VictorJuiz/thesis huggingface dataset:
Mechanisms that Jeopardize Skeletal Muscle Perfusion during Surgery

We assessed potential mechanisms that may jeopardize skeletal muscle perfusion during surgery leading to adverse outcomes including muscle injury and flap hypoxia. In craniotomy patients, we observed an increase in serum lactate and creatine kinase and urine myoglobin; indicative of muscle damage. The early rise in lactate correlated with elevated BMI, suggesting that obesity caused tissue compression and muscle ischemia. In our rodent model, we investigated the effects of flap preparation and phenylephrine on muscle perfusion by assessing microvascular blood flow and tissue PO2. Phenylephrine reduced muscle blood flow by ~20%, yet increased PO2 by ~10% suggestive of decreased O2 metabolism. At baseline, muscle flap blood flow was reduced by ~50% while PO2 was severely reduced ~80% (~5 torr) suggesting that flap perfusion was attenuated and O2 metabolism was increased. Phenylephrine infusion further reduced muscle flap perfusion. These data demonstrate multiple mechanisms by which muscle perfusion is jeopardized during surgery.

Keywords: Muscle Perfusion
Phenylephrine
Serum Lactate
Creatine Kinase
Muscle Damage
Muscle Flap
Neurosurgery
Free Tissue Transfer
Rhabdomyolysis
Craniotomy
Rectus Abdominus Muscle
Oxygen
Body Mass Index
Microvascular Blood Flow
Advisor: Hare, Gregory
Mazer, David
The Role of SIRT1 in Pancreatic Beta Cells

SIRT1 has emerged as a critical regulator of glucose homeostasis and metabolism in the past decade. Glucose homeostasis is tightly regulated by insulin however, the factors affecting insulin release are still incompletely understood. Relatively recent evidence has shown SIRT1 to be a positive mediator of insulin secretion although its mechanism is largely unknown. Therefore, the aim of this study was to determine how SIRT1 regulates insulin release. Using a pancreatic beta cell-specific Sirt1 knockout mouse model (Sirt1BKO), oral glucose challenge revealed a glucose intolerant phenotype with reduced insulin secretion. Isolated Sirt1BKO islets also secreted less insulin without changes to insulin content or islet morphology. Intracellular defects were localized to the mitochondria and showed suppressed bioenergetics negatively affecting downstream glucose-induced calcium influx. This is the first study using a Sirt1BKO mouse model to show novel mitochondrial genes under SIRT1 regulation and when impaired, results in reduced insulin secretion.

Keywords: SIRT1
Diabetes
Advisor: Wheeler, Michael
Reliability and Responsiveness of the Standardized Universal Pain Evaluations for Rheumatology Providers for Children and Youth (SUPER-KIDZ)

Aims: To determine the test-retest reliability and responsiveness of a new computerized 20-item pain measure, SUPER-KIDZ, in children with juvenile idiopathic arthritis (JIA). Methods: A single centre prospective cohort study of JIA patients aged 8-18 years was performed. For each SUPER-KIDZ item, test-retest reliability analysis was done in patients expected to have stable pain, and responsiveness was evaluated after intra-articular steroid injection(s). Results: Fifty-one subjects were included. Good internal consistency (α=0.73-0.92) was demonstrated for the 3 SUPER-KIDZ domains. Acceptable test-retest reliability (intraclass correlation coefficient or kappa ≥0.80) was found for 15 SUPER-KIDZ items. At 2 weeks post-injection, 16 items were responsive to change in pain (standardized response mean=0.66-0.82, significant Wilcoxon signed rank and linear mixed model). Conclusions: The majority of the SUPER-KIDZ items have acceptable test-retest reliability and responsiveness properties. If validity is demonstrated, this measure could be implemented as a standardized comprehensive pain tool for JIA patients.

Keywords: Juvenile idiopathic arthritis
Pain
Advisor: Bayoumi, Ahmed
Collective Epithelial Cell Migration in vitro Driven by Mechanical and Chemical Cues

Cells in vivo respond to chemical and mechanical cues in the environment. In fact, it is the resulting migration of cells as a cohesive group that underlies embryonic morphogenesis, wound repair and cancer tumour development and invasion. Techniques have been developed to investigate chemotaxis, haptotaxis and mechanotaxis &ndash; the directional movement of cells in response to soluble chemical cues, substrate-bound chemical cues and mechanical cues respectively. Most of the existing tools however, have been designed for and applied to the investigation of single cell migration. Given its importance in vivo, there is a need for adapting these methods and applying them to characterize directed collective cell migration. The main objective of my thesis was to engineer tools and quantitative methods to investigate collective cell migration and use them to compare single and collective migration in response to mechanical cues and substrate-adhered chemical cues in vitro.

Keywords: Collective Cell Migration
Mechanotaxis
Haptokinesis
Advisor: McGuigan, Alison P.
Nanostructured Photocatalysis for Water Purification

The integration of photocatalytic advanced oxidation into solar disinfection is a robust method of improving the microbial and chemical quality of treated water. This study evaluates the performance of photocatalytic solar irradiated batch reactors through an analytical model that reduces treatment parameters by simplifying photoreactor geometry and relating performance to reactor configuration. Accompanying experiments compare the performance of titanium dioxide coated foams of varying pore size to suspended and fixed film configurations through degradation of organic dyes (acid orange 24 and methylene blue), Escherichia coli, and 1,4-dioxane. Results indicate that a catalyst immobilized on a foam support can match the performance of a suspension due to effective mass transport and association between analyte and foam. Additionally, the potential treatment capacity of solar photocatalysis was compared to conventional treatment methods. Results of this comparison stress the fundamental limitation of solar photocatalysis if visible light wavelengths are not harnessed.

Keywords: photocatalysis
water treatment
solar disinfection
titanium dioxide
E. coli
Advisor: Hofmann, Ronald
Andrews, Susan
Derivation and Genetic Validation of Clear Cell Renal Cell Carcinoma Cell Lines and Characterization of Their Growth Requirements

While extirpative surgery is curative for localized clear cell renal cell carcinoma (ccRCC), many patients develop recurrences or present with metastatic disease. Several aspects of ccRCC biology have been investigated, but these have been done in cell lines, which are known to poorly represent the tumour. Since cell lines are amenable to a wide array of experimental testing, the studies presented here demonstrate a novel method to generate ccRCC cell lines from primary tumours, which increases the rate of primary tumour cell line generation four fold. Additionally, ccRCC cells do not grow in serum-free media, which has been shown to be beneficial in other cancers. Therefore, we interrogated the effect of exogenous growth factors to optimize our serum-free media growth conditions, among which TGFb1 appeared to elicit the largest mitogenic effect. Once optimized, these findings will provide a valuable tool for understanding ccRCC tumour cell biology and identifying therapeutic targets.

Keywords: Renal Cell Carcinoma
Cell Lines
Advisor: Ailles, Laurie
Investigation of the Mechanism and Structure of the Cage-like Complex formed by the Escherichia coli Inducible Lysine Decarboxylase LdcI and the MoxR AAA+ ATPase RavA

The gram-negative bacteria Escherichia coli, a neutralophile, is remarkable in its defenses against acid stress. Of interest to our laboratory is the inducible lysine decarboxylase (LdcI) system, an acid resistance system which renders acid resistance to E. coli in mild acid stress (~pH 5). It was found that this enzyme forms an extremely large (~3.3 MDa) and tight complex (Kd ~ 0.56 μM) with a MoxR AAA+ ATPase named Regulatory ATPase Variant A (RavA). The cryo-EM structure at 14 Å was determined. Through size-exclusion chromatography (SEC) experiments, the binding sites on both LdcI and RavA have been determined. It is proposed that the complex can form through both charged and hydrophobic interactions. In the course of these studies, unexpected observations led to the characterization of the LARA domain of RavA as an amyloid protein under in vitro conditions. The physiological significance of this observation is still under investigation.

Keywords: Protein Purification
Protein Interaction
NMR
Gel Filtration Chromatography
Cryo-EM
Acid Stress
Advisor: Houry, Walid A.
Probabilistic Siamese Networks for Learning Representations

We explore the training of deep neural networks to produce vector representations using weakly labelled information in the form of binary similarity labels for pairs of training images. Previous methods such as siamese networks, IMAX and others, have used fixed cost functions such as L 1, L2-norms and mutual information to drive the representations of similar images together and different images apart. In this work, we formulate learning as maximizing the likelihood of binary similarity labels for pairs of input images, under a parameterized probabilistic similarity model. We describe and evaluate several forms of the similarity model that account for false positives and false negatives differently. We extract representations of MNIST, AT&T ORL and COIL-100 images and use them to obtain classification results. We compare these results with state-of-the-art techniques such as deep neural networks and convolutional neural networks. We also study our method from a dimensionality reduction prospective.

Keywords: Machine Learning
Neural Networks
Advisor: Frey, Brendan J.
Limited Field-of-view Cone Beam CT Imaging of the Temporomandibular Joint: Comparative Dosimetry and Diagnostic Efficacy

Imaging of the osseous structures of the temporomandibular joint is best accomplished using computed tomography (CT). Cone beam CT offers a reduced radiation dose and improved spatial resolution compared to multislice helical CT. This study evaluates comparative dosimetry for temporomandibular joint imaging using two different cone beam CT systems, the Hitachi CB MercuRay and Kodak 9000 3D. These systems demonstrate differing properties with respect to field-of view sizes, operational technique factors, and spatial resolution. The Kodak 9000 3D unit offers an effective radiation dose reduction of greater than ten-fold compared with the Hitachi CB MercuRay, depending on kVp and mA. A subsequent clinical study evaluating the effect of spatial resolution on the ability to detect osseous changes related to temporomandibular joint degenerative disease found no significant difference in diagnostic efficacy between high and low spatial resolution images, however, observers consistently associated high spatial resolution with superior image quality.

Keywords: temporomandibular joint
cone beam CT
dosimetry
spatial resolution
Advisor: Lam, Ernest W.
Attitude Control Hardware and Software for Nanosatellites

The analysis, verification and emulation of attitude control hardware for nanosatellite spacecraft is described. The overall focus is on hardware that pertains to a multitude of missions currently under development at the University of Toronto Institute for Aerospace Studies - Space Flight Laboratory. The requirements for these missions push the boundaries of what is currently the accepted performance level of attitude control hardware. These new performance envelopes demand new acceptance test methods which must verify the performance of the attitude control hardware. In particular, reaction wheel and hysteresis rod actuators are the focus. Results of acceptance testing are further employed in post spacecraft integration for hardware emulation. This provides for a reduced mission cost as a function of reduced spare hardware. The overall approach provides a method of acceptance testing to new performance envelopes with the benefit of cost reduction with hardware emulation for simulations during post integration.

Keywords: nanosatellites
reaction wheel
hysteresis rod
acceptance test
hardware emulation in software
attitude determination and control
attitude determination
attitude control
torque jitter
Advisor: Zee, Robert E.
Adolescents with Severe Obesity: Outcomes of Participation in an Intensive Obesity Management Program

Objective: To evaluate the SickKids Team Obesity Management Program (STOMP), an obesity management program for severely obese adolescents. Methods: Non-randomized study of 6 and 12 month outcomes in STOMP patients vs. a comparison group of obese adolescents. Results: At 6 months, STOMP patients stabilized their BMI (0.08±0.3 kg/m2;p=0.79) and reported improved psychological and health behaviour measures, whereas comparison participants increased their BMI (0.7±0.2 kg/m2;p=0.004) and had worsening of cardiometabolic outcomes. Between-group differences included improved cardiometabolic, psychological and health behaviour measures in STOMP patients. At 12 months, STOMP patients stabilized their BMI (0.8±0.5 kg/m2;p=0.07), had improvements in anthropometric and cardiometabolic outcomes and reported an increase in health behaviours, whereas comparison participants increased their BMI (1.2±0.4 kg/m2;p=0.001) and had worsening of cardiometabolic outcomes. Between-group differences included improved anthropometric, cardiometabolic and health behaviour outcomes in STOMP patients. Conclusions: Participation in STOMP improved anthropometric, cardiometabolic, psychological and health behaviour outcomes among severely obese adolescents.

Keywords: adolescent obesity
obesity management program
program evaluation
Advisor: Hamilton, Jill
Development and Evaluation of an Online Transcranial Doppler Ultrasonographic Brain-computer Interface for Communication

We investigated an emerging brain-computer interface (BCI) modality, namely, transcranial Doppler ultrasonography (TCD), which measures cerebral blood flow velocity. We hypothesized that a bilateral TCD-driven online BCI would be able to dichotomously classify a user’s intentions with at least 70% accuracy. To test this hypothesis, we had three objectives: (1) to develop a signal classifier that yielded high (>80%) offline accuracies; (2) to develop an online TCD-BCI system with an onscreen keyboard; and, (3) to determine the achievable online accuracy with able-bodied participants. With a weighted, forward feature selection and a Naïve Bayes classifier, sensitivity and specificity of 81.44 ± 8.35% and 82.30 ± 7.39%, respectively, were achieved in the online differentiation of two mental tasks. The average information transfer rate and throughput of the system were 0.87 bits/min and 0.35 ± 0.18 characters/min, respectively. These promising online results encourage future testing of TCD-BCI systems with the target population.

Keywords: Brain computer interface
Transcranial Doppler ultrasound
Advisor: Chau, Tom
Understanding the Role of Sirtuin 3 in a Cell Model of Parkinson's Disease

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta. It is now believed that the mitochondrion is central to the pathologies of PD. Sirtuin 3 (SIRT3) is a mitochondrial nicotinamide adenine dinucleotide dependent protein deacetylase. Within the mitochondria, SIRT3 deacetylates substrates of oxidative phosphorylation and antioxidant pathways to promote cellular functioning. Given that mitochondria impairments are central to PD, and that SIRT3 promotes mitochondrial health, the mechanisms underlying the protective effects of SIRT3 in a catecholaminergic SH-SY5Y cell model of PD were assessed. The results of this current study demonstrated that SIRT3 overexpression is cytoprotective in SH-SY5Y cells since it stabilizes mitochondrial membrane potential and ATP levels and reduces reactive oxygen species after exposure to toxins that mimic cell death mechanisms in PD. Taken together, SIRT3’s beneficial effects presents itself as an excellent candidate for Parkinson’s disease medicine.

Advisor: Nash, Joanne
Stochastic Models For Evolution Of Tumor Geometry for Cervical Cancer During Radiation Therapy

Adaptive radiation therapy re-optimizes treatment plans based on updated tumor geometries from magnetic resonance imaging scans. However, the imaging process is costly in labor and equipment. In this study, we develop a mathematical model that describes tumor evolution based on a Markov assumption. We then extend the model to predict tumor evolution with any level of information from a new patient: weekly MRI scans are used to estimate transition probabilities when available, otherwise historical MRI scans are used. In the latter case, patients in the historical data are clustered into two groups, and the model relates the new patient's behavior to the existing two groups. The models are evaluated with 33 cervical cancer patients from Princess Margaret Cancer Centre. The result indicates that our models outperform the constant volume model, which replicates the current clinical practice.

Keywords: Tumor evolution
Stochastic process
Radiation therapy
Cervical cancer
Advisor: Chi-Guhn, Lee
Timothy, Chan
Antigen-binding Fragments: Production for and Use in Crystallographic Studies

An immunoglobulin (IgG) consists of two antigen-binding fragments (Fab) connected to a crystallisable fragment through hinge regions. This thesis mainly investigates the production methods of Fabs used in structural studies. A cost effective and time saving protocol has been established for the production of recombinant 2F5 Fab, a HIV-1 broadly neutralizing monoclonal antibody fragment, using an Escherichia coli expression system. The integrity of structure and antigen-binding capability of the produced 2F5 Fab was confirmed by determining the crystal structure of the Fab-antigen peptide complex. In parallel, 3H1 Fab, a fragment of an antibody which is involved in detecting misfolded superoxide dismutase, which is related to familial amyotrophic lateral sclerosis, was produced by papain proteolysis of its parent IgG molecule. Both Fab production methods resulted in high yields of pure Fab samples that are crystallisable and ready to be engaged in structural studies using X-ray crystallography.

Keywords: antigen-binding fragment
X-ray crystallography
HIV-1
broadly neutralizing monoclonal antibody
Advisor: Pai, Emil F.
Controlling Early-age Transverse Cracking in High Performance Concrete Bridge Decks

This research was undertaken to study the effects of high performance concrete (HPC) mix design modifications on the propensity of early-age cracking. Seven mixtures were tested: one 35 MPa conventional concrete (CC) mixture made with ordinary Portland cement with blended slag; one typical 50 MPa HPC mixture containing slag and silica fume; and five modified HPC mixtures using extra set-retarder, increased slag replacement, shrinkage-reducing admixture (SRA), pre-saturated lightweight aggregate (LWA), and decreased cement paste content to improve thermal and/or shrinkage properties. The mixtures were tested for durability, mechanical, thermal, and shrinkage properties. All modified HPC mixtures showed reduced shrinkage relative to the HPC control mixture, and the most shrinkage mitigation was observed in the mixture containing LWA. While SRA reduced restrained shrinkage in HPC to the magnitude of CC, it provided very low rapid chloride penetrability, and using LWA in HPC resulted in significant restrained shrinkage reduction compared to CC.

Keywords: High Performance Concrete
Restrained Shrinkage Cracking
Advisor: Hooton, Robert Douglas
Effects of a New Conjugate Drug in a Rat Model of Postmenopausal Osteoporosis

Postmenopausal osteoporosis is a disease characterized by bone loss and increased risk of fracture, and represents a significant burden on the Canadian health care system. Current treatments lack the ability to simultaneously address the therapeutic needs for promoting bone formation and inhibiting resorption. Our approach employs a novel conjugate drug in which an anabolic agent (EP4 receptor agonist) is reversibly joined with an anti-resorptive agent (alendronate) through a linker. This allows the bone-targeting ability of alendronate to deliver the EP4 agonist to bone sites, thereby mitigating the side effects associated with systemic administration of the EP4 agonist. This study investigated the in vivo efficacy of this drug in a curative experiment to treat postmenopausal osteoporosis using an ovariectomized rat model. Results showed that conjugate treatment dose-dependently stimulated bone formation and restored ovariectomy-induced bone loss, and conjugation between alendronate and the EP4 agonist was crucial to the drug’s anabolic effect.

Keywords: osteoporosis treatment
bone formation
anabolic
conjugate
OVX
ovariectomized
rat
in vivo
endocortical
prodrug
dual-acting
EP4 agonist
alendronate
intracortical remodeling
trabecular
prostaglandin E2
Advisor: Grynpas, Marc D.
The Role of BLNK in Avian B-cell Development

BLNK is an adaptor protein that functions in B-cell receptor signalling, and is vitally necessary at signalling checkpoints of mammalian B-cell development. However, its importance to avian B-cell development remains unclear. To explore the function of BLNK in chickens, shRNA-mediated RNA interference was delivered to a chicken B-cell line in vitro by replication-competent avian retrovirus (RCAS), and effective shRNA were determined. To observe an shRNA phenotype on chicken B-cell development, we simultaneously explored whether RCAS penetrance was correlated between red blood cells (RBC) and bursal B-cells by infecting chicken embryos with RCAS expressing a fluorescent tag. We found that RCAS penetrance was correlated between RBC and B-cells, which provides a system to observe any in vivo effects of BLNK shRNA on B-cell development. Furthermore, this system for observing BLNK function may be complemented by genetically-modified BLNK, particularly variants resistant to RNA interference.

Keywords: B-cell development
BLNK
Advisor: Ratcliffe, Michael
Texture Analysis of Optical Coherence Tomography Speckle for the Detection of Tissue Variability

About 50% of cancer patients are treated with X-ray radiation therapy; however, with current treatment feedback, the effects and the efficacy of the treatment are generally detected several weeks/months after treatment completion. This makes the adjustment of the treatment based on early response, and identification of non-responding patients, nearly impossible. In this thesis a novel method combining optical coherence tomography and a gamut of image analysis methods is explored as a potential approach to detecting tissue variability. Applying texture analysis to the optical coherence tomography images may allow for the tracking of radiation therapy induced cell microstructural changes in cancer patients and help in the adjustment of treatment based on early response.

Keywords: Optical Coherence Tomography (OCT)
texture analysis
tissue characterization
Advisor: Vitkin, Alex
Indoor Location-based Recommender System

WiFi-based indoor localization is emerging as a new positioning technology. In this work, we present our efforts to find the best recommender system based on the indoor location tracks collected from the Bow Valley shopping mall for one week. The time a user spends in a shop is considered as an implicit preference and different mapping algorithms are proposed to map the time to a more realistic rating value. A new distribution error metric is proposed to examine the mapping algorithms. Eleven different recommender systems are built and evaluated in terms of accuracy and execution time. The Slope-One recommender system with a logarithmic mapping algorithm is finally selected with a score of 1.292, distribution error of 0.178 and execution time of 0.39 seconds for ten runs.

Keywords: Recommender System
Indoor Localization
Advisor: Chow, Paul