VictorJuiz/thesis huggingface dataset:
Associations of Linear Growth in the First 2 Years with Bone Mass at 4 Years of Age in Children in Dhaka, Bangladesh
Keywords: Bangladesh
Bone mass
Children
Linear growth
Weight gain

Despite attention towards growth faltering in low-and middle-income countries, less is known about childhood bone mass. In a cohort of 4-year-old children in Bangladesh, we aimed to estimate associations between length (conditional length-for-age z-scores, cLAZ) and weight (conditional weight-for-age z-scores, cWAZ) gain measured in 3 intervals (ages 0-6, 6-12, 12-24 months) and bone outcomes (total-body-less-head bone mineral content, BMC, areal bone mineral density, aBMD, and bone area) at age 4-years (n=599). Positive associations of cLAZ in each interval with bone outcomes were rendered null after adjustment for concurrent height at 4-years. cWAZ between 12-24 months was independently associated with BMC (7.5g; 95%CI:3.1,11.8) and aBMD (0.008g/cm2; 95%CI:0.002,0.014) after adjusting for weight and height at 4-years. The associations between linear growth (birth to 2-years) and bone mass are explained by concurrent height. However, weight gain in the second year of life might improve bone mass, irrespective of length growth, in this setting.
Deoxygenation of Respiratory and Limb Muscles during Exercise in COPD and Healthy Adults
Keywords: exercise
inspiratory
limb
NIRS
rehabilitation
training

The overall objective of the thesis is to investigate deoxygenation of limb and respiratory muscles in chronic obstructive pulmonary disease (COPD), and to compare exercises that recruit these muscles in healthy participants.The first study, a scoping review that searched 7 databases, demonstrated that, compared to healthy participants, COPD patients display more rapid increases in vastus lateralis deoxygenated hemoglobin and blood flow; and lower muscle tissue saturation during cycling exercise. For the second study, two different exercises were compared in order to investigate alternative ways to train the inspiratory muscles. In healthy participants, we found submaximal intermittent neck flexion (INF) induced quicker and greater deoxygenation of sternocleidomastoid than inspiratory threshold loading (ITL) in healthy participants. INF induced significant metabolic activity of the sternocleidomastoid at a lower perception of effort than ITL. The merits of INF compared to ITL may be advantageous for applications of respiratory muscle training clinically.
Investigation of Stress Adaptation as a Vulnerability in Ovarian Cancer
Keywords: Asparaginase
ATF4
Cancer therapy
GCN2
Integrated stress response
Ovarian cancer

High-grade serous ovarian cancer (HGSOC) is the most prevalent and lethal ovarian cancer subtype. HGSOC cells experience many stressors—including genotoxic, metabolic, and hypoxic stress—generating a cancer-specific stress state. The conserved integrated stress response pathway is activated by four stress kinases, including general control nonderepressible 2 (GCN2), inducing a transcriptional program driven by activating transcription factor 4 (ATF4). GCN2 and ATF4 are elevated in many cancers and associated with poor prognosis and chemotherapeutic resistance. I hypothesized that HGSOC cells rely on GCN2 to adapt to unique stress conditions. I demonstrated that the GCN2-ATF4 pathway was functional in HGSOC cell lines. Downstream signalling was inhibited using novel GCN2 inhibitors, and GCN2 knockout clones confirmed their specificity. Novel GCN2 inhibitors reduced viability of HGSOC cell lines and patient-derived organoids upon stress induction by L-asparaginase (ASNase). Combining GCN2 inhibitors and ASNase may be a promising therapeutic strategy to improve HGSOC survival outcomes.
Extraction of Clove Oil with Lecithin-based Microemulsions Guided by the Hydrophilic-Lipophilic-Difference (HLD) and Net-Average-Curvature (NAC) Model
Keywords: Bifunctional model
Capillary Displacement
Extraction
HLD-NAC
Microemulsion
Polar oil

Current methods for extracting herbal oils, including steam and solvent extraction, suffer from low yields, using large volumes of solvents, and for being time and energy intensive. Capillary displacement, as an emerging extraction method, uses dilute surfactant solutions to promote low interfacial tensions to reduce the capillary pressure that retains triglycerides on the seed matrix. This work adapts this strategy to extract polar oils, specifically eugenol. Polar oils are compounds with dual, surfactant- and oil-like behaviour and their high affinity for the surfactant alters the phase behavior and make separating them from the surfactant difficult. The Hydrophilic-Lipophilic-Difference and Net-Average-Curvature + polar oil models are applied to predict the influence of eugenol in lecithin-based microemulsions and as a guide to develop an extraction process called Solvent-Addition and Self-Emulsification, that including a recycling step for the aqueous phase, produced 18% yield at room temperature and pressure with 5 minutes of extraction time.
Structures of SUR2 NBD1 / Drug Complexes Determined with NMR Spectroscopy and Data Driven Docking
Keywords: ABC Protein
ATP Sensitive Potassium Channel
KCO Drugs
Molecular Docking
NMR Spectroscopy
Sulfonylurea Receptor

ATP-sensitive potassium (KATP) channels are formed by four inward-rectifying K+ channels and four regulatory sulfonylurea receptors (SURs). ATP binding and hydrolysis at the SUR nucleotide binding domains (NBDs) regulates opening of the KATP channel pore. The SUR NBDs are also the sites of binding for KATP channel opener (KCO) drugs, which are diverse in structure and can be broadly categorized into several classes of molecules, including benzothiadiazines (diazoxide), cyanoguanidines (pinacidil and P1075), benzopyrans (cromakalim and Y26763), and nicotinamides (nicorandil). Through NMR binding studies, the identification of specific NBD1 residues involved in binding various KCO drugs were identified. The NMR titration data were used to calculate models of NBD1/drug complexes using the data-driven docking program HADDOCK. Knowledge of the bound complex structure will be used for rational design of more effective drugs that will be used to treat diseases associated with impaired KATP channel function, including hyperinsulinism and heart disease.
A Randomized Investigation of Icosapent Ethyl in Outpatients with COVID-19: Results from the VASCEPA-COVID-19 CardioLink-9 Trial
Keywords: Anti-Inflammatory
Coronavirus Disease 2019 (COVID-19)
High-sensitivity C-reactive Protein
Icosapent Ethyl
Omega-3 Fatty Acids
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

Coronavirus disease 2019 (COVID-19) has had immense global implications on morbidity and mortality. At present, the development of therapeutic agents to combat COVID-19-related insults are considerably restrained. Safe and effective treatment options are urgently needed to reduce disease proliferation, inflammation and symptomatology. In response, the open-label VASCEPA-COVID-19 trial randomized 100 symptomatic COVID-19-positive outpatients in Toronto, Canada, to icosapent ethyl or usual care. Over a 14+3-day follow-up period, treatment with icosapent ethyl (4 g twice per day for 3 days, followed by 2 g twice per day for 11 days) was shown to significantly reduce high-sensitivity C-reactive protein, as well as, improve symptomatology. This study provides novel evidence of icosapent ethyl to have an early anti-inflammatory impact in a modest sample size of COVID-19 ambulatory patients, including the first demonstration of a well-tolerated icosapent ethyl loading dose. ClinicalTrials.gov Identifier: NCT04412018.
Ultra-strong, Lightweight, and Thermally Conductive Hybrid Graphene Nanoplatelets and Glass Fibre Reinforced Polypropylene-Based Composites
Keywords: Graphene Nanoplatelets
Injection Molding
Mechanical Properties
Polypropylene
Structure-Property Relations
Thermal Conductivity

In this work, ultra-strong, lightweight, and thermally conductive hybrid polypropylene-based composites reinforced with graphene nanoplatelets (GnP) and glass fibre (GF) were fabricated and characterized; demonstrating their ability to be tailored for high-performance applications in the automotive industry. GnPs expedited the crystallization of the polymer matrix by serving as seeds for heterogeneous nucleation, while inducing β-crystals. The hybrid composites yielded improved properties greater than the sum of the properties of the individual reinforcing materials, showing a synergistic effect. The synergistic effect was maximized with 0.5wt.% GnP and increased with lower concentrations of GF, whereby the greatest effect was approximately 54% and 65% for the Tensile and Flexural Modulus, and 37% and 39% for the Tensile and Flexural Strength, respectively. Moreover, an 18% weight reduction was achieved with PPGnP0.5GF40 while maintaining the desirable mechanical strengths of PPGF60. Furthermore, the thermal conductivity was maximized with PPGnP5GF50, exceeding that of Neat PP by 201%.
Examining the Role of RNF8 in R-loop Resolution in BRCA1-deficient Breast Cancer Cells
Keywords: BRCA1
Breast Cancer
DNA Damage
R-Loops

BRCA1 repairs DNA double-strand breaks (DSBs) through homologous recombination, therefore, loss of BRCA1 leads to increased genomic instability and tumorigenesis. Our lab observed that loss of Rnf8 in female mice with mammary-specific deletion of Brca1 rescued these mice from the development of mammary tumors. In vitro, our lab previously found that human breast cancer cell lines lacking BRCA1 displayed elevated levels of DSBs with depletion of RNF8, leading to cell death. In this study, using DRIP and ChIP, we demonstrated that loss of RNF8 in BRCA1-deficient cells led to R-loop accumulation and that RNF8 was enriched at R-loop prone genomic loci. We performed IP/MS to identify whether RNF8 interacted with known R-loop suppressors. We validated one interactor, XRN2, however, we found that XRN2’s recruitment to R-loops was not significantly impaired in the absence of RNF8. It remains to be determined if RNF8 is directly or indirectly involved in R-loop resolution.
Exploring the Rheological, Crystallization, and Tensile Properties of Poly(lactide) Stereocomplexes and their Crystalline Network Structures
Keywords: Biopolymers
In Situ Fibrillation
Poly(lactide)
Self-Reinforced Composite
Stereocomplex
Structure-Property Relationships

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.
Sox10, Olig2 and Nkx6.2 Each Generate Unique Oligodendrocyte Lineage Cells when Delivered to GFAP+ Astrocytes
Keywords: Astrocyte
Oligodendrocyte
Reprogramming

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.
The Impact of Social Isolation on Depressive and Anxiety-related Behavior
Keywords: Age
Anxiety
Depression
Isolation
Sex differences
TRPM2

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.
Understanding Medication Self-management in Community-dwelling Adults with Chronic Medication Experience: An Exploratory Concept Mapping Study
Keywords: chronic disease
community-based participatory research
medication therapy management
patient participation
patient-centered care
self-management

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.
Am I Plurilingual? A Narrative Inquiry into One Chinese Plurilingual Student’s Linguistic and Cultural Repertoire in Canada
Keywords: Chinese Heritage Learners
Linguistic and Cultural Repertoire
Narrative Inquiry
Plurilingual Competence
Plurilingualism
Third Space

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.
Studies on the Relationship between After-ripening Regulated Gene Expression and Reactive Oxygen Species in Arabidopsis thaliana Seed Germination
Keywords: after-ripening
after-ripening regulated gene expression
hydrogen peroxide
reactive oxygen species
seed germination
seed storage

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.
Non-invasive Delivery to the Inner Ear: Investigating Blood-labyrinth Barrier Opening using MRI-guided Focused Ultrasound Combined with Microbubbles
Keywords: cochlea
drug delivery
focused ultrasound
gene therapy
inner ear
non-invasive

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.
The Effect of Protein Quality on Post-exercise Anabolism in Active Children
Keywords: Anabolism
Children
Exercise
Growth
IAAO
Protein Quality

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.
Regulation of Proliferation and the Developmental Emergence of Adult Neural Stem Cells
Keywords: Adult Neural Stem Cells
LRIG1
Neurogenesis
NSCs
Quiescent
V-SVZ

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.
Dis-possessed to SK8: Push Pedagogy as Creative Entrepreneurial Inquiry/Interventions into Urban Poverty with the Grrlz of Oasis Skateboard Factory
Keywords: Design
Patriarchy
Skateboard
Skateboarding
Urban Poverty
White Supremacy

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.
Hyperpolarized 129Xe Magnetic Resonance Spectroscopy in a Rat Model of Bronchopulmonary Dysplasia
Keywords: air-blood barrier
bronchopulmonary dysplasia
hyperoxia
hyperpolarized gas
intermittent hypoxia

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.