title: Protein Turnover in Trained Male and Female Endurance Athletes

contributor:
Atkinson, Stephanie
Biology

subject: protein athletes

abstract: The dietary protein requirements of endurance trained athletes have been previously shown to be higher or no different than those of sedentary persons. However, the current Canadian Recommended Nutrient Intake (RNI) for protein contains no allowance for the effects of habitual physical activity. The discrepancy as to whether the protein requirements of active individuals are elevated, is probably due to: varying study designs, the different training status of the subjects, dissimilar exercise intensities, and the dietary condition of the subjects studied. In addition, previous work (Tarnopolsky, LJ et al. J. Appl. Physiol. 68(1):302-308, 1990), has shown that males may catabolize an increased amount of protein, as a result of endurance exercise, compared to females. The present study examined protein turnover in trained male (n=6) and female (n=6) endurance athletes (runners) • Athletes were selected for equal training status and conditioning and were placed on a diet, isoenergetic with their habitual intake, containing protein at the Canadian RNI. All female athletes were tested during the mid-follicular phase of their menstrual cycle. After being adapted to the diet for 10 days during which the athletes exercised according to their habitual exercise schedule, each athlete completed a three day measurement of nitrogen balance. Nitrogen balance showed that the RNI was inadequate for the female athletes (mean± SE), nitrogen balance= -0.89 ± 0.33 g N·d⁻¹ (-15.9 ± 6.0 mg N·kg⁻¹·d⁻¹), and for male athletes, nitrogen balance = -1.69 ± 0.64 g N·d⁻¹ (-26.3 ± 11.0 mg N·kg1·d⁻¹). To examine the kinetics of leucine metabolism during exercise, each subject received a primed constant intravenous infusion of L-[1-¹³C]leucine while resting for 2.0 hand then during a 90 minute treadmill run at approximately 65% of VO₂ₘₐₓ. Blood samples were taken at steady state and analyzed for ¹³CO enrichment of a-ketoisocaproic acid and expired gas samples were analyzed for ¹³CO₂ enrichment. Corrections were made for changes in background ¹³CO₂/ ¹²CO₂ and changes in bicarbonate retention factor, during exercise, were also determined. Measurements of whole-body leucine kinetics (flux, oxidation, and non-oxidative leucine disposal) were calculated using the reciprocal pool model. Exercise resulted in a significant increase (P<O. 001) in leucine oxidation in both males and females. The increase was 95% above resting in females and 84% above resting in males. Male athletes oxidized a greater amount of leucine during the infusion than female athletes (P=O. 004). Leucine flux increased significantly (P<O. 001) during exercise in both groups of athletes. The non-oxidative portion of leucine flux did not change significantly throughout the infusion in either male or female subjects. Oxidation of leucine could account for 88% of the negative nitrogen balance in the female athletes and 90% of the negative nitrogen balance in the male athletes. It is concluded that the Canadian RNI for protein is inadequate for those persons who continually engage in endurance activities. In addition, leucine oxidation during prolonged sub-maximal exercise is greater in males than females and the increase in amino acid oxidation could account for approximately 90% of the negative nitrogen balance observed in these groups of athletes. Future investigations of protein requirements for athletes should consider males and females as distinct groups.

abstract: Thesis

abstract: Master of Science (MSc)


title: Dominance and "Fall Fever": The reproductive behaviour of semi-free-ranging Male Brown Lemurs (Lemur Fulvus)

contributor:
Saunders, Shelley R.
Anthropology

subject: lemur fulvus, arboreal prosimian, Madagascar

abstract:
Lemur fulvus, the brown lemur, is a cat-sized
arboreal prosimian, native to Madagascar and the island of
Mayotte, in the Comoro Archipelago. A social prosimian,
~ fulvus typically forms cohesive troops of from 5-15
individuals. Troop composition is usually reported to be
at, or near, a 1:1 sex ratio.
The problems examined in this thesis were chosen in
order to address aspects of L. fulvus social dynamics
that are unclear, given the depiction of L. fulvus
social behaviour presented in the primate literature. What
are adult males doing, in the reported absence of
agonistically-determined dominance hierarchies, to gain and
maintain access to estrus females? Given the breeding
season behavioural changes and fluctuations exhibited by
adult males (a behavioural complex here termed,
"fall-fever"), how do these changes and fluctuations
contribute to male L. fulvus breeding opportunities,
and potential reproductive success?
These questions were investigated in the study of a
semi-free-ranging ~ fulvus troop during the 1984
(Northern Hemisphere) breeding season. Utilizing an
extensive ethogram it was found that, contrary to previous literature on the species, hierarchical social dominance
relationships are indeed present in L. fulvus social
groups. Additionally, it was found that these
relationships play a crucial role in the reproductive
behaviour of adult males.
Statistically significant variation in the
behaviour of the focal males is presented for seven
inclusive behavioural categories. The picture of male
L. fulvus reproductive behaviour that emerges from
these considerations is then compared to the view derived
from previous research on the species. Several amendments
to our understanding of ~ fulvus social behaviour are
suggested. An attempt is also made to place ~ fulvus
in the socioecological categorizations of several authors.

abstract: Thesis

abstract: Master of Arts (MA)


title: We Don’t Exist Here: The Tensions, Challenges and Erasure of Muslim Women in Social Work Education

title: We Don't Exist Here

contributor:
Greene, Saara
Social Work

subject:
Muslim
Social Work
Education
Muslim Women
Colonization
Liberalism
Erasure
Oppression
Anti-Racist Feminism
Orientalism
Islamophobia
Islam

abstract: In a field such as social work, where anti-oppressive practice is preached, it is expected that educators and the academy alike work to challenge xenophobic and Islamophobic discourse. However, this may not be the case. Using a Critical Social Science frameworks, this study explores the experience of Muslim women in social work education through a qualitative methodology. A focus group was conducted with current social work students and recent graduates to explore their experience in social work education. What emerged from the data are the signs of an academy that does not embody the values and ethics it purports to teach. Through a thematic analysis of the data, three main themes emerged: the tensions and challenges between and within social work education and Islamic knowledge and Muslim identity; the marginalization and erasure of Muslim women’s voices in social work education; and the ways that Muslim women students navigate these issues. The findings bring light to the challenges Muslim women face as a result of an academy that continuously tells them that they do not belong. Implications for theorists, educators, administrators and students are explored and recommendations are given regarding the importance of the inclusion of Muslim voices in the discourse, creating safe and inclusive spaces for Muslim students, and working collectively to address the tensions and challenges that Muslim women face in social work education.

abstract: Thesis

abstract: Master of Social Work (MSW)


title: THE PATIENT REPORTED OUTCOMES, BURDENS AND EXPERIENCES (PROBE) STUDY

contributor:
Iorio, Alfonso
Health Research Methodology

subject: patient reported outcome measures

abstract:
Outcomes measurement is an important component of routine hemophilia care, clinical trials and economic evaluations. Assessing outcomes in patients living with hemophilia is challenging due to a lack of validated outcome measures. Conventional clinical outcomes, for instance, bleeding rate, structural changes of joints or functional joint scores may be less relevant for the decision-making process. Patient reported outcomes measures has been increasingly interested in routine medical care and clinical research. However, the available validated patients reported outcome measures for patients with hemophilia are not generally implemented in routine care or clinical trials.
The Patent Reported Outcomes, Burdens, and Experiences (PROBE) study aims to develop a validated patient reported outcome measure for patients living with hemophilia. The PROBE questionnaire is organized in 4 sections, comprising 29 questions. Section I contains questions pertaining to demographic data. Section II contains questions pertaining to patient reported outcomes. Section III contains questions pertaining to hemophilia specific problems and treatments. Section IV contains the EuroQol five dimension 5-level instrument (EQ-5D-5L).
The psychometric analysis of revealed that the PROBE questionnaire has a good internal consistency (Cronbach’s alpha coefficient=0.84). PROBE items showed moderate to strong correlations with corresponding EQ-5D-5L domains. The PROBE Score has a known group validity among known groups. The psychometric properties of the PROBE questionnaire demonstrated the validity of the instrument in both patients living with hemophilia and control population (participants without bleeding disorder).
The test-retest reliability analysis demonstrated that the PROBE questionnaire has a substantial agreement when the questionnaire was repeatedly administrated. There were acceptable reliability properties between the paper-based and web-based questionnaires. The reliability properties of the PROBE questionnaire were established in both patients living with hemophilia and control population.
The PROBE questionnaire was cross-cultural implemented in 21 countries. The results showed that the regions of participant contributed a trivial variability of the PROBE score, indicating that the PROBE questionnaire is valid for assessing the health status among hemophilia patients and participants without bleeding disorder across regions.
Sexual health of patients living with hemophilia was evaluated using the PROBE questionnaire. The results showed that sexual difficulty was more prevalent in patients with hemophilia and associated with markers of disease severity. This finding warrants the sexual health assessment in routine hemophilia care.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Immunological Changes in Response to Acute Exercise, Considering Puberty and Sex

title: Immunological Changes in Response to Exercise

contributor:
Bar-or, Oded
Kinesiology

subject: exercise immunology puberty sex

abstract: This research was conducted to elucidate age-, puberty-, and sex-related effects on immunological changes in response to acute exercise. Compared with young men, 9-and 10-yr-old boys experienced smaller natural killer (NK) cell and interleukin-6 (IL-6) changes and a faster neutrophil and IL-6 recovery in response to exercise (Chapter 3). In these boys, exercise-induced neutrophil and NK cell changes were also more sensitive to carbohydrate (CHO) intake. The possible interaction of puberty and CHO intake on NK cell responses to exercise was then investigated in boys at the same chronological age (Chapter 4 ). The magnitude of change in NK cells was greatest in boys at advanced stages of puberty, and responses to CHO intake were most sensitive in prepubertal boys. To further investigate age-, puberty-, and sex-related differences in leukocyte and cytokine responses to exercise, boys and girls ages 12 and 14 were studied (Chapter 5). Neutrophil, lymphocyte, NK cell, and IL-6 responses were more pronounced in 14-yr-old versus 12-yr-old and in mid-versus early-pubertal girls. Age-and puberty-related differences in neutrophil recovery were also observed in the boys. Sex differences (girls> boys) in lymphocytes and NK cells were observed among 14-yr-old, but not 12-yr-old and among mid-, but not late-pubertal subjects. Finally, the effects of sex, menstrual phase (MP) and oral contraceptive (OC) use on leukocyte and IL-6 responses to exercise were studied in adults (Chapter 6). Compared with men, women experienced larger increases in lymphocytes, but MP did not influence immune changes. A novel observation was that OC use increased the magnitude of exercise-induced changes in leukocyte subsets. Collectively, the studies in this thesis represent the first comprehensive examination of age-, puberty-, and sex-related effects on immunological changes in response to exercise and provide the first reports of immune-related responses to CHO intake during exercise in children.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Effect of Carbohydrate and protein Ingestion During Exercise on Cycling Time Trial Performance and Metabolism in Trained MenCa

title: Carbohydrate-Protein Ingestion and Cycling Performance

contributor:
Gibala, Martin
Human Biodynamics

subject: carbohydrate protein exercise performance metabolism

abstract: Two recent studies (Ivy et al., Int J Sports Nutr Exerc Metab 13:382-395, 2003; Saunders et al., Med Sci Sports Exerc 36:1233-1238, 2004) reported dramatic (>25%) increases in endurance time to fatigue during cycling at 75-85% V0₂peak when subjects ingested a ~2% protein (PRO) plus ~7% carbohydrate (CHO) drink as compared to CHO alone. However, the research designs employed in these studies have been criticized for several reasons, including (1) the rate of CHO and fluid provided was less than what is considered optimal for endurance performance (i.e., 6% CHO, ingested at a rate of 15 g in 250 ml of fluid, every 15 min); and (2) the nature of the performance tests did not mimic the way in which athletes typically compete (i.e., a race, in which a given distance must be covered as quickly as possible). Purpose: To determine whether the addition of 2% Pro to a 6% CHO drink (CHO-Pro) improves 80 km cycling time trial performance as compared to a 6% CHO drink and a non-energetic sweetened placebo. Methods: Ten well-trained cyclists (25±5 y; V0₂peak = 63±5 ml/kg/min; means±SD) completed a simulated 80 km time trial (TT) on three separate occasions separated by 5-7 d. In a randomized, double-blind manner, subjects ingested either CHO-Pro, CHO or placebo at a rate of 250 ml every 15 min. All trials were performed on a Computrainer (RacerMate, Seattle, WA) using each subject's own bicycle with no temporal, verbal or physiological feedback. Venous blood samples were obtained periodically during exercise and subsequently analyzed for glucose, lactate, free fatty acids, ammonia and insulin concentrations. Results: Analysis of variance revealed that time to complete the 80 km TT was lower (P≤0.05) when subjects ingested CHO (135±9 min; mean±SD) and CHOPro (135±9) compared to placebo (141±10), with no difference between CHO-Pro and CHO. Average power output was higher (P<0.05) when subjects ingested CHO and CHO-Pro versus placebo, and work intensity averaged 81±1%, 80±1% and 78±1% of heart rate reserve for the CHO, CHO-Pro and placebo rides, respectively. Improved performance of the two CHO trials was primarily attributed to maintenance of blood glucose concentration during the later stages of exercise. Conclusion: Ingestion of a 6% CHO drink at a rate of 1 L/h improves 80 km TT performance, as compared to a non-energetic placebo, in trained male cyclists. However, the addition of 2% Pro to a 6% CHO drink provides no additional performance benefit.

abstract: Thesis

abstract: Master of Science (MSc)


title: Neurocardiac Transfer: Effects of Aerobic Exercise Training on the Neurocardiac Responses to Exercise and Exercise Recovery with the Untrained Limbs

contributor:
McCartney, Neil
Kinesiology

subject:
aerobic training
neurocardiac transfer
exercise

abstract: There have been many attempts at answering the question of whether the cardiovascular adaptations resulting from aerobic exercise training of a particular muscle group are transferable when exercise is performed with the untrained muscles? Through the use of power spectral analysis (PSA) of heart rate variability (HRV) and blood pressure variability (BPV) the present study investigated this question in terms of a training induced modification of neurocardiac control. Fifteen healthy subjects (7 arm trainers & 8 leg trainers) aerobically exercise trained for 9 weeks, 3 sessions/week for 45 minutes/session. Training workload intensities were selected individually to obtain a target training heart rate (HR) between 75-80% HR maximum as determined from the initial pre-training V0₂ₘₐₓ. of the respective limbs. The exercise training program had no effect on supine rest HR, HR V or BPV, or standing HR and HRV. Following training, the arm group demonstrated a significant increase in V0₂ₚₑₐₖ (30.0 ± 1.4 to 34.2 ± 1.8 ml/kg/min.; p<0.05) during arm exercise and a significant reduction in leg exercise V0₂ₚₑₐₖ ( 44.8 ± 2.1 to 41.2 ± 1.6 ml/kg/min.; p<0.05). The leg training group demonstrated a slight post-training increase in leg exercise V0₂ₚₑₐₖ (43.5 ± 1.7 to 44.2 ± 2.4 ml/kg/min.; N.S.) and no change in arm exercise V0₂ₚₑₐₖ. Post-training changes in the maximum power produced during the respective limb group exercise tests corresponded to those of V0₂ₚₑₐₖ results. Mean HR values obtained from the arm trained group during the progressive maximal arm exercise test demonstrated significant post-training reductions at 50 percent (Δ-13 ±3.0 b.p.m.;p<0.05) and 75 percent (Δ-16 ± 5.8 b.p.m.;p<0.05) of the pre-training maximum workload. No change in mean HR was observed during progressive leg exercise in the arm trained group. The leg training group demonstrated non-significant HR reductions in both arm (Δ-3 ± 3.1 b.p.m. at 50% & Δ-6 ± 2.8 b.p.m. at 75%; N.S.) and leg (Δ -6 ± 4.5 b.p.m. at 50% & Δ -9 ± 3.5 b.p.m. at 75%; N.S.) progressive exercise tests. Mean HR and indices of HRV and BPV measured over 15 minutes of recovery following maximal exercise of both limb groups, were unaffected as a result of either training modality. The leg trained group demonstrated non-significant reductions in mean HR during both arm and leg steady-state submaximal exercise tests following training. No significant changes in any HRV components were observed in concordance with these non-significant mean HR reductions. Similarly, the arm trained group failed to demonstrate any significant changes in mean HR or HRV indices during either arm or leg submaximal exercise. Results from the present investigation indicated that a positive exercise training effect had occurred in the arm trained group, while the leg training group demonstrated smaller improvements in exercise performance compared to the arm trainers. Findings from the incremental exercise test further demonstrated the post-training improvements in the arm training group, and negligible improvements within the leg trained group. These improvements, or lack of, were all demonstrated in the mean HR measure with no significant changes in HRV patterns. This would suggest that non-neural factors contributed to most of the post-training adaptations. The discrepancies in results between the two training groups may be attributed firstly to the arm muscles greater potential for peripheral adaptations. Secondly, an inadequate training stimulus for the leg training group probably resulted in their poor post-training improvements. Lastly, the low submaximal exercise test intensities may have limited a clear observation in training improvements of either limb training group. The examination of post-maximal arm and leg exercise recovery failed to disclose any new information on the neurocardiac influences during exercise recovery subsequent to upper or lower limb training. The question of whether training induced neurocardiac control modifications may be transferable between the trained and untrained limbs may still be relevant, but requires more vigorous training of either muscle group.

abstract: Thesis

abstract: Master of Science (MSc)


title: MUON SPIN ROTATION STUDIES OF URU2SI2 AND DICHALCOGENIDE SUPERCONDUCTORS

contributor:
Luke, Graeme M.
Physics and Astronomy

subject:
Superconductor
Condensed Matter Physics
Hidden order
Heavy Fermion
Magnetism

abstract:
This dissertation details studies of two different material classes: isoelectronically doped URu2Si2, and dichalcogenide superconductors, both of which are primarily studied with the muon spin rotation (μSR) experimental technique.

The objective of the work on URu2Si2 was to probe how the low temperature "hidden order" state, which transitions into antiferromagnetism under hydrostatic pressure, evolves when perturbed by isoelectronic chemical doping. μSR measurements of iron doped URu2Si2, which produces positive chemical pressure, show long range magnetic order. Neutron diffraction measurements demonstrate that this magnetic order is antiferromagnetism, and both muon spin rotation and neutron scattering suggest that the magnetic moment increases with increasing doping in contrast to the pressure independent moment seen in the pressure induced antiferromagnetic state of URu2Si2. Inelastic neutron scattering measurements show a significantly larger commensurate gap at the (1 0 0) position compared to that seen in the pressure induced antiferromagnetic phase. Osmium doping, which gives negative effective chemical pressure, shows similar behaviour in μSR measurements to the iron doped samples. This suggests that these samples are also antiferromagnetic and that the evolution from hidden order to antiferromagnetism is not solely caused by changes in the lattice size. This is further supported by μSR measurements on germanium doped samples that do not show magnetic order despite giving similar negative chemical pressure to the osmium doped samples.

Work on the dichalcogenide superconductors involved using transverse field μSR to measure the temperature dependence of the magnetic penetration depth of two different materials, Pt0.05Ir0.95Te2 and PbTaSe2. The μSR data on Pt0.05Ir0.95Te2 were supplemented by magnetometry measurements of the penetration depth. Zero field μSR measurements were also performed on PbTaSe2, and rule out any time reversal symmetry breaking field greater than 0.05 G. These measurements all suggest that both materials are fully gapped superconductors.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: MECHANISMS OF IMINE-BASED INHIBITORS OF DAHP SYNTHASE, AN ANTIMICROBIAL TARGET.

contributor:
Berti, Paul J.
Chemistry

subject:
enzyme inhibitors
DAHPS
imine-based molecules
antibiotics

abstract:
Bacterial 3-deoxy-D-arabinoheptulosonate 7-phosphate synthase (DAHPS) is an antimicrobial target. A transition state (TS) mimic inhibitor of DAHPS, DAHP oxime, was developed in our lab, with Ki = 1.5 μM. Despite being a potent inhibitor, some of DAHP oxime’s properties could hinder its efficacy in blocking bacterial growth.
One problem was that DAHP oxime bound competitively with respect to the metal cofactor, Mn2+. Identifying the origin of this competition was crucial for in vivo success of DAHPS inhibitors, as the abundance of metal ions in living cells could hinder DAHP oxime’s effectiveness. Mutant enzymes and fragment-based inhibitors demonstrated that the competition originated in interactions involving the O4 hydroxyl of DAHP oxime and residues Asp326, and Cys61. This suggested improved inhibitor designs to avoid metal competition.
Another drawback was the highly negatively charged nature of DAHP oxime and other DAHPS inhibitors. The charge hindered cell membrane penetration, and therefore its effectiveness in cells. Truncating DAHP oxime to a fragment reduced its hydrophilicity and charge, while the introduction of fluorine in the oxime’s α-position increased potency. DAHPS-specific bacterial growth inhibition was obtained with this fragment.
DAHPS inhibition by high DAHP oxime concentrations resulted in a 15% residual activity. This residual activity would be sufficient for bacterial survival, so two derivatives, DAHP hydrazone and DAHP O-(2-fluoroethyl) oxime that showed complete inhibition were characterized. DAHP hydrazone was successfully co-crystallized with DAHPS. Its 100-fold higher potency relative to DAHP oxime was attributed to an extra water bound in the active site. The inhibitor bound in all four of the enzyme’s subunits. However, the observed subunit asymmetry showed that the subunits communicate with each other and that there is a significant energetic penalty to enforcing full subunit symmetry.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Antibiotic resistance is imposing a growing disease burden on society that the United Nations calls “…a global crisis that we cannot ignore”. Many traditional antibiotics have now lost their efficacy as bacteria increasingly develop mechanisms of resistance. The development of new treatment options is therefore crucial. The first step towards this goal is the characterization of new antimicrobial targets. DAHPS is an enzyme that is exclusively expressed by bacteria, fungi and plants. Its absence in mammalian cells is expected to reduce side effects in humans. DAHPS inhibitors have previously been developed, but none of them has shown sufficient effectiveness in bacterial cell culture. Possible reasons for this failure were, among others, reduced inhibition in the presence of metal ions, low cell membrane penetration and incomplete enzyme inhibition. This thesis examines DAHPS’s properties and provides solutions on how to successfully inhibit this enzyme, to fight antibiotic resistance with new treatment options.


title: Physician Communication via Information and Communication Technology: Understanding its Role in Health System Performance

contributor:
Randall, Glen E.
Health Policy

subject: Communication

subject: Physicians

subject: Health Policy

subject: Health Services

abstract: Information and communication technology (ICT) can enhance communication among health care providers which may lead to various health system improvements, such as gains in efficiency. However, there is inadequate evidence regarding the extent to which ICT improves communication among specific groups of health care professionals. This dissertation incorporates a mix of methodological approaches across three interrelated research studies to address this gap. Study 1 consists of a systematic review which suggested that ICT can play an important role in enhancing health care related communication among physicians, but the extent of that benefit is influenced by: 1) the impact of ICT on existing work practices; 2) the availability of adequate resources for ICT implementation and use; and 3) the nature of institutional elements, such as privacy legislation. Study 2 consists of a document analysis that examined guidelines for health information protection when using ICT from the provincial regulatory colleges for physicians. These documents were notable for the considerable variation in the scope and detail of guidance provided, which may result in unequal and inequitable protection of health information across the provinces. Study 3 is a case study that examined the use of a relatively novel form of ICT, smartphones, for communication among postgraduate medical trainees (medical residents). Efficiency and convenience were identified as the main reasons that medical residents use smartphones to communicate health care related information with colleagues. In addition, by applying a neo-institutional perspective, it became clear that medical residents base their smartphone use primarily on normative elements (professional norms; what peers/staff are doing) and cultural-cognitive elements (beliefs/perceptions regarding facilitation of task completion). Regulative elements (guidelines/policies) around smartphone use play a smaller role in shaping behaviour, particularly when they: 1) lack clarity; 2) are not seen as credible/legitimate; or 3) are viewed as cumbersome and do not align with workflow needs. Taken together, these studies provide timely insights regarding the use of ICT by physicians, which can be drawn upon by a variety of decision-makers as efforts to improve health system performance continue.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: The goal of this doctoral dissertation was to develop a better understanding of how and why physicians are using information and communication technology (ICT) to exchange health care related information, along with the role of such communication in enhancing health system performance. Findings indicate that physicians use ICT in various circumstances as they perceive it to be more convenient and efficient. However, guidelines for the exchange of health information in digital/electronic format vary by jurisdiction and organization, which may result in different uses of ICT by physicians. Moreover, as these guidelines often lack clarity or are not seen as credible/legitimate, some physicians base their use of ICT primarily on what peers/colleagues are doing or by acting in a manner that they believe facilitates task completion and, hence, patient care. The insights gained from this work can be adopted by decision-makers to improve communication among physicians using ICT and, consequently, health system performance.


title: Coordinated Energy Management in a Network of Microgrids

contributor:
Sirouspour, Shahin
Electrical and Computer Engineering

abstract:
This thesis is concerned with the problem of coordinated energy management in a network of grid-connected microgrids.  In particular, the research investigates methods for optimal coordinated control of storage units and sharing of electricity costs  among the microgrids.  New multi-objective optimization models are proposed for efficient integration of the microgrids local energy storage and renewable energy resources into the power grid. In these models,  individual microgrids can exchange power locally with each other as well as with the utility grid. Components of the objective function are the electricity costs of the individual microgrids over a rolling window of time, e.g, a 24-hour prediction horizon.  A pricing regime is introduced in which differences in the local and grid buy and sell time-of-use rates of electricity incentivize local inter-microgrid exchanges of power over power exchange with the grid. Optimization problems are formulated and  solved on a rolling horizon basis to allow for on-line management of energy resources, using up-to-date forecast of microgrid electricity demand, renewable generation, and electricity rates.

In Chapter 4, a novel formulation of a multiple-objective constrained optimization is presented for solving the microgrids energy management problem under the proposed electricity pricing regime using the concept of compromise programming. This approach minimizes  l1 or l2 distances of the microgrids cost vector to a utopia point in the solution space. Components of the utopia point are defined as the minimum cost achievable by the corresponding microgrid when it always uses the favourable local buy/sell rates.
The proposed optimization models are in the form of convex linear/quadratic programs without any binary or integer variables for l1/ l2 norms, respectively.  In Chapter 5, the multiple-objective optimization is converted to a single-objective optimization by adding up the costs of the individual microgrids. An equivalent linear program free of binary/integer variables is derived from the original nonlinear optimization model, which can be effectively solved using existing solvers. The total cost saving and computational complexity are significantly improved in this method compared to the  compromise programming technique  in Chapter 4.  In Chapter 6,  the multi-objective optimization is formulated as a lexicographic program, to allow for preferential treatment of groups of microgrids based on pre-assigned priorities. This, for example, allows for giving greater incentives to microgrids that bring lager storage and renewable energy capacity into the network. Finally, in Chapter 7, the optimization model is extended to enable dispatch of  reactive power in addition to real power. Simulation results with real data demonstrate that the proposed coordinated energy management strategies can yield substantial cost savings, in some cases in excess of 70 %, for the microgrids in the network compared to a case in which they  manage their resources individually. Moreover, the solution to the convex binary/integer free optimization models can be obtained in real-time for a fairly large network, making the proposed models suitable for on-line energy management.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: A Quantitative Comparison of Monoamine Containing Cells in Fish Gill Epithelia

contributor:
Nurse, C. A.
Biology

subject: quantitative comparison, monoamine, cells, fish gill epithelia, fluorescent immunocytochemical methods

abstract: Serotonin positive (5HT+) and tyrosine hydroxylase positive (TH+) cells were identified using fluorescent immunocytochemical methods and quantified in the gill epithelium of six species of fish. 5HT+ cells were located in the filament epithelium in contact with the basal lamina on the efferent side, and in the lamellar epithelium where they were occasionally exposed to the external milieu. Thus, these cells appear to represent two populations of neuroepithelial cells (NEC) as proposed in other studies. In trout, bass and killi fish, NECs were revealed exclusively in the primary epithelium. In tilapia, NECs were located exclusively in the secondary epithelium, whereas in perch and zebrafish they occurred in both epithelial layers. The two types of NECs varied in number both within and among the species. Seasonal comparisons of NECs in perch revealed a decrease in cell density in the filament between July and November, though there was no significant difference in the density of NECs in the lamellae. TH+ cells were identified in perch, zebrafish and killi fish. In zebrafish TH+ cells occurred in similar numbers to 5HT+ cells, and were generally present in similar locations. It is likely that in this case, many of the labelled cells were positive for both markers. In two of the species, perch and killi fish, the density and distribution was such that the TH+ cells and 5HT+ cells were unlikely to be the same. A quantitative comparison of total catecholamine (CA) stores, using high performance liquid chromatography (HPLC), revealed that gill tissues in general contained higher levels of epinephrine (EPI) than norepinephrine (NOR) and dopamine (DOP). Finally, attempts were made to determine whether NECs would survive in 2-4 day old cultures of dispersed gill cells from perch, using immunocytochemical labelling for 5HT. A few successful cases are presented.

abstract: Thesis

abstract: Master of Science (MSc)


title: Peroxynitrite Effects on Smooth Muscle Contractility

contributor:
Grover, Ashok K.
Biology

subject: peroxynitrite, smooth muscle contractility, blood vessels, depolarization

abstract:
 Peroxynitrite is formed in blood vessels upon reaction of superoxide anion with nitric oxide (NO). It can oxidize proteins and thiols and nitrosylate free or protein bound thiols and tyrosine residues, thereby producing vascular dysfunction. Peroxynitrite therefore, may contribute to hypertension and cardiovascular diseases. We investigated the in vitro effects of commercially available peroxynitrite. De-endothelialized rings from the left descending coronary artery of pig were treated with peroxynitrite for 30 min, washed and then contracted with cyclopiazonic acid (CPA) or by membrane depolarization with KCl. Tissues pre-treated with peroxynitrite showed inhibition of the CPA-induced contraction with an IC50 of ≈100 uM but there was no effect on KCl-induced contraction. Peroxynitrite is stable only at alkaline pH and it may decompose to form superoxide and NO. However, including superoxide dismutase + catalase along with peroxynitrite did not change its effect.

 Next, we used the same protocol to compare the effects of peroxynitrite and NO generating agents: 3-morpholino sydnonimine (SIN-1), s-nitroso-N-acetylpenicilliamine (SNAP), sodium nitroprusside (SNP) and spermine nonoate. The effectiveness of these agents to inhibit the CPA-induced contraction was SNAP > spermine nonoate ≥ SIN-1 > SNP. SNAP was the most effective in inhibiting the KCl-induced contraction with spermine nononoate being less effective and SIN-1 and SNP not producing any significant inhibition. We further investigated the effect of SNAP. Catalase, superoxide dismutase or CPTIO (a NO scavenger) did not prevent the effects of SNAP on the KCl or the CPA-induced contractions. The guanylate cyclase inhibitor ODQ, partially reversed the effects of only low concentrations of SNAP. Thus, pretreatment with NO generating agents such as SNAP and spermine NONOate appear to be more effective in inhibiting the contraction of the pig coronary artery than with peroxynitrite or the peroxynitrite generating agent SIN-1. Since SIN-1, SNAP, SNP and NONOates produce different amounts of peroxynitrite, nitric oxide and S-nitrosylation products, their effects may be used to delineate the molecular basis of the actions of peroxynitrite and NO on the arterial function.

abstract: Thesis

abstract: Master of Science (MSc)


title: The Role of Steroids in Novel-Male Induced Pregnancy Disruptions in Mice (The Bruce Effect)

contributor:
deCatanzaro, D.
Psychology

subject:
steroids
induced pregnancy
mice
bruce effect

abstract:
Mammalian reproduction is vulnerable to psychological and physiological stress. This research focuses on the psychophysiological mechanisms that lead to the disruption of pregnancy by the failure of implantation of fertilized ova into the uterine walls. The underlying hormonal mechanisms of implantation failure are not well understood. It is known that many environmental events have a substantial impact on hormonal dynamics in mammals. These environmentally induced hormonal changes can disrupt implantation. This thesis focuses on the hormonal dynamics of female mice that lose their pregnancy when exposed to a novel male during the implantation period (the Bruce effect).
In Study 1, a repeatable and reliable Bruce effect was established by indirectly exposing inseminated females during the implantation period to novel males housed above them separated by a wire grid floor. Separating the animals allowed for the independent study of the chemical transmission from male to female, and the physiological transduction within the female. The findings from this study suggest that females must come in direct contact with the excretions of the stimulus novel males. The more excretions the females encounter, the greater the chance is of pregnancy disruption. The Bruce effect is known to be dependent on androgens in the stimulus males, since castration eliminates their capacity to disrupt pregnancy. Study 2 showed that surgically removing the androgen-dependent preputial glands from the stimulus males does not diminish their capacity to disrupt pregnancy. Study 3 showed that administering 17β-estradiol to castrated males can restore their capacity to disrupt pregnancy. This suggests that 17β-estradiol as well as testosterone is involved in the chemical transmission of the Bruce effect. It has been hypothesized that 17β-estradiol is elevated in females that fail to implant in the presence of a novel male. Administering an antibody specific to 17β-estradiol to females during their implantation period can lower the hypothesized increase in 17β-estradiol and implantation takes place despite the exposure to novel males. Finally, in Study 4 testosterone, 17β-estradiol and its major metabolites the estrone conjugates were quantified in females' urine and feces while exposed to novel males during implantation. It was found that testosterone and 17β-estradiol were significantly elevated in females that failed to implant while exposed to novel males. In conclusion, this line of research reveals a potential role of steroids in novel male induced pregnancy disruptions in mice. Elevated testosterone and 17β-estradiol are shown to be related to the prevention of implantation in mice. These hormonal dynamics may be partially responsible for the physiological transduction of the Bruce effect.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Intra-Arterial Pressure During Arm Weightlifting Exercise in Cardiac Patients

subject: intra-arterial, pressure, arm weightlifting, exercise, cardiac patients

abstract: This study investigated the circulatory response to double-arm weightlifting exercise and compared the responses during free weight and machine equipment weightlifting in eight patients (mean age = 57.6±10 years) with well-documented coronary artery disease. Subjects performed bench press and overhead press exercises at 40 and 60% of 1 repetition maximum using both the free weights and machine equipment. Intra-arterial pressure was measured in the subclavian artery using a Millar catheter-tip pressure transducer. Arterial pressures rose in parallel with both modes of lifting (free weight and machine equipment), while heart rate did not increase substantially. Mean peak systolic (169 to 197 mmHg) and diastolic (95 to 119 mmHg) pressures recorded during the final repetitions of each weightlifting set did not, however, exceed values considered to be acceptable for dynamic exercise. Individual subjects recorded diastolic pressures as high as 150 mmHg during one or more of the weightlifting exercises, and individual mean arterial pressures reached values as high as 181 mmHg during overhead press machine equipment exercise at 60% of 1RM. While these high arterial pressures associated with weightlifting exercise increased myocardial oxygen demand (RPP=9643 to 15290), the increase in diastolic pressure may have augmented oxygen supply (DPTI=3448 to 3926 mmHg.s.min-1). However, because of the proportionately larger increase in RPP compared to DPTI, the ratio of oxygen supply to demand decreased with arm weightlifting exercise (DPTI:RPP=0.3741 to 0.2629). Nevertheless, the estimated myocardial oxygen supply to demand relationship appears to be more favourable during double-arm weightlifting exercise compared to estimated values from previous maximal cycle ergometer testing. These results suggest that double-arm weightlifting exercise at 40 to 60% of 1RM is safe and appropriate for patients with coronary artery disease and can be performed using either free weights or machine weightlifting equipment.

abstract: Thesis

abstract: Master of Science (MSc)


title: Toward the Crystal Structure of a Type III Antifreeze Protein From Ocean Pout, Macrozoarces Americanus

contributor:
Yang, Daniel S. C.
Biochemistry

subject: crystal structure, Type III antifreeze, protein, ocean pout, Macrozoarces americanus, ice binding, atomic resolution

abstract:
 Four stucturally distinct types of macromolecular antifreezes have been previously isolated from the sera of polar marine fish. When the water temperature surrounding these organisms drops below -0.7°C, the freezing point of their bodily fluids, any contact with surrounding ice will nucleate internal ice crystal growth. The antifreeze proteins (AFPs) and antifreeze glycoproteins (AFGPs) synthesized by the fish act to inhibit the growth of existing ice crystals in their sera through direct adsorption to the ice lattice. The α-helical structure of type I AFP from winter flounder has been solved to atomic resolution and its mechanism of ice binding has been proposed. The NMR solution structure of a type III AFP from ocean pout has identified proteins in this class to exist in a β-sandwich conformation, however their mechanism of action remains uncertain.

 To facilitate the pursuit of an x-ray crystal structure solution, we subcloned the gene for a type III AFP (HPLC6) into pET15b and expressed recombinant His-rHPLC6 AFP in E. coli. Purified rmHPLC6 product has been successfully crystallized, and heavy atom soaks were performed in order to attempt a structure solution by multiple isomorphous replacement. The lone tyrosine in this recombinant AFP has been successfully derivatized in solution with iodine, and the modified protein was crystallized. In order to optimize the measurement of anomalous scattering information, modifications to our data collection system were required. Cryocrystallography techniques were employed to improve the quality of collected data.

 The expression, purification, crystallization and optimized data collection on an iodine-derivatized type III AFP from ocean pout will be presented here. This work has been instrumental in providing the high quality x-ray data required to solve the crystal structure to atomic resolution. Future examination of the solved structure will promote an increased understanding of the ice-binding mechanism exhibited by this class of proteins.

abstract: Thesis

abstract: Master of Science (MSc)


title: High-Accuracy Torque Control and Estimation for Interior Permanent Magnet Synchronous Machine Drives with Loss Minimization

contributor:
EMADI, ALI
CHENG, BING
Electrical and Computer Engineering

abstract:
This thesis studies the high-accuracy torque control for the interior permanent magnet synchronous machine (IPMSM) drives with loss minimization.
A nonlinear flux-linkage model for the IPMSM with twelve coefficients is proposed. It can generally be used to estimate the d-axis flux-linkage, q-axis flux-linkage, MTPA locus, and torque without the information of the machine known, such as the geometry and material of the permanent magnet. The new torque equation and MTPA condition are derived from the proposed flux-linkage model. An optimization problem is formulated to find the appropriate factors for the proposed model based on the measured flux-linkage data at only nine specific operating points. No selection of weight factors is required in the cost function. The desired copper-loss minimization control can be achieved and good torque estimate can be achieved in real-time.
A novel model for IPMSM drives with all the losses considered is proposed. The model-based loss minimization control (LMC) algorithm with respect to motor current contributing to the flux-linkage generation is presented. The analytical solution to the optimization problem is provided. Based on the proposed IPMSM drive model, LMC with respect to the winding current in wide speed range is studied as well. The optimality is proved. The influences of the stator resistance, the equivalent inverter-loss and core-loss resistance in the proposed circuit are researched. Compared to maximum torque per ampere (MTPA) control, LMC introduces more efficient energy utilization.
Due to the nonlinearities, the characteristics of the inverter loss, the core loss, the mechanical loss, the d- and q-axis flux-linkage profiles of the IPMSM drive system are researched. The process of the parameters’ characterization with respect to the speed, the d- and q-axis current is stated. The back-fitting based torque estimation technique is proposed, which eliminates the necessity of the manufacture of the dummy rotor. The separation of the core loss and mechanical loss is not required for the calculation. The accuracy of the prediction of the voltage limit ellipse based on the proposed model is enhanced compared to the conventional method. The torque control system for the IPMSM drives is designed, aiming at accurate motor torque control, high efficiency, and fast dynamic response performance.
2004 Prius IPMSM and one prototype motor are used to validate the proposed algorithms for the parameters’ characterization, torque estimation, and loss minimization control.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Conservation Genetics of the Florida Grasshopper Sparrow

contributor:
Gibbs, H.
Biology

subject:
conservation
florida grasshopper sparrow

abstract:
Thesis
Master of Science (MSc)


title: Characterization of a Novel Circling Mouse (Cr) Generated in a transgenic growth hormone mouse breeding colony

contributor:
Szechtman, Henry
Rollo, C. David
Biology

subject: recessive mutants, dopaminergic alterations, striatum

abstract:
Numerous genetic variants displaying stereotypic circling behaviour have been
described in rodents. The majority are recessive mutants expressing dopaminergic
alterations in the striatum- often with associated vestibular defects. We describe a novel
circling mouse (Cr) with intact vestibular function frequently obtained from crosses of
non-transgenic wild type mice (WT) and transgenic growth hormone mice (TGM). We
have characterized Cr with stereotypic circling, head bobbing, hyperkinesia,
aggressiveness, and elevated dopamine when compared to the transgenic growth
hormone mouse. The Cr also demonstrates self-mutilating behaviour found in mice with
dysregulated striatal dopamine levels. Cr oppositely mirrors most traits of the TGM
including alterations in sleep, activity, eating, and drinking. TGM displayed superior
performance than WT in novel object recognition, but this decreased with aging.
Comparatively, Cr performed poorly in this test. The memory of young TGM exceeded
controls, whereas young Cr displayed poorer memory with an age related improvement.
In a stepdown test of emotionality, TGM step down more readily, while Cr are more
hesitant than WT. TGM and Cr also demonstrate opposite alterations in striatal
dopamine. Further analysis demonstrated differential responsiveness of TGM and Cr
under dopaminergic drugs, and potentially sexually dimorphic differences in behaviour
associated with elevated GH in TGM. TGM are characterized by increased levels of
circulating growth hormone and alterations in sleep and activity. We hypothesize that
frequent generation of Cr may reflect unintended selection of modifier genes that
counterbalance negative consequences of elevated GH in TGM.

abstract: Thesis

abstract: Master of Science (MSc)


title: taste Aversion Motivated by Stomach Distention

contributor:
Siegel, S.
Psychology

subject:
taste aversion
distention
stomach

abstract: Previous research has indicated two distinctive characteristics of flavour-aversion learning in rats: (1) rats very readily associate flavors with an internal malaise (toxicosis) , as evidenced by their subsequent aversion to the flavor, but they do not readily associate flafors with peripherally-applied electric shock. In contrast, rats readily associate auditory and visual stimuli with shock but not with toxicosis; (2) rats associate flavors with a subsequent toxicosis even when the gustatory stimulus is removed hours prior to onset of toxicosis. However, associations are formed between audio/visual cues and shock only if the offset of the signal does not precede onset of shock by more than one or two minutes. It has been suggested that the unique features of flavour-aversionn learning result from the fact that toxicosis is primarily a visceral experience while shock is applied to somesthetic receptors. However, toxicosis differs from shock along a number of dimensions in addition to receptor site. Most notably, toxicosis typically rises to a peak intensity over a period of many minutes and lasts for hours while shock is usually applied with a rapid onset (milliseconds) and short duration (seconds or milliseconds).  Inasmuch as aversion learning experiments have confounded the receptor site of the aversive stimulus with its distinctive temporal features, it is not clear whether receptor site or temporal features is the functionally important characteristic of toxicosis as an aversive stimulus in the taste-aversion learning preparation. To determine the role played by the temporal features of the aversive stimulus in taste-aversion learning, rats were prepared with a stomach balloon and stomach balloon inflation was paired with ingestion of a flavored solution. In contrast to toxicosis, the onset/offset rate and duration of balloon inflation may be directly manipulated thus permitting application of a relatively discrete internal stimulus (in comparison to toxicosis) to visceral receptors. Experiments presented here found: (a) rats associated a flavor with a stomach balloon inflation as indicated by an aversion to the flavor during a two-solution preference test. In contrast to toxicosis, the stomach balloon inflation had a rapid onset (seconds) and short duration (minutes). Control groups demonstrated that the rapid onset, short duration balloon inflation did not produce the long lasting malaise characteristic of toxicosis. (b) Rats associated a flavor with a rapid onset, short duration balloon inflation even when exposure to the flavor was terminated many minutes prior to onset of balloon inflation. (c) Rats readily associated a flavor with balloon inflation but not with shock, and an auditory stimulus with shock but not with balloon inflation, even though balloon inflation and shock were equated in terms of their temporal parameters. These findings clearly indicate that the very slow onset and long duration characteristics of toxicosis are not the functionally important features of toxicosis as the aversive stimulus in the taste-aversion learning preparation. Furthermore, the unique temporal features of toxicosis and shock do not appear responsible for the distinctive characteristics of flavor-aversion learning in rats.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Effects of Isometric Handgrip Training on Resting Arterial Blood Pressure and Arterial Compliance in Medicated Hypertensive Individuals

contributor:
McCartney, Neil
Human Biodynamics

subject: isometric handgrip training, resting arterial pressure, arterial compliance, hypertensive

abstract:
 This study examined the effects of isometric handgrip training (IHG) on resting blood pressure and resting arterial compliance in the carotid and brachial arteries of medicated hypertensive individuals. Previous studies found that isometric training reduced resting arterial blood pressure (RBP) in high-normal and medicated hypertensive individuals. Investigators have also found an improvement in central arterial compliance with aerobic training and a reduction in central arterial compliance with age, cardiovascular disease and resistance training. The effects of isometric training on arterial compliance have not been examined previously.

 Ten participants participated in a one-hand IHG intervention, nine participants in a two-hand IHG intervention and 5 participants served as the non-exercising controls. Each experimental group performed four, 30% maximal voluntary IHG contractions for 2 minutes, 3 days a week, for 8 weeks. The one-hand group trained only their non-dominant hand, while the two-hand group trained both hands. Measurements of resting
arterial blood pressure, and cross sectional compliance of the brachial and carotid arteries
were made pre-training, after four weeks of training and after the completion of the eight-week training protocol.

 There were no changes in resting arterial blood pressure after training. Mean carotid and brachial artery diameters did not change with resistance training. There were no significant changes in brachial or carotid cross sectional compliance with isometric training. In conclusion, moderated level isometric training did not elicit changes in resting arterial blood pressure and resting muscular and elastic arterial compliance in
medicated hypertensive individuals compared to a non-exercising control group.

abstract: Thesis

abstract: Master of Science (MSc)


title: The Effect of Isometric Handgrip and Isometric Leg Muscular Contractions on Resting Blood Pressure and Arterial Distensibility in Persons Medicated for Hypertension

subject: isometric handgrip, leg exercise, resting blood pressure, arterial distensibility, hypertension, cardiovascular disease

abstract:
 Hypertension and reduced arterial distensibility are independent risk factors for cardiovascular disease. Previous research has found that isometric training reduces resting blood pressure (RBP) (Wiley et al. 1992; Taylor et al. 2003) yet the mechanisms responsible remain elusive. Improved arterial distensibility may contribute to this reduction in RBP. The purpose of the present study was threefold: 1) to replicate the RBP lowering effect of isometric handgrip (IHG) exercise; 2) to compare IHG and isometric leg press (ILP) based in their RBP lowering effects; and 3) to determine if central or peripheral arterial distensibility improved with IHG or ILP. The population examined was people whom were medicated for hypertension.

 RBP, as assessed by brachial oscillometry, and arterial distensibility, as assessed by Doppler ultrasound and applanation tonometry in the carotid, brachial and femoral arteries, were measured pre training, after 4 weeks of training, and post training.
Participants performed unilateral IHG exercise (n=10) or ILP exercise (n=9) 3 times/week for 8 weeks at 30% MVC or acted as a non-exercising control group (n=5).

 Results indicated that the present study was unable to reproduce the RBP reductions noted in previous studies using IHG exercise. Also, the ILP exercise group did not experience reductions in RBP. Finally, neither central nor peripheral arterial distensibility improved in the IHG or ILP group when compared to the control group.

 Although these findings are contrary to our hypotheses one must consider that the control group examined contained very few subjects. This may have limited our ability to detect statistically significant changes in RBP and arterial distensibility.

abstract: Thesis

abstract: Master of Science (MSc)


title: Aerobic Training Attenuates Skeletal Muscle Anaplerosis During Exercise in Humans

contributor:
Gibala, Martin J.
Human Biodynamics

subject: tricarboxylic acid, pyruvate production,

abstract:
We hypothesized that the exercise-induced increase in muscle tricarboxylic acid
(TCA) cycle intermediates (TCAI) would be lower after aerobic training (TR), due to a
better match between pyruvate production and subsequent oxidation and lower flux
through the alanine aminotransferase (AAT) reaction. Eight men [22 ± 1 y; maximal
aerobic capacity (V02max) = 3.9 ± 0.2 L/min] cycled at 75% of their pre-TR V02max to
exhaustion (Exh), before and after 7 wk ofTR (1 hr/d, 5 d/wk). Muscle biopsies (v.
lateralis) were obtained at rest, 5 min of exercise and Exh. The effect ofTR was
evidenced by an increased time to fatigue (91 ± 6 vs 42 ± 6 min), increases in resting
[glycogen] and citrate synthase maximal activity, and decreases in glycogen degradation,
lactate accumulation and phosphocreatine utilization during exercise. The sum of 4
measured TCAI was similar between trials at rest, but lower after 5 min of exercise post-
TR (2. 7 ± 0.2 vs 4.3 ± 0.2 mmol.kg-1 dw, P<0.05). Importantly, the [TCAI] at Exh post-
TR (2.9 ± 0.2 mmol.kg-1 dw) was not different compared to 5 min of exercise and thus
fatigue was not attributable to a decline in TCAI. The net change in glutamate (Post: 4.5
± 0.7 vs Pre: 7.7 ± 0.6 mmol.kg-1 dw) and alanine (Post: 3.3 ± 0.2 vs Pre: 5.6 ± 0.3
mmol.kg-1 dw) from Rest-5 min of exercise was attenuated post-TR (P<0.05), which is consistent with lower flux through the AA T reaction. We conclude that changes in
muscle TCAI during exercise are not causally related to aerobic energy provision.

abstract: Thesis

abstract: Master of Science (MSc)


title: The Development of a Tutor Manual for Year One Anatomy and Physiology Teaching Assistants

title: The Development of an Anatomy and Physiology Tutor Manual

contributor:
Fox, J.
Groves, H.
Medical Sciences

subject:
tutor manual
anatomy
physiology
teaching assistants

abstract: A "Tutor Manual" was developed to facilitate the small group learning experience in the laboratory and tutorial component of the introductory Anatomy and Physiology Nursing course at McMaster University. The manual included a comprehensive discussion of the information and important concepts in the laboratory and tutorial sessions, and provided guidelines on how to facilitate the group effectively in its consideration of the topics. Theoretical educational concepts were considered in the development of this manual, including: lifelong learning; principles of adult learning; the use of small-group discussion in teaching and learning; the role of the facilitator: and the use of objectives.

abstract: Thesis

abstract: Master of Science (Teaching)


title: MERGING OMNIPHOBIC LUBRICANT-INFUSED COATINGS WITH DIFFERENT MICROFLUIDIC MODALITIES TO ENHANCE DEVICE FABRICATION AND FUNCTIONALITY

contributor:
Didar, Tohid
Biomedical Engineering

subject:
Microfluidic Devices
Biosensors
Electrochemical Activity Surfaces
Omniphobic
Omniphobicity
Lubricant-infused surface
Surface Wettability

abstract:
Surface science is a multidisciplinary subject which affects us on
a daily basis. Surfaces are of particular interest because the
chemical bonding and atomic structure is different at the surface
compared to the bulk properties of a material. This interface is of
great significance because it is where charge exchange, or new
chemical bonds occur. One essential aspect of surface science is
surface wettability, which can be harnessed to produce self-cleaning
surfaces. This very lucrative notion, where surfaces with low
adhesion to liquids, can result in quick and autonomous shedding,
has inspired a multitude of device fabrication and implementation.
Over the past decade, several self-cleaning surfaces have been
fabricated from superhydrophobic surfaces, which depends on a
stable interface between solid, liquid and gas. These surfaces,
however, are restricted in their applications and fail to operate upon
mechanical damage or nonhomogeneous fabrication processes.
Recent advances in wettability science have produced omniphobic
lubricant-infused surfaces (OLIS). These surfaces are created by
tethering a liquid to a surface, providing a stable liquid interface, which results in excellent aqueous and organic liquid repellency, and high
robustness toward physical damage. This thesis will encompass an
overview of the classical models for surface wettability, new models
for liquid mobility, the criteria required to obtain OLIS, as well as
some of the biomedical engineering applications fabricated from this
technology. Herein, a novel manufacturing process was developed to
produce smooth channeled polymeric microfluidic devices from rough
3D printed molds. Additionally, we integrated OLIS technology with
electroconductive sensors to create high surface area electroactive
material with self-cleaning properties, ideal to combat non-specific
adhesion of biomolecules. Furthermore, our fabrication methods
are inexpensive and have the potential to be easily integrated
into manufacturing processes to create highly functional microfluidic
devices, optimal for lab-on-chip diagnostic platforms.

abstract: Thesis

abstract: Master of Applied Science (MASc)

abstract:
Recent advances in wettability science have produced omniphobic
lubricant-infused surfaces (OLIS) inspired by the Nepenthes pitcher
plant. These surfaces are created by tethering a liquid to a surface,
providing a stable liquid interface, which results in excellent aqueous
and organic liquid repellency, as well high robustness toward physical
damage and high pressure dispensing scenarios.
The motivation for this thesis is to expand on the applications for OLIS
devices. Herein, a novel manufacturing process was developed to
produce smooth channeled polymeric microfluidic devices from rough
3D printed molds. Additionally, we integrated OLIS technology with
electroconductive sensors to create high surface area electroactive
material with self-cleaning properties, ideal to combat non-specific
adhesion of biomolecules.


title: Protein Metabolism and Energy Utilization in Females Participating in Endurance Activity: The Effect of Nutritional Supplement Timing

contributor:
Tarnopolsky, M.A.
Human Biodynamics

subject:
protein
endurance activity
energy use
nutritional supplement

abstract:
Ten healthy young females (age 22.3 ± 0.2 y, V0₂ₘₐₓ > 40 ml·kg⁻¹·min⁻¹) volunteered to participate in a randomized, double-blinded study that examined the effect of both (A) the timing of PRO/CHO/FAT supplementation, pre- and post-endurance exercise, and (B), extra-energy supplementation ( ~ 400 kcal) on indices of protein metabolism. Each subject completed each of three, 7-day supplementation trials
conducted at least 1 week apart: a pre-exercise trial (PRE), a post-exercise (PO) trial, and a post-exercise with extra energy (POE) trial. All females were eumenorheic and tested during the early (days 4-7), middle (days 8-11 ), and late (days 12-14) periods of the follicular phase of their menstrual cycle. Subjects were weighed prior to and following each trial to determine weight loss. During each trial, subjects would consume a checklist diet (days 1-3) and a prepackaged diet (days 4-6) that were isoenergetic, isonitrogenous, and matched for diet composition (carbohydrates, protein, and fat) to the individual's habitual dietary intake. Subjects cycled at 65% V0₂ₘₐₓ for 1 hr, according to their target heart rate on Days 1,3, and 4 and for 1.5 hrs on Day 6 with Days 2 and 5 being rest days. Expired gas and blood samples were collected on Day 6 during exercise (t=0,30,60,90 min) and post exercise for 2 hrs (Blood t=30,60,90,120, Gas t=10,20,30,45,60,90,120 min). On Day 5, expired gas samples were collected post- supplement consumption at the same timepoints as Day 6. 24 h-urine collections were performed on Days 5 and 6. A 75% V0₂ₘₐₓ performance ride to exhaustion was performed in a fasted state on the morning of Day 7.
During each trial, subjects had consumed their daily meals at regular intervals by 1500 h prior to the exercise bout (1600 h). In the PRE trial, a PL can+ PRO/CHO/FAT Supplement (Results® + 0.5 g·kg CHO powder[Gatorade®]) was consumed with breakfast (BKFT), and a PL Supplement (I can+ powder) was consumed immediately following the cessation of exercise. In the PO trial, a PL Supplement (2 cans+ powder) was taken at BKFT and the PRO/CHO/F AT Supplement was consumed post-exercise. The POE trial was identical to the PO trial with the exception that subjects received an extra 400 kcal of energy·d-1 at BKFT (Boost®-250 kcal and an extra 150 kcal CHO powder). During the POE checklist diet (Days 1-3), the extra energy was given by the addition of extra items to their daily food consumption.
Although plasma estrogen levels were significantly higher during the PO trial (P <0.05), plasma progesterone levels were not significantly different between trials, and both hormones indicated that subjects were in the follicular phase of their menstrual cycle. Significant main effects for time occured in which hematocrit, sodium, potassium, and lactate were observed to increase during exercise and decrease post-exercise. Glucose concentration increase was signiciant for time (P < 0.01) increasing post-exercise after consumption of the supplement. Significant main effects for insulin were observed across time (P < 0.000001) and for trial (P < 0.01) with the POE trial having the largest
post-exercise insulin response. No significant differences were observed between the three trials for urinary creatinine (g·24 h⁻¹) and urea (g·24 h⁻¹ and g·g Cr⁻¹). Day 6 urinary 3-methylhistidine (μmol·g Cr⁻¹) was significantly different between trials (POE>PO>PRE)(P < 0.01). Similarly, no significant differences were observed between trials for resting metabolic rate, thermic effect of food, thermic effect of exercise, and excess post-exercise oxygen consumption. However, on Day 5, Apparent Nitrogen Balance trended toward signifcance for trial (P=0.086) becoming significant on Day 6 (P <0.005) wherein POE and PO trials were positive and PRE trial was negative. There was a trend towards increased performance times when comparing the POE and PO trials versus the PRE trial (P =0.074). Furthermore, weight loss was significantly lower with post-exercise supplementation (POE<PO<PRE)(P < 0.01). This study suggests that the protein balance of females regularly engaging in endurance activity may benefit from immediate nutritional supplementation following exercise.

abstract: Thesis

abstract: Master of Science (MSc)


title: Peripheralization and Spatial Structure: Factors Influencing the Sexual Behaviour of Male Japanese Monkeys

title: The Sociosexual Behaviour of Male Japanese Monkeys

contributor:
Szathmary, E.
Anthropology

subject:
sociosexual
japanese monkeys
behaviour
spatial structure

abstract:
The present study examines the concept of peripheralization and spatial structure in the Arashiyama West troop of Japanese macaques (Macaca fuscata) , and employs an objective method to assess the existence of a central-peripheral tendency in the spatial organization of this Japanese macaque troop. By calculating each adult male's mean distance in meters from the 'alpha' male of the troop, it was possible to rank males according to their distances from the alpha male. The resultant linear gradation of males illustrates the troop's spatial organization. This study did not find evidence supporting the notion that a rigid central-peripheral structure exists in the Arashiyama West troop. Indeed, there appears to be no objective criterion whereby some males can be labelled "central" and others "peripheral", for the linear gradation of distances that defines the spatial organization of adult males can be bisected arbitrarily at any point along its continuum. In this thesis "spatial status" is defined as a gradation of the distance between each male and the alpha male, where the shortest mean distance corresponds to the highest spatial status. The predictors age, dominance rank and maternal lineage are examined for their influence in determining a male's spatial status within the troop. The isolated and cumulative effects of the aforementioned variables are also examined to explain variations in male sexual behavior. Results from this study indicate that a male's spatial status is directly influenced by the combined effects of age, rank and lineage, as well as by the isolated effects of any one of the previously mentioned variables. Furthermore, the results indicate that a male's age and spatial status explain the most variability in male mating behavior. Whether the process of peripheralization and the
existence of adult male spatial status are "exaptations", that is, traits which probably were NOT selected for
during the course of evolution of Macaca fuscata, cannot be proved by the data in this thesis. However, the
available evidence does suggest that spatial status in particular is more likely to be an "exaptation" rather
than an "adaptation", and accordingly it probably does not contribute to male fitness.

abstract: Thesis

abstract: Master of Arts (MA)


title: Population Structure and Genetic Diversity of the North Atlantic Right Whale (Eubalena Glacialis)

contributor:
White, Bradley N.
Biology

subject: habitat disturbances, net entanglement,haplotypes

abstract:
The North Atlantic right whale (Eubalaena glacialis) is the most endangered
species of large whale in the world (IUCN). Efforts for the recovery of this species were
initiated almost 20 years ago, yet the North Atlantic right whale shows little signs of
recovery. Reliance on particular habitat areas and the effect of factors such as ship
collisions, net entanglement and habitat disturbances are hampering the recovery of this
species. Therefore, it is important to assess the level of genetic diversity left in this
population and to identify and assess all habitat areas for potentially lethal threats. This
study has identified a subset of the reproductive females that do not use the Bay of Fundy
as a nursery area, through the genetic structuring of mtDNA control region haplotypes.
Genetic structuring of the control region haplotypes was established and maintained by
site fidelity of reproductive females to specific nursery areas. These results have
identified a list of reproductive females that will be the targets of satellite tagging to
elucidate the location of the alternative nursery area(s) to the Bay of Fundy. Analysis of
mtDNA control region haplotypes in North and South Atlantic right whale has identified
five haplotypes in the 180 North Atlantic right whales analyzed compared to 10
haplotypes in the 16 South Atlantic right whales analyzed. The low level ofhaplotypic
variability in the North Atlantic right whale is a direct consequence of the extensive
whaling period endured by this species. The genetic divergence between the North and
South Atlantic right whales was estimated to have occurred 3.0-9.0 mya. This is similar
to the genetic divergence of 2.0-5.3 mya found between the two clades identified in the
South Atlantic samples.

abstract: Thesis

abstract: Master of Science (MSc)


title: The Effect of Body-Weight Support Treadmill Training on Muscle Morphology and Glucose Tolerance in Individuals with a Spinal Cord Injury

contributor:
Phillips, Stuart
Kinesiology

subject:
weight
morphology
muscle
glucose
spinal cord
treadmill training

abstract: Skeletal muscle is the primary site of glucose disposal in the body, and consequently plays a predominant role in the regulation of blood glucose levels after the ingestion of a meal. Following spinal cord injury (SCI), skeletal muscles below the level of an upper motor neuron lesion undergo marked changes in muscular properties that affect glucose tolerance. Recent studies on individuals with a SCI have reported improved glucose tolerance following periods of electrically-stimulated training. This appears to result from improved muscle morphology and post-exercise insulin sensitivity, and increased GLUT 4 content, enzyme activity, and muscle fiber capillary number. It might be expected that the weight-bearing and greater muscular involvement associated with body-weight support treadmill training (BWSTT) would have an even more profound effect on previously observed responses. The purpose of this study was to investigate whether 6 months of BWSTT improved whole-body glucose tolerance and some of the muscular parameters that are expected to influence glucose metabolism, in a group of 9 individuals with an incomplete SCI. A leg biopsy and a resting, 3 hour oral glucose tolerance test (OGTT) were performed on each subject before and after 6 months of training. Analysis of the muscle biopsy revealed significant increases in post-training muscle fiber size for type I (P=0.01) and type IIa (P=0.05) fibers in comparison to pre-training values. A significant increase in type IIa fiber proportion (P=0.03) and a significant decrease in type IIx fiber proportion (P<0.01) were found following training. In addition, significant increases in post-training GLUT 4 protein content (P<0.01), citrate synthase protein content (P<0.01), and citrate synthase activity (P=0.01) were found in comparison with pre-training values. No change was found in the number of capillaries per fiber after training. Plasma insulin area under the time curve (AUC) during the post-training OGTT significantly decreased (P=0.04) in the subjects as a result of BWSTT. Despite the large decrease in plasma insulin concentration, blood glucose AUC also showed a significant decrease (P<0.01) during the post-training OGTT, indicating a training-induced increase in insulin sensitivity occurred in the subjects. According to the findings, we can speculate that the increase in insulin sensitivity was a result of the increase in muscle GLUT 4 content in the exercised muscles, possibly in combination with an increase in leg muscle mass, as indicated by an increased muscle fiber cross-sectional area. The results are the first in this field to provide evidence that BWSTT leads to beneficial morphological and metabolic changes in skeletal muscle fibers that improve glucose tolerance.

abstract: Thesis

abstract: Master of Science (MSc)


title: Purification and Characterization of S-Adenosyl-L-Methionine:Phosphoethaolamine N-Methyltransferase from Spinach

contributor:
Weretilnyk, Elizabeth A.
Biology

subject: osmotic stress, choline, synthesis, chromatography matrices

abstract:
During conditions of osmotic stress, some plants accumulate compatible
osmolytes such as glycine betaine or choline-0-sulphate. Choline is required
as a precursor for synthesis of both osmolytes and choline is also required by
all plants as a component of phospholipids. In the betaine accumulator
spinach, choline synthesis requires three sequential N-methylations of
phosphoethanolamine (PEA) to generate phosphocholine (PCho), with the first
N-methylation being catalyzed by S-adenosyi-L-methionine: PEA Nmethyltransferase
(PEAMeT). Choline synthesis and, more particularly the
activity of PEAMeT, are up-regulated by salinity (Summers and Weretilnyk,
1993). This thesis reports on the partial purification and preliminary
characterization of PEAMeT from spinach.
A variety of column chromatography matrices including DEAE Sepharose,
phenyl Sepharose, w-aminohexyl agarose, hydroxylapatite, phenyl Superose,
Mono Q and adenosine agarose, have been used to purify PEAMeT. A 5403-
fold purified preparation yielded a specific activity of 189 nmol· min-1
• mg-1
protein. SDS-PAGE analysis of this preparation revealed a number of
polypeptide bands but only one which photoaffinity cross-linked to [3H]SAM.
The estimated native molecular weight (MW) of PEAMeT was found to be 77
kDa by gel filtration chromatography and an estimated MW of 54 kDa was determined by SDS-PAGE. SDS-PAGE analysis of samples photoaffinity crosslinked
to [3H]SAM gave a slightly higher estimated MW of 57 kDa.
Effects of various factors on PEAMeT assay conditions were evaluated
using partially purified PEAMeT preparations. PEAMeT activity as a function
of pH gave a unimodal curve with an apparent pH optimum at 7.8 with 1 00
mM HEPES-KOH buffer. In vitro PEAMeT activity was inhibited by phosphate,
PCho, S-adenosyi-L-homocysteine, ca+ 2, Mn+2 and co+2 but not by choline,
betaine, ethanolamine, mono- and dimethylethanolamine or Mg+2
•
Phosphobase N-methyltransferase activities present in preparations enriched
for PEAMeT activity can catalyse the reaction sequence PEA- PMEA - PDEA
- PCho. Under optimized assay conditions using PEA as the sole substrate,
PMEA, PDEA and PCho were quantified and were detected in the order: PMEA
(77%) > PDEA (17%) > PCho (6%). Thus a single enzyme, PEAMeT, is
capable of converting PEA to PCho in leaves of spinach. The existence of a
second enzyme which converts PMEA to PCho has also been reported for
leaves and roots of spinach (Weretilnyk and Summers, 1992). The presence
of two enzymes with overlapping activities raises questions regarding the roles
of these two enzymes in choline metabolism. For example, do these enzymes
also have overlapping functions in choline synthesis, particularly under
conditions of osmotic stress?

abstract: Thesis

abstract: Master of Science (MSc)


title: A Historical Approach to Shifting Technologies of Ceramic Manufacture at Gaspereau Lake, Kings County, Nova Scotia

contributor:
Cannon, Aubrey
Anthropology

subject:
Maritime Woodland Period
Aboriginal ceramics
Gaspereau Lake
Nova Scotia archaeology
Maine-Maritimes Region

abstract:
A lengthy history (1550–950 Cal BP) of ceramic manufacture took place at the Gaspereau Lake Reservoir (GLR) Site Complex in Kings County, Nova Scotia, during which potters shifted their practice from fineware, emphasizing self-expression and signalling affiliation, to “production” pottery, focusing on quick turnaround times and larger scale of production. Researchers in the Maine–Maritimes Region have repeatedly noted the change from hard-bodied, thin-walled, elaborately and carefully decorated pots during the Middle Woodland to coarser-tempered, expediently decorated pottery with many coil breaks evident during the Late Woodland. This has sometimes been interpreted as a decreasing skill level through time, but I argue that these changes instead suggest a manufacturing context in which demand for pottery increased. This created incentives for “cutting corners” and employing strategies that increased the survival rate of pots during firing. Increased production is partly evident in increasing standardization of temper minerals and clay later in time, suggesting that potters increasingly accessed a single reliable source of raw materials rather than many different sources. I further argue that manufacturing occurred at or near the End of Dyke Site.
I present a method of analyzing ceramics that is designed to take full account of the unusually large and nuanced GFC assemblage. This method goes beyond chronological and typological classifications that have sometimes been employed in the Northeast: it seeks to establish a historical understanding of the assemblage through tracing learning lineages. This classification, which I have called a “tradition-based classification,” introduces knowledge transfer as the dominant mechanism behind style at the level of assemblage. The ceramics have been grouped using attribute analysis, after which inferences about the variability have been assessed, and finally, several trends—chronologically situated using AMS dates—are proposed to build a history of ceramic manufacture at Gaspereau Lake.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Ceramics are one means of analyzing the practices of ancient cultures. Ceramics allow archaeologists to trace developments through time. This dissertation looks at how other sources of information are available to archaeologists by carefully tracing the evolution of certain characteristics through time. Some characteristics explored in this dissertation include the changing methods of manufacturing ceramics and the changing materials used by ancient potters. I conclude that ceramic production increased later in time, and that this change probably indicates a change in the larger society as pottery became increasingly in demand.


title: RISK OF BIAS ASSESSMENT FOR STUDIES OF EXPOSURES

title: RISK OF BIAS ASSESSMENT FOR NON-RANDOMIZED STUDIES OF ENVIRONMENTAL EXPOSURES

contributor:
Schünemann, Holger J.
Health Research Methodology

subject:
Risk of Bias
GRADE
Environmental health
Risk assessment
Recommendations
Non-randomized studies
Environmental exposure

abstract:
When using evidence from non-randomized studies (NRS) to answer questions about the effects of environmental exposures on health, it is important to assess risk of bias (RoB) of individual studies as part of determining the certainty in the body of evidence. The recently released RoB in Non-randomized Studies of Interventions (ROBINS-I) instrument has undergone careful development and piloting on NRS of health interventions. A key feature of ROBINS-I is evaluating the RoB of studies against an ideal target trial, therefore establishing a structured comparison of RoB against a reference standard. While several instruments exist to evaluate the RoB of NRS of exposure, none of them use such a structured comparison of RoB. Using the fundamental design of ROBINS-I, we explored development of a version of the instrument to evaluate RoB in studies of environmental exposure. We identified important modifications necessitating a distinct instrument: The RoB instrument for NRS of exposures.
This work highlights the importance of standardized methods for environmental health decision making, proposes a modified instrument to evaluate the RoB of NRS of exposures, provides guidance for the implementation of the instrument and integration into structured evidence-synthesis frameworks (such as GRADE [Grading of Recommendations Assessment, Development and Evaluation]), and presents evidence on the reliability and validity of the instrument. The RoB instrument for NRS of exposures delivers a standardized instrument that systematic review authors and guideline developers can use to evaluate RoB in NRS of exposures. The nature of these methodological changes allow better integration of RoB assessment in the environmental health field with GRADE.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract:
When making a decision about interventions to reduce or remove an environmental exposure, evidence is needed to weigh the desirable and undesirable consequences of the decision. No research study is perfect. Most of the studies documenting environmental exposures cannot control for the fact that people who might be highly exposed may have different characteristics compared to those who have low levels of exposure other than just the exposure itself. For example, people exposed to more environmental air pollution living in inner cities may also be more likely to smoke or have occupational exposures that could predispose them to lung cancer than those exposed to lower levels of air pollution. Understanding limitations in studies that address those questions informs our certainty that the data represents the truth. The greater the confidence we have in the data, the more likely we are to be certain that removing or reducing exposure will lead to a desirable outcome. A tool can be used to walk people through the evaluation of limitations within each study. However, it is important that the tool evaluates the correct limitations within the study. It is also important that people using the tool can apply it reliably. Without a reliable or valid tool to evaluate the limitations of the studies, it can be difficult to inform decisions on whether or not to implement specific policies.
In our study, we tested the ability of a new and well-developed tool (ROBINS for interventions) to identify the limitations in studies linking environmental exposures to health outcomes. Based on the findings from our evaluation, we modified our protocol to see if we could improve our ability to evaluate these studies of environmental exposures. We asked people with an understanding of scientific methods to independently evaluate 35 studies with our modified tool (ROBINS for exposures). We compared those responses to see whether all the reviewers came up with similar decisions and if their decision was similar or different than the conclusion they made using more commonly used tools.
Based on our results, we determined that our modified tool does provide a consistent evaluation of study limitations and accurately measures the limitations present in studies of exposure. This tool can be used to inform decisions about removing or reducing one’s exposure to environmental hazards.


title: PRE-CLINICAL DEVELOPMENT OF SYNTHETIC RECEPTOR-ENGINEERED T LYMPHOCYTES FOR THE TREATMENT OF CANCER: NOVEL RECEPTORS AND UNDERSTANDING TOXICITY

contributor:
Bramson, Jonathan
Medical Sciences

subject:
Immunology
Immuno-oncology
Chimeric antigen receptor
CAR-T cells

abstract:
Advances in our understanding of the molecular events leading to cancer have facilitated the development of next-generation targeted therapies. Among the most promising new approaches is immuno-oncology, where therapeutic agents engage the immune system to fight cancer. One exciting strategy therein is the adoptive transfer of ex vivo cultivated tumor-specific T lymphocytes into a cancer patient. Tumor-specific T cells can be produced by engineering a patient’s own T cells with synthetic receptors (e.g. chimeric antigen receptors (CARs)) designed to redirect T cell cytotoxicity against a tumor target. CAR-engineered T cells (CAR-T cells) were expected to be a non-toxic cellular therapy which would seek out and specifically eliminate disseminated tumors. The clinical experience supports the promise of CAR-T cell therapy (striking efficacy has been observed in the treatment of hematological malignancies), while highlighting areas for improvement; CAR-T cell use has been associated with a host of toxicities and robust clinical efficacy has yet to be replicated in solid tumors.

This thesis uses pre-clinical models to describe previously unappreciated aspects of CAR-T cell-associated toxicity and novel synthetic receptor strategies, including:

i.	The capacity of NKG2D-based CAR-T cells to mediate toxicity.
ii.	The utility of designed ankyrin repeat proteins as CAR antigen-binding domains.
iii.	The discovery that variables intrinsic to human CAR-T cell products contribute to toxicity.
iv.	A novel synthetic receptor capable of redirecting T cell specificity against a tumor target – the T cell antigen coupler (TAC). Unlike equivalent CAR-T cells, TAC-T cells are capable of mediating efficacy against a solid tumor in the absence of toxicity.

We anticipate that these results will contribute towards the development of next-generation synthetic receptor-engineered T cell products that can deliver upon the promise of safe, systemic cancer therapeutics.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: The human immune system has the unique capacity to “seek and destroy” tumor cells throughout the body. A novel class of drugs, immuno-oncology agents, harness this ability to fight cancer. Within this class is a new cellular drug where genetic engineering is used to create killer immune cells (called T cells) capable of recognizing and eliminating tumors. Two of these cellular drugs have recently received FDA approval, supporting the feasibility of this approach. However, further research is needed to improve the safety of engineered-T cells and increase the number of patients whom can benefit from their use. This thesis uses laboratory investigations to better understand the side-effects associated with anti-cancer engineered-T cells and evaluate new engineering strategies. We anticipate that these results will contribute towards the development of next-generation engineered-T cell drugs which retain the ability to function systemically against cancer but offer an enhanced safety profile.


title: The Courtship Behaviour of Female Japanese Monkeys

contributor:
Saunders, Shelley R.
Anthropology

subject: non-copulatory, mating pairs, formation,rejection, sequential analysis

abstract:
rhe non-copulatory estrous behaviour of semi-free
ranging female Japanese monkeys was observed for 3 months,
in order to investigate the role of the female in the
establishment of mating pairs. It was concluded that the
females play a very active role in the formation of mating
pairs, showing three times more solicitation behaviour
than males. They also reject more than 30% of the advances
they do receive. This is interpretated as an indication of
selectivity in the choice of sexual partners. The behaviour
of the female in this courtship context is described, with
emphasis on preceptive or solicitation behaviour. The data
were tested for behavioural differences based on the female's
age, rank, parity, number of offspring and the presence of
an infant, and for differences based on the age, rank and
spatial status of the interacting male. Age of the female
had the greatest effect on behaviour, with older females
behaving in a more calm, sophisticated manner when
soliciting a male. Age was also the most significant male
variable, with females showing more rejection to younger
males. Other than age related findings it must be concluded
that these sociological characteristics of the animals are
not predictive of the females' courtship behaviour. A
number of alternate lines of inquiry for future research are suggested. They include an investigation of the hormonal basis of estrous behaviour, a multivariate
analysis, and a sequential analysis of behaviour.

abstract: Thesis

abstract: Master of Arts (MA)


title: Pimozide and Sham Feeding: Addition of the Postingestive Cues of Cholecystokinin or Glucose

title: Pimozide and Sham Feeding

contributor:
Weingarten, H. P.
Psychology

subject:
pimozide
sham feeding
postingestive
cholecystokinin
glucose

abstract: The present thesis examined the potential interaction between postingestive cues and the dopamine antagonist pimozide on the inhibition of sucrose sham intake. Coadministration of CCK and pimozide IP produced additive inhibitory effects on sham feeding of 4% or 17.1% sucrose. Manipulations of blood glucose levels by infusion of 10% dextrose or injection of 0.1U insulin SC did not interact with pimozide to alter the latter drug's inhibition of 34.2% sucrose sham feeding. Separate experiments verified that these manipulations significantly altered blood glucose levels compared to a control 0.9% saline infusion IV. Infusions of d-glucose into the lateral ventricle significantly enhanced the inhibitory effects of pimozide on 34.2% sucrose sham intake compared to infusions of!glucose or 2-deoxy-glucose. Infusions of d-glucose into the third ventricle, however, significantly attenuated the inhibitory effects of pimozide on 34.2% sucrose sham feeding compared to the control l-glucose infusions. These results collectively suggest that some postingestive cues, such as elevations in third ventricle glucose levels, are indeed capable of inhibiting the suppressive effects of pimozide on sucrose sham feeding.

abstract: Thesis

abstract: Master of Science (MSc)


title: DCMU-Enhanced Fluorescence as an Indicator of Physiological Condition and Light History in Phytoplankton

contributor:
Harris, G.P.
Biology

subject:
Phytoplankton
light history
dcmu-enhanced fluorscence

abstract:
Fluorescence (F), DCMU-enhanced fluorescence (F^DCMU) and a ratio of these two measurements (F ratio) were found to be useful indicators of light history but not physiological condition of natural phytoplankton assemblages. Changes in the fluorescence properties of unialgal continuous and batch cultures at different growth rates and following nutrient addition were observed only during nutrient starvation. Nutrient deficiency in Lake Ontario was not revealed either by seasonal patterns of fluorescence or by short term changes in the F ratio following nutrient additions. This result however is not conclusive evidence of nutrient sufficiency because of the insensitivity of the fluorescence ratio as an indicator of growth rate. The depression of F and F^DCMU observed in surface waters of Lake Ontario occurred during conditions of high light and low mixing rates. The result suggests that ''photoinhibition" of photosynthesis as measured by conventional primary productivity techniques, may occur in nature only under these particular conditions.
A general relationship between temperature gradients or water column stability and the difference in fluorescence between 1 and 10 meters was observed. This relationship was due to both vertical structure in the assemblage and the physiological effect of light on fluorescence. Diurnal patterns of fluorescence were found to be due to the physiological effect of light on fluorescence rather than a circadian rhythm. The physiological effect was dependent on both the duration and intensity of exposure of the cells to light as well as the sensitivity of the assemblage to light. Differences were associated with seasonal changes in species composition with spring and winter populations exhibiting the greatest sensitivity.

abstract: Thesis

abstract: Master of Science (MSc)


title: Elemental Analysis and Microscopical Studies of the Mature Seeds of Eleven Species of Pinus

contributor:
Lott, J.N.A
Biology

subject: Pinus,lipids,proteins,crystalloids,globoid crystals

abstract:
The storage reserves in the mature seeds of eleven
species of Pinus were investigated. Lipids and proteins 1
sequestered in lipid vesicles and protein bodies respectively 1
were found to be the major storage reserves of pine seeds.
All seed tissues of mature Pinus seeds contained protein
bodies with one or more protein crystalloids andjor one or
more globoid crystals. Energy dispersive x-ray (EDX) analysis
of globoid crystals in all species of Pinus that were studied
revealed the presence of P 1 K and Mg 1 a fact that is
consistent with globoid crystals being phytate-rich. Traces
of Ca and Fe were also detected in the globoid crystals of
some seed tissues.
High levels of Fe and significant levels of P1 K and
Mg were detected in small (often .:::; 0. 3 3 J,£m) 1 naturally
electron-dense particles that were distributed throughout the
tissues of the embryo and female gametophyte. Unlike
conventional phytate-rich globoid crystals 1 these Fe-rich
particles were not contained in the proteinaceous matrix of
typical protein bodies. Instead 1 the particles were contained
within membrane-bound structures resembling plastids.
Neutron activation analysis and spectrophotometric
phosphorus analysis were used to provide a quantitative
determination of elements in whole female gametophyte and
embryo tissue samples. High levels of P, K, Mg and S and
significant levels of Cl, Ca, Mn, Zn and Fe were detected in
pine seed tissues. Environment and growth conditions under
which the seed developed did not appear to affect the total
mineral nutrient levels of mature pine seeds.
Seed size and weight varied greatly between the eleven
species of Pinus investigated. A major focus of this study
was to determine whether seed size was correlated to the
distribution of minerals in pine seeds. Previous studies
showed that mineral distribution was related to seed size in
cucurbits. Phosphorus, Mg and Ca concentrations in globoid
crystals and Fe concentrations in electron-dense particles of
Pinus seed tissue were found to be negatively correlated with
seed size.
A comparative study of nutrient reserves in haploid
female gametophyte tissue versus diploid embryo tissues was
made. Within each species of Pinus, the total mineral
nutrient concentrations in whole female gametophyte samples
were similar to total mineral nutrient concentrations within
whole embryo samples. Protein body structure and the types of
mineral nutrients stored in globoid crystals of protein bodies
were also similar between female gametophytes and their corresponding embryos.

abstract: Thesis

abstract: Master of Science (MSc)