VictorJuiz/thesis huggingface dataset:
Techniques for high repetition rate laser wakefield acceleration

I present work on three different techniques in order to contribute towards laser wakefield acceleration (LWFA) experiments which could operate at multi-kHz repetition rates and at low plasma densities ne ~ 1017 cm-3, enabling the acceleration of higher energy electrons in a single stage. Together, these techniques would help to make the next generation of LWFA facilities substantially more competitive with conventional accelerators.
Firstly, I consider the accuracy required to resonantly excite plasma wakefields with trains of many laser pulses, produced by high average-power but lower peak-power laser systems. Through theory, simulations and experimental results, I show a strong constraint on the systematic error acceptable in the separation of pulses. However, I also explore using chirped trains of laser pulses, where the pulse separation increases over time, to increase the efficacy of resonant excitation when the pulse spacing cannot be perfectly matched to the plasma.
Secondly, I describe a recent technique which can measure plasma waves rapidly and sensitively, using temporally encoded spectral shifting (TESS). I generalise the technique to probe pulses with non-Gaussian profiles and demonstrate that it can be extended to measure quasi-linear wakefields which are not sinusoidal. I detail how a TESS analysis can be conducted in practice and present results from a recent experiment using the technique.
Thirdly, I outline a proposed all-optical method of creating plasma waveguides which would be capable of operating at low densities and high repetition rates and are in principle immune to damage from laser pulses. Start to end simulations demonstrate that these hydrodynamic optical-field-ionized plasma channels could meet all of the requirements for next generation laser wakefield acceleration experiments and are used to propose some optimum experimental parameters.

Keywords: Laser Wakefield Acceleration
Laser Guiding
Plasma Diagnostics
Spectral Interferometry
Resonant Excitation
Advisor: Hooker, S
Walczak, R
Visual guidance of target-oriented flight behaviours in birds

Birds are highly dependent on vision to guide their flight during goal-directed tasks. They shift their visual attention primarily through head reorientation, with limited eye movement; however, measuring head orientation in free-flying birds is a significant technical challenge. While the gaze strategies of some birds have been studied in considerable detail in laboratory environments, studies of visual guidance in natural environments have largely been limited to inferences based on GPS-derived flight trajectories. This thesis aims to advance our understanding of how birds use their visual system to guide target-directed flight, using novel instrumentation to measure the gaze strategy of homing pigeons (Columba livia) and peregrine falcons (Falco peregrinus) flying in their natural environments.
We use GPS-derived flight tracks to explore the visual mechanisms available to pigeons to compensate for wind drift, finding that they partially compensate for lateral displacement caused by the wind performing better than a naive strategy requiring no knowledge of the wind. We then describe the development of a custom-built sensor, incorporating a GPS receiver and head-mounted inertial measurement unit (IMU), which measures bird position and head orientation. Using this instrumentation, we find that pigeons coordinate angular head saccades with their wingbeats. Our results also reveal that vertical head stabilisation is enhanced when flying with flock companions, largely via increased wingbeat frequency. The focus of pigeons’ visual attention during homing flight is measured with the sensor, allowing specific points of interest to be identified in the landscape that do not lie on the bird’s track. Finally, we find that in the closing phases of predatory pursuit, peregrine falcons continuously track their target position using either their frontally or laterally facing fovea. Refined iterations of the exploratory technique developed here have the potential to revolutionise our understanding of large-scale spatial cognition and short-range guidance in birds and may, in turn, lead to applications in the design of visually-guided unmanned aerial systems.

Keywords: Flight
Vision
Inertial Measurements
Birds
Advisor: Taylor, G
Numerical methods for structural credit models with mutual liabilities

In this thesis, we study a structural default model of an interconnected banking system with mutual liabilities. We develop novel numerical and analytical methods for the computation of important characteristics of the model and assess their impact on counterparty credit risk. First, we study the case when the banks’ asset values follow a pure diffusion process and develop analytical and semi-analytical methods for default probabilities, which are the first of their kind in the three-dimensional case. Next, we consider a jump-diffusion model and develop new splitting finite difference methods for the resulting partial integro-differential equations, which we test numerically in the case of two banks. Due to the curse of dimensionality, these methods are not extendable practically to a large number of banks. Therefore, we consider a mean-field approximation of the model in this case, which leads to a McKean–Vlasov equation where the drift term depends on the absorption rate on the boundary. We develop and analyse a novel simulation method and an alternative approach based on reduction of the corresponding nonlinear, nonlocal PDE to a coupled system of Volterra integral equations.

Advisor: Lipton, A
Reisinger, C
Musiela, M
Status, signalling and positional competition

The first chapter analyses a game between the desired and undesired agents and the Decision Maker (DM), who only wants to admit the desired agents. To influence the DM’s decision, both types of agents can purchase an ostentatious good at the same price, yet the undesired agent sometimes fails to make the right impression. I investigate how the imposition of a capacity constraint can improve the outcomes for the DM. I show that committing to ignore the message received from the agent is an even better policy for the DM. I then add a second, counterfeit good to the model, which is cheaper than the original and only guarantees success with the same, low probability for both types. I show that while full separation might not be obtainable where it used to be without counterfeits, the DM’s expected payoff may increase compared to the baseline model.
The second chapter analyses markets in which several ex-ante identical brands are of- fered and then purchased by status-conscious consumers. In equilibrium, the brands are acquired by agents with different incomes and their quality, or the status they confer, is thus ex-ante differentiated. I analyse different market structures and provide comparisons vis-a-vis benchmark models of product differentiation. When status matters even to the poorest agent, the monopolist over-produces each brand, which can be rectified by a flat per-unit tax. Moreover, while an equilibrium does not always exist in more competitive market structures, I find that sequential entry and large enough differences in cost structures are sufficient to guarantee one. In such equilibria, however, both consumer surplus and total welfare are lower than they would be under a monopoly.
In the third chapter, I build a model of cardinal positional competition, in which agents compare their own positional consumption to the average positional consump- tion. In equilibrium, agents over-consume compared to the social optimum and lower average positional consumption increases the utilities of all agents. An increase in income inequality raises the average positional consumption if the demand for the positional good is convex in income. I then apply the model in a scenario where agents first have to join one of potentially heterogeneous communities, and only then engage in the positional competition against their fellow community members. I find that moderate differences in qualities of the communities are necessary to support a stratified equilibrium. If assignment to the communities is externally determined, any relocation of agents from the richer to the poorer community reduces average positional consumption in both communities.

Advisor: Beggs, A
Novel protein modification strategies

Site-directed mutagenesis allows the ready variation of proteinogenic amino acids; genetic code expansion permit the incorporation of a few more. The widespread use of these genetic techniques has caused a revolution in molecular biology. A crucial limitation of genetic techniques is the ‘ribosomal filter’, where an amino acid has to be processed by the ribosome or other translational enzymes.
I have developed a chemical technique for the direct modification of proteins allowing the incorporation of a large scope of amino acid side-chains. Notably, this technique is independent of the ribosome. Radical addition to protein backbone dehydroalanine (Dha) forms C(sp3)-C(sp3) bonds directly onto a protein to facilitate “chemical mutagenesis”.
Protein glycosylation is difficult to study due to mixtures associated with biological glycosylation machinery. In Chapter 1: I have employed the above chemical mutagenesis method to create homogenous glycoproteins which retain a native bond. During this study, I have demonstrated the biological relevance of these transformations by showing reactivity with glycosidases and glycosyl transferases, found interesting reactivity of an extremely polarised amide substrate, and have used the method on an aggregation prone periplasmic protein.
In Chapter 2: I used techniques developed in Chapter 1 to create intermediate mimics of the Sirt2 catalysed deacetylation of Histones. I used the mimics of Sirt2 intermediate 2 to determine the geometry around an unstable reaction intermediate. Having atomic control over the amino acid allowed us to create mimics of both the R and S diastereomers. Using analyitical size exclusion chromatography I have obtained qualitative results which show the R isomer is bound by Sirt2 much stronger than the S, hinting that the R isomer is that which is present in biology.
In Chapter 3: I demonstrated a green synthesis of 2,5-dibromohexadiamide (DBHDA); which has been used extensively in the prior two chapters to modify protein Cys residues into Dha. The developed method of producing DBHDA replaces CCl4 with cyclohexane and gives a yield of 31 % over 3 steps and 6 functional group interconversions. The DBHDA produced was found to be of extremely high purity (99.7 % ± 1.21), which was determined by the use of quantitative 13C NMR spectroscopy.

Keywords: dehydroalanine
carbohydrate
DBHDA
Protein
Sirt2
radical
Advisor: Davis, B
Putting human rights to work: the protection of the human rights of workers through the law of dismissal

The disciplinary powers of employers pose a significant threat to the human rights of their workers. To guard against this risk, workers should receive protection against infringements on their human rights by their employer. It will be suggested that safeguarding the fundamental rights of workers has always been one aspect of labour law’s purpose. Consequently, employers are already under an imperfect duty to respect the human rights of their workers, generated by a patchwork of existing legal obligations. Nevertheless, the protections afforded by UK employment law suffer from deficiencies when assessed against human rights standards. This thesis focuses upon the principles of the European Convention on Human Rights, as incorporated into UK law by the Human Rights Act 1998. It discusses the weaknesses and lacunae in the law of unfair dismissal and the common law of wrongful dismissal. The narrow personal scope of employment rights excludes a variety of individuals who benefit from the universality and inclusivity of human rights protection. The statutory law of unfair dismissal has several deficiencies as a mechanism of human rights protection. The three areas that will be examined particularly the manner in which the justification process is applied and the remedies available to successful claimants. There are a number of ways that the common law of wrongful dismissal could provide an alternative route to protection: sympathetic interpretation of the contractual terms, a favourable evolution of the implied obligation of mutual trust and confidence, or a new implied term requiring that employers respect the human rights of their workforce. However, contractual protection could be ousted by the insertion of inconsistent or exclusionary terms. The adequacy of this alternative course is therefore questionable. In response to the many deficiencies exposed in the human rights protection currently granted by UK employment law, a legislative solution will be suggested and outlined. It would provide effective protection to the human rights of workers, safeguarding the workers against the risks that their employers’ powers pose to their most fundamental rights.

Advisor: Collins, H
Investigating the role of IGF-1R in the cellular response to DNA damage

IGF-1R plays an important role in regulating cell proliferation, survival and migration. Its overexpression in a number of cancers has been associated with radio-resistance. Previous studies from our group and others have confirmed that depletion or inhibition of IGF 1R can sensitise cancer cells to ionising radiation. However, the underlying mechanisms remain elusive. Our study aimed to uncover the mechanisms of radio-sensitisation associated with the IGF-1R signalling pathway. This was achieved by investigating changes at the proteome, transcriptome and metabolome levels using siRNA-mediated gene silencing and also IGF-1R mutant isogenic models which we generated from p53 wild-type osteosarcoma U2OS cells using the CRISPR/Cas9 genome editing technique.
We confirmed that suppressing the IGF-1R function through either transient or permanent depletion of the protein enhances U2OS sensitivity to γ-irradiation with average dose enhancement ratios of 3.5 and 3 respectively at 5Gy. Double-strand break induction and resolution were not impaired in IGF1R-deficient cells as determined by γH2AX foci tracking and there was no evidence that the activation of the DNA damage response was compromised in the mutant with evidence of ATM, CHK1 and RPA phosphorylation along with p53 accumulation. Moreover, we did not find defects in cell cycle checkpoint integrity which prompted us to evaluate intrinsic properties associated with IGF 1R deficiency that may affect cell survival following exposure to γ-irradiation.
Transcriptome and metabolome profiling revealed significant differences in genes and metabolites associated with various cellular pathways, particularly the cellular response to stress, intracellular metabolism and, cell motility and migration. The interplay of molecular changes affecting these cellular processes might account for the radio-sensitisation of IGF 1R deficient cells. Future investigations should attempt to explore this possibility given that previous research on this same topic have hinted at the likelihood that the cellular response to ionising radiation is governed by complex multiple factors.

Keywords: IGF-1R signalling and the response to radiotherapy
Generating IGF-1R mutants clones
Type I insulin-like growth factor receptor
Growth factor receptor signalling and DNA damage
Growth factor receptor kinases and the response to irradiation
IGF-1R and DNA damage
CRISPR-genome editing the IGF-1R gene
Advisor: Macaulay, V
Immunogenicity of vaccines for malaria-exposed populations

An efficacious malaria vaccine will be a necessary tool for malaria eradication, however current vaccine candidates have only demonstrated a moderate level of short-term efficacy. Additionally, these vaccines often display reduced immunogenicity and efficacy in the malaria-exposed target populations compared with the malaria-naïve populations in which they are initially tested. Reduced vaccine immunogenicity in malaria-exposed populations may affect vaccines for diseases other than malaria. The 2014-2016 Ebola outbreak in West Africa highlighted the need to produce effective vaccines against emerging infectious diseases. Many of the outbreak pathogens for which such vaccines are being developed have geographical distributions that overlap with areas of malaria transmission. Therefore being able to effectively vaccinate malaria-exposed individuals is a key requirement for this new generation of vaccines. This thesis aims to characterise the immunogenicity of candidate malaria and Ebola vaccines in detail and explores potential mechanisms of reduced immunogenicity in malaria-exposed populations. Experiments demonstrated that concomitant administration of viral vectored and VLP-based malaria vaccines caused a Th1-skewed cytokine response that was associated with reduced antibody titres and efficacy, similar to the immunosuppressive effect of acute malaria infection. Humoral, but not cellular, responses to malaria and Ebola vaccines were reduced in malaria-exposed adults and children but not in infants. Although this reduction was associated with malaria exposure in some cases, it was clear that other factors were involved. Further experiments revealed a role for cytomegalovirus infection in the reduction of vaccine immunogenicity in both malaria-naïve and malaria-exposed young adults. Overall this thesis highlights the importance of understanding what impacts immunogenicity in order to optimise vaccines for the target populations.

Keywords: Ebola
flow cytometry
T follicular helper cells
malaria
controlled human malaria infection
antibody responses
clinical vaccine trials
vaccine immunogenicity
Advisor: Hill, A
Ewer, K
The significance of house and home in China's rural to urban migration

Building on previous work that focuses on rural to urban migration and class formation among urban Chinese youth, this thesis explores ideas of middle-class consolidation dynamics centered on the house, as well as on changes in perceptions of home that come with the migration experience. My research shows that, in contemporary China, the house stands at the center of a hierarchy of privileges in middle-class consolidation processes, especially for the middle-class rural migrant group. With this dissertation, I contribute to research that studies rural to urban migration in China by looking at a social group that has been widely overlooked, i.e. middle-class migrants with rural origins and who are employed in high-end industries of the service sector, and to research that examines class distinction by placing homeownership at the center of class-related hierarchies of privilege. I argue that house, as well as ideas of home, is key in middle-class consolidation and reproduction processes, as it is the principal asset that confers class-related legitimation and power, and that it is able to provide both inter-class and intra-class distinction. As a theoretical basis to support my argument, I avail myself of the Bourdieusian approach, which provides an effective categorization model based on the relational aspects of class membership, as well as the concepts of distinction and class symbolic boundaries, both of which are key to understanding class-related dynamics in contemporary China.
The present project is composed of three empirical chapters that present and analyze the significance of house and home in rural to urban migration from three different perspectives: the effects of migration and class status on perceptions of home; the effects of homeownership on ideas of class and status; and the effects of education on migrant families’ housing strategies.

Advisor: Harrison, H
Murphy, R
The role of histone 3 lysine 27 trimethylation in thymic epithelial cell development and function

Thymic epithelial cells (TEC) create the unique environment for the selection of T cells that are tolerant to self but reactive to foreign antigens. For this purpose, TEC express an almost comprehensive repertoire of self-antigens, through a process referred to as promiscuous gene expression (PGE). The precise molecular mechanisms that account for PGE remain incompletely defined although a subset of promiscuously expressed genes rely for their efficient expression on the presence of the Autoimmune Regulator (AIRE). This transcriptional facilitator preferentially controls the expression of genes that display the repressive histone mark H3K27me3 at their transcriptional start sites.
To address the question whether alterations in the H3K27me3 landscape influence TEC biology, mice with a TEC-specific loss of the H3K27me3 demethylases UTX and JMJD3 were generated. These mice demonstrated that a deficiency in UTX and JMJD3 reduced the frequency of immature medullary TEC (mTEC), while increasing the frequency of mature mTEC. Although the resulting gene expression changes were limited, AIREregulated genes were strongly enriched within the upregulated genes, supporting the hypothesis that H3K27me3 modifications serve as recognition marks for AIRE-regulated PGE. Placement of H3K27me3 marks is mediated by the polycomb repressive complex 2 (PRC2), which gets recruited to its target genes by cofactor JARID2. Mice with a TECspecific deficiency of JARID2 were also generated and investigated. Despite its seemingly different functional role, a JARID2 deficiency had a similar impact on the mTEC phenotype as a loss of H3K27me3 demethylases UTX and JMJD3. The altered TEC compartment of both experimental animal models further altered the frequency of thymocytes undergoing negative selection in the medulla and mildly decreased the generation of single positive thymocytes. Taken together, this work shows that a TEC-specific loss of epigenetic modifiers of H3K27 methylation impacts on TEC differentiation and function.

Advisor: Holländer, G
Imperial portrait practice in the second century AD: Marcus Aurelius and Faustina the Younger

Case studies of Faustina the Younger’s and Marcus Aurelius’ portraits on coins and in sculpture demonstrate that a more flexible approach than currently allowed for is needed to describe ancient practices and processes behind the phenomenon of ‘replicated’ imperial portraits. Possible norms are investigated in this study, and an adjusted model of an imperial portrait ‘system’ in the second century A.D. is outlined.
Key concepts of the prevailing model are the assumption of an official commissioning of all imperial portrait types, the view of a close correspondence between imperial coins and sculpture and the belief that types were created to commemorate specific historical events. All of this, however, is far from certain and a close examination of the preserved evidence makes it necessary to revise the model in certain ways.

Advisor: Smith, R