VictorJuiz/thesis huggingface dataset:
Quantum master equations for spin chemistry

It is a remarkable fact that the interactions between electron and nuclear spins, and their interactions with a magnetic field, can have a profound effect on chemical reactivity, despite the fact that the characteristic interaction energies are orders of magnitude smaller than thermal energy. These observations are explained by the existence of long-lived quantum coherences between spins in certain molecular species (in particular radical pairs), and the study of these spin effects constitutes the field of spin chemistry, a field which spans a wide range of systems, from biochemical reactions to device physics.
Because spin chemistry involves subtle quantum effects, many intuitive models used by Physical Chemists, in particular classical kinetic equations, cannot be universally applied. On the other hand, complete first principles modelling of reactions involving spin effects comes at an impossibly high computational cost in complex systems, and often offers little physical insight. In order to address the shortcomings of these approaches, quantum master equations (QMEs) are employed to describe spin chemical phenomena. These are equations that describe a reduced set of degrees of freedom quantum mechanically, accounting for the effects of remaining degrees freedom implicitly.
In this thesis I explore the use of QME techniques to resolve a range of problems in spin chemistry. These techniques can be used to obtain the correct radical pair spin QME, resolving questions about the role of quantum measurement in these systems. As well as aiding the development of the theory of spin chemistry, QMEs provide a practical tool for modelling radical pair reactions including spin relaxation effects, as I also demonstrate. As a final study of QME techniques in spin chemistry, I use these methods to show when the classical kinetic description of radical pair reactions is and is not valid.

Keywords: Theoretical chemistry
Spin chemistry
Advisor: Manolopoulos, D
The role of cerebellar GABA in visuomotor adaptation

In daily life we must constantly adapt our movements to changes in the environment or changes in our body. Adaptation is a fundamental property of the central nervous system and involves plastic changes across a network of brain regions, in particular in the cerebellum. These changes likely involve the major inhibitory neurotransmitter GABA. How cerebellar GABA changes during adaptation and how these changes are linked to behaviour is currently not well understood. By combining brain imaging (Magnetic Resonance Spectroscopy and Magnetic Resonance Imaging) and brain stimulation (transcranial direct current stimulation; tDCS) with computational modelling of behaviour, this thesis investigates the relationship between GABA, plasticity and motor adaptation.
First, the effects of stimulating the cerebellum with anodal tDCS were investigated. We found no effect of tDCS on adaptation, but an effect of session. We then studied the relationship between M1 GABA concentration and adaptation. We found that GABA concentration at baseline measured from left M1 hand area predicted retention of an adapted movement of the right hand. Next we investigated changes in functional connectivity elicited by adaptation. After performing an adaptation task, cerebellar resting-state functional connectivity was increased. Further, the change in a cerebellar network correlated with adaptation performance. Finally, we explored changes in cerebellar GABA during adaptation. During adaptation, cerebellar GABA decreased in the right compared to the left cerebellar hemisphere, controlling for GABA changes during movement execution.
This work provides first evidence that GABA decreases during adaptation in the right compared to the left cerebellar hemisphere. It strengthens the theory of cerebellar involvement in adaptation and suggests that cerebellar GABA plays an important role during adaptation. It also highlights the importance of M1 GABA in retaining the adaptive movement. Taken together, these results demonstrate a potential mechanism by which adaptation may be achieved in the cerebellum. In order to develop interventions that successfully and reliably enhance adaptation, it is crucial to understand the factors that influence these changes in the cerebellum and across the motor network.

Keywords: Functional Connectivity
Motor learning
Primary motor cortex
GABA
Magnetic Resonance Spectroscopy
Neurochemistry
Plasticity
Neuroimaging
Brain stimulation
Adaptation
Cerebellum
tDCS
Cortico-cerebellar connectivity
State-space modelling
Advisor: Stagg, C
Jenkinson, N
Melioidosis in South-East Asia: contribution to a fever cohort, and in vitro studies of MAIT cell function

Melioidosis is a neglected tropical disease caused by the Gram-negative bacterium Burkholderia pseudomallei (BP). Diabetes mellitus (DM) is a major risk factor. A mathematical model estimated 1,650,000 melioidosis cases in 2015 worldwide with 16,931 cases in Bangladesh, but the disease is rarely diagnosed in Bangladesh. This thesis set out to determine whether melioidosis is a significant cause of fever in Bangladesh, and to characterise the human mucosal-associated invariant T-cell (MAIT) response to BP and other Gram-negative bacteria.
We prospectively determined the aetiology of fever in 201 adult patients in Dhaka, Bangladesh, and found melioidosis to be the joint commonest cause (with E. coli) of bacteraemia. We also noticed high rates of antimicrobial resistance in Gram-negative infections.
We tracked the phenotype, activation and function of MAIT cells during acute melioidosis and other Gram-negative infections. MAIT cells responded rapidly to BP, releasing IFN-γ via both MR1 and cytokine-dependent pathways. The frequency and IFN-γ expression by MAIT cells following BP stimulation was significantly reduced in acute melioidosis patients compared to endemic controls, and significantly reduced in acute patients who died compared to survivors. We then examined the effect of DM on the MAIT cell response. In the endemic control population, IFN-γ expression was reduced in DM compared to non-DM. This was not explained by differences in activation or exhaustion markers (PD-1 and TIM-3) between groups. Finally, we found IFN-γ production by MAIT cells was significantly lower in the Gram-negative sepsis patients compared to healthy controls.
In conclusion, we have demonstrated that melioidosis is one of the commonest causes of community-acquired bacteraemia in Bangladesh. We have also revealed a potential key role for MAIT cells in survival in acute melioidosis, and their significance in host defence against other Gram-negative bacteria.

Keywords: gram-negative bacteria
fever
MAIT cell
sepsis
melioidosis
Burkholderia pseudomallei
Advisor: Dunachie, S
Klenerman, P
The neural representation of multisensory percepts: studying the integration of auditory and tactile stimuli in the somatosensory cortex

Multisensory integration is the constant process through which we combine information across different sensory modalities in order to better interpret our environment. In early models of multisensory integration, primary sensory areas were thought to almost exclusively treat information from their preferred sensory modality and contribute little to the integration process. However, a growing literature now describes cross-modal responses in primary sensory cortices and direct cortico-cortical connections between primary sensory cortices. Therefore, cortical multisensory integration may begin as early as the primary sensory regions.
I built on this literature by examining how training on a multisensory integration task may alter vibrissal primary somatosensory cortex (vS1) responses to vibrotactile whisker stimulation and amplitude modulated pure tones. Unlike most previous studies, ours required the animal to identify a unique combination of vibrotactile and auditory stimulation in order to perform the task correctly. I used chronic in vivo two-photon imaging of vS1 to measure neural responses to stimuli throughout training on the Go/No-Go task. Responses of the same neural populations were compared prior to, during, and following task acquisition.
Mice learned to correctly identify specific combinations of audio-tactile stimulation. I observed vS1 responses to vibrotactile stimuli and found a subset of neurons that were responsive to sounds. I also found neurons that responded only to a single multisensory combination. Training led to an increase in the proportion of responsive neurons during acquisition on all tasks and a decrease in the proportion of responsive neurons after training on the multisensory task.
Most tracked neurons became either responsive or unresponsive during or after training. In contrast, very few neurons maintained constant response properties. While it remains unclear whether or how training may remodel local circuits, my findings suggest that training and experience lead to the recruitment of different populations of neurons in vS1 in a modality-specific manner.

Keywords: behavioural neuroscience
two-photon imaging
vs1
audio-tactile integration
barrel cortex
neuroscience
multisensory integration
primary sensory cortex
Advisor: Walker, K
King, A
Kohl, M
Intensity modulated proton therapy in lung cancer

Proton beam therapy (PBT) has the potential to improve outcome in locally advanced non-small cell lung cancer (NSCLC). However, the technology associated with its delivery is still evolving. Treatment planning for PBT needs to account for various uncertainties to ensure accuracy of dose delivery. Multiple plan comparison studies have now shown that PBT is able to reduce dose to critical organs compared to photon therapy. However, dosimetric benefit does not necessarily translate to clinically meaningful outcome. The initial part of the thesis focused on the treatment planning aspect of intensity modulated proton therapy (IMPT) in conventionally fractionated radiotherapy for NSCLC. The subsequent parts that followed aimed at identifying patient groups where PBT is likely to be of highest clinical benefit. Therefore, the aims of this project were: [1] to evaluate and compare the robustness of IMPT and volumetric modulated arc therapy (VMAT) plans against setup uncertainties using the probabilistic scenarios method. [2] To evaluate the accuracy of the Raystation TPS analytical dose calculation (ADC) algorithm against Raystation Monte-Carlo (MC) algorithm. [3] To identify a sub-group of lung clinical cases where the Raystation TPS analytical algorithm may be clinically acceptable. [4] To identify a sub-group of patients who would benefit most from IMPT over VMAT with respect to cardiac sparing. The probabilistic analysis provides a fast and practical method for evaluating VMAT and IMPT plans sensitivity against setup uncertainty in locally advanced NSCLC. Although target robustness was achieved over the whole course of treatment, fraction doses were sub-optimal when plans were optimised based on the planning target volume. However, fraction VMAT and robust-optimised IMPT doses were comparable. In the presence of mediastinal involvement and absence of range shifters use of the Raystation ADC may be clinically acceptable for treatment planning in lung IMPT. Otherwise, the MC algorithm would be recommended to ensure accuracy of treatment plans. Finally, using the model-based approach, patients with both pre-existing heart disease and disease overlapping with or inferior to T7 vertebrae are likely to benefit most from proton over photon therapy to reduce risk of cardiac toxicity.

Keywords: monte carlo
lung cancer
intensity modulated proton therapy
pencil beam scanning
heart doses
IMPT
proton therapy
Advisor: Van den Heuvel, F
Vallis, KA
Evaluating the low-energy response of the ProtoDUNE-SP detector using Michel electrons

This thesis presents the results of a study of electromagnetic interactions in the ProtoDUNE-SP liquid argon time projection chamber (LArTPC) detector. The LArTPC detector technology provides high spatial resolution on the final states of charged particle interactions, which allows for different interaction modes to be distinguished based on the geometry of the ionisation energy deposition in the event. As a result, the technology has been used in a number of recent neutrino experiments, and is the technology of choice for the Deep Underground Neutrino Experiment. In order to perform high precision measurements of neutrinos in LArTPC detectors, final state particles need to be effectively identified, and their energy accurately reconstructed. This thesis focusses on these challenges with two studies on data from the ProtoDUNE-SP LArTPC: a study of track-shower classification, and a study of Michel electron energy reconstruction. A track--shower classification algorithm was developed based on the use of convolutional neural networks, and its performance was compared to the current track--shower classification algorithm in ProtoDUNE-SP. The results of this network were used to select a sample of Michel electron events, which were then used to develop a Michel electron reconstruction algorithm based on semantic segmentation with a convolutional neural network. This sample of Michel electron events were then used to estimate the energy resolution and bias for low-energy electrons in ProtoDUNE-SP based on this algorithm.

Advisor: Weber, A
The multifarious muse: two palaeologan collections of paraenetic chapters

This thesis discusses the nature, genesis, authorship and audience of two paraenetic chapter collections of the Palaiologan period and offers a partial edition. I have called these collections Chapters in Four Ways (CFW) and Chapters in Political Verse (CPV). Their nature and composition are rather unusual in comparison to other chapter collections, and they are shrouded in an aura of mystery, which is made worse by the limited attention they have received from scholars. The study of these texts provides information on a wide range of topics such as the two main manuscripts, the genre of paraenetic poetry, the composition of CFW and CPV, intertextuality, hypertextuality, and the legacy of literary authorities in Byzantium, and the interaction between secular and monastic circles. It offers new insights on the authorship of the two collections, which this study shows to be closely related. The critical editions provided in this thesis make hitherto unedited texts available to the scholarly community, contribute to a better understanding of the two collections, and enrich our knowledge of late Byzantine literature.

Keywords: Byzantine Poetry
Chapter Literature
Paraenetic Literature
Palaiologan Poetry
Advisor: Lauxtermann, M
Investigation of the biological function of arginine methyltransferase PRMT5 in human cancers

PRMT5 is a major type II arginine methyltransferase and plays a crucial role in tumorigenesis. PRMT5 is overexpressed in multiple tumour cell lines, and a high level of PRMT5 was identified as an independent factor for poor clinical outcomes in patients with cancer. PRMT5 has been identified as a potential clinical target for antitumour therapy to enable the treatment of cancers efficiently and selectively. However, studies on the role of PRMT5 are limited and there is a need to understand the mechanisms underlying the biological function of PRMT5 and its therapeutic potential. In this study, we have uncovered a functional role for the PRMT5-E2F1 axis on different aspects of cancer cell biology, including cancer cell viability, apoptosis, migration, invasion, and adhesion. Additionally, we performed a genome-wide expression analysis and identified a group of E2F1 targets that modulate cell adhesion and cellular migratory pattern, resulting in metastasis and invasion, via a PRMT5- dependent mechanism. Furthermore, the expression of PRMT5 and E2F1 was correlated, with high levels of PRMT5 and E2F1 indicating poor clinical outcomes. This study is the first time to show that the PRMT5-E2F1 axis influences cancer cell growth and division, and also augments the migration and invasive properties of tumour cells. As a positive regulator of the E2F1 axis, this strengthens the case for the use of inhibitors for PRMT5 as a viable therapeutic target, and further suggests the clinical utility of drugs targeting PRMT5.

Advisor: La Thangue, N
An evidence-based approach to the urgent referral of suspected oral cancer in England

Background
Reports that UK outcomes for several cancers, including oral, were inferior to comparable European countries prompted the UK Government’s ‘NHS Cancer Plan’; a central aim was reduction of late presentation. One key policy was the English ‘two-week rule’ (TWR) system for suspected cancer, specifying a maximum of 14 days between referral and specialist consultation. For oral cancer, little research has been undertaken on several key areas including its influence on stage on presentation and how the system might be improved.
Aim
To conduct evidence-based evaluation of the policy for urgent referral of suspected oral cancer in England and conduct 4 studies in areas where important evidence is absent or sparse.
Methods
(1) A time-series study examining stage on diagnosis of oral cancer before and after the TWR (2) A qualitative study comparing the views of specialists in England and the Netherlands on their head and neck cancer referral systems (3) A systematic review comparing oral cancer referrals from doctors and dentists (4) A Delphi study of expert opinion on the priority of the methods of encouraging early oral cancer diagnosis.
Findings
English/UK outcomes for oral cancer are probably genuinely worse than the European best. The causes are multiple and complex, although late diagnosis is an important cause.
A time-series study of 1483 patients between 1992-2012 suggests the TWR system has not influenced the trend in late oral cancer presentation. Socio-economic differences in late presentation are reducing but persist and oral cancer presentation is increasing.
A qualitative study highlighted similarities between the English TWR system and the more flexible Dutch system but also differences. The Dutch system featured more direct professional communication, greater flexibility and more rapid referral of head and neck cancer.
A systematic review confirmed both GPs and dentists refer oral cancer. Overall, dentists may refer earlier stage disease and refer some cancers following routine inspections, in the absence of symptoms.
In a Delphi study experts consider rapid referral systems high priority for oral cancer but a range of measures were also considered useful.
Conclusions
The current TWR urgent referral system alone may be limited in reducing late oral cancer presentations. Earlier referral may be improved by more flexible referral systems with better communication and by improving access to regular dental inspections, particularly for those at high risk.

Keywords: Oral cancer
Urgent cancer referral
English two-week rule for cancer
Advisor: Pluddemann, A
Bankhead, C
Aspects of supersymmetric gauge theories and conformal field theories in five and three dimensions

Supersymmetric gauge theories and superconformal field theories have long played a central role in string theory. In this thesis, which is split into two parts, we explore multiple facets of this rich class of theories.
In the first part we establish a convenient way to describe 5d SCFTs and gauge theories --- generalised toric polygons (GTPs). Based on insights from (p,q) 5-brane-webs we derive a dictionary between a 5d theory 𝑻P and its associated GTP P. We provide an algorithm to describe the Higgs branch of 𝑻P by computing its magnetic quiver. Furthermore, we identify the Hasse diagram and thereby the entire foliation structure of the Higgs branch. We apply this technique to a large class of 5d SCFTs with a weakly coupled SU(N)
gauge theory description. In this way we both recover known results and derive a series of new magnetic quivers.
In the second part we turn to the 3d-3d correspondence, that relates observables of supersymmetric 3d gauge theories T[M3] to partition functions of topological field theories on M3. We study the sensitivity of this setup to the gauging of higher-form symmetries. We find a refinement of the 3d-3d correspondence for the Witten index, associated to the global structure of the gauge group of T[M3]. For M3 a Seifert manifold and gauge algebra 𝖌=𝖘𝖚(2) we verify this explicitly by counting the solutions to the resulting Bethe equations. We complement this analysis by a refined counting of the flat connections on M3, accounting for the higher-form symmetries.
Finally, we investigate the so far unknown 3d-3d correspondences for theories with 𝑵=1 supersymmetry. We study the theories T𝑵=1[M3] and analyse their connection to the geometry of G2-manifolds. On the complementary side of the 3d-3d correspondence we determine the topological field theories whose partition functions compute the Witten index and the S3-partition function of T𝑵=1[M3]. In the process we point out the relevance of a new generalisation of 3d Seiberg-Witten equations.

Advisor: Schäfer-Nameki, S
Allosteric contributions of muscle nicotinic acetylcholine receptor residues in small-molecule interactions, disease and subunit assembly

The nicotinic acetylcholine receptor (nAChR) is a member of the Cys-loop receptor superfamily of heteropentameric ligand-gated ion channels. The nAChR subfamily has 17 different possible subunits in vertebrates that are found in multiple stoichiometric combinations. Compared to other nAChRs, muscle type nAChRs possess a large subunit repertoire with respect to other nAChRs being comprised of four different subunits- namely alpha, beta, delta and either epsilon or gamma in adult or foetal varieties respectively.
The endogenous neurotransmitter of nAChRs, acetylcholine (ACh), binds at the interfaces of alpha(+)delta(-) and alpha(+)epsilon(-) or alpha(+) gamma(-) subunits. By controlling the safety margin of neuromuscular transmission, nAChRs maintain high-fidelity muscle contraction under a range of physiological conditions. The interference of this process as a result of organophosphorus nerve agent (OPNA) exposure or from genetic disorders such as congenital myasthenic syndrome (CMS) can therefore have deleterious consequences.
OPNAs work by covalent modification of acetylcholinesterase, preventing the breakdown of acetylcholine leading to desensitising block of nAChRs. No antidotes that interact with nAChRs currently exist, however a class of non-oxime bispyridinium compounds (BPDs) have been shown to be efficacious in this regard. In the first part of this project, we sought to rationalise the structure activity relationship data of a series of congeneric BPDs using molecular dynamics (MD) simulations, followed by mutagenesis and electrophysiology to elucidate molecular determinants for their interactions.
In part II of this thesis we identify a novel CMS mutation located at the muscle nAChR alpha subunit transmembrane domain and use enhanced sampling MD simulations and patch-clamp electrophysiology to reveal a new CMS pathomechanism caused by a swap in charge selectivity from cationic to anionic.
In the final part of this thesis, we sought to further explore observations from part I regarding functional differences between orthosteric interfaces as well as discern the structural correlates responsible for the fixed stoichiometric assembly of muscle nAChRs. In the first instance, by integrating MD simulation, evolutionary data and electrophysiology we determine the structural correlates for muscle nAChR subunit assembly and show functional differences between WT and ’double delta’ human muscle nAChR subtypes . Further to this, we explore the relative importance of individual domains of the nAChR delta subunit in contributing to this fixed stoichiometric assembly by generating a range of chimeric epsilon and delta subunits and assessing their cell-surface expression with I125-alpha-BuTx binding assays.

Keywords: nAChR
Bispyridinium
CMS
Electrophysiology
MD simulation
Advisor: Biggin, P