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    Healable supramolecular polyurethane elastomers possessing pendant bis-aromatic urea recognition units for use in repairable coatings

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    This paper describes the synthesis, characterisation, and supramolecular assembly of polyurethane elastomers. Bis-aromatic urea hydrogen-bonding motifs have been used to promote the self-assembly of the materials. The materials described comprise a soft block, namely polytetramethylene ether glycol (PTMG) as a telechelic diol and hard crystalline domains that feature a bis-aromatic urea hydrogen bonding motif as chain extenders. Two diols were polymerised (one featuring the bis-aromatic urea hydrogen bonding motif) with a PTMG diisocyanate prepolymer to yield supramolecular polyurethanes with molecular weights ca. 185000 with polydispersities ca. 2.0. The mechanical properties and processing temperatures of the polyurethanes were shown to be tuneable by controlling the feed ratio of the supramolecular chain extenders. These supramolecular polyurethanes were found to be healable in nature offering a useful property for use of these elastomers in applications such as cable coatings

    The impact of dairy proteins on fasting and postprandial glycaemic control

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    Type 2 diabetes (T2D) characterised by abnormal glycaemic control is a major public health concern worldwide. As a result, there is significant interest in dietary components, that could help regulate blood glucose concentrations, lowering the prevalence of this disease in the population. Available epidemiological evidence has suggested that there is a neutral or even a protective inverse association of milk and dairy product consumption with T2D. These beneficial effects of dairy foods have been largely attributed to whey protein (WP); a dairy component rich in branched chain amino acids (BCAAs) which have been proposed to play a key role in the maintenance of glycaemic control. However, few studies have been conducted to investigate how WP controls blood glucose levels, especially when consumed over the longer-term in the diet. To address the lack of knowledge, the literature review (Chapter 1) included randomised control trials (RCTs) evaluating the chronic and acute effects of WP intake on glycaemic control as well as elucidating the underlying mechanisms of action. Findings suggested a more favourable benefit of acute WP intake on markers of postprandial glycaemic control in T2D patients, with inconsistent effects in normoglycaemic individuals. Although there were a limited number of studies determining the chronic effects of dietary WP on measures of glucose control, beneficial effects were reported on fasting insulin but not on glucose levels in normoglycaemic volunteers whereas in T2D patients, favourable reductions were evident on fasting HbA1c, a long-term marker of glycaemic control. L-Leucine, a key BCAA in WP, alone or in combination with other BCAAs, emerged as a potential modulator of the postprandial insulinotropic effect mediated via effects of incretin gut hormones, but evidence was limited. Epidemiological evidence generally supported a favourable relationship between dairy product consumption and reduced risk of T2D (Guo et al., 2019). However few studies have been examined the role of total dairy and different dairy foods on glycaemic control. To explore the association between consumption of total dairy and different dairy products and changes in markers of glucose control a cross-sectional and longitudinal analysis was conducted using data from the Caerphilly Prospective Cohort study (CAPs) (Chapter 2). Cross-sectional analysis in the 1,350 men at baseline revealed no associations between total dairy, milk, cheese, cream, or butter with markers of glycaemic control [plasma glucose, insulin, and indices of insulin resistance (IR)], with a similar relationship evident after a five year follow up. Our findings from this cohort study are in accordance with previous epidemiological studies and support the neutral effect of dairy products on glycaemic control and T2D risk. The long-term consumption of milk proteins in mildly hypertensive people improved their vascular reactivity, biomarkers of endothelial function while WP resulted in a decrease of 24-h ambulatory systolic blood pressure (SBP) and diastolic blood pressure (DBP) in the acute within chronic Whey2Go study. Additionally, the acute ingestion of WP reduced the postprandial BP and improved arterial stiffness while Ca-caseinate improved lipid metabolism. To provide further insights into the impact of milk proteins on glycaemic control and the role of gut hormones as part of the mechanisms and mainly due to limited and unclear evidence available from chronic intervention studies a secondary analysis of the acute within chronic Whey2Go study was performed (Chapter 3). Although chronic consumption of 56 g of whey protein isolate (WPI), Ca-caseinate and maltodextrin intervention had limited impact on fasting glucose, insulin, glucagon, ghrelin, glucagon like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and C-peptide after 8 weeks, differences were evident during the postprandial phase at the beginning of each intervention period. Our findings suggested a greater impact of the milk proteins on postprandial glucose control, potentially mediated by GLP-1. To further explore the role of WP and leucine on postprandial glycaemic control, the randomised controlled Whey2Glo study determined the acute effects of sequential high-fat meals containing 50 g (2 x 25 g) of WPI, partially hydrolysed wheat protein (PHWP), and PHWP supplemented with leucine to match the content in WPI (Chapter 4). Addition of leucine to PHWP was associated with a greater postprandial insulinotropic response compared with PHWP but the effects on postprandial glycaemia were limited between the protein interventions. The divergent effects of WPI and PHWP plus leucine on postprandial C-peptide, GIP and glucagon responses also suggested that WPI and PHWP plus leucine may regulate glycaemic control by different mechanisms, which is worthy of further investigation. Collectively, findings from this thesis suggest that acute, but not chronic, intake of milk proteins has a beneficial effect on glycaemic control and plasma hormone responses. Moreover, the addition of leucine to PHWP was associated with a greater postprandial insulinotropic effect and supports the hypothesis that this BCAA may represent one of the bioactive amino acids for glucose control in WPI. Further sufficiently powered studies should address the impact of milk proteins on risk factors for developing T2D and examine the mechanisms underlying the role of leucine on glycaemic control

    The role of anticyclonic transient eddies in atmospheric blocking dynamics

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    Atmospheric blocks are large, quasi-stationary anticyclones with a lifetime from several days to multiple weeks. While blocks are relatively common in mid-latitudes, their dynamics are not completely understood, contributing to their un-predictability in medium-range numerical weather prediction (NWP). This study quantifies the role of anticyclonic (AC) synoptic-scale eddies towards blocking through a combined Eulerian and Lagrangian technique for block and AC eddy identification, respectively. It is shown for the first time that there is a statistically significant relationship between the mean number of block-AC eddy interactions and block persistence. Longer blocks absorb more AC eddies than shorter blocks, due to the associated increase in area and/or strength of the block after an AC eddy-block interaction, preventing dissipation or downstream advection of the block. However, for blocks with a particular persistence, there is large variability around the mean in the number of AC eddies it absorbs. In analysis of three blocks with similar persistence but different numbers of AC eddy interactions, AC eddies are only important towards the PV budget of a block when they first enter. Furthermore, the relative importance of diabatic processes varies spatially and temporally in each block, but there is no robust relationship between the relative importance of diabatic processes and AC eddies towards blocking dynamics. Accurate forecasts of block-AC eddy interactions are shown to be important for accurate blocking forecasts in medium-range NWP. Forecast errors in AC eddy speed, size, or strength can result in errors in block size, position, strength, or persistence. Conversely, forecasts that better represent AC eddies are more accurate in their forecasts of blocking. These results help to further the understanding of the role of AC eddies towards blocking dynamics, and show that poor AC eddy representation is one of the key reasons medium-range NWP performs so poorly for blocking

    A new approach to navigate uncertainty in climate-related hydrological drought risk

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    Hydrological droughts threaten public water supply and significantly impact the natural environment and other sectors. Quantifying the plausible worst case drought in the present day climate and understanding the impacts of climate change on future droughts help decision-makers formulate plans to enhance resilience. However, existing studies are often dominated by a top-down approach characterised by a cascade of uncertainty which particularly suffers from an insufficient exploration of low-likelihood, high-impact outcomes. This thesis aims to navigate uncertainty in the hydrological impacts of climate change by introducing a physical climate storyline approach. Drought storylines created from process understanding, pooling of ensemble reforecasts and sampling from large ensemble climate model simulations enhances risk awareness and aids robust decision-making for water resources planning. Retrospective storylines of past droughts created by perturbations made to observed events embraces downward counterfactual thinking through identification of different ways in which events could have turned out worse. A more severe precipitation deficit in autumn 1975 for east England or an even drier winter 1975/76, both of which could have arisen from natural climate variability, could have led to a reduction in accumulated river flows by up to >50% at slow-responding catchments in East Anglia. Storylines of the 1976 drought could have surpassed the maximum intensity of the 1921-22 drought by up to >30% to become the most severe post-1891 drought for the region. Similarly, drier preconditions of the 2010-12 drought and a plausible third consecutive dry winter could have led to significantly more severe conditions across the UK. A third dry winter, in particular, could have led to conditions matching the benchmark multi-year drought for east England (1989-1993), highlighting the fact that the drought could be seen as a near miss. Placing the observed drought in a 2°C warmer climate is estimated to exceed mean deficit of the benchmark 1989-93 drought by >60% at some of the worst affected catchments. Initialized large ensemble model simulations is an emerging way to create high-impact, low-likelihood storylines. Storylines of the 2022 drought in East Anglia created by combining observations with pooled ensemble reforecasts enable decision-makers to explore the likelihood of worst-case river flow trajectories, identify high impact combination of physical climate drivers to increase risk awareness during an on-going event. Further, application of the UNprecedented Simulated Extremes using ENsembles (UNSEEN) technique estimates that the chance of unprecedented high (low) summer temperature (rainfall) increases from 5.7% (8.8%) in the present day to 58.3% (18.1%) in a 3°C warmer world. The larger sample simulations are ideal for searching for high impact drought sequences where the physical credibility of simulated events may be verified more easily compared to statistical methods. The utility of the current generation of large ensemble simulations to sample for multi-year drought storylines is further discussed with drawbacks due to spatial resolution, the need for bias adjustment and the under-estimation of weather system persistence (such as atmospheric blocking). The various methods presented in this thesis provide evidence of the magnitude of present and future extreme droughts. Outstanding research gaps to ensure the physical credibility of drought storylines include the need to improve quantification of observational data uncertainty and better characterisation of hydrological model realism during extreme droughts. The demonstrated value of the storyline approach contributes to the diversification of approaches used in water resources planning and could form a core part of planning to assist in stress-testing water resources systems and enhancing resilience to future droughts

    Effects of a novel combination of prebiotics and polyphenols on gut microbiota and stress, with a focus on active military personnel

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    Research suggests that the intake of certain foods – often referred to as nutraceuticals, may affect both gastrointestinal health and wellbeing through manipulation of the gut microbiota. This may be particularly beneficial for those who are experiencing physiological or psychological stressors – which can have a noticeable effect on health and wellbeing. A growing body of research suggests that the use of prebiotic supplementation and high fibre diets may modulate the microbiota and attenuate stress responses, whilst also improving cognitive function. Polyphenols, a putative prebiotic also, have demonstrated similar action in vitro and in animal studies. By combining the two supplements it may be possible to garner the benefits of both, whilst reducing the need for costly pharmaceutical treatments when it comes to reducing the physiological effects of stress. Though stress is ubiquitous in daily life, a subset of the population who are often subject to extreme stressors are active military personnel. Such stressors often result in soldiers having severe gastrointestinal diseases and cognitive perturbations such as Post Traumatic Stress Disorder (PTSD). By exploring the potential of beneficial nutritional interventions, it may be possible to establish whether the increased intake of certain nutraceuticals (such as this novel polyphenols and prebiotics) could improve psychological and gut health in combat soldiers and in the general ‘stressed’ population. This work uses both in vitro fermentation work, and in vivo studies to explore whether a combination of these health positive supplements will have superior efficacy than either supplement alone on both the gut microbiome, and the perceived wellbeing of both healthy general populations, and active military personnel under artificial physical stressors. The in vitro fermentation work within this thesis demonstrated positive evidence for the novel combination to be more efficacious than either supplement alone, and when compared to a negative control, with improvements such as increased serotonin, elevated SCFAs such as acetate, and lactate, and positive changes within the gut microbiota. In both human trials, positive changes within the faecal microbiota occurred, as well as potential reductions in pathogenic bacteria that were more acutely obvious in the presence of the novel combination. As well as this, changes in health-related metabolites such as hippurate were evident in those groups that had consumed the novel combination – as well as potential attenuation of stress related blood pressure increases. Wellbeing scores stayed relatively similar throughout the supplementation period, though more research is needed to confirm the effects on perceived mood. The novel combination, throughout both in vitro and in vivo did seem to present superior efficacy, suggesting that this would be a preferential option to either supplement alone, in both populations

    Women's leadership ambition in early careers

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    Platelet angiopoietin-1 protects against murine models of tumor metastasis

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    BACKGROUND: In addition to their fundamental roles in preserving vascular integrity, platelets also contribute to tumor angiogenesis and metastasis. However, despite being a reservoir for angiogenic and metastatic cytokines, platelets also harbor negative regulators of tumor progression. Angpt1 (angiopoietin-1) is a cytokine essential for developmental angiogenesis that also protects against tumor cell metastasis through an undefined mechanism. Although activated platelets release Angpt1 from α-granules into circulation, the contributions of platelet Angpt1 to tumor growth, angiogenesis, and metastasis have not been investigated. METHODS: Using cytokine arrays and ELISAs, we first compared platelet Angpt1 levels in breast and melanoma mouse tumor models to tumor-free controls. We then assessed tumor growth and metastasis in mice lacking megakaryocyte and platelet Angpt1 (Angpt1Plt KO). The spontaneous metastasis of mammary-injected tumor cells to the lungs was quantified using RTPCR (reverse transcription-polymerase chain reaction). The lung colonization of intravenously injected tumor cells and tumor cell extravasation were determined using fluorescent microscopy and flow cytometry. RESULTS: Platelet Angpt1 is selectively upregulated in the PyMT (polyoma middle tumor antigen) breast cancer mouse model, and platelets are the principal source of Angpt1 in blood circulation. While primary tumor growth and angiogenesis were unaffected, Angpt1Plt KO mice had both increased spontaneous lung metastasis and tumor cell lung colonization following mammary or intravenous injection, respectively. Although platelet Angpt1 did not affect initial tumor cell entrapment in the lungs, Angpt1Plt KO mice had increased tumor cell retention and extravasation. Serum from Angpt1Plt KO mice increased endothelial permeability and reduced VE (vascular endothelial)-cadherin expression at endothelial junctions compared with serum from control mice (Angpt1WT). CONCLUSIONS: Platelets provide an intravascular sourc

    Greek, Graecisms, and bilingual wordplays in Persius’ Satires

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    The confluence of AI and retail: a case study of continuous transformation

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    Evolving digital technologies and unprecedented competition generates numerous challenges to traditional retailers. The emergence of innovative business models in the competitive surroundings disrupt the retail industry. The main objective of the present study is to evaluate the challenges in adopting AI in the retail and influence of AI such as a footfall counting system on consumers’ purchasing decision and performance are investigated. The theory of disruptive business models are analysed to identify the key disruptors. The present study executes mixed method approach, where quantitative analysis use SPSS and qualitative analyse data using thematic analysis. This method employs interview form to gather data. The current study implements quantitative analysis employing the SPSS software and survey method is adopted to collect data from the retailers using a structured questionnaire. Purposive sampling approach has been embraced for analysis. The intention behind the technique is to collect data related to the perception of retailers concerning the adoption of AI in the sector of retail. Descriptive statistics, ANOVA, correlation and one sample T-test are performed in research. The outcomes of the study reveals the impact of digital technologies on the improvised consumer experiences, growth and sustainability in the retail sector. Furthermore, the study also evaluate the challenges faced in implementation of the digital platform in the retailing. And also recommend the retailers to implement an effective framework in the retail industry to enhance customer satisfaction. Finally, the research study aids the retailer to achieve the sustainable business strategy in the competing business environment through AI

    New synonym of Attagenus tigrinus (Fabricius, 1792) (Coleoptera: Dermestidae: Attageninae)

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    The Attagenus bifasciatus species complex (Coleoptera: Dermestidae: Attageninae) surrounds the Mediterranean and extends into Asia. Several species are recognised but all of them are very similar to each other, and brief, old descriptions do not help to distinguish among them. Here the holotype A. tigrinus (Fabricius) and a syntype series of A. bifasciatus rossii Ganglbauer (subsequently raised to A. rossii) all collected from Italy were dissected to facilitate genital examination. From this genitalic study, Attagenus rossii is placed as a new synonym of A. tigrinus

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