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PHYLOGENOMIC AND MOLECULAR SIGNATURE-BASED APPROACHES FOR RESOLVING THE EVOLUTIONARY RELATIONSHIPS AMONG PSEUDOMONAS SPECIES
No full textA sandwich thesis contains four published peer-reviewed articles and one unpublished work on the genus Pseudomonas.The genus Pseudomonas includes genetically diverse groups of species that do not share a common evolutionary history. My research focused on analyzing the genome sequences of different Pseudomonas species to robustly elucidate their evolutionary relationships using multiple independent approaches, which include: (i) Construction of phylogenetic trees based on several large data sets of conserved proteins, and 16S rRNA gene sequences (ii) Determination of pairwise genomic similarities based on AAI and POCP matrices, (iii) Identification of molecular markers such as Conserved Signature Indels (CSIs) and Conserved Signature Proteins (CSPs), specific for different Pseudomonas species clades supported by other methods. Our Phylogenomic analyses revealed three major lineages/groups within Pseudomonas: Aeruginosa, Fluorescens, and Pertucinogena. While the Aeruginosa and Fluorescens lineages include multiple distinct clades, no molecular or biochemical traits were previously known to differentiate them. Our analyses identified >160 CSIs specific to these clades/groups, providing molecular means for their reliable demarcation. Based on phylogenomic evidence, AAI and POCP values, and clade-specific CSIs, we proposed restricting the genus Pseudomonas only to the Aeruginosa clade of species. Prior to this, based on our analyses, we reclassified the Pertucinogena lineage of species as a novel genus, Halopseudomonas, and reclassified several misclassified species into their related genera. Further analyses led to the reclassification of the Aeruginosa lineage of species into 12 novel and emended genera. Ongoing studies on the Fluorescens lineage, comprising 13 clades, have identified CSIs for several of them. Additionally, our studies led to the discovery of a novel species, Pseudomonas paraeruginosa. The resulting CSI-based phylogenetic framework offers a stable, predictive system for classifying new or uncharacterized Pseudomonas species. Using the predictive ability of CSIs, we predicted assigning ~300 uncharacterized strains into 14 Pseudomonadaceae genera. Besides systematic studies, these conserved markers hold promise for diagnostic applications and deeper insights into microbial evolution and function.ThesisDoctor of Philosophy (PhD
The Impact of Brand Equity on Vertical Integration in Franchise Systems
No full textBrand equity and vertical integration are focal, strategic elements of a franchise system that can profoundly influence franchise performance. Despite the recognized importance of these two strategic levers and the longstanding research interest in the topic, our understanding of the interplay between brand equity and vertical integration (company ownership of outlets) in a franchise system remains incomplete. In this study, we revisit the five-decade-old question of how brand equity affects vertical integration in a franchise system and present some novel, nuanced insights into the topic. Evidence from a Bayesian Panel Vector Autoregressive model on a large panel data set shows that brand equity has a powerful, lagging inverse effect on vertical integration, such that higher brand equity leads to less downstream vertical integration in a franchise system. Reverse causality analyses identify a less pronounced but present reciprocal effect. Boundary conditions analyses reveal that the negative effect of brand equity on vertical integration is weaker in franchise systems with international presence and in retail-focused (vs. service-focused) franchises, and stronger in franchise systems with more financial resources. These findings (a) challenge traditional views (e.g., transaction cost theory, resource-based view, ownership redirection hypothesis) on the topic by demonstrating a negative effect for brand equity on vertical integration in franchise systems and showing that greater financial resources amplify this effect, and (b) shed new light on the intricate dynamics (temporal causation, reverse causation) and contingencies of this debated effect. Managerially, this research draws attention to the underrecognized strategic benefit of brand equity in mitigating channel governance issues and advise against unnecessary vertical integration, especially when brand equity is robust.This research is supported by funding for Manish Kacker from the Social Sciences and Humanities Research Council of Canada (SSHRC). Mohammad Kayed is grateful for the generous financial support from the Social Sciences and Humanities Research Council (SSHRC) of Canada, award number 767-2016-2275
Rapid evidence profile #89: Self-testing for gynecological and urological conditions
No full textAn overview of the best available research evidence from around the world (i.e., evidence syntheses) and local research evidence (i.e., single studies) and may include a scan of experiences from other countries and from Canadian provinces and territories, about self-testing for gynecological and urological conditions in response to a decision-maker’s request.This rapid evidence profile was funded by the Chronic Pain Centre of Excellence for Canadian Veterans and the Atlas Institute for Veterans and Families, which in turn are funded by Veterans Affairs Canada
Rapid evidence profile #91: Identifying first-case response plans for clade I mpox
No full textAn overview of the best available research evidence from around the world (i.e., evidence syntheses) and local research evidence (i.e., single studies) and may include a scan of experiences from other countries and from Canadian provinces and territories, about first-case response plans for clade I mpox in response to a decision-maker’s request.This rapid evidence profile was funded by the Public Health Agency of Canada
Model Optimization for Federated Learning and Flow-Based Image Restoration
No full textThis thesis explores model optimization strategies for two fundamental areas in machine learning: Federated Learning (FL) and Image Restoration (IR), both of which must address challenges posed by data heterogeneity and distribution shifts. We present three contributions aimed at improving robustness, adaptability, and performance in these settings.
The first chapter introduces a gradient-based client selection method for FL. We propose a novel -norm cosine similarity metric that captures higher-order gradient structures, allowing the server to prioritize clients whose updates are more aligned and informative. This approach accelerates convergence and improves the final model quality compared to random or traditional -based selection strategies, especially under non-i.i.d. client distributions.
The second chapter presents MoiréXNet, a multi-scale image restoration network designed to remove complex visual distortions such as moiré patterns. Our framework integrates linear attention modules for efficient feature aggregation, test-time training for adaptation to unseen degradations, and a truncated flow matching prior to enforce structural consistency. MoiréXNet achieves state-of-the-art performance across several real-world benchmarks.
The third chapter addresses the "Last Mile" of image restoration through a rectified flow-based refinement process. We design a two-stage restoration framework: a coarse estimate is first optimized for distortion-oriented metrics, followed by refinement using generative model-based methods that learn efficient distribution mappings to enhance perceptual fidelity. This strategy balances distortion reduction and perceptual quality, producing visually realistic results even under severe degradation.
Collectively, this thesis advances gradient-based optimization for federated systems and flow-guided adaptive restoration methods, contributing to the development of AI models that are robust, efficient, and capable of handling messy, unpredictable real-world data.ThesisDoctor of Engineering (DEng
The role of CARM1 in skeletal muscle regeneration and repair
No full textThe skeletal muscle regenerative process is primarily driven by myogenic stem cells, termed satellite cells. The presence of coactivator-associated arginine methyltransferase 1 (CARM1) in satellite cells is necessary for myogenic repair. However, the requirement of skeletal muscle CARM1 for muscle regeneration remains unknown. This project investigated the role of skeletal muscle-specific CARM1 expression in the regenerative response to acute muscle trauma. We hypothesized that the absence of CARM1 in muscle would attenuate its regeneration and repair. The tibialis anterior (TA) and gastrocnemius (GAST) muscles in one hindlimb of 12-week-old adult, male and female wild-type (WT) and CARM1 skeletal muscle-specific knockout (mKO) mice (n = 6 - 10) were injected with cardiotoxin (CTX). The contralateral hindlimb was injected with saline to serve as an uninjured control (Ctrl). Muscles were harvested at 7-, 14-, and 28-days post-injury (DPI) and processed for morphological and biochemical analyses. While we observed no changes in CARM1 protein content up to 28 days following CTX-induced injury, we saw a transient upregulation in the arginine methylation of its downstream target in both genotypes. Morphological indicators of muscle remodeling were evident in histological assays of TA muscles following injury and largely restored by the end of the study period in both cohorts. We observed increased collagen deposition in WT mice at 7DPI, accompanied by greater interstitial area in both WT and mKO mice. Embryonic myosin heavy chain peaked in both cohorts at 7DPI. Finally, satellite cell analysis revealed increased Pax7 positive cells, as well as Pax7/Antigen Kiel 67 (Ki67) positive cells, in mKO mice at 7DPI, alongside an elevation in Ki67 positive cells in WT mice at 7DPI. Collectively, these results suggest that the skeletal muscle-specific deletion of CARM1 induces early alterations, primarily in satellite cell behaviour, that do not impair overall skeletal muscle regeneration and repair.ThesisMaster of Science (MSc)Skeletal muscle can regenerate following injury. Coactivator-associated arginine methyltransferase 1 (CARM1) is a protein that can alter the activity of other proteins throughout the body, including during skeletal muscle repair. While the role of CARM1 in skeletal muscle stem cells, termed satellite cells, has been studied, little is known about CARM1 specifically within the skeletal muscle during regeneration and repair. Therefore, we investigated the role of skeletal muscle-specific CARM1 following damage. We injured the leg muscles of two groups of mice, including a genetically modified mouse model that lacked CARM1 only in skeletal muscle, and studied their recovery over 28 days. We observed that despite some early changes due to CARM1 deletion, the overall ability of muscles to regenerate and repair was unaffected by the absence of CARM1. This study indicates that skeletal muscle can effectively recover from injury without CARM1 and suggests that the skeletal muscle-specific role of CARM1 is not essential for regeneration and repair
A Framework for Christian Spiritual Formation
No full textChristian spiritual formation (CSF) is typically defined as the process of becoming more like Christ. Most definitions and literature are Christocentric, describing what Christlikeness is and the disciplines and practices that help believers achieve it. However, the literature says little about the nature of the process itself. Arguing that CSF is essentially an educative process, I employ learning theory to craft a framework for CSF based on an educative paradigm.
I explored the process of CSF through thirty-four semi-structured interviews during which research participants describe their most spiritually formative experiences, barriers to spiritual formation, outstanding “God moments,” and pivotal experiences. Their narratives identified CSF has three dimensions: mystical, educative, and communal. By mapping these dimensions into learning models, such as Kolb’s experiential learning cycle and Illeris’s 3-dimensional model of learning, I constructed an educative paradigm of CSF.
The educative paradigm of CSF through its three formative dimensions shows how the imago Dei is restored to full effect and function as the believer is spiritually formed. Throughout that process, one adopts the posture of a learner, facilitating reflection and the pursuit of phronēsis or wisdom (knowing), sanctification or holiness (being), and praxis or right action (doing).
Practical application of the framework for CSF is helpful to individuals making choices about the disciplines and practices that are most beneficial to their formation, and to local congregations and higher education institutions in the design of more balanced and spiritually formative curricula
Towards Novel Improved Anti-Kallikrein Agents: Extending the Circulatory Half-Life of C1INH and Identifying Novel Variants of AAT M358R with Enhanced Anti-Kallikrein Selectivity
No full textHereditary Angioedema (HAE) is a rare disorder characterized by recurrent and severe swelling caused by excessive activation of bradykinin due to unregulated plasma kallikrein (Pka). Current therapies, including plasma derived or recombinant C1-esterase inhibitor (C1INH), aim to suppress Pka activity but are limited by short circulatory half-lives, necessitating frequent dosing. Additionally, while the engineered serpin Alpha1-antitrypsin M358R (AAT M358R) can inhibit Pka, it lacks sufficient selectivity, raising concerns about off-target effects on other proteases. This thesis addresses these challenges through three complementary approaches. First, I engineered C1INH-mouse serum albumin (MSA) fusion proteins to prolong in vivo half-life. I found that N-terminal MSA fusions preserved C1INH function and significantly extended circulatory persistence in mice, with orientation-dependent effects on SDS stability and activity. Second, using T7 phage display, I screened AAT M358R libraries mutated at key positions within the reactive center loop (RCL). Third, I performed rational loop-swapping experiments between AAT M358R and C1INH to explore whether segments of the C1INH RCL could improve Pka selectivity. Both the second and third projects identified novel sequence motifs that enhanced reactivity toward Pka, uncovering previously uncharacterized RCL combinations with potential therapeutic relevance. Together, these studies contribute new insights into therapeutic serpin engineering. The half-life extension work highlights the potential of albumin fusions to improve pharmacokinetics without compromising activity. The AAT M358R variant screening uncovers previously uncharacterized RCL sequences that promote Pka selectivity, expanding the known sequence space for functional serpin design. Overall, this thesis advances the development of improved biologics for HAE and provides a framework for engineering more selective, long-acting protease inhibitors for future therapeutic applications.DissertationDoctor of Philosophy (PhD)Hereditary Angioedema (HAE) is a rare genetic disorder that causes painful and potentially life-threatening swelling, triggered by excessive activity of bradykinin. Current treatments, such as C1-esterase inhibitor (C1INH), are effective but have a short half-life in the bloodstream, requiring frequent dosing. The goal of my research was: (i) to extend the circulatory half-life of C1INH through protein fusion, (ii) and to identify new variants of alpha-1 antitrypsin M358R (AAT M358R) that more selectively target kallikrein. By combining molecular engineering with biochemical testing, I generated modified proteins with properties that support their potential as next generation therapeutic candidates. This work contributes to the early-stage development of more durable and targeted treatments for HAE. In the long term, such advancements may lay the groundwork for improved quality of care for patients with rare disorders, and demonstrate how protein design can address unmet needs in medicine
Assessing downstream geomorphic implications of low-impact development (LID) projects in the Spencer Creek watershed
No full textThe Spencer Creek watershed, located in Hamilton, Ontario, plays a complex role in connecting an extensive network of rivers to the western end of Lake Ontario. Over the past decade, the watershed has seen an increase in urban activity, contributing to notable transformations in the natural landscape. Changes in land use have impacted not only zoning patterns in the region but also the overall quality of surrounding fluvial environments. With climate change and urbanization rates advancing, the city of Hamilton has taken measures to implement advanced stormwater management strategies, including low-impact development (LID). The purpose of these techniques is to imitate the behaviour of natural water systems and assist in stormwater management efforts within cities, often by reducing impervious surfaces. This study used stream power-based analyses to assess the effects of land-use change and LIDs on river networks. Stream power, representing energy expenditure per unit time, is a well-established metric for evaluating geomorphic sensitivity. Sample sites were surveyed for bankfull width measurements in summer 2022 and winter 2024. The data was used to derive empirical values specific to the Spencer Creek watershed and applied to the Stream Power Index for Networks (SPIN) tool. The SPIN tool was then used to generate various scenarios to investigate the post-implementation impacts of LIDs. A range of existing LIDs in Hamilton and theoretical land use changes based on the literature were simulated. Overall, the results of this study offer insight for improving river management strategies and addressing water resource concerns amid evolving climate conditions