VictorJuiz/thesis huggingface dataset:
Role of Notch Signaling in Human T Cell Activation using Artificial Antigen Presenting Cells

Adoptive cell transfer of ex vivo-expanded tumor infiltrating lymphocytes (TILs) is an emerging approach for treating cancers. One limitation in this approach is the use of natural antigen presenting cells (APCs) for TIL expansion. Unlike natural APCs, “artificial” APCs (aAPCs) are easily accessible and manipulated cell lines shown to support priming and activation of tumor-associated antigen-specific CD8+ cytotoxic T lymphocytes. We hypothesize that providing Notch signaling during priming and activation using aAPCs will generate CTLs better suited for immunotherapy and long-term tumor regression. K562 erythroleukemia-derived aAPCs were genetically modified to express the Notch ligand, Delta-like-4. Here, we report that provision of Notch signaling during suboptimal priming of human naïve umbilical cord-derived CD8+ T cells supports higher frequencies of activated T cells indicated by CD25+ or CD71+ cells. Having optimized conditions for revealing the effects of DLL4 in early activation, future experiments will determine their impact on anti-tumor functionality.

Advisor: Zuniga-Pflucker, Juan Carlos
Analysis of Hybrid MD-MPC Simulations of Micelle Formation under Neutral pH and Dynamics under Acidic pH Using Different pH-Sensitive Triblock Copolymer Structures

The solubilization of hydrophobic drug molecules in the bloodstream by micelles is a promising method for drug delivery to cancerous cells. Cancerous cells and their surrounding environment can be distinguished easily from healthy cells by their pH: acidic vs neutral respectively. This has led to the design of pH-sensitive micelles that are triggered by cancerous cells. When designing the drug or amphiphilic polymer, the drug loading and release rates are quantities that should be optimized for effective delivery. To better understand the factors affecting these quantities, pH-sensitive micelle dynamics in an acidic environment is studied computationally with molecular dynamics simulations (not experimentally due to constraints in time and length scales). By treating the solvent-solvent interactions implicitly through multiparticle collision dynamics, a coarse-grain model of polymers, drugs, and solvent is used to examine drug distribution and micelle dynamics in an acidic environment for different amphiphilic triblock copolymer structures.

Keywords: drug delivery
Micelle
Molecular Dynamics
Multiparticle Collision Dynamics
pH-sensitive
polymer
Advisor: Schofield, Jeremy
Whittington, Stuart
Performance and Evaluation of Quality Indicators in the Management of Patients with Heart Failure

The systematic evaluation of evidence-based quality indicators (QIs) in patients with heart failure (HF) is important to assess the quality of care provided to these patients. Guideline recommended therapies have proven to reduce clinical event rates, however quality of life (QoL) is frequently missed as an endpoint in the measurement of treatment efficacy. We hypothesized that there was high adherence to the Canadian Cardiovascular Society (CCS) outpatient QIs, and the adherence was positively associated with QoL. We evaluated the performance of the outpatient QIs extracted from the CCS recommendations and examined their relationship with patient-reported QoL, measured by the Minnesota Living with Heart Failure Questionnaire (MLHFQ) and the Kansas City Cardiomyopathy Questionnaire (KCCQ). We found that there was high adherence (89%) to evidence-based QIs and patients reported a clinically significant improvement in QoL (>5 points), however, there appears to be no association between the performance of these indicators and patient-reported QoL.

Keywords: HEART FAILURE
KNOWLEDGE TRANSLATION
MEDICAL GUIDELINES
QUALITY INDICATORS
QUALITY OF LIFE
Advisor: MOE, GORDON
A Security Platform Using Software Defined Infrastructure

In this work, we designed an architecture for cloud network security, leveraging Software Defined Infrastructure, which enables centralized management of compute and networking resources. We show that utilizing SDIâ s service chaining and its Software Defined Networking approach, network security functions such as intrusion detection and prevention, as well as distributed firewalls can be realized as services in the cloud, as modeled in Network Function Virtualization. In our platform, protective resources are located as close as possible to the entity being protected. Furthermore, the design of the user-friendly interfaces for these services to be used is discussed, where the user traffic flows are associated with Enhanced Security Profiles, together forming Enhanced Security Groups. We also discuss our implemented proof-of-concept on SAVI testbed.

Keywords: Autoscaling
Cloud Computing
Intrusion Detection System
Load Balancing
Network Security
Service Chaining
Advisor: Leon-Garcia, Alberto
Decentralized Scheduling and Control in Power Systems

Decentralized control reduces the need for expensive and delay inducing communication infrastructure. In this thesis we will present new algorithms for decentralized control of DC-segmented power systems and energy storages. DC-segmentation is a process in which a transmission system is divided into isolated AC subsystems connected to each other only by DC lines. It improves transient stability and increases the transmission capacity of a transmission system. We construct a poset-causal optimal decentralized controller for this system, which only requires neighbor-to-neighbor communication. In the second part of this thesis, we focus on multiple energy storages located in a distribution system with renewable generation. We use dynamic programming and inventory control theory to obtain optimal scheduling policies for the energy transactions of the storages. These policies are optimal and only require local information.

Keywords: DC-segmented systems
Decentralized control
Dynamics programming
Energy storages
Poset-causal
Advisor: Taylor, Joshua A
Development of a Tissue Oxygen Saturation Detection System for Improving Surgical Training

Delicate tissue encountered in surgery is prone to ischemic damage from grasping and retracting especially by novice surgeons. Currently, there are no existing techniques to quantitatively assess tissue health during surgical maneuver. A transmission and reflectance mode tissue oxygenation (StO2) sensor was developed and integrated into a standard laparoscopic tool and custom forceps to continuously measure tissue oxygenation during surgery. Numerous wavelengths including 470nm, 500nm, 510nm, 560nm, 570nm, 586nm, 660nm and 940nm were tested in reflection mode while 660nm and 940nm were tested in transmission mode. StO2 sensor successfully detected oxygenation changes on the finger and during ex vivo experiment conducted on arterial and venous blood samples. StO2 sensor was unable to monitor changes when grasping small intestine and liver using surgical instruments. Various factors including lack of hemoglobin at the site of measurement, tissue thickness changes during grasps, and motion artifacts limited the use of this technology.

Keywords: surgical training
tissue damage prevention
tissue oxygen sensor
Advisor: Farhat, Walid
Drake, James
Development of a Decision Aid for Evidence-informed Public Health Policy: A Mixed Methods Study

This study contributes to the evolving needs of decision support for evidence-informed health policymaking. Its aim was to bring more formal consideration of context and a broader conception of evidence into public health policymaking, giving due prominence to all relevant types of evidence. A sequential mixed methods approach was used to undertake the development of a decision aid to support evidence-informed public health policy. A meta-narrative review and focus group were conducted to inform the initial development of the proposed aid. Key informant interviews followed, providing preliminary feedback for refinement of the tool. The final deliverable was a beta-version of a decision aid designed to assist policymakers with making evidence-informed public health policy decisions, ready for pilot testing and further development.

Keywords: decision aid
evidence-informed
health policy
Advisor: Dobrow, Mark J
Genetic Variation and Early-life Nutritional Stress Interact to Affect Adult Excretion and Fitness Traits

Life-history strategies are complex and separable into distinct stages, where early experience can affect adult life. In addition, gene-by-environment interactions or individual genetic differences interacting with the environment can influence phenotypes within and between life history stages. Here, using Drosophila melanogaster, I show rover/sitter allelic variants of the foraging gene (for) interact differently with their early nutritional environment affecting adult excreta deposit number, intestinal physiology, and fitness traits and that excretion phenotypes are mediated by differences in for expression. I found rover/sitter differences in intestinal and reproductive physiology that suggest trade-offs between adult gut function and reproductive output. Using transgenic manipulations, I demonstrated that reducing for expression in an organ and tissue specific mannerâ including the gastric systemâ affects phenotypic differences in adult excretion. My findings highlight the importance of investigating individual genetic differences in the context of early environmental experience to fully understand organismal biology and phenotypic complexity.

Keywords: Ecology
Evolution
Life history
Nutritional stress
Advisor: Sokolowski, Marla B
Optimal Conditions for the Monocyte Monolayer Assay and Applications of the Assay

Immune-mediated hemolysis, whether due to transfusion of incompatible red blood cells (RBCs) in hemolytic transfusion reactions or passive transfer of anti-RBC antibodies through intravenous immunoglobulin (IVIG) therapy, contributes to complications and comorbidities in patients. A major mechanism of RBC destruction is Fc gamma receptor (FcÎłR)-dependent phagocytic removal of antibody-bound RBCs by monocyte-macrophage within the mononuclear phagocyte system. The monocyte monolayer assay (MMA) assesses FcÎłR-mediated destruction using primary monocytes from whole blood and predicts in vivo survival of serologically incompatible, allogeneic RBCs. Optimal conditions for MMA were examined in this thesis. Whole blood collected in acid citrate dextrose anticoagulant and stored at room temperature for up to 36 hours best preserved monocyte phagocytic function. Such conditions were validated using clinical samples from patients receiving IVIG. The findings suggest stored autologous patient samples yield clinically relevant MMA results, and thus permit the shipping and testing of properly stored samples.

Keywords: Fc gamma receptor
Hemolysis
Monocyte monolayer assay
Red blood cells
Storage
Transfusion
Advisor: Branch, Donald R
Robotic Path-finding in Inverse Treatment Planning with Continuous Dose Delivery for Stereotactic Radiosurgery

Continuous dose delivery, or continuous path (CP) treatment, in stereotactic radiosurgery has been proven to improve the total treatment time, dose conformity, and dose distribution homogeneity over traditional step-and-shoot delivery. We develop several automated planning methods using robotic path-finding techniques to design CP treatments for SRS with Gamma Knife Perfexion. Using simultaneous localization and mapping (SLAM), we construct paths through the target that pass sufficiently close to a set of pre-selected isocentre locations. To solve SLAM, both the traditional extended Kalman filter (EKF) and incremental smoothing and mapping (iSAM) algorithms are investigated. Steering decision algorithms using heuristic scoring methods and robotic exploration techniques, specifically, frontiers, are investigated. Once a path is found, shot delivery from each sector is optimized along the path using inverse planning optimization. The SLAM methods consistently improve dose metrics and beam-on time compared to the clinical and an earlier graph-based Hamiltonian path CP planning approach.

Keywords: Gamma Knife Perfexion
heuristic methods
inverse planning
radiosurgery
simultaneous localization and mapping
Advisor: Aleman, Dionne M
Extraction of Rare Earth Elements from Phosphogypsum (Fertilizer Production By-product)

The increasing demand for rare earth elements (REEs), used in technologically advanced products, has sparked the development of novel processes to recover REEs from secondary sources. Phosphogypsum (PG), the main by-product of fertilizer production contains some REEs, so it can be used as a secondary source. The current research focuses on: a thorough characterization analysis; acid leaching process; kinetics of the leaching process; recycling of consumed acid and effect of microwave pre-treatment on the REEs leaching. The results show that the leaching efficiency is controlled by the solubility limit of PG. Systematic leaching experiments using three acids under various operating conditions were performed. The results indicate the best operating conditions are 1.5 M, 80째C, solid-to-liquid ratio of 1/8 and 20 min residence time, but the leaching efficiency using nitric and hydrochloric acids are higher than the sulphuric acid. Furthermore, it was found that microwave pre-treatment improves the leaching efficiency of REEs.

Keywords: Acid leaching process
Chemical modelling
Kinetics investigations
Lanthanides
Phosphogypsum
Rare earth elements
Advisor: Azimi, Gisele
Organophosphate Esters (OPEs) as Emerging Contaminants in the Environment: Indoor Sources and Transport to Receiving Waters

Organophosphate esters (OPEs) are high usage chemical additives that are of increasing concern because of growing evidence of potential toxicity and ubiquitous occurrence in the environment. This thesis summarizes the analysis, sources and environmental abundance of OPEs using Toronto as a case study. This was accomplished by documenting concentrations, loadings and factors influencing 19 OPEs in three Toronto streams during high and low flow periods, final effluent from three waste water treatment plants (WWTP), urban rain and near shore water from Lake Ontario. Tris (2-chloropropyl) phosphate (TCPP) was found at the highest concentrations in streams and WWTP effluent. Estimated mass loadings showed that WWTP discharges contributed significantly to the mass of OPEs entering into nearshore Lake Ontario, however, streams and rain could contribute equal or higher loadings during wet periods. These results suggested two major pathways to Lake Ontario: direct discharge from WWTP; and atmospheric deposition and wash-off into streams.

Keywords: Flame Retardants
OPE
Organophosphate Esters
SPF
Spray Polyurethane Foam Insulation
TCPP
Advisor: Diamond, Miriam L
Helm, Paul
Examining Factors of Physical Activity Participation in Youth with Spina Bifida using the Theoretical Domains Framework

Spina Bifida (SB) is a congenital neural tube defect that involves the incomplete development of the spinal cord, resulting in varying health ailments. Given the high rate of inactivity reported for youth with SB and using the Theoretical Domains Framework as a guide, the purpose of this study was to explore the physical, psychological, social and environmental factors influencing physical activity (PA) participation in this population. Nine eligible youth (6 females; mean age = 15.9 years) took part in one, semi-structured individual interview. Subjects most commonly reported self-efficacy, positive consequences of PA, positive affect and social influences as perceived PA facilitators. Pain/fatigue, lack of control over decisional processes, lack of time and inaccessible environmental resources were the most commonly reported perceived PA barriers. These findings can be used to direct further research, testing the theoretical correlates that are most amenable to change in order to promote PA within this population.

Keywords: Spina Bifida
TDF
Advisor: Arbour-Nicitopoulos, Kelly P.
Characterizing the Role of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible poly-ADP-ribose Polymerase (TIPARP) in Estrogen Receptor Signalling

Estrogens exert their effects by activating estrogen receptor alpha (ERα) and beta (ERβ). A number of different co-regulator proteins regulate the activities of both receptors. Identifying new ER co-regulators could lead to improved treatments for diseases, such as breast cancer. This study aimed to characterize the role of TIPARP, a mono-ADP-ribosyltransferase and novel co-regulator of ERs. Gene expression and ChIP studies revealed that TIPARP mRNA levels were regulated by ERs, and that ERα was recruited to TIPARP. TIPARP in turn repressed ERα, but co-activated ERβ activity. Furthermore, TIPARP was recruited to the regulatory regions of estrogen target genes. TIPARP mono-ADP-ribosylated both ERα and ERβ and reversed the effects of the mono-ADP-ribosylase, MacroD1, on ERα/β transactivation. Taken together, this work showed that TIPARP is a mixed function co-regulator of ERs, revealing that TIPARP and MacroD1 dynamically regulate the activities of ERα/β through ADP-ribosylation.

Keywords: Estrogen
Estrogen Receptor
Nuclear transcription factors
Receptor Signalling
TIPARP
Advisor: Matthews, Jason
Possibilities and Challenges in Designing Knowledge Building Environments for Secondary School Mathematics

This research sought to introduce Knowledge Building pedagogy into Ontario secondary school mathematics classes to explore the extent to which discourse aimed at deep understanding could improve math understanding. The thesis describes two design initiatives, first with two grade 9 then two grade 10 classes. In each context students generated diverse mathematical ideas, supported theories with evidence, and requested evidence from peers, with several grade 10 students showing evidence of improving earlier ideas (a key principle of Knowledge Building) . However, implementing Knowledge Building pedagogy required superimposing sustained student-directed discourse on current assessment procedures and syllabus timelines, which created anxiety especially among grade 10 students, who feared negative impact on test performance. Limited student engagement thus precluded establishment of Knowledge Building communities. Results suggest systemic change is needed to address cultural expectations, to introduce new knowledge media that fosters collective and individual achievement, and to realize studentsâ capacity for Knowledge Building in mathematics.

Keywords: education
knowledge building
mathematics
Advisor: Scardamalia, Marlene
Control of Cardiomyocyte Proliferation by p53/MDM2-Regulated microRNAs

Defining the roadblocks responsible for adult cardiomyocyte cell cycle arrest lies at the core of developing cardiac regenerative therapies. Inactivation of the p53/MDM2 tumor suppressor circuitry in the heart caused a significant increase in cardiomyocyte proliferation, through an upregulation of factors involved in cell cycle re-entry. These factors may be regulated by microRNAs (miRNAs), in quiescent cardiomyocytes. Therefore, we hypothesized that inactivation of p53/MDM2-regulated miRNAs could promote the expression of cell cycle activators and induce proliferation of cardiomyocytes. Comparison of miRNA expression profiles from cardiac specific p53/MDM2 double knockout (DKO) mouse hearts and wild type controls revealed 11 miRNAs that were downregulated in the "proliferative" DKO hearts and enriched for mRNA targets involved in cell cycle regulation. Knockdown of these 11 miRNAs in neonatal rat cardiomyocytes significantly increased the occurrence of cytokinesis, revealing a novel subset of p53/MDM2-regulated miRNAs responsible for maintaining cell cycle arrest in the heart.

Keywords: Cardiology
Cell Cycle
MDM2
microRNA
p53
Tumor Suppressor
Advisor: Billia, Filio
A Qualitative Exploration of Pain among Mixed Martial Artists

Athletes often experience pain in sport and in their everyday lives, yet little research has explored how athletes form understandings of pain, and how social interactions contribute to athletes’ understandings of pain. The purpose of this study was to explore MMA fighters’ experiences of pain while training for fight. A multiple case study approach (Stake, 1995) was used to study pain among four amateur and professional fighters and their training partners (total N = 7). Data were collected longitudinally using semi-structured interviews, participant observation, athlete video diaries, and video recordings of training sessions and fights. Results pertained to: (a) distinguishing between physical pain, injury, and emotional pain; (b) social validation of pain; (c) giving and receiving pain; (d) sharing pain with teammates; and (e) reflections on ‘doing’ pain research. The results suggest that pain experiences are socially constructed and shared with others, and teammates influence how fighters understand their pain.

Keywords: Emotional Contagion
Ethnographic Case Study
Mixed Martial Arts (MMA)
Pain
Sport Psychology
Video Diaries
Advisor: Tamminen, Katherine A
Co-Locating Code and Data for Energy-Efficient CPUs

The end of Dennard scaling has brought energy savings to the forefront of processor design. When coupled with massive datasets, traditional memory architectures are becoming a source of excess energy expenditure. In this thesis, we propose to conserve energy through the co-location of code and data, which limits data movement on and off the chip. To that end, we design a data prefetcher called Tempo that reduces useless prefetches by 18% and increases timeliness by 43%. Tempo boosts the performance of the state of the art Spatial Memory Streaming prefetcher by up to 20% (2.54% average). In contrast to data prefetching, we also describe an execution paradigm called Anti-Fetching, which dynamically moves code off-chip to a Near-Data Processor. Using Anti-Fetching on a set of graph processing benchmarks provides up to 31% energy savings in the memory hierarchy (11% average) over an efficient CPU baseline.

Advisor: Enright Jerger, Natalie
Patient-level Social Determinants of Unplanned Hospital Readmission among General Internal Medicine Patients

Hospital readmissions have garnered considerable attention among researchers, clinicians, and policy-makers because they are common, costly, and potentially preventable. The purpose of this study was to understand whether patient-level socio-demographic factors are independently associated with 30-day readmission among General Internal Medicine (GIM) patients. This retrospective cohort study included 1427 patients discharged from the GIM service of an urban teaching hospital in Toronto, Canada between the years 2012 and 2014. Multivariable Cox regression was used to analyze relationships between 13 socio-demographic variables and 30-day unplanned all-cause readmission while controlling for validated clinical risk factors. Socio-demographic factors were not found to be significantly associated with readmission within this cohort. Factors related to illness-level, particularly previous hospital utilization, were significantly associated with readmission. Knowledge generated from this study may inform the efforts of clinicians, hospital managers, and policy makers working to reduce hospital readmission rates and develop health systems which facilitate population health equity.

Keywords: General Internal Medicine
Healthcare Quality
Hospital Readmission
Risk Factors
Sociodemographic
Advisor: Jeffs, Lianne
Kuluski, Kerry