VictorJuiz/thesis huggingface dataset:
Targeted Capture and Sequencing of Immunoglobulin Rearrangements in Multiple Myeloma to Enable Detection of Minimal Residual Disease

Multiple Myeloma (MM) is an incurable plasma cell dyscrasia characterized by recurrent translocations into immunoglobulin loci and a unique V(D)J rearrangement signature that can be used to track disease over time. Modern myeloma therapy results in high response rates, however the majority of patients still relapse, suggesting persistence of minimal residual disease (MRD) beyond current limits of detection. We developed a targeted-capture approach to detect V(D)J rearrangements and recurrent immunoglobulin translocations to enable MRD assessment. We validated this assay in 69 human myeloma cell lines and established a limit of detection of 1/1000 DNA fragments. Our methods agree with MRD measured by multi-parameter flow cytometry in 11/14 patient samples. One sample was MRD positive by MFC and negative by targeted-capture sequencing, two were positive by sequencing and negative by MFC. Targetedcapture sequencing is an alternative strategy to MRD detection and has potential applications for disease monitoring and immune repertoire profiling.

Keywords: Genomics
Immunoglobulin
Lymphoproliferative
Multiple Myeloma
Next Generation Sequencing
Targeted Capture Sequencing
Advisor: Pugh, Trevor J
Effect of Fuel Composition on Particulate Matter Emissions from a Gasoline Direct Injection Engine

The effects of fuel composition on reducing PM emissions were investigated using a Ford Focus wall-guided gasoline direct injection engine (GDI). Initial results with a 65% isooctane and 35% toluene blend showed significant reductions in PM emissions. Further experiments determined that this decrease was due to a lack of light-end components in that fuel blend. Tests with pentane content lower than 15% were found to have PN concentrations 96% lower than tests with 20% pentane content. This indicates that there is a shift in mode of soot production. Pentane significantly increases the vapour pressure of the fuel blend, potentially resulting in surface boiling, less homogeneous mixtures, or decreased fuel rebound from the piston. PM mass measurements and PN Index values both showed strong correlations with the PN concentration emissions. In the gaseous exhaust, THC, pentane, and 1,3 butadiene showed strong correlations with the PM emissions.

Keywords: alternative fuels
emissions
engines
particulate emissions
pentane
Advisor: Wallace, James S
The Impact of Delay to Anterior Cruciate Ligament Reconstruction on Patient-Reported Outcomes and Concurrent Knee Injuries

The ideal timing of anterior cruciate ligament reconstruction is debatable after ligament tear. Purpose: To investigate the effects of delay from time of injury to reconstruction, on the cost-effectiveness, the incidence of concurrent knee pathology, and the patientsâ quality of life. Methods: We performed 2 systematic reviews and 1 multicenter cohort study, looking at the effects of delay, from injury to surgery, on the cost-effectiveness, concurrent knee injuries, and on quality of life, respectively. Results: Despite substantial heterogeneity, ligament reconstruction was costeffective in each study. A significant increase in medial meniscal and cartilage pathology was found as of 3 monthsâ post-injury, at which point, a decline in quality of life was also detected, 2 years post-operatively. Conclusion: An increase in delay from time of injury to surgery can lead to an increase in cost, medial meniscal and cartilage pathology, and a potential decline of quality of life.

Keywords: ACL
cartilage
cost-effectiveness
delay
meniscus
quality of life
Advisor: Wunder, Jay
Liquid Water Saturation and Oxygen Transport Resistance in Polymer Electrolyte Membrane Fuel Cell Gas Diffusion Layers

In this thesis, the relative humidity (RH) of the cathode reactant gas was investigated as a factor which influences gas diffusion layer (GDL) liquid water accumulation and mass transport-related efficiency losses over a range of operating current densities in a polymer electrolyte membrane (PEM) fuel cell. Limiting current measurements were used to characterize fuel cell oxygen transport resistance while simultaneous measurements of liquid water accumulation were conducted using synchrotron X-ray radiography. GDL porosity distributions were characterized with micro-computed tomography (ÎźCT). The work presented here can be used by researchers to develop improved numerical models to predict GDL liquid water accumulation and to inform the design of next-generation GDL materials to mitigate mass transport-related efficiency losses. This work also contributes an extensive set of concurrent performance and liquid water visualization data to the PEM fuel cell field that can be used for validating multiphase transport models.

Keywords: Gas diffusion layer
Oxygen transport resistance
Polymer electrolyte membrane fuel cells
Saturation
Synchrotron X-ray radiography
Water management
Advisor: Bazylak, Aimy
Design and Fabrication of Porous Yttria-Stabilized Zirconia Ceramics for Hot Gas Filtration Applications

Hot gas filtration has received growing attention in a variety of applications over the past few years. Yttria-stabilized zirconia (YSZ) is a promising candidate for such an application. In this study, we fabricated disk-type porous YSZ filters using the pore forming procedure, in which poly methyl methacrylate (PMMA) was used as the pore-forming agent. After fabricating the pellets, we characterized them to determine their potential for application as gas filters. We investigated the effect of sintering temperature, polymer particle size, and polymer-to-ceramic ratio on the porosity, pore size, gas permeability, and Vickers hardness of the sintered pellets. Furthermore, we designed two sets of experiments to investigate the robustness of the fabricated pellets â i.e., cyclic heating/cooling and high temperature exposure. This study ushers in a robust technique to fabricate such porous ceramics, which have the potential to be utilized in hot gas filtration.

Keywords: Gas permeability
Hot gas filtration
Poly methyl methacrylate
Porosity
Porous ceramic fabrication
Yttria-stabilized zirconia
Advisor: Azimi, Gisele
Investigation of Dual-phase Nanocrystalline Ni-Cu Electrodeposits

Ni-Cu alloys are employed on a large scale in the marine industry due to their excellent corrosion resistance in natural sea water. In an effort to enhance the erosion resistance of these alloys as well, nanocrystalline Ni-Cu specimens were synthesized by electrodeposition. However, surface and bulk characterization revealed an unexpected macrostructure that displayed separate Ni- and Cu-rich phases. Detailed characterization showed significant differences between the two phases in terms of chemical composition, grain size distribution, and localization of bulk defects. Furthermore, inhomogeneity of this electrodeposit in terms of hardness was found as well, hindering the application of such electrodeposits in industry. The formation of this macrostructure was investigated through assessing key characterization results, and a formation mechanism is postulated which is related to the diffusion-controlled deposition of uncomplexed Cu species, due to inadequate stability of complexing agents in the electrolyte. Some steps to eliminate this undesirable macrostructure are proposed.

Keywords: Complexing Agent
Diffusion-limited deposition
Electrodeposition
Nanocrystalline
Ni-Cu
Phase separation
Advisor: Erb, Uwe
Modelling, Testing and Optimization of a Passive Solar Updraft Aeration System for Aquaculture in the Developing World

Pond aquaculture is major source of food security and income in the Asia-Pacific region. Over 70% of ponds are operated by smallholder farmers who do not have access to aeration technology for proper management of dissolved oxygen levels. The Solar Updraft Aeration (SUpA) system was developed to provide a low-cost, sustainable alternative to conventional aeration in resource-constrained environments. This thesis presents a framework for identifying a suitable design of the SUpA system for large-scale field testing. A comprehensive model was developed using computational fluid dynamics (CFD) and validated in the bench-scale. The model was used to conduct a broad search of the design space of each configuration. The inverted prism configuration was selected for further optimization based on results from CFD and preliminary field tests. The optimized geometry showed an improvement of 81% over a reference geometry based on previous designs and was selected for testing in the future.

Keywords: Aeration
CFD
Optimization
Pond Aquaculture
Solar Thermal
Surrogate Modelling
Advisor: Bilton, Amy M
Analytics for Decision-Making in Amateur Sport Organizations

In this thesis, we demonstrate the value that analytics can have in guiding decisions at amateur sport organizations. We ďŹ rst use machine learning methods to estimate how the demand for tennis is distributed across Canada on a geographical level; geographical prediction of demand for sport has not been seen in the sport management literature. We develop novel validation techniques to show that our estimates outperform the naive assumption that the same proportion of tennis players lives in each region in Canada. To present the estimated demand to decision-makers, we build interactive maps that display the supply and demand for tennis across Canada. Through a case study in facility location, we show that the predicted demand can be used to determine the optimal locations of new tennis programs. Lastly, we present interactive tools that we built for decision-makers to analyze their membership and make targeted decisions about recruitment and retention strategies.

Keywords: Amateur Sport
Analytics
Facility Location
Sports Analytics
Advisor: Chan, Timothy
Characterization of a Zebrafish Model of X-linked Centronuclear Myopathy for Therapeutic Drug Development

X-linked centronuclear myopathy (XLCNM) is a congenital skeletal muscle disorder caused by mutations in MTM1. Despite being associated with a high rate of neonatal mortality there are currently no effective therapies for this disorder. MTM1 is a phosphoinositide 3-phosphatase that antagonizes class II and III phosphatidylinositol 3-kinases (PI3K). Loss of Pik3c2b, a class II PI3K, rescues lethality in Mtm1 knockout mice. Importantly, Pik3c2b knockout mice are viable and have no apparent phenotype. Therefore, pharmacological inhibitors of PIK3C2B have the potential to be highly effective in the treatment of XLCNM. I have characterized an mtm1 mutant using the zebrafish, Danio rerio, and found that PIK3C2B inhibition improves the mtm1 mutant phenotype. In parallel, a phenotypic drug screen identified valproic acid as a suppressor of an mtm1 mutant phenotype. The work presented herein demonstrates that PIK3C2B inhibitors and drugs like valproic acid may represent putative therapeutics for translation into MTM1 patients.

Advisor: Dowling, James J
COMPARATIVE STUDY BETWEEN STATISTICAL FRAUD DETECTION METHODS ON ECOMMERCE NETWORKS

In the eCommerce industry, the problem of consumer fraud is becoming an increasingly troublesome problem posing a multitude of challenges. Large eCommerce firms, such as Alibaba, eBay, Amazon (to name a few) serve the needs of hundreds of millions customers. On a daily basis, a large number of transactions are made and recorded, as more consumers are becoming susceptible to fraudulent behaviour provided the scale of operations. This research aims to develop a robust real-time fraud detection algorithm based on the construction of a behavioural reference model. Time series features pertaining to a data set of customers on a large eCommerce service are collected and assigned to two classes (non-fraudulent or fraudulent) and modelled using a general stochastic model. The classification performance of this model is compared with more conventional classification techniques, such as logistic regression, tree-based methods, and Na誰ve Bayesian Classifier.

Keywords: ecommerce
fraud
stochastic
Advisor: Makis, Viliam
Characterizing Vascular and Neuronal Defects in Williams-Beuren Syndrome and 7q11.23 Duplication Syndrome Using Induced Pluripotent Stem Cells

Williams-Beuren syndrome (WBS) and 7q11.23 duplication syndrome (Dup7) are caused by the deletion and duplication, respectively, of 26-28 genes on chromosome 7 in humans, affecting the cardiovascular and nervous systems. To model WBS and Dup7, we generated induced pluripotent stem cells (iPSCs) from multiple WBS, Dup7, and healthy control individuals. In iPSC-derived smooth muscle cells (SMCs), I found an increase in proliferation and reduction in differentiation among WBS SMCs, while also finding elevated proportions of SMC marker in Dup7 precursors, indicating premature differentiation. Assessing neuronal morphology in iPSC-derived neurons, when co-cultured and compared with similarly derived control neurons, axon and dendrite lengths were increased in Dup7 neurons and soma size was increased in both WBS and Dup7 neurons. Further characterization of such phenotypes will provide insight into the pathology underlying the cardiovascular and neurobehavioural symptoms of WBS and Dup7 and inform how they can be addressed at a clinical level.

Keywords: 7q11.23 duplication syndrome
disease modelling
induced pluripotent stem cells
neuron
smooth muscle
Williams-Beuren syndrome
Advisor: Ellis, James
IMPROVING THE EFFECTIVENESS OF RADIOTHERAPY IN CERVICAL CANCER: TARGETING THE CXCL12 PATHWAY TO INCREASE TUMOUR CONTROL

The CXCL12/CXCR4 pathway has been shown to promote tumour growth, metastasis and radiochemotherapy resistance in many tumour sites, including in cervical cancer. We hypothesized that the addition of the CXCR4 inhibitor Plerixafor to radiochemotherapy would result in longer tumour growth delay and potentially improve tumour control compared to radiochemotherapy alone, without added toxicity. Two primary orthotopic cervical cancer xenograft models were implanted in the cervices of mice and treated with radiochemotherapy with/without Plerixafor. The addition of Plerixafor to radiochemotherapy resulted in a trend for higher local tumour control in one tumour model, and in faster tumour regression in both tumour models, without evidence of added toxicity. In the late intestinal toxicity study, there was a trend for lower toxicity in mice receiving radiochemotherapy + Plerixafor arm compared to radiochemotherapy. Our work suggests that the addition of Plerixafor to radiochemotherapy results in better primary tumour control, without added toxicity.

Advisor: Milosevic, Michael
Inverse linear optimization for the recovery of constraint parameters in robust and non-robust problems

Most inverse optimization models impute unspecified parameters of an objective function to make an observed solution optimal for a given optimization problem. In this thesis, we propose two approaches to impute unspecified left-hand-side constraint coefficients in addition to a cost vector for a given linear optimization problem. The ďŹ rst approach minimally perturbs prior estimates of the unspecified parameters to satisfy strong duality, while the second identifies parameters minimizing the duality gap, if it is not possible to satisfy the optimality conditions exactly. We apply these two approaches to the general linear optimization problem. We also use them to impute unspecified parameters of the uncertainty set for robust linear optimization problems under interval and cardinality constrained uncertainty. Each inverse optimization model we propose is nonconvex, but we show that a globally optimal solution can be obtained by solving a ďŹ nite number of tractable optimization problems.

Keywords: Inverse optimization
Nonlinear programming
Robust optimization
Advisor: Chan, Timothy C.Y.
Effect of De-Watering Wood Derived Pyrolysis Liquid Biofuel on its Properties, Characteristics, and Combustion Behavior in a Diesel Engine

Two different methods were employed to successfully reduce the water content of Wood Derived Pyrolysis Liquid Biofuel (also known as wood pyrolysis liquid or bio-oil). Removing water increased fuel heating value and improved its storage stability. Removing moderate quantities of water from WPL was found to be favorable for its emulsification with diesel. Atlox 4196 produced most stable emulsions. Stainless steel was the only material that displayed no corrosion. Reducing water content significantly reduced the fuel corrosion rates. Surface XPS analysis stipulated chemical nature of the corrosion. Four different emulsions of pure and water removed WPL were tested in caterpillar diesel engine at various loads for emissions and fuel consumption. Injector clogging and fuel pump failure were identified as two key challenges hindering WPL utilization in a diesel engine. Although, diesel fuel showed least fuel consumption and lower emissions in most cases differences between diesel fuel and emulsions tends to reduce considerably at higher loads indicating WPL potential for fueling a diesel engine.

Keywords: Bio-oil water removal upgrdation
Diesel/ Bio-oil emulsification
Diesel engine operation
Pyrolysis liquid combustion
pyrolysis liquid corrosion
Wood pyrolysis liquid
Advisor: Thomson, Murray J
Advancements in the Design and Fabrication of Ultrasound Transducers for Extreme Temperatures

An ultrasound transducer for operation from room temperature to 800 째C is developed. The device includes a lithium niobate piezoelectric crystal, a porous zirconia attenuative backing layer, and a quarter wavelength matching layer. The manufacturing procedure for porous zirconia is optimized by adjusting pore size and forming pressure to yield good acoustic performance and mechanical integrity. Several acoustic coupling methods are evaluated. A novel silver-copper braze and an aluminum-based braze are found to be suitable at elevated temperatures. Several materials are evaluated for their performance as a quarter wavelength matching layer in the transducer stack. The use of either a nickel-chromium or stainless steel matching layer is established in place of ceramic components. Equipment limitations prevent evaluation at 800 째C, though ultrasound transmission is theoretically achievable with the devices established by this study. Reliable high-amplitude, wide-bandwidth ultrasound transmission is achieved from room temperature to 600 째C with two transducer variants.

Keywords: brazing
high temperature
lithium niobate
non destructive testing
porous zirconia
ultrasound transducers
Advisor: Sinclair, Anthony N
Development of a flexible polarimetric probe for assessment of structural bladder disease

Optical polarimetry uses polarized light to quantitatively characterize the morphology of tissue. It can provide contrast between healthy and pathological tissues otherwise invisible to standard intensity imaging1â 4. In the first half of this thesis a polarimetry study of murine partial bladder outlet obstruction (pBOO) is detailed that assessed a pharmacological muscle response to obstruction-induced myopathy. No significant changes in tissue anisotropy were observed between control and obstructed bladder regions and the pharmaco-treatment enhanced the pathologic response in both control and obstructed bladders. In the second half of this thesis a polarimetric probe is described and validated by accurately measuring 3x3 Mueller matrices of known polarization components. It is later used to probe morphological contrasts between normal and stretched ex vivo tissue. Translating traditional, free-space polarimetry from the optics bench to a flexible, fibre-based probe represents a significant step toward in situ polarization-enhanced endoscopies, such as cystoscopy for pBOO.

Keywords: biomedical optics
Mueller matrix
partial bladder outlet obstruction
polarimetry
probe
urology
Advisor: Vitkin, Alex
Prying of a Large Span Plate Undergoing a Moment Load Applied by a Round Pier

Large span base plates with a moment load applied, in any direction, to the centre of the plate by a round pier are commonly used in the design of anchors for faรงade access systems. There is no current method of predicting the behaviour of these large span plates under a moment load. Six anchor base plate configurations are physically tested. The deflection of the plate is analysed using digital image correlation (DIC) to track the change in location of points on the base plates under various applied loads. The shapes are plotted and used to determine at what point the plates transition from linear to nonlinear deformation. A method of predicting the moment resistance of the base plates for each test was proposed and a finite element model for the base plates was analysed and validated using the test data.

Keywords: base plate
digital image correlation
solid mechanics
Advisor: Naguib, Hani
Knowledge-Based Automated Planning for Oropharyngeal Cancer

We automatically generate intensity-modulated radiation therapy plans for oropharyngeal cancer by combining knowledge-based planning (KBP) predictions with an inverse optimization (IO) pipeline into a single automated treatment planning pipeline. We extended two existing KBP methods, which use patients' anatomical geometry to predict achievable dose volume histograms (DVHs), and developed the first IO method that takes DVHs as direct inputs. The DVH predictions from KBP are put into the IO pipeline to automatically generate treatment plans via an intermediate step using objective function weights and an inverse planning problem. This step enables our automated planning pipeline to seamlessly fuse with the current treatment planning paradigm to increase its efficiency. Our automated pipeline can replicate, and often improve upon the clinical treatment plans by reducing the dose to healthy tissue and increasing primary target coverage. These results have been validated using a large cohort of 217 oropharyngeal cancer patients.

Keywords: Automated planning
Intensity-modulated radiation therapy
Inverse optimization
Knowledge-based planning
Advisor: Chan, Timothy C. Y.
Examining the Fundamental Biology of Primitive Neural Stem Cells

Definitive (d) neural stem cells (dNSCs) are multipotent, self-renewing, neurally committed stem cells. More recently, a novel primitive (p)NSC was identified in the early postnatal brain that persists into adulthood. pNSCs are upstream of dNSCs in the neural lineage and are self-renewing with the capacity to generate neural cells. pNSCs, unlike dNSCs, express the pluripotency genes Oct4, and Nanog and are able to incorporate into the developing blastocyst. Based on these findings we hypothesized that pNSCs are pluripotent cells able to generate cells outside the neuroectodermal lineage. To test this hypothesis, we utilized well established pluripotency assays in vitro embryoid body assay and the in vivo teratoma formation assay. When placed in these assays pNSCs revealed no pluripotentiality, demonstrating consistent neural commitment and no differentiation into mesoderm or endoderm lineages. In addition, pNSCs expressed the epithelial marker Krt18 indicating that their origin may be from an embryonic time before neurulation.

Keywords: Developmental Biology
Neural Stem Cells
Pluripotency vs Multipotency
Primitive Neural Stem Cells
Stem Cell Biology
Advisor: Morshead, Cindi M