VictorJuiz/thesis huggingface dataset:
Fatty acids and the regulation of pyruvate dehydrogenase interconversion

This thesis presents evidence for a novel mechanism of regulation of pyruvate dehydrogenase (PDH) kinase by fatty acids and also results of a study of muscle triacylglycerol concentration. In animals regulation of PDH complex activity is central to the selection of respiratory fuels and to the conservation of glucose during carbohydrate deprivation. The principal means of regulation of PDH complex is interconversion of phosphorylated (inactive) and dephosphorylated (active) forms effected by PDH kinase and PDH phosphatase. Earlier in vitro studies by others had identified both shorter term (min) and longer term (hours) mechanisms of activation of PDH kinase by fatty acid.
In the present study PDH kinase activity (as measured by rates of ATP-dependent inactivation of PDH complex in extracts) was shown to be increased when rat heart mitochondria were incubated with palmitoyl-L-carnitine [PC] (and other CoA utilising respiratory substrates). The activation of PDH kinase persisted through removal of respiratory substrate following incubation with CCCP. A comparable effect of PC was also demonstrable in heart mitochondria from 48h-starved rats (i.e. the mechanism may be distinct from that which increases PDH kinase activity in starvation). Rates of ATP-dependent inactivation of PDH complex were also increased when extracts of rat heart mitochondria were incubated with palmitoyl-CoA (PCoA); the increase was comparable with that seen on incubation of intact mitochondria with PC. The PC effect in intact mitochondria and the PCoA effect in mitochondrial extracts may not be identical as PCoA further increased PDH kinase activity in extracts from mitochondria incubated with PC.
Rates of incorporation of 32P from [γ-32
A method was developed and evaluated for measurement of triacylglycerol in rat soleus muscle strips with the object of investigating factors that may regulate triacylglycerol synthesis in this muscle. This study was abandoned because, although the method was highly reproducible, great variation was found in the triacylglycerol concentration of individual muscles suggesting the possibility of variable contamination with small amounts of adipose tissue.
Peri basileias

The thesis seeks to investigate primarily the philosophical treatises with the title pe?? [?] which were written in the Hellenistic period, that is from the age of Alexander to the end of the Roman Republic. It aims to discover their contents, purposes, similarities and differences, and so to illuminate the attitudes of philosophers and other educated men to the Hellenistic monarchies. Each work discussed is put as far as possible in its historical context in order to demonstrate the relationship between philosophical theory and political practice, and in order to show how philosophers influenced and were influenced by the kings they advised.
The Introduction discusses the origins and growth of ideas about kingship in the archaic and classical periods: it treats in outline the main influences on later thought.
Part I deals with the known evidence for works pe?? [?]. Chapter 1 concerns treatises addressed to Alexander or written during his lifetime. In particular the evidence for Aristotle's relationship with Alexander is discussed in connection with his alleged pe?? [?]; his section on kingship in book iii of the Politics is analysed; and the Arabic treatise recently discovered is shown to be a forgery of Roman imperial date. The works of Xenocrates and Anaxarchus are also discussed. This chapter is particularly concerned with the rivalries between the various philosophers around the figure of Alexander.
Chapter 2 deals with the other Hellenistic treatises whose authorship is known, by philosophical schools - the Peripatetics, Epicureans, Stoics, and 'Pythagoreans'. Chapter 3 gives the fragmentary evidence from papyri and Suidas.
Part II attempts to fill out this picture, and show the inter-relationship between native and Greek traditions in the world of Hellenistic literature, by taking three extant prose works where a theoretical attitude to kingship can be seen. Again these works are discussed in detail, reconstructed where necessary, and an attempt is made to date them and relate them to their historical background. Chapter 1 deals with the work of Hecataeus of Abdera on Egypt, and especially the section on Pharaonic kingship (preserved in Diodorus book i). Chapter 2 discusses the letter of Aristeas to Philocrates, and especially the relationship between the section on kingship which it contains and the purpose of the work as a whole. Chapter 3 is an analysis of Philodemus, On the Good King according to Homer, which attempts to show the purpose of the work, and the limitations on the use of ideas of kingship in the Roman political world of the late Republic.
There are four appendices, the last of which contains a translation of the new text of the Arabic letter of Aristotle to Alexander On Government, by myself and S.M. Stern; it is given here purely for the convenience of the examiners, since it is unpublished, and should not be considered part of the thesis proper.
Women's rights and reform in provincial Morocco : from disenfranchisement to lack of empowerment

Morocco is oftentimes praised by academics, development workers, and women’s rights activists as a trailblazer for the empowerment of women in the Middle East and North African region. Its reforms in the realm of family legislation and progress made in human development place the country at the helm of liberalising Arab Muslim-majority societies, even more so after the Arab Spring and Morocco’s peaceful transition to a ‘new’ constitutional order. However, a closer look at women’s rights discourses, legal reforms, its texts and implementation, and the public attitudes towards the enhancement of women’s rights reveals a less empowering situation. The purported goals of the Family Code, as the extolled document showcasing Morocco’s attempt at ameliorating (married) women’s rights, of ‘doing justice to women’ while ‘preserving men’s dignity’ mask the reformed law’s reconsolidation of patriarchal family relations. Many legal grey areas within this particular law, as well as clashing principles emanating from other laws such as the Penal Code, allow judges and the ʿaduls (religious notaries) to exercise discretion and apply the law as they see fit and, to a large extent, as it conforms to their and the community’s vision of the ideal moral order. Moreover, because ‘doing justice to women’ affects men’s and family’s honour, the project of the enhancement of women’s rights has had as a result retraditionalisation of family relations and hierarchical gender structures. Nowhere is this more poignant than in the status of educated single adult girls from provincial areas. They may be poster girls for the development community, but they are pitied by their own communities because they fail to become complete women––married (non-employed) mothers. The story of Morocco’s professed progress is a story of empowering its citizens, but one which does so on paper only. It is also a story which hides the salient details of poorly written reformed laws, obstructed access to justice, continuing widespread misogyny, material poverty and social marginalisation, and cohesive socio-economic programmes, which are rarely followed through.

Keywords: Family Law Reform
Women
Middle East and North Africa
Poverty
Human Development
Advisor: Willis, M
Twistor theory and the K.P. equations

In this thesis, we discuss a geometric construction analogous to the Ward correspondence for the KP equations. We propose a Dirac operator based on the inverse scattering transform for the KP-II equation and discuss the similarities and differences to the Ward correspondence. We also consider the KP-I equation, describing a geometric construction for a certain class of solutions. We also discuss the general inverse scattering of the equation, how this is related to the KP-II equation and the problems with describing a single geometric construction that incorporates both equations. We also consider the Davey-Stewartson equations, which have a similar behaviour. We demonstrate explicitly the problems of localising the theory with generic boundary conditions. We also present a reformulation of the Dirac operator and demonstrate a duality between the Dirac operator and the first Lax operator for the DS-II equations. We then proceed to generalise the Dirac operator construction to generate other integrable systems. These include the mKP and Ishimori equations, and an extension to the KP and mKP hierarchies.
Studies on deacetoxy/deacetylcephalosporin C synthase

This thesis describes an investigation of the mechanism of the bifunctional, a-ketoglutarate dependent dioxygenase, deacetoxy/deacetylcephalosporin C synthase (DAOC/DACS), which catalyses the ring-expansion of penicillin N to deacetoxycephalosporin C (DAOC) and the hydroxylation of this to deacetylcephalosporin C (DAC).
The conversion of the unnatural substrate 3-exomethylene cephalosporin C by DAOC/DACS has been investigated in detail. A new metabolite was isolated from incubations of the deuterated [4-2H]-3-exomethylene cephalosporin C, and was identified as the 3β-spiroepoxide cepham, (2Ṟ,3Ṟ,6Ṟ,7Ṟ)-l-aza-[2-2H]-3-spiroepoxy-7-[(5Ṟ)-5-amino- 5-carboxypentanamido]-8-oxo-5-thiabicyclo[4.2.0]octane-2-carboxylic acid. The results obtained indicate that this metabolite is a shunt product whose formation is enhanced by the operation of a deuterium kinetic isotope effect on an enzyme-bound intermediate. It has also been found that this 3β-spiroepoxide cepham is further converted by DAOC/DACS to 3-formyl cephalosporoate products.
The mechanism of oxygenation of DAOC/DACS was investigated through 18O-labelling studies. Incubations of [2-13C,3-2H]penicillin N and [4-2H]-3-exomethylene cephalosporin C with DAOC/DACS were carried out under 18O2 or in H218O. Incorporation of 18O-label into the products [3-13C]DAC, [3-13C,4-²H]-3β-hydroxycepham and 3β-spiroepoxide cepham was observed from both sources. The results suggest that intermediates capable of oxygen-exchange are formed during the enzymatic reactions.
Two substrate analogues, the 5-epipenicillin N and the 2β-difluoromethyl penicillin N, have been synthesised in order to probe the substrate specificity of DAOC/DACS with respect to the ring-expansion activity. The 5-epipenicillin N was not accepted as a substrate by DAOC/DACS, and the observations made indicate that it was unstable under the incubation conditions. No product was either observed from incubations of the 2β-difluoromethyl penicillin N with DAOC/DACS, although bioassay tests suggested a cephem product had been formed in very small amounts.
Finally, the results of a substrate specificity comparison between the soluble recombinant enzymes deacetoxy/deacetylcephalosporin C synthase (DAOC/DACS) from Cephalosporium acremonium and deacetoxycephalosporin C synthase (DAOCS) from Streptomyces clavuligerus are described.

Advisor: Baldwin, J
A study of the (₉Be, ₁₀B) reaction

Angular distributions have been measured for the (9Be, 10B0, 1) reactions on 63Cu, 54Fe, 26,24Mg and 16O at 43 MeV and on 40Ca at 45 and 30 MeV. Several of these experiments were performed with the Oxford MDM-2 spectrometer and the design and testing of its 30 cm focal plane detector, which is of the "hybrid" type, is described. Despite the size of the counter, in particular the large cathode to Frisch-grid separation, the resolution of the ionization signals is comparable with that of smaller counters. The position resolution is < 0.6 mm.
Optical potentials have been obtained from the measured elastic scattering of 9Be from 16O, 26Mg and 40Ca, and 10B from 25Mg and 39K. The exact finite-range DWBA calculations have generally well reproduced the shape of the experimental reaction cross-sections. However, inconsistencies of up to 50% between the extracted spectroscopic factors for 10B0 and 10B1 have been found. This anomaly was found insensitive to changes in either optical potential or bound state parameters.
A new method of form factor calculation is described that uses a shell model potential in conjunction with a surface-peaked potential, the depth of which is adjusted to give the correct asymptotic form to the wavef unctions. Whilst this form factor showed some success, it did not account for the 10B0/10B1 anomaly.
Collective model DWBA analyses of the inelastic excitation of the first 2+ state in 26Mg and 3- state in 40Ca have given values for deformation parameters in reasonable agreement with light-ion work. A CCBA analysis of the 26Mg 2+ state was carried out to estimate the effect of the coupling.
Calculations performed for a two-step reaction process through inelastic excitation of a strongly coupled 5/2- state in the projectile showed that this indirect route is important, but it could not solve the 10B0/10B1 problem alone. The conclusion is that other routes (projectile or target excitation) must be included.

Advisor: Jelley, N
The Oxford Vehicle Model

This dissertation addresses the challenges of scoping and sizing components and modeling the tank to wheel energy flows in new and rapidly evolving classes of automotive vehicles. It introduces a system of computer models, known as the Oxford Vehicle Model (OVEM), which provide for the novel simulation of the powertrains of electric (EV) and hybrid electric vehicles (HEV). OVEM has a three-level structure that makes a unique contribution to the field of vehicle analysis by enabling a user to proceed from performing scoping and sizing exercises through to accurately simulating the energy flows in powertrains of EVs and HEVs utilizing existing and emerging technologies based on real world data.
Level 1 uses simplified models to support initial component scoping and sizing exercises in an analysis environment where uncertainty regarding component specifications is high. Level 2 builds on Level 1 by obtaining more refined component scoping and sizing estimates via the use of component models based on well-understood scientific principles that are product-independent – a crucial feature for obtaining unbiased scoping and sizing estimates. Level 3 employs a high degree of fidelity in that its models impose actual physical limits and are based on data from real technologies.
This dissertation concludes with two chapters based on studies published as journal articles that used OVEM to address key issues facing the development of EVs and HEVs. The first study used OVEM to make the novel comparison between high-speed flywheels, batteries, and ultracapacitors on the bases of cost and fuel consumption while functioning as the energy storage systems in an HEV. The second study applied OVEM towards a novel examination of the CO2 emissions from plug-in HEVs (PHEVs) and compares their CO2 emissions to those from similar EVs and ICE-based vehicles.

Keywords: automobile
modeling
simulating
engine
vehicle
ultracapacitor
simulation
emission
car
motor
hybrid
flywheel
electric
powertrain
vehicles
model
battery
Advisor: McCulloch, MD
QED effects in laser-plasma interactions

It is possible to reach the radiation-reaction–dominated regime in today’s high-intensity laser facilities, using the collision of a wakefield-accelerated GeV electron beam with a 30 fs laser pulse of intensity 1022 Wcm-2. This would demonstrate that the yield of high energy gamma rays is increased by the stochastic nature of photon emission: a beam of 109 electrons will emit 6300 photons with energy > 700 MeV, 60 times the number predicted classically. Detecting those photons, or a prominent low energy peak in the electron beam's post-collision energy spectrum, will provide strong evidence of quantum radiation reaction; we place constraints on the accuracy of timing necessary to achieve this.
This experiment would provide benchmarking for the simulations that will be used to study the plasmas produced in the next generation of laser facilities. With focused intensities > 1023 Wcm-2, these will be powerful enough to generate high fluxes of gamma rays and electron-positron pairs from laser–laser and laser–solid interactions. It will become possible to test the physics of exotic astrophysical phenomena, such as pair cascades in pulsar magnetospheres, and explore fundamental aspects of quantum electrodynamics (QED). To that end we will discuss: classical theories of radiation reaction; QED processes in intense fields; and a Monte Carlo algorithm by which the latter may be included in particle-in-cell codes. The feedback between QED processes and classical plasma dynamics characterises a new regime we call QED-plasma physics.

Keywords: QED-plasmas
plasma physics
quantum electrodynamics
high-intensity lasers
Advisor: Bell, A
Investigation of the signalling and function of NOD2

NOD2 is an intracellular innate immune receptor expressed in dendritic cells and gastrointestinal epithelial cells. Polymorphisms in the NOD2 gene convey a strong predisposition to Crohn’s disease (CD), a form of inflammatory bowel disease. Understanding the function of NOD2, and in what way it is aberrant in the presence of NOD2 polymorphisms, would confer a valuable paradigm for understanding Crohn’s pathogenesis.
CD is thought to arise both from defects in the gut mucosal barrier and from a dysregulated Th17 immune response to commensal gut flora. Aberrant expression of IL-23 is present in both human CD and in murine models of colitis. Wild-type NOD2 contributes to NFκB activation and pro-inflammatory cytokine production on recognition of its cognate ligand, a function that is lost in CD-associated mutations. How the predominantly loss-of-function CD-NOD2 contributes to the pro-inflammatory response present in Crohn’s is not yet understood.
In this thesis a set of experiments is described that aim to shed light on the function of NOD2, firstly through identification of negative regulators of immune activation that are dependent on NOD2 for their expression. This work identifies the microRNAs that are expressed following NOD2 triggering in human dendritic cells. Specifically, up-regulation of the miR-29 family was found to be dependent on wild-type NOD2 function. A number of novel miR-29 targets and their functional consequences are presented, including the cytokine subunits IL-12p40 and IL-23p19, directly linking NOD2 polymorphisms and aberrant IL-23 expression.
Secondly, a project aiming to identify components of the NOD2 signalling complex (or signalosome) is described. To this end I employed a model system that involved tagging NOD2, and stable expression in a human cell line. These clones were validated for expression and function before an immunoprecipitation protocol was optimised. Mass spectrometry analysis of these samples identified the known NOD2-interacting protein Erbin.

Keywords: IL-23
Crohn's Disease
NOD2
IL-12p40
microRNA
Advisor: Simmons, A
The science of progress

This thesis reassess the so-called 'Historical School of Economics' of Gustav Schmoller and his colleagues Lujo Brentano, Adolf Held and Georg Friedrich Knapp, analysing the close relationship between the development of historical economics and the rise of social reform in Germany. It reveals that there is little evidence for a cohesive 'Historical School' and suggests that it was not primarily an outgrowth of romantic and historicist currents of thought as is commonly believed. Schmoller and his colleagues were a pragmatic, empirically-inclined group of statistically-trained economists who drew inspiration from the advances made in the natural sciences. Having directly observed the effects of rapid urbanisation, industrialisation, and the rise of labour movements and socialism in Prussia and abroad, they became dissatisfied with classical economic doctrines and laissez-faire, subjecting these to empirical tests and criticism. Drawing inspiration from British reforms and developments throughout Europe, they devised alternative hypotheses and made innovative policy recommendations. They were also important professionalisers of economics, modifying the curriculum, organising professional bodies, and creating new monographs and journals, the latter substantially aided by the interest and generosity of a leading publisher. Using empirical studies, statistics and history as analytical and critical tools, they sought practical solutions to economic and social problems by disseminating information to both the public and government officials through publications, conferences and petitions. They became leading advocates of trade union rights, factory inspection, worker protection laws, education reforms, worker insurance, agricultural reforms, and the democratisation of industrial relations. Their influence on economic and social policy, while indirect, was considerable, especially through government officials. However, the close association of historical economics with reform and social policy also made them a conspicuous target of criticism within academia and politics. Despite this, by the early 1890s the research methods and social legislation they propounded were gaining wider currency not only in Germany but also in Austria.
Induced regulatory T cells in transplantation tolerance

Induced regulatory T cells (iTreg) play an important role in the induction of tolerance to self and non-self antigens. Harnessing their suppressive potential has therapeutic implications for the treatment of autoimmune conditions and transplant rejection. Although the role of TGFβ-conditioned iTreg in natural and therapeutic tolerance is indisputable, their mechanism of action as well as factors that influence their function and stability in vivo remain unclear. Here it is shown that TGFβ-conditioning of T cells in the absence of any Foxp3 expression is insufficient for conferring a suppressive phenotype in vivo, whilst Foxp3 expression is sufficient to enable naïve T cells to become suppressive both in vitro and in vivo. Graft antigen was found to enhance the number of iTreg-derived Foxp3+ cells localising to the draining lymph nodes of recipients, and this was associated with histone modifications at the Foxp3 locus that suggested a stabilisation or 'affirmation' of Foxp3 expression. Finally, iTreg were shown to 'out-compete' naïve T cells in forming clusters with dendritic cells. Activated inflammatory T cells could also 'out-compete' naïve T cells. However, unlike activated T cells, iTreg did not activate interacting DCs to the same extent, and this may potentially be a mechanism of their action in vivo.

Advisor: Waldmann, H
Howie, D