title: INVESTIGATION OF THE HUNTINGTIN-HAP40 INTERACTION IN HUNTINGTON’S DISEASE

contributor:
Truant, Ray
Biochemistry

subject:
HAP40
Huntingtin
Huntington's disease
Nervous System Diseases
Nervous System Diseases

abstract: Huntington’s disease (HD) is a neurodegenerative disorder caused by the expansion of a polyglutamine tract in the huntingtin protein. The huntingtin protein has many roles in vesicular and endocytic trafficking, which can be modified in HD cells. When mutant huntingtin is expressed in HD, protein levels of the huntingtin interacting protein, Huntingtin-associated protein of 40kDa (HAP40) are increased. This increase in HAP40 protein levels causes the formation of a complex between carboxyl terminal huntingtin, HAP40 and active Rab5 on the early endosome. This complex induces a switch from early endosomal movements on microtubules to movements on actin filaments, greatly reducing both the speed and distance of movement. The main objective of this research is to determine where the interaction occurs between huntingtin and HAP40 on the huntingtin protein. Here we show that HAP40 interacts with the amino terminus of huntingtin, specifically the first 17 amino acids (N17). In co-localization studies, we found that HAP40 co-localizes with the carboxyl terminal fragment of huntingtin corresponding to amino acids 2570-2634; however, GFP trap immunoprecipitation analysis revealed no interaction between the carboxyl terminal fragments of huntingtin and HAP40. An interaction was discovered between HAP40 and N17, which was then confirmed by far western blot. These results demonstrate that HAP40 interacts with N17. By identifying the interaction site between HAP40 and huntingtin, modifications can be explored to prevent the interaction of HAP40 with huntingtin. This would restore motility on microtubules reinstating fast, long-range movements of early endosomes.

abstract: Master of Science (MSc)


title: The Human Coronavirus Nucleocapsid Protein and Its Effects on the Innate Immune Response

contributor:
Lichty, Brian
Medical Sciences

subject:
interferon
NF-kappaB
microRNA
immune evasion
Virology
Virology

abstract: Coronaviruses are the largest known RNA viruses and infect a wide range of hosts. Human coronaviruses traditionally have been known to be the cause of the common cold and have been vastly understudied due to low morbidity and mortality. The emergence of SARS-CoV and MERS-CoV has altered the landscape of coronavirus research and proven the deadly capabilities of human coronaviruses. With two recent zoonotic events, it is increasingly important to understand the molecular biology of human coronaviruses. The coronavirus nucleocapsid protein is an essential structural protein that complexes with the viral genome. Though nucleocapsid formation is the protein’s major role, it has also been found to have other functions and effects during infection. The following research aimed to examine how the human coronavirus nucleocapsid protein affects the innate immune response in vitro. Modulation of the type I interferon response by the nucleocapsid was first investigated and the nucleocapsids were shown to have the ability to block interferon signalling. Additionally, the nucleocapsid protein was found to cause a dysregulation of transcription factor NFKB1. We propose a novel mechanism of this NFKB1 negative regulation interference. Taken together, we have further characterized the significant role of the coronavirus nucleocapsid protein in innate immune evasion.

abstract: Doctor of Philosophy (Medical Science)


title: EFFECTS OF PLANT SOCIAL ENVIRONMENT ON THE MUTUALISTIC INTERACTIONS BETWEEN PLANTS AND MYCORRHIZAL FUNGI

contributor:
Dudley, Susan
Balshine, Sigal
Rollo, CD
Biology

subject:
plants
kin recognition
mycorrhiza
phenotypic plasticity
mutualism
Biology
Biology

abstract:
Plants and mycorrhizal fungi form a mutualism in which plants donate carbon to the fungus and, in return, receive benefits such as increased nutrient uptake and water. Mycorrhizal fungi colonize plant roots, forming nutrient exchange structures. The fungi also colonize the soil by growing long strands of hyphae that forage for nutrients and attach plants, forming a common mycorrhizal network (CMN). Plants attached to a well-supported CMN will receive greater benefits than those attached to a lesser CMN because the more carbon donations the fungal partner receives, the more it can grow and colonize the soil, accessing hard to reach soil nutrients. Kin selection theory predicts that relatives should donate more carbon to the fungal partner than non-relatives because benefits gained by neighbouring relatives through the CMN lead to inclusive fitness gains. Thus, social environment, i.e. relatedness of the group, could affect the mycorrhizal mutualism. Moreover, the presence of mycorrhizal fungi in the soil could affect plant responses to their social environment.

For my PhD thesis I have investigated whether mycorrhizal fungi respond to plant social environment and whether the presence of mycorrhizal fungi affects plant responses to relatedness. I have addressed these topics in three greenhouse studies and two field studies, using herbaceous plants and trees. I have found strong evidence that siblings have an increased association with their mycorrhizal partner compared to strangers, resulting in greater benefits for siblings. Taken together, the results from this thesis demonstrate that the ability for plants to recognize kin has implications beyond intra-specific competitive interactions and that plant social environment has important effects on a widespread inter-specific mutualism. Additionally, the recently discovered phenomenon of plant kin recognition has been put into the context of mycorrhizae, and I have shown that mycorrhizal plants respond differently to their social environment than non-mycorrhizal plants.

abstract: Doctor of Philosophy (PhD)


title: STUDY OF RECIPROCAL CROSS DIFFERENCES IN F1 FEMALES OF DROSOPHILA MAURITIANA AND D. SIMULANS

contributor: Richard Morton, Kimberly Dej, Bhagwati Gupta

subject:
maternal effect
speciation
D. simulans
D. mauritiana
fertility
reciprocal crosses
Biology
Biology

abstract: Haldane’s rule states “when in the F1 offspring of two different animal races one sex is absent, rare, or sterile, that sex is the heterozygous sex”. Many studies regarding hybrid male sterility and in-viability have been done in order to better understand the process of speciation in males. Yet the study of speciation in hybrid females has been largely ignored. In our study we re-examined the extent of fertility in F1 reciprocal females of hybridization between Drosophila simulans and D. mauritiana species. Hybridization between these species produces fertile females and sterile males. Our goal was to address the following questions: 1. Are F1 hybrid females fully fertile? 2. Are there any maternal effects observed in reciprocal female hybrids? 3. Are there significant differences in ovariole numbers between the reciprocal hybrids? and 4. What is the state of the hybrid ovaries as a function of age? In order to answer these questions we looked at the level of oviposition and egg hatchability and the differences in ovariole numbers in pure species and F1 females. Our results indicated that the reciprocal hybrid females are not only fully fertile but they also showed heterosis. The heterosis observed in the hybrids can be attributed in part to the presence of maternal effects. The reciprocal hybrids also showed differences in ovariole number compared to each other and to the parental species. Our findings signify the importance of maternal effects as a potentially powerful mechanism for moderating the rates of evolution of speciation in hybrid females.

abstract: Master of Science (MSc)


title: TRUNCATIONS OF THE RESPONSE REGULATOR AGRA INHIBIT STAPHYLOCOCCUS AUREUS QUORUM SENSING

contributor: Medical Sciences (Molecular Virology and Immunology Program)

subject:
Staphylococcus aureus
quorum sensing
dominant negative decoy
peptide mimetic
inhibition
Medical Sciences
Medical Sciences

abstract:
Virulence in Staphylococcus aureus is mediated by the accessory gene regulator (agr) quorum sensing system. This regulatory system is activated by a secreted thiolactone peptide termed autoinducing peptide (AIP) and its receptor histidine kinase, AgrC. Interaction of extracellular AIP with a cognate AgrC receptor generates an intracellular signal that is transduced by conformational changes and phosphorylation events in a two-component sensor histidine kinase system. At the heart of the agr quorum-sensing cascade lies the two-component histidine kinase, AgrC, and the response regulator protein, AgrA. Interaction of AgrC and AgrA, and the resulting phosphotransfer event results in expression from the divergent promoters P2 and P3, inducing expression of the master quorum-sensing regulator RNAIII and upregulating the agr operon respectively. Signal transduction systems function as intracellular information-processing pathways that link sensation of external stimuli to specific adaptive processes. In S. aureus , these include the up-regulation of virulence factors and hemolysis production, biofilm formation, and colonization-based regulation of surface proteins and adhesion factors. As such, the interactions of these systems have become key targets in the design of small inhibitor compounds.

Through the creation of a protein truncation series, we proposed the development of a small protein for the inhibition of key protein-protein interactions involved in S. aureus agr two-component signaling. Herein, we demonstrate the efficacy of these protein truncations as dominant negative inhibitors of AgrC:AgrA interactions, likely acting as a dominant phosphoacceptor in place of endogenous AgrA. We provide evidence of this function through in vitro hemolysis assays and phosphate-detection based gel electrophoresis.

abstract: Master of Science (MSc)


title: LEPTIN IN PREGNANCY: ASSOCIATION WITH BONE HEALTH IN THE OFFSPRING

contributor:
Atkinson, S.A.
Sandy Raha, Stuart Phillips
Medical Sciences

subject:
adiposity
DXA
body composition
young children
nutrition
vitamin D
Medical Nutrition
Medical Sciences
Medical Nutrition

abstract:
Leptin, an adipose derived hormone, has emerged as a regulator of bone metabolism. Recent findings support a role of leptin in the process of fetal bone remodeling during pregnancy; however, the link between maternal leptin during pregnancy and offspring bone status is undocumented. Evidence exists that the intrauterine environment plays a role in programming peak bone mass that is achieved in late adolescence and thus osteoporosis risk later in life. We investigated the association between maternal leptin during the third trimester and offspring bone mass at 3 years of age.

Method: Based on a sub-sample of a prospective birth cohort study, we conducted analysis on 425 mothers from whom maternal blood samples in pregnancy were analyzed for leptin and 25- hydroxyvitamin D, and whole body bone mass by dual energy x-ray absorptiometry were available for both mother and child at 3 years. Data were collected for maternal prepregnancy body mass index (BMI), lifestyle, and nutrition during pregnancy, as well as the child’s nutrition and physical activity at 3 years.

Results: Women obese on entering pregnancy have a two-fold greater circulating leptin during pregnancy than women with normal weight BMIs. Maternal age and skinfold thickness were positively associated with maternal leptin status. However, maternal leptin status was not a significant predictor of offspring BMC z-score at 3 years of age, when adjusted for relevant maternal and child variables. Maternal vitamin D status was also not a predictor of offspring bone status. Rather the key predictors of child BMC z-score were maternal bone mineral density z-score and child’s weight and vitamin D intake at 3 years.

Conclusion: While maternal leptin status during pregnancy is highly variable among women of different BMI categories, in utero exposure to leptin is not a significant factor that influences child bone status at 3 years of age when adjusted for other relevant variables.

abstract: Master of Science (MSc)


title: Surface Characterization and Comparison of Contact vs. Non-Contact Printed Sol-Gel Derived Material Microarrays

contributor:
Brennan, John D.
Capretta, Alfredo
Chemical Biology

subject:
microarrays
sol-gel
x-ray photoelectron spectroscopy
infrared spectroscopy
printing
Analytical Chemistry
Materials Chemistry
Analytical Chemistry

abstract: Fabrication of microarrays using sol-gel immobilization has been utilized as an approach to develop high density biosensors. Microarray fabrication using various printing techniques including pin-printing and piezoelectric ink jet printing methods has been demonstrated. However, only limited characterization to understand the encapsulated biomolecule-material interface has been reported. Herein, Chemical characterization using X-ray photoelectron spectroscopy (XPS) and infrared spectroscopy (IR) on pin-printed microarrays of sol-gel derived acetylcholinesterase (AChE) microarrays is reported. Furthermore, the in situ fabrication of microarrays following the sol-gel process using piezoelectric ink jet printing methods was explored. Through techniques measuring solution viscosity, surface tension and particle size, important aspects of bio-ink formulation for piezoelectric ink jet printing were identified. Combined, a greater understanding towards the fabrication and characterization of sol-gel derived microarrays was achieved through this exploratory research.

abstract: Master of Science (MSc)


title: CHOP IS A KEY REGULATOR OF p20K IN HYPOXIA AND CONTACT INHIBITED CHICKEN EMBRYONIC FIBROBLASTS

contributor:
Bedard, Andre
Daniel, Juliet
Elliot, Marie
Biology

subject: Biology Biology

abstract: Growth arrest specific (GAS) genes are responsible for regulating cell proliferation, gene expression, and apoptosis (Fleming et al., 1997). Given these roles, it is important to study the mechanisms of action and regulation of Gas genes in quiescence (G0). If altered, quiescence can lead to abnormal development, degenerative diseases, and cancer (Liu et al., 2007). The p20K lipocalin is a GAS gene expressed in contact inhibited cells (Kim et al., 1999). Recent studies have also demonstrated that p20K is highly inducible in hypoxia, and its activation in hypoxia and contact inhibition is dependent upon a 48bp promoter region referred to as the Quiescence Responsive Unit (QRU) (Mao et al. 1993; S. Kim et al. 1999; Fielding, MSc. Thesis, 2011). Furthermore, p20K is highly regulated by CAAT/enhancer binding protein (C/EBPβ) as C/EBPβ crucial interaction with different QRU binding sites are essential for the activation of p20K (Kim et al., 1999). CHOP, a C/EBP homologous protein belonging to the C/EBP family, has been identified as an inhibitor of C/EBPβ activity (Sok et al., 1999). Co-immunoprecipitation experiments showed that CHOP induction either by ER stress or starvation promoted the formation of C/EBPβ heterodimers inhibiting p20K expression in Chicken Embryonic Fibroblasts (CEFs). Experiments using a CHOP knockdown by shRNA demonstrated that CHOP repression induced robust expression of p20K in cycling CEF cells after 24 hours in hypoxia, but not at earlier time points. In addition, as documented by RT-qPCR and Western blotting analysis, both p20K and CHOP mRNA and protein expression levels show to have an inverse relationship in hypoxia and contact inhibition. Since CHOP expression is greatly induced during ER stress and starvation, two ER stress inducible agents (tunicamycin and thapsigargin) were used to stimulate high levels of CHOP in CEF, leading to the induction of CHOP and repression of p20K. CEF were also treated with DMOG, a hypoxia mimetic that can stabilize Hypoxia Inducible Factor (HIF) under normoxic conditions (Barnucz et al., 2013). Surprisingly, in DMOG treated cells CHOP levels did not decrease, while p20K was highly induced. At later time points, while DMOG induces modest induction of CHOP, it decreases phospho-ERK levels (a transcriptional repressor of p20K) demonstrating a separate signal/pathway controlling p20K induction in these conditions that requires follow up studies. Collectively, these results demonstrate that the down-regulation of the p20K GAS gene in response to ER stress is mediated by the induction of CHOP and segregation of C/EBPβ as heterodimers.

abstract: Master of Science (MS)


title: INFORMATIC STRATEGIES AND TECHNOLOGIES FOR THE DIRECTED DISCOVERY OF NONRIBOSOMAL PEPTIDES

contributor:
Magarvey, Nathan
Chemistry and Chemical Biology

subject:
nonribosomal peptide
bioinformatics
natural products
drug discovery
genome mining
Biochemistry
Bioinformatics
Biotechnology
Other Microbiology
Biochemistry

abstract:
Nonribosomal peptides (NRPs) are a major class of natural products known for their biological activities and are employed therapeutically as immunosupressants, anticancer agents, and antibiotics. Nonribosomal peptides are microbial products, biosynthesized by large assembly line-like enzymes, known as nonribosomal peptide synthetases (NRPSs) that can be found in large gene clusters within the genome. With the advent of genome sequencing, the gene clusters for known NRPs are easily identified within producing organisms, but more strikingly, this sequencing reveals that microbes often contain many gene clusters with no known products suggesting traditional methods of isolation are overlooking the majority of NRPs.

Extensive studies of NRPS functions have revealed assembly line logic for the biosynthesis of NRPs and using this knowledge, the NRP products of NRPS gene clusters can be predicted. In this research, products from both a simple dimodular NRPS from Staphylococcus aureus and a complex 11 module NRPS from Delftia acidovorans were predicted and used to successfully identify and isolate two novel NRPs, aureusimine and delftibactin. Theses compounds fell outside traditional NRP activities, one being a virulence regulator and the other a gold-complexing metallophore. Subsequent biosynthetic studies of the aureusimine gene cluster within the heterologous host, Escherichia coli, provide insight into NRPS flexibility for the creation of NRP natural variants and highlighted the utility of E. coli for the heterologous production of NRPs.

Realizing single NRP predictions are not always accurate, a strategy was devised to use a genomically predicted NRP fragment barcode databases with the LC-MS/MS dereplication algorithm, iSNAP, to chemoinformatically identify and physically locate genetically predicted NRPs within crude extracts. This final contribution eliminates the need for bioactivity guided approaches to discovery and provides a strategy to systematically discover all predicted NRPs from cryptic gene clusters. This thesis delivers strategies and technologies for the directed discovery of NRPs from microbial sources.

abstract: Doctor of Philosophy (PhD)


title: KNOWLEDGE OF DIAGNOSIS, TREATMENT AND LATE EFFECTS IN ADOLESCENT AND YOUNG ADULT SURVIVORS OF CHILDHOOD AND ADOLESCENT CANCER

contributor:
Klassen, Anne F.
Barr, Ronald D.
Thabane, Lehana
Health Research Methodology

subject:
cancer
neoplasm
knowledge
Adolescent and young adult
survivor
Oncology
Oncology

abstract:
Abstract

Purpose: While most children diagnosed with cancer survive their initial disease, the intensive treatments they receive place them at risk for late effects. Long-term follow-up (LTFU) care is recommended for cancer survivors for surveillance and early detection of late effects. Knowledge, or lack thereof, regarding diagnosis, treatment and late effects is an important barrier and/or facilitator for attending LTFU care in adolescent and young adult (AYA) cancer survivors. The purpose of our study was to examine the extent of knowledge in Canadian AYA survivors of childhood and adolescent cancer, and identify factors associated with such knowledge.

Methods: Survivors of childhood and adolescent cancer, between the ages of 15 and 26 years, were recruited from three pediatric oncology centres. Patients were invited to participate in the study through mail and clinic recruitment. A questionnaire booklet, including the Cancer Knowledge Survey that asked questions about cancer, treatment and late effects, was administered to collect necessary information. Clinical data was extracted from hospital records to validate participants’ answers.

Results: 250 (response rate= 75.5 percent) out of 331 patients invited to participate completed the questionnaire booklet. 18 (7.2 percent) participants lacked information regarding their type of cancer, whereas 25 (10.3 percent) participants were ‘not knowledgeable’ of their treatment. Lack of knowledge regarding treatment was associated with being non-white [odds ratio= 0.3 (0.2-0.6)] compared with white. Also, 83 (33.5 percent) participants were unaware of their late effects. Lack of knowledge regarding late effects was associated with younger age [odds ratio= 1.2 (1.1-1.3)], and having leukemia compared with embryonal tumour [odds ratio= 3.41 (1.10-10.6)].

Conclusion: Results from this study highlights important knowledge deficits, especially in terms of understanding risk of late effects from cancer treatments. Findings from this study can be used to design programs and interventions aimed at increasing cancer knowledge in AYA cancer survivors.

abstract: Master of Science (MSc)


title: THE EFFECTS OF IN UTERO AND POSTPARTUM EXPOSURE TO SELECTIVE SEROTONIN REUPTAKE INHIBITORS ON BONE PROPERTIES IN RATS

contributor:
Wohl, Gregory R.
Biomedical Engineering

subject: SSRI

subject: bone

subject: rat

subject: pregnancy

subject: Biomechanics and biotransport

subject: Biomedical Engineering and Bioengineering

subject: Biomechanics and biotransport

abstract:
Selective serotonin reuptake inhibitors (SSRIs) are the most common drugs prescribed to treat depression during pregnancy. The influence of SSRI exposure during pregnancy on fetus bone properties is not clearly understood. The overall objective of this thesis project was to investigate the short and long-term effects of in utero and postpartum exposure to SSRIs on bone in rats through measuring bone structural and material properties.

Two studies with two types of SSRIs were carried out. Dams in the treated groups were randomly assigned to receive sertraline (10 mg/kg/day, N=5) in the first study and fluoxetine (10 mg/kg/day, N=17) in the second study. Control animals in the studies received saline in a flavoured gelatin vehicle. Rats were exposed to sertraline only during pregnancy, but fluoxetine was administered to the dams during pregnancy and also during breastfeeding. Rat offspring were sacrificed at 3, 7 and 26 weeks of age and left femurs and L6 vertebrae were analyzed for differences in morphology and mechanical properties.

Maternal sertraline exposure resulted in significantly shorter femurs for the offspring at 3 weeks of age. Rat femurs from the sertraline group were also weaker at 3 and 7 weeks of age compared to controls. In comparison, in utero and postpartum exposure to fluoxetine did not have a negative impact on bone properties. In fact, the femurs from fluoxetine exposed offspring were significantly stronger at 3 weeks of age compared to the controls

Findings in this project suggest that the type of SSRI used by pregnant woman should be considered as an important factor. Maternal sertraline exposure has a negative effect on offspring bone properties. Considering the fact that various mechanisms are involved in the influence of SSRIs on bone, further studies should be conducted to determine the mechanisms of this influence on bone properties in utero and through stages of development.

abstract: Master of Applied Science (MASc)


title: Backward Compatibility Effects in Dual-Task Performance: Implications for Central Information Processing

contributor:
Watter, Scott
Psychology

subject:
psychological refractory period
divided attention
dual-task
response selection
bottleneck
backward crosstalk
Cognitive Psychology
Cognitive Psychology

abstract: The psychological refractory period (PRP) paradigm has been used extensively to investigate the cognitive processing stages involved in dual-task performance. Interpretations of PRP data have often attributed the difficulty in simultaneously performing two cognitive tasks to a strict serial processing bottleneck in the response selection stage. However, a number of studies have also demonstrated backward response compatibility effects (BCEs) on Task 1 reaction time in dual-task performance, which suggest that response information for Task 2 may be activated in parallel with Task 1 response selection. The goal of this thesis was to examine the nature of the Task 2 processing that operates in parallel with Task 1 response selection in a PRP task, and to consider the implications of this parallel processing for models of dual-task performance. The results of the empirical studies presented here provide converging evidence that the BCE represents automatically activated response information for Task 2 acting on Task 1 response selection. This Task 2 response information can also contribute to Task 2 performance. Models of dual-task performance must account for both the parallel activation of response information and the serial selection of a response for each task.

abstract: Doctor of Philosophy (PhD)


title: THE ROLE OF THE PHOU PROTEIN IN SINORHIZOBIUM MELILOTI

contributor:
Finan, T.M.
Golding, G.B.
Biology

subject:
PhoU
Sinorhizobium meliloti
Bacteriology
Bacteriology

abstract: Phosphate is of central importance in cellular metabolism and since bacteria are often exposed to various concentration of phosphorous in their environment, they have acquired various Pi transport systems for its uptake. Sinorhizobium meliloti has three Pi-uptake systems: a low affinity system encoded by pap-pit and two ABC type systems encoded by the phnCDET and pstSCAB operons. It is currently known that PstSCAB2, a high affinity, high velocity transporter is induced under Pi limiting conditions and its transcription is controlled mainly in a PhoB-P dependent manner. During excess phosphate conditions, the negative regulation of the Pho regulon seems to involve PstSCAB2 and PhoU. PhoU appears to be a negative regulator of the Pho regulon however; the mechanism by which PhoU accomplishes this task is currently unknown. In Escherichia coli and some other bacteria, mutations in phoU result in constitutive Pho regulon expression as do mutations in the pstSCAB genes. In order to address the function of PhoU in Sinorhizobium meliloti, we report the creation of a Sinorhizobium meliloti ΔphoU mutant strain. Results from the analysis of the S. meliloti ΔphoU strain suggest that this mutant behaves similarly to E. coli phoU mutant where one observes constitutive expression of the Pho regulon.

abstract: Master of Science (MSc)


title: QUANTIFYING THE REGIONAL VARIATIONS IN THE MECHANICAL PROPERTIES OF CANCELLOUS BONE OF THE TIBIA USING INDENTATION TESTING AND CT IMAGING

contributor:
Quenneville, Cheryl E.
Biomedical Engineering

abstract: Finite element (FE) models are a fast and cost-effective way to evaluate stress behavior in bone under various loading conditions. However, accurate material property assignment is required when developing the model. Bone is an inhomogeneous material as there is much variation in the distribution of its mechanical properties. However, there has been limited investigation into the extent of regional variations in the cancellous bone of the proximal tibia. Dynamic FE models simplify bone as a homogeneous material, which may affect their accuracy. However, density-modulus relationships have been successful in assigning accurate material properties in the development of static FE models. There are many such equations in the literature and the most appropriate densitymodulus relationship for cancellous bone of the proximal tibia has yet to be determined. In the first study of this thesis, indentation testing was performed on four slices, each consisting of nine regions, from five cadaveric tibiae. The modulus and yield strength were found to vary regionally, where the bone closest to the joint and in the medial condyle were strongest, and the intercondylar region the weakest. These areas of strength can serve as improved sites of attachment to ensure the long-term success of orthopaedic devices. It also suggests that regional variations in cancellous bone need to be considered in the development of subject-specific FE models. In the second study, density-modulus relationships developed for cancellous bone of the tibia were evaluated for their ability to predict mechanical properties. Computed tomography (CT) was used to determine bone density, which was used in three equations from the literature to compare predicted modulus to experimental elastic modulus. It was

abstract: Master of Applied Science (MASc)


title: IDENTIFYING AND OVERCOMING OBSTACLES TO SAMPLE SIZE AND POWER CALCULATIONS IN FMRI STUDIES

contributor: Clinical Epidemiology/Clinical Epidemiology & Biostatistics

subject:
sample size
power calculations
cost efficiency
fMRI studies
systematic review
reporting quality
guidelines
Biostatistics
Mental Disorders
Neurosciences
Psychiatric and Mental Health
Statistical Methodology
Biostatistics

abstract:
Functional magnetic resonance imaging (fMRI) is a popular technique to study brain function and neural networks. Functional MRI studies are often characterized by small sample sizes and rarely consider statistical power when setting a sample size. This could lead to data dredging, and hence false positive findings. With the widespread use of fMRI studies in clinical disorders, the vulnerability of participants points to an ethical imperative for reliable results so as to uphold promises typically made to participants that the study results will help understand their conditions. While important, power-based sample size calculations can be challenging. The majority of fMRI studies are observational, i.e., are not designed to randomize participants to test efficacy and safety of any therapeutic intervention. My PhD thesis therefore addresses two objectives: firstly, to identify potential obstacles to implementing sample size calculations, and secondly to provide solutions to these obstacles in observational clinical fMRI studies. This thesis contains three projects.

Implementing a power-based sample size calculation requires specifications of effect sizes and variances. Typically in health research, these input parameters for the calculation are estimated from results of previous studies, however these often seem to be lacking in the fMRI literature. Project 1 addresses the first objective through a systematic review of 100 fMRI studies with clinical participants, examining how often observed input parameters were reported in the results section so as to help design a new well-powered study. Results confirmed that both input estimates and sample size calculations were rarely reported. The omission of observed inputs in the results section is an impediment to carrying out sample size calculations for future studies.

Uncertainty in input parameters is typically dealt with using sensitivity analysis; however this can result in a wide range of candidate sample sizes, leading to difficulty in setting a sample size. Project 2 suggests a cost-efficiency approach as a short-term strategy to deal with the uncertainty in input data and, through an example, illustrates how it narrowed the range to choose a sample size on the basis of maximizing return on investment.

Routine reporting of the input estimates can thus facilitate sample size calculations for future studies. Moreover, increasing the overall quality of reporting in fMRI studies helps reduce bias in reported input estimates and hence helps ensure a rigorous sample size calculation in the long run. Project 3 is a systematic review of overall reporting quality of observational clinical fMRI studies, highlighting under-reported areas for improvement and suggesting creating a shortened version of the checklist which contains essential details adapted from the guidelines proposed by Poldrack et al. (2008) to accommodate strict word limits for reporting observational clinical fMRI studies.

In conclusion, this PhD thesis facilitates future sample size and power calculations in the fMRI literature by identifying impediments, by providing a short-term solution to overcome the impediments using a cost-efficiency approach in conjunction with conventional methods, and by suggesting a long-term strategy to ensure a rigorous sample size calculation through improving the overall quality of reporting.

abstract: Doctor of Philosophy (PhD)


title: THE INFLUENCE OF SURFACE MINING ON RUNOFF TIMING AND FLOW PATHWAYS IN ELK VALLEY, BRITISH COLUMBIA

contributor:
Carey, Sean
Geography and Earth Sciences

subject: cathcment hydrology

subject: alpine

subject: coal

subject: water quality

subject: mining

subject: British Columbia

subject: Environmental Indicators and Impact Assessment

subject: Hydrology

abstract: Surface mining is a common method of accessing coal. In high-elevation environments, vegetation and soils are typically removed prior to the blasting of overburden rock thereby allowing access to mineable ore. The removed waste rock is deposited in adjacent valleys where it may bury existing streams. Previous research, predominantly in Appalachia, has focused on downstream water quality impacts with less focus on how streamflow response and flow pathways are affected by surface mining. This study reports on how surface mining affects streamflow hydrological and chemical responses at the headwater catchment scale in the Elk Valley, British Columbia. A paired catchment approach was utilized between May and October 2012, where a reference catch- ment (Dry Creek - DC) was compared to an impacted catchment (West Line Creek - WLC), whose area is 30% covered by deposited waste rock. Hydrometrically, WLC had considerably lower flows and exhibited a damped, slower response to precipitation events than DC. Dissolved ions were an order of magnitude greater in WLC, with conductivity (SpC) ranging between 400 μS/cm at high flow to 1300 μS/cm at low flow. A strong hysteretic pattern was observed between SpC and flow and with specific ions at WLC, suggesting dilution or changing flowpaths as the season progressed. In contrast, patterns of SpC and flow at DC did not exhibit hysteresis. Major ion hydrochemistry at WLC shows dilution affecting ion concentrations whereas results at DC are consistent with chemostatic behavior. Stable isotopes were more depleted at DC compared with WLC, suggesting different sources and timing of water contributing to streamflow. Future research will work towards a conceptual model of surface mining impacts on catchment scale processes in montane environments through increased understanding of residence time and flowpath distributions at a number of impacted and reference catchments.

abstract: Master of Science (MSc)


title: PLASTIC SURGICAL RANDOMIZED CONTROLLED TRIALS: CHALLENGES AND OPPORTUNITIES FOR EVIDENCE-BASED PLASTIC SURGERY, A SYSTEMATIC SCOPING REVIEW

subject:
Plastic Surgery
Randomized Controlled Trial
Systematic Review
Risk of Bias
Clinical Epidemiology
Plastic Surgery
Clinical Epidemiology

abstract:
Background: There is a shifting culture toward evidence-based plastic surgery. The use of high-quality evidence in patient decision-making is essential. To help achieve this goal the best evidence in the field needs to be identified, and the validity of this evidence verified.

Objective: This systematic review was designed to evaluate the plastic surgery literature by focusing on the prevalence of, and examining key components of quality of, Randomized Controlled Trials (RCTs) comparing surgical interventions.

Methods: An electronic search of the pertinent plastic surgery literature identified all RCTs published from 2000 to 2013 that compared one surgical intervention to another surgical intervention. Working in teams of two investigators independently, and in duplicate, assessed each manuscript for potential relevance and performed data extraction. Descriptive statistics, theory-driven multinomial regression, and independent samples t-test were used for data analysis.

Results: Of the 1664 hits obtained, 173 RCTs were included. These RCTs demonstrated the following data: 35% of RCTs performed and reported randomization properly, and 12% of RCTs reported proper allocation concealment methods. Outcome assessors were blinded in 48 (34%) RCTs, and patients blinded in 45 (26%) RCTs. Multinomial regression demonstrated that trials reporting an a priori sample size are significantly more likely to have a low risk of bias. One-third of trials did not state a primary outcome. The mean and median sample sizes were 73 and 43 patients respectively. Funding and conflict of interest reporting improved over time.

Conclusions: This systematic review establishes a baseline of the quality of evidence that currently guides practice for surgical interventions in plastic and reconstructive surgery. For the readers of plastic surgery literature to have confidence in the literature, risks of bias should be minimized and transparently reported. This will encourage plastic surgeons to apply the results and findings from published RCTs in their practice, providing patients them with the best possible treatments.

abstract: Master of Science (MSc)


title: Staples, Political Economy and Trade Flows: A New Interpretation and Quantitative Evidence

contributor:
Weaver, John
Cruikshank, Ken
History

subject:
Canadian Economic History
Intellectual History
Intellectual History

abstract:
The first section of this thesis identifies two schools of economic thought that were prominent between 1923 and the 1960s. Both employed a staples approach to organize, explain and interpret Canada’s history but used different scopes of inquiry, methodologies and time horizons. I call these two schools Innis’ staples thesis and Macintosh’s staple economics. No sooner were these two schools firmly established than the economics profession underwent a fundamental shift. Economic historians abandoned the old Canadian political economy in the 1960s and followed international trends toward increased specialization. Academic economists concentrated on theoretical and deductive methods with little concern for historical time. During this period of rapid transition, Mel Watkins developed a third approach known as the staple theory. If contemporary economists are cognizant of a staples approach, they most likely think about Watkins’ theory which was written during the ascendancy of the ‘new’ economic history in the United States.

One of the legacies of the old political economy was the construction of historical data sets, but they are rarely used in contemporary studies. The collection of historical data related to staples activity waned as the focus shifted to the construction of national accounts. The reconstruction of Canada’s trade flows was abandoned. The last five chapters of this thesis remedy this neglect with a new series of trade flows for all British North America from 1829 to 1960. Economic historians will now have a continuous series of meaningful trade statistics to facilitate future research on the role of staples in international economy of British North America. With this information, research can begin to evaluate the long-run evolution of the structure, behaviour and performance of Canada’s external economy from a simple colonial society to a modern industrial nation.

abstract: Doctor of Philosophy (PhD)


title: NOVEL SELF-ASSEMBLY OF CRYSTALLINE MgAl2O4 NANOSTRUCTURES PROMOTED BY ANNEALING A GOLD OVERLAYER ON A (111) MgAl2O4 SUBSTRATE

contributor:
Preston, John S.
Mascher, Peter
Dalnoki-Veress, Kari
Engineering Physics

subject:
gold
MgAl2O4
spinel
nano
novel
anneal
self-assembly
Nanoscience and Nanotechnology
Nanoscience and Nanotechnology

abstract: The solid state dewetting characteristics of thin gold films sputtered onto (111) MgAl2O4 substrates were investigated. Prior research done on this system reported discovering the self-assembly of intricately shaped nanostructures, consisting of a faceted sphere lying above a truncated triangular pyramid, formed by applying a specific two stage heating profile. The current work was done to provide deeper insight on the odd self-assembly observed in this system. The results indicate that the intricate structures are not purely gold self-assemblies, but in fact consist of three distinct materials: a single crystal or polycrystalline gold faceted sphere, separated by an interfacial boundary layer, from above a crystalline MgAl2O4 necking structure that spontaneously developed from the initially flat substrate. The boundary separating these two assemblies is confined within a thin, sharp region of a third material consisting of Au and O elements. The composition and crystalline nature of the individual nanostructures were studied using high angle annular dark-field imaging, energy dispersive X-ray spectroscopy, and electron energy loss spectroscopy employed by a high resolution transmission electron microscope. Two-dimensional X-ray diffraction texture analysis revealed that the gold nanoparticles are crystalline, with majority of the maximum intensity signal corresponding to the epitaxial alignment of the gold nanoparticles with the substrate. The MgAl2O4 necking structures were found to be sensitive to both the annealing profile, and the thickness of the gold film, which influenced the distinguishable presence, size, and footprint of the MgAl2O4 nanostructures. Atomic force microscopy and scanning electron microscopy results were consistent with the gold overlayer playing an essential role in the self-assembly of MgAl2O4 nanostructures. While the fundamental mechanisms that govern this phenomenon are not entirely clear, the presented results do provide insight into the role of interfaces in heteroepitaxial systems, especially the self-assembly of crystalline nanostructures from a previously stable substrate.

abstract: Master of Applied Science (MASc)


title: Characterization of a Nanocomposite Coating for PV Applications

contributor:
Preston, John
Mascher, Peter
Saravanamuttu, Kalaichelvi
Engineering Physics

subject:
polyurethane
ellipsometry
optical
photovoltaic
indium tin oxide
transparent nanocomposite coating
Materials Science and Engineering
Materials Science and Engineering

abstract:
The development of nanocomposite materials has had significant influence on modern material design. Novel properties can be achieved and controlled for a diverse range of applications. The work presented here focused on characterization of polyurethane based coatings with ITO nano-inclusions. The coatings displayed high transparency in the visible range, and UV/IR shielding properties when studied with UV-Vis spectroscopy. UV/IR shielding improved with greater ITO density, with minor affect on visible transmittance. The effective medium approximation was successfully applied to ellipsometry modeling. Coatings with varying fractions of nanoparticles were analyzed. The modeled volume percent of the nanoparticles followed a strong linear trend with the known weight percentages. SEM and TEM imaging determined that majority of the particles existed in clusters. The nanoparticles were oblong shaped, 10-20nm big, randomly distributed, with no segregation to interfaces. Agglomerates varied in size, with the largest observed agglomerate being 250nm.

Thermal stability was studied by TGA and DSC. No degradation occurred until 238°C. DSC revealed that the matrix continued to undergo modifications with consecutive runs. It was inconclusive whether the changes were from the polyurethane or dispersive agents in the system. Electron micrographs showed that segregation did not occur post-annealing. Average surface roughness increased from 3.5nm to 5nm after annealing at 120°C for several weeks. Ellipsometry results showed that film thickness decreased 20nm and 50nm before equilibriating for the 80°C and 120°C anneals respectively. The optical and thermal measurements demonstrated that the coating has great potential for improving the PV performance.

abstract: Master of Applied Science (MASc)


title: Mechanisms of Th2 Immunity in Peanut Allergic Sensitization

contributor: Jonathan Bramson, Kathy McCoy, and Susan Waserman

subject: Food Allergy and Anaphylaxis

subject: Th2 (type 2) Immunity

subject: Mucosal Immunology

subject: Epithelial Cytokines (TSLP

subject: IL-25 and IL-33)

subject: Innate and Adaptive Lymphocyte IL-4

subject: Intestinal Eosinophils and Dendritic Cells

subject: Allergy and Immunology

subject: Disease Modeling

subject: Gastroenterology

subject: Immune System Diseases

subject: Immunity

subject: Immunology and Infectious Disease

subject: Immunopathology

subject: Medical Immunology

subject: Medical Pathology

subject: Pathology

subject: Pediatrics

subject: Respiratory Tract Diseases

subject: Allergy and Immunology

abstract: Food allergies are immune system-driven diseases that lead to reproducible adverse reactions which can be fatal. These severe systemic reactions are primary mediated by immunoglobulin E (IgE) that is derived from B cells which have been activated by T helper type 2 (Th2) cells. While much work has advanced the clinical and pharmacological management of patients with allergic diseases, much remains to be elucidated about how individuals initially acquire allergy. This Thesis details a mechanism linking initial gastrointestinal exposure to peanut (PN) allergen, to the generation of Th2 cells: PN allergen activates epithelial cell secretion of interleukin (IL)-33 and eosinophil degranulation of eosinophil peroxidase, which causes CD103+ dendritic cell (DC) activation and migration to mesenteric lymph nodes where DC OX40L engages naïve T cells to secrete IL-4 in an autocrine/paracrine manner to promote and consolidate Th2 cell differentiation. These events are followed by B cell activation and PN-specific IgE production, which sensitizes mast cells to be hypersensitive to PN re-exposure by causing immediate allergic reactions including anaphylaxis. This is later followed by eosinophilic inflammation that is partially mediated by innate lymphoid cells. As food allergy also serves as a unique model to better understand mechanisms of adaptive immunity, especially Th2 immunobiology, both basic science and clinical implications are discussed in this Thesis. Major themes include Th2 and disease heterogeneity, identification of ‘the original source of IL-4’, an unprecedented in vivo requirement for eosinophils in priming adaptive immune responses, and the need to weigh basic science findings against the human disease in natura litmus test. Looking forward, many questions remain to be answered in the field of food allergy research, but the findings of this Thesis may be one step towards the prevention, management or cure of a disease with growing public concern, potentially fatal consequences, and an unmet need in understanding its pathogenesis.

abstract: Doctor of Philosophy (Medical Science)


title: Phylogenetic and Comparative Genomic Analyses of Heterocystous Cyanobacteria

contributor:
Schellhorn, Herb E.
Gupta, Radhey S.
Igdoura, Suleiman A.
Biology

subject:
Bioinformatics
Ecology and Evolutionary Biology
Bioinformatics

abstract: Heterocyst-forming Cyanobacterial species encompass the orders Nostocales and Stigonematales. These orders are currently differentiated based solely upon morphological characteristics (such as the formation of true or false branches), which may be unrelated to phylogeny. Thus, these bacteria do not form distinct monophyletic groups in the 16S rRNA tree, and as yet, no reliable molecular markers have yet been identified that allow species of these two orders to be distinguished from each other or from other organisms. Using published genome sequences for these species, we have investigated the relationship of species from these two orders. We describe here detailed phylogenetic analyses based on concatenated protein sequences for 45 proteins from 48 Cyanobacterial species/strains whose genomes are now available. In addition, we have performed comprehensive comparative genomic analyses on eight available Nostocales and Stigonematales genomes to identify conserved signature indels (CSIs) and conserved signature proteins (CSPs) that are specifically present in all Nostocales/Stigonematales or any of their subclades. These analyses have yielded >100 CSIs and CSPs that are specific for distinct coherent clades of Nostocales/Stigonematales. Seventeen of these CSIs and twelve CSPs are present in all sequenced Nostocales and Stigonematales, supporting a distinct relationship of the species from these two orders of heterocyst-forming bacteria. Fifty-four CSIs and forty-one CSPs are specific for different subclades of Nostocales and many others are diagnostic of individual species/strains. The newly-identified CSIs and CSPs, which are specific for different subclades of Nostocales/Stigonematales, may provide novel means for identifying previously unknown members of these orders, for assignment of unsequenced members of heterocystous Cyanobacteria into different identified subclades, and for detecting individual strains from environmental samples by employing CSIs/CSPs as diagnostic tools.

abstract: Master of Science (MSc)


title: Acoustic Emission Monitoring of Electrical Discharge Machining

contributor:
Koshy, Philip
Mechanical Engineering

subject:
Electrical discharge machining
acoustic emission
monitoring
Manufacturing
Manufacturing

abstract: Electrical discharge machining (EDM) is a non-conventional machining process in which material removal is accomplished through spark erosion between a workpiece and tool electrode. Process stability is of great importance to the productivity of the EDM process, especially in the wire EDM configuration where an unstable process could lead to wire breakage having a detrimental effect on productivity. This thesis investigates the application of acoustic emission (AE) in EDM as a process monitoring technique. AE techniques have been applied to almost all machining processes; however its benefit as applied to EDM has not been investigated yet. The AE signal from the EDM process is related to various EDM parameters including, electrical parameters, tool materials, flushing and some process modifications, such as dispersing metallic powder into the gap. Using this knowledge, the benefits of using an AE sensor for a real-time process monitoring technique have been proven.

abstract: Master of Applied Science (MASc)


title: A TRI-MODALITY COMPARISON OF VOLUMETRIC BONE MEASURE QUANTIFICATION USING 1.0 TESLA PERIPHERAL MAGNETIC RESONANCE IMAGING, PERIPHERAL QUANTITATIVE COMPUTED TOMOGRAPHY AND HIGH-RESOLUTION-PERIPHERAL QUANTITATIVE COMPUTED TOMOGRAPHY IMAGES

contributor: Medical Sciences (Division of Physiology/Pharmacology)

subject: pQCT

subject: pMRI

subject: bone

subject: fractures

subject: validity

subject: precision

subject: Analytical, Diagnostic and Therapeutic Techniques and Equipment

subject: Diagnosis

subject: Musculoskeletal Diseases

subject: Musculoskeletal, Neural, and Ocular Physiology

subject: Musculoskeletal System

subject: Radiology

abstract: Dedicated to the memory of Dr. Colin E. Webber

abstract: This comparative study of peripheral (p) QCT, high-resolution pQCT (hr-pQCT) and 1.0 Tesla pMRI technologies quantified short-term test-retest reproducibility, validity, one-year detection limit and clinical sensitivity of each modality’s derived bone measures. Select bone outcomes were evaluated from scans performed on Hamiltonian women above 50 years old and externally validated in a population-based cohort. In the local cohort (age: 74 ± 9 years and BMI 27.65 ± 5.74 kg/m2), Tb.Sp measured on pMRI, Ct.Th and vBMD from pQCT showed significant correlations (r2=0.52-0.85) with hr-pQCT, yielding slopes near unity. Bland-Altman analyses revealed significant relationships between pQCT and pMRI bone outcome values (Tb.Th(-), Tb.N(+), BV/TV(-)) and agreement with hr-pQCT. Short-term reproducibility was < 5% for pQCT but only BV/TV was < 5% for pMRI. Co-registration and excluding individuals with fractures mildly reduced precision error and one-year change. In the local cohort, only Ct.Th and cortical vBMD associated with fractures (OR: 1.09-3.28) using hr-pQCT, which was externally validated in the national cohort. Certain trabecular measures on pMRI and pQCT erred towards increased odds for fractures locally. For pQCT, these became significant in the national cohort (OR:1.04-3.81). This Canadian reference dataset for hr-pQCT showed larger Tb.Sp and smaller Tb.N compared to Americans but age-related decline in Ct.Th and BV/TV was faster in Europeans. This study demonstrated validity of pMRI and pQCT-derived volumetric bone outcomes and reasonable short- and long-term precision error for pQCT but not 1.0T pMRI. A single CT slice from pQCT was comparable to 110 slices from hr-pQCT in associations with fractures.

abstract: Doctor of Philosophy (Medical Science)


title: An Enhanced Latent Heat Thermal Storage System Using Electrohydrodynamics (EHD)

contributor:
Cotton, J.S.
Mechanical Engineering

subject:
Thermal storage
Electrohydrodynamics
Latent heat
Energy balance
Numerical
phase change material
Energy Systems
Heat Transfer, Combustion
Other Materials Science and Engineering
Other Mechanical Engineering
Energy Systems

abstract:
Electrohydrodynamics (EHD) was used to enhance the thermal performance of a latent heat thermal storage cell by reducing the charging time for a given amount of latent heat stored. Paraffin wax, which is an organic dielectric commercially available material was selected as the phase change material (PCM).

Electric field was applied into the cell by using 9 electrodes kept at -8 kV in an effort to establish EHD forces inside the PCM. The EHD effect was studied in an originally conduction dominated melting environment. That was achieved by the cell design which promoted unidirectional melting downwards to prevent natural convection from occurring by assuring a thermally stratified molten phase. The target was to study the EHD mechanisms of enhancement with less interfering physics.

Melting was studied under constant heat flux boundary condition. The temporal thermal profile of the surface heater and the melt front location were used to assess the EHD effect by comparing it to a 0 kV (no EHD) case.

It was found that by using EHD (-8 kV), the time required to melt 7 mm thickness of the PCM can be reduced by 40 % when compared to 0 kV case. Through a four hour experiment time, the amount of molten PCM can be increased by 29 % by using EHD compared to 0 kV. The EHD power consumption was less than 0.17 W which is equivalent to 2.4 % of the thermal energy stored in the PCM.

A new phenomena was discovered when applying EHD in the tested cell, which is Solid Extraction, where the solid dendrites within the mushy zone were extracted from the mushy zone into the liquid bulk towards regions of higher electric field.

A new criteria was developed to quantify the EHD enhancement level and was called EHD enhancement factor. An enhancement factor up to 13 could be reached by using EHD. The effect of changing the heat flux on the enhancement factor was investigated, and it was found that the enhancement factor decreased by increasing the heat flux.

Numerical simulations were performed in an effort to understand the EHD mechanisms of enhancement. The static electric field distribution, the interfacial extraction forces and the body forces acting on suspended dendrites were evaluated. The results of numerical simulations were supported by the high speed imaging and the experimental data to explain the EHD mechanisms of enhancement and the regions where solid dendrites extraction happened.

Finally an analytical model was developed to estimate the energy stored in the different components of the tested latent heat storage cell and to estimate the amount of energy lost to the surroundings in order to quantify the accuracy of the experiment and a maximum of 18 % heat loss was estimated.

abstract: Master of Applied Science (MASc)


title: EXPRESSION OF CYTOCHROME P450 3C AND 3B GENES IN TELEOSTS

contributor:
Wilson, Joanna
Graham Scott, Grant McClelland
Biology

subject:
Cytochrome p450
sex difference
detoxification
mRNA expression
medaka CYPs
zebrafish CYPs
Biology
Biology

abstract: Cytochrome P450s (CYPs) are enzymes that are found throughout the three domains of life. They function in the metabolism of endogenous and exogenous compounds. CYPs are extensively studied in mammalian systems due to their importance in drug metabolism and are highly expressed in detoxification organs like the liver and intestine. Fish CYP3s are not well understood. CYP3s have diversified in fish and subfamilies A, B, C and D constitute the CYP3 clade in fish. In this study, CYP3C1, CYP3C2, CYP3C3 and CYP3C4 in zebrafish (Danio rerio) and CYP3B4, CYP3B5 and CYP3B6 in medaka (Orzyias latipes) were quantified in hepatic and extrahepatic organs. CYP3C genes were quantified throughout development. All CYP3B and 3C isoforms were detected in all organs except CYP3B4 in male organs and in female brain. CYP3C1-C3 were maternally acquired and expressed in all embryonic stages. Higher expression of some of the isoforms occurred in the liver and intestine of zebrafish and medaka. This is indicative of a possible role in xenobiotic metabolism. Differences in expression between males and females gonad was observed, suggesting a possible role for estrogen in gene regulation. Further research will contribute to characterizing the upstream response elements in order to understand whether estrogens or other compounds are responsible for CYP3 regulation in fish. This knowledge will contribute to understanding the potential function these unique families of CYPs serve for fish.

abstract: Master of Science (MSc)


title: Performance Characterisation and Cavitation Detection of Variably Angled V-Shaped Opening Ball Valves

contributor:
Cotton, J. S.
Mechanical Engineering

subject:
Cavitation Detection
Cavitation Scaling
Valve Scaling
Valve Computational Fluid Dynamics
Ball Valves
Hydraulic Engineering
Other Mechanical Engineering
Hydraulic Engineering

abstract:
The objectives of this thesis are to characterise the performance of variably angled V-shaped opening ball valves in terms of pressure drop and cavitation. Both numerical and experimental techniques are utilised here to study the effects of apex angle of the V-opening on pressure drop and cavitation characteristics. Three different ball sizes are used to investigate scalability of the V-ball valves in terms of cavitation inception and pressure coefficient. The results of the pressure drop experiments show that as the size of the ball and the apex angle of the valve increases, the pressure coefficient tends towards a constant value. This means that larger V-opening ball valves can be scaled using pressure coefficient within 15%.

It has been well established that cavitation causes high frequency noise. Therefore dynamic pressure transducers were used to detect acoustic cavitation noise by considering the high energy content in the 2 kHz to 45 kHz frequency band. To measure the energy levels, spectral analysis was performed and the power spectrum density was acquired using fast Fourier transform algorithm and the area under the curve was integrated in three different frequency intervals of 2 to 5 kHz, 5 to 10 kHz and 10 to 45 kHz to capture the frequency band at which cavitation onset occurs. This energy was compared to the reference energy levels in the same frequency intervals when no valve was installed. Two criteria were chosen to represent a cavitating flow, the first criteria was the start of a steep exponential increase in the energy from the reference energy in at least one of the frequency ranges defined and the second criteria is an increase in the coherence function in any of the three frequency ranges. This procedure was performed for all valves tested at 10% opening increments starting at fully open position and the inception cavitation number was recorded to define the onset of cavitation. It was observed that as the apex angle decreases, cavitation number also decreases where the size of the valve did not affect cavitation number. The conclusion was that as the opening decreases, cavitation inception occurs at higher pressure drops. However some deviations from this general trend were observed. These deviations are perhaps due to the turbulent structures such as flow separation and vortices, suggested by the pressure fluctuations in the static pressure.

Finally numerical modelling of 1 inch 60V valves were performed using ANSYS Fluent computational fluid dynamics (CFD) software for three openings using two different turbulence models, standard k-ε and SST k-ω. The results were contrasted against the experimental data to evaluate which model performs the best for this application. From the results obtained, standard k-ε predicts the pressure drop within 15% of the experimental data. Also flow separation is a major cause of high local pressure drops and therefore cavitation and SST k-ω predicts cavitation better than standard k-ε. This is due to better performance of SST k-ω at predicting turbulence characteristics of flow separation region.

abstract: Master of Applied Science (MASc)


title: Experimental Investigation of Air-Knife Geometry in Continuous Hot-Dip Galvanizing

contributor:
McDermid, Joseph R.
Ziada, Samir
Mechanical Engineering

subject:
Multiple-Slot Impinging Jet
Single-Slot Impinging Jet
Galvanizing
Coating Thickness
Other Materials Science and Engineering
Other Mechanical Engineering
Other Materials Science and Engineering

abstract:
This thesis investigates the wall pressure distributions of the single-slot impinging jet and multiple-slot impinging jet as a function of various parameters and compares the results obtained with the computational study of Tamadonfar [2010]. The process of gas wiping is used in many industrial applications such as tempering of the plate glass, the chemical mixing process, and turbine blade cooling. One of the most important industrial applications of gas jet wiping is the production of galvanized steel strip in a continuous hot-dip galvanizing line. In this process, an impinging jet is used to remove the excess zinc alloy from the steel strip and control the final coating weight by applying wall pressure and shear stress on the moving substrate emerging from the bath of molten zinc. Changing the various operating parameters such as jet Reynolds number (Re), the jet to strip distance (z), the jet slot width (d), and jet inclination angles (α) allows manufacturers manipulate the final coating weight on the substrate. Production of high quality sheet steels, which have a very thin coating weight and high uniformity quality, is one of the goals of the automotive industry. In order to obtain thinner and more uniform coating weight, a new model of impinging jet which is comprised of one main jet with two auxiliary jets, one on each side of the main jet, called a multiple-slot impinging jet, is of considerable interest.

For the current study, a multiple-slot impinging jet was designed and manufactured and measurements were performed for both the single-slot impinging jets, the current model used in continuous hot-dip galvanizing lines, and the multiple-slot impinging jet subjected to a wide range of gas wiping parameters which include the main jet Reynolds number (Rem), the auxiliary jet Reynolds number (Rea), and the plate-to-nozzle ratio (z/d). A comparison between the measured results obtained for the two impinging jet configurations and the numerical results by Tamadonfar [2010] has been provided. The similarities and differences between the experimental and numerical results are presented and discussed.

abstract: Master of Science in Mechanical Engineering (MSME)


title: Electron Energy Loss Spectroscopy of Metallic Nanostructures and Carbon Nanotubes

contributor:
Botton, Gianluigi
Materials Science and Engineering

subject:
EELS
surface plasmon
plasmon
TEM
carbon nanotube
CNT
Nanoscience and Nanotechnology
Nanoscience and Nanotechnology

abstract:
In this thesis, a modern transmission electron microscope is used to perform high-resolution electron energy loss studies of metallic nanostructures and carbon nanotubes.

The remarkable optical properties of metallic nanostructures arise from the excita- tion of surface plasmons. With improved instrumentation, surface plasmon resonances are imaged in a variety of nanostructures, enabling a greater understanding of their behaviour in nanoscale systems. It is shown that surface plasmons set up multiple high order resonances in silver nanorods, and they freely propagate around sharp corners in silver nanowires. It is also demonstrated that silver nanorice structures resonate in a similar manner to nanorods, despite the high density of stacking faults in the structure. Finally, a complementary structural pair is found to resonate in a complementary fashion, in agreement with Babinet’s principle.

Carbon nanotubes exhibit unique physicochemical properties that have led to their use in a variety of novel materials science applications. Despite rapid progress in the theoretical and experimental investigation of carbon nanotubes, techniques capable of studying the structural and electronic properties of individual tubes are limited. Here, it is demonstrated that the spectral signature of carbon can be used to identify the electronic character of individual single-walled carbon nanotubes. In addition, a new technique is used to map bonding anisotropy in a multi-walled carbon nanotube.

Also presented in this thesis is the design and construction of a unique laser-TEM system. Early results from the system include in-situ measurements of laser-induced structural and electronic distortions in individual carbon nanotubes.

abstract: Doctor of Philosophy (PhD)


title: The reproductive ecology of plainfin midshipman: variation across time and space in a species with alternative reproductive tactics

contributor:
Balshine, Sigal
Neff, Bryan
Faure, Paul
Psychology

subject:
paternity analyses
genetic reproductive success
ecological variation
sexual selection
cuckoldry
male competition
Ecology and Evolutionary Biology
Ecology and Evolutionary Biology

abstract: Alternative reproductive tactics (ARTs) have been described across taxa numerous times, and are especially common in fishes. The advent of molecular techniques has enhanced our understanding of such mating systems, yet these techniques have only been applied to relatively few species. Furthermore, ecological variation has long since been recognized as an important factor influencing mating patterns and sexual selection, yet it is often ignored. In my thesis, I conducted field studies to investigate the reproductive ecology of a species with well characterized ARTs, the plainfin midshipman (Porichthys notatus), and to explore how these mating patterns varied across time and space. This species is characterized by two male tactics: guarders and sneakers. I show that both tactics are successful at gaining fertilization. Indeed, I found evidence for several behavioural adaptations by the guarder male tactic to gain fitness, including guarding, nest takeovers, and plastic cuckoldry behaviours. I also documented the lowest paternity for guarder males for a species with obligate male parental care. Paternity increased over the course of the breeding season, which was likely a result of a higher occurrence of nest takeovers early in the season. In a cross-population analysis of plainfin midshipman, I found significant differences in nest availability and density between two genetically distinct populations, but this did not translate into significant differences in mating patterns. Taken together, my thesis helps elucidate the reproductive ecology of a classic species with ARTs, and has important implications for our understanding of ecological influences on mating patterns and sexual selection.

abstract: Doctor of Philosophy (PhD)


title: EXAMINING THE ROLES OF DIR1 AND DIR1-LIKE DURING SYSTEMIC ACQUIRED RESISTANCE IN ARABIDOPSIS AND CUCUMBER

contributor:
Cameron, Robin
Weretilnyk, Elizabeth
Biology

subject:
Systemic Acquired Resistance
DIR1
DIR1-like
Arabidopsis
Cucumber
Pseudomonas syringae pv. tomato
Biology
Plant Sciences
Biology

abstract: Systemic Acquired Resistance (SAR) is a plant defense response induced by an initial infection in one part of the plant that leads to broad-spectrum resistance to normally virulent pathogens in distant naïve leaves. As part of the Cameron research team, I contributed to demonstrating that the lipid transfer protein, DIR1 is required for SAR long distance signaling in Arabidopsis and travels from induced to distant tissues during SAR. A highly similar Arabidopsis protein DIR1-like was identified and is thought to be responsible for the occasional SAR-competent phenotype observed in the dir1-1 mutant. This work provides evidence for the idea that DIR1 and DIR1-like are paralogs created by a recent duplication event and that similar to DIR1, DIR1-like may travel to distant tissues during SAR. To better understand DIR1 and DIR1-like contribution during SAR, dir1-1dir1-like double mutant transgenic plants were created as well as transgenic plants expressing epitope- (HA and FLAG) and fluorescent- (iLOV and phiLOV) tagged DIR1 and DIR1-like to facilitate visualization of movement during SAR. Several putative DIR1 orthologs were identified in crop plants and cucumber CucDIR1 was shown to be functionally equivalent to AtDIR1 in dir1-1 complementation studies providing further evidence that DIR1 plays an important role in SAR across plant species. By analyzing conservation between DIR1, DIR1-like and the putative DIR1 orthologs, several protein residues were identified that may be important for DIR1 function during SAR. DIR1 proteins were modified at these sites and the importance of these residues was supported by the reduced binding of the TNS hydrophobic probe in these DIR1 variants. Taken together, this thesis suggests that DIR1 and DIR1-like both participate in SAR in Arabidopsis, that DIR1 crop orthologs are also important for the SAR response and that DIR1 possesses several sites that are critical for its function in long distance SAR signaling.

abstract: Doctor of Philosophy (PhD)


title: CHEMO-PREVENTATIVE EFFECTS OF HYDROGEN SULFIDE-RELEASING NSAIDS IN MURINE COLORECTAL CANCER

subject:
Colorectal Cancer
NSAIDs
Neoplasms
Gastrointestinal Disease
Chemo-prevention
Hydrogen Sulfide
Digestive System Diseases
Medical Pharmacology
Neoplasms
Pharmaceutics and Drug Design
Digestive System Diseases

abstract:
Colorectal cancer leads to more than 600,000 deaths worldwide per year. An abundance of research has shown that several non-steroidal anti-inflammatory drugs (NSAIDs) can exert chemotherapeutic and chemo-preventative effects in colorectal cancer patients. It is important to note, that use of many different NSAIDs carries a significant risk for cardiovascular and gastrointestinal (GI) complications. A recently developed group of NSAIDs, which release hydrogen sulfide (H2S), has been shown to have greatly reduced these side effects as compared to conventional NSAIDs. This is likely attributable to the ability of H2S to increase the resistance of the GI mucosa to injury, as well as to accelerate repair of injury when it occurs. Moreover, H2S has been shown to be a vasodilator, and therefore may offset some of the hypertensive effects of NSAIDs.

We assessed the chemotherapeutic actions of two of these newly developed NSAIDs. ATB-346 is an H2S-releasing derivative of naproxen and ATB-352 is an H2S-releasing derivative of ketoprofen. These drugs were tested in the azoxymethane mouse model and in the APCMin/+ mouse model of Colorectal cancer.

In the azoxymethane model of colorectal cancer ATB-346 caused a significant reduction in number aberrant crypt foci (ACF), which are pre-neoplastic lesions used as markers of colorectal cancer. The reduction was superior to naproxen at all doses tested. ATB-352 also caused a significant reduction in the number of ACF, however the reduction was not superior to that produced by ketoprofen. In APCMin/+ mice treated with ATB-346 for 14 days (14.5 mg/kg) we observed a complete inhibition of the formation of colonic polyps/tumours and a 97.5% reduction in total polyp score. Shorter treatment with ATB-346 also produced similar reduction in total polyp score. We found that ATB-346-treated mice had lower levels of b-catenin and cmyc without significant changes in APC or p53 levels.

These results demonstrate ATB-346 can exert superior chemo-preventative effects in mice models of colon cancer while leading to no gastric or intestinal damage.

abstract: Master of Science (MSc)


title: Investigating the Role of Interleukin-15 in Modulating Adipose Tissue

contributor:
Ashkar, Ali
Medical Sciences

subject: obesity

subject: interleukin-15

subject: adipose tissue

subject: Biochemical Phenomena, Metabolism, and Nutrition

subject: Biological Phenomena, Cell Phenomena, and Immunity

abstract: Obesity is a major global health concern and is associated with the development of numerous non-communicable diseases. A thorough understanding of the onset of obesity is critical to the development of effective therapeutic strategies against this disease state. Recently, obesity has been described as a complex disease characterized by chronic low grade inflammation. Abnormal adipose tissue expansion is accompanied by an increased presence of proinflammatory immune cells, dysregulated adipokine expression, oxidative stress, and is associated with significant changes in the bacterial composition of the gut. While interleukin-15 (IL-15) has been studied extensively for its immunological effects, this cytokine has recently been shown to influence body weight and fat mass. The focus of this thesis was to elucidate the role of and mechanism by which IL-15 modulates adipose tissue. Our first study demonstrated that low levels of IL-15 expression are associated with adiposity and promotes an obese state in IL-15-/- mice and human subjects, while IL-15 overexpression was associated with a lean phenotype in IL-15tg mice when compared to appropriate controls. To uncover the underlining mechanisms by which IL- 15 mediates differences in body weight, we subsequently determined that IL-15 mediated weight loss occurred independently of lymphocytes. In another study, we showed that IL-15tg mice had increased mitochondrial activity and mass specific to adipose tissue compared to IL-15-/- and B6 mice, while acute IL-15 administration induced the expression of FAO markers in adipose tissue. Lastly, IL-15 treatment increased mitochondrial membrane potential and decreased lipid deposition in cultured adipocytes, suggesting that IL-15 may mediate its effects directly on adipose tissue. The experimental results presented in this thesis demonstrate that IL-15 is an important regulator of adipose tissue and body weight. Future studies examining the effects of IL- 15 on adipose tissue will further our knowledge on IL-15 biology, and may contribute to novel therapeutic strategies for the treatment and prevention of obesity.

abstract: Doctor of Philosophy (PhD)


title: EXPERIMENTAL AND NUMERICAL STUDIES OF BUBBLE DEVELOPMENT PROCESS IN ROTATIONAL FOAM MOLDING

contributor:
Vlachopoulos, John
Thompson, Michael R.
Chemical Engineering

subject:
Foam
nucleation
bubble growth
coalescence
rotational foam molding
thermoplastic
Polymer Science
Polymer Science

abstract:
Dedicated to the loving memory of my mother and father,

Zohreh Hojati & Mostafa Emami

abstract:
Commercial interests in polymeric foams continue to increase due to their unique physical characters and the new emerging applications for foamed materials. This thesis investigates the foam development process under non-pressurized conditions as applicable to rotational molding to elucidate the underlying mechanisms in the bubble transformation process and provide an accurate basis for predicting the morphological structure and macroscopic properties of the foamed materials. It was found that the foaming mechanism is comprised of four distinct stages: two stages of bubble nucleation, primary and secondary nucleation, followed by bubble growth and bubble coalescence/shrinkage. Following the nucleated bubbles during the foaming process revealed that primary nucleation was the controlling stage in determining the final cellular structure. Growth and coalescence mechanisms were dynamically active and competed during both heating and cooling cycles.

The influence of the rheological properties on the rate of nucleation and the bubble growth mechanism were investigated. Morphological analysis was used to determine the rheological processing window in terms of shear viscosity, elastic modulus, melt strength and strain-hardening, intended for the production of foams with greater foam expansion, increased bubble density and reduced bubble size. Visualization experiments and theoretical predictions showed that higher viscosity could impede the number of nuclei generated in the foaming system. A bubble growth model and simulation scheme was also developed to describe the bubble growth phenomena that occurred in non-pressurized foaming systems. It was verified that the viscous bubble growth model was capable of depicting the growth behaviors of bubbles under various processing conditions.

abstract: Doctor of Philosophy (PhD)


title: Characterization of a Pleiotropic Protein Promoting DNA Repair

contributor:
Junop, Murray
Biochemistry and Biomedical Sciences

abstract: DNA double-strand breaks (DSBs) represent the most severe form of chromosomal damage. In higher organisms, one DSB represents a lethal event. Unlike any other organism, bacteria of the genus Deinococcus are able to withstand extremely high levels of DSBs caused by ionizing radiation, UV radiation, prolonged desiccation and chemical agents. The remarkable ability of Deinococcus to survive under conditions of extreme oxidative stress is a result of an efficient DSB repair process. Currently, little is known about how several key proteins function in DNA repair in Deinococcus. The goal of this work was to better understand the mechanism through which Deinococcus is able to recover from DNA damage through structural and biochemical characterization of a unique pleiotropic protein promoting DNA repair. Here, we show preliminary X-ray diffraction data coupled with electron microscopy images which showcase unusual filament formation of this protein. Pleiotropic protein promoting DNA repair has been shown by others to bind double-stranded DNA (dsDNA). We have further characterized the interaction of this protein with DNA and found that it binds longer pieces of dsDNA (> 3500 bp) with a higher affinity than shorter pieces of dsDNA (≤ 1000 bp). This protein was also shown to form bundles of long, fibrous filaments by transmission electron microscopy, while gel filtration studies have shown it exists as a very large multimer in solution. Implications for how these filaments function in DNA repair were explored. In vivo damage recovery through complementation studies were also performed. Determining the structure of pleiotropic protein promoting DNA repair, and characterizing its DNA binding ability and filament formation is essential to clarify its proposed function in DNA repair.

abstract: Master of Science (MSc)


title: THE ROLE OF STEROL REGULATORY ELEMENT BINDING PROTEIN (SREBP) IN KIDNEY FIBROSIS

contributor:
Krepinsky, Joan
Bridgewater,  Margetts
Medical Sciences

subject:
SREBP
Apoptosis
Fibrosis
Tubular cells
UUO
Fatostatin
Medical Molecular Biology
Medical Physiology
Medical Molecular Biology

abstract:
There has been a steady increase in the number of patients with chronic kidney disease. The etiology has been linked to excessive fibrosis progression until the kidney function becomes compromised. We are investigating tubulointerstitial fibrosis (TIF) specifically, as it correlates strongly with the decline of renal function.

In our study we investigated the role that active SREBP may play in apoptosis and fibrosis in vivo and in vitro. Treating HK-2 cells with TNFα resulted in the cleavage of SREBP and activation of its SRE promoter. By utilizing a number of inhibitors, we found TNFα induced SREBP cleavage through both a caspase independent and dependent manner.

We used fatostatin, a SCAP inhibitor, to reduce the amount of active SREBP in animals in the unilateral ureter obstruction (UUO) model. This model is well known for its development of TIF. Fatostatin decreased SREBP-1 and SREBP-2 activation in mice after 7 and 14 days. Fatostatin increased glomerulotubular integrity and proximal tubular mass as evaluated using lectin staining, along with reducing the number of cells undergoing apoptosis as evaluated by TUNEL staining. Using the Masson Trichrome, Picrosirius red and fibronectin staining, we found a reduction of fibrosis. Fatostatin was also found to attenuate the accumulation of infiltrating myofibroblasts and T cells. These results point to a pathological role for SREBP in TIF.

abstract: Master of Health Sciences (MSc)


title: THE EFFECT OF THE ER STRESS INHIBITOR, 4-PHENYLBUTYRATE, ON CHRONIC KIDNEY DISEASE IN A MODEL OF SALT SENSITIVE HYPERTENSION

subject:
Medical Sciences
Medical Sciences

abstract: ER stress in the kidney is associated with proteinuria. Clinical studies have linked proteinuria with the progression of chronic kidney disease (CKD) at all stages of GFR decline. We hypothesized that treatment with a chemical chaperone, 4-phenylbutyrate (4-PBA), would reduce the severity of CKD and proteinuria in salt sensitive hypertension. The differences in renal pathology between salt sensitive and insensitive hypertension when animals were fed an 8% NaCl (HS) diet were assessed. The Dahl salt sensitive (Dahl S) rat was used as a model of salt sensitive hypertension, while the spontaneously hypertensive rat (SHR) was used as a model of salt insensitive hypertension. The myogenic response of the arcuate artery was studied to determine whether the differences in renal pathology between these models of hypertension was due to an effect of salt on myogenic constriction. Myogenic constriction displayed salt sensitivity in the Dahl S as there was a significant reduction in blood vessel constriction with increasing intralumenal pressures. Myogenic constriction was reduced, but not completely abolished in the SHR with high salt (HS), providing a possible explanation of why this model of hypertension does not develop an equivalent level of renal damage with blood pressure increase as the Dahl S rat. ER stress induction with tunicamycin in arcuate arteries from normotensive animals resulted in an attenuation of the myogenic response. Myogenic constriction was protected from tunicamycin induced ER stress with 4-PBA. 4-PBA treatment (1g/kg/day) in HS fed Dahl S ameliorated proteinuria, renal intratubular protein casts, and renal fibrosis. This correlated with a protection of myogenic constriction and integrity of the glomerular filtration barrier. This suggests that myogenic constriction of the renal vasculature is an important mechanism to protect against salt sensitive hypertension-induced proteinuria. Further, that high salt feeding may inhibit this protective mechanism by inducing ER stress in the renal blood vessels.

abstract: Master of Science (MSc)


title: Identification of Environmental Alphaproteobacteria with Conserved Signature Proteins in Metagenomic Datasets

subject:
metagenomic
Alphaproteobacteria
molecular marker
bacterial diagnosis
Bioinformatics
Bioinformatics

abstract: Microbial metagenomics is the exploration of taxonomical diversity of microbial communities in environmental habitats using large, exhaustive DNA sequence datasets. However, due to inherent limitations of sequencing technology and the complexity of environmental genomes, current analytical approaches do not reveal the existence of all microbes that may be present. In this study, a new classification approach is proposed based upon unique proteins that are specific for different clades of Alphaproteobacteria to predict the presence and absence of species from these groups of bacteria in published metagenomic datasets. In this work, 264 previously–identified, published conserved signature proteins (CSPs) characteristic of individual taxonomic clades of Alphaproteobacteria are used as probes to detect the presence of bacteria in metagenomic datasets. Although public genome sequence information has increased manifold since these CSPs were initially identified 6 years ago, results indicate that nearly all of these CSPs (259 of 265) are specific for their previously characterized clades. Furthermore, they are confirmed to be present in the newly–identified and sequenced members of these clades. In view of their specificity and predictive ability in different monophyletic clades of Alphaproteobacteria, the sequences of these CSPs provide reliable probes to determine the presence or absence of these Alphaproteobacteria in metagenomic datasets. In this work, CSPs are used to determine the presence of Alphaproteobacteria diversity in 10 published metagenomic datasets (bioreactor, compost, wastewater, activated sludge, groundwater, freshwater sediment, microbial mat, marine, hydrothermal vent and whale fall metagenomes), which cover diverse environment and ecosystems. It is indicated that the BLAST searches with these CSPs can be used to efficiently identify Alphaproteobacteria species in these metagenome dataset and substantial differences can be determined in the distribution and relative abundance of different Alphaproteobacteria species in the tested metagenome datasets. Thus the CSPs, which are specific for different microbial taxa, provide novel and powerful means for identification of microbes and for their taxonomic profiling in metagenomic datasets.

abstract: Master of Science (MSc)


title: The Functional Domains of PHLDA1: Modulation of Intracellular Localization Impacts Apoptotic Cell Death

contributor: Medical Sciences (Blood and Cardiovascular)

subject:
PHLDA1
TDAG51
Medical Biochemistry
Medical Cell Biology
Medical Sciences
Reproductive and Urinary Physiology
Medical Biochemistry

abstract:
Pleckstrin homology like domain family A, member 1 (PHLDA1) is a member of the PHLDA family of homologous proteins recognized for their role in apoptotic cell death. PHLDA1 was first reported as a proapoptotic factor involved in Fas-mediated T-cell apoptosis. The role of this protein with regards to apoptosis remains poorly understood, with literature demonstrating both proapoptotic and antiapoptotic functions in a cell and/or pathway specific manner. Intracellular localization may account for the apoptotic potential of this protein, with nuclear accumulation of PHLDA1 increasing its apoptotic potential. We hypothesize that the functional regions of PHLDA1 including its localization signals (pNLS/pNES), pleckstrin homology like domain (PHLD), and PQ region direct cellular localization of PHLDA1, thereby regulating its apoptotic potential.

In this thesis, well-established molecular and cellular approaches were utilized to better define the functional regions within PHLDA1 and to gain further understanding of the role of its localization on apoptosis. Using an EGFP fusion construct and leptomycin B, we confirmed that PHLDA1 contains a weak, CRM1-responsive NES. Using an EGFP-β-galactosidase fusion protein we examined the putative NLS of PHLDA1 and determined that it was not sufficient to direct nuclear localization. However, the PHLD was found to direct cellular localization, mirroring the distribution and punctate patterning of full length PHLDA1. Evidence of association of the PHLD with the membrane was confirmed using fluorescence and electron microscopy, and changes in cell morphology indicative of EMT were apparent following overexpression of the PHLD.

Although previous reports have suggested that the PQ region of PHLDA1 is responsible for its proapoptotic function, its cellular localization was not clearly defined. Nuclear accumulation of the PQ region was found to be highly cytotoxic, indicating that it is sufficient to induce apoptosis and that its proapoptotic activity occurs within the nucleus. The findings of this thesis provide fresh insight into the functional regions of PHLDA1 and their respective contributions to the protein’s intracellular localization and apoptotic function, demonstrating that localization dictates the apoptotic potential of PHLDA1. This data provides a solid foundation for identifying the cellular mechanisms by which PHLDA1 influences the progression of chronic human diseases including diabetes, cancer and obesity.

abstract: Master of Science (MSc)


title: Investigations into Human Vibrotactile Perception: Psychophysical Experiments and Bayesian Modelling

contributor:
Goldreich, Daniel
Psychology

subject:
Bayesian
Neural coding
Somatosensory
Vibrotactile
Perception
Texture
Systems Neuroscience
Systems Neuroscience

abstract:
A considerable amount of our everyday tactile experience requires interactions between textured surfaces and our fingertips. Such interactions elicit complex vibrations on our skin surface, which are encoded by the mechanosensitive afferents and conveyed to the brain where the perception of the textures emerges seemingly effortlessly. Intuitively, a fundamental question that may be asked is: “what features of the vibration stimuli are behaviourally relevant and what are the neural signatures of these features?” The goal of this thesis is to investigate these questions, which we have done using a combination of theoretical and experimental approaches.

Our theoretical approach (in Chapter 2) has been to create an ideal Bayesian perceptual observer that utilizes all the information available in a spike-rate based neural code and makes optimal inferences regarding the amplitude and the frequency of vibration stimuli. Our experimental approach has been to estimate the performance of human participants in vibrotactile detection (in Chapter 3), and in amplitude and frequency discrimination (in Chapter 4) tasks by using psychophysical procedures.

The results of these approaches suggest that the human perceptual observer, i.e. the human nervous system, probably uses a rate code to represent vibrotactile amplitude, but a non-rate code, such as a spike timing code, to represent vibrotactile frequency. Additionally, we conclude that humans are capable of inferring and separately perceiving the amplitude and frequency of vibrotactile stimuli; however, depending on experimental tasks, humans might also rely on a feature that combines the amplitude and frequency of vibrotactile stimuli.

abstract: Doctor of Philosophy (PhD)


title: ESTABLISHING AN ENTREPRENEURIAL ECOSYSTEM AROUND MID-SIZE TRADITIONAL RESEARCH UNIVERSITIES IN CANADA

contributor:
Kleiman, Rafael
Loutfy, Rafik
Haddara, Yaser
Electrical and Computer Engineering

subject:
Entrepreneurial Universities
Commercialization of Research
Technology Transfer
Other Engineering
Technology and Innovation
Other Engineering

abstract:
Universities have come under increasing pressure to move further along the innovation continuum and supplement their traditional role in the conduct of basic research with more applied research activities. This trend reflects a shift in government expectations that public investments in basic research should produce a tangible economic return. However, it is not believed that conditions for success are presently in place to enable universities to maximize the returns to Canadian taxpayers. The focus of this thesis is to answer one question: How can we create a commercialization ecosystem around universities that lack such a system?

The thesis consists of three studies that address that question from different perspectives. The first study sought an understanding of the role that technology transfer offices can play in growing a new commercialization ecosystem, with appropriate university support and in collaboration with intermediary organizations. In the second study, a value chain centered model was identified to better describe the process of commercializing university research. The model identifies two main stages of the commercialization process. The first upstream stage focuses on de-risking the opportunity, based on the characteristics inherent in an academic spin-off. The second downstream stage focuses on successful entry to the market. In the third study, we examined the role new Masters programs specializing in venture creation can play in commercializing university intellectual property. We addressed the contribution these programs can offer to support both the upstream and downstream stages within our commercialization model.

Together, the three studies examined the current practices of commercialization in universities, identified an analytical framework for the commercialization process in universities, and finally tested the role of students in this framework. This framework leads to a deeper understanding of the commercialization process, specific to the university environment, and provides insights into how to develop a more entrepreneurial university.

abstract: Doctor of Philosophy (PhD)


title: Computational Fluid Dynamic Modeling of Aortic Blood Flow

contributor:
Tullis, Stephen
Mechanical Engineering

subject: CFD

subject: FSI

subject: Inlet Motion

subject: MRI flow profile

subject: Flexible walls

subject: Biomechanical Engineering

subject: Other Biomedical Engineering and Bioengineering

subject: Biomechanical Engineering

abstract: Computational fluid dynamic (CFD) models of aortic blood flow have developed over the past decade from rigid one dimensional models to three dimensional models that include wall flexibility. Although anatomically correct, these models have been significantly idealized as compared to their physiologic in vivo conditions. This thesis investigates the effect of addition of four dimensional MRI inlet flow, motion of the heart at the aortic inlet and addition of wall elasticity coupled with tissue backing support. Results show that the addition of MRI inlet data and aortic inlet motion of the heart significantly change flow in the aorta and should be included in future aortic CFD simulations.

abstract: Master of Applied Science (MASc)


title: Structural and Functional Characterization of Human SNM1A

subject:
DNA Repair
SNM1A
Interstrand Cross-link
Biochemistry
Biochemistry

abstract: DNA interstrand cross-links (ICLs) occur when various chemical agents bind to chromosomal DNA and form a covalent bond between adjacent strands, preventing unwinding of the DNA double helix. The formation of an ICL is therefore extremely toxic to cells and necessitates quick removal and subsequent repair. Human SNM1A is a 5’-phosphate-dependent exonuclease that has been shown to be selectively involved in ICL repair; however the mechanism by which it processes ICL substrates remains unclear. To address this, our research is focused on the structural and functional characterization of SNM1A to determine this mechanism of substrate processing. In this thesis, we report the purification of human SNM1A698-1040 as a His6-NusA tagged protein from 4 L of E. Coli cell culture. This protein was found to possess 5’-phosphate-dependent exonuclease activity, and demonstrated a preference for ssDNA. Additionally, electrophoretic mobility shift assays performed with a D736A/H737A mutant suggest that the binding of SNM1A to DNA is independent of the presence of a 5’ phosphate. Collectively, these results provide insight into the mechanism of SNM1A substrate processing in ICL repair, and establish a platform for future studies of this protein.

abstract: Master of Science (MSc)


title: Analysis of heating systems to mitigate ice accretion on wind turbine blades

subject:
Wind Turbines
Icing
De-Icing
Anti-Icing
Hot air de-icing
Electro-thermal de-icing
Heat Transfer, Combustion
Heat Transfer, Combustion

abstract:
Ice forming on wind turbine blades can cause loading imbalance and reduce power production of the turbine. Heating systems that prevent or remove ice on wind turbine blades are one of the more promising solutions to mitigate ice accretion. Methods to apply heat include direct application through electro-thermal resistance heaters mounted on the external surface of the blade or by indirect heating by forcing hot air through a channel along the leading edge of the blade. Heating systems for aircraft blades have become standardized and in some cases compulsory on aircraft to preserve human life; however, the technology is not directly transferable to the blades on wind turbines. The relative power of the anti-icing or de-icing system is critical to providing a cost benefit of having the system.

This thesis investigates the heat transfer involved for electro-thermal and hot air heating strategies. An appropriate range of operating conditions and blade constructions are considered in order to characterize the effectiveness of both systems. A numerical model is developed to solve the one dimensional, differential heat transfer equations. The heater power required to prevent ice accumulation (anti-icing) on wind turbine blades is determined for electro-thermal heating. Anti-icing with hot air is shown to be unrealistic for a practical range of operating conditions.

The low conductivity of the blade core creates a bottleneck for the de-icing system. It is shown that alternative core materials (Nomex/aluminum honeycomb) can reduce this effect. Electro-thermal and hot air de-icing each have their advantages and cannot be equally compared. In this thesis the suitability of each system has been analysed for a range of operating conditions and wind turbine constructions; the designer can then implement the most suitable strategy for their individual application.

abstract: Master of Applied Science (MASc)