VictorJuiz/thesis huggingface dataset:
An analysis of non-coding RNAs in Plasmodium falciparum and their potential role in antigenic variation

A major virulence factor of the human malaria parasite Plasmodium falciparum is Plasmodium falciparum erythrocyte membrane protein 1(PfEMP-1). This protein is inserted into the erythrocyte membrane, giving cytoadherence properties. A family of genes called var, located sub-telomerically and in chromosome central clusters encode this protein. Var genes are expressed in a mutually exclusive manner, how this is controlled is unclear. A non-coding RNA (ncRNA) termed the GC-rich element (GRE) had been identified that is only located at the central clusters and is transcribed throughout the parasite lifecycle. A screen of the P. falciparum genome for novel ncRNAs identified ncRNAs from known classes. Novel transcripts were identified, but none in the proximity of var genes.
We have investigated the role of the GRE in var gene regulation. A set of qRT-PCR primers have been designed and tested to follow var gene expression in the HB3 isolate, these are not cross-reactive with a published set for the 3D7 isolate. Alterations were made to the 3D7 set to remove cross-reactivity with HB3. Var gene expression was studied in 31 HB3 clones and progeny of the 3D7xHB3 genetic cross. Following var switching over five months in eleven HB3 clones showed that all of the clones ended up expressing var genes from the same central cluster on chromosome 4. GRE Transcription in these clones is linked to a specific class of var gene. Transcription from a single GRE locus occurs only when a var gene of the central UpsC class is expressed from the same cluster. Expression of other classes of var gene gives multiple transcripts from different GRE loci.
Investigations into the in vitro binding properties of the GRE revealed an RNA:protein complex that can be resolved by electrophoresis. Proteomic analysis of the complex revealed predominantly ribosome proteins and translation factors.

Keywords: non-coding RNA
var genes
antigenic variation
Advisor: Newbold, C
Trajectories of suicidality in the course of major depression

The Differential Activation Theory of suicide suggests that once suicidality has occurred during one episode of depression it is highly likely to recur, when depression recurs. However, paradoxically, although depression recurs, for some people their suicidality may stop. Few studies have addressed the psychological factors associated with resolution or persistence of suicidality within recurrent depression but some research has shown pre-adult onset of depression and suicidality can have particularly toxic consequences. For this thesis, baseline data was obtained from the assessments of a large randomised clinical trial in major depression, in particular a novel method of using timeline data was used to explore 153 previously depressed adults’s life history. This data was examined for the presence of sub-groups within those who have been previously depressed based on their history of suicidality. The overall aims of this thesis were to investigate whether distinct suicidal groups, characterised by different patterns of recurrence of suicidality, could be identified within a sample of participants who all had recurrent major depression. If these specific groups existed within our sample, then a further aim was to compare the socio-demographic and clinical characteristics of each group to those who had never been suicidal. The trajectories of onset of depression and suicidality in adolescence were also explored. Results showed that although it was possible to identify resolved and unresolved groups, differences between the groups were limited. The unresolved group reported experiencing more intrusive suicidal thoughts and found suicidal thoughts more comforting. In regards to age of onset, more than half of the sample had an onset of depression during their adolescence. Those with an onset of suicidality in adolescence experienced a greater number of subsequent suicidal episodes. The presence of suicidality within the first episode of depression rendered individuals more vulnerable to experiencing further suicidal episodes in the future. Intervention, prevention and assessment of suicidality should take into consideration onset of depression and suicidality as well as whether suicidality was present in initial depressive episodes, levels of comfort obtained from suicidal thoughts and how intrusive suicidal thought are.

Keywords: mental health
suicide
onset
age
depression
mindfulness
Advisor: Williams, J
Reactions of allenylpalladium intermediates in organic synthesis

This thesis describes our examination of the reactivity of allenylpalladium intermediates generated from the reaction of palladium(0) with propargylic electrophiles.
Chapter 1 provides a general overview of the literature reported to date concerning the nature and reactivity of allenylpalladium intermediates.
The coupling of a variety of propargylic electrophiles with aryl boronic acids to form allenes is examined in Chapter 2. However, when employing diastereomerically pure electrophiles, some erosion of stereochemistry was observed in the allene products. This effect was examined further, and epimerisation of the allene product was found to be the origin of the loss of stereochemistry. Evidence for the species likely responsible for this epimerisation is presented. The serendipitous formation of tetrahydrofurans (THFs) from propargylic 7-membered cyclic carbonates prompted an in-depth examination of this reactivity, as described in Chapter 3. The reaction of these cyclic carbonates was rendered stereoselective and the stereochemical outcome of the reaction elucidated. The methodology was extended to propargylic acyclic carbonates which allowed the formation of tetrahydropyrans (THPs). The effect of ring-size and substituents on the cyclisations was examined, culminating in the formation of two rings in a single step from diol-containing bis-carbonates. Chapter 4 describes the extension of this methodology to the formation of azacyclic products. This built upon foundation work conducted by a Part II student within the group, and further improved the selectivity of the reaction. Two diverse azacyclic skeletons could be formed from the same substrate by the employment of different bidentate phosphine ligands, and a variety of substrates were examined under these conditions.
Chapter 5 draws general conclusions and sets out possible future directions for the methodology, and full experimental details are outlined in Chapter 6.

Keywords: Oxacycles
Azacycles
Asymmetric Synthesis
Allenes
Saturated Heterocycles
Palladium Catalysis
Advisor: Anderson, E
The role of astrocytes in brain metastasis

Brain metastasis is a significant clinical problem, and 20-40% of cancer patients will develop metastatic spread to the brain.There remains, however, an urgent need to better understand the pathogenesis of brain metastasis and, in particular, the contribution of the tumour microenvironment. Astrocytes are activated in response to metastatic growth and in vitro studies suggest that this activation promotes tumour growth and invasion. However, the result of astrocyte activation has yet to be probed in relevant in vivo models.
The primary aim of this thesis, therefore, was to determine the role of astrocyte activation in metastatic progression. To address this question, two routes of metastatic induction were used; intracardiac and intracerebral. Astrocyte activation was demonstrated quantitatively in both models across a protracted time course, increasing both spatially and temporally. Subsequently, a CNTF-lentivirus model of chronic astrocyte activation was used to probe the effect of astrocyte activation on metastasis pathogenesis. No significant changes in either tumour seeding or growth were observed. However, based on subsequent assessment of the molecular phenotype of astrocytes incubated with either CNTF or tumour-conditioned media, I conclude that this lack of effect in vivo is likely to reflect the phenotypic state of the astrocytes in the CNTF-mediated model. For the converse experiment, I aimed to inhibit astrocyte activation with a targeted steroid previously shown to have anti-astrocytic effects. No significant effects on tumour burden were observed overall, although the data suggest a reduction in prefrontal areas in steroid-treated animals. In vitro and ex vivo PCR studies, together, suggested that astrocytic IL-6 may be important in metastasis progression.
Finally, in light of the robust activation of astrocytes in response to metastasis, I hypothesised that astrocyte activation could be used as a diagnostic biomarker for tumour growth, potentially facilitating diagnosis at earlier time points than currently possible. To test this hypothesis, radiolabelled small molecule ligands, targeting the translocator protein (TSPO) on activated glia, were used to image astrocyte activation with either SPECT or PET. Micrometastases were detected with both agents used, and at time points prior to that possible with current clinical methods of passive contrast enhancement across a compromised blood-brain barrier.
In conclusion, a dynamic interaction exists between astrocytes and tumour cells in brain metastases. Although the approaches used here have not yet revealed the contribution of astrocytes to metastatic growth, a framework has been established to further probe the role of astrocytes at the molecular level; in vivo modulation of astrocyte-derived factors will potentially yield not just mechanistic insights, but therapeutic gains. Importantly, regardless of the role of astrocytes, their robust association with tumour growth renders their activation an ideal surrogate for tumour growth.

Keywords: Astrocytes
brain metastasis
Advisor: Sibson, N
A study of the effect of length to diameter ratio on the results of pressuremeter tests

The pressuremeter is one of the most commonly used devices in in-situ testing, because the interpretation method is relatively easy on the assumption that the pressuremeter is infinitely long. However, the effects of length-to-diameter ratio on the test results have been questioned recently, and so this thesis explores the effects of length-to-diameter ratio on the results of pressuremeter tests in soils. First, the finite element method is used to analyse numerically the effects of length-to-diameter ratio on self-boring pressuremeter test results, both in sand and in clay since it is impossible to solve the cavity expansion problem theoretically on the assumption that the length of the pressuremeter is finite. In the analysis of clay, the effects of length-to-diameter ratio on the shear modulus and the shear strength are emphasized. In the analysis of sand, the effects of the length-to-diameter ratio on the friction angle are emphasized. The finite element method is also used to analyse the effects of length to diameter ratio on full-displacement pressuremeter test in clay. The effects of length-to-diameter ratio on the rigidity index, shear strength, shear modulus and initial horizontal stress are emphasized. Finally, several calibration tests are performed to investigate the effects of length-to-diameter ratio on the limit pressure of a full-displacement pressuremeter in sand. Three values of length-to-diameter ratio (5, 10 or 20) are used to investigate the effects.

Keywords: pressuremeter
Advisor: Houlsby, G
Evolution of highly fecund organisms

We develop and study the high-density limit of various new models in mathematical pop- ulation genetics. These models extend the Λ-Fleming–Viot process when there are two genetic types at the locus of study. Given a finite sample from a population undergoing these dynamics, a key tool for understanding the corresponding genealogy is the method of duality.
We introduce the reproduction-linked mutation mechanism and consider how this affects the process of relative allelic frequencies and the genealogy.
The second generalization incorporates two forms of natural selection – differential killing and differential birth. We contrast the structure of their genealogies.
Several properties of the block size spectra of the Kingman and Beta coalescents are also investigated, including their behaviour as they come down from infinity.

Advisor: Etheridge, A
Principles of electrocatalysis by hydrogen activating metalloenzymes

Hydrogenases catalyse the interconversion of H2 and H+. Protein Film Electrochemistry (PFE), a technique in which a redox enzyme is adsorbed directly onto an electrode, enables a detailed description of the catalytic function of these metalloenzymes to be obtained. Unlike small-molecule electrocatalysts, the hydrogenase active site is surrounded by a protein structure ensuring that it is relatively unperturbed by the electrode surface. In this thesis, PFE is used alongside mathematical modelling to explain diﬀerences between [NiFe]- and [FeFe]-hydrogenases, highlighting some important considerations for eﬃcient, reversible electrocatalysis.
This thesis probes the unusual reaction between [NiFe]-hydrogenases and cyanide. Through a detailed study utilising PFE, Electron Paramagnetic Resonance (EPR) and Attenuated Total Reﬂection Infrared spectroelectrochemistry (ATR-IR), it is demonstrated that cyanide promotes the formation of the inactive Ni-B state. Preferred formation of the Ni-B state over more slowly reactivating Unready states is considered an important characteristic of the O2-tolerant class of [NiFe]-hydrogenases.
The nature of the Ni-L state, commonly thought to be an artefact formed when a [NiFe]-hydrogenase is exposed to visible light, is probed via EPR and ATR-IR. In this thesis, the Ni-L state is shown to occur in samples of Hydrogenase-1 from Escherichia coli that have not been exposed to visible light, calling into question the true nature of this state.
Finally, this thesis details the ﬁrst study in which PFE is used to investigate the spontaneous incorporation of a synthetic active site mimic complex into apo-hydrogenase. Incorporation into apo-hydrogenase from Chlamydomonas reinhardtii and Clostridium pasteurianum is discussed, in both cases resulting in fully functional [FeFe]-hydrogenase, electrochemically indistinguishable from the native enzyme.

Keywords: Hydrogenase
Hydrogen activation
Protein Film Electrochemistry
Electrocatalysis
Enzymes
Advisor: Armstrong, FA
Holy scripture and the meanings of the Eucharist in late medieval England, C. 1370-1430

This thesis examines how, in late-medieval England, uses of Scripture and associated written discourses expanded to encompass the sacramental functions hitherto privileged to the bread and wine of the Mass. This process, reflecting the longstanding if implicit importance of scriptural symbolism to the medieval Eucharist, also bears witness to a major cultural shift in this period: the assignment to words of the same powers that had underpinned the function of visual, non-verbal symbols in medieval religion and society.
As Chapter Two demonstrates, this process was starkly exposed in John Wyclif’s vision of an English religion centred upon the sacrament of the preached word of Scripture, rather than on the Mass. As Chapter Three shows, this was the vision that Wyclif’s followers sought to realize, even if they may have achieved their aims only within a limited band of followers. However, Wyclif’s vision was powerful precisely because its relevance was not confined to Wycliffites. Chapter Four charts how the same substitution was taking place through the dissemination in English of ‘Scripture’, which, in its broadest sense, encompassed meditations upon depictions of Christ crucified as well as preaching. The greatest danger of Wycliffite thought to the late-medieval Church rested in its potential to increase lay awareness of this process.
This threat was reflected in the restrictions placed by the English Church upon lay use of religious writings in the early fifteenth century. Nonetheless, as Chapter Five shows through a reading of one of Wyclif’s sternest critics, Thomas Netter, the eucharistic function of ‘Scripture’ had not disappeared but had to be occluded. This occlusion represents the most significant shift in the eucharistic function of ‘Scripture’ in the fifteenth century, allowing its use to develop further without threatening the Mass. This thesis concludes that the unacknowledged yet increasingly central role of ‘Scripture’ helps to explain why, at the Reformation, a scripturally-based religion seemed so quickly to supplant one to which images had been fundamental.

Keywords: Wycliffites
Medieval Mass
Lollardy
Eucharist
Thomas Netter
John Wyclif
preaching
Lollards
Wycliffism
Advisor: Bose, M
Ghosh, K
Propertied society and public life: the social history of Birmingham, 1780-1832

Social history has been much criticised over the past thirty years. This criticism and the consequent turn to cultural history have brought many advances, developing our understanding of the language, discourse, ritual and culture. However, it has also led to a neglect of structural factors and a turn away from the study of collectivities. This has meant that many subjects that class used to explain (social difference, social relationships and collective actions) are often ignored or undertheorized in current historical scholarship. This thesis examines one of these issues: how should historians understand and analyse the process of social-group formation? It does this through a case study of propertied society in Birmingham between 1780 and 1832. Propertied society is a loose category that does not have the connotations of concepts such as ‘middle class’.
This thesis suggests that there were many different types of social group and that historians need to differentiate between them when analysing past societies. The most important distinction is between groups who shared attributes and groups that acted together. However, there was no simple relationship between attributes and actions; individuals who shared attributes did not necessarily act in the same way. The first part of the thesis (chapters 1-3) discusses who was included within the category of propertied society and the social and geographical understandings of those individuals. The second part of the thesis (chapters 4-6) moves from the general material and cultural structures of propertied society to consider three case studies that examine a number of processes by which individuals came together to form groups focused on particular discourses, institutions and events. The three case studies discuss the family and the transfer of social knowledge (chapter 4), local government and the nature of elites (chapter 5), and the process of politicization through examining membership of the Birmingham Political Union (chapter 6).

Keywords: Birmingham
social history
Advisor: Innes, J
Colonizing the Port City Pusan in Korea: a study of  the process of Japanese domination in the urban space of Pusan during the open-port period (1876-1910)

This dissertation aims to analyze the transformation of Pusan by examining the social, political, economic, and cultural changes during the open-port period (1876-1910). Prior to annexation, Pusan, as the first open port in Korea, reflected features of the colonial urban development in which alien power achieved and sustained a hegemonic domination on socio-cultural-economic dimensions of people’s lives.
Colonial history in Korea has been divided and moving on parallel lines. The ‘nationalist school’ and the ‘socioeconomic school’ have failed to come together and move us into a deeper understanding of the Japanese colonial period. In order to narrow the gap between the two schools of thought, this thesis suggests looking at ‘colonial modernity’ through the analytical lens of the colonial city of Pusan. The approach examines changes in the social, economic, and cultural life of people rather than through the traditional binary construction of ‘victim versus victimizer’ or ‘colonial repression versus national resistance.’
In particular, I pay close attention to the fact that colonization is a process of imperial expansion by means of colonialists. In the end, the process of colonization in Pusan was a process by which the Japanese settlers expanded in wealth, population, influence, and power. The cluster of factors – enlargement of settlement (living space), the expansion of the economy (economic opportunity), improvement of public enterprises, such as transportation infrastructure, water supply and hygiene (improving quality of life) – were catalysts for the Japanese settlers to take up residence in Pusan. Based on the transformation of the urban space of Pusan at this micro level, I discuss a hierarchy of power relations within the spatial boundary of Pusan. In other words, I focus on human aspects of these changes rather than on systemic changes. I attempt to demonstrate how studying a city can offer a useful category of analysis for the question of ‘modernity’ in Korea.

Keywords: colonial settlement
Korea
imperialism
colonialism
hygienic modernity
transportation
Japan
Advisor: Lewis, J
Remote sensing of water vapour in Venus' middle atmospere

The Pioneer Venus Orbiter Infrared Radiometer and Venera 15 Fourier Transform Spectrometer observations of thermal emission from Venus' middle atmosphere between 10°S and 50°N were used to determine global maps of temperature, cloud optical depth and water vapour abundance. The spectral regions observed include the strong 15 μtm carbon dioxide band and the 45 μm fundamental rotational water band. The main aim of this thesis is to reconcile the water vapour abundance results from these two sets of observations reported in previous studies. New radiative transfer and retrieval models have been developed for this purpose based on new correlated-k absorption tables calculated with up-to-date spectral line data. The H2SO4 cloud opacity and scattering properties have been recalculated from new refractive index data using Mie theory.
For the first time these two sets of observations have been analysed using the same retrieval tools. From the Pioneer Venus Orbiter Infrared Radiometer observations we report a high abundance of water vapour in the early afternoon at the equatorial cloud-top region and a strong day-night variability in the cloud-top pressure. From the Venera 15 Fourier Transform Spectrometer observations we report medium local variability in water vapour abundance, with highest values in the near-equatorial region and slight decrease towards the polar region.
It is found that serious constraints are placed on the validation of the retrievals by the lack of adequately accurate H2SO4 optical properties data in the shorter wavelengths and by the poor vertical resolution when sensing the complex but interesting cloud region which prohibits its rigorous modelling. The proposed European Space Agency Venus Express mission will carry a number of high resolution infrared and UV instruments that will shed new light to the interesting question of water vapour abundance in Venus' middle atmosphere.

Advisor: Irwin, P
Taylor, F