VictorJuiz/thesis huggingface dataset:
Towards the development of direct methodology to enantioenriched α-alkylated aldehydes

Enantiopure α-alkyl-substituted aldehydes are widely recognised as important building blocks in synthesis. Despite this, methods to prepare such substrates are limited. Strategically, asymmetric intermolecular SN2 α-alkylation represents a highly straightforward transformation, but still remains an elusive feat. This thesis describes efforts to address this challenge, with attempted access to enantioenriched α-alkyl aldehydes by way of C-alkylation of chiral, non-racemic, hindered aldenamines using simple alkyl halides. Enamines derived from four types of auxiliary (a tropane, an oxazolidine, a pyrrolidine and a homotropane) have been prepared, and their alkylation profile examined.
While the desired levels of asymmetric induction were not attained, use of the tropane and homotropane auxiliaries, which differ only by a single methylene group, interestingly, gave complimentary diastereocontrol during alkylation with EtI. The observed stereoselectivity is supported by density functional studies performed for ethylation of both enamines.
Additionally, in the course of preparing the homotropane a highly efficient asymmetric synthesis of a homotropinone bearing gem-α-substitution has been developed.

Keywords: tropinone
oxazolidine
tropane
alkylation
enantioselective
diastereoselective
pyrrolidine
enamine
computation
DFT
auxiliary
aldehyde
asymmetric
Advisor: Hodgson, D
Innate immune responses to tuberculosis vaccines

Tuberculosis, caused by infection with Mycobacterium tuberculosis (M.tb), remains a global health problem. Drug resistance and high rates of HIV infection have fuelled the pandemic and, although a vaccine exists, its ability to protect from pulmonary tuberculosis varies between 0 and 80%. Bacille Calmette Guerin (BCG) has been administered to billions worldwide yet its protective mechanisms remain unknown, as do the reasons for its failure to protect in many parts of the world. Modified Vaccinia virus Ankara expressing antigen 85A (MVA85A) is a novel candidate vaccine designed to boost immune responses to BCG and improve protection. An aim of this thesis has been to characterise the innate immune response to an MVA85A boosting vaccination in both UK adults and South African infants. In the former, volunteers develop a strong innate response following vaccination however this does not always translate into a robust adaptive response to antigen 85A (Ag85A), which is determined in part by Treg expansion and the nuclear protein HMGB1 signaling through the TLR1-2-6 axis. By contrast, not all South Africa infants mount a strong innate immune response to MVA85A yet this response is correlated with the magnitude of the adaptive response. The immune response to BCG in both populations is also characterised and an association found between increased production of IL-17, IL-22 and IFN-γ in response to BCG stimulation and control of mycobacterial growth. The results presented here further the knowledge on the links between innate and adaptive responses to vaccination with BCG and MVA85A and the variation in mechanisms involved in different populations.

Keywords: immunology
MVA
microarray
vaccine
TB
Advisor: McShane, H
Hill, A
Geometric and probabilistic aspects of groups with hyperbolic features

The main objects of interest in this thesis are relatively hyperbolic groups. We will study some of their geometric properties, and we will be especially concerned with geometric properties of their boundaries, like linear connectedness, avoidability of parabolic points, etc. Exploiting such properties will allow us to construct, under suitable hypotheses, quasi-isometric embeddings of hyperbolic planes into relatively hyperbolic groups and quasi-isometric embeddings of relatively hyperbolic groups into products of trees. Both results have applications to fundamental groups of 3-manifolds.
We will also study probabilistic properties of relatively hyperbolic groups and of groups containing hyperbolic directions'' despite not being relatively hyperbolic, like mapping class groups, Out(Fn), CAT(0) groups and subgroups of the above. In particular, we will show that the elements that generate the hyperbolic directions'' (hyperbolic elements in relatively hyperbolic groups, pseudo-Anosovs in mapping class groups, fully irreducible elements in Out(Fn) and rank one elements in CAT(0) groups) are generic in the corresponding groups (provided at least one exists, in the case of CAT(0) groups, or of proper subgroups). We also study how far a random path can stray from a geodesic in the context of relatively hyperbolic groups and mapping class groups, but also of groups acting on a relatively hyperbolic space. We will apply this, for example, to show properties of random triangles.

Keywords: random walk
hyperbolic
Advisor: Drutu, C
The art of war

'The Art of War' studies the transition of the soldier from fighter to settler as it is reflected in the texts he produces. Drawing on texts written by soldiers, in English, between c. 1624 and 1685, it focuses on representations of events in Ireland from 1641-1655, that is to say, during the Catholic Confederation and the Cromwellian campaigns and settlement. The focus and methodology of the thesis seek to restore a more literary reading of seventeenth century texts from, and about, Ireland to the current vibrant historical debate on the period.
It argues that the writings of the Old Irish, Old English, New English, and Cromwellian soldiers in Ireland draw on a variety of literary influences – the traces of Guicciardini and Machiavelli, Sidney and Spenser are clear. It also charts shifts in the genres of military writing from professional handbooks, to documents of civil policy, to romance, poetry, and the theatre. In doing so, it addresses the literary tools which the soldier-writer uses to define the self within a complex network of political, national, religious, and personal allegiances.
The thesis is divided into three parts. The first, chapter one, explores the trafficking of military images between military handbook and literary text. It pays particular attention to Ireland as a borderland for the European Wars and the English colonial enterprise. The second part, comprising three chapters, examines three different perspectives on the Irish Wars. The first, that of the Old English writer Richard Sellings; the second, that of the anonymous Aphorismical Discovery; the third begins with a view of the 'Irish enemy' from England, as it is constructed and enforced in the pamphlet literature of the Civil War period, and ends with the perspective of Richard Lawrence, a Cromwellian soldier-turned-settler in the early 1680s. The third part, the fifth and final chapter, explores the controversies surrounding recent Irish history as they are played out in the wake of the Exclusion Crisis. This is followed by a brief conclusion.
Monotheism and christology in I Corinthians 8. 4-6

The thesis is a description of the relationship between the 'one God, the Father' and the 'one Lord, Jesus Christ' in I Cor. 8. 4-6. It analyses Paul's language about God and Christ against the background of contemporary Jewish language about the one God, making use of methodic concepts gleaned eclectically from the structural movement in linguistics and the social sciences. Accordingly, the study falls into two parts: a determination of Paul's Jewish monotheistic presuppositions, and an analysis of I Cor. 8. 4-6 itself. Part one uses the Greek Old Testament, the Apocrypha, the Pseudepigrapha, the Dead Sea Scrolls, Philo, Josephus, and the New Testament, in particular some two hundred statements of monotheism collected from these sources (presented in an appendix), to illuminate the oblique references to monotheistic belief in Paul's letters. This part of the study concentrates on answering a series of nine questions about Jewish monotheism designed to shed light on Paul's language in our chosen passage. Part two combines the familiar grammatical-historical methods of biblical scholarship with newer, structural methods of exegesis to investigate the doctrinal content of the quasi-confessional language about God and Christ in I Cor. 8 4-6 in the light of our results from part one. The major conclusions of the study can be summarized in three statements. (1) I Cor. 8. 6 contains two classic statements of monotheism using traditional Jewish language, one in reference to the Father and one in reference to Jesus Christ; in each case, the language of monotheism comprehends not only the explicit confession with 'one', but also the prepositional phrases, which contain elements closely associated with belief in one God in Jewish thought. (2) Paul's paradoxical language about God and Christ in this passage certainly expresses the functional subordination of Christ to God, but it very probably presupposes an identity of these two figures at some undefined point, an identity which may well be essential in nature (by comparison especially with Gal. 4.8). (3) The language about Christ in I Cor. 8. 6. is informed not so much by Jewish Wisdom speculation as by Jewish language about the one God: it is best labelled a 'monotheism christology'. Hence the contribution of the thesis to knowledge lies in three areas. (1) It clarifies the nature and associations of Jewish monotheistic language. (2) It provides scientific support for the view, by no means generally accepted, that the New Testament adumbrates the concept of the ontological deity of Christ, using the most current methods of exegesis and working with a comprehensive selection of comparative Jewish materials. (3) It brings to the fore a christological category - the language of monotheism - which has been largely overlooked by researchers in the field of the origins and development of christology in the early church.

Keywords: monotheism
christology
Corinthians
Advisor: Caird, G
Vermes, G
Sanders, E
Immediate knowledge and conditions on knowledge

This thesis explores two sets of issues in contemporary epistemology. The first part explores issues surrounding the category of basic knowledge (or justification) – that is, at a first-pass, knowledge (or justification) which is immediate, in the sense that one’s justification for the known proposition doesn’t rest on any justification for believing other propositions. The second part investigates issues surrounding knowledge-closure and various conditions – namely, conclusive reasons, sensitivity, and safety – which some philosophers have claimed are necessary for knowledge. Each part of the thesis is substantial (there are five chapters in the first part and four in the second), and the two sets of issues – while evidently of independent interest – are interrelated in several ways. In broad outline, part one of the thesis concludes that, even if (in the worst case) the first-pass category of basic knowledge delineated above is not ultimately tenable (on account of credible arguments against it considered in chapter 5), there is a distinct category of knowledge, aptly called ‘basic’, which is, plausibly, tenable. Part two of the thesis, meanwhile, begins by attempting to render the conclusive reasons and sensitivity conditions – conditions the adoption of which involves rejection of knowledge-closure – in as plausible a form as possible. And a rejection of knowledge-closure has implications for the viability of the first-pass category of basic knowledge delineated above, in particular. Part two closes by exploring the safety condition: a start is made at defending a novel safety condition; and a possible application of the safety condition to the legal domain is considered. The Conclusion, which includes a prospectus for further work, ties the safety condition on knowledge (chapters 8 and 9) back to the notion of failure of transmission of epistemic warrant (an absolutely central notion in part one).

Keywords: safety
conclusive reasons
closure
sensitivity
justification
knowledge
Advisor: Davies, M
Novel regulation of SRC family kinase signalling by RASSF1 isoforms

RASSF1A is a tumour suppressor, the silencing of which occurs through promoter methylation in a variety of human cancers. Loss of RASSF1A is associated with decreased sensitivity to DNA damaging agents and worse prognosis in breast, colon and lung cancers amongst others. RASSF1A functions in a number of cellular processes, promoting apoptosis in response to DNA damage or death receptor signalling, or cell cycle arrest at both G1/S and pro-metaphase checkpoints. As a scaffold protein, RASSF1A imparts these functions through direct interaction with target proteins. We have identified a novel interaction between RASSF1A and the SRC activator, OSSA. Further studies identify a role for RASSF1 in SRC signalling. We find that a second isoform of RASSF1, RASSF1C, the expression of which is maintained in cancers, is able to activate SRC. We also identify a novel tumour suppressor role for RASSF1A inhibiting SRC activation through binding of RASSF1C. SRC activation by RASSF1C expression promotes internalisation of adherens junctions leading to subsequent loss of tight junctions and cell polarity markers from sites of cell-cell contact. -catenin is also found to be re-localised throughout the cells from where it is hypothesised to be able to upregulate pro-proliferative genes. In addition, we find that RASSF1C expression promotes cell motility in both scratch wound and transwell assays. Finally, we show that RASSF1C expression enhances tumour cell aggressiveness using a mammosphere growth assay. We conclude that RASSF1C is an oncogene that can promote EMT through the activation of SRC family kinases. This function is inhibited by the tumour suppressor RASSF1A. This work highlights why RASSF1A is lost through epigenetic mechanisms and not mutation and why loss of RASSF1A is associated with more aggressive, metastatic cancers.

Keywords: RASSF1
SRC
SRC Family Kinase
Cell Signalling
Advisor: O'Neill, E
Directors’ perceptions of parent involvement in the Early Head Start and Sure Start early intervention programs: a cross-Atlantic study

This research is a cross-Atlantic study of Sure Start and Early Head Start program directors' perceptions of parent involvement in their early intervention programs, with a focus on the provision and take-up of parenting and employability-focused services. The review of the literature, which informed the survey design and the later data chapters, focuses on poverty and parenting, working parents, welfare reform, and early intervention programs, including early childhood education and care policies in England and the United States. Data was collected via an online survey, administered to all those individuals directing either a Sure Start Local Programme (including those that had been designated as Children's Centres) in England or an Early Head Start program in the USA. There was a 40.3% response rate (231 English and 236 American directors, resulting in a total of 467 respondents). The survey questioned directors on their background, and also sought their views of the area in which their program operated, characteristics of their programs and their perceptions of the families accessing the parent-focused services offered by their early intervention program. The resulting data was used to address the primary theme of parenting and employability, drawing associations between reported parent involvement and directors' perceptions of area, program and family characteristics. The findings also led to the establishment of secondary themes: the targeting and catchment area approach to service provision, engaging disadvantaged families, relationships with partner agencies, issues of funding and resources, particularly for staff, and the expansion of Children's Centres. A summary report was sent to all participating directors. It is hoped that this research has benefited program directors, providing insights into the local-level experiences had by their colleagues both within their own country and across the Atlantic, particularly with respect to parent involvement in early intervention programs.

Keywords: Early Head Start
Children's Centres
Sure Start
early intervention programs
employment
parenting
Advisor: Smith, T
Modelling the Milky Way stellar halo

We motivate the importance of understanding the kinematics and dynamics of the Milky Way stellar halo both in unravelling the formation history and evolution of our host Galaxy and in the more general context of galaxy dynamics.
We present a cleaned picture of the kinematics of the smooth component of the stellar halo: we develop a method to quantify the average distance error on a sample of stars based on the idea of Schoenrich et al. (2012), but adapted so that it uses velocity information only on average. We use this scheme to construct an analytic distance calibration for Blue Horizontal Branch (BHB) field halo stars in Sloan colours and demonstrate that our calibration is a) more accurate than the ones available and b) unbiased w.r.t. metallicity and colour. We measure the rotation of the smooth component of the stellar halo with a tool-set of four estimators that use either only the l.o.s. velocities or the full 3D motion. From two samples of BHB stars from the Sloan Digital Sky Survey, we favour a non-rotating single halo. We critique conflicting results in the literature based on similar samples and trace back the disagreement (either in the sign of rotation or in the morphology of the halo) to sample contaminations and/or neglect account of the halo geometry.
We propose a scheme that generalizes any isotropic spherical model to a model where the potential is axisymmetric and the distribution function is a function of the three actions. The idea is to approximate the Hamiltonian as a function of the actions with a library of quadratic fits to surfaces of constant energy in action space and then make explicit the dependence of the energy on the three actions in the ergodic distribution function. The transparency of the physics implied by the model we achieve, should make it possible to combine our spheroidal models to the f(J)-models of Binney (2010) for the disks and of Pontzen & Governato (2013) for the dark-matter halo, and obtain a complete actions-defined dynamical model of the Milky Way Galaxy.

Keywords: stars: kinematics and dynamics
Milky Way: stellar halo
stars: Horizontal Branch
Advisor: Binney, J
Han dynasty (206BC-AD220) stone carved tombs in central and eastern China

This thesis studies Han Dynasty stone carved tombs in Central and Eastern China. These multi-chambered tombs were constructed from carved stone slabs, and were very popular among the Han people. However, such horizontal stone structures were entirely new, and were a result of outside stimuli rather than an independent development within China. The stone carved tombs were a result of imitating royal rock-cut tombs, while the rock-cut tombs were stimulated by foreign examples. Moreover, many details of stone carved tombs also had Western features. These exotic elements were incorporated to satisfy specific requirements of the Han people, and reflected the desire to assimilate exotica within Chinese traditions.
Some details within stone carved tombs showed high level of stone working technologies with Western influences. But in general the level of stone construction of the Han period was relatively low. The methods of construction showed how unfamiliar the Western system was to the Han artisans. Han Dynasty stone carved tombs were hybrids of different techniques, including timber, brick and stone works. From these variations, Han people could choose certain types of tombs to satisfy their specific ritual and economic needs.
Not only structures, but also pictorial decorations of stone carved tombs were innovations. The range of image motifs is quite limited. Similar motifs can be found in almost every tomb. Such similarities were partly due to the artisans, who worked in workshops and used repertoires for the carving of images. But these also suggest that the tombs were decorated for certain purposes with a given functional template. Together with different patterns of burial objects and their settings, such images formed a way through which the Han people gave meaning to the afterworld.
After their heyday, stone carved tombs ceased being constructed in the Central Plains as the Han Empire collapsed. However, they set a model for later tombs. The idea of building horizontal stone chamber tombs spread to Han borderlands, and gradually went further east to the Korean Peninsula. The legacy and spread of the Chinese masonry tradition was closely related to the political circumstances of late Han and post-Han period. The spread of stone chamber tombs in Northeast Asia is presented as a part of a long history of interactions between different parts of Eurasia.

Keywords: rock-cut tombs
stone tombs
Han Dynasty
sculpture
architecture
Koguryo
Silk Road
pictorial programme
Advisor: Rawson, J
A literary commentary on Claudian's De raptu Proserpinae

This commentary is designed to complement the edition of J.B. Hall and therefore generally avoids reduplication of his material on the manuscripts and textual history of the De Raptu Proserpinae except where germane to a discussion of a particular reading in the text. It is principally concerned with an elucidation of the literary qualities of Claudian based upon a study of this particular poem. It includes notes about the influence of contemporary politics and the Honorian court upon an otherwise purely mythological work, a discussion about the dating of the work with regard to Claudian's career and other literary productions, and an appraisal of his treatment of the myth as epic poetry and of the failure of the grand design in spite of some excellent parts. It also deals with the various sets of images and themes that give the work an overall unity, while the details alter in accordance with the conception of the moment; with Claudian's portrayal of character, his methods of narrative composition and his heavy reliance on speeches and descriptions; with his humanization of the divine and his humorous appreciation of social conventions; with his wide range of learning, his interest in natural curiosities and his keen eye for detail; with his mastery of literary imitation, including a detailed examination of the sources of his motifs and the use he has made of his literary forebears; with his verbal precision, the fertility of his invention, his use of paradox, sententiae and other rhetorical figures, together with a variety of notes upon his elegant and highly polished metre; and with his vivid sense of colour, his gaiety and vivacity and sheer intellectual cleverness, so that one may be able to comprehend the high reputation he has enjoyed as a poet in every age since he wrote up to the present day.