VictorJuiz/thesis huggingface dataset:
Computational modelling and molecular dynamics simulations of ligand-gated ion channels

The Cys-loop ligand-gated super family of ion channels and related proteins have been studied using computational methods. Ligand-gated ion channels (LGIC) are pentameric, neurotransmitter-gated, ion selective receptors which play a key role in synaptic transmission. The nicotinic acetylcholine receptor (nAChR) is the archetypal member of the LGIC family. Found at neuronal-neuronal synapses and neuronalmuscular junctions, it is implicated in a variety of diseases and it plays a key role in nicotine addiction.
Computational techniques are used to investigate different properties of LGICs, such as ion selectivity, the location of the gate, the action of agonists, and the behaviour of the binding pocket. The aim was to apply existing computational methods and develop novel computational methodology to put forth hypotheses relating to both the general function and smaller scale behaviour of this class of membrane proteins. Binding pocket dynamics of AChBP, a high resolution crystal structure homologue of the ligand binding domain of the nAChR, shows increased stability of the binding site in the presence of a ligand. Discreet zones of persistent water molecules were identified, which are involved in bridging ligands to residues in the binding site and may play a structural role. Ensemble docking on ligand-bound and ligand-free molecular dynamics (MD) trajectories illustrates the optimization of the binding site to a bound ligand.
To overcome the lack of complete structures of LGICs, a method was developed to generate model structures of membrane proteins by combining their separate domains. A model of the a? nAChR was generated from homology models of its extracellular and transmembrane domains and the structure was used to analyze various properties such as pore profiles, electrostatics and conformational dynamics. In silico mutagenesis, together with MD and 'ensemble' docking, on the α7 nAChR investigated the role of key residues in the binding site. Residues were identified with computational techniques and verified with experimental work. This illustrates the utility of combining computational and experimental approaches.
During this work, the electron-microscopy structure of the Torpedo marmorata AChR became available. It agreed well with the previously modelled α7 nAChR model. The Torpedo AChR structure was used to make models of other LGICs. Coarse-grain MD allowed the identification of residues in the TM domain interacting with the lipid-bilayer. Born energy profiles through LGIC pores reveal that the EC domain plays a key role in ion selectivity.

Advisor: Sansom, M
Laser trapping of atoms and cavity quantum electrodynamics in fibre-tip microcavities

Constructing a quantum network comprising of matter-based stationary qubits and photonic flying qubits is a key goal towards scalable quantum computing. Individually trapped neutral atoms are amongst the most promising candidates for stationary qubits, while single photons emitted from optical cavities appears to be the best approach to forming flying qubits. This thesis presents a fast and versatile method to trap and transport an array of neutral atoms, with the aid of a spatial light modulator (SLM). We demonstrate trapped 87Rb atoms adapting to the arbitrary and dynamic potential landscapes imposed by the SLM. On top of this we also investigate the inclusion of fibre-tip cavities into the experiment. In these microcavities, the mirrors are replaced by ablated fibre-tip faces, coated in a highly reflective dielectric stack. These have the benefit of small geometries, increasing their scalability; which in turns leads to extremely small mode volumes, allowing for strong coupling with atoms inside the cavity modes. We construct and characterise a high finesse &Fscr; = 120, 000 fibre-tip cavity constructed from two single mode fibres.

Advisor: Kuhn, A
A study of the piezocone penetrometer in normally consolidated clay

The research was intended to enhance the understanding of penetrometer behaviour in normally consolidated clay. The effects of varying penetration rate and clay shear strength were studies and the distribution of pore pressures determined. The meet these objectives laboratory testing was undertaken. Penetration tests were to be performed in tanks of clay consolidated from slurry and maintained under known stresses. An initial series of tests examined the effect of stiff tank walls. These showed unexpectedly high radial boundary stresses were generated with tank to probe diameter ratios of 50:1. This finding dictated laboratory tests with small scale penetrometers in the largest practical size of tank. Field tests with small scale and full size penetrometers demonstrated an absence of scale effect in the penetrometer pore pressures and total stress data. Two consolidation tanks of 580mm diameter and one of 1000mm diameter were built with the facility for maintaining constant stresses on top of the sample during penetration. Piezocone penetrometers of 5cm2 and 1cm2 cross-section were built. Penetration tests were performed from 2cm/s to 3m/s with hydraulic insertion equipment. At lower rates the total cone resistance factor Nkt was shown to be 10.3±0.9 in normally consolidated kaolin. The corresponding pore pressure factor NΔu was 8.25±1.0 at the cone shoulder. A hundredfold increase in the penetration rate increased the Nkt factor by 40% but the NΔu factor was unchanged. Various subsidiary points emerged. The type of strength test used for comparison with penetrometer data is significant. Major strength reductions occur on sample depressurization. These were demonstrated with vane and triaxial tests. Baligh and Levadoux’s method for determining ch from pore pressure dissipation around penetrometers matched experimental data. Ratios of excess pore pressures on the cone face and shoulder show some promise in the evaluation of OCR.

Keywords: cone penetrometer
clay
Advisor: Sills, G
The early years of the Babi movement

This study examines the rise of the Babi movement in its first phase (1844-47), the formative period which has been less fully explored than later phases (1847-52) but deserves a thorough critical examination. An attempt has been made to explain the complex relationship between the intellectual and social aspects of the movement; ideas, events and personalities are seen in a wide historical perspective, and the early impact of the movement on 'ulama, tujjār and other groups in Iranian urban society, and the reactions it evoked from them, are examined.
The first two chapters deal with the intellectual and social climate of Iran in the late 18th and early 19th centuries, with particular attention to the development of millenarian ideas. Chapters III and IV are concerned with the process which eventually gave birth to the movement. The early life of Sayyid 'Alī Muhammad, the Bab, his family background and personal characteristics are discussed in some detail, so as to show the external influences and inner experiences which finally brought him to proclaim a new 'revelation' in 1844. The conflicts and confusions within the Shaykhi ranks, which served as a stimulus to the conversion of those Shaykhi students who formed the first Babi nucleus in Shiraz, are examined; so too the traditional Shi'i ideas and their similarities and differences with the new doctrine.
Chapters Five to Seven study the earliest Babi attempts in the 'Atabāt and Iran to spread the new message to specific groups, and to a wider public in general, and the opposition first of the religious authorities and then of the secular power. Chapter Eight is a case-study of the growth of the early Babi community in Khurasan, within the context of socio-political change, the pattern of the local economy, and inter-communal links in the small rural and urban centres. Chapter Nine, finally, looks at the Bab's own efforts to declare his mission to a wider public; however circumstances forced him to reinterpret the mission in a symbolic way, and for the first time the enormous practical problems which faced the expansion of the movement were realised.
Transatlantic conversations: the art of the interview in Britain and America

This thesis assesses the role of the interview form within literature from the late nineteenth century to the present day. The project contends that the interview, although styling itself as a revealing, authentic, private confession, is a genre of life writing that deeply troubles the model of singular Romantic authorship that it simultaneously promotes. The thesis argues that the interview has been a key site for negotiating conceptions of authorship since its inauguration. Exploring issues of publicity, life writing and gossip, through nineteenth-century newspaper depictions of scandals (chapter one), I argue that the act of interview publication is a staging of the speaking self in the public sphere. In chapter two I triangulate discussions of journalism, celebrity and material modernism to argue that the characteristic modernist authorial persona, far from being revolutionary, avant-garde or iconoclastic, was in fact deeply retrograde. Chapter three examines how the interview operated as a negotiation of the study, the marketplace and the middlebrow in the 1930s, with reference to the popular Everyman magazine series “How Writers Work.” The development of an interrogative interview model in the postwar era forms the subject of chapter four, as I demonstrate how the backdrop of the Cold War transformed the ways in which writers as diverse as Ezra Pound and the Beat poets responded to the interview in their work. The penultimate chapter argues that the Paris Review interview offers a hitherto unrecognised link between New Criticism and New Journalism and can revitalise discussions around the historical institutionalisation of literary studies. Chapter six considers the interview’s prominent contemporary position within world literature as a purveyor of literary value and archive of global cultural memory. Overall, the project illustrates how central the interview has been in the cultural construction of authorship in the last 150 years.

Keywords: Interview; Journalism; Literature in English; Transatlanticism
Advisor: Marcus, L
The effects of gravel extraction on groundwater hydrology

The study which was carried out around gravel pits at Stanton Harcourt (Oxfordshire) and Rinwood (Hampshire) falls into three sections. The first involves an analysis of the groundwater character- istics of the gravels. This includes an estimation of the permeability of the gravels (using single-well dilution methods) and an analysis of the recharge mechanisms operating in them. The latter is based upon observed relationships between groundwater fluctuations and hydrometeorological factors.
Secondly, the hydrological effects of gravel extraction and dewatering are analysed. By monitoring groundwater levels, the nature and extent of the zone of drav/dcvm around the gravel pits is determined. Induced recharge from rivers and recirculation of water from surface ditches into the pits, as a result of dewatering, is identified. Estimates of the proportion of induced recharge in groundwater are then made using chemical evidence. A mathematical model of gravel pit dewatering is developed. The influence of hydraulic conductivity and the initial pumping rate in determining the effects of dewatering is established by a series of sensitivity analyses using this model. As a practical example, the model is used to predict the effects of dewatering a new site near Stanton Harcourt. The extent of the drawdown around each stage in its development is determined, and this is used to evaluate the effects on private sources and agriculture in the surrounding area.
Thirdly, the effects of one type of rehabilitation project (i.e. lake formation) are investigated. A method for predicting the final lake level is explained. Deviation of the observed lake levels from those predicted is explained in terms of the sealing effect of fine sediment plus chemical and biological processes. The effects of lake formation on groundwater levels and flow are described, and the changes in water quality produced by the flow of groundwater through a lake are examined.
The role of protein kinase C in platelet activation

The protein kinase C (PKC) superfamily is a key regulator in platelet activation with individual isoforms playing distinct roles. This thesis focuses on the role of the novel PKC isoforms downstream of several agonists using both pharmacological and genetic approaches and human and mouse platelets. Quantification of the protein levels of PKC isoforms identified different levels of the five major PKC isoforms expressed in human platelets and also differences between levels of the same isoform in human and mouse platelets. Use of a selection of broad spectrum and isoform-specific inhibitors, identified both positive and negative novel roles for PKC in the regulation of human and mouse platelets. A net positive role for PKC was found in GPVI, Clec-2, and PAR receptor signalling, with classical isoforms of PKC playing a major role in aggregation and dense granule secretion. A novel negative regulatory role was also identified in the regulation of ADP-induced platelet activation for PKCβ, and both PKCε and PKCβ in human and mouse platelets respectively. Gene knock-out mouse models confirmed a positive regulatory role for PKCθ in αIIbβ3 outside-in signalling but identified no other regulatory role for PKCθ in agonist induced platelet activation. Despite this relatively minor role, functional redundancy was identified between PKCθ and PKCε isoforms in haemostasis, as tail bleeding was significantly increased in mice deficient in both novel isoforms. The work presented here identifies key roles for the PKC superfamily in the complex regulation of platelet activation, with different isoforms supporting and limiting the process of thrombus formation and haemostasis.

Keywords: regulation
platelets
PKC
signalling
Advisor: Pears, CJ
Behavioral optimal consumption and portfolio selection in continuous time

This thesis mainly concerns a continuous-time behavioral consumption model under Kahneman and Tversky’s cumulative prospect theory. Mathematically this is a non- concave maximization problem because of the presence of an S-shaped functional and the presence of so-called probability distortions. By using a quantile method and divide-and-conquer scheme, we solve the problem quite explicitly and the optimal consumption is in general characterized in two parts: the agent has rich consumption above the benchmark in good situations and suffers from hunger (i.e. no consumption) in bad situations. An example is given to show that judging whether the market is good or bad depends highly on the agent’s benchmark. Finally we give the strategy for optimal consumption and portfolio selection to maximize behavioral utilities from both consumption and terminal wealth.

Keywords: divide-and-conquer
quantile method
cumulative prospect theory
consumption
Advisor: Jin, H
A novel route to trans-THFs and the synthesis of sylvaticin

trans-2,5-Disubstituted-tetrahydrofurans (THFs) are a common structural motif in many biologically active natural products, particularly in the Annonaceous acetogenins. This thesis develops a new route for their synthesis and applies it to the total synthesis of the Annonaceous acetogenin sylvaticin. Chapter 1: Introduction – Synthetic routes to trans-2,5-substituted tetrahydrofurans This chapter reviews methods for the synthesis of trans-2,5-THFs that have been applied to natural products synthesis. Chapter 2: Results & Discussion – A Novel Route to trans-THFs The rearrangement of activated 2,5-disubstituted cis-THFs is reviewed and is developed into a new synthetic method for the synthesis of trans-THFs. The reaction proceeds via a hydride shift mechanism to form an oxonium ion. Intramolecular reduction by a tethered hydrosilane stereoselectively forms the trans-THF. The mechanism of the rearrangement is investigated with the use of different stereoisomers and a deuterium labelling study. A cross-over study is carried out which confirms the reaction occurs via the proposed hydride shift mechanism. Chapter 3: Introduction – The Annonaceous Acetogenins This chapter introduces the Annonaceous acetogenins, a biologically active class of natural products often found with THF rings in their structure. The three key areas for their synthesis are explored- the synthesis of the THF core, the synthesis of the butenolide ring, and their coupling. Chapter 4: Results & Discussion – The Synthesis of Sylvaticin The Annonaceous acetogenin sylvaticin is introduced, and its isolation in nature and biological activity reviewed. With the aid of a model system study to extend the scope of the reaction, the methodology developed in Chapter 2 is then applied to the synthesis of sylvaticin. The synthesis, the first to be reported, is completed in a total of 19 linear steps starting from commercially available tetradecatetraene. In order to prove the obtained structure is that found in nature, a comprehensive investigation is undertaken using Mosher ester derivatives and the synthesis of its bis-epimer, 4,36-epi,epi sylvaticin. Chapter 5: Experimental Full experimental procedures and characterisation of compounds are reported.

Keywords: hydride shift
THF
trans-THF
sylvaticin
osmium
Advisor: Donohoe, TJ
Sex and the party: gender policy, gender culture, and political participation in unified Germany

This thesis explores the relationship between gender policy, gender culture, and political participation in unified Germany. It investigates the extent to which political regimes shape citizens' attitudes towards gender roles and examines the effect of such attitudes on women's participation in politics.
The thesis is divided into three parts: The first part explores the differences in gender regime types between the former German Democratic Republic and Federal Republic of Germany during the Cold War period. Building on existing studies, the analysis considers how generations that were socialised in the divided Germany differ in their attitudes toward gender roles. It finds that citizens from West Germany are more socially conservative than citizens from the East. The second part of the thesis tests the effects of these traditional gender attitudes on citizens' participation, focusing on party membership. The analysis highlights that gender gaps in formal political participation in unified Germany still exist, but that these gaps are smaller in the new federal states. The investigation further shows that traditional gender attitudes exert a negative effect on women’s political engagement beyond the predictive power of socio-economic and demographic factors. The final part of this thesis casts a critical look at the political controversy in Germany over the introduction of a cash-for-care subsidy (the so-called Betreuungsgeld). It explores the normative assumptions and ideas about gender roles that have been promoted by Germany's main political parties throughout the policy negotiation process.
Using a combination of qualitative and quantitative methods, the research presented in this thesis draws on, and contributes to, studies on gender, welfare states, political socialisation, and political participation.

Keywords: German politics
gender culture
women's political participation
unified Germany
gender gaps
Advisor: De Vries, C
Sasse, G
Vaughan Williams, song, and the idea of 'Englishness'

It is now broadly accepted that Vaughan Williams's music betrays a more complex relation to national influences than has traditionally been assumed. It is argued in this thesis that despite the trends towards revisionism that have characterized recent work, Vaughan Williams's interest in and engagement with English folk materials and cultures remains only partially understood. Offering contextual interpretation of materials newly available in the field, my work takes as its point of departure the critical neglect surrounding Vaughan Williams's contradictory compositional debut, in which he denounced the value of folk song in English art music in an article published alongside his song 'Linden Lea', subtitled 'A Dorset Folk Song'. Reconstructing the under-documented years of the composer's early career, it is demonstrated that Vaughan Williams's subsequent 'conversion' and lifelong attachment to folk song emerged as part of a broader concern with the intelligible and participatory quality of song and its performance by the human voice. As such, it is argued that the ways in which this composer theorized an idea of 'song' illuminate a powerful perspective from which to re-consider the propositions of his project for a national music.
Locating Vaughan Williams's writings within contemporaneous cultural ideas and practices surrounding 'song', 'voice', and 'Englishness', this work brings such contexts into dialogue with readings of various of the composer's works, composed both before and after the First World War. It is demonstrated in this way that the rehabilitation of Vaughan Williams's music and reputation profitably proceeds by reconstructing a complex dialogue between his writings; between various cultural ideas and practices of English music; between the reception of his works by contemporaneous critics; and crucially, by considering the propositions of his music as explored through analysis. Ultimately, this thesis contends that Vaughan Williams's music often betrays a complex and self-conscious performance of cultural ideas of national identity, negotiating an optimistic or otherwise ambivalent relationship to an English musical tradition that is constructed and referenced through a particular idea of song.

Keywords: Harry Plunket Greene
landscape
embodiment
subjectivity
Englishness
Toward the Unknown Region
vocal pedagogy
song
Ralph Vaughan Williams
national identity
Flos Campi
A Sea Symphony
nationalism
folk song
The House of Life
organology
Riders to the Sea
Songs of Travel
voice
Advisor: Grimley, D
Theology as dialogue and fragment: saying God with David Tracy

This thesis concerns the ideas of ‘dialogue’ and ‘fragment’ in the work of the American liberal Roman Catholic theologian David Tracy (bn. 1939). Dialogue (or ‘conversation’) established itself as a dominant idea for Tracy in the 1980s, whereas the centrality of fragments first emerged for Tracy in the late 1990s, to complicate and refine his earlier thinking. Despite this historical sequence, however, the organisation of this thesis is thematic rather than essentially chronological.
The first three chapters focus on how in the later 1970s and 1980s Tracy adapted his ideas of conversation-dialogue from the thought of the German philosopher Hans-Georg Gadamer. Chapter Four examines some serious objections to Tracy’s concept of dialogic reason, before defending his basic choices and gesturing towards his more recent work as perhaps resolving real previous difficulties.
Chapter Five explores the ‘ontological`’ thinking of Martin Heidegger, valuable for evaluating Tracy despite the latter’s determination to put his own thinking on a more empirical and pluralistic footing. Chapter Six tackles this theme of Tracy’s ongoingly ‘empirical’ sensibility, as well as the importance he has attached to the experiencing human ‘self.’ Tracy’s ideas of human experience and selfhood owe much to William James and to Bernard Lonergan.
Chapter Seven examines ‘correlational’ concepts that Tracy has forged to facilitate Christian theology over the course of his career since Blessed Rage for Order (1975). As Tracy became philosophically and theologically uncomfortable with theism as the supposed essential horizon for theology (around 1990), so the idea of the ‘mystical-prophetic’ emerged to open a door into new horizons of thinking. Chapter Eight highlights an easily overlooked antecedent of the hermeneutical negativity that Tracy’s recent ideas of ‘fragments’ imply: in Gadamer’s sense of the Christina negative ‘sign’ of the Ecce Homo. Chapter Nine then focuses on Tracy’s ideas of thinking through fragments: their adequacy and possible consequences.

Keywords: fundamental theology
hermeneutics
Advisor: Pattison, G