VictorJuiz/thesis huggingface dataset:
Penetration of a shaped charge

A shaped charge is an explosive device used to penetrate thick targets using a high velocity jet. A typical shaped charge contains explosive material behind a conical hollow. The hollow is lined with a compliant material, such as copper. Extremely high stresses caused by the detonation of the explosive have a focusing effect on the liner, turning it into a long, slender, stretching jet with a tip speed of up to 12km/s. A mathematical model for the penetration of this jet into a solid target is developed with the goal of accurately predicting the resulting crater depth and diameter. The model initially couples fluid dynamics in the jet with elastic-plastic solid mechanics in the target. Far away from the tip, the high aspect ratio is exploited to reduce the dimensionality of the problem by using slender body theory. In doing so, a novel system of partial differential equations for the free-boundaries between fluid, plastic and elastic regions and for the velocity potential of the jet is obtained. In order to gain intuition, the paradigm expansion-contraction of a circular cavity under applied pressure is considered. This yields the interesting possibility of residual stresses and displacements. Using these ideas, a more realistic penetration model is developed. Plastic flow of the target near the tip of the jet is considered, using a squeeze-film analogy. Models for the flow of the jet in the tip are then proposed, based on simple geometric arguments in the slender region. One particular scaling in the tip leads to the consideration of a two-dimensional paradigm model of a filling-flow'' impacting on an obstacle, such as a membrane or beam. Finally, metallurgical analysis and hydrocode runs are presented. Unresolved issues are discussed and suggestions for further work are presented.
Engineering carboxymethylproline synthases towards the biosynthetic productions of carbapenem antibiotics

Mechanistic and biocatalytic studies of two carboxymethylproline synthases (CMPSs), CarB and ThnE, members of the crotonase superfamily of enzymes, both in isolation and in conjunction with the activity of the crotonyl-CoA carboxylase/reductase (Ccr) the malonyl-CoA synthetase (MatB) and the methylmalonyl-CoA epimerase (MCE) are presented.
Protein engineering studies on carboxymethylproline synthases aimed at enabling stereoselective C–C bond formation leading to N-heterocycles via control of trisubstituted enolate intermediates were carried out. Active site substitutions, including at the oxyanion binding site, enabled the production of substituted N-heterocycles in high diastereomeric excesses via stereocontrolled enolate formation and reaction.
The biocatalytic promiscuity of malonyl-CoA ligase and the stereoselectivity of crotonyl–CoA carboxylase/reductase were successfully coupled to the selective tri- substituted enolate forming capacity of engineered carboxymethylproline synthases for the preparation of functionalized 5- and 6-membered N-heterocycles substituted with a variety of alkyl side chains at the C-5/C-6 positions at high diastereomeric excess. The effect of methylmalonyl-CoA epimerase on the diastereoselectivity of the carboxymethylproline synthase-catalysed enolated alkylation was also demonstrated.
The results illustrate the utility of the crotonase superfamily of enzymes for stereoselective biocatalysis and demonstrate the power of coupled enzyme systems to enhance diastereoselectivity and to expand the range of accepted substrates.

Keywords: carbapenems
combinatorial biosynthesis
carboxymethylproline synthases
Advisor: Schofield, C
Social identity theory and intergroup attributions

The central proposition of this thesis is that intergroup attributions and explanations, like any other intergroup behaviour, are affected by the perceived relations between the groups. Social Identity Theory (SIT) was adopted as the theoretical framework within which to investigate intergroup relations. According to this theory, intergroup behaviour is affected by the relative status the groups bear to each other, together with the perceived legitimacy and stability of this status hierarchy. The thesis proposes two amendments to the theory. It is argued that perceived legitimacy and perceived stability have different effects on intergroup behaviour and hence can not be subsumed under the general category of "insecure comparisons". It is also suggested that intragroup variability exists in these perceptions. A study was conducted which confirmed these propositions, and predictions emerging from SIT concerning the effect of these perceptions on intergroup behaviour and attitudes received considerable support.
In examining the effect of the intergroup perception factors on bias in intergroup attributions, the thesis focuses on two types of groups: race and gender. Three types of attribution were considered in different studies: explanations of intergroup inequality, attributions of blame for rape or robbery and attributions for individual group members' actions and outcomes. The results indicate that the relative status of the groups, together with the perceptions of the legitimacy of this status hierarchy influence the first two - the explanations for inequality and the attributions of blame made to the victim and perpetrator of crimes. In general, it appears that the 'prise de conscience' of the illegitimacy of the intergroup situation is the motivating force in rejecting the domination of the high status group over the low status group, by members of both the high and low status groups.
However, the third type of attributions, the intergroup explanations made for individual group members' actions and outcomes were not in general affected by these factors. It was suggested that either the intergroup aspect of these vignettes lacked the salience to elicit an intergroup response, or that the actors in the vignettes were treated as atypical of the groups.

Advisor: Jaspars, J
Jaspers, J
Studies on Pyridine n-oxides

The work described herein is directed towards the Claisen rearrangements and [3+2] cycloaddition reaction of pyridine N-oxide systems. The pyridine N-oxide molecule is a very versatile and useful synthetic intermediate for the construction of more complex pyridines.
Chapter 1 contains a review of work carried out within the group towards Claisen rearrangement of benzene-type systems. The acid catalysed rearrangement of these systems affords a high degree of regioselectivity. A literature survey of the [3+2] cycloaddition reaction of both aliphatic nitrones and aromatic N-oxides with various dipolarophiles is also included. Access to many stereochemically pure products demonstrates that the [3+2] cycloaddition has become a very important ring-forming reaction.
Chapter 2 describes development of two Claisen rearrangement precursors and their subsequent attempted Claisen rearrangement is outlined.
Chapter 3 details the construction of a range of 3-substituted pyridine N-oxides. Their attempted intermolecular cycloaddition, by thermal means and at high pressure, with mono- and di-activated dipolarophiles is described.
Chapter 4 outlines attempts towards and the final synthesis of the ester cycloaddition precursors. Attempted intramolecular [3+2] cycloaddition of these substrates both thermally and under high pressure is summarised.
Chapter 5 describes approaches towards [3+2] cycloaddition precursors that contain mono- and di-activated dienophiles. The synthesis of a variety of 3-substituted pyridines is detailed.

Advisor: Harwood, L
The theological dimensions of F.W.J. Schelling's theory of symbolic language

In this thesis I examine Schelling’s construction of symbolic language in §73 of his Philosophie der Kunst. I approach this construction in three ways. First, I compare Schellingian symbolic language to other contemporary theories of the symbol and language (in particular, those of Goethe, Kant and A.W. Schlegel). While Schelling’s theory of symbolic language possesses properties similar to these other theories (the identity of being and meaning, organic wholeness, the co-existence of opposites), I show that it differs in how they are interpreted.
Second, I excavate the metaphysical and epistemological principles from Schelling’s philosophy of the period which underlie this theory of language. Three tenets from the Identitätssystem (as it is called) are crucial: formation, quantitative differentiation and construction. They illuminate why Schelling interprets symbolic language very differently to his contemporaries.
Third, I consider the theological significance of Schellingian symbolic language. This significance is twofold. First, his theory gives rise to a conception of discourse without reference, and so to the notion of a theology without reference. On this basis, Schelling criticises Christian theology for remaining too concerned with referring to God, when what is at stake is rather the degree of intensity to which it produces God. Theology therefore stands in need of reformation. Second, the way in which theology is utilised by Schelling in order to construct symbolic language in §73 of the Philosophie der Kunst itself provides a model for reformed theological practice. I argue that Schelling conceives of traditional theology as material for intensifying the production of God. In this way, an ‘absolute theology’ is engendered which has no concern for reference or for the integrity of the theological tradition.

Keywords: symbol
Romanticism
Schelling
Goethe
reference
Advisor: Pattison, G
'The most affecting eloquence': Wordsworth and silence

This thesis is the first close study of Wordsworth and silence. It uncovers the comprehensive investigation into monastic history and hagiography (with special emphasis on St Basil) that Wordsworth engaged in between 1807 and 1810, showing that the type of silence he valued came from the monastic tradition. I trace Wordsworth’s material commitment to the power of silence through his use of hermit figures and his habit of visiting ruined monasteries. I concentrate on the poetry he composed from 1807 onwards and mark his eight-month residence in 1806-7 at the home of Sir George and Lady Beaumont as the locus at which his intensive interest in monasticism germinated. I thus reveal a new dimension to this important patronal relationship, while additionally offering an analysis of a previously unstudied manuscript pamphlet ('An account of an English Hermit' by Thomas Barnard) which Lady Beaumont sent to the Wordsworths in 1809. I show how Wordsworth’s fascination with monastic sites and silence influenced his understanding of linguistic and political representation, inheritance, community, and pastoral retreat. At the same time, this critical attention to silence aids a revaluation of the religious vision of his work.
The thesis uses this historical and biographical information as a means of closely reassessing formal, linguistic, and generic features of Wordsworth's poetry. At its root, my work is about the natures of language, poetic representation, and readerly experience. How does Wordsworth communicate via silence? How does he use silence to 'create the taste' for his poetry? Where does silence impact on his renovation of genre and conceptions of form? I conclude that, for Wordsworth, silence is a positive gathering of stillness from within that is nourished by patterns of repeated activity and community. It is one of his most profound heuristic tools.

Keywords: monasticism
silence
Wordsworth
Coleorton
pastoral
Advisor: Stafford, F
The social and political development of a new coalfield

The thesis describes the social and political effects of the transformation of the Dukeries district of Nottinghamshire, where seven new coal mines were sunk between 1918 and 1928. The coal companies responsible for developing the Dukeries field constructed new colliery villages 'at the pit gates' as part of their investment. The thesis deals with the history and characteristics of these townships, planned, built and owned by a single authority. Like other new communities, they suffered 'teething troubles'. It proved difficult to engender a unified community spirit as miners and their families migrated from older coalfields throughout Britain during the early years of high labour turnover. Relationships were strained between the miners and the existing residents of the Dukeries, although the aristocrats whose landed estates gave the district its name came reluctantly to favour mining because of the royalties they obtained therefrom. The first years of the new coinmuniti j:.es were beset by difficulties affecting the provision of facilities for education, religion, shopping, female employment and leisure. But the thesis does not just analyse the problems accompanying industrialisation. The power of the employers in the communities they had created produced much characteristic of company towns. Political representation and control was retained by the colliery companies and the old leaders of Dukeries society, while the Labour Party was not founded until the 194Os. The 'non-political' Spencer Union, a Nottinghamshire phenomenon, monopolised trade unionism in the new pits. Minor regulations were enforced in the villages by uniformed company policemen. As 'benevolent paternalists', the companies sponsored stores, sport, recreation and even religion. The notion of the orderly 'model' village was encouraged as a means of disciplining the workforce. The predominant characteristics of the colliery villages did not disappear until the 194Os, when the war followed by nationalisation destroyed the power of the private owners.
Mathematical modelling of oncolytic virotherapy

This thesis is concerned with mathematical modelling of oncolytic virotherapy: the use of genetically modified viruses to selectively spread, replicate and destroy cancerous cells in solid tumours. Traditional spatially-dependent modelling approaches have previously assumed that virus spread is due to viral diffusion in solid tumours, and also neglect the time delay introduced by the lytic cycle for viral replication within host cells.
A deterministic, age-structured reaction-diffusion model is developed for the spatially-dependent interactions of uninfected cells, infected cells and virus particles, with the spread of virus particles facilitated by infected cell motility and delay. Evidence of travelling wave behaviour is shown, and an asymptotic approximation for the wave speed is derived as a function of key parameters.
Next, the same physical assumptions as in the continuum model are used to develop an equivalent discrete, probabilistic model for that is valid in the limit of low particle concentrations. This mesoscopic, compartment-based model is then validated against known test cases, and it is shown that the localised nature of infected cell bursts leads to inconsistencies between the discrete and continuum models.
The qualitative behaviour of this stochastic model is then analysed for a range of key experimentally-controllable parameters. Two-dimensional simulations of in vivo and in vitro therapies are then analysed to determine the effects of virus burst size, length of lytic cycle, infected cell motility, and initial viral distribution on the wave speed, consistency of results and overall success of therapy.
Finally, the experimental difficulty of measuring the effective motility of cells is addressed by considering effective medium approximations of diffusion through heterogeneous tumours. Considering an idealised tumour consisting of periodic obstacles in free space, a two-scale homogenisation technique is used to show the effects of obstacle shape on the effective diffusivity. A novel method for calculating the effective continuum behaviour of random walks on lattices is then developed for the limiting case where microscopic interactions are discrete.

Keywords: travelling waves
reaction-diffusion
tumour
delay differential equations
oncolytic virotherapy
modelling
stochastic simulation algorithm
Advisor: Chapman, S
Breward, C
Waters, S
Mechanistic and inhibition studies on gamma-butyrobetaine hydroxylase

Carnitine is an essential metabolite in the human body. It carries out several roles in human metabolism, including that in fatty acid metabolism. γ-Butyrobetaine hydroxylase (BBOX) is an Fe(II) and 2-oxoglutarate dependent oxygenase, which catalyses the final step of carnitine biosynthesis, i.e. hydroxylation of γ-butyrobetaine (GBB) to carnitine. Inhibition of BBOX has potential in the treatment for cardiovascular diseases.
The work described in this thesis focussed on mechanistic and inhibition aspects of BBOX catalysis. Firstly, a set of analytical tools for BBOX activity measurements was developed. The synthesis of fluorinated substrate analogues provided the basis for development of two assays for use in vitro with the isolated protein and in lysates, with detection by fluorescence or 19F NMR, respectively. Furthermore, the use of 19F NMR to monitor protein-ligand interactions was exemplified with the work on metallo-β-lactamases.
The developed fluoride-release assay was then used to screen a library of small molecules and led to recognition of scaffolds with potential applications as inhibitors. Further structure-activity relationship studies led to the identification of potent BBOX inhibitors, which were then evaluated for their activity in cells. The crystal structure of human BBOX with one of the lead inhibitors revealed that BBOX can undergo significant conformational changes, involving a movement of an active site loop. BBOX conformational flexibility may have a role in the GBB mediated substrate inhibition observed both with isolated protein and in cells.
In addition to the mechanistic and functional studies, the potential of BBOX as a biocatalytic tool was examined. BBOX has been shown to catalyse a hydroxylation of the symmetrical dialkyl piperidine carboxylic acids, leading to formation of up to three stereocentres in one reaction.
In the last part of this work properties of human BBOX were compared to BBOX from Pseudomonas sp. AK1, revealing differences in kinetic behaviour and substrate specificity. Novel substrates for bacterial BBOX were identified. Pseudomonas sp AK1 BBOX was shown to hydroxylate amino acid analogues leading to formation of 1,2-amino alcohols.

Keywords: gamma-butyrobetaine hydroxylase
carnitine
Advisor: Schofield, C
Stepping dynamics of the bacterial flagellar motor and F1-ATPase

Rotary molecular motors are protein complexes which convert chemical or electrochemical energy from the environment into mechanical work in the form of rotary motion. The work in this thesis examines two of these motors: the F1 portion of F1FO- ATP synthase, which is responsible for ATP production in bacteria and eukaryotes, and the bacterial flagellar motor (BFM), which rotates the flagella of a bacterium, enabling locomotion. The aim of these investigations was to measure the stepping dynamics of these motors, in order to further elucidate details of the stepping mechanism, the mechanism of rotation, and the mechanochemical cycle. A back-scattering laser dark field microscope of unprecedented resolution was designed and constructed to observe the rotation of gold nanoparticles attached to fixed motors. This micro- scope is capable of sub-nanometer and 20μs resolution.
The protocols and algorithms to collect and analyze high resolution rotational data developed for these experiments have yielded novel discoveries for both F1 and the BFM. While most of the previous single-molecule work has been done on F1 from the thermophilic Bacilus PS3 (TF1), only mitochondrial F1 has been well characterized by high-resolution crystal structures, and single-molecule studies of mesophilic F1 are lacking. This thesis presents evidence that mesophilic F1 from E. coli and wild type yeast F1 from S. cerevisiae are governed by the same mechanism as TF1 under laboratory conditions. Experiments with yeast F1 mutants allow a direct comparison between single-molecule rotation studies and high resolution crystal structures. A data set of unprecedented size and resolution was acquired of high speed, low load BFM rotation, enabling the first observation of steps in the BFM under physiological conditions. Preliminary results from this analysis question previously published results of the dependence of speed on stator number at low load and provide novel hypotheses necessitating new models of BFM rotation.

Keywords: Bacterial Flagellar Motor
F1-ATPase
Molecular Motor
Microscopy
Advisor: Berry, R
An integrative framework for computational modelling of cardiac electromechanics in the mouse

This thesis describes the development of a framework for computational modelling of electromechanics in the mouse, with the purpose of being able to integrate cellular and tissue scale observations in the mouse and investigate physiological hypotheses. Specifically, the framework is applied to interpret electromechanical coupling mechanisms and the progression of heart failure in genetically modified mice.
Chapter 1 introduces the field of computational biology and provides context for the topics to be investigated.
Chapter 2 reviews the biological background and mathematical bases for electromechanical models, as well as their limitations.
In Chapter 3, a set of efficient computational methods for coupled cardiac electromechanics was developed. Among these are a modified Newton method combined with a solution predictor which achieves a 98% reduction in computational time for mechanics problems.
In Chapter 4, this computational framework is extended to a multiscale electromechanical model of the mouse. This electromechanical model includes our novel cardiac cellular contraction model for mice, which is able to reproduce murine contraction dynamics at body temperature and high pacing frequencies, and provides a novel explanation for the biphasic force-calcium relation seen in cardiac myocytes. Furthermore, our electromechanical model of the left ventricle of the mouse makes novel predictions on the importance of strong velocity-dependent coupling mechanisms in generating a plateau phase of ventricular pressure transients during ejection.
In Chapter 5, the framework was applied to investigate the progression of heart failure in genetically modified 'Serca2 knockout' mice, which have a major disruption in mechanisms governing calcium regulation in cardiac myocytes. Our modelling framework was instrumental in showing for the first time the incompatibility between previously measured cellular calcium transients and ventricular ejection. We were then able to integrate new experimental data collected in response to these observations to show the importance of beta-adrenergic stimulation in the progression of heart failure in these knockout mice.
Chapter 6 presents the conclusions and discusses possibilities for future work.

Keywords: genetically modified mice
computational biology
electromechanics
cardiac modellling
Advisor: Smith, N