VictorJuiz/thesis huggingface dataset:
Autoimmunity in idiopathic epilepsies and encephalopathies of childhood
Keywords: VGKC-complex
autoimmune encephalitis
epilepsy
NMDAR
antibodies

Immune mechanisms are thought to be involved in the pathological disease process in a number of childhood epileptic syndromes and encephalitis. Of particular interest is the occurrence of autoantibodies to essential neuronal proteins, for example the N-methyl-D-aspartate receptor (NMDAR), in the blood and spinal fluid in some of these patients. The aims of this study were: to examine the sera of newly diagnosed paediatric epilepsy patients for specific neuronal autoantibodies, correlate to epilepsy phenotype and disease outcomes; to investigate the pathogenicity and epileptogenicity of central nervous system autoantibodies (CNS) in vivo; and to test new therapies in vitro and in vivo based on the potential pathogenic mechanisms.
In 290 paediatric patients with new-onset epilepsy and seizures tested for CNS autoantibodies, 11.4% were positive (33/290 versus 8/112 in controls; p=0.01, Fisher's exact test). Previously unreported contactin-2 antibody positive and contactin-associated-protein 2 (CASPR2) antibody positive epilepsy patients were described. Patients with 'focal epilepsy of unknown cause' were more likely to be antibody positive.
To test the pathogenicity and epileptogenicity of these antibodies, a novel in vivo telemetry system was used to continuously record electroencephalogram (EEG) in mice injected into the cerebral lateral ventricle with NMDAR antibody (NMDAR-Ab) positive immunoglobulin (IgG). Although no spontaneous seizures were seen, mice challenged with the pro-convulsant pentylenetetrazole (PTZ) had increased seizure susceptibility, and more epileptiform "spikes" in the EEG after PTZ compared to healthy control (HC) IgG injected mice. Seizure susceptibility strongly correlated with binding intensity of NMDAR-Ab IgG analysed in post-mortem tissue. Given the hypothesis this epileptogenic effect was mediated by NMDAR-Abs internalising cell surface NMDARs, and to try and rescue this deficit, a neurosteroid, pregnenolone sulphate (PregS) known to increase NMDAR cell surface expression, was therapeutically used. This approach worked in vitro, and although in vivo effects were not yet established, treatment with neurosteroids may be beneficial for autoantibody mediated neurological disease.
Application of radiative fluid dynamics scaled from the laboratory to astrophysics
Keywords: Laboratory Astrophysics
Binary Star System
MagnetoHydroDynamics
Scaling Laws
MHD
Radiative Hydrodynamics
Radiation

Since its inception, the laser has found numerous applications beyond anything that could have been foreseen at its creation. With scientific and technological advancements, lasers are now capable of delivering a large amount of energy in very short timescales: giving us the ability to form interesting states of matter such as plasmas. As it became possible to create such material on earth, it made sense to consider applications this could be used for.
Astrophysics typically uses a combination of observation, theory and simulation in order to further our understanding of the cosmos. The ability of the laser to create matter in similar states to those found in many astrophysical phenomena opened up a complimentary research area: laboratory astrophysics.
The thesis begins by describing the basic physics underlying plasmas and fluid theory, before extending this to a non-dimensional form in the ideal hydrodynamic case: the so-called Euler equations. A novel way of including non-ideal terms, such as radiative, magnetic and quantum effects, is shown. Restrictions, and guidelines, to creating suitable lab experiments are drawn from this, and an experimental analogue of a polar star system is described. The design, simulation, execution and analysis of the experiment, led by the author, is given. Good agreement is found between experimental results, simulations and astrophysical theory. An experimentally measurable quantity, the structure factor, is then derived from hydrodynamics, and extended to include radiative effects, using the framework introduced in the first section. The impact of including such effects is discussed and determined to be non-negligible. Finally, we conclude by drawing together all these areas.
Ultrasound-enhanced delivery of therapeutic agents to tumours using submicron cavitation nuclei
Keywords: Ultrasound
Cancer
Virology
Drug delivery
Nanotechnology
Cavitation

Cancer therapy is severely hampered by the poor delivery of agents out of the blood vessels and into tumours. This is due to the irregular vasculature, high interstitial pressure and dense extracellular matrix associated with tumour tissue. As a consequence, high doses of agents must be administered intravenously for effective accumulation in the tumour. This leads to a low therapeutic index, necessitates multiple administrations of the same drug, and for many cancer drugs, also leads to toxic side-effects. Increasingly complex therapeutics, such as antibodies and viruses, only exacerbate this delivery problem as their greater size leads to lower coefficients of diffusion and, consequently, even greater portions of the tumour remain untreated.
There have been studies aimed at improving therapeutic outcomes using microbubble-nucleated, ultrasound-induced cavitation, which provides a mechanical impetus to drive drugs out of the vasculature and into tumours. However, microbubbles are limited by their large size, their instability in the blood and their destruction upon cavitation. This thesis details the formulation of two alternative cavitation nuclei to overcome the limitations of microbubbles: mesoporous carbon particles and polymer cups. These are solid, submicron particles that contain crevices into which nanobubbles can be stabilised. Initial studies of their biocompatibilty have indicated that these formulations may be safe for intravenous administration.
A tumour mimicking phantom was first used to quantify drug delivery caused by cavitation. Both polymer cups and mesoporous carbon particles were found to significantly enhance delivery of a model therapeutic agent by this method.
In vivo the polymer cups were used to enhance the delivery of an oncolytic vaccinia virus: intravenous administration of 1x105 pfu vaccinia virus, polymer cups and ultrasound treatment was shown to cause a 780-fold increase in genome copies in the tumours of a SKOV-3 tumour model, and 5,700-fold, in the tumours of a HEPG2 tumour model 20 days after the treatment. In mice treated with 1x106 pfu of virus cavitation caused by cups and ultrasound was shown to cause regression in 7 of the 8 tumours in comparison to just 1 of the 8 tumours that were treated with virus alone.
The effects of open shelters on the preservation of limestone remains at archaeological sites
Keywords: preventive conservation
heritage conservation
Hagar Qim
open shelters
Witney
stone deterioration
limestone weathering

Shelters, as preventive conservation methods, have traditionally been considered a better option than leaving the site exposed. However, there has been limited research on their effect on the preservation of heritage materials and, as a result, there is no clear scientific evidence to support sheltering. This study aims to provide the first rigorous scientific assessment of the effect of lightweight, open shelters on limestone deterioration at archaeological sites. A method based on the use of low-cost environmental monitoring equipment and limestone blocks and tablets (as indicators of decay) has been developed to determine the degree of protection provided by the shelters at the Bishop’ Palace (Witney, England) and Hagar Qim (Malta). Preliminary visual assessments of the field sites were followed by 12-18 month exposure trials. Temperature extremes and fluctuations, frost events, relative humidity extremes and fluctuations, NaCl crystallisation events, solar radiation, wetting events, salt content, atmospheric pollutants and dust deposition were monitored. In addition, stone decay was studied by analysing changes in weight, elasticity, surface hardness, ultrasonic pulse velocity, surface colour, moisture content and general appearance (microscopic and macroscopic pictures) in stone samples. An exhaustive assessment of the shelter at the Bishop’s Palace was carried out using Chalk, Cotswold and Portland limestone blocks as well as Portland limestone tablets (specifically for studying dissolution, soiling and biological growth). Additionally, a comparative assessment of the effects of the two shelters in contrasting climatic environments, the Bishop’s Palace (temperate maritime) and Hagar Qim (Mediterranean), was undertaken by monitoring Globigerina and Coralline limestone blocks simultaneously at both sites. The research has shown that lightweight, open shelters do not exclude decay completely but minimise it. However, there are some areas at higher risk of decay, i.e. top parts of the walls and the periphery. In addition, problems with the shelter design can enhance some decay mechanisms, such as biocolonisation on the periphery at the Bishop’s Palace and dust deposition under the shelter at Hagar Qim. Therefore, the effectiveness of shelters should not be assumed.
The artistic self: identity and self-representation in Nicholas Maw’s life studies
Keywords: Maw, Nicholas
Author
Deleuze, Gilles
Composition
Self

In his article 'The Death of the Author', Roland Barthes posits that the intentions and identity of an author are irrelevant to the understanding of an artwork. Yet in his analysis of a text by Balzac, Barthes inadvertently demonstrates that there are basic thematic categories associated with an artist's identity, which are intrinsic to a work's interpretation. This thesis proposes that the author of an artwork functions as a semiotic curator, collating signifiers from within these external categories in order to reflect their understanding of the world. Taking as a case study Nicholas Maw's 1976 score Life Studies – a piece described by the composer as being based on his own life – this experiential understanding of identity and self is explored through the lens of David Hume's bundle theory, where the unified experience of self is created through the collection of a series of perceptions. This thesis hypothesises that there are five key categories of perception that constitute Maw's artistic self in Life Studies: simulacra, narrative, design, agency, and nostalgia. Methodologically, these five areas – or rhizomes – are presented through a tripartite study, in an attempt to combine the three distinct disciplines which the philosopher Gilles Deleuze believed approached a holistic understanding of reality: philosophy, analysis, and – in the accompanying portfolio – composition (creativity).
An action research investigation into the use of tailored pedagogic approaches and their effectiveness in terms of male GCSE Geography performance
Keywords: MLT
Geography
MLT2015

This study examines the use of tailored pedagogic approaches within GCSE Geography in relation to the enjoyment, engagement and attainment of boys. Male performance has been a prominent educational focus for many years with numerous researchers encouraging implementation of interventions specifically focused upon raising success standards. This study begins with a literature review to determine what is already known about pedagogical approaches and gender attainment discrepancies within GCSE Geography. Previous intervention schemes (such as single-sex groupings) created to reduce male underachievement are critically evaluated.
The 'diamond structure' at 'Buxton School' is designed to merge academic and pastoral benefits through single-sex classes yet co-educational extra-curricular. It provides an interesting context for investigation into student perceptions of the effectiveness of single-sex teaching and preferred learning techniques.
This is an interpretative action research project. A triangulation of methods assessed a sequence of trial lessons specifically planned to include techniques identified as preferable by boys. Questionnaires, student work and lesson observations provided perspectives on the effectiveness of these techniques.
Initial findings indicated that students did not necessarily need to perceive the lesson activities positively in order to identify with the knowledge to be obtained. Higher ability students had a greater range of enjoyment opinions. Teacher perception of engagement suggested as positive behaviour increased, so too did negative behaviour. Attainment on average was found to improve most, when boys were allowed some ownership over their learning as opposed to simple incorporation of preferred activities.
This research has highlighted the importance of adapting lessons to suit the learning styles of students yet ultimately has emphasised the importance of allowing students independence. In the future it can be taken further by investigating use of tailored pedagogic techniques within a mixed gender sixth form class.
Duelling identities: dimensions of dual identity in contemporary Taiwan
Keywords: Chineseness
Ethnicity
Identity
Nationalism
Emotions
Cultural Studies
Taiwan

The core of the thesis is, taking Chinese and Taiwanese identities in the contemporary Taiwanese society as cases, to discover how people perceive, formulate, and interact with identities. The research implements the grounded theory and in-depth interview research method, conducting 108 interviews in different regions of Taiwan from 2010 to 2013. The main argument is that identity in and of itself is merely a generic label, which does not cause emotions or behaviours—people know they are ascribed to certain categories, but they lack of motivations to take actions for the categorical groups. Only those identities articulated with 'emotion- or value-oriented discourses' can gain the capacity of provoking people's feelings and mobilising people to act. My research identifies and gives explicit discussions on two types of emotion-oriented discourses—imagined nostalgia and ethical narrative (which is also a value-oriented discourse), and three kinds of value- oriented discourses. They are: (1) Ethical narrative sets moral values for its audience; (2) cultural hierarchy defines socio-cultural values in society; and (3) political ideology signifies core political values of its audience. By treating identity as emotion- or value- oriented discourse, the thesis challenges traditional stereotypes of Taiwanese and Chinese identities in the society—such as identifying as Taiwanese means desiring independence, or all waishengren group would claim Chinese identity—and offers adequate theories to explain why it is not the case. The thesis emphasises that there is no determinant identity in the society, and it is possible for people to have a certain degree of free will choosing to accept or to reject the operation of an identity. The thesis takes critical views on identity politics, deeming it as a risky, double-edged sword in the contemporary politics, which should be carefully examined and substituted with another ideology capable to achieve political emancipation.
Studies in the history and epigraphy of Hellenistic Rhodes
Keywords: Hellenistic
Rhodes
Epigraphic

The work is not a full-scale history of Rhodes in the Hellenistic age, the materials for which do not exist. It is rather an analysis of the ancient literary tradition regarding Hellenistic Rhodes on the one hand, and on the other an attempt to analyse, classify and exploit the very large body of epigraphical evidence in so far as it relates to the external aspects of Rhodian life. The results of this scrutiny of the epigraphical basis, here undertaken on a far wider basis than has ever before been possible, are as disappointing as conclusions based solely on epigraphical evidence are apt to be. The first half of the work examines in detail the tradition regarding the political history of Rhodes from 408/7 B.C., the year of the foundation of the city, to 164 B.C., the year in which Rhodes concluded an alliance with Rome, and thereby lost, largely in not wholly, the freedom of action which she had until then retained.
[Continued in thesis]
Investigating ways of preventing students' anxiety during spontaneous Target Language use in the MFL classroom
Keywords: MLT
Target Language
Modern Foreign Languages
MLT2015

Researchers, teachers and learners agree on the importance of spontaneous speech in the second language, though previous research has found that this is the most frightening language skill. A review of the literature has suggested that educators have two options when dealing with anxious students: they can help them learn to cope with the existing anxiety- provoking situation; or they can make the learning context less stressful. The aim of this research project was to discover what impact each of these options had on learners' stated levels of anxiety. Following interventions on three classes alongside a control group, data from questionnaires, interviews and observations indicate that explicit affective strategy training only helped students who were already highly anxious. Making the learning context less stressful had observable positive results on all pupils. Whilst students and teachers believed that a combination of methods would bring about the optimum level reduction in oral communication anxiety, results indicate that this was not the case. Therefore further research is planned to identify how best a mixed-method approach could work for all pupils.
What is the point? Understanding the importance of constructing tasks that engage students and enable them to make progress
Keywords: MLT2015
MLT

This dissertation discusses the importance of task design when planning lessons. This action research project gave me the opportunity to think about the importance of task design and think about what is the point in the tasks as teachers we plan.
I carried out evaluation of my own personal historic lesson plans to help understand the planning of tasks and then planned two schemes of work. These schemes of work were planned and developed with the use of literature, students' feedback and my own personal reflection. Learning diaries were used in the second feedback to give students more ownership of their learning and inform me for future planning.
Findings indicated that knowledge is an important factor when planning lessons and developing task design. Knowledge should be at the forefront of planning. Knowledge has been discussed in detail (Firth, 2015b, Lambert, 2011 & DfE, 2013). The introduction of the new curriculum has allowed knowledge to be at the forefront of planning and given teachers the opportunity to think about task design centred around knowledge. Enquiry learning was also thought about with knowledge. Enquiry learning is a complex idea that needs to be carefully used in lessons to ensure knowledge is not lost.
Role and regulation of TBX2 and TBX3
Keywords: cancer

The T-box family of transcription factors plays a crucial role during embryonic development, especially in heart and limb formation. In the adult organism, two members of the family, TBX2 and TBX3, have been found to be overexpressed in several types of cancer associating them with tumour biology. However, little is known about their regulatory targets and subsequent function aside from their well-described role during development, that would give indications of their overall contribution to tumourigenesis. Here, an agnostic, genome-wide approach is chosen to reveal novel TBX2 and TBX3 regulated target genes in a human melanoma cell line, shedding further light on their regulatory activity. Furthermore, the regulation of the two T-box factors themselves by growth regulating pathways, dysregulated in cancer, is assessed. Both T-box factors are proposed to be involved in cancer homoeostasis, a process balancing nutrient supply and demand within the cancer cell to facilitate long-term proliferation without depletion of nutrients. Moreover, TBX2 and TBX3 are demonstrated to be regulated by the PI3K pathway mediated by PAX3, and that this regulation is implicated in the bypass of oncogene induced senescence.
Loss- and gain-of-function analyses of the role of MAP kinase signalling in testis determination
Keywords: GADD45
Genetics
sex determination
MAPK
testis

Sexual differentiation is the process by which an organism develops as either male or female. In mammals, this process is governed chromosomally, principally by the presence or absence of the Y chromosome. In the mouse, sex determination occurs at 11.5 days post coitum (dpc), when expression of Sry in the XY gonad kick-starts testis determination. SRY drives the subsequent expression of genes that both promote testis differentiation and inhibit ovarian differentiation, leading to specification of the testis. In cases where sex determination is disrupted, disorders of sexual development (DSD) can occur. Many genes have been described that are required for testis determination. However, we still know relatively little about how Sry itself is regulated.
MAP kinase (MAPK) signalling is involved in testis determination in mice and humans. MAP3K4 is required for testis determination in the mouse: loss of MAP3K4 is associated with male-to-female sex reversal in embryos and insufficient expression of Sry at 11.5 dpc. Likewise, loss of function of a protein known to interact with MAP3K4, GADD45γ, also leads to sex reversal. In humans, mutations in the gene encoding the related kinase, MAP3K1, have been identified as a key cause of DSD. Thus, MAPK signalling appears to play a key role in testis determination both in humans and mice.
This thesis describes experiments designed to further elucidate the role of MAPK-related signalling in testis determination. Firstly, an attempt was made to generate mice bearing a human sex-reversing mutation in Map3k1, however this was not successful. Additionally, RNA-seq was employed to investigate transcriptional targets of GADD45γ. Finally, the role of MAP3K4 as a dose-dependent modifier of sensitivity to sex reversal in mice is described, utilising a Map3k4 transgene to rescue sex reversal in B6 mice harbouring a Y chromosome from the Mus poschiavinus strain. These mice undergo sex reversal in the absence of the Map3k4 transgene, and also exhibit delayed Sry expression. By utilising this genetic tool, this thesis investigates the mechanism of sex reversal in these mice, with particular focus on the role pf Map3k4 in Sry expression.
The impact of antigen processing on CD8+ t cell memory inflation
Keywords: CD8+ T cell memory inflation

T cell "memory inflation" is the sustained induction of effector memory cells that home to peripheral tissues and retain their functionality. Defining the mechanisms that drive these non-classical memory responses may contribute towards the development of novel prophylactic or therapeutic vaccines. A model of memory inflation based on responses to β-galactosidase delivered by a non-replicating adenoviral vector provides a robust tool for investigating the underlying mechanisms. This work has shown that these responses are not dependent upon the human cytomegalovirus (HCMV) promoter within the model, this being the only part of the model that is CMV-derived. This model has been used to test the hypothesis that bypassing antigen processing would result in inflationary memory responses to CD8+ T cell epitopes that are not normally the targets of such responses. When the β-gal497-504 restricted epitope (ICPMYARV) was expressed as a minigene in a recombinant adenovirus vector, inflationary CD8+ T cell responses were induced, instead of the classical responses obtained with full-length β-galactosidase. Similar results were obtained with the M45985-993 (HGIRNASFI) epitope from the mouse cytomegalovirus M45 protein. These data demonstrate that the polypeptide context of a CD8+ T cell epitope may determine whether classical or inflating memory responses are induced. This could be relevant to the design of recombinant antigens in adenoviral vectors, which have emerging therapeutic and prophylactic applications.