VictorJuiz/thesis huggingface dataset:
Mathematical models of the retina in health and disease
Keywords: Retina
Eye
Hypoxia
Reaction-diffusion Equations
Photoreceptors
Ordinary Differential Equations
Hyperoxia
Asymptotic Analysis
Partial Differential Equations
Neuroglobin
Retinitis Pigmentosa

The retina is the ocular tissue responsible for the detection of light. Its extensive demand for oxygen, coupled with a concomitant elevated supply, renders this tissue prone to both hypoxia and hyperoxia. In this thesis, we construct mathematical models of the retina, formulated as systems of reaction-diffusion equations, investigating its oxygen-related dynamics in healthy and diseased states.
In the healthy state, we model the oxygen distribution across the human retina, examining the efficacy of the protein neuroglobin in the prevention of hypoxia. It has been suggested that neuroglobin could prevent hypoxia, either by transporting oxygen from regions where it is rich to those where it is poor, or by storing oxygen during periods of diminished supply or increased uptake. Numerical solutions demonstrate that neuroglobin may be effective in preventing or alleviating hypoxia via oxygen transport, but that its capacity for oxygen storage is essentially negligible, whilst asymptotic analysis reveals that, contrary to the prevailing assumption, neuroglobin's oxygen affinity is near optimal for oxygen transport. A further asymptotic analysis justifies the common approximation of a piecewise constant oxygen uptake across the retina, placing existing models upon a stronger theoretical foundation.
In the diseased state, we explore the effect of hyperoxia upon the progression of the inherited retinal diseases, known collectively as retinitis pigmentosa. Both numerical solutions and asymptotic analyses show that this mechanism may replicate many of the patterns of retinal degeneration seen in vivo, but that others are inaccessible to it, demonstrating both the strengths and weaknesses of the oxygen toxicity hypothesis. It is shown that the wave speed of hyperoxic degeneration is negatively correlated with the local photoreceptor density, high density regions acting as a barrier to the spread of photoreceptor loss. The effects of capillary degeneration and treatment with antioxidants or trophic factors are also investigated, demonstrating that each has the potential to delay, halt or partially reverse photoreceptor loss.
In addition to answering questions that are not accessible to experimental investigation, these models generate a number of experimentally testable predictions, forming the first loop in what has the potential to be a fruitful experimental/modelling cycle.
Novel adenovirus vaccine vectors
Keywords: vaccines
adenovirus
Viral vectors

Replication defective adenoviruses have emerged as promising vectors for delivery of vaccine antigens. The development of new vaccine vectors has recently focused on serotypes to which the human population is less exposed in order to circumvent pre-existing anti vector immunity. This thesis describes the construction and optimisation of ChAdOX1, a new vector based on chimpanzee adenovirus Y25, which has recently been manufactured to clinical grade for a Phase I human trial.
Comparative immunogenicity studies between vectors of different serotype were performed in mice, with careful consideration of the infectious titer of vector preparations, since this parameter can confound studies based solely on viral particle estimation. After intramuscular administration, HAdV-5 (Human adenovirus C) based vectors elicited superior transgene product specific T cell and antibody responses compared to a selection of chimpanzee adenovirus vectors (from Human adenovirus E) including ChAdOX1.
The construction of ChAdOX1 in a bacterial artificial chromosome (BAC), enabled precise and flexible modification of the genome by recombination mediated genetic engineering (recombineering). Reverse genetics was performed to identify vector determinants of immunogenicity. Chimeric ChAdOX1 vectors were created by replacement of native virus associated RNA (VA-RNA) and fiber sequences with the corresponding sequences from HAdV-5. Using these chimeric vectors, the importance of innate immunity and vector transduction in determining vector immunogenicity was investigated. Though the mechanisms responsible ultimately remain unclear, superior transgene product specific immune responses with HAdV-5 correlated with higher levels of transgene expression in vivo after vector administration. The current study has conclusively demonstrated that neither VA-RNA sequences, nor the fiber protein, are responsible for differences in immunogenicity between vectors, contrary to hypotheses based on previous studies.
New insights into Cenozoic Silicon cycling in the Southern Ocean: refined application of silicon isotope ratios in biogenic opal
Keywords: Eocene
Diatom
Silicon Isotope
Oligocene

The marine silicon and carbon cycles are intrinsically linked by a unique group of primary producers; the diatoms. These siliceous-walled phytoplankton play a significant role in carbon export, making them a critical component of the global biological carbon pump with the power to affect climatic change. In this thesis, the silicon isotope composition (δ30Si) preserved in diatom opal is used together with the δ30Si of sponge opal, a powerful new proxy for deepwater silicic acid concentration, to document the Cenozoic Silicon cycle, shedding light on its role in carbon cycling and global climatic change. This study has developed a novel size-separation methodology to produce the first core top calibration of diatom δ30Si. The calibration demonstrates that diatom δ30Si exhibits a strong negative correlation with surface water silicic acid concentration, supportive of its application as a proxy for silicic acid utilisation. The refined method is used to produce a diatom δ30Si record, for the first time combined with sponge δ30Si, to gain insight into the Southern Ocean silicon cycle over one of the largest Cenozoic climatic shifts; the onset of Antarctic glaciation (~33.7 Ma). The two δ30Si records yield the first geochemical footprint to demonstrate that diatom proliferation, coincident with the onset of Antarctic circumpolar current flow, was a precursor event to the Eocene-Oligocene Transition. Diatoms are shown to have played a role in climate cooling through enhanced export and burial of organic carbon on the seafloor. The first long term reconstruction of silicic acid concentration in subsurface waters of the Southern Ocean, which spans the Late Eocene to the earliest Pliocene, provides new evidence that oceanic vertical mixing rates, coupled with the efficient removal of silicon from the surface by the diatoms, have been the most important factor in controlling the silicon chemistry of the ocean over the Cenozoic.
A single-photon source for quantum networking
Keywords: single photons
quantum optics
LOQC
cold atoms
Awesome
STIRAP
quantum computing
cavity QED

Cavity quantum electrodynamics (cavity QED) with single atoms and single photons provides a promising route toward scalable quantum information processing (QIP) and computing. A strongly coupled atom-cavity system should act as a universal quantum interface, allowing the generation and storage of quantum information. This thesis describes the realisation of an atom-cavity system used for the production and manipulation of single photons. These photons are shown to exhibit strong sub-Poissonian statistics and indistinguishability, both prerequisites for their use in realistic quantum systems. Further, the ability to control the temporal shape and internal phase of the photons, as they are generated in the cavity, is demonstrated. This high degree of control presents a novel mechanism enabling the creation of arbitrary photonic quantum bits.
Synthesis of taurospongin A and other biologically active natural products
Keywords: Total Synthesis
natural products
structural elucidation

This thesis firstly describes a synthesis of the natural product taurospongin A, a potent DNA polymerase beta inhibitor. Sharpless asymmetric dihydroxylation on olefin E-1.60 followed by selective deoxygenation at C(2) via Barton‒McCombie reaction delivers the desired C(1)–C(10) carboxylic acid core. Subsequent esterification of the C(1)–C(10) fragment with C(1′)–C(25′) fatty acid furnishes the natural product in 13.5% yield.
The structure of an unnamed natural product 2.14 isolated in 1974 is proven to be misassigned by previous studies within the Robertson group. As described in this thesis, two proposed structures A and B are obtained via total synthesis in order to reveal the identity of the natural product. A synthesis of key intermediate spirocycles 2.148 and 2.158 with desired trans- diol moiety is described by a dihydroxylation reaction on an electron deficient gamma-keto unsaturated acid with subsequent spirocyclisation reaction.
Finally, methodology for generating high-value synthetic intermediates by an asymmetric, one-pot enzymatic di/polycarbonyl reduction is described. The concept of such methodology is first proven by the synthesis of (3R)-hydroxybutyl (3R)-hydroxybutanoate 3.20. This thesis then describes substrate scope studies and corresponding stereochemical proof to provide more information about this methodology.
Quantitative laser diagnostics for combustion
Keywords: air/fuel ratio
laser
diagnostic
quantitative
stratification
LIGS
fuel distribution
cyclic variability
thermal grating
modelling
LITGS
PLIF
IC engine
fluorescence
optical

Quantitative Planar Laser Induced Fluorescence (QPLIF) is developed as a diagnostic technique and then applied to a prototype Jaguar optical internal combustion engine. QPLIF derives quantitative, two-dimensional, spatially-resolved measurements of fuel concentration. This work reports the first demonstration of a fully-fractionated surrogate fuel which exhibits all the characteristics of a typical gasoline. This 'pseudo' fuel, developed in association with Shell UK, is blended to accept a fluorescent tracer which may track one of the light, middle or heavy fractions of the fuel, each of different volatility. The traditional weaknesses of PLIF for quantitative measurements are addressed by use of a fired in-situ calibration method, which maps the quantum efficiency of the tracer and concurrently corrects for window fouling and exhaust gas residuals (EGR). Fuel distributions are presented with an estimated super-pixel accuracy of 10% at different operating conditions, and then compared to the computational fluid dynamics (CFD) predictions of an in-house Jaguar model.
Fuel/Air Ratios by Laser Induced thermal Gratings (FARLIG) is developed theoretically, and results of validation experiments conducted in a laboratory setting are reported. FARLIG conceptually enables the measurement of fuel concentration, oxygen concentration and temperature within a spatially-localised probe volume. Uniquely, the technique exploits the dominant influence of molecular oxygen on non-radiative quenching processes in an aromatic tracer molecule. The changing character of a model quenching mechanism potentially allows the oxygen concentration in the measurement volume to be derived. Absolute signal strength is used to determine fuel concentration, while the oscillation period of the signal provides a precise measurement of temperature (~0.3% uncertainty), with accuracy limited by knowledge of the gas composition.
Olefin metathesis for site-selective protein modification
Keywords: protein modification
olefin metathesis
bioconjugation chemistry
alkene metathesis

Site-selective protein modification has become an important tool to study protein functions in chemical biology. In the preliminary work, allyl sulfides were found to be reactive substrates in aqueous cross-metathesis (CM) enabling the first examples of protein modification via this approach. In order to access the enhanced CM reactivity of allyl sulfide on proteins, facile chemical methods to install S-allyl cysteine on protein surface were developed. In particular, a cysteine-specific allylating reagent – allyl selenocyanate was used on protein substrate for the first time.
The substrate scope of allyl sulfide-tagged proteins and factors that affect the outcome of CM was also investigated. A range of metathesis substrates containing different olefin tether of various lengths were screened; allyl ethers were found to be most suitable as CM partners. By reducing the steric hindrance around the allyl sulfide on protein surface through a chemical spacer, the rate and conversion of metathesis reaction on proteins was greatly enhanced. Moreover, allyl selenides were found to be more reactive than allyl sulfides in CM and enabled reactions with substrates that were previously impossible for the corresponding sulfur-analogue. Through this work, substrate selection guidelines for successful metathesis reaction on proteins were established.
Rapid Se-relayed CM was further investigated through biomimetic chemical access to Se-allyl selenocysteine (Seac) via dehydroalanine. On-protein reaction kinetics revealed rate constants of Seac-mediated CM to be comparable or superior to off-protein rates of many current bioconjugations. This CM strategy was applied to histone proteins to install a mimic of acetylated lysine (K9Ac, an epigenetic marker). The resulting synthetic H3 was successfully recognized by antibody that binds natural H3-K9Ac. A Cope-type selenoxide elimination subsequently allowed the removal of such modification to regenerate dehydroalanine. Finally, preliminary research efforts towards metabolic incorporation of allyl sulfide-containing amino acid into proteins, and CM on cell surfaces were discussed.
Architecture and the public in interwar Britain
Keywords: planning
civic
practice
public
modern
design
culture
architecture
professionalism
interwar
history
england
british

This thesis explores how the practice and profession of architecture was increasingly understood and discussed in terms of the public in the first half of the twentieth century through six case studies. In the age of universal suffrage, architects began to recognise that, in order for the profession to flourish, the built environment would have to respond to the demands of public opinion and publicity, and that design would need to appeal to the 'man in the street' if the profession was to establish its position in the new culture of democracy.
'Architecture and the Public in Interwar Britain' thus challenges the view that the mainstream of interwar British architecture was parochial and backward looking, and seeks to reintegrate the stories of many well-known but academically neglected projects and controversies into twentieth century architectural history, which remains dominated by attempts to nuance the privileged narrative of the growth and 'triumph' of Modernism and the International Style. Instead, I argue that architecture is better conceived as a broad discourse involving a number of agents of diverse positions and attitudes struggling with common critical and professional challenges.
The first section of the thesis considers architecture in the Imperial Metropolis. After offering a re-reading of 66 Portland Place, the headquarters of the RIBA, through the lens of professional anxieties in the interwar years, it considers two controversial rebuilding projects: Regent Street and Waterloo Bridge. The thesis then considers architecture and publicity in the suburbs, offering close readings of factories along the new arterial roads out of London, in particular the Guinness Brewery and Gillette Factory amongst others. The final section of the thesis unpicks the idea of the civic centre in interwar Britain through the contrasting examples of Southampton Civic Centre and lastly Norwich City Hall.
Short-time structural stability of compressible vortex sheets with surface tension
Keywords: Compressible Fluid Dynamics
Hyperbolic Conservation Laws
Free Boundary Problems
Existence and Uniqueness Theory
Vortex Sheets
Euler Equations
Partial Differential Equations
Contact Discontinuities

The main purpose of this work is to prove short-time structural stability of compressible vortex sheets with surface tension.
The main result can be summarised as follows. Assume we start with an initial vortex-sheet configuration which consists of two inviscid fluids with density bounded below flowing smoothly past each other, where a strictly positive fixed coefficient of surface tension produces a surface tension force across the common interface, balanced by the pressure jump. We assume the fluids are modelled by the compressible Euler equations in three space dimensions with a very general equation of state relating the pressure, entropy and density in each fluid such that the sound speed is positive. Then, for a short time, which may depend on the initial configuration, there exists a unique solution of the equations with the same structure, that is, two fluids with density bounded below flowing smoothly past each other, where the surface tension force across the common interface balances the pressure jump.
The mathematical approach consists of introducing a carefully chosen artificial viscosity-type regularisation which allows one to linearise the system so as to obtain a collection of transport equations for the entropy, pressure and curl together with a parabolic-type equation for the velocity. We prove a high order energy estimate for the non-linear equations that is independent of the artificial viscosity parameter which allows us to send it to zero. This approach loosely follows that introduced by Shkoller et al in the setting of a compressible liquid-vacuum interface.
Although already considered by Shkoller et al, we also make some brief comments on the case of a compressible liquid-vacuum interface, which is obtained from the vortex sheets problem by replacing one of the fluids by vacuum, where it is possible to obtain a structural stability result even without surface tension.
Model systems for exploring new therapeutic interventions and disease mechanisms in spinal muscular atrophies (SMAs)
Keywords: drug screening
Charcot-Marie-Tooth (CMT) disease
Drosophila melanogaster
survival motor neuron (SMN)
model organisms
Caenorhabditis elegans
neuromuscular junction (NMJ)
spinal muscular atrophy (SMA)
neuropathy
motor neuron
CMT2D
neuromuscular disease

Spinal muscular atrophy (SMA) and Charcot-Marie-Tooth disease type 2D (CMT2D)/distal SMA type V (dSMAV) are two incurable neuromuscular disorders that predominantly manifest during childhood and adolescence. Both conditions are caused by mutations in widely and constitutively expressed genes that encode proteins with essential housekeeping functions, yet display specific lower motor neuron pathology. SMA results from recessive inactivating mutations in the survival motor neuron 1 (SMN1) gene, while CMT2D/dSMAV manifests due to dominant point mutations in the glycyl-tRNA synthetase (GlyRS) gene, GARS. Using a number of different model systems, ranging from Caenorhabditis elegans to the mouse, this thesis aimed to identify potential novel therapeutic compounds for SMA, and to increase our understanding of the mechanisms underlying both diseases. I characterised a novel C. elegans allele, which possesses a point mutation in the worm SMN1 orthologue, smn-1, and showed its potential for large-scale screening by highlighting 4-aminopyridine in a screen for compounds able to improve the mutant motility defect. Previously, the gene encoding three isoforms of chondrolectin (Chodl) was shown to be alternatively spliced in the spinal cord of SMA mice before disease onset. I performed functional analyses of the three isoforms in neuronal cells with experimentally reduced Smn levels, and determined that the dysregulation of Chodl likely reflects a combination of compensatory mechanism and contributor to pathology, rather than mis-splicing. Finally, working with two Gars mutant mice and a new Drosophila model, I have implicated semaphorin-plexin pathways and axonal guidance in the GlyRS toxic gain-of-function disease mechanism of CMT2D/dSMAV.
"It made our eyes get bigger:" Youth filmmaking and citizenship in London
Keywords: education
participation
gangs
youth
film
media studies
citizenship
anthropology
visual culture

This thesis explores the ways in which discourses of citizenship are circulated and incorporated into the practice of non-formal educational filmmaking initiatives for young people in London. I utilise an ethnographic approach focusing on young participants, adult facilitators and funders to demonstrate how youth filmmaking facilitates an exploration of abstract conceptions of citizenship with the on-the-ground reality of young peoples’ “practice” as citizens. To provide context for this material, I present both a theoretical overview of the heady yet labile term “citizenship” and a historical narrative of youth filmmaking, particularly in its relationship to wider political economies of funding and youth policy.
Although discourses of citizenship in youth filmmaking have changed subtly over time, the youth filmmaking programmes considered here marshal three central conceptions of citizenship; “engagement,” “empowerment” and “belonging.” To explore each of these notions, I draw on case studies to show how these citizenship discourses become operationalised. First, I consider the Reelhood project for young Muslims, which aimed at encouraging “political engagement.” I demonstrate how young people challenge notions of “disengagement” and operate as “justice-oriented” citizens, in contradistinction to the premise of the funding source itself.
Second, I use the example of the This is My Story project, amongst other films that dealt with youth violence, to explore discourses of “empowerment.” Using the metaphor of the “shot/reverse shot” sequence, I demonstrate how youth filmmaking projects situate themselves as an alternative to the representation of young people in mainstream press. Finally, I describe the River Lea project in which the sensory and technological processes of filmmaking became a means for young people to “focus in” and attune their sensory and perceptive faculties to the experience of “place-making.” Each of these case studies exhibits how the creative, social and technical processes of filmmaking provide a challenge to or re-interpretation of citizenship discourse.