VictorJuiz/thesis huggingface dataset:
An investigation of T cell immunity and the HIV reservoir during primary HIV infection: implications for cure strategies
Keywords: Primary HIV infection
Immune checkpoint receptors
Post-treatment control

This work focuses on aspects of T cell immunity during the early stages of human immunodeficiency virus (HIV) infection, termed primary infection. Individuals who commence antiretroviral therapy (ART) during primary infection may have preserved immune function, making them a target group for curative strategies. The efficacy of HIV cure interventions are assessed by stopping ART and measuring how long it takes until plasma viraemia recurs. Here, the normal dynamics of this viral rebound in treated and untreated primary infection were characterised, showing that transient control of viral replication is not uncommon at this time. The prospect of HIV cure is heavily reliant on an immune response to eliminate the virus - but such responses become rapidly dysfunctional. During primary infection, changes in T cell activation, memory distribution and the expression of immune checkpoint receptors (which are associated with a type of T cell dysfunction termed exhaustion) occurred. Not all of the demonstrated perturbations in these had normalised following a year of ART which is started during primary infection. This work then turns to the HIV reservoir itself; this is the pool of cells in which the virus persists during long-term therapy and which is the barrier to HIV cure. A longitudinal analysis showed that the size of this reservoir is determined during primary infection where it is linked with aspects of the T cell response measured above. A final chapter shows that CD32, a proposed marker of the reservoir, does not appear to mark cells that comprise the reservoir as specifically as originally reported. Overall this work highlights some of the barriers to current HIV cure strategies and contributes to a body of knowledge which may in the future inform rational design of targeted therapeutic interventions.
Modelling secondary cancer risk from photon and proton therapy in medulloblastoma
Keywords: Proton therapy
Medulloblastoma
Radiation therapy
Radiotherapy
Secondary cancer
Uncertainty testing

More than half of cancer patients receive radiotherapy for radical or palliative purposes. Increasing survival rates in cancer patients makes it important to study long-term side effects, especially secondary cancers. Medulloblastoma (MB), a posterior fossa tumour, predominantly a childhood disease, is an example of a clinical scenario where proton therapy could have significant advantages. It is therefore used as an exemplar in this thesis to investigate the relationship between malignant induction probability (MIP) and secondary cancer risk in 3D conformal photon therapy (3DCRT) and actively scanned proton therapy by using MATLAB-based code, models, relevant parameters and input values from voxel-by-voxel dose maps.
In this thesis, work started by modelling MIP for different treatment plans to assess the relative MIP values. MIP for different modalities was investigated whilst explicitly incorporating the uncertainty in the model parameters in the modelling process. Results showed that proton therapy is less likely to induce malignancy when compared to 3DCRT (p-value &LT; 0.05). To be able to compare our results with published absolute secondary cancer risk estimates and across patients, model parameters were calibrated and benchmarked, and absolute risk values were calculated. This thesis also addresses, in part, some of the other uncertainties that affect secondary cancer modelling. The effect of spatial dose averaging on predicting MIP was studied by modelling risk using mean, and voxel-by-voxel dose. The effect of changes in radiobiological effectiveness (RBE) on modelling MIP was also studied.
This work showed that independent of the model chosen, and independent of the uncertainty in parameters, proton therapy is less likely to induce malignancy and cause secondary cancer than 3DCRT in patients with medulloblastoma. It was also shown that models used could be benchmarked and calibrated against published models, enabling the calculation of clinically realistic absolute secondary cancer risk estimates. The use of mean dose was shown to introduce a systematic error in regions of high dose inhomogeneity in comparison to the voxel-by-voxel method, making use of the high resolution voxel-by-voxel MIP calculation a necessary step in decreasing uncertainty in modelling outcomes. The work also demonstrated that using an RBE of 1.1 could lead to errors in the range of 5%, leading to potentially higher NTCP or lower local control, which is in agreement with what published literature suggests.
Modelling solidification of binary alloys
Keywords: Binary alloys
Stefan problem
Mathematical modelling
Solidification
Asymptotic analysis

Solidification processes are crucial for many industrial applications, and understanding these processes is important if one wants to improve various material production techniques. The dynamics of some solidification processes can be modelled using Stefan problems, a type of free boundary problem. The aim of this dissertation is to study different aspects of the extended Stefan problem for the solidification of binary alloys with a special interest in the manufacturing of metallurgical grade silicon. First, we derive the extended Stefan problem in an arbitrary n-dimensional domain from basic physical principles, and from this we derive more specific models for different geometries of interest. Then, we perform a linear stability analysis for the exact self-similar solutions that can be found in the semi-infinite and infinite one-dimensional planar geometries. Introducing self-similar perturbations, we find that the solutions to both problems are unstable regardless of the parameter choice, and that the instability that arises is driven by the moving boundary. Having understood the relevant dynamics in unbounded domains, we next direct our attention to the extended Stefan problem in finite domains, which are of greater relevance to realistic applications. We first consider a one-dimensional finite planar geometry. In order to obtain analytical solutions we use the method of matched asymptotic analysis in the large Lewis number limit. The analysis requires us to consider ten different layers, spread over four different time regimes. We find good agreement with numerical simulations calculated using a fixed boundary method, and with experimental data from the cast of metallurgical grade silicon performed by our industrial sponsor, Elkem. Finally, we study the three-dimensional spherically symmetric geometry, in order to model the inward solidification of a binary alloy taking the form of a sphere. To determine the asymptotic solutions, we consider the large Lewis number limit and the small Stefan number limit. We distinguish several layers, and we notice qualitative differences between the spherical and planar geometries. To validate the asymptotic results, we compare them with numerical simulations, finding good agreement.
From cat to dog: Investigating organisation in the infant lexicon
Keywords: Child Language Acquisition
Lexical access
Lexical Priming
Word Comprehension
Semantic Networks
Toddlers
Eye gaze

Do infants learn their early words in isolation? Or do they integrate new words into an inter-connected semantic system? Between the ages of one and two, infants develop a prodigious word-learning ability (P. Bloom, 2002; Fenson et al., 1994; Hamilton et al., 2000). Little is known, however, about how and when infants integrate their accumulating word-knowledge into an adult-like lexical network – one sensitive to relationships such as association and semantic category organisation.
For adults, context has a strong effect on the ease and speed of linguistic processing, and on behavioural responses to language. In lexical priming studies, both visual and auditory context are known to influence the speed of lexical processing (Antos, 1979; Meyer & Schvaneveldt, 1971; Radeau, 1983) and ambiguity resolution (Swinney, 1979), as well as guide predictive looks to contextually relevant areas of a complex scene (Huettig & McQueen, 2007; Kamide et al., 2001). And while priming studies have been conducted with children (Betjemann & Keenan, 2008; Duncan & Kellas, 1983; Hartfield & Conture, 2006; Hashimoto et al., 2007; McCauley et al., 1976; Nation & Snowling, 1999; Radeau, 1983; Schvaneveldt et al., 1977) and toddlers (Krackow & Gordon, 1998), the currently available methods are not applicable below the age of three.
This thesis presents a body of research which combines two experimental paradigms into a single new method which allows investigation of relationships within the developing infant lexicon. Over a series of experiments, this thesis develops a version of the infant-friendly Inter-modal Preferential Looking (IPL) task within the lexical priming paradigm. The method combines fine-grained temporal sensitivity with an intuitive, infant-friendly task. Priming effects were observed during lexical access for children two years-of-age and older, providing a promising new direction for investigations into the development of semantic organisation during development.
Theory and practice of shortcut fusion
Keywords: natural transformation
compiler optimisation
fusion
haskell
proof obligation

There are a number of approaches for eliminating intermediate data structures in functional programs by rewriting a composition of recursive functions as a single recursive function. Such a transformation is called fusion. One such approach is to encapsulate a structured recursion scheme in two combinators for consumption and production of data, and use algebraic transformations to rewrite these where possible, letting local compiler optimisations fuse the remaining nonrecursive portions of the program. This approach is called shortcut fusion, which has been implemented using various recursion schemes in the programming language Haskell. Despite their obvious similarities, however, the relationship between these techniques has not been formalised.
In this thesis, three techniques, chosen for their success in practical applications and prominence in previous literature, are analysed. Their relationship is examined on three different levels: theory, practice, and pragmatics. Theoretically, the relationship between their underlying recursion schemes is examined. In the right setting, it is possible to compare them side-by-side, which makes clearer their differences in expressibility as well as the foundations for their correctness. On the practical level, the similarities in their implementations in Haskell can be generalised using the concept of data abstraction, and a general semantic framework is developed for shortcut fusion without reference to a specific recursion scheme. Finally, the pragmatics of these techniques are investigated, and it turns out that the these, too, are not dependent on the specific technique used.
The results from this analysis demonstrate that shortcut fusion is actually a single program transformation, defined by a general semantic framework that can be instantiated for a variety of recursion schemes. Furthermore, it is possible to use this information to create a declarative infrastructure for implementing shortcut fusion within a compiler. This results in a more robust program transformation that is less complicated to implement than before.
Implementing segmented ion trap designs for quantum computing
Keywords: Simulation
Laser
Calcium
Matlab
Ion trap

With all the key elements of quantum computing in ion traps demonstrated by the research community, the focus is now placed on building more sophisticated traps with larger numbers of ions to allow practical scale information processing. One promising avenue is to store ions in and shuttle them between many independent traps which serve as potential interaction sites.
The core of the work described in this thesis is the experimental evaluation of a microfabricated segmented ion trap, built by Sandia National Laboratories ("Sandia trap"). These experiments required construction of a wholly new optical setup including laser and detection systems, a vacuum system and control electronics. Among our experimental achievements were: successful loading of single and pairs of ions in the microscale trap, measurement of ion storage lifetime, measurement of the motional heating rate with a time-resolved Doppler-cooling method — which showed above than average heating, and implemented a single-ion shuttling method — which reliably transferred the ion through a distance of 360 μm (two DC electrode widths away) and back. These results have been used to improve the next version of the Sandia trap design.
We also used computer modelling to study several aspects of ion traps: a mesoscopic ion trap designed for fast ion separation, simulated ion loading to quantify requirements for successful trapping in small and shallow traps, and analyzed a precise shuttling method — where the time dependence of the trapping potential is engineered such that there is minimal motional heating.
The results show that ion trap arrays at the 100 μm distance scale are feasible and suggests that such multiple trap designs merit further study.
A multi-country study of dengue vaccination modelling using econometric and GIS approaches in three dengue-endemic countries: Vietnam, Thailand, and Colombia
Keywords: immunization
vaccines

The overall theme of this thesis is to generate innovative health-economic outcomes which are needed prior to the introduction of population-level dengue immunization programs in three dengue-endemic countries: Vietnam, Thailand, and Colombia. This thesis consists of six chapters which are distinctive but inter-related. Following the introductory chapter, where the existing literature search is carried out, in Chapter 2 I begin by conducting a multi-country study of the economic burden of dengue fever based on standardized field studies in the three dengue-endemic countries.
In Chapter 3, an Early Warning Signal (EWS) model is developed based upon climate and non-climate factors. In particular, this chapter adopts a theory of elasticity, which is not common in the field of health economics but which is a key notion in economics, to predict geographically-dispersed dengue outbreaks in Colombia.
The econometric technique used in the third chapter is further extended to the mixed-effects modeling work in Chapter 4 where high-risk areas for dengue fever are identified at the 5 km by 5 km geographical unit, and the number of dengue vaccine doses is estimated at the population-level in Vietnam, Thailand, and Colombia. The concepts and methodologies applied in both Chapter 3 and 4 are unconventional but clearly underscore the needs for innovative approaches in order to respond to existing public health problems.
Based on the findings from Chapter 1 to Chapter 4, the vaccination impacts and cost-effectiveness of dengue vaccination strategies are estimated in the three dengue-endemic countries in Chapter 5. Vaccination impact is derived from a spatially explicit, individual-based meta-population transmission model developed by the Oxford/Exeter group for the WHO Strategic Advisory Group Experts (SAGE) working group exercise. In addition, country-specific health economic parameters are taken from the economic burden field studies in the second chapter of the thesis. In particular, Chapter 5 is designed to reflect the most up-to-date information on the dengue vaccine development: including controversial debates over CYD-TDV, introducing a new vaccine candidate (NVC) with no safety concern identified in CYD-TDV.
Lastly, Chapter 6 summarizes the roles of the four core chapters as a country-specific investment case, and underscores the importance of an evidence-based decision-making process prior to implementing vaccination campaigns at the population-level.
Mathematical modelling of silicon furnaces
Keywords: Reaction Kinetics
Heat Transfer
Silicon Production
Mathematical Modelling

Silicon is a widely utilised material, with use in the production of semiconductors, textiles, and metallic alloys. It is produced by feeding quartz rock and carbon into huge furnaces, which are heated by electrodes. In this thesis, we develop mathematical models to better understand furnace behaviour. Of particular interest is crust formation, a phenomenon whereby a blockage emerges, preventing the raw materials from falling naturally under gravity to the lower, hotter part of the furnace where the necessary chemical reactions occur.
We begin by developing a continuum model for the evolution of chemical concentrations, temperature, and gas flow in a vertical cross-section of the furnace. This model is analysed in the context of 'pilot furnace' experiments, which are smaller, cylindrical furnaces heated in laboratory conditions. Numerical simulations of our model are shown to compare well with these experiments. We further perform parameter sweeps of our model, to give recommendations for operating strategies.
Next, we undertake an asymptotic analysis of this model, to identify the dominant chemical and thermal behaviour within the pilot furnace. We determine chemical balances in different spatial and temporal regions by imposing a temperature profile. We also obtain a simplified thermo-chemical furnace model, which captures the main behaviour of our original model, but comprises only two partial differential equations.
We then present a model of crust formation, in which furnace crust is treated as a single fluid of thermally-dependent viscosity, located between two moving boundaries. Numerical simulations show that solutions of this model can either tend towards a steady state, indicative of crust formation in practice, or the raw materials can fall indefinitely. The latter case is desirable in real furnaces, although it may not always be feasible. We discuss bifurcations between these two behaviours in our model, and the significance of such bifurcations to avoiding the build-up of crust.
Finally, we focus on the reaction between solid carbon particles and silicon monoxide gas. This motivates us to develop a homogenised model for reactions between solid particles and gas, which has many possible applications. We comment on simplifications of this model for both diffusion-limited and chemically-limited reactions.
Information-theoretic foundations of thermodynamics in general probabilistic theories
Keywords: general probabilistic theories
quantum thermodynamics
sharp theories with purification
quantum foundations
purification
quantum information theory
majorisation

In this thesis we study the informational underpinnings of thermodynamics and statistical mechanics. To this purpose, we use an abstract framework— general probabilistic theories—, capable of describing arbitrary physical theories, which allows one to abstract the informational content of a theory from the concrete details of its formalism. In this framework, we extend the treatment of microcanonical thermodynamics, namely the thermodynamics of systems with a well-defined energy, beyond the known cases of classical and quantum theory. We formulate two requirements a theory should satisfy to have a well-defined microcanonical thermodynamics. We adopt the recent approach of resource theories, where one studies the transitions between states that can be accomplished with a restricted set of physical operations. We formulate three different resource theories, differing in the choice of the restricted set of physical operations.
To bridge the gap between the objective dynamics of particles and the subjective world of probabilities, one of the core issues in the foundations of statistical mechanics, we propose four information-theoretic axioms. They are satisfied by quantum theory and more exotic alternatives, including a suitable extension of classical theory where classical systems interact with each other creating entangled states. The axioms identify a class of theories where every mixed state can be modelled as the reduced state of a pure entangled state. In these theories it is possible to introduce well-behaved notions of majorisation, entropy, and Gibbs states, allowing for an information-theoretic derivation of Landauer’s principle. The three resource theories define the same notion of resource if and only if, on top of the four axioms, the dynamics of the underlying theory satisfy a condition called “unrestricted reversibility”. Under this condition we derive a duality between microcanonical thermodynamics and pure bipartite entanglement.
Tales from topological oceans
Keywords: Potential vorticity
Rossby waves
Multivalued function
Reeb graph
Topology
Neutral surfaces
Geostrophic stream function
Southern Ocean
Instability

Functional relationships between variables can offer great illumination to hard problems. In geophysical fluid dynamics these often arise via alignment of gradients, in which case the functional relationship is multivalued; its branches are determined by a topological analysis of the connectedness of level sets, accomplished by the Reeb graph.
The neutral tangent plane, along which mixing in the ocean predominantly occurs, is defined by ∇nρ = ρp ∇n p, thus a multivalued function relates the in-situ density ρ and the pressure p. With topological analysis, a new approximately new surface is presented, called a topobaric surface. This surface possesses an exact geostrophic stream function, namely the exact geostrophic stream function for neutral surfaces, which ΜcDougall (1989) proved must exist. A closed form expression for this stream function is presented.
For a steady, inviscid, buoyancy conserving fluid, a multivalued function relates the potential vorticity Q and the Bernoulli potential B on buoyancy surfaces. In the Antarctic Circumpolar Current (ACC), level sets of B are dominated by one circumpolar contour, so Q is studied as a single-valued function of B. A tight linear relationship is discovered. Its slope, appropriately non-dimensionalised, provides information about the degree of PV homogenisation on a buoyancy surface, and about the shear stability of the flow regime via Arnol'd's stability theorems.
The real ocean does not obey these assumptions, and Q is not exactly materially conserved. In the time-mean ACC, it is found that Q can vary along streamlines by up to 50%. The causes for these fluctuations are studied, revealing a balance between two large and opposite-signed forcings---mean vertical advection and eddy interfacial form stress---with friction significant near topography. Variation of Q along B contours adds complexity on top of a background state defined by constant Q along B contours.