VictorJuiz/thesis huggingface dataset:
The role of the lysosome in innate immune function

Niemann-Pick disease type C (NPC) is a rare autosomal recessive neurodegenerative lysosomal storage disease caused by a mutation in the NPC1 or NPC2 genes. The functions of the proteins these genes encode are not fully understood, but are thought to be involved in cholesterol egress from the acidic compartment. The pathogenic cascade in proposed to begin with sphingosine accumulation followed by reduction of acidic store calcium levels. This results in impairing intracellular trafficking and storage of multiple lipid substrates in the late endosome/lysosomal compartment including cholesterol and multiple sphingolipids.
Although clinically characterized by progressive neurodegeneration, there is also evidence of altered innate immune responses, such as neuroinflammation, that promotes disease progression. In this thesis, we initiated an investigation into whether phagocytosis, an important innate immune activity and the process by which particles are ingested by professional phagocytes, is defective in NPC. Our results indicate a global defect in phagocytosis that is not particle or size specific. We further found evidence of altered phagocytosis in vitro and in vivo that is likely contributing to NPC disease pathology and disease progression and may contribute to iron deficiency and Crohn’s disease susceptibility in NPC patients.
We next analysed lipid content on the plasma membrane. We found evidence to support the hypothesis that intracellular accumulation of lipids (e.g.glycosphingolipids) in NPC directly contributes to abnormal actin dynamics at the plasma membrane, leading to defective formation of phagocytic cups. When we reintroduced certain glycosphingolipids exogenously to the cells we were able to partially rescue the phagocytic defect suggesting that GM1 ganglioside may be a regulator of actin: plasma membrane contact sites. Lastly, we present evidence showing that some current NPC therapeutics partially correct the phagocytic defect.
Taken together, this thesis provides insights into a novel aspect of NPC pathogenesis (innate immune dysfunction) and provides new knowledge of underlying immune defects in NPC, that in the future may act as novel targets for treatments.

Advisor: Platt, N
Platt, F
New scandium and titanium borylimido chemistry

This Thesis reports the synthesis and reactivity of scandium and titanium borylimides. New, versatile synthetic routes to such complexes of these two metals were targeted, and their reactions with small, unsaturated compounds were explored, with a particular focus being the reactivity of alkynes with these systems.
Chapter One provides a background on Group 4 imido and hydrazido complexes. Group 4 alkoxyimides are also reviewed, as well as the developing field of rare earth imides. The Chapter focuses on the synthesis, structure, and stoichiometric and catalytic reactions of these complexes with unsaturated substrates, and ends with a description of the handful of known transition metal borylimides.
Chapter Two first describes the synthesis and structures of new titanium borylimido synthons prepared from Ti(NMe2)2Cl2. From the borylimide Ti{NB(NAr'CH)2}Cl2(py)3 are then formed five new compounds supported by a range of tridentate, nitrogen-based ligands.
Chapter Three describes the synthesis of half-sandwich titanium borylimides through tertbutylimide/borylamine exchange. A sandwich compound is also described, and the electronic structures of these complexes are analysed by DFT, QTAIM and NBO studies. Reactivity with heteroallenes, and exchange reactions with amines are also explored.
Chapter Four describes the reactivity of diamide-donor-supported titanium borylimides with terminal alkynes. The principal reaction outcomes are [2+2] cycloadditions and C–H bond activations, and an interesting C–F bond activation is also described. Kinetic studies of some reactions are presented, and will be supported by further DFT studies.
Chapter Five explores attempts to prepare the first rare earth borylimide. Kinetic and computational evidence is presented for the existence of a transient scandium borylimide which rapidly undergoes interesting sp, sp2 and sp3 C–H bond activations.
Chapter Six presents full experimental procedures and characterising data for the new complexes reported.

Keywords: Scandium
Borylimides
Titanium
Early transition metals
Alkynes
Metal-nitrogen multiple bonds
Advisor: Mountford, P
iPads in action: an investigation into how the use of iPads can help improve Year 7 student engagement and attainment in a secondary grammar school

Digital technologies continue to increase in their popularity and use throughout all forms of education. In recent times windows devices with keyboards have been most popular in many schools but there may now be a shift towards using tablet devices. Therefore, it is important to ask what is the impact upon student engagement and attainment within computing of using iPads? In a selective girls grammar school, where all students in Years 7 to 9 had access to a netbook previously, this investigation looked at the implications of the move away from netbooks to iPads instead. It considered how the use of iPads could alter students’ engagement with regards to their learning and whether there are any benefits to attainment within computing lessons where they already have access to more traditional digital technologies. The investigation was carried out via an online survey which was completed by those students in Year 7 with access to an iPad. Once the survey had been completed 2 small focus groups were then selected and interviewed so as to further investigate the findings from the survey responses. Using computing as a case study, this investigation also considered the implications the use of iPads had on attainment. During this investigation is was discovered that the use of iPads did increase student engagement. There were a number of different reasons why students felt that the inclusion and use of iPads in their lessons increased their attainment. These included more competitiveness, increased independence speed and ease of use. The results found indicated that there were some benefits to student attainment in computing due to the use of iPads. These benefits were seen with regards to the value added results of the students in the study.

Keywords: ICT
MLT
MLT2016
How does the use of explicit ‘talk for learning teaching’ improve students’ collaboration, understanding and independence in English lessons?

Talk plays a crucial role in the classroom from teacher discourse (Tolmie et al. 2010, Mercer, 2008) to pupils' social exchanges (Levine, Resnick and Higgins, 1993; Alexander, 2004; Mercer and Dawes, 2014; Gillies, 2014). The benefits for effective collaborative dialogue include intrinsic and extrinsic motivation, independence, internalisation of problem solving methods and a way of learning that uses discovery and peer interaction and questioning rather than monologic teacher talk and whole class pedagogies. After reviewing a range of research from the UK and internationally that sets out the importance of talk including leading research from Mercer (2000) and Alexander (2004), an English Department in an International School undertook practitioner research, drawing on these researchers' ideas and publications. The aim was to ascertain whether explicitly taught talk for learning techniques would improve understanding and independence in the 10-16 age range. The indications were that by raising the importance of talk, building opportunities into planning and working together as a Department towards a common goal, the quality of talk in the classroom improved. Additionally, greater opportunities for EAL and SEN learners were created and teachers developed professionally within the school context.

Keywords: MLT
MLT2016
Does the use of a specific language-learning IT programme have the potential to improve both the quantity and quality of pupils' French oral production in a Year 11 iGCSE class?

This research project looks at the impact of using language software in the classroom to enhance pupils' oral skills. After defining the notions of quality and quantity as pertains to language learning, the study essentially involves a three-pronged approach, using my class of 17 pupils and a colleague’s class of 18 pupils as a control group, in examining the extent to which using technology in the language laboratory affects learning.
Firstly, pupils’ levels of confidence and fear as regards speaking French in classroom situations were identified and explored via questionnaires and semi-structured group interviews. Secondly, pupils engaged with the software in the language lab once per two- week cycle over the course of five months. During this time, they used headsets to focus on tasks related to oral skills for the entire 55-minute lesson, all the while adhering to a 'checklist' of key desirable linguistic features to succeed at the iGCSE oral exam. Finally, changes in confidence and fear levels as well as quantity and quality of language were measured via pupils’ own uploads of their audio recordings, the same questionnaires, further group interviews and official exam grades.
Findings indicate the potential for effective integration of ICT within MFL for speaking tasks. This is evidenced by a reduction in fear with a concomitant rise in pupil confidence levels as per teacher observations and pupil feedback in questionnaires and interviews. Quality and quantity of language produced also increased, considerably for some. However, it appears that pupils do not wish to engage solely with ICT and prefer to retain face-to-face communication for most language lessons, despite feeling unconfident in front of others at times, with ICT complementing traditional lessons rather than replacing them.

Keywords: MLT
MLT2016
Modern Foreign Languages
Citizenship and the politics of poverty definition during the segregation, apartheid and democratic eras in South Africa: 1910-2010

In social policy, there is a direct relation between citizenship with social rights and the understanding of poverty. The notion of citizenship with rights informs the conceptualization of poverty. The relation between citizenship and the conceptualisation and definition of poverty is explored in South African society covering segregation, apartheid and post-apartheid democratic periods. Marshall’s theory of citizenship with its three elements of social political, civil and social rights is the theoretic-analytic framework employed in the thesis. In the segregation era there was a link between the denial of full citizenship to blacks and how poverty was understood. This is evident in the adoption of policies and laws such as the civilized labour policy, discriminatory Wage Acts, Wage Boards to determine the level of wages of black workers and interventions such as the 1932 Carnegie Commission aimed at addressing the poor white problem. In the apartheid era, a system founded on racial discrimination, it was Edward Batson’s PDL that he pioneered to demonstrate that there were many South Africans living below this ‘barest minimum’ that stood for ‘existence at the lowest possible level’ that was used to define poverty among blacks and adopted in fixing the wages of black workers. The wages of black workers remained lower than the PDL. The Household Subsistence Level (HSL) and the Minimum Living Level (MLL) were derivatives of the PDL (the HSL was exactly the PDL, the MLL was lower in value) and were conceptually similar were used as poverty definitions and poverty lines to fix the wages of black workers, thus showing the link between the denial of citizenship and the politics of poverty definition.
In the post-apartheid era with a Constitution that enshrines a Bill of Rights with explicit and specific social and economic rights, and human dignity, social justice and the commitment to improve the quality of life of all citizens as foundational values aimed at addressing extensive multi-dimensional poverty, apartheid era concepts and definitions of poverty (mainly the HSL and MLL) continue. This has been reinforced by the analyses of poverty undertaken by the World Bank in the post-apartheid era. There is, therefore, a conceptual discord and contradiction between the understanding of poverty expressed in social and economic rights in the Constitution and the use of absolute, minimalist, physical efficiency definitions of poverty. In the democratic era there are emerging studies and analyses of poverty that go beyond absolute measures and consider poverty as fundamentally multi-dimensional. However even these studies do not seek to operationalise the Constitutional provisions.

Advisor: Noble, M
Diffusion of Western loanwords in contemporary Japanese: a sociolinguistic approach to lexical variation

The present research attempts to develop a general model of the diffusion of Western loanwords in contemporary Japanese within the variationist framework. It describes and predicts, based on empirical evidence from apparent- and real-time data, the elaborate process of changes in favor of loanwords as opposed to their existing native equivalents.
First, people's self-reporting shows a consistent tendency for a younger generation to show a stronger preference for loanwords than an elder one. This indicates changes in favor of loanwords are in progress in apparent time (Chapter 4).
Second, the above-mentioned age gradient is attested to by corpus-based data. It also reveals that the occurrence of loanwords is accounted for multi-dimensionally by a wider range of language-external factors such as generation, education, register and style (Chapter 5).
Third, an in-depth study of the individual loanword keesu (&LT; case) reveals that not only external factors but also internal ones, e.g., usage and collocation of the word, have impacts on its occurrence (Chapter 6).
Fourth, an investigation of the loanword sapooto (&LT; support) shows that a stylistic variable comes into play in its diffusion in interaction with an educational variable. The loanword is disfavored when the speech setting shifts to formal in particular by the most educated speakers (Chapter 7).
Fifth, a real-time approach to loanword adoption verified that individuals can change their language attitude or behavior throughout their lifetime. It highlights importance of longitudinal observation of the phenomenon in making a more accurate prediction of change (Chapter 8).
The present research confirms that the occurrence of loan variants is bound by various social and linguistic contexts. The above empirical findings contribute to the field of variationist study by opening up the possibility of analyzing linguistic variation in Japanese at the lexical level.

Keywords: Japanese
logistic regression analysis
lexical variation
loanwords
Advisor: Frellesvig, B
Multi-dataset electron density analysis methods for X-ray crystallography

X-ray crystallography is extensively deployed to determine the structure of proteins, both unbound and bound to different molecules. Crystallography has the power to visually reveal the binding of small molecules, assisting in their development in structure-based lead design. Currently, however, the methods used to detect binding, and the subjectivity of inexperienced modellers, are a weak-point in the field.
Existing methods for ligand identification are fundamentally flawed when identifying partially-occupied states in crystallographic datasets; the ambiguity of conventional electron density maps, which present a superposition of multiple states, prevents robust ligand identification. In this thesis, I present novel methods to clearly identify bound ligands and other changed states in the case where multiple crystallographic datasets are available, such as in crystallographic fragment screening experiments. By applying statistical methods to signal identification, more crystallographic binders are detected than by state-of-the-art conventional approaches.
Standard modelling practice is further challenged regarding the modelling of multiple chemical states in crystallography. The pervading modelling approach is to model only the bound state of the protein; I show that modelling an ensemble of bound and unbound states leads to better models. I conclude with a discussion of possible future applications of multi-datasets methods in X-ray crystallography, including the robust identification of conformational heterogeneity in protein structures.

Keywords: PanDDA
Advisor: von Delft, F
Deane, C
Kelm, S
Shi, J
The use of romanized Chinese by first- and second-grade pupils:  challenges in learning pinyin

The challenges in learning pinyin, the romanized Chinese orthography, faced by 5-to-7-year-olds, have received little attention. This study represents an attempt to better understand learning an alphabetic writing system from the viewpoint of the alphabetic principle, in the context of the Chinese language, by examining both reading aloud and spelling, with a particular focus on spelling.
To detect the challenges, a pinyin syllable-type test (STT) was developed, in which syllables were classified into seven spelling types guided by the alphabetic principle, where there is a letter‒sound correspondence. Syllables of all the lengths under each type of spelling pattern were given to two age groups, 6-year-old first-grade pupils and 7-year-old second-grade pupils, at the start of their school year. The sample consists of a total of 192 pupils.
In spelling, the STT reveals that challenges appear when the spelling type departs from the alphabetic principle. The results show that the hardest type of spelling is not the type containing the longest syllables, but a type one-half of that length, for which the correspondence between letters and sounds is abridged, but explicitly taught. In contrast, the latter type poses no problem in the reading-aloud test, where the results show little variation between the spelling types.
Comparing the students' performance on the STT shows an order of challenges among the seven types emerging in the first grade. This order is confirmed in the second grade in some types but not others. The pupils' raw data reveal not only what is challenging but also why it is so. Along with an indication of the influence from the local speech, the data also point to the effect of the teaching method, which is more or less uniform all over China. Thus, there is a possible application of the findings to a larger population.

Keywords: Chinese language
children
education
pinyin writing system
reading aloud
spelling
primary school
China
Putonghua
Advisor: Relly, S
Learning to serve time: troubling spaces of working class masculinities in the UK

This thesis is an exploration of the classed and gendered trajectories that lead to 'revolving door' incarceration for a group of men from working class backgrounds. Considering that men commit most crime and, in the UK, account for over 95% of the prison population, there is relatively little scholarship that explores the links between masculinity and crime and almost a dearth of ethnographic enquiry into the links between the social construction of masculinities and incarceration. In response, this study, employing qualitative in-depth life history interviews with thirty male prisoners housed in an East Yorkshire prison, examines the cyclical interrelations between cultural representations of masculinity, place, schooling, employment, crime and incarceration. Influenced by Connell's theoretical framework, including the relational concept of protest masculinities, and by the Teesside School's work on transitions and alternative careers, the main aim of this research is to examine if, and to what extent, significant cultural and institutional spaces were complicit in the construction and maintenance of versions of protest masculinities. The study reveals that masculinities negotiated over interconnecting sites of deprived neighbourhoods, inadequate children’s residential 'care' homes and failing schools better prepared most respondents to serve time in prison than to work in contemporary deindustrialised labour markets. Formative teenage years spent negotiating impoverished prison regimes and living up to extreme prison masculinities contributed to many of the respondents spending more time inside prison than 'on the out'. The thesis concludes with recommendations for policy approaches to better facilitate crucial sites, such as schools and prisons, undoing, rather than reinforcing, troubling gender performances for young boys and men like these respondents. Reducing rising male prison populations, mainly made up of men from deprived neighbourhoods, might be more effectively tackled through innovative, gender informed, policy, ensuring that institutional spaces of learning, 'care', punishment and rehabilitation work harder to open up more positive avenues to doing masculinity.

Keywords: class
breadwinner
unemployment
youth transitions
prison masculinities
prison
deindustrialisation
crime
education
men
masculinities
Advisor: McDowell, L
Probing the structure and size of dark matter couplings at the Large Hadron Collider

The mystery of dark matter (DM) is undeniably one of the greatest in modern physics. For decades, evidence has accumulated from astrophysical and cosmological experiments suggesting that the Universe contains a large amount of mass yet unaccounted for. In particular, present research indicates that approximately 84% of the total matter content in the Universe is non-baryonic DM. Together with the well-known limitations of the Standard Model of particle physics (SM), some of which could be remedied by theories which necessarily include additional particles, a particle physics solution to the DM problem is certainly well motivated. In this thesis the Large Hadron Collider (LHC) phenomenology of three models of DM is studied. In particular, the focus is on signals due to final states containing hadronic jets in association with a large amount of missing transverse energy, corresponding to DM which escapes detection. For the first model, it is found that studying events with one jet in the final state can allow constraints to be derived on the size of the couplings between DM and SM particles, but it is not possible to extract any information about the structure of the couplings. This motivates an analysis of events which feature two jets. For the second model, it is found that measurements of the azimuthal angular separation of these jets lead to contrasting distributions depending on the Lorentz structure of the interactions. These spectra are shown to be stable under various corrections and, more importantly, are clearly produced whether or not one performs the calculation using an effective field theory framework. For the third model, which differs from the first two in that DM now couples to the SM gauge bosons rather than the quarks, recent experimental searches are used to derive bounds on the fiducial cross sections for a variety of final states featuring missing transverse energy. This facilitates a comparison to be made between the various search strategies, identifying which of these most strongly constrain the operators under consideration. Considering the final state containing two jets, the azimuthal angular distributions are then plotted and are again found to be strongly dependent on the Lorentz structure of the underlying interactions. Prospects for the 14 TeV LHC run are then studied and it is found that a clear distinction between the spectra should be possible once 300 fb-1 has been collected.

Advisor: Haisch, U