VictorJuiz/thesis huggingface dataset:
Structural studies of PCM scaffold assembly in Drosophila melanogaster

Centrosomes are the major microtubule (MT) organising centres in most animal cells, and they play important roles in many cellular processes. Centrosomes comprise a pair of centrioles surrounded by a matrix of proteins known as the pericentriolar material (PCM). Centrosomes assemble around the mother centriole when the PCM is recruited to nucleate and organise the MTs. For decades, the PCM has been viewed as an amorphous cloud of proteins. Although there are hundreds of PCM proteins, a small number of these are thought to assemble an underlying PCM scaffold that extends around the mitotic centriole and subsequently recruits other mitotic PCM proteins. In flies, Centrosomin (Cnn) and Spindle-defective protein 2 (Spd-2) are such essential proteins, and Asterless (Asl) helps recruit these proteins to the mother centriole. However, it is unclear how these proteins assemble into a scaffold at the centrosome, and none of these core PCM assembly proteins have been characterised at a structural level.
In this thesis, I have identified and recombinantly expressed functional domains of Cnn, Spd-2 and Asl in order to characterise them in vitro. In collaboration with colleagues in the laboratory, the biological significance of these domains has been investigated in vivo.
I define a Phospho-Regulated Multimerisation (PReM) domain within Cnn that is phosphorylated by Polo kinase in vitro, that dimerises via a leucine zipper, and that can form higher order oligomers when phospho-mimicking mutations are incorporated into the protein in vitro. In vivo, forms of Cnn that cannot be phosphorylated in the PReM domain cannot efficiently assemble a Cnn scaffold, while phospho-mimicking forms can spontaneously assemble into scaffold structures. I show that the Centrosomin-Motif-2 (CM2) domain of Cnn is also required to promote Cnn scaffold assembly. The crystal structure of CM2 reveals an unusual asymmetric dimer that further assembles into a tetramer in crystallo. Strikingly, Cnn-CM2 demonstrates a zinc-binding activity that stabilises the dimer, and preliminary in vivo studies indicate that the tetramer interface is essential for Cnn scaffold assembly in vivo. Finally, I show that Cnn-CM2 exhibits a weak interaction with the first of three ASPM, Spd-2, Hydin (ASH) domains in Spd-2, and that this domain facilitates Spd-2 expansion into the PCM region. The structure of two of the Spd-2 ASH domains has been investigated using X-ray crystallography and Nuclear Magnetic Resonance spectroscopy, revealing an Immunoglobulin (Ig)-like protein fold. These studies provide the first atomic insights into the molecular mechanism underlying mitotic PCM assembly, and reveal how the assembly of a Cnn scaffold may be controlled to ensure robust centrosome assembly in vivo.

Keywords: Structural biology
PCM assembly
Advisor: Raff, J
Lea, S
Reading associations in England and Scotland, c. 1760-1830

This thesis examines provincial literary culture in the late eighteenth and early nineteenth century, through the printed and manuscript records of reading associations, the diaries of their members, and a range of other print materials. These book clubs and subscription libraries have often been considered to be polite and sociable institutions, part of the cultural repertoire of a new urban, consumer society. However, this thesis reconsiders reading associations’ values and effects through a study of the reading materials they provided, and the reading habits they encouraged; the intellectual and social values which they embodied; and their role in the performance of gender, local and national identities. It questions what politeness meant to associational members, arguing for the importance of morality and order in associational conceptions of propriety, and downplaying their pursuit of structured sociability. This thesis examines how provincial individuals conceived of their relationship to the reading public, arguing that associations provided a tangible link to this abstract national community, whilst also having implications for the 'public' life of localities and families. The thesis also considers how these institutions interacted with enlightenment thought, suggesting that both the associations' reading matter and their philosophies of corporate improvement enabled 'ordinary' men and women to participate in the Enlightenment. It assesses English and Scottish associations, which are usually subjected to separate treatment, arguing that they constituted a shared mechanism of British literary culture in this period. More than simply a 'polite' performance, reading, through associations, was fundamentally linked to status, to citizenship, and to cultural participation.

Keywords: reading associations
Advisor: Dabhoiwala, F
Female aggression in flies

Competition among individuals for access to resources crucial for survival and reproduction is ubiquitous across the animal kingdom. However, most research has focused on male-male competition over access to mates. Female-female competition (hereon "female competition") over resources vital for reproduction, such as food to provision offspring, nesting sites, or social dominance, has been largely neglected. In this thesis, I aim to contribute to the growing body of literature examining female competition by investigating female competition over food in two species of fly.
start by assessing the role of an exaggerated secondary sexual trait (eyespan) as a signal in female competition in the stalk-eyed fly Teleopsis dalmanni. Sexual selection theory argues that females only possess exaggerated traits as a result of correlation with males and that they play no functional role. I find that eyespan is an honest indicator of condition but does not appear to function as a signal in either male or female intrasexual encounters, as previously argued.
Next, I consider the effects of mating on female aggression in the fruit fly Drosophila melanogaster. I find that mating doubles the amount of time females spend fighting over food. The ability to produce eggs is not required for this effect, but the receipt of sperm is essential. I also find that the magnitude of the effects of mating is determined by a female’s developmental environment – mating significantly increases a female’s chance of winning if she is raised at high larval density, but has no effect on her chances of winning if she is raised at low larval density. Finally, I find suggestions that variation in males and their ejaculates could alter levels of post-mating female aggression, suggesting that post-mating female aggression could potentially be under sexual conflict.

Advisor: Wigby, S
Seddon, N
Tobias, J
Investigations into novel enzymatic glycosylation methods

Glycosylation is one of the most prevalent post-translational modifications found on human proteins. There is a great interest in developing new methodologies for the synthesis of glycoproteins, both to elucidate the functions of glycans on proteins and to exploit the beneficial properties they can confer on biotherapeutics. Here, research was carried out investigating enzymatic techniques to achieve the formation of homogenous glycoproteins.
EndoS was the first enzyme investigated. EndoS natural activity is for the hydrolysis of glycans specifically from IgG, yet there has been research into its use for the opposite reaction and for glycan extension reactions. Here, a number of EndoS mutants were formed and investigated for this reaction, with a number of novel constructs giving a moderate yield of the glycosylated product. Structural investigations of EndoS were also conducted.
In addition, research was conducted into the use of PglB in vitro for the direct glycosylation of an asparagine reside on a peptide with GlcNAc. Studies here demonstrate that it is possible to use far simpler glycan donor substrates with PglB. Additional studies showed that it was possible to conduct further enzymatic glycosylation reactions with GalT and EndoA after the initial PglB reaction.
Further research was undertaken with EndoA, with it being desired to investigate whether it could catalyse the formation of a thioglycosidic linkage between two glycans, with the thiol bearing glycan acceptor to be attached to a peptide using PglB. After the successful synthesis of all the substrates, disappointingly, neither of the two enzymatic reactions were successful.
Finally, the use of a glycal donor in an EndoA catalysed glycosylation was investigated. Unfortunately, no consumption of the glycan was observed in this reaction.

Keywords: EndoA
EndoS
PglB
Advisor: Davis, B
Synthesis, characterisation and transfer of CVD graphene for high-resolution structural analysis and surface force measurements

This thesis describes an alternative approach to graphene research. It puts forward that the concept of graphene as a "miracle" material largely differs from the reality. The thesis describes high-resolution characterisation of commonly seen imperfections in graphene and a new application for graphene that overcomes such defects.
The thesis is divided into two main areas; high-resolution transmission electron microscopy (HRTEM) characterisation of naturally occurring defects in CVD graphene; and the synthesis and transfer of CVD graphene for the creation of the first graphene surface force balance (gSFB). The HRTEM work focuses on the thorough characterisation of "real" graphene and hence analyses the quality of the graphene that is likely to be used in research laboratories and industry. The creation of the gSFB has not only provided an instrument for novel surface force measurements of graphene but has also provided a new ultra-smooth transfer technique which can be further used elsewhere. The work undertaken in both of these areas is beneficial, not solely in graphene terms, but also for other 2D materials. For example, the gSFB has the potential to be altered to measure 2D chalcogenides and hBN interactions, and similar high-resolution characterisation of common defects in other 2D materials will also provide information on their synthesis, transfer and hence feasibility of industrial production. The research in this thesis is positioned between the pristine, flawless graphene portrayed in the literature, and the real material which will eventually be used in applications on the larger scale.

Keywords: Graphene
CVD
Surface force measurements
Nanotechnology
Advisor: Nicholls, R
Grobert, N
Essays on the pricing of financial and human wealth

This thesis presents three empirical analyses on the systematic risk exposure that global and domestic asset holders face. Each paper investigates a distinct source of macroeconomic risk, but they all stem from the premise that holding human capital and financial assets is risky. This ultimately affects agents' optimal consumption choices. The first paper, The International CAPM Redux, proposes a novel empirical model to price international assets. Building on recent advances in asset pricing research on currency markets, it documents that investors are compensated for bearing exposure to currency risk when investing in foreign equity, either directly or via delegated portfolios of international assets. The second paper, One Central Bank To Rule Them All, shows that while global investors demand a premium to bear risks associated with Federal Reserve decisions, there is no comparable result for other major central banks. This puzzling finding points to the uniqueness of the Federal Reserve for global investors, that does not simply stem from the size and importance of the U.S. economy. The third paper, Human Capital, Unemployment Risk and Asset Prices, relates the riskiness of human capital to uncertainty in the labour market and documents a role for unemployment as a determinant of human wealth. Sorting U.S. industry-level portfolios by differential exposure to unemployment risk yields a novel cross-section of average excess returns. High risk-premia are consistent with less income-constrained highly educated workers willing to take financial risk beyond hedging their labour income risk. Taken together, these three studies contribute to the empirical asset pricing literature and open the door to further theoretical and empirical research in the field.

Keywords: risk
equity
unemployment
human capital
currencies
Advisor: Ramadorai, T
The power of government to make contracts

This thesis examines why the British central government can make contracts without statutory power. It argues that, to bear contractual rights, 'government' must be a legal person with legal personality extending to those rights. This constitutes a requirement for positive legal authorisation for government action with legal effect akin to that of natural persons' actions (including contracting). Further, government contracting power is subject to judicial review, which constrains the purposes and manner of its exercise. This makes wholesale comparisons with the contracting power of natural persons inappropriate.
The thesis next examines and rejects two commonly advanced explanations of government contracting power: the 'third source' and 'the Crown' as corporation sole. The 'third source' theory — that government is free to act absent some prohibition — fails altogether to identify what legal person 'government' is and to explain the extent of its legal personality. The view that because it is a corporation sole 'the Crown' (here seen as a separate legal person from the Sovereign) has contracting power is also flawed: historical legal material suggests corporations sole were not separate legal persons and that the only legal effects of sole corporateness were property descending to the corporator’s successors (not heirs) and limits on dispositive power; for the Sovereign even this is doubtful in view of the prerogative.
This thesis then argues that the best explanation of government contracting power is that the Sovereign is a natural person and, for that reason, has power to contract (subject to judicial review constraints). 'The Crown' simply means 'the Sovereign'; government officers act as her agents when placing contracts. This view has explicit Commonwealth and implicit English support in authority. Academic objections are unpersuasive. While further conceptual possibilities may exist, the natural person explanation of government contracting is conceptually coherent and best represents the law.

Keywords: Legal basis of government contracts
Third Source
Government power to contract
Government contracts
Judicial review of government contracts
Government power to make contracts
Advisor: Davies, A
Becoming Paul, becoming Christ: the Nag Hammadi "Apocalypse of Paul" (NHC v,2) in its Valentinian context

This thesis seeks to demonstrate the Apocalypse of Paul’s position within the broader Valentinian literary corpus from the Nag Hammadi codices. Previous scholars, notably William Murdock and Michael Kaler, have gestured in this direction, but no attempt has been made to systematically situate the Apocalypse of Paul in relation to other Valentinian sources. Quite possibly this desideratum exists because although the Apocalypse of Paul’s debt to Jewish apocalypticism is self-evident, scholars of Valentinianism have generally neglected those ideas in Valentinian literature which are derived ultimately from Judaism, often received via Paul or other New Testament writers. These would include the notion of the Name of God as a saving power, even a soteriological agent, and the image of a surrogate heavenly temple through which favoured adepts may ascend in the present. These come to be combined in Valentinian thought through a high-priestly Christology in which it is by virtue of bearing the Divine Name that one may enter this ideal temple in the fashion of the old Jewish high priest, and now Christ. On the other hand, Valentinians downgrade the biblical creator-God to the level of an imperfect demiurge, placing him in an inferior heavenly temple while supplanting the Pleroma atop him as the true spiritual temple housing the Father of Christ.
The development of this constellation of ideas is traced principally from Valentinus himself, through the Gospel of Truth and the Excerpts from Theodotus, to the Gospel of Philip, where it receives its most extensive explication. It is argued that the Apocalypse of Paul consciously builds on this intellectual current using the apostle’s image in order to construct an ideal authoritative account of how such ascent ought to appear among Valentinian initiates and thereby contribute to the rhetorical and psychological construction of future experiences among the elect community.

Keywords: Apocalypse
Saint Paul
Valentinian
Advisor: Edwards, M
Is home where the heart is? Landscape, materiality and aesthetics in Tibetan exile.

In 2000, Tim Ingold argued: 'people do not import their ideas, plans or mental representations into the world, since that very world … is the homeland of their thoughts. Only because they already dwell therein can they think the thoughts they do' (2000: 186). He thus stressed the importance of place in the construction and reproduction of culture. How does this play out, however, among refugees who by virtue of their displacement must 'import' cultural concepts into alien environments? For those outside a 'homeland' how do they make sense of the world? In this thesis I examine the relationship between Tibetan refugees, the landscapes of their exile and their wider material environment. Drawing on theory in material anthropology and thirteen months’ ethnographic fieldwork conducted in two contrasting Tibetan refugee settlements in northwest India, I analyse how Tibetan refugees are affected by, and in turn exert agency over their material world.
Through this discussion, I reflect on the multiple and mutable meanings of home for Tibetan refugees, many of whom were born and/or raised in India. Few scholarly discussions of home encompass both its affective and imaginary dimensions; this thesis achieves this by focusing on the material and aesthetic aspects of home. Through this lens, I explore how refugees both work hard to develop a sense of home in exile, yet simultaneously destabilise this by orienting themselves towards an imagined home in a future 'free Tibet'. The discussion unfolds thematically, through chapters focusing on several material categories: landscape, the built environment, dress and objects. I develop my analysis via existing theoretical literature in material anthropology and its sub-disciplines, transnational and migration studies, and area-specialist literature in Tibetology.

Keywords: Social Anthropology
Materiality
Aesthetics
Anthropology
Refugee
Material Culture
Home
Tibet
Ethnography
Landscape
Advisor: Harris, C
Structural studies of peptide binding to chicken class I MHC molecules, the CD6-CD166 interaction and enzymes involved in bacterial sulfur metabolism

T cell activation is critical for the initiation of the adaptive immune response against both pathogens and malignant cells. This process depends on a complex set of finely tuned interactions, not only between the T cell receptor (TCR) and peptide-MHC complexes, but also between numerous accessory molecules. Chapter 2 of this thesis examines CD6, a transmembrane glycoprotein predominantly found on the surface of T cells, and its interaction with CD166, another transmembrane glycoprotein found on the surface of antigen presenting cells (APCs), amongst others. This interaction is required for optimal T cell activation. I have solved the X-ray crystal structures of the three extracellular SRCR domains of CD6 and the two membrane distal IgSF domains of CD166. In collaboration with colleagues, the ligand binding sites on both CD6 and CD166 have been further defined. We have also shown that a single nucleotide polymorphism (SNP) in CD6 caused glycosylation, hindering the CD6/CD166 interaction. Finally, native mass spectrometry revealed competition between the heterophilic CD6/CD166 interaction and the homophilic CD166 interaction.

Keywords: Class I MHC
Activated leukocyte cell adhesion molecule (ALCAM)
Bacterial sulfur metabolism
T cell activation
CD166
Major histocompatibility complex (MHC)
CD6
X-ray crystallography
Chicken MHC
Advisor: Lea, S
Active and passive aeroelastic control of long-span suspension bridges

Long-span bridges constitute landmark projects, whose iconic impact blends together aesthetic creativity and structural competence. The simplicity of their form is contrasted by the magnitude of their scale, and the span length, in particular, relates to the structure's technical efficiency as well as to its visual impression. Simple extrapolation of rather conventional concepts, however, does not usually lead to great progress in technological development and this might prove to be the case for the aeroelastic performance of such structures as the trend to increase their slenderness continues.
The aim of this work is to establish a framework for implementing control devices, primarily in the form of aerodynamic appendices, for suppressing aeroelastic instabilities and mitigating wind induced vibrations in long-span bridges. First, a simplified, sectional structural bridge model is created, and its interaction with a constant velocity airstream is analysed using thin-aerofoil theory. Two different passive control strategies are then considered, separately and in combination. The first makes use of trailing and leading-edge flaps adjacent to the bridge deck. The rotating motion of the flaps is triggered by the deck’s movement through a combination of connecting springs, dampers and the newly introduced inerter device. The second approach combines the aerodynamic stabilizing effect of the flaps with a driving force provided by a suspended mass, placed inside the box girder. For both strategies, special attention is given to ensuring that the proposed passive control system attains optimum robustness margins, that is, maximum tolerance to the uncertainties which accompany any physical system.
The analysis is then generalized by extending it to a discretized bridge aeroelastic model, which considers full multimodal interaction. The structural component of the modelling makes use of a reduced-size finite element formulation, in which the contribution of both the girder and the main cables is combined into single structural elements, thus reducing computation effort. The introduction of aerodynamic forces follows both thin-aerofoil theory and the flutter derivatives approach and the fluid-structure interaction is cast in a state space form in the Laplace domain. This framework is particularly convenient for control analysis and design. Two control approaches are considered: an active approach, which demands an external power source and digital control system, and a purely passive mechanical network approach, building on the earlier sectional investigation. The passive control configuration proposed has the advantages of: simultaneously increasing flutter and torsional divergence limits, being easily implementable while avoiding the use of external linkages and finally dispensing the need to be anchored to a ground reference point. Implementation of the proposed feedback mechanism to the bridge aeroelastic model proves its effectiveness during the early construction stages of a suspension bridge as well as in its completed stage.

Advisor: Williams, M
Limebeer, D