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Time-temperature indicators (TTIs) are simple sensors that can tackle the global issue of food, vaccine, and medicine wastage. TTIs reveal true product quality by showing the cumulative effects of time and temperature. TTIs have not seen mainstream use due to drawbacks of cost, safety, adaptability, and reliability. A potential solution is to use polymeric colloidal crystals (CCs) that mimic natural opals. CCs contain arrays of polymer particles with diameters around half the wavelength of visible light, resulting in structural colour from the Bragg reflection of light. The polymeric basis of the CCs makes the structural colour highly temperature sensitive; thus, it is expected that CCs can act as novel TTIs, which has been investigated in this work. Evaporation-driven self-assembly of a latex polymer was used to fabricate pristine CCs that were transparent when dried but bright white when hydrated. However, with 0.01 wt.% graphene inclusion, vibrant structural colours were achieved. The stopband midpoint was controlled by varying the particle diameters between 200-305 nm, resulting in CC colours across the visible spectrum. The novel application of ellipsometry to doped CCs found the stopband midpoint to be dependent on incident angle the midpoint blue shifted by ~ 125 nm as the incident angle changed from 15 to 85°. An increase in CC thickness from 0.3 mm to 2 mm caused the stopband midpoint to be redshifted by ~ 20 nm. A novel approach to explain the shift is reported, which attributed the redshift to a 4% reduction in the average polymer packing fraction as the thickness increased. A unique in-house setup was built that recorded CCs during heating at different temperatures to quantify colour change over time. A refined setup based upon BS7901:1999 is now ready for large-scale testing. The activation energy EA was tuned, for the first time, by thickness and graphene content in the range of 36 - 55 kJ mol-1, which fell in the range of perishable products (8 - 210 kJ mol-1). The first known mapping of self-assembled CC formation parameters used a modified Routh-Russell model. The model maps the dimensionless Péclet number (Pe) and control parameter λ ̅, which are the ratios of particle diffusion and deformation against time, respectively. The necessary conditions for CC formation were 1 ≤ Pe ≤ 10 and 105 ≤ λ ̅ ≤ 106. Brightly coloured iridescent thin film CCs were made by adding 10% butyl glycol; however, un-hydrated CCs had a preferable subtle colour. The first-ever production of CC-based TTI labels used CC thicknesses of 25 - 100 µm, and the labels had two EA separated by the Tg (~35 °C) and the main EA (68 - kJ mol-1) was driven by dry-sintering. This TTI system can monitor one of the widest reported EA ranges, with potential for further extension. The CC-based TTI also combined colour change with a change in symbol, as demonstrated with a vanishing tick. The work is the first-ever demonstration of a CC-based TTI label made with scalable techniques that has a measurable, accurate, and tuneable time-temperature response. The technology is now ready for the next challenge of transitioning from lab to industrial scale.

The CD28-CTLA4 system is central to the regulation of T cell responses, with dysregulation associated with autoimmune disease and cancer progression. CD28 and CTLA4 are homodimeric T cell receptors providing co-stimulatory and inhibitory functions, respectively, through their shared ligands, CD80 and CD86. Whilst CD86 exists as a monomer, CD80 can form non-covalent dimers in the cell membrane and is therefore able to form higher-order lattice structures with CTLA4, providing an avidity advantage and a unique membrane organization compared to CD86. CD80 also interacts in cis with PDL1 at the CD80 dimer interface, although the function of this interaction is unknown. Functionally, CTLA4 removes CD80 and CD86 from opposing cells, targeting ligand for destruction via transendocytosis. However, why two ligands are required for this regulation, and how the properties of ligand:CTLA4 interactions contribute to this mechanism are poorly understood. We removed the avidity influence on receptor-ligand interactions by creating mutants unable to form functional dimers. We demonstrate that following transendocytosis, CD80 remains bound to CTLA4, resulting in ubiquitination and reduced CTLA4 availability. We show this is due to CD80:CTLA4 lattice formation, as dimer disruption by mutation or presence of PDL1 averts CTLA4 ubiquitination. We show loss of avid CD80:CTLA4 paradoxically enhances sensitivity to CTLA4 mediated transendocytosis, as the ability of CD80 to dissociate from CTLA4 following transendocytosis is augmented, permitting CTLA4 recycling and further transendocytosis - a feature normally seen with CD86. Finally, we detected signs of altered CD28 engagement resulting from mutant CD80 co-stimulation indicating monomeric ligands may have improved CD28 signalling. Our results provide further detail on CTLA4 transendocytosis, where dimerisation and avidity of ligand interactions, (including those regulated by PDL1), are significant in altering the fate of CTLA4, and influencing CD28 mediated co-stimulation.

Robotic minimally invasive surgery provides multiple improvements over traditional laparoscopic procedures, but one significant issue still encountered is their limited force control during the grasping and retraction of tissue, as the surgeon is separated from the instrument, and therefore denuded of their sense of touch and the applied forces. Prior solutions have largely looked towards haptic feedback to resolve this issue, but an alternative approach is to detect and monitor the occurrence of tissue slip events. This would allow the force to be automatically adjusted to prevent slip, minimising the clamp force used to maintain control, thus reducing the probability of tissue trauma. The aim of this work is to develop a method for the early detection and mitigation of tissue slip during robotic surgical manipulation tasks, helping to reduce tissue trauma and minimise tissue slip events. Initial investigations into literature, and evaluation of the slip mechanics when grasping soft, lubricated, deformable materials, indicated that small localised slips occur before the onset of macro slip. Two phenomena were identified in the slip mechanics investigation that could be employed to induce these slip in a measurable and repeatable manner. Firstly through using the tissue's deformable properties to create slip differentials between the front and rear of the grasper face, and secondly through using a curved surface to create a variation in the normal force, and thus frictional force, across the surface. Two instrumented grasper faces were developed, based on each of these phenomena, that were capable of monitoring the occurrence of localised tissue slip through monitoring the displacement of a series of independent movable islands that made up the grasper face. These were then demonstrated to be capable of automatically detecting slip events for a range of test conditions with tissue simulants, before being utilised to automatically control the grasping forces during a tissue retraction task. Both sensor systems provided similar levels of tissue control to one which utilised the maximum clamp force throughout the task, whilst applying lower forces during the early stages of retraction, reducing the probability of tissue damage. In addition the normal force based method, with the curved grasper face, was demonstrated to be effective for the early detection of slip when grasping porcine liver tissue, successfully detecting incipient slip in 77% of cases. This work provides a strong basis for further development of incipient slip sensing for surgical applications. It provides novel contributions in the understanding of slip mechanics of soft tissues, as well as presenting two separate novel sensing approaches for the automatic detection and mitigation of slip events, offering an opportunity for reducing the occurrence of tissue slip events whilst minimising tissue trauma, as well as surgeon fatigue.

The Icelandic mantle is lithologically and chemically heterogeneous. This had led to the identification of geochemically enriched and depleted domains within the Icelandic mantle. Enriched domains have been prescribed to the presence of recycled oceanic lithosphere in the form of pyroxenite. Halogens are highly incompatible and fluid mobile elements which are concentrated in the Earth's crust, particularly in altered oceanic crust and serpentinised oceanic lithosphere from hydrothermal alteration. During subduction these halogen-rich domains are returned to the mantle in the down-going slab. Therefore halogens are potentially excellent tracers of recycled oceanic lithosphere in the mantle. This thesis uses the halogen concentration of melt inclusions and basaltic glasses from Iceland and the Reykjanes Ridge to address this potential. Firstly, the influence of pyroxenite-derived melts to melt compositions across Iceland is assessed. Pyroxenite-derived melts have the greatest influence in the flank zones of Iceland, far from the rift and plume centre. Concentrations of halogens measured in melt inclusions and glasses from Iceland are highest in the flank zones. Additionally, the highest halogen concentrations in glasses from the Reykjanes Ridge are in those closest to Iceland and correlate with enriched melt compositions. Therefore halogen concentrations appear to be a promising tracer of the influence of recycled oceanic lithosphere, with higher concentrations indicating higher influence on erupted melt compositions. Ratios of halogens to elements of similar compatibility show a different behaviour to the concentrations. The influence of recycled oceanic lithosphere has no influence on these ratios and they cannot be used as tracers of its contribution. Heterogeneity in the ratios can be used to identify recycled mantle domains with differing ratios. Differences in the ratios may be caused by individual recycled lithologies retaining unique halogen contents which can be identified in high density study of particular locations. On a global scale halogens are likely recycled throughout MORB and OIB mantle domains. Recycled oceanic lithosphere is likely present in the upper mantle and recycling is not confined to entrainment of residue slabs at the core-mantle boundary. Over time this recycling has created mantle halogen ratios which are similar to that of MORB. Thus on a global scale mantle halogen ratios are consistent, however smaller scale studies with high sampling density are able to identify heterogeneities which may reflect heterogeneity in subducted lithologies.

Auroral Kilometric Radiation (AKR) is Earth's most powerful, naturally-emitted radio emission. It is a direct result of the dynamics of energetic electrons along high latitude magnetic field lines in the magnetosphere-ionosphere coupling region and is useful for inference of the spatial morphology and activation of the auroral acceleration region. In this thesis, a novel technique is developed to retrieve calibrated AKR observations from the Wind spacecraft, without the presence of solar and other contaminating radio emissions. Wind houses a remote-sensing radio observatory and has been active since 1995, providing the longest dataset of AKR from many viewing positions around the Earth. For AKR, which is anisotropically beamed, this breadth of data allows the effect of the observer position to be characterised. Subsequently, the data are used to explore AKR dynamics and corresponding changes in the auroral acceleration region during substorms and other disturbed periods. Firstly, the AKR selection is applied to a 30 day period during the Earth flyby of the Cassini spacecraft for a multipoint observation. Comparing the temporal modulation of the AKR power from both spacecraft during this period, it is shown that a diurnal modulation is likely due to the geometrical effect of the rotating magnetic dipole, but also sees intrinsic source modulation common to both hemispheres. Secondly, the selection is applied to 10 years of observations that overlap with published lists of substorm onsets. After accounting for viewing, the average AKR power in low and high frequency bands was examined during the substorm timeline. This demonstrated that higher altitude AKR sources provide a greater contribution during substorm onset on average, and that this relative contribution scales with the level of disturbance. Finally, dayside observations of AKR were used during the arrival of a coronal mass ejection (CME) at Earth. While showing that Wind's dayside observations can be used as a metric for magnetospheric activity, coincident observations of the UV aurora were used to constrain the auroral origin, namely intense, dayside auroral dynamics related to an ongoing substorm.

In this Thesis I present a study of the ionised outflowing winds within four active galactic nuclei (AGN): NGC 7469 (Seyfert type 1), NGC 1068 and NGC 5643 (both type 2), and NGC 3227 (type 1 during obscuration). The aim of this work, based on high-resolution X-ray spectroscopy using the XMM-Newton Reflection Grating Spectrometer (RGS), is to understand the ionisation state and kinematics of the outflowing winds and determine their locations with respect to the central supermassive black hole (SMBH). The emission line region within NGC 7469 is found to be made up of two narrow components and a possible broad component. The distances of these ionised plasma phases from the SMBH depend strongly on the volume filling factor, which is currently unknown. The 0.3 - 10 keV spectrum of NGC 1068 is analysed by simultaneously modelling the XMM-Newton RGS and EPIC-PN data, comparing observations taken in 2000 and 2014. I find that four photoionised components are required to explain the emission features in both epochs. I also find strong evidence for collisionally ionised emission. NGC 5643 is the target of an XMM-Newton AO20 proposal which I submitted and was accepted, with the aim of studying the possible X-ray outflow-induced star formation as seen in the optical band. Analysis of archival observations and preliminary modelling by simulating data with larger exposure times than previously available are presented here. Finally, NGC 3227 was observed to undergo an obscuration event at the end of 2019. I study the EPIC-PN spectrum in order to investigate what drives the observed variability. My analysis of the outflowing winds in AGN show that the kinematics and ionisation states are similar in different types of objects, suggesting that similar plasma clouds inhabit type 1 and type 2 AGN, thus giving support to the standard model of AGN.

Physical inactivity in older adults presents a significant problem within contemporary society. Governments around the world are recognising this importance and the large impact of physical inactivity on health and health-related expenditure, yet interventions promoting physical activity have typically produced only small or short‐lived behaviour change. Through three related studies, this thesis aims to develop a person-centred, multi-level physical activity intervention within a residential estate of older adults. The first study used qualitative methods to develop a person-centred understanding of the multi-level influencers of physical activity engagement within the targeted individuals. These findings were then applied within study 2, which implemented a 12-week physical activity intervention within the residential estate and used a mixed-methods approach to assess its implementation and explore personal experiences of the intervention strategies designed by the person-centred approach. The final study explored the transitions associated with older adults to develop an understanding of purpose, meaning and identity in later life, and how this can influence physical activity behaviour. The findings of the third study were presented within a composite vignette of the transition experiences of 4 older adults within the residential estate. The thesis presents an effective and appropriate strategy for developing person-centred, multi-level physical activity intervention for older adults. Contrary to the health-focused emphasis that is predominantly adopted by public health initiatives, the findings of this thesis highlight the importance of purpose, and related constructs such as meaning and identity for understanding and promoting physical activity behaviour in older adults. The findings suggest that future person-centred physical activity interventions for older adults should take into consideration the changes in sense of purpose as individuals become older and design intervention strategies to maximise a sense of purpose in life, and to provide more meaningful sources of physical activity.

Polycrystalline lithium metatitanate (Li2TiO3) is an attractive material for a range of applications including battery materials and microwave dielectrics, it has also attracted a great deal of attention as proposed tritium breeder material for use in nuclear fusion reactors. During the continued development of Li2TiO3, and similar Li-containing ceramics, for these advanced applications, transmission electron microscopy (TEM) is likely to be employed to study the nano-structure of these materials and, in the case of nuclear fusion applications, their response to radiation induced damage. In this project, the effects of ceramic processing conditions on the microstructure of Li2TiO3 ceramics was first identified. The effects of ceramic microstructure on the behaviour of Li2TiO3 under electron irradiation was subsequently investigated. Results show that electron irradiation in a conventional TEM results in the formation of nanometre sized vacancy-type defects at room temperature, and that the size and number density of the vacancy-type defects are linked to ceramic microstructure and crystallographic disorder. Electron beam induced vacancy-type defect formation is discussed in terms of electron beam heating, electron beam induced radiolysis and electron beam induced displacement damage; the displacement of Li and O lattice atoms is proposed to be primarily responsible for the observed damage. Results suggest that the formation and growth of vacancy-type defects is initially driven by the supersaturation of vacancies due to the preferential loss of interstitials to the surfaces of thin film TEM specimens, followed by coalescence of larger vacancy-type defects, which leads to cavity growth. Results from X-ray diffraction suggest that growth at room temperature may be facilitated by the presence of CO2, produced by the decomposition of a Li2CO3 surface reaction layer under the electron beam. These results highlight that care must be taken when interpreting TEM data and undertaking the associated analysis, especially in Li-containing oxides. Following the discovery of electron beam induced cavity formation in Li2TiO3, the thermal evolution of these cavities at temperatures relevant to fusion breeder blanket operating conditions was investigated using in-situ thermal annealing experiments, which were carried out under electron irradiation in a TEM. The effects of temperature, electron beam exposure time, and ceramic microstructure on cavity growth dynamics are discussed. The rate and extent of cavity growth was found to be significantly enhanced at elevated temperature, this is primarily attributed to the increased mobility of defects introduced as a result of electron beam induced displacement damage. Minimising exposure of thin-film TEM specimens to the electron beam was found to significantly 14 reduce the extent of cavity growth, particularly at high temperatures, indicating that cavity growth is strongly dependent on electron fluence. The microstructural properties of low porosity and large grain size may increase the resistance of Li2TiO3 to electron beam damage. This is attributed to the longer diffusion path to defect sinks associated with large grain size and low porosity, resulting in a reduction of preferential interstitial loss and increased probability of defect recombination; thus reducing the excess vacancy concentration responsible for cavity growth in the bulk. A distinct correlation between the temperature at which significant quantities of CO2 were released from bulk Li2TiO3 samples (revealed by the results of thermal desorption spectroscopy (TDS) experiments) and accelerated cavity growth in thin film specimens was identified. Hence it is proposed that enhanced cavity growth under electron irradiation at elevated temperature in Li2TiO3 may be facilitated by CO2 gas produced as a result of the thermal decomposition of an Li2CO3 surface reaction layer. The accumulation of helium in Li2TiO3 samples with different microstructural properties was investigated using in-situ helium ion implantation. The influence of the interactions of implanted helium with electron beam induced radiation defects on cavity / gas bubble growth at elevated temperatures was investigated using complimentary in-situ thermal annealing experiments. Helium was found to accumulate to a greater extent in samples of low porosity and large grain size. The extent of cavity / bubble growth was found to be significantly exacerbated at elevated temperatures in samples which exhibited high helium retention. Such cavities have the potential to trap tritium in a working breeder blanket, thereby impeding its release and increasing tritium inventory, both of which would be detrimental to material performance. In the absence of implanted helium, the microstructural properties of large grain size and low porosity appear to increase the radiation tolerance of Li2TiO3 to displacement damage induced by electron irradiation. However, since the presence of helium has been shown to severely exacerbate cavity growth in Li2TiO3, the increased helium retention by specimens of low porosity and large grain size in fact resulted in a greater extent of cavity growth in such specimens at temperatures relevant to breeder blanket operating conditions. As such, the properties of high porosity and small grain size are likely to be beneficial for the optimisation of the performance of Li2TiO3 ceramic breeder materials from the perspective of reducing cavity formation at breeder blanket operating temperatures when the effects of helium are taken into account.

The development of new classes of ligands is a fundamental and ongoing challenge in modern chemistry, and a cornerstone in modern catalysis, supramolecular assembly and biomimetics. The current world of coordination chemistry is dominated by ligands based on organic frameworks. However, there is a developing field of coordination and supramolecular chemistry using inorganic frameworks, and this thesis is focused on fundamental research in the synthesis and design of ligand molecules of this type. In Chapter 1, a concise account of previous studies of tris 2-, 3- and 4-pyridyl based ligands E(py)3 (where E = a main group bridgehead atom or group, and py = a pyridyl donor arm) is presented. The main conclusion from this survey of the literature is that, despite recent developments in this area, there are some significantly unexplored fields. This is particularly the case for metal-based Group 13, 14 and 15 pyridyl ligands containing 4-pyridyl functionality, which may open new avenues of supramolecular coordination chemistry. In addition, the elaboration of this type of metal-bridgehead by the incorporation of other polycyclic aromatic N-donor groups has been almost completely ignored so far. The aims of the thesis (Chapter 2) are primarily to expand our understanding of the structural effects of moving the donor-N atoms in ligands of this type to different positions in the ring substituents - closer to or further away from the main group bridgehead atoms. Chapter 3 explores one of the primary aims of the program of research, focusing on tris- and bis-8-quinolyl ligand arrangements containing Group 13 (Al), Group 14 (Sn) and Group 15 (Sb) bridgehead atoms, in which the N-donor atoms are more remote from the bridgeheads than in pyridyl counterparts. A highlight in this area is the development of bis-8-quinolyl ligands and the potential interaction of the bridgehead alkyl substituents with coordinated metals - illustrated by the structure of [{Me2Al(2-Me-8-qy)2}Li(THF)] [(4a)Li(THF)]. In Chapter 4, the synthesis of the first examples of heavy Group 14 and 15 4-pyridyl ligands E(4-py)3 (E = PhSn, Sb, Bi) and their coordination chemistry are reported. It is shown that moving the N-donor atoms within the pyridyl ring to the 4-position results in the ability to build an extensive range of new metal organic frameworks (MOFs). An important conclusion from this work is that underlying periodic behaviour (s-p separation and the inert pair effect) has a major effect on the ligand coordination modes, providing the basis for modulation of ligand character (N,N,N- vs N,N,N,E-donor behaviour). Chapter 5 describes more complex research in which, instead of using a bridgehead atom, a bridgehead group is employed (in this case a cyclodiphosphazane ring unit), to separate pyridyl donor functionality and expand the ligand bite. General conclusions and suggestions for future work are gathered in Chapters 6 and 7. Overall, the research provides new types of main group metal-based ligands which have potential applications in catalysis and in the building of porous networks. As such, it develops new aspects of coordination and supramolecular chemistry which have significant promise for future studies.

Several studies have noted the frequent use of fashion brand names in contemporary fiction, but to date there has been little academic research into this phenomenon and the effect that it has on the reader. This study therefore set out to address this research gap. Focusing specifically on chick lit (a type of contemporary popular fiction, typically featuring and aimed at young women), the present study aimed to explore the use of fashion brand names in women's fiction, concentrating on the relationships between fashion brands, authors, fictitious characters and readers, with a view to establishing whether there might be potential commercial benefits of fashion brand product placement in chick lit novels. A mixed methods approach was used to explore the topic from multiple perspectives. A summative content analysis was undertaken to investigate the frequency, variety and types of fashion brand names used in a corpus of 19 chick lit novels drawn from the Bridget Jones, Shopaholic and I Heart series. A qualitative analysis of the novels in the corpus focused on the ways in which the characters interacted with fashion brands in the text. An online survey of 166 chick lit authors was used to explore why writers use fashion brand names in their work, and a survey of 96 female students was used to investigate readers' response to fashion brand names in novels. The study findings indicated that chick lit authors use fashion brand names to support characterisation due to the ability of fashion brands to express the values, self-concepts and stereotypes of their typical brand users. The outcomes of the consumer survey suggested that readers use textual cues, including those related to fashion consumption, to help them to develop their impressions of characters in novels, however the study was unable to demonstrate a clear relationship between readers' perceptions of character personality and brand personality. In terms of product placement, the findings confirmed that readers demonstrated high levels of recall and recognition of fashion brand names used in chick lit narratives, but no evidence was found to indicate that the appearance of brand names in the text had an impact on consumers' brand attitudes. Readers were found to be broadly positive about the use of brand names in novels, indicating that they preferred to see real brands, rather than fictional brands, in books. Readers appeared to have no significant objection to commercial product placement in fiction books, provided that such placements were accompanied by a disclosure. The results of the study therefore provide support for the proposal that chick lit novels are a potential product placement medium for fashion brands seeking to generate brand awareness. The frequent mentions and positive treatment of fashion brand names in chick lit mean that it would be relatively easy to incorporate paid-for placements of fashion brands in chick lit novels without compromising the narrative.

Syncollin is a 16-kDa protein that was originally isolated from the pancreatic zymogen granule. It is now known also to be expressed in the gut, the spleen and in neutrophils. The protein contains intramolecular disulphide bonds and is present both free within the ZG lumen and tightly associated with the luminal leaflet of the ZG membrane; it is also secreted into the pancreatic juice. Syncollin is able to oligomerize, and assemble into doughnut-shaped structures, which might explain its known pore-forming activity. Syncollin appears to be involved in a number of gut-based disease states. For instance, syncollin expression was found to be down-regulated in the colon when a bacterial suspension was administered to germ-free mice, and in mice with chemically-induced colitis-associated cancer. The available evidence suggests that syncollin plays an important role in the gut, and possibly elsewhere. This dissertation describes my attempts to understand this role and its structural basis. I first assessed various methods for purification of recombinant syncollin. Syncollin was expressed with various epitope tags (including His, GST and Strep) in bacteria, insect cells and mammalian cells. The best results were obtained by expressing syncollin bearing a double-Strep tag at its C terminus (syncollin-Strep) in mammalian (tsA-201) cells and purifying the protein from the cell supernatant using the Strep-Tactin XTTM system. Syncollin-Strep purified in this way contained intra-molecular disulphide bonds and recapitulated the ability of the native protein to bind to syntaxin 2 and permeabilize membranes. In the pancreatic juice, syncollin will encounter an environment rich in proteolytic activity. One might expect, therefore, that its structure would be highly stable. To test this hypothesis, I assessed the thermal stability of the protein using circular dichroism (CD) spectroscopy. The CD spectrum of syncollin-Strep indicated a predominantly beta-sheet structure. When the protein was subjected to a temperature ramp up to 90°C, the spectrum became flattened, although complete unfolding did not occur, indicating that the protein does indeed have a very high thermal stability. A model for syncollin, based on its primary sequence, predicts a predominantly beta-sheet structure, consistent with my CD data, and suggests the presence of intramolecular disulphide bonds. When I disrupted potential bonds by mutation of appropriate cysteine residues, syncollin-Strep retained its antibacterial efficacy, but its thermal stability was reduced, suggesting the involvement of disulphide bonding in stabilizing the structure of the protein. With regard to its potential role in the gut, I found that syncollin-Strep binds to bacterial peptidoglycan, and restricts the growth of representative Gram-positive (Lactococcus lactis) and Gram-negative (Escherichia coli) bacteria. Syncollin induces propidium iodide uptake into E. coli (but not L. lactis), indicating permeabilization of the bacterial membrane. In support of this idea, I confirmed that syncollin-Strep, like native syncollin, has pore-forming properties. Syncollin-Strep causes surface structural damage in both L. lactis and E. coli, as visualized by scanning electron microscopy. In addition, syncollin-Strep had additive effects on L. lactis when combined with either ampicillin (bactericidal) or tetracycline (bacteriostatic) in L. lactis. In light of these results, I propose that syncollin is a previously unidentified member of a large group of antimicrobial polypeptides that control the gut microbiome. I found that expression of syncollin in neutrophils is punctate and granular. Upon activation of the neutrophils, syncollin became mobilized at the plasma membrane, and was also secreted from the cells. Secreted syncollin bound to decondensed chromatin structures characteristic of neutrophil extracellular traps (NETs). Further, when neutrophils were activated in the presence of bacteria, the bacteria became coated with secreted syncollin, consistent with the anti-bacterial role proposed above. In conclusion, the results presented in this dissertation indicate that, through its antibacterial effects, syncollin plays a role in host defence in both the gut and the bloodstream.

Section A is a systematic literature review, examining possible factors which may impact on the risk of experiencing postnatal mental health difficulties for women who had an unplanned pregnancy. Sixteen papers were found to be relevant for inclusion in the review. Findings are summarised under six key themes; pre-existing mental health difficulties, sociodemographic factors, mother's perception of the pregnancy, obstetric factors, social factors and paternal factors. Findings are discussed in relation to their clinical relevance, and recommended further research is outlined. Section B is an empirical study using Interpretative Phenomenological Analysis to explore the experience of a pregnancy that was not planned, for women postnatally. Eight first time mothers who had a baby aged between six and twenty-four months were interviewed. Five subordinate themes, with subthemes, are discussed in the findings. These include unique considerations for women who had a pregnancy that was not planned. Limitations of the study and research and clinical implications are considered.

The recovery approach is now a central tenet of mental health policy in the UK. Despite its ubiquity there is evidence of confusion over its meaning and practice. In addition, recovery is accused of being a new iteration of neoliberalism with a focus on self-responsibilisation. Drawing on historical, ethnographic and discursive research conducted within mental health services in South Wales, this thesis explores how the contemporary recovery approach to mental health has arisen, how practitioners and service users enact it and the challenges and tensions that arise in practising in this way. The study draws on Foucauldian ideas of power and knowledge, with a focus on the role of language in recovery practices. The historical study showed how a range of past approaches to mental health are reflected in the contemporary recovery approach and explored how these approaches gained the power to define how recovery has been understood over the last few centuries. The ethnographic findings show that practitioners of different professions work to a consistent version of recovery, focussing on 'what works' and promoting service user responsibilisation. Practitioners facilitated recovery through the use of pastoral power and specific discursive strategies. Service users exercised agency in aligning with or rejecting the recovery discourse and the process of engendering recovery subjectivities in service users was complex, unpredictable, and sometimes unsuccessful. I draw on Hacking's (1996) work on looping effects to show how professionals' categorisations of service users had important consequences for the service they received. In considering recovery as a neoliberal solution to mental health problems, the study highlights the complex assemblages of people, policy, practices, laws and emotions that constitute recovery practice and concludes that in the field of neoliberal rationalities, recovery appears to be struggling to fulfil its programmatic aspirations and goals.

Nano-technologies such as heat-assisted magnetic recording, magnetic particle hyperthermia and skyrmion racetrack memory have been developing rapidly in recent years. However, there have been a number of issues relating to the finite-size of materials relevant to prospective nano-technologies. FePt is the leading candidate material in the development of heat-assisted magnetic recording. In recent years, there have been conflicting reports of the phase transition behaviour and critical exponents of FePt which have been attributed to its complex, long-ranged internal interactions. This thesis identifies anisotropy as the cause of the inconsistent measurements of the critical exponents, and introduces a two-dimensional finite-size scaling framework which is capable of overcoming the anisotropic interactions of FePt. Using this new technique, the critical exponents of FePt are shown to be those of the Heisenberg model. Granular technologies, such as heat-assisted magnetic recording and magnetic particle hyperthermia, have been shown to have a distribution of Curie temperatures. Identifying the Curie temperature distribution is an important step in accelerating the development of granular technologies which operate across the magnetic phase transition. This thesis presents a new characterisation technique which can be used to identify the parameters of the Curie temperature distribution. This technique only requires measurements of the temperature dependent magnetisation, realisable from standard magnetometry. Other materials, such as MnSi and FeGe, are being targeted towards applications such as skyrmion racetrack memory. The internal magnetisation of these helimagnetic materials has a tendency to twist, forming complex topological structures known as skyrmions. The finite-size effects of such materials is little understood and work is needed to quantify them. This thesis presents a qualitative exploration of the finite-size effects of helimagnetic materials. We demonstrate that both finite-size and choice of experimental protocol can significantly impact on the extent of the skyrmion phase. This thesis also identifies the critical exponents of the Dzyaloshinskii-Moriya interaction by using finitesize scaling. This is a key step towards proper finite-size scaling of general helimagnetic materials in the future.

As new applications for wireless communications are developed, system designers are turning more frequently to unplanned networks. While cheaper to deploy, such networks suffer a deficit in control and planning which have a negative impact on the network's ability to manage interference. The lack of centralised power control and scheduling increases the impact of collisions which manifest as in-band interference, negatively impacting performance. This thesis examines several aspects of interference management and determines the parameters that a system designer can manipulate to control the behaviour of the network. First we determine the optimal update rate for a subspace-based distributed interference alignment scheme, reducing convergence time to within 100 iterations. While this improves the convergence time of the algorithm it offers no capacity improvement due to a lack of power-awareness in the algorithm. An altered algorithm is then proposed that offers power-awareness and is found to improve convergence time to less than 10 iterations at a cost to sum interference levels and network capacity. We then propose training sequences that enables users to determine the number of antennas another user possesses with less than 1% error, using this information to recover the training signal for channel estimation. These sequences are found to perform better than the equivalent chaotic training sequences in estimating channel coeffcients. This approach continues to function in channels with unequal transmit and receive antennas, permitting its use in heterogeneous networks. Finally we derive an analytic expression for the upper bound of the likelihood an arbitrary number of neighbours can be detected by a user using SIC on transmissions from directional antenna arrays during neighbour discovery. The expression found permits the system designer to optimise system parameters such as SIR threshold, user array directivity, and transmission rate given the expected user density of the network.

The objective of this thesis was to understand how the iron chelating drug, Deferiprone (DFP), mediates its effects in mitophagy through Parkin/PINK1 independent mechanisms. DFP is an iron chelating drug currently in clinical trials for the treatment of Parkinson’s disease and has been shown to induce mitophagy independently of the PINK1/Parkin mitophagy pathway. Parkin/PINK1 mutations are the most common causes of autosomal-recessive Parkinson’s disease. However, little is known about the action of DFP in this alternative pathway. Mitophagy is the lysosomal degradation of mitochondria. In sporadic and familial Parkinson’s disease, mitochondrial function can be defective. Mitophagy overcomes this by removing damaged mitochondria, however this can also be impaired, particularly in patients with mutations in Parkin/PINK1. Evidence from the work carried out in this thesis suggests that SENP3 is important for DFP-induced mitophagy. SENP3 is a deSUMOylation enzyme involved in removing SUMO-2/3 modifications from target proteins. One potential target is Fis1, a mitochondrial membrane protein with links to mitophagy. Through biochemical and microscopy techniques, it was shown that both SENP3 and Fis1 play important roles in DFP-induced mitophagy, with SENP3 acting to deSUMOylate Fis1, a novel SUMO substrate. It is believed that Fis1 in its deSUMOylated state localises better to the mitochondria and is capable of inducing mitophagy. The work carried out in this thesis highlights an alternative mitophagy pathway through which DFP acts to induce mitophagy. The superfluous nature of Parkin/PINK in this pathway makes it an attractive avenue to explore.

Existing Anglo-American scholarship on the films of Paul Verhoeven is overwhelmingly concerned with the director’s Hollywood productions and tends to apply frameworks of analysis based on Cartesian dualist thought. Much of this scholarship consequently finds contradictions between the politically progressive qualities of Verhoeven’s work and the reactionary politics assumed to be inherent to the popular form. This study aims to re-contextualise Verhoeven’s films as a cinema of immanence, which does not think in those dualist terms. Building on existing work that centres the body and sensation in film scholarship, and drawing on the writings of Deleuze and Guattari, this thesis asks about Verhoeven’s body of work: what is a cinema of immanence, what does it do and how is it different? In this context, immanence means thinking of everything as inherent to the material world. Through close readings of Verhoeven’s films, the thesis makes the argument in three stages over three chapters. The first chapter defines what is meant by a cinema of immanence through a consideration of how bodies are presented on-screen in Verhoeven’s pre-Hollywood films. This chapter identifies a body of work that consistently decentres subjectivity in favour of a presentation of the human body as a multiplicity, also collapsing planes of the symbolic and fantasy into the world of bodies. Consequently, the film-worlds are shown to think in terms of immanent ethics, rather than a transcendent morality. Building on the definition of a cinema of immanence in Chapter One, the second chapter looks at what a cinema of immanence does by reframing the encounter between the spectator and Verhoeven’s Hollywood films in terms of immanence, affect and habit. The chapter determines that Verhoeven’s films can express the formation of rigid Hollywood frameworks of realism, genre and sexual difference, arguing that they operate as popular Hollywood genre films through camouflage or as simulacra. This opens up potential becoming-others to the spectator as habits and expectation are disrupted. The third chapter shows how Verhoeven’s films are different from films that think in terms of dualism by comparing Verhoeven’s RoboCop (1987) and Total Recall (1990) with their contemporary remakes. Through this comparison, Verhoeven’s films can be seen to show a supple segmentarity and micropolitics of the individual, whereas the remakes present unified models of individuality that resonate with the interests of the nation-state and capitalism. The study concludes that the capacity to think in terms of immanence allows Verhoeven’s films to express what Deleuze and Guattari call the molecular dimension of the film world. This disrupts the function of dualist thought, which works to unify, centre, hierarchise and impose finality. Further research is recommended to shift emphasis away from scholarship that imposes dualist frameworks of analysis on the popular form, toward how a film thinks.

This research investigates the extent and possible causes of property valuation variance in Dubai (United Arab Emirates). It complements the wide body of academic research examining valuation in new global markets. A literature review was undertaken and two questionnaire surveys circulated to local commercial property valuers. The surveys revealed that valuers in Dubai are on par with variance observed in other international case studies. The surveys found the main cause of variance to be a result of information efficiency; including sparse transactional evidence; wide yield assumptions; and a lack of standardisation in key areas of the valuation process. Individual client behavioural influences were also pertinent in the cause of valuation variance. An exam-based analysis of postgraduate real estate valuation students also highlighted a number of critical observations relating to variance and valuation methodology. The research, through an industry focus group, recommends a range of solutions to manage variance. Greater market transparency through the pooling of property data and more detail within transactional evidence would ensure more consistent valuation advice. It is expected with an improvement in temporal data the local valuation profession will be better informed and client pressure exerted when finalising the valuation figure will subside. This new research is a useful starting point to expand the range of global studies in property valuation. In addition, the findings undoubtedly assist in improving valuation practices in Dubai and wider GCC/Middle Eastern markets.

This thesis explores the reliance on diverse economic networks in the margins of the neoliberal Mongolian state. Despite wanting to be included in contemporary economic and political narratives, residents of the border town of Magtaal feel largely neglected by the contemporary state and its political representatives. The remoteness of Magtaal, the recent Mongolian economic crisis and the inflation of cash money have submerged the township into a 'regime of debt' (Sneath 2012) manifested in what locals call 'living from loan to loan'-subsisting off temporally-spaced cash influxes from bank loans and other sources. Yet, residents have appropriated these local economic, political and legal ambiguities through the creation of debt-motivated and/or resource extractive networks that engender monetary returns for the township. Through experience living and traveling with cross-border natural resource bulkers, local moneylenders and debt-based trade participants, this thesis explores debt-motivated economic networks that function to mobilize and distribute diverse sources of value. The power of these lies in their ability to bridge the multiple disjunctures between the bank-based formal system and the temporalities and values of the local social world. For one, these networks are driven by bank-based debt, yet enabled by social-based, 'gift-like' (Pedersen 2016) debt. Additionally, these chains can 'translate' (Tsing 2015) across moral worlds through the inclusion of local registers of patronage, care, assistance and prestige into economic calculi. As a result, these networks are increasingly utilized and morally sanctioned for their provisioning and distribution functions in lieu of the state. But in doing so, cosmoeconomic narratives are reconceptualized to sanction the increasing monetization, financialization and resource extraction in the Mongolian economic landscape.

This thesis used Interpretive Phenomenological Analysis to explore the lived experience of harmful sexual behaviours (HSB) at school. Nine participants from two special schools and one mainstream school from within two local authority boundaries were involved in the study. Various levels of experience of HSB existed, with these behaviours often interpreted as play or a normal part of growing up, or a mental health issue; humour and own experience of parenting was used to respond to the lived experience of HSB. Children were described as difficult to like and could say things that might ruin careers and jeopardise livelihoods meaning participants relied on each other for support. When HSB occurred, schools were blamed by the local authority which threatened the school's reputation as a safe establishment. Although safeguarding officers were the first point of contact for staff, no support existed for this group. Whilst the literature revealed special schools to be ideal places in which staff could recognise and respond to HSB, participants did not consider themselves professionally equipped to carry out this work. Poor Information sharing meant other children, who were potential victims, were exposed to HSB. The complexities of the education system was therefore seen to fail schools and children because of metaphorical holes in the system. The experiences described confirmed high participant awareness and acceptance of HSB in schools, even though individual experiences differed. Acceptance of these behaviours, blame, confusion and inconsistency were all observed. However, this study has revealed new understandings around silence and denial, caused by the lack of local authority support for the schools when HSB had occurred. This established HSB consistently as the elephant in the room, 'that which was not discussed and was undiscussable'.

This thesis examines the relationship between the early modern understanding of female melancholia and women's depression today. Working with proto-medical treatises and Shakespearean drama from the early modern period (1580-1665), alongside contemporary diagnostic frameworks and psychosocial research (1960-2017), it investigates how female melancholics and depressed women speak to each other across the historical divide. Late sixteenth- and early seventeenth-century experiences of melancholia shed new light, in particular, on the neglected area of women's experience of depression today. I interrogate the notion, prevalent in early modern literature and culture, that female melancholia is equated with weakness; and demonstrate how this assumption was explored and challenged on the early modern stage by William Shakespeare, John Fletcher, and George Wilkins. I argue that melancholia emerges in early modern drama as a potential site for identity and agency, and emphasise the importance of sympathetic recognition for sufferers in the past and the present. The terms 'melancholia' and 'depression' are only accessible to women under certain circumstances, however, and not all women are equally successful in eliciting a sympathetic response. In The Two Noble Kinsmen, women's social class determines their degree of success in receiving sympathy, as I discuss through the sharp disparity between the grieving Queens and the greensick Jailer's Daughter. In King John, royal position affects how much sympathy Queen Constance receives in her maternal grief. And in Pericles, a surprising relationship emerges between recognition, chastity and melancholia through the complex figure of Pericles' daughter Marina. These three plays reveal important and counterintuitive links between early modern feminine selfhood and melancholia which, I argue, can illuminate in new ways the experience of female depression today. This thesis does not propose a seamless continuum from the early modern period to the present, but instead sets out to show how certain important cultural trends and assumptions are retained in more recent diagnostic and psychosocial studies. By exploring the narrative of these two periods together, in an open and interdisciplinary manner, my project seeks to improve our understanding of the way melancholic women were treated in the early modern period; and, in so doing, to reconsider the ways women experiencing depression are recognised and supported today.

This research had two aims. The first aim was to investigate the support mechanisms available to learners with dyslexia on programmes of higher education (HE), and the second aim was to assess the effectiveness of any inventions used to improve access to learning for this group of learners. Since the introduction of the National Student Survey (NSS) in 2005, efforts have been ongoing to improve the quality of the educational experience for students on HE programmes. Although the general trend in satisfaction scores is an improving one, this is not the case for learners experiencing disabilities. Around 43% of these learners will have dyslexia. The research consists of two distinct parts. The first is a cross-sectional website survey and documentary analysis, and the second is a systematic review. The cross-sectional website survey and documentary analysis located and extracted data that detailed the learning support available to learners with dyslexia, from a representative number of higher education institution (HEI) websites in England. The systematic review analysed 10 single studies of experimental or quasi-experimental design and one literature review. These studies focused upon interventions provided to learners with dyslexia in higher education (and its international equivalents). The combined findings suggest that support for learners with dyslexia in these settings is fragmented and inconsistent, and that there are many areas of existing practice that could be modified to improve opportunities for learning. There is an absence of any model of good organisational practice. There are examples of ‘in-class’ curricular adaptations and ‘outside-class’ additional learning and study skills support, including the use of information communications technology and assistive technology, which have shown some success in supporting the learning of those with dyslexia, but they are not implemented consistently or widely.

The impact of randomized controlled trials is frequently diminished by disparate outcome reporting, precluding the comparison of results between trials or synthesis of data in meta-analyses. This is particularly problematic in lower incidence conditions such as oropharyngeal squamous cell carcinoma (OPSCC), where the need to synthesise data from competing trials is greater. Minimum outcome reporting standards, known as Core Outcome Sets (COS) have been shown to increase the consistency of outcome reporting between trials of comparable interventions, thus facilitating the comparison or synthesis of trial data. The objective of the work in this thesis was to identify outcomes of importance to patients, carers and healthcare professionals and define a COS for OPSCC. The methods used comprised a systematic review of OPSCC RCTs to identify the outcomes reported and establish whether there was outcomes heterogeneity as suggested by other studies; semi-structured qualitative interviews with patients and carers to establish their outcomes of importance; a Delphi Study of patients, carers and healthcare professionals, to reach consensus on the outcomes that should be included in a COS for OPSCC. The systematic review described in chapter two identified significant heterogeneity in outcome reporting; 58 outcomes were reported in 43 RCTs, only three outcomes were measured in more than 50% of studies, and only 41% of outcomes were measured in more than one study. The qualitative study identified 136 outcomes. Survival and late adverse effects of treatment are of greatest priority to patients and carers. The Delphi study successfully reached consensus on eight outcomes for inclusion in the COS. There is substantial heterogeneity in the outcomes measured in contemporary RCTs in OPSCC. Yet, there is strong consensus between stakeholder groups in the outcomes of importance. Implementation of the COS will increase the consistency of outcome reporting thus facilitating the comparison of data from competing trials and synthesis of data in meta-analyses. Further consideration must be given to ways in which the uptake of COS can be maximised to have the highest impact. The COS is applicable to trials of interventions used in current clinical practice, however the advent of new treatment strategies may require that this is reviewed and adapted.

The goal of this thesis is to set out an argument which demonstrates that the Principle of Alternate Possibilities (PAP), which holds that an agent may only be blameworthy for performing a given action if they were able to do otherwise than it, can be logically derived from a certain interpretation of the common moral principle that "ought implies can" (OIC). In pursuing this "Derivation", I follow David Copp in claiming that both PAP and OIC are in large part motivated by the same considerations about fairness and the role that our genuine moral obligations may play in our processes of moral deliberation. I begin by outlining a case in favour of my preferred sense of OIC which is grounded in these shared motivations, before protecting it from a varied range of counterexamples. I then turn my attention to defending what I call the "connecting premises" of the Derivation- a set of reasonably uncontroversial moral beliefs which, in conjunction with my understanding of OIC, show that PAP is true. In arguing for these premises, I draw on a broader normative picture in which our moral obligations, blameworthiness for failing in those obligations, and the morally relevant sense of ability which underpins both of them are inherently linked. I conclude my argument in support of the Derivation with an extensive discussion of the concept of fairness as it applies to discussions of blameworthiness and moral obligation, and develop the aforementioned normative picture into an argument that all genuine moral obligations are necessarily fair in this sense. Hence, the Derivation will serve not only as a proof of PAP, but also as evidence for an interrelated set of moral principles which govern the conditions under which an agent may be obligated to act and/or be correctly said to have acted wrongly

This thesis describes selected reactivity studies of the N-heterocyclic carbene, IPr, towards a range of main group compounds. The synthesis and characterisation of sixty-three compounds, all of which incorporate IPr as a ligand in one of three coordination modes, are detailed herein. The deprotonation of IPr allowed for the isolation of an anionic source of the aIPr: ligand which was synthesised as a novel potassium salt and along with the previously reported lithium salt, was employed in reactions with group 12 and 14 bis(trimethylsilyl)amides and tetrahalides. The further chemistry of such novel products was investigated towards both electrophilic and nucleophilic reagents making use of both the pendant nucleophilic carbene functionality and the electrophilic main group centre. An alternative route to such species was investigated by the spontaneous isomerisation of IPr in the coordination sphere of group 14 tetrabromides and group 15 tribromides. The scope of this reactivity was subsequently investigated and was found to provide a simpler route to access the abnormal coordination mode of IPr. The aIPr ligand which is generated may be deprotonated by additional IPr thereby affording aIPr: ligands. The addition of halide abstracting agents allowed for the synthesis of cationic species stabilised by the coordination of either IPr or aIPr ligands. A unique, spontaneous reductive coupling of two phosphorus centres was discovered to take place upon heating a THF solution of (IPr)PBr3. This allowed for the isolation of a bromide bridged P–P bond with reduced phosphorus centres. This facile reduction chemistry was further explored by reaction with mild reducing agents which provide access to low oxidation state phosphorus compounds in high yields. This chemistry was found to be possible (and more effective) due to the presence of the weaker phosphorus bond to bromine relative to the commonly employed chlorine ligands.