Techniques for subtle mid-air gestural interaction using mmWave radar

Users need to be able to interact with mid-air gesture systems in ways that are efficient, precise, and socially acceptable. Subtle mid-air micro gestures can provide low-effort and discreet ways of interaction. This thesis contributes techniques for recognizing and utilizing subtle mid-air gestures with millimeter wave radars, a rapidly emerging sensing technology in human-computer interaction. The first contribution focused on the problem of addressing a system. By analyzing the frequency components of various hand motions, subtle activation gestures were identified which produced high-frequency signals through deliberate, rhythmic movements. A novel activation gesture recognition pipeline was then developed using frequency analysis to recognize these gestures and ignore incidental hand motions. Tested across three types of sensors, the pipeline demonstrated robust performance in recognizing subtle high-frequency activation gestures and producing zero false activations for broad hand motions. Further improvements were also explored to enhance robustness to reduce false activations during activities like typing, writing, and phone usage. The second contribution focused on recognition of subtle gestures from mmWave radar data using deep learning. A new dataset was developed, capturing the temporal dynamics and motion patterns of 10 different subtle gestures from 8 users with a mmWave radar. Multiple neural network architectures were trained and evaluated using the dataset, achieving a high recognition accuracy of 90%. The results demonstrated that hybrid neural networks combining convolutional and recurrent layers can effectively recognize subtle gestures from mmWave radar signals and generalize across different users. The final contribution progressed from offline evaluations to practical, real-time assessments. The neural network models were integrated into prototype applications that enabled real-time subtle gesture interactions for tasks such as selecting photos and adjusting media playback. A user study demonstrated significant improvements in task completion, accuracy, and user experience compared to traditional macro gestures. The findings suggest that subtle gestural interaction, enabled by mmWave radar sensors, signal processing, and deep learning, can significantly enhance usability of virtual interfaces

Developing novel viral vectors to facilitate gene therapies for neuropathic pain

Neuropathic pain (NeuP) is a chronic pain condition arising following injury or disease to the somatosensory system and affects 7-10% of the population worldwide. Despite its prevalence, currently available treatments for NeuP have limited efficacy and are often complicated by issues such as addiction. Spontaneous activity, a hallmark of NeuP, occurs in both injured and intact primary afferents and their relative contribution to pain remains a controversial subject, with the majority of evidence pointing towards an important role for injured afferents. Adeno associated viral (AAV) vector-based gene therapies are an attractive option for treating NeuP, however, their use is limited by immunogenicity and dorsal root ganglion (DRG) toxicity concerns. In this thesis, we designed viral vectors capable of delivering therapeutic transgenes and restricting their expression to injured, but not intact primary afferents. To achieve this, we initially developed a pipeline of in vitro and in vivo model systems to test the targeting of our vectors. Following this, we first investigated the capacity of the endogenous activating transcription factor 3 (ATF3) P1 promoter to target AAV gene expression. While the ATF3P1 AAV9 selectively limited transgene expression to injured sensory neurons in vitro, these results were not replicated in vivo. We next generated an epigenomic atlas of naïve DRG neurons using single nucleus Assay for Transposase Accessible Chromatin sequencing (snATAC-seq) and gained insight into the epigenomic signatures of injured and intact primary afferents. This data provides a resource for exploring the epigenomic mechanisms governing gene expression in the DRG and can be used to identify putative regulatory elements capable of targeting AAV gene expression to injured primary afferents. Finally, we trialled a microRNA (miRNA)-based approach, whereby miR-182 target sites were introduced into an AAV-PHP.S vector and successfully restricted expression to injured primary afferents in vivo

The role of physical activity in relation to later suicidal outcomes. Longitudinal exploration using quantitative prospective cohort design

Abstract available at each chapter

The role of IL15 in Angiotensin II-mediated cardiac remodelling

Abstract not currently available

Trust, testimony, and transmission: Essays in social virtue epistemology

This thesis consists of five distinct essays within social virtue epistemology, each of which can stand independently, yet all engage with fundamental ideas surrounding trust, testimony, and knowledge transmission. The first two chapters explore knowledge transmission and testimony through a virtue epistemological lens, emphasising the challenges of accounting for testimonial knowledge while maintaining a connection between knowledge and credit. I introduce types of knowledge transmission that do not rely on joint agency or shared intentions, challenging a prominent view in virtue epistemology. I present a type of a credit view that can defend one of the fundamental doctrines of credit views, that knowledge always entails credit, from challenging counterexamples. Trust and testimony both facilitate connections between individuals, making them central to our understanding of how knowledge is shared in social contexts. The third chapter aims to further our understanding of the nature of trust by placing the spotlight on trust features that have gone largely unnoticed, namely, their temporal elements. By expanding on these features, we can make meaningful distinctions between instances of trust that have generally been considered interchangeable. These distinctions and related concepts highlight the subtle differences that meaningfully impact how we approach trust. In the fourth chapter, the focus shifts to epistemic groups in the context of gatekeeping. Epistemologists should be interested in trust, testimony, and transmission as they relate to individuals, but groups are an interesting epistemic subject in their own right. This chapter examines the distinct epistemic roles groups play in shaping the beliefs of their members, and how individuals can benefit from being part of a collective. I then present conditions for justified epistemic gatekeeping and consider what kinds of groups are most capable of fulfilling those conditions. In the last chapter, I consider how to define general artificial intelligence. It is difficult to place large language models within epistemology. At times, they act like epistemic agents, seemingly capable of producing and transmitting knowledge, yet they often appear incompetent and incapable of performing simple tasks. I propose a virtue-theoretic distinction between narrow and general artificial intelligence, in the hopes that it can contribute to our understanding of what makes AI trustworthy, and whether we should think of their predictions as knowledge

Characterising Plasmodium falciparum cyclin dependent like kinase 1 (PfCLK1) as a potential antimalarial target

The widespread and indiscriminate use of antimalarial drugs has contributed to recurring parasite resistance that threatens a global resurgence of malaria with increasing morbidity and mortality rate towards the verge of endemicity. The dual specificity protein kinase family, CLKs, play crucial roles in the regulation of transcript splicing by phosphorylating SR proteins. Global phospho-proteomic studies of the Plasmodium kinome have shown such splicing events to be an essential process across developmental stages of the parasite life cycle. Thus, members of the CLK family have been considered as potential therapeutic targets in present antimalarial drug development pipelines for new molecules which demonstrate the required efficacy and selective toxicity to the parasite without the propensity to induce parasite resistance. A member kinase PfCLK3 was validated as a cross species multistage drug target in a previous study by our group using a selective and specific small drug like inhibitor TCMDC-135051. However, to achieve poly-pharmacology or develop drugs for combination therapy as an approach to circumvent potential drug resistance, a second target PfCLK1 with similar therapeutic potential was identified. This thesis aimed to extend the previous study by characterising potent selective inhibitors for PfCLK1 and explore the role of the kinase in Plasmodium falciparum. The primary screen at GlaxoSmithKline from the previous study yielded four distinct chemical series of small molecule inhibitors with specific nanomolar activity towards PfCLK1. In this study, two potent members JZ208105-178D1 and HGC-0017530023-NX-1 were further characterised through enzymatic and cellular analyses to investigate their mode of inhibition and determine their interaction with the target kinase. First, the enzymatic parameters of the biochemical assays were determined using recombinant PfCLK3 and kinase domain PfCLK1 proteins. In addition, a robust assay measuring ATP consumption was developed that proved suitable for high throughput screening. Substrates that were recognised and efficiently phosphorylated by both kinases were identified and used to establish optimal concentrations of protein and ATP for inhibition assay conditions. Second, a detailed analysis of the inhibition mechanism, target specificity, timing of peak activity during life cycle and the rate of parasite reduction was completed to identify the most potent inhibitor that could be optimised to the status of lead compound through further in vitro and in vivo studies. In vitro inhibition results showed that both compounds displayed low nanomolar inhibition of kinase domain PfCLK1 and further demonstrated selective inhibition towards PfCLK3 suggestive of an affinity for the highly conserved domain between both kinases. Additionally, JZ208105-178D1 demonstrated a mode of binding suggestive of ATP competitive inhibition, in contrast to the non-ATP competitive inhibition observed for HGC-0017530023-NX-1. Both inhibitors emerged effective at high nanomolar to low micromolar concentrations against asexual blood stages of P. falciparum 3D7 wild type. For chemical validation, a PfCLK1-like PfCLK3 mutant parasite, G449P demonstrated the same sensitivity as wild type parasites to both inhibitors suggesting PfCLK1 inhibition is linked to their parasitical activity. Susceptibility profiling of P. falciparum 3D7 asexual blood stages to both inhibitors revealed a variety of stage-specific profiles that differentiated the modes of action including TCMDC-135051 and identified trophozoite-specific peak activity for JZ208105-178D1 and TCMDC-135051. Given that JZ208105- 178D1 conferred higher inhibitory effect in vitro and in vivo, further investigations were carried without HGC-0017530023-NX-1. The morphological analysis of asexual blood stages following treatment with JZ208105-178D1 confirmed that parasite development was completely arrested at the early trophozoite stage. This contrasted with the progression of untreated parasites to late trophozoites at comparable time points. In addition, JZ208105-178D1 impaired the maturation of P. falciparum NF54 gametocytes, stages responsible for transmission, by an ~11-fold reduction in gametocyte number at 1x EC50 concentration. The parasite reduction rate assay was used to quantify the speed of therapeutic capacity, JZ208105-178D1 demonstrated activity levels similarly to TCMDC-135051 and standard antimalarial artemisinin. The combined data in this study suggests the malaria parasite's response to JZ208105-178D1 inhibition are PfCLK1 dependent and corroborate previous functional characterisation studies relating to PfCLK1 expression in the parasites. Thus, pointing to the PfCLK1 kinase as a promising target for antimalarial and transmission blocking chemotherapy strategies

Exploring the relationship between body composition, systemic inflammation, and outcomes in vascular surgical disease

Cardiovascular disease remains the leading global cause of death, with a predicted increase in the future due to a range of demographic and social factors. Within this spectrum of illnesses, vascular surgical conditions are an important group of problems. The typical underlying pathophysiology is atherosclerosis, which has a well described risk factor profile. The disease entities which comprise the majority of vascular surgical practice are aortic aneurysm (AAA), chronic limb threatening ischaemia (CLTI), and cerebrovascular disease (CVD). Sarcopenia, defined as a progressive loss of skeletal mass and function (EWGSOP2 definition), has recently emerged as an important factor associated with a range of chronic illnesses. It has been evaluated as a potential prognostic factor, with the largest amount of evidence coming from patients with cancer. CT-derived body composition analysis (CT-BC) is a technique used to quantify sarcopenia through measurement of cross-sectional tissue areas, allowing muscle and fat indices to be derived and quantitatively analysed. A key aetiological factor in the development of both cardiovascular disease and sarcopenia is the systemic inflammatory response (SIR). The SIR can be quantified using inflammation-based prognostic scoring systems, such as the neutrophil:lymphocyte ratio (NLR), platelet:lymphocyte ratio (PLR), and modified Glasgow Prognostic Score (mGPS), both of which have been independently associated with inferior survival in patients with cancer. In vascular surgical conditions, both sarcopenia as measured by CT-BC, and the SIR, are less widely reported than in other conditions. The aim of the present thesis was to describe the existing evidence base describing these factors, and evaluate their associations and potential prognostic value, in patients with AAA, CLTI, and CVD. In chapter 2 the literature describing the potential prognostic role of CT-BC in patients undergoing elective endovascular repair (EVAR) of AAA was reviewed, and on meta-analysis a clear association between low skeletal muscle mass and inferior survival outcomes was observed, however the existing studies had limited methodology. In chapter 3, CT-BC parameters were evaluated in a multicentre cohort of patients undergoing EVAR for AAA. There was an independent association between low skeletal muscle index (SMI) and inferior survival outcomes in this cohort. In chapter 4 the literature describing the association between elevated NLR and PLR and outcomes in patients undergoing intervention for AAA was reviewed. Elevated NLR and PLR were generally associated with inferior long-term survival., despite limitations in methodology observed. In chapter 5 the NLR and mGPS were combined into the systemic inflammatory grade (SIG), which aims to provide a more comprehensive assessment of the SIR. There was an independent association between increasing SIG and inferior survival outcomes in patients undergoing intervention for AAA. In chapter 6 Combining the factors of interest from chapters 3 and 5 in chapter 6 allowed for a description of the combined potential prognostic value of both CT-derived sarcopenia (as measured through CT-SS, a novel observation in this patient group) and the SIR (as measured through SIG). There was a marked observation of significantly inferior survival in patients with both low skeletal muscle mass/density and elevated SIG. In chapter 7 a possible association between sarcopenia and inferior physiological fitness as assessed by cardiopulmonary exercise testing (CPEX) was explored, with sarcopenia assessed using the CT-Sarcopenia Score (CT-SS), which combines muscle mass and density. There was no significant association between sarcopenia and CPEX parameters. compared to CPEX parameters, CT-SS demonstrated greater association with survival. In chapter 8 patients undergoing intervention for AAA were compared to patients undergoing resection for colorectal cancer (CRC). The magnitude of the SIR and low skeletal muscle density (SMD) were more prevalent in patients with CRC, and there was an association between increasing age and decline in CT-BC parameters in both patient groups. In chapter 9 the post-operative SIR was examined in relation to survival following both elective and emergency repair of AAA. Elevated day 3 CRP was associated with inferior survival outcomes in both the elective and emergency cohorts, though at different timepoints. In chapter 10 the literature describing survival outcomes, disease severity, and technical success of intervention in patients with CLTI, in relation to NLR and PLR, was reviewed. Methodology was heterogenous in the 34 studies, however the majority of studies report an association between elevated NLR/PLR and the outcomes of interest. In chapter 11 the effect of frailty (as measured by the clinical frailty score, CFS), CT-BC, and the SIR on survival in a cohort of patients with CLTI was described. CT-SS, mGPS, and CFS were independently associated inferior survival outcomes. In chapter 12 the association between CT-BC, the SIR, and survival was described in a cohort of patients undergoing carotid endarterectomy for symptomatic carotid lesions. The SMD at C3 and elevated SIG were shown to be independently associated with inferior survival. In chapter 13 the longitudinal change in CT-BC was investigated in patients undergoing intervention for AAA. A decline in both SMI and SMD was observed following intervention for AAA. The decline in SMD was of a greater magnitude than SMI. Statin therapy was associated with a lower risk of baseline low SMI. In chapter 14 the cross sectional liver area was recorded in patients with AAA at baseline and at follow-up CT, and the association between survival and relationship to CT-BC parameters was tested. Low liver area was associated with inferior survival. There was a decline in liver area, but a preservation of liver density. CT-BC muscle parameters had a greater associated with survival than liver parameters. The present thesis reports a multitude of novel observations which demonstrate an association between CT-BC, the SIR, and survival, as well as their associations, in patients with vascular surgical conditions. These results support the work performed in different conditions, and highlight the possible role of these factors in clinical risk prediction and patient selection

Structural performance of a novel sustainable and demountable composite floor system - recycled aggregate concrete-steel composite beam utilising demountable shear connectors

This study examines sustainable construction methods, particularly the reusing of steel beams and the recycling of concrete materials. This study specifically looks at how recycled aggregate concrete (RAC) and demountable shear connectors could be used in composite floor systems, an area that has yet to be looked into enough in the past. The demand for sustainable solutions in the construction sector is rising, and this research responds to that necessity by offering an innovative flooring system that integrates RAC with demountable shear connectors, specifically for application in temporary and short-term leasing structures. A literature study on concrete microstructure indicated that residual mortar on recycled aggregate alters the interfacial transition zone (ITZ), influencing the mechanical properties of RAC. A review was conducted on the structural uses of RAC, encompassing RAC-filled steel tubes and composite slabs. For the development of the proposed innovative floor system, two types of demountable shear connectors were evaluated, with the bolted type chosen for its practicality. Bondek II was chosen for profiled steel decking because of its benefits and prevalent application in the local market. A study gap was identified: the majority of studies on RAC employ a fixed mix design, altering the percentage of recycled aggregate instead of sustaining a consistent goal concrete strength. This complicates the assessment of whether diminished structural resistance results from the utilisation of recycled aggregates or from a reduction in design strength relative to normal aggregate concrete (NAC). A fixed design strength approach was suggested to provide target strength by augmenting recycled aggregate replacement and diminishing the water-to-cement ratio. The primary scientific challenge is ascertaining the ideal water-to-cement ratio to facilitate recycled aggregates substitution and attain the requisite concrete strength. Two main tests are proposed. The first assessment is the push-off test, frequently employed to assess the shear behaviour of shear connections. Two categories of push-off specimens have been developed, each comprising four identical geometries, distinguished by shear connector dimensions: M20 and M24. The M20 bolts are positioned in closer proximity to establish a complete connection, whilst the larger M24 bolts are arranged at greater intervals for apartial connection. The recycled aggregate substitution ratio ranges from 0% to 30%, 70%, and 100%, delineating the four specimen categories. Test results demonstrate that the shear resistance of bolted connectors in RAC increases by up to 40% with a higher proportion of recycled aggregate, corresponding to a lower water-to-cement ratio. Full bending tests were performed to evaluate the overall structural performance of the proposed composite floor system. Five test specimens were produced and classified into two categories according to the size of the shear connectors. The first type employed M20 connectors at 200 mm intervals, aligning with the push-off test, and utilised three concrete mixtures: 0% recycled aggregate (baseline), 30%, and 100% replacement. The second variant employed M24 connectors at 400 mm intervals, adhering to the identical push-off test design, utilising two mixtures: 30% and 100% replacement. Test results indicate that composite beams with bolted connectors provide up to a 10% enhancement in flexural resistance in RAC relative to NAC. Subsequent to testing, the pertinent codes were employed to compute resistances and juxtapose them with experimental outcomes. EC3 and EC4 appropriately forecasts shear resistance for bolted connectors in NAC but underestimates it in RAC by 16–51%. AISC and ACI provide more precise average projections; nonetheless, they yield unsafe estimates for NAC, underestimating by as much as 13%, and do not reliably identify the failure mode. Both EC4 and AISC accurately forecast the bending resistance of composite sections, with a mere 2% overestimation of NAC resistance. Nonetheless, they underestimate the bending resistance of RAC by as much as 9%, with AISC exhibiting better precision compared to EC4. Furthermore, the findings demonstrate that bending resistance predictions derived from push-off test data closely correspond with experimental bending test outcomes, indicating that push-off tests function as a reliable indirect approach for evaluating bending resistance with enhanced precision

Environmental literacies for regenerative and sustainable futures: indigenous and traditional perspectives

Education for Sustainability (EfS) as practiced within formal higher education institutions (HEIs), colleges and schools is seldom evidenced to engage deeply with indigenous and traditional environmental literacies (ITELs) (Blenkinsop et al., 2017; Van Poeck and Vandenabeele, 2012). Indigenous refers to environmental literacies originating from indigenous knowledge systems and traditional to those developed through long standing faith, spiritual, and/or cultural traditions. This research inquiry explores and investigates the use of ITELs for EfS and regeneration in non-formal educational contexts in Scotland and Malawi. Foregrounding ITELs, this post-qualitative inquiry utilises a decolonial and pluriversal approach that decentres universalised, dualist, Euro-Western narratives of humans and nature as separate entities (Vásquez-Fernández and Ahenakew, 2020). Contributing to the industrial revolution, these narratives have globally propagated capitalist, materialist, notions of socio-economic development at the cost of the natural environment (Stein, 2019). This research inquiry, therefore, centres historically marginalised knowledge systems, philosophies, and literacies specifically as they relate to human-nature relationality to respond to contemporary sustainability challenges. The decolonial and pluriversal approach informs the theoretical framework for the study that recognises plural ways of knowing and being and brings together three distinct but intertwining theoretical spaces from across geographies and time. The framework draws from: ecopedgagogy as it has developed from the theory and practice of critical pedagogy, originating from the work of Brazilian philosopher Paulo Freire (Kahn, 2010); deep ecology and the concepts behind the long-range deep ecology movement as envisioned by Norwegian philosopher and activist Arne Naess (Naess, 1986); and traditional and contemporary philosophies of Islamic Environmentalism (IE) as they relate to human-nature relationality (Gade, 2019; Nasr, 1987). These three spaces create the decolonial and pluriversal theoretical lens for the study intertwining modern educational theory with faith-based paradigms, bridging “Eastern” and “Western” thought and practice. The theoretical lens enables the creation of educational spaces that allow for a diversity of individuals and plurality of knowledges to come together and create effective responses to the environmental crisis. It also informs the participatory and creative methodologies used for the data generation activities of the study. I designed a series of themed workshops to revive, apply, and celebrate ITELs and facilitated them with student and community participants at a HEI and community organisation in Scotland, including a condensed workshop with members of the Sustainable Futures Global Network (a social enterprise with a focus on creating ethical, equitable, partnerships for sustainability research and practice) in Malawi. I used a range of participatory methods including reflective discussions, problem solving with Ketso, Sharing Circles, embodied expressions, and arts-based inquiry to generate multimodal data. My findings demonstrate that the use of ITELs for EfS promoted holistic material and spiritual conceptions of human-nature relationality, including reflections on articulation of interconnectedness, enabling participants to revive this core ITEL literacy. The findings also show that using an ITEL approach to problem solve for contemporary sustainability challenges enabled the articulation of strong resistance to environmentally destructive norms, greater understanding of the “other”, and expressions of hopeful resilience. Further, using an ITEL focused ecopedagogy enabled the acknowledgement and honouring of each other’s diversity, allowing us to celebrate each other and the plurality of knowledges and literacies we brought to the workshop spaces

Derived symmetries induced by relatively spherical contraction algebras

This thesis constructs homological symmetries (or, more precisely, derived autoequivalences) of algebras and varieties. In more detail, given a surjective ring morphism p: A → B, this thesis constructs endomorphisms T : D(Mod A) → D(Mod A) and C: D(Mod B) → D(Mod B) called the twist and cotwist around the extension of scalars functor induced by p. Moreover, we prove that these endomorphisms are equivalences in two settings: (1) twists for Gorenstein orders, and (2) twists induced by Frobenius exact categories. (1) When A is a Gorenstein order and B is self-injective, then the twist T and cotwist C are equivalences provided that B is perfect as an A-module and satisfies a certain Tor-vanishing condition. In fact, under these assumptions, C is a shift of the Nakayama functor of B. If, moreover, A is an order over a three-dimensional ring, then we prove that the Tor-vanishing condition is equivalent to the ring-theoretic condition that ker p = (ker p) 2 . (2) Given a Frobenius exact category E and an object x ∈ E, let A = EndE(x), B = EndE (x) so that there is a natural surjection p: A → B. In this setting, we show that the functors T and C are equivalences if B satisfies "hidden smoothness" and "spherical" criteria. We furthermore apply the technology developed in (1) and (2) to construct derived autoequivalences of varieties. More specifically, given a crepant contraction f : X → Y between varieties satisfying mild conditions, there is an associated epimorphism of OY - algebras π: A → Acon which, affine locally, induces a surjection of algebras. Therefore, using techniques in non-commutative geometry, we apply the technology of (1) and (2) to construct autoequivalences of D b (coh X). These results extend the construction of the noncommutative twist, introduced by Donovan and Wemyss, to more general settings. As a corollary, we also obtain that the noncommutative twist is in fact a spherical twist, and we discuss how our results extend previous works on spherical twists induced by crepant contractions