VictorJuiz/thesis huggingface dataset:
Identification of Novel Substrates of the Ubiquitin E3 Ligase RNF126 and Characterization of its Role in Lipid Droplet Homeostasis

Ubiquitin E3 ligases confer specificity by recognizing target substrates and mediating the final step of the ubiquitination process. Despite this critical role, our understanding of their physiological partners and biological functions remains limited. Here we use a proximity-based protein screen called BioID to explore novel interacting proteins and substrates of the ubiquitin E3 ligase RNF126. We demonstrate that RNF126 can associate with p97 as well as its co-factors UBXD1 and UBXD8 and show that UBXD1 and UBXD8 are bonafide substrates of RNF126. To determine a functional role, we explored the role of RNF126 in UBXD8 mediated functions. We found that stable knockdown of RNF126 in HeLa cells results in smaller LDs following oleate stimulation and that this is due to defective expansion. Together, this work demonstrates the successful use of BioID to identify substrates of ubiquitin E3 ligases and furthers our understanding of the role of ubiquitin in LD biology.

Keywords: BioID
Lipid droplet
p97
RNF126
ubiquitin
UBXD8
Advisor: McGlade, Jane
Behaviour of Multi-layered Laminated Glass under Blast Loading

This thesis outlines a three-phase research program that was developed to determine the accuracy and applicability of various software packages in predicting the behaviour of multi-layered laminated glass windows under blast loading. Experimental data was collected through the completion of full-scale field blast tests. Two unique window compositions were examined at two different scaled distances, with a total of eight specimens being tested. Small-scale laboratory testing followed on beams of the same composition to investigate the behaviour of multi-layered laminated glass and to derive a static resistance function for the layup. Finally, the windows were modelled using predictive software, and the outputs of these programs were compared to the field-collected data.

Advisor: Packer, Jeffrey A
Seica, Michael V
Using Computers to Assess Cognition in MS: Improving Tried and Tested Indices to Capture Real World Challenges

Cognitive dysfunction is common in people with multiple sclerosis (MS) and causes limitation in activities of daily living. Current cognitive screens are limited by time and cost requirements and they lack ecological validity. The objective of the present study was to develop an improved method of cognitive assessment using real-world distracters. A sample of 102 MS subjects and 69 healthy controls underwent testing with a modified computerized Symbol Digit Modalities Test (c-SDMT) and the Minimal Assessment of Cognitive Functioning in MS battery. Half completed the distracter c-SDMT and half non-distracter. Relative to the traditional SDMT, significantly more MS subjects were impaired on the distracter c-SDMT, but not on the non-distracter test. The distracter test had a sensitivity of 82% and specificity of 80% in detecting global cognitive impairment. The incorporation of distracters improves the sensitivity of the c-SDMT and offers a quick and easy method for detecting cognitive dysfunction.

Keywords: Cognition
Multiple Sclerosis
Advisor: Feinstein, Anthony
Modeling of Interior Beam-column Joints for Nonlinear Analysis of Reinforced Concrete Frames

Beam-column connections are often assumed rigid in traditional frame analysis, yet they undergo significant shear deformations and greatly contribute to story drifts during earthquake loading. Although local joint models are available in the literature for the investigation of single, isolated joints, there is a lack of holistic frame analysis procedures simulating the joint behavior in addition to important global failure modes such as beam shear, column shear, column axial, and soft story failures. The objective of this study is to capture the impact of local joint deformations on the global frame response in a holistic analysis by implementing a joint model into a previously-developed global frame analysis procedure. The implemented joint element simulates joint shear deformations and bar-slip effects. Concrete confinement effects are also considered so that both older and new joints can be modeled. The developed procedure provides better overall load-deflection response predictions including the local joint response.

Advisor: Vecchio, Frank J
Guner, Serhan
The Short-term and Long-term Effects of High-fat Diet on Adult Hippocampal Neurogenesis

Diet is an important factor in regulation of adult hippocampal neurogenesis (AHN). Diets that are high in saturated fatty acids have been shown to be associated with reduction in AHN specially in early developmental stages of the animal. Furthermore, these observed diet effects on AHN may be involved in mediating the cognitive impairments in animals on high-fat diets. The experiments presented in this thesis aimed to examine the short-term and long-term effects of a 4-week or 8-week period of high-fat diet (HFD; 45% of total energy contributed by saturated fatty acids) on AHN in young adult rats. Different stages of AHN were examined in this study including the proliferation, differentiation and maturation stages. Overall, contrary to what was expected, HFD did not cause a significant change in the level of AHN in any of the stages studied.

Keywords: Adult neurogenesis
Dentate gyrus
Diet
High-fat diet
Hippocampus
Advisor: Wojtowicz, Martin
The Characterization of TiO2-coated Quartz Membranes and Their Application in NOM Degradation

This research characterized novel TiO2-coated porous quartz disks (membranes) physically and chemically. Uncoated and TiO2-coated membranes were examined and compared using SEM images among other methods, which confirmed the presence of TiO2 deposits. The general adsorption characteristics and photoreactivity of these membranes was evaluated with methylene blue, MB, degradation experiments conducted in both batch configuration and in an enclosed reactor operated in down-flow and up-flow modes. Up-flow mode was found to be the most reliable reactor configuration, and 40 -- 70% MB removal was achieved in this mode using 0.2 -- 0.5 mg/L MB. The degradation of natural organic matter, NOM, has been evaluated using both lab-prepared and river waters under photolytic, dark and photocatalytic conditions. Unexpectedly, no significant decrease in DOC or UV-254 was observed in photocatalytic experiments compared to results from the adsorption or photolytic experiments, suggesting that adsorption was the prominent process of NOM removal under the conditions tested.

Keywords: advances oxidation processes
membranes
NOM
photochemistry
TiO2 photocatalysis
water treatment
Advisor: Andrews, Susan
Exploring the Acceptability of Exercise in Students Seeking Treatment for Depression: 'Another tool in the tool-box.'

The high prevalence of depression in university students is placing an increasing demand on campus mental health services to provide adequate and timely treatment. Exercise is an effective and accessible treatment for depression; however, acceptability of exercise as a treatment remains unclear. By employing a qualitative research design that incorporated the use of semi-structured interviews, the current study explored the perceptions of exercise as a potential depression treatment among fifteen students (thirteen females; 18-30 years) seeking treatment for depression. Students' acceptance of exercise for treating depression was informed by prior interest in exercise and physical activity, belief in the benefits of exercise on psychological well-being, and an open attitude towards alternative approaches to managing depression. Referral to supervised exercise may be required to facilitate exercise participation. Findings strengthen the case for recommending exercise within University mental-health services and provide useful insights into students preferences for designing exercise for depression interventions.

Advisor: Faulkner, Guy E
ERP-based Detection of Brain Pathology in Rat Models for Preclinical Alzheimer's Disease

Early pathological features of Alzheimer's disease (AD) include the accumulation of hyperphosphorylated tau protein (HP-tau) in the entorhinal cortex and progressive loss of basal forebrain (BF) cholinergic neurons. These pathologies are known to remain asymptomatic for many years before AD is clinically diagnosed; however, they may induce aberrant brain processing which can be captured as an abnormality in event-related potentials (ERPs). Here, we examined cortical ERPs while a differential associative learning paradigm was applied to adult male rats with entorhinal HP-tau, pharmacological blockade of muscarinic acetylcholine receptors, or both conditions. Despite no impairment in differential associative and reversal learning, each pathological feature induced distinct abnormality in cortical ERPs to an extent that was sufficient for machine classifiers to accurately detect a specific type of pathology based on these ERP features. These results highlight a potential use of ERPs during differential associative learning as a biomarker for asymptomatic AD pathology.

Keywords: Alzheimer's disease
Asymptomatic preclinical stage
Cholinergic deficiency
Event-related potentials
hyperphosphorylated tau
support vector machine classifier
Advisor: Takehara-Nishiuchi, Kaori
Examining Audiovisual Integration in Amblyopia using the Sound-induced Flash Illusion

Amblyopia is a neurodevelopmental disorder associated with reduced vision in one or both eyes, caused by abnormal visual experience during early childhood. The sound-induced flash illusion is a task in which flashes and sounds are presented concurrently, and the number of sounds influences the number of perceived flashes. This study examines the temporal binding window of audiovisual integration in amblyopia using the sound-induced flash illusion at different stimulus onset asynchronies of flashes and sounds. Eleven participants with amblyopia and sixteen visually normal controls were tested on the sound-induced flash illusion. Participants with amblyopia were equally susceptible to the illusion as controls, and showed a widening of the temporal binding window on the "fission" subset of the illusion (two sounds, one flash, percept of two flashes) when viewing binocularly and when the sounds precede the flash. This binocular-specific difference implies potential abnormal temporal integration in real-world situations.

Keywords: amblyopia
audiovisual integration
multisensory integration
sound-induced flash illusion
temporal binding window
visual deprivation
Advisor: Wong, Agnes
Goltz, Herbert
Detailed Modelling of CO2 Addition Effects on the Evolution of Particle Size Distribution Functions in Premixed Ethylene Flames

This study investigates computationally the influence of CO2 addition on the sooting behaviour in premixed ethylene/ oxygen/ argon burner stabilized stagnation flames at the atmospheric pressure. The discrete sectional approach combined with a reversible nucleation model and a novel model of reversible polycyclic aromatic hydrocarbon (PAH) condensation were employed to solve the size evolution of the particle size distribution function (PSDF). The predicted temperature profiles and PSDFs are in reasonably good agreement with the experimental data for nascent soot measured in the burner stabilized stagnation configuration. The evolution of the PSDFs shows that CO2 addition reduces the soot nucleation and mass growth rates, consequently lowering the soot yield. The addition of CO2 reduces the concentrations of H, C2H2, and C6H6, which all suppress the soot formation process through a chemical effect, while its thermal effect is negligible.

Keywords: CO2 addition
Particle size distribution function
Premixed ethylene flame
Sectional approach
Sooting behaviour
Advisor: Thomson, Murray J.
Explorations into the Nucleophilicity of Aziridine and Utilization of Boron-containing Building Blocks in Organic Synthesis

Synthetic methods that achieve a high level of molecular complexity in a minimal number of steps using simple starting materials are highly valuable transformations in organic chemistry. Borylated ketenimines, representing a new class of [1,2]-amphoteric reagents, have been shown to be valuable intermediates in the rapid synthesis of alpha-borylazetidimines and 3-boryliminocoumarins. Herein, a successful expansion of the scope of these reactions has been demonstrated through trapping the borylated ketenimine intermediate in situ with various imines and salicylaldehyde derivatives. In addition, efforts toward synthesizing MIDA-boryl formate and MIDA-boryl formic acid (both [1,1]-amphoteric) via oxidation of hydroxymethyl MIDA boronate are reported. This led to the synthesis of a diboronate ester containing a BC(O)O structural motif. Also, for the purpose of better understanding the reactivity of aziridine aldehydes ([1,3]-amphoteric reagents), preliminary investigations into quantifying the nucleophilicity of aziridine suggest its nucleophilic character is weaker than that of other small, cyclic secondary amines.

Keywords: amphoteric molecules
aziridine
organoboron chemistry
Advisor: Yudin, Andrei K
The Impact of STEM Outreach Programs in Addressing Teacher Efficacy and Broader Issues in STEM Education

This study explores the potential of the Outreach Workshops in STEM (OWS) to affect Science, Technology, Engineering, and Mathematics (STEM) teachers’ content knowledge, self-efficacy, and pedagogical approaches, as well as its viability as a potential form of professional development (PD). The data for the thesis is taken from a larger longitudinal study looking at the potential of OWS to influence middle school students’ and teachers’ attitudes and beliefs around STEM. The study employs a mixed-methods design, utilizing surveys, open-ended questions, interviews, and observations. The findings show that there were no significant changes in teachers’ content knowledge, confidence, or pedagogical approaches. However, the majority of participants reported that they learned new teaching ideas and considered the workshops to be an effective PD opportunity.

Keywords: outreach programs
professional development
STEM
teacher efficacy
Advisor: Gitari, Wanja
Residual Effects of Cannabis on Young Drivers' Performance of Driving-related Skills: An Interim Analysis

The effects of cannabis may not be limited to the time period immediately after use. This current study examines the residual effects of cannabis on driving-related skills in young drivers using a high-fidelity driving simulator. The study is a randomized, double-blind, placebo-controlled mixed design trial. Eligible participants are regular cannabis-using drivers, aged 19-25, who smoke cannabis 1-4 days per week. Measures of simulated driving performance, cognitive and psychomotor functions, and subjective drug effects are collected concurrently with levels of cannabinoids in biological fluids before and after a one-time cannabis administration of active (12.5% THC) or placebo (

Keywords: Cannabis
Cognitive behaviours
Driving performance
Residual effects
Simulated driving
THC
Advisor: Le Foll, Bernard
Altered Expression of Cellular Markers in Molecular Brain Aging

The molecular aging of the human brain encompasses pervasive transcriptome changes associated with â normalâ brain aging that occur in local cortical circuits comprised of GABA neurons, pyramidal cells, and astrocytes. Cortical samples obtained from a novel postmortem human cohort were analyzed using RT-qPCR technology to assess changes in the expression of nine markers representative of neuropeptide signalling, synaptic function, calcium regulation, and glial activation within cortical cellular networks that occur in congruence with a pervasive molecular program mediating brain aging. Presynaptic interneuron markers displayed decreases in expression in aged subjects compared to young controls, whilst postsynaptic interneuron marker expression was increased, as was the expression of glial markers. Although changes in extrasynaptic glutamate marker expression were not significantly different, there was a nominal decrease in their expression in aged subjects. Altogether, these results replicate findings of pervasive molecular changes in the aged cortex, and suggest consequences for cortical network function.

Advisor: Sibille, Etienne
The Sparse Engram of the Lateral Amygdala

Memories are stored by discrete changes in the brain, collectively referred to as an engram, that allow activity related to an experience to be reactivated in the future. Associative memories related to threatening stimuli are stored in the lateral amygdala (LA), where the engram is composed of a sparse proportion of neurons. The work in this thesis tests the prediction that this proportion is consistent between memories and investigates mechanisms that may contribute to this consistency. First, it is shown that the proportion of LA engram neurons remains constant between memories of different strengths. Then, it is shown that this proportion increases when inhibitory, parvalbumin-positive interneurons are suppressed during learning. Together, these results provide additional support for the idea memories are stored in sparse assemblies of neurons and suggest a novel role for parvalbumin-positive interneurons in memory formation.

Keywords: Amygdala
Engram
Interneurons
Memory
Parvalbumin
Advisor: Josselyn, Sheena A
Effectiveness of Standard vs Individualized Treatment on Smoking Cessation and Cue Reactivity: An fMRI Study

Greater smoking cue reactivity has been associated with a higher likelihood of relapse; however, titrated dosing of the nicotine patch (tNRT) may have the potential to lower relapse rates. This study assessed the efficacy of titrated, standard dose tNRT and combination nicotine replacement therapy (NRT) as well as evaluated their impact on cue reactivity. Eighteen individuals began standard dose tNRT and those who failed to quit smoking after the second week of treatment were randomized to one of the other two treatments. The participants receiving standard dose tNRT were the only ones to display a change in reactivity in brain areas involved in cue-elicited craving and incentive salience. Despite its inability to modify cue reactivity, titrated therapy was associated with higher cessation rates (75%) than combination NRT (43%) and it was comparably safe. Therefore, titrated therapy may be a superior alternative for smokers who find standard dose tNRT ineffective.

Keywords: Clinical Trial
fMRI
Neuroimaging
NRT
Smoking Cessation
Advisor: Zawertailo, Laurie
Selby, Peter
Msh2-deficiency Affects the Differentiation and Proliferation of Small Intestinal Epithelial Cells

Mutations in mismatch repair genes, such as MSH2, are common lesions in Hereditary Nonpolyposis Colorectal Cancer and approximately 15% of all sporadic human colorectal cancers. Using organoids extracted from Msh2-/- murine intestines, we uncover structural differences in crypt development that can be attributed to Msh2-deficiency. Compared to Msh2+/- organoids, Msh2-/- organoids show a stunted ability to form new crypt protrusions during the first week of development. FACS analysis showed Msh2-/- freshly extracted intestinal epithelial cells and cultured organoids display a highly proliferative phenotype, marked by an increased percentage of EdU+ cells. Differentiation of intestinal epithelial cells is also affected by Msh2-deficiency as Msh2-/- epithelial cells and organoids display an increased CD24+ compartment, relative to Msh2+/-. The addition of butyrate to organoid culture media differentially affects proliferation across genotypes. Using the knowledge acquired in this study, we gain a further understanding of how Msh2-deficiency impacts intestinal structure and function.

Keywords: Butyrate
Colorectal Cancer
Glucose
Mismatch repair
Msh2
Organoids
Advisor: Martin, Alberto
Mental Health Outcomes in Survivors of Childhood Cancer

The current literature surrounding their mental health outcomes is limited. This study addresses limitations in the field by using healthcare administrative databases to compare the rates of mental health care utilization and the risk for a severe mental health episode between pediatric cancer survivors and matched population controls. Additionally, this study assesses the impact of demographic, disease, and treatment level predictors on mental health outcomes. Overall, pediatric cancer survivors were more likely to utilize mental health care (Adjusted Rate Ratio 1.31, 95% CI 1.16-1.48), but were not at greater risk of severe mental health episodes (Hazard Ratio 1.11 95% CI, 0.99-1.25). Pediatric cancer survivors were identified to be at increased risk of mood/affective disorders and psychotic disorders. In general, predictors of mental health outcomes in survivors were similar to those in the general population. This study provides novel information to a limited field, and a strong platform for future studies.

Keywords: mental health
pediatric cancer
survivorship
Advisor: Nathan, Paul
A Chemical Genetics Approach to Explore Anthocyanin Regulation in Nitrogen-deprived Arabidopsis Seedlings

Plants often experience varying soil nitrogen levels during their life cycle, and adjust growth and development to accommodate these changes. In the present study, a chemical genetics approach was implemented to discover molecular components involved in the induction of anthocyanin biosynthesis, in response to altered nitrogen levels. Using a robust high-throughput approach, a chemical library was screened to discover compounds capable of attenuating anthocyanin levels in nitrogen-deprived Arabidopsis seedlings. Chemical screens were successful in identifying four compounds that appear to mis-regulate anthocyanin accumulation during nitrogen deprivation. A chemical-induced phenotype was characterized, and the results indicate that chemical application must occur at a specific developmental stage. Furthermore, low nitrogen-induction of anthocyanins is highly sensitive to chemical application, and chemicals appear to exert their effect throughout early seedling growth. Future mutational and genome-wide studies will bridge the gap in understanding the link between anthocyanin biosynthesis and nitrogen availability.

Keywords: Anthocyanins
Arabidopsis thaliana
Chemical genetics
Nitrogen deprivation
Advisor: Campbell, Malcolm M
Concordance between Need and Receipt of Social Support, Independence and Associations with Well-being in Women with Systemic Lupus Erythematosus

Women living with Systemic Lupus Erythematosus (SLE) have the potential for increased support needs due to SLEâ s often severe and unpredictable symptoms. However, they may also strive to maintain their independence. A cross-sectional survey examined need for and evaluations of three types of social support in five diverse life domains and their associations with well-being and disease appraisals, demographic, clinical and social network characteristics. One hundred sixty-three (163) women, aged 19 â 88, were surveyed, drawing on an existing clinical cohort. Across domains, occurrences of concordance between the respondentsâ reported need for support and the support they received were associated with significantly greater well-being than occurrences of discordance. These findings held regardless of whether respondents were independent or dependent on others. This study highlights the need for interventions that emphasize optimizing social support - balancing independence and support needs - rather than assuming that maximizing support is always desirable.

Keywords: lupus
SLE
support
Advisor: Beaton, Dorcas
Gignac, Monique