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Type d'Item : Item , The Role of PGC-1α in Breast Cancer Liver Metastasis(Université d'Ottawa / University of Ottawa, 2026-09-09) Rahimi, Elena; St-Pierre, JulieBreast cancer liver metastasis is a clinically devastating event associated with poor prognosis and limited treatment options, yet the metabolic determinants that govern whether disseminated breast cancer cells can successfully colonize the hepatic microenvironment remain poorly understood. Liver-tropic breast cancer cells exhibit unexpectedly low expression of PGC-1α, a master regulator of mitochondrial biogenesis and oxidative phosphorylation (OXPHOS), and instead rely predominantly on a glycolytic metabolic program. Whether this glycolytic phenotype constitutes a metabolic optimum for hepatic colonization, or alternatively reflects a suboptimal default state whose reprogramming through PGC-1α gain-of-function could enhance metastatic fitness, had not been directly tested. Equally unresolved is whether the PGC-1α-dependent oxidative metabolic state of host hepatocytes independently influences the permissiveness of the hepatic microenvironment for metastatic colonization. This thesis addressed these questions through a dual-compartment seed-and-soil experimental strategy. Stable PGC-1α-overexpressing and matched empty-vector control variants of the liver-tropic 2792 murine breast cancer cell line were generated by lentiviral transduction and characterized by Seahorse extracellular flux analysis, genome-wide RNA sequencing, and targeted LC-MS/MS metabolomics. Hepatocyte-specific Ppargc1a knockout (KO) mice were generated using Alb-Cre-mediated loxP recombination and validated by PCR genotyping. Metastatic colonization efficiency was assessed using orthotopic mammary fat pad implantation and intrasplenic portal vein injection with blinded digital quantification of hepatic and pulmonary metastatic burden. PGC-1α overexpression in liver-tropic breast cancer cells significantly increased basal and maximal mitochondrial ATP production rates and enlarged spare respiratory capacity, while concurrently reducing maximal glycolytic output. PGC-1α selectively increased the expression of Sod2 (manganese superoxide dismutase) and Uqcrc1 (respiratory Complex III subunit). Genome-wide RNA sequencing identified "Oxidative phosphorylation" as the overwhelmingly dominant activated KEGG pathway. Targeted metabolomics confirmed enrichment of serine-glycine one-carbon metabolism, tricarboxylic acid cycle (TCA), and OXPHOS metabolite sets, with O-phosphoserine and adenosine as the two metabolites elevated in PGC-1α-overexpressing cells, providing multi-omic convergence on the same core biological programs. In vivo, PGC-1α overexpression had no effect on orthotopic primary tumor growth yet increased pulmonary metastatic area more than threefold following spontaneous dissemination. In the intrasplenic liver colonization model, PGC-1α overexpression dramatically increased hepatic lesion number. In striking contrast, hepatocyte-specific Ppargc1a deletion produced no significant change in hepatic metastatic colonization efficiency across all host genotypes. These findings establish that PGC-1α-driven metabolism in the tumor cell is a potent, cell-autonomous amplifier of breast cancer hepatic metastatic colonization competence, operating through enhanced mitochondrial bioenergetic reserve, antioxidant capacity, and serine-one-carbon metabolic flux. The metabolic state of the host hepatocyte is dispensable as a determinant of colonization efficiency, demonstrating that in the seed (breast cancer cell)–soil (liver tissue) PGC-1α-dependent metabolic duality, the seed’s PGC-1α metabolic programming is the decisive variable. This work resolves a previously unaddressed biological paradox, identifies PGC-1α-driven metabolic pathways as targetable vulnerabilities in metastatic breast cancer, and provides a molecularly grounded rationale for stratifying patients with PGC-1α-high metastatic disease for metabolically targeted therapeutic intervention.Type d'Item : Item , On the Clock? An Empirical Investigation of Psychological Time Distortions(Université d'Ottawa / University of Ottawa, 2026-09-09) Walker, Jesika; Cousineau, DenisThe study of time perception typically involves asking people to guess how long a task took to complete. This is called a duration estimate. The accuracy of their estimate is then compared with the actual task's duration. This approach is widely used for brief tasks and it underpins several models of psychological time distortion. However, duration estimates may not fully capture the subjective experience of time. This thesis was thus an investigation into additional measures of temporal experience (estimate uncertainty and passage of time judgements). These measures were tested across varying experimental conditions (increasingly longer task durations; levels of task difficulty; intentional vs. incidental encoding of time). The first chapter of this thesis synthesizes the extant literature on duration estimates, estimate uncertainty, and passage of time judgements. The second chapter outlines a series of three experiments investigating two main questions: 1) At what timescales traditional models accurately predict duration estimation? 2) Under what conditions are passage of time judgments and duration estimates related? The third chapter synthesizes and discusses the results. Although there was no direct, consistent relationship between subjective pace of time experienced throughout the task (passage of time judgements) and duration estimate accuracy across experiments, an indirect relationship emerged. The two forms of time judgements are perhaps indirectly related through the information processing demands of the task. Passage of time judgements rely heavily on internal task appraisals (e.g., boredom), which vary with task difficulty and duration, whereas duration estimates fit better within traditional models of time perception that predict estimation accuracy in single-task versus dual-task conditions. Together, these findings highlight important distinctions between different forms of temporal judgment and provides insight into the complexity of how time is experienced and reported.Type d'Item : Item , Discrimination and Identification of Speakers in Native and Non-Native Languages: A Comparison of Monolingual and Bilingual Infants(Université d'Ottawa / University of Ottawa, 2026-09-09) Guerra, Julia; Fennell, Christopher T.The ability to recognize and track voices is paramount in language development. Voice recognition occurs by discriminating auditory information provided by the speaker. Personal differences create unique voice characteristics and affect the sounds produced in speech, which helps listeners recognize a speaker as uniquely different from others. Discriminating voices is an important process, beginning prenatally and developing in the first stages of language acquisition. This dissertation has as its objective to evaluate bilingual infant's perception of speaker traits and discrimination of voices across and within a native language (i.e., code switching). Study 1 used a sample of 21 bilingual infants (n 7-months=13; n 11-months=8) to explore bilingual ability to track changes in speakers and languages produced. Results showed that bilingual infants at 7- and 11-months track new voices and languages in a native language. Study 2 used a sample of 30 infants (n bilingual=12; n monolingual=18) to explore bilingual ability to track changes in speakers and languages produced within a varied language environment (i.e., one speaker code switching). A monolingual group was added as a point of comparison. Results demonstrated that bilingual infants at 7- and 11-months track speaker identity and notice changes in voices and languages produced in a varied language environment. Bilingual infants at 11-months of age reduced their attention towards language code-switching and maintained focus on changes in speakers. The monolingual infants were able to track changes in speaker and languages despite being tested in a mixture of native and non-native languages. Results from this dissertation highlight the nuances to bilingual and monolingual language development, specifically in the ability of tracking voices. Results add to our understanding of the interconnected development of tracking linguistic and speaker information.Type d'Item : Item , Measuring Plutonomy Intensity Under Data Deprivation: An Axiomatic Index(2026-09-09) Makdissi, Paul; Yazbeck, MyraMeasuring top-income inequality typically requires household surveys merged with tax records, or Pareto tails fitted to survey data, resources unavailable across much of the developing world. In this note, we propose a simple plutonomy intensity index estimable from alternative sources. Three axioms, within-group irrelevance, joint income scaling invariance, and plutocratic income monotonicity, characterize the class of indices ranking distributions exactly as the plutocrat-to-ordinary mean income ratio does. The index also satisfies anonymity, population invariance, and a restricted transfer principle. We illustrate its use in the Arab region, approximating it using the Forbes Billionaires List and World Bank macroeconomic data.Type d'Item : Item , Does a Regular Menstrual Tampon or an Intravaginal Pessary Mitigate Urine Leakage While Running Among Females Who Experience Exercise-Induced Urinary Incontinence?(Université d'Ottawa / University of Ottawa, 2026-09-08) Collins, Grace; McLean, LindaExercise-induced urinary incontinence (EI-UI), urine leakage experienced predominantly during exercise, affects nearly 40% of females who participate in high-impact activities and is a common barrier to exercise participation. In this randomized assessor-blind crossover trial, 30 adult females with EI-UI completed three standardized treadmill protocols: one without intervention, one with a self-fitted Uresta® pessary, and one with a regular menstrual tampon, with the latter two administered in randomized order. The primary outcome was the EI-UI Severity Index, a composite of self-reported leakage frequency and perceived volume during the run. Secondary outcomes included pad weight gain during the run, exercise-induced pelvic floor tissue strain assessed via transperineal ultrasound imaging, and user self-reported experience. Both devices significantly reduced EI-UI Severity Index scores compared to no intervention, with the pessary offering significantly greater symptom reduction compared to the tampon. The pessary significantly reduced pad weight gain while the tampon did not. Neither device influenced the extent of exercise-induced pelvic floor tissue strain. These findings support the use of the self-fitted Uresta® pessary and a regular menstrual tampon as effective, self-administered conservative management strategies for EI-UI in active females, with the pessary being superior to a menstrual tampon.