VictorJuiz/thesis huggingface dataset:
The study of the deubiquitinase USP8 in Parkinson’s disease Pathogenesis

Parkinson's disease is the second commonest neurodegenerative disease currently treated symptomatically. It is a multifactorial disease involving mechanisms ranging from protein aggregation to mitochondrial dysfunction, oxidative stress and dopamine dysregulation. The levels of α-synuclein have been causatively linked to the development and progression of Parkinson's disease. Therefore α-synuclein lowering strategies are valid approaches in Parkinson's disease. Neuropathologically, Lewy Bodies in the vulnerable substantia nigra of Parkinson's disease patients are less ubiquitinated and specifically less K-63 ubiquitinated than Lewy bodies in the cortex, suggesting differential activation or regulation of ubiquitin interactors. A targeted screen for such interactors revealed that the Deubiquitinating enzyme Usp8 is upregulated in the substantia nigra of Parkinson’s disease brains and is inversely correlated with the degree of total and K-63 ubiquitination. Using genetic knockdown and overexpression techniques, Usp8 was found to colocalize and directly interact with α-synuclein. It was found to de-ubiquitinate α-synuclein and increase its half-life. Its knockdown increased the total and K-63 α-synuclein ubiquitination and decreased its levels by 35% at least partly by increasing its degradation via the lysosome. In vivo in the Drosophila melanogaster, Usp8 knockdown demonstrated protection against α-synuclein toxicity. It rescued in a specific manner the rough eye phenotype, the age-dependent locomotive defect and the loss of dopaminergic neurons caused by the expression of α-synuclein. Specific and effective pharmacological Usp8 inhibition also has the potential to lower α-synuclein levels. Collectively, the evidence produced in my thesis suggests that Usp8 could be a potential target for the future disease-modifying therapies in Parkinson's disease.

Keywords: Parkinson's disease
Neurology
Molecular Medicine
Neuroscience
Medicine
Neurodegeneration
Advisor: Tofaris, G
Fulga, T
From individuals to settlement patterns.

This thesis describes and contextualises the Population & Cemetery Simulator (PCS), which represents agent-based demographic modelling software that can be used to model living populations based on archaeological and historical data as well as their cemeteries. The data used by the PCS are demographic in nature, e.g. age and sex data generated by osteoarchaeologists from excavated cemeteries or historical demographic data. This thesis seeks to provide a methodological foundation for modelling the demographics of archaeological populations. It focusses on case studies using data from early medieval Anglo-Saxon (South England) and Alamannic (South Germany) cemeteries, although excursions into neighbouring periods and regions are included as validation studies. The case studies show how the PCS can be used in archaeological research and the software is presented as a solution to various problems caused by the difference between the living population and the ‘dead’ cemetery data in archaeology.

Keywords: Archaeological Demography
Early Medieval Archaeology
Agent-Based Modelling
Palaeodemography
Medieval Demographics
Demographic Modelling
Medieval History
Physical Anthropology
Medieval Archaeology
Advisor: Hamerow, H
Winning the West: the creation of lower Normandy, c. 889-c. 1087

This thesis re-evaluates the chronology of Lower Normandy’s integration into the duchy growing around Rouen from the tenth century onwards. The introduction argues that modern accounts of Normandy’s development remain dependent on the works of Dudo of Saint-Quentin and Flodoard of Rheims. Difficulties with these authors and alternative approaches to Normandy’s early history are identified. It is argued that regional distinctions throughout the later duchy hindered efforts to bring about political cohesion. Chapters One and Two identify the ninth-century Breton occupation and early tenth-century Scandinavian settlement of Lower Normandy as the twin sources of ongoing regional divisions. The early dukes’ interest in and influence over the west are also called into question. Chapters Three and Four instead posit that ducal interest in Lower Normandy was a product of the late tenth century, with direct intervention following in the favourable circumstances of the early eleventh century. Ducal success in this period depended upon the co-operation of regional aristocrats and ecclesiastical institutions and continuing constraints on Rouen’s influence and authority are emphasised. Chapter Five argues that Robert the Magnificent was a more assertive ruler, who actively strengthened ducal authority in Lower Normandy in spite of renewed opposition. Chapter Six considers how rebellion against William the Conqueror in 1047 reveals growing local interest in the conduct of ducal government. Victory allowed William to consolidate ducal authority in Lower Normandy, encouraging further expansion beyond its borders. Local landholders, however, resultantly received little direct ducal patronage, including scant reward in the post-Conquest settlement of England. In conclusion, while Lower Normandy had been brought firmly under ducal control by 1087, it is argued that it was only under William’s son, Henry I, that the region’s aristocrats acquired any major influence over ducal policy and secured an equal position within the wider Anglo-Norman nobility.

Advisor: Garnett, G
Procreative justice: the ethics of creating and raising children

Despite its immense personal significance, procreation is an inherently other-regarding endeavor. By its very nature, the decision to procreate is the decision to bring into existence another morally considerable being, one who will be exposed to the full range of harms, benefits, and risks that accompany a typical human life, and one who cannot by its nature ever consent to being born. Moreover, when this decision is undertaken in a community of persons, it is also a decision to affect the lives of others in a host of profound (if often underappreciated) ways, from its effects on population size and environmental sustainability, to its consequences for a community’s distribution of resources. In many cases, of course, these interests coincide: adults need children for their parenting projects, societies need citizens for the maintenance of their institutions, and children themselves are often happy to have been brought into existence. However, as a burgeoning literature is beginning to demonstrate, the various interests that are implicated by procreative decision-making can also come into conflict as well, and in ways that raise basic questions of justice.
This thesis explores five of these questions, and in so doing, seeks to contribute to our understanding of the normative significance of procreation. Chapter One considers the relationship between procreation and child welfare, asking what role (if any) prospective children’s interests play in limiting the scope of the right to procreate. Chapters Two and Three consider the relationship between procreation and parenthood, asking whether the act of creating a child generates special rights and/or obligations to parent that child. Chapter Four considers how the significant costs of procreation and parenting ought to be distributed through society, asking whether parents are responsible for paying the full cost of their childrearing projects, or whether childrearing costs should be shared in some way among parents and non-parents alike. Finally, Chapter Five considers our moral obligations to orphaned children, asking whether it is permissible to create new children in conditions where there are already existing children in need of parental care. While numerous positions are defended on each of these interrelated questions, one general conclusion runs through all of them: rather than being viewed as something that is immune from moral scrutiny, or as something that individuals have an unqualified right to do, procreation ought to be viewed as the site of potentially conflicting interests that must be carefully balanced against one another.

Keywords: Procreative Ethics
Children's Rights
Family Justice
Intergenerational Justice
Advisor: Caney, S
Highlighting hair: what can be revealed about reading hair in medieval Welsh literature

In this thesis I examine in detail the role hair plays in Welsh medieval literature, predominantly in the work of the poets of the fourteenth and fifteenth centuries known as the Cywyddwyr, but also in the Mabinogion. While the messages are sometimes ambiguous, the exercise of examining them can nevertheless deepen our understanding of the cultural and social context in which the men and women of Wales played out their lives.
In a short Part One, we see how in recent decades many studies have considered the semiotics of the body, but how in medieval scholarship, opportunities have been missed by taking for granted some of the social constructs such as the traditional link between a woman's hair and her beauty, and the dominance of the male figure, omissions which this thesis will seek to redress. To help interpret the signs transmitted by different hairstyles in the period, this first part also outlines some relevant aspects of the value systems of medieval society, in particular the division between men and women, and the conflicting expectations imposed on women by contemporary notions of virtues and ideals.
The main body of the thesis focuses on the texts themselves, and for the first time draws together the plethora of references to the hair of both men and women, offering translations into English of all the extracts examined. Part Two looks in detail at women's hair, considering briefly how a close analysis of the poems to hair might pose a challenge to the traditional distinctions between the Canu Serch and Canu Mawl categorisation. Part Three considers men's hair, including, of course, their beards. This side-by-side approach is important as it goes part of the way towards bucking the trend of treating men and women in isolation, appreciating that to understand either sex fully, they need to be discussed in the same arena.

Advisor: Charles-Edwards, T
A structural study of host-guest chemistry in zeolites

Petrochemical products have played an inarguably key role in the activity of mankind since the turn of the last century. The conversions of fossil fuels such as crude gas and oil into olefins and aromatics are very important catalytic reactions, producing platform chemicals used in the syntheses of numerous commodity chemicals and polymer materials. Zeolites are one of the most commonly used catalysts for these conversions. The recent development in the catalytic conversions of biomass to petrochemical products and environmental applications over zeolites is of great significance. Due to the inherent acidity in zeolites that is caused by the Brønsted and Lewis acid sites, zeolites catalyse many hydrocarbon reactions, such as isomerisation, oligomerisation, alkylation and cracking. In addition, the combination of the intrinsic shape and size selectivity of internal channels and pore mouths along with mass transport effects makes zeolites a great candidate in selective molecular sorption and for catalysis reactions.
Despite the extensive applications of zeolites, the catalysis chemistry in zeolites is in fact not well understood from the structural perspective. This is largely due to the fact that most spectroscopic and thermal methods provide limited structural information about the local atomic information of the molecular adsorbates with respect to the acid sites. Despite many theoretical calculations of zeolites have studied the acid properties and the mechanistic study of catalysis reactions, there are however various application limitations. In fact, the recent progressive advancement in the diffraction techniques has allowed the structural study of organic molecules in different microporous materials.
In this thesis, using high resolution synchrotron X-ray diffraction (SXRD) as the primary characterisation technique, we propose a novel methodology in understanding the molecular chemistry in zeolites (with H-ZSM-5 as an illustration) from the structural perspective. The following topics are discussed in a systematic manner:
(i) the acid-base interactions with functional molecules,
(ii) the locations of the substituted Al sites (the Brønsted acid sites),
(iii) the structural chemistry of various organic adsorbates in the framework,
(iv) the potential storage capability for functional gases,
(v) the mechanistic study of a novel biomass reforming reaction, and
(vi) the mechanistic study of the initial step of the industrially important methanol-to-hydrocarbons process.
It is also envisaged that this methodology can be broadly applied to the study of other zeolites or crystalline microporous materials.

Advisor: Tsang, E
Appliance-level demand side management for power network stress mitigation

Power networks are under increasing pressure to maintain operation within permissible voltage and current limits with higher penetrations of renewable energy. This thesis aims to develop and evaluate a practical and economical way to control key domestic appliances to alleviate stress caused by high level of renewable energy penetration.
The first objective in this thesis is to develop a network stress identification technique that does not rely on communication infrastructure. Traditionally, there is an emphasis on using centralized control strategies for demand side management (DSM) involving a central brain which collects information from each individual device and sends out commands to them which schedules their operation. This approach relies heavily on communication infrastructure and introduces security challenges, which are not problems for distributed or decentralised control. Whilst the latter two approaches have the virtue of scalability and flexibility, they require a good network model or good estimation of network condition without real time communication for effective control. A tap change detection approach via local voltage measurement has been developed and validated to enable the domestic smart appliance to perceive the network stress in three different levels across the power network without any real-time communication.
The second objective is to explore the economic benefits associated with the usage of electric hot water tanks (EHWTs) as an alternative to home batteries or electric vehicles for demand response. To do this, an optimization approach for sizing of the EHWT is proposed. Real-world hot water usage data is analysed and applied, revealing four typical hot water usage patterns and 100-litre as the most common optimal tank size for UK consumer.
Finally, since increasing PV generation has risen voltage concerns in various locations across the UK, such as in Cornwall, this thesis investigated to what extend intelligent EHWTs can be used to alleviate the LV network stress caused by the high level of PV penetration. A Monte-Carlo simulation is carried out on real UK LV networks, showing that the presence of intelligent EHWTs could improve both the voltage and current performance of the LV network and allow 50% more PV installations beyond the network’s original capacity.

Advisor: McCulloch, M
Antiseptic religion: missionary medicine in 1885-1910 Korea

The thesis explores the intersection between medicine and religion in the context of colonisation in Korea in the late nineteenth and early twentieth century. I will focus on the work of medical missionaries from Europe and North America that pursued perfect cleanliness in body, mind and society, including total abstinence and spiritual cleanliness, by spreading biomedical concept of hygiene.
One of the points that I will articulate is the ways in which medicine as a colonising force in its own right worked in the mission field to produce 'the docile bodies of people' in the Foucauldian sense. I will argue that what mission medicine in Korea utilised and relied on for its work was a new concept of cleanliness based on biomedical knowledge, the germ theory, rather than the power of colonisation. It was because mission medicine in Korea often worked without collaborating with direct colonial powers. In this sense, Protestant Christianity and biomedicine shared a common foundation in 'cleanliness.' Consequently, I will try to emphasise the multi-dimensional and multi-directional role of the use of cleanliness as an efficacious tool for control of the body. In relation to the historiography of medicine in Korea, I will argue that Confucianism served the social and cultural control of bodies as a medicalised form and that Christianity tried to replace it by providing new knowledge concerning body, disease, health, and cleanliness.
In the same respect, I will explore the historical relationship between the germ theory and missionary medicine in Korea. The germ theories of disease were not simply a new etiology but also an effective cultural implement to change people's lives. Thus, the theories did not simply remain in the realm of medicine but were introduced, disseminated, and applied to all matters relating to the body, including its mental and spiritual aspects, through the concept of cleanliness.

Keywords: East Asia and Korea
Protestant Mission
Epidemic Disease
Religion
History of Medicine
Advisor: Harrison, M
International normative commitments to multi-ethnicity: the case of Kosovo, 1999-2012

Following the war in Kosovo in 1999, the international community embarked on the most extensive international peace- and state-building project to date. From the early UN administration of Kosovo until the end of ‘supervised independence’ in 2012, various international organisations played a critical role in shaping the post-war polity. Throughout this engagement, the international community was driven by normative commitments to multi-ethnicity. However, while international organisations were committed to making Kosovo ‘multi-ethnic’, lack of clarity prevailed about what this goal entailed, or why it was so important. The thesis seeks to answer two inter-related questions: what was meant by multi-ethnicity on the part of its proponents, and what explains the prominence of commitments to this idea. Taking the form of three sections, the thesis examines these commitments’ origins, manifestations, and explanations. International normative commitments to multi-ethnicity are found to originate in a shifting conception of the relationship between ethnic diversity and legitimate statehood during the twentieth century. Their manifestations in Kosovo are studied in three policy domains: the return of displaced persons, decentralisation of government to the local level, and minority rights. The thesis finds that international efforts in the pursuit of multi-ethnicity in Kosovo exhibited conflicting notions of multi-ethnicity, which shifted from integrationist ambitions to notions that reconciled the reality of segregation between ethnic groups on the ground through a ‘politics of recognition’. The goal of multi-ethnicity remained, but was transformed. Explanations for the commitments to multi-ethnicity are found in both normative and consequentialist considerations, by uncovering unspoken underlying assumptions, and in the identity and self-image concerns of international actors. These findings indicate the power of the normative environment in shaping the actions of international organisations and provide insights into the thus far under-theorised normative dimension of the international state-building project in Kosovo.

Keywords: Post-Conflict
Multi-Ethnicity
Diversity
Minority Rights
Kosovo
Multiculturalism
State-building
Advisor: Caplan, R
Investigating the molecular regulation and morphological dynamics of the Visceral Endoderm

Cell migration is of huge importance in the field of development, where the correct positioning of signaling centers and functional structures is of paramount importance. An example of this occurs within the Visceral Endoderm (VE), an extra-embryonic epithelium that is involved in patterning the embryo. A specialized subset of VE cells known as the anterior visceral endoderm (AVE) is induced at the distal tip of the egg&Tilde;cylinder, and is responsible for specifying anterior embryo pattern. AVE cells migrate in a stereotypic manner towards the prospective anterior. Failure of this migration leads to dramatic mis-patterning of the primary body axis and renders the embryo unviable. The main aim of my D.Phil is to investigate cell movements throughout the VE, in order to understand the behaviour of both the AVE and non-AVE cells and to give insight into the global cell dynamics of reorganizing epithelial tissues during development.
After using DIC and fluorescence microscopy to visualize migratory processes I then applied cell-tracking analysis to the resultant data. Confirming and furthering work that quantified cell movement on the anterior face of the embryo, I performed time&Tilde;lapse microscopy to visualize the entire surface of the embryo as the AVE migrated, in higher temporal and axial resolution than has been demonstrated to date. Cell&Tilde;tracking analysis of this data indicates that these areas exhibit different cell behaviour to that previously quantified for the anterior side of the embryo. Further to this, I have developed a novel method of imaging the distal tip of the egg&Tilde;cylinder embryo. Using this technique, I have generated high definition time&Tilde;lapse sequences of induced AVE cells prior to migration, allowing previously uncharacterized behavior to be described.
In order to fully understand the cell dynamics of the VE, I took extremely high spatial resolution fluorescence microscopy of the VE from live embryos in culture and manually segmented the tissue in 3D. This allowed the description of regional differences of cell shape within the tissue.
The Wnt/PCP pathway has been implicated in coordinating AVE migration. The second major aim of my project is to investigate how Planar Cell Polarity (PCP) signaling controls the behaviour of cells in the VE. I investigated the PCP core component Vangl2 using mice that contain a dominant negative version of this protein, and determined that there was no overt AVE migration defects in mutant embryos. In order to investigate the role of the Vangl2-binding PCP component Dvl-2, specifically examining whether localized recruitment of Dvl-2 in the VE is obligatory for normal AVE migration, I have generated genetic tools for use in transient transgenics. Further to this, I have demonstrated a role for the Dvl-2-binding protein β- arrestin2 in AVE migration, using mice null for this protein.

Advisor: Srinivas, S