### Loss of β-cell identity in diabetes: Significance of miR-7-mediated chromatin remodelling

Yorrick Von Ohlen
Type 2 diabetes (T2D) affects 10% of the adult global population and is a multifactorial disease characterised by insulin resistance of peripheral organs. Insulin resistance results eventually in failure of pancreatic β-cells and subsequent apoptosis. Recent research revealed that β-cell dedifferentiation is contributing to decreasing their function in T2D. Dedifferentiated β-cells express atypical non-β-cell hormones, suggesting transdifferentiation into other cells. Our group previously showed that miR-7 levels are increased in T2D. Upregulation of miR-7a2 in...

### Nonlinear dynamics and control of evolving fluid interfaces

Ruben Tomlin
In the present work, we consider the nonlinear dynamics of thin liquid films controlled by either external electric fields or fluid-mass actuators located on the substrate surface. For the former, we investigate two canonical cases, in which we are able to destabilise or stabilise a liquid film interface depending on the set-up of the electric field. We construct hierarchies of reduced-order models for the two problems, which predict and provide insight into novel electrohydrodynamic phenomena,...

### Elastic wave propagation in polycrystals

Ming Huang
Scattering occurs as elastic waves propagate through a random polycrystalline medium, exhibiting scattering-induced attenuation and velocity dispersion. These behaviours carry bulk information about microstructure and can therefore be used for microstructure characterisation. The purpose of this thesis is to gain knowledge about the behaviour of elastic waves in polycrystals in order to facilitate the characterisation of microstructure. This thesis contributes mainly in six aspects. First, a theoretical second-order approximation (SOA) model is developed to calculate...

### Structural diagenesis using clumped isotope paleothermometry: applications and potential caveats

Fluid flow commonly results in mineral precipitation in fractures which can yield a chemical archive of the physico-chemical conditions during tectonic deformation. However, interpreting subsurface conditions from traditional geochemical proxies can be ambiguous. Here we test clumped isotope thermometry as a tool to provide better understanding of the relationship between deformational structures and diagenetic processes. Three main questions are addressed by this PhD thesis. The first question regards the reliability of clumped isotope compared to...

### The immunological basis of preterm birth in HIV-1 infected pregnant women

Charlotte-Eve Short
Hypotheses HIV infection and combination antiretroviral therapy (cART) used to prevent mother-to-child-transmission of HIV in pregnancy increase the risk of preterm birth (PTB). We hypothesise that the use of cART, particularly protease inhibitor (PI) regimes, induce a pro-inflammatory environment at the fetal maternal unit, which triggers labour to occur at an earlier point in gestation than would occur without HIV-1 infection or cART. We also hypothesise that local cervicovaginal fluid (CVF) will be more informative...

### Experimental investigation of the effects of soil and environmental conditions on smouldering wildfires

Eirik Gaard Christensen
Smouldering peat-wildfires are the largest fires on earth and are responsible for vast economic damage, negative health effects, and significant quantities of greenhouse gas emissions. Despite their importance, limited research has focused on understanding their dynamics. Here I systematically study the influence of the three most important soil conditions: moisture content, inorganic content, and density, as well as three prevalent natural environmental conditions: wind, slope and temperature. Two novel experimental rigs were developed to study...

### Impact of surgical and of bronchoscopic lung volume reductions in patients with emphysema and hyperinflation on lung structure, function and inflammation

Background – A robust biomarker for predicting and evaluating the response to lung volume reduction (LVR) interventions remains elusive. We investigated the hypothesis that LVR will be accompanied by measurable changes in novel indices of lung structure, function, and inflammation that can be correlated with changes to the conventional clinical parameters and that reliable identifiers of baseline predictors of therapeutic response (minimal clinically important difference, MCID, of at least 10% reduction of residual volume) will...

### Refining and improving the assessment and treatment of faecal incontinence

Cosimo Alex Leo
Faecal incontinence (FI) is a common symptom. There are a variety of invasive treatments available, however, the benign nature of this problem and the varying degrees of severity, mean that conservative management is usually pursued first. The aims of this thesis were to investigate: the current practice of continence advisors who deliver conservative management in the community in the UK; assess and evaluate a new portable manometric device (THD® Anopress); investigate a new first line...

### Report 43: Quantifying the impact of vaccine hesitancy in prolonging the need for Non-Pharmaceutical Interventions to control the COVID-19 pandemic

D Olivera Mesa, A Hogan, O Watson, G Charles, K Hauck, A Ghani & P Winskill
Vaccine hesitancy – a delay in acceptance or refusal of vaccines despite availability 1 – has the potential to threaten the successful roll-out of SARS-CoV-2 vaccines globally 2 . Here, we evaluate the potential impact of vaccine hesitancy on the control of the pandemic and the relaxation of non-pharmaceutical interventions (NPIs) by combining an epidemiological model of SARS-CoV-2 transmission 3 with data on vaccine hesitancy from population surveys. Our findings suggest that the mortality over...

### On tilts of certain infinite level shimura varieties

Raffael Singer
Scholze's Siegel modular varieties $\cX_{\Gamma(p^\infty)}$ over a mixed characteristic perfectoid field are known to be perfectoid, yet their tilt remains somewhat elusive. We give two different methods to describe the tilt of spaces related to $\cX_{\Gamma(p^\infty)}$. The first, following an idea of Lurie, uses Drinfeld level structures to construct integral perfectoid models of infinite level Shimura curves. For the second method we show how to recover the Tate module of the universal family of abelian...

### Microstructure control in Ti-6246

Abigail Ackerman
Titanium alloys are widely used in gas turbine engines due to their high specific fatigue strength and ability to retain that strength up to temperatures in the range of 600°C. The alloy Ti-6Al-2Sn-4Zr-6Mo is used in the intermediate pressure compressor of the gas turbine engine, with a yield strength of around 1.1GPa. It has a microstructure of primary α laths within a β matrix. Between the primary α are much finer secondary α laths, creating...

### Circulating microvesicles as mediators of acute pulmonary vascular inflammation

Ying Ying Tan
Acute lung injury (ALI) resulting from remote ‘indirect’ causes is a major problem in sepsis and systemic inflammatory response syndrome (SIRS) but the underlying mechanisms are poorly understood. Circulating microvesicles (MVs) have been implicated as long-range mediators of vascular inflammation and their role as biomarkers in sepsis and SIRS has been widely investigated in clinical studies in recent years. However, the in vivo functional roles of MVs in sepsis and ALI have received less attention....

### Arithmetic topological models for the attractors of infinitely satellite renormalisable maps

In this thesis we propose an arithmetic topological model for the post-critical set of infinitely quadratic-like renormalisable quadratic polynomials of satellite type. This is inspired by the near-parabolic renormalisation scheme of Inou and Shishikura. This model only depends on the combinatorics of the renormalisations, which is a sequence of rational numbers in (-1/2, 1/2]\{0}. We also introduce an optimal arithmetic condition on such sequences that determines when the model is a Cantor set. We show...

Aizat Bin Alias
This thesis investigates the behaviour and performance of steel-concrete composite floors with profiled decking subjected to uplift blast loading. In conventional composite floor design, primary actions are resisted by the capacity of the composite floors in sagging/positive bending moment. However, in the case of uplift blast loading, the same composite floors are subjected to a hogging/negative bending moment whose resistance is not generally considered in simple construction design. According to a literature survey, numerous studies...

### Signal and system design for wireless information and power transfer: Prototype, experiment and validation

Junghoon Kim
A new line of research on system and signals design for Wireless Information and Power Transfer (WIPT) has recently emerged. Various system architectures and signal design strategies are proposed based on various different modelling of the energy receivers. To a great extent, the study of those strategies and architectures has so far been limited to theoretical performance analysis. In this thesis, we study the real over-the-air performance of the system architectures and signal strategies for...

### Simulation of nuclear observables in inertial confinement fusion experiments

Aidan Crilly
The neutrons and gamma rays created in nuclear reactions provide a way to measure conditions in Inertial Confinement Fusion (ICF) experiments. Interpretation of nuclear measurements requires detailed theoretical models and numerical simulations. This thesis presents a computational study of the nuclear observables based on radiation hydrodynamics simulations of ICF experiments. Current measurement techniques are replicated to highlight their strengths and shortcomings. Novel analyses are developed to measure conditions in experiments which are currently unmeasured. Novel...

### Novel methodology for the optimisation of turbocharger turbine design for improved engine performance

Karl Georg Hohenberg
Turbocharging has established itself as a key technology in the downsizing of internal combustions engines, with the aim of reducing fuel consumption and tailpipe emissions. For a turbocharger to be effective, both the compressor and the turbine need to be care- fully designed to match the engine’s requirements. This thesis presents a methodology for modelling the effect of turbine design on the engine performance, enabling an optimised match to be found. This ultimately leads to...

### Asymptotic description of transitional and turbulent flows: effects of surface roughness on the boundary layer and the evolution of coherent structures in free shear flows

Csaba Bence Katai
In this thesis we investigate, using high-Reynolds-number asymptotic techniques, three fluid dynamics problems linked to transition and turbulence. The first problem concerns the impact of spanwise periodic, streamwise elongated surface roughness elements on the boundary-layer stability. We are mainly interested in their effects on the so-called lower-branch modes, therefore, the spanwise spacing of the roughness is chosen to be comparable to the characteristic wavelength of the instability modes which is on the triple-deck scale. The...

### Lifecycle portfolio choice

Jialu Shen
Using the Panel Study of Income Dynamics, I find that stockholders subject to more negative skewness in earnings growth hold a lower share of their financial wealth in stocks. Moreover, I also find that skewness in earnings growth affects the mean and skewness in consumption growth, and this effect is stronger for stockholders than nonstockholders. Using a life-cycle model incorporating business cycle variation in expected growth and skewness in earnings shocks, I investigate these relationships...

### Gaussian processes for hybridisation of analytical and data-driven approaches for design of experiments

Simon Olofsson
In many areas of science and engineering, gathering data and making measurements of a system is costly and time-consuming. Whether the data comes from real-life experiments or computer models, we wish to maximally utilise already existing data to make informed and optimal decisions. The decisions might have to do with where next to evaluate the system, or how to control the system. Our focus is on design of experiments to aid model discrimination, i.e. discarding...

### Investigation of the potential role of RORα in Parkinson’s disease: novel evidence for neuroprotection using post-mortem human tissues and in vitro studies

Parkinson’s disease (PD) is characterised by the loss of dopaminergic neurons from the midbrain substantia nigra pars compacta (SNpc). Current therapies aimed at replacing dopamine do not halt disease progression and long-term use is associated with reduced efficacy and debilitating side effects, hence there is an urgent need for a better understanding of disease mechanisms leading to novel therapeutic approaches. Interestingly, being male is a major risk factor after aging for developing PD, with the...

### On inverse problems and finite elements in shape analysis

Andreas Bock
Shapes are nonlinear, multifarious objects and it is a nontrivial task to attach meaning to statements about their comparison. A central problem in the field of shape analysis is therefore to make sense of the notion of a metric on an abstract shape space. Through the lens of infinite-dimensional Riemannian geometry one can endow such spaces with different metrics stemming from nonrigid group actions to compute so-called geodesic matchings between shapes that share diffeomorphic or...

### Motion robust acquisition and reconstruction of quantitative T2* maps in the developing brain

Serhiy Vasylechko
The goal of the research presented in this thesis was to develop methods for quantitative T2* mapping of the developing brain. Brain maturation in the early period of life involves complex structural and physiological changes caused by synaptogenesis, myelination and growth of cells. Molecular structures and biological processes give rise to varying levels of T2* relaxation time, which is an inherent contrast mechanism in magnetic resonance imaging. The knowledge of T2* relaxation times in the...

### Towards physical realisations of quantum thermodynamics

Zoe Holmes
Quantum thermodynamics seeks to extend the laws of thermodynamics to equilibrium and non-equilibrium systems on the nano-scale. Over the last decade a large body of theoretical research into quantum thermodynamics has been produced; however, experimental research is yet to catch up with the impressive lead set by theory. This is especially true of quantum information theoretic approaches which have proven an effective means of incorporating quantum effects into thermodynamics but seem resistant to experimental implementation....

### Development and testing of an idiopathic pulmonary fibrosis (IPF) patient reported outcome measure (PROM)

Anne-Marie Russell
Patients with Idiopathic Pulmonary Fibrosis (IPF) experience debilitating symptoms which impact their health-related-quality-of-life (HQOL). Treatment options are limited but new approaches are being explored; a robust endpoint model that includes a patient reported outcome measure (PROM) to determine the impact of new treatments on patients’ symptom experience and HQOL in IPF populations is needed. The IPF-PROM study employed a mixed-methods approach, incorporating qualitative and consensus methodologies, embedding patient-centredness throughout. This enabled a robust approach to...

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#### Affiliations

• Imperial College London
806
• Technological University Dublin
3
• University of Orléans
1
• French National Centre for Scientific Research
1
• Fraunhofer Institute for Applied Polymer Research
1
• University of Birmingham
1
• University of Cape Town
1