title: Engineering Functional Interfaces for Biosensing, Minimization of Protein Adsorption, and Structural Self-Healing

contributor:
Filipe, Carlos
Hoare, Todd
Chemical Engineering

abstract:
This thesis describes strategies on how to efficiently modify biological interfaces either effectively to reduce nonspecific protein binding in various contexts or to encourage specific interfacial interactions following exposure to a ligand or following the disruption of a biomaterial.  Nonspecific protein adsorption at interfaces is a significant issue in the development of robust biosensors and implantable biomaterials, and modifying surfaces to achieve this goal is currently a complicated and relative inefficient process. On the other hand, current protein immobilization methods, including physical and covalent attachment, can interfere with specific binding sites, thus reducing the efficiency of bio-recognition events and resulting in a loss of specific binding potential that, for example, significantly compromises biosensor performance. In addition to the protein binding, dynamic interfacial interactions are sometimes desirable to allow for rapid and reversible responses to external stimuli when particular applications are targeted. In this thesis, I report on new approaches for efficient protein passivation and immobilization as well as a new type of self-healing hydrogel that can serve as platforms for the development of functional biosensors and biomaterials.
In the first part of the thesis, a simple, scalable procedure to passivate paper against non-specific protein adsorption is introduced. This method is based on a simple sequential dipping protocol inspired by the polyelectrolyte layer-by-layer approach, but instead using covalently reactive hydrazide and aldehyde-functionalized poly(oligoethylene glycol) oligomers (both of which can be easily synthesized via one or two-step chemistries). This sequential dipping method creates a thin hydrogel layer around the cellulose fibers within the paper network without affecting the fiber morphology or macropore network of the paper that effectively lowered non-specific adsorption of a broad range of proteins to the paper by at least one order of magnitude. This method was subsequently applied in the fabrication of paper-based microfluidic sensors that enable protein transport in lateral flow assays as well as paper-based enzyme-linked immunosorbent assays (ELISAs) that exhibit both lower limits of detection and higher dynamic ranges relative to papers blocked with the conventional blocking agents. The simplicity of this surface modification method has great potential to be applied in various paper-based biosensors or for coating other porous media (e.g. membranes) to counteract biofouling.
The next part of this thesis was dedicated to developing a simple, mixing-based protocol for conjugating hyaluronic acid (HA) on the surface of a contact lens, again using hydrazone chemistry to perform the coupling. This simple conjugation method, based on a two-step preparation technique consisting of laccase/TEMPO-mediated oxidation of the surface of poly(2-hydroxyethyl methacrylate) (PHEMA)-based contact lenses followed by covalent grafting of hydrazide-functionalized HA via simple immersion, can be achieved under ambient conditions without the need for any external crosslinkers or energy. The resulting lenses were significantly more wettable, more water-retentive, and less prone to protein adsorption than the native lenses, all of which are key factors in improving the comfort and functionality of the lens for a patient. These characteristics were achieved without causing any significant changes in terms of the transparency, refractive index, or key mechanical properties of the lens.
The third part of this thesis describes a new approach for performing highly sensitive immunosorbent assays by combining the adsorption capacity of graphene oxide with the high sensitivity of the quartz crystal microbalance (QCM).  Specifically, by functionalizing graphene oxide with biotin and subsequently complexing with avidin, the irreversible adsorption of graphene oxide to the surface of a gold QCM biosensor is used as a linking layer for functionalizing a QCM sensor with antibodies. Given the broad availability of multiple types of biotinylated capture antibodies, such an interface provides a flexible substrate for performing a variety of immunoassays of interest. Furthermore, the whole immunoassay process takes less than 5 hours, faster than (or at least comparable with) other approaches that are practically and chemically more complex. As a proof-of-concept, rabbit IgG at concentrations ranging from 0.1 ng/mL to 10 μg/mL (six orders of magnitude) could be quantitatively detected with high sensitivity and selectivity.
Finally, I developed a new method to prepare fast self-healing hydrogels from hyaluronic acid and poly(vinyl alcohol), exploiting the dynamic crosslinking of boronate esters at both neutral and acidic pH. The hydrogel underwent fast (<1 minute) and effective self-healing in both macroscopic cleave/heal tests and microscopic rheological shear tests, providing a hydrogel scaffold with dynamic crosslinking capability over a broad pH range relevant to physiological applications.
Overall, these fabrication techniques can be widely used for the simple and scalable preparation of stable, functional and unique biological interfaces for both therapeutic and diagnostic applications.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Microstructural Analysis of Mild Traumatic Brain Injury in Pediatrics Using Diffusion Tensor Imaging and Quantitative Susceptibility Mapping

contributor:
Noseworthy, Michael
Biomedical Engineering

subject:
MRI
Diffusion Tensor Imaging
Quantitative Susceptibility Mapping
mild traumatic brain injury

abstract:
Each year in the United States, approximately 1.35 million people are a ected by
mTBI (aka concussion) and subsequent cognitive impairment. Approximately 33% of
mTBI cases results in persistent long-term cognitive de cits despite no abnormalities
appearing on conventional neuroimaging scans. Therefore, an accurate and reliable
imaging method is needed to determine injury location and extent of healing. The goal
of this study was to characterize and quantify mTBI through DTI, an advanced MRI
technique that encodes voxel-wise tissue water microstructural di usivity as a tensor,
as well as QSM, which measures iron deposition within tissues. We hypothesized that
personalizing the analysis of DTI and QSM will provide a better understanding of
trauma-induced microstructural damage leading to improved diagnosis and prognosis
accuracy. Through regression analysis, a preliminary comparison between DTI data
to QSM measurements was performed to determine potential correlations between
the two MRI techniques. Further, a large database of healthy pediatric brain DTI
data was downloaded and each was warped into a standardized brain template to
ultimately use for voxel-wise z-score analysis of individual mTBI patients (n=26).
This allowed localization and quantitation of abnormal regions on a per-patient basis.
Signi cant abnormalities were commonly observed in a number of regions including
the longitudinal fasciculus, fronto-occipital fasciculus, and corticospinal tract, while
unique abnormalities were localized in a host of other areas (due to the individuality
of each childs injury). Further, through group-based Bonferroni corrected T-test
analysis, the mTBI group was signi cantly di erent from controls in approximately
65% of regions analyzed. These results show that DTI is sensitive to the detection
of microstructural changes caused by mTBI and has potential to be a useful tool for
improving mTBI diagnosis accuracy

abstract: Thesis

abstract: Master of Applied Science (MASc)

abstract:
Concussions affect over one million people in the United States each year. In a number
of cases, these individuals must cope with persistent long-term cognitive impairment
resulting from the injury. A current, significant problem is that concussion cannot
be reliably diagnosed using conventional CT and MR imaging methods. Therefore,
an accurate and reliable imaging method is needed to determine both injury location
and severity, as well as to monitor healing. The goal of this study was to quantify concussion through MR imaging techniques known as Di ffusion Tensor Imaging
and Quantitative Susceptibility Mapping, which accurately model the brain's mi-
crostructure. Analysis utilizing these MRI methods found signifi cant abnormalities
in a number of brain regions of concussed subjects relative to healthy individuals.
These results suggest that DTI, in particular, is sensitive to microstructural changes
caused by concussions and has the potential to be a useful tool for improving diagnosis
accuracy.


title: Positive Aging: Indigenous Peoples Aging with HIV/AIDS

contributor:
Gabel, Chelsea
Health and Aging

subject:
Indigenous peoples
Successful Aging
HIV/AIDS
Decolonizing Research
Indigenous knowledge
Community Based Participatory Research

abstract:
As a result of advances in treatment over the past 30 years, the number of older people living with HIV is growing. This is of particular concern for Indigenous populations in Canada given continuing over representation in HIV diagnoses. While there has been an increase in research on aging with HIV within the general population, little is known about the experiences of older positive Indigenous peoples.
Research was conducted in partnership with the Canadian Aboriginal AIDS Network (CAAN) at CAAN's Wise Practices V conference. Participants were conference delegates, representing a sample of First Nations, Inuit and Métis people living with HIV and/or service providers from across Canada. Participants ranged in age from 32 to 63 and had been positive for 5 to 29 years. Data was collected through four sharing circles (two with women, one with men and one with service providers) and four interviews (n=34).
An open analytic approach was used to explore the content of the transcripts and codes were collaboratively developed by the research team through an inductive and iterative process. From our analysis we were able to develop an Indigenous model of successful aging (SA). This proposed Indigenous model of SA represents a holistic and subjective model that is far more achievable than traditional models of SA. Within this model five dimensions of health and wellness emerged as facilitators of SA: physical, emotional, spiritual, mental and social health. Additionally, resilience, age and culture were found to be protective factors to SA.

The goal of this project was to identify facilitators and individual strategies which enable SA within this population, in order to develop culturally mediated responses. Ideally, this knowledge can be used to help structure community and primary health services to promote SA with HIV in ways which are congruent with Indigenous culturally-defined notions of health.

abstract: Thesis

abstract: Master of Arts (MA)


title: Semantic Processing of Morphologically Complex Words: Experimental Studies in Visual Word Recognition

contributor:
Kuperman, Victor
Humanities

subject:
Psycholinguistics
Morphology
Reading
Word recognition
Semantics

abstract:
This thesis examines the semantic processing of morphologically complex words
during visual word recognition. In a series of three experiments this thesis addresses
(i) the role semantic transparency during compound word reading, (ii) the nature of
the conceptual structure of compound words and its effect on visual word recognition,
and (iii) the time-course of semantic access during the visual comprehension of derived
words.
Chapter 2 documents evidence that the outcome of the compound semantic
transparency effect is dependent upon the amount of language experience of the
reader. We report that high compound transparency inhibits less experienced
readers during naturalistic reading, yet facilitates processing among relatively more
experienced readers. This study is the first to demonstrate that semantic processing
of compound words is driven by individual reading skill.
The study reported in Chapter 3 tests the hypothesis that the conceptual representation
of a compound is based on a relational structure linking the compound’s
constituents. Across two lexical decision datasets, Chapter 3 reports that greater entropy
(i.e., increased competition) among a set of conceptual relations associated with
a compound gives rise to longer lexical decision latencies. This finding indicates that
the same compound word form is associated with many potential relational meanings,
and that these meanings compete for selection during visual word recognition.
Chapter 4 concerns the time-course of lexical-semantic access during derived
word recognition. Existing accounts of derived word recognition widely disagree
about whether access to conceptual information is granted prior to morphological
decomposition. We report evidence which shows that the semantics of derived words
and their stems are accessed in concert with morphological sources of information.
These results challenge theoretical accounts that advocate strictly serial access to
(morpho-orthographic then morpho-semantic) lexical cues.
Overall, the empirical evidence presented in this thesis suggests that morphological
processing involves rapid and concurrent access to many sources of conceptual
information. These findings align with a view of complex word processing in which
the cognitive system utilizes as many cues as possible in order to maximize the
opportunity of obtaining the meaning of the word.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Testing Group Effects in Experimental Design From Type I Censored Normal Samples

contributor:
Tiku, Moti Lal
Statistics

subject: testing, group effects, experimental design, censored, normal, samples

abstract: The estimators of the mean, standard deviation and group effects for one-way-classification experimental designs are obtained from type I censored samples. The bias and the variances and covariances of these estimators are evaluated. A test statistic is proposed for testing a linear contrast of the group-effects. Two numerical examples are presented.

abstract: Thesis

abstract: Master of Science (MSc)


title: The Regulation of Nitrate Reductase on Corn Roots

contributor:
Oaks, Ann
Biology

subject: regulation, nitrate, reductase, corn roots, induction, protein synthesis, enzyme

abstract:
 The experiments described in this thesis were performed to study the:
1. Role of nitrate in the induction of nitrate reductase.
2. Effect of nitrate on the in vivo regulation of nitrate reductase.
3. Role of atrazine on the regulation of nitrate reductase.

 The nitrate reductase assay system was improved up to 10 fold over that previously used (28). This improvement included the addition of oxalacetic acid and malic dehydrogenase to the system, thereby oxidizing all the NADH at the end of the reaction. NADH, which was a required co-factor in the assay system, interfered with the nitrite colour formation.

 When the induction kinetics of the enzyme are followed in root tip sections (0 -10 mm) of corn, a 25 minute lag period followed by a period of rapid nitrate reductase synthesis is seen. Neither the lag period nor the rate of increase in enzyme activity is affected by the concentration of the inducer used (1.0, 10.0 or 25.0 mM nitrate), However, with concentrations of nitrate from 0.1 mM to 10.0 mM, there is an increase in the final level of nitrate reductase. Nitrate levels between 10.0 mM to 100.0 mM did not alter this maximally induced level of enzyme.

 In mature root sections (25-35 mm from the tip), a longer lag time and a slower rate of increase in enzyme activity is seen. The system is not saturated with nitrate concentrations up to 100.0 mM.

 Cycloheximide, a protein synthesis inhibitor, was added to the roots after the enzyme had been maximally induced. This allowed one to study the in vivo turnover of the enzyme. Nitrate did not alter the in vivo turnover of nitrate reductase in corn roots.

 Atrazine is a herbicide that has been reported to increase nitrate reductase levels in corn (34). When used in the experiments described here, it was found to be ineffective in altering the nitrate reductase activity of the roots and leaves of corn.

abstract: Thesis

abstract: Master of Science (MSc)


title: Design of Controlled Rocking Heavy Timber Walls For Low-To-Moderate Seismic Hazard Regions

title: Controlled Rocking Heavy Timber Walls

contributor:
Wiebe, Lydell Andree
Civil Engineering

subject:
Controlled Rocking
Heavy Timber
Low-to-Moderate Seismic Hazard
Post-tensioned timber
Force-based design
Non-linear time-history analysis

abstract:
The controlled rocking heavy timber wall (CRHTW) is a high-performance structural solution that was first developed in New Zealand, mainly considering Laminated Veneer Lumber (LVL), to resist high seismic loads without sustaining structural damage. The wall responds in bending and shear to small lateral loads, and it rocks on its foundation in response to large seismic loads. In previous studies, rocking has been controlled by both energy dissipation elements and post-tensioning, and the latter returns the wall to its original position after a seismic event. The controlled rocking response avoids the need for structural repair after an earthquake, allowing for more rapid return to occupancy than in conventional structures.
Whereas controlled rocking walls with supplemental energy dissipation have been studied before using LVL, this thesis proposes an adapted CRHTW in which the design and construction cost and complexity are reduced for low-to-moderate seismic hazard regions by removing supplemental energy dissipation and using cross-laminated timber (CLT) because of its positive economic and environmental potential in the North American market. Moreover, whereas previous research has focussed on direct displacement-based design procedures for CRHTWs, with limited consideration of force-based design parameters, this thesis focusses on force-based design procedures that are more common in practice. A design and analysis process is outlined for the adapted CRHTW, based on a similar methodology for controlled rocking steel braced frames. The design process includes a new proposal to minimize the design forces while still controlling peak drifts, and it also includes a new proposal for predicting the influence of the higher modes by referring to previous research on the capacity design of controlled rocking steel braced frames. Also, a numerical model is outlined, including both a baseline version and a lower-bound model based on comparison to experimental data. The numerical model is used for non-linear time-history analysis of a prototype design, confirming the expected performance of the adapted CRHTW, and the model is also used for incremental dynamic analyses of three-, six-, and nine-storey prototypes, which show a low probability of collapse.

abstract: Thesis

abstract: Master of Applied Science (MASc)

abstract:
The controlled rocking heavy timber wall (CRHTW) is a high-performance structural solution that was developed to resist high seismic loads without sustaining structural damage. The wall responds in bending and shear to small lateral loads, and it rocks on its foundation in response to large seismic loads. In previous studies, rocking has been controlled by both energy dissipation elements and post-tensioning; the latter returns the wall to its original position after a seismic event. This controlled rocking behaviour mitigates structural damage and costly repairs.
This thesis explores the value of an adapted CRHTW in which the design and construction costs and complexity are reduced for low-to-moderate seismic hazard regions by using post-tensioning but no supplemental energy dissipation. A design and analysis process is outlined; numerical analysis confirms the expected performance of the adapted CRHTW; and the system is shown to have a low probability of collapse.


title: Precise Mathematical Models for Electromagnetic and Permanentic Motors

subject: mathematical models, electromagnetic, permanentic, motors

abstract:
 La présente étude traite de l'établissement d'un modèle mathématique, comprenant toutes les non-linéarités, d'un moteur à courant continu.

 Il a été nécessaire de rechercher pour cela de nouvelles techniques de mesures afin d'obtenir les différents paramètres avec un maximum de précision. L'originalité de ces mesures tient dans le fait que la machine est étudiée dans des conditions dynamiques d'expérience.

 A l'aide de ce modèle non-linéaire, il a été possible alors de montrer un éventail de comparaisons entre un moteur électromagnetique et un moteur à aimants permanents, dans le domaine des systèmes asservis.

 Cette étude démontre l'efficacité de l'outil que fournit ce modèle.

abstract: Thesis

abstract: Master of Engineering (MEngr)


title: The Pearcey function and the cusp catastrophe

contributor:
Sprung, Donald
Physics and Astronomy

subject:
Pearcey function
cusp catastrophe
Theoretical physics
optics

abstract: The subject of this work is a theoretical analysis of the Pearcey function. In optics, thin lens theory supposes that all rays focus at a unique point where the field converges. For a real lens, the focal point is replaced by a cusp, which is the end point of a caustic curve dividing the bright field region from the dark. My particular interest is the pattern of nodal points within the cusp. By investigating the stationary points for the cusp catastrophe, asymptotic approximations are found for the Pearcey function. This in turn leads to the development of finding the positions of nodal points inside, and outside a caustic. Also values for $|P|$ on a small circle surrounding a node are examined and show reasonable accuracy of order $10^{-8}$.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Identifying the nodes of the Pearcey function.


title: A Study of Evaporated Thin-Film Voltage-Controlled Tunable Distributed RC-Filters

contributor:
Campbell, C. K.
Electrical Engineering

subject: evaporated, thin-film, voltage-controlled, tunable, RC-Filters, insulator, semiconductor

abstract:
 The analysis, construction and performance of a new type of evaporated thin-film filter is described. It has the capability of frequency tuning by means of a single bias voltage.

 The device is basically a uniformly distributed resistance-capacitance network (URC) with a thin semiconductor film incorporated in the structure. The resistive film, insulator and semiconductor films constitute a metal-insulator-semiconductor system (MIS) whose capacitance is bias dependent. The device differs from other proposed tunable thin-film filters in the fact that the capacitance can be altered independently of the distributed resistance.

 A theory is developed to account for the effects of MIS-losses and parasitic inductance on the performance of URC-null networks. These parasitic effects manifest themselves in four different ways:
(i) A shift of the null from the position predicted by the ideal theory.
(ii) A change in the notch parameter α for an optimum null.
(iii) A detuning effect in the case of tunable notch filters.
(iv) A reduction in the available tuning range; the so-called "tuning range compression".

 Experimental units were made by vacuum evaporation of Nichrome, Y2O3, CdS and Al onto alumina substrates. An attempt is made to relate the device characteristics to the material properties. In this respect, the relative dielectric permittivity and thickness of the insulator, the doping density of the semiconductor, the semiconductor-insulator interface states and the bulk states in the semiconductor are found to be the most important parameters.

 Filters were built which operated in the frequency range 600 kHz to 6 MHz. The best notch filter has a tuning capability of 30% with a ±15V bias voltage. The notch depth is over 60 dB in most cases. A tunable bandpass amplifier which was constructed, has a centre frequency which can be shifted between 6 MHz and 7 MHz with a ±3.5V bias voltage. The Q of this particular device was measured to be 742.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Mass Transfer and Shear Stress at the Wall for Cocurrent Gas-Liquid Flows in a Vertical Tube

contributor:
Banerjee, S.
Engineering Physics

subject: mass transfer, shear stress, gas-fluid, flows, vertical tube, two-phase, electrochemical

abstract:
 An investigation of the technique of obtaining the wall shear stress in a two-phase flow, by measuring the mass transfer coefficient at the wall with the electrochemical method, has been completed.

 The experiments involved the measurement of flow rates, pressure drops, void fractions and mass transfer coefficients, for a cocurrent upwards gas-liquid flow in a vertical tube, 13 mm in diameter. The liquid phase was an electrolyte consisting of 1.0 to 3.0 molar sodium hydroxide, and 0.005 to 0.010 equimolar potassium ferricyanide and potassium ferrocyanide. The gas phase was nitrogen. The flow regimes studied were slug, churn and annular.

 Emphasis is placed on the measurements obtained with the electrochemical method. Its application, advantages and disadvantages are detailed. A series of single-phase experiments were performed to explore the characteristics of the method and to serve as benchmarks for the two-phase experiments.

 The space-time-averaged values of the mass transfer coefficient were found to give the wall shear stresses to an
accuracy of ±20%. Frequency analysis of the local fluctuating values indicate that measurements of the local mass transfer coefficient can be used for flow regime identification.

 The theoretical flow regime map of Dukler and Taitel successfully predicted the flow regimes. The correlations of Griffith and Wallis, and Lockhart and Martinelli as modified by Davis, predicted the pressure drops and void fractions to an accuracy ±15% when applied to the appropriate flow regimes. As a further exercise, the force interactions between the phases, referred to as the interfacial shear terms, were calculated from both the measured and predicted void fractions and pressure drops.

abstract: Thesis

abstract: Master of Engineering (MEngr)


title: MIS Tunnel Diodes: Application to Solar Energy Conversion

subject: MIS tunnel, diodes, solar, energy, conversion, metal, open circuit voltage, semiconductor

abstract:
 The MIS tunnel solar cell has recently attracted most of the attention in the solar energy conversion field. Construction is very simple and eliminates the costly diffusion of dopants. As in the Schottky type, a metal of proper work function is chosen to induce an inversion layer at the surface of the semiconductor (Al in the case of p type Si). An ultra thin (< 1.5 nm) oxide between the semiconductor and the metal passivates the surface by reducing surface states while permitting tunneling from the semiconductor to the metal.

 Good fill factors (> .7) have been obtained but high reflectivity of the Al has reduced the current output. Open circuit voltages greater than .61 volts and short circuit current density of 21 ma/cm^2 have been measured. Experimental evidence of the presence of an oxide different from SiO2 within 1.4 nm of the surface will be given and related to the thickness variation of the open circuit voltage. A maximum in VOC around 1.4 nm was found. A maximum efficiency of 7% was achieved without anti reflexion coating and a curve factor of .81 was observed in one of the cells. A slight variation in efficiency with the cell area was also observed.

abstract: Thesis

abstract: Master of Engineering (MEngr)


title: An Evaporation Model for High Latitude Upland Lichen Surfaces

contributor:
Rouse, W. R.
Geography

subject: evaporation, high latitude, upland, lichen, surfaces, energy-budget, equilibrium

abstract:
 Energy-budget calculations and equilibrium model estimates of evaporation from a lichen-dominated upland site in the Hudson Bay low-lands are presented. The energy budget calculations reveal that the lichen surface is relatively resistant to evaporation with an average of only 54 percent of the daily net radiation being utilized in the evaporative process. Equilibrium estimates of evaporation consistently overestimate actual evaporation by 5 and 8 percent for hourly values and daily totals respectively. A simple model, a function of the equilibrium model, is derived from a comparison of actual and equilibrium evaporation. The
only inputs required for the model are net radiation, soil heat flow and screen temperatures. Tests of the model indicate that it will predict actual evaporation within 5 percent and that it can probably be applied to any high latitude surface which exhibits a relatively large resistance to evaporation.

abstract: Thesis

abstract: Master of Science (MSc)


title: A Riemannian Distance Approach to Probing Signal Design for MIMO Radar

contributor:
Wong, Kon Max
Davidson, Tim
Electrical and Computer Engineering

abstract: We consider the problem of designing probing signals for a Multi-Input Multi-Output (MIMO) radar. The goal is to design a signal vector having a desired covariance  while ensuring the sidelobes of the ambiguity functions are small. We will also consider cases in which a bandwidth constraint is placed on the signal. Since covariance matrices are structurally constrained, they form a manifold in the signal space. Hence, we argue that the difference between these matrices should not be measured in terms of the conventional Euclidean distance (ED), rather, the distance should be measured along the surface of the manifold, i.e., in terms of a Riemannian distance (RD). An optimization problem for the design of the probing signal is formulated for each distance metric, with the waveform being represented as a linear combination of a set of orthonormal signals. In both cases, the optimization problem is quartic in the coefficients. An efficient algorithm based on iterative convex quadratic optimization is developed and is effective in producing good solutions. In addition, we show that by optimizing over the manifold, the number of iterations can be significantly reduced in comparison to optimizing in the Euclidean space. Several orthonormal signal sets are used  in our design examples, including the Walsh functions, the cosine functions and a set of functions designed for optimal time-frequency concentration. When the time-frequency constraints are tight, the selection of the orthonormal set plays a significant role in the design, with the functions with optimal time-frequency concentration.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: The Decay of Krypton 89

contributor:
Johns, M. W.
Physics

subject: decay, krypton, detectors, gamma rays, nuclear

abstract: The decay of 3.5 minute 89Kr to levels in 89Rb has been investigated with small and large volume Ge(Li) detectors used singly and in coincidence. A total of 160 gamma rays have been attributed to the nuclear process, 120 of which have been incorporated into a proposed decay scheme.

abstract: Thesis

abstract: Master of Science (MSc)


title: Fabrication of organic-inorganic nanocomposites by colloidal processing

contributor:
Zhitomirsky, Igor
Materials Engineering

subject:
EPD
dispersing agent
composite
dispersion
adsorption
chelate
nanoparticles

abstract:
Colloidal processing has been widely used for many industrial application. Electrophoretic deposition (EPD) is an important colloidal technique, which plays an important role in the fabrication of organic-inorganic composites.
In this work, advanced dispersing agents with excellent adsorption, dispersion and film forming properties have been developed. The adsorption mechanism and the deposition kinetics of EPD have been studied. It is shown that catechol and salicylic groups of dispersants can form chelation bonding with metal atoms on inorganic particle surface and provide particle charging, dispersion and deposition. The aromatic dispersants can adsorb on carbon nanotubes due to π-π interactions. The long chain ionic polymeric dispersants were investigated, which provide efficient electrosteric stabilization. The film forming properties of dispersants allow dispersants with dispersed materials to deposit and form composite films on the substrate.
Universal dispersing agents have been developed for the colloidal processing. These dispersants show possibilities to adsorb and disperse various organic and inorganic materials and pave the way for the fabrication of multi-functional materials for various applications. The composite materials, prepared using new dispersants showed promising corrosion protection of metals, flame retardant and energy storage properties.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Master's thesis of Tianshi Zhang

title: Electrochemical and Chemical Methods for the Fabrication of Nanocomposites

contributor:
Zhitomirsky, Igor
Materials Science and Engineering

subject:
Master's thesis
Nanocomposites
Electrodeoposition
Dispersants

abstract:
Novel electrocchemical and chemical strategies have been developed for the fabrication of functional nanocomposites. New scientific and engineering contribution of this work to colloidal nanotechnology included the development of advanced chelating dispersing agents, such as various small organic molecules and chelating polymers. The unique feature of such dispersion agents is their strong adsorption on the surface of different materials, which allows superior dispersion. The chelating monomers of chelating polymers, such as PAZO and PMSS provided multiple adsorption sites for bonding to metal atoms on the particles surface. We analyzed and developed new fundamental adsorption and dispersion mechanisms. An important finding was the possibility of co-dispersion and co-deposition of advanced materials such as oxides, nitrides, complex oxides and minerals using universal dispersing agents and formation of composites by EPD method.
It was found that Caffeic acid (CA) can be used as an efficient dispersing agent for the synthesis of ZnO nanorods of reduced size and a dispersing agent for the EPD of ZnO films. Another important achievement of this work was the application of tannic acid as an efficient capping and dispersing agent for synthesis and EPD of inorganic materials and composites. An important discovery was the use of lauryl gallate dispersant as a reducing agent for the synthesis of AgNp and a vehicle for particle dispersion and extraction in the liquid-liquid extraction method.
Further advancements in our new technologies allowed us to develop composite films using anodic EPD using weak polyelectrolytes, such as alginate. The composite coatings exhibited protective and flame retardant properties. We analyzed the deposition mechanisms and kinetics as well as microstructure of the coatings. In another strategy, we developed electrochemical strategies for the deposition of composites, based on strong polyelectrolytes. The approach is based on the EPD of the polyelectrolyte molecules and electrosynthesis of EPD of ceramic particles. The electrostatic heterocoagulation mechanism was proposed for the deposit formation. We investigated the deposition kinetics, composition and microstructure of the composites prepared by the new strategies. The new electrochemical strategies can be used for the deposition of other composites, based on functional polymers with pH independent charge.
New methods have been developed for the chemical synthesis of PPy based composites, using PMSS, PMSS–SR11 and PMSS–SR31 as anionic dopants for chemical polymerization and dispersants for MWCNT. The composites showed promising performance for application in electrodes of electrochemical supercapacitors. Good electrochemical performance was achieved at high active mass loadings. The electrodes showed high capacitance, large voltage window and low impedance. The analysis of electrochemical testing results and chemical structure of PMSS, PMSS–SR11 and PMSS–SR31 provided an insight into the influence of the anionic functional groups on the capacitance and capacitance retention a high charge-discharge rates.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Humour in the Underworld of Ovid's Metamorphoses

contributor:
Murgatroyd, Paul
Classics

abstract: The Underworld, a realm of misery, pain, and both literal and figurative darkness, is perhaps an unlikely place for humour and levity, yet in the Metamorphoses, not even it is exempt from Ovid’s characteristic wit. While scholars have explored Ovid’s use of humour in the poem overall, little focus has been given to the Underworld itself. The introduction will serve as an overview of Ovid’s Underworld, providing a catalog of the flora and fauna (both mortal and immortal, human and beast) present there, as well as its geography (the location of the entrance to the Underworld, the regions and the structures within it). Each subsequent chapter will explore a specific passage, presenting a detailed critical appreciation that examines the tone, structure, style, plot, language, sound, and narrative techniques (such as irony, imagery, allusion, similes, etc.), and also compare each episode with its corresponding literary model. Relevant passages include the descent of Aeneas and the Sibyl into the Underworld (Met. 14.101-157), the retrieval of Cerberus by Hercules (Met. 7.404-424), the destruction of Athamas and Ino at the hands of Juno and Tisiphone (Met. 4.432-511), the abduction and rape of Proserpina by Pluto (Met. 5.356-571), and the descent of Orpheus into the Underworld to revive Eurydice (Met. 10.1-11.66). This thesis will demonstrate that Ovid’s Underworld is depicted as dark and dismal – perhaps as expected – but it is also erudite, cleverly crafted, complex in tonality, and often a source of humour. Ovid consistently lightens the mood of traditionally serious myths and pokes fun at his predecessors, often achieved at the expense of the Underworld’s inhabitants, by diminishing their dangerous and fearsome nature to exaggerate their ineffectuality and absurdity. Ultimately, the Underworld of the Metamorphoses effectively exhibits Ovid’s wit and ingenuity.

abstract: Thesis

abstract: Master of Arts (MA)


title: THE IMPACT OF CIGARETTE SMOKE EXPOSURE ON BACTERIAL COLONIZATION AND INFECTION IN THE MOUSE RESPIRATORY TRACT

title: CIGARETTE SMOKING AND BACTERIAL-HOST INTERACTIONS

contributor:
Stampfli, Martin
Medical Sciences

subject: Smoke, mouse model, bacterial infection, COPD, COPD exacerbation, microbiome

abstract: Over 1.1 billion people smoke worldwide despite the association of smoking with numerous diseases including chronic obstructive pulmonary disease (COPD). The decline in lung function observed in COPD patients is thought to be related to smoke-induced inflammation. COPD patients are also at increased risk of acquiring lung bacterial infections that are associated with exacerbations, characterized by worsened disease symptoms and inflammation. The focus of this thesis is on how cigarette smoke impacts bacterial-host interactions and bacterial community interactions to promote infection and disease. In chapter 3.1, we sought to understand how cigarette smoke primed the lungs towards an amplified inflammatory response to bacterial infection reflective of COPD exacerbations that accelerate disease progression. We present a novel finding that exacerbated neutrophilia elicited by nontypeable Haemophilus influenzae (NTHi) lung challenge in smoke-exposed mice occurred dependent on IL-1α. Smokers and patients with COPD are additionally at increased risk of acquiring bacterial infection that may be related to impaired containment of nasally colonizing pathogens. In chapter 3.2, we found that cigarette smoke predisposed mice to invasive pneumococcal disease (IPD) following nasal pneumococcal colonization associated with attenuated nasal inflammatory responses. To our knowledge, this is the first study to describe the progression from asymptomatic nasal pneumococcal colonization to the development of IPD in the context of cigarette smoking. It has been suggested that smokers have higher rates of pathogen colonization as a consequence of cigarette smoke-induced nasal microbiome dysbiosis. The last study in chapter 3.3 advanced knowledge in the field by testing this hypothesis. We observed that cigarette smoke alone did not alter the mouse nasal microbiome and concluded that microbiome dysbiosis observed in smokers likely occur as a consequence of nasal pathogen colonization. Overall, work presented in this thesis advanced our understanding of how cigarette smoking alters bacterial-host interactions to promote infection and disease.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Over 1.1 billion people smoke worldwide and can develop chronic obstructive pulmonary disease (COPD), a serious inflammatory disease compromising lung function. Additionally, smokers and COPD patients have higher rates of bacterial infection. The goal of this thesis is to understand how smoking impacts our ability to combat infection. Lung infection in COPD patients causes exacerbation, with worsened disease symptoms. Using mouse models, we learned how smoking causes increased lung inflammation following bacterial infection, contributing to damage reflective of COPD exacerbations, and identified a potential intervention. We elucidated smokers may have increased infections due to impaired immune responses in the nose, a major pathogen entry point. It is thought smoking reduced beneficial bacteria that counter pathogen acquisition in the nose. We confirmed smoking did not impact these bacteria, directing research focus towards other ways smokers acquire pathogens. Overall, this thesis advanced knowledge and will help efforts to control disease in smokers.


title: Design, Fabrication, and Characterization of Multi-Scale Materials for Integration on Lab-on-a-Chip Devices

contributor:
Soleymani, Leyla
Biomedical Engineering

abstract:
Currently, molecular diagnosis is conducted by professionals in centralized laboratories, which can be time consuming, expensive, and not readily available in remote locations. This motivates the efforts to develop highly accurate, highly sensitive, and high speed lab-on-a-chip (LOC) platforms for inexpensive point-of-care (POC) diagnostics. Multi-scale materials – with tunable features from the nanometer to millimeter length-scales – have shown to enhance performance of electrodes in LOC biosensing and bioprocessing applications. The controlled fabrication of three-dimensional metallic hierarchical electrodes using standard lithographic, machining, printing, etc. techniques is complex and not suitable for rapid, dynamic, and inexpensive prototyping. The work presented herein addresses the need to develop a benchtop rapid prototyping approach to create tunable multi-scale electrodes for integration in LOC devices.
In this work, rapid benchtop fabrication is carried out through a combination of xurography, to create electrodes with specific configurations, and controlled thin film wrinkling using pre-stressed polymer substrates, to structure sputtered electrodes on the nanoscale and microscale. This method creates wrinkled structures with sufficient adhesion (no peeling) and conductance (<1 Ω/ sheet resistance) for electrical applications. Further development of this method allows fabrication to be carried out completely on the benchtop using all-solution processing methods to deposit high quality thin films, with similar adhesion (no peeling) and conductance (<1 Ω/sq sheet resistance) as sputtered films, on the polymer substrates. Moreover, this fabrication technique is extended to create wrinkled nanoparticle films presenting sub-100 nm wavelengths and a dual degree of tunability, as the nanoparticles tune both the thickness and mechanical properties of the films. Structural tuning of the nanoscale and microscale architectures of wrinkled electrodes is studied with scanning electron microscopy (SEM), transmission electron microscopy (TEM), atomic force microscopy (AFM), and white light interferometry, and then related to functional tuning via four-point probe measurements and electrochemical measurements. As the structure is shown to determine key functional parameters, such as resistance and surface area, various electrodes structures are designed and applied to important LOC bioprocessing and sensing applications. For example, structurally optimized electrodes are applied to low voltage cell lysis and are able to lyse bacteria at only 4 V. Furthermore, the problem of integrating three-dimensional, multi-scale wrinkled electrodes into microfluidic devices is investigated. New approaches combining surface treatment and partial curing of microchannels are developed to solve these issues and create fully contained, functional electro-fluidic devices that can withstand flow rates greater than 25 mL/min and pressures of greater than 125 kPa.
Ultimately, we are able to create and integrate high quality, tunable, functional, multi-scale electrodes on the laboratory benchtop at low cost and high speed. Thus, this research enables the expedited development of LOC electrode devices that are functionally optimized through structural tuning.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: The incorporation of multi-scale materials, with features that span the nanoscale and microscale, has been found to be beneficial for a variety of applications, including lab-on-a-chip (LOC) devices. Rapid prototyping is advantageous over large volume manufacturing in the LOC research and development phase. However, it is challenging to create complex three-dimensional and multi-length-scale materials, critical components for optimizing LOC performance, with current rapid prototyping methods. In this thesis, we seek to develop robust, affordable, and high-speed fabrication techniques to rapidly prototype tunable, hierarchically structured, three-dimensional electrodes on the benchtop. We explore methods to structurally tune these electrodes and study the structural evolution of the electrodes with thorough characterization of the features at the nanoscale, microscale, and macroscale. We translate the electrode structural tuning into functional tuning of application-driven properties, and employ them in optimized LOC electrode devices and sensors. Finally, we combine these multi-scale electrodes with microfluidic chips to produce fully integrated LOC devices.


title: “You people have your stories; we have ours”: a narrative analysis of land use in settler Canada

contributor:
Storey, Robert
Sociology

subject: settler colonial relations, liberal order framework, racialization

abstract: This dissertation uses storytelling to examine the nature of settler colonial relations (SCRs) in Canada. It examines testimonies about land use in settler Canada from the Royal Commission on Aboriginal Peoples (RCAP). Utilizing a combined Tribal Critical Race Theory (TCRT) and Critical Race Theory (CRT), this study compares testimonies about land use from the perspective of Indigenous peoples and non-Indigenous peoples and asks the question what, if anything, does this comparison tell us about settler Canada? The comparison reveals how settler Canada depends on the liberal racialization of Indigenous peoples’ national identity. To undertake this comparison I narrated the RCAP testimonies into small stories and analyzed their morals, or the point of these stories, using dialogical narrative analysis. The narrated stories laid bare a stark contrast in the way Indigenous peoples spoke of their social relations with the land and the way non-indigenous Canadians spoke of theirs. This study demonstrates how the narrated testimonies from Canadians, or what are referred to as cultural narratives in the language of CRT, are about land use that racialized the national identity of Indigenous peoples through the discourse of the liberal order, whereas the narrated testimonies from Indigenous peoples, considered as counter stories in this study, contradict the cultural narratives and reveal a national identity rooted in language, spirituality, the Creator, and the consequences for Indigenous peoples from settler colonial relations. The narrated counter stories in this study not only contradict the cultural narratives from settlers by describing the consequences of settler colonial relations but they also provide a blueprint in a narrative sense to decolonize land use in contemporary settler Canada.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)


title: CARDIOPROTECTION BY HIGH DENSITY LIPOPROTEIN IS MEDIATED BY THE SCAVENGER RECEPTOR CLASS B TYPE 1

contributor:
Trigatti, Bernardo
Medical Sciences

abstract: Cardiovascular disease and cancer are the leading causes of death in Canada and are a major burden to the health of developed societies.  Three quarters of all cardiovascular related deaths are due to ischemic heart disease and heart attack.  Doxorubicin is an effective and commonly used chemotherapeutic that has deleterious side effects including cardiotoxicity and heart failure, thereby limiting its long term use.  In a recent study both reconstituted and native high density lipoprotein particles provided protection against doxorubicin-induced cell death in vitro, and a number of studies have implicated high density lipoprotein in protection against myocardial ischemia.  As high density lipoprotein provides protection to cardiomyocytes undergoing cardiotoxic stress, or ischemic stress, we postulate that it may be a notable target for protection against the deleterious effects of cardiac stress.  The scavenger receptor class B type I is a high-affinity high density lipoprotein receptor, and its role in facilitating high density lipoprotein mediated signaling in the cardiomyocyte has yet to be assessed.  Here we have evaluated whether increasing high density lipoprotein protects cardiomyocytes and the heart against cardiotoxic or ischemic stress, and the signaling mechanisms involved.  We have shown that increasing plasma high density lipoprotein attenuates the cardiotoxic effects of doxorubicin, and that high density lipoprotein protects isolated cardiomyocytes against necrosis induced by simulated ischemia.  Our findings presented here demonstrate a critical role for cardiomyocyte scavenger receptor class B type 1 in facilitating high density lipoprotein mediated protection.  We have also identified phosphoinositide 3-kinase and protein kinase B as downstream mediators in the cardioprotective signaling cascade by high density lipoprotein and the scavenger receptor class B type I.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: High density lipoproteins are known to protect against cardiac stress and cardiovascular disease.  The scavenger receptor class B type I is a high affinity high density lipoprotein receptor, though its role in mediating the protective effects of high density lipoprotein on the heart has yet to be thoroughly examined.  We have shown that high density lipoprotein protects against different types of cardiomyocyte death induced by various stressors on the heart, and that in each case, high density lipoprotein requires the scavenger receptor class B type I to trigger downstream cardioprotective signaling through phosphoinositide 3-kinase, and protein kinase B.


title: An Assessment of the Water Table Dynamics in a Constructed Wetland, Fort McMurray, Alberta

contributor:
Carey, Sean
Environmental Science

abstract: Oil sand mining removes the wetland and forestlands of the Boreal Plains, and replaces this landscape with open pits, tailings ponds and overburden piles to access the oil-bearing formations below. In turn, mine regulators are forced to reclaim the disturbed, post-mined land to pre-disturbance conditions. In 2012, Syncrude Canada Limited (SCL) constructed one of the first of two reclaimed wetlands, the Sandhill Fen Watershed (SFW), to evaluate wetland reclamation strategies. SFW is a 52-ha system atop soft-tailings that includes an inflow/outflow pump system, underdrains, upland hummock areas, and a fen lowland. This study examines trends in water table position and lateral gradients that are developing, as well as observe system response to pump management. Spanning May- Oct 2014 and 2015, precipitation was measured at three meteorological stations across the fen, artificial inflows and outflows were recorded using a series of pumps, and water table position was measured using a network of 27 near-surface wells instrumented with transducers. Water table was maintained near the peat surface for both study seasons, indicating the potential for maintenance of wetland conditions. Though data is limited, upland-lowland interactions are beginning to develop, suggesting the uplands are beginning to supply water to the lowland fen. Flow reversals are reported along the fen lowland in dry periods, and the east and west fens become hydrologically disconnected as the season progresses. Comparison with analogue sites provides reference for hydrologic processes within SFW and provides insight on the influence of pump management on the system.

abstract: Thesis

abstract: Master of Science (MSc)


title: RESPONSES OF BOYS AND MEN EXERCISING IN THE HEAT

title: BOYS AND MEN EXERCISING IN THE HEAT: THERMOREGULATION, DEHYDRATION AND PERFORMANCE, AND SUBSTRATE UTILIZATION

contributor: Medical Sciences (Division of Physiology/Pharmacology)

subject:
Children
Exercise
Heat
Temperature regulation
Muscle strength
Hydration
Substrate utilization
Sweating

abstract: There is a common belief that children compared with adults are at a greater risk for exercise-induced heat illness. However, a limitation of previous studies involves different exercise intensities used in the comparison between children and adults. Dehydration impairs aerobic performance, but its effects on strength are not well understood. Sports drinks are often used as ergogenic aids. There is some evidence to suggest children have a greater reliance on exogenous carbohydrate compared to adults, which could require special considerations when children exercise in the heat. The overall purpose of this thesis was to compare physiological and metabolic responses during exercise in the heat between boys and men. Three studies were conducted to 1) compare the thermoregulatory responses of boys and men exercising in the heat at a fixed absolute metabolic heat production or a fixed metabolic heat production per unit of body mass; 2) compare the effects of 2% hypohydration or, euhydration with and without carbohydrate ingestion during exercise in the heat on subsequent strength in boys and men; and 3) examine the effects of exogenous carbohydrate on endogenous metabolism in boys and men exercising in the heat.  Age and body size differences between boys and men did not influence thermoregulatory responses at a fixed metabolic heat production per unit of body mass. No differences in strength were observed among trials. When exercising in the heat, the relative contribution of ingested carbohydrate and endogenous substrate to total energy yield were not different between groups. These findings together have practical implications for boys and men who exercise in the heat. Specifically, moderate exercise in the heat is equally safe for boys and men. The effects of hypohydration and a carbohydrate drink compared to water on muscle strength performance following exercise in the heat are minimal. An important practical application is that carbohydrate intake spared endogenous fuels during exercise in the heat in both groups.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Children may not adapt to temperature extremes as effectively as adults. Thermoregulatory differences may be due to variable exercise intensities prescribed in available child-adult comparisons. Dehydration affects aerobic performance, but its effects on strength are not well understood. Sports drinks are often used to offset dehydration and improve performance; however, the body may have a harder time using sugar drinks when exercising in the heat. The purpose of this thesis was to compare bodily responses of boys and men during exercise in the heat. Our findings have important practical implications for boys and men who exercise and play sports in hot temperatures. Specifically, exercise in the heat is equally safe for boys and men. The effects of hypohydration and a sports drink on muscle strength performance following exercise in the heat are minimal. Finally, although exercise in the heat may affect the use of a sugar drink, boys and men may use this drink to improve aerobic performance, while maintaining hydration levels.


title: Factors of Service Utilization and Participation Outcomes of Children with Disabilities

contributor:
Law, Mary C.
Rehabilitation Science

subject:
participation
complexity
children with disabilities
rehabilitation services
Andersen Health Care Utilization Model

abstract:
Home and community participation is measured by a multitude of determinant factors based within the context of a health system. Three studies were completed to understand relationships between environment and personal factors with service utilization and outcomes of participation among children with disabilities.
In the first study, a scoping review was completed to identify factors that influenced rehabilitation service utilization among Canadian children with disabilities. Key findings of this review indicated higher rates of service utilization are associated to younger age, males and those with lower cognitive or motor functioning. Occupational therapists, physiotherapists and speech-language pathologists were the most commonly utilized disciplines. Higher perceptions of service satisfaction related to increased presence of family-centered practices. Areas requiring further research include family needs, barriers, personal health practices and participation outcomes.
Based on the findings of this review, a survey was created to administer to parents using a large children’s rehabilitation treatment centre in Ontario. Findings from the survey conducted with 279 parents are reported in the second study by providing a descriptive profile of families and children using geographically-based rehabilitation services. Families using the centre typically have younger aged children, with more boys than girls, and a large proportion use the centre for speech services. Complexity scores correlated significantly and positively with service need and service utilization, indicating children with lower functioning desired and received more rehabilitation services. Age, sex, and diagnosis did not predict total time in therapy, but complexity was a significant predictor of total time in therapy. Participation frequency scores showed weaker relationships to complexity in comparison to participation involvement scores.
The final study explored the relationship between environmental and personal factors of service utilization and participation using structural equation modeling. Predictors of participation include child’s age, environmental barriers, complexity, and mother’s participation. Findings support that exploring children’s complexity and promoting mother’s participation by removing environmental barriers and modifying inaccessible structures are important to examine from a young age.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)

abstract: This study examines the relationship between factors of service utilization and participation outcomes for children with disabilities. Currently, there is little knowledge pertaining to the characteristics of children receiving rehabilitation services and the influence of these services on health outcomes. Such information is vital to understand how health conditions, service utilization, service planning, and service satisfaction differ across children with disabilities.  Use of health services (type and number of rehabilitation services used, duration of services), environmental barriers, maternal leisure practices, and socioeconomic factors are examined with consideration to the child’s diagnosis and complexity in relation to scores of participation. This is the only study in Canada so far to comprehensively explore relationships between rehabilitation utilization and participation. The study informs health care providers and researchers about patterns and variations in children’s needs that can be utilized to improve service quality and plan services, as well as to understand participation patterns.


title: Polymer Nanoparticles as a Degradable, Mucoadhesive Drug Delivery System

contributor:
Sheardown, Heather
Chemical Engineering

subject:
nanoparticles
ophthalmic
drug delivery
biomaterial

abstract:
One of the most common methods of drug delivery to the anterior segment of the eye is topical application of an ophthalmic solution or suspension. The ophthalmic solution may contain various particle based materials, such as nanoparticles, to control the rate at which the drug is delivered to the eye. The issue with this delivery method is that there are several barriers at the front of the eye. These barriers, which include a high tear film turnover rate and induced lacrimation, reduce the residence time of the drug at the site of administration and result in 95% of the administered drug being removed systemically or via nasolacrimal drainage. Additionally, once the material has left the target location it should degrade in a controlled manner so that it can be safely removed from the body.
The current work focuses on the development of polymeric nanoparticles that can serve as a delivery system for ophthalmic drugs. The material proposed for the nanoparticle synthesis is poly(2-hydroxyethyl methacrylate (HEMA)), a polymer with a long history of ophthalmic compatibility. The original nanoparticle formulation was modified to allow for degradation and mucoadhesion. To facilitate degradation, a crosslinker which degrades under ocular conditions was incorporated. A mucoadhesive polymer was incorporated into the particles to enhance the residence time of the particles at the front of the eye.
Size and morphology analysis of the final polymer products showed that nano-sized, spherical particles were produced. FTIR spectra demonstrated that the nanoparticles were comprised of poly(HEMA) and that 3-(acrylamido)phenylboronic acid (3AAPBA) was successfully incorporated. Degradation of nanoparticles containing N,N’-bis(acryloyl)cystamine (BAC) after incubation with DL-dithiothreitol (DTT) was confirmed by a decrease in turbidity, measured by absorbance, and through transmission electron microscopy (TEM). Based on zeta potential results, poly(HEMA, BAC, 3AAPBA) samples C3 to C6 were found to be mucoadhesive. Dexamethasone release from poly(HEMA) nanoparticles and poly(HEMA, BAC, 3AAPBA) nanoparticles, loaded with efficiencies of 15.0% ±1.4% and 5.3% ±0.4%, resulted in rate constants of 0.001 and 0.002, and release exponents of 0.607 and 0.586, respectively. The toxicity of the nanoparticles was tested by incubation in the presence of human corneal epithelial cells (HCEC). In the presence of the poly(HEMA), poly(HEMA, BAC), and poly(HEMA, BAC, 3AAPBA) samples the HCEC viability was found to be 123.6% to 182.5%, 88.5% to 111%, and 69.8% to 85.1%, respectively. The viability of HCEC after incubation with poly(HEMA) was significantly higher compared to poly(HEMA, BAC) samples with a dilution factor of 0 and 2. Additionally, the HCEC viability in the presence of poly(HEMA, BAC, 3AAPBA) sample C6 was found to be significantly lower compared to samples C2 and C3 from Table 3. The previously summarized results suggest that the poly(HEMA) based nanoparticles produced in this work have the potential for drug delivery to the front of the eye.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Transition Experiences of Caregivers of Older Adults with Dementia and Multiple Chronic Conditions: An Interpretive Description

contributor:
Ploeg, Jenny
Nursing

subject:
dementia
multimorbidity
transitions
caregivers
older adults
comorbidity

abstract: Family caregivers of older persons with dementia (PWD) and multiple chronic conditions (MCC) provide high levels of in-home care. Caregiving is complicated by transitions such as changes to one's environment, roles, relationships, and overall health. Although PWD often have MCC, few studies have focused on the influence of MCC on dementia caregiving and transitions. The purpose of this study was to explore the transition experiences of caregivers of PWD and MCC. This study is a sub-study of a larger pragmatic mixed methods randomized controlled trial called MyTools4Care (MT4C). Using interpretive description methodology, semi-structured interviews were conducted across Ontario with a subset of caregivers (n=19) and clinicians working with dementia caregivers (n=7). Purposive theoretical sampling and concurrent data collection and analysis were used. Participants described their transition experiences, factors that influenced these experiences, potential outcomes of transitions, and the influence of MCC on dementia caregiving. Participants identified five key transitions which included: (a) There's no turning off (progressive increase in responsibilities); (b) I'm filling in many roles (changes in roles and relationships); (c) I'm sick, too (changes in overall health and well-being); (d) Dementia defines my social life (changes in social boundaries), and; (e) I know that day will come (changes in preparing for the future). Study findings emphasized how the co-existence of dementia and MCC resulted in added complexity and burden to care management and decision-making for caregivers. Findings suggest that health care professionals (HCP) are an important extension of caregivers' support networks. Thus, HCP need to be comfortable, trained, and knowledgeable in diagnosing and managing dementia and MCCs in order to support caregivers in their transitions. Future research should explore the experience of dementia within the broad context of MCC in order to understand the impact on the dementia caregiving experience.

abstract: Thesis

abstract: Master of Science (MSc)


title: A new approach for simultaneous DNA-based monitoring of the polluted environments.

contributor:
Golding, Brian
Biology

subject:
Metabarcoding
DNA-based environmental monitoring
Metagenomics
Amplicon HTS

abstract:
Taxon composition and biodiversity analyses are known powerful parameters for environmental
site status and environment diagnosis. Many ecological studies assess taxon
composition through traditional species identification and use bioindicator species to
evaluate environmental conditions. The recent breakthrough in bulk sample sequencing
combined with DNA barcoding has created a new era for environmental monitoring.
Metabarcoding approaches are more robust in studying alpha, and beta diversity compare
to the DNA barcoding and the conventional method of species identification, particularly
for rare and cryptic species. Here we built upon ecological studies of bioindicator
species and transferred the traditionally named taxa to DNA-based approaches. We
developed a small customized DNA database for biodiversity assessment and taxonomic
identification of environmental DNA samples using high-throughput amplicon sequences.
It contains macroinvertebrate species that are known as indicators of specific environmental
conditions. By implementing this small database into the KRAKEN algorithm
for the first time, we were able to assess environmental biodiversity compared to other
popular methods of taxonomic classification, especially in polluted environments where
the taxonomic composition globally change by the presence of anthropogenic drivers.
Our method is incredibly faster, and it requires significantly less computational power
in contrast to common homology-based techniques. To evaluate our approach, we have
also studied the importance of database’s size and the depth of sequencing in taxonomic
classification of high-throughput DNA sequences.

abstract: Thesis

abstract: Master of Science (MSc)


title: The Temporal Window of Visuotactile Integration

contributor:
Shore, David
Psychology

subject:
Multisensory integration
Simultaneity judgment
Temporal order judgment

abstract: The simultaneity judgment (SJ) and temporal order judgment (TOJ) tasks are the two widely used methods for measuring the window of multisensory integration; however, there are some indications that these two tasks involve different cognitive processes and therefore produce unrelated results. The present study measured observers’ visuotactile window of integration using these two tasks in order to examine whether or not SJs and TOJs produce consistent results for this particular pairing of modalities. Experiment 1 revealed no significant correlations between the SJ and TOJ tasks, indicating that they appear to measure distinct processes in visuotactile integration, and in addition showed that both sensory and decisional factors contribute to this difference. These findings were replicated in Experiment 2, which, along with Experiment 3, also showed that the reliability of the SJ and TOJ tasks may in part be responsible for the lack of agreement between these two tasks. A secondary result concerned the point of subjective simultaneity (PSS), which were tactile-leading across all three experiments.  This contradicts some of the previous literature in visuotactile integration. Manipulating the spatial distance between the visual and tactile stimulus (Experiment 2) and the certainty of stimulus location (Experiment 3) did not lead to significant changes of the location of the PSS.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Perception often involves the use of more than one sensory modality at the same time; for example, touching an object usually produces sensory signals in the visual and tactile modalities. Since the amount of time needed to transmit and process sensory signals is different among the modalities, the brain allows for a certain time difference between signals of various pairs of modalities that it will consider as coming from one event. Two tasks commonly used to measure these allowable time differences are the simultaneity judgment (SJ) and temporal order judgment (TOJ) tasks. Although they are usually used interchangeably, the present data show that the results from these tasks in the visuotactile pairing of modalities are unrelated, and a major contributing reason appears to be that these tasks are not the most reliable.


title: Genetic and environmental influences on the germination of basidiospores in the Cryptococcus neoformans species complex

contributor:
Xu, Jianping
Biology

subject:
Inter-specific cross
intra-specific cross
temperature
medium
genome structure
post-zygotic reproductive isolation
pathogenesis

abstract:
In basidiomycetous fungi, the viability of gametes is an important component of sexual
fitness and can have implications for speciation events. Prior estimates of basidiospore
germination are highly variable and the occurrence of reproduction between these lineages
suggests that reproductive isolation is incomplete. Genetic incompatibilities during
meiosis have been attributed to much of the offspring inviability. However, the influence
of environmental factors on basidiospore germination in Cryptococcus are not well
known. In this study, we used human opportunistic yeast pathogens, Cryptococcus neoformans
and Cryptococcus deneoformans, as models to investigate the potential effects
of selected genetic and environmental factors on basidiospore germination. We evaluated
basidiospore germination of six genetic crosses by pairing a total of five strains,
three intraspecific crosses and three interspecific crosses, between C. neoformans and
C. deneoformans. The offspring of genetic crosses were incubated under multiple media
and temperature treatments and scored for their germination ability. In general, spores
from intraspecific crosses had greater germination potential than those from interspecific
crosses. Growth under high temperatures was the most significant influence on basidiospore
germination on these crosses. Furthermore, there were notable interaction effects
between environmental factors and parental strains or strain pairs on basidiospore
germination. The interaction between the sex-specific genes and environmental pressures
impact reproductive barriers and blur species distinctions within the Cryptococcus
neoformans species complex. And so, reduced viability of hybrid offspring can have implications for Cryptococcus speciation, ecology, and pathogenesis as hybridization events
are an effective method of increasing pathogenicity, expanding species distributions and
increasing tolerance to novel environments or hosts.

abstract: Thesis

abstract: Master of Science (MSc)

abstract:
In basidiomycetous fungi, the viability of gametes is an important component of sexual
fitness and can have implications for speciation events. The Cryptococcus neoformans
species complex are a group of opportunistic pathogens, for which hybridization can
be facilitated readily under laboratory conditions, creating offspring that are generally
completely inviable or have low germination potential. Antagonistic genetic interactions
are mostly responsible for offspring inviability, yet the impacts of environmental factors
is not known. Multiple genetic crosses between Cryptococcus strains were used as
a model to investigate species relationships by examining the impacts of genetic and
environmental factors on offspring germination potential.


title: Longitudinal Clustering via Mixtures of Multivariate Power Exponential Distributions

contributor:
McNicholas, Paul
Statistics

subject:
longitudinal data
model-based clustering
mixture models
power exponential distribution

abstract: A mixture model approach for clustering longitudinal data is introduced. The approach, which is based on mixtures of multivariate power exponential distributions, allows for varying tail-weight and peakedness in data. In the longitudinal setting, this corresponds to more or less concentration around the most central time course in a component. The models utilize a modified Cholesky decomposition of the component scale matrices and the associated maximum likelihood estimators are derived via a generalized expectation-maximization algorithm.

abstract: Thesis

abstract: Master of Science (MSc)


title: PROCESSING METAL-ORGANIC FRAMEWORK MATERIALS INTO COMPLEX ARCHITECTURES

contributor:
Zhu, Shiping
Chemical Engineering

subject:
metal-organic framework
processing

abstract:
The metal-organic framework (MOF) research activities can be classified into MOF preparation, MOF processing, and MOF application. Processing MOFs into specially ordered shapes and morphologies is of great importance, since it bridges MOFs to real-life applications. Additionally, creating higher-order mesoscopic architectures with MOF particles as building blocks can introduce novel properties besides the inherent features of MOFs, thus opening a door to enhancing their performance in various applications. This thesis focused on the fabrication of MOFs into zero-dimensional and three-dimensional MOF architectures via various concepts inspired by polymerization and interfacial techniques.
•	A raspberry-like MOF-polymer microsphere was prepared via dispersion polymerization. MOFs were found to be a good stabilizer and could be bound to polymer core with the help of polyvinylpyrrolidone. The prepared microsphere could be further developed into a polymer@MOF core-shell structure.
•	A multilayered MOF colloidosome (MOFsome) was prepared through transient Pickering emulsion. The obtained MOFsome could be used as a stimulus-responsive carrier and as a general platform for construction of multicomponent colloidosomes.
•	A porous MOF monolith was obtained using high internal phase emulsion template (HIPE). MOF particles were able to stabilize HIPE with internal phase up to 90 % of the volume. The obtained monoliths were ultralight with density as low as 12 mg/cm3.
•	 A flexible and porous nanocellulose aerogel with high MOF loadings was prepared through a straightforward sol-gel process, followed by freeze-drying. The hierarchical porous hybrid aerogel remained intact under compression and was demonstrated to be an ideal absorbents for water purification.
•	A shapeable and versatile platform was demonstrated for in situ growth of MOF particles. The metal ion cross-linked alginate hydrogels were converted into MOF-alginate composites through a post-treatment of the hydrogels with MOF ligand solution. The macroscopic shape of the composite could be controlled and it was demonstrated to be an effective absorbent for water purification.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)


title: MASS TRANSFER ON SOLUBLE WALLS WITH DEVELOPING ROUGHNESS IN PIPES AND BENDS

contributor:
Ching, Chan
Mechanical Engineering

subject:
Heat and mass transfer
Fluid mechanics
Flow accelerated corrosion
Nuclear engineering

abstract:
Flow accelerated corrosion is a piping degradation mechanism that results in pipe wall thinning due to the dissolution of the magnetite oxide layer on carbon steel surfaces to the bulk flow. The rate limiting process of flow accelerated corrosion in piping system is the diffusion-controlled mass transfer.  The surface roughness develops due to the mass transfer and can subsequently have a significant effect on the mass transfer. The naturally developing surface roughness in many dissolving surfaces, including carbon steel pipes, is a densely packed array of saucer shaped depression called scallops, which can have several length scales. Heretofore, the developing roughness on soluble walls has not been quantified, mainly due to the lack of a reliable measurement methodology.
The overall objective of this research is to investigate the developing roughness and the corresponding mass transfer on soluble walls in different piping geometries. A wall dissolving method using gypsum test sections dissolving to water in a closed flow loop was used to mimic the mass transfer in carbon steel pipes due to a similar Schmidt number of 1200. A novel non-destructive measurement technique using X-ray CT scans was developed to measure the development of surface roughness and the corresponding mass transfer. The method was validated by performing experiments using straight pipe test sections and comparing against traditional measurements method using ultrasonic sensors, coordinate measurement machine and laser scans.
The time evolution of surface roughness and the corresponding mass transfer were measured in pipe test sections at Reynolds number of 50,000, 100,000 and 200,000. The roughness scallops were observed to initiate locally and then develop until the surface is spatially saturated. The surface roughness was characterized by the RMS height, peak-to-valley height, integral length scale, density and spacing of the scallops. Two time periods of roughness development were identified: an initial period of slower growth in the roughness height followed by a relatively higher growth rate that corresponded to the period before and after the surface saturates with the scallops. The mass transfer enhancement due to the roughness in each of these time periods was also found to be different, with a higher increase in the first period followed by a slower increase once the streamwise spacing was approximately constant. Both the height and spacing of the roughness elements was found to affect the mass transfer enhancement. A new correlation is proposed for the mass transfer enhancement as a function of the height-to-spacing ratio of roughness, with a weak dependence on Reynolds number.
The measurement methodology was extended to study the mass transfer and developing roughness in a complex S-shaped back to back bend at Reynolds number of 200,000. The mass transfer in bend geometry can be enhanced by both the local flow due to the geometry effect and the developing roughness. Two high mass transfer regions were identified: at the intrados of the first and second bends. The height-to-spacing ratio of the roughness was found to increase more rapidly in these high mass transfer regions. An additional one-time experiment was performed at a Reynolds number of 300,000. A higher surface roughness with smaller values of spacing-to-height ratio was found in the regions with high mass transfer.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: The impact of the dose and timing of epicutaneous allergen exposure on the manifestation of allergic responses in vivo

title: The effect of allergen dose on allergic responses

contributor: Medical Sciences (Molecular Virology and Immunology Program)

subject: Allergy immunology eosinophils

abstract:
Exposure to sufficiently high allergen levels of some allergens appears to protect
against the development of allergic diseases, and has also been used to treat
established allergic diseases. A reduced prevalence of sensitization and, in some
cases, asthma was reported among individuals living in homes with high allergen
levels. Furthermore, allergic patients treated with high allergen doses during
immunotherapy experienced improved allergic symptoms. The mechanisms for
how high allergen exposure may prevent disease are not known and thus, a model
in which these mechanisms could be studied in detail is warranted. The objective
of this thesis was to model and further characterize the phenomenon of high
allergen dose-dependent protection against the development of allergic responses,
using a mouse model of epicutaneous sensitization. The impact of exposure to a
high dose of cat dander in established allergic disease was also evaluated.
Epicutaneous exposure to a high dose of cat dander (150 μg) prevented airway
inflammation and airway hyperresponsiveness in genetically different strains of
mice, including Th2 prone BALB/c mice. The protective effects against airway
inflammation appeared to wane between 10 and 120 days after exposure. When
the high dose of cat dander was applied with a sensitizing dose of peanut, peanut induced anaphylaxis was prevented. Exposure to a high dose of another allergen,
ovalbumin, was also able to prevent the development of allergic airway disease.
In contrast, the high dose of cat dander did not improve established states of
allergic disease. Thus, in our mouse model, a high dose of cat dander prevented
the development of allergic responses and reflected characteristics of the
phenomenon reported in humans. As such, this model may be useful for
investigating mechanisms and potential prophylactic options for allergic diseases.
As the high dose of cat dander either had no effect or worsened established
allergic responses in our model, it is possible that the dose was not high enough to
improve disease in sensitized mice. It is also possible that established disease
cannot be modified by epicutaneous exposure.

abstract: Thesis

abstract: Master of Science (MSc)


title: ESSAYS ON THE ECONOMIC IMPACT OF INTANGIBLE CAPITAL AND INVESTMENT

contributor:
Letendre, Marc-Andre
Economics

subject:
International business cycles
Productivity
Intangible capital
Intangible investment

abstract:
This thesis investigates the role of intangible capital and intangible investment (the intangibles) in explaining modern economic activity. It presents an in depth analysis of the context in which the intangibles are studied in the economic literature, and modifies existing theoretical real business cycle (RBC) models to account for the presence of the intangibles. The newly developed models are further used to address previously documented issues such as the Canadian productivity puzzle and the quantity anomaly.
Chapter 1 provides a detailed explanation of the concept of the intangibles in the economic literature. It also highlights the importance of accounting for the intangibles during economic analysis and presents a detailed analysis of how they are measured and modeled in practice. The main findings indicate that the intangibles have contributed positively to economic growth and productivity. The need for improvements in the measurement and modeling of the intangibles is also identified. Specifically, there is a need to improve the estimates of the depreciation rates and price deflators that are used in the measurement of intangible assets; and a need for proper model specification testing to validate the inclusion of the intangibles when modeling economic activity.
Chapter 2 explores the role of the intangibles in explaining business cycles in a small open economy. The benchmark two-sector model developed in this chapter is tailored to the Canadian economy and allows for the examination of the relationship between intangible investment and the trade balance, which has not been attempted to date in the RBC literature. Overall, this chapter finds that technological change in the production of intangible investment plays an important role in explaining labour productivity and business cycles in a small open economy. Simulations based on the benchmark two-sector model highlight the circumstances under which the trade balance to business sector output ratio tends to be procyclical. The extended model is further used to make predictions about the Canadian productivity puzzle, where the main findings reinforce the need to re-evaluate the traditional measure of productivity in business cycle models.
Chapter 3 is motivated by the rising levels of intangible investment in the U.S. and Europe. These investments have been expensed in the national accounts rather than capitalized (unmeasured investment) and this practice has resulted in the traditional measures of investment, productivity and output underestimating their true levels. In order to investigate the economic impact of this practice in an international setting, the standard two-country business cycle model is extended to include such intangibles. The main results imply that the traditional measures of output and labour productivity differences across countries are understated when intangible investment is not properly accounted for. The modeling of intangible investment also improves the fit of the model based upon recent data on international business cycles. This is most evident in the international correlation of investment, which the standard model predicts to be low (0.13) and the extended model correctly predicts to be high (0.66) as seen in the data (0.74).

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)


title: Late stationary phase-specific gene expression in Escherichia coli

contributor:
Schellhorn, Herb
Elliot, Marie
Morton, Richard A.
Biology

abstract: Interest in stationary phase and adaptation mechanisms to non-optimal conditions led to the discovery of RpoS as a growth phase-dependent sigma factor. Subsequently, studies aimed at profiling members of the RpoS regulon have provided insights into the stationary phase of growth. At the same time, stationary phase physiology, which now includes formation of biofilms and persistence, is characterized by many RpoS-independent but growth phase-dependent genes, which have received less attention. Obtaining a comprehensive understanding of stationary phase requires a comprehensive profiling of these genes. We employed a plasmid-based promoter gfp::mut2 fusion library of 1920 promoters to screen for promoters active in planktonic culture during long-term incubation. Two hundred and twenty nine identified promoters fall into molecular function categories of catalytic activity, transport, stress-response, replication inhibition, and transcription. Only 35 of these are positively-regulated by RpoS and 15 are negatively-dependent during early stationary phase. We found that levels of rpoS transcript peak during fast growth conditions of early stationary phase (OD600 = 1.5) and decrease thereafter. Induction of tryptophanase, which produces indole, was discovered to be RpoS-independent but stationary phase-specific at the transcript and protein levels. Furthermore, RpoS serves to limit TnaA levels following initial induction in a dose dependent manner. At the transcript level, RpoS positively regulates TnaA in exponential phase (OD600 = 0.3) but negatively in early stationary phase (OD600 = 1.5). The mechanism underlying this switch is unknown. Thus, mature stationary phase cultures are characterized by a physiology that is at least partially, if not completely, distinct from early stationary phase cells and RpoS-independent but stationary phase-specific genes play an important role during prolonged starvation.

abstract: Thesis

abstract: Master of Science (MSc)


title: Maternity Care Collaboration in Ontario: The Perspectives of Obstetricians and Midwives

contributor:
Murray-Davis, Beth
Dore, Kelly
Miller, Patricia
Health Science Education

abstract:
Introduction:

Interprofessional collaborative care is the gold standard in maternity care and has been proposed as the best way to manage the impending maternity care crisis in Ontario.  This thesis researched the benefits and barriers to interprofessional collaboration from the perspectives of obstetricians and midwives.  The goal was to understand how obstetricians and midwives view collaborative practice, how the different professions perceive collaboration, and to explore the attitudes and perceptions regarding collaboration of clinicians practicing in each discipline.

Methods:

This study adopted a mixed methods design.  A province-wide survey was distributed to actively practicing obstetricians and midwives in Ontario.  Following completion of the survey, participants were invited to contribute further opinions and perceptions in semi-structured interviews, conducted using a grounded theory approach.

Results:

Quantitative and qualitative data revealed three key findings.  First, when comparing the opinions of obstetricians and midwives, scope of practice was viewed as a contentious issue with fee structures and turf protection being contributory factors.  Second, the definition of interprofessional collaboration, and its application to clinical practice, varied by profession, and was viewed as a barrier to effective communication between disciplines.  Finally, philosophy of care, particularly surrounding the provision of homebirth and women-centered care, varied starkly across the disciplines.

Conclusion:

Members of each profession need to develop strategies to ensure mutual respect is given in cases of philosophical and scope differences, an essential component to successful implementation of collaborative initiatives.  Governing bodies and professional associations of each discipline need to strive for mutual agreement on appropriate scope of practice to ensure buy-in from members of each profession.

abstract: Thesis

abstract: Master of Health Sciences (MSc)

abstract: This thesis examines the perceptions of interprofessional collaboration from the perspectives of midwives and obstetricians, and contrasts how these perceptions vary by the profession.  Data was collected in two ways: through an online survey and semi-structured interviews.  Midwives and obstetricians were asked about their experiences with collaboration, their perspectives on the barriers to collaboration and thoughts about an improved system in Ontario to facilitate enhanced maternity care collaboration.  The results demonstrate the key barriers to collaboration including contentious views on scope of practice, the definition and interpretation of interprofessional collaboration and varying philosophies of care.  The changing landscape of maternity care in Ontario is imminent; family doctors who provide obstetrical care are on the decline, increasing the workload for obstetricians and midwives necessitating the need to eliminate barriers to achieve successful interprofessional collaboration.


title: EXPLORING THE PRO-APOPTOTIC FUNCTION OF BIM

contributor:
Andrews, David
Chemical Biology

subject:
apoptosis
cell death
cancer
Bcl-2 family

abstract:
Apoptosis is a type of programmed cell death which plays a fundamental role in maintaining homeostasis in multi-cellular organisms. The Bcl-2 family has been identified as the central players in regulation of apoptosis. It consists of anti-apoptotic proteins (e.g Bcl-XL) and pro-apoptotic proteins which are further classified as BH3 proteins (e.g Bim, Bid) and effector proteins (e.g Bax, Bak). BH3-proteins regulate apoptosis by activating the pro-apoptotic proteins Bax and Bak to permeabilize mitochondria, and/or by inhibiting anti-apoptotic proteins such as Bcl-XL and Bcl-2.
In this study, we employed fluorescence spectroscopy and functional assays with full-length Bim and showed that major Bim isoforms have similar activities in vitro. Bim preferably activates Bax over Bak while Bid preferably activates Bak. Bim displayed a unique binding to Bcl-XL so that the Bim-Bcl-XL complex is resistant to BH3-mimic drug ABT-263 treatment while Bid does not. A Bcl-XL enhancer BH3 TCTP was also shown to interact with Bim-Bcl-XL and Bid-Bcl-XL complex differently, where a single mutation abolished its enhancement of Bid-Bcl-XL but not Bim-Bcl-XL.
Closer investigation of the dual apoptotic functions of the BH3-protein Bim revealed that the C-terminal membrane binding domain (MBD) is unexpectedly also involved both in binding of Bim to Bax in solution and in activating Bax. Multiple mutations in this domain reduced or abolished binding to membranes but did not affect binding to Bax or correlate with Bax activation. Deletion eliminated binding to and activation of Bax, but not binding to or inhibition of Bcl-XL. Thus MBD mediates binding to both membranes and Bax separately. On the other hand, although the MBD is not the determining factor for interactions with Bcl-XL, our data demonstrates Bim MBD also plays a major role in binding to Bcl-XL. The C-terminal MBD was shown to be contributing to the ABT-263 resistance of Bim-Bcl-XL complex by directly interacting with Bcl-XL. We discovered additional interactions between the MBD of Bim and both Bcl-XL and Bcl-2. Our data suggested a novel topology and mechanism for the Bim-MBD that positions the central hydrophobic residues of the MBD appropriately for binding to Bcl-XL.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Apoptosis is a type of programmed cell death which plays a fundamental role in maintaining homeostasis in multi-cellular organisms. The Bcl-2 family has been identified as the central players in regulation of apoptosis. It consists of anti-apoptotic proteins (e.g Bcl-XL) and pro-apoptotic proteins which are further classified as BH3 proteins (e.g Bim, Bid) and effector proteins (e.g Bax, Bak). Here we showed that Bim is constitutively active in vitro and preferably activates Bax, distinguishing itself from Bid which preferably activate Bak. We showed that the C-terminus membrane binding domain (MBD) of Bim plays a crucial role in reguating binding and activation of Bax, as well as providing extra binding support to Bcl-XL, independent of its membrane binding feature.


title: Capacity of Eccentrically Loaded Slender Concrete Block Walls

contributor:
Drysdale, R. G.
Civil Engineering

subject: eccentrically, loaded, slender, concrete, block walls, capacity, finite, two-dimensional

abstract:
 The behavior of concrete block walls subjected to vertical compressive loads with out-of-plane eccentricities was investigated both experimentally and analytically. Particular attention was devoted to the effect of wall slenderness on capacity.

 In the experimental study, 14 full scale walls and numerous small specimens were tested to provide complete and reliable data concerning the behavior of concrete block walls and its components. Plain walls and partially grouted reinforced walls were tested in symmetric single curvature under compressive loads with out-of-plane eccentricities. Reinforced walls were tested in pure bending, as well.

 Prisms were tested to analyze the behavior of concrete masonry in
compression with no slenderness or eccentricity effects. Bond tests were carried out to determine the behavior at interfaces of grout and steel reinforcing bars as well as between mortar and concrete blocks. Material tests were conducted to determine the mechanical properties of the blocks, mortar, grout and steel reinforcement used.

 A two-dimensional finite element model for the vertical cross section of block masonry walls was developed. It is capable of modeling local failure modes such as cracking, crushing and debonding. Material properties of the concrete blocks, mortar, grout, and steel bars were
treated individually. The large deformation analysis allowed for consideration of the slenderness effect. The model was verified through comparison with experimental results. Fairly good agreement was obtained.

 The material properties of specimens tested during the experimental investigation were the basis of a parametric study. Results of this study were used to investigate the effect of the wall slenderness and the eccentricity of applied loads on the capacity of concrete block walls. They were used to evaluate the current provisions in the Canadian Masonry Code, CAN3-S304-M84. An attempt was made to
develop original design equations based on the reduction coefficient approach. The proposed equations for plain and reinforced blockwork were shown to provide more consistent predictions of capacity than current design methods.

abstract: Thesis

abstract: Master of Engineering (MEngr)