VictorJuiz/thesis huggingface dataset:
“...Jalanan are also the nation’s children...”: street­-associated youth identities in Yogyakarta, Indonesia

Identity is seen by several academic disciplines as a concept critical to adolescent development. A singular, stable identity is often considered the idealised outcome of the bio-psycho-social development process. However, performing multiple distinct identities tailored for diverse contexts can be argued to be adaptive and productive for young people in difficult circumstances, such as those who are economically or socially marginal. This thesis explores if, how, and why street-associated youth in Yogyakarta, Indonesia perform distinct identities in diverse social and spatial contexts. The findings from a year-long ethnographic study form a basis for understanding better how youth perceive and enact their agency towards crafting identities as workers, as members of communities, as peers, as occupants of public space, as citizens, and on social media, within the context of rapidly changing urban landscape.

Advisor: Boyden, J
Time-critical design methods for suction caisson foundations

This thesis is centred around the development of a family of computationally efficient design methods called ‘oxCaisson’, that can predict the behaviour of suction caisson foundations under six degrees-of-freedom loading. These design methods were developed for applications where timeliness or speed is a crucial factor; hence the term ‘time-critical design methods’.
oxCaisson is based on the Winkler framework, in which the soil response is represented by Winkler-type soil reactions that are either distributed along the caisson skirt length or concentrated at the caisson base. These soil reactions were calibrated against the results of rigorous, three-dimensional finite element (3DFE) analyses, making ox- Caisson effectively a surrogate model for the 3DFE method.
The design methods developed are hierarchical in nature, where each subsequent design method builds upon previous ones. First, a design method called ‘oxCaisson-LE’ was developed for a ‘toy problem’, in which the soil was idealised as a homogeneous, linear elastic material. Then, the assumption of soil stiffness homogeneity is relaxed as an energy-based design method was developed for non-homogeneous stiffness profiles. Following that, the assumption of a fully rigid caisson is relaxed as the caisson skirt is modelled using deformable frame elements, which allows the prediction of flexible caisson behaviour (i.e. caissons with deformable skirts).
Next, a design method called ‘oxCaisson-NLE’ was developed to predict the caisson behaviour in small-strain, non-linear elastic soil. Then, a new elasto-plastic design method called ‘oxCaisson-LEPP’ was developed to predict the caisson behaviour in linear elastic, perfectly plastic soil. oxCaisson-LEPP combines the previously developed linear elastic soil reactions with plastic yield surfaces. To model cohesive soil, the plastic yield surfaces were calibrated against 3DFE analyses using linear elastic, perfectly plastic soil with a von Mises yield criterion.
Altogether, these design methods allow a rapid turnover of ‘3DFE-approximate’ design evaluations, which is crucial for time-critical applications such as large scale foundation design optimisation.

Advisor: Byrne, B
Burd, H
Experimental demonstration of quantum effects in the operation of microscopic heat engines

An account of experimental investigations into quantum effects in the operation of heat engines on the atomic scale. It consists of a description of the physical realisation of a heat engine implementation using the negative nitrogen vacancy centre in diamond. Theoretical results extending the idealised theory of quantum heat engines to account for experimental conditions are derived, along with results relating to the limit cycles of cyclic quantum heat engines. Finally the empirical existance of quantum thermodynamic signatures in the operation of microscopic heat engines are presented.

Advisor: Walmsley, I
Nunn, J
Ledingham, P
Transcriptional mechanisms influencing glycaemic traits and risk of type 2 diabetes

Genome-wide association studies (GWASs) have identifified many genetic variants associated with type 2 diabetes (T2D) risk and glycaemic traits, most of which are noncoding. Although existing islet RNA sequencing (RNA-seq) studies have identified genes regulated by T2D-associated variants, sample sizes are small, and most known regulatory targets are messenger RNAs RNAs). The work presented in this thesis aims to characterise long noncoding RNA (lncRNA) expression in islets, identify candidate lncRNA regulatory mechanisms, and through incorporation of genetic data, identify genes with potential causal mediation of T2D-associated genetic variation.
Using data from 43 GTEx tissues, I first showed that lncRNAs are more tissue specific than mRNAs. Using 38 human islet samples with paired ribosomal rRNA depletion (RD) and poly-A-tailed RNA selection (PA) RNA-seq, I then showed that RD more comprehensively isolates lncRNAs, but the relative effective sequencing depth is approximately half that of PA. Using RD RNA-seq from 54 islet samples, I identified previously unannotated expressed regions, but comparison to lncRNAs from recently published islet-specific annotations showed high discordance between studies. Thus, although RD better captures lncRNAs, its use in transcriptome-wide islet analyses is not practical until sample sizes increase.
By analysing differential expression (DE) by T2D status in islets (n = 207) and 48 tissues from GTEx, I found 89 unique lncRNAs with DE in at least one GTEx tissue, and 75 with DE in islets. To give these functional context, co-expression modules were constructed in each tissue with lncRNAs and mRNAs. One common gene module between pancreas and islet was enriched for lncRNAs with DE, and contained mRNAs associated with insulin secretion regulation, ultimately pointing to lncRNA CTB-12O2.1 as a candidate regulator of T2D-relevant gene expression.
I next incorporated genetic data with islet RNA-seq (n = 426) to demonstrate a modelling approach for identifying sparse, robust genetic models of gene expression. My approach is replicable, robust, and provides models that are sparser and explain more expression variation than LASSO or elastic net models.
Using these models along with expression quantitative trait locus models, I identified 33 candidate expression mediators of genetic associations with T2D and glycaemic traits. Amongst these were two lncRNAs that were transcriptionally associated with biologically relevant mRNAs, making them candidate regulatory targets of corresponding T2D-associated noncoding genetic variants.
The data presented throughout has therefore implicated previously unstudied lncRNAs in T2D risk and the regulation of insulin secretion, and has demonstrated how integration of disease-focussed islet RNA-seq and large-scale public datasets such as GTEx and GWAS meta-analyses can effectively identify novel regulatory mechanisms underlying genetic associations with T2D.

Keywords: islet
lncRNA
RNA-seq
eQTL
T2D
Advisor: McCarthy, M
Lindgren, C
Characterizing the function of the Arl15 gene and its role in the development of metabolic traits

The ARL15 human Genome Wide Association (GWA) locus is associated with increased risk of type 2 diabetes, lower plasma adiponectin, higher fasting plasma insulin, sexually dimorphic altered body composition, lower HDL cholesterol and lipodystrophy. Knocking down ARL15 in a human β cell line is reported to result in impaired insulin secretion. ARL15 belongs to the small GTPase ARF family and is predicted to be involved in vesicle trafficking. The aim of this thesis was to test the Arl15 gene as a functional candidate for metabolic traits.
Subcellular localisation studies using overexpression of tagged ARL15 and subcellular ultracentrifugation proved that ARL15 is predominantly localized to the Golgi apparatus. Knocking down full-length Arl15 (Arl15-201) in preadipocytes reduced cell proliferation, resulting in increased differentiation following induction, suggesting that Arl15-201 has a role in cell cycle control during early differentiation. In addition, adiponectin protein levels increased significantly from Day 5 of differentiation with altered assembly of adiponectin oligomer.
CRISPR/Cas9 germline knockout of Arl15 showed that homozygous KO mice die postnatally due to a complete cleft palate while heterozygous KO female mice have reduced fat mass on a normal diet. On an HFD KO female mice have reduced body weight, gonadal fat depot weight, brown adipose tissue weight and plasma adiponectin levels. Heterozygous KO mice have altered insulin secretion, normal insulin sensitivity and unaltered glucose homeostasis. Investigation of homozygous Arl15 KO in adult adipose tissue generated by crossing to adiponectin Cre showed no consistent phenotype which may be due to problems with the Cre, which is still being evaluated, or to deletion occurring only in mature adipocytes.
In summary my data supports Arl15 as a candidate vesicle trafficking gene for craniofacial development, regulation of plasma adiponectin levels and sexually dimorphic altered body composition. The in vitro studies show a role for Arl15 in adipose tissue development.

Advisor: Cox, R
Nanostructured molybdenum disulfide thin film based electrocatalysts for hydrogen evolution reaction

2H-Molybdenum disulfide (2H-MoS2) with catalytically active edges has emerged as a promising catalyst for the hydrogen evolution reaction (HER), 2H+ + 2e− → H2. Towards designing highly active MoS2 catalyst with maximized edge density and activated basal surfaces, this DPhil project focused on the synthesis of nanostructured MoS2 thin film based HER electrocatalysts, using chemical vapor deposition (CVD), gas phase treatments and thermal annealing (TA) methods, followed by characterisation and electrochemical testing of their structural and catalytic properties.
Firstly, a reproducible and scalable synthesis method for high-quality 3D edge rich (3D-ER) MoS2 nanoplatelets utilizing single-step CVD approach was developed. Tailoring CVD parameters resulted in the optimized structure for HER that consists of larger MoS2 platelets with smaller layered MoS2 sheets growing perpendicularly, which increases the total number of edge sites within a given geometric area. By systematically controlling the growth temperature, tunable film thickness and surface morphology were achieved, enabling the optimized combination of edge density, inter-planar charge transport and sufficient binding with the substrate as well as fast removal of gas bubbles via a superaerophobic surface.
Subsequently, gas phase treatments for post-growth modification was applied to activate the catalytically inactive basal plane sites of 3D-ER-MoS2. Hydrogen (H2) annealing and oxygen (O2) plasma etching were utilized to generate defects (cracks, pits, holes, and vacancies) that can catalyze HER in the basal surfaces. By controlling O2 plasma exposure time and H2 annealing temperature, tunable defect density, surface area, and catalytic activity enhancement can be obtained. Optimum treatment conditions led to dramatic improvements in electrocatalytic activity.
Lastly, a hybrid electrocatalyst was prepared by growing Pt nanocrystals on the surface of 3D-ER-MoS2 via TA of Pt precursor. By varying synthesis conditions – precursor loading and TA temperature – average size and specific surface area of Pt nanoparticles can be precisely controlled. Results show that higher Pt loading yields better HER performance despite a smaller specific surface area; higher TA temperature delivers a larger average particle size of the Pt crystals and lowers HER activity. Larger average size led to fast sintering and thus poor durability of the catalyst. The outstanding HER activity of Pt/MoS2 is attributed to highly-dispersed Pt nanoparticles grown on MoS2 basal surfaces, large MoS2 edge density and Pt – S bonding effect induced activity improvement of MoS2 as well as 3D porous network assisted superaerophobic surface.

Keywords: Molybdenum disulfide
Water splitting
Nanostructure
Hydrogen evolution reaction
Catalysis
Advisor: Warner, J
Tsang, S
Mathematical modelling of cell cycle network motifs controlling M-Phase progression

Eukaryotic cells must coordinate growth, replication of their genetic material, and cell division in order to generate two progeny cells from a single progenitor. M-phase is a critical phase of this process during which newly replicated DNA is precisely segregated into two distinct fractions, followed by cell division to produce two new daughter cells. M-phase is a component of both the mitotic cell cycle, during which each daughter cell should inherit an exact copy of the genetic material from the parent cell, and of meiosis, during which each daughter should receive only half of the genetic material from the parent cell to generate a haploid gamete. Despite these differences, both mitotic and meiotic M-phases share many of the same regulatory components.
In this thesis we present work from four different studies in which mathematical modelling is used to analyse the behaviour of the biochemical reaction networks controlling M-phase progression in mitosis and meiosis. We firstly present a theoretical analysis of a conserved network motif (termed here the Feedback-amplified Domineering Substrate or FADS motif), which is responsible for creating bistable switches controlling cell cycle progression at multiple points, including progression through and exit from mitotic M-phase.
We then present three sets of work using mathematical models in combination with data provided by experimental collaborators to examine the regulation of M-phase progression in mitosis and meiosis. We present evidence for how variations on common regulatory themes can generate the distinct outcomes required in each case.

Keywords: Mathematical Modelling
APC/C
Bistability
Cyclins
Cell Cycle
Advisor: Novak, B
A mathematical and computational framework for modelling epithelial cell morphodynamics

Mathematical and computational modelling provides a useful framework within which to investigate the organisation of biological tissues. As experimental biologists generate increasingly detailed descriptions of cellular behaviour, models that consider cells as discrete entities have become a common tool to study how cell-level processes affect collective dynamics, form and function at the tissue level.
To date, however, models incorporating detailed biophysical descriptions of cell shape dynamics have gained little traction among the modelling community. Few model implementations are publicly available, and there often remains no comprehensive account of their method of solution, computational implementation, or analysis of parameter scaling, hindering our ability to utilise such models in practice. In addition, the quality of software underpinning such models (and academic research more widely) is coming under increasing scrutiny, with a growing recognition of the need for correct, reliable and sustainable research software tools.
This thesis aims to address these needs for one such cell-based modelling approach, the immersed boundary method. We develop and analyse the immersed boundary method and provide an efficient, open source implementation for simulating cell populations. The implementation is undertaken within Chaste, an open source C++ library that allows one to easily change constitutive assumptions, and is designed and built with software best practices in mind.
We explore such best practices and refine and add to the infrastructure and functionality of Chaste. We then carefully compare the immersed boundary method with the vertex model, a competing cell-based modelling approach for epithelial tissues, clearly elucidating relative strengths and weaknesses of the immersed boundary method. This furthers our understanding of the circumstances under which the immersed boundary method and similar cell-based approaches are an appropriate computational tool. Finally, to demonstrate the efficacy of the immersed boundary method, we investigate the mechanics underpinning a novel form of epithelial bending, advancing our understanding of the formation of placodes, structures of epithelial thickening in the cranial region of developing embryos. Together, the contributions in this thesis advance the use of reproducible software development approaches in cell-based modelling.

Advisor: Baker, R
Fletcher, A
Molecular flexibility of DNA as a major determinant of RAD51 recruitment

The timely activation of homologous recombination (HR) is essential for the maintenance of genome stability, in which the RAD51 recombinase plays a central role. In vivo, RAD51 polymerises on single-stranded DNA (ssDNA) at double-strand breaks (DSBs) to catalyse HR-dependent DSB repair. Biochemically, human RAD51 polymerises faster on ssDNA compared to double-stranded DNA (dsDNA), raising a key conceptual question: how does it discriminate between them? Throughout this thesis, I tackled this problem by systematically assessing RAD51 binding kinetics on ssDNA and dsDNA differing in length and flexibility using surface plasmon resonance. By fitting detailed polymerisation models informed by the experimental datasets, I suggest that RAD51 is a mechano-sensor that polymerises faster on flexible ssDNA compared to rigid ssDNA or dsDNA. Furthermore, I suggest that the energy released during RAD51 polymerisation is sufficient to overcome any entropic penalty to binding flexible ssDNA. This model presents a new general framework suggesting that the flexibility of DNA, which may increase locally as a result of DNA damage, plays an important role in recruiting repair factors that multimerise at sites of DNA damage.

Keywords: polymerisation
ssDNA
dsDNA
RAD51
surface plasmon resonance (SPR)
mathematical model
homologous recombination
Advisor: Esashi, F
Dushek, O
Neolithic occupation and stone working on the Yorkshire Wolds

This thesis explores the evidence for Neolithic occupation and stone working on the Yorkshire Wolds based on stray finds and lithic scatters from surface contexts. Traditional models for Neolithic occupation are based largely on evidence from excavated contexts, in particular the groups of Neolithic pits at Rudston, and Neolithic houses on the Holderness coast. Extensive scatters of worked flint, however, have been identified on the Yorkshire Wolds. These scatters have not been incorporated into accounts of Neolithic occupation for two reasons: 1) the lithic scatters are typically characterised by low-densities of artefacts, and; 2) the scatters typically contain few artefacts which are typologically diagnostic. A methodology that addresses both of these problems was developed, using: 1) an implementation of Tobler’s resel-based GIS to apply focal functions/spatial filters to polygon features in order to identify spatial patterning in survey data characterised by low-densities of artefacts, and; 2) a method for assigning dates to stone tools and lithic debitage using artefact scores based on diagnostic traits identified through the analysis of lithic assemblages from excavated contexts. The methodology was developed using case studies drawn from a study area centred on the parish of Fimber that had previously been investigated in the nineteenth century by J.R. Mortimer. Analysis of lithic assemblages from sixteen of the Neolithic burial mounds excavated by Mortimer and a surface scatter at Wharram-le-Street close to the former source of the Gypsey Race was carried out. This analysis indicates that traditional models of Neolithic occupation based on a distinction between the High Wolds and Low Wolds cannot be sustained on the basis of evidence from surface contexts and that Neolithic stone working traditions on the Yorkshire Wolds were constrained by the nature of the raw materials available to local communities.

Keywords: Yorkshire Wolds
Lithic analysis
Surface scatters
Mobility
Advisor: Gosden, C
The cusp of capacity: empowering and protecting people in decisions about treatment and care

The law’s cliff-edge approach to mental capacity denies those who lack capacity any right to determine what will happen to them. Consequently, the test for capacity (contained in section 3 of the Mental Capacity Act 2005) must accurately distinguish between those who can and cannot make autonomous decisions.
However, the test relies on too narrow a conception of autonomy, preventing it from capturing impairments in the content of the person’s beliefs or values, rather than their decision-making processes. Moreover, whether a decision is autonomous is rarely as clear-cut as the threshold approach presupposes, and there is substantial ambiguity on the cusp of capacity, exacerbated by the realities of assessing capacity in practice. Faced with this uncertainty, decision-makers have sought to manipulate the test through straining the ‘use or weigh’ criterion in section 3, and more readily rebutting the presumption of capacity where the person wishes to do something that will harm them. This thesis therefore advocates introducing a new authenticity limb to the test that asks whether the person’s values or beliefs are the product of an illness or disorder, as well as greater guidance to enhance the consistency with which the test is applied.
Even so, as no test can infallibly distinguish autonomous from non-autonomous decisions, the law’s cliff-edge approach needs softening. To address concerns that the best interests provisions currently facilitate risk aversion and paternalism, a new framework is proposed to encourage decision-makers to prioritise the wishes of the individual, through a rebuttable presumption that their wishes be determinative of their best interests unless giving effect to them would expose the person to a serious risk of significant harm. If this is rebutted, the weight accorded to the person’s wishes ought to be proportionate to the strength of those wishes when determining what is in their best interests.

Keywords: Autonomy
Decision-making
Mental capacity
Best interests
Mental health
Advisor: Goold, I
Herring, J
Oxonium ions, rearrangements, and natural products

This thesis focuses on the studies of a set of biologically relevant oxonium ions pertinent to the natural product biosynthesis of the red algae of the genus Laurencia. The total synthesis of these oxonium ions is reported along with their structural elucidation supported by extensive NMR spectroscopic analysis and DFT computations. The biosynthetic significance of these oxonium ions is demonstrated by their direct derivatisation into 12 natural products, namely (Z/E)-bromofucins, (Z/E)-chlorofucins, (Z/E)-elatenynes, laurendecumenyne B, laurefurenyne E, laurefurenyne F, ent-(Z/E)-laurefucins and ent-acetyllaurefucin.
Furthermore, 6 additional natural products are synthesised indirectly from the oxonium ions, namely (Z/E)-notoryne, laurefurenyne C, laurefurenyne D, ent-deacetyllaurencin and ent-laurencin. The total synthesis of laurefurenynes C-F also enabled their structural reassignment.
Chapters 1-3 of this thesis introduce the project, provide a brief summary of the chemistry of oxonium ions, and an overview of the proposed biosyntheses of Laurencia natural products.
Chapters 4-6 report the total synthesis of the oxonium ions, their characterisation and their direct derivatisation into various natural products.
Chapters 7-8 concerns the total synthesis of ent-deacetyllaurencin, ent-laurencin and the total synthesis of laurefurenyne C-F and their structural reassignment.

Keywords: Oxonium Ions
Advisor: Burton, J