VictorJuiz/thesis huggingface dataset:
Connecting the British Pacific: Naval surgeons in the mid-nineteenth century Pacific

This thesis examines British naval medical officers’ observations of Pacific geographies, environments, peoples and societies, drawing on the official and private records produced during their naval service. It argues that naval surgeons produced the British Pacific in the mid-nineteenth century. The British Pacific was connected by naval officers, including surgeons, who developed a collecting and corresponding network in collaboration with Kew Gardens. The naval contribution to this Pacific network was considerable, but at the same time, the network included non-naval contributors. The role of the Navy was crucial within this network because its surgeons were one of the first cadres that conceptualized Pacific geography: they not only mapped the lands and coastlines but also produced meanings for each place that defined its relationship to Britain and the Empire. Hence, the British Pacific was shaped by both physical boundaries and produced meanings. Also, naval surgeons’ observations and activities in each naval station show that they were, in various ways, connected to metropolitan Britain and its society. Focusing on the idea of the Pacific as a vulnerable, risky and unstable place, this thesis shows how naval surgeons coped with this space and turned it to the ‘British Pacific’.
British expeditions during the mid-nineteenth century are worth examining because there was a different sense of the Pacific from previous expeditions. Records of naval medical officers show that naval expeditions in the late eighteenth and early nineteenth centuries were understood as a different period from those of earlier times, the latter becoming a reference point for medical officers in the 1840s and 1850s. Throughout their naval voyages, naval officers developed an idea of the ‘British Pacific’ which was aimed to make alien lands seem familiar and to delineate their most and least hospitable areas. This entailed making geographical, environmental, medical and social observations. In the face of uncertain and insecure circumstances even in times of the growing Empire in the Pacific, naval surgeons realized how vulnerable they were to alien environments, societies and peoples. Measures were adopted to overcome such vulnerabilities: they maintained connections with Britain or developed familiar views of the Pacific. On the whole, the Pacific environment was not seen as particularly detrimental to European constitutions and Pacific settler societies seemed to be on path to becoming ‘British’, even if they still disappointed in some respects.

Advisor: Harrison, M
Educating awareness: Using variation theory in task design

Researchers claim that implementing highly demanding cognitive tasks helps students improve their mathematical thinking, which is critical for a deep understanding of mathematics (Stein et al., 1996; Charalambous, 2010). In this action research, I investigate how participation in a professional development program on variation theory increases teachers’ awareness about the cognitive demands of the tasks they use in class. This study’s data were collected from various sources: classroom observations, semi-structured interviews, field notes from meetings, and classroom artefacts. The main finding is that teachers source their tasks from the published curriculum materials and do not implement higher cognitive demand tasks than those in the textbooks or past exam questions. This research takes an original approach by using variation theory to increase teachers’ awareness of cognitive demands and improve their subject matter and pedagogical knowledge.

Keywords: MTED 2020
MTED
Statistical Inference in fMRI using Random Field Theory and resampling methods

This thesis provides a set of tools for analysing random images with a specific focus on applications in functional Magnetic Resonance Imaging (fMRI). To do so we employ Random Field Theory (RFT), a set of theoretical parametric results that can be used to analyse multidimensional random processes (known as random fields), and resampling methods, which draw samples from the data (with or without replacement).
We extend the voxelwise inference framework of Worsley et al so that it provides accurate control of the familywise error rate in neuroimaging. We drop the standard RFT assumptions of high smoothness and stationarity and develop a quick parametric framework that provides powerful and valid inference even when the underlying data is non-Gaussian. We validate this using a massive resting state analysis, involving brain imaging data from 7000 subjects from the UK Biobank.
We further use RFT techniques to derive an asymptotic distribution for the extent of a cluster above a threshold u in a non-stationary Gaussian random field as u → ∞. To do so we define the notion of horizontal-window (HW) conditioning and take advantage of recent advances (Cheng and Schwartzman (2015a)) on the HW-distribution of the height of a peak in a non-stationary Gaussian random field. Our results extend those of Nosko (1969) in which the asymptotic cluster size distribution is derived under the assumption of stationarity.
In order to infer upon random fields whose mean is non-zero we derive asymptotic confidence regions for the location of a peak of the true signal given multiple realizations of random fields. These results are valid under non-stationarity and are derived using the theory of extremum estimators. Under the assumption of stationarity we improve upon these asymptotic results using a Monte Carlo approach that provides confidence regions for peaks of the mean which have better coverage in the finite sample.
A second quantity of interest when considering fields whose mean is non-zero is the height of the true signal at the location of a peak in the observed random field. These peaks are typically subject to the winner's curse, which causes inflated effect sizes at peak locations (Vul et al., 2009). We develop a resampling based procedure that obtains low bias estimates of the true signal at the location of the peak. We validate this using task data from over 8000 subjects from the UK Biobank, setting aside 4000 subjects to compute a ground truth, and dividing the remaining subjects into small samples on which to test the results.

Keywords: random field theory
resampling
multiple testing
Advisor: Nichols, T
Schwartzman, A
Terahertz spectroscopy of charge-carrier transport in metal-halide perovskites and narrow-gap semiconductors

Organic-inorganic metal-halide perovskites and narrow-gap semiconductors have been studied extensively over the last few decades. Their peculiar optoelectronic properties make them ideal candidates for future photovoltaic applications and ultrafast electronic devices. Specifically, knowledge of the charge-carrier transport and electronic band structure is key to understanding the fundamental principles that underpin their optoelectronic behaviors, and hence to improve the performance of devices based on them.
Terahertz spectroscopy provides an ideal pathway to probe the optoelectronic properties of these semiconductor materials not only because of its non-contact nature which avoids damaging the sample and removes the complications arising from metallic contacts, but also due to its ability to measure the charge-carrier dynamics on an ultrafast (sub-picosecond) timescale. The versatility of terahertz spectroscopy allows a large phase space of optoelectronic parameters to be probed, such as charge-carrier mobility, carrier diffusion length, and photoconductivity.
A comparative study on the prototypical metal-halide perovskite MAPbI3 as both single crystals and polycrystalline films suggests that Frohlich scattering is the dominant mechanism limiting charge-carrier mobility, which arises from the electron-phonon coupling effect. Further investigations of the phonon modes in MAPbI3 show a phonon-hardening effect under photo-excitation, which is attributed to the increase in dielectric screening due to photo-induced electron doping. In addition, grain-boundary scattering is shown to further reduce mobility in polycrystalline films at cryogenic temperature. By taking into account the effect of photon reabsorption, the wide range of values for charge recombination parameters and charge diffusion lengths reported previously is reconciled. The benign grain boundaries observed in polycrystalline films offer great promise for future high-performance devices.
Time-resolved magneto-terahertz spectroscopy is utilized to investigate the cyclotron effective mass of a narrow-gap semiconductor InSb. A significant reduction of effective mass observed in the first 50ps after photoexcitation indicates a fast hot-electron cooling process. Meanwhile, the increase in effective mass with increasing carrier density agrees with the non-parabolic conduction band predicted by the ab initio calculations of the quasiparticle band structure based on the Kane model.
This thesis, which combines a thorough experimental study utilizing terahertz spectroscopy with a complementary theoretical study based on first-principles calculations, helps to uncover a complete picture of the fundamental optoelectronic properties of metal-halide perovskites and narrow-gap semiconductors.

Keywords: Metal-halide perovskites
Charge-carrier mobility
Terahertz spectroscopy
Narrow-gap semiconductors
Non-parabolicity
Advisor: Johnston, M
The British Conservative Party and the state, 1929-1940

This thesis examines the Conservative Party’s attitude towards the role of the state between its loss of the 1929 election and the downfall of the National Government in May 1940. The appropriate extent of government intervention was one of the most important political debates in the twentieth century, and is critical to understanding the social and economic policies of a controversial decade. Despite this, how the governing Conservatives viewed the state remains neglected. Historians of 1930s Tory domestic policy have variously argued it was too interventionist, not interventionist enough, or quite reasonable. This thesis answers this question by examining an extensive range of archival and other primary sources. In doing so, it provides the first overview of the National Government’s domestic policymaking.
The thesis has six chapters. Chapter one outlines the evolution of Conservatism from the advent of the mass electorate up to 1929. Chapter two explores the development of Conservative policy in opposition up until the party’s unexpected return to government via the multi-party National Government 1931. This is treated separately to the remaining chapters to better assess the impact being in coalition had on policymaking. For the 1931-40 period, the thesis breaks into four case studies: industrial reorganisation, welfare, housing, and education. These four topics were chosen because they were of great contemporary significance. Additionally, because the Conservatives reacted differently in each policy area, comparing them reveals where Tory ideological boundaries lay.
This thesis argues that while most Conservatives were reluctant to turn to the state at first instance, they would at least tolerate state intervention when they believed a key institution was threatened. It further argues that while Conservatism was open to outside influences, whether from coalition partners, ex-Liberals, or civil servants, this was only where those ideas were in accordance with what they understood as Conservative principles.

Keywords: domestic policy
interwar
rationalisation
Conservatism
Conservative Party
welfare policy
Advisor: Grimley, M
Legal and other fictions of civil recovery: is it possible to reconcile the civil recovery of the proceeds of grand corruption with criminal justice and human rights?

Owing to corruption, between USD20 billion and USD40 billion is estimated to be in flight from developing countries annually - with only USD5 billion in stolen assets having been successfully repatriated in the past 15 years. The Arab Spring served only to strengthen the view that civil recovery is a helpful tool in the fight against the evils of corruption. However, difficult tensions exist between civil recovery and principles of criminal justice and human rights, including the presumption of innocence and the right to property. This thesis is centrally concerned with the civil classification of the civil recovery regime of England and Wales, as provided for in Part 5 of the Proceeds of Crime Act 2002 (POCA 2002), and its use to recover the proceeds of grand corruption. I conclude that grand corruption is a serious criminal wrong requiring it to be, except in a very limited number of exceptions, prosecuted in the criminal law. I also conclude that there are strong human rights-based objections to the court’s classification of civil recovery as ‘civil’, and that Part 5 powers ought to be considered criminal in substance thereby attracting the procedural protections of the criminal law and the European Convention for the Protection of Human Rights and Fundamental Freedoms. The core values of liberty, autonomy and freedom that underpin human rights are threatened by Part 5 proceedings since assets are recovered without any criminal conviction or any of the enhanced protections of the criminal law. Yet, at the same time, the recovery and repatriation of illicit assets through civil recovery can enhance human rights, in particular social and economic rights, and corrupt acts can in themselves constitute a violation of human rights. The thesis concludes that despite the important potential human rights benefits of civil recovery, the weakening of certain protections of Article 6 by the use of civil recovery can only be justified in extreme cases when clear criteria are met.

Keywords: asset recovery
social and economic rights
human rights
criminal justice
civil and political rights
Advisor: Lazarus, L
Speciation and adaptation of senecio

Speciation was thought to be initiated by geographical isolation only. However, more and more research has shown that there are other drivers of speciation, such as divergent selection, and that speciation could happen in the face of gene flow with mechanisms to maintain reproductive isolation. This thesis presents similar findings on a case of recent speciation with gene flow found on Mount Etna (Sicily), where closely related high- and low-elevation adapted species, Senecio aethnensis and S. chrysanthemifolius live and hybridise. I used different methods to examine the processes during their speciation and the maintenance of their reproductive isolation. Their homoploid hybrid species, S. squalidus, was also studied to explore various aspects of hybrid speciation. I started by exploring the demographic history of the two species, and revealed several crucial features during their speciation, including heterogenous gene flow, bidirectional gene flow and historical gene flow. Although a secondary contact scenario and a gene flow since divergence scenario could not be determined, the rest of the thesis focused on the evolutionary processes that happened during speciation. Cline analyses and genome scans revealed the presence of divergent selection and positive selection widespread across all linkage groups and that selective agents had various strengths and ages, supporting the multifarious selection hypothesis. These two analyses also provided a list of candidate genes that are related to adaptation to different elevations on Mount Etna, such as those regarding metal ions defence and UV response. In the final chapter of the thesis, I investigated hybrid breakdown using multiple F2 families. Not only was hybrid breakdown confirmed, new breakdown traits were discovered. I also uncovered phenotypic evidence of nucleocytoplasmic incompatibility in the system, and showed that the level of hybrid breakdown likely depended on the level of incompatibility between different S. aethnensis and S. chrysanthemifolius pairs. Last but not least, the hybrid species ex situ, S. squalidus, exhibited significant phenotypic differences from artificial F2 hybrids, hinting morphological novelties during its evolution and establishment in the UK. Overall, this thesis presents research on both the intrinsic and extrinsic mechanisms during the speciation of Etnean Senecio. At the same time, it illustrates the value of these young non-model systems in studying speciation and demonstrates that evolution of new traits for adaptation can happen very quickly.

Keywords: nucleocytoplasmic incompatibilities
genetic incompatibilities
speciation
senecio aethnensis
senecio chrysanthemifolius
selection
clines
Mount Etna
hybrids
adaptation
Advisor: Filatov, DA
Hiscock, SJ
Exploring the substrate scope of histone demethylases

Post-translational modifications of histones play key roles in regulation of eukaryotic transcription and in epigenetics. Lysine methylation of histones is a dynamic balance between activity of methyl transferases and demethylases (KDMs). Fe(II) 2-oxoglutarate (2OG)-dependent Jumonji C (JmjC)-KDMs are current targets for medical chemistry. Defining the extent and role of their substrates is important from a translational perspective and is of basic scientific interest.
The work described in this thesis concerned investigations into the substrate scope of the JmjC-KDM family of 2OG oxygenases. Catalysis by JmjC-KDMs was validated and extended to include new enzymes and substrates. The KDM and RDM activities of a JmjC-KDM (KDM4E) were shown to be inhibited by compounds developed to modulate KDM activity, raising questions about the biological effects of the inhibitors.
Novel non-histone protein substrates of lysine methyltransferase and demethylases were explored and identified using peptide fragments.
Although further investigations are required to determine whether the new findings are relevant in cells, the results highlight a need to consider activities of JmjC-KDMs beyond histone demethylation.

Keywords: JmjC demethylases
histone demethylases
HIF1α
demethylases
G3BP1
Hypoxia-inducible factor 1-alpha
arginine hydroxylation
epigenetics
alpha-ketoglutarate oxygenase
arginine demethylation
2-oxoglutarate oxygenases
lysine N-methylation
KDM1A
Ras GTPase-activating protein-binding protein 1
histones
androgen receptor
lysine demethylation
KDM4E
histone H2a
JmjC proteins
Advisor: Schofield, C
Kawamura, A
MAIT cells in the liver environment

MAIT cells are an important innate T cell population capable of recognising riboflavin-derived ligands presented by the evolutionary conserved MR1 molecule. The ability to activate MAIT cells either through their TCR or cytokines alone enables them to respond to both bacterial and viral infections. The liver is a common site of bacterial and viral infection, due partly to its anatomical setting and partly its tolerogenic environment. MAIT cell enrichment and function in the liver and their impairment in liver and non-liver diseases is not fully defined/understood. In this project I looked closely at the individual, liver resident, cell-specific influence on MAIT cells and their possible role in liver protection or pathogenesis. Using liver cell lines and primary MAIT cell co-cultures and flow cytometry I investigated the ability of liver resident cells to influence primary MAIT cells derived from healthy donors. I have identified that MAIT cells could be activated by LECs using both MR1 and cytokine pathway in response to bacterial stimuli which was not seen with hepatocytes or hepatic stellate cells. MAIT cells were suppressed indirectly in a contact-independent manner, by a small, soluble, COX-dependent, hepatocyte specific mediator/s. Strong suppression of MAIT IFN- by prostaglandins and a partial recovery with COX inhibitor treatment of hepatocytes strongly indicate the role of prostaglandins as well as other factors in controlling MAIT cell activation and function. Prostaglandins can be produced by several liver cell types, are primary involved in liver homeostasis and regeneration but can also impact MAIT cell function by potently suppressing their pro-inflammatory and cytotoxic capacity. The role of MAIT cells in liver disease was analysed by high dimensional, multiparametric spectral flow cytometry. MAIT cell numbers declined significantly in cirrhosis and LT, displayed an exhausted phenotype and were highly dysfunctional. Unsupervised analysis of the same cohort reveals exhaustion and loss of several MAIT cell-related populations which had reduced cytotoxic and inflammatory potential. Overall our data identifies the potential for MAIT cell activation by liver resident cells which can be altered by paracrine signals from neighbouring cells. Furthermore, the loss and functional defects in MAIT cells results in reduced liver protection.

Advisor: Willberg, C
Klenerman, P
Structural and functional studies of metabolic enzymes and their complexes

Enzymes in Intermediate metabolism participate in highly complex protein-protein interactions to carry out their cellular functions. To gain insight into these complexes, an integrative structural biology approach is adopted. Here the novel human structures of aminolevulinate synthase 2 (hsALAS2), involved in haem biosynthesis, and the ATP specific succinyl-CoA synthetase complex (hsA-SCS), involved in the tricarboxylic acid cycle are solved. In both cases, the structures unveil novel enzymatic regulatory features important in the catalytic mechanism for the enzymes and provide insights into enzyme dysfunction in disease. The drugability of hsALAS2, for the treatment of haem related porphyria, is assessed with X-ray fragment screening campaigns and attempts are made to substantiate literature evidence of a quaternary complex between ALAS2 and A-SCS. In addition, the structures of protein complexes in the propionate catabolism pathway are pursued to understand conformational dynamics that underpin their respective reaction mechanisms. The data together builds our understanding of the complexity of protein-protein interactions and their proposed involvement in regulating metabolic flux and pathway cross talk.

Advisor: Yue, W
Froese, S
Kopec, J
Microfluidics with fluid walls

A high variety of microfluidic platforms that aim to miniaturize and automate biomedical assays have been developed in the last decades, but these have failed to be integrated as common equipment in laboratories. This is due to concerns about biocompatibility, issues about the ease of use and the limited range of readouts that the system can accommodate.
This thesis describes a powerful and versatile alternative to conventional microfluidics, in which solid, obscuring walls are replaced by morphing fluid walls. Various methods are used to reshape cell media on Petri dishes into almost any imaginable pattern. The simplicity of the technique eliminates the need for expensive machinery and equipment. The system is shown to be biocompatible and to have potential for high-throughput cell-based analysis. This technology allows the user to fabricate a wide variety of microfluidic devices truly on demand (within minutes).
Beyond simple proof-of-concept applications, this technology produces several important results: miniaturized CRISPR-Cas9 assays in volumes smaller than 1 µl, a fluorescent method for measuring small volumes, a method to reconfigure cellular environments around living cells, a way to accelerate single-cell cloning, beating the Poisson distribution in single-cell cloning, designing and creating a perfusion device which can continuously feed cells over days, and a method for dislodging attached cells and creating wounds in vitro. In its entirety, this thesis puts forward a set of methods to model and reshape cellular environments using apparatus accessible to common biology laboratories: a 3-axis traverse, syringe pumps, petri dishes, cell media and FC40.

Keywords: microfluidics
fluid walls
Advisor: Walsh, E