VictorJuiz/thesis huggingface dataset:
Studies of five dimensional superconformal field theories, localization and geometry
Keywords: supersymmetric localization
Seiberg-Witten geometry
superconformal field theories

In this thesis, we study the U-plane of rank-one 5d N = 1 superconformal field theories (SCFTs), which is the one-dimensional Coulomb branch (CB) of such theories on R4×S1
. This circle compactification gives us 4d N = 2 supersymmetric field theories of ‘Kaluza-Klein (KK) type’, and thus the Coulomb branch physics can be described by its Seiberg-Witten (SW) geometry. The total space of the SW geometry, which consists of the SW curve fibered over the CB, can be modelled as a rational elliptic surface. As such, a classification of all possible Coulomb branch configurations, for the 5d field theories and their 4d descendants, is given by Persson’s classification of rational elliptic surfaces. This formalism trivializes renormalization group flows, while also containing information about the global form of the flavour symmetry group and the one-form symmetry, through the Mordell-Weil group of the SW geometry. Moreover, in a number of important instances, the U-plane is a modular curve, and we use its beautiful modular properties to investigate aspects of the low-energy physics, such as the spectrum of light particles at strong coupling and the associated BPS quivers.
A related approach to studying the strong-coupling dynamics of these theories is to consider them on curved backgrounds M5. Our focus is on closed five-manifolds M5 which are principal circle bundles over simply-connected K\"ahler four-manifolds, M4
. Starting with the topologically twisted 4d N = 2 KK theory on M4
, we propose a new approach to compute the supersymmetric partition function on M5
through the insertion of a fibering operator in the 4d theory, which introduces a non-trivial fibration over M4
. We determine the so-called Coulomb branch partition function on any such M5
, which is conjectured to be the holomorphic ‘integrand’ of the full partition function. We precisely match the low-energy effective field theory approach to explicit one-loop computations, and we discuss the effect of non-perturbative 5d BPS particles in this context. When M4
is toric, we also reconstruct our CB partition function by appropriately gluing Nekrasov partition functions.
A techno-socioeconomic investigation of the Husi kiln complex in the middle Yangtze River Valley
Keywords: geochemical analysis
archaeological field work
experimental archaeology
Middle Yangtze River Valley
Husi kiln complex

This thesis presents an initial investigation of the Husi kiln complex (Husi), a significant yet understudied archaeological site in the middle Yangtze River valley. By examining the archaeological background, sociohistorical context, nature of production, geological context, and distribution of ceramics associated with Husi, this research aims to enhance our understanding of its role in the broader regional context of ceramic production in China.
One of the contributions of this research is the critical analysis of the – so far fairly limited – previous studies on Husi, identifying gaps in our knowledge and providing a foundation for subsequent research. By synthesizing the findings from these studies, this thesis offers a holistic understanding of Husi, its role in the ceramic industry, and its impact on the socio-economic and cultural landscape of the region during its period of operation.
This study then advances our understanding of this understudied sight significantly by investigating the nature of ceramic production at Husi through bulk chemical and microstructural analyses on a diverse range of ceramic samples. The exploration of the geological context of Husi is another important aspect of this research. By conducting archaeological fieldwork surveys and collecting geological samples, this study provides crucial insights into the characteristics and properties of the raw materials used in ceramic production at Husi. This understanding is further deepened through replication work, which sheds light on the production processes employed.
Moreover, this thesis contextualizes Husi within the broader regional production and distribution of ceramics through a comparative analysis with other prominent kiln sites, particularly the Jingdezhen kiln, across different periods. This comparative approach elucidates the role and contributions of Husi to porcelain production at the time and provides a deeper understanding of the unique aspects and characteristics of each site. Additionally, this study identifies shared trends, technological changes, and stylistic developments across the broader ceramic industry, as well as the specific factors that contributed to the success or decline of each kiln complex.
Overall, this thesis significantly enriches the current understanding of Husi by situating it within a broader context and shedding light on its unique contributions to the ceramic production history in China. The study's findings are expected to be of interest to scholars and researchers in the fields of archaeology, art history, and cultural heritage, enriching the current knowledge of Husi's historical and cultural significance.
On designing an algorithmically enhanced NHS: towards a conceptual model for the successful implementation of algorithmic clinical decision support software in the National Health Service
Keywords: ethics
information infrastructure
design
NHS
artificial intelligence
healthcare
clinical decision support software

Established in 1948, the National Health Service (NHS) has lasted 75 years. It is, however, under considerable strain: facing chronic staff shortages; record numbers of emergency attendances; an ambulance wait-time crisis; and more. Increasingly, policymakers are of the view that the solution to these problems is to rely more heavily on one of the NHS’s greatest resources: its data. It is hoped that by combining the NHS’s data riches with the latest techniques in artificial intelligence (AI), that the means to make the NHS more effective, more efficient, and more consistent, can be identified and acted upon via the implementation of Algorithmic Clinical Decision Support Software (ACDSS). Yet, getting this implementation right will be both technically and ethically difficult. It will require a careful re-design of the NHS’s information infrastructure to ensure the implementation of ACDSS results in intended positive emergence (benefits), and not unintended negative emergence (harms and risks). This then is the purpose of my thesis. I seek to help policymakers with this re-design process by answering the research question ‘What are the information infrastructure requirements for the successful implementation of ACDSS in the NHS?’. I adopt a mixed-methods, theory-informed, and interpretive approach, and weave the results into a narrative policy synthesis. I start with an analysis of why current attempts to implement ACDSS into the NHS’s information infrastructure are failing and what needs to change to increase the chances of success; anticipate what might happen if these changes are not made; identify the exact requirements for bringing forth the changes; explain why the likelihood of these requirements being met by current policy is limited; and conclude by explaining how the likelihood of policy meeting the identified requirements can be increased by designing the ACDSS’s supporting information infrastructure around the core concepts of ‘utility, usability, efficacy, and trustworthiness’.
Essays in decision-making and organizational behaviour in public bureaucracies
Keywords: organizational behaviour
bureaucracy
public organization

Public servants, no matter how carefully they are selected or incentivized, are only imperfectly able to discharge the objectives of the organizations they work for. They may suffer from bounded rationality, or make systematically biased decisions. They may be pursuing goals at odds with the stated or implied organizational mandate. Or they may suffer from low engagement in their work, and be difficult to retain over time. Through three quantitative essays, I examine how decisions are made in public sector organizations, and in particular how the behaviour of agents who vary in their ability, motivation and the incentives they are responding to contribute to public service (dys)function. In my first paper, a survey experiment in a large UK public sector organization, I find exposure to politician preferences (orthogonal to organizational mandate) increases the rate at which junior decision-makers provide advice contrary to the evidence they are provided with, but no such effect is found for senior officials. In my second paper, an observational study drawing on a large and novel dataset on projects implemented by the same organization, I show that a peer review process induced substantial avoidance of the system around the threshold for eligibility, but available metrics of project quality show only weak evidence of an effect around this threshold. And in my third paper, I use a survey experiment with a sample of public servants from 28 countries to investigate the effect of varying the framing of the gains to organizational initiatives on likelihood of participation, finding few overall effects but some heterogeneity according to pre-existing variation in public servant characteristics. These three papers have implications for how public organizations should structure their work.
Generation of 12-lead patient-specific electrocardiogram and risk prediction of cardiovascular disease using deep learning
Keywords: ECG generation
variational autoencoder
cardiac MRI
risk prediction
electrocardiogram

This thesis presents a novel deep learning framework based on Variational Autoencoders (VAEs) for the generation and analysis of 12-lead electrocardiograms (ECGs), and its use for cardiovascular disease (CVD) risk prediction. It focuses on three major aspects:
First, we propose a model for 12-lead ECG generation that is capable of generating realistic 12-lead ECG data. Comparison with existing methods shows that ours produces lower Maximum Mean Discrepancy and more lead information, while maintaining generation diversity. The model provides an interpretable latent space to explain the generation process and allows for a deeper understanding of the relationships between ECG features.
Second, we introduce patient-specific characteristics by extending the VAE to a conditional VAE, incorporating essential subject-specific information such as age, sex, Body Mass Index (BMI), and anatomical properties of heart and torso into the ECG generation process. This integration enables our model to generate ECGs that are representative of subjects with diverse profiles. The generated ECGs demonstrate strong correspondence with established models and in-silico experiments. To the best of our knowledge, our model is the first deep learning method to integrate heart information into ECG generation. This brings the potential to improve personalized medicine and contribute to a better understanding of the relationship between heart anatomy and ECG morphology.
Lastly, we focus on future cardiovascular disease risk prediction by leveraging the latent space derived from the VAE. We develop an additional classifier that effectively stratifies patients into low and high-risk groups for CVD. This finding shows the presence of informative ECG features for CVD prediction and demonstrates our model’s ability to extract these features, offering new insights for early CVD risk detection and prevention.
In summary, this work contributes to the growing body of research exploring the potential of deep learning techniques in electrocardiography, and their implications for personalized medicine, improved diagnostics, and early CVD risk detection. The proposed VAE-based framework serves as a robust and versatile tool for advancing the field of ECG analysis and risk prediction.
Inhibitory superagonistic antibodies as novel therapeutics
Keywords: receptor agonism
bispecific antibodies
immunology
surface plasmon resonance (spr)

Immune cells express many different receptors capable of modulating their behaviour, with inhibitory immunoreceptors being especially important for maintaining immune tolerance by suppressing autoreactivity. Therapeutic antibodies capable of inducing inhibitory immunoreceptor signalling could, in principle, be useful tools for the treatment of autoimmune diseases. The mechanistic basis of signalling by so-called “superagonist” antibodies reactive with immunoreceptor family receptors are becoming increasingly well understood, with the simultaneous binding of a membrane proximal epitope on the immunoreceptor, and Fc receptor engagement, both appearing to be critical requirements. We sought to examine whether the superagonistic activity of an inhibitory antibody against hBTLA could be directed to specific tissues, by making it engage a tissue cell surface antigen in lieu of the Fc receptor in vivo. For this, murine bispecific antibodies were generated, and the approach showed early promise, although further experiments are needed to confirm and extend the initial findings. It is also unknown whether the requirements of immunoreceptor superagonists apply to other receptor families such as the cytokine receptors. To investigate this, we sought to generate murine bispecific IL-10R agonist antibodies capable of dimerising IL-10R and IL-10R. However, none of the anti-IL-10R bispecific antibodies exhibited agonistic activity in vitro or in vivo, indicating that merely co-localising the two receptor chains is insufficient to trigger signalling and that there are likely to be additional strict geometric requirements for signalling. Both sets of experiments relied on the generation of murine bispecific antibodies and two different methods described in the literature were tried. Only one of these was found to produce high quality bispecific antibody. Finally, this thesis describes the use of new surface plasmon resonance (SPR)-based techniques for assessing the functional bispecificity of such molecules. Both a sandwich SPR-based assay and an Rmax comparison SPR-based assay were each developed, with the two complementary approaches producing similar results. Overall, the thesis strengthens the idea that there is considerable scope for generating a large variety of potentially useful therapeutic agonists.
Active tectonics and palaeoseismicity of the Northern Tien Shan and Dzhungaria
Keywords: Palaeoseismicity
Tien Shan
Dzhungaria
strike-slip fault
intra-continental earthquakes
InSAR
quaternary dating

This thesis focuses on the active tectonics and the palaeoseismicity around the Dzhungarian Basin. The study of surface ruptures is crucial to comprehending the earthquake occurrences of faults. I investigate geomorphic displacements along the boundary strike-slip Dzhungarian Fault using high-resolution drone and Pléiades satellite imagery. The results reveal possible single-event fault slip along the Dzhungarian Fault in the most recent earthquake. I suggest this earthquake is likely linked with a previously identified palaeo-earthquake rupture on the Lepsy Fault. With a joint rupture of the two faults, it could generate an earthquake with a magnitude up to Mw 8.4, which would be amongst the largest magnitude inferred for a continental earthquake. I further use Quaternary dating techniques and InSAR time-series analysis to determine the geological and geodetic slip rates of the Dzhungarian Fault. The results show that the northern Dzhungarian Fault has a long-term uplift rate of 0.6 ± 0.2 mm/yr, whilst the southern Dzhungarian Fault has geological and geodetic strike-slip rates consistent with a range of 2.1 – 4.7 mm/yr. I also re-investigate three historical earthquakes with magnitudes greater than Mw 7.0: the 1812 Nilke, the 1906 Manas and the 1944 Xinyuan Earthquakes in the Borohoro Shan. By re-analysing source parameters and integrating published data, seismological analysis results, and remote-sensing mapping, the study demonstrates the significance of both reverse and strike-slip faulting in the regional seismotectonics, which also indicates the deformation kinematics of the Borohoro Shan as being in a transpressional zone. I collate my results with those from the literature to propose updated earthquake scaling relationships of intra-continental earthquakes. Finally, this study suggests that the Dzhungarian Basin and its surrounding tectonic units are rotating anticlockwise to accommodate both the N-S crustal shortening and the left-lateral shearing within a large-scale zone from the SW Tien Shan to the Altay Mountains.
DNA sequence driven machine learning for modelling replication timing
Keywords: replication
replication timing
machine learning
genetics

All human somatic cells copy their entire genome during mitotic replication, in the S-phase of the cell cycle. Replication timing (RT) is the temporal order of genome replication in S-phase and has been shown to have consistent global “profiles” across a wide range of tissues and diseases. We demonstrate that while there are many factors that influence the specific RT characteristics of individual cell types, there is a strong link between the DNA sequence composition and the overall RT behaviour. This is achieved by accurately modelling the aggregate profiles from 131 RT experiments constituting 56 unique human cell types, using only engineered features of the DNA sequences as input. We then derive insight into how the composition of DNA sequences impacts RT values, by observing the impact of in silico sequence modifications on model predictions. We further extend our modelling towards cell-type specific predictions with a single model by incorporating a minimal source of extra information, ATAC-seq, which provides context for chromatin organisation. The obtained machine learning models, along with the underlying exploratory data analyses and feature engineering, are both useful for prediction of RT and shed light on the underlying DNA sequence basis of the replication phenomenon.
Antibodies, B cells, and immune tolerance in immunotherapy treated oesophageal cancer
Keywords: immunotherapy
autoantibodies
immune related adverse events
cancer
immune tolerance
B cells
oesophageal cancer
clinical trial

Oesophageal cancer (OC) is a leading cause of cancer mortality that is rapidly rising in prevalence in many parts of the world. Immune checkpoint inhibitors (ICI) have revolutionised treatment of many cancer types and were recently approved by the FDA to treat advanced OC. However, there are still many patients who do not exhibit an improved outcome in response to ICI therapy, and predictive biomarkers are lacking. Studies of multiple cancer types have shown that development of immune related adverse events (irAEs) during ICI treatment is associated with good clinical outcome, suggesting that the baseline immune activation of an individual may influence their response. Similarly, the presence of tertiary lymphoid structures, which are sites in which B cells differentiate into antibody secreting cells, in tumours hasrecently been shown to predict improved clinical outcome to ICI treatment, suggesting that production of tumour-reactive antibodies by intra-tumour B cells may contribute to an effective anti-tumour immune response. Despite this, there is a lack of studies of ICI treated OC which either evaluate markers of baseline immune activation, such as autoantibodies (AAbs), as predictive biomarkers of clinical outcome, or characterise antibodies produced by intratumour B cells. In this thesis, I extensively profile the circulating AAbs and peripheral blood mononuclear cells (PBMCs) of ICI treated OC patients from the LUD2015-005 clinical trial to identify novel and distinct signatures predictive of good clinical outcome and development of irAEs during ICI treatment. Further, through transcriptional profiling of OC tumours I show evidence of fully mature B cell responses and identify B cells expressing tumour-reactive antibodies. In summary, this work characterises the role of baseline immune activation in ICI patient clinical outcomes, and expands our understanding of mechanisms that predispose to good clinical outcome or irAE development during ICI treatment. The validation of these results in larger independent cohorts could inform patient treatment decisions based on biomarkers predictive of clinical outcome.
Description of a novel MHC class II restricted allogeneic TCR T cell therapy for acute myeloid leukaemia
Keywords: bone marrow transplantation
acute myeloid leukaemia
immunotherapy

Acute myeloid leukaemia (AML) is an aggressive blood cancer that can be treated with allogeneic haematopoietic stem cell transplantation (allo-HSCT). Although allo-HSCT reduces the chance of relapse because of the Graft-versus-leukaemia (GvL) effect, it is also associated with the Graft-versus-Host Disease (GvHD). This and other treatment or disease related complications mean that only around half of transplanted AML patients survive at 3-years[1]. To harness the GvL effect, on-going research is trying to identify novel GvL-specific allogeneic peptide antigens presented by the major histocompatability complex (MHC), called minor histocompatability antigens (miHA). However, it remains unclear which miHAs mediate a successful GvL effect and what GvL-specific T cell functions are associated with it. This work describes a novel HLA-DP-restricted PADI4 miHA response identified as part of a previous allogeneic antigen screen in a cohort of AML patients with long-term remission post-transplant. Antigen-specific allogeneic T cells were successfully isolated and their T cell receptor (TCR) transferred to third-party primary T cells. PADI4 TCR T cell activation was seen to cancer cell lines, where it could also exert a growth inhibitory effect. Although this work did not show evidence of direct T cell activation to primary leukaemia samples, leukaemia-derived antigen was successfully presented by primary monocyte-derived dendritic cells. PADI4 miHA expression is haematopoietically restricted, suggesting no reactivity to the GvHD target tissues. However, PADI4 TCR T cell activation, without target cell killing, was seen to healthy monocytes. Overall, this data supports the idea that the PADI4 miHA response could exert an anti-leukaemic or a broader anti-haematopoietic effect. This work provides an important starting point to further investigate the PADI4 TCR for its anti-leukaemic effect and the importance of the PADI4 miHA response in other AML patients. It also highlights the role of CD4+ MHC class II-restricted T cell responses in GvL.