VictorJuiz/thesis huggingface dataset:
Ligand-macromolecule interactions

The optimisation of ligand-macromolecule interactions is fundamental to the design of therapeutic agents. The GRID method is a procedure for determining energetically favourable ligand binding sites on molecules of known structure using an empirical energy potential. In this thesis, it has been extended, tested, and then applied to the design of anti-influenza agents.
In the GRID method, the energy of a hydrogen-bond is determined by a function which is dependent on the length of the hydrogen-bond, its orientation at the hydrogen-bond donor and acceptor atoms, and the chemical nature of these atoms. This function has been formulated in order to reproduce experimental observations of hydrogen-bond geometries. The reorientation of hydrogen atoms and lone-pair orbitals on the formation of hydrogen-bonds is calculated analytically.
The experimentally observed water structures of crystals of four biological molecules have been used as model systems for testing the GRID method. It has been shown that the location of well-ordered waters can be predicted accurately. The ability of the GRID method to assist in the assignment of water sites during crystallographic refinement has been demonstrated. It has also been shown that waters in the active site of an enzyme may be both stabilized and displaced by a bound substrate.
Ligands have been designed to block the highly conserved host cell receptor site of the influenza virus haemagglutinin in order to prevent the attachment of the virus to the host cells. The protein was mapped energetically by program GRID and specific ligand binding sites were identified. Ligands, which exploited these binding sites, were then designed using computer graphics and energy minimization techniques. Some of the designed ligands were peptides and these were synthesised and assayed. Preliminary results indicate that they may possess anti-influenza activity.

Advisor: Goodford, P
A model study of the end bearing capacity of piles in layered calcareous soils

The results of a series of over 120 model tests to study the end bearing capacity of piles in layered calcareous soils are described. The tests were carried out on samples enclosed in a cylindrical testing chamber, 450 mm diameter and 450 mm high, which allowed independent control of horizontal and vertical stress in the range 25 kPa to 500 kPa. The samples consisted of a loose, uncemented calcareous sand consisting predominantly of foraminifera and mollusc micro-organisms (D50 = 0.2 mm, calcium carbonate content 92%). Into this was built a layer of the same material artificially cemented by a gypsum plaster. The layer had similar properties to naturally cemented deposits, and layers with unconfirmed crushing strengths in the range 500 kPa to 4000 kPa have been prepared. All samples were tested dry. Closed end model piles of 16mm diameter were jacked at 0.1mm/s into the sample, and continuous profiles of end bearing capacity obtained during penetration. A parametric study has been carried out to examine the effects on the bearing capacity of stress level, K0, cemented layer thickness (0.5 pile diameters to 5.0 pile diameters) and layer strength. In addition, tests have been conducted with different pile geometry, multiple cemented layers, and using dynamic installation techniques. The study has identified ranges of parameters for which brittle failure of the cemented layer occurs (low stress levels and high layer strengths) and ranges where the failure is ductile (high stresses and low layer strengths). Characteristic patterns have been observed of the variation of end bearing with position as a layer is penetrated. Examination of the samples after testing has revealed details of failure mechanisms. Simple procedures are proposed for modelling the bearing capacity of such layered systems, and some implications of the results for design methods are discussed.

Keywords: piles
foundation
carbonate soil
Advisor: Houlsby, G
The tailors of London and their guild, c.1300-1500

This thesis examines the roles played by craft organisations or 'guilds' in medieval urban society through a case study of the tailors of London in the fourteenth and fifteenth centuries. Using the records of the City and of the guilds themselves, including the important early records of the Tailors, this study seeks to answer important questions about the nature of these organisations and the impact which they had upon urban society. Far from being the mere 'agents' of municipal governments, craft guilds often performed important and constructive functions on behalf of the artisans themselves. The first two chapters examine the extent to which voluntarism characterized the activities of many of these associations: the guild of London tailors, though unusual in the scale and scope of its spiritual and charitable provision, embodied widely shared principles of association which were not articulated solely through parish guilds. Subsequent chapters look at the ways in which the Tailors' guild expressed and articulated other concerns of their members and those outside the ruling guild: in the sphere of City politics, for instance, the Tailors came to represent the aspirations of many poorer citizens through their struggle for civic prominence. Likewise, in the sphere of economic regulation, this thesis demonstrates the ways in which the Tailors' guild, among others, was able to introduce flexible and pragmatic policies of enforcement, based upon the shared interests of those inside and outside the decision-making groups. The final section of the thesis then examines more closely the limitations of impressions of economic structures derived purely from guild statutes. First, the nature of apprenticeship and servanthood in medieval London is examined with particular emphasis upon the differing perceptions of these 'life-cycle institutions' by all concerned. Secondly, a systematic analysis of the structure of the tailoring industry in London is carried out and explores the remarkable diversity of economic life in the capital.
The New Hellenism: Oscar Wilde and ancient Greece

I examine Wilde’s Hellenism in terms of the specific texts, editions and institutions through which he encountered ancient Greece. The late-nineteenth-century professionalisation of classical scholarship and the rise of the new science of archaeology from the 1870s onwards endangered the status of antiquity as a textual source of ideal fictions rather than a material object of positivist study. The major theme of my thesis is Wilde’s relationship with archaeology and his efforts to preserve Greece as an imaginative resource and a model for right conduct. From his childhood Wilde had accompanied his father Sir William Wilde on digs around Ireland. Sir William’s ethnological interests led him to posit a common racial origin for Celts and Greeks; thus, for Wilde, to read a Greek text was to intuit native affinity. Chapters 1–3 trace his education, his travels in Greece, his involvement with the founding of the Hellenic Society, and his defence of the archaeologically accurate stage spectaculars of the 1880s, arguing that in his close association with supporters of archaeology such as J.P. Mahaffy and George Macmillan Wilde exemplifies the new kind of Hellenist opposed by Benjamin Jowett and R.C. Jebb. Chapter 4 makes a case for Wilde’s final repudiation of archaeology and his return to the textual remains of Greek antiquity, present as an intertexual resource in his mature works. Thus I examine the role of Aristotle’s Ethics in 'The Soul of Man Under Socialism’ and of Platonism in the critical dialogues, The Picture of Dorian Gray and ‘The Portrait of Mr W.H.’ I present The Importance of Being Earnest as a self-conscious exercise in the New Comedy of Menander, concluding that Wilde ultimately returned to the anachronistic eclecticism of the Renaissance attitude to ancient texts.

Keywords: Wilde
Greece
homosexuality
nineteenth-century
archaeology
Greek
theatre
Victorian
Oscar
Hellenism
Advisor: Sloan, J
Social mobilisation and the pure presidential democracies of Latin America

This thesis seeks for an explanation of social mobilisation by examining the nuts and bolts of the institutional design of democracies. Since the nature of executive-legislative relations in democracy is an important influence on the distribution of policy outcomes between actors in society, and consequently on the extent of support (or inclusion) of citizens to the way power is exercised, the present work investigates how pure presidentialism (and the whole range of institutional accessories that can be combined with this particular executive) affects the opportunities and constraints for social mobilisation. This is done by conducting a within-format comparison across pure presidential regimes in Latin America, where most pure presidential regimes are located.
The thesis is grounded in both quantitative and qualitative methods of research. Quantitatively, protest events are measured across time and space and the parameters are estimated through pooled cross-sectional time-series models for count data. Qualitatively, three case studies are examined: Bolivia (electoral rules), Ecuador (non-legislative and legislative presidential power) and Venezuela (party system). The main findings of this study are: Within presidential systems social mobilisation is more likely to occur whenever: (1) presidents are selected in runoff elections in the assembly, and (2) constitutions allow the immediate re-election of the president. However, the prospects for social mobilisation are not significantly affected by the extent to which electoral formulae promote the entry of parties to the assembly.
As regards to the relative powers of the presidency and the legislature, the extent of the decree and veto powers of the president do not affect the occurrence of social mobilisation. Instead, the probability of contentious action is greater whenever (3) the capacity of legislatures to censure and sanction the members of the executive is low; and (4) legislatures have weak authority over public spending. Lastly, it is shown that the probability of social mobilisation does not vary across majoritarian and minority governments; neither is social mobilisation susceptible to the levels of electoral volatility in the legislature. Rather, (5) social mobilisation is highest whenever the pro-presidential contingent in the legislature is dominated by one large political party.
The thesis thus concludes by strongly advocating for the inclusion of the format of the executive as an important variable in the comparative study of social mobilisation and of the substantive outputs of a democracy, in general.

Keywords: social movements
Latin American politics
Executive-legislative relations
Advisor: Foweraker, J
The mechanism of Nov (CCN3) function in haematopoiesis

Haematopoietic stem cells (HSC) are strictly regulated by intrinsic regulators and extrinsic signals from the microenvironment. Nov (CCN3), a matricellular protein of the CCN family, has been reported as a suppressor gene in solid tumours and chronic myeloid leukaemia (CML). Recent study identified Nov as a positive regulator in human cord blood CD34+ stem cells. However, the functions of Nov in haematopoiesis and adult HSC remain largely unknown.

Keywords: Haematopoietic stem cells
Nov(Ccn3)
Haematopoiesis
Advisor: Enver, T
Vyas, P
An edition of Owayne Miles and other Middle English texts concerning St. Patrick's Purgatory

St. Patrick's Purgatory is today a pilgrimage centre on Station Island in Lough Derg, County Donegal, Ireland. From the late twelfth to fifteenth centuries the site was one of the most famous pilgrimage centres in Western Europe. Its popularity was spread principally through transmission of a late twelfth century Latin work, the Tractatus de Purgatorio Sancti Patricii, by a Cistercian monk usually known as Henry of Saltrey, or Sawtry in Huntingdonshire. This work tells of the founding of the Purgatory by St. Patrick. During his conversion of the pagan Irish, Patrick prayed to Christ for assistance, and the Purgatory was revealed to him as a physical entrance to the otherworld. Pilgrims spending a day and a night in the 'cave' of the Purgatory would pass bodily through purgatory, and if firm of faith, would also enter the Earthly Paradise. Provided that no unshriven mortal sins were subsequently committed, such a sojourn was deemed sufficient penance to exempt the pilgrim from purgatory after death. The Tractatus also tells of the visit to the Purgatory by an Irish knight, Owayne. His experiences were reported to Henry of Saltrey by another Cistercian monk, Gilbert, former abbot of Basingwerk, Flintshire. In various versions this Tractatus was widely copied throughout Europe, and translated into most Western European vernaculars from Dutch and Spanish to Norwegian. Pilgrims from as far afield as Italy and Hungary have, amongst others, left reports of their visits to the Purgatory, nearly all drawing to a greater or lesser degree on Henry of Saltrey's Tractatus. Six Middle English verse versions were made of Owayne's adventures in the Purgatory.
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The performative construction of identity in the Shang and Zhou dynasties

Judith Butler’s theory of performativity can be productively used to analyse how identity at burial would have been created, sustained and rendered coherent through extended periods of time. Moreover, Heideggerean phenomenology offers us insights into the mechanism underlying the process of performing an identity. Using mortuary data from Shang and Zhou burials, I offer (a) an analysis of how the identity of the deceased might have been (re)constructed and (re)produced through structured burial deposits as well as (b) a Heideggerean account of the heritage inherent in the sets of bronze objects interred in graves. These sets of bronze objects would have been used in a performance within the mortuary sphere as part of an elaborate but recognisable process of producing an identity for a tomb occupant. Furthermore, a gendered identity would have also been reified and materialised through burial assemblages. These post-processual analyses might be taken as examples that can be generalised to a method for further investigating other identities, and the processes underlying their production and reproduction, that Chinese archaeologists theorising burials and identity may use to advance the field.

Keywords: Grave Goods
identity
burials
Bronze Age China
performance
gender
Advisor: Rawson, J
Deformable lung registration for pulmonary image analysis of MRI and CT scans

Medical imaging has seen a rapid development in its clinical use in assessment of treatment outcome, disease monitoring and diagnosis over the last few decades. Yet, the vast amount of available image data limits the practical use of this potentially very valuable source of information for radiologists and physicians. Therefore, the design of computer-aided medical image analysis is of great importance to imaging in clinical practice. This thesis deals with the problem of deformable image registration in the context of lung imaging, and addresses three of the major challenges involved in this challenging application, namely: designing an image similarity for multi-modal scans or scans of locally changing contrast, modelling of complex lung motion, which includes sliding motion, and approximately globally optimal mathematical optimisation to deal with large motion of small anatomical features. The two most important contributions made in this thesis are: the formulation of a multi-dimensional structural image representation, which is independent of modality, robust to intensity distortions and very discriminative for different image features, and a discrete optimisation framework, based on an image-adaptive graph structure, which enables a very efficient optimisation of large dense displacement spaces and deals well with sliding motion. The derived methods are applied to two different clinical applications in pulmonary image analysis: motion correction for breathing-cycle computed tomography (CT) volumes, and deformable multi-modal fusion of CT and magnetic resonance imaging chest scans. The experimental validation demonstrates improved registration accuracy, a high quality of the estimated deformations, and much lower computational complexity, all compared to several state-of-the-art deformable registration techniques.

Keywords: medical image analysis
respiratory motion
multi-modality fusion
image registration
Advisor: Schnabel, J
Jenkinson, M
Brady, M
Antihypertensive drug class effects on inter-individual blood pressure variability and the associated risk of stroke

Visit-to-visit variability in systolic blood pressure (SBP) predicts the subsequent risk of stroke, independent of mean SBP. It was reduced by amlodipine and increased by atenolol in the ASCOT-BPLA and MRC randomized controlled trials (RCTs), explaining the difference in risk of stroke between treatment groups that was not explained by mean SBP. Therefore, I performed a series of systematic reviews to examine the effects of all antihypertensive drugs in RCTs and how these effects relate to the risk of stroke.
Cochrane and Medline databases were searched for systematic reviews and RCTs of antihypertensive drugs. Baseline and follow-up data for mean (SD) SBP and DBP were extracted. Differences in inter-individual variance (SD2) in BP were expressed as a ratio (VR) and risk of stroke was compared by odds ratios (OR). Estimates were pooled by random-effects meta-analysis.
Compared to all other drugs, variability in SBP was reduced by randomization to calcium channel blockers (CCB: VR=0.81 95%CI 0.76-0.86, p<0.0001) and non-loop diuretics (0.87, 0.79-0.96, p=0.007), and increased by ACE-inhibitors (1.08, 1.02-1.15, p=0.008), angiotensin-receptor blockers (1.16, 1.07-1.25, p=0.0002) and beta-blockers (1.17, 1.07-1.28, p=0.0007). Across all trials, effects of treatment on VR SBP (r²=0.372, p=0.0006) and on mean SBP (r²=0.328, p=0.0015) explained effects on stroke risk. Randomization to a CCB reduced the subsequent risk of stroke (OR=0.88, 0.83-0.94, p=0.0002). These effects on VR-SBP were dose-dependent and persisted when drugs were used in combination. Randomisation to a non-selective beta-blocker increased VR more than β1-selective agents (VR=1.23, 1.03-1.47, p=0.03), probably explaining the markedly increased risk of stroke in patients randomized to propranolol in the MRC-mild trial. Effects were not explained by changes in the incidence of new-onset atrial fibrillation.
Effects of antihypertensive drug classes on visit-to-visit variability in SBP explain effects of these drugs on the risk of stroke. CCBs are indicated for patients at increased risk of stroke due to episodic or variable systolic hypertension, but higher doses are required either as monotherapy or in combinations. Non-loop diuretics have smaller benefits, but beta-blockers are associated with increased variability in SBP and risk of stroke, particularly due to non-selective beta-blockers. These should be avoided in patients at an increased risk of stroke.

Keywords: meta-analysis
systematic review
blood pressure variability
hypertension
stroke
antihypertensives
Advisor: Rothwell, P
Elastic wave scattering from a strained region

This dissertation considers elastic wave scattering from a micro-sphere embedded in a rubber substrate which has been initially strained. Its aim is to ascertain the extent to which the strained region affects the scattering process. It is proposed that under hydrostatic loading a micro-sphere will compress nonlinearly. This is justified by calculating the compressed radius of a micro-sphere for different forms of the stored energy function corresponding to linear and nonlinear elasticity. It is shown that linear elasticity, as used in current TMSL models, predicts that the micro-sphere compresses to a smaller radius than that predicted by standard nonlinear elastic models of rubber-like materials. The initial strain modifies the Lame moduli and therefore further experimental work is necessary in order to calculate the full equations of motion for small displacements superposed on top of the initial finite strain. Without this further experimental knowledge the equations are correct only to leading order. The low frequency scattering problem is solved at leading order so that we can ascertain how monopole scattering is affected by the strained region. It is shown that the monopole scattering cross section for scattering from a spherical cavity in a strained region is three orders of magnitude smaller than that for an isotropic region. Hence, the scattering process is significantly affected by the strained region. Two modifications to the current TMSL model are proposed. Firstly, the prediction of the compressed radius should be made according to nonlinear elasticity. Secondly, scattering effects due to the strained region should be included in the model since they contribute significantly to the scattering process.
Society, Community and Power in Northern Spain: 700-1000

The period from c.718 to c.1000 oversaw the reconquest of a significant part of the Iberian Peninsula by the Kingdom of Asturias (718–910) and its successor in León (910–1037); the study of this process of Reconquista has in recent years focused on two broader social changes: the increasing exploitation of the peasantry, and the eclipse of public power. In the Introduction, I argue that it is necessary to integrate the study of peasant societies with analyses of royal and aristocratic power; reframing the subject in this way, we are able to appreciate the diversity of social experience which characterized both peasant and aristocratic life across the two case studies here examined, Southern Galicia, and the Liébana. I argue that the tenth century must be seen on its own terms, and without the benefit of hindsight, if we are to characterize it fairly.
Chapter Two discusses the source material I have used in the elaboration of this thesis, highlighting its uses and problems from a critical perspective. In Chapter Three I show that fluid social structures allowed a family to rise to power from amongst the village inhabitants of the Liébana. Public officials such as counts were not able to impose themselves frequently upon this society. In Chapter Four, I show how a rich and aristocratic family of lay magnates, based in southern Galicia, were major political operators from the ninth century, but only came to exercise significant social influence amongst local society after the construction of the monastery of Celanova in 936.
My Conclusion contextualizes these changes; it also argues that more nuanced and less schematic approaches to social relations demonstrate that peasants retained considerable autonomy in this period, and that factional politics influenced the stability of kingship far more than the supposed eclipse of public power.

Keywords: Social Structures
Political Power
Local Societies
Settlement Patterns
Social History
Advisor: Wickham, C
Davies, W