title: Synthesis and Evaluation of Radiopharmaceuticals for Imaging Bacterial Infection

contributor:
Valliant, John
Chemistry

subject:
bacterial infection
imaging
SPECT
gallium-67
siderophores
deferoxamine
antibiotic
vancomycin

abstract:
Despite recent advances, radiopharmaceuticals to detect and characterize bacterial infections have a number of limitations. Many of the clinically approved radiopharmaceutical agents are not specific to bacterial infections and accumulate at lesions of inflammation. Hence, new approaches are necessary to detect bacteria with high specificity and selectivity. A library of desferrioxamine B (DFO) derivatives were prepared to create radiolabeled siderophores to create a bacteria-specific imaging probe by exploiting the mechanism bacteria use to scavenge iron, which plays a key role in  bacterial growth and biofilm formation  Compounds were synthesized using two convenient carbamate forming strategies in 30% to 92% yield. The cold and radioactive gallium (67Ga) complexes were prepared and characterized and their uptake by S. aureus bacteria were assessed in vitro and in vivo. In vivo studies revealed that 67GaDFOethoxycarbamate had uptake comparable to GaDFO that was blockable, showing the compound was actively taken up via the siderophore pathway. In vivo studies in a mouse model resulted in a good infected to non-infected thigh ratio (11:1) and non-specific uptake by the GI tract.
Bioorthogonal chemistry was also explored as an approach for imaging infection using trans-cyclooctene (TCO) functionalized vancomycin and a tetrazine functionalized 67GaDFO (67GaDFO-Tz) complex.2,3 In vitro results revealed that allowing vancomycin-TCO to bind S. aureus prior to the addition of 67GaDFO-Tz (pretargeting) showed higher (63%) uptake than with a conjugate formed prior to incubation with the bacteria (direct targeting, 28%). For the bioorthogonal approach, the distribution of the 67GaDFO-Tz was assessed in a S. aureus infection murine model, which showed significant uptake of 67GaDFO-Tz in the GI tract 1 h post intravenous injection. However, uptake in the infected joint was evident at 71 h post infection. The data suggests targeting bacteria using TCO-labeled antibiotics and radiolabeled tetrazines is a feasible strategy, but that further optimization of the vancomycin injection dose and injection time are necessary.

abstract: Thesis

abstract: Master of Science (MSc)


title: DEVELOPMENT OF A NOVEL ERGONOMICS METHOD FOR DETERMINING MANUAL ARM STRENGTH

contributor:
Potvin, James Robert
Kinesiology

subject: manual arm strength, strength capabilities, acceptable hand forces, digital human models.

abstract: The primary purpose of this thesis was to develop, validate and implement a novel ergonomics tool for manual arm strength (MAS) prediction. In Chapter 2, an empirical study was conducted to: 1) fill in gaps in our MAS database, and 2) examine the relationships between MAS and shoulder/elbow moments, to help identify important sources of variance for future predictive modeling attempts. Chapter 3 focused on the evaluation of artificial neural network (ANN) and traditional multiple regression approaches for MAS prediction, and revealed that ANNs provided a more accurate and generalizable prediction of MAS for our specific dataset. Chapter 4 drew on the data and findings of Chapters 2 & 3, and described the development of the ‘Arm Force Field’ (AFF) method for MAS prediction. The AFF method can be used to predict the MAS for any percentage of the population, given only the simple inputs of force vector direction, hand location (relative to the right shoulder), and torso orientation. In Chapter 5, a theoretical examination of the relative changes in wrist strength, due to interacting forearm and wrist postures, was conducted. That study resulted in a set of regression equations that can be used to predict wrist strength correction factors in complex wrist and forearm postures, allowing for more accurate estimations of the limiting joint once the MAS is calculated. An example of the AFF method’s implementation is provided and discussed in Chapter 6. The four studies, presented in this thesis, add to the current knowledge related to strength prediction in ergonomics, and the AFF method has the potential to be easily integrated within digital human models, for more valid estimates of manual force capabilities for the population.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)


title: THE OBSOLESCENCE OF THE WESTPHALIAN MODEL &THE RETURN TO A MAXIMUM STATE OF EXCEPTION

contributor: Political Science - International Relations

subject: Factuality versus Legality, War and Civil war , Maximum and Minimum State of Exception, Westphalian Model, Revolution in Military Affairs (RMA), Nonstate actors,  Sovereignty ,Global War on Terror (GWOT), High-point, Plausible deniability, Global war, Republican Contract, Citizen-soldier.

abstract: Major Research Paper

abstract: The international system is based on the modern conception of the Westphalian model, which organizes and monopolizes violence under the exclusive authority of a sovereign state. This conception only began to characterize global politics in the 19th century and more so at the beginning of the 20th century, contrary to the political myth that perceives the year 1648 as the moment where world state leaders monopolized, organized and structured violence. I characterize the international system prior to the Westphalian model to be a period of maximum state of exception because states de-monopolized violence and authorized the use of nonstate actors to conduct violence which dominated the international system. The international system transitioned from a maximum state of exception to a minimum state of exception when the Westphalian model began characterizing the international system. In a minimum state of exception, the Weberian state entailed a state monopolization on the authority to deploy violence beyond its borders and the states acceptance of responsibility for violence emanating from its territory. Violence in a minimum state of exception shifted from nonstate actors to citizen-soldiers. It is the objective of this research paper to highlight three consecutive Revolutions in Military Affairs (RMA) that occurred in the international system which have modified the actors involved in war. The latest RMA that occurred at the highpoint of the coldwar, but more so after the declaraction of the Global War on Terror (GWOT), has rendered the Westphalian model obscolescent. The modification of the primary actors in combat has consequently reverted the international system to a maximum state of exception where war is now global and an everlasting state in global affairs.


title: MECHANISMS OF BDNF DOWN-REGULATION BY THE PATHOLOGICAL CORRELATES OF ALZHEIMER’S DISEASE

contributor:
Fahnestock, Margaret
Neuroscience

abstract:
Alzheimer’s disease is a progressive neurodegenerative disorder that is the leading cause of dementia among the elderly. Alzheimer’s disease presents as global cognitive decline with associated memory loss and altered personality. The neuropathological hallmarks of Alzheimer’s disease include extracellular beta-amyloid-containing plaques and intracellular neurofibrillary tangles formed by hyper-phosphorylated tau protein. There is increasing evidence that although the primary insult in Alzheimer’s disease may be over-expression of amyloid-β, it may ultimately lead to cognitive dysfunction and neurodegeneration by inducing alterations in tau. While the precise toxic mechanism of these accumulated proteins is not well understood, our hypothesis is that both amyloid-β and tau exert their neurotoxicity via down-regulation of brain-derived neurotrophic factor (BDNF). BDNF is crucial for synaptic function, neuronal survival and learning and memory and is decreased in Alzheimer’s disease, tauopathies and in several relevant animal and cellular models of Alzheimer’s disease.
	Using differentiated, human neuroblastoma cells, we found that treatment with oligomeric Aβ down-regulates basal levels of BDNF as a consequence of Aβ-induced CREB transcriptional down-regulation. Similarly, these cells, when made to over-express wild-type tau, also exhibit reduced BDNF expression. They specifically lose the major CREB-regulated BDNF transcript, transcript IV. Using transgenic mice, we showed that neither tau mutations nor neurofibrillary tangles are required for BDNF reduction, but that wild-type tau over-expression is sufficient to down-regulate BDNF. Lastly, we crossed APP23 mice, which over-express Aβ and exhibit reduced BDNF, with Tau knockout (TauKO) mice. BDNF levels were partially rescued in the APP23xTauKO animals, indicating that tau is an intermediate in Aβ-induced BDNF down-regulation.
These results demonstrate that both soluble Aβ and tau down-regulate BDNF, which likely contributes to learning and memory deficits. Furthermore, the partial rescue of BDNF levels by tau knockout suggests that tau contributes to Aβ-induced BDNF down-regulation. Thus, loss of BDNF may mediate tau neurotoxicity down-stream of Aβ, which has profound implications for therapeutic intervention in Alzheimer’s disease and tauopathies, suggesting that current treatments used to alleviate AD symptoms by targeting Aβ pathology alone may not be sufficient, and that combined treatments targeting tau may be required.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: ADVANCED THERMAL MANAGEMENT FOR A SWITCHED RELUCTANCE MACHINE

contributor:
Emadi, Ali
Schofield, Nigel
Mechanical Engineering

subject:
Toroidal Switched Reluctance Machine
Cooling
SRM
Pyrolytic Graphite Sheet
PGS
Inter Laminate Cooling
ILC
Electric Machine

abstract:
The thermal management of electric machines is investigated with the application of techniques to a Switched Reluctance Machine and a high-speed Switched Reluctance Machine.  Two novel concepts for said management of a Switched Reluctance Machine are proposed and developed: Inter-Laminate Cooling and a Continuous Toroidal Winding.
	The Inter-Laminate Cooling concept is developed with application to an iron core inductor which serves as a proxy for the electric machine.  The experimental results confirmed the capability of the method, expressed by the effectiveness, which defines the performance measure of the applied cooling method; a concept which itself is equally applicable to other cooling methods that may be applied to any electric machine.  The effectiveness also describes the gain in allowable input power to the machine which is realized to reach the same thermal limit versus the case without Inter-Laminate Cooling.  The Inter-Laminate Cooling was not applied in experimental test to a Switched Reluctance Machine due to the present economic and fabrication limitations.
	The Continuous Toroidal Winding concept, originally conceived to permit the consideration of a fluid capillary core type of winding to enhance machine cooling, is developed to allow for peripheral cooling of the machine windings and end windings.  The Continuous Toroidal Winding version of the Switched Reluctance Machine is investigated for both its thermal and electrical performance in the context of a machine that is equivalent electromagnetically to its conventional counterpart.  The Continuous Toroidal Winding Switched Reluctance Machine was found to perform thermally as tested, in a manner superior to that of the conventional machine where the Toroidal machine was simulated and researched at an equivalent level of operation to the conventional machine.  The electrical performance of the Toroidal Switched Reluctance Machine although supportive of the simulation analysis used to develop the machine, was not fully conclusive.  This may have been due to problematic iron cores used in the construction of the experimental machines.
	The application of the Inter-Laminate Cooling method to a Switched Reluctance Machine is considered on an analytical basis for the special case of a High Speed Switched Reluctance Machine and found to be of net positive benefit as the machine’s iron losses are dominant over its copper losses.  Application of the Inter-Laminate Cooling method to a lower speed machine, whilst beneficial, is not sufficient to significantly impact the temperature of the machine’s windings such that it would offset the loss of specific torque and power.  As such, Inter-Laminate Cooling is only applicable where the net benefit is positive overall; in that the gain in input power realized is sufficient to overcome the loss of specific power and torque which will occur due to the increased machine volume.
	The “effectiveness” and “gain” approach for the evaluation of cooling methods applied to electric machines is a concept which should be adopted to aid in the comparative understanding of the performance of myriad different cooling methods being applied to electric machines both in research and practice, of which there is only minimal understanding.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Exploring Metabolic Factors and Health-Related Behaviours In Relation to Suicidal Behaviours

title: Metabolic Risk Factors of Suicidal Behaviour

contributor: Clinical Epidemiology/Clinical Epidemiology & Biostatistics

subject: Suicidal Behaviour, Suicide, BMI, Metabolic Factors

abstract:
Background: Suicidal behaviour devastates families, communities, and societies, as well as the millions of individuals who survive suicide attempts. This thesis addresses an urgent need to develop new treatment and intervention strategies for millions of at-risk people by exploring potential metabolic risk factors of suicidal behaviour.
Methods: A systematic review and meta-analysis was performed to assess the association between BMI and suicidal behaviour. We explored the association between attempted suicide and various metabolic factors and health behaviours using data from the Determinants of Suicide Conventional and Emergent Risk (DISCOVER) study. DISCOVER is an age and sex matched case-control study comparing adult psychiatric inpatients who had made a recent suicide attempt (n=84) to psychiatric inpatients (n=104) and community members (n=93) who have never attempted suicide. The following potential risk factors were assessed using logistic regression analyses: BMI, waist-circumference, serum total cholesterol, physical activity, tobacco use, and dietary food groups.
Results: The systematic review included 38 studies. A meta-analysis established an inverse association between BMI and completed suicide, whereby being underweight is associated with the greatest risk of suicide and being obese or overweight is associated with a deceased risk of suicide relative to normal weight. Evidence for an association between BMI and attempted suicide remains equivocal. The review suggests no association between BMI and suicidal ideation. Analysis of DISCOVER data demonstrated that even a small amount of regular physical activity is significantly associated with decreased risk of attempted suicide. Tobacco use was associated with an increased risk of attempted suicide. Contrary to prior research, obesity, serum-total cholesterol, and diet were not found to be significant risk factors.
Conclusion: BMI is inversely related to completed suicide. Obese individuals may be more likely to choose less lethal methods of suicide or may be less susceptible to fatal overdose or self-poisonings. Clinicians should monitor underweight patients for increased risk of suicide. Contrary to prior research, serum total cholesterol, BMI, and waist-circumference were not significantly associated with risk of attempted suicide. Increased physical activity was associated with a decreased risk of attempted suicide, and tobacco use was associated with an increased risk of attempted suicide. While people at risk of attempting suicide tend to use more tobacco products and exercise less than non-suicidal community members, so do non-suicidal psychiatric patients. For this reason, it remains unclear whether smoking habits represent a useful clinical predictor of suicide risk.

abstract: Thesis

abstract: Master of Science (MSc)


title: Inhibition of Plasmin Generation in Plasma by Heparin, Low Molecular Weight Heparin and a Covalent Antithrombin-Heparin Complex (ATH)

contributor: Medical Sciences (Blood and Cardiovascular)

abstract:
Unfractionated heparin (UFH) and low molecular weight heparin (LMWH) are
commonly used anticoagulants to treat thrombotic diseases. However, these anticoagulants are
associated with some limitations such as increased bleeding, variable dose response, and the
necessity for frequent monitoring. This led to the development of the antithrombin-heparin
covalent complex (ATH) which has been shown to overcome many of these limitations.
Numerous past studies have proven ATH to be a better anticoagulant in comparison to UFH.
More recent studies aimed at studying its interaction with the fibrinolytic pathway. It was
observed that ATH inhibited free and fibrin bound plasmin (Pn), the main serine protease of
fibrinolysis. As well, the rates of Pn generation on fibrin clots decreased in the presence of ATH.
These studies were conducted in purified systems and did not elucidate the interaction of ATH
with Pn in the presence of its natural inhibitors, α2-macroglobulin (α2-M) and α2-antiplasmin
(α2-AP). Thus, this study focuses on analyzing the effects of ATH in comparison to UFH and
LMWH on Pn generation in plasma, to allow for a better understanding of such mechanisms
under more physiological conditions. In comparison to the absence of anticoagulants, total Pn
generated decreased in the presence of 0.7 U/ml of UFH or ATH and 2.1 U/ml of ATH. This
confirms previous in vitro studies in which UFH + AT and ATH can inhibit Pn activity. In
addition, quantified Pn bound α2-M complexes showed a reduction at 0.7 U/ml of ATH
suggesting that ATH may be able to compete with α2-M for Pn. However, the amount of
quantified Pn bound α2-AP complexes were not affected as α2-AP is a much faster inhibitor of
Pn. It was noted that LMWH did not affect Pn generation. As a result, this study adds to our
understanding of ATH mechanisms of action and aids in its development for clinical use.

abstract: Thesis

abstract: Master of Science (MSc)


title: DESIGN, SYNTHESIS, AND EVALUATION OF MOLECULAR IMAGING PROBES FOR CATHEPSIN B

contributor:
Valliant, John F.
Chemical Biology

abstract:
Cathepsin B is a cysteine protease that is overexpressed in cancers that are likely to metastasize. Molecular imaging can be used to non-invassively detect cathepsin B in vivo in order to characterize cancer progression and treatment response. This thesis describes the development of four different strategies to develop cathepsin B targeted probes. First, an SAR strategy was used to synthesize and test a number of AOMK inhibitors that incorporated iodine. A high affinity (Ki = 180 nM) lead 2.23a was converted to its radioactive analogue [125I]2.23a by optimizing radiolabelling procedures to maximize radiochemical yields (>26%) and radiochemical purities (> 95%). In vivo evaluation showed low tumour uptake (0.05% at 23 h p.i.) due to high in vivo deiodination (thyroid = 20% ID/g at 23 h p.i.).
Next, AOMK inhibitors with greater stability were developed using the [ReCO3]+ core either via a direct linkage or a dendrimer platform. The binding affinities of these probes were lower than 2.23a (Ki > 350 nM). A pretargeted approach was then developed that could be used to image cathepsin B in vitro and in vivo.
Third, an affinity label was developed using the AOMK warhead linked to TCO giving 4.5 (Ki = 190 nM). A cell assay was developed and intracellular targeting of cathepsin B was observed, something that has not been observed previously with a pretargeted agent in nuclear medicine. Of the five tetrazine based bioorthogonal pairs tested with 4.5, three were sufficient for this approach.
The final approach was to use a cathepsin B substrate to link a radiopharmaceutical such as an iodobenzamide used for melanoma imaging. Synthetic strategies were explored to develop the radioactive and non-radioactive analogues. Challenges were encountered during the development of these probes due to stability, which require further optimization.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: CMOS SINGLE PHOTON AVALANCHE DIODES AND TIME-TO-DIGITAL CONVERTERS FOR TIME-RESOLVED FLUORESCENCE ANALYSIS

contributor:
Deen, Jamal
Electrical and Computer Engineering

subject:
CMOS
Single photon detector
fluorescence lifetime
Time to Digital Converter

abstract:
Fluorescence lifetime imaging (FLIM) has the potential to provide rapid screening and detection of diseases. However, time-resolved fluorescence measurements require high-performance detectors with single-photon sensitivity and sub-nanosecond time resolution. These systems should also be compact, reliable, inexpensive, and easily deployable for laboratory and clinical applications. It is with these applications in mind that the development of single photon avalanche diodes (SPAD) and time-to-digital converter (TDC) prototype integrated circuits (IC) in standard digital CMOS have been pursued in this thesis.
SPAD and TDC ICs were designed and fabricated in 130 nm IBM CMOS technology and then intensively studied. Several different SPAD pixels were modeled and designed, and the electro-optical performance was characterized and comparatively studied. By repurposing existing design layers of a standard CMOS process, the fabricated SPAD pixel test structures achieved up to 20× improvement of dark count rate (DCR) compared to previous designs. Optical measurements also showed up to 10× improvement in the detection limits for low-level light. Detailed dark noise characterization was performed at various temperatures using free-running and time-gated modes of operation. Optimal operating conditions were found for minimal afterpulsing effects. The SPAD’s capability to accurately measure fast fluorescence decays was also demonstrated in a practical setting with the lifetime measurements of two fluorophores, Rhodamine 6G and Ruby crystal, which have fluorescence lifetimes of approximately 4 ns and 3 ms, respectively.
A fast and accurate TDC prototype circuit for time-correlated single-photon counting (TCSPC) applications was designed, fabricated and characterized. With a coarse-fine delay line architecture, the TDC size was reduced without compromising its linearity and jitter performance. Extensive characterization of the fabricated SPAD and TDC ICs shows that the measured performance met the stated design goals.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: IN VIVO STUDIES OF CELL-FREE DNA AND DNASE IN A MURINE MODEL OF POLYMICROBIAL SEPSIS

subject:
Sepsis
Neutrophil Extracellular Traps (NETs)
Cell-free DNA
Animal Model
Cecal Ligation and Puncture
Murine Model
Inflammation
Coagulation
Critical Care
Sepsis Therapy

abstract:
Sepsis is a clinical syndrome characterized by the systemic activation of inflammatory and coagulation pathways in response to microbial infection of normally sterile parts of the body. Despite considerable advances in our understanding of sepsis pathophysiology, sepsis remains the leading cause of death in non-coronary intensive care units (ICU) with a global disease burden between 15 and 19 million cases per year (Dellinger et al., 2008). Severe sepsis, defined as sepsis associated with organ dysfunction is associated with mortality rates of 33% to 45%. The incidence of severe sepsis continues to increase by 1.5% per annum due to the aging population, a rise in the prevalence of comorbidities, and the wider use of immunosuppressive agents and invasive procedures (Angus et al., 2001). Over the past several decades, many potential treatments for sepsis have shown early promise, yet have failed to improve survival in over 100 Phase II and Phase III clinical trials (Marshall, 2014) suggesting that some fundamental knowledge is lacking in our understanding of sepsis pathophysiology.
Emerging studies on cell-free DNA (cfDNA), DNA released extracellularly into the circulation, demonstrate that cfDNA is a crucial link between inflammation and coagulation . In various conditions characterized by excessive inflammatory responses or aberrant prothrombotic responses, cfDNA has been implicated in exacerbating disease pathology (Atamaniuk, Kopecky, Skoupy, Säemann, & Weichhart, 2012; Fuchs, Brill, & Wagner, 2012; Swystun, Mukherjee, & Liaw, 2011). In clinical sepsis, levels of cfDNA upon admission into the ICU have strong prognostic value in predicting mortality (Dwivedi et al., 2012; Saukkonen et al., 2008). However, it is unclear whether these increases in cfDNA are an epiphenomenon during sepsis progression, or whether cfDNA actively plays a role in sepsis pathophysiology. In this work, in vivo studies were conducted to characterize the role of cfDNA in sepsis, the effects of DNase administration, and the potential mechanism by which cfDNA is released during experimental sepsis. In addition, mortality studies were conducted to identify surrogate markers of death to promote the design of humane and ethical animal studies in conducting sepsis research.
Polymicrobial sepsis was induced via a surgical procedure whereby the cecum is exteriorized, ligated and punctured twice to introduce a continuous source of microorganisms, a model termed cecal ligation and puncture (CLP). In our CLP sepsis model, levels of cfDNA increased in a time-dependent manner. These increases accompanied an early pro-inflammatory response marked by increased pro-inflammatory IL-6, a transient increase in anti-inflammatory IL-10, and elevated lung myeloperoxidase (MPO) activity. Septic mice with elevated cfDNA levels also had high bacterial loads in the lungs, blood, and peritoneal cavity fluid. Organ damage was also observed in mice following CLP surgery versus mice subjected to the non-septic sham control surgery marked by increased levels of creatinine and alanine aminotransferase (ALT) indicative of kidney and liver injury, respectively. Histological analyses further confirmed lung and kidney damage following CLP surgery. Changes in coagulation were also observed in septic mice as mice subjected to CLP had sustained increases in thrombin-antithrombin (TAT) complexes. In addition, plasma from CLP-operated mice had increased thrombin generation (i.e. increased endogenous thromin potential, increased peak thrombin, decreased time to peak, and decreased lag time) mediated by FXIIa and enhanced by platelets. Following CLP-induced sepsis, elevations in cfDNA levels accompanied pro-inflammatory and pro-coagulant responses.
The effects of in vivo DNase treatment in septic mice were time-dependent. Early DNase treatment when cfDNA levels were low resulted in an exaggerated pro-inflammatory response marked by increased plasma IL-6 levels and increased lung damage. In contrast, delayed DNase treatment at time-points when cfDNA levels were elevated suppressed inflammation characterized by an increase in anti-inflammatory IL-10 and reductions in cfDNA, IL-6, lung MPO, and ALT activity. Furthermore, delayed DNase administration resulted in decreased bacterial load in the lungs, blood, and peritoneal cavity fluid. Delayed DNase treatment also resulted in blunted pro-coagulant responses as levels of TAT complexes were suppressed and thrombin generation from septic mouse plasma was normalized. Moreover, DNase treatment when cfDNA levels were elevated increased survival in CLP-operated mice by 80% and reduced lung and liver damage. These findings suggest that administration of DNase when cfDNA levels are elevated may reduce pro-inflammatory and pro-coagulant responses and that delayed DNase treatment may infer protection in the CLP model of sepsis.
One mechanism by which cfDNA is released is via the formation of neutrophil extracellular traps (NETs). Upon inflammatory stimulation, some neutrophils release chromatin material and antimicrobial proteins (i.e. neutrophil elastase, MPO, and histones) in an active process termed NETosis. Although NETs ensnare bacteria and exert antimicrobial properties, NETs may also exert harmful effects on the host by activating inflammation and coagulation. While some in vitro evidence suggest that neutrophils are the main source of cfDNA released following inflammatory stimulation, others have reported that neutrophils are not the main source of circulating cfDNA following septic challenge. To determine whether NETs contribute to cfDNA released during CLP sepsis, genetically modified mice that are incapable of forming NETs, PAD4-/- mice, were used. Levels of cfDNA in PAD-/- mice were significantly lower than cfDNA levels in C57Bl/6 mice following CLP surgery, suggesting that NETs were a source of cfDNA in our model. Levels of IL-6, MPO, and bacterial load in the lungs, blood, and peritoneal cavity were significantly reduced, indicating that NETs exert pro-inflammatory effects in CLP sepsis. Thrombin generation was also suppressed in PAD4-/- mice which suggests that NETs contribute to thrombin generation following CLP sepsis. NETs contribute to increases in circulating cfDNA and may exacerbate pathology by driving pro-inflammatory and pro-coagulant responses in CLP-induced sepsis.
	Appreciating the implications of conducting research using animals, it is pertinent that researchers ensure the highest ethical standards and design animal studies in the most humane, yet scientifically rigorous manner. Using mortality studies, we validated the utility of physiological and phenotypic markers to assess disease severity and predict death in murine sepsis. Temperature via a rectal probe monitor and sepsis scoring systems which assess components such as orbital tightening, level of consciousness, and activity were effective surrogate markers of death. These tools offer a non-invasive assessment of disease progression which do not artificially exacerbate sepsis pathology and immediate information regarding any changes in the health status. Surrogate markers of death also provide reliable monitoring to meet increasing standards of ethical, humane animal research and a feasible and cost-efficient means to obtain vital signs in small rodents. We have proposed a scoring system which can be used for assessing disease severity, endpoint monitoring, and predicting death to obviate inhumane methods of using death as an endpoint in sepsis studies.
In summary, cfDNA levels are elevated in CLP-induced sepsis and these elevations accompany pro-inflammatory and pro-coagulant responses. NETosis may be a mechanism by which cfDNA is released and NETs may drive inflammation and coagulation in CLP sepsis. Delayed DNase administration may suppress inflammation and coagulation and may be protective in polymicrobial sepsis. In future animal sepsis studies, surrogate markers of death and a sepsis scoring system can be used in place of death as an endpoint to raise the standards in conducting ethical, humane sepsis research.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Towards a nuanced understanding of inclusion and exclusion: A Bourdieusian interpretation of Chinese students’ higher education experience in Canada

subject: inclusion and exclusion, Bourdieu, higher education, Chinese students, Canada

abstract:
At the heart of this study is a desire to unravel a puzzle of why I and other self-identified Chinese students share common experience of exclusion in the Canadian academy, despite our differences as individuals and as Chinese. Our experience of exclusion is made invisible by the stereotypical image of Asian students as the paragon of success within the academy. It is again made invisible by policy addressing inclusion in the academy that uses largely outcome measures to paint pictures of success, and keeps the less concrete parts of processes unpainted. There is a lack of attention to and an under-theorization of the less perceptible and less tangible processes of inclusion and exclusion.

The central question of this study is: How do Chinese students’ experiences in higher education, as viewed through Bourdieu’s framework of culture, inform a nuanced understanding of inclusion and exclusion? I draw on Bourdieu’s framework along with its core concepts to analyse the narratives of sixteen self-identified Chinese students from six Ontario post-secondary institutions. Methodologically, I draw on a theme-based approach from Thematic Inquiry and a case-based approach from Narrative Inquiry to form a Bourdieusian methodological framework that stays true to the anti-dualistic epistemological foundation of Bourdieu’s theory.

Captured in this study is a complex picture of inclusion and exclusion centred on a boundary that is so intangible and masked that it is largely imperceptible and hence unarticulated. The boundary is imperceptible because:

1) inclusion and exclusion is mediated through an unspoken system of meanings and values inscribed in disposition and practices; the boundary takes the form of a normalized way of being (disposition) and doing (practice)

2) inclusion and exclusion is unintentionally enacted; the boundary takes the form of unintentional domination and ‘voluntary’ exit (as if no external force is driving the exclusion)

3) inclusion and exclusion is diffused by the conversion of the boundary from an overt form to a neutralized or ‘normalized’ form such as social network.

While the boundary is obscured, it is at the same time fluid and permeable when capital is strategically positioned and deployed.

This study concludes by suggesting the need to take into consideration intangible and unintentional processes of inclusion and exclusion, and a two-way approach (again staying true to Bourdieu’s anti-dualistic framework) to broaden policy and research conversations about inclusion and exclusion. Only when invisible processes of inclusion and exclusion are brought to the fore can we begin to redress them.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)


title: PHENOTYPIC AND CHEMOTHERAPY RESPONSE PROFILING OF P53 WILD-TYPE AND MUTANT HUMAN BREAST CANCER CELL LINES

contributor:
Draper, Jonathan
Biochemistry and Biomedical Sciences

subject:
breast cancer
p53 mutation
chemotherapy response
phenotypic screening
cytological profiling
structure–activity relationship

abstract: Anthracycline-based chemotherapy is the mainstay neoadjuvant therapy for breast cancer. However, it is efficacious in only 60% of patients while carrying substantial toxicity. The application of a predictive marker of response may spare predicted ‘poor responders’ from the toxicity. Previously, we demonstrated a gene expression signature that predicts chemotherapy resistance which is linked to TP53 integrity. Further investigation showed that p53 signatures predict response in only ER+ tumors. We hypothesized that the loss of p53 confers an elevated chemotherapy sensitivity in ER+ breast tumors. We engineered isogenic p53 mutant ER+ breast cancer cell lines and assayed their cell cycle kinetics and chemotherapy sensitivity. Our results demonstrated that the loss of p53 is necessary to abrogate p53-mediated cell cycle arrest and produce an increase in apoptosis. Therefore, p53 signatures may be utilized as a predictive marker of response for patients with ER+ breast tumor and spare ‘poor responders’ from toxicity. Since ER+ p53 wild-type breast tumors are associated with anthracycline resistance, new anticancer drugs against that subgroup of tumors are needed. Phenotypic drug screening approach, which do not focus on isolated targets but instead classify compounds by their impact on cell physiology, is highly suitable for this purpose. Current cell-based phenotypic assays require fixation and staining for phenotypic markers, which reduce screen throughput and introduce potential variations and artifacts. Here we describe a high-content live-cell phenotypic assay, which streamlines the process of cytological profiling and provides a consistent platform for empirically evaluating drug action. Importantly, when combined with chemical similarity clustering, the phenotypic assay provided an inference of structure-activity relationships. Finally, a small-scale phenotypic screen of natural products enabled classification of unknown compounds against the cytological profiles of commercial compounds. Hence, the phenotypic screen provides a new and robust opportunity for accelerating the evaluation of compound activity during high-throughput drug screens.

abstract: Thesis

abstract: Master of Science (MSc)


title: Issues related to optimizing chronic non-cancer and disability management

title: Optimizing chronic pain and disability management

subject:
chronic pain management
disability management
health research methodology
clinical epidemiology
insurance medicine

abstract: Chronic non-cancer pain (CNCP) is a complex phenomenon that affects multiple dimensions of daily life. Optimal therapies for managing CNCP must, then, demonstrate clinically important benefits that go beyond reductions in pain and adverse events. The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) has recommended that clinical trialists who are evaluating treatments for chronic pain consider reporting treatment effects across nine patient-important outcome domains. This thesis begins with an investigation of the extent to which clinical trials evaluating the effects of opioids for CNCP report IMMPACT-recommended core outcome domains. Further, it explores optimal therapeutic strategies for specific CNCP conditions; specifically, it features a systematic review of randomized controlled trials of all pharmacological and non-pharmacological therapies for central post-stroke pain, as well as a plan for a network meta-analysis of all therapies for all chronic neuropathic pain syndromes. Chronic pain is also a common reason for disability, and this thesis concludes with a retrospective cohort study focused on identifying predictors of claim duration following acceptance for disability benefits among Canadian workers.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: CHINESE, BRAZILIAN, AND RUSSIAN INVESTMENT INTO THE EX-COLONIAL WORLD: THE POLITICS OF SOUTH-SOUTH INVESTMENT

title: THE POLITICS OF SOUTH-SOUTH INVESTMENT

contributor:
Sajed, Alina
Political Science

subject: imperialism development

abstract: The major emphasis of this thesis is on the state to private sector relationships formed at a domestic level of each case study. The developmental trajectories of these relationships in China, Russia, and Brazil are examined through the beginning of the 2008 crisis to 2014. As argued below, these relationships are determinant in the ways in which local capital and state power transplants and reproduces in the ex-colonial world. To examine these relationships, this thesis offers a re-conceptualization of dialectics and the theory of uneven and combined development in a broader Marxist ontology of international capitalist political economy. In analyzing state-based methodologies of transnational firm movement, this thesis speaks to gaps in critical political economy concerning the contemporary characterization of Brazilian, Chinese, and Russian investment into the ex-colonial world. This course of argumentation is propelled by new discoveries within an analysis of secondary OECD and firm data. Macro investment data is used in conjunction with data gathered from financial and non-financial firms in Brazil and Russia. The allocation and movement of financial and productive resources is traced in this way. Legal policies and structural mechanisms of state agencies such as development banks and export credit agencies are explored. In analyzing these two factors in the relationships Brazil, Russia, and China have with the ex-colonial world the case is made that the underlying feature is one of neo-coloniality.

abstract: Thesis

abstract: Master of Arts (MA)

abstract: The goal of this thesis is to explore the relationships that Brazil, Russia, and China have with the developing world. Specifically observed is the relationship that the governments of Brazil, Russia, and China have with domestically owned private capital to facilitate investment into Africa, Latin America, and Asia. The argument made is that these state-to-private sector relationships in the domestic economies of the case countries perpetuate new forms of colonial relationships abroad. Investment and inter-state relations are the areas examined to make this case. From the perspective of my problematic, my contributions to scholarship include: an analysis of changes in the Brazilian financial sector in 2005 and 2014; an analysis of Russian multinational corporate revival post-2014; an analysis of Chinese investment patterns; and a theoretical insertion of uneven and combined development into the study of the contemporary relations of developing areas.


title: A DEVELOPMENTAL EVALUATION OF THE COMMUNITY NURSE NETWORKER PILOT

contributor:
Valaitis, Ruta
Nursing

subject:
System Navigation
Community Health
Primary Care
Nurse Navigation
Social Determinants of Health
Community Development

abstract: The Community Nurse Networker (CNN) pilot project represents an innovative collaboration between primary care, public health and municipal stakeholders, including a local neighbourhood resident planning team in a priority neighbourhood in Hamilton, Ontario. This pilot linked primary care to ongoing community development work. The goal of the CNN pilot was to address issues beyond physical health, and to consider issues related to the social determinants of health, or where people, live, work, and play. This developmental evaluation study used a qualitative descriptive approach (Sandelowski, 2000, 2010). Multiple perspectives and sources were used to describe the implementation of the CNN pilot, the following were collected and analyzed: Interviews (N=5), a focus group (participants = 11), documents (N=90), and a survey (N=1). The implementation of the pilot was described by the following foci: (a) conceptualization of the CNN’s roles and activities, (b) perceived barriers and enablers in implementing the CNN pilot, (c) perceived impacts of the intervention, and (d) perceptions surrounding the value of a nurse in the CNN position. The CNN pilot is a unique intervention, demonstrating how primary care can be a leader within the community, engaging with health and social services organizations and hard to reach populations. The findings of this study supported the ongoing development of the CNN position. It provided an example of a nurse-led intervention, with an integrative approach to primary care, community development, social, and health services. This study illustrates the potential for strengthened partnerships between primary care and the community within priority neighbourhoods.

abstract: Thesis

abstract: Master of Science (MSc)


title: Social Burden or Social Resources: Understanding Chinese Senior Immigrants’ Contributions in Canada

contributor:
Zhou, Y. Rachel
Social Work

subject:
Chinese Senior Immigrants
Contributions in Canada

abstract: The thesis stresses these non-economic contributions by senior immigrants should be considered and incorporated in policy making process, including policies relating to the criteria of immigration. This study shows that immigrant sponsorship policy and senior immigrants’ service programs play a large role in deterring or assisting senior immigrants to play a role in Canadian society.

abstract: This thesis aims to explore how Chinese senior immigrants perceive individual strengths and how they use these strengths to help their adult immigrant children’s families and participate in community activities. I also examine how they understand their contributions in Canada and the barriers to their active participation in the Canadian society.

abstract: Thesis

abstract: Master of Social Work (MSW)

abstract: The study was carried out through conducting two focus groups in Toronto with Mandarin-speaking Chinese senior immigrants aged 55-80 who came to Canada 2-15 years ago. Informed by the anti-oppressive practice (AOP) approach in social work, findings suggest that those these Chinese seniors play a critical role in stabilizing the immigrant family economy and in subsidizing Chinese newcomer families in the process of early settlement. Chinese senior immigrants actively take part in community works and volunteer in helping others, which have direct and indirect benefits to Canadian economic development.


title: Hybrid Model for Monitoring and Optimization of Distillation Columns

contributor:
Mahalec, Vladimir
Chemical Engineering

subject:
hybrid model
optimization
distillation
modeling

abstract: Distillation columns are primary equipment in petrochemical, gas plants and refineries. Distillation columns energy consumption is estimated to be 40% of the total plant energy consumption. Optimization of distillation columns has potential for saving large amount of energy and contributes to plant wide optimization. Currently rigorous tray to tray models are used to describe columns separation with high accuracy.  Rigorous distillation models are being used as part of design, optimization and as a part of on-line real-time optimization applications. Due to large number of nonlinear equations, rigorous distillation models are not suitable for inclusion in optimization models of complex plants (e.g. refineries), since they would make the model too large.  For this reason, current practice in plant-wide optimization for planning or for scheduling is to include simplified model.  Accuracy of these simplified models is significantly lower than the accuracy of the rigorous models, thereby causing discrepancy between production planning and RTO decisions. This work describes reduced size hybrid model of distillation columns, suitable for use as stand-alone tool for individual column or as part of a complete plant model, either for RTO or for production planning. Hybrid models are comprised of first principles material and energy balances and empirical models describing separation in the column. Hybrid models can be used for production planning, scheduling and optimization. In addition this work describes inferential model development for estimating streams purity using real time data. Inferential model eliminates the need for Gas Chromatography GC analyzers and can be used for monitoring and control purposes. Predictions from the models are sufficiently accurate and small size of the models enable significant reduction in size of the total plant models.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Quadrupole Coupling Tensor for 11B in Datolite

subject: quadrupole, nuclear, magnetic, datolite, crystal, tensors

abstract: The electric quadrupole splitting of the 11B nuclear magnetic resonance signal have been studied in a single crystal of datolite (H Ca B SiO5) placed in a magnetic field of 6350 Gauss and the methods developed by Volkoff and coworkers have been used to analyse the data. The space group of datolite, P 2 1/C, permits two different orientations of the otherwise identical quadrupole coupling tensors existing at the four boron sites in the unit cell. The observed five line 11B (I = 3/2) spectrum is consistent with the crystal symmetry. The quadrupole coupling constant, eqQ/h, and asymmetry parameter, η, at the unique boron site have been determined as well as the orientation of the principal axes of the electric field gradient tensor. The value of 172±1 Kc/sec found for eqQ/h in datolite is consistent with the overall range of values observed for BO4 tetrahedra in other crystals.

abstract: Thesis

abstract: Master of Science (MSc)


title: Proton Resonance Studies of Two Ferroelectric Sulfates

contributor:
Petch, H. E.
Physics

subject: nuclear magnetic resonance, sulfate, ferroelectric, transition, temperature

abstract: The nuclear magnetic resonance spectrum of the protons in rubidium hydrogen sulfate, and the spin-lattice relaxation time for the protons in lithium hydrazinium sulfate have been examined as a function of temperature, in order to obtain information about the motions of the protons in the different states of these substances. Rubidium hydrogen sulfate becomes ferroelectric below -15°C, and the possibility of a change in the proton resonance linewidth associated with this transition was investigated. The free-precession (spin echo) NMR technique was used to obtain the proton spin-lattice relaxation time in lithium hydrazinium sulfate, over a wide temperature range. The observed changes in relaxation time gave further data on the hydrazinium ion motions that were inferred from proton NMR studies by Cuthbert and Petch in 1963.

abstract: Thesis

abstract: Master of Science (MSc)


title: A Study of the Springs in the Upper Sulphur Creek Basin

contributor:
Ford, D.C.
Geography

subject: Sulphur Creek, basin, Ancaster, springs,

subject: aquiclude, clay, Wisconsin, glaciation

abstract:
Sulphur Creek, which occupies a basin to the north and west of Ancaster, Ontario, is fed by approximately 100 springs. This is the first detailed investigation of these springs. The results of this study are presented and a number of interesting conclusions have been drawn from them.Several directions for further research are also indicated.

 Physical analysis of the springs has revealed that they are on a planar, lacustrine blue clay aquiclude, which was formed as a result of meltwater ponding against an ice lobe, during the late Wisconsin glaciation. The meltwater lake covered most of the Sulphur Creek Basin, as indicated by the fact that blue clay was found all along the Creek's course. However, further research is required to determine the exact extent of this proglacial lake.

 A preliminary study of six springs was also undertaken in hope of determining the residence time of the groundwaters feeding the springs. It was found that there are significant short term trends in spring temperature, solute abundancies and 180 composition with season, suggesting that the residence times are surprisingly short. Also, the trends in the above variables suggest that groundwater residence time tends to vary from spring to spring. However, there are contradictions in trend when different variables are compared, which again suggests that further research is warranted.

abstract: Thesis

abstract: Bachelor of Science (BSc)


title: Proton Resonance Study of Hydrated Gallium Sulfate

contributor:
Petch, H.E.
Physics

subject:
nuclear, magnetic, resonance, spectrum
hydrated, gallium, sulfate, protons,

abstract: The nuclear magnetic resonance spectrum and the spin lattice relaxation time of protons in powdered hydrated gallium sulfate have been investigated and compared in order to determine the probable proton configurations. The second moment and the relaxation time of the proton resonance were studied over a wide range of temperature. The NMR evidence is compatible with the existence of protons in OH-and H30+ configurations supporting the suggestion of Johansson (1962) based on an x-ray structure analysis.

abstract: Thesis

abstract: Master of Science (MS)


title: The Effects of Olanzapine on Trophoblast Invasion

contributor:
Raha, Sandeep
Medical Sciences

abstract: Olanzapine (OLN) is one of the most commonly taken antipsychotics during pregnancy. Exposure of the fetus to OLN during gestation leads to altered birth weight. This is of concern because altered fetal growth increases the risk of metabolic syndrome later in life, which negatively impacts an individual’s quality of life, lifespan, and increases the burden on the healthcare system. However, the mechanisms of how antipsychotics, such as OLN, contribute to fetal growth effects have yet to be determined. The placenta plays a critical role in modulating the in utero environment to promote optimal fetal growth and is dysfunctional in pregnancies complicated by fetal growth restriction. However, no previous work has examined the direct effect of OLN on the placenta. We assessed whether OLN can impact the placenta by exposing a human trophoblast cell line (HTR-8/SVneo cells) to OLN and determining its effects on trophoblast invasion. Altered invasion is heavily implicated in adverse pregnancy outcomes such as preeclampsia, and intrauterine growth restriction. This thesis demonstrates that OLN increases trophoblast cell invasion, as well as integrin gene expression and the amount of active extracellular MMPs, which are important for invasion. Although the cellular signaling pathway(s) by which OLN mediates these effects remains unclear, it may involve OLN’s ability to decrease the maximal activity of the mitochondrial electron transport chain complexes. These findings provide the first evidence that OLN has the potential to affect placentation. This thesis contributes to the current understanding of how antipsychotic drugs can result in adverse fetal outcomes and allows healthcare providers to better predict and manage fetal outcomes of women taking OLN during pregnancy.

abstract: Thesis

abstract: Master of Science (MSc)


title: An Automatic Facility for Neutron Activation Analysis

subject: automatic, neutron, activation, facility, algorithm

abstract: The development of a unified system for the automatic neutron activation analysis of large numbers of samples is described. The realization of the system entailed the automation of a gamma ray spectrometer system by means of a data and control link to a small computer (PDP-15) and the development of a reliable and fast data reduction algorithm suited to the small computer system. A detailed study of the algorithm and the errors associated with it has been included.

abstract: Thesis

abstract: Master of Science (MSc)


title: Energy Levels in Pt192 and Pt194

contributor:
Johns, M. W.
Physics

subject: energy, levels, nuclei, platinum, coincidence, beta

abstract: The technique of recording coincidence events has been applied in the study of several nuclei. Two platinum nuclides have been investigated experimentally through the use of two types of coincidence spectrometers. For both these nuclei, Pt^192 and Pt^194, the investigation included beta-gamma experiments which measured the intensities of the beta groups feeding some of the levels in these nuclei and directional correlation experiments which determined the spins of some of their excited states. A study of the gamma-gamma coincidences of Pt^194 confirmed the decay scheme proposed by previous workers. The directional correlation of the one cascade in Co^58 forms the part of the paper present in Chapter IV. Finally, the appendices contain a description of an apparatus for the preparation of beta sources and an explanation of a set of experiments designed to calibrate the gamma-gamma coincidence spectrometer for its tasks.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Not Quite There Yet: Jurisprudence, Utopia and Intentional Community

contributor:
Silcox, Mary
English

subject: jurisprudence, utopia, intentional community

abstract: This thesis examines the role of concepts of jurisprudence, utopian theory and intentional community in three novels that are based on actual attempts to construct utopian intentional communities. Chapter one focuses on Nathaniel Hawthorne’s The Blithedale Romance, applying Ronald Dworkin’s interpretive theory in order to evaluate the Blithedale commune’s attempt to construct its own legal community. Questions of “why does it fail?” are pervasive in this thesis, but in this chapter, I pull apart the various roles of individual members in order to decipher both the role of the individual and the community in self-created legal systems. Chapter two adds to the consideration of constructive interpretivism by looking at the role of associative obligations in T.C Boyle’s Drop City. In particular, I analyze how associative obligations change when the commune relocates to Alaska, considering the effects of space in shifting associative obligations. The final chapter considers the meaning of legal death in Richard Brautigan’s In Watermelon Sugar. I explain the implications of a commune based on negative intent in order to determine whether this community can still maintain integrity to its cause.

abstract: Thesis

abstract: Master of Arts (MA)


title: The Role of the Halides as Addition Agents During the Electrodeposition of Copper

contributor:
Tomlinson, R. H.
Chemistry

subject: halides, agents, electrodeposition, copper, chloride, ion

abstract: The amount of chloride ion incorporated into a copper electrodeposit prepared from an aqueous copper sulphate solution has been determined at low chloride concentrations by the use of radiotracers. It has been found that the electrodeposits have a surface layer which is enriched in chloride ion. Evidence has been obtained that incorporation of chloride is preceded by the formation of cuprous chloride. The incorporation of chloride has been found to be increased by the presence of organic additives in the solution. The polarization during the first 30 seconds of electolysis has been interpreted using the knowledge obtained from the radiotracer work.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Aspects of Zero-Valent Nickel, Palladium and Platinum Chemistry

contributor:
Maitlis, P. M.
Chemistry

subject: zero-valent, palladium, platinum, complexes

abstract: The work describes the preparation and properties of some novel dibenzylideneacetone complexes of palladium and platinum. The structure and bonding in these complexes is discussed in view of their infrared and nuclear magnetic resonance spectra. The cyclotrimerization of acetylenes by zero-valent nickel complexes is discussed and the synthesis of a new cyclobutadiene-platinum complex is reported.

abstract: Thesis

abstract: Master of Science (MSc)


title: The Study of Assessed Farm Values in Grey County

contributor:
Reeds, L. G.
Geography

subject: farm, values, grey county, buildings

abstract:
 The problem studied in this thesis is variations in assessed farm values in a selected area of Grey County, Ontario. A random sample of eighty farms was taken from four townships located in the vicinity of the city of Owen Sound.

 Data was collected on distance to the city, farm size, quality of buildings, soil, land use and type of road. Hypotheses were developed and tested with the use of multiple regression. The analysis provided empirical proof of the validity of the a priori hypotheses. The directional impact of the variables can be predicted.

 Two of the variables, quality of buildings and size of farm were found to be statistically significant. The low level of explanation of the variation in farm values is related to the size of the sample and to the relative uniformity of conditions in the area being investigated.

 The use of actual sale values, a larger sample and a more diverse area near a city that is an important market centre is recommended as a basis for further research.

abstract: Thesis

abstract: Candidate in Philosophy


title: A Study of the Geochemistry of an Arctic Watershed

contributor:
Harriss, R. C.
Geology

subject: geochemistry, arctic, watershed, mineralogy, soil, sediments, oceans

abstract:
 The clay mineralogy and elemental chemistry of soil and sediment samples from a small area of the Canadian Arctic Archipelago were examined. The importance of mineral-water reactions and the distinctive features of the geochemical cycle in polar regions are discussed.
New data are presented for Hg, Au and Pd in near-shore sediments. In the case of Au and Pd the study was extended to include pelagic sediments from other oceans, and these results are discussed in an appendix.

abstract: Thesis

abstract: Master of Science (MSc)


title: A Versatile, High Speed, Raster Scan Video Graphics Terminal

contributor:
Hicks, G. J.
Redish, K. A.
Computation

subject: speed, raster scan, video, graphics, terminal, microprogrammable, commands

abstract:
 The design of a flexible, high speed, raster scan graphics terminal is presented. The design is presented in general architectural terms rather than from a detailed circuitry point of view.

 Control is divided between the 'main' microprocessor, an Intel 8086, and a subservient graphics controller which consists of a microprogrammable, bit-sliced, AM2903/2910 special purpose microprocessor. The high speed graphics controller is microprogrammed to accept basic line and circle generating commands. The configuration is felt to represent an efficient balance between simplicity and speed.

abstract: Thesis

abstract: Master of Science (MS)


title: Evaluation of Exposure to Combustion Products Using Multidimensional Chromatography and Ultra High Resolution Mass Spectrometry

contributor:
McCarry, Brian E.
Jobst, Karl J.
Chemistry and Chemical Biology

subject:
Combustion products
Mass Spectrometry

abstract:
This thesis investigates the exposure of humans to organic combustion products. Combustion of natural and anthropogenic materials can lead to highly complex mixtures of gas-phase and particle-bound chemical compounds, whose composition and health effects have been studied extensively. Nevertheless, the analysis of other potentially toxic products remains a challenge due to lack of analytical standards and methodologies. The research that encompasses this thesis is a progression from the analysis of known combustion products to the identification of previously unknown products.
Targeted analytical techniques, such as gas chromatography tandem mass spectrometry (GC-MS/MS), were utilized to evaluate firefighter exposure to wood smoke chemicals during training exercises. The results suggest that a subset of the firefighters were at higher risk of exposure which could be related to specific operational roles and the use of personal protective gear. Comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GCGC-TOF) was used for the identification of novel wood smoke markers and the results indicate that firefighters are equally exposed to gas-phase and particle phase compounds..
Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry is a non-targeted technique that is complementary to GCGC. Together, these tools enabled the identification of a suite of halogenated PAHs (haloPAHs) in samples obtained from the Plastimet Inc. fire, one the largest industrial fires in North America. HaloPAHs are similar in structure to toxic polychlorinated dibenzo-p-dioxins (PCDDs), a notorious class
iv
of toxic chemicals, and they were detected at much higher concentrations. In addition, highly substituted and high molecular weight haloPAHs were detected for the first time in an environmental sample. Finally, negative ion atmospheric pressure chemical ionization (NI-APCI) was explored as an alternative ionization technique for the analysis of mixed bromo/chloro dioxins (PXDDs) in the ash sample. PXDDs, with 1550 possible congeners, are potentially more toxic than their chlorinated counterparts (PCDDs). NI-APCI derived structure diagnostic fragments enabled the differentiation of co-eluting PXDD isomers in the ash sample which has not been possible using traditional ionization techniques (EI/CI) associated with GC-MS.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Topics in the Theory of Superconductivity

contributor:
Carbotte, J. P.
Physics

subject: theory, superconductivity, energy, transition, temperature, anisotropy

abstract:
 Simple theoretical expressions for the zero temperature energy gap and the transition temperature of a weak coupling superconductor are derived and applied to an investigation of several phenomena.

 The anisotropy of the energy gap in aluminium arising from the anisotropy in the phonon spectrum is calculated. The effect of this energy gap anisotropy on some thermodynamic properties of superconducting aluminium is investigated.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Sulfur Isotope Abundances and Base Metal Zoning in the Heath Steele B-1 Orebody, Newcastle, New Brunswick

contributor:
Crocket, J. H.
Geology

subject: sulfur, isotope, base metals, heath steele, orebody, deposits, temperatures

abstract: S^32/S^34 ratios have been determined between some coexisting sulfides from the Heath Steele B-1 orebody and five other stratiform deposits in the Bathurst-Newcastle area, New Brunswick, and in crushed ore samples and pyrites from three across deposit profiles in the B-1 orebody. Zn, Cu, Pb and Ag abundances have been established across the orebody. Fractionations of S^32/S^34 ratios between coexisting sulfides have been determined in heating experiments at temperatures of 350 to 500°C and isotope effects measured in aqueous precipitation and exchange experiments at 25°C. S^32/S^34 fractionations between given coexisting sulfides from all the sulfide deposits are found to show only small variations. Isotope exchange is generally rapid in dry sulfide systems. Metal sulfides in aqueous solutions are slightly enriched in S^32 relative to the H2S with which they precipitate or communicate. It is concluded that the sulfide deposits have been regionally metamorphosed. The origins that have been proposed for the deposits so far are discussed and a model is suggested to explain the sulfur isotope and base metal abundances in the B-1 orebody.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Biosynthesis of Lythraceae Alkaloids

contributor:
Spenser, Ian D.
Chemistry

subject: biosynthesis, lythraceae, alkaloids, units, plants

abstract:
 The biosynthesis of the alkaloids of Decodon verticillatus, (L.)Ell, a member of the Lythraceae family, was studied by tracer methods. These alkaloids contain a phenylquinolizidine system, whose biosynthetic origin has not previously been investigated.

 Labelled samples of lysine, △^1-piperideine and phenylalanine yielded radioactive decodine and decinine, the two major alkaloids of D. verticillatus. Systematic degradations of these labelled alkaloids show that lysine, △^1-piperideine and phenylalanine serve as specific precursors. Whereas lysine and △^1-piperideine entered the quinolizidine ring, the biphenyl ring system of these alkaloids was derived from two units of phenylalanine. In a further experiment, labelled pelletierine was administered to the plants. But this experiment yielded an inconclusive result.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Digital Separation Techniques Applied to a Temperate Karst Terrain

contributor:
Drake, J. J.
Geography

subject: digital, spatial, surface, separation, elevation

abstract:
 An important aspect in spatial analysis is a digital separation technique. There are several techniques possible, but trend-residual techniques and filtering techniques are emphasized in this report. The areas studied were a 9.6 km^2 gridded area in the Mammoth Cave region in Kentucky and the Lewisburg region in West Virginia. The basic geology and surface patterns are described. Although they are similar in respect to geology, the doline distribution is much smaller and more dense in Kentucky than in West Virginia. Both areas appear stable and subsidence dolines appear dominantly. The two doline development models are presented and the evidence cited tends to support the MDCP model. The predicted clustering of daughters about uniform/randomly distributed parents is found in Kentucky, no study was found for West Virginia. Both areas show that doline long axis are oriented parallel to regional joint sets.

 A uniformly dense grid proves accurate and unbiased when the elevation data are contoured. The Surface II Graphics package proves more than adequate in producing all the maps needed for this study despite the lack of flexibility in some areas.

 A trend-residual analysis was conducted to the fourth order for both the Kentucky and West Virginia areas. Despite minor technical problems, the results are positive. The method clearly separates the local doline variance from the regional trend, but there does appear to be a consistent bias towards nearby ridges. It also appears that there is an enhancement-suppression effect from the residual analysis such that certain doline forms are enhanced while others are suppressed as the trend order progresses from the first to the fourth order.

 The filtering technique also shows some excellent results from the digital separation method. Several filter types are discussed and the theory of their design is also presented. Very successful results were achieved by a zero summed filter as well as a 3 x 3 moving average filter. Several maps are produced from the analyses and are computer generated and these are also presented. There are several conclusions given at the end.

abstract: Thesis

abstract: Candidate in Philosophy


title: The Geography of Intermunicipal Relations: A Case Study in the Grimsby Area, Ontario

contributor:
Burghardt, Andrew F.
Geography

subject: geography, intermunicipal, literature,

abstract:
 The thesis examines the causes of intermunicipal cooperation and noncooperation in Grimsby, North Grimsby, Saltfleet, and South Grimsby. After reviewing the geographical literature on municipal government and the literature on interlocal relations, the thesis
records the territorial and functional evolution of the study area's municipalities. The thesis then examines specific examples of intermunicipal cooperation and noncooperation in the Grimsby area. Stress is placed on identifying those variables that play a key role in
producing agreement and disagreement between local governments. The final chapter attempts to rank the factors thus identified into categories of their relative importance and to evaluate the methodology of the thesis. Two appendices discuss the Regional
Municipality of Niagara and present the master interview schedule used in the thesis.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Finite Element Method for Soil Deformations

contributor:
Wilson, Nyal E.
Civil Engineering

subject: finite, element, soil deformations, geological, formations

abstract: A finite element method, incorporating the Hellinger-Reissner variational principle, has been developed for calculations of stress-strain and pore pressure for undrained and drained soil deformations. The soil is considered as cross-isotropically elastic material to account for the anisotropy of soil behaviour resulting from geological formations. A general expression for pore pressure parameters, taking into account the consolidation condition, has been hypothesized. Experimental investigations of consolidated undrained triaxial tests have been performed to study the validity of this expression.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Offshore Drilling: An Emerging Issue in Arctic Food Security, a review

contributor:
Eyles, John
Moffat, Christina
Yiannakoulias, Niko
Global Health

subject:
Offshore drilling
Food security
Arctic Indigenous
Global health
Traditional food
Marine environment

abstract: This thesis looked at the effects of offshore drilling on food security prospectively. The thesis aimed to understand the effects of offshore drilling and the importance of traditional foods to the Canadian Arctic Indigenous People. Furthermore this thesis aimed to contribute to food security research that is conceptualized within an indigenous context.

abstract:
Background: Due to global climate change, the melting of arctic ice has increased geopolitical interest in the land due to newly accessible oil reservoirs on the continental shelf. With the imminent rise in offshore gas drilling, this presents an additional threat to Arctic food security. Indigenous populations living in the circumpolar north face many challenges in accessing adequate and nutritional food sources. One of the most significant factors impacting food security is the availability of traditional food.
Objectives:  To critically examine existing data and literature to discuss the impact of offshore gas drilling on traditional marine food sources. Additionally, the cultural, spiritual and physical health aspects of traditional food consumption will be determined.
Methods: Arksey and O’Malley’s scoping review framework was adopted to examine the effects of offshore drilling activities on marine fauna. Furthermore, a literature review was used to determine the significance of traditional food to Canada Arctic Aboriginals.
Conclusions: Offshore drilling activities may impact the four dimensions (access, availability, utilization and stability) of food security, therefore threatening food security in the Canadian Arctic.

abstract: Thesis

abstract: Master of Science (MSc)


title: Constructing a Global Account of Reason

title: Discourse, Moral Engagement and Ecological Truth

contributor:
Igneski, Violetta
Philosophy

subject: discourse knowledge indigenous ethics

abstract:
In this dissertation I argue that Jürgen Habermas’ discourse ethics is our best understanding of morality, but that as it stands it has some serious deficiencies that need to be overcome before it can live up to its own promise. In particular, its insistence that facts, norms and self-expressions constitute the full range of validity claims available to us privileges Western voices in discourse, and undermines its own principles of equality and coercion-free dialogue. According to Habermas, others who do not utilise validity claims in the same way that Western speakers do are merely blurring the lines between these three categories and hence fall short of the ideal practices of discourse. In other words, they are less than fully rational.
Rather, I argue that these three categories do not exhaust the full range of possible reasons. I suggest that we ought to understand statements that do not fit as one of these kinds of validity claim as instances of different kinds of claims entirely. Instead of being a confused blurring-of-the-lines, expressions on the part of indigenous and “traditional” societies that do not conform to Habermas’ categories of fact, norm or self-expression are just as likely to be instances of an expanded ontology of reasons that are equally legitimate.
After examining some alternative explanations regarding claims that do not fit into Habermas’ categories, I finally suggest and describe a different, place-based kind of validity claim that I refer to as “ecological truth”, and suggest that it shows up the limitations of Habermas’ ontology of reasons. Ecological truth is a potential kind of reason available in discourse that is rooted in a close intertwining of practices and communities with particular ecologies and environments. This kind of reason cannot be subsumed into the categories of fact, norm and self-expression.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)

abstract: This dissertation argues for a method of resolving moral disagreement by the exchange of reasons by those affected by the disagreement under certain conditions. However, it suggests that typical Western accounts of the varieties of reasons admissible in these kind of conversations is limited, privileges Western ways of looking at the world, and devalues non-Western and, in the focus of this dissertation, particularly indigenous worldviews. As such, a fuller and more just account of reason is needed, one that includes the kinds of reasons used by all, if we are to have just, fair and equitable conversations in order to resolve moral disagreements.


title: Wire Electric Discharge Machining of Curvilinear Swept Surfaces

title: WEDM of Curvilinear Swept Surfaces

contributor:
Koshy, Philip
Mechanical Engineering

subject:
Electric Discharge Machining
EDM
Fir Tree Root Form
FTRF
Wire Electric Discharge Machining
WEDM
Curvilinear
Swept
Design of Experiments
DOE
Turbine disk

abstract: Fir tree root forms are one way to retain turbine blades in turbine disks. These features are ruled surfaces that span the entire thickness of the disk and are usually machined by broaching. With increasing use of new heat resistant and difficult-to-machine materials, mechanical machining methods exhibit severe problems with tool wear and surface integrity. To mitigate these problems, thermal material removal processes such as Wire Electrical Discharge Machining (WEDM) are being considered in the aerospace industry. Developments in turbine design have led to a root form geometry in the form of an arc across the thickness of the disk in order to decrease the contact stress by increasing the contact area between blade and disk. A curved surface such as this cannot be produced by conventional WEDM as it is not a ruled surface. A novel WEDM process is being developed where an arc shaped curve is formed from an axially moving wire to allow for the production of such curved surfaces.

abstract: Thesis

abstract: Master of Applied Science (MASc)

abstract: Turbine blades are attached to turbine disks with specially shaped, straight slots called Fir Tree Root Forms (FTRF) that can be cut with broaching tools. Broaches wear out quickly because the disk is made of very difficult to cut material and the aerospace industry is starting to use Wire Electric Discharge Machining (WEDM), instead of broaching, to cut these slots since it can easily cut the material used. New turbine disk designs have curved slots, which can not be cut with a straight broach or wire, and a new process is therefore being developed which uses an arc-shaped wire to cut the desired curved shapes.


title: A Family of Symmetric Distributions and Best Linear Unbiased Estimators of its Parameters

subject: symmetric, linear, unbiased, estimators, family, variances

abstract: A family of symmetric distributions is introduced. The means, variances and covariances of ordered observations from the family are calculated. The best linear unbiased estimators of the mean and standard deviation are constructed for complete and censored samples. A computer technique is developed to evaluate range-dependent double integrals.

abstract: Thesis

abstract: Master of Science (MSc)


title: INVESTIGATING THE EFFECTS OF HYPERGLYCEMIA ON THE VASA VASORUM IN THE DEVELOPMENT OF ATHEROSCLEROSIS AND ESTABLISHMENT OF NOVEL MOUSE MODELS OF DIABETES

title: Effects of Hyperglycemia in Mouse Models of Atherosclerosis

contributor:
Werstuck, Geoff
Biochemistry and Biomedical Sciences

subject:
Diabetes
Mouse Models
Atherosclerosis
Microvascular complications
Macrovascular complications
Sex Effects

abstract:
The prevalence of diabetes is increasing rapidly around the world. People with diabetes are 2–4 times more likely to die from cerebro and cardio-vascular causes than people with no history of diabetes, even after controlling for other risk factors. Atherosclerosis, the underlying cause of most cardiovascular disease (CVD), is accelerated in people with diabetes, but several clinical trials have questioned the efficacy of glucose lowering therapies. A better understanding of the molecular pathways by which diabetes accelerates atherosclerosis will expand the scope of current targets and strategies for more effective therapies. In this thesis we investigate a novel mechanism and establish and characterize new hyperglycemic mouse models for the study of diabetic atherosclerosis.
	Firstly, we investigate the effects of hyperglycemia on the vasa vasorum, the microvascular network that surrounds and supplies large vessels, and correlate those effects to the development of atherosclerosis. In normoglycemic ApoE-/- mice, the vasa vasorum expands as atherosclerotic lesions grow. However, in hyperglycemic ApoE-/- mice there is no significant neovascularization of the vasa vasorum despite the enhanced atherosclerotic development. We hypothesize that the ability of hyperglycemia to disrupt vasa vasorum neovascularization may promote the development and progression of atherosclerosis in diabetes.
	Secondly, we establish, characterize and manipulate a new model of hyperglycemia-induced atherosclerosis: the ApoE-/-:Ins2+/Akita mouse. We describe sex-specific differences of the ApoE-/-:Ins2+/Akita mouse model. Male ApoE-/-:Ins2+/Akita mice develop chronic hyperglycemia and accelerated atherosclerosis. Castration slows atherosclerosis in ApoE-/-:Ins2+/Akita mice but enhances it in normoglycemic controls. Female ApoE-/-:Ins2+/Akita mice are only transiently hyperglycemic but still present with accelerated atherosclerosis. Ovariectomized ApoE-/-:Ins2+/Akita mice are chronically hyperglycemic and show indications of advanced atherosclerosis.
	Lastly, we investigate the effects of a western-type diet on the hyperglycemic ApoE-/-:Ins2+/Akita mice. We demonstrate the pernicious phenotype of the mice leading to a significantly shortened lifespan correlated with massive atherosclerosis that extends to the aortic sinus, ascending and descending aorta, brachiocephalic artery and coronary arteries.
	In conclusion we provide insights for a new mechanism by which hyperglycemia may accelerate atherosclerosis and possible role of the vasa vasorum in the progression of atherosclerosis in hyperglycemic mice. We also establish new mouse models that illuminate the action of sex hormones on pancreatic beta-cell function and the vasculature. These models will provide a test bed to further study sex hormone effects, as well as the diabetic pathways that promote atherosclerosis.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Reversing Antibiotic Resistance with Inhibitors of Bacterial Acetyltransferases

contributor:
Wright, Gerry
Biochemistry and Biomedical Sciences

subject:
antibiotic resistance
acetyltransferase
streptogramin
aminoglycoside
Vat
AAC(3)

abstract: Hospitals worldwide are becoming increasingly plagued by antibiotic-resistant pathogens; concomitantly, the number of patients who die from antibiotic-resistant pathogens is increasing.  The rise of multi-drug resistant (MDR) pathogens has rendered many antibiotics obsolete.  The streptogramin and aminoglycoside antibiotics are drugs of last resort against life-threatening, MDR Gram-positive (e.g., methicillin resistant Staphylococcus aureus (MRSA)) and -negative (e.g., Pseudomonas aeruginosa) pathogens, respectively; however, as microbial drug resistance continues to emerge, the efficacy of these two important drug classes is decreasing.  One of the most common mechanisms by which pathogens become resistant to streptogramin and aminoglycoside antibiotics is enzymatic inactivation: the Vat and AAC(3) acetyltransferases are employed by pathogens to inactivate streptogramin and aminoglycoside antibiotics, respectively.  There currently is a dire need to not only develop new antibiotics, but to find new, creative strategies to outwit microbial resistance mechanisms.  One of these strategies is to rescue the activity of antibiotics through the discovery of antibiotic adjuvants.  In the current study, adjuvants which rescue the activity of streptogramin and aminoglycoside antibiotics through inhibition of the resistance acetyltransferases, VatD and AAC(3)-Ia, have been discovered—through the development of a cell-based screening method, we have found the first inhibitors of VatD, as well as of AAC(3)-Ia and its homologues, AAC(3)-Ib, AAC(3)-Ic, and AAC(3)-Id.  We have demonstrated that streptogramin and aminoglycoside resistance can be reversed both in vitro and in vivo by the protein kinase inhibitors, GW5074 and rottlerin.  Steady state kinetics revealed these compounds to inhibit VatD and AAC(3) enzymes mainly through noncompetitive or mixed mechanisms.  This study has also demonstrated that eukaryotic kinase inhibitor libraries may be repurposed for the discovery of not only new antibiotic adjuvants, but also new antimicrobial targets.  The inhibitors described herein may someday serve as effective adjuvants of streptogramin and aminoglycoside antibiotics.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: WALL-DIAPHRAGM OUT-OF-PLANE COUPLING INFLUENCE ON THE SEISMIC RESPONSE OF REINFORCED MASONRY BUILDINGS

contributor:
El-Dakhakhni, Wael
Civil Engineering

subject:
Asymmetrical buildings
Backbone model
Damage states
Diaphragm out-of-plane influence
Displacement-based design
Diaphragm coupling
Forced-based design
Masonry buildings
Reinforced masonry
Robustness
Resilience
System-level damage
Seismic risk assessment
System-level response
Seismic loads
Shear walls
Slab coupling

abstract: Recent research interests in studying the performance of different seismic force resisting systems (SFRS) have been shifting from component- (individual walls) to system-level (complete building) studies. Although there is wealth of knowledge on component-level performance of reinforced masonry shear walls (RMSW) under seismic loading, a gap still exists in understanding the response of these components within a complete system. Consequently, this study’s main objective is to investigate the influence of the diaphragm’s out-of-plane stiffness on the seismic response of RMSW buildings. In addition, the study aims to synthesize how this influence can be implemented in different seismic design approaches and assessment frameworks. To meet these objectives a two-story scaled asymmetrical RMSW building was tested under quasi-static cyclic loading. The analysis of the test results showed that the floor diaphragms’ out-of-plane stiffness played an important role in flexurally coupling the RMSW aligned along the loading direction with those walls orthogonal to it. This system-level aspect affected not only the different wall strength and displacement demands but also the failure mechanism sequence and the building twist response. The results of the study also showed that neglecting diaphragm flexural coupling influence on the RMSW at the system-level may result in unconservative designs and possibly undesirable failure modes. To address these findings, an analytical model was developed that can account for the aforementioned influences, in which, simplified load-displacement relationships were developed to predict RMSW component- and system-level responses under lateral seismic loads. This model is expected to give better predictions of the system response which can be implemented, within the model limitations, in forced- and displacement-based seismic design approaches. In addition, and in order to adapt to the increasing interest in more resilient buildings, this study presents an approach to calculate the system robustness based on the experimental data. Finally, literature shows that the vast majority of the loss models available for RMSW systems were based on individual component testing and/or engineering judgment. Consequently, this study proposes system damage states in lieu of component damage states in order to enhance the prediction capabilities of such models. The current dissertation highlights the significant influence of the diaphragm out-of-plane stiffness on the system-level response that may alter the RMSW response to seismic events; an issue that need to be addressed in design codes and standards.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)


title: Temporal Trends of Coliform Bacteria in Spencer Creek, Hamilton

contributor:
Eyles, C. H.
McCann, S. B.
Geography

subject: temporal, trends, coliform, bacteria, patterns, temperature, Spencer Creek

abstract: Coliform bacterial pollution was studied in the Spencer Creek in Hamilton, Ontario. Data, derived from the Ontario Ministry of the Environment files in Hamilton, were used in the determination of whether distinctive temporal patterns of coliform bacterial counts and loads exist in Spencer Creek at Cootes Drive in Dundas. An initial investigation of the general streamflow trends showed that the peak flow period is during the spring snowmelt (March) and a secondary peak flow occurs in late fall due to frontal storms passing through the area. This coincides with the minimums of coliform counts and loads which consistently occur during these times of high flow, particularly March and April. Peak coliform counts and loads occur 70% of the time in late summer with varying starting times in June, July, August and September. This is attributed to the low flow and high temperature of the water in the summer. The average coliform count is 334,154 coliform bacteria per 100 mL water, well above the water quality objectives set by the Ontario Water Resources Commission for Ontario Ministry of the Environment. Approximately 80% of the coliform counts, measured in Spencer Creek in this study, were well above this water quality objective. Therefore, in terms of coliform bacteria, Spencer Creek is polluted, particularly in the summer months. This study simply points out the necessity for further study and continued water quality testing in Spencer Creek.

abstract: Thesis

abstract: Candidate in Philosophy


title: Restoring hepatic TDAG51 expression improves insulin signalling and reduces weight gain.

contributor:
Austin, Richard
Health Sciences

subject: Diabetes Obesity

abstract: 1.5 million Ontarians, representing 10.2% the population, lived with diabetes in 2015. Treating this number of people with diabetes cost the public healthcare system approximately $6 billion. A staggering 2.3 million Ontarians, representing 13.5% of the population, are projected to have diabetes in the year 2025. This will raise public spending on diabetes to approximately $7.7 billion. Current therapies for Type 2 diabetes only focus on controlling glucose levels and do not target or reverse disease progression and complications, which allows the prevalence of diabetes to continue to rise unchecked. Targeting the source of insulin resistance, as opposed to attempting to control the symptoms of insulin resistance, represents a better strategy for the discovery of novel therapies. We have recently reported that loss of T-Cell Death-Associated Gene 51 (TDAG51) is associated with mature-onset obesity, Type 2 diabetes, and fatty liver. TDAG51 expression is significantly diminished in mice fed a high fat diet, which leads to insulin resistance and obesity, as well as in the leptin-deficient mouse model, a well-established genetic model of Type 2 diabetes and obesity. We have now discovered that restoring TDAG51 protein expression in the livers of TDAG51-null and leptin-deficient mouse models improves response to insulin and reduces total weight gain. We have shown that exogenous TDAG51 protein expression is significantly reduced in two mouse models of insulin resistance compared to healthy controls. The potential for post-translational degradation of TDAG51 protein in insulin-resistant livers is supported by five independent models of fatty liver in which TDAG51 protein expression is diminished while TDAG51 mRNA expression remained unchanged. We have also explored a number of mechanisms by which TDAG51 protein may be regulated post-translationally, and have provided suggestions of how TDAG51 protein may be modified in a fatty liver that would impact its stability. Collectively, we have highlighted the therapeutic potential of increasing liver TDAG51 expression in Type 2 diabetic conditions, and have laid a strong foundation for discovering how TDAG51 expression is regulated.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: 1.5 million Ontarians, representing 10.2% the population, lived with diabetes in 2015. Treating this number of people with diabetes cost the public healthcare system a staggering $6 billion. Current therapies for Type 2 diabetes do not target or reverse disease progression and its complications, which allows the prevalence of diabetes to continue to rise unchecked. We have recently reported that loss of the protein T-Cell Death-Associated Gene 51 (TDAG51) is associated with mature-onset obesity, Type 2 diabetes, and fatty liver. Additionally, TDAG51 protein expression is nearly diminished in three different mouse models of insulin resistance and hepatic steatosis, though the mechanism by which the protein is reduced is unknown. We have now discovered that restoring TDAG51 expression in two mouse models of Type 2 diabetes can reduce weight gain and improve insulin signalling. We have also explored a number of mechanisms by which TDAG51 protein is regulated, and have devised a method for determining how TDAG51 protein might be regulated in normal versus fatty liver. Collectively, we have highlighted the therapeutic potential of increasing liver TDAG51 expression in Type 2 diabetic conditions, and have laid a strong foundation for discovering how TDAG51 expression is regulated.


title: State Space Modelling and Multivariable Stochastic Control of a Pilot Plant Packed-Bed Reactor

contributor:
MacGregor, J. F.
Wright, J. D.
Chemical Engineering

subject: modelling, multivariable, stochastic, reactor, pilot

abstract: This study is concerned with the multivariable stochastic regulatory control of a pilot plant fixed bed reactor which is interfaced to a minicomputer. The reactor is non-adiabatic with a highly exothermic, gaseous catalytic reaction, involving several independent species. A low order state space model for the reactor is developed starting from the partial differential equations describing the system. A parameter estimation method is developed to fit the model to experimental data. Noise disturbances present in the system are identified using two methods, and two alternative dynamic-stochastic state space models are obtained. Multivariable stochastic feedback control algorithms are derived from these models and are implemented on the reactor in a series of DDC control studies. The control algorithms are compared with each other and with a single loop controller. The best of the multivariable control algorithms is used to regulate the exit concentrations of the various species from the reactor and the results are compared to data.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: On the Vibration and Buckling of Orthotropic Plates of Variable Thickness

contributor:
Dokainish, M. A.
Mechanical Engineering

subject: vibration, buckling, orthotropic, plates, thickness, linearly, frequencies, polynomial

abstract: The problem of a thin, orthotropic skew plate of linearly varying thickness for vibration and buckling analyses is formulated under the assumptions of small-deflection theory of plates. Using the dimensionless oblique coordinates, the deflection surface of the plate is expressed as a polynomial series, each term of which satisfying the required polar symmetry conditions, and the natural frequencies are computed using Galerkin method. As is required in Galerkin method, the assumed deflection function satisfies all the boundary conditions on all the edges of the plate. For the skew plate, clamped on all the four edges, numerical results for the first few natural frequencies are presented for various combinations of aspect ratio, skew angle and taper parameter. Convergence study has been made for typical configuration of the plate and the limited available data is inserted therein along with the computed results, for comparison.

abstract: Thesis

abstract: Master of Engineering (MEngr)


title: Optimization Approaches to Image Enhancement

contributor:
Wu, Xiaolin
Electrical and Computer Engineering

abstract:
To human viewers, sharp edges and rich details in an image are often interpreted as high perceptual quality.  Due to various types of degradation during the acquisition of an image and the limitations of display devices and human visual system, some information that exists in the acquired image can be difficult to distinguish when the image is displayed directly, affecting its perceptual quality.  Many image enhancement techniques have been proposed to fully utilize the dynamic range of the image data and reproduce a visually more appealing and informative image.

In this dissertation, we present two image enhancement techniques.  The first is a global approach that utilizes advanced image statistics and finds the best compromise among the factors that affect image quality; the second is a local approach exploiting the fact that the maximum discrimination power of human vision system can only be achieved in a relatively small locality of an image.  These two approaches produce visually pleasing results consistently over a wide range of images.

Besides the various types of artifacts, another practical problem affecting the perceptual quality of an enhanced image is the compression noise.  Due to the low pass nature of image compression, the high-frequency components of a compressed image with sharp edges often carry large compression error, which can be amplified by image enhancement operator deteriorating the perceptive quality of enhanced image.  By incorporating the non-linear DCT quantization mechanism into the formulation for image enhancement, we propose a new sparsity-based convex programming approach for joint quantization noise removal and enhancement.  Experimental results demonstrate significant performance gains of the new approach over existing enhancement methods.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)


title: Fast Head-and-shoulder Segmentation

subject:
head-and-shoulder
segmentation
learning-based
dynamic programming

abstract:
Many tasks of visual computing and communications such as object recognition, matting, compression, etc., need to extract and encode the outer boundary of the object in a digital image or video. In this thesis, we focus on a particular video segmentation task and propose an efficient method for head-and-shoulder of humans through video frames. The key innovations for our work are as follows: (1) a novel head descriptor in polar coordinate is proposed, which can characterize intrinsic head object well and make it easy for computer to process, classify
and recognize. (2) a learning-based method is proposed to provide highly precise and robust head-and-shoulder segmentation results in applications where the head-and-shoulder object in the question is a known prior and the background is too complex. The efficacy of our method is
demonstrated on a number of challenging experiments.

abstract: Thesis

abstract: Master of Applied Science (MASc)