VictorJuiz/thesis huggingface dataset:
Sri Lanka and the Indian Ocean contacts: internal networks and external connections

This study reconceptualises Sri Lanka’s external trade and interactions from the middle of the first millennium BC to the early second millennium AD. Unlike earlier analyses, mine draws on the excavated material culture from three port-cum-urban centres—Mantai, Kantharodai and Kirinda—which were linked to major urban complexes, interior resource bases and Indian Ocean maritime networks. The scale and intensity of their external trade and connectivity, crafts and industries varied greatly over time and location.
My findings illustrate Sri Lanka's earliest cultural-commercial connections with India from the middle of the first millennium BC. By the beginning of the CE, islanders were trading with the Middle East and the Mediterranean in the west and Southeast Asia and China in the east. The Middle East was a particularly strong connection from about the mid-3rd century. Materials from Southeast Asia and China arrive by the late 7th/8th centuries, with the focus of external trade shifting away from the Middle East to the Far-East around the end of the 10th century, lasting until the 12th/13th centuries and beyond.
My findings demonstrate that internal developments in irrigated agriculture, iron technology, crafts, industries and procurement–distribution networks were crucial for external trade and connectivity. Contrary to the traditional view, I identify local agency as an important driving force behind both internal and external trade in ancient Sri Lanka. The island's external connectivity did not depend on a single factor but was based on specific historical realities which were constantly redefined and reformulated in response to the changing dynamics within and outside Sri Lanka.

Keywords: Kantarodai
Sri Lanka's Maritime trade
Indian Ocean trade
Mantai
Kirinda
Sri Lanka
Sri Lankan archaeology
Sri Lanka's external connections
Jambukolapattana
Mahatittha
Advisor: Robinson, D
Boivin, N
Kennet, D
The role of LKB1 (STK11) in non-small cell lung cancer

LKB1 is the second most commonly altered tumour suppressor gene in lung adenocarcinoma, the most prevalent form of lung cancer. LKB1 is a "master kinase" that has been shown to phosphorylate up to 13 downstream targets. We hypothesised that LKB1 loss is associated with an increased dependency on alternative, targetable pathways. The overall aims of this project were to better understand the role of LKB1 loss in lung cancer and to identify novel approaches to selectively target LKB1 mutated cells.
We generated isogenic cells with or without LKB1 and used these to study the effect of LKB1 on cell proliferation. Importantly, we used a range of models including 2D culture, 3D spheroids and, sub-cutaneous and orthotopic xenograft models. To understand the role of LKB1 loss in lung cancer, the effect of LKB1 on mRNA expression was analysed using whole genome RNA Sequencing. To identify novel approaches to selectively target LKB1 mutated cells, we used biological screening methods and also investigated the effect of several metabolic inhibitors.
We found that loss of LKB1 expression had no effect on cell proliferation in 2D culture, but was associated with increased growth in 3D spheroids, sub-cutaneous and orthotopic xenografts, as well as greater metastasis in a lung orthotopic model. Gene ontology analysis of the transcriptome identified that genes associated with cAMP signalling and cytoskeletal organisation were differentially expressed between LKB1 deficient and proficient cells. We confirmed that cAMP signalling was increased in LKB1 deficient cells, though there was no difference in sensitivity between LKB1 deficient and proficient cells to cAMP signalling modulators. The bioactive small molecule screen showed that LKB1 deficient cells underwent apoptosis more slowly and therefore, were less sensitive to many compounds, compared with LKB1 proficient cells. Screening in 3D spheroids was a novel approach that we used to identify microtubule inhibitors as potentially selective compounds acting in LKB1 deficient cells. Our RNASeq data suggests that there was a metabolic shift from oxidative phosphorylation to aerobic glycolysis in LKB1 deficient cells, although this did not affect sensitivity to complex I inhibitors. Importantly, LKB1 deficient cells were more sensitive to glucose and glutamine deprivation which suggests that targeting these metabolic pathways may hold the greatest promise to selectively inhibit proliferation in LKB1 mutated cells.

Keywords: Bioactive small molecule screen
Metabolism
3D spheroids
Sub-cutaneous xenografts
RNA Sequencing
Othotopic mouse model
Advisor: Ryan, A
The literary Chinese cosmopolis

The thesis is set against the backdrop of literary Chinese as the cosmopolitan written language across East Asia and examines two contemporary literary Chinese writers in the ninth century: Ch'oe Ch'iwŏn from Silla Korea and Sugawara no Michizane from Heian Japan. Though composition in Chinese characters on the peninsula and the archipelago was ancient, a high-water mark within this community appeared in the ninth century. At that time, literary Chinese was embraced by mainstream literati as the medium for poetry and prose, and competent composition in this international written language came to have political as well as cultural significance. The importance of Ch'oe Ch'iwŏn and Sugawara no Michizane as the great masters of Chinese letters in Korea and Japan derives in part from their talents and in part from the social and political acceptance of Chinese.
This comparative research primarily draws inspiration from Sheldon Pollock's comparison of the Sanskrit cosmopolis and the Latin cosmopolis. Pollock describes the Latin cosmopolis as coercive and the Sanskrit cosmopolis as voluntaristic. I argue that the history of literary Chinese in East Asia provides a third cosmo-political model for the history of interactions among language, literature, and cultural and military power. The literary Chinese cosmopolis can be characterized not as coercive or voluntaristic but as hegemonic. I compare Ch'oe Ch'iwŏn and Sugawara no Michizane for their cosmopolitan identities, transnational experiences, and diglossic worlds. Though there is debate over the appropriateness of the terms "diglossia," "Chinese cosmopolis," and "Sinographic cosmopolis" to describe the world in which Ch'oe and Michizane lived, I argue in favor of "literary Chinese cosmopolis," because I pay attention to the common grammar, syntax, and other linguistic features one must bear in mind when composing in literary Chinese (as opposed to reading). Localism produced vernaculars, but the unity of the community was based on composition in a cosmopolitan language. That cosmopolitan language was literary Chinese, a hyperglossic language, a language that allowed universal communication in East Asia.
Intersecting with various disciplines and bringing several critical fields into conversation, this work contests and refreshes a series of key issues at the heart of discussions on globalization, namely the intrinsic relationship between language and power. How does cultural power emerge from language? How does writing in a "foreign" script articulate ethnic, local identities? As a meditation on language politics, ethics, and the historical situation of an earlier cosmopolitan ecumene (ninth century CE), this work will, I hope, offer insights into the specificities and mechanisms of a past cosmopolitan era in East Asia, even as it establishes a broader historical and ethical context for contemporary debates on globalization.

Keywords: Silla Korea
Ch'oe Ch'iwon
Inter-Asian studies
Heian Japan
Sugawara no Michizane
Advisor: Lewis, J
All-at-once solution of time-dependent PDE problems

In this thesis, we examine the solution to a range of time-dependent Partial Differential Equation (PDE) problems. Throughout, we focus on the development of preconditioners for the all-at-once system, which solves for all time-steps in a single coupled computation. The preconditioners developed are used with existing iterative methods and, due to their specific block structure, could be applied in parallel over time.
We first develop solvers for the heat equation and the transient convection-diffusion equation. For both of these forward problems, the all-at-once system is non-symmetric. Despite this, in certain cases, we are able to provide rigorous termination bounds for non-symmetric iterative methods, contrary to what is generally possible for non-symmetric systems.
The ideas developed for evolutionary PDEs are extended to develop preconditioners for time-dependent optimal control problems. By incorporating the methods designed for the forward problem, we are able to develop block diagonal Schur complement based preconditioners, which also could be implemented in parallel over time. We provide extensive eigenvalue analysis for each preconditioner and demonstrate their effectiveness through numerical computations for a variety of problems. We are able to describe solvers that are robust to various parameters, including the mesh size and number of time-steps.

Advisor: Wathen, A
A study of the cellular and environmental context of Barrett's esophagus

Barrett’s esophagus is a pre-malignant lesion leading to esophageal adeno- carcinoma, where presence of Barrett’s carries a seven fold increase in risk of developing cancer. The histology of Barrett’s esophagus is diverse, containing squamous, gastric, and intestinal features, and the origin of the lesion is still under considerable debate. Professor Lu’s research group aims to define the molecular features underlying the Barrett’s lesion and elucidate the functional origin of the lesion. Because pathogens and commensals have previously been reported to be important in other cancers of the upper gastro-intestinal tract, we also aim to explore the role of microbes and viruses in Barrett’s esophagus. We sequenced 3069 single cell RNA samples from endoscopic biopsies of the Barrett’s lesion and relevant normal tissue in the upper gastro-intestinal tract and positive and negative controls. In order to draw meaningful conclusions from these single cell RNA data concerning the functional origin of Barrett’s, we needed to identify robust relationships between single cell observations across tissue types. However, technical variance is a major confounding factor in single-cell RNA sequencing and could distort any such observed relationships. Therefore, I developed BEARscc, a tool that evaluates cluster robustness to noise by simulating experiment-specific technical replicates. I demonstrate that the tool improves the unsupervised classification of cells and aids the interpretation of single-cell RNA-seq experiments. I apply BEARscc to our single cell RNA-sequencing cohort and find striking similarity between the esophagus submucosal glandular ducts and a subset of Barrett’s cells with undi erentiated characteristics. Using BEARscc, I also provide a robust description of the substructure of normal esophageal, gastric, and duodenal tissues. In order to characterize any microbial or viral presence in the microenvironment of Barrett’s, I developed a pipeline, poshTitan, to identify pathogens and commensals in next generation sequencing data. I demonstrate that the poshTitan identifies pathogens with known associations in nasopharyngeal squamous cell carcinoma whole tissue RNA-sequencing and gastric adenocarcinoma whole genome sequencing data. I apply the poshTitan to whole tissue and single cell RNA-sequencing samples of Barrett’s esophagus and normal controls and find no clear pattern of pathogen or commensal association with disease.

Advisor: Lu, X
Schuster-Böckler, B
Opinion formation in dynamic social networks

Opinion dynamics in a society of interacting agents may lead to consensus or to the coexistence of different opinions. The interplay between social network change and opinion formation is complex, because the agents, their social interactions and the changing social structure over time, are themselves complex.
DeGroot proposed a prescriptive model for achieving consensus, where agents revise their opinions at each time step by taking a weighted average of the opinions of neighbours. This thesis contains three main contributions. First, we introduce a generalisation of the DeGroot model and examine the long-time behaviour of the model, with and without insistent agents. Second, we consider opinion formation on networks which are themselves dynamic, where the dynamics may be completely random or based on homophily and triadic closure. The weights that agents place on the opinions of neighbours are also dynamic, based on a rule where weights decrease with increased difference in opinions. Third, we examine the effect of a sudden, temporary or permanent shift in the opinions of some agents.
Two dynamics are considered for the network change over time; random switching (RS) network dynamics, and homophily and triadic closure (HT) network dynamics. We prove that the RS network dynamics enhances consensus formation and network connectivity, compared to the HT network dynamics where we show by simulation that different opinions can persist.
We investigate the in uence of the presence of a minority of insistent agents and prove that for a connected static network, insistent agents with the same opinion in uence the final opinions to converge to their own opinion, thus leading to consensus. In contrast, lack of consensus persists when insistent agents have different opinions. This conclusion also holds for the RS network dynamics model. However, for the HT network dynamics model, coexistence of different opinions can persist even when insistent agents have the same opinion. This finding regarding the HT dynamics is of particular interest as it relates to observations in the real-world.
We also investigate the in uence of a sudden shift in the opinions of some agents on the outcome of final opinions. The case of either a temporary shift in opinions or a permanent shift in opinions is examined. Additionally, the in uence of the time of the introduction of a shift, the number and the network positions of initial recipients of the shift in opinions is investigated. The overall effect of an opinion shift is measured by its in uence on the stabilisation time of the final opinions.

Keywords: Opinion formation
Social networks
Advisor: Reinert, G
Farmer, C
Development and application of speleothem-based proxies for past climate change

This thesis develops and applies new techniques for reconstructing past environments from the speleothem archive. Chapter 3 introduces Ca isotopes as a novel palaeo-aridity proxy. Recent dripwater, farmed calcite and bedrock data show that, in the modern environment, 36% of initial dripwater Ca is removed by prior calcite precipitation at the HS4 dripsite (Heshang Cave, Central China). A speleothem record spanning the 8.2kyr event suggests this value increased to 60% during the event, in response to a decrease in effective rainfall of approximately a third.
Modern Ca isotope systematics, and the cycling of other Group II metals, are studied further in Chapter 4. Data from Heshang Cave monitoring samples explore the temporal and spatial controls on these proxy systems. Results highlight the importance of secondary calcite as a potential source of dripwater metals, as well as the significant contribution of particulate calcite to bulk dripwater chemistry. At the HS4 dripsite, over a third of bulk dripwater Ca is present as particulate calcite. This influences bulk dripwater Ca concentrations and isotopes, as well as potentially impacting speleothem growth and chemistry.
Chapters 5 introduces CaveCalc, a new numerical model for dripwater and speleothem chemistry and isotopes based on PHREEQC. Key strengths of CaveCalc include its ability to model multiple proxy systems in a single framework, the ability to quantify the extent of open-system dissolution, and the extensible nature of its design.
Chapter 6 applies CaveCalc to disentangling the controls on dripwater and speleothem δ13C values. Model results are compared with speleothem data. At Heshang Cave, anomalously high δ13C is quantitatively explained as the result of CO2 degassing and prior calcite precipitation, an interpretation made possible by the availability of coupled δ13C, a14C and Ca isotope data. This approach provides a powerful tool to help researchers better interpret dripwater and speleothem δ13C data.

Advisor: Day, C
Henderson, G
The effect of colloidal aggregates on fat crystal networks

The effect of fumed silica aggregates on fat crystal networks is studied using a combination of rheology, differential scanning calorimetry and polarized light microscopy. We probe a model system for fat-structured foods with the aim of reducing the amount of fat whilst retaining the desirable mechanical and thermal properties. We begin with oscillatory rheology to investigate the effect of added silica and different fat concentrations on the resulting gel networks. The addition of silica is shown to increase the linear viscoelastic region, without significantly changing the storage modulus within this region. Differential scanning calorimetry measurements show that the presence of silica slightly increases the crystallization temperature but does not act as a seed for nucleation or significantly affect the melting profile of the system. We propose the formation of a composite gel network structure with a layer of silica on the surface of the fat crystal chains. We demonstrate that it is possible to create reduced-fat alternatives with similar rheological behaviour and thermal properties as the full-fat systems through the addition of colloidal silica. Next, we look at the effects of silica concentration, surface area and surface chemistry on the model system. In particular, we focus of the storage modulus, the length of the linear viscoelastic region and the rate of network breakdown after the linear region. We interpret these results in terms of hydrogen bonding between the silica aggregates and its role in reinforcing the fat crystal networks. Then, we study the time-dependent rheological behaviour of this system using the three interval thixotropy test. We measure the deformation under an applied stress and the recovery of structure once the applied stress is removed. We show that, under certain conditions, both fat and silica networks are thixotropic, leading to a full recovery after an applied deformation. We observe a synergistic effect leading to much stronger gel networks when fat and silica are present together. We use polarized light microscopy to gain a more direct insight into the effect of silica aggregates on the fat crystal microstructure. In particular, we study the effects of different fat concentrations, cooling rates, silica concentrations and silica surface chemistries. We use various image analysis techniques to quantify the fat crystal microstructure and find no significant difference in the presence of silica, at low concentrations.

Keywords: Fat Crystal Networks
Rheology
Advisor: Aarts, D
Halogen bonding, hydrogen bonding and Lewis acidic receptors for anion recognition

This thesis describes the preparation of acyclic, macrocyclic and interlocked receptors for the recognition of anions in competitive organic and aqueous solvent media.
Chapter One introduces the field of anion supramolecular chemistry, with a particular focus on the non-covalent interactions used for anion recognition and the synthesis of mechanically interlocked molecules.
Chapter Two discusses the preparation of halogen bonding and hydrogen bonding acyclic and interlocked pyridinium-based receptors. Investigations into their anion selectivity trends are undertaken using 1H NMR titration experiments. The anion sensing properties of analogous hosts containing a fluorescent quinolinium motif are also described.
Chapter Three presents the synthesis of acyclic and macrocyclic receptors containing the dicationic 1,2-bis(pyridinium)ethane motif. Attempts towards the preparation of interlocked receptors containing the motif are also discussed.
Chapter Four focuses on a series of water-soluble receptors based around functionalised α-cyclodextrins. Isothermal titration calorimetry experiments are used to investigate differences in the thermodynamics of anion binding to halogen bonding and hydrogen bonding analogues.
Chapter Five details the preparation of a [2]rotaxane containing a Lewis acidic triarylborane motif. Investigations into its anion binding properties are conducted using multinuclear NMR and UV-visible spectroscopies.
Chapter Six provides the experimental details and characterisation data for the compounds discussed in Chapters Two to Five. Protocols for the titration experiments conducted are also described.
Full crystallographic data is provided in the Appendix.

Keywords: Anion
Rotaxane
Hydrogen bonding
Cyclodextrin
Halogen bonding
Advisor: Beer, P
Aspects of the topological Kondo effect

We investigate theoretically the topological Kondo effect (TKE) and related non-Fermi-liquid (NFL) phenomena in correlated mesoscopic devices containing Majorana fermions. Using the numerical renormalisation group (NRG), we confirm and extend results obtained by conformal field theory (CFT) and we calculate numerically exact conductance curves for several different devices over large temperature ranges, which could be compared directly to future experiments. Our calculations uncover a wide range of physics in these mesoscopic devices and we derive several effective models to explain this behaviour.
We first consider the prototypical model proposed by Béri and Cooper [B. Béri and N. R. Cooper. Phys. Rev. Lett., 109, 156803 (2012).] in which a non-local spin-1/2 is coupled to spin-1 conduction electrons. This model was proposed as the minimal model for the TKE, arising as the low-energy effective model of a superconducting grain connected to three leads containing Majorana fermions at the ends. We study the model in detail, confirming asymptotic CFT results and calculating the full conductance curves. We show that the NFL physics is robust to asymmetric Majorana–lead couplings, and uncover a duality between weak- and strong-coupling regimes using Abelian bosonisation. We also show how inter-Majorana couplings destabilise the NFL behaviour.
We next consider the device beyond the effective spin-1/2 model, working instead with an Anderson-type model where charge fluctuations can be taken into account. We consider various possibilities for the energy levels on the superconducting grain and calculate and compare the behaviour in each case. We show that the NFL physics is robust to charge fluctuations, and is not restricted only to the regime of a non-degenerate ground state on the superconductor with large charging energy. We also derive various low-energy effective models for the different charging states.
Finally, we investigate the device with a fourth lead attached. This gives rise to an effective two-channel Kondo model, but the device geometry means that the conductance is distinct from that studied previously. We also consider the full Anderson model, showing again that the conductance results are robust to charge fluctuations.

Advisor: Galpin, M