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The development of novel antifungals capable of eliminating Aspergillus fungal infections and improving patient outcomes in Aspergillosis is essential. This work has focussed on Uric Acid Permease, a nucleobase-ascorbate transporter from Aspergillus nidulans, as a potential antifungal carrier. The existing crystal structure of UapA-G411VΔ1-11 in complex with xanthine (PDB 5I6C)1, has provided invaluable information about the substrate binding site, and allowed for the structure-guided design of derivatised xanthine analogues. Competitive uptake assays were used to obtain the binding affinity of each of the analogues for UapA in Aspergillus nidulans. 3-benzylxanthine (5) was identified as a novel ligand of UapA, binding with 35x higher affinity (KI = 0.2 μM) than the native substrates xanthine (KM = 7 μM) and uric acid (KI = 7 μM). This work describes the functional characterisation of 3-benzylxanthine (5) using fungal growth assays, and fluorescence microscopy. The effect of this substrate on UapA-WT and the thermostabilised mutants UapA-G411VΔ1-11 and UapA-Q408EΔ1-11 was assessed using cellular thermal shift assays (CETSA), fluorescence size-exclusion chromatography (FSEC), CPM-based thermostability assays and nano-differential scanning fluorimetry (nano-DSF). While these approaches had their challenges, they all demonstrated that 3-benzylxanthine (5) did not significantly destabilise UapA-WT or the thermostabilised mutants UapA-G411VΔ1-11 and UapA-Q408EΔ1-11. The later part of this work describes attempts to structurally characterize the binding interaction between 3-benzylxanthine (5) and UapA using X-ray crystallography, hydrogen-deuterium mass spectrometry (HDX-MS) and cryo-electron microscopy (cryo-EM). While the structure of UapA-WT or its mutants with 3-benzylxanthine (5) has not yet been resolved, preliminary results from hydrogen-deuterium mass spectrometry (HDX-MS) suggest that 3-benzylxanthine (5) may bind an outward or occluded conformation of UapA-Q408EΔ1-11. Structural characterisation of UapA with 3-benzylxanthine (5) using cryo-EM is ongoing. Once resolved, this will form the basis of future structure-guided xanthine analogue design initiatives.

The Iranian taʿziyeh tradition commemorates the martyrdoms of Ḥusain b. ʿAlī b. Abī Ṭāleb and his supporters at Karbala in 61 AH /680 CE. It includes a largely anonymous cycle of plays, the main episodes portraying the martyrdoms of Ḥusain, his relatives and supporters. This study examines four such episodes, The Martyrdom of ʿAbbās, The Martyrdom of Qāsem, The Martyrdom of Imam Ḥusain and Bāzār-e Shām (The Damascus Market). Comparing versions of their scripts from the Zand period (the earliest extant examples), through the Qajar period, and up to the mid-20th century, I analyse their literary features and how they developed. The majority of my sources are manuscripts drawn from the Vatican Library's Cerulli Persian Collection. Through tracing the trajectory of these particular episodes, I make an important contribution to the understanding of the development of the taʿziyeh genre as a whole. I show the strong influence of the Iranian storytelling traditions naqqālī and pardeh-dārī, evidenced by narrative content, characterisation of the protagonists as heroes of epic, and by the presence of compositional features such as type-scenes and a composition-scheme (common in oral art forms). I also identify a societal connection between the early taʿziyeh composers and the storytellers of Selseleh-ye ʿAjam (the ʿAjam dervish order). In the dramatists' embellishments of the Karbala narrative I find stories that assert the breadth of the Shiʿi community by connecting believers of different stripes to Ḥusain. I see the increased treatment of female characters, and find this to be a reflection of the taʿziyeh's most active audience contingent. I see evidence of the dramatists' impressions of European visitors to Qajar Iran, and find a hint of satire.

Introduction: Compassion-focused Therapy (CFT; Gilbert, 2005) has increasingly been shown to have a positive impact for people experiencing a range of difficulties, and online self-help formats could provide a way of increasing its accessibility and scalability. This study explored adult participants' subjective experiences of engaging with online self-compassion training drawn from Compassionate Mind Training (based on the CFT model). Methods: Semi-structured interviews were conducted with 15 participants who had completed online self-compassion training, and the interview data was analysed using reflexive thematic analysis (Braun & Clarke, 2006). Results: The analysis generated four main themes and 17 sub-themes. The four main themes generated were 'A way of being in the world', 'Old habits die hard', The learning process, and Context and resources. These themes showed that while the process of developing self-compassion was often challenging, most participants described experiencing positive changes in their ways of relating to themselves and others. Participants identified many facilitators and barriers to change, including factors related to the training format and their wider social contexts. Discussion: These findings support previous research into CFT, particularly in relation to some common positive changes people experience and some of the difficulties with this process (e.g. fear of compassion). Participants' descriptions offer promise that approaches based on the CFT model can be experienced as acceptable and helpful by people engaging through an online self-help format as well as through individual and group-based interventions. The facilitators and barriers to change that participants described indicate the strong influence of people's contexts and the need for these to be considered when designing and implementing approaches.

This thesis presents a model-theoretical analysis of some theories of linear orders in monadic and weak monadic second order logic. In particular, the pseudofinite monadic second order theory of linear order and the weak monadic second order theory of a dense linear order. The analysis of the former plays a key role in the analysis of the latter. We adopt a one-sorted first-order setup for dealing with monadic and weak monadic second order logic, which is described in full detail. In both instances the model-theoretical analysis involves presenting an axiomatisation which gives insight into non-standard models, and obtaining a model-completeness result after suitably enriching the signature. For the pseudofinite monadic second order theory of linear order, we also classify the completions using residue functions and establish a connection to the free profinite monoid on one generator using extended Stone duality. Throughout, an emphasis is placed on non-standard models of monadic and weak monadic second order theories. Towards our analysis of the weak monadic second order theory of a dense linear order, we present a definable composition theorem, inspired by Shelah's composition theorem, which is more easily applied in the case of non-standard models.

Recent developments in immersive media provide opportunities for content creators, but new tools and skills are required to negotiate spatial audio production. Production tools such as digital audio workstations have traditionally been designed for single users, whereas audio production (e.g. music, games, film) is often a collaborative process. For spatial audio production, virtual reality (VR) could transform how groups work on content together. However, there are gaps in our understanding of spatial audio production regarding (i) collaboration, and (ii) design knowledge of VR tools, especially for expert users. This thesis explores these issues across two complementary threads: Context Mapping, which involves design ethnography studies in studio settings, and Design Intervention, which focuses on the design and evaluation of VR artefacts. The first ethnographic study focused on the role of spatial communication and embodied interaction when studio producers make aesthetic assessments of audio content. A follow-up ethnographic study addressed spatial audio production, investigating how gestures support situated practices. Strong interrelationships between spatial communication, technology, and audio content were observed. To explore how technology impacts collaborative processes, multi-user VR music production systems were designed and evaluated. The first design study (Polyadic), analysed how different media, VR and desktop, affects communication and engagement in the creative process. Findings yielded significant differences between media with a preference for VR. Linguistic analyses suggest that media affects the use of referencing. The second design study (Invoke) explored joint idea projection for spatial audio production. Users appropriated virtual resources (avatars, workspaces, and objects) in sense-making processes endogenous to the collaborative spatial audio production activity. Findings also suggest that social-space formations change compared to face-to-face interaction. Both the VR artefacts were judged positively as creativity support tools. Thematic analyses of qualitative user feedback provided insight on expert user needs related to collaborative VR audio production.

Graphene and other 2d materials have shown great promise for their ability to sense chemicals. This ability is attributed to the chemical nature of graphene, but also the fact that 2d materials have a large surface-to-area ratio, thus sensitivities towards sensing the single molecule have been achieved, however there is little to no selectivity between analytes. At present, researchers are primarily looking at pollutants or other small molecules using pristine graphene. Alternative sensing motifs are to functionalize graphene; covalent attachment to the graphene lattice, which destroy some properties and lead to irreproducibility across devices. We use a supramolecular approach to non-covalently functionalize the graphene using metal-organic cages. The metal-organic cages can encapsulate a small range of guests, however their binding inside the cage has not been investigated in the presence of graphene. Therefore, we present a novel investigation into the use of pristine graphene as a transducer for the host-guest interactions, in hopes of improving the selectivity of graphene whilst retaining the single molecule sensitivity. We tackle this through Raman spectroscopy and other surface techniques, then move onto fundamental electronic characterisation of graphene with a pyrene-edged metal-organic cage and show that the presence of C60 within the cage influences the electronic characteristics of chemical vapour deposited graphene. After the model system has been established, we extend the prospect into a commercial and scalable setting using liquid phase exfoliated graphene with a sulfonate-edged metal-organic cage with the intent to create an inkjet-printable selective sensor. We encountered expected successes and unexpected failures. Our aim is to establish research towards the field of using 2d materials decorated with 3d architectures that interact non-covalently to sense analytes that are specific to the 3d architecture.

For the past thirty years, much work on Breton has highlighted various apparent differences between two groups of speakers, roughly equivalent to the categories of new speakers and traditional speakers used more universally in more recent work. In the case of Breton, the conceptualisation of these two categories entails a number of stereotypes; one of the most salient concerns the lexicon, specifically issues around newer and more technical vocabulary. Traditional speakers are said to use French borrowings in such cases, influenced by the dominance of French in the wider environment, while new speakers are portrayed as eschewing these in favour of a “purer” form of Breton, involving in particular the use of neologisms based on existing Breton roots. This thesis interrogates this stereotypical divide by examining language used in the media, a context where new speakers are likely to be highly represented. The bulk of the analysis presented in this work refers to a corpus of Breton gathered from media sources, comprising radio broadcasts, social media and print publications. Insights are also provided from interviews that were carried out with employees of Breton-language media to gain additional information on speakers' individual practices and beliefs. The findings show that in these contexts, speakers often avoid some of the more extreme features associated with the new speaker stereotype, and that medium and register can be relevant factors in what sort of lexicon is used; also, notably, the traditional dialects of Breton to a certain extent serve as target varieties for many new speakers, showing that the two groups are not as separate from each other has some research has implied. New speakers, and others with new speaker characteristics, do not form a homogeneous community, but instead have diverse ways of speaking and engaging with Breton and the rest of its speaker population.

The research contained within this thesis focuses on understanding and interrogating nanometrically confined ultrafast plasmon-phonon interactions. Nanometric plasmonic confinement is achieved by coupling the charge oscillations of a single gold nanoparticle to a gold substrate. This confines the plasmonic field to the single nanometre gap separating the two and is known as the NanoPar- ticle on Mirror (NPoM) structure. The first half of this thesis demonstrates the viability of using the coupling between confined plasmonic and acoustic modes as a sensitive nanomechanical probe. Initially this coupling allows us to discover the NPoM “bouncing mode” by performing ultrafast pump- probe spectroscopy on single constructs. Thorough finite element method simulations allow us to create a simple analytical model relat- ing the nanoparticle-substrate contact area to the bouncing mode period. This means that by measuring the bouncing mode period of a single NPoM structure we can calculate the size of the contact; a task impossible by any other means. The second half of this thesis is dedicated to furthering our under- standing of ultrafast molecular-phonon plasmon interactions. To fa- cilitate this we develop and utilise a fully automated time-resolved Coherent Anti-Stokes Raman Spectroscopy (tr-CARS) setup to mea- sure an acceleration of the vibrational decay of 2-mercaptopyridine within NPoM from 0 . 96 ps (determined from bulk Raman linewidth measurements) to far below 0 . 5 ps . To understand the origin of this acceleration we perform a series of power dependent Surface En- hanced Raman Spectroscopy (SERS) measurements on over 1000 NPoM constructs. We determine the acceleration to be most likely due to anharmonic phonon coupling driven by the high phonon pop- ulations induced by ultrafast pulses in plasmonic cavities. The power- series also reveals the presence of a previously unknown saturation effect due to intermolecular anharmonicity.

Despite the increased focus on families of prisoners within research, policy and practice, there has been a lack of recognition of the distinct experiences of young people affected by familial imprisonment. More specifically, there has also been a failure to consider experiences of sibling imprisonment. This thesis addresses both of these gaps in knowledge. It draws on qualitative data from two groups of participants: the first were young people from KIN, a project which creatively explores experiences of familial imprisonment; the second were a group resident within a Young Offenders Institution (YOI). Both were interviewed about their experiences of a family member's imprisonment, though their contrasting current situations created differences within the research process which are reflected upon in a specific 'methodology as finding' chapter. In respect of the substantive topic of familial imprisonment, I challenge the dominant narrative within academic literature and policy of a family member's imprisonment only being a disruptive force (one that creates distance) in relationships. Instead, narratives of closeness also emerged. These were mainly from the experiences of those within the YOI. The inclusion of this group of participants, along with an exploration of their inter / intra-prison relationships, represents a novel contribution to familial imprisonment literature. While the existing literature tends to assume an over-simplified binary between 'prisoners' family member' and 'prisoner', this thesis recognises that these terms are not exclusive; it is possible to hold both of these identities simultaneously. As well as questioning the assumption of the disruptiveness of imprisonment, where it does occur this thesis also challenges the idea that imprisonment is the only, or even the main, disruptive force within the lives of the young people it affects. While partly reinforcing and contributing to literature which says this disruption occurs and needs to be dealt with, this thesis also argues for the need to re-situate this experience within the wider set of disruptions experienced by some young people in their lives. I explore the range of issues a young person may be dealing with in their day-to-day lives and the various disadvantages they can experience. Therefore, this challenges the idea that prison is the only place in which this group's problems can be both located and resolved.

Mitochondrial cytochrome c (Cc) is a small haem protein, primarily involved in electron transfer, but is an example of an extreme multifunctional protein with roles in several stages of apoptosis through interaction with phospholipids and Apaf-1. The switch in function is associated with an interaction with cardiolipin (CL) and gain of peroxidase activity. Mutations in the Cc gene lead to Thrombocytopenia 4, a disease associated with enhanced apoptotic activity. The Y48H variant is found in the 40-57 W-loop, the lowest free-energy foldon. A 1.36 Å resolution X-ray structure of the Y48H variant reveals minimal structural changes to that of the wild-type protein and G41S variant (also associated with Thrombocytopenia 4). Despite this, the intrinsic peroxidase activity is enhanced, implying that a penta-coordinate haem species is more prevalent in the Y48H variant, corroborated through determination of a Met80 off-rate of > 125 s-1 compared with ~ 6 s-1 for the wild-type protein. Heteronuclear NMR experiments with the ferric Y48H variant have revealed heighted dynamics relative to the WT protein in the 40-57 and 71-85 W-loops, the latter being the loop containing the Met80 ligand, suggesting communication between these two substructures. When these results are considered in relation to the G41S variant, a dynamic picture emerges in which heightened dynamics in key substructures of the Cc fold facilitate an increased population of a penta-coordinate, peroxidase active species of the order wild-type < G41S < Y48H. Studying the alkaline transition through pH jump stopped-flow 2 spectroscopy has revealed that not only is the pK695 is reduced by ~ 1 pH unit compared to that of the wild-type protein, but also the pK of the trigger is lowered. In contrast, variants in the 71-85 W-loop do not alter the pK of the trigger but are nevertheless associated with enhanced peroxidase activity relative to the wild-type protein, due to enhanced local dynamics within the haem crevice.

This study adopts a landscape approach to all the rock-art sites on Rombalds Moor in West Yorkshire, 252 unmoved sites, to consider views of and from the sites. British rock-art is generally believed to date from the later Neolithic to the later Bronze Age, but a case is made for it perhaps beginning in the later Mesolithic. What is known of environments for the Moor over this whole period provides a basis for a reconstruction of rock-art landscapes. A case is made for the applicability of ethnography from the whole circumpolar region to the personal construction of people’s landscapes in prehistoric Britain. All sites were visited, and the sites and their views recorded, both as written records and as photographs. The data was analysed at four spatial scales, from the whole Moor down to the individual rock. Several large prominent carved rocks, interpreted as natural monuments, were found to be visible from many much smaller rock-art sites. Several clusters of rock-art sites were identified. An alignment was also identified, composed of carved stones perhaps moved into position, and other perhaps-moved carved stones were also identified. The possibility that far-distant views might be significant was also indicated by some of the findings. The physicality of carving arose as a major theme. The natural monuments are all difficult or dangerous to carve, leading to considerations of risk, including being seen to embrace risk. Conversely, the more common, simple sites mostly required the carver to kneel or crouch down. This leads to comparisons with what is known of North American rock-art, where some highly visible sites were carved by religious specialists, and others, much smaller and inconspicuous, were carved by ordinary people. This was not an expected finding for British rock-art, and further research is indicated.

This study is aimed at exploring how female partners experience their male partners’ use of pornography. It is reported that therapists are increasingly being called upon to support female partners presenting with difficulties relating to their male partners’ porn use (Hall, 2015), but that clinicians feel under-prepared to work effectively with these clients due to a lack of training and the limited availability of empirically based literature (Ayres & Haddock, 2009). Consequently, there appears to be a growing need for research in this area that can provide insight and guidance for clinicians. The phenomenological epistemology and relativist ontology that underpin this study place an emphasis on understanding the subjective lived experiences of the participants; a focus which seems congruent with the philosophical underpinnings of counselling psychology. Using a qualitative approach, semi-structured interviews were conducted with six female participants. The interviews were transcribed and analyzed using Interpretative Phenomenological Analysis through which four master themes were identified: ‘Pushing her limits of acceptance: The ongoing discoveries’; ‘The female partner’s meaning-making’; ‘A lonely experience’; and ‘The layers of loss’. New insights regarding the interplay between the female partners’ meaning-making and their responses highlight the multi-layered and complex experiences of these participants. A number of implications for practice are discussed including the importance of clinicians moving away from a model of pathology to one of promoting well-being and validating female partners’ emotions and experiences regardless of whether a diagnosis (of porn or sexual addiction, for example) is present. The findings may serve to inform individual and group work with both female partners and male users, as well as couple work. Finally, it is hoped that providing insight into the lived experiences of female partners may encourage a more empathetic and understanding response from male porn users and society when female partners seek their support. The limitations of the study are discussed as well as further areas for research.

Leishmania protozoa are the etiological agent of human disease known as leishmaniasis. There are three main forms of this disease, whose manifestation depends on a number of factors including the infecting Leishmania species and the immunological status of the individual. Disease development requires extracellular form of the parasite, the promastigotes to be internalised, transform and replicate as intracellular amastigotes within mammalian cells. Once inside host cells parasites they regulate and control immune responses from inside the host cells through the modulation of protein expression including cytokines. The changes involving Leishmania promastigote and host cells is well documented during the early stage of infection. However, little is known on the modulative effect of L. aethiopica and L. mexicana during infection of host cells. It is key to have an altruistic approach to when studying the different Leishmania spp during host infection, as it is a key factor in the outcome of type of leishmaniasis. The study of infection is complicated by the inherent difficulty of detecting intracellular parasites, as many methods are laborious and time consuming (microscopy with Giemsa staining). Implementation of fluorescent expressing parasites has been successfully used in a number of species to observe and quantify cellular infection. Although successful stable genetically modified Leishmania parasites are not available for L. mexicana and L. aethiopica, this research aims to investigate survival mechanisms such as cytokine and protein expression during the early stages of infection. This requires monitoring infection as the first step, which involved developing for the first time constitutively expressing GFP in L. aethiopica, L. major, L. mexicana and L. tropica. The effect of infection on host macrophages was directly quantified via comparative proteomics which identified significant differences in protein expression not only between uninfected and infected cells at late stages of infection but also between different species. The effect of infection on the ability of controlling host and neighbouring cells was further characterised by looking at cytokine & antimicrobial peptide expression, including TNFα, IL-10, TGFβ, IL-1RA and cathelicidin at various time points during L. aethiopica infection. As cytokine expression is closely linked to manipulation of T-cells, which are also know to be ultimately responsible for disease exacerbation/resolution, the effect of the parasites on such cells was further investigate. A novel role for T cells on infection was explored, specifically their ability to host parasites. The successful stable integration of GFP expression in four Leishmania spp. was confirmed by PCR, western blot, fluorescent microscopy and flow cytometry (N=3). These parasites allowed the monitoring of infection in macrophages whilst investigating the expression of cytokines, proteins, and novel human cell types. Cathelicidin expression was shown to increase during the early stages of infection at 8hrs following by a steady decline towards 48hrs post infection. The anti-inflammatory cytokine IL-10 expression was shown to increase from 2-48hrs peaking at the latest point with >3-fold difference post infection. Interestingly, the inflammatory cytokine TNFα showed expression increased from 2-48hrs, peaking with >5-fold at 48hrs post infection. Both these cytokines have been shown to peak at 8 hours followed by a decline, which may indicate subtle differences at a species (Lapara and Kelly 2010). Proteinomic study revealed L. mexicana and L. aethiopica both up-regulated a total of eight proteins with only two that were influenced by both species (N=3). In addition, down regulation was only identified during infection with L. aethiopica and not L. mexicana. However, during upregulation, the proteins identified were found to be involved in endocytosis (actin), immunological responses (MHC I), free radical scavenging and apoptosis (metallothionein). When comparing with similar proteomic studies by Singh et al, all modulation effects identified by L. aethiopica and L. mexicana were not previously shown during L. donovani infection. Infection was tested against human T lymphocytes as they have been implicated in the production of cytokines for the activation of macrophages allowing the elimination of intracellular parasites within macrophages. This novel work has shown L. aethiopica and L. mexicana are capable of infecting Jurkat cells (N=3) and enriched human T lymphocytes extracted from five different individuals. This finding has uncovered that infection is not only includes T cells (including CD4+ subsets) but percentage of infection is dependant on the species of parasites and the donor lymphocytes. In conclusion, this research showed for the first time that L. aethiopica and L. mexicana modulate a repertoire of protein expression at 24hrs post infection. The changes of cytokines expression highlights differences between different species and the discovery that Leishmania has the ability to infect human T cells may commence the start of the complete understanding of the survival mechanisms imposed by the parasite on the wider cellular network. This will change the approach to studying immunology of leishmaniasis infection and potentially clarifying the role of these cells for which contrasting evidences in human and mice models have caused much debate.

This thesis presents the design, development and efficacy of antimicrobial nanotherapies, to overcome the challenges faced by conventional antimicrobial delivery for the treatment of Pseudomonas aeruginosa respiratory infections in cystic fibrosis (CF). In the CF lungs, mucus and biofilms pre.sent complex barriers to the optimal delivery of antimicrobial therapy, leading to low antimicrobial exposure to resident bacteria and inadequate eradication. Respiratory disease, associated with chronic respiratory infection, is ultimately the main cause of morbidity and mortality in CF patients. There is a need to develop improved antimicrobial and anti-biofilm therapies in this patient group. Firstly, alginate/chitosan polymeric nanoparticle (NP) delivery vehicles for the antimicrobial tobramycin were formulated. Tobramycin NPs demonstrated antimicrobial efficacy against laboratory and clinically isolated strains of P. aeruginosa in vitro and in vivo against infected Galleria mellonella. Next, functionalisation of the mucolytic DNase to tobramycin NPs was investigated with the aim to improve penetration of the mucus and biofilm barriers, to increase the accessibility of tobramycin to the difficult-to-reach sites of infection. Functional activity of both drugs was established against DNA, P. aeruginosa strains and in CF sputum. DNase functionalisation was found to improve the sputum penetration of NPs and these DNase tobramycin NPs possessed anti microbia! activity in sputum samples from CF patients. Finally, the antimicrobial activity of the developed nanotherapies against P. aeruginosa biofilms was studied. DNase tobramycin NPs have the potential to target both the biofilm matrix and bacterial cells through the combined DNA degradation and bactericidal actions of DNase and tobramycin. Against established P. aeruginosa biofilms, both tobramycin NPs and DNase tobramycin NPs were found to be effective antimicrobial agents. The developed antimicrobial nanotherapies represent a promising therapeutic strategy for improving tobramycin delivery to mucus-embedded, biofilm-associated respiratory infections in CF.

Perovskite materials possess a broad range of novel and useful properties. This has lead to perovskites being used in a broad range of applications, with considerable ongoing research being invested into them. While the bulk structure of these materials have been thoroughly investigated and documented, the polar surface and nanocluster structures of these compounds are relatively unknown. This is largely due to conventional structural determination techniques, such as X-ray and neutron scattering, proving ine ective on these non-bulk phases. In this thesis computational methods have been used to model the ABZ3 type perovskite materials KTaO3, KMgF3, and KZnF3. Global optimisation techniques have been employed to predict the structure of the compounds in non-bulk phases. The global optimisations were performed using interatomic potentials, with the lowest energy candidates being re ned through density functional theory. Reconstructions of the (001) polar KTaO3 surface were investigated. It was found that the lowest energy reconstructions involved the migration of the Ta ions from the surface, towards the bulk, where they were able to achieve a fuller coordination. The K ions moved in the opposite direction, migrating towards the surface. Defects in the form of neutral K and O vacancies were introduced to the surface. It was found that both types of vacancy resulted in an upward band bending towards the surface. This indicated an accumulation of holes at the surface for K vacancies, and an accumulation of electrons in the bulk for O vacancies. The structures of small nanoclusters, containing 5 - 100 atoms, were predicted for the compounds KMgF3 and KZnF3. The low energy structures revealed that it was energetically favourable for the B cations, Mg or Zn, to adopt positions close to the cluster centre, while the K cations resided at the edges of the clusters. The optical gap of the clusters was found to vary with the size of the cluster. This indicates the properties may be tuned by controlling cluster size.

Responding to referrals regarding children who display sexually harmful behaviour (SHB) is a complex area of practice for qualified social work practitioners working in generic social work intervention, for example in Local Authority safeguarding teams. The government guideline Working Together to Safeguard Children (2006) was the first document to officially recognise this particular group of children in policy and suggest guidelines for intervention. It confirmed that children who display SHB were classified, and so should be responded to, as children in need and therefore required at least a Section 17 Child in Need Assessment (Children Act, 1989). This thesis examines the extent to which these guidelines were followed within a Local Authority by accessing 30 cases from their Integrated Children’s System (ICS) – examining the recordings made by the social workers to explain their decision making and action taken. Taking a critical realist grounded theory approach for social work research as recommended by Oliver (2012), ethnographic content analysis was used to analyse qualitative data from these recordings. Following this, semi-structured narrative interviews were used to explore the experiences of generic social work practitioners in this area of practice (children who display SHB), as well as the experiences of parents and other carers. These are presented in the form of thick description (Geertz 1973) in order to interpret the meaning of the actions and behaviour of the participants (Ponterotto 2006). This was completed from the perspective of a social work practitioner-researcher embedded in social work practice during the research process. There is value in practitioner participation in research as this, in effect, values the opinions and theories of social workers and ensures that the research conducted in local and specific (Oliver 2012). These two areas of research reveal the individual journeys of children displaying SHB showing how they can be invisible to CSCS concluding that, initially, this was because when they were referred to CSCS they did not receive a consistent response, and it was difficult to find information regarding these children within ICS. The thesis went on to conclude that specifics about the children’s behaviour were not recorded accurately, e.g. ‘inappropriate sexualised behaviour’ was a common term used. Finally, in relation to intervention, there was evidence of delays, and referrals to specialist services not being followed up – because sexually harmful behaviour was not always identified as such, opportunities for early intervention were missed. Following these findings are recommended guidelines for how CSCS can work with children who display sexually harmful behaviour to ensure they become more visible and go on to receive the appropriate intervention. Generative mechanisms (i.e. the what) were identified for further research, in order to develop a theory using grounded theory. These include: societal norms; gender; age; class; professional judgement; focus of child protection; and bureaucracy.

There has been limited success in tackling the spread of the HIV epidemic among young people, despite years of interventions. This research contributes to an understanding of why intervention success has been limited by examining HIV prevention among young people in the rural Eastern Cape of South Africa. Shifting the focus from the specifics of individual interventions, it draws on the theoretical work of Foucault to examine how young people and their sexuality are being constructed and understood within policy discourse, and how this relates to young people’s own everyday experiences of the virus. In doing so it highlights both the disjuncture between these understandings, and the ways in which, despite this, young people are engaging with policy narratives in often unexpected ways. Using qualitative approaches the research was carried out in four rural communities. Repeat dependent interviews (n=108) were conducted with young people (n=56) over a 10 month period. These were supplemented by participant observation, key informant interviews (n=15), and analysis of policy documentation. The study finds that the ways in which evidence is used to make knowledge claims about young people and their engagement with the virus is problematic. It argues that the dominance of particular forms of knowledge within policy processes work to exclude those forms of knowledge which are grounded within young people’s everyday lived experiences of their sexuality and the virus. As a result, in claiming to ‘know’ young people, this decontextualized knowledge works to construct a particular subject position of youth in which agency is ascribed to fit within dominant gendered and medicalised narratives of the virus. These constructions are in stark contrast to how young people themselves understand and perform their own sexual identities, which are spatially and temporally located. The research finds that young people come to construct and perform their, often multiple, identities in ways which reflect their subjective interaction with the context of their daily lives. It finds that young people’s narratives of sexuality and HIV are embedded in discourses of pleasure and poverty, and are shaped by a complex web of social and gender relations. Despite this disjuncture, the research finds that young people are not simply ignoring, but rather are engaging, with these policy narratives in complex ways, as they become part of their context of interaction. Drawing upon Long’s interface model the research finds that as policy narratives come to intersect with young people’s lifeworlds, new forms of knowledge and social practice are produced. Within this interface ‘youth’ as an identity emerges as an asset which young people can draw upon and utilise to make sense of their situation, as well as provide access to opportunities. At the same time young people appropriate the policy narratives of individual responsibility and the medicalised discourse of HIV to rationalise, and make sense of, their own risk taking behaviours. The thesis' methodological contribution examines research practices themselves as sites of knowledge production about young people. Turning the analytical lens on my own work, as well as that of others, it examines the challenges in conducting such research and the ways in which it can serve to reproduce the narratives it seeks to uncover. In going beyond identifying the disjuncture between policy narratives of youth sexuality, and those that young people construct for themselves, the research generates new insights on how we think about young people, their identities and behaviours, in relation to the virus. By moving from the specifics of interventions themselves to the assumptions and conceptualisations which underpin them, it draws attention to the importance, and problematic nature, of what we do know, what we can know, and the implications of these knowledge processes in the everyday lives of young people. In doing so it generates a number of key implications for policy and future research.

In this thesis analytical and numerical methods are used to investigate the stability and propagation of waves in various fluid-filled elastic-walled channels. In Chapter 2 a linear temporal stability analysis is performed for various channel wall configurations, the results of which are compared to determine how different physical effects contribute to the stability. In Chapter 3 a linear spatial stability analysis is performed for flow between linear plates, this is a limiting case of the wall configuration in Chapter 2. Roots of the dispersion relation are found and their stability and direction of propagation determined. Chapters 4 and 5 focus on the propagation of nonlinear waves on liquid sheets between thin infinite elastic plates. Both linear and nonlinear models are used for the elastic plates. One-dimensional time-dependent equations are derived based on a long wavelength approximation. Symmetric and antisymmetric travelling waves are found with the linear plate model and symmetric travelling waves are found for the fully nonlinear case. Numerical simulations are employed to study the evolution in time of initial disturbances and to compare the different models used. Nonlinear effects are found to decrease the travelling wave speed compared with linear models. At sufficiently large amplitude of initial disturbances, higher order temporal oscillations induced by nonlinearity can lead to thickness of the liquid sheet approaching zero. Finally, in Chapter 6, an extension of the model from Chapters 4 and 5 is considered, the elasticities of the two channel walls are allowed to differ. The effect of this difference is determined through a mix of techniques and the limiting case of one wall having no elasticity is discussed.

Zinc oxide (ZnO) has a desirable combination of opto-electronic properties that, when combined with magnetic transition metal dopants such as cobalt, place it at the forefront of next generation materials to harness both electron charge and spin in the field now known as spintronics. In this thesis the polar (0001) surfaces of ZnO single crystals are revisited and used as a basis for the growth of ultrathin cobalt films before subsequent processing in an effort to produce a CoZnO dilute magnetic semiconductor. A method using Zn sublimation partial pressures is given that provides reliable preparation of clean ZnO(0001) surfaces and comparisons between these two surface terminations are made on the basis of LEED, STM, UPS and XPS arguments.

Based upon the premise that both exercising (E) and non-exercising (NE) muscle play major roles during exercise, oxygen consumption and blood flow (BF) have been extensively monitored at the tissue level. Near infrared spectroscopy is a non-invasive technique that measures haemodynamic changes within muscle, indicating very specific oxygenation patterns and blood distribution. This series of studies investigated, initially, the contribution of E and NE arm muscle during small muscle mass, upper body activity (one-arm cranking) and, subsequently, greater muscle mass exercise (traditional leg cycling with (G) or without (NG) grip). The initial pilot study determined considerable differences between oxygenation status in both E and NE triceps brachii (TB) and biceps brachii as exercise intensity increased and concluded further investigation was warranted in TB. Study 2 confirmed that NE tissue suffered reduced oxygen supply at workloads above 70% peak power (PP), the E TB deoxygenating at intensities between 40% and 60% PP. The wearing of a restraint made little difference to stabilization at the highest intensities and increased activity was found within the NE ann. Study 3 concluded that a probable initial metabolite increase had an effect on NE tissue, although only at the highest workload (70% PP), a reflection of lactate (La) consumption. However, in contrast, E muscle was influenced between the two lower intensities (40% and 60% PP). BY increased in both E and NE tissue. Study 4 isolated the forearm and noted significant haemodynamic changes in NG at the highest work intensities, but also that body position effected leg oxygenation. It is proposed that a balance between vasoconstriction and vasodilation, instigated by La production, exists to redistribute BF. The withdrawal of the vasoconstictory signal post-exercise adjusts BF to E and NE arm tissue similarly. The NE tissue, therefore, plays a diverse, yet vitally important role during exercise and recovery.

This thesis focuses on the guppy, Poecilia reticulata, as an invasive species. Its non-native distribution, the biology behind its success and the reasons for its introduction are examined. A worldwide email survey revealed that the guppy is established in at least 73 countries outside of its native range and that mosquito control schemes and the release of unwanted aquarium fish are the two primary routes of introduction. Knowledge gaps were identified; primarily the scarcity of scientific evidence for negative impacts of guppy introductions and similarly for mosquito control efficacy. Replicated mesocosm experiments demonstrated that female guppies are capable of routinely establishing populations, and that these retain behavioural viability over several generations. The first mesocosm study suggested that founders with very different evolutionary histories were equally good at establishing populations. The second mesocosm study suggested that monandrous females were extremely successful at establishing behaviourally viable populations, with no decline in behavioural variation. The effectiveness of guppies as mosquito control agents was examined in two related foraging experiments. The first study found little evidence for the presence of ‘prey switching’ in guppies, questioning the validity of previous work advocating their introduction to stabilise prey populations. The second study revealed a preference for non-vector mosquito larvae in a two-prey system. However, both mosquito species were consumed equally readily when habitat complexity increased. The presence of conspecifics affected female foraging behaviour. The presence of males reduced the strength of prey preference in the first study, and the presence of conspecifics of either sex removed prey preference in the second. Both demonstrate that multi-prey systems have important implications for the efficacy of poeciliids in biological control. Despite severe demographic bottlenecks, their adaptability and ability to rapidly increase in numbers enable guppies to establish and persist when introduced. Such bottlenecks are typical of introduction scenarios, warning that particular caution should be exerted when introducing this species, or other livebearing fish, to natural water bodies.

The paedophile is the bogeyman of our age. The very word itself has become a conduit for fear and public loathing, often beyond all moderation. Indeed, despite the fact that the overwhelming majority of paedophiles are male, commentators reach easily for parallels with a reviled figure from a bygone age - the witch. While we haven't yet reinvented the ducking stool or trial by water, we have found a pretty effective 21 st-century equivalent in trial by newspaper. And, after being named and shamed, the "guilty" are hounded from the community by a mob baying for blood. (Silverman & Wilson 2002: 1)

A micron-scale laser-wire system was constructed and tested at the Accelerator Test Facility (ATF) extraction line at the High Energy Accelerator Research Organisation (KEK) in Japan. The system was evaluated through collision tests, electron beam tests, laser beam measurements and simulations. Beam halo measurements were carried out in order to compare the beam halo to a theory of its production through gas scattering and towards evaluating it as a source of background for diagnostic instruments at ATF2 and the International Linear Collider (ILC). Simulations were carried out to test the signal extraction of the system at the future ATF2 and of a similar system in the proposed ILC beam delivery system, with implications for sharing the signal extraction region with the polarimeter.

Polyethyleneglycol (PEG) conjugates of peptides, proteins and an aptamer are in routine clinical use as first generation nanomedicines. Here a new family of polymer therapeutics based on PEG conjugates containing a coiled-coil peptide motif as a molecular switch are proposed. The coiled-coil motif is adopted by many naturally occurring proteins/peptides, including transcription factors key to cancer progression (E2F1/AP-1) and Ebola virus proteins (VP35/GP2). These were chosen as the first targets, however there is potentially a much wider role for this novel family of therapeutics. First studies selected coiled-coil motif peptide sequences (using computational prediction software and published literature) that were then synthesised using a solid phase approach, purified and characterised. To facilitate subsequent PEGylation, peptides were engineered to include an N-terminal cysteine residue. mPEG-maleimide (-5,500 g mol 1) was then conjugated site-specifically via the cysteine thiol. A purification method optimised using cation-exchange chromatography enabled the removal of both unreacted mPEG-maleimide and free peptide purity was > 95 % for each conjugate. Proof of concept was obtained with mPEG-FosWc, which was designed to inhibit coiled-coil heterodimerisation of native c-Jun and c-Fos proteins (AP-1). 1H, 15N HSQC spectroscopy confirmed target hybridisation of heterodimeric coiled-coils FosWc : c-Jun and mPEG-FosWc : c-Jun. In addition, both NMR and CD spectroscopy showed that both heterodimers adopted very similar structures under physiological conditions, irrespective of the presence or absence of PEG. Further studies using fluorescently labelled conjugates investigated cellular uptake in MCF-7 cells, and biological activity was assessed using the MTT assay with and without the use of a cationic transfection reagent. These studies demonstrate the potential of mPEG-coiled-coil motifs as therapeutic agents. However, demonstrating reproducible biological activity was not possible with the intracellular targets. Investigating the biological activity of the conjugates designed to target the extracellular Ebola virus fusion proteins remains an exciting prospect.

Dietary creatine supplementation (CrS) has been shown to augment high-intensity exercise training in athletes and healthy elderly, thereby increasing muscle mass. Uptake is increased by exercise and is likely to be most beneficial when combined with training. Previous small studies looking at the effects of CrS during pulmonary rehabilitation in subjects with COPD have shown conflicting results.;Hypothesis: CrS in association with aerobic exercise and resistance training will usefully augment the benefits of pulmonary rehabilitation.;Methods: This hypothesis was tested by a randomised double blind, placebo-controlled, parallel group trial of CrS during PR in patients with COPD. One hundred subjects with COPD (mean (SD) age 68.2 (8.2) years, FEV1 44.0 (19.6) percent predicted) were randomised to receive creatine (22g/day loading for 5-days, maintenance 3.76g/d throughout PR) or placebo (lactose) supplements during 7-weeks of PR encompassing aerobic and resistance exercises. Baseline, post-loading and post-rehabilitation measurements included pulmonary function, body composition, peripheral muscle strength and functional performance (shuttle walking tests and cycle ergometry).;A protocol was developed for testing isokinetic strength in subjects with COPD, using a Cybex II dynamometer.

Since the 1990s, a regional tier of governance has emerged in England, in a country which historically has not been noted for its regional identities. The vying for European Union (EU) structural funds has been seen as a key factor in the mobilisation of regions across Europe. It is within the context of UK membership of the EU, and the effects of the Europeanisation processes, that some scholars have placed the appearance of English regions. Other scholars have sought to explain the growth of English regional governance principally in terms of a response to globalisation. New Regionalism offers an insight into the renewed interest in regions as the focus for economic governance in an increasingly globalised world. With its emphasis on clusters, skills and innovation as a way to promote a competitive advantage, links have been made with New Labour’s economic agenda. Economic rescaling, on the other hand, has been seen to offer a more nuanced understanding of the relationship between the state and the regions. On this view, the state is actively rescaling economic governance in response to the pressures of globalisation, but at the same time still retains its traditional authority. The emergence of governance more generally has also been cited as a factor in English regionalisation. The extent to which the state is being “hollowed out” is a feature of this debate. Again, links have been made specifically to New Labour’s agenda that included plans for devolution for Scotland and Wales and plans for elected regional assemblies in England. This thesis examines the East of England and the South West English regions within the context of these debates. The central argument is that regionalisation in England is a centrally orchestrated process by central government as the nature of governance, but not the state, changes.

Anyone seeking to understand the physical processes of star formation must make reference to the spectrum of masses (mass function) produced by such processes. The low mass end of this mass function in particular is poorly constrained. The two leading environments in which to measure the mass function are in open clusters and star forming regions and in the solar neighbourhood. Studies of some star forming regions claim to constrain the mass function down to a few tens of Jupiter masses. However the validity of results in young clusters and star forming regions has been called into question, with the accuracy of the evolutionary models that all studies are based on being considered debatable at young ages. Hence a study in the field, where there is a spread of ages, provides a useful, possibly more robust, method for measuring the mass function. Low mass stars and brown dwarfs in the field are usually identified by either infrared surveys or by proper motion surveys. Here these techniques are combined for the first time to produce an infrared proper motion survey. This has produced a sample of over 7000 low mass objects with proper motions greater than 0.1"/yr . It has also found several common proper motion binary systems and SIPS1259-4336, an M8.5 dwarf within l0pc. This sample on its own will not yield a constraint on the mass function. In the field the range of ages and the luminosity evolution of objects leads to the mass function being intertwined with the stellar birthrate. Here this problem is dealt with by detailed simulations. By drawing ages from a birthrate and masses from a mass function, simulated objects can have space positions, velocities and absolute magnitudes assigned using a simple model of the Galaxy, evolutionary models of low mass objects and empirical relations. These can then be converted into observables and passed through a survey selection mechanism. By varying the underlying birthrate and mass function the effect these have on the survey results can be found. These results can then be compared with those of the actual survey to constrain the mass function and birthrate. Here the mass function parameter α is found to be 0.66 ± 0.44 in the range O.2M⊙ > m > O.O75M⊙, that the birthrate parameter β is -0.01 ± 0.10 and that the space density of objects in the mass range O.O9M⊙ < m < O.1M⊙ is 0.0053 ± 0.0002 /pc³. It should be noted that due to noise in the probability surface, the constraint on β should be treated with caution. Finally the results of the future infrared surveys by UKIDSS are simulated and the potential constraints that could be set by them outlined.

The role of the optometric factors in migraine headache is still controversial. The aim of this thesis was to investigate the optometric correlates of migraine. Following a detailed literature review a wide-ranging study of the optometric correlates of migraine is described. This study showed that in people with migraine, pupil responses associated with both sympathetic and parasympathetic autonomic nervous system changes are altered in the interictal phase of migraine. This indicates an effect of migraine on the autonomic nervous system between migraine attacks. Low degrees of astigmatism were more common in people with migraine, and the most significant finding was the horizontal component. Subtle binocular vision anomalies and reduced stereoacuity were also detected in people with migraine. It was shown that visual fields remain unaltered in migraine, increasing our understanding on how and where in the visual pathway deficits in migraine may occur. A second cohort of patients was recruited to investigate this area more fully. Using visual field and optical coherence tomography data this second, complimentary study, confirmed that visual fields measurements and retinal nerve fibre layer measurements are unaltered in relatively young people with migraine. It was found that pattern glare is a correlate of migraine and that migraine is associated with visual triggers such as light sensitivity, aversive patterns and other visual stimuli. A factor analysis was used to investigate the interaction between these visual triggers. This revealed two aspects of pattern glare; the overall number of illusions seen in striped patterns was associated with visual triggers whilst pattern glare, use of coloured filters and interictal light sensitivity together formed a component interpreted as visual stress. It is possible that some of the optometric correlates of migraine identified might play a causal role in some migraine episodes. This hypothesis was investigated using seven single subject double-masked placebo controlled trials. Spectacle lenses to correct astigmatic refractive error, prism spectacles to correct for subtle binocular vision anomalies and precision tinted lenses to reduce pattern glare were amongst the interventions assessed. In two individuals, prism spectacles relieved some migraine symptoms. However neither precision tinted spectacles nor the correction of refractive errors influenced migraine factors in those individuals assessed. In conclusion, there are distinct optometric correlates of migraine and visual triggers of migraine are important. Relieving optometric conditions in people with migraine may reduce co-morbid ocular disorders but may not alter migraine head pains.

This thesis examines the role of the British News Media in broader processes of state retrenchment that have occurred in Britain since the 1980s. This issue is examined through a range of empirical case studies, which are, respectively: (a) news reporting of the introduction of the poll tax; (b) news media relations and coverage of the voluntary and charitable sector; (c) the mediation of social scientific research; (d) trends in electoral news coverage; (e) coverage of quasi-autonomous non-governmental organisations. Collectively, this work demonstrates the importance of communication and media factors in the systemic changes that have occurred over recent decades, and the need to attend to issues of context and process when theorising their nature and significance. The introduction also outlines the methodological and theoretical positions that have shaped this work.

Territory remains a focus for identification and territorial identity an enduring topic of scholarly research. This dissertation explores the territorial identity of Cornwall in the late eighteenth and nineteenth centuries. The study does three things; it defines Cornish identity on the basis of concepts of distinction, integration, process, narrative, context and scale; it applies the model of regional identity formation proposed by Anssi Paasi; and it develops the disciplinary approach of the new Cornish Studies. The subject of the dissertation is the period after the fragmentation of a linguistically based ethnic identity and before the reconstruction of a 'Celtic' Cornish identity. A comparative investigation of this phase of the history of identity transformation restores continuity between Cornwall's industrial and post-industrial periods and provides an account of modern Cornish identity. The first part of the dissertation reviews representations of Cornwall and its people in the early nineteenth century. The focus then shifts to discuss the structures and institutions - economic, social and religious - around which identities cohered. The argument of the thesis is that industrialisation based on deep metal mining gave the Cornish a renewed pride as inhabitants of one of Europe's first centres of industrialisation. In this sense Cornwall resembled other industrial regions in the early nineteenth century British Isles. However, it also differed from them, most notably in its demography, in the social relations produced by rural industrialisation and in the way its historians had re-fashioned a history of the Cornish as a distinct group. By the later nineteenth century a hybrid identity had emerged, one based on a regional pride induced by industrialisation but one that also looked back to symbols of ethnic distinctiveness. This regional identity nested within identities of Englishness and Britishness that constrained its political potential.

The dissertation explores the motivational significance of delay for children with ADHD from an information processing perspective. The literature review discusses Sonuga-Barke's proposal that delay aversion represents a mediating link in a motivational pathway to ADHD. Preliminary findings suggest that hyperactive children display attentional biases towards delay cues, indicating they are motivated to detect delay. Information processing models suggest that attentional biases are often associated with other information processing biases, leading to a cognitive pattern that is more likely to maintain emotional disorder. Implications for the application of information processing models to understanding the motivational significance of delay in ADHD are discussed. In the empirical paper attentional and interpretative biases for delay were investigated using modified versions of the forced choice dot probe task and the ambiguous situations task. Previous findings of an attentional bias towards delay in hyperactive children were not replicated with a clinical sample, some support for an interpretative bias towards delay was found. Delay situations were found to be more associated with anger than anxiety for all participants. No differences were found in participant's reports of how they would respond to delay situations. The findings of the study give mixed support for the motivational significance of delay in ADHD; limitations and directions of future research are discussed.

This study is a natural follow on from previous work by M. T. Anderson and I. Fiebrig. The goal of those latter and of the present study is to find a mucoadhesive system for improving the oral bioavailability of a number of drugs, for example bioactive peptides and proteins. This current work evaluates the adhesive properties of a cationic polymer and a cationic protein to mucus glycoproteins as a step towards the future development of a mucoadhesive drug delivery system. Four different mucin populations were analysed in solution (a freshly purified sample PGM-MD, and three purified from different regions of the porcine stomach cardiac, antrum and fundus). Their interaction with two groups of chitosans differing in degree of deacetylation (FA = 0.11 and 0.25) and a protein purified from the foot of the blue mussel Mytilus edulis foot protein-1 (Mefp-1) were studied. Interaction was determined using analytical ultracentrifugation and with the chitosan/mucin interaction specifically atomic force microscopy. The influence of ionic strength on the interaction was studied in detail studied as was the effect of the oligosaccharide composition of the mucin population on the interaction. It was found that both groups of chitosans (FA = 0.11 and 0.25) formed a large complex with a freshly purified mucin population (PGM-MD). Ionic strengths above 0.2 M were found to inhibit the interaction. The three mucin species differed in terms of their net charge, with cardiac being the most negatively charged and antrum the least negative. It was found that the cardiac species interacted the most and antrum the least, as would be expected for an ionic interaction. Increasing ionic strength was found to inhibit the interaction. There was also evidence for a hydrophobic interaction at high ionic strengths. The atomic force microscopy results allowed the complex to be visualised under atmospheric conditions and to get away from the harsh sample preparation techniques employed by electron microscopy. Large spherical complexes were seen as entanglements of mucin and chitosan strands.

Despite the fact that the main advantage of robot manipulators was always meant to be their flexibility, they have not been applied widely to the assembly of industrial components in situations other than those where hard automation might be used. We identify the two main reasons for this as the 'fragility' of robot operation during tasks that involve contact, and the lack of an appropriate user interface. This thesis describes an attempt to address these problems. We survey the techniques that have been proposed to bring the performance of current industrial robot manipulators in line with expectations, and conclude that the main obstacle in realising a flexible assembly robot that exhibits robust and reliable behaviour is the problem of spatial uncertainty. Based on observations of the performance of position-controlled robot manipulators and what is involved during rigid-body part mating, we propose a model of assembly tasks that exploits the shape invariance of the part geometry across instances of a task. This allows us to escape from the problem of spatial uncertainty because we are 110 longer working in spatial terms. In addition, because the descriptions of assembly tasks that we derive are task-invariant, i.e. they are not dependent on part size or location, they lend themselves naturally to a task-level programming interface, thereby simplifying the process of programming an assembly robot. the process of programming an assembly robot. However, to test this approach empirically requires a manipulator that is able to control the force that it applies, as well as being sensitive to environmental constraints. The inertial properties of standard industrial manipulators preclude them from exhibiting this kind of behaviour. In order to solve this problem we designed and constructed a three degree of freedom, planar, direct-drive arm that is open-loop force-controllable (with respect to its end-point), and inherently accommodating during contact. In order to demonstrate the forgiving nature of operation of our robot arm we implemented a generic crank turning program that is independent of the geometry of the crank involved, i.e. no knowledge is required of the location or length of the crank. I11 order to demonstrate the viability of our proposed approach to assembly we programmed our robot system to perform some representative tasks; the insertion of a peg into a hole, and the rotation of a block into a corner. These programs were tested on parts of various size and material, and in various locations in order to illustrate their invariant nature. We conclude that the problem of spatial uncertainty is in fact an artefact of the fact that current industrial manipulators are designed to be position controlled. The work described in this thesis shows that assembly robots, when appropriately designed, controlled and programmed, can be the reliable and flexible devices they were always meant to be.