VictorJuiz/thesis huggingface dataset:
The role of DOCK8 in the maintenance of  CD8+ T cell memory and invariant NKT cells

The use of genome wide ENU mutagenesis screening has uncovered vast numbers of novel genes involved in the control of the immune system. This thesis describes the characterization of a novel mutant, Captain Morgan (CPM), originally identified in an immunization screen designed to evaluate both the initial antibody response to antigen and the ability to sustain antibody production. Mapping of this mutant lead to the identification of a single base pair mutation in a novel guanine nucleotide exchange factor, dedicator of cytokinesis 8 (DOCK8). The mutation was found to result in altered gene splicing of the DOCK8 protein leading to the truncation of the protein and loss of catalytic function.
The importance of understanding the role of DOCK8 in host immunity has been recently underlined by the discovery that cohorts of patients suffering from autosomal recessive forms of hyper-IgE syndrome have loss-of-function or deletions in this novel guanine nucleotide exchange factor. Disease in these patients is characterised by recurrent viral and bacterial infections mainly of the skin and lungs, with reduced levels of peripheral CD4+ and CD8+ T cells in the blood of patients. Patients also have high levels of IgE and eosinophilia in the blood and are highly atopic with increased prevalence of allergic diseases including asthma.
Loss of DOCK8 function results in a number of phenotypes in CPM mice, which may help understand the immunodeficiency syndrome experienced by DOCK8 deficient patients. CPM mice, like DOCK8 deficient patients, are lymphopenic with losses of both CD4+ and CD8+ T cells in the blood and secondary lymphoid organs. Challenge of CPM mice with modified vaccina virus (MVA) and influenza strain X31 demonstrated normal primary anti-viral responses. However, similar to the loss of germinal centre B cells previously described in these mice, memory T cell responses were diminished, which may explain the susceptibility of DOCK8 deficient patients to recurrent infections. In addition to the loss of peripheral T cells, rare populations of lymphocytes such as invariant natural killer T cells (iNKT) were also reduced in the liver and thymus. Due to their roles in bacterial and viral responses and cancer immunosurveillance it is expected that loss of these cells will contribute to disease severity.
Together these findings illustrate the importance of the ENU mutagenesis model for generating new mutants, which can enhance our understanding of mammalian genes and create disease models of human disease. Further characterization of DOCK8 deficiency and the molecular mechanisms of DOCK8 function will have important implications for disease diagnosis and ongoing treatment for patients.

Keywords: memory CD8 T cells
DOCK8
GEF
NKT cells
Advisor: Cornall, R
Nudging young ESL writers: Engaging linguistic assistance and peer interaction in L2 narrative writing at the upper primary school level in Brunei Darussalam

Motivated primarily by a cognitive approach, with consideration of interactional processes from a sociocultural perspective, the present study examined the use of linguistic assistance and peer interaction to facilitate second language (L2) writing of young ESL learners. A total of 257 Year 5 children (age 10) from twelve intact classes (from six different schools) took part in this eight-week intervention-based study. Using a quasi-experimental design, the classes were randomly assigned to one of three treatment groups or the control group. Pretests, interim tests, immediate posttests and delayed posttests were administered. As the study concerned both the processes and products of L2 development, peer interaction and children's written production were taken as the two primary sources of data for this study.
For the written production, four criteria were used to rate learners’ writings: Quality of ideas, Story shape and structure, Vocabulary and spelling and Implicit grammar. Partial correlation was employed to examine if there were any statistical relationships between treatment and learners’ written performance while controlling for prior attainment. Results show that the provision of enhanced and basic linguistic assistance may have a positive influence on only certain aspects of L2 writing, while opportunities for peer interaction does not appear to have an impact on learners’ L2 performance.
For peer interaction, a subset of 60 learners were selected from the two treatment groups which received basic and enhanced linguistic assistance, to compare their dialogic performance. Based on quantitative analyses of their recorded interactions, the findings suggest that the provision of varying degrees of linguistic assistance may affect, not the content of peer discussions, but how peer assistance is given during task. The results also show that through the provision of linguistic assistance, peer interaction mediates the participants’ performance on Quality of ideas, Story shape and structure and Implicit grammar in their subsequent individual writing.

Keywords: young learners
peer interaction
linguistic assistance
second language writing
Advisor: Walter, C
Rationality, foraging, and associative learning

One basic requisite for rationality is that choices are consistent across situations. Animals commonly violate rationality premises as evidenced, for example, by context-dependent choices, and such apparent irrationalities stand as paradoxes that instigate re-examination of some assumptions in behaviour ecological modelling. The goal of the present thesis was to study the psychological mechanisms underlying apparent irrationalities in order to assess the functional implications of general processes of valuation and choice. A common thread through the different studies is the hypothesis that most animal 'irrationalities' are due to misinterpretation of what the optimum would be in natural circumstances, and hence of the maximised currency in the theoretical predictions. I believe that the trait that may have been of paramount influence in many organisms' selective history was the ability to learn about the predictability of events and their biological value, and that this is implemented in an overriding force of associative learning mechanisms.
In chapters 2 and 3, I present evidence of context-dependent foraging choices in European starlings, Sturnus vulgaris, in the laboratory, and I implement a version of the Rescorla- Wagner learning model to account for both present data and apparent irrationalities reported by other authors. In chapter 4, I test the notion that context dependence may in fact be adaptive when animals face sequential choices, namely when they have to decide whether to take a prey item or to skip it in order to search for better alternatives. In chapter 5, I explore the functional implications of starlings' relative responding to incentives during an unexpected shortfall in reinforcement, and I also examine the extent to which information about the new environmental status helps them avoid energetic and time costs commonly seen in uninformed individuals. Last, in chapter 6, I present a brief summary of the main discussions considered and conclusions reached along this thesis.

Advisor: Kacelnik, A
Essays on the credit channel of monetary transmission

This thesis is a collection of three essays with contributions to the empirical literature on banking and the lending channel of monetary policy. The first essay on monetary policy identification addresses the endogeneity of the monetary policy measure employed in most bank level studies of the lending channel. It shows how an identified, exogenous measure of policy evokes different lending dynamics in U.S. commercial banks compared to the standard endogenous measure of monetary policy. The second essay empirically assesses the impact of financial deregulation on the lending channel in the U.S. In particular, it analyses how the gradual phasing out of deposit rate ceilings commonly known as Regulation Q significantly altered bank level frictions as well as the transmission of monetary policy to individual bank lending. While the first two essays consider U.S. bank level data, the third essay analyses individual bank level lending responses in the euro area. Its contribution lies in the construction of a range of exogenous and unanticipated monetary policy shocks as well as in the introduction of a financial conditions index into standard lending regressions. It finds that the lending responses of individual banks to monetary policy do not support the existence of a separate lending channel in the euro area. Further, equilibrium lending responses to policy as measured by a range of policy shocks is non-linear in financial conditions. Specifically, financial conditions as measured by the relative performance of a broad index of euro area banking stocks to the overall euro area stock market reverse the impact of monetary policy on lending.

Keywords: policy identification
finance
deregulation
financial intermediation
economics
money and banking
Advisor: Bowdler, C
The stress corrosion of a sensitised stainless steel

The following work divides into two parts:
a: a study of the effect of stress on the inter-granular stress assisted corrosion attack of sensitised 20% Cr, 25% Ni, 0.7% Nb in HNO3 environments. This problem was suggested by the C.E.G.B. and relates to the potential corrosion problems of AGR fuel cladding during storage after use. The aim of this work was therefore to determine how metallurgical condition, test potential and mechanical test variables affect corrosion behaviour. Low frequency cyclic loading offers a way to investigate the stress corrosion of systems at realistic stress levels and strain rates found in practice.
b: an investigation into the effect of a low frequency cyclic stress on the process of stress assisted corrosion. The aim of this work was to gain information on the effect of stress cycling on the process of stress assisted corrosion attack.
Tensile specimens were subjected to static loads both alone and with superimposed low frequency (10-4 to 10-2 Hz) saw-tooth stress cycles. Cycling was carried out potentiostatically in HNO3 environments, at below yield stress levels and ambient temperatures. Different frequencies, cyclic amplitudes and levels of background tensile stress were used. Irrespective of loading conditions the optimum potential for accelerated stress assisted corrosion attack was found to be -200mV (SCE).
The results of tests showed that test potential, cycle frequency, cycle amplitude and level of background stress strongly affect rates of attack. Grain boundary penetration rates were found to increase as frequency decreased and as peak stress and stress amplitude increased. Different kinetics of penetration were seen for cyclic and static loading. Increase of penetration depth with time for cyclic loading experiments was found to vary with (time) 0.5 whilst that for static loading experiments increases linearly with time.
A number of reasons are discussed to explain the difference in observations between cyclic and static penetration rates. Such reasons included the difficulty of ion transport down narrow paths, blunting of the penetration front, the possibility of local strain induced martensite transformation leading to hydrogen embrittlement and plastic strain enhanced dissolution resulting during cyclic loading.
The anomalous effects observed during cyclic loading (such as "strain softening") were examined for tensile specimens cycled under a range of mechanical conditions. It was found that the extent of plastic strain increased for higher stress and larger cycle amplitudes.
The process of thermal sensitisation of 20 wt% Cr, 25 wt% Ni, 0.7 wt% Nb stainless steel in three different material starting conditions (bar, "reworked bar" and tube) was investigated. Both Cr depletion and impurity segregation are discussed as mechanisms of sensitisaton. An attempt was made to correlate response in chemical and electrochemical tests with both microanalytical (STEM/EDX) observations on the shape of Cr depletion profiles and with analytical modelling. The collector plate model was found to describe AEM measured Cr depletion profiles well.

Advisor: Sykes, J
Minor arts and regional styles in East Greece, 700-500 B.C

This study attempts to establish a body of material that can be attributed to East Greek workshops in the Archaic period. All bronze work, ivory and wood carving, jewelry and works in precious metal, rings, engraved gems, and coins are categorized and discussed. A corpus of all these materials is intended, with the exception of coins, where only an outline for future work is suggested. Special attention is given to findsites, contexts, and chronological problems.
Individual workshops for the various minor arts are identified, and their stylistic traits and development is discussed. In the seventh century, East Greek bronzework, ivories, and even iconography were dependent especially on the more advanced Mainland Greek schools as well as on Oriental models, but during the sixth century several distinctively Ionian stylizations and sculptural types were developed. Other minor arts, notably the jewelry in Ionia, were more innovative and appear to have been created late in the seventh century, perhaps under Lydian patronage. Gem engraving was a relatively late (mid-sixth century) orientalizing art that was quickly developed in East Greek schools, although they are difficult to localize.
The extent of an East Greek koine style is also examined. In many cases, a common style is not shared by different media, but some distinctive stylizations, especially those based on sculptural prototypes in the sixth century, can occur in a range of minor arts.
Judging without scales

This thesis is about the nature of value incommensurability and its significance for judicial reasoning. It argues that there can be incommensurable values and that this incommensurability can have significant implications for judicial reasoning. I argue that incommensurability gives rise to a range of reasonableness, within which it is reasonable but in a sense also arbitrary to decide either way, and that this range is wider than is suggested by the notion that some options are roughly equal, because even a large improvement to one option may not make it the uniquely correct option. The thesis goes on to consider the effect that the authority of law can have on choices between incommensurable options. Although I argue that the authority of law can sometimes provide a conclusive reason to choose one of two incommensurable options, I also argue that it has limits and may not do so in every case of incommensurability. Moreover, the introduction of an authoritative directive may even give rise to incommensurable options where none previously existed.
The thesis then draws out the implications of these claims, first, for human-rights adjudication—where my claim is that ‘balancing’ is appropriate both in the specification of rights and in assessing the justification for their infringement, provided we acknowledge the limits of balancing in cases of incommensurability—and, secondly, for adjudication involving common law reasoning and statutory interpretation. Finally, I suggest that we can distinguish between different ideals of the rule of law, and that the arbitrariness of judicial decisions involving incommensurable options has different implications for those different ideals. The arbitrariness involved in choosing between undefeated reasons may be necessary contrary to one ideal of the rule of law, understood as the rule of authority, but not contrary to an ideal of the rule of law understood as the rule of reason.

Keywords: law
philosophy
Advisor: Green, L
Prophets reading prophecy: the interpretation of the Book of Revelation in the writings of Richard Brothers, Joanna Southcott and William Blake

This thesis examines the use and interpretation of Revelation in the writings of the contemporary prophets Richard Brothers, Joanna Southcott and William Blake. Contributing to an emerging scholarly interest in the reception of biblical texts within marginalised interpretative traditions, the thesis offers a detailed exploration of how Revelation is incorporated into these authors' prophetic texts, and how it informs the identity of readers who see their activities as bringing about the fulfilment of the text's visions on the historical plane. This aim is achieved by engaging with extant comparative studies of Brothers, Southcott and Blake within historical and literary studies; a comparison with similar contemporary prophetic figures and the contribution of Revelation to their prophetic self-understandings; and contextualising these figures against contemporary constructions of Revelation as a prophetic text, and the recognition of the poetic nature of biblical prophecy in the eighteenth century. In particular, the thesis advocates for the continued exploration of "emic" approaches to these figures, a process started by members of Oxford's Prophecy Project. The thesis thus argues that "prophecy", rather than "millenarianism," is the most appropriate way of characterising these authors' scriptural engagement, and explores how prophecy is understood in their writings to delineate commonalities in their understanding of the prophet's role. Finally, it surveys how Revelation is interpreted within the respective works of the writers who are the focus of this thesis. The conclusion offers a hermeneutical reflection on the relationship between the prophetic interpreter and the texts they engage with. It suggests that the reader who claims to be "inspired" faces a tension between offering an interpretation of the authoritative text, and claiming an equivalent level of authority for their own works.
The thesis makes three contributions to existing scholarly debates. Firstly, it demonstrates that attention to these three authors' interpretations of Revelation shows how attention to neglected voices illuminates the history of interpretation of this biblical book. Secondly, it justifies comparing these three authors under the framework of "prophecy", rather than the anachronistic terminology of "millenarianism." Thirdly, it explores their readings of Revelation to shed light on how interpretation of a scriptural text such as Revelation is key to the evolution of prophetic vocation; how Revelation’s images are developed and transformed in their own prophetic texts; and finally, their sensitivity to hermeneutical questions raised by Revelation’s relationship to other biblical texts and the problems posed by its eschatology.

Keywords: Biblical Interpretation
William Blake
prophecy
Joanna Southcott
Richard Brothers
Book of Revelation
Advisor: Rowland, C
Out of school support for gifted and talented learners

This thesis explored the potential of engaging gifted and talented learners in an online community of inquiry promoted by the use of asynchronous discussion forums. It employed a mixed-method, case-study approach where non-participant observation of online interactions and focus group meetings with the tutors contributed to the qualitative analysis of how the members realised participation in the forums. Quantitative analysis of membership data and online questionnaire responses revealed member characteristics of the sample members and patterns of active (vocal and silent) participation. Analysis was inductive and interpretive, informed by an original synthesis of the theoretical perspectives of two theories: the online learning theory suggested by Garrison, Anderson and Archer (2000); and the cognitive and affective domains for learning skills, proposed by Bloom et al. (1956) and Krathwohl et al. (1964).
Content analysis of over 3000 messages posted or read by approximately 4500 members revealed community-based and ability-based characteristics that enabled the group to deal with social stigma, co-construct knowledge and promote meta- learning skills.
The study concluded that participation in online discussion forums held the potential to address several of the needs identified by research for gifted learners: The need for the company of like-minded and similar ability peers; the need to develop higher order thinking skills; and the need to become independent learners. In this online network, the gifted learners could receive communal support from other members and tutors who acted as 'mentors' and role models for honing interpersonal and thinking skills such that they were motivated to pursue their interests to their full potential.

Advisor: Furlong, J
Ellis, V
Investigating TDP43 biological dysfunction through the characterisation of Tardbp ENU mouse mutants: implications for neurodegeneration

TDP43 is a highly conserved ubiquitously expressed protein which performs multiple roles in RNA metabolism, including regulation of gene expression, pre-mRNA splicing and the regulation of micro-RNA biogenesis. It belongs to the hnRNP family and interacts extensively with other proteins and RNA to perform its known biological functions and, analogously to other proteins from the same family, is proposed to autoregulate its own protein levels.
TDP43 biological dysfunction plays a pivotal role in the aetiology and pathophysiology of ALS and FTLD-TDP given that abnormally cleaved mislocalised fragments of TDP43, which are polyubiquitinated and hyperphosphorylated, constitute histopathological hallmarks of these diseases. Moreover, mutations in TARDBP (the gene encoding TDP43), most of which located in exon 6 that encodes the Glycine-rich C-terminal of the protein, are causative of ALS and FTLD-TDP. Additionally, widespread dysfunction in RNA metabolism involving TDP43 target genes is found in tissue samples from patients who suffered from these two neurodegenerative diseases.
Mechanistic dissection between TDP43 dysfunction and downstream neurodegeneration has remained elusive given that both over-expressor cellular and mouse models and conditional deletion or knockdown models have been shown to develop behavioural dysfunction and, in some cases, neurodegeneration with associated dysfunction in RNA metabolism.
In this thesis a reverse genetics approach was taken and two Tardbp ENU mutant mouse models were characterised, TardbpF210I (mutation in the RRM2 of TDP43) and TardbpM323K (mutation in the C-terminal domain of TDP43). Strikingly, both mutants showed significant phenotypes in TDP43-dependent splicing, with the F210I mutation leading to a "loss of normal splicing function" and the M323K mutation an "augmented alternative exon selection" leading to a splicing phenotype opposite to the observed as a consequence of the "loss of normal splicing function" caused by the F210I protein at the genome-wide level.
Full behavioural characterisation of heterozygous mice for these two ENU mutations did not identify any phenotypes associated with neurodegeneration, but preliminary data suggests that homozygous mice for the M323K mutation may suffer from synaptic dysfunction. Therefore, despite developing genome-wide splicing changes as a consequence of TDP43 biological dysfunction, neither of the mutant mouse lines developed neurodegeneration.
In conclusion, the characterisation of Tardbp ENU mouse mutants has revealed that TDP43 dysfunction leading to "loss of normal splicing function" or "augmented alternative exon selection" is not sufficient to cause, on its own, neurodegeneration in the laboratory mouse within its normal lifespan.

Keywords: mouse models of neurodegeneration
amyotrophic lateral sclerosis
TDP43 proteinopathies
TDP43
frontotemporal demential
neurodegeneration
Advisor: Acevedo-Arozena, A
Oliver, P