VictorJuiz/thesis huggingface dataset:
The neuropathology of the social cognitive network in autism

Potential differences in developmental trajectory were investigated in autism at both the macro- and micro-scopic scale, using regional volumetric measurements from in-vivo scans and measurements of minicolumnar organisation of the cortex in post-mortem tissue. In addition, a study was carried out to investigate the sensitivity of measures of cortical diffusion to cortical architecture. Three key regions of interest were studied throughout this thesis, orbital frontal cortex (BA11), primary auditory cortex (BA41) and part of the inferior parietal lobe (BA40).
Subjects with ASD showed increases in grey matter in left parietal cortex and decreases in left BA11 compared to controls. In addition, subjects with ASD showed increased grey matter volume with age in both BA41 and the inferior parietal lobe, whereas controls only showed a negative correlation between grey matter volume in BA41 and age.
Wider minicolumns were found in ASD in all regions, suggesting pathology is not restricted to higher order association areas. Differences seemed more pronounced at younger ages suggesting an altered developmental trajectory in ASD. Such an increase in minicolumnar width arguably underlies the feature-based processing style seen in ASD.
A pilot study using post-mortem DTI scans of MS brains revealed a relationship between measures of the directionality of diffusion and the width of axonal bundles in the cortex, an aspect of the minicolumnar arrangement. When extending this investigation to a set of ASD and control brains, evidence was found for different relationships between axon bundle width and measures of the directionality of diffusion in the cortex, suggesting that although differences in axon bundle width were not seen between groups, there may be differences in the composition of the axon bundles between ASD and control groups.

Keywords: DTI
axons
cortex
minicolumns
autism
Advisor: Chance, S
Jenkinson, M
Representations of gender and sexuality in Brazilian popular cinema

This study investigates the representation of gender and sexuality in Brazilian popular comedies. Due to its responsiveness to contemporary trends, popular cinema is a privileged locus for the analysis of social and cultural change. Comedy, in particular, is a fecund corpus for the study of power relations due to its ambivalent relation with the hegemonic power. While inherently relying on the status quo, comedy constantly pushes the boundaries of the socially acceptable; by transgressing and therefore expanding the boundaries of traditional gender representations, new models of femininity and masculinity emerge in these films in line with the changes of their time. This argument is supported by the close analysis of ten influential films spread across the three most prominent cycles of Brazilian popular cinema history: the chanchada in the 1950s, the pornochanchada in the 1970s and the Globochanchada in the 2000s. In the light of Mikhail Bakhtin's theorisation on the carnivalesque, and with the support of psychoanalytical theory, this study demonstrates that times of profound economic and political change call for a revision of gender models, and that comedy has been the preferred genre for Brazilian directors to provide a means of addressing, and coping with, the new demands on femininity and masculinity.

Keywords: Brazil
cinema
gender
media
Advisor: Williams, C
Synthesis of heterocycles via palladium-catalysed direct arylation

Chapter 1 is a brief review on some of the recents developments in palladium-catalysed C-H functionalisation chemistry. The synthesis and functionalisation of heterocycles using these methodologies was particularly emphasised.
Chapter 2 presents our efforts to identify a new catalytic system to promote the intramolecular coupling of vinyl bromides with unfunctionalised aryl C-H bonds for the formation of benzofurans. Dihydrobenzofurans were obtained efficiently under mild conditions in the presence of Pd(OAc)₂, X-Phos and K₂CO₃ in DMA at 80 °C and a subsequent one-pot isomerisation under acidic conditions afforded the desired benzofurans. A new strategy has also provided access to more complex benzofurans by functionalisation of the exocyclic alkene isomer in both a chiral and achiral manner.
In Chapter 3, mechanistic studies were performed on the benzofuran formation reaction. The analysis of substituent effects on the aromatic ring is in accordance with an electrophilic aromatic substitution mechanism (SEAr); however, the existence of both intra and intermolecular kinetic isotope effects suggest a SE3 type pathway rather than a pure SEAr.
In Chapter 4, the intramolecular coupling of vinyl bromides with unfunctionalised aryl C-H bonds was further extended to the synthesis of six-membered heterocycles by direct arylation of alkenyl bromide derivatives in the presence of Pd(OAc)₂, dppf and K₂CO₃ in DMA at 120 °C. The synthetic utility of this methodology was exemplified by the synthesis of substituted isoquinolines in six steps. Moreover, we have applied our methodology to the direct arylation of sulfonamides, leading to an interesting synthesis of widely used sultams. Both these new routes are currently being investigated and should provide access to a variety of differently substituted cyclic sulfonamides and isoquinolines.
Finally, Chapter 5 presents a new strategy for the synthesis of benzo[b]furan was briefly investigated. It consists in consecutive Tsuji-Trost and C-H functionalisation reactions. This methodology requires simpler and more versatile substrates, allowing access to various heteroaromatics in a single step. We successfully proved the viability of this reaction through the synthesis of a range of benzofurans in modest yields. To our knowledge, this is the first example of a single palladium catalyst performing these different reactions in tandem in a simple procedure.

Keywords: C-H functionalisation
palladium catalysis
synthesis
heterocycles
Advisor: Willis, M
Philosophic historiography in the eighteenth century in Britain and France

The subject of this thesis is the by now traditional grouping of certain innovative works of historiography produced in eighteenth-century Britain and France; namely the historical works of Voltaire, and the historical writings of the philosophes; and, in Britain, the histories of Hume, Robertson, and Gibbon. This thesis gives a historical and expository analysis of the individual strategies of literary self-fashioning and generic appropriation which underlie this impression of resemblance. It particularly demonstrates that the major characteristics of the contemporary vision of philosophic historiography – the idea of a European history of manners or l’esprit humain, and the insistence on the rejection of the practices of the érudits – which have become incorporated within scholarly definitions of ‘Enlightenment historiography’, are well-established generic tropes, adapted and affected in France as in Britain, by authors of diverse ambitions. The invitation to assume inauthentic connections contained within the practice of philosophic historiography is shown to be embraced by Gibbon, in a notable literary challenge to the paradigms of intellectual history. This study contrasts the textual evidence of these authors’ experience of literary, personal, and political challenges regarding the definition of their role as public, intellectual writers, to the acquired image of an ideal of ‘Enlightenment writing’. It considers the Frenchness of philosophie, and the potential Britishness of Hume, Robertson, and Gibbon. As part of its wider analysis of the practice of intellectual writing with a historical focus, its scope includes the writings of British clerics and writers on religion; of French academicians; and of the late philosophe Volney, and Shelley his interpreter. The major conclusion of this thesis is that eighteenth-century British and French history writing does not support any synthesis of an Enlightenment historical philosophy, narrative, or method; while it is suggested that one of the costs of the construct of ‘Enlightenment’, has been the illusion of familiarity with eighteenth-century intellectual culture, in France as well as Britain.

Keywords: Voltaire
Robertson
Volney
Hume
Warburton
Gibbon
Diderot
Shelley
historiography
Enlightenment
Advisor: Womersley, D
Electrophysiological indices of graded attentional and decision-making processes

In everyday life we regularly update our expectations about the locations at which sensory events may occur, and about the motor responses that are appropriate in a given situation. The experiments in this thesis investigated the neural correlates of perceptual processes and motor preparation during human decision making, and the regions that causally contribute to decision making in the human brain. In Chapter 3, I used electroencephalography (EEG) to investigate whether alpha-band (~8-14 Hz) oscillations provide a graded index of participants’ preparatory attentional states. Time-frequency analysis revealed that manipulating spatial certainty regarding the location of an upcoming visual target led to parametric changes in the lateralization of preparatory occipito-parietal alpha oscillations, and to parametric modulation of parieto-central beta-band (~15-25 Hz) power typically associated with response preparation. In Chapter 4, I used EEG to investigate whether evolution of lateralization of sensorimotor alpha- and beta-band activity reflected participants’ evolving expectations about an upcoming motor response. Lateralization of activity in both frequency bands varied parametrically with the available evidence, suggesting such lateralized activity correlates with participants’ internal decision variables. Further analysis identified unique contributions to lateralized and non-lateralized oscillatory activity due to the prior evidence, evidence update, and surprise related to the observed information at each stage of the task. In Chapter 5, I extended the paradigm developed in Chapter 4 for use with online repetitive transcranial magnetic stimulation (TMS) and concurrent EEG recording. Delivery of TMS during decision making allowed investigation of the causal role played by a left hemisphere medial intraparietal region that is the putative human homologue of the macaque medial intraparietal cortex (MIP). MIP stimulation disrupted decision-making behaviour by biasing participants’ decisions against contralateral-to-stimulation (i.e., right-handed) responses. Comparison of the magnitude of TMS-induced changes in behaviour and beta-band activity demonstrated that the intraparietal cortex plays a causal role both in decision making and in the appearance of beta-band activity over the motor cortex. In Chapter 6, the broader consequences of the experimental work presented in this thesis are discussed, in addition to promising directions for future research.

Keywords: beta-band
electroencephalography
transcranial magnetic stimulation
decision making
attention
neural oscillations
alpha-band
Advisor: Rushworth, M
Nobre, A
Towards religious polarisation in post-industrial societies? Mutations and effects of religious commitment in North America, Europe and Oceania

For over a century, many have been predicting the demise of religion within Western societies. However, while individual religiosity has mutated since the Victorian era, many studies since the 1960s have shown that the contemporary social realities of religion are complex and varied. More recently, evidence has been pointing towards a new development: one of a growing divide between the religious and the secular, or in other words of religious polarisation. The present research explores the logistics of how, where, when and why this polarisation has been developing in post-industrialised countries. In so doing, we thoroughly test a hypothesis that has long been an afterthought to many a secularisation theory. Analysing repeated cross-sectional data from a variety of national and regional contexts, we find examples of non-Nordic, mainly Protestant areas with higher initial rates of non-affiliation being characterised by a form of religious polarisation. These areas have seen a shrinking of their middle-ground group of nominally affiliated individuals, their populations splitting more and more into two camps: a larger group severed from institutional religion contrasts a small but proportionally steady core of affiliated individuals frequently attending religious services. Additionally, in areas with more advanced secularisation, average differences between these unaffiliated and religiously committed individuals regarding many attitudes, beliefs and personal practices are greater. Yet, these polarisation configurations and trends are not universally found across post-industrialised nations. Even within polarised contexts, social distance between the religiously committed and the unaffiliated has not necessarily grown. For example, levels of intermarriage and intercohabitation have not changed beyond the constraints of the marriage market. With these findings, we begin to establish the degree to which religious polarisation is becoming a new reality, and to what extent policy makers will have to contend with a new social cleavage along secular/religious lines.

Advisor: de Graaf, N
A model-independent approach to mixing in prompt D° → Ks° pi+ pi- decays at LHCb

This thesis presents a measurement of the charm mixing parameters xD and yD in prompt D0→ K 0S π&plus; π− decays using 1 fb-1 of data collected by the LHCb experiment during 2011.
Mixing in charm is predicted to be small within the Standard Model, but there are significant uncertainties associated with calculating the long range contributions to the decay. Recent measurements made by LHCb and others have confirmed that mixing in charm exists at a rate of less than 1 %. With LHCb due to collect more data and Belle II being commissioned, the reduction of systematic uncertainties will become increasingly important.
The D0→ K 0S π&plus; π− decay provides sensitivity to both the magnitude and relative sign between the mixing parameters. It is also one of the few channels that can measure xD directly. It is therefore crucial to study this mode in detail as more data becomes available. The work presented in this thesis utilises a model-independent description of the K 0S π&plus; π− Dalitz plot decay for the first time in the context of charm mixing. Previous mixing measurements with this final state have used a Dalitz plot amplitude model, and the associated systematic uncertainty is not straight forward to estimate or control. In its place, this analysis uses external, statistically-limited measurements of the strong-phase difference between D0 and ¯D0 obtained by CLEO as input. In addition, a data-driven technique is used to correct for decay time biases induced by the selection removing any systematic effects due to extracting this from simulated data. As the amount of available data increases, both of these techniques will become vital to improving our understanding of mixing in charm.
In the CP convention used by Babar and adopted for this thesis, the measured mixing parameters are
xD
= -(0.863 ± 0.527 (stat.) ± 0.171 (syst.)) %,
yD
= -(0.026 ± 0.463 (stat.) ± 0.134 (syst.)) %.
Both xD
and yD are consistent with the current world averages.

Keywords: charm
mixing
physics
flavour physics
LHCb
particle physics
Advisor: Charles, M
Harnew, N
An investigation into the molecular mechanism of the fibrillin1 - LTBP1 interaction

Many studies have demonstrated a connection between the fibrillin matrix and TGFβ signalling, but at present the mechanistic basis for this link is unclear. An interaction between the C-terminus of Latent TGFβ Binding Protein 1 (LTBP1) and the N-terminus of fibrillin1 has previously been identified, and may have the potential to directly link the fibrillin matrix to TGFβ signalling.
To investigate the structural basis for this interaction, several multi-domain fragments of fibrillin1 and LTBP1 were expressed prokaryotically and refolded in vitro. After initial characterisation to confirm folding, the structure, dynamics, and interdomain interactions of these fragments were investigated in more detail using NMR techniques. Domains in both LTBP1 and fibrillin1 appear to demonstrate folds consistent with homologous structures, and while the LTBP1 C-terminal cbEGF14-TB3-EGF3-cbEGF15 region contains many flexible linkers and few interdomain interactions, the fibrillin1 EGF2-EGF3-hyb1-cbEGF1 region appears rigid, with interfaces forming between all domains present.
SPR studies were used to demonstrate binding between distinct LTBP1 and fibrillin fragments, suggesting interactions between multiple domains are involved in the LTBP1-fibrillin1 interaction. The binding sites involved were then mapped to specific residues using HSQC titration studies, and structural models for the LTBP1-fibrillin1 interaction were generated based on these data. Predictions from these models were used to target residues for site-directed mutagenesis, based on their potential involvement in salt bridges, and when certain residues were replaced with those of opposite charge, reductions in binding could be seen in the SPR assay. These key residues were consistent with a particular model of the LTBP1-fibrillin1 interaction, as derived from the HSQC titration data. The conservation of potential binding site residues through deuterostome evolution also supports an important biological role for the LTBP-fibrillin interaction.

Keywords: LTBP
TGFbeta
NMR
extracellular matrix
microfibril
surface plasmon resonance
structural biology
TGFb
SPR
marfan syndrome
fibrillin
EGF
Latent TGF beta binding protein
fibrillin 1
nuclear magnetic resonance
LTBP1
transforming growth factor beta
Advisor: Handford, P
The expected signature of a stochastic process

The signature of the path provides a top down description of a path in terms of its eects as a control. It is a group-like element in the tensor algebra and is an essential object in rough path theory. When the path is random, the linear independence of the signatures of different paths leads one to expect, and it has been proved in simple cases, that the expected signature would capture the complete law of this random variable. It becomes of great interest to be able to compute examples of expected signatures. In this thesis, we aim to compute the expected signature of various stochastic process solved by a PDE approach. We consider the case for an Ito diffusion process up to a fixed time, and the case for the Brownian motion up to the first exit time from a domain. We manage to derive the PDE of the expected signature for both cases, and find that this PDE system could be solved recursively. Some specific examples are included herein as well, e.g. Ornstein-Uhlenbeck (OU) processes, Brownian motion and Levy area coupled with Brownian motion.

Keywords: diffusion process
Rough Path Theory
expected signature
Advisor: Lyons, T
Cascade approaches to decahydroquinoline ring systems

The aims of this project were to develop a cascade approach towards decahydroquinoline frameworks (Scheme I) and apply this to the synthesis of decahydroquinoline-containing natural products such as lycopodine, cermizine B and lepadin D (Scheme I).
Scheme I.
Several linear precursors were synthesized via a modular strategy. For example, lycopodine linear precursor i was synthesized in a total of 12 steps (Scheme II).
Scheme II.
Conditions for cyclization and hydrogenation were tested, with the diastereoselectivity examined in each system. For example, the lepadin linear precursor ii produced two decahydroquinolines iii and iv upon cyclization (Scheme III).
Scheme III.
It was found that the diastereoselectivity was dependent on the ring substituents and variation of the hydrogenation conditions could change the facial selectivity of enamine reduction.

Keywords: complex synthesis
decahydroquinolines
cascades
Advisor: Smith, M
Regulation of E2F-1 by methylation and NEDDylation

E2F-1 has a central role in cell cycle orchestration, and its activity is tightly regulated. One of the ways E2F-1 activity is controlled is by direct modification by post translational modifications such as acetylation, ubiquitination and phosphorylation. Here it was demonstrated that E2F-1 is targeted by two novel modifications, namely methylation by Set7/9 and NEDDylation, both within the DNA binding and heterodimerisation domain of the protein. NEDDylation and methylation of E2F-1 both decrease the stability and diminish the transcriptional activity of E2F-1. Lysine residues in E2F-1 involved in NEDDylation are also targeted by methylation, allowing the potential for interplay between these modifications. Methylation of E2F-1 was demonstrated to be a prerequisite for its NEDDylation and the multi-domain protein UHRF1 implicated in mediating this effect. The results define a new level of control on E2F-1 and suggest a protein code with pleiotropic effects involved in E2F-1 regulation.

Keywords: post translational modification
E2F-1
methylation
NEDDylation
UHRF1
Set7/9
Advisor: La Thangue, N
Synthesis and conformational analysis of fluorinated pyrrolidines

The aim of this thesis was to investigate the synthesis and the conformational analysis of fluorinated pyrrolidines. We focused on two strategies namely, the iodoamination and fluoroamination of fluorinated precursors.
Iodoamination
Our first approach for the synthesis of fluorinated pyrrolidines relied on the iodocyclisation of allylic fluorides bearing pendant nitrogen nucleophiles. These allylic fluorides were obtained by fluorodesilylation of suitably functionalised allylsilanes. After validation of this methodology, the scope and limitations of the iodoamination were investigated. Furthermore, we were able to probe the influence of the fluorine moiety on the level of diastereocontrol of the cyclisation.
Fluoroamination
The second route focused on a key reaction: an unprecedented electrophilic fluoroamination of an aminated allylsilane. From a mechanistic point of view, the presence of the silyl group act as a 1,2-dipole and activate the double bond towards electrophilic fluorination. This methodology required the initial screening of a silyl directing group that would promote electrophilic addition, without subsequent desilylation. Finally, we investigated the level of diastereocontrol displayed by these cyclisations as a function of the E/Z geometry of the starting aminated allylsilane.
Conformational analysis
Moreover the 3-fluoropyrrolidines obtained via iodoamination served to investigate the stereoelectronic influence of the fluorine gauche effect on ring conformations. Solid state single crystal X-ray analysis and solution phase NMR spectroscopy were used for this purpose. Due to complicated conformational analysis of saturated five-membered rings in solution, 1D 19F-1H heteronuclear nOe (HOESY) experiments have been optimised for applications to this type of small molecules. These have been employed to estimate 19F-1H internuclear distances and were combined with vicinal 3JFH and 3JHH scalar coupling constants in order to analyse the ring conformations.

Keywords: NMR
Fluorine chemistry
Advisor: Gouverneur, V