VictorJuiz/thesis huggingface dataset:
Knot theory and entanglement in biopolymers

This thesis is divided into two parts, each summarising one of the main projects I have undertaken since the beginning of my DPhil. In the first project, we study the graph associated to a knot K, whose vertices are diagrams representing K, and edges represent single Reidemeister moves. We prove that the isomorphism type of this graph is a complete knot invariant, up to mirroring. This framework suggests a discretised model to study the action of some enzymes on knotted DNA molecules. More specifically, we use a grid diagrams based model to investigate the topological consequences of intersegmental passages occurring in circular DNA molecules. We suggest a grid diagrams-based calculation as a new and computationally convenient framework for investigating knotting probabilities in biopolymers. Recent studies classify the topology of proteins by analysing the distribution of their projections using knotoids. In the second project, using a double branched cover construction, we prove a correspondence between knotoids and strongly invertible knots. This correspondence allows us to study knotoids through tools and invariants coming from knot theory. By using the theory we developed, we investigate the toplogical relation between knotoids differing by small perturbations on the direction of projection. We then apply our results to infer information on the global topology of knotted proteins.

Advisor: Lackenby, M
Buck, D
Harrington, H
Morphology, systematics and palaeoecology of pachycormid fishes

Pachycormiformes are one of the earliest diverging groups of stem teleosts, and are distinguished by substantial ecomorphological disparity: from mid-sized predators, to giant suspension-feeders. Despite this, and their relatively abundant fossil record, they lack detailed study. Here, I use computed tomography scanning to re-examine and redescribe well-preserved suspension-feeding (Martillichthys) and predatory (Pachycormus) pachycormiforms. I report previously unobserved aspects of the gill skeleton (Martillichthys), neurocranium (both) and pectoral girdle (Pachycormus). I also identify features previously unreported in pachycormiforms, including a median vomer (Martillichthys: considered a teleost character but likely convergent), a urohyal (Pachycormus: considered a teleost character), and a metapterygium-like radial (Pachycormus: considered a primitive actinopterygian character). These morphological observations, along with molecular and stratigraphic data, inform phylogenetic analyses using maximum parsimony and Bayesian methods in order to resolve pachycormiform interrelationships, estimate divergence times, and test a hypothesized second origin of suspension-feeders within the group. Results corroborate previous hypotheses of pachycormiform relationships, but the inclusion of stratigraphic data results in an alternative pattern of relationships. Finally, I use quantitative biostratigraphic models, incorporating fossil record heterogeneity, to estimate credible intervals of suspension-feeding pachycormiform extinction and suspension-feeding chondrichthyan emergence. I find some chondrichthyan lineages may have appeared as early as the Early Cretaceous, and cannot reject that pachycormiforms may have persisted into the Eocene. However, the presence of other putative suspension-feeding chondrichthyans in the Cretaceous that are absent in the Cenozoic suggests modern lineages may (as hypothesized here and elsewhere) have emerged following the faunal turnover of the end Cretaceous. This thesis builds a clearer picture of pachycormiform morphology and interrelationships, which can be used as a model to interpret the ecology and evolution of other fossils of pachycormiforms and stem teleosts. It also provides further context for the evolution of modern teleosts and how the extinction of pachycormiforms impacted modern marine diversity.

Keywords: suspension-feeding
palaeontology
Bayes
morphology
systematics
CT scanning
pachycormiforms
ecology
phylogenetics
Advisor: Giles, S
Friedman, M
Computational and neural mechanisms of human aversive learning

Aversive learning is characterised by rapid learning which is highly resistant to extinction. This has likely developed as an evolutionary mechanism but it often becomes maladaptive. In this thesis I investigate computational mechanisms governing the learning of aversive beliefs, neural structures that are involved in the process and test whether pharmacological intervention can be used to amend learning.
In a series of three experiments in healthy volunteers ranging in trait anxiety I employ a probabilistic aversive learning paradigm in behavioural (study 2 and 3) and neuroimaging setting (study 1). I first characterise the difference between acquisition and extinction, identifying that while acquisition learning is fast and reaches the target level, during extinction aversive expectations are consistently higher than true reinforcement rates. This extinction-specific overprediction increases over time but only in the low anxious group. High trait anxiety was associated with increased dissociability between acquisition and extinction which was driven by the activity in the dorsal anterior cingulate cortex. Computational modelling revealed that high anxiety is associated with the tendency to internally represent the learning environment as distinct states and switch between them. This finding was later supported by behavioural and computational evidence in study 2. The neuroimaging analysis suggests that state learning is processed by the dorsal anterior cingulate cortex, ventro-medial prefrontal cortex and the inferior parietal lobule. This finding highlights increased context-dependence of anxious individuals which bears importance to clinical practice. In study 3, I test the effect of Angiotensin-II receptor antagonist losartan on aversive learning showing that losartan specifically decreases learning rates without influencing perception or updating.

Keywords: state learning
fear extinction
reinforcement learning
anxiety
dorsal anterior cingulate cortex
neuroimaging
pupilommetry
aversive learning
Advisor: Wiech, K
Bogacz, R
Development of tuberculosis imaging probes based on sugars and proteins

Tuberculosis (TB) is one of the oldest known human diseases, caused by Mycobacterium tuberculosis. The techniques currently employed for diagnosis are generally insensitive and non-specific. Positron emission tomography (PET) combined with computed tomography (CT) is used extensively in clinics and is among the advanced molecular imaging modalities for disease diagnosis and for monitoring the response to treatment.
In this thesis we described new probes based on sugars and proteins. We used an optimised biocatalytic approach for the synthesis of 2-fluoro-2-deoxy-D-trehalose (FDT). We scaled up synthesis for pre-clinical studies giving strong consideration to the expression host for enzymes. The use of rare biocatalytic methods employed in the synthesis was unique for the development of a radioisotope probe.
We then sought to develop an LC-MS based method for the detection of FDT in vitro and in vivo. Toxicity of the synthesised sugar compound was assessed in two different animal models. FDT administered to naïve marmosets labeled very little tissue in the lung, but when the animals were infected with M. tuberculosis, the tubercular lesions took up the radiolabelled FDT and [18F] FDT monomycolate was isolated from tubercular lesions indicating that the probe reached the site of bacterial incorporation. In addition, FDT labelling of tubercular lesions was reduced with 4-drug standard TB treatment in marmosets. This work has permitted the development of specific PET imaging probe for TB diagnosis towards the clinic.
We demonstrated that a connvergent protein synthesis using a "tag-and-modify" approach allowed the creation of homogenous, modified CCL2 variants bearing dual labels. We incorporated an unnatural amino acid azidohomoalanine (Aha) in the wild type CCL2 to obtain modified variants. Through initial work we have shown the successful modification of various potential PET imaging probes for TB diagnosis.

Keywords: protein chemistry
CCL2
biocatalyst
FDT
Azidohomoalanine
Imaging
Tuberculosis
PET
enzymatic sugar synthesis
Advisor: Davis, BG
Rational herds and endogenous fluctuations in consumer sentiment

This thesis models \textit{endogenous} fluctuations in consumer sentiment and sentiment driven endogenous business cycles in the context of a general equilibrium model with rational herds and social learning in consumer durable goods sector about a hidden state of nature. I want to understand the theoretical conditions under which one gets endogenous and asymmetric cycles in this class of models. The learning dynamics are very sensitive to the variances specified for signal distributions and also to how difficult it is to distinguish the two unobservable states. For some values, convergence of public beliefs to the truth is very slow and one gets rational herds on the wrong action and for others, one gets endogenous cycles in public beliefs and investor mass, leading to fast convergence to truth. In addition to endogenous cycles, my theoretical results also show evidence of asymmetric effects of consumer sentiments across business cycle regimes, which I compare with stylized facts about asymmetric causal effects from local projections. I do not aim to achieve precise quantitative goals with this model, but my qualitative impulse responses provide a sentiment, social learning and information based theory of endogenous and asymmetric business cycles.

Keywords: informational cascades
resolution method
rational herds
information frictions in macroeconomics
bayesian learning
nonlinear business cycle models
endogenous business cycles
two sector new Keynesian models
social learning
asymmetric business cycles
consumer sentiment
Advisor: McMahon, M
The synthesis, post-polymerization functionalization and applications of oxygenated polymers

This thesis focuses on the synthesis and properties of block polyesters and polycarbonates, proposed as sustainable alternatives to existing petrochemicals. The polymers are prepared using efficient catalysed reactions, including the ring opening copolymerization (ROCOP) of epoxide/anhydride or CO2 and lactone ring opening polymerization (ROP). The thesis comprises an introduction, providing a review of the literature and setting out the thesis aims, followed by three related research chapters which examine different aspects of these block polymers.

Advisor: Williams, C
Africans in Britain, 1500-1640

This study of Africans in Britain 1500-1640 employs evidence from a wide range of primary sources including parish registers, tax returns, household accounts, wills and court records to challenge the dominant account, which has been overly influenced by the language of Shakespeare’s Othello and other contemporary literature. I explain the international context of growing trade and increased diplomatic relations with Africa and a concomitant increased level of contact with Africans in the Atlantic world. I then explore the ways in which Africans might come to Britain. Some travelled via Europe in the entourages of royals, gentlemen or foreign merchants; some came from Africa to train as trade factors and interpreters for English merchants; large numbers arrived as a result of privateering activity in which they were captured from Spanish and Portuguese ships. Once in Britain, they were to be found in every kind of household from those of kings to seamstresses. Some were entirely independent, some poor, though few resorted to crime. They performed a wide range of skilled roles and were remunerated in the same mix of wage, reward and gifts in kind as others. They were accepted into society, into which they were baptized, married and buried. They inter-married with the local population and had children. Africans accused of fornication and men who fathered illegitimate children with African women were punished in the same way as others. The legacy of villeinage coupled with the strong rhetoric of freedom in legal and popular discourse ensured that Africans in Britain were not viewed as slaves in the eyes of the law. Neither were they treated as such. They were paid wages, married, and allowed to testify in court. Those scholars who have sought to place the origins of racial slavery in Elizabethan and early Stuart England must now look elsewhere.

Keywords: Tudor England
Caribbean
Africans
Renaissance England
Tudor
early modern
early modern Scotland
slavery
Stuart
black British history
Africa
West Africa
black history
black presence
maroons
Advisor: Davidson, N
Holmes, C
Fluid injection and migration in layered aquifers

Large-scale fluid injection into the subsurface is important for a number of industrial applications, including the injection and storage of CO2 for the mitigation of anthropogenic climate change. A vast amount of seismic data suggests that vertical heterogeneity dominates the distribution of fluids in layered aquifers. However, most studies of fluid injection typically neglect layering. This thesis aims to characterise the fundamental dynamics of subsurface fluid injection and migration in a layered aquifer system. This goal is achieved via the derivation of a novel theoretical model that is both accurate and computationally efficient. This vertically integrated sharp-interface model utilises a weakly compressible gravity current formulation that accounts for vertical flow of water and gas across a stratified system consisting of relatively thick higher permeability aquifers, alternating with thinner and much lower permeability seals. The coupling with vertical water leakage, and the corresponding vertical dissipation of pressure out of the injection aquifer, is found to have a leading-order role on lateral gas migration. Results demonstrate that vertical pressure dissipation acts to significantly reduce the lateral extent of the plume. Furthermore, vertical pressure dissipation has a significant impact on gas leakage which occurs when a capillary entry threshold is exceeded by controlling the magnitude, and style, of capillary pressure buildup. Results further indicate that distributed CO2 leakage during CO2 injection into layered aquifers such as at Sleipner is more likely than previously considered. As the model developed here retains the plume shape and pressure field at the end of injection, the model can be used to provide unique insights into post-injection migration. Results suggest that due to the strongly tongued shape present at the end of CO2 injection, a period of stagnant lateral migration occurs after an initial phase of depressurisation, and before the transition towards late-time self-similar spreading.

Keywords: gravity currents
geophysical fluid dynamics
carbon capture and storage
Advisor: MacMinn, CW
Cartwright, JA
The effects of antibiotic exposure on selection of antimicrobial resistance in the human gut microbiome 

The gut is a major reservoir of human pathogens, and increasing antimicrobial resistance (AMR) in these organisms is an important problem. Selection of AMR by antimicrobials occurs against a background of disruption in a rich bacterial ecosystem, the gut microbiome. Our understanding of this has recently been transformed by new techniques, such as metagenomic sequencing, that can describe the whole community and directly detect AMR genes. Efforts to control AMR would be greatly helped by reliable measures of the impacts of different antimicrobials on the gut microbiome, but these are generally not available. The aim of this thesis is to address this problem.

A significant limitation of using metagenomic sequencing to study AMR is its inability to detect important resistance genes present at low abundance, and in initial work I explore methods to improve the detection of these using plasmid DNA extraction and selective culture-enrichment. These approaches improve the limit of detection of specific resistance mechanisms, but prove unsuitable for use in a quantitative assay.

I then analyse data from an observational study that I conducted, which recorded antimicrobial exposures and collected stool samples from hospital patients and healthy volunteers. Using multiple regression models with data from metagenomic sequencing, I estimate the effects of specific antimicrobial exposures on global microbiome diversity, the abundance of specific taxa, and the abundance of specific classes of AMR genes. The study utilised both cross-sectional and longitudinal sampling frames, which I analyse separately, providing independent estimates that are supportive of one another. These data allow the direct, quantitative, comparison of many different antimicrobials used in the study. The work also develops approaches to the analysis of these types of observational data that could be used in future studies.

Keywords: gut microbiome
metagenomic DNA sequencing
antimicrobial resistance
Advisor: Llewelyn, M
Walker, S
Perovskite nanocrystals for optoelectronics and photovoltaics

Lead halide perovskite nanocrystals, APbX3, are an astounding candidate for optoelectronic and photovoltaic applications. Their tunable band gap, through both composition and quantum size effects, allows for a wide colour gamut spanning the visible to infra-red region. The colour purity achievable through narrow full width at half maximum (FWHM) in their emission spectra, and bright emission with reports of near unity photoluminescence quantum yield (PLQY), place lead halide perovskite nanocrystals at the forefront of research into display technologies. Despite a vast research effort into these materials over the past five years, questions remain regarding their surface chemistry, optimal synthesis for compositional breadth, and their stability.
In this thesis, a mixed cation mixed anion lead halide perovskite nanocrystal synthesis is investigated. Although fine tuning of the band gap is achieved, the miscibility of the inorganic cation, cesium (Cs), and organic cation, formamidinium (FA), is unclear due to concurrent changes in size and shape of the nanocrystals across the compositional range. To resolve this, a new synthesis to perovskite nanocrystals is investigated utilising a phosphine oxide, with the aim to simplify the ligand shell. This is motivated to decouple size and shape control from composition in a mixed cation perovskite nanocrystal synthesis. All inorganic CsPbX3 nanocrystals are synthesised through this phosphine oxide assisted synthesis, and achieve up to 70 % PLQY whilst maintaining monodispersity at high reaction yields close to the theoretical limit. A simple oleate-only ligand shell is achieved, and confirmed through nuclear magnetic resonance spectroscopy (NMR) and X-ray photoelectron spectroscopy (XPS). The synthesis is translated across to form FAPbBr3 nanocrystals. Although similar PLQYs are achieved, the size and shape control is lost. This lack of control is attributed to the interaction of the labile ammonium protons on FA with the ligands used in the synthesis, which is determined via NMR.

Keywords: optoelectronics
perovskite
nanocrystal
halide
lead
colloidal
synthesis
Advisor: Snaith, H
Towards HANK: Investigating interactions between labour and credit-market frictions in a new Keynesian economy

How can the presence of unemployment affect the properties of economic fluctuations and the effectiveness of monetary policy when a fraction of households are also credit-constrained? This paper presents a New Keynesian model with limited asset market participation combined with a search & matching model of the labour market. The resulting framework uncovers a novel mechanism whereby aggregate shocks affect the hiring incentives of firms and the prevailing wage through fluctuations in the total expected surplus from an employment relationship. In the presence of credit-constraints, this will have implications for the distribution of consumption across households. Quantitative evidence suggests that these effects are indeed significant, leading to a greater volatility in labour market tightness and aggregate labour income. In response to a contraction in monetary policy, the fall in output is found to be much greater due to the interaction between credit and labour frictions, whilst the response of inflation remains quantitatively close to the baseline New Keynesian model.

Keywords: Search &amp; matching
New Keynesian models
Two-agent model
Household heterogeneity
Advisor: Zanetti, F
International coordination of macroprudential policy

Given cross-border spillovers from macroprudential policy, international policy coordination may improve global welfare. This paper's contribution is to investigate the benefits of policy coordination in a setting where some countries are "foreign-banked", meaning their bank sector assets are mostly held by foreign credit institutions. I use a two-country model where one of the countries is foreign-banked, and where each country has a borrower subject to a collateralised borrowing constraint. The constraint depends on the value of the borrower's housing and the country's loan-to-value ratio limit, which is the instrument of macroprudential policy. The main finding is that policy coordination is beneficial for welfare. Specifically, in the uncoordinated steady state, the foreign-banked country exerts direct control over net foreign assets through its loan-to-value ratio, which it uses to its advantage. In effect, in a foreign-banked country, borrower-targeting macroprudential policy doubles as a capital control. In reality, the effect is not limited to strongly foreign-banked countries. Rather, it may apply to any country whose bank sector assets are not purely domestically owned. Given that coordination is beneficial, I use the model to characterise the coordinated optimal policy response to a housing demand shock. Such policy consists of moving each country's loan-to-value ratio inversely proportionally to its house price, which nullifies the shock's effect on debt. Coordinated policy thereby maintains household consumption and welfare at their steady state levels, preventing any adverse effects of the shock.

Keywords: Loan-to-value ratio
Macroeconomics
Collateralised borrowing constraint
Optimal policy
International cooperation
Macroprudential policy
Advisor: Ferrero, A
Asymptotic analysis of outliers dectection algorithms using a new empirical process result

The Robustified Least Squares and the Impulse Indicator Saturation are iterative algorithms concerned with detecting outliers and other unsuspected structures in data. These two algorithms are constructed when the full or split sample least squares are chosen as the initial estimators for the iterated 1-step Huber-skip M-estimator. These methods classify observations as outliers or not. This paper establishes an asymptotic theory considering the role of the varying cut-off in such algorithms. In particular, we demonstrate the tightness property for estimates in each iterated step with the varying cut-off. Moreover, a Poisson exceedence theory to the gauge is built for all iterations. The argument involves a theory for a new class of the weighted and marked empirical process.

Keywords: weighted and marked empirical processes
The iterated 1-step Huber-skip M-estimator
Poisson approximation to gauge
Outliers robustness
Advisor: Nielsen, B