VictorJuiz/thesis huggingface dataset:
Ionic basis for variability in repolarisaion and its implications in pathological response

Sudden cardiac death represents one of the leading causes of death worldwide, with the majority of these deaths caused by arrhythmias derived from ischæmic events. However, the mechanisms leading from ischæmia to re-entry, arrhythmia and eventual death are poorly understood. Furthermore, variability in the action potential of cardiac tissue, while important in determining arrhythmic risk, is only recently being addressed in computational modelling, with little known about the causes and mechanisms underlying it, nor regarding its evolution in response to pathological conditions such as ischæmia.
This dissertation investigates the causes of variability in the repolarisation of the action potential of the rabbit ventricular myocyte, and the response of this variability to ischæmia. The effect of variability in ion channel conductances is investigated by means of a complete search of the parameter space revealed by simultaneous variation in multiple parameters describing ion channel conductances in computational models of the rabbit ventricular action potential. Rabbit data and models are used in this thesis due to the similarities to human data, both in terms of electrophysiology generally, and the response to ischæmia specifically. The response of two different model frameworks is assessed to determine similarities and differences between model frameworks that are designed to reproduce the same system. Those models producing action potential durations that fall within an experimentally derived range at multiple pacing rates are used to define model populations that thus reproduce experimental variability in repolarisation. These model populations are used to investigate the effects of ischæmic conditions on population variability. Variability is measured not only for action potential duration, but also for other biomarkers commonly implicated in the development of re-entry.
The work presented in this dissertation is significant for: (1) presenting a comprehensive study of the effect of simultaneous variation in ion channel conductances, with details regarding the interactions between conductances and how these interactions change depending on the pacing rate; (2) detailed examination of the differences between two models of the same system; (3) production of the largest extant populations reproducing experimentally observed variability in action potential duration; (4) the first time model populations have been used to investigate the effects of ischæmia on variability.

Keywords: Population Modelling
Action Potential
Cardiovascular disease
Variation
Ischemia
Computational Biology
Rabbit Ventricular
Advisor: Rodriguez, B
Burrage, K
Quinn, T
Short wavelength lasers and their applications

Most of this thesis describes experiments conducted in order to generate soft x-rays of energy >67 eV from a laser-generated plasma, in order to pump the Xe III Auger laser at 109 nm.
In attempts to obtain the optimal sub-nanosecond laser pulses for amplification in a very simple KrF (248 nm) laser a compact KrF oscillator was used to obtain 1 ml pulses of FWHM duration 2 ns, and plasma-truncated reflection of a focused KrF beam from metal targets gave 1.8 ns pulses. Longer pulses were obtained by truncated stimulated Brillouin scattering (TRUBS), and by plasma-truncated spatial-filtering.
Experiments were conducted to pump the Xe III laser using the leading edge of a 20 ns KrF laser pulse. An off-axis spherical mirror produced a 3 cm line plasma on a tantalum target. A poor conversion efficiency to soft x-rays was observed. Unexpectedly poor KrF beam quality was shown to have been a potential cause, a fault in the detection system having been ruled out. A repeat experiment was started, employing tighter focusing and better KrF beam quality.
A 7 ps KrF laser system was also investigated for the generation of the necessary plasmas. No 109 nm lasing was observed, and a low conversion efficiency into soft x-rays was measured. The short duration of the KrF pulse was suspected as the cause, and some attempts were made to compensate for this by means of preformed plasmas.
Over the course of the work, several aspects of KrF laser technology were improved, including: the characterisation of a novel, safe, solid-state source of fluorine (F2); the quantitative characterisation of nitrogen dioxide (NO2) as a variable attenuator for KrF radiation; and the manufacture of uniform, transparent, electrodes led to the laser system having the highest single pulse energy (2.55 J) of any UV-preionised, discharge-excited, conventional-aperture KrF laser.
Finally, separate work led to the development and absolute characterisation of a laser-plasma source of tunable VUV/EUV/XUV radiation (30 nm to 200 nm; 6 eV to 41 eV), as well as a sodium salicylate scintillator-based detection system. After optimisation of the target material, laser focusing, and micro-channel-plate (MCP) focusing of the plasma emission, an output of between 106 and 107 photons per shot in a 4 nm bandwidth could be delivered on target.
Australian company borrowing, 1870-1893: a study in British overseas investment

In the last three decades of the nineteenth century British capital played a major part in Australian economic development. The flow of capital to the Australian colonies comprised government borrowing on the one hand, and private borrowing by companies on the other. The present study concerns the flow of capital to the private sector of the Australian economy, most which reached the colonies through the medium of finance companies from the mid 'seventies to 1891.
The crux of the study are the new estimates of the annual flow of British capital to the private sector of the Australian economy, excluding mining activity (for which estimates are available), in the 'seventies, 'eighties and 'nineties. Capital reached the colonies through a group of powerful finance companies which employed British capital in the Australian pastoral industry. These companies raised most of their funds in Britain in two ways: first, by issuing short-term debenture bonds, and second, by raising deposits. Debentures were issued by pastoral mortgage and investment companies, and deposits were collected by Australian banks. As the available estimates of this flow of capital are wholly inadequate, the present study contributes a new annual series of Australian company borrowing which was calculated directly from balance-sheets and other data, and not by taking a residual of the balance of payments. In addition, a calculation was made, from 1881 to 1891, on an annual basis, of the total burden of indebtedness of the Australian colonies accruing from government borrowing and this form of company borrowing.

Keywords: economic development
Australia
borrowing
Performing a political shift: avant-garde music in Cold War Spain

In my thesis, Performing a Political Shift: Avant-Garde Music in Cold War Spain, I argue that towards the end of the 1950s the Spanish ultra-conservative regime of Francisco Franco started to promote avant-garde music. This music contrasted with the aesthetically conservative one that had been promoted since the end of the Civil War (1936-1939). I examine the causes of this shift and reveal for the first time that they are connected to specific trends in Spanish politics and policies.
In terms of national politics, the second phase of the Spanish dictatorship, from the late 1950s until Franco’s death in 1975, was dominated by young ministers who wanted to distance themselves from previous cabinets, mostly controlled by ultra-nationalist fascist politicians. These younger politicians styled themselves as part of a ‘technocratic’ regime. Thanks to its supposed ‘objectivity’ and ‘purely musical’ ideology-free concerns, avant-garde music sat well with these technocrats’ views of modern Spain, that is, a country benefitting from ‘objective’, ideology-free progress. On an international level, the defeat in the 1940s of Mussolini and Hitler, Franco’s main allies, had resulted in isolation for Spain. In order to break this isolation, the Spanish regime started to make a sustained effort at the end of the 1950s to establish diplomatic relations with other Western countries. These relations resulted in cultural, economic and military agreements with European democracies and the US.
I also consider why recent Spanish musicology has failed to confront the political implications of the promotion of avant-garde music under Franco. I connect this void with the Spanish transition to democracy (1975-1978), which recent historians have called an exercise in amnesia, a discourse of forgiveness meant to promote reconciliation between Spaniards. As a result of this transition, the political implications of the activities of the composers and musicologists during the Franco years have been ignored or forgotten.
The results of my thesis challenge the widely accepted view of the European avant-garde as a left-leaning movement. The main contribution of my thesis is precisely its substantial consideration of the cultural and political meanings of the avant garde and its context, using Franco’s Spain as a case in point.

Keywords: propaganda
Falla
Spain
Cold War
Opus Dei
Franco
Halffter
avant-garde music
Advisor: Senici, E
A study of the expression of a protein proteinase inhibitor from sweet corn

Sweet Corn Inhibitor (SCI), a small (11811Da.) protein from the seeds of opaque-2 corn is a potent and specific inhibitor of trypsin and the activated Hageman Factor (Factor βXIIa) of the human blood plasma coagulation system. With the eventual aim of obtaining insight into the structure- function relationships of the selective SCI-pXIIa interaction, a synthetic gene for SCI was cloned into Saccharomyces cerevisiae (yeast) and Escherichia coli (E.coli) expression systems in an attempt to obtain overexpression of the recombinant gene product. The establishment of functional expression, together with an isolation and purification procedure for SCI would provide a system for obtaining selected reactive-site mutants of SCI by cassette- and oligonucleotide-directed mutagenesis.
A yeast secretion vector for a truncated form of SCI (tSCI) was constructed by cloning the gene for α-factor prepro-tSCI fusion, downstream to the α-mating factor (MFα1) promoter of yeast. Yeast transformants containing the expression vector failed to express and secrete the desired product.
The synthetic gene encoding the complete SCI sequence was cloned into E.coli expression vectors that directed both cytoplasmic and periplasmic expression. In cytoplasmic expression, the SCI gene was cloned directly downstream to the powerful, inducible λ-phage PL- and trc-promoters. No expression was obtained with the latter. With the former, expression levels of up to 3% of the total bacterial protein were obtained. These levels were improved 3- to 4-fold on incorporation of the E.coli dnaY gene product. Solubilisation and refolding of the purified SCI inclusion bodies failed to yield the active, correctly folded product. Failure to obtain an N-terminal sequence indicated an incompletely processed N-terminal methionine. For periplasmic expression, SCI, fused in-frame to the signal sequence of OmpA, a major E.coli outer membrane protein, was cloned into the same λ-phage PL promoter vector. High levels (=10%) of expression of insoluble SCI were obtained. The nearly homogeneous product was obtained by a two-step procedure, involving ion-exchange chromatography, followed by hydrophobic interaction chromatography. Characterisation by N-terminal sequencing, SDS-PAGE and electrospray mass spectrometry, confirmed the presence of correctly processed SCI in the form of covalently associated dimers. Refolding studies are at present in progress.

Advisor: Lowe, G
Enterprise in orbit

The objective of this study is to develop a general understanding of the evolution of the commercial communication satellite industry. Initial information classifies the industry as an oligopoly with the vendors as price setters. The approach to this thesis is to examine the supply and demand of satellites as a capital good.
Assuming the demand curve slopes downwards, the study examines the change in the price of a standard unit satellite. The underlying motivation is the conventional identification problem. Over three generations, the technical attributes of communication satellites are advancing. Taking the hedonic regression approach, the price of satellites is shown to decrease over time. Exploring the relationship between price and complexity, it is demonstrated that in the short-run the oligopoly structure of this industry is accompanied by a simple form of cost-plus price-setting. This finding solves the identification problem, so that simultaneous equation methods are not required. Assuming a constant degree of monopoly power in the industry, changes in multi-factor productivity are estimated. Productivity growth increases until 1980, but decreases slightly afterwards. The learning coefficients estimated for this industry are smaller than those found for the airframe industry.
The fall in quality-corrected prices, however, is not big enough to support the interpretation that the expansion of satellite capacity was due to supply shifts along a stationary market demand schedule. Factors driving demand lead to a faster rate of expansion outside the original western world, but in the second half of the period, the ability to use software data compression moderated the rate of growth of demand for new satellites. The study explains the adjustment of the stock of satellite capacity in response to the desired stock: the speed at which countries adjust their stock depends on their characteristics and regional profile.
Structural and thermogravimetric studies of alkali metal amides and imides

This work presents an in-depth study of the crystal structures and hydrogen sorption potential of the Li - N - H and Li - Na - N - H systems. The structures of the materials have been studied using X-ray and neutron diffraction, Raman spectroscopy and inelastic neutron scattering. The behavior of the materials during heating was studied using variable temperature X-ray diffraction, intelligent gravimetric analysis in conjunction with neutron diffraction, intelligent gravimetric analysis combined with mass spectrometry and differential scanning calorimetry.
The role of cation disorder in the Li - N - H (D) system has been explored, indicating that crystallographic ordering of the Li+ ions within lithium amide and lithium imide significantly affects the hydrogen sorption properties of the materials. Order-disorder transitions were observed both during hydrogen desorption from ordered LiNH2 and during deuterium adsorption on ordered Li2ND. Such transitions were not observed in disordered samples of the materials. The intrinsic disorder and the stoichiometry of Li - N - H(D) materials was shown to depend strongly on the techniques used during their synthesis.
Studies regarding the synthesis, crystal chemistry and decomposition properties of the mixed Li / Na amides are presented. Two distinct mixed Li / Na amides of formulae Li3Na(NH2)4 and LiNa2(NH2)3 were observed in the LiNH2 / NaNH2 phase space. Na was also seen to be soluble in LiNH2, forming sodium-doped LiNH2 . Li3Na(NH2)4 and Na-doped LiNH2 were found to exhibit significant cation non-stoichiometry, whereas LiNa2(NH2)4 was shown to exist as a line phase material.
Thermogravimetric and calorimetric studies of the mixed Li / Na amides suggested that these materials decompose primarily with loss of H2.

Keywords: alkali metal imidies
scanning calorimetry
alkali metal amides
gravimetric analysis
neutron diffraction
x-ray diffraction
Advisor: Edwards, P
Structure and dynamics of picornavirus capsids to inform vaccine design

The physical properties of viral capsids are major determinants of vaccine efficacy for several picornaviruses which impact on human and animal health. Current picornavirus vaccines are frequently produced from inactivated virus. Inactivation often reduces the stability of the virus capsid, causing a problem for Foot and Mouth Disease Virus (FMDV) where certain serotypes fall apart into pentameric assemblies below pH 6.5 or at temperatures slightly above 37°C, destroying their effectiveness in eliciting a protective immune response. As a result, vaccines require a cold chain for storage and animals need to be frequently immunised.
FMDV is a member of the Aphthovirus genus of the Picornaviridae. Globally there are seven FMDV serotypes: O, A, Asia1, C and SAT-1, -2 and -3, contributing to a dynamic pool of antigenic variation. As part of collaboration between the Division of Structural Biology, Oxford University, The Pirbright Institute, Reading University and ARC, Ondespoort, South Africa we sought to rationally engineer thermo-stable FMDV capsids either as infectious copy virus or recombinant empty capsids with improved thermo-stability for improved vaccines. In this project, in silico molecular dynamics (MD) simulations, molecular modelling, free energy calculations, X-ray crystallography, electron microscopy and various biochemical/biophysical techniques were used to design and help characterise the capsids.
For the most unstable FMDV serotypes (O and SAT2), panels of stabilising mutants were characterised by MD. Promising candidates were then engineered and shown to confer increased thermo- and pH-stability. Thus, in silico predictions translate into marked stabilisation of both infectious and recombinant empty viral capsids. A novel in situ method was used to determine crystal structures for quality assessment and to verify that no unanticipated structural changes have occurred as a consequence of the modifications made. The structures of the wildtype and two of the stabilised mutants were solved and the antigenic surfaces shown to be unchanged.
Animal trials showed stabilised particles can generate a similar or improved neutralising antibody response compared to the traditional vaccines and may therefore lead to a new generation of stable and safe vaccines.

Keywords: Picronavirus
Viruses
FMDV
Vaccine
Advisor: Stuart, D
John Chrysostom’s discourses on his first exile

The Sermo antequam iret in exilium and the Sermo cum iret in exsilium are two homilies allegedly pronounced by John Chrysostom in Constantinople at the end of summer 403, some time between the verdict of the Synod of the Oak and the day he left the city for his first exile. The aim of the thesis is to demonstrate that a new critical edition of these texts is needed before any study of their literary and historical value can be conducted.
Chapter one sketches the historical background to which the text of the homilies refers and a concise survey about previous scholarship on the homilies on the first exile, from the time of Montfaucon’s edition until our days. The problem of the authenticity occupies the last part of the chapter.
Chapter two investigates the history of the texts and takes into account both the direct and indirect traditions. It discusses the existence of double recensions hitherto unknown and provides the prefatory material for the new critical edition of recensio α of Sermo antequam iret in exilium and of the Sermo cum iret in exsilium.
Chapter three comprises the Greek editions of the two homilies, as well as a provisional edition of the Latin version of the Sermo antequam iret in exilium.
Chapter four is divided into two parts, each presenting a philological commentary on the text of the new editions. Systematic analysis of all the most important variant readings is offered.
The final chapter summarizes the new findings and assesses the validity of previous criteria used for discerning the authenticity of the homilies on the exile.

Keywords: Alexandria
Constantinople
patristics
translations
Armenia
history of the Church
Antioch
textual criticism
Byzantine studies
John Chrysostom
Syriac studies
Greek and Latin palaeography
Armenian studies
Advisor: van Lint, T
Wilson, N
Within-host evolution of HIV-1 and the analysis of transmissible diversity

The central problem for researchers of HIV-1 evolution is explaining the apparent design of the virus for causing pandemic infection in humans: understanding how HIV-1 spreads is key to halting the pandemic. Current knowledge of how HIV-1 spreads from host to host is based upon experimental observation and indirect inferences informed by theory. The hypothesis of this thesis is that diversity of HIV-1 around the time of transmission is important for viral adaptation to a new human host, rather than intrinsic superiority of particular strains found in infectious fluids from human donor hosts, and that studying recombination is important for understanding this behaviour. To demonstrate the apparent randomness of transmission, I test the null-hypothesis that hard selection accounts for between-host viral divergence in a rare case study of contemporaneous infection. I explain how the experimental data that I have generated and the analyses I have carried out address certain basic assumptions and predictions about HIV-1 transmission and may inform current strategies for vaccine design. Specifically, my approach contributes to the current literature on HIV-1, by investigating an alternative hypothesis to the single virion theory of sexual transmission and by characterizing the role of recombination in a pseudodiploid virus following multiple-infection.

Keywords: bioinformatics
HIV/AIDS
evolution
clinical virology
Advisor: Phillips, R
Klenerman, P
Optical holography in dichromated gelatin

Coupled wave theory is used to investigate the properties of high quality holograms recorded in dichromated gelatin. Initially, the properties of planar reflection gratings are studied in order to characterize the behaviour of the recording material in detail. Dichromated gelatin is then used to fabricate more sophisticated holograms for several applications.
Chapter 1 contains an introduction to holography, holographic optical elements and coupled wave theory. Chapter 2 contains a detailed review of dichromated gelatin based on published literature and on experimental observations made during work for this thesis. In Chapter 3 the non-linearity of the recording characteristic and changes in the bulk properties of the material during processing are determined. In Chapter 4 the non-uniformity of planar gratings is investigated by making a detailed comparison with a coupled wave theory in which the grating parameters are functions of depth. The effect of different processing procedures on these non-uniformities is demonstrated. In Chapter 5 the mechanism behind the formation of real-time gratings in dichromated gelatin is determined by applying a dynamic form of coupled wave theory. The source of diffraction is found to be a pure absorption grating. In Chapter 6 the use of dichromated gelatin as a medium for copying holograms and for recording efficient noise gratings is demonstrated. In Chapter 7 a theoretical model of holographic optical elements based on vectorial coupled wave theory is presented and is used to investigate the effects of polarisation. In Chapter 8 an optical method for the measurement of distance is developed using the dispersive properties of an on-axis holographic lens. Conclusions are then presented in Chapter 9.

Advisor: Solymar, L
Ward, A