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Cellular and Functional Role of Melanin-Concentrating Hormone in the Lateral Septum
No full textMelanin-concentrating hormone (MCH) is a neuropeptide exclusively produced in the lateral hypothalamus and zona incerta with diverse functions including prominent effects on energy balance and anxiety that can impact the development of obesity and mood disorders. MCH neurons project to many brain regions, and MCH can have site-specific effects on neuronal activity and behavioural outcomes. Thus, in addition to global manipulations of MCH function, it is important to characterize the role of MCH at specific target sites. The lateral septum (LS) possesses MCH receptors and receives the strongest projection from MCH neurons. However, the function of MCH in the LS is not known. The LS has known roles in the regulation of feeding and anxiety-related behaviours, and such overlapping functions with those of MCH suggest the LS is a key target site of MCH in the brain. This thesis focused on understanding the role of MCH in the LS by 1) determining the mechanisms of MCH action on LS cells; 2) defining the behavioural significance of MCH on feeding and anxiety-like behaviour in the LS; and 3) elucidating the properties of MCH release and action within the LS. We found that MCH directly inhibited cells in the lateral LS through a novel chloride-mediated mechanism (Chapter 2), and this inhibition promoted a context-dependent increase in feeding behaviour (Chapter 3). Furthermore, MCH was released and inhibited nearby cells predominantly separate from those that were directly innervated by MCH neurons, revealing three distinct populations of LS cells within this circuit. The activation of these parallel glutamate and MCH-mediated circuits increased feeding and decreased anxiety-like behaviour, respectively (Chapter 4). Together, we have shown that the LS is an important target of MCH neurons and that MCH and glutamate interactions are important for mediating behavioural outcomes. This work will improve our understanding of MCH action in the brain, as well as identify novel neural mechanisms underlying feeding and anxiety-like behaviour
Mindreading in Great Apes: Dissolving the Logical Problem and a New Multiple Soft-Indicators Model
No full textThis thesis explores the debated capacity of great apes to mindread, addressing the 'logical problem of mindreading' and advancing an alternative 'multiple soft-indicators' model of mindreading. The logical problem is that no experimental protocol can be designed (even in principle) that produces evidence that supports a mindreading hypothesis, which posits the inference of unobservable mental states on the part of the ape, over a behaviour-reading hypothesis, which posits that the ape relies solely on observable cues. Challenging this, I utilize Daniel Dennett's framework of the intentional stance to argue that mindreading does not conform to a binary classification but rather exists on a continuum, thereby dissolving the traditional logical problem by reframing it. In chapter four, I introduce a Wittgensteinian-inspired conception of ‘mindreading’ suggesting that mindreading varies in degree based on the presence and intensity of multiple soft-indicators compared to paradigmatic human cases
Application of an αSyn-Binding Aptamer to Reduce Protein Aggregation in a Cell Model of Parkinson’s Disease-Associated Pathology
No full textParkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the misfolding and aggregation of alpha-synuclein (αSyn). In this study, the efficacy of a DNA aptamer (a-syn-1), which binds to monomeric αSyn to inhibit fibrillization, was assessed using an in-vitro preformed fibril (PFF) model of PD. Evaluation of the seeding capacity of PFFs corroborated the recruitment of endogenous αSyn monomers, as evidenced by the progressive increase in the size and quantity of aggregates over time. Administration of the a-syn-1 aptamer in conjunction with PFFs led to a reduction in aggregation levels. Conversely, a-syn-1 treatment following the seeding of pathological aggregates did not affect the aggregation of αSyn. Internalization of the a-syn-1 aptamer was observed within one hour of treatment and is unlikely to be attributable to clathrin-mediated endocytosis. These findings emphasize the potential benefits of utilizing the a-syn-1 aptamer to target αSyn pathogenesis to slow or prevent PD progression
Rethinking VR Input: Co-design with Gamers with Upper Limb Motor Impairments and VR Designers
No full textVirtual Reality (VR) offers immersive gaming experiences, yet accessibility for gamers with upper limb motor impairments (ULMI) remains underexplored, particularly regarding interaction methods. This thesis investigates the challenges these gamers face and identifies their needs for accessible VR input. First, we conducted an online survey to understand the experiences of these gamers in VR gaming, focusing on the interaction difficulties they encounter and the design limitations of VR controllers. Then, we conducted co-design workshops involving gamers with ULMI and VR designers to gain a comprehensive understanding of accessibility challenges and how these gamers currently engage with games, leading to the co-creation of design solutions for more accessible VR interactions. Finally, we weave findings of both phases to present design considerations as actionable items. These contributions are valuable for guiding the development of more inclusive VR interactions, so that gamers with ULMI can fully participate in the immersive potential of VR
Indoor Wireless Coexistence Between Wi-Fi and Next-Generation Wireless Technologies
No full textThis thesis presents an experimental evaluation of the coexistence of Wi-Fi with technology-agnostic Gaussian test signals. Given the recent introduction of new unlicensed portions of the 6 GHz frequency spectrum in both North America and Europe, harmonizing wireless coexistence has become paramount. In this work, the impacts of Gaussian traffic on Wi-Fi's Clear Channel Assessment (CCA) mechanism and the robustness of packet reception are investigated. Narrowband and broadband coexistence with commercial Wi-Fi devices is assessed using technology agnostic Gaussian signals. The results demonstrate inconsistencies in device implementation especially as it pertains to narrowband signals compared with broadband signals. The findings of this thesis demonstrate inconsistencies between manufacturers and between the IEEE 802.11-2020 standards, particularly as it pertains to coexistence with narrowband traffic
“Can we revive Arabic in an Arab country?” Tracing the Dynamic Motivational Trajectory of Non-Arab learners living in the United Arab Emirates
No full textThis study takes on a cross-disciplinary approach and draws on concepts from Dörnyei’s Second Language Motivational Self System (Dörnyei, 2005) and a complex dynamic system theory (Larsen-Freeman & Cameron, 2008a) to examine non-Arab learners’ (n=100) experience and motivations in learning Arabic as a second language (L2) in the United Arab Emirates. Specifically, the investigation explores the immediate environment around the language learner to capture the evolving nature of L2 motivation and to trace the dynamic trajectory for existing language learning outcomes. The use of such rarely employed methodologies as concept mapping (Kane & Trochim, 2007) and retrodictive qualitative modeling have identified a motivational system (along with its causal mechanisms) shared by these learners and probed the voices of educators’ (n=25) to help explain the learners’ views. The results also point to the varying roles of self-efficacy, coping, and early exposure as core constructs in the development of learner motivational profiles. Additionally, they provide empirical evidence for educators and educational systems alike to recognize mechanisms that may be key in not only determining a learner’s success in L2 learning, but also assuring it
Shield Through Rejuvenated-Stage Volcanism and the Evolution of Alkalic Lavas on West Maui, Hawaii – Insights on Magma Source and Processes Along the Hawaiian Island Chain
No full textHawaiian volcanoes develop through age-progressive growth stages that reflect passage of their volcanic edifice over the Hawaiian Plume. West Maui is the youngest volcano to have experienced a shield, postshield, and rejuvenated-stage of development and is unique in that tholeiitic shield-stage volcanism is abruptly followed by the appearance of felsic lavas i.e. benmoreite and trachyte. This absence of mafic-intermediate alkalic lavas on West Maui forms a “Daly Gap”. ~0.6 Ma after cessation of shield and postshield-stage volcanism, West Maui experienced a brief period of rejuvenation which produce four discrete eruptions of basanite. This study aims to explain the unique temporal changes on West Maui and better constrain spatial heterogeneities in the source of Hawaiian lavas. Rejuvenated lavas on West Maui are enriched in incompatible elements yet have steep 206Pb/204Pb versus 208Pb/204Pb and 143Nd/144Nd versus 176Hf/177Hf well below the mantle array that trends toward Pacific MORB lavas. Our models indicate a depleted upper asthenosphere metasomatized by the Hawaiian Plume as the source of rejuvenated lavas on West Maui. This source is now identified to be long-lived on northern or Kea-trend volcanoes and invokes more recent models of plume-lithosphere interaction. West Maui’s postshield lavas have overlapping radiogenic isotope signatures with shield lavas suggesting a similar plume source. They however have less radiogenic Pb (208Pb*/206Pb*) and relatively high 206Pb/204Pb at a given 87Sr/86Sr indicating a more depleted signature than shield-stage lavas. A transition to a more depleted signature is common among other Hawaiian postshield lavas and indicates that enriched components are consistently exhausted during shield-stage volcanism and/or the shift towards the plume’s periphery allows entrained upper-mantle to be preferentially melted. In the absence of continental crust, felsic oceanic lavas are thought to originate by partial melting of hydrated basalt or as products of extensive fractionation. Major and trace element trends of mafic-intermediate lavas from Kohala’s postshield indicate a similar source to West Maui’s postshield. Mass-balance calculations show that West Maui trachytes are a 14% residual liquid after fractional crystallization from an inferred mafic source similar to alkalic basalts from Kohala. Postshield lavas evolved at depths of >20 km and erupted along established shield-stage rifts
Neo Salt Road: A Story of Salt
No full textThis thesis is a speculative fiction exploring the implications of salt-battery technology as alternative energy storage systems. These energy storage systems are posed to replace nuclear energy use in a highly seismic Japan. The speculative fiction draws inspiration from two seminal Japanese animated films, Princess Mononoke and Nausicaä of the Valley of the Wind. The narrative examines the relationship of salt as both culture and technology. The pervasiveness of salt in a culture influenced by Shintō reinforces the cultural value of salt. Additionally, salt-based batteries are described as safer and cleaner alternatives, due to resource abundance and non-combustibility. In conclusion it argues the appeal of salt as a cultural and technological substance, able to replace nuclear energy production with large scale salt battery technology
Heroes, Huddles, and Habitats: Enabling Big Data for Advanced Analytics at the Government of Canada
No full textThe recent proliferation of big data for advanced analytics (BDA) in the Government of Canada (GC) is emerging as an opportunity with potential for reshaping how the GC conducts operations in its core functions: policy analysis, public administration, and service delivery. Nonetheless, there remain notable barriers that make the integration of BDA difficult in many areas within the GC. However, there is a clear dichotomy between projects in the GC that fail and those that succeed at integrating BDA as a transformative change force. This thesis uncovers the enablers behind those projects in the GC that succeed at harnessing the power of BDA, despite barriers. Digital government innovation literature is the theoretical framework that structures this research. The existing literature shows that the most prominent barriers in adopting BDA are organizational (hierarchy, silos, and risk aversion), digital skills gap, and shortcomings of BDA. On the other literature identifies enablers as leadership, collaboration, and environmental factors. To date the literature on BDA uptake in the public sector/digital government innovation bases most of its conclusions on theory without significant empirical testing and with little detail as to how the enablers manifest themselves in practice and their interplay with the barriers. Hence, in the endeavour to test theory against practice and provide details on process and barrier/enabler relationships, this thesis identifies and examines four case studies of successful BDA adoption in the GC, drawing on interviews with 35 public servants and systematic review of GC documents related to these initiatives. The analysis confirmed the validity and provided more depth to the enablers found in the literature, as well as revealed areas requiring further effort to enhance BDA adoption within the GC. The analytical chapters present the findings in a nested framework. Heroes is about the individuals in the organization that help enabler BDA. Huddles is about the teams that these individuals work in. Finally, habitats is the broader organizational environment in which those heroes (individuals) and huddles (teams) work. The environment includes both internal (organizational culture and resources) and external (public pressures)
Reason, Hierarchy, and Political Stability in the English Enlightenment
No full textInterpretations of Enlightenment political thought often view the concept of reason as a subversive tool that was deployed in the seventeenth and eighteenth centuries to undermine frameworks for political life that maintained inequality. This dissertation, through an analysis of the English Enlightenment between 1679 and 1750, challenges this colloquial understanding and argues that, throughout important moments of English history, reason was deployed to maintain hierarchical arrangements in the name of political stability. Although many scholars have propounded increasingly complex understandings of the Enlightenment in recent years, the concept of reason has maintained its historical status as a subversive tool deployed to dismantle systems of hierarchical political power. This account of reason endures and helps to defend ideas of neutrality and objectivity that are vital to maintaining the legitimacy of liberal democratic institutions. By showing how the concept of reason was used to safeguard political stability through the maintenance, rather than the destruction, of religious, social, and political inequality, this dissertation not only departs from traditional accounts of reason’s role in modernity and Enlightenment but asks whether ideas of reason are still used to promote similar hierarchies today