VictorJuiz/thesis huggingface dataset:
Characterisation of novel phosphorylation sites on FANCD2 and their role in the Fanconi anaemia pathway

Interstrand crosslinks (ICLs) are a highly deleterious form of DNA damage because they link the two strands of DNA, blocking replication, transcription and chromosome segregation. At the center of ICL repair is the FANCD2/FANCI complex, recruitment of which onto the ICL is a critical step for repair. Monoubiquitination of both FANCD2 and FANCI lead to their retention on chromatin and is essential for subsequent repair. However, recent evidence shows that FANCD2 monoubiquitination takes place only after recruitment to DNA (Liang et al., 2016). If the monoubiquitination is taking place after recruitment to DNA, the question of how the recruitment to DNA is regulated remains open. Our objective is to study the role of FANCD2 phosphorylation in regulating recruitment to DNA and repair.
We report a new cluster of phosphosites on FANCD2 whose phosphorylation by CK2 inhibits FANCD2 activation. Specifically, phosphorylation of FANCD2 in this cluster abrogates recruitment to ICLs and inhibits monoubiquitination in vitro and in vivo. Furthermore, phosphorylation of the cluster leads to a dramatic reduction in affinity of the FANCD2/FANCI complex towards DNA, which in turn blocks its monoubiquitination and the activation of the FA pathway. We describe a new regulatory mechanism where FANCD2 must be dephosphorylated prior to the loading of the FANCD2/FANCI complex onto DNA and activation of the FA pathway. This step could act as a safeguard against spurious activation of repair in the absence of damage.

Advisor: Cohn, M
Preconditioning for Toeplitz-related systems

This thesis concerns preconditioning for Toeplitz-related systems. Specifically, we consider functions of Toeplitz matrices, i.e. h(Tn)xn=bn, where h(z) is an analytic function and Tnϵ&Copf;n×n is a Toeplitz matrix.
We propose the absolute value circulant matrix |h(Cn)| as a preconditioner for h(Tn), where Cnϵ&Copf;n×n is the optimal circulant preconditioner, the superoptimal circulant preconditioner, or Strang's circulant preconditioner derived from Tn, and show that |h(Cn)|-1h(Tn) has clustered spectra that account for the effectiveness of such preconditioner.
When h(Tn) is a real matrix, we can first premultiply it by the anti-identity matrix Ynϵ&Ropf;n×n to obtain a (real) symmetric matrix Ynh(Tn) without normalizing the original matrix. To ensure |h(Cn)| is an effective preconditioner for Ynh(Tn), we show that |h(Cn)|-1Ynh(Tn) has clustered spectra around ±1. As YnhTn) is symmetric yet possibly indefinite, we can use the minimal residual method for the corresponding linear system with guaranteed convergence that depends only on its eigenvalues.
We further show that the ideas of symmetrization and absolute value preconditioning for Toeplitz systems can be extended to the block Toeplitz matrix case. An application on time-stepping methods for evolutionary ordinary/partial differential equation problems is also discussed.
Numerical results are given to demonstrate the effectiveness of our proposed preconditioners.

Advisor: Wathen, A
Electronic structure of clusters of tetrel elements containing endohedral transition metal ions

This thesis presents a series of computational investigations into problems relating to the electronic structure of tetrel clusters containing one or more endohedral transition metals. The electronic properties of this class of cluster have been the focus of research for some time, driven in part by the diverse and typically highly symmetric structures that they adopt and also by the desire to miniaturise silicon-based electronic devices. Computational studies are of great importance in this field, particularly for the lighter tetrel clusters where structural information in the form of crystallographic data is entirely absent. Perhaps as a result of the absence of benchmarking data, many controversies have emerged in the literature, with different but apparently equally valid computational methodologies delivering very different conclusions on the structure of specific clusters. Our purpose in this thesis is to provide a deeper understanding of the factors that determine structural preference in this family of clusters, and hence shed some light on the reasons for the disagreements in the literature.

Keywords: silicon cluster
computational chemistry
Advisor: McGrady, J
Semantic dogmatics in outline: Cornelius Ernst's 'meaning of meaning' as Michael Polanyi's absent doctrine of God

Cornelius Ernst’s doctrine of God as the meaning of meaning corresponds to the implicit theological ontology around which Michael Polanyi’s fiduciary epistemology coheres. Conversely, Polanyi’s account of cognitive dynamics supplements Ernst’s metaphysics of meaning with a concrete account of the involvement of the embodied subject. Both Polanyi and Ernst seek to re-orientate their respective disciplines of theological and natural science within an intrinisicist perspective of meaning. Ernst’s theological ontology secures a thematic metaphysics in which the unity of the semantic cosmos is located in the divine triunity of Meaning. This is achieved by a doctrine of creation, in which the world is always already charged by God’s self-communication (corresponding to Polanyi’s efforts to generate a biosemiotic ontology). Within this proposed ontology of meaning, the unicity of theological knowledge is safeguarded by an account of the incarnation as an ‘ontological metaphor’, which is non-identically repeated in the act of faith. As an ontological metaphor, faith has a vocative character, addressing God in an act of worship that is simultaneously doxological and doxastic. This is framed by the action of the Holy Spirit, mediated by the Church: doctrinal frameworks are semantic tools that are indwelt in worship in such a way that theological knowledge becomes connatural. The result is a ‘semantic dogmatics in outline’ which emphasises the pedagogical role of theology, balancing the necessary integrity of dogmatics with its proper eschatological provisionality.

Keywords: semantic dogmatics
christology
theological ontology
Cornelius Ernst
Wittgensteinian Thomism
Polanyi
dogmatic theology
worship
Advisor: Ward, G
Exploring the influence of privacy awareness on the Privacy Paradox on smartwatches

While the public claim to be concerned about privacy, they rarely express protective behaviour. This disparity has been labelled the Privacy Paradox. The Internet-of-Things (IoT) is ubiquitous and data-collecting. It has therefore been considered a privacy risk. However, the Paradox has not been assessed in this context. Hence, we explored whether the issue could be mitigated in novel environments. Before analysing these devices, we began by confirming the Paradox's prevalence. This was undertaken through street surveys, which suggested that views had little relationship with behaviour. We continued by comparing user perceptions across a range of technologies. Through an online survey [n = 170], participants rated 'IoT' devices as most concerning. They were also considered less usable, potentially placing constraints on protection. To dissect the issue, we then conducted detailed interviews. Discussions were undertaken with 40 users, 20 of which had an IoT product. Protection was less common in the IoT, contributing to greater Paradox prevalence. Wearables were particularly prone, and therefore we scoped our focus to smartwatches. Through analysing participant rationale, a lack of awareness appeared the greatest IoT issue. Since educational games had proved effective in the literature, we developed privacy apps. Our online prototype was trialled by 504 smartwatch owners. In our treatment group, we found the Paradox was mitigated in posttest results. Therefore, for our final study, we implemented the first smartwatch privacy game. Through a two-month longitudinal study, we analysed empirical behaviour. Users were given an (Android) Wear OS watch, with half playing the game. Protection increased and persisted in this group, with the Paradox mitigated over an extended period. Our research has novelty, in that this has not been achieved in previous work. Furthermore, by analysing smartwatch behaviour, we provide novel insights into user rationale. As the IoT expands, it is crucial that individuals are informed to make privacy decisions.

Keywords: Security
Privacy
IoT
Smartwatch
Behaviour change
Advisor: Nurse, J
Creese, S
An evidence-based evaluation of systematic conservation planning

Systematic conservation planning is a discipline focused on applying spatial ecological data to help advise those faced with value-laden conservation decision-making. It holds the potential to ensure the most important areas of land and sea are retained for biodiversity and ecosystem services, whilst simultaneously helping to avoid conflict with human uses. In this thesis my aim was to outline the factors which influence the effectiveness of systematic conservation planning in terms of achieving biodiversity conservation outcomes alongside broader social and financial objectives. I began by developing a conceptual framing of impact and evaluation methods in relation to systematic conservation planning. Following this I catalogued the literature on systematic conservation planning from across 29 academic and non-academic sources, using a gold standard evidence synthesis method, systematic mapping. This involved screening over 10,000 articles, from which three constituted high-quality impact evaluations, and a further 43 discussed the outcomes of plans but lacked appropriate study designs. To improve the efficiency of conducting large evidence syntheses like this, I reviewed 22 specialist software packages used across multiple disciplines. Finally, I chose a case study approach to understand barriers to evaluation and perspectives of effectiveness amongst a range of elite interviewees responsible for systematic conservation planning exercises in Australia in the 1990s and 2000s. This thesis highlights a shortfall in efforts to monitor and report on the outcomes of systematic conservation planning interventions. One reason is the inherent challenge of interpreting impact when counterfactual analyses are difficult to conduct, but my results also suggest insufficient academic focus on implementation and evaluation in this discipline. The three high-quality impact evaluations and Australian case studies provide valuable examples of how to overcome barriers to evaluation and point to the range of factors which influence interpretations of effectiveness. Conservation academics are ideally positioned to assist in the design and conduct of rigorous evaluations and evidence synthesis activities going forwards.

Keywords: wildlife conservation
conservation planning
systematic map
key informant interview
evaluation
Advisor: Grenyer, R
Stabilising and visualising devices of the gastrointestinal tract

Flexible endoscopic systems have revolutionised both diagnostic and therapeutic standards of care for a variety of health conditions. Extending the capacity and safety of these devices, could enable broad deployment of endolumenal therapeutic actions, preventing unnecessary surgery. Although previous biocompatible inflatable balloon systems for invivo use have demonstrated some utility in small-bowel locomotion, little is known about the potential for double balloon systems to facilitate surgeries within the gastrointestinal tract. While considerable advances have been demonstrated in other clinical specialties due to innovative technology, these have been historically absent in gastrointestinal therapy, where reliance on formal surgery as the primary treatment modality for benign and malignant disease has persisted. Such innovations seen in other fields have shifted diagnosis and treatment to an earlier stage with minimally invasive approaches.
In this thesis, I present my DPhil work that shows evidence of the design and operation of a double-balloon oversheath for flexible endoscope stabilisation and visualisation through the development of a lumenal inter-balloon zone. The device delivered an increased visible mucosal surface area and improved tumour removal strategies through immersion and retraction capabilities in the lower gastrointestinal tract of large animals. Following this, I go onto consolidate this pre-clinical work in a clinical context with an emphasis on safety as well as some of the challenges encountered during this process.
Taken together, these data indicate that such devices could provide endolumenal surgical capabilities to the next generation of flexible endoscopic systems for the gastrointestinal tract.

Advisor: Simmons, A
Milsom, J
Knotted polymers and filaments

The behaviour of knotted polymers and non-Brownian knotted ﬁlaments is investigated using bead-spring models, simulated using three different dynamical methods. We focus on knotted polymers under conﬁnement, and on the dynamics of knotted polymers and ﬁlaments.
Langevin Dynamics is applied to study polymers conﬁned in a slit. We ﬁnd that, for relatively wide slits, knots decrease the force exerted by the polymer on the walls, whilst for narrower slits, they increase it. We interpret the results in terms of the effect of knots on the ability of polymers to spread out as the width is decreased.
We simulate knotted polymers migrating through a designed channel with sections of two diﬀerent depths under an electric ﬁeld. Trends in the mobility as a function of knot type depend on the depth of the narrower section. We discuss possible links to experimentally important knot electrophoresis.
We employ a Stochastic Rotation Dynamics algorithm to investigate knots diffusing in polymers under tension. We focus on two knot groups to demonstrate the effect of topology on effective friction coeffcients and length relaxation. The latter is controlled by a breathing mode.
We use the Rotne-Prager tensor in simulations of knotted ﬁlaments under shear in the non-Brownian regime. We discover rich dynamical modes, which we classify into families. The modes show regular and chaotic motion with migration in the vorticity direction. We propose that, as ﬁlament deformability is varied, the onset of knot-tightening is determined by a dimensionless knot deformation number.
We study the effect of knotting on the ejection of ﬂexible and semi-ﬂexible polymers from a spherical, virus-like capsid. The polymer ejection rate is primarily controlled by the knot, which moves to the hole in the capsid and then acts as a ratchet. More complex knots lead to slower ejection.
Finally, we show preliminary results that indicate an interesting interplay between persistence length and tension in determining the location of a knot in a polymer of non-uniform ﬂexibility. For lower tensions, the knot may be more likely to be found in a stiffer part of the polymer.

Advisor: Yeomans, J
Louis, A
Mercenaries in the eastern Mediterranean from the late Bronze Age to the Iron Age

The thesis investigates the presence of mercenaries in the Eastern Mediterranean, specifically in Egypt and the Levant, from the Late Bronze Age to the end of the sixth century B.C.E. The time frame predates the ubiquitous mercenaries of the Classical period onwards, and traces the origins of the profession and how it manifested in the archaeological record.
The examination begins with the earliest evidence for non-local contingents hired in armies during the Bronze Age, based on the sources and archaeological remains, in order to address how to define mercenaries in antiquity. From these instances, the thesis posits a new definition for mercenaries in antiquity that encompasses the activities and characteristics of such foreign groups. The investgation then turns to the Iron Age, when the contemporary sources are scarce, but the archaeology is telling of numerous calamitous, historical events that precipitate the need for mercenaries.
Past scholarship argued that specific sites in the Iron Age Levant and in Egypt exemplify evidence of mercenary activity, based primarily on different ceramic repertoires. An evaluation of the case studies reassesses whether this is indeed the case; how do the archaeological remains function as indicators of mercenaries? What factors are revealing of nonlocal contingents situated in a different context? The material remains, and whether they indicate non-local cultural practices and activities, are investigated. By considering the available remains, in addition to the ceramics, including architecture, burial rites, ritual practices, weapons, and the contexts in which the finds are discovered, it is then possible to assess where and when mercenaries are traceable. The discoveries and interpretations from the thesis shed light on archaeological indicators for mercenary activity, and which sites suggest such evidence, and which do not.

Keywords: Sea Peoples
Saite Dynasty
Egypt
Material Evidence
Naukratis
Levant
Greek Soldiers
Mercenaries
Weapons
Advisor: Lemos, I
The iridium-catalysed alkylation of aromatic ketones via hydrogen borrowing

This dissertation explores how the scope of hydrogen borrowing reactions can be further expanded to use both primary and secondary alcohols to form α-, β- and α,β-branched aryl ketones. ortho Substituents were critical in enabling the hydrogen borrowing alkylation by inducing a non-coplanar geometry of the aryl–ketone motif, which provides various beneficial effects that contribute to the success of the reaction.
The versatility of the hydrogen borrowing reaction was further improved by introducing a vinylcyclopropane rearrangement into the reaction manifold prior to enone reduction. Control studies and modified substrate provide insight into the mechanism of the reaction.
The synthetic utility of pentamethylphenyl (Ph*) ketones was enhanced through electrophilic cleavage to form various carboxylic acid derivatives. Phenol derivatives of Ph* ketones were also found to undergo a related oxidative cleavage of the derivatised Ph* group to form esters and carboxylic acids.
Phenol and aniline derivatives of Ph* ketones formed tetrasubstituted α-keto centres in the hydrogen borrowing reaction, a remarkable result that could not have been possible using conventional aldol chemistry. Attempts were made to explore the formation of tetrasubstituted α-keto centres in the hydrogen borrowing reaction with other aryl ketone derivatives.
Structural changes were observed by X-ray crystallography that were consistent with the alleviation of steric interactions between the aryl group and ketone substituent, providing evidence that ortho-substitution provides multiple benefits that drive the hydrogen borrowing reaction. Substituents at the meta and para positions of the aryl ring result in structural distortions that are directly responsible for the "buttressing" effect. IR, 13C and 15N NMR spectroscopy were also employed to study the effects of non-coplanar geometries of the amino, nitro and carbonyl groups.

Keywords: Hydrogen Borrowing
Organic Synthesis
Catalysis
Advisor: Donohoe, T
Non-contact monitoring of respiration in the neonatal intensive care unit

Camera-based monitoring is an emerging sensing modality which has attracted widespread interest due to its potential to offer comfortable and concurrent measurements of the cardiorespiratory vital signs: the cardiac pulse rate, respiratory rate and peripheral capillary oxygen saturation.
In recent years, several methods have been proposed for the processing of visible and infrared video data and subsequent extraction of the respiratory rhythm. However, due to the low signal-to-noise ratio (SNR) of these signals, their application has so far been limited to adult subjects and controlled research environments. In this thesis, we aim to improve the signal processing aspects of non-contact respiratory measurements by developing a novel technique for extracting this signal in a clinical setting. The main contribution of this work is a multi-channel source separation method which combines information from multiple image domains and uses a priori information about the distinctive temporal structure of the signal of interest to improve the quality of the respiratory signal extracted.
Considering the neonatal breathing component as an extreme case of poor SNR in video signals, we present a case study of the extraction of respiratory signals from video signals recorded from a CCD camera placed above an incubator inside which critically-ill infants are nursed. Evaluation results were obtained from recordings on 30 neonatal patients nursed in the Neonatal Intensive Care Unit at the John Radcliffe Hospital, Oxford, UK. The respiratory signals extracted using the methodology described compare favourably against those derived from direct and indirect sources during periods of manual breath counts. In addition, we show that a classification algorithm which uses features of these signals to identify periods of cessation of breathing can successfully distinguish between true and artefactual decreases in respiratory rate in a range of critically low values of this vital sign.

Keywords: neonatal
breathing rate
camera
physiological signs
respiratory rate
apnoea
non-contact monitoring
respiration
vital signs
Advisor: Tarassenko, L
Authentication and pairing using human body impedance

The electrical properties of the human body are an unexplored source of much potential in Computer Security and Biometrics. The body is an electric conductor with very interesting features: at lower frequencies it can be treated like a resistive cable and at higher frequencies it behaves similar to an electric antenna. These physical phenomena allow the construction of electrical circuits that interface the human body or even build on it as the core element. In particular, one can use the human body as a transmission medium for electromagnetic signals. Using so-called body channel communication techniques, it is possible to send information wirelessly through the body of a person. In addition, the electrical properties of the body can be measured and constitute physiological characteristics unique to the every individual.
Although these properties could prove very useful in the context of Computer Security, their potential for security applications is largely unexplored. We find, however, that extracting the body’s distinctive impedance characteristics or using the body as a communication medium entails many interesting application scenarios. The human body can serve as an additional layer to augment the security in existing protocols or enable the design of entirely new methods.
In this thesis, we propose solutions to two challenging problems in the area of System Security: user authentication and secure device pairing. In order to address these problems, we conceptualize and develop solutions that make use of the electrical properties of the human body.
Keeping simplicity and universality in mind, we primarily focus on applications where the human body can be interfaced in ways that require little to no user involvement and are completely noninvasive.
We find that it is most natural, even for novice users, to interface the body through the person’s hands. Our proposed solutions therefore connect to the body through (capacitive) electrodes that the user has to touch with their hands. In case of user authentication, we propose a method that measures the human body impedance from one hand to the other, and for device pairing, we present an approach that allows two devices to communicate with each other when a person touches them both, one with each hand.

Advisor: Rasmussen, K
Martinovic, I