VictorJuiz/thesis huggingface dataset:
Investigating the regulation and functioning of RNT-1 and BRO-1 in C. elegans

The stem cell-like seam cells of the nematode, Caenorhabditis elegans, represent a tractable and powerful model for studying stem cell biology. rnt-1, the worm homologue of the mammalian RUNX family of transcription factors, together with the CBFβ homologue bro-1, is essential for the proliferation of the seam cells. RUNX genes and CBFβ are important regulators of stem cell development in mammals, and are associated with a variety of cancers. The worm seam cell model offers an opportunity to examine how these genes function in stem cell biology. The aim of this work was to shed light on the genetic network in which bro-1 and rnt-1 function, and to reveal the identity of regulators of these genes as well the downstream targets of the bro-1/rnt-1 pathway.
Here, a number of genes that interact with bro-1 and rnt-1 have been identified. ELT-1, a GATA transcription factor, is shown to be a direct regulator of bro-1. Findings which show that the MEIS gene unc-62 acts upstream of bro-1/rnt-1 and regulates the symmetry of seam cell divisions are also presented. The seam cell marker, scm::gfp, is widely used in studies of the seam cells; here the results of an investigation into its identity and functional links are described. In addition, the mechanism underlying spatial regulation of rnt-1 was examined; this led to the discovery of distinct tissue-specific enhancer modules within an intron of this gene. Finally, interactions between pal-1 and bro-1/rnt-1 are reported and described.
Together, these findings provide a framework for furthering our understanding of the mechanisms and genes associated with the functioning of bro-1 and rnt-1 in the worm.

Keywords: proliferation
C. elegans
enhancers
differentiation
development
stem cells
niche
seam cells
Advisor: Woollard, A
An investigation into the regulatory capacity of invariant natural killer T (iNKT) cells during the innate and adaptive immune response to influenza infection

Influenza A virus (IAV) infection is a highly contagious respiratory disease, which can cause substantial morbidity and occasionally death. Invariant natural killer T (iNKT) cells, a subset of CD1d-restricted T lymphocytes, have been identified as important modulators of immunity, mediating both pro- and anti-inflammatory responses. We show that iNKTs play an important role for the generation of protective innate and adaptive immune responses to IAV, and enhance heterotypic immunity to influenza virus following vaccination with a novel pseudotyped virus, S-FLU, which lacks HA expression.
iNKT-deficient mice (Jα18-/-) showed increased susceptibility and lung pathology following IAV infection, which correlated with an exaggerated accumulation of inflammatory monocytes and neutrophils in the lung. Consistent with these findings, we demonstrated in IAV-infected CD1d-/-:CD1d&plus;/&plus; mixed bone marrow chimeric mice, that the lack of CD1d expression on myeloid cells purified from the lungs of IAV-infected mice significantly increased expression of genes linked to cell activation, survival and polarisation between pro- and antiinflammatory responses. We extended these results by examining the role of chemokine signalling during IAV infection, and identified a novel role for fractalkine (CX3CL1) and its receptor (CX3CR1) in innate immune cell recruitment. The use of CX3CR1-iNKT cell double knockout mice revealed that, although upregulated in Jα18-/- mice, CX3CR1-CX3CL1 signalling is not required for cell migration during exacerbated IAV-responses.
Finally, we showed that iNKT-deficient mice displayed reduced longevity of peripheral IAVspecific CD8&plus; T cells following S-FLU vaccination, compared with wild-type mice. S-FLU vaccination protected mice following 5 day heterotypic challenge, however vaccinated mice exhibited reduced viral clearance, and importantly a significant reduction in IAV specific memory T cell response, suggesting a possible role of iNKT cells during T cell priming in modulating the lifespan of antigen-specific T cell responses. Although additional experiments are warranted, these results suggest that harnessing iNKT cells should be considered to modulate the innate and adaptive immune response to optimise heterotypic vaccine design and for therapeutic intervention against acute influenza infection.

Keywords: Influenza
invariant Natural Killer T cells
Myeloid Cells
Advisor: Cerundolo, V
Audience, playhouse and play in Restoration theatre, 1660-1710

This thesis addresses three aspects of the relationship between audience, playhouse and play in Restoration theatre from 1660 to 1710. It provides a comprehensive account of the composition of the Restoration audience, an examination of the effect this group of men and women had upon the plays they attended and an account of the ways in which the plays and playhouses of the Restoration touched the lives of London's inhabitants.
In the first part of this dissertation I identify the audience. Chapter 1 deals with London's playhouses, their location, archictecture and decoration. It shows how the playhouses effectively created two sets of spectators: the visible and the invisible audience. Chapter 2 is a detailed examination of those audiences, and the social and occupational groupings to which they belonged. Chapter 3 deals with the support the stage received. It analyses attendance patterns, summarizes evidence of audience size, presents case studies of attendance patterns and outlines the incidence and effects of recurrent playgoing.
In the second part of the dissertation I deal with theatricality, with the representation of human action on and off the stage. I examine the audience's behaviour in the playhouses and the other public places of London. I focus on the relationships between stage and street to show how values and attitudes were transmitted between those two realms. To do this, I analyse three components of theatrical behaviour--acting, costume, and stage dialogue and look at their effect on peoples' behaviour in and ideas about the social world. Chapter 4 is an introduction to late seventeenth century ideas of theatricality. Chapter 5 examines contemporary ideas of dress and fashion and of their relationship to stage costuming. Chapter 6 considers how contemporary ideas about conversation and criticism affected and were in turn affected by stage dialogue.
An investigation of the effects of electroconvulsive shock on mesolimbic dopamine and amino acid transmitter system

Electroconvulsive therapy (ECT) is an effective, yet controversial, treatment of major depressive illness, though its mechanism of action is not known. Several areas of research suggest a key role of the mesolimbic system, and the nucleus accumbens in particular, in the antidepressant effects of ECT. Anatomical, biochemical and behavioural evidence indicates that dopamine, GABA and glutamate neurotransmitter systems interact in the accumbens to mediate the functional output of this region.
The aim of the research described in this thesis was to study the effects of electroconvulsive shock (ECS) administration on dopamine and amino acid neurotransmitter systems in the nucleus accumbens of the rat. Several neuropharmacological techniques were employed; neurotransmitter release was studied using in vivo microdialysis, gene expression was studied using in situ hybridization, and neurotransmitter function was studied using behavioural assessment.
Results indicate that repeated ECS has a number of effects on accumbens dopamine and amino acid neurotransmitter function. Specifically, ECS induced an increase in dopamine receptor expression in accumbens which was accompanied by enhanced dopamine function. GABA release was decreased in accumbens following repeated ECS, though it was not possible to prove that this was mediated by the increase in dopamine function, as certain data predict. However, a role of glutamate in the dopamine-enhancing effects of ECS was suggested by studies showing that an NMDA antagonist (MK-801), like ECS, increased dopamine function and decreased GABA release. Consistent with this idea, microdialysis experiments showed a marked decrease in glutamate in the nucleus accumbens following repeated ECS.
These results suggest that a reduction in glutamate function in the nucleus accumbens may play an important role in the neuropharmacological effects of ECS. It is argued that the likely consequence of such an effect in man would be an enhancement of psychomotor function and antidepressant action.

Advisor: Sharp, T
Semantics, meta-semantics, and ontology

In this thesis, Semantics, Meta-Semantics, and Ontology, I provide a critique of the method of truth in metaphysics. Davidson has suggested that we can determine the metaphysical nature and structure of reality through semantic investigations. By contrast, I argue that it is not semantics, but meta-semantics, which reveals the metaphysically necessary and sufficient truth conditions of our claims. As a consequence I reject the Quinean (semantic) criterion of ontological commitment. In Part I, chapter 1, I argue that the metaphysically primary truth bearers are not propositions, but rather concrete representations, either beliefs or sentences. I show, in chapter 2, that we can give sense to a truth predicate applying to sentences, given a truth operator and quantification into sentence position. I argue that this strategy does not commit us to the existence of propositions serving as truth bearers. In Part II I argue that although we must assign semantic values to sentences and/or predicates, the meaningfulness of these expressions is not thereby explained. In chapter 3 I articulate Davidson’s problem of predication and his solution, but argue that he was wrong to attribute this solution to Tarski. In chapter 4 I examine the semantics of modal languages; I conclude that although they require semantic values for predicates and/or sentences we should be instrumentalists about these theories. In Part III I consider the relationship between truth and existence. In chapter 5, I defend Pluralism about truth: in some (though not all) domains of discourse, I claim, semantic reference plays a merely instrumental role in explaining truth. In chapter 6, I show that Hume’s Principle, which is committed by the Quinean criterion to the existence of numbers, can be true even though numbers do not exist. In doing so, I appeal to meta-semantic and diachronic considerations. In the conclusion I compare my views on ontology and commitment to Jody Azzouni’s; and in the appendix I suggest how one might pursue diachronic linguistics.

Keywords: metaphysics
philosophy of language
semantics
ontology
Advisor: Edgington, D
Hawthorne, J
An investigation of some heat transfer and gas flow problems relevant to miniature refrigerators

The performance of regenerative miniature refrigerators is governed by heat transfer and pressure drop losses, particularly in the regenerator.
Steady flow experiments have been performed on various regenerator matrices at cryogenic temperatures and heat transfer from helium gas to the matrix, and pressure drop across the matrix have been determined. These data have been found to be in reasonable agreement with data obtained by other workers using transient flow techniques.
In order to determine the applicability of such data to the performance of a cooling engine, experimental methods have been developed to measure the performance and losses in a working Stirling-cycle miniature refrigerator. These techniques have led to the analysis of pressure drop and shuttle heat transfer losses, regenerator efficiency, and to the measurement of other losses in the refrigerator.
An energy balance is performed on the machine.
These novel techniques, which allow the factors determining poor performance of a working refrigerator to be measured in situ, may be applied profitably to other cyclic machines.

Advisor: Davey, G
Sensitivity enhancement in micro-electromechanical systems for sensor applications

Micro-mechanical sensors are typically fabricated both in large numbers and economically using the photolithographic processes that were originally developed in the integrated circuit industry. The magnitude of a change in resonant frequency of a micro-me chanical structure can be used to quantify a change in mass of such a device. Hence, when packaged with integrated measurement, actuation and control electronics, it is possible to deliver a low-cost and small system in a package using fabrication techniq ues that are both mature and widely available. A micro-mechanical resonator has been designed for this project and samples of the prototype resonator were used to investigate various methods for detecting a change in resonant frequency using discrete elec tronic components. The system that has been designed can eventually be integrated with a small micro-mechanical structure to create a mass sensor. Resonators have been fabricated at QinetiQ as part of the Europractice Foundry Access Program and characteri sation of typical devices is described in this thesis.
A popular method for controlling the behaviour of resonant micro-mechanical sensors is a force feedback technique designed to increase the effective quality factor of the resonant system. In this thesis, an increase in the effective quality factor of the prototype system has been demonstrated. When the resonator operates in air at atmospheric pressure, an improvement in the effective quality factor of two orders of magnitude was achievable. This meant that it was possible to assess the potential benefits offered by the force feedback technique by testing the various detection schemes that have been implemented at the natural quality factor and also at a high effective quality factor. A prototype control system has been built using simple digital electroni cs, a key component of which is a direct digital frequency synthesis chip used to provide a stable and accurate driving frequency. Methods for determining a change in the resonant frequency of a micro-mechanical resonator using this control system have be en investigated. A method has been developed for determining the magnitude of a shift in resonance when the frequency of the excitation force is fixed. This thesis contains a description of the technique and also results demonstrating the corresponding de tection capability of the prototype sensor.

Keywords: velocity feedback
sensors
NEMS
mass detection
Q-factor
MEMS
Advisor: Collins, S
Inter- and intra-speaker variation in Liverpool English

This thesis presents experiments and interviews which investigate pronunciation variation in the Liverpool accents of young speakers. Experiment One investigates inter-speaker variation, Experiment Two investigates intra-speaker variation, and Experiment Three investigates both inter- and intra-speaker variation.
These three experiments are conducted from a sociophonetic perspective, with controlled elicitation of natural speech and acoustic analysis of speech data. The experimental investigations are complemented by interviews, which incorporate the perceptions and opinions of speakers of Liverpool English into the study.
The study makes several contributions to the field of sociolinguistic research. It provides a new examination of Liverpool English. Experiment One is specifically designed to explore one of its most complex and ill-defined phonetic features, the realisation of plosives as affricates or fricatives. In addition to this phonetic investigation, Experiment One also examines sociolinguistic variation in this feature, and shows that speakers' individual attributes (such as their social networks and their plans for the future) are as relevant to variation as their socio-economic status.
The study also makes important methodological contributions. Instrumental phonetic techniques and standards are successfully applied to sociolinguistic investigation conducted in the field. An interdisciplinary approach, bringing together qualitative interviews and sociophonetic experiments, is adopted. A new quiz-questionnaire technique for data collection, which should prove useful for many kinds of future sociolinguistic research, is developed for Experiment Three.
Finally, Experiment Three tests many accounts and models of intra-speaker variation. Speakers are shown to vary their pronunciation as the speech situation varies, but not all the seven phonetic variables investigated show the same patterns of variation. Speakers vary their pronunciation according to audience, and also according to topic. Speakers with a high level of ambition vary their pronunciation of certain phonetic variables more than those with a lower level of ambition, and female speakers vary their pronunciation more than male speakers.

Advisor: Coleman, J
Making do in the city

Youth homelessness is a pressing problem in contemporary British urban politics. The emergence of youth homelessness, in the context of wider homelessness, has been conditioned by economic, political and social changes in British society. Young people have been particular casualties of these social changes. Whilst homelessness has been the consequence of larger structural changes, the character of youth homelessness has very much been determined by the homeless themselves. The relationship between human agency and structural constraint, and the implicit power relations therein are explored by recourse to Structurationist theory. In this context, a theoretically composite approach is posited drawing on livelihood analysis and Michel de Certeau's "Science of Singularity". Livelihood analysis is developed by recourse to Grounded theory to produce an ethnography of homeless survival tactics rooted in the experience of young homeless people living on the streets in London's West End. The emergent ethnography is subjected to the insights of Michel de Certeau, who provides a means for understanding the relationship between critical action and social constraint. Recognising the implicit social criticism of homeless life, this approach posits a regime of commodities, skills and sources (the resource regime) as a basis for homeless critical livelihood. This critical livelihood contextualised by structural constraint, and explored by creative endeavour, is used by the homeless to make their lives and to forge identity. This approach is implicitly spatial because the homeless draw on urban spaces to forge livelihood, and their trajectories in the city both contribute to social reproduction and are central to the criticisms they make. Correspondingly, homeless identity, forged through the processes of critical livelihood, is at times contradictory. Homeless identity emerges as one that is purposive and critical, whilst at the same time being dependent on the very circumstances of marginality for its substance and character.
The incarnate God from Hegel to Marx

The thesis argues that from Hegel's early critique of Kant to Marx's early critique of Hegel, the Judaeo-Christian incarnate God underlies a German metaphysical impulse to embody transcendental ideals in historical and political forms. Four motifs, alienation/humanisation, mediation, idealised Prussia and philosophical anti-Judaism, integrate the study's "incarnation thematic" into a secular framework.
In terms of common Enlightenment values and a moralistic view of God, a Judaeo- Kantian convergence is developed as the "anticipatory" climate for Hegel's speculative thought. From the Pauline law/love dichotomy of the Frankfurt period, through the System, and three thematic components (the elevation of representations to concepts, becoming, and mediation), it is shown how the self-othering of God in Christ is reformulated by Hegel as the Absolute's coming to knowledge of itself in a particular historical form, the Prussian State. After challenging "liberal conventionalist" and hellenic interpretations of Hegel's political thought, the incarnation thematic is applied: 1) speculatively, as the ethical mediating realm between the individual and freedom; structurally, in that the supersession of law by love recurs in the morality/ethical life and civil society/State tensions of the Philosophy of Right. A transitional chapter revises the Prussian State to accord with Hegel's idealisation, and explores Young Hegelian speculative christology in terms of: 1) individual versus collective embodiments of the divine Idea and their political correlates (Strauss); future-orientated praxis (Cieszkowski); 3) the negation of Judaeo-capitalism (Hess). While hostile to institutional religion, Marx inherits the incarnation thematic via: 1) Feuerbachian christological love as communal being; 2) a proletarian rather than statist embodiment of freedom; 3) the communist transcendence of Judaeo-Kantian bourgeois Liberalism. Conclusions explore other variants of the incarnation thematic in political thought and argue that since the Second World War, liberal and secular prejudices have obscured the speculative theological and Christo-Germanic dimension of the Hegel-Marx lineage.
Multicultural harmony? Mirpuris and music in Bradford

Focusing on Mirpuris and music in Bradford, this doctoral thesis offers an ethnomusicological dimension to continuing debates on multiculturalism in Britain, within the fields of anthropology, sociology and political science. I engage ethnographically with three spaces of Mirpuri music making – the mehfil, the street, and the festival – in order to develop a ground-level perspective on what it means to live in an increasingly diverse society. By paying close attention to intra-communal generational discourses and practices of music, a synchronic picture of multiculturalism is developed that takes into account local, national and transnational histories. I argue that discursive senses of belonging, articulated through and by music, offer alternative and more broadly inclusive insights into what it means to migrate to Britain, what it means to be born in Britain, and, ultimately, what it means to ‘be’ British. Drawing on theories of multiculturalism, music and migration, nationalism and segregation, my broad argument is that an ethnographic map of Mirpuri music making in Bradford provides a more contemporarily relevant picture of multicultural society than one drawn along racial, or religious, lines alone.

Keywords: diaspora
mirgation
Mirpuri
multiculturalism
Islam
Advisor: Stokes, M