title: Cost Optimization of Modular Data Centers

contributor:
Puri, Ishwar K.
Mechanical Engineering

subject:
Data Center
Design

abstract: During the past two decades, the increasing demand for digital telecommunications, data storage and data processing coupled with simultaneous advances in computer and electronic technology have resulted in a dramatic growth rate in the data center (DC) industry. It has been estimated that almost 2% of US total energy consumption and 1.5% of worlds total power consumption is by DCs. With the fossil fuels and earth’s natural energy sources depleting every day, greater efforts have to be made to save energy and improve efficiencies. As yet, most of the DCs are highly inefficient in energy usage. A significant part of this inherent inefficiency comes from poor design and rudimentary operation of current DCs. Thus, there is an urgent need to optimize the power consumption of DCs. This has led to the advent of modular DCs, newer scalable DC architectures, that reduces cost and increases efficiency by eliminating overdesign and allowing for scalable growth. This concept has been particularly appealing for small businesses who find it difficult to commit to setting up a traditional DC with huge upfront capital investment. However, their adoption and implementation is still limited because of a systematic approach of quickly identifying a module DC design. Considering many different choices for subcomponents, such as cooling systems, enclosures and power systems, this is a non-trivial exercise, especially, considering the complex multiphysics interactions among components that drive system efficiency. For designing such DCs, there is no research available. Therefore, most of the time, the engineers and designers rely on experience, to avoid lengthy elaborate engineering analysis, particularly during the conception stages of a DC deployment project. Here, we are developing a design tool that will not only optimize the design of modular DCs but also make the design process much faster than manually done by engineers. One of the major problem in designing modular DCs is finding optimum placement of the cooling unit to keep the temperature under ASHRAE guidelines (recommended safe temperature threshold). In addition to finding the optimum selection and placement of the cooling units and its auxiliary components, the tool also gives an optimum design for the power connection to the cooling units and IT racks with redundancy. Also, a bill of materials and key performance index (KPI) for those designs are generated by the tool. Overall, this tool in the hands of the bidders or sales representatives can significantly increase their chance of winning the project.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: A Comparison of Zinc and Cadmium Uptake Via the Intestinal Tract of Rainbow Trout

contributor:
McDonald, D. Gordon
Biology

subject: absorption and distribution of metals, gut tissues

abstract:
The absorption and distribution of metals via the gut of fish is not well known.
Consequently, the aim of the present study was to describe the movement of metals along
the gut, their absorption and binding to gut tissues, and their distribution to the internal
tissues following model dietary exposure. Two different approaches were employed, an
in vivo gastric dosing procedure, and an in vitro gut bag protocol and two different metals
were studied: an essential metal, zinc, and a non-essential (and more toxic) metal,
cadmium.
The dietary uptake and distribution of zinc and cadmium to 0.3 kg rainbow trout
(Oncorhynchus mykiss) was examined at l5°C at 1, 2, 3, or 7 days following a single
bolus dose to the stomach of 0.5 mM of radio labelled metaL After exposure, all internal
organs and the remaining carcass were individually counted for radioactivity. Uptake,
distribution and excretion of both zinc and cadmium was rapid, occurring largely within
the first 24 h of exposure. By 24 h, fish exposed to Zn had absorbed 20.0% of the dose,
21.0% was bound in the gastrointestinal tissues and the remainder was either excreted
(38.1 %) or was present in the gut lumen (20.9%). Cadmium showed a much different
pattern of uptake, with only 2.9% of the dose absorbed after 24 h, and the remainder
found either in the gut tissue (30.2%) and the lumen (19.0%) or excreted (47.9%). Over
the following six days, very little uptake and internal metal redistribution occurred.When exposed to higher doses of metal in vivo (0.5 - 50 mM), there were distinct
differences in the handling of the two metals. Zinc concentrations in the gut tissues
continued to rise at higher doses until apparent saturation. In contrast, gut tissues were
saturated with cadmium at the lowest dose employed (0.5 mM). Both metals bound most
avidly to the distal intestine but all gut tissues had a higher binding capacity for zinc, as
compared to cadmium. Target tissues (liver, gills, kidney) all saturated with zinc at high
doses. In contrast, cadmium concentrations in these tissues continued to rise in a linear
fashion with increasing dose.
In vitro studies revealed that the most important region of the gut for metal uptake
in rainbow trout was the mid-intestine. Studies using the metabolic uncoupler, 2,4-DNP,
suggested that the transfer of both zinc and cadmium across intestinal cells was passive at
the brush border membrane, but was at least partly dependent on A TP for movement
across the basolateral membrane. Furthermore, this transport mechanism was not shared
by calcium, as the presence of calcium had no inhibitory effect on the transport of either
metal.
Mucus within the intestinal lumen appears to have a higher binding affinity but
lower capacity for cadmium than zinc. Calcium did not displace cadmium from the
mucus layer. In contrast, zinc was displaced by an equimolar exposure to calcium in the
medium. Gut mucus apparently impedes the movement of metals along the intestine
with the extent of the delay likely being related to the binding affinity of the metal. The
impediment was greatest for cadmium, as 10% of the metal remained in the lumen of fish exposed in vivo, after a period of7 days. In contrast, only 2% ofthe original dose of zinc
remained in the gut lumen after only 3 days.

abstract: Thesis

abstract: Master of Science (MSc)


title: The Consequences of Pulsed DC Electrofishing and Air Exposure on Rainbow Trout

title: Consequences of Electrofishing and Air Exposure on Trout

contributor:
McDonald, D. G.
Biology

subject:
DC electrofishing
trout

abstract:
Electrofishing, which is widely used for fish collection, is a procedure that is often followed by handling and air exposure before the fish are released. Although the consequences of electrofishing are not fully known, some studies suggest that physical damage such as skeletal injury and mortality can result. Physiological disturbances resulting from stimulation of the stress axis and impaired ventilation have also been reported following electroshock. In the present study, rainbow trout treated with pulsed DC electroshock, in fact, showed no evidence of direct mortality, and skeletal damage was only induced under the most severe conditions. Physiological disturbances in the absence of physical damage consisted of a lactacidosis and stimulation of the stress response. The lactacidosis was likely induced by tetany during immobilization and impaired ventilation during immobilization and early recovery. These disturbances, which persisted for at least 4h, were greater than those reported following DC electrofishing. They were, in fact, similar in magnitude and duration to 2-3 min bout of exhaustive exercise. Swim performance following pulsed DC electroshock was also impaired for at least 1 h. If fish were air exposed immediately following pulsed DC electroshock the stress response and lactacidosis tended to be more severe
and swim performance was further impaired.

abstract: Thesis

abstract: Master of Science (MSc)


title: Regulation of Human Platelet Cyclic Nucleotides and Platelet Aggregation by cGMP-Stimulated Phosphodiesterase

contributor:
Haslam, R. J.
Biochemistry

subject: platelet nucleotides cGMP Phosphodiesterase

abstract: Cyclic nucleotides are important inhibitory regulators of platelet function. These second messengers are hydrolysed by cyclic 3' ,5'-nucleotide phosphodiesterases (PDEs). Three PDEs have been detected in human platelets: cGMP-stimulated phosphodiesterase (PDE2), cGMP-inhibited phosphodiesterase (PDE3), and cGMP-binding, cGMP-selective phosphodiesterase (PDE5). This research investigates the contribution of PDE2 to the regulation of platelet cyclic nucleotide concentrations, and the effects that PDE2 activity has on the inhibition by cAMP and cGMP of platelet aggregation in response to thrombin or collagen. Increases in platelet cAMP were initiated by stimulation of adenylyl cyclase with prostacyclin (PGI₂), whereas the accumulation of cGMP was induced by nitroprusside (NP). The contributions of PDE2 to the hydrolysis of these cyclic nucleotides were evaluated using a novel inhibitor of the enzyme, 𝘦𝘳𝘺𝘵𝘩𝘳𝘰-9-(2-hydroxy-3-nonyl)adenine (EHNA). Before EHNA was used in experiments on platelet function, its effects on partially purified preparations of the three platelet PDEs were studied. These investigations demonstrated that EHNA is a selective and potent inhibitor of platelet PDE2, and indicated that this compound is a more effective inhibitor of cAMP hydrolysis in the presence than in the absence of cGMP. To measure changes in cyclic nucleotide concentrations, platelets were preincubated with [³H]adenine and ³H]guanine to label the metabolic nucleotide pools. NP caused large concentration-dependent increases in platelet [³H] cGMP levels, and this was associated with highly significant but much smaller increases in [³H] cAMP accumulation, which were optimal with 10 μM NP. Higher concentrations of NP had much less effect on platelet [³H] cAMP. A previous study had shown that the increases in platelet cAMP caused by NP were attributable to the inhibition of PDE3 by cGMP (Maurice and Haslam, 1990a), but the inhibitory component observed with high concentrations of NP had not been explained. The present research showed that the accumulation of cAMP and cGMP induced by high NP concentrations is enhanced by EHNA, and so provides the first demonstration that PDE2 activity restricts NP-induced cyclic nucleotide accumulation. To assess whether these changes in platelet cyclic nucleotide levels were important, platelet aggregation in response to thrombin and collagen was monitored. In these studies, EHNA markedly increased the inhibitory action of NP on platelet aggregation. All the effects of NP on cyclic nucleotide accumulation and on platelet aggregation were blocked by a guanylyl cyclase inhibitor, 1𝘏-[1,2,4] oxadiazolo [4,3-α] quinoxalin-1-one, confirming that NP acts solely through activation of this enzyme and that the increases in cAMP are secondary to cGMP formation. However, experiments with the adenylyl cyclase inhibitor, 2',5'-dideoxyadenosine, which diminished the accumulation of cAMP but not that of cGMP, indicated that the inhibition of platelet aggregation is more closely correlated with the increases in cAMP than with those in cGMP. In experiments in which platelet PDE3 was selectively blocked by lixazinone, the accumulation of [³H]cAMP was greatly increased and a corresponding inhibition of thrombin-induced platelet aggregation was observed. Both of these effects were greatly diminished when PDE2 was stimulated by NP (or cGMP). This research demonstrates for the first time that activation of PDE2 by cGMP has marked effects on platelet function, restricting the inhibition of platelet aggregation by agents that increase platelet cAMP. To investigate the importance of PDE2 in regulating different platelet cAMP levels, the effects of EHNA were studied in the presence of 1 or 20 nM PGI₂. Whereas no significant increase in cAMP accumulation was caused by EHNA in the presence of 1 nM PGI₂, at the higher PGI₂ concentration a marked increase was detected when PDE2 was inhibited. NP potentiated the increase in cAMP seen with low PGI₂ but inhibited that seen with a high PGI₂ concentration, indicating a shift in the relative importance of PDE3 and PDE2 as platelet cAMP was increased. These studies show that in the presence of a high concentration of cAMP alone, or of regulatory cGMP, PDE2 makes a major contribution to the hydrolysis of platelet cAMP. Moreover, the results suggest that PDE2 inhibitors could be of value in the therapeutic modification of platelet responses.

abstract: Thesis

abstract: Master of Science (MSc)


title: Sire Behaviour in the Context of Novel Males: The Sire Protection Effect

contributor:
deCatanzaro, Denys
Psychology

subject: female mammals, pregnancy failure, various stimuli, female mice, Bruce effect,sire protection effect

abstract:
Female mammals are known to exhibit pregnancy failure when exposed to
various stimuli during the implantation phase of pregnancy. When newly inseminated
female mice are exposed to novel males in the absence of the sire, implantation is
disrupted. This phenomenon is known as the Bruce effect. When females are exposed to
novel males in the presence of the sire, pregnancy failure does not occur. This latter
effect has been referred to as the sire protection effect. In these studies we examine the
nature of female and sire behaviour in the context of novel males. Female interactions
with novel males significantly decrease in the presence of the sire. This reduction in
female-novel male interaction in seen irrespective of whether sires are free or confined
within the female's cage. Novel-male exposed females exhibit pregnancy failure and this
pregnancy block is removed when either free of corral-confined sires remain present in
the cage. Finally, sires are highly motivated to engage in aggressive conflicts with novel
males both in the presence and absence of the pregnant female. Sires were observed to
behave aggressively towards novel males through a wire-mesh grid and in this context
were able to inflict severe wounding upon novel males through the wire-mesh partition.
In a direct exposure paradigm, sires were also witnessed to exhibit this aggression and
were found to initiate and win all conflicts with novel males.
The sire protection affect is likely to involve a complex of both pheromonal and
behavioural cues. Sire aggression towards novel males, pheromonal communication and
limited behavioural interaction between the sire and the female, and reduced femalenovel
male interaction are all likely components of the effect.

abstract: Thesis

abstract: Master of Science (MSc)


title: The Study of Ctp:Glycerol 3-Phosphate Cytidylyltransferase (Tard) From Staphylococcus Aureas

contributor:
Brown, Eric D.
Biochemistry

subject: nucleotide, byosynthesis, homogeneity

abstract:
The CTP:glycerol3-phosphate cytidylyltransferase (TarD) from Staphylococcus
aureus catalyzes the formation of the nucleotide activated form of glycerol 3-phosphate
(CDP-glycerol) used in the construction ofteichoic acid, a structure shown to be essential
in Bacillis subtilis 168. The CTP:glycerol 3-phosphate cytidylyltransferase from B.
subtilis 168 (TagD) involved in teichioc acid biosynthesis has high sequence identity (69
%) and similarity (86 %) to TarD and its characterization has been well documented. In
these studies, TagD was shown to carry out the CTP:glycerol 3-phosphate
cytidylyltransferase reaction via a random mechanism where there is negative
cooperativity in the binding of substrates but not in catalysis. The work described here
illustrates that the kinetic reaction mechanism for TarD is vastly different from TagD in
spite of their high sequence similarity. Recombinant TarD was over-expressed in
Escherichia coli and purified to homogeneity. Steady state hi-substrate experiments were
performed utilizing a high-performance liquid chromatography assay in order to deduce
the kinetic mechanism for TarD. In this analysis, data were globally best fit to the model
that describes the formation of a ternary complex of substrates (CTP and glycerol 3-
phosphate) and enzyme before catalysis. This examination yielded Km values for CTP
and glycerol 3-phosphate of 21 ± 4.1 ).lM and 36 ± 5.8 ).lM respectively, while the kcat
was measured to be 2.6 ± 0.2 s -I. From the pattern observed in product inhibition studies,
a classic ordered Bi Bi reaction mechanism was inferred where glycerol 3-phosphate is
the initial substrate to bind followed by CTP and the release ofCDP-glycerol precedes the release of pyrophosphate. A Keq of 16 ± 15 was calculated using data obtained from
exploring the kinetic parameters of the reverse reaction where data was also fit to the
equation that describes the formation of a ternary complex before catalysis. The
equilibrium constant was also determined experimentally to be 6. To illustrate the
biological role ofTarD with respect to TagD, the integration plasmid, pSWEET, was
used to introduce a copy of tarD, under xylose control, into the chromosome of a strain of
B. subtilis 168 possessing a temperature sensitive mutation (tag-12) mapped to tagD.
Successful complementation of the temperature sensitive mutant by tarD at the restrictive
temperature indicated that despite their apparent uniqueness in kinetic mechanism, TarD
and TagD have similar roles in vivo.

abstract: Thesis

abstract: Master of Science (MSc)


title: The diversity of soil yeast in Cameroon and Saudi Arabia

contributor:
Xu, Jianping
Biology

subject: Yeast diversity

abstract:
Yeasts are unicellular microorganisms that belong to the kingdom of fungi. Yeasts are found in a diverse range of habitats, including soil, sugar-rich surfaces on the fruit and flowers of plants, and on the surface of plants and animals. Yeast plays an important role in soil by participating in nutrient cycles and
mineralization processes. In contrast to the various studies investigating soil yeasts in Western countries, there is a dearth of research investigating soil yeasts in Africa and the Middle East. In these projects, we
collected 493 soil samples from nine different geographical locations in Cameroon, and 562 soil samples from six geographical locations in Saudi Arabia. I identified yeast isolates by using the culture-based method and the fungal barcode sequence at the ITS region. In addition, the yeast species were analyzed
using PCR- fingerprinting to investigate the genetic variation among strains within the same species. In sum, we have isolated and identified a total of 110 yeast isolates from Cameroon as well as a total of 114 yeast isolates from Saudi Arabia. Our results showed that soil samples from different regions in Cameroon had different yeast colonization (0%-56%), with the highest found in northwest Cameroon. The Saudi
Arabian yeast isolation was different from those in Cameroon, with less diversity; the isolation rate ranged from 0.7 to 40.2 %, with the highest found in western Saudi Arabia. PCR-fingerprinting results suggested
that yeast migration was common among the geographic regions within each country. However, local climatic conditions can significantly impact yeast diversity at the local and continental levels.

abstract: Thesis

abstract: Master of Science (MSc)

abstract:
Yeasts are single-celled microorganisms that are widely dispersed in a wide variety of natural and human-related habitats such as plant leaves, flowers, fruits, water, and soil. Yeast is probably one of the earliest domesticated organisms; people have used yeast for fermentation and baking through much of the recorded human history. My project focused on studying yeast diversity in two geographically distinct countries, Cameroon and Saudi Arabia, in the context of environmental factors such as climate conditions and pH. I identified yeast present in soil samples morphologically, sequenced them at the ITS locus, and determined
the genetic variation among isolates within individual yeast species using PCR fingerprinting. The analysis revealed differences in yeast species distribution and in yeast genotypic diversity among the analyzed geographic regions. These results suggest that Cameroon and Saudi Arabia contain significant novel yeast
diversity.


title: The Relationship Between Bone and Muscle Measures in Elite Adolescent Male Cross-Country Skiers Compared to Normally Active Matched Controls

contributor:
Blimkie, Cameron J.R
Kinesiology

subject: osteogenic effects, density, radius, tomography

abstract:
Exercise associated muscle induced bone strain has potential osteogenic effects that may
increase skeletal density, bone cross-sectional area and structural strength. Whether the
effects of exercise and the muscle-bone relation are similar in weight bearing and nonweight
bearing bones remains to be determined. This study compared bone density,
geometry and biomechanical properties, and bone and muscle cross-sectional areas of 13
elite adolescent male cross-country skiers with height, weight, age and maturity matched
non-athletic controls. Total bone mineral density (BMDror), and trabecular bone mineral
density and total bone cross-sectional area (CSAror) were measured at the distal 4% of
the radius (DR) of the dominant (D) and non-dominant (ND) arms, and tibia (DT) using
peripheral quantitative computed tomography (pQCT); BMDror, CSAror, cortical BMD,
cortical thickness (CrtTH) and area (CSAcoRr), stress-strain index polar, x, y, polar
moment of inertia, axial moment of inertia, and muscle cross-sectional area (mCSA) were
measured at the 66% length of the proximal tibia (PT) and proximal radius (PR) of the D
and ND arms. Whole body BMD, whole body bone area, and hip areal bone mineral
density were measured using dual energy X-ray absorptiometry (DXA). Speed of sound
along the bone was measured using quantitative ultrasound (QUS) at the 1/3 DR and PT.
There were no differences between the skiers and controls for any of the descriptive
measures, however, there was a trend (p=0.06) for skiers to have lower percent body fat
than controls. There were no differences between skiers and controls for the bone
outcome measures using pQCT, DXA or QUS, except for CrtTH at the PT which was
significantly higher in skiers (5.42±0.25mm, p=0.03) than controls (5.18±0.28mm).
Cross-country skiers had increased CrtTH at the PT suggesting little differential effect of
mechanical loading on bone density, geometry or biomechanical properties associated
with skiing.

abstract: Thesis

abstract: Master of Science in Kinesiology


title: The Influence of Demonstrator Quality on The Social Transmission of Food Preference in the Norway Rat (Rattus norvegicus)

contributor:
Galef, B.G
Psychology

subject: observer rat,demonstrator, flavoured food, social transmission, relatives

abstract:
An observer rat that interacts with a conspecific, a demonstrator that has eaten a
flavoured food, is subsequently more likely to eat that food than an alternative, novel food
(Galef & Wigmore, 1983). In the first part of this thesis, four experiments were
undertaken to determine the influence of unreliable demonstrators on observer food
preference. In the first three experiments, observers were poisoned after interaction with
demonstrators; a demonstrator that demonstrated a food that led to poisoning was
considered an unreliable demonstrator. The first experiment compared the influence of an
unreliable demonstrator and an unfamiliar demonstrator on observers' food preferences.
Experiment 2 compared the influence of demonstration from an unreliable conspecific and
a familiar conspecific that had only provided irrelevant information. The third experiment
compared the influence of an unreliable and a reliable demonstrator. Experiment 4
compared the influence for protein-deficient observers of a demonstrator that had
previously demonstrated a protein-deficient diet and a demonstrator that was unfamiliar.
None of the first four experiments showed a significant difference in effectiveness of social
transmission due to demonstrator quality.
In the second part of the thesis I investigated the influence of familiarity on
demonstrator effectiveness. In Experiment 5, the influence of local sisters was compared with that of unfamiliar non-relatives as demonstrators. Sisters were not better
demonstrators than unfamiliar non-relatives.

abstract: Thesis

abstract: Master of Science (MSc)


title: Joint Routing and Resource Management for Multicasting Multiple Description Encoded Traffic in Wireless Mesh Networks

contributor:
Zhao, Dongmei
Electrical and Computer Engineering

subject:
Multiple Description Coding
routing
Wireless mesh networks
power

abstract:
This thesis studies multicasting high bandwidth media traffic in wireless mesh networks (WMNs). Traditional multicast methods use a single multicast tree to reach all destinations, and adapt the multicast rate to the destination with the worst path quality. This approach does not fully utilize the network resources nor distinguish the quality of service (QoS) requirements of different users. It also penalizes the users having better path quality and requiring higher QoS. In multi-hop transmissions, the end-to-end transmission rate is limited by the link with the worst transmission conditions. This makes it difficult to multicast high-bandwidth media traffic with good quality. Using multiple description coding (MDC), the source traffic can be split into multiple sub-streams, referred to as descriptions, each of which requires a much lower bandwidth and can be transmitted along separate paths. In this thesis, we study routing and QoS provisioning jointly for multicasting multiple description (MD) encoded media traffic in WMNs. Routing for the multiple descriptions is jointly studied, while considering the channel quality of different links in the network and QoS at individual destinations. The work in this thesis is divided into two parts.

The first part (Chapters 3 and 4) considers balanced descriptions, each of which contributes equally to the quality of the recovered media at a destination, and we study the problem of power efficient multicasting for the MD-encoded media traffic in WMNs. In Chapter 3, single-hop transmissions are considered. That is, the access points (APs) that store the source traffic communicate with the destination nodes directly. We study two problems jointly, description assignments and power allocations. The former is to assign a description for each AP to transmit, and the latter is to allocate the transmission power for the APs. Different power efficiency objectives are considered, subject to satisfying the QoS requirements of the destination nodes. For each objective, an optimization problem is formulated and heuristic solutions are proposed. Chapter 4 extends the work to multi-hop transmissions, where relay stations (RSs) are available to forward the traffic from the APs to the destinations. We consider two different routing structures based on whether an RS is allowed to forward more than one description. The objective is to minimize the total transmission power of the APs and the RSs in the network, subject to the QoS requirements of the destinations. An optimum problem is formulated and then translated to an integer and linear programming problem, and a centralized scheme with much lower complexity is proposed. Following that, a distributed scheme, referred to as minimum weight k-path scheme, is proposed, which builds one multicast tree for each description. By permitting only neighboring nodes to exchange related information, the scheme allows each node to find its best parent node based on the additional transmission power needed to establish the link.

The second part (Chapter 5) of the thesis considers unbalanced descriptions. Routing for the multiple descriptions is jointly considered with application layer performance,  so that the maximum distortion of recovered media at the destinations is minimized. An optimization problem is first formulated, and a centralized scheme with lower complexity is proposed. The centralized scheme first finds a set of candidate paths for each destination based on a predefined set of criteria, then it iteratively expands the multicast trees by only merging the paths that minimize the maximum distortion for all destinations. A distributed scheme is also proposed by modifying the minimum weight k-path scheme. In the modified scheme, each RS makes a local decision to join different multicast trees based on the expected distortion among its connected downstream nodes. The proposed multicasting schemes require much lower implementation complexity, compared to the optimum solutions. The centralized scheme is more suitable for small size networks, and achieves close-to-optimum performance for a wide range of parameter settings. The distributed scheme only requires neighboring nodes to exchange information, and can be implemented to  networks with a relatively large number of APs, RSs, and destination nodes.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Three Essays in Health Economics

contributor:
DeCicca, Philip
Economics

subject:
Infant Health
Defensive Medicine

abstract:
This thesis focuses on infant and maternal health through the examination of different government regulated policy interventions.  Specifically, this thesis comprises of three essays.  First, I examine the effect of a reduction in coal-fired power plant emissions on infant health outcomes of downwind counties.  Second, I analyze how limiting lawyers’ contingency fees affects physicians’ decision to perform C-sections on women and, ultimately, its effect on infant mortality.  The third, and final, paper investigates whether or not medical malpractice tort reforms have altered physicians’ decision to take part in defensive medicine.
     Chapter 1 examines the Clean Air Interstate Rule (CAIR) which mandated the reduction of power plant emissions in the eastern United States. This policy improved air quality in neighbouring downwind counties, greatly reducing exposure to a specific form of pollution—fine particulate matter.  I investigate the impact of this reduction exposure on birth outcomes using data from the U.S. Natality Detail Files. I find that female babies experience improvements in premature birth and low/very low birth weight status which are driven by the reduction in prematurity. I also focus on full-term babies to better isolate the impact of prematurity from fetal growth on birth weight.  Consistent with recent work, I find that full-term male babies experience an increase in birth weight, demonstrating an improvement in intrauterine growth due to lower exposure to fine particulates.  Finally, I find a reduction in infant mortality for babies whose mothers were categorized as “high-risk” pregnancies, suggesting that reduced exposure may lead to improved birth outcomes among those most at risk.
     Chapter 2 analyzes a limit on contingency fees for lawyers in medical malpractice cases enacted in Nevada.  Generally, such limits are thought to change the composition of liability cases as they induce lawyers to drop more frivolous cases in favour of ones involving death and serious injury. Inadvertently, obstetricians faced a greater fear of litigation. Applying synthetic control methods, I find a 2.8 percentage point increase in the C-section rates of high school dropout patients, translating to a ten percent increase after the reform. There is no statistically significant difference in C-section rates after the enactment of the reform on patients with at least a college degree, and further, no statistically significant effect on infant mortality.  Limiting contingency fees in medical malpractice cases induces obstetricians to engage in defensive medicine by performing more C-sections on low income patients, illustrating that tort reform can alter physician procedural patterns, albeit in heterogeneous ways.
     Chapter 3 continues with the theme of government regulated policy intervention by examining the effects of medical malpractice tort reform on maternal and infant health.  Numerous papers examined the effects of tort reforms on physician behaviour using data from the 1990s. However, a medical malpractice “crisis” in the early 21st century saw many US states adopt tort reforms to alleviate this issue.  Using data from 1995 to 2012 I observe that tort reforms are not as effective as they once were.  However, I find evidence that physicians’ procedural choices are affected by tort reforms.  Not only are C-section rates and “preventable” complications affected by tort reforms, but I also observe that tort reforms influence physicians’ decisions with non-risky patients.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Isolation of y-Aminobutyrate (GABA) Utilizing Mutant Strains and Characterization of Factors Sufficient for GABA Utilization as a Carbon and Nitrogen Source

contributor:
Schellhorn, H. E.
Biology

subject:
GABA
carbon
nitrogen
mutant strains

abstract: We have previously found that the 𝘨𝘢𝘣 operon of 𝘌𝘴𝘤𝘩𝘦𝘳𝘪𝘤𝘩𝘪𝘢 𝘤𝘰𝘭𝘪 is RpoS regulated suggesting that it plays an important role during stationary phase growth. The specific role of the 𝘨𝘢𝘣 operon is metabolism of γ-aminobutyrate (GABA). GABA, a four carbon amino acid, is the product of the glutamate decarboxylase reaction in 𝘌. 𝘤𝘰𝘭𝘪 and can serve as a source of carbon and nitrogen for members of the 𝘌𝘯𝘵𝘦𝘳𝘰𝘣𝘢𝘤𝘵𝘦𝘳𝘪𝘢𝘤𝘦𝘢𝘦. Interestingly, we found that we could isolate GABA utilizing mutants even when they carried mutations that were predicted to abolish gab function. However, we were only able to isolate GABA utilizing mutants in the 𝘳𝘱𝘰𝘚⁺ background. This suggests two additional features of GABA metabolism in 𝘌. 𝘤𝘰𝘭𝘪. One, that the 𝘨𝘢𝘣 operon in 𝘌𝘴𝘤𝘩𝘦𝘳𝘪𝘤𝘩𝘪𝘢 𝘤𝘰𝘭𝘪 is indeed dispensable for GABA utilization. Secondly, other RpoS regulated functions, independent of 𝘨𝘢𝘣-encoded functions, may allow the cell to metabolize GABA Finally, we have also investigated the inducing effects of GABA on 𝘨𝘢𝘣 expression in minimal and rich media and the role of glutamate in osmo-tolerance and acid adaptation.

abstract: Thesis

abstract: Master of Science (MSc)


title: Acute High Density Lipoprotein Changes with Exercise at Different Intensities

contributor:
MacDougall, J. D.
Muckle, T. J.
Physical Education

subject: lipoprotein exercise

abstract: It is known that endurance-trained athletes possess higher levels of high density lipoprotein cholesterol (HDL-C) than sedentary controls, and it has been shown in previous studies that acute exercise may elevate these levels even further. The purpose of this study was to investigate the acute exercise response of the plasma HDL's and to determine if the magnitude of the acute response would be affected by the intensity of the exercise. Twelve men (19-41 yrs) ran an equivalent distance (9-12 km) on a treadmill on two separate occasions. On one occasion the exercise was performed at a speed corresponding to 60% of the subject's VO₂ max, and on the other occasion at a speed corresponding to 90% of VO₂ max. Changes in total cholesterol (TC), triglycerides (TG), HDL-C, HDL Apoprotein A (HDL-A), HDL Saturation (HDL-C/HDL-A), lactate (LA) and free fatty acids ( FFA) were measured, and all values were corrected for changes in plasma volume. There were significant increases (p<.01) in HDL-C, HDL-A, and HDL saturation with exercise at both intensities, but greater increases in HDL-C (25% vs 14%) and HDL-A (18% vs 8%) were observed with the higher intensity exercise. Plasma FFA and TG were no different between conditions, although LA concentration rose significantly during the high intensity exercise. The results indicate that increases in HDL components can occur with a relatively moderate exercise session, and that these increases are directly related to the intensity of the exercise.

abstract: Thesis

abstract: Master of Science (MSc)


title: Effects of Fluoride and of Vanadate on Secretion from Electropermeabilized Human Platelets: Relationship to the Activation of Phospholipase D and Phospholipase C

contributor:
Haslam, Richard
Biochemistry

subject: fluoride vanadate platelets phospholipase

abstract:
Platelets permeabilized by high voltage electric discharges have provided a valuable model system in which to analyse the roles of Ca²⁺ ions and guanine nucleotides in the regulation of secretion by exocytosis. In the present study, the effects of fluoride or fluoroaluminate and of vanadate or pervanadate on secretion of platelet dense granule constituents, and the roles of activation of phospholipase D (PLD), phospholipase C (PLC) and protein kinase C (PKC) in secretion, have been investigated. Electropermeabilized human platelets containing [¹⁴C]5-HT in their dense granules were suspended in a glutamate medium containing ATP and incubated for 10 min at 25°C with, variously, Ca²⁺ buffers, KF/AlCl₃, vanadate/H₂O₂, guanine nucleotides and phorbol 12-myristate 13-acetate (PMA). KF/AlCl₃, which activates heterotrimeric G proteins but not low-M, GTP-binding proteins, caused a Ca²⁺ -dependent [¹⁴C]5-HT secretion; maximal effects were obtained with 10 mM KF plus 10 μM AlCl₃ at a pCa of 6, when 53% of [¹⁴C]5-HT was released. Secretion induced by KF/AlCl₃ in the presence of Ca²⁺ correlated with
the stimulation of [3H]diacylglycerol accumulation in permeabilized platelets containing [³H]arachidonate-labelled phospholipids. KF/AlCl₃ also stimulated the phosphorylation of pleckstrin (P47) in permeabilized platelets incubated with [γ-³²P]ATP, indicating the activation of PKC. In the absence of Ca²⁺ (pCa > 9), KF/AlCl₃ caused none of the above effects. These actions of KF/AlCl₃ were attnbutable to the activation of PLC, since KF/AlCl₃ also stimulated the formation of [³H]inositol phosphates in [³H]inositol-labelled permeabilized platelets in the
presence of Ca²⁺. PLD activity, measured as the formation of[³H]phosphatidylethanol (PEt) from [³H]arachidonate-labelled phospholipids in the presence of ethanol, could not be detected after stimulation of platelets by KF/AlCl₃ in the absence or presence of Ca²⁺. However, KF/AlCl₃ inhibited the [³H]PEt formation (PLD activity) induced by GTPγS. In the absence of Ca²⁺ (pCa >9), the inhibitory effects of KF/AlCl₃ on [¹⁴C]5-HT secretion induced by GTPγS alone or GTPγS plus PMA correlated well with their inhibitory effects on [³H]PEt formation. At pCa 6, KF/AlCl₃ had only a small inhibitory effect on GTPγS-induced secretion
and inhibited GTPγS-induced PLD activity more strongly than GTPγS-induced PLC activity. These results suggest that PLD is important for Ca²⁺ -independent secretion, and that, although both PLD and PLC may play roles in Ca²⁺ -dependent secretion, PLC is likely to be the more important. In the presence of Ca²⁺, either vanadate or H₂O₂ caused concentration-dependent stimulations of [¹⁴C]5-HT secretion, [³H]DAG formation and [³H]PEt formation. At pCa 6, low concentrations of vanadate and H₂O₂, which would be expected to form pervanadate, acted synergistically to stimulate [¹⁴C]5-HT secretion, which correlated with [³H]DAG formation. However, vanadate with H₂O₂ had a biphasic effect on PLD activity that did not correlate with secretion. In addition, at pCa 6, GTPγS-induced PLD activity was abolished by vanadate with H₂O₂, whereas GTPγS-induced secretion and PLC activity were only partially inhibited. These results support the idea that both PLC and PLD are involved in the regulation of secretion but have different contributions to Ca²⁺ dependent and Ca²⁺ -independent secretion. The results are consistent with activation of platelet PLC by a heterotrimeric G protein, but suggest that different mechanisms, possibly involving a low-M, GTP-binding protein, may be involved in the regulation of PLD activity.

abstract: Thesis

abstract: Master of Science (MSc)


title: The Effect of Gymnastic Training on Bone Density in Prepubescent Females

title: Bone Density and Gymnastics

contributor:
Blimkie, C. J.
Human Biodynamics

subject: gymnastics bone density prepubescent female

abstract:
The effect of intense gymnastic training on bone mineral density was investigated in 16 elite prepubertal (9.82 ± 0.89 years) (mean ± SD) gymnasts (GYM) and 16 normoactive (9.87 ± 0.75 years) controls (CON). Pubertal status was determined according to the criteria of Tanner. Additionally the mother of each subject was recruited, and was included in all measurements as an estimate of hereditability. GYM were in elite pre-competitive or competitive programs for at least two years, and trained on average 18 hr per week. Areal bone mineral density (BMD) and body composition (%BF) was measured for the whole body, and BMD for the left hip and lumbar spine (L1-L4) by dual energy x-ray absorptiometry (DXA), and volumetric BMD for the distal
radius by peripheral QCT (pQCT). There were no significant differences between groups for age, pubertal status or body mass; however GYM were significantly shorter (129.3 ± 5.7 vs. 136.7 ± 4.4 cm; P<0.01) and leaner (15.12 + 1.95 vs. 19.58 + 4.29 %BF) than CON. In an attempt to account for inter-group height differences, areal DXA measurements were converted to apparent bone mineral density (BMAD). GYM had significantly (P<0.05) greater femoral neck (0.698 ± 0.058 vs. 0.648 + 0.064 g.cm⁻²) and trochanteric (0.616 ± 0.060 vs. 0.530 + 0.084 g.cm⁻²) BMD. Additionally GYM had significantly greater whole body (0.101 ± 0.009 vs 0.094 ± 0.007 g.cm⁻³) BMAD than CON. GYM also had significantly greater total 367.75 ± 51.61 vs 307.37 ± 27.59 mg.cm⁻³), trabecular (207.93 ± 45.35 vs 163.76 ± 31.41 mg.cm⁻³) and cortical (496.94
± 67.51 vs 429.80 ± 33.78 mg.cm⁻³) volumetric BMD than CON at the distal radius. There were no significant differences between mothers of GYM or CON for any of the variables studied. Significant daughter mother correlations existed only for lumbar spine BMD (r=0.55). These results suggest that participation in elite gymnastics prior to puberty elicits favourable whole body adaptations in bone mineral density, and also that striking regional differences are observed at the wrist, a site subjected to repetitive high impact loading during training.

abstract: Thesis

abstract: Master of Science (MSc)


title: Non-targeted metabolite profiling of leaf intercellular washing fluids reveals a novel role for dihydrocamalexic acid in the Arabidopsis age-related resistance response against Pseudomonas syringae

contributor:
Cameron, Robin K
Biology

subject:
Arabidopsis
Pseudomonas syringae
age related resistance
plant immunity
camalexin biosynthesis
plant biochemistry
metabolomics
specialized metabolism

abstract: Many economically important crop systems exhibit an Age-Related Resistance (ARR) response whereby mature plants become resistant to pathogens they were susceptible to when younger. The signaling pathways and mechanisms of ARR have not been well studied. Arabidopsis displays ARR in response to P. syringae pv tomato (Pst). Several studies provide evidence that intercellular salicylic acid (SA) accumulation is required for ARR and SA acts as a direct antimicrobial agent to limit bacterial growth and biofilm-like aggregate formation. SA accumulation mutants are ARR defective; however, a modest level of resistance is occasionally observed leading to the hypothesis that other compounds contribute to ARR as antimicrobial agents. Previous studies demonstrated that CYP71A13 (a key enzyme in indolic biosynthesis) is expressed during the ARR response. I demonstrated that CYP71A12 functionally compensated for CYP71A13 during ARR, as cyp71a12/cyp71a13-1 mutants were consistently ARR-defective compared to their respective single mutants. I demonstrated that dihydrocamalexic acid (DHCA) accumulated in intercellular washing fluids (IWFs) collected from plants during the ARR response using high resolution mass spectrometry-based profiling. DHCA was detected in IWFs collected from wild-type ARR-competent plants and, was absent in IWFs from ARR-incompetent cyp71a12/cyp71a13 mutants. In vitro DHCA antimicrobial activity against P. syringae was not observed, but exogenous infiltration of DHCA into the leaf intercellular space restored ARR in cyp71a12/cyp71a13 mutants Unlike SA which exhibits direct antimicrobial activity against P. syringae, DHCA does not and instead may affect pathogen virulence in other ways. My research provides evidence that intercellular DHCA contributes to ARR in response to P. syringae in Arabidopsis. Understanding the genes and metabolites contributing to ARR will provide useful information for future crop breeding and genetic modification that will mitigate agricultural losses due to disease.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: During Age-Related Resistance (ARR), mature plants including some crop plants become resistant to pathogens they were susceptible to when younger. How ARR works is poorly understood. My objective was to identify potential antimicrobial metabolites contributing to ARR in Arabidopsis against the bacterial pathogen Pseudomonas syringae. Genetic analyses combined with mass-spectrometry based metabolite profiling demonstrates that two cytochromes P450, CYP71A12 and CYP71A13 contribute to ARR. My research provides evidence that DHCA accumulates in the leaf intercellular space in ARR-competent plants, where it may act to inhibit the bacterial infection process. DHCA has low antimicrobial activity against P. syringae suggesting its mechanism of action is not directly antimicrobial. Importantly, application of DHCA to the leaf intercellular space of cyp71a12/cyp71a13 restored ARR, confirming that DHCA contributes to ARR in Arabidopsis. Understanding ARR will provide useful information for future crop breeding and genetic modification that will mitigate agricultural losses due to disease.


title: THE INFLUENCE OF ESTROGEN AND SPRINT INTERVAL EXERCISE ON BRACHIAL ARTERY ENDOTHELIAL FUNCTION IN HEALTHY ADULTS

title: FACTORS INFLUENCING ENDOTHELIAL FUNCTION

contributor:
MacDonald, Maureen
Kinesiology

subject:
arteries
endothelial function
flow-mediated dilation
sex hormones
estrogen
exercise
interval training

abstract: Endothelium-dependent vasodilation is an important marker of vascular function. Brachial artery flow-mediated dilation (FMD) is a noninvasive assessment of peripheral artery endothelial function that is associated with coronary artery endothelial function and is an index of cardiovascular health. This thesis sought to investigate factors that may influence the brachial artery FMD response in humans, particularly the sex hormone estrogen and low-volume sprint interval training (SIT). We first demonstrated the intra-individual consistency of the FMD response pattern in healthy young adults and introduced visual data screening as a tool for improving data accuracy. Having established best practices for FMD data analysis, we investigated the brachial artery FMD response in adults with different estrogen profiles: men, premenopausal women with a natural menstrual cycle (NAT), and premenopausal women using combined oral contraceptive pills (OCP). Our findings suggest that estrogen does not augment FMD during high-estrogen phases of a NAT or OCP cycle compared to low-estrogen phases or to men. We also investigated the acute and chronic brachial artery FMD response to a 3x20-s low-volume SIT model. Following a single SIT session, FMD was unchanged in men or women. These findings demonstrate that estrogen does not influence endothelium-dependent dilation at rest or following intense intermittent exercise, but also suggest that low-volume SIT may be an insufficient stimulus for eliciting changes in endothelial function. This stimulus magnitude postulation was further supported by a 12-wk exercise training study, whereby vascular changes were evident following moderate-intensity continuous training but not SIT. Taken together, this work suggests that controlling for menstrual cycle phase and/or OCP use in premenopausal women may not be necessary, making it more feasible to include women as research participants, and highlights the need for future characterization of the minimum low-volume interval stimulus that evokes improvements in endothelial function in healthy young adults.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: The endothelium is the inner lining of an artery that separates it from the flowing blood. A healthy endothelium responds to increases in blood flow by producing substances that enable an artery to widen. The projects in this thesis examined whether the responsiveness, and overall function, of the endothelium in healthy young adults is enhanced by the sex hormone estrogen or by “all-out” cycling sprints, an exercise protocol that has gained appeal for its time-efficiency. We demonstrated that estrogen does not enhance endothelial function in women, compared to men, at any phase of a menstrual or birth control pill cycle. A single session or 12-weeks of the intense but brief interval exercise also does not enhance endothelial function. This work suggests it may be easier to include women in future research assessing this measure and that this particular interval exercise protocol may not enhance endothelial function in healthy adults.


title: Advances in EP and ERP signal processing

contributor:
de Bruin, Hubert
Reilly, Jim
Electrical and Computer Engineering

abstract:
Our understanding of brain function is still very limited. Much research is being conducted to further our understanding and develop new treatments, diagnostics and devices that not only could be more effective in helping us deal with neurological and psychiatric disorders and rehabilitation, but also make cognitive enhancement possible. However, none of this is possible without signal processing capabilities to extract information from electroencephalography (EEG) signals and especially event related potentials (ERPs) and evoked potentials (EPs). This thesis presents new developments in EP artifact rejection, ERP brain source localization and dynamic causal brain network estimation during an ERP.
Chapter 2 presents a new method for reducing contamination from compound muscle action potentials (CMAPs) recorded along with EEG activity during repetitive transcranial magnetic stimulation (rTMS). This development improves the visibility of short latency cortical activity as a result of rTMS.
In the application of brain source localization methods, especially beamforming, head modelling errors can cause significant performance degradation. The robust minimum variance beamformer (RMVB) developed in Chapter 3 improves beamformer performance relative to the MVB and its regularized and eigenspace variations in the face of these head modelling errors. The RMVB specifically optimizes for the worst-case estimate of the uncertainty.
Lastly, Chapter 4 describes the Adaptive Sparse ERP Tracking (ASET) algorithm for estimating dynamic and causal networks that are involved in processing ERPs. The ASET algorithm is applied to investigate the dynamics in auditory processing, specifically resulting from the β-band and its envelope.

abstract: Thesis

abstract: Doctor of Science  (PhD)


title: Radar Target-tracking and Measurement-origin Uncertainty

contributor:
Haykin, Simon
Computational Engineering and Science

subject:
Target Tracking
Filtering

abstract: Target tracking refers to the process of estimating the state of a moving object from remote and noisy measurements. In this thesis we consider the Bayesian filtering framework to perform target tracking under nonlinear models, a target moving in continuous time, and measurements that are available in discrete time intervals (known as continuous-discrete). The Bayesian filtering theory establishes the mathematical basis to obtain the posterior probability density function of the state, given the measurement history. This probability density function contains all the information required about the state of the target. It is well documented that there is no exact solution for posterior density under the models mentioned. Hence, the approximation of such density functions have been studied for over four decades. The literature demonstrates that this has led to the development of multiple filters. In target tracking, due to the remote sensing performed, an additional complication emerges. The measurements received are not always from the desired target and could have originated from unknown sources, thus making the tracking more difficult. This problem is known as a measurement origin uncertainty. Additionally to the filters, different methods have been proposed to address the measurement origin uncertainty due to its negative impact, which could cause a false track. Unfortunately, a final solution has yet to be achieved. The first proposal of this thesis is a new approximate Bayesian filter for continuous-discrete systems. The new filter is a higher accuracy version of the cubature Kalman filter. This filter is developed using a fifth-degree spherical radial cubature rule and the Ito-Taylor expansion of order 1.5 for dealing with stochastic differential equations. The second proposal is an improved version of the probabilistic data association method. The proposed method utilizes the maximum likelihood values for selecting the measurements that are used for the data association. In the first experiment, the new filter is tested in a challenging 3-dimensional turn model, demonstrating superiority over other existing filters. In a second and third experiments, the proposed data association method is tested for target tracking in a 2-dimensional scenarios under heavy measurement origin uncertainty conditions. The second and third experiments demonstrate the superiority of the proposed data association method compared to the probabilistic data association.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: THREE ESSAYS IN APPLIED ECONOMICS

contributor:
Johri, Alok
Economics

subject: Economics

abstract:
In this thesis, I apply economics analysis tools in various settings. My three essays in applied economics study the Great Trade Collapse in 2008-2009, policymaker's choice of intellectual property rights enforcement, and households' fertility decision under a cash-incentive pro-natalist policy.

            Chapter \ref{trade_collapse}, ``Financial Shocks, Supply-chain Relationships and the Great Trade Collapse'', studies the Great Trade Collapse during 2008-2009 using a two-country business cycle model enhanced with long-term supply-chain relationships. With limited resources, firms choose whether to invest in the domestic market or foreign market. In the model, firms endogenously reallocate scarce resources from international to domestic supply-chains, which are acquired and maintained at lower cost. Under a financial shock (mimicking the event of financial crisis), firms reallocate resources back home and drive the total trade to GDP ratio to fall.

            Chapter \ref{ipr}, ``Productivity, Political Economy, and Intellectual Property Rights'', examines how policymakers' political considerations lead to a sub-optimal level of intellectual property rights enforcement. Assuming stricter intellectual property rights enforcement would lead to more firms adopting frontier technology. Without any political constraint, policymakers would maximize the level of enforcement. However, due to the resistance from low productivity firms, policymakers may make a trade-off between staying in power and strict intellectual property rights enforcement, and choose a weak Intellectual Property Rights enforcement.

            My last chapter, Chapter \ref{baby_bonus}, ``Baby Bonus, Anyone? Examining Heterogeneous Responses to a Pro-Natalist Policy'', examines the heterogeneous response of having a child to a universal pro-natalist program in Quebec, using the Census Masterfile. Here, family make trade-off between having children and forgone income due to rearing child, childcare, etc. In particular, we find that mid-income households and highly-educated women responded the most. Also, the policy affects both completed fertility and birth spacing.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Three Essays in Macroeconomics

abstract: This thesis contains three chapters on topics in macroeconomics. Chapter 1 explains why unemployment is more persistent than average hours worked following a financial crisis. Chapter 2 assesses the performance of different monetary policy rules in stabilizing macroeconomic fluctuations in response to adverse financial shocks. Chapter 3 studies the links between U.S. monetary policy uncertainty and the default incentives of emerging nations' governments.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Three Essays on Modeling Asset Returns: A Nonparametric Approach

contributor:
Maheu, John
Business Administration

abstract:
This thesis examines three important topics in empirical finance: The nonparametric conditional beta, the propagation of risks between markets, and the predictability of the market return density using economics and financial variables.
First, I introduce a model that links the conditional beta to the second order conditional moments of returns. A key insight of my approach is that if the joint distribution of stock returns and market returns are correctly specified, then it follows that their contemporaneous pricing relationship is completely determined by the associated conditional distribution. The model that I propose is able to study the effects of a big shock in the market on the beta of an individual stock or a portfolio. This approach allows the beta to be a flexible function of the sign and size of the market portfolio which is absent in the finance literature. My results demonstrate that beta does depend on the market portfolio in a nonlinear manner. This carries implications for systematic risk measurement significantly different than what we have in a fixed parametric model. My model nests the Gaussian and Student-t distribution as special cases but importantly allows for deviations from the elliptic family of distributions. This includes asymmetric distributions. I extend the model to include more assets and provide a test to see if other factors are priced. My empirical results illustrate that in the event of big shocks in the market the firm's beta coefficient can go down or shoot up, depending on the market conditions (volatility).
Second, I extend the literature on the spillover effects or contagion effects that focus on the transmission of shocks through moments to spillover effects on the conditional density and seek to shed greater light on the contemporaneous information transmission between markets. The objective is to develop a joint model of returns on two different markets governed by an in infinite mixture model from which the conditional density of the first market given the returns of the other market can be derived. This enables us to study how a shock in one market influences the contemporaneous and future (one-day-ahead, one-week-ahead, and one-month ahead) conditional density of the other market. This makes it possible to explore the contemporaneous spillover effects of big shocks in one market on various features of the density of the other market such as conditional expected return, volatility, skewness and kurtosis, and value at risk.
Third, I investigate the predictability of the market return density using financial and macroeconomic variables. The objective is to develop a Bayesian nonparametric model of the distribution of market returns where the weights of the mixture change over time. Available information on financial and macroeconomic variables is employed to predict the weights of the mixture components in the predictive density of market returns over time. This permits the density of market returns to be unknown and to change over time. Moreover, the proposed model examines whether certain financial and macroeconomic variables convey any useful information about the predictive density which extends the literature on an important question in empirical finance, the predictability of market return. Using the proposed stick-breaking model, instead of focusing only on the conditional mean or variance of market return, I investigate whether these variables are useful in predicting the entire density of stock returns through predicting the time-varying weights of the mixture density. I seek to predict features of the market return density in addition to what is captured by the first and second moments. This matters in empirical distributions in finance and economics where we might have heavy tails and asymmetry. I provide evidence that these features can be of great value in applications such as asset allocation and risk management. I evaluate the incremental improvement in the predicted density of market returns statistically by the log predictive likelihood criteria and economically by a portfolio selection application.

abstract: Thesis

abstract: Doctor of Science  (PhD)


title: GRAIN GROWTH IN HIGH MANGANESE STEELS

contributor:
ZUROB, HATEM
Materials Science and Engineering

subject: Grain Growth, High Manganese Steel, Annealing Twins, Mobility

abstract:
The automotive industry, has been innovating in the field of materials development in order to meet the demand for lower emissions, improved passenger safety and performance. Despite various attempts of introducing other lightweight materials (Al, Mg or polymers) in car manufacturing, steel has remained as the material of choice till date due to its excellent adaptability to systematic upgradation and optimization in its design and processing. One of the outcomes is the development of second generation high Mn TWin Induced Plasticity (TWIP) steels with excellent strength-ductility balance suitable for automotive applications.
Cost effective high performance TWIP steel design is mostly based on its alloy design and advanced up and down stream processing methods (thermomechanical controlled processing (TMCP)) which can help achieve suitable microstructure to meet the property requirements. It has been observed that grain boundary migration (GBM) in austenite during high temperature TMCP stage dictates grain growth to control the final microstructure. This research work initially investigates the grain growth in Fe-30%Mn steel within a temperature regime of 1000-1200°C. Compared to conventional low Mn steel, austenite boundary mobility in Fe-30%Mn was found to be 1-2 orders of magnitude smaller. Atom probe tomography results showed no Mn segregation at austenite high angle grain boundaries (γ-HAGB) which rules out the effect of Mn solute drag on growth kinetics in Fe-30%Mn steels. Grain boundary character distribution (GBCD) study showed that the sample consists of two different population of grain boundaries. 50% of the grain boundaries are random HAGBs with high mobility. Remaining 50% are special in nature which introduce low mobility boundary/boundary segments in the global boundary network. The special boundaries are mostly in the form of Σ3 CSL boundaries or its variants like Σ9, Σ 27. These boundary/ boundary segments were introduced by the formation of annealing twins and their interactions with the random HAGBs. An attempt to investigate the effect of Mn on growth kinetics at 1200°C showed that Mn slows down growth kinetics up to 15 wt% predominantly by the formation of annealing twins. A qualitative study of the microstructures showed that as Mn concentration is increased from 1% to 15%, the annealing twin density increases resulting in Σ3 frequency to be 30%. The increased twinning frequency is attributed to the effect of Mn on lowering the stacking fault energy (SFE). Annealing twins, belonging to Σ3 CSL family, intersect the HAGBs resulting into twin induced boundary segments which possess very low mobility. In the light of this idea, slow grain growth in high Mn steel was attributed to the population of low mobility boundaries. The proposed ‘twin inhibited grain growth’ model clearly points to the low mobility boundary/boundary segments to be the rate controlling factor during grain growth in high Mn steels. The effect of carbon on grain growth in Fe-30%Mn steel showed that the presence of carbon makes the growth kinetics faster by a factor of 4 and 6 at 1200°C and 1100°C respectively. Although, atom probe tomography results indicated that in presence of carbon, Mn segregation takes place at γ-HAGBs in Fe-30%Mn steel, solute drag does not appear to play a role as it was seen that with increase in Mn content beyond 1%, the solute effect of Mn in slowing down HAGB migration becomes weak. Also, abovementioned higher mobility values are obtained from the growth kinetics of Fe-30Mn-0.5C. This once again highlights the fact that effect of Mn in slowing down grain growth is due to the low mobility of twin/twin related boundaries or boundary segments.
Controlling grain growth has been commonly proposed to be accomplished through small addition (<0.1%) of microalloying elements (Nb, V and Ti) which can slow down GBM at high temperature by solute drag and at low temperature by precipitate pinning (Zener drag). This research work has also experimentally quantified the solute drag of Nb in a series of Fe- 30%Mn steels. Grain boundary mobility was estimated for various temperatures and niobium contents. An attempt was made to calculate the grain boundary mobility in presence of niobium using Cahn’s solute drag model. This calculated mobility, when used in the proposed ‘twin inhibited grain growth’ model, the predicted growth kinetics which showed very good fit with the experimentally obtained growth kinetics in case of Fe-30Mn-0.03Nb and Fe-30Mn-0.05Nb steels at 1100°C. The effect of Nb solute drag, thus captured using Cahn’s model, was shown to be slowing down only the HAGB migration in the microstructure, whilst the special boundary mobility was not affected by solute Nb.
Another attempt was made through grain boundary engineering (GBE) to control grain growth in Fe-30Mn-0.5C steel. Using different TMCP schemes, GBCD was modified to produce maximum frequency of special boundary. Preliminary studies on grain growth of single step-grain boundary engineered samples did show a significant lowering of grain size compared to a no-GBE sample after grain growth. However, the effect of iterative GBE didn’t show any significant effect in controlling grain growth in spite of the fact that it increased Σ3 frequency to 64%. This probably indicates that the effect of GBE on grain growth by the formation of annealing twins/special low mobility boundaries is a complicated process which might involve twin/special boundary morphology, annihilation kinetics and formation of grain clusters in the microstructure other than the formation of immobile special triple junctions through the intersection of twins/special boundaries with the random HAGBs.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Using NMR Spectroscopy to Measure Natural Abundance ^13 C Kinetic Isotope Effects on the Acid Catalyzed and Enzymatic Hydrolysis of Methyl Glucosides

title: Natural Abundance ^13 C Kies on Glucoside Hydrolysis by NMR

contributor:
Berti, Paul
Chemistry

subject: NMR hydrolysis glucosides

abstract: Kinetic isotope effect (KIE) study of enzymatic mechanisms has the potential for aiding the design of tight binding inhibitors, but is hampered by the need for isotopically labeled substrates. Recently, however, methods for measuring ¹³C and ²H KIEs at natural abundance by NMR spectroscopy have been developed, allowing KIEs to be measured at every NMR resolvable nucleus without isotopic substitution. Until this study, this technique had yet to be applied to an enzymatic system. KIEs provide information about transition states (TS) and since enzymes tightly bind structures resembling the TS, TS analogs can be used as powerful inhibitors and potential drugs. Glycosidases are enzymes that hydrolyze the acetals of carbohydrates. Inhibition of glycosidases has a large potential for therapeutic value. Methyl glucoside hydrolysis was used as a model substrate in the measurement of natural abundance KIEs. ¹³C KIEs were successfully measured on the acid and glucosidase catalyzed hydrolysis of methyl glucosides. The values of the primary ¹³C KIEs show that hydrolysis of β-methyl glucoside by β-glucosidase a more concerted ANON reaction. KIEs on the corresponding α-anomer suggest the opposite result, a ON*AN reaction. The experimental KIEs also matched well with calculated equilibrium isotope effects, lending support for the accuracy of the measurements.

abstract: Thesis

abstract: Master of Science (MSc)


title: In Vivo X-Ray Fluorescence of Bone Lead in the Study of Human Lead Metabolism

contributor:
Chettle, D. R.
Medical Physics

subject:
x-ray
in vivo
bone
fluorescence
human
metabolism

abstract: It is well known that lead is toxic. Since the full effects, particularly of long term, low level exposure are not well understood, further knowledge of lead metabolism has significant public health implications. Traditionally, clinical studies of lead's effect on health have relied heavily on blood lead levels as an indicator of lead exposure. However, this is unsatisfactory, because blood lead levels principally reflect only recent exposure and lead in serum is more readily bioavailable than whole blood. Over 90% of the lead body burden is in bone, where it has a long residence time. Therefore, bone lead measurements are reflective of cumulative exposure. The bone lead detection system at McMaster University uses a ¹⁰⁹Cd source, which is positioned at the centre of the detector face (HPGE). This arrangement allows great flexibility, since one can sample lead in a range of different bone sites due to a robust normalization technique that eliminates the need to correct for bone geometry, thickness of overlying tissue, and other related factors. Lead in both the tibia and the calcaneus, whole blood lead, and serum lead have been measured in a group of 49 active lead workers (Nova Pb bone lead survey). Before studying the interrelationships between the above measurements, work was done to improve the programs which fit the bone lead spectra. That is, work was done to link the amplitudes of the alpha and beta peaks and to investigate the sensitivity of the analysis on the channel ranges and start parameters. The main goal of this project was to carefully study the interrelationships between the major components of any human lead metabolism model, bone, whole blood, and serum, in order to establish a solid basis for computer modelling of lead metabolism.

abstract: Thesis

abstract: Master of Science (MSc)


title: Symmetric Generalized Gaussian Multiterminal Source Coding

contributor:
Chen, Jun Jr
Electrical and Computer Engineering

subject: Gaussian source;mean squared error;multiterminal source coding;rate-distortion;reverse water-filling

abstract: Consider a generalized multiterminal source coding system, where 􏱡(l choose m) 􏱢 encoders, each m observing a distinct size-m subset of l (l ≥ 2) zero-mean unit-variance symmetrically correlated Gaussian sources with correlation coefficient ρ, compress their observation in such a way that a joint decoder can reconstruct the sources within a prescribed mean squared error distortion based on the compressed data. The optimal rate- distortion performance of this system was previously known only for the two extreme cases m = l (the centralized case) and m = 1 (the distributed case), and except when ρ = 0, the centralized system can achieve strictly lower compression rates than the distributed system under all non-trivial distortion constaints. Somewhat surprisingly, it is established in the present thesis that the optimal rate-distortion preformance of the afore-described generalized multiterminal source coding system with m ≥ 2 coincides with that of the centralized system for all distortions when ρ ≤ 0 and for distortions below an explicit positive threshold (depending on m) when ρ > 0. Moreover, when ρ > 0, the minimum achievable rate of generalized multiterminal source coding subject to an arbitrary positive distortion constraint d is shown to be within a finite gap (depending on m and d) from its centralized counterpart in the large l limit except for possibly the critical distortion d = 1 − ρ.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: The Consequences of Short Term Exercise, Various Levels of Stress and Training on Ion Regulation in Different Species of Fish

title: Effects of Exercise, Stress and Training on Ion Regulation

subject:
exercise
stress
ion regulation
fish

abstract: Initially, this study examined the mechanisms by which Na+ and Cl-are regulated in freshwater rainbow trout during exercise and stress. Aerobic exercise (~2 body lengths sec⁻¹) caused a brief increase in diffusive Na⁺ efflux (Jₒᵤₜᴺᵃ⁺) and a brief decline in plasma Na+ and Cl⁻. This disturbance was rapidly compensated by a 3 fold increase in Jᵢₙᴺᵃ⁺ and Jᵢₙᶜˡ⁻(over the first 10-12 h exercise), and by a reduction in Jₒᵤₜᴺᵃ⁺ to 40% of routine by 7 h of exercise. The compensation produced a significant increase in whole body Na⁺ while whole body Cl⁻ remained unchanged. In contrast, confinement stress (for 4 or 8 h) caused an 8 fold increase in Jₒᵤₜᴺᵃ⁺and Jₒᵤₜᶜˡ⁻ which was sustained for at least the first 5 h of stress and resulted in large decreases in whole body Na+ and Cl-. Compensation of the losses was not complete until 24 h post-stress and was achieved by increases in Jᵢₙᴺᵃ⁺ and Jᵢₙᶜˡ⁻ (of similar magnitude and timing to that of exercise) as well as reductions in Jₒᵤₜᴺᵃ⁺ and Jₒᵤₜᶜˡ⁻ to nearly zero. We conclude that Jᵢₙ increased because of an activation of inactive transport sites in the gills while Jₒᵤₜ was reduced by a reduction in branchial ionic permeability, both responses mediated hormonally. Although the hormonal control mechanisms are as yet poorly defined, we argue that growth hormone and prolactin are responsible for the Jᵢₙ and Jₒᵤₜ regulation, respectively, and rule out either cortisol or epinephrine as having any role, at least with respect to the rapid NaCI regulation evident during exercise. The ability of rainbow trout to rapidly regulate ion balance was then investigated to determine whether it is unique to rainbow trout, exists in stream-dwelling animals or whether it is wide spread in fish regardless of preferred habitat. Common shiners, considered to be an active species and smallmouth bass, considered to be less active, were the two species of comparison. Common shiners demonstrated rapid increases in Jᵢₙᴺᵃ⁺ during exercise and confinement, a lack of change in whole body Na⁺ and Cl⁻ during exercise and a large Na⁺ and Cl⁻ loss during stress. In contrast, smallmouth bass experienced minimal increases in Jᵢₙᴺᵃ⁺ during exercise and no change during stress with ion loss occurring during both exercise and stress. It was concluded that the relative ability to regulate ion balance in response to stress and exercise may reflect the frequency with which the animal experiences that challenge in its natural habitat. Consequently, common shiners probably possess a similar uptake mechanism to that of rainbow trout while the mechanisms in smallmouth bass may exist, but in attenuated form. The final analysis investigated whether or not exercise training affected the magnitude of the disturbance to Na⁺ balance produced by both acute and chronic stress. This was important in that it could be applied to the improvement of fish stocking techniques. Trained fish demonstrated the ability to reduce ion loss produced by stress despite significantly high levels of cortisol, glucose and oxygen consumption. Similar results were produced by both acute and chronic stress and it was established that the rainbow trout's ability to regulate ions during stress, without altering the release of cortisol and catecholamines was improved by training.

abstract: Thesis

abstract: Master of Science (MSc)


title: Synthesis and Properties of Polyampholytes and their Application to Cell Cryoprotection

contributor:
Stöver, Harald
Chemistry and Chemical Biology

abstract:
Polyampholytes are known as polymers comprising both cationic and anionic groups that can have pronounced isoelectric point behavior and strong responses to ionic strength, such as the anti-polyelectrolyte effect. This thesis focusses on exploring the solution properties of fully ionized random polyampholytes, their phase separation behavior, and their application in cell cryoprotection.
The reactivity ratios of different monomer pairs were measured by NMR to guide the subsequent formation of a series of polyampholytes with different charge ratios, molecular weights and compositions by free radical copolymerization with little compositional drift. The polyampholytes, comprising different ratios of N-(3-aminopropyl)methacrylamide hydrochloride (APM) and acrylic acid (AA), show phase separation at their isoelectric point, pH(I), anti-polyelectrolyte effects, and temperature responsive solubility. The latter include lower critical solution temperature (LCST) and upper critical solution temperature (UCST) behaviors, depending on composition and conditions. At the pH(I), liquid to solid phase separation is shown to be driven by a combination of electrostatic interactions and hydrogen bonding. The stoichiometric APM/AA polyampholytes with different molecular weights reveal significant molecular weight effects on polyampholyte properties, including their phase separation efficiency, anti-polyelectrolyte effect and LCST, but not their pH(I). High molecular weight polyampholytes were crosslinked into permanent hydrogels using THPC, and used to explore organic dye absorption from water.
Stoichiometric polyampholytes based on different monomers showed that the hydrophobicity of the comonomers also contributes to the polyampholyte phase separation. Depending on the balance of electrostatic interaction and polymer hydrophobicity, polyampholytes may show no phase separation, liquid to liquid, and liquid to solid phase separations. Finally, polyampholytes made from N-[3-(dimethylamino)propyl methacrylamide (DMAPMA) and acrylic acid (AA) were used as macromolecular, non-penetrating cryoprotective agents for NIH 3T3 cells. The results show that to work as cryoprotective agents the polyampholytes need to have a moderate excess of negative charge at physiological conditions, with post-thaw cell viability further improved by high MW and with presence of about 10 mol% hydrophobic comonomer. As non-penetrating cryoprotective agents, these polyampholytes show good protection of the cell membrane from interstitial ice damage and 70-80% post-thaw cell viability, by bonding on cell surfaces and phase separating around the cells upon freezing. However, the absence of intracellular protection leads to low cell attachment and growth after thawing, which can be improved by introducing as little as 2% DMSO prior to freezing. As a result, polyampholytes cryoprotective agents can significantly decrease DMSO levels required for cell cryoprotection from 10% to 2%.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Rings of Conditions of Rank 1 Spherical Varieties

contributor:
Harada, Megumi
Mathematics and Statistics

abstract: In this thesis, we define and describe the rings of conditions of rank 1 spherical homogeneous spaces G/H. A procedure for computing the ring of conditions of a spherical homogeneous space in general is not known. For the special case of rank 1 spherical homogeneous spaces, we give a proof of the unpublished result of A. Khovanskii that the ring of conditions is isomorphic to the cohomology ring of a certain compactification of G/H. We illustrate this result through the fully worked example of affine n-space minus the origin.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: We study an algebraic object that describes intersections of certain geometric spaces. An algorithm or formula for computing this object for a given geometric space is not known in general. We provide a technique for computing this algebraic object in a special case.


title: Source-Utilization Movement and the Synoptic Problem: A Study in Ancient Compositional Practice

contributor:
Runesson, Anders
Religious Studies

subject: Synoptic Problem, Synoptic Gospels, Matthew, Mark, Luke, Farrer Hypothesis, Augustinian Hypothesis, Two-Document Hypothesis, Ancient Compositional Practices

abstract:
This study concerns the composition of the Synoptic Gospels—Matthew, Mark, and Luke, and is part of a scholarly discussion within New Testament studies known as the “Synoptic Problem.”
In this study, the composition of the Gospels is considered in light of ancient compositional practice, a field of study within the Synoptic Problem that has grown in popularity in recent decades. It specifically looks at the way that Matthew and Mark and Luke would have moved through their sources or exemplars (source-utilization movement) when they composed, presuming that some sort of direction of dependence is the case. Each of the Simple Solutions is considered in this regard—the Augustinian Hypothesis, the Büsching Hypothesis, the Farrer Hypothesis, the Griesbach Hypothesis, the Lockton Hypothesis, and the Wilke Hypothesis, as well as the Two-Document Hypothesis. It may be presumed some sort of direction of dependence is the case between the Synoptic Gospels, whatever direction this might be, and the form these sources took would have likely been bookrolls (or scrolls).
The thesis introduces a neglected factor in Synoptic Problem studies. Whereas historically each Gospel text has been presumed to be a single bookroll, in this study, a multiple-bookroll hypothesis is also tested. Instead of there being one bookroll per Gospel, the possibility that each Gospel was distributed over several bookrolls is also tested. Additionally, the study takes into consideration the role of memory and memory-access of traditions in the process of composition. Several other matters concerning ancient compositional practice is also treated throughout.
When the various Hypotheses are examined in terms of how the Gospel-authors would have moved through their texts, in light of a multiple bookroll hypothesis, among other factors, the result seems to favour strongly Lukan Absolute Posteriority (i.e., the Augustinian and Farrer Hypotheses).

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: This study concerns the composition of the Synoptic Gospels—Matthew, Mark, and Luke, and is part of a scholarly discussion within New Testament studies known as the Synoptic Problem. It considers the composition of the Gospels in light of ancient compositional practice. It specifically looks at the way that Matthew and Mark and Luke would have moved through their sources or exemplars during composition (source-utilization movement), according to a number of different hypotheses. Each Gospel may be presumed to have used sources when their authors composed, and the sources would have likely been bookrolls (or scrolls). A number of Hypotheses have been presented over the last two centuries concerning how the Gospels were composed and what direction of dependence that composition took. When these various Hypotheses are examined in terms of how the Gospel-authors would have moved through their texts, the result seems to favour two possibilities above others. Both of these possibilities have it that the author of Luke was the utilizing author of both Matthew and Mark.


title: Study of Reactive Intermediates: 1. Transient Stannylenes in Solution; 2. Time-resolved Spectroscopic Studies of Di-tert-butylsilylene in Solution

contributor:
Leigh, William
Chemistry

subject: Stannylene

abstract:
The transient Sn(II) compounds dimethyl-, diphenyl-, methylphenyl-, and dimesitylstannylene (SnMe2, SnPh2, SnMePh, and SnMes2, respectively) have been successfully detected and characterized in solution. The stannylenes were generated by photolysis of appropriately substituted 1-stannacyclopent-3-ene derivatives, which have each been shown to extrude the respective stannylene cleanly, through stannylene trapping studies using dichlorodimethylstannane (Me2SnCl2) as the substrate. Quantum yields for stannylene extrusion have been measured in three cases, and found to be in the range of 0.4 - 0.8.
Laser flash photolysis of the stannacyclopent-3-ene derivatives in deoxygenated hexanes affords promptly-formed transient absorptions assigned to SnMe2 (λmax = 500 nm; λ500 = 1,800 ± 600 M-1cm-1), SnPh2 (λmax = 300, 505 nm; λ500 = 2,500 ± 600 M-1cm-1), SnMePh (λmax = 280, 500 nm) and SnMes2 (λmax < 270, 330(sh), 550 nm), which decay on the microsecond timescale with second order kinetics, consistent with dimerization being the major reaction in the absence of a substrate. Dimerization of SnMe2 and SnMes2 affords species exhibiting λmax = 465 nm and λmax = 490 nm, respectively, which were assigned to the expected Sn=Sn doubly-bonded dimers, tetramethyl- and tetramesityldistannene, respectively. In contrast, the spectrum of the dimer formed from SnPh2 exhibits strong absorptions in the 280 - 380 nm range and a very weak absorption at 650 nm, on the basis of which it is assigned to phenyl(triphenylstannyl)stannylene (SnPh(SnPh3)).
 The reaction of acetic acid (AcOH) with SnPh2 and SnMes2 proceeds via arene elimination. With SnMe2, the products are derived from the elimination of methane and O-H insertion, while SnMePh reacts to afford both benzene and methane in a ca. 3:2 molar ratio. σ-Bond insertion of SnMe2 with tributylchlorostannane (Bu3SnCl) yields the formal Sn-Cl insertion product, Bu3SnSnMe2Cl.
	Lewis acid-base complexation with simple aliphatic O, S, and N donors proceeds rapidly and reversibly, generating the corresponding stannylene-donor pairs, and exhibiting absorption maxima λmax ~ 310 - 385 nm. Equilibrium constants (Keq) upon O-donor coordination afford stabilization energies of -1.9 to -4.0 kcal mol-1 for SnMe2 and SnPh2, and suggesting a Lewis acidity order SiR2 > SnR2 > GeR2 (R = Me, Ph). Complexation of SnMes2 with O, S and N donors proceed with a reduction in reaction exergonicity relative to SnPh2. Reactions of SnMe2 and SnPh2 with Bu3SnH and C-C unsaturated compounds proceed with the characteristics of reversible complexation, affording short-lived Lewis acid-base products detectable by transient UV-vis spectroscopy (λmax = 375 - 430 nm).
	Di-tert-butylsilylene (Sit-Bu2) has also been successfully detected and characterized in solution by laser flash photolysis methods, via the photolysis of 7,7-di-tert-butyl-7-silabicyclo[4.1.0]heptane and hexa-tert-butylcyclotrisilane. This transient silylene exhibits a UV-vis absorption band centred at λmax = 515 nm and decays with second order kinetics to afford a long-lived product assigned to tetra-tert-butyldisilene (λmax = 290, 435 nm). Absolute rate constants (kQ) were determined for the reactions of Sit-Bu2 with several silylene substrates in hexanes at 25 °C. Sit-Bu2 is seen to react slower compared to SiMe2, with krel (= kQSiMe2/kQSitBu2) ranging between 0.8 - 310, cycloaddition reactions having exhibited the largest sensitivity to the tert-butyl for methyl substitution.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: A Comparative Study of the Enzymatic and Non-Enzymatic Breakdowns of the Tetrahedral Intermediate of the MurA Reaction

title: Breakdown of the MurA Tetrahedral Intermediate

subject: enzymes Mura tetrahedral

abstract: The mechanism of the non-enzymatic breakdown of the tetrahedral intermediate of MurA (a carboxyvinyl transferase) was determined in order to better understand the corresponding enzyme catalyzed reaction. The breakdown was general acid-catalyzed, with simultaneous C-O bond cleavage and protonation at the bridging oxygen of the phosphate leaving group. The carboxyl was shown to play an important role in the breakdown, with its pKₐ of 3.2 appearing in the rate 𝘷𝘦𝘳𝘴𝘶𝘴 pH profile. The product distribution varied with pH. At pH 1, the products were predominantly UDP-GIcNAc, pyruvate and phosphate. Increasing proportions of MurA ketal arising from intramolecular attack of the 4'-0H, and EP-UDP-GicNAc resulting from elimination were observed with higher pHs. The MurA ketal was structurally characterized, and shown to be analogous to the ketal formed by AroA, a related enzyme. pKₐs corresponding to those expected of phosphate monoesters (1.6 and 6.2) were found in the product distribution 𝘷𝘦𝘳𝘴𝘶𝘴 pH profile. Observation of these pKₐs supported the initial product of phosphate departure being an oxocarbenium ion-phosphate tight ion pair complex. A corresponding oxocarbenium ion intermediate in the enzymatic reaction could not be demonstrated.

abstract: Thesis

abstract: Master of Science (MSc)


title: Tetx2-A Tetracycline Inactivating Enzyme

contributor:
Wright, G. D.
Biochemistry

subject: tetracycline antibiotics enzymes

abstract: Resistance to the tetracycline antibiotics occurs primarily by efflux and ribosome protection mechanisms, however a tetracycline inactivating enzyme, TetX, was identified 15 years ago, although little is known about this mechanism. The gene encoding this enzyme was identified on a 𝘉𝘢𝘤𝘵𝘦𝘳𝘰𝘪𝘥𝘦𝘴 transposon and results from DNA sequence analysis and studies of bacterial culture media suggested that 𝘵𝘦𝘵𝘟's protein product might be a NADPH-requiring oxidase (𝘚𝘱𝘦𝘦𝘳 𝘉𝘚 𝘢𝘯𝘥 𝘚𝘢𝘭𝘺𝘦𝘳𝘴 𝘈𝘈. 𝘑 𝘉𝘢𝘤𝘵𝘦𝘳𝘪𝘢𝘭. 171(1): 148-153, 1989). We have expressed a copy of 𝘵𝘦𝘵𝘹 gene, 𝘵𝘦𝘵𝘹2, in Escherichia coli, and purified the enzyme to high purity. We showed that TetX2 is a monomeric 44 kDa cytoplasmic protein and UV-Vis and HPLC studies established that TetX contained an FAD cofactor. Continuous and stopped enzyme assays have been developed and established that that the enzyme requires 0₂ and NADPH for tetracycline degradation. Liquid chromatographic mass spectrometry (LC -MS) analysis of TetX reaction products using oxytetracycline (461 Da) as a substrate indicated that the enzyme catalyses the incorporation of one oxygen atom into oxytetracycline, resulting in a compound of 477 Da with no antibiotic activity. Steady state kinetic analysis demonstrated that TetX2 has a broad substrate specificity with the capacity to inactivate several members of the tetracycline family tested. Identification of the inactivated tetracycline product revealed that the tetracycline inactivation process is a TetX2 catalyzes tetracycline oxidation reaction. These studies provide the first biochemical analysis of a tetracycline inactivating enzyme.

abstract: Thesis

abstract: Master of Science (MSc)


title: Fallen feathers in Thunder Bay: How Canada's newspapers implicate Indigenous youth

contributor:
Freeman, Bonnie
Social Work

subject: Indigenous youth, First Nations, Thunder Bay, decolonization, media, racism, discourse analysis

abstract: This study asks how the media perpetuates the cycle of racism, colonialism and stereotyping of Indigenous youth in Thunder Bay, and how Indigenous news sources participate in giving voice to Indigenous peoples. The research methodology is a discourse analysis examining both mainstream and Indigenous newspaper articles on the subject of the First Nations youth deaths in Thunder Bay. The methodology is also influenced by critical and decolonizing theories. Findings show that Indigenous newspaper articles are overall more inclusive of Indigenous voice, therefore providing an Indigenous perspective on the issue of First Nations youth dying in Thunder Bay and leaving out racist portrayals. On the other hand, non-Indigenous newspaper articles include less Indigenous voice and use the opinion of individuals in powerful positions. They also tend to portray Indigenous people in a negative light when compared to Indigenous newspapers. Outcomes from this research include implications for social workers such as: developing an understanding of how the media perpetuates racism, colonialism and stereotyping against Indigenous youth, advocating for and empowering Indigenous youth so they can come together and fight for change in First Nations education, and improving education within schools of social work regarding advocacy in the media.

abstract: Thesis

abstract: Master of Social Work (MSW)


title: Blueprint for an Embedded Researcher-led Transformation of a Large Community Hospital into a Learning Health Centre

contributor:
Thabane, Lehana
Health Research Methodology

subject:
Learning health system
embedded researcher
antimicrobial stewardship
clostridium difficile infection
integrated knowledge translation
health services research
local research

abstract:
There is a pandemic of low-value clinical care that threatens the sustainability of our publicly funded healthcare systems.  Over 30% of the health services provided to patients provide no benefit or may actually result in harm.  Health services research is needed to critically evaluate our clinical practices and programs to ensure we create systems that consistently deliver high-value care.  Unlike drug trials, health services research is complicated by enormous heterogeneity across cultures, environments, behaviours and systems.  Ideally, local research communities should devise and conduct health services research to ensure that both the research questions and outcomes are relevant to community members, and thus more likely to result in sustainable healthcare systems.
	Embedded researcher models are emerging as a viable approach to supporting local research activities.  Embedded researchers are part of the community they serve, provide research expertise to local investigators and community members, and help develop local research systems that facilitate health services research activities.  While they may still collaborate with academic partners, this is not necessary for their research success.
	This thesis documents the transformation of a large community hospital in Ontario into a learning health centre through the use of an embedded researcher model.  The first part of the thesis is focused on the results of incorporating an embedded research plan into the hospital’s new antimicrobial stewardship program.  The research that emerges from this work contributes new knowledge about the value of antimicrobial stewardship to important patient outcomes such as reduced lengths of hospital stay and rates of Clostridium difficile infections.  The thesis concludes with a discussion of the implementation of all the necessary components needed to support a learning health centre and how an embedded researcher model facilitated this transformation and could be used by any similar organization to achieve the same result.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Over 30% of the health services provided by our healthcare systems does not benefit and may actually harm patients.  Health services research is therefore a necessary activity required to reduce this waste.  In Ontario, over 65% of patients receive their acute care in large community-based hospitals, and yet, these hospitals have minimal research activity and capacity despite repeated attempts by the academic research community to engage these institutions through a variety of collaborative models such as integrated knowledge translation.  This thesis provides a blueprint for the transformation of a large community hospital into a learning health centre through the use of a locally created, locally relevant, embedded researcher model.  Starting with a proof of concept through the systematic evaluation of an antimicrobial stewardship program, the thesis ends with a ‘how to’ guide for the implementation of the foundational elements needed to support health services research in similar organizations.