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Photonic quantum information processing is a key element for scalable quantum technologies, and has applications in secure long-distance quantum communication and connecting nodes of a quantum computation network. However, logical photon-photon gates and state-of-the-art single photon sources rely on probabilistic processes. Quantum memories are devices that enable storage and on-demand recall of quantum states of light, and have been highlighted as a vital component in photonic networks to overcome the scaling problem by synchronising probabilistic processes. The Raman memory has a large storage bandwidth and high synchronising capacity, and is an ideal candidate for local synchronisation. However, previous demonstrations of the Raman memory suffer from four-wave mixing noise, which prohibits quantum level operation. In this thesis I investigate methods to increase the signal to noise ratio in the Raman memory. I investigate increasing the light-matter coupling strength to boost the memory efficiency, and then explore two different methods to suppress four-wave mixing noise. I demonstrate that operating the Raman memory in a cavity is successful in reducing four-wave mixing, but it is technically challenging to maintain a high memory efficiency. I investigate a new method of noise suppression by introducing an absorption feature at the frequency of the unwanted noise field. This technically simple method is successful in reducing the noise by an order of magnitude, and will be applicable to many quantum memory protocols. In the final section of this thesis I explore the temporal mode properties of the Raman memory. I demonstrate that the Raman memory is single mode and can be used to separate and manipulate temporal modes of light. This positions the Raman memory as a key device for enabling high-dimensional photonic quantum information processing, and enhancing light-matter interactions. These results pave the way towards an efficient, low-noise, mode-selective quantum memory.

The Anthropocene epoch calls for new narratives which accurately relate the experiences of our times from a diversity of perspectives. As humans make an irreversible impact on the geological record, I suggest that such narratives should engender more democratic and generative sharing of earth with other life forms - on the page as in life. Drawing upon my own transformative experiences of reciprocal living with human and non-human Others in the remote Westfjords of Iceland, I present a memoir, The Raven's Nest, as my experiment towards such de-centred and 'entangled' writing (Haraway 2016). Covering the period of 2008 - 2014 it includes a variety of instabilities characteristic of the Anthropocene - economic, social, geological, and ecological - in the context of the everyday concerns of a sheep farming and fishing community at sixty-six degrees North. I argue that Anthropocenic narratives should resist a linear trajectory of beginning - middle - end, which is often wrongly conflated with the shape of 'progress', and instead find a new shape which can contain the 'ongoingness' of life, broken as it is. Drawing on Donna Haraway's concept of 'entanglements' (2016), and applying Ursula Le Guin's 'Carrier Bag Theory of Fiction' (1989) to memoir, pulled together by Ingold's ideas about 'weaving' as a way of being in the world (2000), I propose a woven, many threaded, container-shape composed of plant, animal and man-made materials: a 'raven's nest'. I highlight that the North as an idea - which includes Iceland - has been shaped by masculinist cultural representations which are a legacy of the era of polar exploration and remain dominant. This representation of North as an empty space; a wilderness; an extreme to be conquered or pentrated is in need of revision in our times. In search of an 'ancestry' that reflects my own experience of being a woman dwelling in the North and dependent on others for my survival, I find a number of women. From them, I focus on a canon of writers and a film-maker, identifying the tropes they share with my memoir and with each other which might be usefully incorporated into Anthropocenic narratives. Finally, I discuss the ethical implications of entanglement as it manifests in living, and in writing a memoir in the context of the academy. Acknowledging human 'entanglements' with other-than-human agents involves acknowledging the impact writing about them might have. This is true for places as much as for people. This thesis explores what happens when place speaks through human stories.

Breast cancer is the most common cancer diagnosis in the UK, with most cases being diagnosed in females. With advances in treatment, it is being increasingly recognised as a chronic condition, which has an impact not only on the patient, but also on the patient’s family. Research suggests that partners often become the primary caregivers for these women, and yet there has been very little research exploring the impact of this diagnosis on partners. The literature review aimed to explore the information needs of male partners of women with breast cancer. Following a systematic literature search, a total of 13 papers were identified. A synthesis of the findings revealed that men prioritised information about their partner’s diagnosis, prognosis and treatment options. They preferred information from the patient or from healthcare professionals, but difficulties with communication were found to be a barrier to accessing information. Recommendations were made for healthcare professionals to aid communication with male partners. The research report explored the experiences of male partners of women with breast cancer, who had received the diagnosis within the last year. Semi-structured interviews were carried out with five men whose wives were accessing an Oncology Unit. The transcripts were analysed using Interpretative Phenomenological Analysis (IPA). From the analysis four super-ordinate themes emerged, with a total of 13 sub-themes. The themes were considered in relation to previous research and relevant psychological theories. The discussion led to a number of clinical implications, highlighting the vital role played by healthcare professionals, and the importance of psycho-educational interventions for men. Finally, the critical appraisal provides the researcher’s reflections on the research process and brings to light learning points to be taken forward.

Consideration of the ‘social dimensions’ is increasingly gaining currency within the conservation community. A growing body of literature indicates the importance and influence people and societal practices have on the effectiveness of biodiversity conservation. As such, conservationists and their organisations are being urged to embed more social components within their projects and programmes. However, there is self-reported lack of understanding, skills and confidence by many conservationists about the scope and nature of this social dimension within the biodiversity conservation context. This thesis aims to recast the social dimensions of conservation. Specifically, to explore its boundaries and how current understanding can be supplemented using a social practice theoretical lens. It aims to strengthen conceptual understanding and develop pathways of practical application within conservation organisations. This research was undertaken within the context of my own institution, the Zoological Society of London which is a UK zoo-based conservation organisation. The research was exploratory in nature due to the complexity and relatively undefined status of the social dimensions within biodiversity conservation. A mixed method approach was employed using key informant interviews and an online survey instrument to depict and describe practices within the social dimensions of conservation, and to gather perceptions about these practices. The thematic results offer both a recasting of the definition of the social dimensions of conservation and a conceptual model of the ‘ecologies of practices’ at the Zoological Society of London. These new knowledge resources provide a basis to foster further understanding of how people and their practices fit into the conservation landscape. They also offer recommendations for both the Zoological Society of London and the wider biodiversity conservation community, to build individual and organisational capacity towards the social dimensions through future research, training and organisational development.

Glycosaminoglycans (GAGs) are linear polysaccharides found on most animal cell surfaces and in extracellular matrices. Their key biological roles include cell signalling, cell-to-cell recognition, bacterial and viral adhesion, and antibody production. They are composed of disaccharide repeating units, containing uronic acid and amino sugar residues, and may be highly heterogeneously sulfated. Protein-GAG complexes are thought to play an important role in a number of aspects of cancer development, but are an under-studied area due to a lack of enabling tools to facilitate their analysis as discussed in Chapter 1. To obtain homogenous GAG structures, a range of conditions for the separation of GAG oligosaccharides by Zwitterionic Hydrophilic Interaction Liquid Chromatography (ZIC-HILIC) were developed using commercial chondroitin sulfate standards; these are discussed in Chapter 2. Mixed-modal separation mechanisms were explored across a different buffer compositions and elution programs to optimise the conditions to suit individual classes of native and modified glycosaminoglycans. These methods were then applied to the separation of chondroitin sulfate mixtures and heparin oligosaccharides. ZIC-HILIC may also be coupled to Mass Spectrometry to produce an online analytical method for GAG mixtures. A range of optimised conditions for the analysis of low molecular weight glycosaminoglycan oligosaccharides by Electrospray Mass Spectrometry were developed using commercial chondroitin sulfate disaccharide standards; as discussed in Chapter 3. These conditions were then employed in the tandem mass spectrometry (MS/MS) of chondroitin sulfate to identify diagnostic fragmentation patterns and this was applied in the characterisation of chondroitin sulfate disaccharides derived from enzymatic cleavage. The position of ring substituents can also be identified using this methodology, which is desirable in the analysis of chemically-labelled GAG structures. To allow for high resolution EPR and NMR studies of protein-GAG interactions, synthetic procedures for the incorporation of paramagnetic centres into GAG oligosaccharides and proteins were developed and these are discussed in Chapter 4. A propargyl-modified lysine was synthesised for recombinant expression into myoglobin. Copper-Catalysed Azide-Alkyne Cycloaddition (CuAAC) was employed in the spin labelling of myoglobin, however traditional experimental conditions were found to reduce the TEMPO-based spin labels used. Alternative conditions were developed using glutathione to stabilise the copper (II) catalyst without reducing the spin label. Spin labelling of the modified lysine was monitored by EPR. Modification of the non-reducing end was explored for the spin labelling of GAG oligosaccharides, to avoid the ring opening that typically occurs in reducing end labelling, and make use of the unsaturated uronic acid that is derived when obtaining GAGs through enzymatic depolymerisation. A hydrazide labelling of uronic acids was initially adopted, however due to concerns regarding selectivity and availability of hydrazide spin labels, an alternative Thiol-Ene Click (TEC) method was developed. TEC labelling of monosaccharides and unnatural amino acids was found to proceed efficiently under aqueous conditions and was monitored by NMR and HPLC. Preliminary studies in the TEC labelling of chondroitin sulfate disaccharides proved promising, however further optimisation is required for this method to be utilised in the study of protein-GAG interactions by NMR.

Beech bark disease (BBD) is an invasive insect and pathogen disease complex that is currently devastating American beech (Fagus grandifolia) in North America. The disease complex consists of the sap-sucking scale insect, Cryptococcus fagisuga and sequential attack by Neonectria fungi (principally Neonectria faginata). The scale insect is not native to North America and is thought to have been introduced there on seedlings of F. sylvatica from Europe. Conventional control strategies are of limited efficacy in forestry systems and removal of heavily infested trees is the only successful method to reduce the spread of the disease. However, an alternative strategy could be the use of biological control, using fungi. Fungal endophytes and/or entomopathogenic fungi (EPF) could have potential for both the insect and fungal components of this highly invasive disease. Over 600 endophytes were isolated from healthy stems of F. sylvatica and 13 EPF were isolated from C. fagisuga cadavers in its centre of origin. A selection of these isolates was screened in vitro for their suitability as biological control agents. Two Beauveria and two Lecanicillium isolates were assessed for their suitability as biological control agents for C. fagisuga and nine Trichoderma isolates were screened for their antagonistic ability against Neonectria spp. Colonisation of beech saplings with Beauveria, Lecanicillium and Trichoderma isolates was attempted using three inoculation techniques.

American schools are becoming increasingly diverse, with an estimated 17 million first- and second-generation refugee and immigrant children residing in the United States. English learners navigate the challenges of learning how to read, write, and speak a new language, all while being expected to stay on grade level. Classroom teachers nationwide are looking for engaging ways to meet the needs of their students, despite resource and budget deficits. The purpose of this study was to explore the role that student-created vodcasts, or video podcasts, may play in the English acquisition of a Haitian learner. This research question morphed to focus on the perceptions and practices of this student's middle school teacher of English for Speakers of Other Languages (ESOL) in using vodcasting and other technologies to facilitate his English acquisition. A second research question explored the role of sociocultural learning regarding the learner's creation of vodcasts. Guiding bodies of research in this work included second language acquisition research, particularly regarding identity formation involving brain-compatible teaching, sociocultural learning, and culturally relevant pedagogy (CRP). Data collection occurred between January 2015 and May 2015. The student and his teacher shared their perspectives in six interviews each during the data collection process. Other data sources included 2 student-created vodcasts, 1 created in a group and 1 created by the student alone, a writing sample, and results from the previous school year of the state English as a Second Language Achievement Test (ESLAT). The teacher found that the vodcasts, in combination with other factors, helped the student reflect on his writing, particularly regarding punctuation, and that he overcame an error with comma splices immediately after recording a vodcast. The student found that the practice of vodcasting, in combination with other factors, helped him practice academic language, as required by his teacher for the assignment. The teacher allowed the student to work individually for the second vodcast assignment, and stated that the result was of much higher quality overall, particularly noting an increase in the amount of time the student spent speaking. The data indicated that vodcasting, in conjunction with other strategies supporting language acquisition, might have played a positive role in the student's progress in his ESOL class. Furthermore, according to both the student and the teacher, independent creation of the video was more effective for him than collaborative group work, which the teacher explained may have had causes rooted in the student's home culture. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com/en-US/products/dissertations/individuals.shtml.]

This thesis examines the late mediaeval Church in the Hebrides from 1266 until 1472. The late mediaeval Church was culturally significant: it imposed rules and regulations on lay society throughout western Christendom. Hitherto, studies of the Hebridean Church have focused on its organisation and its bishops. My research goes beyond these studies to examine the effectiveness of the Church in bringing Christian religion and piety to mediaeval Hebridean society. This is accomplished through a prosopographical study of the clergy in the Hebrides and analysis of the church and chapel sites. The mediaeval Church transcended countries and peoples and through the provision of parish clergy, it managed to establish and maintain a certain level of Christian faith and belief. The majority of the recorded clergy were Gaels who came from the dioceses of Sodor and Argyll and were therefore able to communicate with their parishioners. Some of the clergy can be identified as belonging to the territorial, professional and ecclesiastical kindreds and can be described as of high social status. Determining educational status is particularly tricky, given the absence of any evidence for any schools in the Hebrides. However, we can reasonably conclude that the high status clergy undoubtedly were educated, although not all to university level. The scarcity of accusations of non-residence implies that non-residence was not widespread. An examination of rectors and perpetual vicars at the parish churches reveals that there was usually one or the other at the parish churches. A more common accusation regarded pluralism, although we have to acknowledge that sometimes the accusations might be exaggerated. Whilst allegations of offences such as simony are rare, failure to comply with canon law on clerical celibacy is clear from all supplications seeking dispensation for illegitimacy as the son of a priest. The churches, chapels and grave-yards were a focal point for these priests and for secular society. As important as the provision of clergy are the adequate numbers of, and maintenance of, church buildings. The church building had enormous significance for both mediaeval theologians and the laity. The parish church, in particular, was very important as the central focus for baptism and burial and therefore access is very important. The key issues are, therefore, access to the parish church, the visibility of the churches and their relationship with secular settlements. Access is determined by location and the location of the forty-three parish churches in the Hebrides can, on the whole, be described as accessible. None of them are inaccessible locations, indeed most can be accessed both from land and from the sea. They are relatively visible, but not outstandingly so. However, their visibility would have been enhanced with use of plaster on the exterior of the buildings. Secular settlements were dispersed and consequently there were always some settlements nearby the parish church and others more distant. A major issue which has arisen is the identification of categories of chapels. Using models established by Orme, there are four main categories of chapel – dependent, cult, locational and oratory chapels. Effectively, the numerous small chapels meant that, in general, it can be said that people were never very far from some kind of church building. Identifying the type of chapel allows us to understand how the parishes functioned. The final two chapters consist of case-studies of the islands of Tiree, Coll and Skye. There are a total of 12 parishes on these islands and within these parishes 68 church and chapel sites. The relationships between parish church and chapel have been analysed in each and we have been able to identify some dependent chapels. It is also clear that we have a number of early mediaeval chapel sites which may have been abandoned by the late Middle Ages. However, other early mediaeval sites may have continued in use, perhaps as cult chapels for particular saints. The cults of saints such as St Columba, St Comgan and St Maelrubha were especially strong in Skye whilst St Columba, St Finnan and St Findoca were popular on Tiree and Coll. Above all else, this study demonstrates the vitality of the late mediaeval Church in the Hebrides; its parish churches were not overwhelmingly appropriated and there were sufficient numbers of apparently educated clergy available to serve the churches. The range of ecclesiastical sites also shows the breadth of provision.

Peter Lorre often described his acting as merely "face-making". This disparaging attitude is reflected within critiques which read the life of Peter Lorre as a tragic narrative of wasted opportunities and his career as a screen performer as restricted by the nature of his employment in studio-era Hollywood. Working in the United States, he was unable to escape from the notoriety of his first major role in the German film, M (1931), or from the murderous persona that evolved from his portrayal of a psychopathic serial killer. His status as an emigre positioned him as a European "artist" whose talent was misused by American filmmaking practices which typecast the actor in line with his nefarious public image. This thesis proposes to investigate the accuracy of these perceptions which approach the actor via a binary split between "person" and "persona". It will offer an alternative methodology for analysing the career of the screen actor which recognises that persona-based analyses can obscure complex negotiations between performance, image and the conditions of employment. Rather than attempting to reveal the "real" Peter Lorre behind the image, the context of Lorre's mutable position as an employee within the Hollywood industry and the misconstrued association between his screen labour and his public persona will be examined. The creative agency of the actor will also be examined in order to question Lorre's definition of himself as "face-maker" whose work was reliant upon performative gimmicks. This alternative approach to the screen actor will be pursued through a chronological investigation of Lorre's professional labour. Also necessary are an exploration of the features of Lorre's persona and an understanding of the role played by other media in the construction of this public image. My methodology will combine close textual analysis of Lorre's screen performances, archival research into the terms of his employment and extensive analysis of promotional discourses pertaining to the actor throughout his career. My historiography of Lorre will consider the relationship between the actor and a number of his employers to suggest that conditions of employment help to shape screen performance. Lorre's status as a "face-maker" will also be challenged through a demonstration of the actor's use of complex performative techniques within his film work. This thesis will demonstrate the limitations of interpreting Lorre's career as Hollywood's mismanagement of a problematic performer. Instead, his career can be considered indicative of industrial strategies that exist between acting labour, promotional personas and employers. One consequence of my research is the reevaluation of Lorre's persona as "extra-filmic" and his career as "transmedial". As such, this thesis highlights how the significant labour of a screen performer can potentially become superseded by the personas used by employers to promote actors away from the cinema screen.

Hugo von Hofmannsthal, Austrian poet, dramatist, and essayist (1874-1929), published with the Insel-Verlag from its inception in 1901 until his death. This work examines Hofmannsthal's relationship with his publisher Anton Kippenberg (1874-1950). The author was drawn to the Insel-Verlag initially through his association with its founders, Alfred Walter Heymel and Rudolf Alexander Schröder, who published the short-lived periodical Die Insel. Known for its emphasis on aesthetics, the magazine set a tone that became characteristic for the firm. As a poet, Hofmannsthal found the climate beneficial and the audience of the Insel-Verlag receptive to his early lyrical works and certain other writings outside the mainstream of his later production. Under Anton Kippenberg's direction, these works were assured careful attention to detail; typeface, binding, illustrations, and all aspects of the physical book were designed to harmonize with its contents, enabling Hofmannsthal to present his writings in a format which did his creations honor. Hofmannsthal published four categories of material with the Insel-Verlag: his early lyrical works; republications issued as deluxe editions; reprints of selected texts in the inexpensive but elegantly designed Insel-Bücherei, and other Insel publications such as the Insel-Almanach or Inselschiff; and introductions and essays composed in his role as editor of compilations appearing under the Insel imprint. Hofmannsthal showed a great awareness of the Insel's particular Verlagsprofil in his selection of texts issued under its signet. Anton Kippenberg brought financial stability, business-like organization, and sound aesthetic judgement to the Insel-Verlag, creating an atmosphere in which Hofmannsthal's works could thrive. Early in his association with the Insel-Verlag, Kippenberg advanced a program which echoed many of Hofmannsthal's concerns and thus further solidified their relationship. Kippenberg proposed to give a book the design and format appropriate to its contents, to serve world literature, to expand the market for these titles without sacrificing quality to economics, and to support a select group of contemporary authors. Hofmannsthal's association with publisher Anton Kippenberg was a complex and often stormy one. United through shared goals, the two men worked to achieve a relationship mutually beneficial to each, one in which both the reputation of the individual and that of the firm were enhanced by their cooperation.

First-generation and low-income (FGLI) individuals currently represent a large percentage of the total undergraduate student enrollment in U.S. colleges and universities. Student loan debt in the United States is also at an all-time high with approximately 43 million Americans sharing the $1.75 trillion total. Because FGLI individuals, like many other college students, often take on large amounts of student loan debt to successfully graduate college, it is worth learning more about the long-term effects that student loan debt has on the experiences of FGLI college graduates within the first ten years of graduating with a baccalaureate degree. The purpose of this phenomenological research study is to understand how FGLI college graduates experience student loan debt within the first ten years of graduating from a four-year, private institution. Utilizing a phenomenological approach allows participants the opportunity to describe both facets of the phenomenon – both the phenomenon itself and how they experienced it. The phenomenological approach is important, as it allows the essence of the shared experience to be discovered through the research.

Introduction: Surrogate information seeking (SIA), or the act of seeking information on behalf of another, is a common health behavior. However, the phenomena remains under studied. The first study tests key propositions of the Lay Information Mediary Behavior (LIMB) model in order to understand surrogates’ motivations for SIA, engagement in active and passive SIA behaviors, and willingness to share information with care recipients. The second study tests an extended Cognitive Mediation Model (CMM) to further understand the cognitive mechanisms linking surrogates’ seeking and sharing behaviors. Study 1: Semi-structured interviews were conducted with caregivers of breast, endometrial, and ovarian cancer patients (n = 19). Thematic analysis of these interviews suggested that caregivers engaged in active and passive SIA for intrinsic and extrinsic reasons. Caregivers predominantly sought information to close their own knowledge gaps, but they still shared new or novel information with their care recipient. Study 2: A cross-sectional survey was administered to the caregivers of breast cancer patients diagnosed within the last two years (n = 130). Partial support was found for the proposed model. Distal variables including surveillance gratifications, information requests, and caregivers’ perception of patient information gathering capacity were associated with active and passive SIA behaviors. SIA behaviors, in turn, were associated with attention and elaboration. Perceived knowledge and elaboration were associated with sharing information with care recipients, but cognitive processing did not play a role in caregivers’ perceptions of knowledge. Conclusion: Taken together, the studies in this dissertation suggest that while information surrogates are occasionally extrinsically motivated, most SIA is intrinsically-motivated. Caregivers engage in active and passive SIA, and share with their care recipients. Additional motivations, such as surveillance gratifications and perceived patient information gathering capacity, were associated with SIA behaviors, which were in turn associated with deeper elaborative processing. However, deeper elaborative processing was not associated with greater perceived knowledge. The inability of the CMM to predict how surrogates learn information, and the infrequency of extrinsically motivated searches suggest that future research should focus on identifying additional mechanisms connecting seeking to processing, including traditional theories of information seeking. Interventions should focus on making caregiver education accessible and identifying patient and caregiver information needs.

Normal movement execution requires proper coupling of motor and sensory activation. An increasing body of literature supports the idea that incorporation of sensory stimulation into motor rehabilitation practices increases its effectiveness. Paired associative stimulation (PAS) studies, in which afferent and efferent pathways are activated in tandem, have brought attention to the importance of well-timed stimulation rather than non-associative (i.e., open-loop) activation. In patients with tetraplegia resulting from spinal cord injury (SCI), varying degrees of upper limb function may remain and could be harnessed for rehabilitation. Incorporating associative sensory stimulation coupled with self-paced motor training would be a means for supplementing sensory deficits and improving functional outcomes. In a motor rehabilitation setting, it seems plausible that sensory feedback stimulation in response to volitional movement execution (to the extent possible), which is not utilized in most PAS protocols, would produce greater benefits. This capability is developed and tested in the present study by implementing a brain-computer interface (BCI) to apply sensory stimulation synchronized with movement execution through the detection of movement intent in real time from electroencephalography (EEG). The results demonstrate that accurate sensory stimulation application in response to movement intent is feasible in SCI patients with chronic motor deficit and often precedes the onset of movement, which is deemed optimal by PAS investigations that do not involve a volitional movement task.

Older people and people with Alzheimer's disease (AD) show increased sensitivity to antipsychotics, including atypical antipsychotics such as amisulpride. Studies suggest that alterations at the blood-brain barrier (BBB) might cause the increased sensitivity to amisulpride due to increased uptake of the drug in the brain for a given blood drug concentration. In this thesis we aim to examine which transporters are involved in amisulpride transport at the BBB, to verify whether the 5xFamilial Alzheimer's Disease (5xFAD) mouse model is suitable for studying the increased permeability of amisulpride in the brain seen in AD patients, compared to healthy controls, and to understand how the BBB changes in AD compared to healthy ageing. We hypothesise that amisulpride, which is predominantly positively charged at physiological pH, interacts with solute carrier (SLC) transporters at the BBB, and that alterations in the function and/or expression of these BBB transporters are responsible for the increased permeation of amisulpride into the brain in AD compared to healthy ageing. To test this hypothesis we used a combination of literature review, in silico simulations, in vitro studies, mouse model of AD (5xFAD), and studies in human brain tissue from AD and control cases. The increased permeation of atypical antipsychotics like amisulpride into the brain might contribute to the hypersensitivity associated with antipsychotic medication prescribed in Alzheimer's disease. We performed a literature review and analysis of the molecular weight and charge of the established substrates and inhibitors of SLC transporters transporting organic cations and molecules involved in glucose metabolism. These transporters were plasma membrane monoamine transporter (PMAT), multidrug and toxin extrusion transporter 1, 2 (MATE1, 2), organic cation transporter 1 (OCT1), organic cation transporter novel 1, 2 (OCTN1, 2), glucose transporter 1 (GLUT1), monocarboxylate transporter 1 (MCT1). Also, we reviewed the ATP binding cassette (ABC) transporter: P-glycoprotein (P-gp). Next, we used in silico molecular docking to study the interactions between amisulpride and the transporters of interest. In vitro we aimed to confirm the interaction or lack of interaction of the transporters studied in silico with amisulpride in the human cerebral microvessel endothelial cells/D3 (hCMEC/D3). We incubated the cells with [ 3H]amisulpride (3.8-7.7 nM) and [14C]sucrose (0.7-1.5 µM) with or without transporter inhibitors. Also, in a pilot experiment, we studied the effect of amisulpride, and the effect of another antipsychotic – risperidone, on the uptake of [14C]D-glucose into the hCMEC/D3 cells in order to understand the interaction between the antipsychotics and GLUT1. In vivo, we investigated the ultrastructure of the brain capillaries in wild type (WT) and 5xFAD mice using transmission electron microscopy (TEM). We also studied the BBB transport of amisulpride in WT and 5xFAD mice (12-15 months old) via in situ brain perfusions with [3H]amisulpride (6.5 nM) and [14C]sucrose (vascular space marker)(9.4 µM). Western blot (WB) was used to study SLC and ABC transporter expression in isolated mouse brain capillaries. We investigated the ultrastructure of the brain capillaries of an AD case with TEM, as well as the expression of PMAT, GLUT1, MCT1, and P-gp in human control and AD brain capillary samples from the frontal cortex and the caudate, using WB. We compared levels of expression between the control and AD patients, and between the frontal cortex and the caudate. Our molecular docking simulation data suggested that amisulpride interacts with PMAT, MATE1, OCT1, and GLUT1 and MCT1, but not with MATE2, OCT2, OCT3, OCTN1, OCTN2, and P-gp. The interaction of amisulpride with PMAT, MATE1, OCT1, and to an extent GLUT1 is in accord with the typical profile of molecules these transporters interact with, according to our literature review. In hCMEC/D3 cells, PMAT inhibition led to a significant increase in [3H]amisulpride cell accumulation (F (1, 4) = 12.30; p=0.0247; Holm-Sidak multiple comparisons post hoc test; p=0.0332 at 30 minutes, p=0.0116 at 60 minutes, and p=0.0116 at 120 minutes). No effect of amisulpride or risperidone on the accumulation of [14C]D-glucose in the cells was observed. The TEM studies revealed that WT mice and 5xFAD mice at 4.5-6, and 12 months of age had intact brain capillaries. Compared to WT (n=6), the 5xFAD (n=4) mice had increased [ 3H]amisulpride uptake in the brain supernatant (containing the brain parenchyma and interstitial fluid) by 104.86% (t=2.550, df=8, p=0.0342, two-tailed unpaired Student's ttest) but not significantly increased [14C]sucrose passive permeability. WB studies confirmed PMAT, MATE1, GLUT1, MCT1, and P-gp expression in WT and 5xFAD brain capillaries. From our TEM and WB studies in human samples, we can confirm ultrastructural signs of neurodegeneration in an AD case, as well as expression of PMAT, GLUT1, MCT1, and Pgp in control and AD cases. A significant decrease in P-gp expression was observed in the caudate of AD patients compared to controls (t=2.841, df=16, p=0.0118, two-tailed unpaired Student's t-test). Overall, we conclude that SLC transporters (PMAT, MATE1, OCT1, GLUT1, and MCT1) could be implicated in the transport of amisulpride at the BBB. We confirm that the 5xFAD mouse model shows increased brain supernatant permeability to [ 3H]amisulpride compared to WT mice but no significant change in [14C]sucrose permeability. This suggests altered BBB transporter function. In the future, increased number of mice in the perfusion study could allow us to detect specific regional changes in brain permeability. Changes in transporter expression in the mice were not observed which could be because we studied brain capillaries from the whole brain, and regional transporter expression changes can be present in the model. In our human tissue studies we confirm changes in BBB transporter expression with AD. Our evidence for interaction between amisulpride and SLC transporters, as well as present and past evidence for transporter expression changes at the BBB in AD, give further support to the hypothesis that alterations in the function and/or expression of BBB transporters are responsible for the increased permeation of amisulpride into the AD brain, which could be related to the increased sensitivity of AD patients to amisulpride compared to healthy ageing individuals.

More cancer survivors than ever before are living five years or longer past their initial diagnosis. Cancer and its treatment are often not the end of chronic health issues among survivors. The comorbidity of interest in this study is obesity. Cancer survivors often gain weight during treatment, and rarely return to their pre-treatment weight. The purpose of this study to explore how to best frame nutrition messages for cancer survivors, which may help to reduce obesity and ultimately improve the quality of life among survivors. Utilizing the Integrated Model of Behavioral Prediction (IMBP), it was predicted that messages would predict attitudes, norms, and perceived behavioral control, which would in turn predict fruit and vegetable intentions. A mixed methods design was used to test the effectiveness of two message formats, narrative and non-narrative. Messages were pre-tested among (N = 10) cancer survivors using semi-structured interviews. The message pre-test revealed that both narrative and non-narrative formats were equivalent in content. The main study utilized an experimental design whereby (N=211) saw either the experimental (narrative) or control (non-narrative) message on fruit and vegetable consumption. Results indicated no significant differences between condition. Of the determinants of intention in the IMBP, only perceived behavioral control predicted fruit and vegetable intentions at follow-up. Future research in this area should consider tailoring narrative formats, and focus on the multifaceted nature of energy balance.

Human African trypanosomiasis (HAT) is fatal unless treated. Pentamidine has been used to treat first-stage (hemolymphatic) HAT since the 1940s, but it is ineffective against second-stage (meningoencephalitic, or central nervous system) infection. Research has suggested that hOCT1 and P-gp are involved in the transport of pentamidine across the blood-brain barrier (BBB). The aim of this study was to investigate if through the formation of ion-pairs the passive diffusion and hOCT1 and P-gp mediated BBB transport of pentamidine could be improved.

The U.S. shortage of qualified nursing teachers and researchers is affecting national health care outcomes. Methods such as fast-tracking Baccalaureate nurses into graduate programs and embedding leadership development early into nursing curricula have been proposed to address faculty and research shortages. Early interest in nursing research careers increases likelihood of enrollment in graduate education. One way undergraduate nursing students may develop an interest in research careers is through a mentored apprenticeship with research-active faculty. In this thesis, the author uses an autoethnography methodology to examine the benefits that a mentored research apprenticeship model brought to her undergraduate experience. Her experience incorporated a variety of roles in an adolescent intervention program with Dr. Anne Norris (PI) at the University of Central Florida College of Nursing. Several themes about the experience were defined in the results. Early research exposure that socializes a student to the nursing research world may provide a means for addressing the nursing faculty shortage. This socialization can generate interest in a research career and promote undergraduate students with the essential tools and insights needed to pursue this career pathway. However, findings from this study suggest a student-mentor relationship early in the undergraduate education experience is essential.

This thesis investigates the use of the variable regions of novel shark antibody fragments. Sharks possess a heavy chain only antibody, known as the immunoglobulin novel antigen receptor (IgNAR). The variable domain of IgNAR (VNAR) can potentially be used as a molecular Trojan horse to deliver therapeutics to the brain. Currently, as many as 98% of therapeutics fail to reach the brain, due to the presence of the blood-brain barrier (BBB) at the level of the cerebral capillary endothelium. The BBB is a highly specialised interface that keeps the internal environment for the central nervous system (CNS) constant and provides the brain with nutrients, but prevents entry of potentially harmful substances. To overcome the problems surrounding delivery of therapeutics to the brain, VNARs have been engineered that target the Transferrin 1 receptor (TfR1), which is highly expressed on the luminal side of the capillary endothelium. The hypothesis is that by binding to the TfR1 receptor, VNARs can transcytose (pass through) brain endothelial cells to the brain parenchyma and potentially deliver therapeutic cargo. In this thesis, VNARs were selected using a functional in vitro phage display methodology, screening a library of bacteriophage (virus that infects and replicates within Bacteria and Archaea) that display VNAR on their surface, henceforth referred to as VNAR phage, for those that were transported across a hCMEC/D3 (human BBB cell line) monolayer, mimicking permeability in vivo. The hCMEC/D3 cells were grown on Transwell® filters and at 7 days post-seeding, VNAR phage were added to the apical chamber of the cells (representing the luminal side). After 1 and 3 hours, medium was collected from the basolateral chamber of the cells (representing the abluminal side), which contained transported VNAR phage. These VNAR phage were recovered from the medium and added to the apical chamber of hCMEC/D3 cells grown on Transwell® filters in the next cycle of selection. Three cycles of selection were carried out and the transported VNAR phage were then assessed for binding to mouse and human TfR1 by ELISA. 182 VNAR phage that were positive for TfR1 binding were sequenced and 30 were re-formatted as VNAR-human-Fc constructs (henceforth referred to as VNAR-Fc) in the form of plasmid DNA, which was then transfected into Expi293F™ (human embryonic kidney (HEK)) cells to produce VNAR-Fc protein. VNAR-Fc binding to mouse TfR1 and human TfR1 was tested again, by ELISA, before nine candidates were chosen for use in in vivo mouse brain uptake experiments. One VNAR-Fc was found in the brain at concentrations ~1.5-fold higher than the baseline concentration seen from the negative control (p = 0.0013 (1-way ANOVA with Dunnett's post-hoc test)). A library of ~48,000 VNAR mutants was then created from the VNAR-Fc which showed the highest brain uptake (VNAR-Fc 8). This was achieved by mutating the complementarity determining region (CDR) 3 of the VNAR-Fc using partial overlapping mutagenesis. Mutant VNAR-Fcs were then randomly picked and assessed for TfR1 binding. Mutant VNAR-Fcs were sequenced, and 40 candidates were chosen for re-formatting as VNAR-Fc as described above. 21 that bound mouse TfR1 as VNAR phage were chosen and 19 that did not bind mouse TfR1 as VNAR phage were chosen. Both the mouse TfR1 binding and non-binding groups were used for further mouse brain uptake studies, to investigate if higher brain uptake could be achieved by mutagenesis. The amino acid sequences of all VNARs were obtained to compare which mutations may influence TfR1 binding in vitro, and brain uptake in vivo. One VNAR-Fc (VNAR-Fc 8.5) showed roughly twice as much uptake as the original parent VNAR-Fc 8 (p < 0.0001 (1-way ANOVA with Dunnett's post-hoc test)). It was found that the amino acid residues at positions 1-6 of the CDR3 - IAQLSS (isoleucine, alanine, glutamine, leucine, serine, serine)- were the least important amino acids involved in mouse TfR1 binding as VNAR phage and VNAR-human-Fc, due to amino acids in this region being the most substituted, whilst retaining mouse TfR1 binding. It was also found that amino acid residues 14-16 of the CDR3 - RKH (arginine, histidine, lysine) - were important for mouse TfR1 binding as few mutations in this area were seen in VNAR phage and VNAR-Fcs that retained mouse TfR1 binding. However, it appeared this was not the case for in vivo mouse brain uptake, as IAQ residues were not substituted in the VNAR-Fcs with highest brain uptake, whilst RKH was substituted in some VNAR-Fcs that showed brain uptake. In conclusion, VNARs that bind mouse TfR1 and human TfR1 can be selected from a VNAR phage library using a functional in vitro assay in hCMEC/D3 cells. This method can yield VNARs that enter the brains of mice in vivo, and the mouse TfR1 binding capabilities of VNARs can be enhanced by partial overlapping mutagenesis of the CDR3 region.

Drug delivery to the central nervous system (CNS) by passing the blood-brain barrier (BBB) is limited to a small number of lipophilic and small molecule drugs. As a consequence, many brain-related conditions leading to neurodegeneration remain untreatable. This project investigates new modes of brain delivery, which improve the shortcomings of conventional dosage forms and avoid undesired side effects. Such is the case of the nasal route of administration, which is fast and non-invasive. It is proposed that small molecular weight drugs would reach the brain and avoid the BBB, by being transported through the olfactory and respiratory regions, in the upper part of the nasal cavity. Vaporised drugs could be transported intra or extracellularly through this pathway and address neurodegenerative diseases. The specific objectives of this study were to explore i) if Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) can be produced in vapour form by sublimation (the change from solid to gas without passing through the liquid phase) or vaporisation (the change from liquid to gas) using electronic cigarette technology, to potentially administer it to the CNS via the upper region of the nose, and ii) the effect of NSAIDs on microglial activation which can be used to measure neuroinflammation and potentially prevent neurodegeneration. For the first objective, thermogravimetric and calorimetric analyses investigated if the test compounds (nambumetone, ibuprofen, indomethacin, and salicylic acid) could sublime. Microscopic observations of these compounds before, during, and after heating were recorded along with an evaluation of their crystallinity. Then, compound solubility in e-cigarette liquid was assessed by spectrophotometry. For the second objective, the toxicity and inflammatory response of these NSAIDs and the endogenous prostaglandin (PGJ2) was assessed in N9 microglia mouse cultures. The toxicity of the proposed drugs and their concentrations were evaluated as cell viability by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT)-reduction assay. Then, the anti-inflammatory effect of NSAID treatment in response to lipopolysaccharide (LPS)-induced activation was investigated by quantifying the levels of the cytokines tumor necrosis factor alpha (TNF)-α and interleukin 1 beta (IL-1β) with ELISA. Complementary to cytokine levels, NO production was assessed by measuring nitrite with the Griess reaction. Finally, the expression of inhibitor IkBα and transcription factor p65 (or nuclear factor NF-κB p65 subunit), by Western blot was semi-quantitatively analysed to determine if the nuclear factor kappa B (NF-κB) pathway was inhibited and therefore, causes the lower production of pro-inflammatory cytokines. To conclude, e-cigarette technology continues to have potential to deliver therapeutics to the CNS whilst avoiding side effects. Further studies are needed to develop a reliable tool to confirm efficacy of NSAIDs against microglia activation.

This study examined the influence an overseas teaching experience has on teaching decisions. Previous research has focused on preservice teachers and student teachers, but none have looked at licensed teachers and how their teaching decisions were different when they returned to teach in their home country. Through a questionnaire, face-to-face interviews, and classroom observations, the study found four areas that are influenced by an overseas teaching experience: global perspective, cultural empathy, culturally relevant pedagogy and curriculum choices, and personal growth. No clear differences among the teachers were found for factors such as gender, race, or experience. Results suggest teachers who have taught overseas may have more cultural empathy for students of other backgrounds and English-language proficiency and a willingness to develop curriculum that encompasses more of a global perspective.

This study examines the rise of executive women in public relations in both the nonprofit and corporate sectors. The focus of this study was on feminist and masculine values and their effects on female executives. A survey of 121 female executives from the corporate, nonprofit, and agency settings was conducted to analyze their views on feminist and masculine values in public relations and their effects on managerial positions. Results indicated that women who place greater value on masculine traits are more likely to obtain management positions in the corporate sector. Those who place greater value on feminist values do not necessarily elevate to positions of leadership in the nonprofit sector. Also, women believe men are lacking feminist traits, whole women contain both masculine and feminine traits.

This thesis explores the phenomenon through which numerous directors, from emerging and established film industries from East Asia, have been collectively recognised as auteurs in the West in the last two decades. The thesis proposes a multi-dimensional approach that investigates contexts, discourses, and agencies closely associated with three representative directors that shaped their auteur reputations, as revealed in different forms of archival materials which are treated as auteur paratexts. These paratexts are archival materials associated with the Rotterdam International Film Festival in relation to Apichatpong Weerasethakul, home video promotional materials in relation to Kim Ki-duk, and YouTube user-generated content in relation to Wong Kar-wai. Drawing on and expanding from the method of Foucauldian critical discourse analysis, the findings reveal persistent discourses on geo-politics in relation to national and regional cinema, and an expanded discourse on art cinema in relation to transnational multimedia art forms and diverse taste cultures. Further multi-modal textual analysis of sample materials, which take into account multiple individuals involved, illustrates how directors and associated agents negotiate discursive framings and assert their own pleasure and personal politics through language, voice and performance. Each case study also discusses wider networks of relationship, drawing on and expanding from Pierre Bourdieu's frameworks, which facilitate or undermine the process of auteur reputation-making associated with the three case study directors. In the context of the film festival, Apichatpong has been promoted as a modernist auteur as part of festival branding. Emerging through the commercial context of film distribution, Kim Ki-duk and associated distributors have drawn on and moved away from Kim's restricted cult reputation generated by influential distributors over time. The case study of Wong Kar-wai points to the importance of individual users on YouTube, who are not represented by film-related institutions but exhibit shared taste cultures through maintaining and expanding the director's reputation. As a whole, the thesis offers a multifaceted perspective on the East Asian auteur phenomenon and highlights collective cultures that sustain fascination with the auteur figure.

The physical, transport, and metabolic barriers presented by the cerebral microvessel endothelium - the blood- brain barrier (BBB) - protect the brain from damage from toxic substances and ensure the delivery of nutrients required for the functioning of the brain thus creating a stable neuronal microenvironment. However, the BBB poses a challenge to many CNS-active drugs which must cross the BBB to reach their target. Of the drugs that target the brain, many are cationic at physiological pH making their transport into the brain even harder with the additional potential for drug-drug interactions. Therefore, this thesis has been an attempt to understand the transport characteristics of cationic therapeutic drugs across the BBB. One of the foci of this study has been the anti-human African trypanosomiasis (HAT) drugs pentamidine and e ornithine, both positively charged at physiological pH. Pentamidine is a stage 1 drug for HAT that was previously found in our laboratory to not cross the mouse BBB in vivo as it was a substrate for eux transporters, particularly P-glycoprotein. The present study observed that pentamidine is taken up by Organic Cation Transporter 1 (OCT1) in hCMEC/D3 (human) and bEnd.3 (mouse) cell lines where it accumulates and is euxed by ATP-dependent mechanisms out of the cell. In addition, the predominant localisation of OCT1 at the luminal membrane of the BBB may explain the low permeability of pentamidine into the brain. Considering pentamidine is a substrate for P-glycoprotein at the BBB, inhibitors of Pglycoprotein were used to increase pentamidine delivery into the brain. Pluronic® triblock polymers P85, P105, and F68 were thus chosen for their proven ability to inhibit P-glycoprotein and for their promising results from clinical trials. They were used at concentrations of 0.01%, 0.025%, 0.1%, and 0.5% along with pentamidine in an attempt to increase its delivery across the BBB, concomitantly reducing any side-e ects. In vitro assays carried out on MDCK-hMDR cell line suggested high concentrations of P85 and P105 were cytotoxic even though P85 was able to signi cantly increase pentamidine permeability at 0.5% and 0.1%. Greater speci city to a target could circumvent toxicity issues in the future. The second anti-HAT drug studied was e ornithine that treats stage 2 of HAT. To treat stage 2 of the disease it must cross the BBB, yet it was not found to cross the BBB in the in vivo study on mice carried out in our laboratory. Results obtained from assessing the accumulation of e ornithine in hCMEC/D3 and bEnd.3 cell lines, the in vitro models of the BBB, also suggested limited entry of e ornithine into the BBB. Nonetheless, the assays indicated that e ornithine could be a weak substrate for system y+ at the BBB. There was also evidence for its interaction with OCTs in the bEnd.3 cell line. Second part of the thesis focussed on the antipsychotic drugs haloperidol and amisulpride, both cationic drugs at physiological pH. Haloperidol, an extensively used drug both as an antipsychotic and for palliative care, has the potential to interact with other drugs at the BBB. Haloperidol was found to be a substrate for OCTs at the BBB in both hCMEC/D3 and bEnd.3 cell lines and was found to accumulate readily inside the BBB cells. Similarly, amisulpride is an antipsychotic that is also used to treat delusions and aggression in Alzheimer's disease (AD). Previous studies found increased central dopamine receptor occupancy in AD patients when amisulpride was administered at very low doses. Unlike haloperidol, amisulpride had very low accumulation inside the BBB cells. Results suggested amisulpride to be a substrate for the OCTs and the eux transporters MATE1 and PMAT at the BBB. Amisulpride entry into the brain was also tested in wildtype and transgenic AD mice to nd that amisulpride entry into the transgenic mice brains was signi cantly greater than wildtype mice brains and this was not due to a `leaky' BBB of the AD model. Changes to the expression levels of OCT1, 2, 3 and P-glycoprotein transporters in wildtype and AD model mice BBB were determined using Western blotting and no di erences were found. Further exploration of capillaries isolated from human brain samples from control and AD a ected patients was carried out and signi cant region-speci c changes to the expression levels of MATE1 was observed. There was also a tendency for region-speci c decrease in PMAT expression levels. MATE1 and PMAT are proton-dependent transporters that eux substrates out of the BBB. This decrease in eux transporter expression at the BBB of AD patients could explain the increased sensitivity in AD patients to amisulpride.

This thesis offers an analysis of the British marketing and reviewing of three films from the 1970s which have been seen as controversial, through to their most recent DVD releases, as well as their more recent remakes, in relation to the changing public construction of cultural taste. The films are Straw Dogs (Peckinpah, 1971/Lurie, 2011), Last House on the Left (Craven, 1972/Iliadis, 2009) and The Texas Chain Saw Massacre (Hooper, 1974)/The Texas Chainsaw Massacre (Nispel, 2003). The methodological design of the thesis is based firmly in traditions of historical reception studies, following Barbara Klinger (1994), Janet Staiger (1992, 2000) and Kate Egan (2007), and employs methods of analysis primarily drawn from Lisa Kernan (2004) and Martin Barker and Kate Brooks (1998). By employing a historical reception studies approach to the material, the thesis resists the tendency to treat film remakes as inherently 'inferior' to authentic originals. The public construction of taste in relation to these films is figured in relation to Pierre Bourdieu's concepts of cultural capital, cultural distinction, and developments of these, such as Sarah Thornton's notion of subcultural capital (1995). Through such an analysis a discrepancy emerges between the two sorts of material under scrutiny, whereby a sense of 'the generic' is figured as either positive in marketing or negative in reviewing, suggesting difference conceptions of an imagined audience. Overwhelmingly, the remakes are positioned negatively by critics in relation to the original films and these negative appraisals are often asserted through the discourses which have rehabilitated the original films from their own negative reception during the 1970s and 1980s.