VictorJuiz/thesis huggingface dataset:
Development of Synthetic Processes and Characterization of BsubPcs with High Crystal Densities for Application in Organic Photovoltaic Devices

The original goal of this thesis was to develop process chemistry to yield boron subphthalocyanine (BsubPc) derivatives which were previously difficult to access. Retrospectively, it was found that these compounds show extremely high density crystal packing in comparison to other known BsubPcs, and thus this also became a focus of the thesis. A process to synthesize and purify fluoro-BsubPc was developed. This led to a detailed comparison of the physical and chemical properties of the three halo-BsubPcs in order to answer the question of which halo-BsubPc is appropriate for different purposes. Through this work, the previously unpublished crystal structure of the oxygen bridged dimer, µ-oxo-BsubPc, was found. A process was subsequently developed for the practical synthesis of µ-oxo-BsubPc for use in vacuum deposition and a number of µ-oxo-BsubPc crystal polymorphs were found and analyzed. The properties of this group of compounds are discussed in the context of other known BsubPcs.

Keywords: subphthalocyanine
boron
organic
photovoltaic
halo
dimer
oxygen
bridge
bridged
synthesis
Advisor: Bender, Timothy
Goal Management Training: A Web-based Approach

This study was undertaken to introduce an innovative approach to cognitive rehabilitation intervention (Goal Management Training- GMT) delivery, through a web-based platform administered to adults with cerebrovascular disease (CVD) or suffering from CVD risk factors who presented with executive function impairments. The feasibility of this approach was investigated by developing a semi-quantitative-qualitative tool to measure therapist competence and group engagement adapted from the Cognitive Therapy adherence-to-protocol scale. Results from two raters analyzing random web-based GMT session recordings showed no compromise in any aspect measured. In addition, the efficacy of the intervention was established using neuropsychological and functional outcome measures, with significant results observed on the Goal Attainment Scale functional measure. To our knowledge, this study is the first of its kind to a) employ videoconferencing technology to overcome accessibility barrier to cognitive rehabilitation and b) develop an adherence to protocol tool to measure various aspects of GMT.

Keywords: cognitive rehabilitation
cognitive psychology
Advisor: Black, Sandra
Turner, Gary R.
On Mesh Convergence and Accuracy Behaviour for CFD Applications

Computational Fluid Dynamics (CFD) is a main field that contributes to the development of high efficiency aircraft. CFD accuracy depends on the flow solver and the meshing of the geometry, and while it is doable to determine why a certain solver is more accurate than another, it is much more difficult to discern why two meshes produce differently accurate solutions. A framework is presented to evaluate the performance or ``goodness" of a mesh and to compare meshes. The framework is composed of quantifiable mesh parameters which define a mesh, and three performance measures: functional accuracy, their order of convergence, and their behaviour under the adjoint correction method. Although it seems that the relationships between parameters and results are not trivial, there are trends from which optimal mesh parameters are deduced. The H topology performs best, and the most important parameters are related to spacings and cell quality around the aerofoil leading edge.

Keywords: engineering
aerospace
mesh
topology
aeronautical
aircraft
aerofoil
convergence
accuracy
adjoint method
Advisor: Zingg, David W.
Microfluidics for Steam Assisted Gravity Drainage and Petroleum Applications

Petroleum research is responsible for making previously unusable reservoirs economically viable and for limiting the environmental impact of petroleum development. Microfluidics, the study of fluid flow at the micro-scale, is predominantly used to study biological phenomena. Adapting microfluidics to study petroleum requires the use of materials and methods not commonly used. This thesis focuses on applying microfluidics to the study of petrochemical fluid flow at high-pressure and high-temperature. The first problem addressed is the study of fluids during alkaline steam assisted gravity drainage (alkaline SAGD). The addition of an alkaline additive is found to improve the bitumen production rate by 35-67%. Secondly, two high-pressure, high-temperature, solvent resistant microfluidic interfaces for glass chips are designed to be operated up to 140 bar and 70 degrees Celsius. Lastly, a novel method for fabricating solvent resistant microfluidic devices from Teflon film is demonstrated by measuring the viscosity of toluene-heavy oil blends.

Keywords: Microfluidics
Steam Assisted Gravity Drainage
Advisor: Sinton, David
Rational Design of sym-Triazines For Multitarget-directed Modulation of Cholinesterases and Amyloid-beta in Alzheimer’s Disease

Alzheimer’s disease (AD), a progressive age-related neurodegenerative disorder is characterized by impairments in memory and cognitive functions. The two main pathogenic hallmarks associated with the progression of this multifactorial disease include accumulation of amyloid-beta (Aβ) plaques and the deterioration of the cholinergic system in the brain. Using cost-effective synthetic procedures, mono-, di-, and tri- substituted sym-triazine derivatives incorporating acetylcholine substrate analogues and aromatic phenyl moieties were synthesized for the targeted modulation of Aβ aggregation and acetylcholinesterase (AChE) activity. A subset of these sym-triazines demonstrated dual inhibition of Aβ fibrillization and AChE hydrolytic activity in vitro studies. These highly effective compounds were also shown to be well tolerated by differentiated human neuronal cells in cell viability tests. These novel compounds have the potential to undergo future in vivo pharmaceutical analysis and have a positive impact on the quality of life of the people living with this devastating disease and their caretakers.

Keywords: Alzheimer's disease
amyloid-beta
acetylcholinesterase
Advisor: Kerman, Kagan
Saprolite Leaching and Iron Control in Concentrated Magnesium Chloride Brines

MgCl2 brines present a number of potential advantages for the processing of saprolite ores for nickel production. Concentrated MgCl2 solutions enhance the activity of acid used, allow atmospheric leaching at elevated temperature and inhibit magnesium dissolution, which reduces acid consumption and increases metal selectivity. However, with a chloride system it is economically requisite to recover hydrochloric acid, conventionally accomplished by pyrohydrolysis. This work was performed in conjunction with a novel flowsheet for the processing on saprolite ores, which recovers HCl by the precipitation and subsequent decomposition of magnesium hydroxychlorides, alleviating some of the issues with pyrohydrolysis. Leaching and iron control experiments have been conducted in concentrated MgCl2 brines, up to 4.5 m, to determine the most amenable process conditions. It was determined that > 95% extraction of metals was possible using both aqueous and gaseous HCl. In addition, the feasibility of iron control by precipitation with MgO addition was proven.

Keywords: Saprolite
Magnesium Chloride
Atmospheric Leaching
Nickel
Advisor: Papangelakis, Vladimiros G.
Davis, Boyd
Insulin Receptor Signaling is Necessary for the Maintenance of Epithelial Phenotype in MCF10A Cells

Obesity is an adverse factor in the development and severity of breast cancer. Obesity is often accompanied by an increase in circulating insulin, which is also associated with poor BC prognosis. Although not expressed in normal breast tissue, the insulin receptor (IR) is highly expressed in BC, therefore insulin signaling in BC cells may be responsible for the negative prognostic effects associated with hyperinsulinemia. This thesis describes the development of a cell-based system to study how insulin affects BC. My work shows that MCF10A, untransformed human breast epithelial cells that express the IR, require insulin for normal proliferation and morphology. Interestingly, I discovered hyperactivation of ERK1/2 in MCF10A cells in response to insulin withdrawal, resulting in a loss of epithelial phenotype. Unexpectedly, while losing epithelial phenotype, MCF10A cells depleted of insulin failed to migrate. In conclusion, breast cells that express IR require insulin for migration and maintenance of epithelial characteristics.

Keywords: Breast Cancer
Insulin
Cell Signalling
Obesity
Type 2 Diabetes
Advisor: Stambolic, Vuk
Design of a Shape Optimized Metallic Nano-heater

The absorption of the energy in the form of heat from electromagnetic radiation is strongly dependent on the shape of the surface. Also, the transfer of this generated thermal energy is dependent on the surface area of the object in contact with the surrounding medium. Here in this thesis, we present a structural optimization method for metal nanostructures based on the shape dependency of their electromagnetic heat dissipation and thermodynamic transfer to the surroundings. We have used a parallel genetic algorithm (GA) in conjunction with a coupled electromagnetic (FDTD) and thermodynamic modeling of the metallic nanostructures for the optimization. The optimized nano-structure demonstrates significant improvement in electromagnetic heating in the spectral window of optimization as well as expedited cooling properties. The symmetry of the structures which is inherent in the design procedure makes them independent of the polarization at normal incidence and insensitive to the azimuthal direction of incidence.

Keywords: Photothermal
Shape optimization
Metal nanostructure
Advisor: Mojahedi, Mohammad
James, Daniel
Tumor Gene Expression Purification Using Infinite Mixture Topic Models

There is significant interest in using gene expression measurements to aid in the personalization of medical treatment. The presence of significant normal tissue contamination in tumor samples makes it difficult to use tumor expression measurements to predict clinical variables and treatment response. I present a probabilistic method, TMMpure, to infer the expression profile of the cancerous tissue using a modified topic model that contains a hierarchical Dirichlet process prior on the cancer profiles. I demonstrate that TMMpure is able to infer the expression profile of cancerous tissue and improves the power of predictive models for clinical variables using expression profiles.

Keywords: Bayesian methods
Gene expression purficiation
Bayesian Nonparametric
Topic models
Advisor: Wong, Willy
Vocal Frequency Estimation and Voicing State Prediction with Surface EMG Pattern Recognition

Most electrolarynges do not allow hands-free use or pitch modulation. This study presents the potential of pattern recognition to support electrolarynx use by predicting fundamental frequency (F0) and voicing state (VS) from neck surface EMG and respiratory trace. Respiratory trace and neck surface EMG were collected from 10 normal, adult males (18-60 years old) during different vocal tasks. Time-domain features were extracted from both signals, and a Support Vector Machine (SVM) classifier was employed to model F0 and VS. An average mean-squared-error (MSE) of 8.21 ± 3.5 semitones2 was achieved for the estimation of vocal frequency. An average classification accuracy of 78.05 ± 6.3 % was achieved for the prediction of voicing state from EMG and 65.24 ± 7.8 % from respiratory trace. Our results show that pattern classification of neck-muscle EMG and respiratory trace has merit in the prediction of F0 and VS during vocalization.

Keywords: vocal frequency
EMG
voicing state
respiration
prediction
Advisor: Chau, Tom
Investigating the Use of Hair to Assess Polybrominated Diphenyl Ether (PBDE) Exposure Retrospectively, and in Male Infants with Genitourinary Tract Malformations

Polybrominated diphenyl ethers (PBDEs) are synthetic chemicals that are added to a variety of consumer products as flame-retardants. The ubiquitous nature and endocrine disrupting properties of PBDEs are a public concern. A pilot study was performed to investigate whether in utero PBDE exposure, as measured in maternal hair, is associated with genitourinary tract malformations in male infants. In addition, we compared PBDE levels in maternal and infant hair and used segmental analysis to investigate how PBDEs varied along the shaft. Preliminary results suggest a trend toward an elevated PBDE body burden in mothers whose infants were born with genitourinary tract malformations; this was significant for some PBDEs. The sum of PBDEs (ΣPBDEs) in maternal hair did not correlate with infant hair levels; children had significantly greater levels. A significant increase in the ΣPBDEs was observed in distal hair suggesting hair PBDEs may be reflective of both internal and external exposure.

Keywords: environmental exposure
hair
polybrominated diphenyl ethers (PBDE)
genitourinary tract malformations
male reproduction
brominated flame retardants
Advisor: Koren, Gideon
Targeting Aberrant STAT3 Signaling as a Therapeutic Strategy for Multiple Myeloma

The oncogenic transcription factor STAT3 is aberrantly activated in over 70% of human tumours, including Multiple myeloma (MM). The present studies use both genetic and chemical tools to validate STAT3 as a therapeutic target, and demonstrate the anti-MM activity of a novel small molecule STAT3 inhibitor, BP-4-018. We show that shRNA-mediated STAT3 knockdown induces apoptosis in human myeloma cell lines (HMCLs). We translate these findings to a therapeutically relevant setting by demonstrating the broad anti-MM activity of BP-4-018 against HCMLs and primary patient samples, and demonstrate that BP-4-018 remains active against HMCLs co-cultured with bone marrow stroma. Inhibiting STAT3 via shRNA knockdown and BP-4-018 suppresses STAT3 transcriptional activity and down-regulates anti-apoptotic and proliferative STAT3 target genes. Finally, we show that BP-4-018 has activity in vivo, both alone and combined with subtherapeutic doses of bortezomib, without significant toxicities. Taken together, these data support the utility of STAT3 inhibitors for MM treatment.

Keywords: STAT3
Targeted therapeutics
Multiple Myeloma
Small molecule inhibitors
Advisor: Trudel, Suzanne
Rosie - A Recovery-oriented Security System

Recovery is a time-consuming and computationally expensive operation. If an attacker can affect heavily-shared objects on the machine, then many other processes and files can be compromised from accessing them. This would greatly increase the recovery effort. Since intrusions start with a network connection, we argue that the integrity of heavily-shared objects should be protected from the network, in order to minimize the recovery effort. We discuss our prototype Rosie, which is designed with incident response and post-intrusion recovery in mind. Rosie predicts how heavily-shared each file or process is, based on the previous system activities observed. Rosie enforces appropriate mandatory access control and uses techniques such as sandboxing, in order to protect heavily-shared objects’ integrity. Rosie provides an important recovery guarantee that the maximum number of files need to be recovered is at most equal to the dependency threshold, a value that can be adjusted by a system administrator.

Keywords: computer system
dependency analysis
recovery
computer security
Advisor: Goel, Ashvin
Exploring the Reactivity of S-cis-methylaziridine Aldehyde

In 2006, an amphoteric molecule containing both an aldehyde and an unprotected amine was reported in the Yudin group by Dr. Ryan Hili. The unprotected aziridine aldehyde exists as homochiral dimers. Furthermore, due to the reversibility of the hemiacetal formation, the free aldehyde is available to undergo a wide array of reactions including an Ugi multicomponent reaction to give the final peptide macrocycle. Thus far, the mechanistic pathway involved in the Ugi reaction between S-trans aziridine aldehyde dimer and L-amino acids in the presence of tert-butyl isocyanide has given high diastereoselectivity whereas low diastereoselectivity is observed if the aziridine dimer is of the opposite stereochemistry. Herein, preliminary results show that a S-cis aziridine aldehyde with either a D or L-secondary amino acid gives high diastereoselectivity showing that the reaction is under Felkin-Ahn control.

Keywords: peptide macrocyclization
Ugi four component condensation
Advisor: Yudin, Andrei
Over the Hill and Under the Radar: Participation in Physical Activity of Older People at the St. George Campus of the University of Toronto

An examination of data from 21 older members of the University community aged 59 and older, including those who do and those who do not use the campus gyms, and six athletic programming staff from the two facilities to attempt to understand how older adults choose to negotiate their physical activity as they age. The study demonstrates that those respondents most comfortable in the gym spaces in the university setting are those who have occupied those spaces over many years, or those who have been habituated to gym culture through their activities outside the university setting. Using the ’mask of ageing theory’ in combination with Bourdieu’s concepts of habitus, capital and field, this study is an attempt to understand the individual and cultural practices that older adults engage in to manage their physical activities at the University, their other activities outside, as well as the performative aspects of their engagement.

Keywords: older adult
physical activity
Advisor: Donnelly, Peter
Identification of Molecular and Functional Heterogeneity of Epithelial Progenitor Cells in the Upper Airway

Upper airways are lined with a pseudostratified mucociliary epithelium maintained by basal cells. To investigate functional and phenotypic heterogeneity within the human basal cell compartment, we used a combination of limiting dilution assays and surface marker profiling on primary cultures of basal cells with verified progenitor activity. The limiting dilution assay suggested functional heterogeneity in the ability of basal cells to repopulate a filter and maintain a barrier at ALI. The frequency of cells with this activity varied between patient strains and ranged from 0.08%-1% of basal cells. Validation of large-scale comprehensive surface marker profiling on basal cells led to identification of 74 antigens demarking consistent subpopulations. Preliminary functional analyses suggest differences in differentiation potential of some subpopulations. This work supports the idea that the basal cell compartment may be functionally heterogeneous, and provides new molecular tools for interrogation of human basal cells.

Keywords: airway epithelium
lung progenitor cells
Advisor: Moghal, Nadeem
Rspondin-1 Deficiency Enhances Beta Cell Neogenesis in a Murine Model of Diabetes

The cWnt activator, Rspondin-1 (Rspo1), has been identified as a regulator of β-cell growth and function, although its role in pathophysiological conditions such as streptozotocin (STZ)-induced diabetes is unknown. Hence, I hypothesized that Rspo1 deficiency stimulates β-cell neogenesis in STZ-diabetes. There was no difference in oral glucose handling between STZ-induced Rspo1mice, although, Rspo1-/- mice demonstrated increased insulin sensitivity compared to wild-type littermates. Moreover, β-cell mass and the total number of islets did not differ between STZ-induced Rspo1+/+ and Rspo1-/- mice, although mice with Rspo1 deficiency had reduced β-cell apoptosis and significantly enhanced numbers of insulin-positive ductal cells suggestive of β-cell neogenesis. Furthermore, the increased β-cell regeneration observed in knockout animals appeared to be associated with a more differentiated/mature β-cell phenotype in Rspo1-/- versus Rspo1+/+ mice. Collectively, these findings indicate a role for Rspo1 as a negative regulator of in vivo β-cell neogenesis and survival in the face of STZ-induced diabetes.

Keywords: Rspondin-1
beta-cell
neogenesis
apoptosis
diabetes
Advisor: Brubaker, Patricia
Organic Matter Biomarker Fingerprinting of Glacial Deposits

The goal of this thesis was to test the applicability of biomarker analyses to better understand the glacial stratigraphic record of the Hudson Bay Lowlands and Oak Ridges Moraine. A biomarker analysis conducted on three geologic deposits from the Hudson Bay Lowlands showed that they can be differentiated based on organic matter (OM) inputs and stage of diagenesis, relating to paleoclimate and depositional environments. In the second study, a biomarker analysis was applied to samples from ten deposits in the Oak Ridges Moraine. These deposits were differentiated based on OM inputs relating to paleovegetation. Additionally, reincorporation and post-deposition alteration led to sample heterogeneity confirming the current understanding of glacial depositional processes and environments. This thesis shows that biomarker analyses can effectively differentiate and contextualize geologic deposits based on OM inputs and stage of diagenesis. This in turn will provide a more robust understanding of the stratigraphic record.

Keywords: organic matter biomarkers
glacial deposits
Oak Ridges Moraine
Hudson Bay Lowlands
Advisor: Simpson, Myrna J.
Evaluating Psychosocial Variables and their Link to Hypertension Using Mindfulness-based Stress Reduction

Previous research has reported positive associations between anger, perceived stress and blood pressure. These associations have largely been based on cross-sectional data and a small number of longitudinal works. Using a prospective longitudinal cohort design, this study more directly tested the relationships between anger, perceived stress and blood pressure by using a psychological therapeutic intervention (mindfulness-based stress reduction) to manipulate anger and perceived stress. Anger and perceived stress were in turn evaluated for association with blood pressure. Despite improvements in psychosocial functioning and reductions in blood pressure, findings from this study failed to demonstrate an association between change in anger or perceived stress with change in daytime or 24-hour ambulatory blood pressure. A model where these variables interact indirectly via stress coping mechanisms or health behaviours may be the linking mechanism in this study. Results from this thesis have contributed evidence to a divided field dominated by cross-sectional research.

Keywords: Hypertension
Perceived stress
Anger
Mindfulness-based stress reduction
Ambulatory blood pressure monitoring
Advisor: Tobe, Sheldon
Nolan, Robert
Measurement of Spine Density in Mouse Models of Hypodopaminergia

Dopamine (DA) is a key catecholamine neurotransmitter involved in motor control, cognition, and neuroendocrine regulation. Reduced DA transmission is associated with Parkinson’s disease, depression, and anhedonia. An overexpression of the dopamine transporter in mice (DAT-tg) results in a 40% reduction in extracellular DA, and can be classified as a genetic model of hypodopaminergia. Reserpine treatment depletes extracellular DA, and is a pharmacological model of hypodopaminergia. The aim of this study was to determine morphological and proteomic changes to medium spiny neurons (MSNs), which receive dopaminergic input, as a consequence of reduced DA transmission. To achieve this, MSNs were fluorescently labelled using a diolistics method and immunofluorescence. There were no observable changes to morphology or proteomic profile of MSNs in DAT-tg animals. Reserpine treatment resulted in reduced spine density in MSNs. DAT-tg animals may present a level of DA depletion that is below the threshold to induce morphological changes to MSNs.

Keywords: dopamine
medium spiny neurons
Parkinson's disease
Advisor: Salahpour, Ali
George, Susan