VictorJuiz/thesis huggingface dataset:
Informed modeling of disorder

Understanding structure is paramount in developing structure-property relationships in all categories of materials, from hard to soft matter. Developing this understanding becomes particularly challenging in the realm of disorder, where the notion of periodicity breaks down. For systems of increasing disorder, the experimental probes of canonical crystallography contain diminishing information content, and traditional methods prove insufficient for structural solution. This thesis uses the methodology of informed modeling to gain insight into the structures of disordered materials, and investigate the limits of using reciprocal space information to derive meaningful real space structures.
Informed modeling procedures are data-driven approaches to extracting structural solutions from the total scattering pattern, that incorporate some instance of prior information. This inclusion of priors — which can from complementary experiments or from first principles — is an inherently Bayesian approach to modeling structure. To establish this methodology, I investigate a series of three distinct systems with increasingly severe levels of disorder, that also possess increasingly powerful prior information. This thesis is comprised of a series of monographs on structural modeling, tied together by a central inquiry, and spanning crystalline, amorphous, and solution phase materials.
The anomalous hydration behavior of ZrW2O8 is modeled using a set of local rules derived from experimental scattering and ab initio calculations. The propagation of deformations associated with these local rules throughout the structure is described by a series of spaghetti states which map onto the population of many negative thermal expansion phonons. The developed mixed modeling procedures effectively incorporate prior information from first principles, and cast a meaningful structure solution that is validated by total scattering and lattice dynamics.
Next, a system of unique topological disorder is considered. Total scattering data are combined with rigid local constraints to develop the first ever squareplanar continuous random network (CRN), which is subsequently used to model an amorphous Pd/Pt(im)2 phase. This model is refined against the total scattering data using reverse Monte Carlo (RMC).
Finally, an explicitly Bayesian approach is developed for refining solution phase protein structures against the pair distribution function (PDF). Although the protein PDF has very few features and limited information content, continuous prior probability distributions of local conformations are implemented in a Bayesian RMC. This proof of concept study vindicates the utility of the PDF in structure prediction, so long as a set of robust prior information is available.
The three systems are considered in concert to demonstrate when structure solution is tractable: as the data becomes less discriminating, more judicious prior information is necessary in order to approach a meaningful structural solution.

Advisor: Goodwin, A
An analysis of contact stiffness and frictional receding contacts

The tangential contact stiffness for ground Ti-6Al-4V surfaces is measured to linearly decrease with the application of tangential load. At the beginning of the application of tangential load, for ground surfaces, the ratio of the tangential contact stiffness to the normal contact stiffness is seen to be approximately half the Mindlin ratio. This is consistent with many other published experimental studies. Measurements of normal contact stiffness for ground surfaces conform to a model that posits a linear relationship between normal contact stiffness and normal load. An equivalent surface roughness parameter is defined for two surfaces in contact; and the normal contact stiffness for ground surfaces is observed to be inversely proportional to this parameter.
Single asperity models were constructed to simulate the effect of different frictional laws and plasticity on the tangential displacement of an asperity contact. Further, multi-asperity modelling showed the effect of different normal load distributions on the tangential behaviour of interfaces. In addition, normal contact stiffness was modelled for a grid of asperities taking into account asperity interactions.
A receding contact problem for which the required form of the distributed dislocations is bounded-bounded was solved. Then, a fundamental 2D frictional receding contact problem involving a homogeneous linear elastic infinite layer pressed by a line load onto a half-plane of the same material was analysed. This was done by the insertion of preformed distributed dislocations (or eigenstrains), which take into account the correct form of the separation of the interface at points away from the area of loading, along with corrective bounded-bounded distributions. The general method of solution was further refined and adapted to solve three other receding contact problems. The solutions demonstrated the robustness and applicability of this new procedure.

Keywords: Contact stiffness
Linear elasticity
Receding contact
Advisor: Nowell, D
Hills, D
The supply of building materials to construction projects in Roman Oxfordshire: logistics, economics, and social significance

Whilst Roman architecture has long stood as a discrete branch of classical studies, investigated for its artistic merit and cultural importance, the technical details of Roman construction have only recently started to receive considerable attention. This thesis contributes to a growing trend in Roman scholarship, that of the investigation of the processes, materials, and technologies behind the Roman built environment. The most prestigious buildings of the Empire often remain the focus of many of these studies, and so this thesis turns to explore the use of more everyday buildings and building materials, seeking a Romano-British vernacular, and investigating the processes of construction, building material production, and transport.
It is argued, through using theoretical calculations of building material quantities, that even for relatively minor constructions, considerations of building material supply must have represented highly significant economic and logistical investment. To comprehend fully the subject it is asserted that building materials should not be treated, as they often are, as disparate artefacts, divided by substance into stone, ceramic, mortar, metal, etc., but rather they should be considered as related fragments of a building. They require synthetic analysis, through which a far truer understanding of the incredible effort involved in construction in the ancient world can be gained.
The built environment of Roman Oxfordshire, and the Roman building material assemblage from Dorchester on Thames, are used as case studies. Primary analysis of building materials is carried out using an integrated analytical approach, combining thin section petrography with scanning electron microscopy and energy dispersive x-ray analysis. The outcomes of these analyses are interpreted against a background of archaeological and historical evidence for construction and material supply, in both the Roman and later periods, in the region and beyond.

Keywords: Roman Building Materials
Petrography
Roman Trade
Classical Archaeology
Roman Britain
Scanning Electron Microscopy
Archaeological Science
Advisor: DeLaine, J
Doherty, C
Identity politics and discrimination law: addressing essentialism and assimilationism in disability and transgender discrimination law

Essentialism and assimilationism work hand in hand as well as in tension to oppress groups that are different from dominant norms in society. While integrating different groups into society, discrimination law may place undue assimilationist demands on these groups. Yet at the same time, identifying and addressing these assimilationist demands also risk essentializing these identities and ignoring the needs of individuals within these groups. This thesis aims at showing that disability discrimination law provides a framework that can perform anti-assimilationist and anti-essentialist functions, through elements such as non-essentialist grounds of discrimination, more relaxed uses of comparators and duties of reasonable accommodation. Furthermore, this framework can be applied to tackle similar concerns of other different groups in, for example, transgender discrimination law.

Keywords: Disability
Transgender
Discrimination
Assimilation
Essentialism
Law
Identity Politics
Advisor: Khaitan, T
The role of the transcription factor BRN2 in melanoma

Expression of the POU-domain transcription factor BRN2 is crucial for the developing brain and drives proliferation and invasiveness in cancers of neural crest origin including melanoma. However, our understanding of BRN2 function and how its behaviour is modulated remains incomplete. We therefore aimed to investigate how protein:protein interaction and post-translational modification might influence the activity of BRN2 and how this impacts on melanoma cell phenotype.
We show that, surprisingly, BRN2 binds DNA-damage response proteins rather than transcriptional co-factors and that following UVB irradiation, BRN2 rescues cells from apoptosis. Expression of apoptosis-induction genes in response to UVB is enhanced following knockdown of BRN2. Significantly BRN2 expression in tumours also correlates with an increased mutational burden. Mechanistically, BRN2 is rapidly recruited to DNA-damage sites in a PARP-dependent manner and requires DNA binding for efficient recruitment and rescue from apoptosis. Furthermore, post-translational modification of the transactivating domain of BRN2 by the UV-induced p38 stress kinase modifies the recruitment kinetics of BRN2 and its DNA binding ability, and p38 signalling disrupts a key BRN2 protein:protein interaction.
Our findings identify a novel role for BRN2 in promotion of survival of melanoma cells in the face of genomic insult. These findings help us to understand the mechanisms that melanoma cells employ to tolerate high levels of genome instability with potential implications for neuronal development and tumours such as small cell lung cancer and neuroendocrine prostate cancer.

Advisor: Goding, C
Middleton, M
The effect of resource abundance and dispersion on the ecology of African lions (Panthera leo) in a semi-arid landscape

In natural ecosystems, resources are often heterogeneously distributed and one of the key challenges in ecology is to understand how environmental heterogeneity influences population dynamics, species distributions, community composition, social structure and individual behaviour. In this study, the spatial and temporal heterogeneity of the Hwange National Park landscape and the ability to measure and quantify the abundance, dispersion and the richness (characterised by herd size and prey size) of prey at the lion home range scale provided us with a unique opportunity to examine the effects of resources on the ecology of a social large carnivore. The abundance, dispersion and richness of prey patches is expected to influence various aspects of the ecology of African lions, including patterns of sociality, ranging behaviour and foraging behaviour. In this study I first assessed the applicability of the spoor count method in estimating relative abundance of herbivores and found it to be a useful index (Chapter 2). I then tested the effect of prey availability on the ranging behaviour (home range size) and the broad-scale social structure (group size) of lions by applying the four main prediction of the Resource Dispersion Hypothesis (RDH) (Chapter 3). Results revealed that all four predictions of the RDH were supported. Indeed home range size increased with increase in the dispersion of prey while lion group size increased with increase in patches richness. I then went on to test the effect of prey availability on the fine-scale social structure (community structure) of lion prides using the social network toolbox and advanced analytical methods (Chapter 4). Results showed that all prides demonstrated strong patterns of within-pride sub-grouping, or ‘communities’, and that the intensity of sub-grouping behaviour is linked to resource availability. More specifically, communities were more strongly defined as prey dispersion increased and when the body size of available prey decreased. Finally, I applied the optimal foraging and social foraging theories to understand the drivers of lion foraging behaviour (prey preference) (Chapter 5). Results revealed that the richness of prey patches both in terms of prey body size and herd sizes as well as lion hunting group size were important factors in influencing prey preference of lions. The foraging behaviour of this lion population suggested that they seek to maximise energy gain and optimise foraging success. Together the results of this thesis reveal that the dispersion and richness of resource patches are important factors in influencing lion ecology.

Advisor: Loveridge, A
Macdonald, D
Valeix, M
Measurement of pH using Chemical Exchange Saturation Transfer Magnetic Resonance Imaging

Altered metabolic phenotypes, with consequential alterations in tissue pH, are commonplace in a number of pathologies. The metabolic reprogramming common in cancer leads to acidification of the tumour microenvironment and alkalosis of the intracellular space, whereas the cessation of blood flow in ischaemic stroke results in systemic acidification of the affected tissue. Thus far, however, measurement of pH is under-utilised as a physiological parameter of interest in the clinic, despite its potential ability to measure treatment response or stratify patients to optimal therapeutic strategies. This lack of interest in pH is likely a result of a lack of non-invasive, clinically translatable measurement methods.
One modality that may be able to be used for non-invasive pH measurements in vivo is Chemical Exchange Saturation Transfer (CEST) Magnetic Resonance Imaging (MRI). CEST MRI measures changes in signal from water protons owing to their association with other biomolecules and metabolites, particularly via exchange of protons in amide and amine functional groups. The rate at which chemical exchange of these protons occurs affects the measured CEST MRI signal, and is sensitive to the environmental pH. Hence, through careful calibration, CEST MRI may be used to measure pH in vivo.
The development of CEST MRI to enable measurement of pH in vivo is the focus of this thesis. Firsly, novel, realistic phantom models of the in vivo intracellular environment of brain metastases and naïve mouse brain were developed to determine that the CESTR* metric with compensation for water T1 and T2 relaxation effects overcomes many challenges facing interpretation of CEST MRI data. An extension to this metric – isoCESTR* – was developed, and shown to potentially permit measurement of pH using simulated data.
Subsequently, three separate animal models of human disease were used to examine the ability of isoCESTR* to measure pH. Through combination of in vivo CEST MRI data and ex vivo protein concentration measurements, tissue pHwas estimated using CEST MRI data from rats with brain metastasis and ischaemic stroke. Additionally, the pH change induced by alleviation of tumour hypoxia was measured in mice with subcutaneous tumours.
Finally, a novel pulse sequence combining stimulated echo diffusion and CEST methods was developed and validated as a means of separating intra- and extracellular CEST effects. This pulse sequence was used to estimate the proportion of CEST signal originating from the intracellular space for the first time.
CEST MRI is an imaging technique with great potential to permit pH measurement in vivo in clinical as well as research settings. It is hoped that the work presented here goes some way to improving the understanding of CEST effects from endogenous sources, and exploiting these effects for measurement of tissue pH.

Advisor: Sibson, N
Chappell, M
Molecular determinants of phleboviral cell entry

Phleboviruses are emerging zoonotic pathogens which constitute a global threat to human and animal health. The mosquito-borne Rift Valley fever virus (RVFV) is a widespread problem across the African continent and causes regular deadly outbreaks in ruminants. The recently emerged severe fever with thrombocytopenia syndrome virus (SFTSV) is a serious human public health concern in China which has rapidly spread to Japan and Korea with fatality rates as high as 16-30%.
Phleboviral cell entry is mediated by two viral glycoproteins: the class II fusion protein Gc and the lesser known Gn. Initial cell attachment is glycan dependent and the penetration into the cell cytoplasm is mediated by the Gc fusion protein which catalyses viral and cell membrane merger. The entry mechanism is not well understood from a structural perspective which limits mechanistic insights. The purpose of this thesis is to further our understanding of the cell entry process by filling in the missing structural information on the phleboviral glycoprotein layer. To this end, an integrated structural approach using cryo-EM and X-ray crystallography was adopted.
The crystal structure of the Gn ectodomain is presented which reveals an unprecedented structural relationship with seemingly unrelated viruses. Single-particle cryo-EM and localized reconstruction reveal the glycoprotein layer of the RVFV and a pseudo-atomic model of the RVFV is presented. The assembly shows the shielding of the Gc fusion protein and suggests that the Gn functions as a fusion chaperone. The post-fusion crystal structure of the Gc protein from SFTSV further consolidates a mechanism of membrane fusion by class II fusion proteins. Finally, preliminary data on receptor binding and mechanism of antibody mediated neutralization are presented. The work presented herein provides a novel platform for studying and understanding entry and assembly of phleboviruses as well as the design of novel therapeutics.

Keywords: glycoprotein
phlebovirus
Advisor: Huiskonen, J
Bowden, T
The physiological basis of motor cortical oscillations in humans

β- and γ-frequency oscillations are the dominant oscillatory activities in the human motor cortex (M1). However, their mechanisms and functional significance remain poorly understood. Controlled modulation of brain oscillations using transcranial alternating current stimulation (tACS) holds promise to advance this knowledge. The primary goal of this thesis was to investigate the neurophysiological mechanisms underlying β and γ oscillations. To this end, tACS was combined with transcranial magnetic stimulation (TMS; Chapters 4 and 5) and ultrahigh field (7T) Magnetic Resonance Spectroscopy (MRS; Chapter 6). Additionally, the relationship between MEG-measured oscillations and TMS-assessed physiological measures was examined (Chapter 7).
The findings presented in Chapter 4 demonstrated that γ tACS led to a duration-dependent decrease in resting-state synaptic GABAA inhibition in M1; this effect was positively correlated with baseline GABAA decrease during movement preparation, when γ activity in motor circuitry is known to increase, suggesting that tACS may have similar physiological effects to endogenously driven local oscillatory activity. In addition, γ tACS-induced change in GABAA inhibition was closely related to performance in a motor learning task.
Chapter 5 provided evidence on β tACS-induced modulation of corticospinal excitability (tACS phase-dependent) and extrasynaptic GABAA inhibition (tACS phase-independent) during movement preparation. Further, β tACS slowed down response time independently of its physiological effects.
In Chapter 6, it was shown that β tACS reduced M1 GABA concentration; this change was dependent on the match between stimulation frequency and endogenous β-frequency, potentially reflecting a complex relationship between local tonic inhibitory activity and β oscillations. In contrast, no effect of β tACS on M1 glutamate levels was observed.
Chapter 7 revealed an inverse relationship between endogenous β oscillatory power and movement-related corticospinal excitability. Moreover, peak frequency of movement-related γ synchronisation was related to performance in a motor learning task; local synaptic GABAA-mediated inhibition played an important role in this association.
In conclusion, the results of the studies contained in this thesis offer a novel insight into the mechanistic basis of human motor cortical rhythms and provide evidence supporting the role of γ oscillations in motor learning, opening an interesting avenue for further research in the motor domain. Nevertheless, further study focused on addressing the limitations of tACS-based approaches is warranted.

Advisor: Stagg, C
Brown, P
Symbolic regulation: human rights provisions in preferential trade agreements

While the multilateral trading system views human and labour rights issues as outside of its remit, states increasingly incorporate regulation in these areas into their bilateral reciprocal preferential trade agreements, "HR-PTAs. This dissertation investigates the emergence of HR-PTAs, testing alternative explanations derived from conventional “public interest" and “private interest” theories of regulation against a new theory of "symbolic regulation." According to the public interest theory of regulation, regulation is motivated by benevolent legislators’ commitment to correcting market or social problems. The private interest theory of regulation instead views regulation as the result of private interest groups capturing the regulatory apparatus in order to regulate in their own self-interest. Unlike its counterparts, the symbolic theory of regulation suggests that regulation may also be created for the primary purpose of reassuring regulatory advocates that their demands have been heard, rather than to regulate a given issue area.
This dissertation argues that for the states behind them, HR-PTAs are primarily a symbolic form of regulation. Legislators create HR-PTAs to appease domestic human and labour rights organizations, while defending their trade interests through the non-enforcement of their provisions. Using longitudinal network analysis to analyse original data from 415 preferential trade agreements in force from 1989 to 2009, paired with case study evidence from the EU, US, and Canada, this dissertation finds support for the symbolic regulation explanation of HR-PTAs. It shows that a state’s commitment to HR-PTAs depends less on the public interest or the desires of private interest groups than on its need to accommodate human and labour rights advocates. Symbolic regulation however should not be dismissed. It sets precedents, creates policy space, facilitates softer forms of cooperation, and can fuel political accountability politics. When this occurs, states may use HR-PTAs or other forms of symbolic regulation to achieve their seeming purpose.

Keywords: statistical network analysis
non-trade issues
symbolic regulation
regulation theory
public interest groups
Advisor: Snidal, D