VictorJuiz/thesis huggingface dataset:
Characterizing Novel Interactions of Transcriptional Repressor Proteins BCL6 and BCL6B

B-cell Lymphoma 6 (BCL6) and its close homolog BCL6B encode proteins that are members of the BTB-Zinc Finger family of transcription factors. BCL6 plays an important role in regulating the differentiation and proliferation of B-cells during the adaptive immune response, and is also involved in T cell development and inflammation. BCL6 acts by repressing genes involved in DNA damage response during the affinity maturation of immunoglobulins, and the mis-expression of BCL6 can lead to diffuse large B-cell lymphoma. Although BCL6B shares high sequence similarity with BCL6, the functions of BCL6B are not well-characterized. I used BioID, an in vivo proximity-dependent labeling method, to identify novel BCL6 and BCL6B protein interactors and validated a number of these interactions with co-purification experiments. I also examined the evolutionary relationship between BCL6 and BCL6B and identified conserved residues in an important interaction interface that mediates corepressor binding and gene repression.

Keywords: BCL6
BCL6B
BioID
BTB-ZF
Proteomics
TLE
Advisor: PrivĂŠ, Gil G
In-situ visualization of Steam Assisted Gravity Drainage with Chemical and Solvent Additives

The introduction of steam-assisted-gravity drainage (SAGD) brought a significant improvement in the recovery of extra heavy oil, bitumen. The viscosity of bitumen being heavily dependent on temperature, makes the steam injection in SAGD highly effective in mobilizing the oil. The porous geometry of the reservoir structure plays an important role in the oil recovery process, along with the multiphase flow that takes place during the oil recovery process. Visualization of SAGD and the addition of chemical and solvents additives were conducted in this thesis at reservoir matching temperature and pressures (0.7-1.3 MPa, 170-210째C). Results of the experiments showed that alkaline additives brought improvement in oil recovery through wettability alteration, and solvents improve oil recovery through combination of mass transport and heat transfer effects. For the hexane-SAGD run, compositional separation of bitumen based on polarity difference was observed.

Keywords: condensation
Enhanced oil recovery
Microfluidics
Petroleum
solvents
Steam asssisted gravity drainage(SAGD)
Advisor: Sinton, David
Applying Machine Learning with Spatio Temporal Analysis to Classify Crowdsourced Data from the 2010 Haiti Earthquake Relief Efforts

Text categorization of incidental data crowdsourced from a crisis scenario is time-sensitive and requires knowledgeable human input. Instead, this study runs data collected from the 2010 Haiti earthquake relief efforts through a machine learning model. Linear supervised classification with Support Vector Machines, in combination with feature selection using Term Frequency-Inverse Document Frequency, was identified to achieve good performance in comparable literature. The feature sets were extended by spatio-temporal attributes for exploratory analysis and evaluating changes to the modelâ s performance. All phases of the experiments report consistent accuracy rates (87th percentile), with no statistically significant variance in precision, recall and F1 performance measures. Results demonstrate that using class labels alone is sufficient for such classification. Given the absence of known studies utilizing this data-driven approach, this study provides a benchmark analysis, laying the groundwork for further studies on adapting text classification models to similar crowdsourced, emergency relief data.

Keywords: classfication
Crowdmap
Crowdsource
Machine learning
spatio
temporal
Advisor: He, Yuhong
Insights into the Mechanism of Idiosyncratic Drug-induced Agranulocytosis

Many drugs are known to cause idiosyncratic drug-induced agranulocytosis, although the mechanism is not well understood. This adverse event is suspected to be the result of the drugâ s reactive metabolite binding to endogenous proteins and creating a foreign body capable of eliciting an immune response. In particular, clozapine has been shown to form reactive metabolites by neutrophil myeloperoxidase (MPO). These studies set out to further characterize MPOâ s role in bioactivating drugs that cause idiosyncratic drug-induced agranulocytosis and to characterize the immune response seen due to clozapine. Overall this work further characterized the early immune response seen due to clozapine treatment using in vitro and in vivo methods. Through this work we have a better understanding of the immune response that may lead to clozapine-induced agranulocytosis. Understanding the clozapine-induced immune response may provide avenues for early detection of clozapine-induced agranulocytosis and ultimately limit the magnitude of this adverse event.

Keywords: Adverse Drug Reactions
Agranulocytosis
Animal Model
Clozapine
Idiosyncratic Drug Reactions
Myeloperoxidase
Advisor: Uetrecht, Jack
Risk Factors for Death or Heart Transplant for Patients with Right Ventricular Dysfunction after the Norwood Procedure: A Secondary Analysis of the Single Ventricle Reconstruction Trial

We investigated patient and procedural factors associated with failure of staged palliation after the Norwood procedure in patients with right ventricular dysfunction (RVDfx). Patients from the Pediatric Heart Network Single Ventricle Reconstruction (SVR) Trial dataset were selected if RVDfx was present, defined as an ejection fraction of less than 44% and a fractional area of change of less than 35% on the post-Norwood echocardiogram. Transplant-free survival after the Norwood procedure was analyzed using multiphase parametric hazard analysis and factors associated with death or transplant were identified. In the SVR cohort, 123 (34%) infants had RVDfx. The six-month transplant-free survival was 87% (70%CI 82-91%). The independent factors associated with increased risk of death or transplant were BT shunt, increased RV size, infectious disease complications and low surgeon volume. Patient factors can help identify which patient with RVDfx is at higher risk of death and help decision making around early transplant listing.

Keywords: heart transplant
Hypoplastic left heart syndrome
Parametric hazard modeling
survival
ventricular dysfunction
Advisor: McCrindle, Brian W.
Vision-based Flap Planning Software Tool for Reconstructive Facial Plastic Surgery

The success of reconstructive facial plastic surgery is determined not only by the treatment of the given pathology but also the restoration or maintenance of normal morphological features and the reduction of scarring. Failure to consider these aesthetic components can have significant negative psychological effects for the patient. A vision-based approach to automatic lesion segmentation and incision planning is proposed. Optical camera images of the face will be analyzed for lesions and estimated lines of relaxed skin tension using feature-based registration. Simulation of stresses within wound closures will consider skin mechanical properties and craniofacial structures to implement a constitutive model for finite element stress analysis. The objective of this research is to develop a consistent and effective approach to flap planning for reconstructive facial plastic surgery. This system has applications for surgical training, surgical automation and control, and the improvement of patient care through the reduction of treatment variation.

Keywords: fea
fem
flap
plastic
surgery
vision
Advisor: Forte, Vito
Molecular Pathways Responsible for NMDA Receptor-mediated Behavioural Plasticity

Neurodevelopmental disorders occur from genetic and environmental risk factors that impair the formation of networks involved in learning and memory. Impaired NMDA receptor signaling has been implicated in the pathobiology of schizophrenia and autism. A mouse model of NMDA receptor knockdown and inducible rescue was used to determine the reversibility of neurodevelopmental insults on hippocampal function. Mice were studied for their ability to learn and remember using the fear-conditioning paradigm, which engages the hippocampus in the formation and recall of contextual memory. In addition, studies were performed to determine whether immediate-early genes were induced in the hippocampus of NMDA receptor deficient mice. The findings of this study show that NMDA receptor deficient mice lack the ability to form fear memories, and that this can be partially rescued by increasing the levels of NMDA receptors in adult mice. Furthermore, several immediate early genes are induced without a resulting formation of fear memory.

Keywords: Behavioural Plasticity
Fear Conditioning
Hippocampus
Immediate Early Genes
Learning and Memory
NMDA receptor
Advisor: Ramsey, Amy
Predicting Short-term Hospital Inpatient Bed Needs for Up to Four Days in Advance

The Scarborough Hospital embarked a corporate initiative called Bed Mapping, which maps a better path for inpatient care and has patients in the right bed. A tool is needed to perform short-term predictions of inpatient bed needs. This thesis provides an inpatient demand predictive tool that uses historical, scheduled surgery, and current occupancy data to predict inpatient bed needs for up to four days in advance. It uses staff generated Estimated Discharge Date (EDD), Length of Stay (LOS) distributions, and a Monte Carlo simulation model by Liu [36] to make predictions. First, the tool was tested using retrospective CIHI expected patient LOS data to calculate EDD, and showed that the tool’s error is within 12 beds (5.52%) on day-1 and increases as we go further from day-1. The tool was further tested and showed that if EDD’s were accurate then the tool’s error is within two beds (0.88%) on day-1.

Keywords: EDD
Forecasting
Hospital
Inpatient Beds
Prediction
Advisor: Carter, Michael W.
Transport and Development of Microemulsion- and Surfactant-Stabilized Iron Nanoparticles for In Situ Remediation

This work describes the mobility assessments of microemulsion-stabilized iron oxide nanoparticles and anionic surfactant sodium diethyl hexyl phosphate (SDEHP)-stabilized nanoscale zero valent iron (NZVI) particles in laboratory porous media. The two formulations tested in this work achieved stable iron nanoparticle suspensions for months and prepared via a simple â one-potâ synthesis method developed by Wang et al. Both formulations were tested under field scale velocity of 5 m/day with no mechanical aid during the injection. A three-compartment model, involving colloid diffusion theory, diffusion theory and tailing was applied to describe the breakthrough curves of the studies. The obtained breakthrough curves of both formulations implied excellent transport in porous media with steady plateau C/Co at 0.8-0.9 and recovery of up to 0.95 for SDEHP stabilized NZVI. Post analysis on the retention of iron on the porous media implied ideal transport with consistent data to the breakthrough curves.

Keywords: Column Study
Groundwater Remediation
Iron Oxide Nanoparticles
Microemulsion
Mobility
NZVI
Advisor: Acosta, Edgar J
Finite Element Modelling of Corrosion Damaged Reinforced Concrete Structures

Corrosion of steel is the predominant deterioration mechanism of reinforced concrete structures throughout the world. This thesis presents the work performed on VecTor2, a nonlinear finite element analysis program developed at the University of Toronto, for analysis of corrosion damaged reinforced concrete structures. Two well-known types of corrosion, namely uniform and pitting, were considered for modelling. Corrosion damage was incorporated in the algorithms of VecTor2 through reduction of the sectional area of reinforcing steel, the bond strength between the reinforcement and concrete, and the mechanical properties such as yield strength of a corroded reinforcing bar. The employed techniques for incorporating corrosion damage in VecTor2 successfully reproduced the load-deflection response of published experiments. Stochastic simulation of the same experiments, performed by employing the stochastic tools of VecTor2, demonstrated the sensitivity of response quantities to changes in various input parameters forming the basis for further research.

Advisor: Vecchio, Frank J.
FDEMTunnel Modelling in Georgian Bay Shale

This work describes the experimental and numerical study undertaken to understand potential failure mechanisms associated with the excavation of a tunnel in Georgian Bay shale. The Georgian Bay Formation consists of interbedded shale and limestone layers and was characterized through a laboratory testing program. From the results, shale is classified as relatively weak, soft, not very abrasive, easily weathered and is governed by anisotropic properties; whereas the behaviour of limestone is the exact opposite. Based on laboratory data and specimen photographs, the shale and limestone numerical input parameters were calibrated to match the experimental elastic and strength properties, within Âą 11%, and the observed fracture patterns. Numerical simulations were then used to investigate the failure around a circular excavation. Field-scale modelling suggested tunnel stability is sensitive to increased principal in situ stress ratios, rotation and the presence of limestone layers.

Keywords: FDEM
georgian bay
modelling
shale
tunnel
Advisor: Grasselli, Giovanni
Peterson, Karl
Designing the Next-generation Oncolytic Vaccinia Virus

Many oncolytic viruses (OVs), such as double-deleted vaccina virus (vvDD), are engineered with enhanced tumor-selectivity based on increased cell proliferation in cancer cells. We proposed that OVs with improved tumor efficacy and equal tumor-selectivity could be generated by exploiting the dysregulated immune response in tumors. Vaccinia virus (VV) proteins that inhibit the interferon response are redundant for replication in tumors, which often already have a decreased interferon response. We deleted VV immunomodulatory genes (N1L, K1L, K3L, A46R, or A52R) from VV and compared these candidate VVs to vvDD. Candidate VVs demonstrated equal or superior in vitro viral replication, spread, and tumor cytotoxicity in colon cancer cells compared to vvDD and were potent against ovarian cancer cells. At doses 20-1000 times less than the vvDD treatment dose, the best in vitro candidate VVs (â K1L, â A46R, â A52R VVs) demonstrated tumor-selectivity and equal or prolonged survival in mouse models of peritoneal carcinomatosis.

Keywords: Cancer therapy
Interferon
Oncolytic virotherapy
Peritoneal Carcinomatosis
Vaccinia Virus
vvDD
Advisor: McCart, Andrea J
Classification of Pre-clinical Seizure State Transitions in Scalp EEG using Global Cross-frequency Coupling Index

In 30% of individuals that suffer from epilepsy, seizures remain uncontrolled by drug therapy. The unpredictability of clinical seizures reduces patient quality of life, ability to function in society, and increases their risk of SUDEP. This work aims to improve the state of the art of pre-clinical seizure detection systems so that they can be implemented to monitor patients, particularly, in the home environments outside the clinic. Simultaneous intracranial and scalp EEG recordings from patients with drug resistant epilepsy were used to examine cross-frequency coupling (CFC) features as a marker for the detection of a pre-clinical seizure state transition. Machine learning based classifiers were trained and combined in an expert system to identify pre-clinical seizure state transitions in a multi-patient, multi-seizure data set. This work shows that CFC features could be implemented in a home monitoring system to give advanced warning to patients and caregivers of an upcoming clinical seizure.

Keywords: Cross Frequency Coupling
EEG
Epilepsy
Seizure Detection
Advisor: Bardakjian, Berj L
Fracture Strength of Implant-supported Full-contoured Titanium and Zirconia Single Crowns Connected to Titanium Cores

Objectives: To investigate the fracture strength and failure mode of implant-supported screw-retained customized 2-piece zirconia and 1-piece titanium restorations, and to evaluate the effect of aging on the mechanical performance of zirconia restorations. Materials and Methods: Thirty identical specimens simulating maxillary first premolar replacements were divided in 3 groups. Groups ZrA and ZrNA consisted of zirconia and Group Ti consisted of titanium restorations, anchored to implants embedded in PMMA. Specimens in Group ZrA underwent chewing simulation. Static load was applied until failure. Results: Group Ti showed the highest fracture strength. The difference was significant between Groups ZrA and Ti. Failures included partial or complete fracture of titanium insert or deformation of restoration with screw fracture. Conclusion: Evidence was inadequate to reject similarity in fracture strength between non-aged zirconia and titanium restorations, or between zirconia restorations with different aging conditions. Aging affected the failure mode of zirconia restorations.

Keywords: Artificial aging
Customized crown
Dental implant
Fracture strength
Titanium insert
Zirconia
Advisor: De Souza, Grace
Tam, Laura
Development of a Multiplexed Panel Assay for the Rapid Detection of Bacterial Resistance to β-Lactam Antibiotics using Liquid Chromatography – Tandem Mass Spectrometry

Antibiotic susceptibility testing (AST) can involve automated platforms that produce results in 10 hours following bacterial colony growth. However, the total time can vary between 10-72 hours before definitive treatment can begin. An assay was developed for the detection of bacterial resistance conferred by enzymatic degradation of β-lactam antibiotics with the goal of designing a liquid chromatography – tandem mass spectrometry method capable of performing AST at an accelerated rate. The assay consisted of a one-hour bacterial incubation with a multiplexed panel of ampicillin, cefazolin, cefotaxime, and imipenem at 0.5 μg/mL, and a concurrent incubation of cefoxitin at 2 μg/mL. The assay used the extent of antibiotic hydrolysis as a means of measuring resistance quantitatively. Hydrolysis percentages were obtained by chromatographic peak area integration. The assay was able to differentiate carbapenemases, Class A β-lactamases, and AmpC β-lactamases. A resistance profile could be obtained in 2 hours, 35 minutes following colony growth.

Keywords: antibiotic resistance
antibiotic susceptibility testing
beta-lactamase enzyme
gram-negative bacteria
multiplexed panel rapid assay
tandem mass spectrometry
Advisor: Thompson, Michael
Romaschin, Alexander
Carbon Sequestration Strategies in Cement Based Material: Carbon Nano Platelet Admixture Interaction and Long term Carbonation of CO2 Injected Concrete Blocks

Two novel approaches to sequester carbon in concrete were examined in this study. First, carbon nano platelets exposed to CO2-laden flue gas were explored for possible use as a concrete additive to improve mechanical properties. However, carbon nano platelets also have the potential to interfere with the performance of air entraining admixtures (AEAs) in concrete. The capacity for carbon to adsorb AEAs is already widely recognized in terms of unburnt carbon residues present in coal combustion fly ash. In this research, adjustments to Vinsol resin and synthetic AEA dosages necessary to maintain adequate air void parameters in mortars were determined using a combined adsorption isotherm test based on chemical oxygen demand (COD). Second, the long-term carbonation of industrially produced concrete blocks manufactured using early-age CO2 injection was explored using an accelerated carbonation chamber. Carbonation rates were found to be similar for CO2-injected and non CO2-injected blocks.

Keywords: adsorption
air entrainment
carbonation curing
carbon nano platelet
carbon sequestration
Advisor: Peterson, Karl
Identifying and Characterizing Putative Neural Progenitor Cells within the Adult Drosophila melanogaster Central Brain

Adult neural stem cells (NSCs) and neural progenitor cells (NPCs) have been the subject of significant research in recent times. Model organisms, including Drosophila melanogaster, have been used to gain insight into the origin and function of NSCs. To date, NSC-like cells, called neuroblasts, have been identified in Drosophila larvae. Whether NSCs or NPCs are also present in adults is unclear. The goal of my research is to identify and characterize NSCs/NPCs in theadult Drosophila brain and determine whether these cells are affected by aging. My findings indicate more cell division is present within the adult brain than previously thought. The majority of the dividing cells also do not appear to be glial or neuronal in nature suggesting the distinct possibility that these cells may be NSCs/NPCs. Insight into the function of NSCs/NPCs in Drosophila may lead to greater understanding of how injury, disease, and aging may effect NSC/NPC populations in mammals.

Advisor: Boulianne, Gabrielle
Characterizing the Contribution of First and Second Heart Field-derived Cells in Zebrafish Cardiac Development

Vertebrate heart development occurs through contribution from two spatio-temporally distinct progenitor populations termed the First Heart Field (FHF) and Second Heart Field (SHF). In the mammalian heart, the FHF gives rise to the left ventricle and parts of both atria, whereas the SHF contributes to the right ventricle, inflow and outflow tracts, and portions of the atria. Here I employed a cmlc2 driven CreERT and switch reporter lines to lineage trace the two populations in the adult zebrafish heart. Late differentiating cells, as displayed through EGFP-positive cells consistently made a significant contribution to the cortical layer of the adult heart, which has been shown to be a major source of new cardiomyocytes following cardiac injury. Cells derived from the proposed SHF population give rise to the primordial layer, as well as the trabeculae in the ventricular base. The cortical and primordial layers are partially derived from the SHF progenitor population.

Keywords: Cardiac Development
Developmental Biology
Second Heart Field
Advisor: Scott, Ian C
Genetic Counsellors' Preferences for Preimplantation Genetic Diagnosis: A Discrete Choice Experiment

Preimplantation genetic diagnosis (PGD) is a way of testing for a genetically affected embryo. Provincial PGD coverage differences along with ambiguity around scope of testing and patient inclusion criteria create a lack of clarity for public coverage options. A discrete choice experiment was undertaken with Canadian genetic counsellors (GC) to quantify their stated preferences for public PGD coverage, considering the following attributes: PGD indication, risk of the condition, fertility status, family history and number of cycles covered. The completed response rate was 41% with 126 GC completing the survey. Multinomial logit regression was used to estimate part-worth utilities. Key demographic and practice characteristics were considered as preference influences. Risk of the condition was the most important attribute. Overall, GC preferred scope of testing criteria over patient inclusion criteria. This is the first study to quantify GC preferences for PGD coverage and provides insight to help promote discussion about PGD policy.

Keywords: Discrete Choice Experiment
Genetic Counsellors
Health Policy
Preimplantation Genetic Diagnosis
Public Coverage
Advisor: Miller, Fiona A
Ungar, Wendy J