Optical skyrmions and polarizations of highly focused structured light

Structured light refers to the controlled tailoring of light fields, encompassing customized attributes such as intensity, phase, and polarization. The study of structured light is motivated by its broad applications, including optical tweezers for trapping and manipulating microscopic particles, multiplexed optical communication, advanced imaging techniques like super resolution microscopy, and quantum information processing. Additionally, structured light offers unique properties such as orbital angular momentum (OAM), which allows information encoding in the twisted phase of light, and spatially varying polarization patterns, which facilitate precise control over light-matter interactions. In this thesis, we investigate various topics related to structured light, including the Faraday effect in strongly focused fields, optical skyrmions, and a two-sphere method for analyzing 3D polarization fields generated by strong focusing. We demonstrate that, for structured light, magneto-optical interactions, specifically the well-known Faraday effect, exhibit a more intricate pattern, which we term the secondary Faraday effect. This effect, arising from the same mechanism as the linear Faraday effect, becomes significant in a strong focusing system, where it reaches a magnitude comparable to the linear effect. We also introduce skyrmionic beams, a class of structured light that has attracted significant research attention. Building on existing methods for calculating skyrmion numbers, we propose a novel approach that explicitly links these numbers to their topological definitions. Furthermore, we identify that skyrmions and bimerons—configurations involving two distinct regions of opposite topological charge—are topologically equivalent by generalizing the definition of their parameters. Emphasis is placed on the geometrical interpretations, which lead to an extended definition of singularities. Throughout the thesis, we are particularly interested in highly focused systems, where additional spatial dimensions play a crucial role compared to paraxial optics. To investigate this, we introduce a two-sphere method to comprehensively describe general 3D polarization fields and apply it to a focused, hence non-paraxial skyrmion beam, as an example

Timed bigraphs for formal verification of sensor network routing protocols

Given that more end-user applications depend on the Internet of things (IoT) technology, which relies heavily on wireless sensor networks (WSNs), it is essential that the routing protocols underpinning these applications are reliable. Using formal methods for reasoning on protocol specifications is an established technique but, due to their perceived difficulty and mathematical nature, they receive limited use in practice. This thesis proposes an approach based on Milner’s bigraphs – a flexible diagrammatic modelling language – that allows developers to “draw” the protocol updates as a way to increase the use of formal methods in protocol design. Bigraphical reactive systems (BRSs) are a graph-rewriting formalism describing systems evolving in two dimensions: spatially, e.g. a person in a room, and non-spatially, e.g. mobile phones communicating regardless of location. To show bigraphs in action, this thesis models part of the routing protocol for low-power and lossy networks (RPL), popular in wireless sensor networks. The model is implemented using the BigraphER toolkit and verified with the PRISM model checker. Simulation, on the other hand, is a common approach in the field of protocol analysis and validation. However, it does not extensively verify protocols in the same way as formal methods do. This thesis experimentally compares the two approaches, the results of which show that analysing the bigraph model often finds more valid routes than simulation while providing comparable performance. The bigraphs model is open to extension with less implementation effort than simulation, which is shown by adding more features to the initial model. Bigraphs seem to be a promising approach for protocol design; this is the first step in promoting their use. Despite the use of bigraphs in domains that include communication protocols, agent programming, biology, and security, there is no support for real-time systems. Therefore, this thesis extends BRSs to support real-time systems by using a modelling approach that employs multiple perspectives to represent digital clocks. It uses Action BRSs, a recent extension of BRSs, where the resulting transition system is a Markov decision process (MDP). This allows a natural representation of the choices in each system state: to either allow time to pass or perform a specific action. The effectiveness of this approach is demonstrated using examples, including extending the RPL initial model with timed aspects using the BigraphER toolkit

Monitoring and managing oil spillage and environmental degradation through geoinformation

The Niger Delta region of Nigeria is a major oil-producing area which experiences frequent oil spills which severely impacts the local environment and communities. Effective environmental monitoring and management remain inadequate in this area due to negligence, slow response times following oil spills, and difficulties regarding access and safety. This thesis investigates the pervasive issue of oil spills in the Niger Delta region, employing a multidisciplinary approach to provide insight into their spatiotemporal patterns, environmental impacts, and socio-economic consequences on local communities. The research integrates advanced geospatial techniques, remote sensing analysis, and community based participatory methods to provide a framework for oil spill impact assessment and quantification. Utilising the spNetwork package in R, Network Kernel Density Estimates (NKDE) and Temporal Network Kernel Density Estimates (TNKDE) were employed to analyse oil spill patterns along the pipeline network. By transforming pipeline data into 500-metre lixels (linear pixels), this network-based approach uncovered chronically high-risk oil spill hotspots zones and tracked their temporal evolution, thereby offering a vital evidence base for targeted intervention and remediation. This method surpasses traditional spatial analyses by incorporating network constraints and revealing critical spatiotemporal patterns where spills recur over time. Furthermore, a remote sensing approach was developed, leveraging geospatial cloud computing and machine learning to evaluate vegetation health indices (SR1, SR2, NDVI, EVI2, GRNDVI, GNDVI). These indices were analysed using Slow Moving Average (SMA) regression, which revealed significant declines in vegetation health following oil spill events. The contaminated landcovers exhibit a Spearman’s correlation coefficient (ρ) ranging from -0.68 to -0.82, p < 0.005 and P-values below 0.05 in most landcover categories, suggesting a clear and consistent downward trend in the indices’ values, reflecting a decrease in vegetation health in contaminated areas between 2016 and 2023. A Random Forest (RF) classifier further quantified the extent of contaminated land cover, demonstrating the effectiveness of this method for monitoring environmental damage in this challenging terrain. The classifier revealed that landcovers, including contaminated vegetation, wetland, farmland, and grassland cover approximately 4% (1,180 hectares) of the total area. Conversely, the non-contaminated prioritised landcovers (non-contaminated vegetation, wetland, farmland, and grassland) account for 96% (32,215 hectares) of the total landcover area

The use of betaine as a novel senotherapy

Background: The global population demographic comprising those aged 65 years and over is increasing. Despite an increase in human life expectancy over the past 150 years, this has not been matched by a similar increase in health span (i.e. years of disease free living). Consequently, ageing populations present with more age-/lifestyle related diseases such as cardiovascular disease (CVD), chronic kidney disease (CKD) and cancer as part of a diseasome of ageing. Betaine is a key component of one-carbon metabolism required physiologically as an osmolyte, an antioxidant and a methyl donor for maintenance of the epigenetic landscape of ageing and mitochondrial function. Objectives: The present study aims to assess how dysregulated ageing underpins the development of vascular ageing and the effects of betaine to mitigate this. Methods: A series of experiments using real time cell analysis (RTCA), transcriptomics, immmunohistochemistry, immunocytochemistry and real-time PCR for a range of validated biomarkers of vascular ageing have been investigated in primary and induced pluripotent stem cell (iPSCs)-derived vascular smooth muscle cells (VSMCs) from human subjects. Betaine was then examined in in vivo models for its geroprotective effects on Drosophila melanogaster (D. melanogaster) and Caenorhabditis elegans (C. elegans). Results: Our data indicate that betaine is a potent senotherapeutic able to extend primary VSMCs life span and diminish expression of biomarkers of cellular senescence (p16, p21, Nrf2, SerpineB2, cytoplasmic chromatin fragments), and the senescence-associated pro-inflammatory secretome (IL1β, IL6), as well as biomarkers of VMSCs damage (FOXO4, LMNA). In iPSCs-induced VSMCs, betaine has also displayed potential geroprotective effects by downregulating vascular calcification, extracellular vesicles and oxidative damage. Additionally, it increased total mitochondria content while protecting mitochondria membrane potential against DMSO treatment. Our vivo models (C. elegans, D. melanogaster) exhibited up to 20% lifespan extension after supplementation with betaine. Conclusion: Our data indicate that betaine may be a powerful naturally occurring senotherapy and suitable for safe future clinical development

Stratification of respiratory disease through early diagnostic sampling

Both lung cancer and Coronavirus Disease 2019 (COVID-19) present with a wide range of prognoses and eventual outcomes. In both conditions early diagnosis and commencement of treatment (where appropriate) can improve survival. Given the spectrums of disease seen in lung cancer and COVID-19, stratification of patients also aids in the selection of the most appropriate individual management options to further optimise patient outcome. The overall aim of this thesis is to examine the stratification of respiratory disease through early diagnostic sampling. Chapter 2 describes the design and delivery of the multi-centre, prospective STRATIFY study (Staging by Thoracoscopy in potentially radically treatable Lung Cancer associated with Minimal Pleural Effusion). It has been established from retrospective data that those presenting with early stage, otherwise potentially radically treatable non-small cell lung cancer (NSCLC) and minimal pleural effusion do significantly worse in terms of survival than those without such effusions. Based on this previous retrospective data it has been hypothesised that this difference in survival is due to the presence of occult pleural metastases (OPM) not otherwise detected in the routine diagnostic work up of those with suspected NSCLC and minimal pleural effusion. STRATIFY was therefore designed as the first prospective, multicentre, observational study with the primary aim of determining the true prevalence of OPM in this cohort of patients through the addition of thoracoscopy to the diagnostic pathway. Unfortunately, due to a multitude of issues many of which stemmed from the COVID-19 pandemic, recruitment to STRATIFY was slower than expected and therefore the decision to close the trial to recruitment was taken in May 2024. Primary outcome data including the prevalence of OPM and important safety data for the 27 recruited patients are however included here. Patients with lung cancer (and many other common malignancies) often present with large pleural effusions which go on to be proven malignant through simple aspiration. The diagnostic yield of pleural fluid cytology is well documented at 60% on average but varies considerably by tumour type. The yield of predictive markers from effusion cytology, which are now mandated in the diagnostic work up of lung and breast adenocarcinoma, is less well established. Chapter 3 of this thesis therefore aimed to assess the utility of pleural fluid cytology for the detection of predictive markers in lung and breast adenocarcinoma in a real-world setting. This multicentre, retrospective cohort study found that the full panel of predictive marker (PM) testing required by contemporaneous international cancer treatment guidelines was returned in only 20% of cases where these were requested on pleural fluid cytology. Performance differed by individual marker with yields for many markers improving over the time period of the study. No clinico-radiological factors were significantly associated with PM testing yield to guide pre-aspiration likelihood of success. Perhaps even to a greater extent than lung cancer, outcomes from COVID-19 are markedly heterogeneous with some patients complaining of little to no symptoms while others go on to develop potentially fatal pneumonitis. Although risk factors for poor prognosis are well documented, less is understood about the individual immune response and how these immunological events affect disease outcome. In chapter 4 individual immune response at the time of COVID-19 diagnosis and how this relates to disease severity was examined. In keeping with previous work, severe COVID-19 (as defined by the need for supplemental oxygen) was associated with obesity and hypertension (p= 0.0456, p= 0.0071 respectively) in this cohort. Flow cytometry of baseline serum samples revealed lower activation (phosphorylation) of STAT 5 in response to stimulation across almost all immune cell subpopulations in those with severe disease. Interrogation of potential mechanisms linking metabolic syndrome and the altered STAT5 signalling observed are ongoing by collaborators at the time of writing

Controlled design of human-like agents with context-guided learning for automated video game playing

The video game industry state-of-the-practice ad hoc behaviour authoring techniques produce transparent and highly controllable autonomous agent artificial intelligence (AI) representations, but show limitations in adaptive and human-like behaviour design. Machine learning (ML) methods can cope with such constraints, but the black-box nature, high training costs in terms of data volume and time, as well as incompatibility with iterative workflows, make ML models unsuitable for commercial game development. To address the shortcomings of both these approaches, we investigate a non-disruptive, modular design approach to integrating small-scale learning models featuring performance and execution guarantees, as well as embedded human designer intent, into behaviour tree (BT) architecture for autonomous video game agents. We deployed the proposed design in the environment of a published, commercial video game 60 Seconds!, which we instrumented for agent training and evaluation using an off-the-shelf game engine, BT and a learning library. After quantitative analysis of the mass-scale gameplay telemetry dataset of 8,244,111 trajectories from real game users, we clustered the player population with respect to estimated play skill, using a gameplay context-based score metric. Output agent models were then developed and trained in the game’s environment by applying the design, guided by game context-relevant segmentation of logic and behaviour of the top play skill persona model, derived from the trajectory data of the 7% top-scoring player cluster. The output agent’s gameplay performance was benchmarked against that of a reference agent, and experimentally evaluated in a normalised game scenario against 18,947 human players. It was found to be valid in the context of the game environment, functional, and capable of pursuing gameplay objectives in unseen scenarios with competency. However, it was unable to outperform human players due to the suboptimal performance of its trained learning models. We determined that software stability issues of the learning library used, limited observation space, and egocentric data adversely affected agent training. While further work to improve the training process is necessary, the successful application of the context guided agent design in a commercial video game environment confirmed its potential for industrial applications. By contributing the design, the mass-scale dataset, and the tools used in our research, we enable the context-guided agents to be deployed in alternative contexts

Empagliflozin to prevent worsening of left ventricular volumes and systolic function after myocardial infarction

Background Heart failure following an acute myocardial infarction (MI) is associated with significant morbidity and mortality, making its prevention a key therapeutic goal. Progressive adverse ventricular remodelling, characterised by ventricular dilation and declining systolic function, is a key precursor to the development of heart failure after MI. Early reperfusion therapy and medications that reduce mortality and heart failure post-MI, such as angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and beta-blockers, also prevent adverse remodelling. The mineralocorticoid receptor antagonist (MRA) eplerenone improved outcomes post-MI but showed a significant anti-remodelling effect only after adjusting for baseline covariates. Sacubitril/valsartan did not reduce the risk of developing heart failure or cardiovascular mortality in high-risk post-MI patients and had minimal impact on remodelling. Sodium-glucose co-transporter 2 (SGLT2) inhibitors lower the risk of heart failure progression and mortality in patients with chronic heart failure across all ranges of left ventricular ejection fraction (LVEF). One of their key mechanisms of benefit in heart failure with reduced ejection fraction (HFrEF) is a positive effect on ventricular remodelling. Empagliflozin did not significantly reduce the primary outcome of heart failure hospitalisation or all-cause mortality in high-risk post-MI patients, but did lower the incidence of first and total heart failure hospitalisations and other adverse heart failure events. Whether this is related to a remodelling effect remains uncertain. In lower-risk post-MI patients, dapagliflozin improved cardiometabolic outcomes but did not significantly impact the composite outcome of cardiovascular death or heart failure hospitalisation. I conducted the EMpagliflozin to PREvent worSening of left ventricular volumes and Systolic function after Myocardial Infarction (EMPRESS-MI) randomised, placebo-controlled trial, which was designed to test the hypothesis that empagliflozin, when added to standard care, would mitigate adverse left 3 ventricular remodelling in high-risk post-MI patients, as assessed using cardiovascular magnetic resonance (CMR) imaging. Aims and methods The aim of the EMPRESS-MI trial was to examine the effect of empagliflozin on left ventricular remodelling in patients with left ventricular systolic dysfunction after an acute MI using the gold-standard method, CMR. I performed a randomised, placebo-controlled trial comparing empagliflozin 10mg once daily with placebo, in addition to standard care, in patients within 12 hours and 14 days of an acute type 1 MI and an LVEF<45% by CMR. Key exclusion criteria were a history of HFrEF or contraindications to SGLT2 inhibitors. Patients with an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2 (measured using the modification of diet in renal disease formula) were excluded. Patients with permanent or persistent atrial fibrillation or an implanted cardiac device were excluded to avoid potential CMR image degradation. The primary outcome was the change in left ventricular end-systolic volume index (LVESVI) from baseline to 24 weeks as measured by CMR. The secondary outcomes, measured as change from baseline to 24 weeks, were: left ventricular end-diastolic volume index (LVEDVI), LVEF, left atrial volume index (LAVI), left ventricular mass index (LVMI), N-terminal prohormone of B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin I (hs-TnI), and infarct size measured using CMR. Exploratory outcomes included the change in biomarkers relevant to the actions of empagliflozin (uric acid, glycated haemoglobin, and haematocrit), kidney function, and body weight. I also examined the relationship between intramyocardial haemorrhage (IMH) and left ventricular remodelling and the effect of empagliflozin. Results In 104 patients included in the final analysis set, mean±standard deviation age was 63.0±11.2 years and 90 (86.5%) patients were male. The median time from MI to randomisation was 3.0 days (interquartile range 2.0-5.0). 92 (88.5%) patients had an ST-elevation MI (STEMI) and 12 (11.5%) had a non-STEMI (NSTEMI). 83 (79.8%) MIs were in the anterior location. Nearly all patients (103 4 [99.0%]) had percutaneous coronary intervention (PCI) or thrombolysis. At randomisation, 97 (93.2%) patients were taking an ACE inhibitor or an ARB, 89 (85.6%) a beta blocker, 66 (63.5%) an MRA, and 30 (28.8%) were on a loop diuretic. 46 (44.2%) patients received a loop diuretic at any point during the index admission before randomisation. The mean LVEF by echocardiography was 35.0±4.9% and by CMR was 34.8±6.0%. In the placebo group, LVESVI decreased by 7.8±16.3 mL/m2, LVEDVI did not change (-0.3±18.7 mL/m2) and LVEF increased by 8.5±7.4% from baseline to 24 weeks. Empagliflozin had no effect compared with placebo on the change in LVESVI from baseline to 24 weeks; adjusted between-group difference 0.3 mL/m2 (95% confidence interval [CI] -5.2 to 5.8); P=0.92. Empagliflozin had no effect on the change in LVEDVI, LVEF, LAVI, LVMI, NT-proBNP, hs-TnI or infarct size but did increase haematocrit (P=0.006) and reduced uric acid (P=0.006) and body weight (P=0.006). At baseline, of 93 patients with complete data, 45 (48.4%) patients had IMH and 48 (51.6%) did not. In patients with IMH, LVESVI did not change between baseline and 24 weeks whereas in patients without IMH LVESVI decreased (-0.9±11.4 mL/m2 vs. 14.7±14.7 mL/m2; P<0.001). In patients with IMH, LVEDVI increased whereas in patients without IMH LVEDVI decreased (9.1±12.7 mL/m2 vs. - 7.8±16.8 mL/m2; P<0.001). LVEF improved in patients with and without IMH but to a lesser degree in those with IMH (7.4±7.1% vs. 10.7±7.7%; P=0.004). Empagliflozin had no effect on remodelling in patients with and without IMH at baseline. Conclusion In patients with left ventricular systolic dysfunction after an acute MI treated with contemporary reperfusion and medical therapy, the addition of empagliflozin to standard care did not have any effect on improving left ventricular volumes or function compared with placebo, and did not reduce biomarkers of left ventricular wall stress (NT-proBNP) or myocardial injury (hs- TnI). Progressive adverse cardiac remodelling did not occur in the majority of patients

Role of ER stress in vascular dysfunction and damage during hypertension

Hypertension is a major risk factor for cardiovascular diseases and involves complex molecular mechanisms that are not fully understood. Recent evidence indicates that endoplasmic reticulum (ER) stress plays a crucial role in hypertension, particularly by affecting vascular function. This thesis explores the hypothesis that ER stress contributes to hypertension through mechanisms involving oxidative stress, calcium signalling dysfunction, and changes in microRNA (miRNA) expression. These processes can lead to increased vascular contractility, which may ultimately contribute to elevated blood pressure. This study utilised both human vascular smooth muscle cells (VSMCs) and animal models to investigate the molecular mechanisms linking ER stress to hypertension. Using miRNA microarray analysis, 242 differentially expressed (DE) miRNAs were identified when comparing VSMCs from hypertensive (HT) individuals to those from normotensive(NT)individuals, each represented by one sample derived from three different individuals. These (DE) miRNAs were associated with key genes and proteins related to oxidative stress and calcium signalling, including Noxs, SOD2, catalase, and ER calcium channels, as determined through Ingenuity Pathway Analysis (IPA). Notably, ER stress induced by tunicamycin significantly altered the expression of oxidative stress markers (Noxs, SOD2,catalase) and calcium channels in HT VSMCs compared to NT VSMCs, indicating that ER stress regulates oxidative stress and potentially contributes to calcium signalling dysfunction. Further insights were gained from studying a chronic Ang II-induced hypertensive mice model (LinA3). ER stress was found to specifically activate the PERK pathway, indicating selective ER stress activation in VSMCs under hypertensive conditions. In this model, oxidative stress was characterized by increased O2 -• generation, lipid peroxidation, irreversible protein oxidation, and altered antioxidants system of VSMCs compared to wild-type mice. The role of Nox4 in modulating the interaction between oxidative stress and ER stress was highlighted, as Nox4 deficiency led to changes in the expression of ER stress markers, including increased BIP and Chop in the kidneys of wild-type mice and increased PDI in the kidneys of LinA3 mice. These findings suggest a potential roleforNox4 in modulating ER stress in hypertension. This study found that the pre-hypertensive factor endothelin-1 (ET-1) induces ER stress and that ER stress contributes to vascular hypercontractility, using spontaneously hypertensive rats (SHRSP) compared to normotensive Wistar Kyoto (WKY) rats. Our findings demonstrated elevated levels of ER stress in the hearts and VSMCs of SHRSP compared to normotensive controls, indicating a link between ER stress andhypertension.ET-1 was found to induce ER stress through both ETA and ETB receptors, leading to increased expression of ER stress markers such as ATF4, XBP1s, and BIP. Inhibition of ER stress resulted in reduced activation of the contractile machinery, establishing a connection between ER stress, calcium signalling dysfunction, and the enhanced contractile response observed in hypertension. Lastly, in vivo treatment with the ER stress inhibitor 4-phenylbutyric acid(4PBA)in spontaneously hypertensive rats (SHR) demonstrated reduced blood pressure, improved endothelial function, and a tendency toward improved vascular structure. These findings suggest that ER stress is a critical mediator of vascular dysfunction and structural changes in hypertension and present ER stress inhibition as a potential therapeutic strategy for managing hypertension. In conclusion, this thesis highlights the role of ER stress in mediating vascular dysfunction in hypertension, emphasizing its interactions with oxidative stress, calcium dysfunction, and the potential involvement of miRNA regulation. These findings lay the ground work for the development of novel therapeutic strategies targeting ER stress to treat hypertension

The impact of blockchain technology implementation on supply chain collaboration

Abstract not currently available

In the face of diversity: revealing the influence of ethnicity and culture on social trait face perception

On a daily basis, people make spontaneous judgements about who to trust or avoid based on facial appearance. Because of their considerable downstream consequences, a longstanding goal has been to understand which facial features drive social trait judgements. Despite emerging evidence showing that ethnic and cultural diversity influence social trait perception, most knowledge remains centred on White Western observers perceiving White faces. This bias questions the generalizability of prominent theories and feature-based models. In this thesis, I combine a data-driven reverse correlation approach with a generative model of 3D human faces to model the specific facial features of 3D shape and 2D complexion that drive perceptions of trustworthiness and dominance from three face ethnicities—Black African, East Asian, and White European—in two observer cultures—White Western and East Asian. Using information-theoretic analyses, I show that both White Western and East Asian observers perceive trustworthiness and dominance from a core set of facial features which are shared across face ethnicities, and map onto previous findings, plus novel face ethnicity-specific variations. These variations challenge the generalizability of prominent feature-based models and characterize the causal influence of face ethnicity on social trait perception. Further, while conceptually similar, the results for White Western and East Asian observers comprise different facial features. To formally test these differences, I next examine the cultural specificity of the modelled facial features across face ethnicities. Results show that, while White Western and East Asian observers provide similar social trait ratings for each face ethnicity, the features they base their ratings on differ. This questions previous claims of universality based only on rating comparisons. Further analyses reveal that the facial features specific to Western culture resemble specific emotion cues (e.g., smiling, frowning), whereas those specific to East Asian culture do not. This contrasts prominent theories such as emotion overgeneralization and highlights the Western-centric bias of current knowledge. Finally, I use a machine-learning approach and information-theoretic analyses to examine how face ethnicity, observer culture, and their synergistic interaction causally influence social trait perception. Results show that, across face ethnicities and observer cultures, social trait perception is driven by four feature sets: those that are shared, those that are face ethnicity-specific, those that are culture-specific, and those that are synergistic. Subsequent examinations of these feature sets confirm that they represent key sources of variance in social trait perception. These findings extend current efforts to quantify the relative contributions of the face, the observer, and their interaction and offer direct empirical support for modern theories of social trait perception. Together, this thesis responds to mounting calls to diversify psychological science by showing that ethnic and cultural diversity systematically alter the causal facial features for perception of key social traits, with direct implications for current knowledge and theory development