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Type d'Item : Item , Clinically Relevant Approaches for Targeting Triple-Negative Breast Cancer Stem Cells While Enhancing Anti-Tumor Immunity(Université d'Ottawa | University of Ottawa, 2026-08-11) Mediratta, Karan; Wang, LishengTriple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype characterized by high rates of therapeutic resistance, disease recurrence, and poor survival outcomes. Although chemotherapy is the current standard of care, recent advances in immunotherapy have provided only modest clinical benefit. These limitations are driven in part by cancer stem cells (CSCs) that promote treatment resistance, tumor heterogeneity, and immune evasion. This thesis investigates three translational approaches aimed at targeting heterogenous CSC populations while enhancing anti-tumor immunity in clinically relevant TNBC models. Using in silico molecular docking, I first identified the over-the-counter flavonoid supplements quercetin and luteolin as potential inhibitors of the immune-suppressing ectoenzyme CD73, and the CSC-associated YAP and Wnt signaling pathways. In combination with the chemotherapeutic agent paclitaxel, quercetin and luteolin antagonized the enrichment of CSCs and reduced CD73 in human TNBC cell lines, patient-derived tumor fragments, and syngeneic immune-competent mouse models. Next, I showed that combining the chemotherapeutic agent doxorubicin with the clinically approved ALDH inhibitor disulfiram broadly upregulated PD-L1 expression on CSCs, sensitizing these otherwise resistant populations to the anti-PD-L1 atezolizumab, irrespective of baseline PD-L1 status. Mechanistically, CSC-associated STAT3 signaling was identified as a potential mediator of this phenotypic shift, providing a rationale for leveraging PD-L1 intrinsic signaling vulnerabilities across heterogenous CSC populations. Lastly, I explored the repurposing of pathogenic bacterial effector proteins OspG from Shigella flexneri and SseL from Salmonella enterica to preferentially inhibit CSC-associated NF-κB signaling without inducing the acquired tolerance commonly observed with preclinical NF-κB inhibitors. Co-expression of OspG and SseL significantly suppressed tumor growth in an orthotopic TNBC mouse model, supporting their potential as novel therapeutic candidates for overcoming CSC-driven treatment resistance. Together, these studies concurrently address the challenges of CSC heterogeneity and immune evasion in TNBC. By showing the therapeutic potential of rationally designed combination strategies at clinically achievable dosage, this thesis establishes a translational foundation for the development of more effective, durable, and accessible therapeutic approaches for TNBC.Type d'Item : Item , Climate Change Science Communication: Exploring Environmental Scientists’ Views and Engagement on Social Media(Université d'Ottawa | University of Ottawa, 2026-08-11) Wenghofer, Alysha; Reis, Giuliano; Brown, AdamSocial media is becoming a necessary tool for modern science communication about climate change. When done responsibly, social media science communication can not only inform the public but also help to advocate for climate activism and evidence-based environmental policy change. However, little is known about the engagement of Canadian climate change experts, such as environmental scientists, on social media. This research explores a small sample of Canadian environmental scientists’ views and engagement on social media as a tool for climate change communication. Focusing on participants affiliated with an environmentally oriented faculty at a university in Eastern Canada, this study employs a thematic analysis of in-depth interviews and social media content to examine how professional engagement on social media (or lack thereof) for climate science communication is shaped by the affordances of the platforms. The study further explores the platforms employed, motivations, challenges, and what institutional support may be necessary to promote social media science communication. It was found that the participants of the study do engage on social media to communicate their research, but at varying capacities. The number of challenges that they face when engaging on social media outweighs the number of motivations. However, there is still motivation to utilize the affordances of social media to communicate science and encouragement for other environmental scientists to do the same. According to the participants, support from scientists’ institutions through resources and tools, social media etiquette and skill training, or simply a positive institutional culture toward social media, may provide the skills and confidence needed for this evolving form of public outreach. These findings provide a preliminary snapshot of eastern Canadian environmental scientists’ contribution to climate change communication using social media platforms, and it may serve as a jumping point for further investigation.Type d'Item : Item , Engineered Neural Stem Cells for Targeted Glioblastoma Therapy: Strategies for Cell Recognition and Response and Cytotoxicity(Université d'Ottawa | University of Ottawa, 2026-08-11) Verge, Hannah; Lorimer, IanGlioblastoma (GBM) remains the most aggressive primary brain malignancy, with median survival of 12–15 months despite maximal treatment. Its resistance to conventional therapy is driven by intratumoral heterogeneity, diffuse invasion, an immunosuppressive tumor microenvironment, and the blood-brain barrier, which restricts delivery of systemic biologics. Engineered neural stem cells (NSCs) offer a promising solution to these challenges owing to their intrinsic tumor tropism, which enables localized and sustained therapeutic delivery directly within the GBM microenvironment. This study describes the engineering of peripheral blood-induced NSCs (PBiNSCs) derived from adult blood through OCT4-free epigenetic reprogramming as a dual-strategy therapeutic platform for GBM. In the first strategy, PBiNSCs were engineered with a SyNthetic Intramembrane Proteolysis Receptor (SNIPR) system to couple tumor antigen recognition to inducible expression of light-chain leader PTEN-Long (lclPTENL), a secretable isoform of the tumor suppressor PTEN. This represents the first demonstration of SNIPR functionality in PBiNSCs, establishing them as a new cellular vehicle for synthetic receptor platforms. Initial validation using an anti-CD19 SNIPR confirmed antigen-dependent, dose-responsive activation in both bead-based and cell-based co-culture systems. The SNIPR was subsequently retargeted toward two GBM-associated antigens: IL13Rα2, using a mutant IL13(E13Y) ligand domain, and EGFRvIII, using the tumor-specific MR1 single-chain variable fragment. The MR1-EGFRvIII SNIPR demonstrated highly selective activation, with 74–81% BFP-positive cells in EGFRvIII-expressing primary GBM co-cultures compared to near-background levels in wild-type controls, an effect maintained in a 3D onco-neurosphere model. By contrast, the IL13(E13Y)-based SNIPR exhibited high sensitivity activation, attributed to residual IL13Rα2 cross-reactivity and the ultra-high affinity of the protein-based binding domain. SNIPR-driven lclPTENL expression was confirmed in CD19 co-culture conditions, and conditioned media from PBiNSCs constitutively expressing lclPTENL induced a statistically significant increase in p16 expression in primary GBM cells, demonstrating downstream biological activity and validating the therapeutic rationale for PTEN restoration. In the second strategy, PBiNSCs were engineered to constitutively secrete a bispecific Fc fusion protein simultaneously targeting CD47 a ubiquitous "don't eat me" signal overexpressed on GBM cells and either IL13Rα2 or EGFRvIII. The construct employs knob-into-hole Fc engineering and a P2A/furin co-expression strategy to produce a stable heterodimeric bispecific from a single transcript. Both the IL13/SIRPα and MR1/SIRPα variants were successfully expressed and secreted by engineered PBiNSCs, and binding to primary GBM cell lines was confirmed by Western blot. A novel antigen-affinity purification strategy using biotinylated EGFRvIII as a capture ligand enabled selective isolation of functionally intact bispecific protein. Collectively, these findings establish a proof-of-concept for a modular, cell-based delivery platform that combines the tumor-tropic properties of PBiNSCs with SNIPR-controlled therapeutic gene expression and innate immune checkpoint blockade, addressing multiple mechanisms of GBM treatment resistance simultaneously.Type d'Item : Item , Reinforcement Learning for Pricing American Options(Université d'Ottawa | University of Ottawa, 2026-08-11) Heydari, Shamimeh; Boire, François-Michel; Fraser, MaiaThis thesis develops a martingale-based reinforcement-learning (RL) framework for pricing European and American options. For each learning mode, a shared European option price surface is learned from risk-neutral paths and then used as the baseline for an American early-exercise correction. Offline learning uses complete simulated paths, whereas online learning uses one-step martingale increments. The American option premium-learning stage uses a penalized, entropy-regularized two-action stopping formulation, and prices are evaluated through the deterministic stopping rule obtained after training. Under Black–Scholes dynamics, maximum American execution-price errors are 2.40% offline and 2.97% online. Under Merton jump–diffusion dynamics, a direct transfer of the Black–Scholes implementation did not adequately capture early exercise. Improving state-space and exercise-date coverage and reorganizing the updates while retaining the two-stage formulation yields offline and online mean errors of 1.31% and 1.09%, with maxima of 2.28% and 2.09%, respectively. Both methods recover meaningful early-exercise behaviour.Type d'Item : Item , TOP 2025: An update to the Transparency and Openness Promotion Guidelines(2026-08-05) Grant, Sean; Corker, Katherine S.; Mellor, David; Stewart, Suzanne L. K.; Mayo-Wilson, Evan; Cashin, Aidan G.; Lagisz, Malgorzata; Moher, David; Umpierre, Daniel; Barbour, Virginia; Buck, Stuart; Collins, Gary S.; Hazlett, Haley F.; Hrynaszkiewicz, Iain; Lee, Carole J.; Parker, Timothy H.; Rethlefsen, Melissa L.; Toomey, Elaine; Nosek, Brian A.Abstract Background Transparency and openness are core scientific values that enable independent verification of reported research results. The Transparency and Openness Promotion (TOP) Guidelines, first published in 2015 (TOP 2015), provided a flexible framework for journals to design and implement publication standards promoting these values. Over the past decade, widespread use of TOP 2015 contributed to valuable evidence and feedback for refinement. Main Text The TOP Advisory Board undertook a comprehensive update of TOP 2015 that went into effect in 2025 (TOP 2025). The update introduces an explicit conceptual framework clarifying its primary objective: improving the verifiability of empirical research claims. Standards are reorganized into three categories (Research Practices, Verification Practices, and Verification Studies) that resolve conceptual and structural limitations of TOP 2015. Research Practices include seven discrete practices implemented in three ways: Disclosed, Shared and Cited, and Certified. Verification Practices introduce standards for computational reproducibility and results transparency, while Verification Studies enumerate empirical research designs and publication formats that support verification of results. Language now centers on researchers and studies (rather than journals) to facilitate adoption by funders, research organizations, preprint servers, evidence curators, and other interest-holders. These changes promote flexible implementation and contextual tailoring. Conclusions TOP 2025 retains the core strengths of TOP 2015 while addressing feedback from a decade of implementation and advances in open science. Rather than a universal mandate, it provides a shared, adaptable framework to coordinate the design, implementation, and communication of open policies across interest-holders.