VictorJuiz/thesis huggingface dataset:
Exploring the Rheological, Crystallization, and Tensile Properties of Poly(lactide) Stereocomplexes and their Crystalline Network Structures

Despite numerous benefits, commercialization of poly(L-lactide) (PLLA) is limited due to its low melt-viscosity and poor crystallization kinetics. This work demonstrates that the production of self-reinforced PLLA by a cost-effective, single-step Spunbond process, can overcome these limitations. Herein, poly(D-lactide) (PDLA) and PLLA were melt-blended to form stereocomplex (SC) crystallites that were drawn using blown air. Morphological observations illustrated that upon stretching, the SC crystallites were no longer visible owing to their high compatibility with the matrix but were detectable by calorimetry. Furthermore, rheological analysis revealed the polymorphic nature of network structures in blends after stretching. Interestingly, blend crystallization kinetics and rheological response were greatly enhanced at low PDLA concentrations, after the application of extensional flow. Slight improvements in tensile modulus were also achieved upon stretching. Hence, the use of a strong extensional flow during cooling effectively reduces the amount of PDLA needed to enhance PLLA’s bulk properties, without compromising PLA’s biodegradability.

Keywords: Biopolymers
In Situ Fibrillation
Poly(lactide)
Self-Reinforced Composite
Stereocomplex
Structure-Property Relationships
Advisor: Lee, Patrick C
Accessing New Synthetic Pathways for Asymmetric Boron Subphthalocyanines and Considering a More Sustainable Boron Source

While the selective synthesis of semi-symmetric ABAB- or AABB-type phthalocyanines has been published, no known synthetic pathway has been developed for asymmetric AAB-type boron subphthalocyanines (BsubPcs). A set of templated BsubPc approaches was investigated by pre-arranging the macrocyclic sub-units and ultimately forming the macrocycle through addition of a boron trihalide reagent. The methods employed however were unable to yield any result of interest. Separately, the syntheses of boron subnaphthalocyanines (BsubNcs) occurring between dicyanonaphthalene and a boron trihalide to form the macrocycle of interest are known to also introduce random bay-position halogenation. In addition, the standard usage of boron trihalides as the boron source presents recurring issues relating to the low boiling points, toxicity and reactivitiy to air and moisture they possess. The usage of triphenyl borates as alternative boron sources was considered, being a more sustainable boron source. A synthetic pathway using triphenyl borates to BsubPcs and BsubNc was developed.

Advisor: Bender, Timothy P
Sox10, Olig2 and Nkx6.2 Each Generate Unique Oligodendrocyte Lineage Cells when Delivered to GFAP+ Astrocytes

Direct lineage reprogramming (DLR) is a novel strategy which directly converts one cell type to another without the need for a pluripotent intermediate. To date, the role of target and starting cell heterogeneity in DLR has not been well studied. Using GFAP-driven lentiviruses, cortical astrocytes were transduced with either Sox10, Olig2 or Nkx6.2 and assessed for markers of the oligodendrocyte cell lineage 14 days post-transduction. Ectopic expression of Olig2 resulted in the generation of early oligodendrocyte precursors, whereas expression of Sox10 produced cells with an intermediate precursor phenotype. Ectopic expression of Nkx6.2 did not significantly increase the number of oligodendrocyte lineage cells. An in vitro culture system and novel in vivo mouse model to specifically target neurotoxic A1 astrocytes was optimized and validated for future astrocyte to oligodendrocyte DLR applications. These findings lay the groundwork for novel, DLR-based therapeutic approaches for diseases involving oligodendrocyte loss that considers astrocyte heterogeneity.

Keywords: Astrocyte
Oligodendrocyte
Reprogramming
Advisor: Faiz, Maryam
The Impact of Social Isolation on Depressive and Anxiety-related Behavior

The social distancing measures, although necessary to contain the current Covid-19 pandemic, may nonetheless incur a cost of negative mental health impact. Social isolation is an accepted model of psychosocial stress leading to neuropsychiatric and developmental disorders. Social isolation in rodents results in changes to neurotransmitter systems that are implicated in psychiatric pathology and social isolation in rodents is shown to results in neuroinflammation. Studies conducted in rodents suggest the importance of animal strain, duration of isolation, and age at induction of isolation in varying effects of isolation protocols. This study assessed the effects of chronic social isolation in adolescence and in adulthood on anxiety- and depression-related behaviors in male and female C57BL/6J mice. While the results mostly failed to detect significant effect of social isolation on anxiety, depression, and motor function, interesting age- and sex-dependent trends were elucidated suggesting changing vulnerability.

Keywords: Age
Anxiety
Depression
Isolation
Sex differences
TRPM2
Advisor: Feng, Zhong-Ping
Understanding Medication Self-management in Community-dwelling Adults with Chronic Medication Experience: An Exploratory Concept Mapping Study

Existing medication self-management frameworks are primarily adherence-focused and often do not consider physiological, psychological, and sociocultural factors that affect medication experiences. Thus, this study explored what Canadian adults with chronic medication experiences can contribute to our understanding of medication self-management. Using concept mapping, nine thematic clusters were identified on what matters to individuals about their medications: 1) researching and becoming educated about medications; 2) social support; 3) effectiveness of medication; 4) self-ownership of medication; 5) ease of use; 6) convenience and accessibility; 7) information provided by health care provider; 8) personal interactions with health care provider; and 9) patient involvement and trust. Statements within these clusters were generally rated highly on both importance and feasibility, regardless of participant characteristics. Themes generated by participants complement and extend current conceptualizations of self-management by including medication-specific priorities.

Keywords: chronic disease
community-based participatory research
medication therapy management
patient participation
patient-centered care
self-management
Advisor: Guilcher, Sara
Two-dimensional Parallel Tempering for Solving Constraint-satisfaction Problems

A Boltzmann machine (BM) is a symmetrically connected neural network with binary-valued neurons. BMs can solve optimization problems when combined with Monte Carlo methods such as Simulated Annealing and Parallel Tempering. In this thesis, we exploit the Boltzmann machine with Two-Dimensional Parallel Tempering to solve combinatorial optimization problems with linear inequality constraints. These problems have a wide range of applications in industry and science. A new parallel method for handling the constraints is proposed and implemented on GPU.We considered the Quadratic Multiple Knapsack Problem (QMKP) as a case study as it can be extended to many other combinatorial optimization problems. We beat 21 best-known solutions and 28 average solutions among 30 benchmark instances compared to the state-of-the-art QMKP solvers.

Advisor: Sheikholeslami, Ali AS
Am I Plurilingual? A Narrative Inquiry into One Chinese Plurilingual Student’s Linguistic and Cultural Repertoire in Canada

Grounded in the theory of plurilingualism and narrative inquiry, this study focuses on one 14-year-old Chinese plurilingual boy, and his lived experiences with plurilingualism and pluriculturalism at home and at school in Canada. Plurilingual learners’ perceptions and attitudes toward their linguistic repertoires play a key role in language proficiency development, language choice and language use in life. By narrating one plurilingual boy’s lived experiences of language, this study not only presents his rich linguistic and cultural repertoire, but also creates a space for education practitioners, parents and researchers to reflect on the complexity behind fostering plurilingual competence.

Keywords: Chinese Heritage Learners
Linguistic and Cultural Repertoire
Narrative Inquiry
Plurilingual Competence
Plurilingualism
Third Space
Advisor: Bale, Jeff JF
Studies on the Relationship between After-ripening Regulated Gene Expression and Reactive Oxygen Species in Arabidopsis thaliana Seed Germination

After-ripening (AR) is a process promoting seed germination, which occurs in the dry seed when storage time is extended. AR increases the seed’s response to environmental signals such as nitrate, which then regulates expression of AR-regulated genes upon imbibition. However, this mechanism is unknown. In this study, the role of reactive oxygen species (ROS) in expression of AR-regulated genes was investigated. Using the promoter:β-glucuronidase reporter system, AR was shown to alter spatial expression patterns of CHOTTO1 (CHO1), an AR repressor, enhancing its expression in the vasculature. Interestingly, AR seeds of the cho1 mutant enhanced superoxide accumulation in the vasculature. Pharmacological experiments suggest H2O2 decreases expression of CHO1, while increasing expression of CYP707A2, another AR-regulated gene. Furthermore, H2O2 application increases nitric oxide release, but nitrate inhibits it, through NIN-Like Protein8, involved in nitrate signalling. These findings suggest ROS is involved in AR-regulated seed germination through regulating expression of CHO1 and CYP707A2.

Keywords: after-ripening
after-ripening regulated gene expression
hydrogen peroxide
reactive oxygen species
seed germination
seed storage
Advisor: Nambara, Eiji
Non-invasive Delivery to the Inner Ear: Investigating Blood-labyrinth Barrier Opening using MRI-guided Focused Ultrasound Combined with Microbubbles

Non-invasive therapeutic delivery to the inner ear remains challenging due to the anatomical complexity,its location within the dense temporal bone, and the presence of the blood-labyrinth barrier (BLB). Here, I investigated the safety and feasibility of using magnetic resonance imaging-guided focused ultrasound (MRIgFUS) combined with intravenously administered microbubbles to enhance the BLB permeability and to deliver an adeno-associated virus serotype 9 (AAV9) expressing the green fluorescent protein (GFP) to the inner ear. AAV9-GFP, microbubbles, and MRI contrast agents were delivered intravenously in rats with simultaneous FUS exposure, and hearing function was assessed using auditory brainstem response measurements. My data shows increased BLB permeability post-FUS+MB exposure, as indicated by gadolinium contrast enhancement and AAV9 transduction in treated inner ears relative to controls with no effects on auditory function. Taken together, my data supports the feasibility of MRIgFUS towards clinical development for non-invasive delivery of various therapeutics to treat inner ear disorders.

Keywords: cochlea
drug delivery
focused ultrasound
gene therapy
inner ear
non-invasive
Advisor: Dabdoub, Alain
The Effect of Protein Quality on Post-exercise Anabolism in Active Children

Leucine-enriched proteins (e.g., dairy) are more effective than plant-based sources for supporting post-exercise rates of muscle protein synthesis in adults. However, the impact of protein quality on protein synthesis and acute markers of growth in active children are unknown. Using a randomized crossover design, eight children completed three metabolic trials providing 0.32g/kg FFM of either milk protein concentrate (MPC), rice protein isolate (RPI), or soy protein isolate (SPI) following a bout of variable intensity exercise with whole-body protein kinetics (i.e., oxidation, synthesis, breakdown, and net balance) determined by oral [13C]phenylalanine tracer methodology. Although phenylalanine oxidation was not different between protein sources, protein synthesis was greater with MPC compared to SPI and RPI. In contrast, RPI ingestion apparently attenuated breakdown rates compared to MPC and SPI. MPC and RPI ingestion resulted in greater net-protein balance compared to SPI. Although post-exercise protein ingestion is critical to support anabolism, our results indicate that protein quality may be a consideration for children.

Keywords: Anabolism
Children
Exercise
Growth
IAAO
Protein Quality
Advisor: Moore, Daniel R
Design and Synthesis of Novel Aryl Sulfonamide Tubulin Inhibitors as Antimitotic Cancer Therapeutics

Microtubule targeting agents (MTAs) are one of the most successful classes of cancer therapeutics to date. This work focuses on the development of novel tubulin inhibitors in the treatment of cancer. Currently approved tubulin inhibitors targeting the vinca- and taxane- sites encourage gene mutations and multidrug resistance over prolonged dosing. The compounds discussed herein target the colchicine binding site. Compounds that bind this site can evade these resistance mechanisms. Despite several advantages over traditional inhibitors, no small molecule targeting this region has been approved for clinical use in cancer. A structure-activity-relationship (SAR) study was conducted to optimize the biological response in several cancer cell lines. Two lead compounds, 1a and 2b, were identified. Both molecules show promising potency in cellulo but employ separate interaction mechanisms: 2b reacts selectively and covalently with Cys239 within the tubulin dimer, whereas 1a achieves sub-micromolar potency via favorable non-covalent interactions.

Advisor: Gunning, Patrick T
Regulation of Proliferation and the Developmental Emergence of Adult Neural Stem Cells

Following acute or chronic injury, the adult mammalian brain may sustain significant neural cell loss. Interestingly, the brain can regenerate these lost cells by activating endogenous quiescent adult neural stem cells (NSCs). But this repair response is short-lived, and not very robust. Developmentally, NSCs emerge from embryonic radial precursor cells (RPs), by entering a ‘slow-dividing’ state. However, this transition is not well understood. Recently, our lab showed the protein LRIG1 increases embryonic RP proliferation by negatively regulating EGFR. In this thesis, I investigated whether LRIG1 expression affects NSC proliferation similarly in the adult brain. In vivo, I showed the absence of Lrig1, stably increases NSC proliferation with advancing age. In addition, I have shown LRIG1 specifically marks ‘slow-dividing’ cells in the V-SVZ. This thesis contributes to our understanding of how quiescent NSCs emerge developmentally, which may enable therapeutic strategies designed to robustly activate endogenous NSCs following brain injury.

Keywords: Adult Neural Stem Cells
LRIG1
Neurogenesis
NSCs
Quiescent
V-SVZ
Advisor: Yuzwa, Scott
Dis-possessed to SK8: Push Pedagogy as Creative Entrepreneurial Inquiry/Interventions into Urban Poverty with the Grrlz of Oasis Skateboard Factory

This activist practitioner research thesis thinks with/skates alongside a research-creation project that attempts to land a sk8trick of push pedagogy as creative entrepreneurial inquiry/interventions into urban poverty. Push pedagogy is a new concept of public pedagogy and radical design in(ter)vention activated by the collaborative production of skateboard materials frictioning mainstream skateboard culture and economics, schooling and educational research. Grinding an intersectional critique on capitalist designs for the neoliberal city concretized by patriarchy and white supremacy, this research-creation methodology moves by collaboratively producing critical design products with the OSF GRRLZ SK8 CREW at Oasis Skateboard Factory (a Toronto District School Board alternative school / professional design studio). Exploring how a research-creation project activated student-designed skateboard materials in the city of Toronto to push against youth experiences of marginalization/dispossession/exclusion and push toward future feminist/anti-racist movements, this thesis is also a pro/motion for radical form/function/futures of knowledge creation by student skaters and creators.

Keywords: Design
Patriarchy
Skateboard
Skateboarding
Urban Poverty
White Supremacy
Advisor: Springgay, Stephanie
Hyperpolarized 129Xe Magnetic Resonance Spectroscopy in a Rat Model of Bronchopulmonary Dysplasia

Bronchopulmonary Dysplasia (BPD) is a chronic lung disease linked to prematurity and the mechanical ventilation and oxygen therapy used to treat respiratory distress in neonates. BPD is a major cause of mortality and lifelong morbidity and is characterized by fewer enlarged distal lung air sacs and pulmonary vascular stunting. Hyperpolarized (HP) 129Xe magnetic resonance spectroscopy (MRS) can be used to non-invasively obtain signals from inhaled HP 129Xe that are potentially sensitive to BPD-like changes and could benefit diagnosis and treatment by identifying physiologically-based biomarkers of BPD. In this thesis, MRS signals sensitized to HP 129Xe uptake in an oxygen exposure rat model are fit to the model of xenon exchange (MOXE) to extract parameters related to the pulmonary vasculature and distal airspaces which are then compared to histology. MOXE-derived mean chord length (Lm) and local capillary hematocrit (HCT) were significantly higher in exposed rats and Lm correlated with histological findings.

Keywords: air-blood barrier
bronchopulmonary dysplasia
hyperoxia
hyperpolarized gas
intermittent hypoxia
Advisor: Santyr, Giles
The Evolution and Molecular Basis of Substrate Specificity in 3-Ketoacyl-CoA Synthases from Populus trichocarpa

3-Ketoacyl-CoA synthases (KCSs) catalyze the substrate specific elongation of very-long-chain fatty acids (VLCFAs), precursors to membrane lipids and plant cuticular waxes. Though members of the large KCS family have been shown to use diverse substrates, the molecular basis for their substrate specificity is still unclear. In this thesis, a KCS gene cluster in poplar (Populus trichocarpa) was used to examine the evolution and molecular determinants of VLCFA substrate specificity. Characterization of five paralogs showed differential preferences towards substrates based on carbon length, saturation, and stereochemistry. Furthermore, the paralogs showed differential inhibitor sensitivity in response to K3 herbicides. Homology models, site-directed mutants, and chimeric proteins were used to identify two key regions (helix-4 and position 277) as being major determinants of substrate specificity, results which were corroborated with a more distantly related KCS. Together, these results shed light on key molecular changes driving the evolution of KCS substrate specificity.

Keywords: fatty acid biosynthesis
lipid synthesis
natural product biosynthesis
plant biochemistry
substrate specificity
very-long-chain fatty acids
Advisor: Gonzales-Vigil, Eliana
Effects of High-intensity Interval Training on Blood Lactate Levels and Cognition in Healthy Adults: Systematic Review and Meta-regression

Background. High-intensity interval training (HIIT) may confer cognitive benefits through apathway involving lactate – an exercise metabolite. R1: Individually, what is the work-interval duration, work-interval volume, work-to-rest ratio, and session volume that is most effective in increasing peripheral lactate accumulation. R2: What is the relationship between peripheral lactate levels and post-exercise cognitive performance in healthy adults? Methods. R1: Network meta-analysis, categorical meta-analysis, and mixed effects meta- regression were performed. R2: Correlation and determination coefficients were generated. Results. R1: A low work-interval volume, medium session volume, and low work-to-rest ratio may elicit peak peripheral lactate accumulation. R2 Hypotheses: i) higher blood lactate post- HIIT increases interference performance for a longer duration, and ii) predicts better interference performance at 30 mins post-HIIT. Discussion. The above parameters may elicit peak peripheral lactate levels, which may be related to improved interference performance post-exercise. Our findings need to be validated using randomized controlled trials.

Keywords: cognition
exercise
high-intensity interval training
lactate
Advisor: Green, Robin
Improving Biosensor-based Circuits for Dynamic Control of Metabolic Pathways

Bioproduction of chemicals in microorganisms using renewable feedstocks is a sustainable and greener alternative to traditional processes. Dynamic control of metabolism using biosensors has evolved as a common approach to partition cellular resources efficiently However, biosensor development requires several iterations of DBTL cycles to optimize for any application. In this work, we modeled and studied the effect of various parameters on the switching characteristics of an autonomous biosensor-regulator system, qCRIPSRi by simulating the dynamics of the circuit and performing sensitivity analysis. In addition, the effect of stringency of transcriptional activator LuxR on the switching characteristics and dynamics was investigated and validated through in vivo experiments. We also designed and modeled a novel biosensor architecture that enables tuning dose-response curve using small molecule inducers. Furthermore, we demonstrated the ability of the system to tune dynamic range, threshold, and sensitivity of dose response curves of adipic acid and resorcinol biosensors in silico.

Keywords: Biosensor
Dynamic control
Metabolic Engineering
Model-based analysis
Synthetic Biology
Advisor: Mahadevan, Radhakrishnan
Relating Patient-specific Computational Fluid Dynamics Simulations to Coronary Artery Bypass Graft Remodeling

The benefits of coronary artery bypass graft (CABG) surgery are limited by graft failure, and the underlying mechanisms remain incompletely understood, though they are likely related to hemodynamics. Contributing to a better understanding of the mechanisms that lead to graft failure is the goal of this thesis. Patient-specific image-guided computational fluid dynamics (CFD) simulations were performed in 24 bypass grafts of 10 participants 1 month after surgery. Several hemodynamic measures were obtained from the 1-month CFD simulations and compared to existing clinical measures of bypass graft function. All measures were then correlated to graft lumen remodeling measured 1 year after surgery, as remodeling may precede graft failure. This thesis demonstrated for the first time prospectively a significant correlation between 1-month abnormal wall shear stress area derived from CFD and 1-year graft lumen remodeling, which suggests that abnormally low WSS could potentially play a mechanistic role in graft failure.

Keywords: computational fluid dynamics
coronary artery bypass graft
patient-specific modeling
vascular remodeling
wall shear stress
Advisor: Triverio, Piero
Jimenez-Juan, Laura
Improving Metabolic Modelling by Considering Small Molecule Regulation

Metabolism is a densely connected network of enzymatic reactions, and regulatory interactions, which fuel the cell with biomass building blocks. Organisms modulate their metabolism by changing the capacity of metabolic enzymes– termed proteomes when exposed to environmental stresses. Small Molecule Regulation (SMR) is an essential component of the metabolism that enables cells to adapt to environmental fluctuations. However, it has not been incorporated into the metabolic models extensively. In this project, we have proposed a workflow to assess the accuracy of mathematical models for proteome demand calculation after integrating them with the kinetics of metabolic regulation. Here, we have developed a standard database that provides in vitro kinetic parameters of 9,814 species. Then, this database was used to generate the inhibition power imposed on 3,883 enzymes of 972 organisms. Finally, we showed that the accuracy of traditional models improved after incorporating the SMR into protein abundance calculation in Escherichia coli.

Keywords: Enzymatic Reaction
Kinetic Parameter
Mathematical Modelling
Metabolic Regulation
Metabolism
Proteome
Advisor: Mahadevan, Radhakrishnan RM