VictorJuiz/thesis huggingface dataset:
Essays in human capital development

Human capital is the term used to describe the skills, experience, attitudes, aptitudes of an individual. It encompasses a wide array of skills that are contribute to the macroeconomic performance of an economy and the successful functioning of an individual. It is important for productivity, per capita incomes and sustaining growth. Insights from other disciplines such as psychology, child development and education can inform economic models. These disciplines have a long history of research on human capital, albeit using diﬀerent labels. Overall, this thesis incorporates both constructs and methods from other disciplines, to help examine important research questions through an economic framework. These chapters contribute to our understanding of the development of human capital and socio-economic position.
Chapter 2 and 3 examine the role of speciﬁc inputs in the human capital process. Both of these chapters focus on the earliest years of a childs’ life, recognising their importance as critical periods of development. Chapter 2 expands the existing literature of human capital production function estimation by including preschool as an important input for explaining cognitive and health skills at age 5 and 8. It compares these estimates for four lower-middle income countries; Ethiopia, India, Peru and Vietnam. Chapter 3 examines if the existing understanding of human capital production functions can be improved by including a measure of an infants’ disposition - temperament - using a dataset from Ireland.
In contrast to the other two chapters, Chapter 4 focuses on the full period of childhood and adolescence up to early adulthood. It proposes that existing measures of socio-economic status, such as education or income, may not be the most appropriate. It proposes a more composite measure that accurately captures the complex socio-economic positions of young people in today’s economy. It examines the role of distinct types of negative shocks that occur at diﬀerent points in the lifespan and how these impact the likelihood of being advantaged or disadvantaged in adulthood. It also links this measure of SES to parenting behaviours and human capital at 9 months, providing some insight into intergenerational transmission of human capital.

Advisor: Adams, A
Keane, M
Awkward adolescence: developing an age appropriate approach to public praise and recognition for Year 10 students

This research explores how an understanding of mid-adolescent preoccupations (self-concept, peer group influence and the social nature of public praise) can enable schools to develop systems of public praise and recognition for Year 10 students. Using Bronfenbrenner’s ecological model (1979) to summarise the findings from the literature review, it highlights the overlapping influences of school, home and friends and the significance of the differing roles adopted by the students. The literature review points towards the need for increased student engagement and agency in mid-adolescence in order to develop of a system for public praise and recognition.
Through a mixture of phenomenological and quasi-participatory research methods, and by working with friendship groups, a system for public praise and recognition is trialled and refined. The student involvement problematizes the conflicting perspectives of the school and the student within the peer group, but offers a solution which accommodates mid-adolescent needs (peer approval, minimum social awkwardness) with a form of public recognition. The creation of a celebration breakfast, involving friends and allowing privileges (such as the use of mobile phones) is a first step in developing an age appropriate approach to public praise and recognition for Year 10 students. The findings reinforce the importance of student agency, as well as the need for mid adolescents to be seen as individuals within the wider institution of the school. They also point towards the need for further training for educators on the phases of adolescent development.

Keywords: MLT
MLT2019
Regulation of IRF5 activity in inflammatory diseases: novel kinases

Interferon regulatory factor 5 (IRF5), is a multifunctional regulator of immune responses, with a critical role in controlling pro-inflammatory responses of macrophages. IRF5 contributes to the pathogenesis of several inflammatory and autoimmune diseases. Given the importance of IRF5 function in physiology and disease, IRF5 represents a therapeutic target. However, the mechanisms regulating IRF5 activation and the kinases responsible for its phosphorylation in vivo have been unclear. The purpose of this study was to identify novel IRF5 kinases as potential targets for specific control of IRF5-driven inflammatory conditions. Based on a kinase inhibitor library screen and rounds of validation PYK2 and MEKK3 have been prioritised as candidate IRF5 kinases.
Using the CRISPR-Cas9 system I have generated PYK2 and MEKK3 deficient macrophages. Deficiency in PYK2 had an effect on IRF5 activation, IRF5 recruitment to the genomic loci and transcription of IRF5 target inflammatory genes. Moreover, I have identified the PYK2 dependent tyrosine site within IRF5 and demonstrated its importance in IRF5 activation. PYK2 inhibition led to a comparable impact on macrophage transcriptomic signature as IRF5 deficiency, and suppressed cytokine production in biopsies taken from the inflamed gut mucosal tissue of patients with ulcerative colitis. The molecular dissection of the PYK2/IRF5 axis carried out in this thesis has a direct translational potential for inflammatory conditions such as ulcerative colitis, where both the PYK2 and IRF5 gene loci have been associated with increased genetic risk.
Deficiency in MEKK3 had an effect on IRF5 activity and inflammatory gene expression. In the absence of MEKK3 inhibitors, clinically validated kinase inhibitors with off-target MEKK3 potency, were used as initial leads to design MEKK3-specific inhibitors. Chemical modifications of the lead compound Neratinib resulted in the identification and synthesis of analogs with comparable biochemical potency on MEKK3, improved selectivity on a small panel of pathway relevant kinases, with reduced IRF5-driven TNF activation in an IRF5- and MEKK3- specific manner.

Keywords: Kinase
Macrophage
IRF5
Innate immunity
Advisor: Udalova, I
Kessler, B
Metal-catalysed desymmetrizations of meso-compounds

The work contained in this thesis describes transition metal-catalysed desymmetrizations of a diverse range of meso-bisphosphates to afford enantiopure compounds with multiple contiguous stereocenters. The projects focus on the resolution of pro-quaternary centers in the meso-substrates, as these desymmetrizations are underrepresented in organic synthesis.
The first part of the thesis demonstrates the copper-catalysed asymmetric allylic alkylation of cyclic and acyclic meso-bisphosphates using alkylzirconium nucleophiles. The reaction was applied to increasingly complex starting materials, allowing access to products with up to 3 contiguous stereocenters and all-carbon quaternary centers with high enantioselectivity. Unsymmetrical bisphosphates were investigated to allow insight on the reaction mechanism and also underwent kinetic resolution successfully.
In the second part, rhodium-catalysed asymmetric allylic arylation was applied to mesobisphosphates using boronic acid nucleophiles, which expanded on previous asymmetric sp2- sp3 couplings developed in the Fletcher group. Although the reaction was limited in substrate scope, high enantioselectivity was obtained. In addition, cyclic thiophosphates were investigated as electrophiles in a range of catalytic transformations.
Preconditioning for thermal reservoir simulation

Multiphase flow through porous media can be modelled as a complex system of partial differential equations. Such models can be used to optimize the recovery of oil and gas from subsurface reservoirs. In the case of highly viscous oils, thermal recovery techniques are typically used to enhance their extraction. To simulate this, models describing the flow of fluids (typically oil, water, and gas) are coupled with a model for heat flow. Thermal reservoir simulation entails solving these highly coupled systems. Their complexity and the computational effort needed to solve them motivate the need for highly efficient solvers.
In reservoir simulation, most of the computational time is spent on solving linearized systems with a preconditioned Krylov subspace iterative method. Industry-standard preconditioning techniques are based on the approach introduced by Wallis in 1983, the Constrained Pressure Residual method (CPR). This preconditioner is a two-stage process involving the solution of a restricted pressure system.
While initially designed for isothermal reservoir simulation, CPR is also the standard for thermal cases. However, its treatment of the conservation of energy equation does not incorporate heat diffusion, which is often dominant in thermal cases. We are interested in preconditioners specifically designed for thermal reservoir simulation. In this thesis, we present an extension of CPR: the Constrained Pressure-Temperature Residual (CPTR) method, where a restricted pressure-temperature system is solved in the first stage. To study the effects of both pressure and temperature on fluid and heat flow, we first consider a model of non-isothermal single-phase flow through porous media. For this model, we develop a block preconditioner with an efficient Schur complement approximation. Then, we extend this method for multiphase flow as a solver for the first stage of CPTR. We present a comparison of the algorithmic performance of the different preconditioning approaches under mesh refinement and parallelization.

Keywords: Iterative methods
Thermal
Porous media
Reservoir simulation
Multiphase flow
Schur complement
Preconditioning
Advisor: Wathen, A
Jönsthövel, T
Lemon, C
Biophysical studies on the structure and function of Archaerhodopsin-3

Light is indispensable for most life forms, and all organisms have evolved in order to harness or utilise its energy. Microbial rhodopsins are lightactivated proteins that generate an electrochemical gradient across the membrane for vital functions of organisms. Recently, the use of lightactivated proteins that generate an electrochemical gradient have gained attention in the field of optogenetics as tools to hyperpolarise or depolarise membranes, thus achieving neural silencing or as uorescent voltage indicators, as well as in bioelectronics to develop biosensors or photovoltaic cells. Here we explore the biophysical characteristics of a microbial rhodopsin, AR3, resolving its structure for the first time, to give new insights into activity, and permit development of a mutant library of AR3, identifying target residues to achieve spectral tuning. This biophysical characterisation allows the identification of key molecules and networks that enhance the photocurrent of AR3 transferrable to other homolog microbial rhodopsins, thus providing new insights into better protein design for optogenetics and bioelectronics.
AR3 has been purified from its native organism (Halorubrum sodomense) and crystallised giving structures of the light-adapted (LA) state and the dark-adapted (DA) state with resolutions of 1.07 Å and 1.2 Å, respectively. The resolution of these structures has allowed the identification of complex hydrogen bonding networks and residues important in ion transport, as well as water molecules. The differences between the DA and LA states have been also shown, as well as identifying key differences between AR3 and bR internal rearrangements. Furthermore, we use high-speed AFM, serial crystallography and X-ray free electron lasers to identify conformational changes that take place in the protein during the photocycle in the early stages (using XFEL) and in the later stages (using HS-AFM).
AR3 has recently gained importance in the world of microbial rhodopsins due to its high photocurrent change upon illumination enabling neural silencing in optogenetics applications. Here we study the photocurrent properties of AR3 using a novel droplet interface bilayer system. We study the activity of AR3 over long periods of illumination and address the role that chromophores bound to the protein, such as retinal or bacterioruberin, might have in the photocurrent and bleaching of the protein.
Finally, we develop a mutant library of AR3 mutants with different spectral properties. We assess the proton pumping of the different mutants developed, as well as the photocurrent change and the action spectra, and study the effect in absorbance and photocurrent that different mutations have in key residues responsible for the proton pumping activity of the protein. Such mutants have potential applications for improved use in optogenetics, especially in red-shifted mutants.

Advisor: Watts, A
Motion tracking and modelling of the forefoot for clinical gait analysis

Multi-segment foot models (MSFMs) are often used in clinical gait analysis (CGA) for the diagnosis and treatment planning for patients with foot deformities. Thus far, close to 40 MSFMs have been proposed, and each differs in terms of segmentation, marker placement protocol, tracking technology, and joint motion. By representing individual segments as a series of linked rigid body segments, the computation and interpretation of foot biomechanics can be greatly simplified. While this approach may be acceptable for lower-limb segments such as the thigh, shank, or hindfoot, the assumption that this is also valid for the forefoot has been met with criticism. Out of all the segments, there is least agreement on how the forefoot should be represented in an MSFM. In general, Whether or not the flexibility of the forefoot is clinically meaningful is controversial.
Therefore, the aims of this thesis were to investigate the most appropriate way of segmenting the forefoot based on a rigidity criteria and to develop a clinically relevant and practical forefoot model based on the recommended segmentation. It was hypothesised that minimising the violation of rigid body assumption in the proposed novel MSFMs will produce the most relevant forefoot representation that is both practical and useful for clinical gait analysis.
This study first validated the use of sigmaRBE to quantify MSFM segment rigidity through a Monte-Carlo based global sensitivity analysis, which showed that for a typical forefoot segment the sigmaRBE represented 86.7% of the deformation magnitude, with a linear relationship that can be predicted using a simple regression model. Experimental data were used to compute rigidity and track deformation of the Oxford Foot Model segments and the metatarsal markers (attached to the heads and bases of all metatarsals) over the full gait cycle. These data were used to determine appropriate segmentation and marker-placement strategies in the design of novel MSFMs.
Several novel forefoot models were proposed and tested through comparison of visual and descriptive statistics of kinematic output and repeatability analysis. A single novel forefoot model was selected based on practicality and kinematic advantages, and piloted in five individual clinical case studies. The research has contributed to the evidence that the forefoot should not be treated as a single segment, and a new forefoot model suitable for CGA has been proposed.

Keywords: Biomedical engineering
Forefoot
Gait analysis
Human motion analysis
Multi-segment foot model
Biomechanics
Engineering
Advisor: Zavatsky, A
Stebbins, J
Not bringing things to a standstill: Plato's Theaetetus on how (not) to speak about a world in which knowledge is perception.

This thesis is concerned with Theaetetus' definition of knowledge (‘Knowledge is perception') and Protagoras' Measure Doctrine (‘Man is the measure of all things') as discussed in Plato's Theaetetus (151e-187a). I shall argue that Protagoras' Measure Doctrine is best understood as a doctrine of infallibilism: all beliefs are true. I shall argue that Theaetetus' definition commits Theaetetus to perceptual infallibilism: all perceptual beliefs are true. Further, I shall argue that Protagoras' Secret Doctrine (152d-160c) underpins perceptual infallibilism by means of a process ontology: perceptual properties are processes involving objects and perceivers. I shall argue that this process ontology explains three key components of the Secret Doctrine: the Relationalist Thesis (‘Nothing is one thing just by itself'), the Flux Thesis (‘Nothing ever is, but things are always becoming') and the linguistic reforms (the rejection of ‘to be' in favour of ‘to become'). I shall provide a detailed analysis and criticism of the relativist interpretation, according to which the Measure Doctrine amounts to relativism about truth: each belief is true (not simpliciter, but) in relation to the believer. In particular, I shall argue that the refutation of the Measure Doctrine (170c-171c) targets infallibilism rather than relativism about truth. I shall argue that the refutation of the Radical Flux doctrine (‘Everything is always changing with every kind of change in every respect'; 179d-183c) hinges on the view that Radical Flux precludes universals from being instantiated. This view explains both the incompatibility between Radical Flux and Theaetetus' definition and the incoherence of Radical Flux. Further, I shall argue that neither Theaetetus nor Protagoras is committed to Radical Flux: the refutation targets proponents of Theaetetus' definition and of the Secret Doctrine who also endorse Radical Flux. Finally, I shall argue that the refutation of Theaetetus' definition (at 184b-187a) hinges on the view that perceiving does not—and knowing does—involve making true judgements.

Keywords: Theaetetus
radical flux
Measure Doctrine
relativism
Protagoras
perception
Advisor: Peramatzis, M
Castagnoli, L
Spin-ice physics and phase transitions in cadmium cyanide

There is increasing interest in the role of materials with correlated structural disorder in mimicking the exotic properties exploited in electronic condensed matter phases. Spin ices, for example, are important class of frustrated magnets in which the spin configuration obeys the `two-in two-out' ice rules that govern proton order in water-ice. Such ice rules are implicated in a wide range of functional responses in different materials, from heavy-fermion behaviour to superconductivity. Ice-rules-obeying states are characterised by an absence of long range order, leading to a manifold of degenerate ground states, extensive residual entropy and exotic excitations; in spin-ices, these excitations correspond to topological defects in the form of effective magnetic monopoles. The main barrier to experimentation and application of these topological defects is the extremely low temperatures (~ 1 K) at which the spin-ice correlations develop. This thesis explores the structural ice analogue cadmium cyanide, Cd(CN)2, a cubic negative thermal expansion (NTE) material, in which the orientation of cyanide ions maps onto the spin orientation in spin-ices. Cd(CN)2 is shown here to display spin-ice physics at room temperature.
Chapter 3 outlines the extreme sensitivity of Cd(CN)2 to X-ray irradiation, including unit-cell contraction, and the selection or suppression of particular phase transitions. These results explain earlier discrepancies regarding the phase behaviour and negative thermal expansion in Cd(CN)2 and motivated the development of a synthesis of isotopically-enriched 114Cd(CN)2 suitable for neutron scattering studies. The synthesis of Cd(CN)2 directly from Cd metal forms the basis of Chapter 4. The structure of previously-unreported intermediate phase, Cd(NH3)2[Cd(CN)4], is characterised, as well as its thermomechanical response. This represents the first variable-temperature study of this type of framework (PtS), shown to display anisotropic NTE and negative linear compressibility.
The main result of this thesis is to demonstrate that by replacing the magnetic dipole in spin-ice with the electric dipole of the cyanide ion, cadmium cyanide displays spin-ice behaviour at temperatures nearly sixty times higher that in its magnetic analogue. I present the results of neutron scattering measurements on 114Cd(CN)2 along with density functional theory calculations, Monte Carlo simulations, total scattering and nuclear magnetic resonance measurements. Having confirmed the importance of spin-ice physics, chapter 6 explores the pressure and temperature dependence of the ice-like correlations. At least two phase transitions are identied at low pressure, kinetic trapping is observed and the extreme compressibility shown to be a function of cyanide reorientation and ice-like coordination. It is hoped that increase in energy scale, identified here, will enable further exploration that may shed further light on the physics of the spin and water-ices themselves.

Keywords: spin-ice
correlated disorder
negative thermal expansion
Advisor: Goodwin, A
Cyanide responsive lanthanide complexes and supramolecular lanthanide architectures

This thesis describes the development of new lanthanide-based luminescent architectures with potential as chemosensors, exploring how the luminescence properties of lanthanide complexes can be altered as a consequence of changes in key analyte concentrations.
Chapter 1 provides some background to the field, relating the fundamental properties of lanthanide complexes to their interactions with their surroundings. It also outlines key objectives for sensing cyanide and fluoride in competitive media.
Chapter 2 describes the synthesis and properties of a series of lanthanide complexes which incorporate a phenacyl group attached to the well-known DO3A lanthanide binding domain. These complexes show a very limited response to fluoride ions as a consequence of their weak affinity for the charge-neutral lanthanide complex. By contrast, cyanide ions interact with the phenacyl carbonyl group, modulating emission from the lanthanide as a consequence of cyanohydrin formation.
These ideas are pursued further in chapter 3. In this chapter, a series of methods are used to explore whether selectivity can be enhanced by using bimetallic complexes. A variety of ligand structures were explored, but the best results were obtained using systems in which two lanthanide-containing complexes were linked together by click reactions. Of these, both the TbEu and EuYb complexes showed the ability to detect cyanide ratiometrically. The EuYb system is probably destined to remain a curiosity, owing to the weak (and hard to detect) emission from the ytterbium centre. However, the TbEu complex has significant potential - offering cyanide selectivity and two-colour emission.
Chapter 4 takes a different approach, describing the synthesis of a lanthanide binding rotaxane in which rotaxane formation generates a lanthanide binding site. Studies on this system reveal lanthanide binding in the assembled hosts, albeit with relatively low affinity for lanthanide ions.
Chapter 5 draws conclusions from the whole body of work and suggests some avenues that might be explored in future
Chapter 6 contains the experimental detail.

Advisor: Faulkner, S