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The Ecological and Evolutionary Significance of Functional Variation in Mitochondria in the Three-spined Stickleback.
Full text linkMitochondria are widely known as the ‘powerhouse of the cell’ due to their importance in energy metabolism, and the mitochondrial DNA (mtDNA) plays a central role as it encodes subunits of the oxidative phosphorylation pathway, responsible for the majority of this energy production when oxygen is available. Despite this fundamental role, the adaptive significance of mtDNA variation has often been overlooked. It is now well established that the mitogenome is not evolving neutrally as once assumed, with studies across numerous taxa identifying evidence of positive selection, or showing that mtDNA variation has functional consequences which can be associated with adaptation. However, pure mitochondrial effects have rarely been separated from nuclear genetic effects in natural study systems, mainly due to a lack of populations or species wherein variation in the mtDNA can be studied independent of potentially confounding variation in the nuclear genetic background. In this thesis, I focus on Atlantic three-spined stickleback (Gasterosteus aculeatus) on the Scottish island of North Uist, where, in migratory populations, two deeply diverged mitochondrial lineages segregate against a common nuclear genomic background. I show that the stickleback provides a valuable model to determine the adaptive significance of mtDNA variation. I first assessed the development of migratory stickleback, and examined the effect of anaesthetics on mitochondrial function. I then focused on variation between the two highly diverged mitochondrial lineages that likely diverged in allopatry on opposite sides of the Atlantic, but are now both widespread. Migratory populations were a mix of the two lineages, but resident populations in fresh water and saltwater lagoons were predominantly one lineage, suggesting differing adaptive potential. Using phylogenetic selection analyses, I found evidence that the mitogenomes of the Atlantic three-spined stickleback evolved under positive selection, so the mtDNA variation itself may be adaptive. Unlike previous work in natural populations, I was able to show that mtDNA variation had temperature-dependent consequences for mitochondrial respiration independent of the nuclear genetic background. By combining phylogeography, ecology, selection analyses and mitochondrial physiology, I show that mitochondrial variation makes an important contribution to the ecology and evolution of the Atlantic three-spined stickleback. To my knowledge, this research may be the first to explicitly link mtDNA variation to physiological mitochondrial differences and adaptive potential in natural populations, independent of the nuclear genome
Internal constructions in homotopical type theory
Full text linkThe aim of this thesis is to investigate certain constructions that resist satisfactory full internalizations in plain homotopy type theory, i.e. intensional Martin-Löf type theory with the univalence axiom.
In Part I, we study internal higher categorical models of homotopical type theory, via wild categories with families (cwfs). We formulate coherence conditions on wild cwfs that suffice to recover properties expected of models of dependent type theory. The result is a definition of a 2-coherent wild cwf, which admits as instances both the syntax and the "standard model" given by a universe type. We also identify a higher "splitness" coherence condition that is satisfied by all set-level cwfs and univalent 2-coherent wild cwfs.
In Part II, we apply some of the theory developed in Part I and report on a partial investigation into the construction of type-valued Reedy-fibrant inverse diagrams in plain HoTT
Random Walk Approach to predict electromagnetic emissions for multiple power electronic converters
Full text linkThis thesis addresses the increasing Electromagnetic Compatibility (EMC) challenges posed by multiple Power Electronic (PE) converters operating simultaneously within a network. As current EMC standards predominantly focus on single-device evaluation, a significant research gap exists in modelling and predicting aggregate electromagnetic interference from multiple converters. The research proposes a new application of Pearson’s Random Walk (PRW) theory to characterise Common Mode (CM) electromagnetic emissions in multi-converter configurations.
The investigation demonstrates that Pearson’s Random Walk provides an effective statistical framework for modelling electromagnetic emissions from multiple PE converters, where traditional deterministic approaches have proven inadequate. The model is based on the assumption that the sole variable under control is the switching-on time of the converters. The model employs vectors that represent the phase of waveforms being produced by each converter, associating converter switch-on times with vector angles to predict aggregated electromagnetic interference. This approach was verified through both simulation studies of eight identical converters and experimental measurements with three DC/DC converters.
Statistical verification through empirical and theoretical cumulative distribution function (cdf) confirmed the model’s validity regardless of harmonic number. Furthermore, the research presents the first explicit computation of the probability that electromagnetic interference is reduced in a multi-converter configuration compared to a single-converter arrangement. Results indicate that whilst electromagnetic interference reduction is possible, this probability diminishes with an increasing number of converters.
The developed methodology offers manufacturers and network operators a robust framework for predicting worst-case electromagnetic emissions in multi-converter systems, thereby addressing requirements specified in current electromagnetic compatibility directives. This contribution advances the standardisation efforts of the IEC CISPR Working Group 4 concerning the impact of increased device quantities on electromagnetic compatibility
Combinatorial screening of glycosaminoglycans for immune-instructive properties
No full textBiomaterials are extensively utilised in implantable medical devices (IMD), but their use can trigger varying degrees of immune responses in the human body. Macrophages play a critical role in mediating the immune response and maintaining tissue homeostasis. Upon activation by cytokines, endotoxins, or other danger signals, macrophages can adopt a spectrum of functional phenotypes, with pro-inflammatory M1 (classically activated) and anti-inflammatory M2 (alternatively activated) representing the extremes of this spectrum, which secrete various soluble molecules, including cytokines and chemokines, regulating inflammation and promoting tissue healing. Understanding how macrophages respond to biomaterials is essential for modulating specific biological outcomes. Consequently, the development of immune-instructive biomaterials that focus on macrophage phenotype modulation is of considerable interest.
Glycosaminoglycans (GAGs), key constituents of the extracellular matrix (ECM), are linear polysaccharides composed of repeating disaccharides that can be divided into four main types: hyaluronic acid (HA), chondroitin sulphate/dermatan sulphate (CS/DS), heparin/heparan sulphate (HP/HS) and keratan sulphate (KS). They have been recognised for their role in regulating macrophage activity and immune responses, positioning them as promising candidates for therapeutic applications in tissue regeneration and wound healing. Despite their potential, the optimal composition and combination of GAGs for these purposes remains undefined. The overall goal of this study was to investigate the effect of different combinations of GAGs on the macrophage phenotype using an unbiased screening strategy to identify ‘hit’ GAGs with immunomodulatory properties capable of modulating immune responses during wound healing.
This thesis employs a systematic and combinatorial screening strategy to explore the immune-modulatory properties of GAGs, using a library of 82 mixtures comprising 10 individual GAGs and 72 combinations, varying in type, molecular weight, and degree of sulphation. Peripheral blood monocytes from healthy human donors were cultured with GAGs and allowed to differentiate into macrophages over a 6-day period, after which their phenotype was characterised. Here, the phenotype of the macrophages was determined by quantifying pro-inflammatory and anti-inflammatory cytokines and chemokines, as well as through immunostaining of specific cell membrane protein markers.
Optimal conditions for GAG activity were identified, with CS (a representative GAG) being shown to promote macrophage polarisation in a concentration-dependent manner. ‘Hit’ GAGs were selected through multi-dimensional comparative analyses, including hierarchical cluster analysis, principal component analysis (PCA), and GAG fraction comparison, based on the cytokine profiles produced by macrophages cultured on GAG-coated surfaces for 6 days. The screening process identified key GAG formulations, including GAG-comb 33 (DSH001/2) and GAG-comb 63 (70% HEP-POLY4 and 30% CS-EI), which effectively modulated macrophage polarisation, showing immune-instructive properties. These formulations were subsequently tested in wound healing models. In vitro studies demonstrated that these GAGs promoted human foreskin fibroblast-mediated wound closure. 3D OrbiSIMS analysis revealed significant changes in the metabolic profiles of macrophages following treatment with the GAGs, which may explain the observed acceleration of wound closure, facilitated by their conditioned media. In vivo studies further confirmed the therapeutic efficacy of GAG-comb 63, which facilitated immune modulation and tissue regeneration, significantly improving wound healing outcomes in a diabetic model after 7 days of treatment.
This thesis provides a comprehensive evaluation of the immunomodulatory properties of GAGs, identifying key combinations that promote macrophage polarisation and support tissue regeneration and wound healing. The findings offer valuable insights into the therapeutic potential of GAGs, particularly for diabetic wound healing, and establish a solid foundation for their broader application in immune modulation and regenerative medicine
Novel thermochemical energy storage system: from material development to evaluation
Full text linkThe building sector is a major contributor to global energy consumption and carbon emissions, with heating demand predominantly met by fossil fuels. As the integration of variable renewable and waste heat sources into urban heating networks expands, thermochemical energy storage (TCES) presents a promising solution, offering high energy density and the potential for long-duration storage. However, the practical deployment of TCES has been limited by material and reactor inefficiencies critical for industrial waste heat recovery.
This research aimed to develop and evaluate a novel TCES material tailored for medium-temperature waste heat applications. A new composite based on Mg(OH)₂ doped with 5 wt% KNO₃ and 15 wt% Al₂O₃ was synthesized and characterized. The doped material exhibited a reduced dehydration temperature from ~317 °C to 293 °C, enabling more efficient waste heat capture within the 293–400 °C range. The energy storage capacity increased from 1246 J/g to 1317 J/g. Molecular simulations predicted a thermal conductivity of 0.708 W/mK, an enhancement of 12.9% over pure Mg(OH)₂, which aligned well with experimental values (0.6484 W/mK).
Reactor-scale numerical modelling of 1.5 kg of the composite in an agitated fluidized bed reactor showed that dehydration began at 300 ℃ with an airflow of 28.95 kg/h, achieving a minimum fluidization velocity of 0.1850 m/s and a 99.99% reaction efficiency, releasing +5 kW of heat. Hydration initiated at 200 ℃ using a humidified air stream, with a minimum fluidization velocity of 0.01598 m/s and a 99.21% reaction efficiency, releasing −4.8 kW of heat. A water vapour to MgO molar ratio beyond 4:1 showed saturation effects, indicating water as a limiting factor in hydration.
These findings demonstrate the potential of the developed Mg(OH)₂-KNO₃-Al₂O₃ composite for efficient medium-temperature TCES. Future work should focus on long-term material stability, advanced reactor modelling, and full-scale validation to support real-world deployment in building energy systems
Investigating lyssavirus glycoprotein interactions
Full text linkThe Lyssavirus genus contains the viruses responsible for the disease rabies, an acute progressive encephalomyelitis which is fatal in over 99% of human cases without treatment prior to the onset of symptoms. The genus is made up of three distinct phylogroups representing genetic distance and antigenic properties. The primary causative virus of rabies is the rabies virus which is involved in over 99% of human infections. Despite its highly pathogenic nature and the fact it causes over 59,000 deaths annually, particularly in developing nations, it is considered to be a neglected pathogen. While the human burden of lyssavirus infection is great, there are available treatments both pre and post infection. However, current treatments suffer from high costs, inconvenient and extensive treatment regimens, cold chain necessity and lack of inter-phylogroup neutralisation. These issues have generated interest in a novel vaccine.
For lyssaviruses, there is only one surface protein, the trimeric spike glycoprotein. This protein is involved in many important viral processes such as host receptor attachment and cell entry. It is because of this importance and the many remaining questions surrounding lyssaviruses that this study has focused on the glycoprotein and its interactions.
In order to study the glycoprotein in isolation a three plasmid pseudo-virus system was used. This system can be used to express a viral glycoprotein of interest on a vector such as a lentivirus in order to produce a non-replicative and safe pseudo-virus. This was used to infect immortalised cell lines such as BHK-21 to examine changes in outcome from both modifications of the glycoprotein and neutralisation using non-human primate sera or monoclonal antibodies. Additionally, this system was used to infect primary NK cells to determine their susceptibility to rabies virus infection.
Results of neutralisation assays performed by this study demonstrate that a novel medoid vaccine presented cross-phylogroup neutralising properties beyond any currently available vaccine, indicating a potential solution for divergent lyssavirus infection concerns. The vaccine was able to elicit significant neutralisation against MOKV and WCBV by week 5, and IKOV following a boost at week 50.
Glycosylation of the lyssavirus glycoprotein was also investigated and shown to be important in the infection capability and neutralisation susceptibility of the protein. The removal of fixed virus glycan Asn204 was found to significantly reduce infectivity and increase neutralisation susceptibility whereas removal of Asn37 increased infection though had no impact on neutralisation. The strongest change was in their combined removal. Asn319 removal also completely removed any infectivity. Common amino acids used in substitutions to knock out glycans aspartic acid (D), glutamine (Q) and alanine (A) were also examined for their impact and it was found that differing amino acids produced significantly different results. Finally, NK cell infection was found to not occur, however further work needs to be done to confirm this finding.
Research into rabies is both important and inadequate with many important questions remaining unanswered. The lyssavirus glycoprotein and its interactions are essential in understanding lyssaviruses and developing novel therapies for them. This study aimed to further elucidate some of the questions surrounding the glycoprotein. It also provides a foundation for more exciting discoveries and findings
Pragmatic and performative populism across the 2015, 2017 and 2019 UK general elections
Full text linkPopulist parties have made significant progress worldwide. However, despite populism’s electoral growth and extensive literature, there remains no consensus on its definition. This lack of clarity presents a key research puzzle: How can a single, unified theoretical approach address the shortcomings of existing approaches and encompass all the nuances of populism? To tackle this question, I build on current studies to create a comprehensive framework for analysing both core and peripheral themes of populism. While the term populism generates considerable debate, key themes persist within the progressive theoretical framework. The framework analyses the prevalence of populism in political parties and their leaders’ political discourse. I identify two types of populism: pragmatic populism, which utilises only populism’s core features, and performative populism, which incorporates both core and peripheral features of populism. I apply the framework through an in-depth discourse analysis, examining the extent to which populism is present in the 2015, 2017, and 2019 UK General Elections. I consider the variation among the Conservatives, Labour, and UKIP/Brexit Party (BXP), alongside changes across elections. The findings indicate that populism is prevalent in both UKIP/BXP and Labour discourse, while the Conservatives exhibit limited populist elite antagonism. While populism increases across elections for Labour and the
Conservatives, UKIP/BXP contradict this trend. I also identify various forms of populism, ranging from non-populism to pragmatic populism. In summary, populism appears to penetrate the British political mainstream and increase across elections
FGE-catalysed modification of CAZymes: A new approach for monitoring protein-cellulose interactions
No full textFossil fuels dominate the global energy sector and are considered the primary reason for the rise in greenhouse gases. Renewables represent a sustainable alternative yet lack investment in infrastructure. Biofuels are one alternative that may allow us to achieve the goals outlined in the 2015 Paris agreement. 2nd Generation biofuels use waste biomass from primary feedstock production. Lignocellulosic biomass is the most abundant biomass source globally, making it a promising energy source. Organisms across nature are known to produce enzymes capable of degrading polysaccharides, which are exploited in commercial bioethanol synthesis. Despite this little is understood about how these enzymes bind to extended cellulose surfaces. Expanding this knowledge may allow us to exploit these enzymes industrially.
Techniques like Nuclear Magnetic Resonance (NMR) spectroscopy and X-ray crystallography cannot be applied to insoluble polysaccharides which are often the natural substrates of these enzymes. Electron Paramagnetic Resonance (EPR) spectroscopy can use solids and has been used to characterise the binding of lytic polysaccharide monooxygenases (LPMOs) to cellulose surfaces. Unlike LPMOs, glycoside hydrolases (GHs) and carbohydrate binding modules (CBMs), lack the paramagnetic species required for this technique.
Traditional protein labelling methods typically utilise long flexible linkers and are not site specific. Formylglycine generating enzyme (FGE) represents the opportunity to introduce a small, versatile aldehyde functionality in a site-specific manner which can be reacted with a variety of aminooxy and hydrazine functionalised reagents.
Here we present the methods to site selectively modify CBMs and GHs using FGE which can then be reacted with a hydrazone functionalised ligand scaffold, capable of chelating copper. In turn, this will provide the paramagnetic species required to expand the EPR methodology to other classes of CAZymes.
This work outlines the synthesis and characterisation of a ligand scaffold, its reactivity and its copper coordinating abilities. Using commercially available aldehydes we developed a library of Schiff base ligands to test the reactivity of the ligand scaffold. Using NMR and X-ray crystallography confirmed that the ligand reacts with aldehydes at the hydrazone moiety. We then investigated these ligands copper coordinating properties using UV-vis, electron diffraction, EPR and X-ray crystallography. UV-vis data suggested the ligand binds copper in a 2:1 stoichiometry (ligand:copper). However, resolving the structure of the complex by electron diffraction showed a 1:1 stoichiometry.
A form of FGE was cloned, expressed and purified. Its activity was confirmed using a synthetic peptide substrate, where we detected the aldehyde product by mass spectrometry and reverse-phase liquid chromatography. The reactivity of the modified peptide with the ligand scaffold was demonstrated using similar techniques. We also showed that FGE prefers hydrophobic residues within its recognition sequence, using a series of synthetic peptides with varying sidechains. It was proposed that this preference is likely due to the topology of the active site only accommodating short hydrophobic side chains.
The methods for introducing the site-specific recognition motif into a recombinant CBM of Clostridium thermocellum are outlined alongside a coexpression method to obtain a modified CBM with an aldehyde functionality. We were able to show that the mutant CBM folded into its natural β-sandwich structure and binds to crystalline cellulose. We were able to coexpress the mutant CBM wit FGE and detect the formylglycine residue using a fluorescent probe in combination with gel electrophoresis. The aldehyde product was reacted with the ligand scaffold which we were able to detect using mass spectrometry methods. EPR spectroscopy of the modified CBM suggests an adventitious binding site within the proteins structure. The EPR data shows that the coordination environment of this adventitious binding site is likely composed of oxygen and nitrogen atoms. It was hypothesised that the copper is coordinating with a calcium binding site that stabilises the secondary structure however, this needs experimental confirmation
Deciphering soil structure: linking soil physics, water dynamics, carbon storage, and agricultural resilience in long-term experiments
No full textBackground and Objectives: Soil structure is a key component of soil health, governing processes like water retention, gas exchange, root growth, and carbon storage. However, quantifying its impact on long-term agricultural productivity and ecosystem functions remains challenging. This thesis addresses that gap by leveraging long-term field experiments to explore how soil structure influences (i) crop yield resilience to drought, (ii) soil organic carbon (SOC) dynamics, and (iii) the development of improved measurement techniques for soil structural properties. The overarching aim was to advance our understanding of soil structure and functional relationships in agricultural soils. Methods: Four complementary studies were undertaken. (1) Yield resilience under drought was analysed using decades of data from the Broadbalk Wheat Experiment (Rothamsted, UK), where treatments with varying fertiliser and organic inputs have created differences in soil properties. We related soil physical indices, notably the saturated hydraulic conductivity (Kₛₐₜ) and air-entry value (α) derived from soil water retention curves, to wheat yield performance in identified drought years. (2) Soil structure and SOC were investigated at the North Wyke farm platform (UK) by comparing permanent grassland, improved grass, and arable plots maintained over long periods. We measured changes in SOC stocks alongside soil water release characteristics and performed high-resolution X-ray Computed Tomography (CT) scans of soil aggregates, using image analysis and modelling to quantify pore network connectivity and substrate transport capacity. (3) To improve structural assessment, we developed a novel multi-tension infiltration method based on the Green–Ampt infiltration model. This technique was deployed in the Highfield Ley-Arable Experiment (Rothamsted) to partition soil macroporosity from capillary matrix porosity, allowing us to track how long-term grass vs arable management affected macropore volume and its seasonal dynamics. (4) We developed a new method to measure daily root water uptake, root water potential, and radial root water permeability at different soil depths under field conditions. Using this approach, we monitored wheat and grass plants throughout drying and rewetting cycles and found that both species adjusted their root permeability depending on soil moisture conditions. This allowed us to uncover how plants actively coordinate water uptake from shallow and deep soil layers to optimise water use during periods of water stress.
Key Findings: (1) In the Broadbalk study, nutrient management outweighed soil structural differences in determining yield stability. Yields under severe drought were sustained best in plots with optimal nitrogen fertilisation (around 144 kg N/ha), while unfertilised or excessively fertilised plots showed larger yield reductions. Notably, soil structural parameters (Kₛₐₜ, α) varied across treatments, but these did not correspond to improved yield resilience during drought years. This suggests that in a long-term, high-input system, adequate fertility and baseline soil water availability are the primary buffers against drought, whereas incremental differences in physical structure have a limited effect on yield in extreme conditions. (2) The SOC and soil structure investigation revealed a strong linkage between soil physical architecture and carbon storage. Soils with more connected pore networks accumulated significantly higher SOC than those with a fragmented structure, despite decades of similar climate and soil type. SOC content increased with the calculated substrate transport capacity of soil pores, approaching an asymptotic maximum. This implies a physical limit to carbon sequestration set by soil structure: once pore connectivity and volume reach a certain point, additional carbon inputs result in diminishing increases in stable SOC. These findings provide novel evidence that pore-scale connectivity facilitates microbial access to substrates, enhancing carbon stabilisation, and that without a well-developed structure, added organic matter may not fully convert to long-term SOC. (3) The new infiltration-based method successfully quantified macroporosity differences induced by long-term land use. Grass ley management produced substantially greater macropore volume than annual cultivated or bare fallow soils, confirming qualitative expectations with quantitative measurement. Macroporosity remained relatively constant between years, whereas capillary matrix porosity exhibited seasonal fluctuation. Additionally, the macropore hydraulic conductivity did not differ much between treatments, indicating that while the number of macropores changed with land use, the flow efficiency per macropore was similar. This methodology innovation is a key outcome. Furthermore, (4) plants reduce water uptake from dry topsoil by lowering the permeability of shallow roots and increase uptake from deeper soil by boosting permeability there. After rainfall, they quickly reverse this pattern, highlighting a dynamic strategy to optimise water use based on soil moisture.
Implications: Collectively, the results emphasise that soil structure matters for both agricultural performance and environmental outcomes, but its impact is context-specific. In intensive cropping systems with high inputs, structural improvements alone may not translate to immediate yield benefits under extreme weather unless coupled with sufficient fertility, highlighting a potential risk of “false resilience” if soils are degraded but compensated by inputs. On the other hand, for long-term soil sustainability and ecosystem services, good structure is indispensable: it underpins greater carbon sequestration potential and regulates hydrological behaviour, which in turn benefits climate adaptation and resource use efficiency. These findings also show that plants use more than just root depth; they actively adjust root function to manage water uptake, which helps them cope with drought. This insight opens new possibilities for breeding crops with dynamic root traits that improve resilience to changing climate conditions. This thesis's successful use of long-term experiments demonstrates their importance in revealing slow-building effects and complex interactions that short experiments miss. From a management perspective, the findings support strategies that integrate soil physical management with prudent nutrient management. Such integrated approaches can achieve more resilient crop production, combining healthy, well-structured soils that hold water with adequate nutrition to support crops during drought. Additionally, the new measurement technique for macroporosity could be adopted in soil monitoring programs or further research, improving our ability to detect and quantify structural improvements or degradation in situ
How has anti-Muslim speech by Conservative Party politicians contributed to Islamophobia?
Full text linkThis research investigates the Conservative party’s approach to Islamophobia while in government between 2010 and 2025, highlighting its failure to address the issue seriously. Drawing upon a neo-Orientalist approach, this dissertation demonstrates how passing comments uttered by Conservative political elites reproduced the process of 'othering' in their depictions of Muslims. It explores how this anti-Muslim rhetoric was not dealt with in full accordance with some of the Seven Principles of Public Life. It also explores how far-right actors were emboldened to foster a prejudiced environment. Situating these failures within broader historical and socio-political contexts, this research contributes to a deeper understanding of how Conservative political elites inadvertently gave legitimacy to a permissive space for anti-Muslim hate in British society
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