Durham E-Theses

Durham University

Durham E-Theses
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    13506 research outputs found

    Surface Modification of Hydrophobic Polymer Films with Amphiphilic Molecules

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    The surface segregation of additive molecules within hydrophobic polymers is of great importance to a range of industrial systems. This thesis specifically addresses the segregation of surfactants within hydrophobic polymer films similar to those used in the babycare and feminine hygiene industry. The aims are to identify the key drivers of surface segregation, and be able to predict this behaviour. Pentaethylene glycol monododecylether (C12E5) exhibits surface segregation in both crystalline and amorphous polymers, with the degree of matrix crystallinity shown to significantly influence surfactant segregation. Greater crystallinity has been shown to reduce the surface enrichment of these films which was attributed to the inhibition of movement of surfactant by the highly ordered crystalline domains. The surfactant layers also display different temperature and water resistance depending on the matrix, with the surface layer on amorphous polymers appearing to be more resistant to loss. However, both sample types appear to show two types of surfactant structures on the surface, with some surfactant appearing to remain anchored to the surface while the remaining surfactant is lost. Nanometre scale strands were found on C12E5-containing films which were resistant to temperature elevation and water exposure. These were not seen in dodecyldimethylamine oxide (DDAO) / LDPE films. Instead small islands were seen but these islands show little surface activity. The effect of surfactant hydrophilicity on surface segregation has also been studied by comparing C12E3 and C12E5 in polymer matrices. A larger head group size has been shown to produce a larger surface excess on the surface and this has been related to the greater compatibility of surfactants with a smaller hydrophilic head group. Initial exploration of the influence of shear stress on interfacial segregation has shown that C12E5 segregates to the interface under shear and quiescent conditions. The lack of any strong influence of shear rate or temperature suggests that additive chemistry and matrix crystallinity are the most important factors in promoting surface modification with surfactant additives

    Constraining New Physics at the LHC

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    We analyse constraints that can be placed on CP-violating operators in the dimension-six Standard Model Effective Field Theory. We consider the associated production of a Higgs boson and a photon in weak boson fusion. We construct an asymmetry in a CP-sensitive observable which we use to analyse the sensitivity of this channel to possible CP violation. Additionally, we constrain CP-violating charged and neutral anomalous triple gauge couplings with diboson and VBF VjjVjj production at the LHC. We analyse charged triple gauge couplings in the dimension-six Standard Model Effective Field Theory using asymmetries to place constraints of CP-violating Wilson coefficients. For neutral triple gauge couplings we present bounds in terms of a general anomalous coupling framework using high energy transverse momentum bins. Finally, we consider next-to-leading order electroweak virtual corrections to WW+jets production at the LHC. We investigate the ability of a neural network to learn electroweak kk-factors for partonic channels with two, three and four final partons

    BEYOND THE TEE - NAVIGATING THE COURSE: The player journey for golfers with a disability, lessons learned, and changes made.

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    Although there is a plethora of research on disability and sport, there are several gaps related to golf and disability. This thesis aims to reduce the gaps, discover more about what we don’t know about golf for the disabled [G4D], examine the factors that limit or inhibit the playing of golf by individuals with disabilities [IwD], and offer recommendations for how the game can be improved to enable more IwD to sample, participate and compete in golf. The study is timely as all sports must adhere to growing legislation around accessibility, equity, and inclusion, along with greater public scrutiny of how establishments interact with society. The overall purpose of this research is to understand how IwD can better enjoy full, active, and inclusive participation in the game of golf. Desk research that included a scoping review was conducted to gain an understanding of the barriers and facilitators to playing golf for IwD and contextualise the work. Qualitative methods were also utilised to acquire knowledge of the subjective lived experiences of 77 golfers with a disability [GwD]. Data collection comprised of interviews and observation. A reflective thematic analysis was used to analyse the qualitative data. Chapter four presents the results of the scoping study. It was found that it is necessary to increase the knowledge of golf as a viable sporting option for IwD with disabilities, promote the availability of inexpensive golf and remove barriers such as lack of services, transport, support, equipment and ableist attitudes and practices. Based on the analysis of empirical data collected over a five-year period, the results first present the participants’ journeys into and through golf. Chapter five highlights the perceived barriers, benefits, and facilitators the participants expressed and I observed. Grounded in the experiences of the participants, chapter six provides recommendations for how golf can adjust. Chapter seven then focuses on how the conceptual framework known as Integrated Knowledge Translation [iKT] was utilised to support moving knowledge into action before providing case studies of two assets developed and deployed, from conception to construction and subsequent dissemination. Chapter eight turns to the impact of this research and how the research that underpins impact will take time to be visible. Preliminary impacts that are beginning to filter through are highlighted. The thesis concludes with empirical and practical recommendations and reflections on opportunities for future research

    An Algebro-Geometric Approach to Twisted Indices of Supersymmetric Gauge Theories

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    This thesis studies the algebro-geometric aspects of supersymmetric abelian gauge theories in three dimensions. The supersymmetric vacua are demonstrated to exhibit a window phenomenon in Chern-Simons levels, which is analogous to the window phenomenon in quantum K-theory with level structures. This correspondence between three-dimensional gauge theories and quantum K-theory is investigated from the perspectives of semi-classical vacua, twisted chiral rings, and twisted indices. In particular, the twisted index admits an algebro-geometric interpretation as the supersymmetric index of an effective quantum mechanics. Via supersymmetric localisation, the contributions from both topological and vortex saddle points are shown to agree with the Jeffrey-Kirwan contour integral formula. The algebro-geometric construction of Chern-Simons contributions to the twisted index from determinant line bundles provides a natural connection with quantum K-theory

    Negative regulation of Ire1 during the unfolded protein response

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    When cells undergo endoplasmic reticulum stress due to a build-up of unfolded or misfolded proteins, the cell must adapt to this stress and does so through the unfolded protein response (UPR). Ire1, a protein kinase endoribonuclease, is a protein found in the endoplasmic reticulum (ER) of Saccharomyces cerevisiae and plays a major role in the cell’s adaptive response to ER stress. Upon accumulation of unfolded proteins in the ER, Ire1 becomes active and splices HAC1 mRNA. After splicing the HAC1 mRNA is translated to produce the Hac1i protein, the Hac1i protein contains a bZIP transcription factor which leads to alleviation of ER stress by promoting inducing expression of UPR-associated genes. Previous work has shown that although phosphorylation is not essential to RNase activation, it still plays a critical role. Therefore, this study investigates previously identified phosphatases, Dcr2 and Ptc2, which were proposed to be negative regulators of Ire1. This study shows that out of the two investigated phosphatases, only Ptc2 was observed to negatively regulate the UPR. The mechanism of activation for the way in which the UPR was inactivated determined that interference of IRE1 clustering was affected by overexpression of either phosphatase, which suggests an alternative mechanism

    Functional characterization of CRISPR-Cas interactions with DNA

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    The recent Nobel-prize-winning CRISPR technology has revolutionised the gene-editing field with its ability to precisely modify any target DNA sequence and its relevance in a wide range of applications, from functional characterisation of gene variants in biological sciences to mutation of plant genomes in agriculture. New prospectives for CRISPR-therapeutic applications are also rapidly advancing, particularly for the modification of disease-causing genes and ex-vivo editing of immune cells for cancer treatment. However, off-target editing exists as collateral damage and it represents a significant hurdle to realise CRISPR’s full potential. To date, the scientific community lacks extensive knowledge regarding the impact of the eukaryotic cellular context on Cas nucleases activity, and how this affects Cas efficiency and specificity on human DNA. In this thesis, I use a combination of cellular and single-molecule assays to investigate this specific topic. First, I developed a strategy to demonstrate that Cas9 specificity is diminished by a local distortion of the DNA 3D structure in human cells. Next, by using the CRISPR system as a tool for gene expression regulation, I investigated the correlation between target transcription in cells and Cas9 editing efficiency. Together this first part of my work suggests that in vivo processes, which occur in eukaryotic cells and destabilise the DNA structure, have the potential to induce off-targets. However, this effect is highly dependent on the target itself and its genomic context. Finally, I extended my study to two other CRISPR-Cas systems: Cas12a and a new engineered Cas (AZ-Cas9). By applying single-molecule technologies, I contributed to the characterization of these nucleases, and obtained new information about the mechanisms underlining the DNA target search, the binding and cleavage kinetics and the off-target discrimination. These findings fill important knowledge gaps for future applications of these variants, and will be useful for the rational design of new high-fidelity nucleases

    Beyond the Shikimate pathway: The novel role of photosynthetic electron transport in mediating hormesis and lethal responses to glyphosate

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    Glyphosate is the most widely used herbicide in agriculture, with a truly global market dominance. The existence of a range of glyphosate-resistant crops has led to a surge in glyphosate usage in countries where genetically modified crops are deregulated. This makes glyphosate a key environmental chemical pollutant sourced from agriculture and understanding its impact on non-target organisms is paramount. With this high level of usage, an inevitably increasing number of glyphosate-resistant weeds emerged over the past few decades. Therefore, there is pressing need to design appropriate countermeasures for controlling such weeds to protect food production systems. This requires a clear understanding of how glyphosate kills cells. Glyphosate inhibits the shikimate pathway, resulting in aromatic amino acid depletion and subsequent protein starvation. However, recent studies identified a clear link between glyphosate toxicity and exposure to high levels of light, suggesting that glyphosate-induced cell death involves mechanisms far more complex than imagined previously. This presents a key research question, what is the mechanism underpinning glyphosate toxicity? Remarkably, shikimate pathway-possessing organisms bereft of chloroplasts have very high glyphosate lethal dose concentration, in comparison to equivalent organisms with chloroplasts. Therefore, our group proposed the hypothesis that glyphosate inhibition of the shikimate pathway activates cell death through generation of damaging reactive oxygen species (ROS) triggered by constricting photosynthetic electron transport (PET) in the presence of light. To test this hypothesis, we used two model organisms (Synechocystis sp. PCC 6803 and Chlamydomonas reinhardtii CCAP 11/32B) to evaluate the impact of glyphosate on cell growth. Growth assays revealed two distinct responses to glyphosate viz. (i) hormesis, characterised by activation of growth at sublethal glyphosate concentrations and (ii) growth arrest and cell death at lethal doses. Crucially, whether cells responded by hormesis or cell death was controlled by the presence of as yet unidentified extracellular signals secreted by cells into the growth medium. To unravel the molecular basis for the hormetic and lethal responses, a global proteomic analysis of glyphosate-treated Synechocystis cells was conducted using isobaric tags for relative and absolute quantitation (iTRAQ) technology. This highlighted the key proteins differentially-expressed in the two responses. Gene ontology analysis revealed that a majority of the identified proteins are photosynthetic proteins located in thylakoids. The overall pattern emerging from the protein data is that the lethal response was associated with a collapse in the abundance of key components of the electron transport chain, while in hormesis the same components remained unaffected or were increased. Furthermore, the protein profile in the hormetic response was consistent with redirecting fixed carbon away from the inhibited shikimate pathway to re-establish photosynthetic electron transport flow to prevent reduction of O2 and ROS generation. This study has revealed the light driven mechanism of glyphosate toxicity. This entails excessive ROS generation by the photosystems regulated by complex metabolic feedback signalling centred around reconfiguration of metabolite distribution from the Calvin-Benson cycle. The implications of this research are 3-fold. First, redirecting Calvin-Benson cycle metabolites to alternative pathways constitutes a viable escape from toxicity and may be a potential mechanism of glyphosate resistance in agriculture. Secondly, hormesis driven by secreted extracellular signals could be the basis for pollution-induced algal blooms, which have far-reaching environmental consequences. Finally, these results could be exploited in industrial algal cultivation to generate biomass for commercial applications

    Portrait Drawing in Three Generations of the Bacon Family

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    This thesis takes as its subject the substantial group of portrait drawings made by members of three generations of the Bacon family from the last decades of the eighteenth century through until c. 1859. Although this shared practice was initiated by the prominent sculptor John Bacon RA (1740-99), and was continued by his son and fellow sculptor John Bacon Junior (1777-1859), the drawings appear to have been separate from their professional concerns. As such, the Bacons’ portraits are valuable evidence of amateur drawing during the period, and this analysis points to the continued vitality of both the practice itself and the portrait genre specifically. The Bacons’ close links to evangelicalism in England, particularly in the first two generations, bring their drawings into dialogue with the history of the spiritual revival, particularly as it intersects with historiographies of domesticity and associational activity. The drawings are examined for what they reveal about the emotional and spiritual lives of individuals within the family, with a particular emphasis on Bacon Junior. Read alongside diverse texts, including diaries and wills, the family’s collection of portraits in other media and the architectural settings in which these were deployed, the family’s portrait drawings are identified as records of affective relations as well as vehicles for narratives of gentility and faith. As a register of sociability that extended beyond his kinship network, Bacon Junior’s drawings also point to the scope of his engagement with spiritual, charitable and political causes. Whether analysed in formal terms, or as objects circulating within a kinship network, the Bacons’ portrait drawings offer valuable insights into the ways in which amateur drawing in this period bridged the gap between the public and the private, functioning not only as records of intimacy, but also as a means of fashioning memory and identity within one family over several generations

    Novel Antimicrobial Coatings

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    Antimicrobial coatings play an important role in stopping the spread of pathogens and diseases. This thesis is about the synthesis of novel antimicrobial coatings via wet chemical methods and plasmachemical deposition methods. Chapter 1 provides an overview of the threat posed by bacteria, and the various methods used to stop the spread of pathogens. It also briefly reviews the different types of coating systems used throughout this thesis. Chapter 2 provides a brief synopsis of the analytical and experimental techniques used in this thesis. Chapter 3 details the synthesis of a coating that combines polydopamine and cinnamaldehyde. The coating is characterised, including its antibacterial activities. The coating method is extended to tannic acid and polyethyleneimine, both of which also produce antibacterial coatings. The use of porous substrates to absorb cinnamaldehyde to produce long-lasting antibacterial surfaces is also described. Chapter 4 describes coatings that are produced by combining tea, cinnamaldehyde, and a metal salt. Both copper and silver salts are utilised. The coatings are found to have strong antibacterial efficacies, and are also found to be antiviral against murine coronavirus (mouse hepatitis virus A59), a potential surrogate for SARS-CoV-2. Chapter 5 describes how pulsed plasma polymer coatings can be combined with liquid lubricants to produce slippery surfaces. A range of different monomers and lubricants are tested, with many forming slippery surfaces that exhibit excellent water repellency. Fluorinated systems are used to produce omniphobic slippery surfaces. Use of cinnamaldehyde as a lubricant endows the slippery surfaces with strong antibacterial efficacy. Chapter 6 details how pulsed plasma coatings may be used to prevent (or encourage) fouling of microalgae on surfaces. Hydrophilic coatings produce the best anti-biofouling results, and are non-toxic towards the microalgae species tested

    SUMO: a heavyweight post- translational modification wrestling between plant stress responses.

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    Post-translational modifications (PTMs) enable plants to modify proteins in response to environmental stimuli. Better understanding these PTMS is important to help crops adapt to the changing environment caused by climate change. This thesis has studied the role of a PTM called Small Ubiquitin Like Modifier (SUMO) which is stress induced. Conjugation of SUMO to target proteins alters the target protein, some of these proteins have been examined in this thesis. The research has specifically examined the role of SUMO in the Abscisic Acid (ABA) pathway. The work has deduced the ABA sensitivity of SUMO protease knockout mutants. It has established the SUMOylation sites in the ABA negative regulator Protein Phosphatase 2CA (PP2CA) and generated transgenic Arabidopsis thaliana expressing both a SUMOylatable and non-SUMOylatable form of PP2CA to determine the ABA phenotype. ABA mediated root inhibition and expression of ABA response genes has indicated that SUMOylated PP2CA may aid ABA signalling. It was hypothesised this may be in part due to a SUMO Interacting Motif (SIM) site located in the PYLS, a SIM site was identified in PYL8 and was not present in PYL1. Arabidopsis thaliana transgenics were generated to enable further understanding of the role of SUMO in the ABA pathways. Additionally the role of SUMO in root hair formation was examined, based on the double SUMO protease knockout mutant ots1 ots2 being found to have longer and fewer root hairs. A transcription factor required for root hair development RHD-Six Like 4 (RSL4) was found to contain three SUMO sites. Transgenic Arabidopsis thaliana was generated to examine the role of SUMOylatable and SUMO site mutated RSL4, however this led to contradictory results. Protein stability indicated that SUMOylatable RSL4 may be more stable and/or transcribe more RSL4 promoted genes than SUMO site mutated RSL4, but has smaller root hairs when grown on ethylene supplemented media. These contradictory results may be due to different roles of the three SUMO sites in RSL4. Lastly research was continued on a project that had been started by Dr Vivek Verma, who had determined that a SUMO site in the GRAS domain of DELLA protein, Gibberellic Acid Insensitive (GAI) altered interactions with transcription factors. A SIM site was identified in Phytochrome Interacting Factor 4 (PIF4), which may be responsible for increased interaction of PIF4 when GAI is SUMOylated. Wild-type and SIM mutated PIF4 transgenic Arabidopsis thaliana was generated to understand the role of SUMO in GAI PIF4 interactions. The GAI SUMO site mutated transgenic Arabidopsis thaliana which had been generated by Dr Vivek Verma were analysed for Jasmonic acid phenotype and hypocotyl elongation phenotype

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