VictorJuiz/thesis huggingface dataset:
Development of Flexible-rib Morphing Wing System

This study is concerned with the development of a novel morphing wing system for use in relatively small (10 kg) Unmanned Aerial Vehicles (UAVs). To achieve improved flight performance with limited weight penalty, camber-adjustable morphing wing strategy was adopted and realized via the use of Flexible Rib Morphing Wing System (FRMWS). Detailed morphing wing structure was designed using a novel flexible-rib mechanism which adheres to the safety requirements specified by FAR23 standards. Finite Element structural and aerodynamic analyses were conducted to validate the advantages and suitability of the design. Furthermore, wind tunnel and actual load tests were conducted in order to validate the new design. In addition, a test plane was refitted and flight test were conducted. The result of the flight test demonstrated the improved performance and the reliability of the new morphing wing system.

Advisor: Meguid, Shaker A
PRIMA-1met Induces Apoptosis in Waldenström's Macroglobulinemia Independent of p53, Alone and in Combination with Bortezomib

PRIMA-1met has shown promising preclinical activity in various cancer types. However, its effect on Waldenstrรถm's Macroglobulinemia (WM) as well as its exact mechanism of action is still elusive. In this study, we evaluated the anti- tumor activity of PRIMA-1met alone and in combination with dexamethasone or bortezomib in WM cell line and primary samples. Treatment of WM cells with PRIMA-1met resulted in induction of apoptosis, inhibition of migration and colony formation. Upon PRIMA-1met treatment, p73 was upregulated and Bcl-xL was downregulated while no significant change in expression of p53 was observed. Furthermore, siRNA knockdown of p53 in WM cell line did not influence the PRIMA-1met-induced apoptotic response whereas silencing of p73 inhibited latter response in WM cells. Importantly, combined treatment with PRIMA-1met and dexamethasone or bortezomib induced synergistic reduction in cell survival in WM cells. Our study demonstrates the anti-tumor activity of PRIMA-1met in WM and provides the rationale for its clinical evaluation in patients with WM.

Keywords: p53
p73
PRIMA-1met
Waldenström's Macroglobulinemia
Advisor: Chang, Hong
Novel Halogenated and Organophosphate Flame Retardants: Do Novel Flame Retardants have the Same Environmental Fate as the Compounds they are Replacing?

In the wake of the listing by the Stockholm Convention of PBDEs, an increasing number of novel flame retardants (NFRs) are being used in products. It is well documented that the properties which make for desirable FRs can also lead to negative health effects, long environmental residency times and an affinity for organic matrices. Though currently in use, there is very little information regarding the physical-chemical (p-c) properties and environmental fate of the NFRs. This Master's project evaluated the suitability of 86 halogenated and organophosphate NFRs as PBDE replacements given their persistence and long-range transport potential. To do this, measured and modelled p-c properties were compiled and used to model the NFRs' environmental behaviour. It was found that 79-84% of the NFRs have a persistence of high to medium level of concern and that over 1/3 of the NFRs have a persistence similar to the PBDEs they are replacing.

Keywords: Environmental Modelling
Environmental Persistence
Long-Range Transport Potential
Novel Flame Retardants
Persistent Organic Pollutants
Physical-Chemical Properties
Advisor: Chan, Arthur
Dittrich, Maria
Pre-injury Variables and Risk of Sport Concussion

A retrospective study explored the predictive ability of pre-injury cognitive functioning (CF), history of concussion (HOC), and sex in a sample (n=708, 41.2% female) of University of Toronto varsity athletes. A series of logistic regressions were conducted. HOC was a significant predictor in both sexes. For every previous concussion, the risk of sustaining another sport concussion increased by 1.5 (CI: 1.1, 2.1 [females]; 1.2, 1.9 [males]). Males with HOC had three times the odds of sustaining another concussion than those without a HOC (CI: 1.7, 5.6). For females, these odds were two times higher (CI: 1.1, 4.0). CF (as measured by the Automated Neuropsychological Assessment Metrics), and sex were not meaningful predictors of risk of concussion. The results support previous findings on HOC and sex as predictors of sport concussion, provide novel findings on the predictive ability of CF, and may be useful in informing concussion prevention and management practices.

Keywords: cognitive functioning
history of concussion
pre-injury
risk factor
sex
sport concussion
Advisor: Mainwaring, Lynda
Elucidating Vacuolar H+-ATPase Subunit Interactions: A Systematic Structural Analysis

Osteoclasts resorb bone by expressing proton-pumping vacuolar type H+-ATPases (V-ATPases) on their cell surfaces. V-ATPases are composed of two domains (V1 and V0) containing many subunits, with some subunit isoforms being tissue/cell specific. a3, d2, and B2 isoforms are osteoclast enriched. Though the overall organization of the V-ATPase is understood, exact subunit interactions remain largely unknown. We hypothesize that delineating sites of the a3-B2 and a3-d2 interactions will identify novel targets for development of anti-osteolytics. We propose to narrow down the interaction regions to allow for future in silica drug discovery schemes. Truncated B2 and d2 fragments used in ELISA binding assays with purified NT-a3 suggest two interaction regions in B2 exist, reinforcing that, structurally, NT-a3 may be composed of two processes. The interactions of NT-a3 with B2 and d2 may be in a fluid flux where one interaction may occur during assembly, and another to stabilize the structure.

Keywords: Anti-resorptives
Osteoclasts
Subunit Interactions
V-ATPase
Advisor: Manolson, Morris F
Design of DC-link Capacitor of High Power Switch Module of an Aircraft Power & Thermal Management Controller

DC -Link Capacitor used in power converters as an energy buffer is one of the key components of aircraft Power and Thermal Management Controller (PTMC). Several factors in order to reduce the cost of the PTMC have been identified including the integration of the DC-link capacitors, DC bus bars and Snubber caps. The key factor of this redesigned DC-link capacitor is to justify its structural functionality subjected to random vibration and temperature loadings. Finite Element Method (FEM) using ANSYS is used to predict the life cycle of the structure (redesign DC link capacitor integrated with DC bus bar and Snubber caps) subjected to random loading. The impact of temperature loading and the resulting deflection and stresses induced in various parts of the structure are also investigated. Finally the new design is verified by fatigue life and thermal stress analyses and the reduction of cost is evaluated in terms of the weight and cost saving factors.

Keywords: ANSYS
Fatigue Life
FEM
Pro/Engineer
PTMC
Thermal Stress
Advisor: Behdinan, Kamran
Characterizing the Role of Podocalyxin in Breast Carcinoma

Lymphatic invasion (LVI), the presence of tumour emboli within the peritumoural lymphatics of the breast, is an independent prognostic marker for axillary node negative breast cancer. Podocalyxin (PODXL) was the most differentially expressed protein between LVI+ and LVI- tumours in our cohort. Paradoxically, PODXL correlated with increased long term disease free survival as well as poor prognosis characteristics such as large tumour size. This thesis studied the effect of PODXL overexpression using in vitro techniques. In EpH4 three dimensional cultures, PODXL conferred resistance to TGF-β induced acinar collapse. Immunofluorescent staining of PODXL and cell polarity marker Scribble indicated loss of cell polarity in collapsed acini. Immunofluorescent staining of EMT markers showed that a classical EMT response is not the cause of the acinar collapse observed. This acinar architecture maintenance function of PODXL may be a potential component by which PODXL overexpression may be protective as is suggested by our cohort.

Keywords: 3D culture
acini
Breast Cancer
Lymphatic Invasion
Podocalyxin
TGF-β
Advisor: Andrulis, Irene
Sources of Particulate Matter Emissions Variability from a Gasoline Direct Injection Engine

Ultrafine particulate matter (PM) emissions from gasoline direct injection engines are a concern due to their associated health effects. This experimental study investigated sources of PM emissions variability observed in previous work, along with the effect of ethanol content in gasoline on PM emissions. Engine operating parameters and test conditions were studied and controlled, but could not account for the level of variability observed. FTIR measurements of gas phase hydrocarbon emissions provided evidence that fuel composition changes were responsible for this variability. Exhaust emissions of toluene and isobutylene were interpreted as markers of gasoline aromatic content and gasoline volatility, respectively. Tests with gasoline containing added toluene (10%) supported this hypothesis and showed that the PM emissions variability can be attributed to changes in the composition of the pump gasoline. Tests with gasoline containing added ethanol (10% and 30%) increased PM emissions at steady-state operation and decreased emissions during engine start-up.

Keywords: Emissions
Ethanol
Gasoline Direct Injection
GDI
Particulate Matter
SIDI
Advisor: Wallace, James S
Effect of Superhydrophobic Titanium Surface on Initial Salivary Pellicle Acquisition and Oral Biofilm Formation

Colonization by oral microorganisms on dental abutment surfaces can result in inflammatory reactions such as peri-implantitis creating patient discomfort that may ultimately jeopardize the long-term prognosis of the dental implant. Previous studies have shown that superhydrophobic surfaces reduced bacterial colonization and subsequent biofilm formation. The aim of this study was to investigate the influence of superhydrophobic modified titanium (SH-Ti) surface on salivary pellicle acquisition and development of a multi-species oral biofilm. Our results showed that SH-Ti substrates significantly reduced the volume of salivary pellicle. Surprisingly, superhydrophobicity did not prevent biofilm formation. In fact, live cells were observed in higher numbers in 72-h-old biofilm on SH-Ti substrates in comparison with non-treated titanium surfaces. In contrast, dead cells were found in lower numbers on SH-Ti vs. non-treated surfaces under the same growth conditions. Scanning electron microscopy confirmed that SH-Ti surfaces increased bacterial colonization preferentially in the micro-topographical crevices. In conclusion, our results indicate that modification of surface wettability may affect the biological response at the implant to bone or implant to soft tissue interface.

Keywords: Dental abutment
Dental implants
Oral biofilm
Salivary pellicle
Superhydrophobic
Advisor: LĂŠvesque, CĂŠline M.
The In Silico Search for a Novel Lithium Receptor

This thesis aimed to showcase the in silico search for a novel lithium receptor. Lithium, a frequently prescribed mood stabilizer, has an unknown therapeutic mechanism. Using molecular mechanics and dynamics, it was first argued that serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) function as receptors for lithium. Numerous studies revealed that Li+ favorably bind these molecules, inducing changes in their conformation. Later, homology modeling, in silico docking and further molecular mechanics experiments revealed lithium's ability to influence the receptor interaction profiles of 5-HT and 5-HIAA at 5-HT1A R and 5-HT2B R. These interactions were electrostatically robust, but came at a cost to van der Waals potential. Experimental studies of these systems, including x-ray crystallography and in vitro 5-HT receptor assay did not prove fruitful. Hyperactivation of the serotonergic receptors provides a mechanism of action for lithium. Overall, these results offer novel insight into the therapeutic profile of this important mood stabilizer.

Keywords: Bipolar disorder
In silico
Lithium
Protein modelling
Advisor: Weaver, Donald F
Oestrogen Receptor-alpha Regulates Non-canonical Hedgehog-signalling in the Mammary Gland

Mesenchymal dysplasia (mes) mice harbour a truncation in the C-terminal region of the Hedgehog (Hh)-ligand receptor, Patched-1 (Ptch1) and display a block to mammary ductal elongation at puberty. Our lab previously demonstrated that epithelial cell-directed expression of activated c-src rescued this block to mammary development and induced estrogen receptor-alpha (ER) expression. Using a genetic approach where a conditional allele of ER was expressed on the mes background, we demonstrated that restricted expression of ER also rescues mes mammary morphogenesis with similar kinetics as the MMTV-c-srcAct mice. We further demonstrated distinct cell-type specific canonical Hh signalling in primary mammary epithelial and mesenchymal cells, and identified a novel Erk1/2 activating Hh signalling system that requires the activities of c-src and ER, but not Smoothened (smo). These data reveal a novel Hh-signalling cascade operating through c-src and ER that is required for mammary gland morphogenesis at puberty.

Keywords: estrogen receptor
hedgehog
mammary gland
mouse model
Advisor: Hamel, Paul A
A Population-based Analysis of the Clinical Course of Colonic Diverticulitis and its Evolving Management

Evidence has accrued to support change in the management of colonic diverticulitis. Advances in imaging and medical management suggest more patients may be managed non-operatively; while various new operative approaches have been proposed as an alternative to Hartmann's procedure when urgent surgery is necessary. Furthermore, published reports suggest the clinical course of the disease may be characteristically benign; suggesting interval elective colectomy may be unnecessary for the majority of patients, even those with known risk factors. Reports to date consist predominantly of institutional cohort studies with high loss to follow-up and failure to account for competing risks. To address the gaps in knowledge, we performed a population-based retrospective cohort study. The objectives of this study were to (a) evaluate temporal trends in the management of diverticulitis, and (b) characterize the clinical course of the disease following initial non-operative management. Results from this study will help to inform best practice recommendations.

Keywords: Colectomy
Diverticular disease
Diverticulitis
Epidemiology
Surgery
Advisor: Nathens, Avery B
Community Diversity and Functional Capabilities of Benzene­‐Degrading Enrichment Cultures

Benzene is prevalent, toxic, and persistent in anaerobic environments. Anaerobic benzene degradation has been proven, but is not well understood. The goals of this research were to determine the community composition of anaerobic nitrate-reducing benzene-degrading enrichments and propose likely metabolic roles of organisms present. Highly diverse communities were present in the enrichments, with multiple organisms capable of carrying out similar roles. A metagenome assembly was generated from a nitrate-reducing, benzene- degrading enrichment culture. Further evidence for fermenting Peptococcaceae as the initiator of benzene degradation was established. The potential for benzene degradation to be linked to other terminal electron acceptors (i.e., CO2) was confirmed, further supporting that the initial benzene degradation steps are carried out in a fermenting syntroph. An understanding of the functions of different organisms can inform culturing techniques to increase culture growth and benzene degradation rates. Genes present in the metagenome could be used as biomarkers for benzene degradation.

Keywords: Benzene
Bioremediation
Community diversity
Metagenomics
Advisor: Edwards, Elizabeth A
Evaluation and Visualization of Multi-level Contingencies in Power Systems

Contingency analysis is a critical technique for evaluating the operational capability of power systems and characterizing their vulnerability to component faults. The traditional requirement for reliable operations has been an n-1 security constraint --- an electrical network should be resilient to contingencies involving any one element.Contingency analysis is critical to evaluating the operational capacity of power systems and characterizing their vulnerability to component faults. As we look to increase the resilience of networks to element failure, the instance of multiple contingencies is of growing concern for planners and operators in identifying weak points in the system. Multi-element contingencies introduce new challenges for how to reliably and consistently measure the severity of a fault, how to perform contingency analysis on an expanding range of contingency scenarios in a timely manner, and how to interpret the increasingly hierarchical data obtained by contingency analysis. This research explores techniques that can be used to generate, summarize and display the results of multi-element contingency analyses in power systems, including high-performance computational methods for evaluating contingencies and new visualization techniques that leverage visual summarization and live interaction to extract valuable insights from the resulting data.

Keywords: Contingency
Continuation Power Flow
Power System
Tree
Treemap
Visualization
Advisor: Tate, Joseph Z
Synchronization Control of Interconnected Systems with Applications to Neuronal Models

This thesis investigates the control of synchronization for a general class of compartmental models. The system consists of interconnected compartments. Each compartment is an interconnection of subsystems called species, which are modeled as input-output operators in the extended L_2 space. Compartmental models are ubiquitous in biological networks modeling. The distinctive feature of this thesis is the presence of an external feedback loop that can be used to modify the behavior of the network. Our main results provide controllable bounds on the level of synchrony of the network. The problem ofselecting the feedback parameters to achieve the desired bounds is also addressed and the approach is applied to a number of neuronal network models. The application is motivated by the feedback control of pathological synchronization of neuron firing in the brain, often responsible for neurological diseases such as Parkinsons

Keywords: Input Output Approach
Parkinson's Disease
Synchronization Control
Advisor: Scardovi, Luca
Strategic Management of Flammable Boreal Forest Landscapes that are Subject to Large Scale Windstorm Damage

A linear programming model was developed and used to evaluate how best to manage blowdown disturbances when carrying out strategic forest management planning in the boreal forest region of Ontario. Blowdown occurs when strong winds disturb large areas of standing timber, often more than several 100 hectares in size. My model accounts for wildfire and natural blowdown burning processes that should be considered when deciding if, when and where to initiate harvesting, salvage logging or prescription burning operations in order to maximize the economic value of the forest. Sound blowdown management calls for a mix of salvage logging, prescription burning and leaving some blowdown areas alone. My results suggest that some large blowdown disturbances should be set aside and neither salvage harvested nor prescription burned. Current policy may be inadequate at preparing forest managers for multiple large, infrequent and uncertain disturbance events as contingency may need to be increased at least two-fold.

Keywords: Blowdown
Compounded disturbance
Natural disturbance
Operations research
Strategic planning
Wildfire
Advisor: Martell, David L
Lanthanum-mediated Aminoacylation on Dinucleotides

Developing methods that can insert unnatural amino acids at specific locations within proteins is a topic of considerable recent interest. In vitro pathways using chemically aminoacylated tRNA have previously been developed. However, the multi-step protection and deprotection pose limits on this method. Biochemical methods have also been developed using orthogonal tRNA/aminoacyl-tRNA synthetase pairs. However, the variety of available unnatural amino acids is limited by the high specificity of aminoacyl tRNA synthetases. To overcome these problems, an improved chemical lanthanum-mediated aminoacylation method has been developed. Previous studies have shown the success of aminoacylating nucleosides/nucleotides with both protected and native amino acids. In this study, the reaction was studied with dinucleotides using N-t-Boc-protected aminoacyl ethyl phosphates. Successful aminoacylation on dinucleotides was observed. Optimal pH and buffer compositions were determined for this reaction. These results are expected to provide information in developing a lanthanum-mediated catalytic chemical method to unnatural aminoacylated tRNA in general.

Keywords: Aminoacylation
dinucleotide
Lanthanum
tRNA
Advisor: Kluger, Ronald
Clinical and Biological Studies of the Alternative Lengthening of Telomeres in Paediatric Brain Tumours

Certain cancers maintain telomeres using the alternative lengthening of telomeres (ALT), which is associated with mutations to specific genes in several cancers. ALT has not been characterized in paediatric brain tumours (PBTs).We hypothesized that ALT is present in PBTs, is associated with mutations to ALT-associated genes, and impacts survival.517 PBTs and 163 control tumours were screened for ALT using the c-circle assay.ALT was found in high grade PBTs of mesenchymal/neuroepithelial tissue origin characterized by a high incidence of mutant TP53. ALT was associated with TP53 (p = 7.32x10-8) and ATRX (p = 5.23x10-4) mutations. ALT abrogated poor survival in TP53 mutant paediatric malignant gliomas (p = 0.03). Association with improved survival approached significance in TP53 mutant choroid plexus carcinoma (p = 0.07).ALT is found in PBTs harboring somatic TP53 mutations, and impacts survival. Stratification using ALT is important for the management of these cancers in children.

Keywords: Alternative Lengthening of Telomeres
ATRX
C-circles
Paediatric Brain Tumours
Survival
TP53
Advisor: Tabori, Uri
Patellar Tendon Loading during Laboratory - Controlled Vertical and Horizontal Jump-Landing Tasks - Towards the Development of a Tool to Assess the Risk of Developing "Jumper's Knee"

Empirical and theoretical evidence support the notion that patellar tendinopathy can develop due to the loads associated with various movement patterns. The objective of the current study was to determine whether visually observable trunk and lower extremity kinematic variables were related to patellar tendon loading. Full body three-dimensional kinematics and force platform data were collected for 35 participants. Patellar tendon stress values were estimated through a single equivalent model. Three relationships were found to be consistent across all studied tasks; a smaller trunk flexion angle, and greater knee flexion range of motion and peak knee flexion angles were associated with an increased peak patellar tendon stress, and an increased patellar tendon stress impulse, respectively. If a causal relationship between patellar tendon loading and risk of patellar tendinopathy exists, there may be a basis for using the four tasks for patellar tendinopathy prediction and prevention.

Advisor: Beach, Tyson