VictorJuiz/thesis huggingface dataset:
The behavioural and molecular characterisation of a novel LRRK2 BAC transgenic rat model of Parkinson’s disease

Mutations in the leucine-rich repeat kinase II (LRRK2) gene cause autosomal-dominant Parkinson’s disease (PD) which is indistinguishable from sporadic forms of the disease. However, the mechanism by which LRRK2 mutation promotes PD pathology and the functions of the LRRK2 protein itself are currently unknown. Transgenic animal models, expressing PD-linked genes, have been crucial in developing a clearer picture of the mechanisms behind PD progression. Bacterial artificial chromosome (BAC) transgenics, in particular, allow for physiologically relevant disease models to be generated, encompassing entire gene sequences and using endogenous promoters, which result in an accurate recapitulation of spatiotemporal gene expression. We have, therefore, developed BAC transgenic rats expressing human LRRK2. These lines express either human wild-type, G2019S mutant (the most common LRRK2 mutation) or R1441C mutant (the LRRK2 mutation leading to a more aggressive pathology) LRRK2. These rats display LRRK2 transgene expression patterns in the brain which highly resemble human LRRK2 expression. We subsequently aged these lines for the purposes of behavioural and molecular analysis. Additionally, we have performed a number of in vitro studies in neurons cultured from these rats to further investigate the effects of pathological forms of LRRK2. Mutant LRRK2 transgenic rats displayed progressively impaired striatal dopaminergic release along with corresponding behavioural deficits, both motor and cognitive. These motor deficits could be rescued by treatment with levodopa, implying a similar underlying pathological process to PD. These phenotypes occurred in the absence of any overt degeneration of the dopaminergic neurons of the substantia nigra pars compacta or other PD-associated neuropathological markers. We also detected a number of molecular alterations associated with mutant LRRK2 expression including altered LRRK2 phosphorylation and in vitro evidence of altered autophagic processes. In conclusion, these rats recapitulate a number of the key features of Parkinson’s disease and provide clues as to the progression of pathology in PD.

Keywords: LRRK2
Transgenics
Parkinson's Disease
Advisor: Wade-Martins, R
Magnetism and superconductivity in iron pnictides and iron chalcogenides 

This thesis presents a study on several series of unconventional Fe-based superconductors; namely, derivatives of NaFeAs and LiFeAs, as well as molecular-intercalated FeSe. Primarily using muon spin rotation (SR), but also x-ray diffraction (XRD) and magnetic susceptibility measurements, the nature of both magnetic and superconducting phases within these systems is studied. Particular attention is focussed on how these states compete or coexist with one another.
The aforementioned experimental techniques are first used to explore the phase diagram of NaFe1xCoxAs. This phase diagram includes regions of long-range antiferromagnetism and short-range order, that both coexist with superconductivity. Magnetism is gradually destroyed, primarily through a diminishment of the size of the ordered moment, as superconductivity is enhanced by Co substitution. This interplay is explored in detail. By contrast, superconductivity in LiFeAs cannot be enhanced by transition metal substitution, suggesting that it is intrinsically optimally-doped. I investigate this conclusion by studying the evolution of the penetration depth in superconducting compositions of LiFe1xCoxAs and LiFe1xNixAs, and comparing these data to those from other electron-doped systems. I also study an unusual and emergent magnetic phase in Li1yFe1+yAs. This work suggests that LiFeAs supports a superconducting phase that resembles those in other Fe-pnictides, but is uniquely close to an additional magnetic instability.
I then move on to the study of a recently discovered series, based on FeSe intercalated with ammonia and various metals. I study both the penetration depth and the intrinsic magnetic phases in these systems using SR and compare them with other compounds based on FeSe. I find that these intercalated systems support spacially separated regions of dynamic magnetism and superconductivity and I discuss how much these phases depend on the precise chemical details of the intercalated layer. Finally, I return to the experimental study of NaFe1xCoxAs, extending the range of techniques employed by using high-field magnetometry and high-pressure SR. These studies reveal new features of this system that were not accessible using low-field and ambient-pressure methods. In particular, I show that the magnetic moment size in NaFeAs unexpectedly increases with pressure, suggesting that the electronic structure of this compound may be unique amongst known Fe-based superconductors.

Keywords: muon spin rotation
magnetism
superconductivity
Advisor: Blundell, S
Clarke, S
Studies of cerebral laterality in early onset schizophrenia

Accumulating evidence suggests that schizophrenia is associated with altered cerebral laterality secondary to a deviation from normal brain development. A number of findings suggest that age of onset of psychosis and gender may have a significant bearing on the nature and extent of the deviation. In order to examine this, early onset patients (12-19 years of age) were compared to healthy controls and later onset patients in a series of studies using standard neuropsychological techniques, experimental divided visual field (DVF) measures and magnetic resonance imaging (MRI). Specific attention was directed to examining the influence of sex and age of onset on hemispheric specialisation.
In the neuropsychological studies, early onset patients (n=35) demonstrated significant impairment of intellectual functioning relative to normal adolescents (n=35) but no significant VIQ-PIQ discrepancy. Earlier age of onset was significantly correlated with reduced VIQ and FSIQ. Early onset patients showed significant reduction in hand skill, increased incidence of non-right eye preference and crossed hand-eye dominance. In addition, patients demonstrated reduced right ear advantage (REA) in dichotic listening and inability to modulate ear advantage by directing attention.
In the DVF experiments, early onset patients (n=20) demonstrated normal lateralisation in phonological word recognition but sexually dimorphic anomalies in lexico-semantic processing relative to normal controls (n=20). Males showed impairment in imageable word recognition whereas females were more impaired in emotional word recognition. In both cases, the observed anomalies implicated a disturbance in the semantic network subserved by left hemisphere ventromedial and superior temporal heteromodal cortex.
In MRI investigations, early onset patients (n=33) had smaller cerebral hemispheres and larger lateral ventricles than controls (n=32). Male patients showed reduction of leftward asymmetry in temporal lobe volume and female patients showed reversal of rightward asymmetry. Significant correlations were found between left ventricular brain ratio and reaction time to phonological word processing. Together, the combined results indicate that early onset schizophrenia is associated with a significant but selective alteration of cerebral laterality, that age of onset is likely to be a determinant of this alteration and that, to some extent, these changes are mediated by gender. The results are discussed within the context of neurodevelopmental aetiology.

Advisor: Crow, T
Are cultural rights human rights? A cosmopolitan conception of cultural rights

The liberal conception of the state is marked by an insistence upon the equal civil and political rights of each inhabitant. Recently, though, a number of writers have argued that this emphasis on uniform rights ignores the fact that the populations of most states are culturally diverse, and that their inhabitants have significant interests qua members of particular cultures. They argue that liberals should recognize special, group-based cultural rights as a necessary part of a theory of justice in multicultural societies. In this thesis I examine the idea of special cultural rights. In the first part (Chapters 1 to 4), I begin by setting out some of the different conceptions of culture and multiculturalism that are involved in the debate over cultural rights. I then discuss three claims made by supporters of special cultural rights: (1) that having culture is an essential part of individual autonomy; (2) that people have morally significant interests qua members of particular cultures; and (3) that these interests are inadequately protected by existing liberal conceptions of human rights. Although I conclude that (1) is correct, I argue that both (2) and (3) are mistaken. Among other things, I suggest that the version of culture relied upon by supporters of special cultural rights is an implausible one and I outline what I take to be a more plausible, cosmopolitan conception of culture. In the second part (Chapters 5 to 9), I begin by looking at specific instances of cultural rights-claims, and analyzing the concept of cultural rights qua rights. I consider the practical and conceptual difficulties with special cultural rights at great length. But the core of my thesis is that our interest in culture lies in its contribution of worthwhile goals and options, and that this interest lies in culture generally rather than in particular cultures. Hence, adopting a special or group-based distribution of any right to culture would seem to be inconsistent with liberal egalitarian principles. If there are such things as cultural rights, I argue, they are general rather than special rights. I conclude by offering a very preliminary account of what a cosmopolitan conception of cultural rights might involve in the case of the right to free association and language rights.

Keywords: multiculturalism
human rights
political theory
liberalism
minorities
cultural rights
law
cosmopolitanism
Advisor: Miller, D
Gardner, J
Finite element seismic analysis of guyed masts

Guyed masts are a specialized type of structure commonly used in the broadcasting industry to support equipment at substantial heights. The dynamic analysis of these structures under seismic loading is a much understudied field that requires investigation. The complex nature of their analysis arises from the nonlinear force-deflection relationship of the cable supports as well as P-D effects in the mast. These lead to the structure exhibiting significant nonlinear characteristics even under working load conditions. Full nonlinear analysis of guyed masts is rarely performed as it is complex and time consuming. Masts are usually designed by equivalent static methods for wind and ice loading only, with the seismic load case often assumed to be less onerous. The validity of this assumption is investigated as part of this research. In this project four existing guyed masts in the UK with heights ranging from 99m to 312m are accurately analysed under various seismic loading conditions using SAP2000 structural analysis software. The research aims to gain an understanding into the distribution and magnitudes of forces developed during typical seismic and design wind events, establish indicators and trends that may aid in guyed mast design, and identify the circumstances in which seismic loading may be the governing load case. Investigations into the ‘travelling wave’ effect, the significance of vertical motion, and the suitability of a response spectrum analysis are also undertaken. Applicable sections of Eurocode 8 are followed wherever possible. It is shown that when subjected to substantial seismic events with peak ground accelerations in the region of 4m/s2, significant forces can develop in masts that are comparable to those produced during a wind assessment using the Patch Load method. The distribution of forces can be appreciably different from a wind loading analysis and any regions with irregular or inconsistent distribution of wind response forces can be vulnerable to seismic loading, particularly when mean hourly design wind speeds are less than 22m/s. It is also shown that enough common or predictable seismic behaviour exists between masts to suggest that the development of a simplified seismic analysis method for guyed masts is feasible.

Keywords: dynamics
Advisor: Williams, M
Blakeborough, A
Imperfect socialisers: international institutions in multilateral counter-terrorist cooperation

This thesis examines the effects of cooperation within multilateral counter-terrorist fora on the process of preference formation of a selected group of Western countries: the United States, the United Kingdom and Italy. The analysis focuses on the global counter-terrorist regime, a set of complex and multifaceted institutional arrangements, which were developed in the aftermath of the September 11, 2001, attacks in order to harmonise state counter-terrorist responses worldwide.
The study looks at three sets of formal international institutions within the regime: the United Nations, the Financial Action Task Force (FATF) and the European Union. It also selects a sample of three issue areas in multilateral counter-terrorist cooperation: counter-radicalisation policies, the inclusion of human rights safeguards within the main counter-terrorist sanctions provisions, and counter-terrorist financing standards.
The thesis identifies as the visible symptom of institutional effects the progressive convergence of policy outputs at member state level, and proceeds with an exploration of the processes of regime creation, evolution, reform, and participation on the part of the three country case studies.
The analysis reveals that the instances of pro-institution behaviour displayed by state actors are occasioned by image-related group-pressures, triggered by considerations of the maximisation of status markers and social praise, and the related avoidance of shame and social devaluation. The thesis labels this process social influence. The study further outlines the specific conditions under which interaction within a group can activate the social influence phenomenon and identifies the main triggers of state actors’ particular sensitivity to image and shame.

Keywords: the FATF
the European Union
International Organisations
social influence
Counter-Terrorism
the United Nations
Advisor: Foot, R
Human rights and the problem of ethnocentrism

Despite its prominence as a pejorative term in moral and political philosophy, the phenomenon of ethnocentrism has escaped the focused attention of moral and political philosophers. Little sustained effort has been devoted to its in-depth analysis. This thesis attempts to fill in that gap in the philosophical literature, with a particular focus on the analysis of ethnocentrism as a problem, or rather a set of problems, facing the theory and practice of human rights. The thesis begins by drawing a core distinction between ethnocentrism as a moral phenomenon (i.e., a form of moral partiality), on the one hand, and as an epistemological phenomenon (i.e., a mode of judgment), on the other. After singling out the epistemological aspect of ethnocentrism as its main focus, the thesis argues for four interlocking claims. The first claim is that ethnocentrism represents an unwarranted mode of judgment, and thus an epistemic hazard that ought to be avoided if at all possible (Chapter One, §3). This claim is defended at length against the version of political constructivism advanced by John Rawls, which, by grounding political argument exclusively in ideas and values embedded in a common public culture, implicitly justifies a form of ethnocentrism (Chapter Two). The second claim is that moral argument cannot avoid ethnocentrism by grounding itself, as some have thought, in judgments upon which there is broad moral consensus, or rather by avoiding any appeal to judgments that are the subject of marked dissensus (Chapter Three and Chapter Four). Thirdly, the thesis argues that ethnocentrism is, if avoidable, only so to a limited extent (Chapter Six, §2). And fourthly, it offers an outline of how this limited form of avoidance might work (Chapter Five and Chapter Six, §3).

Keywords: the philosophy of human rights
moral philosophy
political philosophy
political liberalism
human rights
ethnocentrism
cultural diversity
Advisor: Waldron, J
Crisp, R
Tasioulas, J
Phonological awareness, literacy, and biligualism

This thesis examines phonological awareness and literacy in monolingual and bilingual children.
Experiment 1 shows that 5-6 year old Spanish-monolingual, English-monolingual and Spanish-English-bilingual children show the same pattern of development of phonological awareness. However, the degree of awareness of each unit is influenced by linguistic background. Spanish children are more aware of vowels and rimes than English children. English children are more aware of syllables than Spanish children. Bilingual children are more aware of syllables in Spanish than Spanish-monolinguals and more aware of vowels in English than English-monolinguals. Hence they show transfer of phonological awareness across languages. All three groups also show a different relationship between phonological awareness and reading.
Experiment 2 shows that bilinguals are more aware than English monolinguals of vowels that exist in both languages (tense-vowels). Moreover, this enhanced awareness extends to vowels that do not exist in Spanish (lax-vowels). It is concluded that exposure to two languages enhances analysis of phonology as well as encouraging transfer of awareness.
Experiment 2 also shows that Spanish-speakers read and spell vowels more accurately than English-speakers. Bilingual children read English vowels more accurately than English-monolinguals. This suggests they understand the orthographic representations of English vowels at least as well as monolinguals. However, they spell vowels less accurately. This may be because bilinguals misapply Spanish phoneme-to-graphemecorrespondences when spelling English vowels.
The English and Spanish vowel systems differ more than their consonant systems. Experiment 3 shows that sensitivity to the four consonant types (stops, fricatives, nasals and liquids) is similar, and correlates with reading ability, in all groups. This suggests that bilinguals may only transfer awareness between English and Spanish of units that are linguistically dissimilar in each.
Experiment 4 compared the awareness of the two consonants in word-medial double-consonants (e.g. the 'c' and 't' in mactan). Although only Spanish-speakers used syllable boundaries to analyse these consonants they made a similar number of errors to English-speakers. However, all groups used syllable boundaries to read and spell wordmedial double-consonants.
Collectively, these results suggest that differences in phonological and orthographic structure between languages encourage different approaches to the acquisition of literacy. Future research should investigate how these differences may be exploited to facilitate literacy acquisition in each group.

Advisor: Bryant, P
Towards robust steganalysis: binary classifiers and large, heterogeneous data

The security of a steganography system is defined by our ability to detect it. It is of no surprise then that steganography and steganalysis both depend heavily on the accuracy and robustness of our detectors. This is especially true when real-world data is considered, due to its heterogeneity. The difficulty of such data manifests itself in a penalty that has periodically been reported to affect the performance of detectors built on binary classifiers; this is known as cover source mismatch.
It remains unclear how the performance drop that is associated with cover source mismatch is mitigated or even measured. In this thesis we aim to show a robust methodology to empirically measure its effects on the detection accuracy of steganalysis classifiers. Some basic machine-learning based methods, which take their origin in domain adaptation, are proposed to counter it.
Specifically, we test two hypotheses through an empirical investigation. First, that linear classifiers are more robust than non-linear classifiers to cover source mismatch in real-world data and, second, that linear classifiers are so robust that given sufficiently large mismatched training data they can equal the performance of any classifier trained on small matched data.
With the help of theory we draw several nontrivial conclusions based on our results. The penalty from cover source mismatch may, in fact, be a combination of two types of error; estimation error and adaptation error. We show that relatedness between training and test data, as well as the choice of classifier, both have an impact on adaptation error, which, as we argue, ultimately defines a detector's robustness. This provides a novel framework for reasoning about what is required to improve the robustness of steganalysis detectors. Whilst our empirical results may be viewed as the first step towards this goal, we show that our approach provides clear advantages over earlier methods.
To our knowledge this is the first study of this scale and structure.

Keywords: big data
domain adaptation
steganography
information hiding
machine learning
heterogeneous data
steganalysis
Advisor: Ker, A
Signals in two-sided search

We introduce signals to search models of two-sided matching markets and explore the implications for efficiency. In a labour market model in which firms can advertise wages and workers can choose effort, we find that advertisements can help overcome the Diamond paradox. Advertisements fix workers' beliefs, so that workers will react if firms renege on advertisements. Firms then prefer to advertise truthfully. Next, we consider a market with two-sided heterogeneity in which types are only privately observable. We identify a simple condition on the match output function for agents to signal their types truthfully and for the matching to exhibit positive assortative matching despite search frictions. While our theoretical work implies that the efficiency of matching increases as information technology spreads, empirical matching functions typically suggest that it declines. By estimating more general matching functions, we show that the result of declining efficiency can partly be attributed to omitted variable bias.

Keywords: signals
Diamond paradox
sorting
matching function
matching
search
Advisor: Keller, G
Postel-Vinay, F