VictorJuiz/thesis huggingface dataset:
Comparing optogenetic approaches to visual restoration in a model of retinal degeneration

The inherited retinal degenerations (IRDs) are the most common cause of irreversible visual loss in the young - but therapeutic options have traditionally been limited. While genetically heterogeneous, the IRDs are linked by a final common pathway of visual loss secondary to photoreceptor death, with cells of the neural retina surviving relatively intact. The technique of optogenetics (inducing light sensitivity by exogenous expression of light sensitive proteins within cells) is developing as a therapeutic method to stimulate these surviving cells: returning light signals to the degenerate retina and ultimately restoring lost vision.
The aim of this thesis was to compare different optogenetic tools and cellular targets for optogenetic visual restoration in a model of inherited retinal degeneration in order to inform future translational work.
Three novel mouse models of retinal degeneration, additionally devoid of native melanopsin and incorporating cell specific Cre recombinase expression were devolved and validated to allow cell population specific targeting of genetic constructs both delivered transgenically and by using intravitreal injections of adenoassociated viral vectors (AAVs).
These models were used to isolate ON-bipolar cells from dissociated degenerate retina in the first comparison of gene expression profiles in such cells to their wildtype counterparts. This demonstrated a lack of changes likely to preclude these attractive cellular targets for therapeutic optogenetics.
Cell targeted delivery of a candidate optogenetic tool (melanopsin) using these models was compared to conventional (non-specific) AAV delivery. This showed restoration of retinal electrophysiological light responses on ex vivo multiple electrode array recordings with kinetics differing between delivery approaches. Targeted delivery of three candidate tools (melanopsin, rhodopsin and ReaChR- channelrhodopsin) were similarly compared with markedly differing response characteristics demonstrated between tools
Finally, translatable, compressed ON-bipolar cell specific promotors were used to produce a potentially translatable cell specific AAV delivery system. This was demonstrated to successfully deliver functional optogenetic tools to a degenerate retina in vivo.
Together, these data indicate that the described mouse lines form a useful model system with which to compare optogenetic vision restoration approaches. In addition, while no one optogenetic tool or target was demonstrated to be overall superior to another, the diversity of responses seen could in themselves represent a great opportunity to improve the quality of responses restored by this technique as it moves towards clinical translation for the treatment of inherited retinal degenerations.

Keywords: Retinal dystrophy
rd1
Gene Therapy
ReaChR
Channelrhodopsin
Optogenetics
IRDs
IRD
Inherited retinal degenerations
Melanopsin
Advisor: Hankins, MW
Downes, S
The European refugee crisis in Greece: understanding host communities

This thesis explains how Greeks, despite having consistently revealed high levels of xenophobic sentiments in cross-European surveys, behaved in a prosocial manner towards asylum seekers in the context of the European refugee crisis. It draws on data collected over six months of ethnographic fieldwork in Greece and is composed of three independent, yet interrelated, papers, each of which examines a unique research question and simultaneously contributes to addressing this overarching empirical puzzle. Specifically, the first paper examines whether self-reported prejudice is a good predictor for actual discrimination in this context of crisis. It argues that cases of discordance emerge from the fact that this construct does not capture the affective dimension of relevant attitudes; emotional dynamics emerging from interpersonal interaction seem to have played an important role in guiding action in the case considered. Exploring the triggers of prosocial behavior, the second paper uncovers the central role of situational dynamics in leading ingroup members to offer help to asylum seekers. The ability to discern individuals, rather than groups, as well as the degree of emergency asylum seekers faced in the course of intergroup contact determined the actions of host community members. To a large extent, this explains why Greeks became so immersed into helping asylum seekers. This contradicts an explanation that is highly articulated within the public discourse, namely that this behavior was a result of the refugee heritage of host community members. The third paper conceptualizes the latter explanation as a perspective- taking intervention that ultimately underlined the shared identity of Greeks with contemporary asylum seekers and identifies the ways in which this resonated with host community members. Based on the emerged typology suggestions for increasing the effectiveness of such interventions are introduced. Overall, this thesis makes a number of contributions to ethnic relations literature.

Keywords: European refugee crisis
prejudice
discrimination
Greece
Advisor: Biggs, M
On the application of coding to adaptive steganography: robustness, efficiency, and coding loss

Steganography is the process by which we hide payloads (secret messages) into covers (inconspicuous mediums of data) resulting in stego ob- jects (original mediums of data with subtle changes to encode our message), with the aim of these objects appearing to be indistinguishable from the cover. Steganography aims to compromise the adversaries' ability to classify an object as innocent or not. The most successful steganography is adaptive embedding, which uses a distortion function to associate individual cover changes with a cost of change (higher costs implying a more detectable change), and a code which embeds the payload whilst minimising the sum of distortion (a proxy for detectability).
This thesis explores approaches to codes, for adaptive embedding on the subjects of robustness, efficiency, and simulating. Since the wide adoption of adaptive embedding, the significant focus of most researchers in the field has been on distortion algorithms. Our work has aimed to explore the potentials around codes instead, building on the highly successful Syndrome Trellis Codes (STC) algorithm.
On the area of robustness, we explore the ability to create stego objects able to withstand the noisy (non-adversarial) channel. Since syndrome codes are fragile by design, syndrome-encoded stego objects are a bad choice: amplifying the channel error rate into unacceptably high payload error rates. Our work on improving the efficiency of STCs looks at how H matrix construction can influence the fficiency of the algorithm. Expanding on existing research around minimising outliers, we look at how moving from a block-based matrix to one constructed with rows can improve the embedding efficiency.
Finally, we explore the area around simulated steganography. Because of speed constraints, many researchers omit the use of a code, to speed up experiments. The justification is clear: not using a code saves both time and experimental complexity, when you can simulate stego objects on the rate- distortion bound. If we cannot achieve the rate-distortion bound with a code, and more parameters are influencing this than which are taken into account when simulating, is this a sensible option? We propose a method which samples the code with the given parameters and is then able to simulate objects not on the rate-distortion bound, but at the distortion and detectability of a code.

Keywords: Simulated embedding
Steganalysis
Adaptive embedding
Steganography
Robustness
Advisor: Ker, A
Investigating pseudotyped lentiviral vectors for gene delivery to the lung

Recombinant lentiviral vectors (LV) are an attractive vehicle for gene delivery to the lung due to their ability to achieve stable, long-term, expression and the opportunity to add glycoprotein pseudotypes for efficient lung cell-targeting. Two LV pseudotypes derived from sialic acid- binding Sendai virus and influenza virus, referred to as F/HN and Rostock respectively, can facilitate efficient in vivo transduction of the murine airway and were compared alongside a new influenza-based pseudotype (Shanghai) which, in contrast to F/HN and Rostock, is based on a strain that infects humans. Lectin staining confirmed a sialylated receptor distribution that is different between murine and human lung, with a greater abundance of a2,6 and relative lack of an a2,3 subtype in the human airway, such that transduction of mouse lung is likely a poor predictor of performance in humans. Ex vivo transduction of murine precision cut lung slices (PCLS) recapitulated results from in vivo experiments. However, PCLS from resected human lung did not contain airways, and therefore cultures of human airway epithelial cells, maintained at an Air-Liquid Interface (ALI), were used to model transduction of the polarised airway epithelium. Different cellular source materials and ALI culture protocols showed differences in the abundance of human sialylated receptor subtypes available, as well as subsequent transduction efficiency by F/HN pseudotyped LV. Importantly, transduction of human ALI cultures was more efficient using vectors based on human as opposed to simian immunodeficiency virus. A greater transduction efficiency was observed for Shanghai pseudotyped LV compared with Rostock but, overall the F/HN pseudotype demonstrated superior efficiency, transducing all human airway cell types characterised. This was consistent with the greater affinity of the F/HN pseudotype for the a2,3 sialylated (N-acetyllactosamine) receptor present in all models investigated, and also explained the broad range of pulmonary cell-types (including the repopulating/progenitor cells of murine airway) transduced in all models investigated. These data support the strong translational potential of the F/HN pseudotype.

Keywords: hemagglutinin
air-liquid interface
neuraminidase
airway
sialylated receptor
gene therapy
influenza virus
lentiviral vector
pseudotyping
Sendai virus
lung
Advisor: Gill, D
Mitrophanos, K
Investigating the role of home environment in bilingual language development: a study on young Turkish children in England

This thesis presents the results of a cross-sectional, mixed-method study investigating the role of proximal and distal factors in the home environment that are associated with bilingual language development of 3- to 6-year-old Turkish children in England. In so doing, it addresses some of the gaps in the literature and becomes the first study to demonstrate the factors related to bilingual language skills of Turkish children in England. The findings from this study add to the literature by demonstrating the relative importance of the quality of language use in the home language and literacy environment of children with a focus on mother-child interactions and the role of language attitudes in children’s language preferences and thereby language development drawing on the accounts of children.
The main sample of the study is first-generation Turkish parents (N=168), and their 3- to 6-year-old children. All the parents participated in an interview concerning their life in England. During this interview, a structured questionnaire was administered to obtain information on the demographic and socioeconomic characteristics of the families and their home language and literacy environment. Then, a subgroup of mothers and children (N=67) was visited twice at home for observations of mother-child interactions and child assessments. During the home visits the interactions between the dyads were observed and recorded using a structured observation method. Children were assessed for their Turkish and English vocabulary; Turkish sentence repetition; and non-verbal abilities. Lastly, a sub-group of children (N = 27) was interviewed about their attitudes towards the Turkish and English languages using a semi-structured interview method.
The study findings suggest that the home environments of children from first-generation Turkish families may be related to the family characteristics; further the home environment is likely to be associated with variations in children’s language learning experiences. Among the components of the home language and literacy environment, language exposure at home and language quality in maternal speech were found to be the most significant predictor in statistical models of both Turkish and English language skills. This indicates that stimulating language and literacy experiences at home can facilitate gains in both Turkish and English and can buffer the effects of socioeconomic disadvantage. The interviews with children demonstrated that children’s language attitudes informed their language preferences, and vice versa. Negative language attitudes towards a language or a culture were associated with children’s avoidance of the language and had a negative emotional effect on children’s language preferences and perceptions.

Keywords: child interviews
home environment
family background
ethnic identity
bilingual language development
immigration
Advisor: Melhuish, E
Working the border : contact and cooperation in the border region, Ireland 1949-1972

The Irish border runs for 450 kilometres across a previously undifferentiated landscape. Along its length, two political entities struggled for political identity and recognition. Their national posturing reverberated at the local level, where residents continued to live, attempting both to maximise the advantages of their peripheral location and to minimise its disadvantages, while effectively carrying out their economic roles despite, around, and through the political divide.
The thesis examines the local contact networks which operated across the Irish border in the years between the declaration of the Republic in 1949 and the early years of the Northern Ireland Troubles. Focusing on the experiences of border communities and organisations which sought to deliver similar services on either sides of the divide, it aims to shed light on the reality of international frontiers for those living immediately around them.
The thesis focuses on five contexts of interaction: personal and economic; and professional contact between police, tourism, and local government authorities. Through these, the factors necessary for successful interaction across an international border are examined. Over the length of the period, the effects of different states of unrest or rapprochement at the national level on local and professional networks are examined.
The thesis makes extensive use of interview data with participants, both major and minor; published personal recollections; the local press; and local council reporting, in order to explore a border community within a cross-section of time. The focus is on local communities’ own words and self-perceptions, in order to counteract top-down discussions of the frontier, to illuminate the effects of political decision-making on the ground and the local factors which help shape national policy.

Keywords: geopolitics
Northern Ireland
Irish question
border region
boundaries
Optimisation and evaluation of antibody-based immuno-PET/SPECT imaging of intranuclear epitopes

PET and SPECT imaging of intranuclear epitopes using antibodies (IgG) tagged to cell penetrating peptides (CPPs), such as TAT (GRKKRRQRRRPPQGYG) has great potential given the versatility, specificity and sensitivity typical of antibodies. However, this process is technically challenging because of the location of the target. Previous research has demonstrated a variety of intranuclear epitopes that can be targeted with TAT-IgG-based radioimmunoconjugates (RICs). In this thesis, I set out to determine the technical limitations of intranuclear PET/SPECT using IgG-TAT-based RICs, notably the lower target abundance detection threshold.
I stably transfected the lung adenocarcinoma cell line H1299 with an enhanced green fluorescent protein (EGFP)-tagged histone protein (H2B-EGFP) and generated four cell lines expressing increasing levels H2B-EGFP. EGFP levels were quantified using western blot, flow cytometry, and ELISA (0 - 1 Mcopies/cell, including H1299 WT cells). In parallel, a murine anti-GFP monoclonal antibody was produced, purified and validated for selective binding to H2B-EGFP.
Having established a model system for interrogating the limits IgG-TAT RICs, I developed a novel conjugation strategy to label antibodies with azide modified derivatives of the CCP TAT (TAT-N3) and chelator DTPA (N3-Bn-DTPA) using strain-promoted alkyne-azide cycloaddition (SPAAC) click chemistry. This method of conjugation, referred to as the DBCON3 method, was optimised and followed by radiolabeling with 111In (111In-DTPA-GFP-G1- TAT) prior to in vitro comparison with the conventional method of IgG-TAT RIC conjugation (EDC-NHS crosslinking), using the H2B-EGFP / GFP-G1 model system.
With this new conjugation strategy in place, the cellular uptake of 111In -DTPA-GFP-G1-TAT across the H2B-EGFP transfected clones was evaluated to determine the lower abundance detection threshold in vitro. Using the same model, tumour uptake in xenograft-bearing mice was quantified to determine the smallest amount of target epitope that could be detected using 111In-DTPA-GFP-G1-TAT in vivo.
Finally, I attempted to apply IgG-TAT RICs to a practical application by imaging the DNA damage response (DDR) by targeting the serine/threonine protein kinase ataxia telangiectasia mutated (ATM), an apical regulator of the cellular response to DNA double strand breaks (DSBs).
Here, I present a proof-of-concept demonstration of what is currently possible with RIgG-TAT based RICs whilst simultaneously providing a platform for further exploration and optimisation of this technology, potentially yielding a new generation of more potent whole-body immunoimaging devices.

Keywords: Molecular imaging
PET/SPECT
Antibody based molecular imaging
Advisor: Cornelissen, B
The Bohun and Lancaster lordships in Wales in the fourteenth and early fifteenth centuries

The present thesis is a study of three of the greater marcher lordships of mediaeval Wales - Monmouth, Cydweli and Brecon, as well as of smaller units, both within and outside the marches, which were administratively attached to them - Ogmore, Caldicot and a few manors in Herefordshire and Gloucestershire, These lordships were part of the landed inheritances of two of the greatest fanilies of later mediaeval England - the house of Bohun (until its failure in the male line in 1273) and the house of Lancaster, and it is on the relatively abundant records of these families, supplemented wherever possible by other non-seignorial sources, that the study is based. It is essentially a study in three dimensions.
Continued in thesis ...

Keywords: March
lordships
fifteenth century
fourteenth century
Wales
Marches
Bohun
15th century
Lancaster
14th century
Welsh Marches
Somewhere between Memaw and the Academy: a compositional balancing act

This essay, accompanying a portfolio of compositions, is being submitted for a doctoral degree in composition. It describes the results of my engagement with questions of classical music, how it fits within the wider world, and how these ideas are encompassed in the accompanying music. The questions of how the marketplace mentality of the world affects its thinking about classical music, classical music’s subsequent relevance, and how classical music is presented via the concert, lead to points of increasing musical specificity such as my use of discourse, determinacy, tonality and modality in the compositions, and my belief in the validity of the classical concert ritual. To make these points, I specifically turn to the musicological work of Julian Johnson, Christopher Small, and Milton Babbitt, engaging with and questioning each so as to describe how I decided on various aesthetic positions. Following this, I analyse three pieces of music by Arvo Pärt, Howard Skempton, and Martyn Harry to demonstrate how these ideas have been realised by other composers and what inspiration I took from them in my own compositions. The essay is closed with a detailed discussion of two large projects; one that was undertaken in 2013, and one that is currently in progress. In doing so, I hope to show how my engagement with larger questions has affected not only the music I have written, but also the way in which the music is presented. The essay is intentionally written with a more personal tone so as not to cause a discrepancy with the music in my portfolio, all of which was written with genuineness as the paramount concern. Lastly, I begin my argument by starkly contrasting different viewpoints. It has admittedly been challenging to find a balance in describing the extreme positions in a way that isn’t unnecessarily provocative to my aims. Provocation is certainly not my intention. So, in short, stick with me; all will be made clear as the dissertation progresses.

Keywords: aesthetics
contemporary classical Music
composition
Georgia
Advisor: Harry, M
Connecting theories and practice of governance networks and sustainability policies in cities

This research analysed the effectiveness of governance networks on the design and implementation of sustainability strategies of two European cities – Glasgow and Copenhagen. European municipalities are actively developing strategies that require collaboration between a plethora of stakeholders, often found in networks. Stakeholder collaboration was examined through three features of governance network theory: inter-dependency, coordination and pluralism. The research explored network management and normative issues in relation to network leadership, power and accountability challenges in order to better understand the stakeholder interactions and their impact on sustainability decision-making.
The design of sustainability strategies was explored through a comparative analysis of governance networks and implementation was analysed through projects in each city. Data collection was informed by a literature review which was analysed to shape key themes. Qualitative data was collected through semi-structured interviews of network stakeholders. Interview questions directly correspond to key features identified. Social network analysis was then employed to categorise and standardise data into a schematic network diagrams by mapping and quantifying patterns of connection between stakeholders in each network. Qualitative data collected enabled an exploratory analysis of why patterns and relationships exist and how they impact the design and implementation of sustainability strategies.
Research has shown that the key features of governance networks are evident in Glasgow and Copenhagen, however, future studies could consider integrating more flexibility to reflect regional contexts. The ‘transition’ cities experience between formal and informal governance must be integrated. Networks can effectively enable municipalities to leverage stakeholder resources within decision-making. However, clarity on sustainability objectives and indicators is necessary, as well as more ambitious target setting in city’s sustainability strategies. There is no recipe for a ‘successful’ decision-making process; results identified elements that help and hinder governance networks which must be addressed to accelerate the reduction of carbon emissions in 21st century cities.

Keywords: sustainability strategy
sustainable urban development
network governance
Advisor: Howard, D