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UWSpace

UWSpace is the University of Waterloo’s institutional repository for the free, secure, and long-term home of research produced by faculty, students, and staff.

Depositing Theses/Dissertations or Research to UWSpace

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Recent Submissions

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Mobile Realities: Designing for the Medium of Smartphone-VR
(ACM, 2019-07-19) Harley, Daniel; Tarun, Aneesh P.; Elsharawy, Sara; Verni, Alexander; Tibu, Tudor; Bilic, Marko; Bakogeorge, Alexander; Mazalek, Ali
We present two proof of concept experiences for a virtual reality (VR) game that draws on several medium-specific qualities of mobile, location-based, and tangible storytelling. In contemporary smartphone-VR, experiences are limited by short playtimes, limited interactions, and limited movement within a physical space. To address these limitations, we suggest a reconceptualization of smartphone-VR. Rather than design that deems the smartphone the least capable VR platform, we propose design that adds VR to an already rich mobile storytelling platform. We argue that by drawing on otherwise separate storytelling media, designers can circumvent limitations related to smartphone-VR while also extending the range of smartphone-based storytelling. We conclude by reflecting on possible implications of this extended design space.
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Widespread yet Unreliable: A Systematic Analysis of the Use of Presence Questionnaires
(Interacting With Computers, 2025-02-01) Eugene Kukshinov; Joseph Tu; Kata Szita; Kaushall Senthil Nathan; Lennart E Nacke
Presence, as a psychological state, is typically assessed using questionnaires. While many researchers in this field assume that these self-report instruments are standardized, the reliability of such questionnaires remains uncertain. This knowledge gap challenges the accuracy and validity of data derived from studies assessing presence. Ensuring reliable and precise data collection and reporting is essential for the credibility of findings in presence research, because inaccuracies may cause errors in conclusions, which affects theoretical understandings, methodological approaches and practical applications. To address this issue, we conducted a systematic analysis of 397 empirical quantitative studies on presence. We investigated the use of presence scales, including applications, modifications, a variety of measures and reporting practices. We found that the majority of the presence studies modify questionnaires, do not re-validate them and improperly report their methods. Based on these findings, we propose solutions to enhance transparency and validation of the presence measurements.
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Symbols, Dynamics, and Maps: A Neurosymbolic Approach to Spatial Cognition
(University of Waterloo, 2025-03-12) Dumont, Nicole Sandra-Yaffa
The discovery of various spatially sensitive neurons in the hippocampal formation, such as place, grid, and boundary cells, has provided valuable insights into the neural mechanisms underlying spatial representation and navigation. However, neural activity and connectivity data alone cannot fully reveal the brain’s algorithms. Bridging this gap requires computational models that not only explain the low-level activity of spatially sensitive cells but also link it to higher-level symbolic representations manipulable within a cognitive framework – models capable of binding spatial representations to discrete abstractions, while also supporting hierarchical and probabilistic structures that enable reasoning and decision-making. The Semantic Pointer Architecture (SPA; Eliasmith, 2013), in combination with the Neural Engineering Framework (NEF; Eliasmith et al., 2003), provides a mathematical and computational framework to represent symbols and implement dynamical systems in spiking neural networks. Spatial Semantic Pointers (SSPs; Komer et al., 2019), an extension to the SPA, encode continuous variables, such as spatial locations, while supporting the binding of spatial information with other features – continuous or discrete – into compressed, multi-domain representations. This flexibility allows SSPs to model diverse cognitive processes, ranging from spatial memory to abstract reasoning, offering a unified theory for how continuous variables might be represented and manipulated in the brain. In this thesis, we leverage these tools to model key components of spatial cognition, including path integration, cognitive map creation, and reinforcement learning. Our contributions include the development of SSP-PI, a SSP-based path integration model that combines velocity controlled oscillators with attractor dynamics to integrate continuous spatial variables. We also introduce SSP-SLAM, a biologically inspired spiking neural SLAM system capable of constructing semantic cognitive maps that bind and associate spatial and non spatial features. Furthermore, we propose spiking RL models that demonstrate how SSP embeddings can effectively represent successor features, reward distributions, and stochastic policies. Finally, we use the SPA and SSPs to construct state embeddings for deep RL networks, demonstrating their utility in tasks requiring mixed semantic-spatial representations. Our findings underscore the potential of SSPs to act as a unifying framework for understanding spatial representation in the brain while advancing biologically inspired approaches to navigation and learning in artificial systems. This work bridges theoretical neuroscience and artificial intelligence, laying the groundwork for future explorations of shared principles across spatial and abstract cognition.
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Development of Novel Human Aggrecanse-2 Dual-Binding Bis-Squaramide Inhibitors
(University of Waterloo, 2025-03-12) Ratto, Amanda
Osteoarthritis (OA) is a degenerative joint disease that affects millions of individuals worldwide. OA is characterized by the breakdown of articular cartilage, including the proteoglycan aggrecan, which plays a crucial role in enabling cartilage to withstand compressive loads. A Disintegrin and Metalloproteinase with Thrombospondin Motifs-5 (ADAMTS-5; aggrecanase-2), has been reported to be the predominant aggrecanase in mice, and in vitro studies revealed ADAMTS-5 exhibits high efficiency at cleaving aggrecan. Although no disease modifying OA drugs have been developed, it is hypothesized that inhibitors against ADAMTS-5 could slow the progression of OA. Typical inhibitors of ADAMTS-5 include zinc-binding groups (ZBGs) that interact with the catalytic zinc. Recently, an exosite that inhibitors can target has been identified at a nearby domain, not within the catalytic site. Here we present the development of novel potential dual-binding inhibitors which aim to target both the catalytic site and exosite of ADAMTS-5. The inhibitors investigated in this thesis incorporate a squaramide nucleus, which is an excellent molecular scaffold due to its ease of derivatization, known synthetic pathways, and commercial availability. To identify potential dual-binding bis-squaramide inhibitors, a large in silico library was constructed, consisting of the squaramide nucleus linking potential exosite binding groups and ZBGs. Numerous computational techniques were utilized to identify inhibitors, including molecular docking to evaluate potential interactions with both the binding pocket and exosite of ADAMTS-5, as well as molecular dynamics simulations to assess inhibitor stability and predict binding affinities. The four bis-squaramide molecules identified from the computational screening were successfully synthesized using a one-pot, microwave-assisted synthetic approach, which facilitated a high-throughput process through reaction automation. A range of bis-squaramide compounds were enzymatically screened with micromolar IC50’s for ADAMTS-5.
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Harnessing Exosomes from Human Dermal Fibroblasts and Pirfenidone-exosomes as Innovative Strategies for Scarless Tissue Repair in Wound Healing
(University of Waterloo, 2025-03-11) Wang, Jin
The wound healing process often leads to scar formation that can negatively affect patients both physically and psychologically. The management and treatment of scars also place a considerable financial burden on healthcare systems. Significant efforts are being made to improve wound healing outcomes by accelerating closure while simultaneously minimizing scar formation. To facilitate scarless wound healing, developing an anti-scarring treatment that modulates dermal fibroblast activity is a promising strategy, with pirfenidone (PFD) showing potential due to its anti-fibrotic properties by targeting intracellular pathways that regulate collagen disposition. PFD, particularly when delivered via dermal fibroblast-derived exosomes, may further enhance therapeutic effectiveness and promote scarless healing. To achieve this goal, we began by isolating high-purity exosomes from in vitro cultured human dermal fibroblasts. Two common isolation methods—PEG precipitation and affinity-based techniques—were compared to identify the most efficient approach for obtaining high-purity and relatively homogenous exosomes. A range of characterization techniques, including transmission electron microscopy (TEM), atomic force microscopy (AFM), antibody arrays, and enzyme-linked immunosorbent assays (ELISA), confirmed the successful isolation of high-purity exosomes. The affinity-based method demonstrated superior performance, yielding well-dispersed and highly pure exosomes. Due to the difficulties in achieving efficient drug encapsulation in exosomes, the following chapter specifically focused on the encapsulation and formulation optimization of the antifibrotic compound PFD and explored the use of exosomes as a drug delivery platform. We optimized an active drug loading method using sonication to enhance encapsulation efficiency (EE%) and loading efficiency (LE%), ensuring that careful control of the sonication process maintained exosome integrity. The optimal formulation of PFD-exosomes achieved an EE% of 11.14% ± 1.27% and an LE of 10.01% ± 1.03%, with a particle recovery rate of exosomes at 64.21% ± 8.49%. Then, we investigated how to harness exosomes from dermal fibroblasts and PFD-exosomes as innovative strategies for achieving scarless tissue repair in wound healing. Our findings showed that exosomes enhanced fibroblast migration and proliferation through an autocrine mechanism, highlighting their potential as a stand-alone cell-free therapy for wound healing. Additionally, this study was ground-breaking in demonstrating that exosomes can improve the efficacy of PFD as a drug carrier, amplifying its anti-fibrotic effects in both in vitro and in vivo models. The in vivo results indicated that PFD-exosomes accelerated wound healing while organizing the extracellular matrix (ECM) by reducing excessive collagen deposition. Overall, PFD-exosomes present an innovative strategy for pre-scarring interventions, offering benefits of enhanced wound healing outcomes while minimizing scarring.