotent stem cells, we identify that alteration of the extrinsic environment highlights explicit differences between human and mouse intrinsic pluripotent regulation, which ultimately controls differentiation efficiency.

abstract: Master of Science (MSc)


title: The Role of Periostin in Promoting the Progression of Clear Cell Renal Cell Carcinoma

contributor:
Tang, Damu
Medical Sciences

subject:
Periostin
ccRCC
stroma
fibroblasts
metastasis
Medical Sciences
Medical Sciences

abstract: The majority (75%) of renal cell carcinoma (RCC) is comprised of clear cell renal cell carcinoma (ccRCC). Despite ccRCC being the most aggressive form of RCC, our knowledge regarding the pathogenesis of the disease remains limited. We have identified upregulation of the extracellular protein periostin (POSTN) in ccRCC. Western blot analysis of ccRCC tumours from 27 patients demonstrated high POSTN protein expression in 26 tumours compared to their respective adjacent normal kidney tissue (ANK). Immunohistochemistry (IHC) analysis revealed high levels of stromal POSTN protein in the ccRCC primary tumours and 16 metastasized ccRCCs. Intriguingly, abundant stromal POSTN in the tumour and non tumour boundary were observed in local and metastaized ccRCC, and in A498 ccRCC cell-derived xenograft tumours. Collectively, these results suggest that the ccRCC-associated POSTN was derived from the stroma. This notion was supported by the co-existence of POSTN with α-smooth muscle actin (αSMA) in both local and metastasized ccRCC tumours. αSMA is a marker of activated stromal fibroblasts (myofibroblasts). Furthermore, co-culture of NIH3T3 murine fibroblasts with human A498 or 786-0 ccRCC cells dramatically enhanced POSTN transcription and secretion from NIH3T3 cells. Extracellular POSTN significantly enhanced A498 cell attachment. Upregulation of POSTN in NIH3T3 cells enhanced their proliferation. Taken together, my research demonstrates that 1) ccRCC induces fibroblast-mediated accumulation of extracellular POSTN, 2) stromal POSTN enhances ccRCC attachment, and 3) high levels of POSTN promotes fibroblasts' proliferation. These observations suggest a critical role for POSTN in mediating the co-evolving process between ccRCC and its stroma during ccRCC pathogenesis.

abstract: Master of Science (MSc)


title: Influence of maternal atopy and innate and adaptive immune stimuli on cord blood hematopoietic progenitor cells

subject:
toll-like receptors
cord blood
CD34+ cells
eosinophil-basophil
lipopolysaccharide
Medical Immunology
Medical Immunology

abstract: The recent and dramatic rise in allergic disease, coupled with the manifestation of the disease within the first years of life, suggests that in utero events are likely critically important to the inception of allergy. Epidemiological and experimental evidence suggest that both genetic predisposition and prenatal environmental exposures (e.g., in utero microbial exposures) play a role in modulating neonatal immunity and subsequent development of allergy. Of relevance to the work in this thesis, reports suggest that bacterial agents can directly alter myelopoiesis and, in connection to allergy, we have previously shown that cord blood (CB) progenitors from high-atopic risk infants demonstrate altered hematopoietic responses. However, whether CB progenitor cell hematopoietic responses are directly altered by microbial stimulation, and what effect maternal atopy has on these responses are unclear. Therefore, this thesis examines the influences of bacterial lipopolysaccharide (LPS) stimulation (innate immunity), maternal atopy, and adaptive immune stimuli (representative of an atopic milieu) on CB progenitor cell eosinophilopoiesis. We show that CB progenitors from healthy, pregnant women respond to LPS through increased eosinophil-basophil (Eo/B) colony forming units (CFU) via the mitogen-activated protein kinase (MAPK) signalling pathway (Chapter 2), whereas the presence of maternal atopy (as defined by skin prick test positivity) is associated with reduced CB CD34+ cell LPS-induced Eo/B CFU formation (Chapter 3). To investigate the potential mechanism of reduced eosinophilopoiesis in high-atopic risk infants, CB progenitors stimulated with IL-4 (a surrogate ex vivo for maternal atopy), but not IL-13, demonstrate reduced LPS-induced MAPK activation and Eo/B CFU formation (Chapter 4). This novel work provides insight into mechanisms relating to the influence of maternal atopy and/or potential intrauterine exposures (e.g., prenatal cytokines) on the responsiveness of CB progenitor cells to LPS, which may be of key importance for the development of atopic illnesses. These observations may help in the generation of novel biomarkers and therapeutic targets for childhood atopy.

abstract: Doctor of Philosophy (PhD)


title: Predicting the occurrence of major adverse cardiac events within 30 days after a patient’s vascular surgery: An individual patient-data meta-analysis

contributor:
Thabane, Lehana
Mathematics and Statistics

subject:
Biostatistics
meta-analysis
systematic review
cardiovascular epidemiology
logistic regression
generalized estimating equations
Biostatistics
Biostatistics

abstract:
Background: Major adverse cardiac events, MACE – a composite endpoint of cardiac death and nonfatal myocardial infarction (MI) – are severe harmful outcomes that commonly arise after elective vascular surgeries. As current pre-operative risk prediction models are not as effective in predicting post-operative outcomes, this thesis will discuss the key results of an individual patient data meta-analysis that is based on data from six cohort studies of patients undergoing vascular surgery.

Objectives: The purpose of this thesis is to determine optimal thresholds of continuous covariates and create a prediction model for major adverse cardiac events (MACE), within 30 days after a vascular surgery. The goals include exploring the minimum p-value method to dichotomize cutpoints for continuous variables; employing logistic regression analysis to determine a prediction model for MACE; evaluating its validity against other samples; and assessing its sensitivity to clustering effects. The secondary objectives are to determine individual models for predicting all-cause mortality, cardiac death, and nonfatal MI within 30 days of a vascular surgery, using the final covariates assessed for MACE.

Methods: Both B-type naturietic peptide (BNP) and its N-terminal fragment (NTproBNP) are independently associated with cardiovascular complications after noncardiac surgeries, and particularly frequent after noncardiac vascular surgeries. In a previous study, these covariates were dichotomized using the receiver operating characteristic (ROC) curve approach and a simple logistic regression (SLR) model was created for MACE [1]. The first part of this thesis applies the minimum p-value method to determine a threshold for each natriuretic peptide (NP), BNP and NTproBNP. SLR is then used to model the prediction of MACE within 30 days after a patient’s vascular surgery. Comparisons were made with the ROC curve approach to determine the optimal thresholds and create a prediction model. The validity of this model was tested using bootstrap samples and its robustness was assessed using a mixed effects logistic regression (MELR) model and a generalized estimating equation (GEE). Finally, MELR was performed on each of the secondary outcomes.

Results:A variable, ROC_thrshld, was created to represent the cutpoints of Rodseth’s ROC curve approach, which identified 116pg/mL and 277.5pg/mL to be the optimal thresholds for BNP and NTproBNP, respectively [1]. The minimum p-value method dichotomized these NP thresholds as BNP: 115.57pg/mL (p

Discussion: One key limitation to this thesis is the small sample size received for NTproBNP. Also, determining only one cutpoint for each NP concentration may not be sufficient, since dichotomizing continuous factors can lead to loss of information along with other issues. Further research should be performed to explore other possible cutpoints along with performing reclassification to observe improvements in risk stratification. After validating our final model against other samples, we can conclude that MINP_thrshld, the type of surgery, and diabetes are significant covariates for the prediction of MACE. With the simplicity in only requiring a blood test to measure NP concentration levels and easily learning the status of the other two factors, minimal effort is needed in calculating the points and risk estimates for each patient. Further research should also be performed on the secondary outcomes to examine other factors that may be useful in prediction.

Conclusions: The minimum p-value method produced similar results to the ROC curve method in dichotomizing the NP concentration levels. The cutpoints for BNP and NTproBNP were 115.57pg/mL and 241.7 pg/mL, respectively. Further research needs to be performed to determine the optimality of the final prediction model of MACE, with covariates MINP_thrshld, type of surgery, and diabetes mellitus.

abstract: Master of Science (MSc)


title: Rapid Re-optimization of Prostate Intensity-Modulated Radiation Therapy Using Regularized Linear Programming

contributor:
Anand, Christopher
WIerzbicki, Marcin
Computer Science

subject:
Computational Engineering
Computational Engineering

abstract: This thesis presents a new linear programming approach for re-optimizing a intensity modulated radiation therapy (IMRT) treatment plan, in order to compensate for inter-fraction tissue deformations. Different formulations of the problem involve different constraints, but a common constraint that is difficult to handle mathematically is the constraint that the dose be deliverable using a small number of multi-leaf collimator positions. MLC leaves are tungsten alloy attenuators which can be moved in and out to shape of the radiation aperture. Since leaves are solid, photon fluence profiles will follow a staircase function and this constraint is not convex, and difficult to formulate. In this thesis, we propose a relaxation of this constraint to the `1-norm of the differences between adjacent radiation fluxes. With the appropriate bound, this constraint encourages the dose to be deliverable with a series of shrinking or growing openings between the leaves. Such a solution can be made realizable by rounding, which is beyond the scope of this thesis. This approach has been tested on an anonymized prostate cancer treatment plan with simulated deformations. Without rounding, solutions were obtained in five of nine cases, in less than 4 to 5 seconds of computation on a NEOS server. Solved cases demonstrated excellent target coverage (minimum dose in the target was 95% of the prescribed dose) and organ sparing (mean dose in normal tissues was below 25% of the prescribed dose).

abstract: Master of Science (MSc)


title: INDUCTION OF NEUROTROPHIC AND DIFFERENTIATION GENES IN NEURAL STEM CELLS BY VALPROIC ACID

contributor: Medical Sciences (Division of Physiology/Pharmacology)

subject:
Neural Stem Cells
Valproic acid
neuronal differentiation
neuroprotection
Neurotrophins
Histone acetylation
gene expression
Medical Cell Biology
Medical Molecular Biology
Medical Neurobiology
Medical Pharmacology
Medical Sciences
Medicine and Health Sciences
Medical Cell Biology

abstract: Valproic acid (2-propylpentanoicacid) has long been in use as an anticonvulsant and mood-stabilizer. Recently, VPA has been shown to inhibit the activity of histone deacetylases (HDACs), resulting in chromatin remodelling and changes in gene expression. Although the molecular mechanism for VPA action in the central nervous is not well understood, many signalling pathways have been suggested as targets for this HDAC inhibitor. For instance, VPA was found to induce differentiation in adult hippocampal neural progenitor cells via the β-catenin-Ras-ERK pathway. Also, VPA up regulated Bcl-2, a neurotrophic/neuroprotective protein, with association of extracellular signal-regulated kinase (ERK-1) and phosphatidylinositol 3- kinase (PI3) pathway activation. In this study, C17.2 neural stem cells were used to examine the effects of VPA on the expression of several neurotrophic factors including; cerebral dopamine neurotrophic factor (CDNF) and mesencephalic astrocyte-derived neurotrophic factor (MANF), glial cell-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF). Other genes including; the orphan nuclear receptor-related factor1 (Nurr-1), the early growth response protein 1(Egr-1), and the sex determining region Y-box-2 (Sox-2) were examined. Histone H3 acetylation and the ERK1/2 pathway were examined as possible targets for VPA action. Treatment with clinically relevant concentrations of VPA (1mM, and 3 mM) induced a significant increase of CDNF protein concentrations. Also, increases in the mRNA expression of GDNF, Nurr-1, and Egr-1 were detected following 24 hours VPA treatment at clinically relevant concentrations. Moreover, an increase of histone H3 acetylation was noticed in C17.2 NSCs. These findings might support the role of VPA in neuronal differentiation and neuroprotection.

abstract: Master of Science (MSc)


title: IMPROVING ONCOLYTIC VESICULAR STOMATITIS VIRUS THROUGH MODULATION OF THE ANTI-TUMOUR IMMUNE RESPONSE

contributor:
Lichty, Brian D
Medical Sciences

subject:
Oncolytic Virus
VSV
cancer biotherapeutics
p14 FAST
IL-15
Virology
Virology

abstract:
Despite improvements in detection and treatment, cancer is the leading cause of death worldwide. Current treatment modalities have not been able to improve the mortality rates and significant toxicities limit efficacy. Therefore there is a need for development of novel therapeutics.

Oncolytic viruses have the ability to efficiently replicate in and destroy tumours while leaving normal tissues unharmed. These treatment platforms have been gaining momentum in recent years due to pre-clinical and clinical successes. Oncolytic viruses are extremely safe with limited toxicity observed in phase I/II clinical trials, and objective responses have been observed in some patients treated with oncolytic viruses. However, there is still room to improve on these therapeutic platforms.

Recently, the importance of the induction of anti-tumour immunity during oncolytic virotherapy has been realized and harnessing this immune response can be used to improve current oncolytic virus platforms. To this end we have conducted numerous studies assessing our ability to improve oncolytic VSV through the addition of transgenes to enhance the immunostimulatory properties of oncolytic VSV treatment. These studies showed that only the addition of a highly secreted form of human IL-15 was able to improve VSV therapy through enhanced anti-tumour immunity. However, expressing cell-autonomous transgenes from oncolytic VSV was unable to modify the therapeutic efficacy of VSV due to limited replication, both temporally and geographically within the tumour, and the indirect vascular shutdown induced by VSV infection of tumours. We believe that the drastic vascular shutdown observed following VSV therapy is an important component to the success of VSV and we have investigated which steps in this process are critical for induction of anti-tumour immunity.

The research presented in this thesis further enforces the requirement for induction of anti-tumour immune responses in the success of OV therapy. Our findings also indicate that manipulating the tumour as a whole, rather than the virus, will lead to improved oncolytic therapeutics.

abstract: Doctor of Philosophy (PhD)


title: EFFECTS OF VALPROIC ACID ON EXPRESSION OF THE MELATONIN RECEPTORS MT1 AND MT2, AND THE NEUROTROPHIC FACTORS BDNF AND GDNF IN VIVO

contributor: Medical Sciences (Neuroscience and Behavioral Science)

subject:
Valproic acid
melatonin
melatonin receptors
GDNF
BDNF
HDAC inhibitor
epigenetic
in vivo
Molecular and Cellular Neuroscience
Neuroscience and Neurobiology
Molecular and Cellular Neuroscience

abstract:
Valproic acid (VPA) is clinically utilized as an anti-convulsant and mood stabilizer, though its mechanism of action has not been fully elucidated. Evidence suggests an interaction between VPA and the melatonergic system as VPA up-regulated the melatonin MT1 receptor subtype in rat C6 glioma cells. To determine if the observed effects can translate to an in vivo model, we investigated the effects of chronic VPA administration in a rat model on the expression of MT1 and MT2 receptors in the hippocampus. We also investigated the effect of chronic VPA treatment on the expression of the neurotrophic factors BDNF and GDNF in the rat hippocampus and striatum.

(1) Animals were separated into two groups with the experimental group receiving VPA (4 mg/mL) for 17 days, and the control receiving vehicle. The hippocampus was dissected and MT1, MT2, BDNF and GDNF mRNA were analyzed with RT-PCR. (2) Animals were separated into three groups with the first group receiving VPA (4 mg/mL), the second receiving VPA (3 mg/mL) for 16 days, and the control receiving vehicle. MT2 mRNA in the hippocampal subregions were analyzed with in situ hybridization.

VPA induced the expression of MT1 and MT2 mRNA in the hippocampus in the experimental group compared to the control group. VPA also increased MT2 mRNA expression in the subregions of the hippocampus. Additionally, BDNF and GDNF mRNA expression were increased in the VPA treatment group.

These findings raise the interesting question of whether the diverse clinical effects of VPA involve an interaction with the melatonergic system.

abstract: Master of Science (MSc)


title: Complex Rare-earth Antimonide Suboxides for Thermoelectric Applications

contributor:
Mozharivskyj, Yurij
John E Greedan, Jacques Barbier
Chemistry and Chemical Biology

subject:
Semiconductor
Thermoelectric
Solid-state Chemistry
Crystallography
Rare-earth Elements
Electronic Structure
Condensed Matter Physics
Inorganic Chemistry
Materials Chemistry
Semiconductor and Optical Materials
Condensed Matter Physics

abstract: Thermoelectric (TE) materials are able to convert heat directly into electricity and vice versa. This special property makes them valuable for a variety of applications involving power generation and refrigeration. In the search for potential high-performance TE materials, a number of rare-earth (RE) antimonide suboxide phases have been investigated.This presentation will focus on two classes of rare-earth antimonide suboxides: the RE3Sb3O3 and RE8Sb3-dO8 phases (C2/m space group) based on the RE–O frameworks and the anti-ThCr2Si2 type RE2SbO2 compounds (I4/mmm space group). The physical property measurements on the high-purity bulk samples revealed unexpected semiconducting properties in the non-charge-balanced systems, i.e. RE8Sb3-dO8 and RE2SbO2. Since the electronic structure calculations suggest that the anionic Sb states dominate the valence band at the vicinity of the Fermi level, the local structure of the Sb atomic site is believed to dictate the observed physical properties. The charge transport properties are explained within the framework of Anderson/Mott-type localizations. Ultimately, systematic investigation of the RE2SbO2 and Ho2Sb1-xBixO2 series reveal the large variability of the electrical properties caused by the local structural perturbations.

abstract: Doctor of Philosophy (PhD)


title: Pax7 is Required for Muscle Satellite Cell Specification and Regenerative Myogenesis

contributor:
Rudnicki, Michael A.
Biology

subject: Biology Biology

abstract:
Muscle satellite cells are a distinct population of myogenic progenitors that mediate the postnatal growth and regeneration of skeletal muscle. To gain insight into the genetic regulation of satellite cell function during muscle regeneration, genes expressed specifically in these cells were identified by representational difference analysis of cDNAs. Notably, the paired-box transcription factor Pax7 was isolated as a gene specifically expressed in quiescent and activated satellite cells. Cell culture and histological analysis of Pax7-deficient muscle revealed a complete absence of satellite cells. This result demonstrates a requirement for Pax7 upstream of MyoD and Myf5 in the specification of muscle satellite cells. Consistent with their lack of satellite cells, adult Pax7 mice displayed an aggravated muscle wasting phenotype characterized by spinal kyphosis and reduced muscle mass. Acute muscle damage led to extensive calcification and deposition of adipose and fibrotic tissues with the appearance of rare regenerated myofibers. Importantly, analysis of Pax7 muscle suspensions indicated that myogenic cells expressing Pax3 and MyoD were responsible for this low level of regeneration.

To characterize the role of adult stem cells in skeletal muscle, we investigated the myogenic potential of muscle-derived CD45+:Scal+ cells in vivo during regeneration and in vitro using coculture assays. CD45+ and Scal+ cells isolated from uninjured muscle were uniformly non-myogenic. Strikingly, 7-10% of CD45+:Scal+ cells purified from regenerating muscle activated the myogenic program by a Pax7-dependent mechanism in response to activation of the Wnt signaling pathway. Furthermore, expression of Pax7 was sufficient to induce myogenic commitment in CD45+:Scal+ cells from uninjured muscle. This result demonstrates that non-satellite cell derived myogenic progenitors possess a physiological role in muscle regeneration and tissue homeostasis.

Taken together, this work establishes a requirement for Pax7 in the specification of muscle satellite cells and for the myogenic recruitment of adult stem cells populations during tissue repair. Importantly, these studies also suggest that targeted therapies to activate Wnt signaling and Pax7 expression in adult stem cells will be effective for promoting muscle regeneration in patients with degenerative neuromuscular diseases or muscular dystrophies.

abstract: Doctor of Philosophy (PhD)


title: ON THE CRYSTALLOGRAPHY OF BAINITIC TRANSFORMATION IN STEELS

contributor:
Purdy, Gary
Botton, Gianluigi
Hoyt, Jeffrey
Materials Science and Engineering

subject:
bainite
phase transformations
interface
dislocations
O-Lattice
nucleation
Structural Materials
Structural Materials

abstract:
Bainite is a low temperature transformation product of austenite decomposition in steels. Its unique range of microstructures offers promising combinations of strength with ductility. At low transformation temperatures the crystallography of a phase transformation often plays an important role in the overall microstructure and how it develops. Therefore in this study the structures of ferrite/cementite and ferrite/austenite interfaces in bainite were investigated from a crystallographic viewpoint. After describing these interfaces, the idea of interphase boundary nucleation of cementite on a ferrite/austenite interface was investigated.

An O-line model (a special case of the O-Lattice) was used to explain the observed experimental results on orientation relationship, habit plane and good matching direction between ferrite and cementite. The calculated orientation relationship was used in an NCS (near coincident site) model to describe several possible edge facets of cementite precipitates. The major observed edge facet in cementite is deviated from the more favored interfaces based on the NCS model. This deviation could imply that the edge facets are non-equilibrium interfaces whose orientations and morphologies are kinetically determined.

Focused Ion Beam sectioning, conventional transmission electron and optical microscopy were used to shed more light on the three dimensional nature of a complex cementite-free bainitic microstructure. The faceted interfaces of bainitic ferrite were characterized and it was shown that the habit plane contains edge misfit dislocations. The orientation of the bainitic ferrite lath did not match an O-line model. Transformation time was considered to play an important role on the orientation and morphology of the bainitic laths and interfacial dislocation character.

Finally, with the aid of known crystallographic relations and interfaces between the ferrite/cementite, ferrite/austenite and austenite/cementite phases, a model for cementite nucleation was proposed. This interphase boundary nucleus is assumed to form on a coherent ferrite/austenite interface and to possess ferrite/cementite and austenite/cementite calculated habit planes as two main facets surrounding the nucleus. It was shown that cementite nucleation would be viable if interfacial energies of all surrounding facets of a nucleus are in a semi-coherent energy range.

abstract: Doctor of Philosophy (PhD)


title: HIGH PERFORMANCE WORK SYSTEMS: A CAUSAL FRAMEWORK OF TRAINING, INNOVATION, AND ORGANIZATIONAL PERFORMANCE IN CANADA

contributor:
Zeytinoglu, Isik U.
Catherine Connelly, Willi H. Wiesner
Business

subject:
High Performance Work System (HPWS)
innovation
organizational performance
training
strategy
product leadership
operational excellence
human capital
resource-based theory
technology
Human Resources Management
Human Resources Management

abstract: The processes that link High Performance Work System (HPWS) practices and organizational performance are not fully understood. Using resource-based theory, this research focuses on training, by separating it from other HPWS practices, and human capital development as a source of sustained competitive advantage. The first purpose of my research is to examine the relationships between the HPWS practice of training, innovation, and organizational performance, and look at the mediating effect of innovation over time at the workplace level. The results indicate that the temporal pathway from training to innovation to organizational performance is positive and significant even after controlling for reverse-causality. Strategic activity is also explored and is found to be a significant moderator. This study contributes to knowledge by identifying the importance of aligning business strategy with training, as well as other HPWS practices and innovation to achieve improved organizational performance outcomes. The second purpose of this research is to explore the factors that act to expand or limit the HPWS practice of training, with a focus on the outcomes of employers' decisions to offer training, employees' decisions to accept or decline training, and the job-related training received by employees. The results indicate that the employee-level factors: participating in HPWS practices, use of technology, and using new technology are significant contributors to employers' decisions to offer and employees' receipt of training. Further, employees' perception of the existence of a gap between the skills required for the job and their current skills contributes to employees accepting employer offers of training.

abstract: Doctor of Philosophy (PhD)


title: Nonlinear waves in weakly-coupled lattices

contributor:
Pelinovsky, Dmitry
Mathematics

subject: nonliner lattices

subject: discrete nonlinear Schrodinger equation

subject: Klein-Gordon lattice

subject: nonlinear waves

subject: discrete breathers

subject: discrete solitons

subject: Non-linear Dynamics

subject: Ordinary Differential Equations and Applied Dynamics

subject: Partial Differential Equations

subject: Non-linear Dynamics

abstract:
We consider existence and stability of breather solutions to discrete nonlinear Schrodinger (dNLS) and discrete Klein-Gordon (dKG) equations near the anti-continuum limit, the limit of the zero coupling constant. For sufficiently small coupling, discrete breathers can be uniquely extended from the anti-continuum limit where they consist of periodic oscillations on excited sites separated by "holes" (sites at rest).

In the anti-continuum limit, the dNLS equation linearized about its discrete breather has a spectrum consisting of the zero eigenvalue of finite multiplicity and purely imaginary eigenvalues of infinite multiplicities. Splitting of the zero eigenvalue into stable and unstable eigenvalues near the anti-continuum limit was examined in the literature earlier. The eigenvalues of infinite multiplicity split into bands of continuous spectrum, which, as observed in numerical experiments, may in turn produce internal modes, additional eigenvalues on the imaginary axis. Using resolvent analysis and perturbation methods, we prove that no internal modes bifurcate from the continuous spectrum of the dNLS equation with small coupling.

Linear stability of small-amplitude discrete breathers in the weakly-coupled KG lattice was considered in a number of papers. Most of these papers, however, do not consider stability of discrete breathers which have "holes" in the anti-continuum limit. We use perturbation methods for Floquet multipliers and analysis of tail-to-tail interactions between excited sites to develop a general criterion on linear stability of multi-site breathers in the KG lattice near the anti-continuum limit. Our criterion is not restricted to small-amplitude oscillations and it allows discrete breathers to have "holes" in the anti-continuum limit.

abstract: Doctor of Philosophy (PhD)


title: THE ASSESSMENT AND PROCESSING OF TACTILE SENSORY LEARNING

contributor:
Lee, Timothy D.
Kinesiology

subject:
tactile learning
morse code
vibrotactile
somatosensory evoked potentials
masking
paresthesia
Cognition and Perception
Sense Organs
Cognition and Perception

abstract:
This dissertation examined perturbation effects during complex tactile information transmission. The four experiments provide evidence regarding sensory and information processing demands in early stages of complex tactile learning.

Experiment 1 established complex tactile learning behavioural performance. Vibrotactile stimuli representing Morse code letters were communicated to participants with or without induced perturbation to the finger of letter reception. Response performance was measured and augmented feedback was provided retroactively. Perturbation conditions lead to poor performance during tactile acquisition, but improved performance during application of knowledge.

Experiment 2 determined if the experiment 1 results demonstrated masking or response competition paradigms. Target “masking” is the reduced ability to detect or interpret a stimuli pattern by presentation of other information (Craig, 1985; Verrillo, 1985). Response competition is the competition or distraction from target response generation by secondary stimuli (Craig, 2000; Bolanowski et al., 2000). Experiment 2 tested response competition by spatially separating the perturbation and tactile information delivery sites.

Experiments 3 and 4 served to replicate behavioural acquisition data from experiments 1 and 2. They also extended the findings of the first two experiments by introducing neurophysiological measurement to reflect the changes associated with the two perturbation conditions. The study discerned whether the masking and response competition paradigms from experiments 1 and 2 were predominantly impacting the peripheral or central information processing.

Results from the four studies collectively demonstrate that increased demands are placed on the sensory system during early stages of complex tactile learning when perturbation is spatially congruent with tactile information delivery. Experiments 1 and 2 revealed that attention does not supersede spatial location of perturbation, and perturbation location is paramount to yield sufficient interference to impede acquisition yet lead to enhanced knowledge retention and transfer. Experiments 3 and 4 determined that cortical information processing associated with complex tactile information acquisition are neurophysiologically differentiated when relative locations of meaningful and perturbation stimuli are congruent or spatially separated. The findings from this dissertation serve as an advancement of our understanding of masking and response competition phenomenon as they pertain to complex tactile learning.

abstract: Doctor of Philosophy (PhD)


title: SINGLE CRYSTAL SILICON SUBSTRATE PREPARED BY VAPOUR-LIQUID INTERFACE GROWTH

contributor:
Kitai, A.
Materials Science and Engineering

subject:
Silicon
Semiconductor
Liquid phase epitaxy
Crystal growth
Other Engineering Science and Materials
Semiconductor and Optical Materials
Other Engineering Science and Materials

abstract:
Preparing silicon wafers is a tedious multi-step process that includes etching, polishing, and cleaning. The minimum wafer thickness attainable in current high volume wafer production processes is generally 160 to 300 μm, and the kerf loss for these processes is up to 40% of the total volume. Thin silicon wafers (~30 to 100μm) are very expensive to produce and the wafering process is not cost effective due to the high amount of material loss (more than 80% at these dimensions) during the process and the risk of breakage of the wafers during wafering. In this thesis, a new method called Vapour-Liquid Interface Growth (VLIG) is proposed. VLIG is capable of directly growing a sheet of single crystal silicon without wafering with a thickness of about 30 to 50μm. The features of the process are 1) low temperature operation; 2) the resulting silicon sheet is easily detachable and self-supporting; 3) the resulting sheet has uniform thickness and is single crystal. The system operates in a supersaturated growth solution of an indium-silicon melt. A seed line in a substrate facing down is employed. A layer of single crystal silicon grows on the seed line at the melt surface due to surface segregation during the super cooling process. The grown silicon can grow laterally due to the limited thickness of the melt depth that minimizes growth in the vertical growth direction. The grown silicon can be easily peeled off from the seed line substrate due to the presence of a gap between the grown silicon sheet and the oxide layer on the seed line substrate. The self-supporting silicon sheet now comprises a very thin silicon substrate or sheet.

VLIG silicon sheet is characterized by X-ray diffraction to determine the crystallinity. Hall Effect measurements are performed to measure the electrical properties. VLIG silicon sheet is (111) oriented single crystal and it exhibits the same orientation as the substrate. The growth temperature is from 975 to 850oC, and the VLIG silicon is p-type doped with indium. The resistivity is 4.181x10-3 ohm-cm, and the doping level is around 5.3.0x1018 /cm3. The measured mobility is ranging from 280 cm2/V.s. In this study, VLIG demonstrates the potential of growing thin sheet of single crystal silicon with qualities that feasible for photovoltaic application.

abstract: Master of Applied Science (MASc)


title: INVESTIGATION OF THE STRUCTURAL DETERMINANTS STABILIZING THE OPEN CONFORMATION OF THE CLPP AXIAL CHANNEL

contributor:
Ortega, Joaquin
Gerry Wright, Marie Elliot
Biochemistry

subject: ClpP

subject: ClpA

subject: ADEP

subject: Biochemistry

subject: Biochemistry, Biophysics, and Structural Biology

subject: Life Sciences

subject: Biochemistry

abstract: Caseinolytic protease P (ClpP) is a compartmentalized bacterial protease tightly regulated by AAA+ proteins such as ClpA and ClpX within Escherichia coli. It is known that the amino terminus is required to gate the axial entry pores of ClpP however the conformation adopted during activation by ClpA and ClpX has not been properly characterized. Recently it has been determined that binding of a group of antimicrobials termed acyldepsipeptides induces the open conformation of the axial channel independent of ClpA or ClpX to mediate the translocation of unfolded proteins. To determine the structural determinates required to stabilize the open conformation of the axial channel during acyldepsipeptide binding we generated amino terminal variants by site directed mutagenesis. It was found that the formation and anchoring of a β-hairpin element at the amino terminus was crucial for the effective translocation of protein substrates. These results describe the structural requirements that mediate substrate translocation during acyldepsipeptide induced activation and provide a model for the structural requirements of the ClpP amino terminus during formation of the ClpAP and ClpXP holocomplexes.

abstract: Master of Science (MSc)


title: DYNAMIC IT CAPABILITIES: THEORY DEVELOPMENT AND EMPIRICAL EXAMINATION

contributor:
Montazemi, Ali Reza
Business Administration

subject: dynamic capabilities

subject: IT governance

subject: technology enactment

subject: knowledge management

subject: Business Administration, Management, and Operations

subject: Management Information Systems

subject: Strategic Management Policy

subject: Technology and Innovation

abstract: This thesis examines dynamic IT capabilities: firms’ abilities to integrate, build, and reconfigure information technology resources concurrently with organizational business process and managerial processes in pursuit of performance advantages in a changing or uncertain environment. Research in dynamic IT capabilities has increased with the recognition that organizational survival and growth requires organizational change to resolve a range of management challenges that emerge over time. In prior research, specific constructs of dynamic IT capabilities have been the subject of independent empirical investigation. This has resulted in conflicting conceptualizations of dynamic capabilities that obfuscate theoretical definition, empirical grounding and measurement. We seek to contribute conceptual coherence to the discourse on dynamic IT capabilities in three respects. First, we advance a theoretical framework to tease apart the common versus idiosyncratic elements of firms’ dynamic capabilities to exploit IT in practice. Our empirical findings serve to integrate conflicting (common versus idiosyncratic) conceptualizations of dynamic IT capabilities. Second, we advance a theoretical framework of firms’ dynamic capabilities to explore for IT innovations that are likely to improve firm performance. To that end we examine CIOs’ use of external advice networks to mindfully identify rewarding IT innovations. In so doing we clarify the concept of mindfulness. We find mindful external advice seeking is atypical in practice, contrary to assumptions of the technology diffusion and institutional literatures. Our empirical findings elucidate the significance of IT governance in motivating mindful search for rewarding IT innovations. Third, we demonstrate the importance of qualitative and configurational methodologies in investigating such complex phenomena as dynamic IT capabilities. We also propose promising future research directions, theoretical grounding and analytical techniques that, by building on the concepts advanced in this study, can further advance our understanding of how firms acquire and realize dynamic IT capabilities in support of sustained performance advantages.

abstract: Doctor of Philosophy (PhD)


title: Frailty Models for Modelling Heterogeneity

contributor:
Balakrishnan, Narayanaswamy
R. Viveros-Aguilera, A. Childs
Statistics

subject:
Statistics and Probability
Statistics and Probability

abstract: In the analysis of lifetime data, heterogeneity may be present in many situations. This heterogeneity is also referred to as frailty. Analysis that ignore frailty when it is present leads to incorrect inferences. In lifetime analysis, Cox proportional hazards model is commonly used to measure the effects of covariates. The covariates may fail to fully account for the true differences in risk. This may be due to an existence of another variable that is ignored in the model but can be explained by random frailty. Including frailty in the model can avoid underestimation and overestimation of parameters and also correctly measure the effects of the covariates on the response variable. This thesis presents an extension of Cox model to parametric frailty model in which the exponential and Weibull distributions are used as the distributions of baseline hazard, and the gamma and Weibull distributions are used as frailty distributions. We examine the maximum likelihood estimation procedures and propose the use of Monte Carlo integration method or quadrature method in complicated cases where explicit solutions to the likelihood functions can not be obtained. The gamma distribution is one of the most commonly used distributions for frailty. It has a closed form likelihood function that can be readily maximized. In this thesis, we study the performance of the Weibull distribution as a frailty distribution and compare with the gamma frailty model. Through simulation studies, the performance of the parameter estimates are evaluated. The effects of increasing the sample size and cluster size separately are also studied through Monte Carlo simulations. The Akaike Information Criteria (AIC) is used to compare the performance of the gamma and Weibull frailty models. The developed methods are then illustrated with numerical examples.

abstract: Master of Science (MSc)


title: Durability of Repair Techniques of Fine Cracks in Concrete

contributor:
Chidiac, Samir E.
Civil Engineering

subject:
Concrete Repair
Cracks
Durability
Freeze-Thaw
Service Life
Non-Destructive Evaluation
Civil Engineering
Structural Engineering
Structural Materials
Civil Engineering

abstract:
Aging public infrastructure in North America continues to challenge engineers and scientists to develop repair and rehabilitation strategies that are practical, durable and cost effective. Of specific interest is the state of concrete and concrete repair in buildings and civil engineering infrastructures that are in deteriorating condition. In particular, cracks pose a threat to the durability and ultimately the structural integrity of concrete. Cracks in concrete may form for several reasons, e.g. plastic shrinkage, thermal contraction, mechanical loading or as a result of overloading. Once formed, cracks present a combination of problems to the service life and performance of the structure. Therefore cracks must be repaired for the following reasons: to prevent the ingress of deleterious agents such as water, other liquids, vapour, gas, chemicals and biological agents; to either restore or increase the structural load-bearing capacity of the cracked concrete member; to restore the aesthetic condition of the structure.

The effectiveness of two different repair methods, crack injections and cementitious overlays, were examined. Two repair materials, a low viscosity epoxy and polyurethane were injected into the cracks, and a thin polymer-modified cementious overlay was applied on the cracked surface. Two types of cement were used, an ordinary Portland cement and a blended cement with 8% silica fume. The specimen properties were evaluated using non-destructive testing, prior to being subjected to a series of freeze-thaw conditioning regimes. From the experimental program, it was determined that the epoxy injection repair was more effective in restoring the air tightness than the thin overlay. The polyurethane material was unsuccessful. Following the freeze-thaw regimes, an overall improvement of conditions for all three repairs was observed, with the cementitious overlay seeing the greatest improvement in air tightness. These results indicate that the on-going cement hydration mechanism had a greater effect on the performance in comparison to the deleterious effects of the environmental loads.

abstract: Master of Applied Science (MASc)


title: Simulation and Optimization of an Existing Ethylbenzene Dehydrogenation Reactor.

contributor:
Crowe, C. M.
Chemical Engineering

subject:
Chemical Engineering
Chemical Engineering

abstract:
The main purpose of this research was to find, from a simulation of an existing reactor under rather heavy constraints, how upon removal of these limitation the same reactor could be operated more economically and, efficiently. An accurate, simplified model of the process was developed and used in the design of single and double bed reactors with very consistent results. A better understanding of the process variables, reactions and constraints was obtained by extrapolation of the model within reasonable bounds.

The usefulness of a multivariate search technique applied to a relatively complicated process was proven. Such techniques as Pontryagin's Maximum Principle l and dynamic programming2 become unwieldy for processes involving many state variables. An engineer can quickly grasp the ideas of multi-variable search methods whereas it is difficult to understand the above more elaborate techniques without much study. This report may be particularly useful to plant-process engineers who seek a practical optimum-seeking method.

abstract: Master of Engineering (MEngr)