title: METAL ION SEPARATION USING ELECTRICALLY SWITCHED ION EXCHANGE

contributor:
Dickson, Sarah
Younggy, Kim
Civil Engineering

subject: metal ion separation

abstract:
Cs137 is generated from fission nuclear reactor operations. It has a half-life time of 30 years, and it is considered to be an excellent source of gamma radiation. Cs137 needs to be separated from nuclear waste before its disposal. Electrically switched ion exchange (ESIX) is one method which can be used for its separation from nuclear waste.

ESIX consists of an ion exchange film that is deposited onto a conductive electrode surface. Typically, for Cs+ removal, this film is composed of nickel hexacyanoferrate, which is known for its selectivity for that ion. The ESIX method involves the sequential application of reduction and oxidation potentials to an ion exchange film to induce the respective loading and unloading of Cs+. ESIX can be used to separate Cs137 from nuclear radioactive waste as well as Cs+ from industrial wastewater.

The goal of this research was to enhance the capacity of the nickel hexacyanoferrate ion exchange film deposited on nickel electrodes by modulating the applied potential for the ESIX film preparation. This goal was achieved by preparing an ESIX film on a nickel substrate using a two-step process in which voltage is applied to a nickel electrode surface prepared prior to the film deposition using diamond sand paper 2500 grit. The results show the preparation of a film with capacity 63 times higher than that which is previously reported in the literature.

Another four ESIX films composed of nickel hexacyanoferrate were deposited on nickel substrates with varying potentials, again in a two-step process and with surface treatment using 800 grit diamond sand paper prior to the film deposition. The surface morphology of the films was studied using scanning electronic microscope (SEM) to note any differences which could have occurred from the changes in deposition procedures. Electrospray ionization-mass spectroscopy was used to quantify the Cs+ loaded and unloaded onto the film. The results show that all of the four prepared ESIX film have a high capacity compared to those reported in the literature and that their performance regarding Cs+ loading was affected by the applied potential used for the ESIX film preparation.

Another goal of this research was to enhance the capacity of the nickel hexacyanoferrate ESIX film by changing the substrate from nickel to graphite. This goal was achieved by adsorbing the film into the pores of graphite electrodes. X-ray tomography was used to visualize the nickel hexacyanoferrate film inside the graphite electrodes. Cyclic voltammetry was conducted to detect the response of the prepared film with Cs+. Electrospray ionization-mass spectroscopy was used to quantify the amount of Cs+ adsorbed and desorbed by the electrode. The x-ray tomography results show that the graphite electrode adsorbed nickel hexacyanoferrate material. The cyclic voltammetry figures confirm that the response of each electrode prepared with Cs+ was related to the concentration of nickel hexacyanoferrate in the graphite electrode. Finally, the results obtained from electrospray ionization-mass spectroscopy about how much Cs+ was adsorbed and desorbed confirms that the two prepared electrodes have a higher capacity for Cs+ adsorption based on their interaction with a prepared Cs+ solution as a test solution.

Another goal was to observe the performance of a new ESIX film material, namely nickel hexacyanocobaltate. This film was also adsorbed by graphite electrodes. Cyclic voltammetry was conducted to measure the performance of the hexacyanocobaltate film with regard to Cs+, and the results show a significant increase in the nickel hexacyanocobaltate material inside the graphite electrode and Cs+ in the test solution. Electrospray ionization-mass spectroscopy was used to quantify the Cs+ adsorbed and desorbed by the electrode. The Results show that nickel hexacyanocobaltate as an ESIX have high capacity for Cs+ adsorption from test solution.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Electro-Hydrostatic Actuator (EHA) Position Tracking and Correction

contributor:
Habibi, Saeid R.
Mechanical Engineering

subject: EHA Control

abstract:
The Electro-Hydrostatic Actuator (EHA) is a self-contained and modular hydraulic actuation system using feedback control. EHAs are being increasingly used in engineering and industrial systems that require high precision and efficiency such as aircrafts (Airbus 380), off-highway hydraulic hybrids and construction machineries. In this research, mathematical models (linear and nonlinear) with different control strategies (that include PID, PID with feedforward compensation, and Sliding Mode Control (SMC)) are developed and experimentally applied to an EHA prototype. These methods are then compared to a new control strategy that is a combination of Interacting Multiple Model concept, Sliding Mode Control (IMM-SMC) and the Smooth Variable Structure Filter (SVSF). The IMM and the SMC strategies are also applied with the Kalman Filter (KF) for comparison.
The above mentioned control strategies were implemented on an EHA prototype for position control under a range of fault conditions that were physically simulated. Both simulation and experimental results showed that the new IMM-SMC with SVSF outperformed all the other control strategies in terms of robustness and precision in trajectory tracking.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Model Wavefunction Forms to Describe Strong Correlation in Quantum Chemistry

contributor:
Ayers, Paul W.
Van Neck, Dimitri
Bultinck, Patrick
Chemistry and Chemical Biology

abstract: Standard approaches to approximating solutions to the Schroedinger equation rely upon the assumption that there is a single dominant electronic configuration with a small number of low-lying excited states. As such, they are referred to as single reference approaches and are accurate only when the band gap is small in comparison with the inter-electronic repulsion of the valence electrons. Systems for which this is the case are weakly-correlated. If the inter-electronic repulsion larger than the band gap, then a single electronic reference is not an appropriate ansatz for the physical wavefunction. As the strength of the interaction is increased many Slater determinants become near-degenerate, each providing non-negligible contributions. Such systems are strongly-correlated. The goal of the thesis was to employ wavefunctions which are: non-trivial, tractable, size-consistent and extensive, and not given in an active space. We have outlined approaches based on wavefunction forms more suited to describe strong correlation. Built on the Lie algebra su(2), our first trial wavefunction was the Bethe ansatz solution to the reduced BCS Hamiltonian derived by Richardson. This wavefunction is expressed as a product of quasi-particles each parametrized in terms of quasi-momenta. Consistency among the quasi-momenta is ensured by a set of non-linear equations to be solved numerically. This approach is feasible in both variational and projected flavours. We next considered a wavefunction of the same form without requiring it to be an eigenvector of the reduced BCS Hamiltonian. A variational approach in this case is only feasible provided there are two equivalent descriptions in terms of particles and holes. In any case, a bivariational principle and a projected approach are both feasible. Also based on su(2), there is AP1roG (coupled cluster pair doubles). Open-shell singlets and triplets were constructed with the Lie algebras sp(N) and so(4N). The resulting formulae appear to be infeasible unless it is possible to efficiently compute generalizations of determinants to three-dimensional objects. Treating each spatial orbital individually, all four possible occupations close the Lie superalgebra gl(2|2).

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: CAREGIVER QUALITY-OF-LIFE AND THE CARE PROVIDED TO PERSONS WITH ALZHEIMER'S DISEASE

contributor:
Oremus, Mark
Health Research Methodology

subject:
Alzheimer's disease
quality-of-life
caregiving
level of care
quality of care
quantitative study
qualitative study
mixed-methods

abstract:
Primary informal caregivers are mainly responsible for the care of persons with Alzheimer's disease (AD). Research has shown that the quality-of-life (QoL) experienced by unpaid caregivers of persons with AD is generally lower than the QoL of caregivers of persons who do not have AD. The literature does not report on any studies undertaken to examine whether caregivers' QoL is related to the level or quality of care that they provide to persons with AD.
This thesis investigated the association between caregiver QoL and the level or quality of care provided. I conducted a systematic review and found no study designed specifically to examine this association. I included only one study in the systematic review because it contained variables that were relevant to caregiver QoL and the level or quality of care. However, this single included study did not specifically examine the association between QoL and level or quality of care. In addition, I could not find an instrument designed specifically to measure level or quality of care in AD.
To answer this question, I contacted the authors of the single study included in the systematic review and obtained their dataset. Quantitative analysis of these data did not show a statistically significant association between caregiver well-being (surrogate for QoL) and level or quality of care.
Further, I conducted a qualitative study of AD caregivers to obtain data on the components of a useful questionnaire for measuring level or quality of care. Caregivers suggested the development of a questionnaire that addresses the following areas: case management approach, increasing care demands due to declining status of the care recipient, social support, and the role of hired help.
The thesis concludes with an integrative discussion of the aforementioned studies. I discuss important areas for future research, including the need for a longitudinal study.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: The Dynamical Implications for Stars, Star Formation, and Dark Matter Cores in Dwarf Galaxies

contributor:
Couchman, Hugh M. P.
Wadsley, James
Astrophysics

subject:
dark matter
galaxies: dwarf
galaxies: evolution
galaxies: formation
galaxies: star clusters
globular clusters: general

abstract: I investigate the observational signatures of the formation of dark matter cores in dwarf galaxies.  I adopt the paradigm where the energy from star formation feedback is injected into the orbits of dark matter particles, forming a constant density core consistent with observations of dwarf galaxies.  Using physically motivated constraints I show there is ample feedback energy available given the average stellar mass of dwarf galaxies to form cores in $10^{8}$--$10^{11}$\thinspace M$_{\odot}$ halos, and predict the maximum core size as a function of stellar mass.  I describe how observational features of the old stellar content of dwarf galaxies are due to this core formation paradigm.  As both dark matter and stars are collisionless fluids, the stars responsible for the feedback form in the centres of dwarf galaxies and have their orbits grown by subsequent star formation.  This will naturally lead to age and metallicity gradients, with the younger and more metal rich stellar population near the dwarf centres.  This process also prevents the destruction of globular clusters by driving them out of the dwarf nucleus --- the decrease in central dark matter density reduces the strength of dynamical friction --- and increases the likelihood of being stripped onto the stellar halos of larger galaxies.  It also offers a model for forming multiple populations in globular clusters, with the only assumption being that the source of the polluted gas resides within the dwarf progenitor.  As the orbit of a globular cluster grows, it will experience multiple accretion events with each pass through the gas-rich galaxy centre.  The simple accretion model exhibits two traits revealed from observations --- a short accretion timescale and a sensitive dependence on mass --- without requiring an exotic initial stellar mass function or the initial globular cluster mass function to be 10--25 times larger than at present.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)


title: COMPARISON OF THE PROCOAGULANT AND IMMUNOMODULATORY PROPERTIES OF NUCLEAR, MITOCHONDRIAL, AND BACTERIAL DNA WITH RELEVANCE TO SEPSIS

title: NUCLEAR, MITOCHONDRIAL, AND BACTERIAL DNA IN SEPSIS

contributor:
Liaw, Patricia
Health Sciences

subject: sepsis DNA coagulation neutrophils mitochondria bacteria

abstract:
Objective – Sepsis is a syndrome in which infection triggers a systemic inflammatory and procoagulant response. Cell-free DNA (CFDNA) is elevated in sepsis, and correlates with mortality. This DNA may come from nuclear, mitochondrial, or bacterial sources. CpG motifs on bacterial and mitochondrial DNA can stimulate inflammatory responses via TLR9. CFDNA can activate coagulation via the contact pathway. CFDNA may thus play an important pathogenic role in sepsis. This study elucidates the relative effects of nuclear, mitochondrial, and bacterial DNA on inflammatory and pro-coagulant pathways with relevance to sepsis.
Results – Mitochondrial DNA as well as nuclear DNA are elevated in plasma from septic patients compared to healthy controls. Bacterial, but not mitochondrial or nuclear, DNA increased neutrophil IL-6 secretion. Both mitochondrial and bacterial DNA increased neutrophil viability. Nuclear, mitochondrial, and bacterial DNA increased thrombin generation in both platelet-poor plasma and platelet-rich plasma to a similar degree. This effect was reduced by addition of corn-trypsin inhibitor and in FXII-depleted plasma, and abolished in FXI-depleted plasma, indicating dependence on the intrinsic pathway of coagulation. Independently of coagulation, DNA from all three sources was capable of causing activation of platelet integrin αIIbβ3.
Conclusions – CFDNA from nuclear, mitochondrial, and bacterial sources have varying pro-inflammatory effects, although all three have similar pro-coagulant potential. The pathophysiological effects of CFDNA in sepsis may vary with the source of DNA.

abstract: Thesis

abstract: Master of Science (MSc)


title: Senstivity of Lattice Physics Modelling of the Canadian PT-SCWR to Changes in Lateral Coolant Density Gradients in a Channel

contributor:
Luxat, John
Novog, David
Engineering Physics

subject:
Nuclear Physics
PT-SCWR
Lattice Codes
Neutronics
Coolant Density Variation
Benchmark

abstract:
The Pressure Tube Super Critical Water Reactor (PT-SCWR) is a design with a
light water coolant operating at 25 MPa above the thermodynamic critical pressure,
with a separated low pressure and temperature moderator, facilitated by a High
E ciency Channel consisting of a pressure tube and a porous ceramic insulator
tube. The 2011 AECL reference design is considered along with a 2012 benchmark.
In the 2011 reference design the coolant is permitted to
ow through the insulator.
The insulator region has a temperature gradient from 881 K at the inner liner tube
to 478 K at the pressure tube wall. The density of light water varies by an order of
magnitude depending on the local enthalpy of the
uid. The lateral coolant density
is estimated as a radial function at  ve axial positions with the lattice physics codes
WIMS-AECL and Serpent. The lateral coolant density variations in the insulator
region of the PT-SCWR cause strong reactivity and CVR e ects which vary heavily
on axial location due to the changes in the estimated mass of coolant and the physical
relocation of the coolant closer to the moderator, as the coolant is estimated to be
least dense closer to the fuel region of the coolant
ow. The beta version of Serpent
2 is used to explore the lateral coolant densities in the subchannel region of the
insulator in the 2012 version of the PT-SCWR. A more advanced coolant density
analysis with FLUENT is used to estimate the subchannel coolant density variation,
which is linked to SERPENT 2s multi-physics interface, allowing the lattice code
to measure the sensitivity of the model to the analysis of the subchannels. This
analysis increases the reactivity of the PT-SCWR through the displacement of the
coolant. Serpent 2 is accepted as a valid lattice code for PT-SCWR analysis.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Factors Involved in the Codon Usage Bias Among Different Genes in a Genome, And Among Different Sites Within a Gene

contributor:
Higgs, Paul G.
Physics and Astronomy

subject: codon usage bias, E. coli, context dependent mutation, mRNA folding, codon adaptation, translation efficiency

abstract:
In this study we have focused on the codon usage bias in E. coli. In chapter 3, we use the population genetics model and the data available on the protein and mRNA levels of the E. coli genes to understand the pattern of codon usage in different genes with different expression levels and see which measure best explains the codon usage pattern. Besides codon bias, by testing for the over-parametrization of the model, we are able to test for the existence of context dependent mutation. We have also fitted the model for the codon usage patter in the Yeast and also tested for the context dependent mutation in this organism.

In chapter 4, we focus on the first 10-15 codons in the genes of E. coli. Motivated by the fact that in this region we observe two phenomena, reduction in translation efficiency and suppression of mRNA secondary structures, we investigate whether the former is a side effect of selection for the latter. For this matter we have generated a set of synonymous randomized sequences, and then by selecting the ones which show weak secondary structures in the mentioned region, we would be able to test the theory. We will also look at the frequencies of the amino acids in E. coli genes and see whether the selection for weak secondary structures in the translation initiation region could be strong enough to not only affect the codon usage, but also the choice of amino acids. We would also provide information on the correlation between the strength of the mRNA secondary structure in the first 13 codons and the overall translation efficiency of the genes.

abstract: Thesis

abstract: Master of Science (MSc)


title: THE INTESTINAL MICROBIOTA AND NONSTEROIDAL ANTI-INFLAMMATORY DRUG-INDUCED SMALL INTESTINAL DAMAGE

contributor: Medical Sciences (Division of Physiology/Pharmacology)

subject:
NSAID
Small Intestine
Microbiota
Dysbiosis
Physiology
Pharmacology
Probiotics
Antibiotics
Inflammation
Acetate
Environmental Enteropathy

abstract: As one of the most common medications, it is reasonable to assume that the adverse effects from nonsteroidal anti-inflammatory drugs (NSAIDs) are well understood.  While this is the case for NSAID-induced gastropathy, NSAID-induced enteropathy is often clinically overlooked and has a pathogenesis that is incompletely understood.  The goal of this study was to determine how alterations in the microbiota impact NSAID-induced intestinal injury.  Initial studies explore how gastric acid secretion suppression substantially decreases Bifidobacteria in the small intestine, and emphasize how replenishment of these bacteria results in an amelioration of NSAID-induced enteropathy.   Follow-up studies involved pretreating rats with specific bacteria that have conferred protection in other models of small intestinal injury.  We examined the role that acetate may play in reducing the damage by evaluating bacteria that had an acetate production gene knocked out via homologous recombination.  Protection levels were similar between wildtype and knockout bacteria, and it did not appear that acetate had a key role in damage reduction. Moreover, we found that changes in intestinal damage were dependent not only on the strain of bacteria used but also on the NSAID administered.  None of the bacterial pretreatments tested protected against indomethacin- or diclofenac-induced small intestinal injury, and pretreatment with one specific bacterial strain resulted in a significant worsening of damage.  To gain further insight as to the potential role of the microbiota in exacerbation of injury, we conducted studies using single antibiotics and antibiotic cocktails.  No single antibiotic treatment conferred protection against naproxen-induced small intestinal injury, but an antibiotic cocktail decreased damage scores by ~46%.  Furthermore we explored the effects of L-lactic acid supplementation of drinking water but this was unable to reduce naproxen-induced intestinal damage.  Collectively, the work presented in this thesis provides novel insights on the relationship between alterations in the microbiota and susceptibility to NSAID-induced enteropathy.

abstract: Dissertation

abstract: Doctor of Philosophy (Medical Science)


title: Up-regulation of antioxidants in the glia protects Drosophila from oxidative stress

contributor:
Campos, Ana R.
Biology

subject: oxidative stress, glia, Drosophila, sub-perineurial glia, blood-brain barrier, paraquat

abstract: In Drosophila melanogaster oxidative stress (OS) decreases  lifespan and  motor function (Coulom & Birman, 2004; Hosamani, 2013)  through  degeneration of dopaminergic (DA) neurons (Brooks et al., 1999). The mitogen-activated protein kinases, P38, c-JUN-NH2 terminal kinase (JNK) and extracellular-signal related kinase (ERK) are activated in response to OS (Apel & Hirt, 2004). My thesis investigated the protective role of up-regulation of the antioxidants superoxide dismutase (Sod) and catalase (Cat) in the glia of Drosophila against oxidative stress induced by paraquat (PQ). Exposure to PQ killed ~20-80% of flies and impacted motor functions as measured in a negative geotaxis assay. Pan-glial expression of Sod2 using Repo-GAL4 did not reduce the lethality caused by PQ exposure. These flies displayed a marked reduction in locomotion even when not exposed to PQ. However, their motor functions were not affected by PQ exposure. Pan-glial expression of Cat was not sufficient to prevent the negative effects of PQ exposure (viability and locomotion). Pan-neuronal expression of Sod2 using Elav-GAL4 protected the locomotive ability but not the lethality caused by PQ exposure. Pan-neuronal up-regulation of Cat protected against both the lethality and motor defects caused by PQ exposure. Over-expression of Sod2 and Cat in all sub-perineurial glial (SPG) cells using NP2276-GAL4 protected the motor function from exposure to PQ. Up-regulation of Sod1 and Sod2 in the SPG cells that form the blood brain barrier (BBB) using Spg Moody-GAL4 protected the motor function but not the lethality caused by PQ exposure. Over-expression of  Sod2 in the SPG cells that form the BBB protected DA neurons from the deleterious effects of PQ exposure. A cluster of DA neurons, the paired posterior lateral 1 (PPL1), was identified as important for motor function. In both the parental lines and in flies in which Sod2 was up-regulated at the SPG cells, phospho-JNK and phospho-ERK were detected after 1h, 6h and 24h of PQ exposure by Western blot. Phospho-P38 levels were markedly reduced after 24h exposure to PQ in the parental controls. During all time points of PQ exposure, phosphorylated form of P38 was detected when Sod2 was up-regulated at the BBB. In conclusion, up-regulation of Sod2 in the SPG cells forming the BBB protects DA neurons from PQ exposure, maintains the phosphorylation status of P38, which may ultimately translate into protection of the motor function. It is possible that increased Sod2 expression at the BBB sustains phospho-P38 levels which may play a role in increasing the tolerance of the flies to oxidative stress induced by PQ.

abstract: Thesis

abstract: Master of Science (MSc)


title: Modeling of damage propagation in cohesive-frictional materials

contributor:
Pietruszczak, S.
Civil Engineering

subject: Crack propagation

subject: Constitutive law with embedded discontinuity

subject: Extended FEM

subject: Damage

subject: Plasticity

abstract:
The primary focus in this research is on proposing a methodology for modeling of discrete crack propagation in geomaterials such as soil, rock, and concrete. Structures made of such materials may undergo damage due to several reasons. Here, mechanical loading and chemo-mechanical interactions that result in degradation of strength parameters are considered as the sources of damage initiation. Both tensile and compressive cracks are investigated.
For analysis of crack propagation, two different methodologies are employed; the Constitutive Law with Embedded Discontinuity (CLED) and the Extended Finite Element Method (XFEM). The CLED approach is enhanced here to describe the discrete nature of crack propagation. This is done by coupling the CLED with explicit modeling of crack path using the Level-Set method. The XFEM is used as a verification tool to check the results from CLED analysis. An algorithm is proposed for crack initiation and propagation that results in stable and a mesh-independent solution. The CLED approach is further improved by developing the return-mapping and closest-point projection algorithms. Extensive numerical investigations are conducted that include mode I cracking in a three point bending test, mode I cracking in notched cantilever beam, mixed cracking mode in a plate subjected to shear and tension, and a mixed mode cracking in a notched beam under four point loading. For frictional interfaces, the shear band formation in a sample subjected to bi-axial compression and the shear band formation in a geo-slope are studied.
The thesis also addresses the topic of the response of unsaturated cohesive soils undergoing an infiltration process. The problem is approached within the framework of Chemo-Plasticity. It is assumed that the complex chemo-mechanical interactions are the controlling factors for degradation of strength parameters during this process. A return mapping integration scheme is developed and the approach is employed to investigate the stability of a geoslope subjected to a heavy rainfall.
Analysis of shear band formation is further investigated in the context of sedimentary rocks. The microstructure tensor approach is used to describe the inherent anisotropy in this class of materials. The orientation of the shear band is defined by invoking the Critical Plane approach and the closest-point projection algorithm is developed for numerical integration of the governing constitutive relations. The model is used along with CLED for analysis of the mechanical response of Tournemire argillite. It is shown that the friction between loading platens and sample can play an important role in the process of shear band formation and the associated assessment of the ultimate load. A mesh-sensitivity analysis employing the CLED framework is also conducted here.
The research clearly demonstrates that the discrete representation of crack path propagation is essential for an accurate analysis of failure in various engineering structures. It is shown that if the classical smeared Constitutive Law with Embedded Discontinuity is enhanced to simulate the discrete nature of the damage process, it can yield very accurate results that are virtually identical to those obtained from discrete approaches such as XFEM.

abstract: Thesis

abstract: Candidate in Philosophy


title: Integrating sphere-based spectrally constrained total diffuse reflectance for in vivo quantification of hemoglobin in skin

contributor:
Farrell, Thomas
Medical Physics

abstract: The ability to monitor changes in skin redness through the hemoglobin concentration in skin has the potential to personalize patient care by providing a quantitative objective way of monitoring patient response to interventions such as radiation therapy and plastic surgery. Currently available commercial systems for monitoring skin redness rely on total diffuse reflectance spectroscopy and can only accurately measure hemoglobin changes relative to a baseline measurement when all other skin chromophores, such as melanin, remain constant. This work investigates the application of a spectrally-constrained diffusion theory model for analyzing total diffuse reflectance spectra obtained with an integrating sphere-based system. A low cost integrating sphere-based system was designed, constructed, and characterized to yield accurate total diffuse reflectance spectra. The system was first used with an absorbance-based erythema index to investigate the time to maximal effect of epinephrine – a vasoconstrictor used in plastic surgery. A spectrally-constrained diffusion theory model was developed to improve the interpretation of the reflectance spectra obtained with the integrating sphere-based system. Correction factors necessary to apply the developed model to the obtained spectra were determined through Monte Carlo simulations, and then confirmed with tissue-simulating liquid phantoms. The model was tested for sensitivity and specificity, as well as how it responded to variations in the experimental parameters. The system and model were then used to monitor radiation-induced erythema in head and neck intensity modulated radiation therapy patients. Analysis of the results enabled earlier detection of erythema by 1-19 days compared to visual assessment. The work completed in this thesis illustrates a cost-effective, user-friendly diffuse reflectance spectroscopy system which has potential applications in a number of clinical settings.

abstract: Thesis

abstract: Candidate in Philosophy


title: ADVANCES IN LATE TRANSITION METAL CATALYSIS, OLEFINATION REACTIONS AND APPLICATIONS

contributor:
McNulty, James
Chemistry and Chemical Biology

subject:
Homogeneous catalysis
Nostodione
Indole carboxylates
Suzuki-Miyaura coupling
phosphines
phosphonium salts

abstract:
Two series of stable palladium and silver complexes ligated to hemilabile ligands were prepared. The stability and applicability of these well-defined complexes in promoting various reactions (cycloaddition, hydroamination, cross-coupling reactions, etc.) was investigated. Structure-activity studies with a series of related ligands led us to find a pronounced ligand effect on these reactions.
The dichotomous reactivity of triethyl phosphonium hydrobromide salt with dialkyl acetals was used for the synthesis of alkoxy phosphonium salts. Reactivity and applications of these phosphonium salts were described for the synthesis of the biologically active cinnamyl triazoles and ethyl indole-2-carboxylates. Total synthesis of the natural product nostodione A, was developed in eight chemical steps and with 21.6% overall yield from ethyl-2-indolecarboxylates. The synthesis of a mini-panel of structural analogs allowed for the discovery of anti-parasitic biological activity of nostodione A and its analogues for the first time.

abstract: Thesis

abstract: Doctor of Science  (PhD)


title: THE SYNTHESIS AND EVALUATION OF SMALL MOLECULE INHIBITORS AS MOLECULAR IMAGING AGENTS FOR UROKINASE PLASMINOGEN ACTIVATOR

contributor:
Capretta, Alfredo
Valliant, John
Chemical Biology

subject:
Urokinase-type plasminogen activator
Molecular imaging probes
125I-labelled tetrazine

abstract:
Urokinase-type plasminogen activator (uPA) protein is a serine protease of the trypsin family that is overexpressed by tumors cells seeking to metastasize. Molecular imaging methods using molecular imaging probe designed to target uPA could provide a method for the detection of aggressive cancers and monitoring response to treatment. Four classes of high affinity uPA inhibitors, three which were reversible and one irreversible, were used as platforms to develop radiolabeled probes for uPA. Based on structure-activity relationships, lead compounds were modified to allow for the introduction of a radiohalogen (radioiodine) at different sites in the corresponding molecules. Suitable synthetic strategies were developed to create libraries of iodinated phenyl guanidine, peptide, naphtamidine and phosphonate derivatives. For the phenylguanidines colorimetric assays showed the product had micromolar affinity while for the peptide derivatives low nanomolar affinity for the iodinated analogue was observed (1.4 nM to 2.53 nM). Unfortunately quantitative biodistribution studies showed low tumour uptake (<0.5% ID/g). More promising results were obtained for the irreversible iodinated phosphonated derivative which had an affinity of 2.1 nM. This reagent showed 1.95% ID/g tumour uptake and lower blood uptake in vivo which demonstrates advantageous properties over existing uPA probes in terms of tumour-to-blood ratios.
A complementary development was also achieved in that the first example of a 125I-labelled tetrazine was prepared. This new reagent can be used in pre-targeted strategies that utilize bioorthogonal coupling between stained trans-cyclooctene (TCO) and tetrazines. The product was prepared using a concomitant oxidation iodo-destannylation reaction and the product isolated in 80% radiochemical yield. The reaction with transcycloctene proceeded rapidly to produce various isomers which were fully characterized through NMR analysis of the non-radioactive analogues.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Implementability of Requirements for Safety-Critical Embedded Systems

contributor:
Lawford, Mark
Maibaum, Thomas
Computing and Software

abstract:
Computer systems are used for controlling physical processes in many safety-critical applications. These systems are embedded into the larger system of the application and are interfaced with their physical environment using input hardware (sensors, analog-to-digital converters) and output hardware (digital to analog converters, actuators). A challenging task in designing such systems is finding the right combination of input hardware, output hardware, and software such that their integration produces systems that satisfy their requirements.
In this thesis we propose a mathematical basis for checking, without the need for developing and verifying a detailed implementation, if acceptable soft- ware exists given the chosen hardware interfaces. The requirements framework we use is the relational four-variable model proposed by Parnas and Madey. This model helps to clarify the behaviour of, and the boundaries between, the system’s physical environment, hardware interfaces, and software, which are all described as input-output relations without detail about internal state.
The semantics of the four-variable model proposed by Parnas and Madey, which may be seen in relation algebraic terms as an angelic semantics, allows system descriptions that are not completely consistent with the natural laws of the physical environment. To address this issue, we redefine in the demonic calculus of relations the notion of feasibility of system requirements proposed by Parnas and Madey such that the system requirements specify for every input possible in the environment only behaviours allowed by the environment. We also redefine in the demonic calculus of relations the system and software acceptability criterion of Parnas and Madey to reject nonterminating or empty implementations, and prove a necessary and sufficient existence condition for
acceptable software. This condition has a constructive flavour and yields the weakest (least restrictive, or least refined) specification of the software requirements.
A practical implication of the necessary and sufficient condition is that in a relational four-variable model, as opposed to the functional case, the input and output hardware interfaces are mutually dependent and changes to either may require changes to the other. We prove two stronger conditions that allow the decoupling of the hardware interfaces while still guaranteeing the ability of the software to meet the system requirements.
For the cases when the system requirements are feasible, but an accept- able implementation does not exist, a typical engineering approach is to relax the requirements by allowing tolerances. We show how the necessary and sufficient condition can be used in the derivation of tolerances on the requirements for a pressure sensor trip in the shutdown system of a nuclear reactor such that the requirements become implementable.

abstract: Dissertation

abstract: Doctor of Science  (PhD)


title: Wake Effects on Drift in Two-Dimensional Inviscid Incompressible Flows

contributor:
Protas, Bartosz
Computational Engineering and Science

subject:
drift
wakes
Föppl flow
Kirchhoff flow

abstract:
This investigation analyzes the effect of vortex wakes on the Lagrangian displacement of particles induced by the passage of an obstacle in a two-dimensional incompressible, inviscid fluid such that the flow is potential and time-independent in a suitable frame of reference. In addition to the trajectories of individual particles, we also study their drift and the corresponding total drift areas in the Föppl and Kirchhoff potential flow models. Our findings, which are obtained numerically and in some regimes are also supported by asymptotic analysis, are compared to the wakeless potential flow which serves as a reference. We show that in the presence of the Föppl vortex wake some of the particles follow more complicated
trajectories featuring a second loop. The appearance of an additional stagnation point in the Föppl flow is identified as a source of this effect. It is also demonstrated that, while the total
drift area increases with the size of the wake for large vortex strengths, it is actually decreased for small circulation values. On the other hand, the Kirchhoff flow model is shown to have an unbounded total drift area. By providing a systematic account of the wake effects on the drift, the results of this study will allow for more accurate modeling of hydrodynamic stirring.

abstract: Thesis

abstract: Master of Science (MSc)


title: Shear-Associative Polymers for Ophthalmic Applications

contributor:
Hoare, Todd
Chemical Engineering

abstract:
Most existing eyedrop formulations consist primarily of dilute solutions of water-soluble polymers. While these solutions provide temporary relief of dry eye or a means to transport a drug to the cornea, dilute solutions are quickly cleared from the eye via blinking, resulting in low drug uptake and the need for multiple treatments per day. In contrast, more viscous polymer solutions can cause discomfort or irritation of the ocular surface. Highly shear-thinning polymer solutions that can flow upon the application of shear but form gels at rest and (even more ideally) act to stabilize the tear film would instead be ideal for eyedrop formulations.
Poly(oligoethylene glycol methacrylate)-based hyperbranched polymers (prepared by the Strathclyde methodology using dodecanethiol as a chain transfer agent to graft hydrophobes on chain ends in a single step) represent a unique polymer building block intermediate between a nanoparticle and a linear polymer. These hyperbranched polymers exhibit shear thinning properties over at least 4 orders of magnitude in addition to a distinct internal domain with potential for drug delivery. Mixing linear, hydrophobically-modified polymers with cyclodextrin-functionalized hydrophobic-grafted hyperbranched polymers results in the formation of inclusion complexes between the hydrophobic cavity of cyclodextrin and the hydrophobic groups, introducing additional benefits in terms of generating extremely stiff gels at zero shear while maintaining the lubricity in the eye at high shear rates.
In addition, dual hydrophobe-boronic acid grafted copolymers based on a poly(vinylpyrrolidone-co-vinylformamide) graft platform polymer offer significant potential as artificial tear additives. The mucoadhesive properties of phenylboronic acids (PBA) improves the bioavailability of the drugs delivered to the front of the eye with eye drops while the hydrophobic grafts on the polymer provides shear-induced lubrication for these materials.

abstract: Thesis

abstract: Master of Chemical Engineering (MChE)


title: Design and Formal Verification of an Adaptive Cruise Control Plus (ACC+) System

contributor:
Lawford, Mark
Computing and Software

subject: Robust adaptive cruise control plus (ACC+) design

subject: Stop and Go adaptive cruise control

subject: Formal verification

subject: Hybrid system

subject: Collision freedom

subject: Safety

subject: Differential dynamic logic (dL)

subject: KeYmaera verification tool

subject: Robust feedback control

subject: Cyber physical system

subject: Linear Quadratic Regulator (LQR)

subject: H-infinity

abstract:
Stop-and-Go Adaptive Cruise Control (ACC+) is an extension of Adaptive Cruise Control (ACC) that works at low speed as well as normal highway speeds to regulate the speed of the vehicle relative to the vehicle it is following. In this thesis, we design an ACC+ controller for a scale model electric vehicle that ensures the robust performance of the system under various models of uncertainty. We capture the operation of the hybrid system via a state-chart model that performs mode switching between different digital controllers with additional decision logic to guarantee the collision freedom of the system under normal operation. We apply different controller design methods such as Linear Quadratic Regulator (LQR) and H-infinity and perform multiple simulation runs in MATLAB/Simulink to validate the performance of the proposed designs. We compare the practicality of our design with existing formally verified ACC designs from the literature. The comparisons show that the other formally verified designs exhibit unacceptable behaviour in the form of mode thrashing that produces excessive acceleration and deceleration of the vehicle.
While simulations provide some assurance of safe operation of the system design, they do not guarantee system safety under all possible cases. To increase confidence in the system, we use Differential Dynamic Logic (dL) to formally state environmental assumptions and prove safety goals, including collision freedom. The verification is done in two stages. First, we identify the invariant required to ensure the safe operation of the system and we formally verify that the invariant preserves the safety property of any system with similar dynamics. This procedure provides a high level abstraction of a class of safe solutions for ACC+ system designs. Second, we show that our ACC+ system design is a refinement of the abstract model. The safety of the closed loop ACC+ system is proven by verifying bounds on the system variables using the KeYmaera verification tool for hybrid systems. The thesis demonstrates how practical ACC+ controller designs optimized for fuel economy, passenger comfort, etc., can be verified by showing that they are a refinement of the abstract high level design.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: The effect of aging on spatial suppression

contributor:
Sekuler, Allison B.
Bennett, Patrick J.
Neuroscience

subject: aging, spatial suppression, center-surround antagonism, masking, GABAergic inhibition, visual cortex

abstract: The research discussed here examines how normal healthy aging affects spatial suppressive mechanisms in a variety of visual tasks using both static and dynamic stimuli. Prior research has suggested that younger adults demonstrate a center-surround antagonistic pattern in which they show spatial summation at low contrast and spatial suppression at high contrast in brief motion direction discrimination tasks. Older adults have been shown to have reduced spatial suppression at high contrast and this is thought to be related to reduced GABAergic inhibition in the visual cortex. The results obtained from this program of research suggest that age-related changes in optical and neural visual mechanisms do not affect spatiotemporal mechanisms for static stimuli when the target is presented with the mask (embedded masking). However, when the mask appears immediately before (forward masking) or after (backward masking) the target, older adults require more contrast to detect the target (Chapter 2). In addition, spatial suppression is not reduced for older adults in a task with moving stimuli presented at long durations, even with increasing speed (Chapter 3). In Chapter 4, we used static stimuli presented at brief durations to induce a sudden motion onset and found that although there was no significant age difference in spatial suppression, there was a trend showing reduced levels of spatial suppression in older adults. These results taken together suggest that inhibitory neural mechanisms in the visual cortex may mediate spatial suppression for briefly presented stimuli only.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Assessing the Influence of Contamination on Fixed-Effect Meta-Analysis for a Continuous Outcome: A Simulation Study

contributor:
Beyene, Joseph
Mathematics and Statistics

subject: Meta-analysis, Fixed-effect, Contamination

abstract:
Important research questions are typically studied and analyzed more than once, often by different research teams in different locations. However, in many instances, the results of these multiple small studies are diverse and conflicting, which makes decision-making difficult. The need to arrive at decisions fostered the momentum towards synthesizing the results of these multiple studies. Therefore, meta-analysis, also referred to as the standard or traditional meta-analysis,  is a statistical technique for combining the results or findings from multiple independent studies to address a specific research question. The applications of meta-analysis have been extended to many fields of research including medicine, psychology, ecology, education, business and many others.

Prior to carrying out a meta-analysis or statistically synthesizing data, a researcher must undertake a systematic review. Systematic review attempts to collate empirical evidence that fits pre-specified eligibility criteria to answer a specific research question. That is to determine which studies will be included or excluded from the analysis.
Standard meta-analysis methods are used to obtain the relative efficacy (or safety) of a particular intervention versus a competing intervention in the presence of a direct or head-to-head comparison. Thus only a pair-wise comparison can be made. The outcome of these interventions could be continuous, binary or count data.

A number of methodologies related to meta-analysis, assessments of underlying assumptions and strategies for the presentation of results have been proposed by several researchers. A commonly used model for estimating effect sizes in meta-analysis is the fixed-effect model. However, various factors can determine the performance of the model which needs to be considered before using the results for decision making.

This project aimed to investigate the performance of hypothesis properties and estimation properties on selecting data points from an underlying contaminated distribution under different scenarios for modeling a continuous outcome. Different levels of contamination, levels of significance, number of studies, number of individual study sample sizes, standard deviations and effect sizes were investigated in our simulation study for a continuous outcome.

The results of our simulation study shows that, the fixed-effect meta-analytic model does not perform well in the presence of contamination. As the level of contamination in the treatment group increases, the properties of estimators and hypothesis are greatly influenced. The method performs well as expected in the absence of contamination but performs poorly as we observe 50% contamination in the treatment group regardless of the individual sample size, the number of studies, the standard deviation and the effect size.

abstract: Thesis

abstract: Master of Science (MSc)


title: ROLE OF CHEMOTHERAPY IN IMPROVING DYSPHAGIA FREE SURVIVAL IN PATIENTS WITH ADVANCED ESOPHAGEAL CANCER TREATED WITH HIGH DOSE RATE BRACHYTHERAPY

contributor: Radiation Sciences (Medical Physics/Radiation Biology)

subject: chemotherapy, dysphagia free survival, esophageal cancer, high dose rate brachytherapy

abstract:
BACKGROUND
High dose rate Intraluminal Brachytherapy (HDRILBT) is one of the most used palliative treatment options for advanced esophageal cancer. The present study evaluates the role of additional chemotherapy in improving dysphagia free survival (DFS) and overall survival (OS) in patients with inoperable advanced esophageal cancer treated with brachytherapy.

MATERIAL and METHODS
132 patients with advanced metastatic esophageal cancer with total or near total dysphagia were given HDRILBT to a dose of 18 Gray (Gy) in 3 fractions on alternate days. Intraluminal brachytherapy alone was performed on 98 patients. 34 patients received Epirubicin, 5-Fluorouracil, and Cisplatin (ECF) chemotherapy regimen after HDRILBT. The mean age of the whole group was 65 years (HDRILBT-71.41, HDRILBT+ECF-59.98; p<0.0001). Male: Female was 101:31 (HDRILBT 72:26; HDRILBT +ECF 29:5; p>0.05). The location incidence was GEJ: Lower Esophagus: Mid Esophagus: Cervical Esophagus 24:81:17:5 respectively; for the whole group HDRILBT- 17:57:16:4; HDRILBT+ECF-7:24:1:1; p>0.05. 78 patients presented with co-morbidities (cardiac) (HDRILBT- 59; HDRILBT+ECF- 19; p>0.05). 74 patients presented with distant metastasis (54 with HDRILBT and 20 with HDRILBT+ECF; p>0.05). The ECOG scores were as follows 0:1:2:3:4 15:52:51:12:2 (HDRILBT- 10:35:41:10:2; HDRILBT+ECF- 5:17:10:2:0; p=0.0014). All patients completed 3 fractions of HDRILBT. 34 patients received additional chemotherapy with ECF regimen. Selection of patients was done by the medical oncologist. Statistical analysis of data was done using the SAS statistical analysis software system. Univariate and multivariate analysis was done using the log rang test.

RESULTS
Patients who received additional ECF were younger (p< 0.001) and with a better performance status than those who received HDRILBT alone (p=0.0014). Mean DFS was higher for patients who had further chemotherapy treatment (232 days) vs. patients who had HDRILBT only (155 days) (p>0.05). The mean OS for HDRILBT + ECF was 266 days (p = 0.0010) compare with HDRILBT alone which was 155 days, when the effect of 10 prognostic factors was analyzed for DFS and OS. Only additional ECF after brachytherapy impacted on DFS while age (p<0.001) and performance status (p=0.0014) impacted on overall survival on univariate analysis. On multivariate analysis tumor length and nodal presentation (p<0.000) impacted on OS. The incidence of stricture and fistulae were similar. Chemotherapy related side effects: gastrointestinal tract (25 patients), neurotoxicities (2) and nephrotoxicities (2) were seen as a result of 5-FU and Cisplatin respectively. 18 patients completed at least 3 cycles of ECF.

CONCLUSION
Additional chemotherapy with ECF after HDRILBT improves the DFS and OS in selected patients with advanced esophageal cancer. These patients tend to be younger with better performance status, small tumor length and nodal metastasis. The incidence of complications is similar with more than 50% patients completing at least 3 cycles of chemotherapy.

abstract: Thesis

abstract: Master of Science (MSc)


title: Essays on the Income-Health Gradient in Childhood

contributor:
Spencer, Byron G.
Denton, Frank T.
Dooley, Martin D.
Racine, Jeffrey S.
Economics

subject: essays, income-health relationship, children, age, chronic conditions,

abstract: This dissertation is comprised of three essays, the goals of which are to provide an empirical understanding of how the income-health relationship evolves with child age and the underlying mechanisms. Previous research, conducted in US and Canadian settings, has found a positive association between household income and child health, which strengthens with age. One reason for this relationship may be that low-income children are more likely to suffer from chronic conditions than high-income children. While US research has controlled for the effects of parental health when examining the gradient, Canadian work has not. In Chapter 1, we seek to determine whether the Canadian findings persist after controlling for parental health status. Our results show that this adjustment reduces the size of the gradient in childhood and, importantly, indicates that it does not increase with age. In Chapter 2, we contribute to this literature by applying more flexible estimation techniques, namely nonparametric models, to understand the gradient in childhood. Our results provide evidence that our nonparametric model is closer to the true data generating process than the parametric model. Furthermore, our estimates confirm that the gradient does not increase with age, regardless of whether we control for parental health. In Chapter 3, we examine the relationship between family income, chronic conditions and child health. Generally, our results suggest that income does not have a significant impact on chronic conditions. Furthermore, we do not find the effect of chronic conditions on the probability of being in poor health differs by income levels, with the exception of asthma and mental handicap.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Material and Process Models for the Forming of Oriented Polymer Tubes

contributor:
Jain, M.K.
Mechanical Engineering

subject:
oriented thermoplastic tubes
strength
automotive structural part
ram extrusion
oriented polypropylene tubes

abstract:
The lightweight and good strength of oriented thermoplastic tubes, produced through the ram extrusion process, renders this class of material advantageous from an automotive structural part forming perspective. An analytical model, capable of predicting the forming limits for these materials at elevated temperatures, would avoid the need for difficult and time-consuming tube forming experiments.

 The uniaxial tensile stress-strain properties of the oriented polypropylene (OPP) tubes along the axial and hoop direction wene determined while methods were developed for obtaining the uniaxial compressive properties of the tube. The uniaxial and biaxial testing of the OPP tubes enabled representation of the experimental plastic work contours for the material at a range of temperatures. The use of the pressure-modified Hill criterion, the concept of plastic work contours in stress space, and the stress strain data from uniaxial testing of the tube allowed accurate prediction of the plastic work contours for the OPP tubes as a function of temperature. The analytical prediction was able to capture the anisotropy, pressure dependency and anisotropic hardening exhibited by the material at elevated temperatures. In addition, the use of a localized necking criterion, which involved the point at which the maximum force along the hoop direction of the tube was reached, allowed the temperature dependent forming limits for the material to be predicted. The forming limits increased with temperature for all of the strain paths considered. In addition, at a given temperature, the forming limits decreased with increasing strain ratio. The limiting strains achieved with axial end feeding were markedly higher than those in which no axial end feeding was used.

 Good agreement was observed between the predicted forming limits and the results from tube forming tests of the material, along a range of strain paths and at various temperatures.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Phosphonium Salt Ionic Liquids in Organic Synthesis (Sandwich Thesis)

subject: phosphonium, bistriflimide, ionic, liquid, Kornblum, esterification,

abstract:
A survey of substitution reactions conducted in a phosphonium bistriflimide ionic liquid is presented. The results demonstrate high selectivity favoring substitution over typically competitive elimination and solvolytic processes even when challenging secondary and tertiary electrophiles are employed. The first reports of Kornblum substitution reactions in an ionic liquid are described that proceed with very high chemoselectivity in favor of nitro over nitroso products and elimination side products. The structure-reactivity study indicates that these reactions proceed through a narrow spectrum of pathways ranging from straight SN2 to a preassociation pathway along a saddle point that approaches the SN1 limit. The lack of any basic entity in the phosphonium bistriflimide ionic liquid appears to prevent any potential base-mediated elimination reactions, which makes this a highly selective medium for use in general substitution reactions. A general, high yielding procedure is described for the esterification of carboxylic acids through carboxylate alkylation in phosphonium salt ionic liquid. The product ester can be readily isolated using a standard extraction protocol or by direct solvent freedistillation allowing ionic liquid re-use. The reaction takes place at relatively low temperature in comparison to other processes reported in ionic liquids. Biologically important BZE (benzoate) esters were synthesized and a proposed solvolysis mechanism investigated in ionic liquids. The Pd-mediated Buchwald-Hartwig amination reaction of aryl halides in phosphonium salt ionic liquid consisting of a trihexyl(tetradecyl)phosphonium cation with a range of anions has been investigated. A pronounced anionic effect was uncovered with the reaction proceeding readily with weakly nucleophilic diarylamines only in the presence
of non-coordinating anions. A mechanism is postulated to explain these results involving a rate limiting ligand exchange step that proceeds through a dissociative pathway. A novel non solvated crystal structure of tris(dibenzylideneacetone) palladium(0) in phosphonium salt ionic liquids is reported. This research provided insights concerning the use of ionic liquids in palladium catalyzed Buchwald-Hartwig amination reaction. New synthetic methods were developed for the preparation of trialkyl (methyl) phosphonium ionic liquids, with this novel "green" protocol, the use of iodomethane is eliminated and oxidation of trialkyl phosphines can be reduced.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Learning to Process Faces: Lessons from Development and Training

contributor:
Maurer, Daphne
Psychology

subject:
facial recognition
facial identity
children
adult

abstract:
The present collection of studies examined the development of the ability to recognize facial identity rapidly and accurately, using two complementary approaches: comparing the performance of children and adults, and by training observers to learn novel stimuli in a laboratory setting. Across studies, children 8 to 10 years old performed less accurately than adults, a finding that confirms previous research that face processing takes many years to develop. However, results from two studies suggest that by 8 years of age, children encode individual facial identities relative to the average of previously experienced faces, in a manner similar to adults. The findings suggest that the basic mental architecture supporting face recognition is in place by 8 years. Additionally, children improved their ability to recognize unfamiliar faces from various viewpoints after just two, one-hour sessions of training, although the rate of learning was more variable than that observed in adults. The results from two studies also revealed that children's recognition accuracies of facial identity were lower than those of adults. An examination of children's similarity judgments of facial identity revealed that such immaturities in children's face processing may stem from greater variability in the mental representation of facial identities, rather than from
immaturities in the encoding process per se. Findings from a final study suggest that the ability to make fine perceptual discriminations among individual faces arises, in part, from experience differentiating faces at the individual level, unlike
the experience with non-face objects that typically involves recognition at the category level. The findings from the studies presented in this thesis suggest that such perceptual expertise may arise only with years of experience recognizing individual faces, and with sufficient neural development to support a stable mental representation of individual facial identities.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: From Narcissism to Schizophrenia: The Subject and Method in Jean-Luc Marion, Emmanuel Levinas and Edmund Husserl

contributor:
Sassen, Brigitte
Philosophy

subject:
phenomenology
subjectivity
Jean-Luc Marion
Emmanuel Levinas
Edmund Husserl
schizophrenic ego
reciprocity
ethics

abstract:
This work explores three phenomenological views of subjectivity in light of
methodological transitions within phenomenology since its inception. Jean-Luc Marion offers a critique of Husserl 's transcendental ego in Cartesian Questions. This critique characterizes Husserl's transcendental ego as a 'schizophrenic ego'. This criticism is aimed at phenomenology's intentionality thesis as well as the method of reduction(s). Marion is influenced by Emmanuel Levinas' ethics and takes issue with a 'theoretical
bias' within Husserl 's thought, a bias that characterizes subjectivity in the same terms as objectivity. I frame Marion's and Levinas' views of subjectivity in terms of two seemingly opposed 'origins' of subjectivity: Marion's notion of subjectivity embraces a notion of an originally auto-affected subject, while Levinas' position privileges an originally hetero-affected subject. I argue that both these views of subjectivity remain within dualist perspectives. Both thinkers try to overturn a hierarchy of reason over sensation/ emotion/ feeling by calling for a radically passive institution of subjectivity through either a givenness prior to subjectivity (Marion) or the face to face encounter
with an Other (Levinas). However, both positions end up instituting a new hierarchy, one where reason is subjugated to feeling. Rather than dismantling dualism both thinkers end up defending a revised hierarchical thinking. I argue that Husserl's transcendental ego is indeed a 'schizophrenic ego' (i.e., a split ego) in Marion's sense but that this is not a problem for classical phenomenology but an alternative to either an auto-affected subject
or a hetero-affected subject. Husserl's works on internal time-consciousness and passive and active synthesis illustrate a necessary correlation between passivity/ activity, matter/ form, reason/ emotion, ego/ world and self/ other which moves beyond the hierarchical thinking associated with traditional dualist thought. Husserl's notions of correlation and synthesis actually suggest a subject that is always intentionally related to the world and others and is also intentionally self-related. The implicit aim of this work is to suggest an alternative to an ethics of irreducibility endorsed by both Marion and Levinas. Husserlian phenomenology offers the possibility of an ethics of reciprocity, which paradoxically does not undermine the irreducibility of the subject, others or the world.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Fabrication of Advanced Organic-Inorganic Nanocomposite Coatings for Biomedical Applications by Electrodeposition

contributor:
Zhitomirsky, Igor
Materials Science and Engineering

subject:
electrodeposition
electrophoretic deposition
zirconia
coatings for biomedical implants
nanocomposite coatings
hydroxyapatite

abstract:
Novel electrodeposition strategies have been developed for the fabrication of
thick adherent zirconia ceramic and composite coatings for biomedical applications. The new method is based on the electrophoretic deposition (EPD) of polyelectrolyte additives combined with the cathodic precipitation of zirconia. The method enables the room- temperature electrosynthesis of crystalline zirconia nanoparticles in the polymer matrix. Adherent crack-free coatings up to several microns thick were obtained. The deposits were studied by thermogravimetric and differential thermal analysis, X-ray diffraction analysis, scanning and transmission electron microscopy, and atomic force microscopy. Obtained results pave the way for electrodeposition of other ceramic-polymer composites. Novel advanced nanocomposite coatings based on bioceramic hydroxyapatite (HA) have been developed for the surface modification of orthopaedic and dental implant metals. HA nanoparticles prepared by a chemical precipitation method were used for the fabrication of novel HA-chitosan nanocomposite coatings. The use of chitosan enables room-temperature fabrication of the composite coatings. The problems related to the sintering of HA can be avoided. A new electrodeposition
strategy, based on the EPD of HA nanoparticles and electrochemical deposition of chitosan macromolecules, has been developed. The method enabled the formation of dense, adherent and uniform coatings of various thicknesses in the range of up to 60μm. Bioactive composite coatings containing 40.9-89.8 wt% HA were obtained. The deposit composition and microstructure can be tailored by varying the chitosan and HA concentrations in the deposition bath. A mathematical model describing the formation of the HA-chitosan composite deposit has been developed. X-ray studies revealed preferred orientation of HA nanoparticles in the nanocomposites. Obtained
coatings provide corrosion protection of the substrates and can be utilized for the fabrication of advanced biomedical implants. For further functionalization of the HA-chitosan composite coating, Ag and CaSi03 have been incorporated into the coating. Novel HA-Ag-chitosan and HA-CaSiO3-chitosan nanocomposite coatings have been deposited as monolayers, laminates, and coatings of graded composition. The obtained results can be used for the development of biocompatible antimicrobial coatings with controlled Ag+ release rate, and nanocomposite coatings with enhanced bioactivity.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Single-Step Analysis of Metabolites by Capillary Electrophoresis Using On-Line Sample Preconcentration with Chemical Derivatization

contributor:
Britz-McKibbin, Philip
Chemistry

subject:
capillary electrophoresis
enantiosensitivity
single-step analysis
SPCD-CE

abstract:
New strategies for integrating sample pretreatment with chemical analyses under a single format is required for rapid, sensitive and enantioselective analyses of low abundance metabolites in complex biological samples. Capillary electrophoresis (CE) offers a unique environment for controlling analyte/reagent band dispersion and electromigration properties using a discontinuous electrolyte system allowing for highly efficient separations to be achieved. A fundamental study of the thermodynamic and electrokinetic parameters influencing enantioselectivity in chiral CE separation is first examined. A new strategy for single-step analysis of low abundance metabolites via online sample preconcentration with chemical derivatization by CE (SPCD-CE) is then detailed within. In-capillary sample preconcentration serves to enhance concentration sensitivity via electrokinetic focusing of long sample injection volumes for lower detection limits, whereas chemical derivatization by zone passing of single or multiple reagents is used to expand detectability and selectivity, notably for enantiomeric resolution of metabolites lacking intrinsic chromophores. Together, on-line SPCD-CE
can provide over a 100-fold improvement in concentration sensitivity, shorter total analysis times, reduced sample handling and improved reliability for a variety of biologically relevant amino acid and amino sugar metabolites, which is also amenable to automated high-throughput screening. The basic method development and optimization parameters relevant to SPCD-CE, including applications to bacterial metabolite flux and biomarker analyses are discussed. Insight into the mechanism of analyte focusing and labelling during electromigration by SPCD-CE is also presented, as well as future directions for continued research using this unique integrated analytical platform.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: The Influence of Jacques Ellul, Martin Heidegger and Simone Weil on George Grant's Changing Understanding of Technology

contributor:
Planinc, Zdravko
Religious Studies

subject: Jacques Ellul, Martin Heidegger, Simone Weil, theology, technology

abstract:
The dissertation considers the influence of Jacques Ellul, Martin Heidegger, and Simone Weil on Grant's understanding of technology. Chapters One and Two analyze Ellul's influence on Grant, while Chapter Three examines Heidegger's influence on Grant's understanding of technology. Chapter Four examines the consequences of Grant's ambiguous evaluation of Ellul and Heidegger. Grant's unwillingness to entirely accept either account of technology leads to a tension in which aspects of Ellul 's account of technology are held simultaneously with elements of Heidegger's account. As a way to overcome the tension between these explanations, Grant becomes open to gnostic elements in Weil's theology, which manifest themselves in radical dualism and esoteric wisdom.
The purpose of the dissertation is to clarify the significance of Ellul for Grant's thought. Scholars often overlook the extent of Ellul's contribution for Grant's account of technology, particularly in Grant's refinement of concepts such as technological necessity and his critique of liberal ideology. Furthermore, the dissertation seeks to reveal the pliability of Grant's account of technology, which is closely linked to Grant's theological, philosophical, and political judgments. The dissertation suggests that Grant's understanding of technology leads Grant to espouse gnostic elements from Weil's theology (such as radical dualism and esoteric wisdom) as a palliative to the arid technological necessity and moral inarticulacy of technological civilization.
The dissertation challenges the scholarly orthodoxy that exists in the interpretation of Grant's work. Through a fresh reading of primary and secondary sources, the dissertation advocates an alternative approach to understanding Grant's thought.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Optical and Mechanical Characterization of Optical Fibers and Fiber Cables

contributor:
Abe, K.
Engineering Physics

subject:
optical fiber
cable evaluation
Bell-Northern Research
telecommunication

abstract: This paper describes optical fiber and cable evaluation carried out at Bell-Northern Research during the summer period of May- August, 1980. Contemporary fibers and cables designed for telecommunications use were evaluated and the results on the following three areas are reported: (1) Resistance of fiber optics cables to temperature extremes and mechanical abuse. (2) Fiber tensile strength, both fast-fracture and fatigue, and a test method to predict longevity of the fibers. (3) Pulse broadening, measured as a function of link lengths in order to establish engineering rules which can predict performance for 10km lengths (typical repeater spacing) from the individual fiber characteristics.

abstract: Thesis

abstract: Master of Engineering (MEngr)


title: Homotopy Self-Equivalences of Four-Manifolds

contributor:
Hambleton, Ian
Mathematics

subject: homotopy, self-equivalences, four-manifold, Hambleton, Kreck,

abstract: In this thesis, we study the group of base-point preserving homotopy classes of homotopy self-equivalences of a four-manifold. Based on the approach of Hambleton and Kreck, an explicit description of this group is obtained when the fundamental group of the manifold is either a free group or a two-dimensional Poincare duality group. As a byproduct, a classification of such four-manifolds up to s-cobordism is obtained by using the modified surgery theory of Kreck.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: ‘Because It Was Hardcore and It Was Cool’: Masculinity as the Basis of Consent in Geochemical Sampling

contributor:
Lewchuk, Wayne
Work and Society

subject: Masculinity, Gender, Geochemical Sampling, Mineral Exploration, Worker Consent, Subjectivity, Labour Effort, Wilderness, Fraternalism

abstract: Geochemical samplers carry out manual labour in difficult and dangerous conditions while largely unsupervised. This paper explores questions regarding the labour effort provided by these workers which often goes above and beyond the level necessary to maintain employment and at times endangers their personal safety. This extra effort is provided despite relatively  high levels of worker autonomy, low levels of supervision, and little apparent economic incentive. Analysis of worker-level interviews using a number of possible theoretical frameworks indicates that more coercive factors such as direct managerial control and employment insecurity are unable to fully explain sampler behaviour and, instead, participant accounts indicate a form of active worker consent to increased labour effort and risk taking. This is a gendered worker consent based on a form of contingent upon the specific context of geochemical sampling. These specific contingent factors are: a working class masculinity derived from the hard manual labour of the work; the wilderness context that facilitates tropes of ‘man versus nature’ reinforcing the masculine workplace culture and obscuring the appropriation of surplus by more easily allowing the workplace to be interpreted as non-capitalist; and a fraternal masculinity resulting from the crew-based workplace organization and highly male dominated workforce composition, intensified by the conforming pressure of isolated camp life. This specific masculinity forms a basis of consent by which the autonomy afforded to workers by the labour process of geochemical sampling helps rather than hinders the imperative of management to encourage workers to exert the maximum effort.

abstract: Thesis

abstract: Master of Arts (MA)


title: Postcolonial Encounters in the Maghreb. Transgressing International Relations

title: Postcolonial Encounters

contributor:
Coleman, William D.
Political Science

subject: Franco-Maghrebian postcolonial native narratives

abstract:
This dissertation examines the production of the "native" in literary and photographic narratives in the Franco-Maghrebian postcolonial context. More specifically, I selected a group of a few well-known Maghrebian intellectuals who write in French, who act as mediators of postcolonial difference between France and the Maghreb, while living between the "East" and the "West." In my dissertation fieldwork, I looked at the politics involved in the production of "home", "exile", and of "the native" within literary and photographic engagements of these North African diasporic intellectuals.

Here, I argue that a reading of literary texts offers an alternative understanding of the International Relations of migration and of linkages between postcolonies and postmetropoles. Such an examination involves exploring unexpected claims to a 'native' status that brings about a re-thinking of disciplinary boundaries; an incursion into practices of spectrality in visual and literary narratives, whereby the postcolonial diasporic intellectual is engaged in the practice of collecting 'endangered authenticities.' Moreover, an alternative understanding of IR can also be perceived from the politics of language and hybridity, which arise for Maghrebian intellectuals living and writing about "home", and deciding upon audiences in their writings. Out of this politics emerge the categories of the immigré(e) and exilé(e) that reflect a lived experience of international relations, and an absence of relations that adds to our understanding.

The importance of this insight becomes clear when we confront a contemporary IR of migration written from a more mainstream perspective. Its ahistorical presentation and state-centrism are blind to the continuities of imperialism, where the postcolony is as much within the lived space of the postmetropole as it is outside. Thus I attempt to amplify this understanding of the IR of migration and imperialism through recourse to literary and visual narratives of Franco-Maghrebian intellectuals.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Algorithms for Passive Localization and Tracking

contributor:
Kirubarajan, T.
Electrical and Computer Engineering

subject:
passive localization
tracking
multiple sensors
angle of arrival
time difference of arrival

abstract:
This thesis considers passive localization and tracking. Here, passive refers to passive observations - the type of observations for which the full position estimate of the target cannot be obtained using a single measurement, like those are from a sonar. Hence, localizing or tracking targets based on these measurements calls for the use of multiple sensors. This poses a different set of challenges to tracking with passive observations as opposed to active observations where full target position is available from a single measurement.

We identify different issues that are related to passive localization and tracking and propose algorithmic solutions to these problems. We consider the angle of arrival (AOA), which is the passive measurement that is often considered in target tracking and time difference of arrival (TDOA) as representative passive measurements to illustrate our algorithms. Whereas, the AOA measurements from different sensors can be considered independent, TDOA measurements, on the other hand, are not independent. That is, they are correlated. We would, however, like to note that the proposed algorithms can be applied with straightforward, but simple, modifications to other types of passive measurements.

In particular, this thesis provides solutions to the following problems. First, it provides efficient and improved algorithms to the data association problem when tracking with multiple passive synchronous sensors. These solutions are based on the assignment formulation. Whereas one of the algorithms proposed, the gated assignment algorithm, uses the validation gates to reduce the computational cost, the other is a new extension to the multidimensional assignment algorithm that associates the measurements directly to the tracks. This is called the (S + 1)-D assignment-based data association, where S is the number of synchronous sensors available in the tracking system. An approximation to this new (S + 1)-D algorithm is also presented.

 In literature one finds algorithms to localize a single target using TDOA measurements. None of these algorithms considered the issues that might arise in tracking the localized targets. This thesis provides a framework to localize and track targets based on TDOA measurements. The localization algorithm uses a formulation based on the sensor-emitter geometry. This formulation is considered as a constrained optimization problem and two relaxation-based algorithms are provided to solve this optimization problem. The assignment-based data association provides an additional challenge because the TDOA measurements are correlated. This problem is identified and a solution is provided by modifying the calculation of the association cost.

 Finally, this thesis also provides an efficient algorithm to form AOA mono tracks using the fast Fourier transform (FFT) and the assignment algorithm. Formation of the mono tracks is very useful in distributed tracking and is the well-known direction of arrival tracking problem in the signal processing community.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Stopping randomized trials early for futility: error in estimating the treatment effect

contributor:
Walter, Stephen
Mathematics and Statistics

abstract:
In the past few decades, interim analyses in long-term clinical trials have become increasingly popular. If a new treatment or intervention is truly ineffective or have lower effect than expected, it is better that the trial be stopped early for futility so as not to expose further patients to clinically inefficient or harmful treatment, and thus save time, resources and money by avoiding recruitment of more patients. Conditional power is one of the typical methods of futility monitoring.
In this paper, I develop expressions for the error in estimating the treatment effect in studies stopped early for futility, the over-estimations in completed studies and the overall bias for a study with a stopping rule for futility. I also discuss the probability of stopping and the weight of such stopped studies in a meta-analysis. Then I evaluate the expressions using commonly used parameters. The numerical results show that the error in estimating the treatment effect in studies stopped early for futility is usually substantial but fortunately the overall bias in single study is quite small. Corresponding biases are a little bit greater if two interim analyses are planned instead of only one interim analysis, thus it is expected that the under-estimation of treatment effect in truncated studies and the overall bias of a single study would increase with the number of planned interim analyses.

abstract: Thesis

abstract: Master of Science (MSc)


title: Resource Allocation In Energy Sustainable Wireless Mesh Networks

contributor:
Todd, Terence D.
Electrical and Computer Engineering

subject:
Wireless LAN
Wi-Fi
outdoor applications
sustainable energy
wind power
solar power

abstract:
Wireless LAN (WLAN) mesh networks are now being used to deploy Wi-Fi
coverage in a wide variety of outdoor applications. In these types of networks,
conventional WLAN mesh nodes must be operated using continuous electrical
power connections. This requirement may often be very expensive, especially
when the network includes expansive outdoor wireless coverage areas. An alternative is to operate some of the WLAN mesh nodes using an energy sustainable source such as solar or wind power. This eliminates the need for a fixed power connection, making the node truly tether-less and allowing for more flexibility in node positioning. The cost of the battery and the solar panel or wind turbine can be a significant fraction of the total node cost, therefore the resource allocation must be performed optimally.

In this thesis we investigate this problem. First, we present geographic
provisioning results for solar and wind powered WLAN mesh nodes. The results
suggest that in certain geographic locations a hybrid wind/solar powered
WLAN mesh node is the optimum minimum cost configuration. The results
also provide strong motivation for introducing power saving to the IEEE 802.11 standard. We then consider the problem of cost-optimal node placement in a hybrid network containing traditional and energy sustainable nodes. Our results show that there is a significant improvement in cost that can be obtained using the proposed methodology. Finally, we consider the problem of energy management in these networks. A control algorithm is proposed that uses access to publicly available meteorological databases. We show that the proposed algorithm minimizes node outage and performs favorably compared to the analytic performance bounds. Overall, the work in this thesis develops analytical and simulation models which investigate the key aspects pertaining to resource allocation in energy sustainable WLAN mesh networks.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Structural and Compositional Analysis of Pristine and Cycled Li Ion Battery Cathode Material LiwMnxCoyNizO2

contributor:
Botton, Gianluigi
Materials Science and Engineering

subject:
Li-ion battery
Cathode NMC material
Electron microscopy characterization

abstract:
Rechargeable lithium ion batteries are common materials in everyday applications. The most frequently used cathode material, LiCoO2, provides high energy density and stable charge/discharge performance. However, LiCoO2 is toxic and relatively expensive, therefore, other alternatives are being sought after in the development of battery materials, such as LiMn0.33Ni0.33Co0.33O2 (identified commonly as 333 compound). The 333 compound is now popular due to its comparable performance with LiCoO2, lower price, enhanced stability, and more environmentally friendly characteristics. In addition, Li1.2Mn0.54Ni0.13Co0.13O2 (HENMC) is still on the stage of testing and it attracts wide attention due to its higher rechargeable capacity and thermal stability. However, there are still challenges confronted: cycle stability and low rate capability.
In order to verify all the roles played by different elements shown in NMC materials and explore the corresponding performance with different formula units, compositional analysis is needed. ICP-MS (inductively coupled plasma mass spectrometry) can provide bulk compositional information and has been used in recent work,  giving a general idea of the composition of NMC materials. However, compositional inhomogeneity analysis has usually been neglected in these studies. Therefore, the objective of this work was to explore this variation in composition locally with higher spatial resolution, at the NMC particle level. This work was carried out through the use of scanning electron microscopy – energy dispersive spectroscopy (SEM-EDS) and Auger electron spectroscopy (AES). Furthermore, nano-scale quantitative analysis was done with transmission electron microscopy – energy dispersive spectroscopy (TEM-EDS). Moreover, an optimal approach and procedure of compositional analysis by using EDS and AES was explored with proper standards and operation conditions to provide consistent and stable results.
The optimal quantification method was applied to investigate the compositions of 333 compound before and after ball milling and HENMC specimen before and after cycling. The results support the structural changes and in turn the electrochemical performance of the battery material. In the 333 compound, the electrochemical performance of the battery was deteriorated due to ball milling, during which Zr was introduced and particles were more compact. In HENMC, during cycling, the Mn distribution was homogeneous at the beginning, then inhomogeneous and homogeneous again, supporting the hypothesis of the transformation of phases: formation of spinel phase and potential SEI layer.
In-depth structural analysis of different NMC materials has been reported previously by other groups. However, the structural effects due to cycling, within particles still needs investigation. Therefore, X-ray diffraction (XRD) was used to investigate the bulk material crystalline structure. Local nano-scale level structural variations amongst different isolated primary particles were investigated by the electron diffraction pattern based on TEM. The 333 compound and HENMC cycling was examined before and after cycling. After cycling, in the 333 compound, the O1 phase domains with P-3m1 space group appear inside the O3 phase with R-3m lattice. With more cycling, more domains appear. For HENMC, the original pristine samples exhibit the rhombohedral and monoclinic phases. After cycling, more and more spinel phase appear. Finally, after 100 cycles, we observe evidence of the potential solid electrolyte interphase (SEI) formation.
In all, all the results above support the phase changes of 333 compound and HENMC. More investigations are needed to understand the degradation process of both compounds.

abstract: Thesis

abstract: Master of Materials Science and Engineering (MMatSE)


title: Soft Demodulation Schemes for MIMO Communication Systems

contributor:
Davidson, Timothy N.
Electrical and Computer Engineering

subject: computationally-efficient, (MIMO), demodulation, semidefinite relaxation (SDR),

abstract:
In this thesis, several computationally-efficient approximate soft demodulation schemes are developed for multiple-input multiple-output (MIMO) communication systems. These soft demodulators are designed to be deployed in the conventional iterative receiver ('turbo') architecture, and they are designed to provide good performance at substantially lower computational cost than that of the exact soft demodulator. The proposed demodulators are based on the principle of list demodulation and can be classified into two classes, according to the nature of the list-generation algorithm. One class is based on a tree-search algorithm and the other is based on insight generated from the analysis of semidefinite relaxation techniques for hard demodulation.
The proposed tree-search demodulators are based on a multi-stack algorithm, developed herein, for efficiently traversing the tree structure that is inherent in the MIMO demodulation problem. The proposed scheme was inspired, in part, by the stack algorithm, which stores all the visited nodes in the tree in a single stack and chooses the next node to expand based on a 'best-first' selection scheme. The proposed algorithm partitions this global stack into a stack for each level of the tree. It examines the tree in the natural ordering of the levels and performs a best-first search in each of the stacks. By assigning appropriate priorities to the level at which the search for the next leaf node re-starts, the proposed demodulators can achieve performance-complexity trade-offs that dominate several existing soft demodulators, including those based on the stack algorithm and those based on 'sphere decoding' principles, especially in the low-complexity region.
In the second part of this thesis it is shown that the randomization procedure that is inherent in the semidefinite relaxation (SDR) technique for hard demodulation can be exploited to generate the list members required for list-based soft demodulation. The direct application of this observation yields list-based soft demodulators that only require the solution of one SDP per demodulation-decoding iteration. By approximating the randomization procedure by a set of independent Bernoulli trials, this requirement can be reduced to just one semidefinite program (SDP) per channel use. An advantage of these demodulators over those based on optimal tree-search algorithms is that the computational cost of solving the SDP is a low-order polynomial in the problem size. The analysis and simulation experiments provided in the thesis show that the proposed SDR-based demodulators offer an attractive trade-off between performance and computational cost.
The structure of the SDP in the proposed SDR-based demodulators depends on the signaling scheme, and the initial development focuses on the case of QPSK signaling. In the last chapter of this thesis, the extension to MIMO 16-QAM systems is developed, and some interesting observations regarding some existing SDR-based hard demodulation schemes for MIMO 16-QAM systems are derived. The simulation results reveal that the excellent performance-complexity trade-off of the proposed SDR-based schemes is preserved under the extension to 16-QAM signaling.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Caloxins: A Novel Class of Plasma Membrane Ca2+ Pump Inhibitors

contributor:
Grover, A.K
Biology

subject: Ionized Calcium, Ca2+, Plasma, membrane, pump, inhibitors,

abstract:
Ionized calcium (Ca2+) is a signaling messenger that controls numerous
cellular processes essential for life. The fidelity of Ca2+ signaling depends on the
mechanisms that dynamically regulate its cytosolic concentration and maintain it
at a low level in a resting cell. Plasma Membrane Ca2+ ATPase (PMCA) is a high
affinity Ca2+ extrusion pathway involved in Ca2+ homeostasis and signal
transduction. PMCA are encoded by 4 genes (PMCA1-4), which are expressed in
a tissue dependent manner. The diversity of PMCA isoforms is further increased
by alternative splicing. Changes in PMCA activity occur in heart failure and
hypertension. Specific inhibitors of other ion transporters such as thapsigargin and
digoxin, have made their mark in cell biology, but the currently used inhibitors of
PMCA (vanadate and eosin) are non-specific. Thus, selective inhibitors of PMCA
are needed to discern its role in Ca2+ signaling in physiology and pathophysiology.
We introduced the concept of caloxins - peptides that specifically inhibit the
activity of PMCA by binding to one of its five extracellular domains (exdoms) 1
to 5. The earlier caloxins including 2a1 and 3a1 were obtained by screening a
phage display random 12-amino acid peptide (Ph.D-12) library for binding to
synthetic peptides based on the exdom sequences. However, they all had low
affinity.
The objective of this research was to develop caloxins with high affinity
and PMCA4 isoform selectivity. A two-step screening method was developed to
screen the Ph.D-12 library to first bind to the synthetic exdom of PMCA4, followed by affinity chromatography using PMCA protein purified from human erythrocyte ghosts (mainly PMCA4). This method was used to obtain caloxins 1b1 and 1b2 to bind to the N and C-terminal halves of the exdom 1 of PMCA4, respectively. Both caloxins 1b1 and 1b2 had a 10-fold higher affinity than the prototype caloxin 2a1 and showed slight PMCA4 isoform preference. To engineer inhibitors with greater affinity and PMCA4 isoform selectivity, Ph.D caloxin 1b1 like peptide library was constructed. Most of the peptides expressed in this
library differed from caloxin 1b1 in 0, 1, 2 or 3 amino acid residues at random.
The library was screened to obtain several peptides one of which was caloxin 1c2.
Caloxin 1c2 had 200-fold higher affinity than caloxin 2a1 and was isoform
selective, with greater than 10-fold affinity for PMCA4 than for PMCA isoforms
1, 2 or 3. Thus, caloxin 1c2 is the first high affinity PMCA inhibitor that also is
selective for an individual PMCA isoform.
The second aim of this research was to establish that caloxin 1c2 binds to
PMCA protein in erythrocyte ghosts. Two photoreactive caloxin 1c2-derivatives
containing the photoactivable residue benzoylphenylalanine (Bpa) and a C-terminal
biotin tag were used. Bpa substituted tryptophan at position 3 (3Bpa1c2-biotin) and serine at position 16 (16Bpa1c2-biotin) in caloxin 1c2. Both the derivatives inhibited PMCA activity in the erythrocyte ghosts. The intensity of the biotin label in the photolabeled erythrocyte ghosts was much stronger with 3Bpa1c2-biotin, which was then used in the subsequent experiments. The photolabeled proteins in erythrocyte ghosts were detected as a 250-270 kDa doublet in Western blots using streptavidin and the PMCA specific antibody. The
degree of photolabeling depended on the UV-crosslinking time, and on the
concentrations of 3Bpa1c2-biotin and the ghost protein. The selectivity of the
photolabeling site was confirmed by decreased photolabel incorporation at 250-270 kDa doublet in the presence of excess caloxin 1c2 and the synthetic exdom
1X peptide of PMCA4. The photolabeled erythrocyte ghosts were solubilized and
analyzed by immunoprecipitation with the PMCA specific antibody. The
immunoprecipitate showed a 250-270 kDa doublet in Western blots using
streptavidin. This confirmed that PMCA protein was photolabeled by the
photoreactive derivatives of caloxin 1c2. Thus, caloxin 1c2 inhibits PMCA
activity by binding to the exdom 1X of PMCA4.
My work in M.Sc. initiated the concept of caloxins in the literature. This
research has taken it to the stage where we can obtain caloxins selective for
individual PMCA isoforms. This contrasts with the relative paucity of inhibitors
specific for individual isoforms of other ion pumps. The high affinity isoform
selective caloxin 1c2 and previous caloxins are being used to study PMCA
physiology in our lab and by other researchers. Since caloxins act when added
extracellularly and it is possible to obtain PMCA isoform selective caloxins, it is
anticipated that they will aid in understanding the role of PMCA in signal
transduction and homeostasis in health and disease.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Nonlinear Filtering Algorithms for Multitarget Tracking

contributor:
Kirubarajan, T
Electrical and Computer Engineering

subject:
Probability Hypothesis Density filter
multitarget tracking
SNR targets
sensors

abstract:
Tracking multiple targets with uncertain target dynamics is a difficult problem, especially with nonlinear state and/or measurement equations. Random finite set theory provides a rigorous foundation to multitarget tracking problems. It provides a framework to represent the full multitarget posterior in contrast to other conventional approaches. However, the computational complexity of performing multitarget recursion grows exponentially with the number of targets. The Probability Hypothesis Density (PHD) filter, which only propagates the first moment of the multitarget
posterior, requires much less computational complexity. This thesis addresses some of the essential issues related to practical multitarget tracking problems such as tracking target maneuvers, stealthy targets, multitarget tracking in a distributed framework. With maneuvering targets, detecting and tracking
the changes in the target motion model also becomes important and an effective solution for this problem using multiple-model based PHD filter is proposed. The proposed filter has the advantage over the other methods in that it can track a timevarying number of targets in nonlinear/ non-Gaussian systems. Recent developments in stealthy military aircraft and cruise missiles have emphasized the need to t rack low SNR targets. The conventional approach of thresholding the measurements throws away potential information and thus results in poor performance in tracking dim targets. The problem becomes even more complicated when multiple dim targets are present in the surveillance region. A PHD filter based recursive track-before-detect approach is proposed in this thesis to track multiple dim targets in a computationally efficient way. This thesis also investigates multiple target tracking using a network of sensors. Generally, sensor networks have limited energy, communication capability and computational power. The crucial consideration is what information needs to be transmitted over the network in order to perform online estimation of the current state of the monitored system, whilst attempting to minimize communication overhead. Finally, a novel continuous approximation approach for nonlinear/ non-Gaussian
Bayesian tracking system based on spline interpolation is presented. The resulting filter has the advantages over the widely-known discrete particle based approximation approach in that it does not suffer from degeneracy problems and retains accurate density over the state space. The filter is general enough to be applicable to nonlinear/non-Gaussian system and the density could even be multi-modal.

abstract: Thesis

abstract: Candidate in Philosophy