VictorJuiz/thesis huggingface dataset:
Information updating and autobiographical memory in posttraumatic stress disorder

Cognitive theories suggest that information updating and autobiographical memory characteristics may play a role in the development and maintenance of PTSD symptoms (e.g., Ehlers & Clark, 2000). This thesis presents five studies that examine memory updating of negative and neutral associated memories, negative and positive appraisals about strangers, and disorganised trauma memories in posttraumatic stress disorder (PTSD). Study 1 demonstrated that low mood but not anxiety tended to be associated with difficulties with updating negative compared to neutral associative memories (Chapter 2). Study 2 found that relative to a sample of control participants, people with PTSD had difficulties with updating neutral compared to negative associative memories. Updating performance for neutral material was related to changes in memory characteristics with PTSD treatment (Chapter 3). Study 3 demonstrated that compared to controls, trauma survivors with PTSD showed more change in negative appraisals about strangers with negative information, compared to change in positive appraisals with positive information. Interpersonal distressing events in both groups tended to be associated with difficulties in updating appraisals about strangers (Chapter 4). Study 4 demonstrated that compared to controls, trauma survivors with PTSD reported poorer memory recall and more memory disjointedness of their traumatic event, but not of a negative control event. Poor recall and memory disjointedness improved with PTSD treatment (Chapter 5). Study 5 demonstrated that in healthy participants, exposure to a trauma film led to more disjointed memories of the film compared to exposure to a neutral film. Memory disjointedness partly mediated the relationship between peri-traumatic cognitive processing and re-experiencing symptoms after trauma film exposure (Chapter 6). The findings provide support for the cognitive model of PTSD (Ehlers & Clark, 2000), and suggest that difficulties in updating neutral information, the development of negative appraisals, and poor memory recall and memory disjointedness of trauma memories may contribute to the maintenance of PTSD symptoms.

Advisor: Ehlers, A
Clark, D
Laser cooling of high temperature superconductors

In this dissertation, we theoretically demonstrate laser light induced control and cooling over the order parameter of superconducting cuprates. We predict a non-equilibrium state with enhanced robustness against thermal fluctuations when pumped with coherent pulses. This might ultimately increase the critical temperature of the cuprate.
In particular, we propose a parametric cooling scheme for a bilayer cuprate modelled phenomenologically as a stack of long intrinsic Josephson junctions. We identify a parameter regime, which according to the switching current distribution allows a reduction of the effective system temperature by approximately 25%. This cooling scheme suppresses the thermal excitation of Josephson vortices. This might lead to an indirect mechanism for controlling topological excitations in the phase of the superconducting order parameter.
We further find that the strong driving of the cuprates can lead to parametric instabilities. To investigate the effect strong driving can have on the dissipative dynamics, we derive a FloquetMarkov master equation. We find that strong driving is a measure for probing the bath spectral density of otherwise inaccessible condensed matter systems.

Advisor: Jaksch, D
Development of high-throughput imaging mass spectrometry

Mass specific surface images with micron and sub-micron spatial resolution can be recorded with a mass spectrometer. Ion microscope mass spectrometry imaging uses a defocused laser or ion beam to simultaneously analyse large sample areas. The ions are subsequently separated by their time-of-flight (ToF) and their spatial location is electrostatically transferred onto a two-dimensional position-sensitive detector. The detected ions are converted to light and recorded by either, a charged coupled device (CCD) camera and a photo multiplier tube (PMT), or an event-triggered complementary metal-oxide semiconductor (CMOS) sensor. CMOS sensors such as the Timepix3 cam and a PImMS camera are capable of multi-mass ion imaging. The result is a series of images corresponding to each recorded m/z, further demonstrating the high-throughput capability of the instrument.
An ion microscope has three drawbacks when compared to microprobe MSI: low mass resolution, a small mass range and poor spatial resolution. For each of these limitations, this thesis presents a solution that can be applied simultaneously to improve the performance and applicability.
An ion microscope, incorporating a reflectron, was used to simultaneously image mass-resolved ions generated from a 0.3mm diameter surface. Mass and spatial resolutions of 8100±700m/Δm and 14 μm were obtained by using post extraction differential acceleration (PEDA) ion optical focusing to create a pseudo-source plane for a single-stage gridless reflectron. The obtainable mass resolution was limited only by the response time of the position-sensitive detector, and could potentially reach 30 200±2900m/Δm.
Single-field PEDA has a mass-resolved window that is approximately 19% of the spatially-resolved mass window. A time-dependent pulse applied after ions have exited the extraction region facilitates an increase in the mass resolution over the entire spatially resolved mass range. The potential energy surface of the time-dependent pulse is chosen so that it approximates the dependency between the ion ToF and molecular weight. Mass resolution between 2500 - 8100m/Δm has been achieved for ions between 300 - 625 Da, whilst preserving approximately 14 μm spatial resolution.
The spatial resolution has been improved in silico with the introduction of a four-plate ion optic. The electrode arrangement and potentials have been optimised using minimisation routines. An 800 nm spatial resolution has been achieved with the optimised ion optics.
The Timepix3 cam has recorded time resolved ion images from a reflectron ion microscope. The camera has been operated in continuous readout mode and the individual experiments have been separated using optical fibre that directs part of the laser pulse onto the sensor. This provides an alternative to the expensive readout systems that are typically used. The resolutions achieved with this technique are comparable to those obtained using a CCD/PMT combination.

Keywords: Imaging mass spectrometry
high-throughput
high resolution
data analysis
genetic algorithm
broad mass range
Advisor: Brouard, M
Adaptive timestepping for SDEs with non-globally Lipschitz drift

In this thesis, we focus on the numerical approximation of SDEs with a drift which is not globally Lipschitz, and corresponding sensitivity calculations.
First, we propose an adaptive timestep construction for an Euler- Maruyama approximation of these SDEs over a finite time interval. It is proved that if the timestep is bounded appropriately, then over a finite time interval the numerical approximation is stable, and the expected number of timesteps is finite. Moreover, we extend this scheme to ergodic SDEs with contractivity over an infinite time interval and prove that the bound for moments and the strong error of the numerical solution are uniform in T, which allow us to introduce the adaptive multilevel Monte Carlo (MLMC) method to further improve the efficiency.
Next, we apply a new MLMC method for the ergodic SDEs without contractivity. By introducing a change of measure technique, we simulate the paths with contractivity and add the Radon-Nikodym derivative to the estimator. It is shown that the variance of the new level estimators increases linearly in T, which is a great reduction compared with the exponential increase in the standard MLMC.
Lastly, we derive a new pathwise sensitivity estimator for chaotic SDEs by introducing a spring term between the original and perturbed SDEs. The variance of the new estimator increases only linearly in time T; compared with the exponential increase of the standard pathwise estimator. We also consider using this estimator for the SDE with Richardson-Romberg extrapolation on the volatility parameter to approximate the sensitivities of the invariant measure of chaotic ODEs.
All of the analysis is supported by numerical results.

Keywords: Chaotic System
Multilevel Monte Carlo
Numerical method
Adaptive
Ergodic SDE
Advisor: Giles, M
The role of PAM in pancreatic beta cell dysfunction and diabetes

Genome wide association studies (GWAS) have been critical to the identification of >400 signals at around 200 loci involved in Type 2 Diabetes (T2D) risk. However, the functional interrogation at these loci has been slow. Coding alleles in PAM, D563G (minor allele frequency, MAF=4.98%) and S539W (MAF=0.65%), were identified in association with increased Type 2 diabetes (T2D) risk and reduced insulinogenic index. These were recently shown to mediate risk through alterations to PAM amidating activity and expression in the β cell. Peptidylglycine -amidating monooxygenase (PAM) was also recently shown to function in mediating insulin secretion and content. The work in this thesis has explored the role for PAM in pancreatic beta (β) cells and the cellular mechanisms by which its dysfunction alters diabetes risk across a range of diabetes phenotypes ranging from classical T2D through early onset diabetes pathogenesis.
First, I characterised the role for PAM in human pancreatic β cells using an authentic cell model, EndoC-βH1 cells. Examination of endogenous PAM expression identified the predominant isoform to be membrane-integral, which localised to insulin-containing secretory granules and was post-translationally cleaved to generate 2 further isoforms. Gene silencing and PAM catalytic inhibition studies identified that auxiliary proteins present in the secretory granule, such as chromogranin A, are amidated by PAM and that this may impact their stability and localisation. In addition, reduced intracellular insulin content mediated through impaired PAM activity was shown to be mediated through reduced INS gene expression.
Next, I determined the impact of a rare coding allele (p.R36S) on PAM and β cell function, identified in a proband with early onset diabetes mellitus. I compared the T2D-associated low frequency allele, S539W, which results in a loss of PAM function, with this novel allele to explore how these alleles might differ in their effect on β cells. Comparison of the cellular dysfunction between these two alleles identified that R36S-PAM caused β cell loss in contrast to the T2D-risk allele S539W which impaired insulin secretion.
Finally, I established a strategy to characterise rare variants identified in a gene-level signal for T2D risk in PAM. A comprehensive functional characterisation is needed to fully elucidate the relationship between altered PAM function and T2D risk. A pilot study of 5 of the 35 variants underlying the association identified a further PAM allele which caused reduced protein expression.
In summary, my work has uncovered the complex biology pertaining to PAM function in β cells and distinct mechanisms by which dysfunction may lead to diabetes of differing clinical severities. A more comprehensive understanding of these mechanisms may potentially inform diagnosis and drug development for diabetes along the spectrum of clinical severity.

Advisor: Gloyn, A
Hastoy, B
Cox, R
Characterisation of alternative H2A.X mRNAs during the cell cycle and under DNA damage conditions

Replication-dependent (RD) histone genes employ a unique RNA processing mechanism that generates non-polyadenylated messenger RNA (mRNA), ending in a stem-loop (SL) structure. This is mediated by a U7 snRNP-dependent mechanism that distinguishes this mRNA class from “bulk” poly(A)+ mRNA. However, recent studies have shown that RD histone genes express a subset of polyadenylated mRNA in differentiated cells, as a source for replacement histones. My results now show that the formation of read-through poly(A)+ histone mRNA from RD histone genes is not only a result of the differentiation program, as highly proliferating HeLa cells also express some of these mRNA isoforms. Furthermore, these poly(A)+ histone mRNA isoforms in HeLa cells were also detected in the cytoplasm making them potential translation substrates.
The gene encoding for H2A.X, H2AFX, is the best known histone gene that expresses both SL and poly(A)+ mRNA isoforms, so showing replication-dependent and replication-independent characteristics. My data indicate that the H2A.X poly(A)+ mRNA is mainly generated by H2AFX transcription outside of the S-phase. A minor fraction may be produced in S-phase as a consequence of inefficient U7-dependent processing. Furthermore, H2A.X poly(A)+ mRNA levels are upregulated in G2/M in both HeLa and HCT116 cells.
By specifically depleting either of these two mRNA isoforms, using RNAi and CRISPR-Cas9 gene editing, I show that their requirement for efficient γH2A.X foci formation upon DNA damage induction depends on their relative levels. Thus cells that express lower levels of the H2A.X SL mRNA, such as HeLa and RPE-1 cells, mainly depend on the H2A.X poly(A)+ mRNA for de novo H2A.X protein production outside of S-phase but possibly also for sufficient H2A.X incorporation into newly synthesised chromatin during S-phase. In contrast, cells that express high levels of the H2A.X SL mRNA, such as HCT116 cells, mainly depend on this mRNA isoform. In these cells, the incorporated H2A.X in the chromatin during S-phase is sufficient for efficient γH2A.X signalling following DNA damage induction.
Only vertebrate H2AFX genes have evolved to contain the SL structure. Apart from allowing formation of H2A.X SL mRNA by U7-dependent processing, the function of the SL in the H2A.X poly(A)+ mRNA was unknown. I now show that the SL structure has a role in restricting H2A.X poly(A)+ mRNA accumulation in S-phase, possibly through interaction with the conserved region upstream of the polyadenylation site.

Advisor: Proudfoot, N
Aspects of Richard Strauss's late aesthetic

This study of Richard Strauss’s late aesthetic develops the following general theses: 1. Strauss’s late works fall within what Frederic Jameson calls the ‘cultural dominant’ of modernism. 2. Strauss’s music finds intellectual meaning through the tradition of liberal humanism. 3. The musical work in the age of Strauss is both art and commodity.
The term aesthetic denotes the category of material that is my primary concern—not uncritically, the musical work. I do not hold the aesthetic aspect of Strauss’s music to be abstracted from its social, historical, or material properties but to be formed through them; and by engaging with Strauss’s works through the idea of the aesthetic I aim to grasp something of their musical subjecthood without equating them directly with human subjectivity.
Each chapter focuses on one of Strauss’s later works: Daphne, Op. 81; Oboe Concerto, TrV 292; Metamorphosen, TrV 290; ‘Beim Schlafengehn’, TrV 296.c; ‘Malven’, TrV 297. It is not my aim to produce a comprehensive set of stylistic analyses or to distinguish a singular ‘late aesthetic’. Rather, the repertoire under consideration has been chosen from different genres to demonstrate the complexity and variety of music at hand. I employ a combination of analytical and historical frames to consider Strauss’s music via its relationship to the conditioning influences of its social and historical situation. This ‘situation’ is conceived both broadly (in the context of long-standing artistic and intellectual traditions) and particularly (the immediate circumstance of composition).
The dissertation is presented in seven parts, with five chapters offering independent arguments through original analyses of Strauss’s music. Of all the music examined in the course of the dissertation Metamorphosen is the only work to bring liberal humanism and musical modernism together in a progressive way and it has therefore been positioned centrally in the structure, which falls into three unofficial sections: Chapters 2 and 3 ‘bourgeois music’, Chapter 4 ‘radical music’, Chapters 5 and 6 ‘late music’.

Advisor: Tunbridge, L
The interaction between reward-driven learning and selective attention

Selective attention is the prioritisation of certain pieces of information over others, and is often guided by task goals or by physical salience. Attention can also be guided by stimuli previously learned to be associated with reward which can capture attention in the absence of task relevance or physical salience—a phenomenon termed value-driven attentional capture (VDAC; reviewed in Chapter 1). The first part of this thesis examines the cognitive and neural mechanisms of VDAC. Chapter 2 shows that stimuli with reward history can rapidly capture spatial attention without being currently task-relevant (akin to exogenous cues) and can also sustain attention over intervals as long as one second. Chapter 3 examines the neural mechanisms of VDAC using multivariate pattern analysis of magnetoencephalography data. Learned value modulates spatial representations of stimuli within posterior visual, parietal, and inferior temporal cortex, and this relates to the magnitude of the behavioural VDAC effect. No evidence was found suggesting that non-spatial features are similarly modulated. A stimulus-independent value signal was also found in insular and posterior visual and parietal cortex. However, the relatively late onset of these modulations during visual processing (~250ms) suggests that value signals may first arise elsewhere. The second part of this thesis describes a behavioural and functional magnetic resonance imaging (fMRI) study in macaques which examines the impact of stimuli with reward history on reward learning and decision-making, and the brain regions that represent reward history and other parameters relevant to these processes. Chapter 4 shows that the reward history of a currently unrewarded option interferes with decision-making, possibly by slowing subjects’ learning rates. Chapter 5 describes fMRI analyses showing that regions within the ventromedial prefrontal cortex (vmPFC) and ventrolateral prefrontal cortex (vlPFC) track the learned value of stimuli. Analyses also revealed activity consistent with value comparison signals in the vmPFC, reward prediction error (RPE) signals in the amygdala and putamen, and unsigned RPE (“attention”) signals in the putamen, anterior cingulate cortex, and the vlPFC. However, fMRI analyses were not able to clearly explain the impact of reward history in the current study; possible reasons for this are discussed. Chapter 6 summarises the findings and their limitations and places them in the broader context of the interaction between learning and attention.

Keywords: fmri
visual attention
reward learning
magnetoencephalography
selective attention
reinforcement learning
functional magnetic resonance imaging
Advisor: Stokes, M
Rushworth, M
Atomic politics: Romania’s cold war nuclear acquisition strategy, 1962–1979

This thesis examines Romania’s Cold War acquisition of nuclear technology from Western suppliers during the period of détente. This first account of the Romanian nuclear programme is based on multi-archival research that relies extensively upon recently declassified documents from both sides of the former Iron Curtain. It complements supplier-centric explanations of nuclear assistance and restores agency to recipient countries, in this case Romania. The thesis argues that Romania was an ‘international nuclear entrepreneur’ which turned to the West for atomic assistance because Moscow delayed transfers of the technology that the leadership in Bucharest had requested. Romania then discovered that the Soviet policy of ‘denial by postponement’ contrasted with more positive attitudes in the West. Over this period, Romania managed to secure nuclear technology thanks to its ingenuity and its political entrepreneurship with the West. In particular, Romania obtained atomic assistance by offering its good offices to the United States during the Vietnam War and the Sino-American rapprochement, and by playing West European nuclear suppliers off against one another.
This thesis thus offers a new interpretation of how and why a country like Romania could gain the access it did to Western nuclear technology during these years, revealing lessons about nuclear acquisition strategy and non-proliferation more generally. It challenges the conventional view of atomic assistance, which holds that superpower nuclear suppliers provided nuclear assistance because of an ideology shared with recipient countries and because they felt pressured by international institutions. This historical analysis is based upon a new, multi-archival reading of primary sources, and contributes to a post-revisionist and more nuanced interpretation of the ‘nuclear’ dimension of the détente period in the Cold War by examining the remarkable agency of one smaller East European power.

Advisor: Deighton, A
Multiscale turbulence in magnetic confinement fusion devices

Turbulence in magnetised plasmas is driven by microinstabilities which exist at the spatial scales of the ion and the electron thermal gyroradii, with time scales corresponding to the ion and the electron thermal speeds, respectively. Hence, plasma turbulence can have a well-separated long wavelength "ion scale" (IS) and short wavelength "electron scale" (ES), where the separation is controlled by the electron-to-deuterium mass ratio (me/mi)1/2 = 1/60. Resolving multiscale plasma turbulence in direct numerical simulations (DNS) is costly due to the small value of (me/mi)1/2; nonetheless, several DNS have been performed which show that interactions between the long wavelength and the short wavelength pieces of the turbulence can be important for determining the character of the turbulence. In this thesis we find scale-separated, coupled equations for the IS and the ES pieces of the turbulence, valid in the limit that (me/mi)1/2 → 0. These equations can be efficiently simulated in a system of coupled flux tubes. The equations provide insight into the mechanisms and the impact of the cross-scale interactions between the IS and the ES pieces of the turbulence, whilst avoiding the cost of DNS. We find that to leading order the IS turbulence evolves independently of the ES turbulence. The ES turbulence is sheared by parallel variation in the IS E × B drift, and the drive of instability at the ES is modified by the gradient of the IS distribution function. We study the effect of IS turbulence on the linear stability of the electron temperature gradient (ETG) mode. We find that a strongly driven ETG instability is stabilised by strongly driven IS turbulence, but is only weakly suppressed by IS turbulence driven near marginal stability. We identify the dominant suppression mechanism as parallel-to-the-field shear in the IS E × B drift: the simple nature of this suppression mechanism may explain why short wavelength turbulence saturates at a low level in the presence of strongly driven long wavelength turbulence in DNS.

Keywords: Ion Scale
Cross-scale Interaction
Magnetised Plasma Turbulence
Gyrokinetics
ITG
ETG
Electron Scale
Multiscale
Magnetic Confinement Fusion
Advisor: Barnes, M
Roach, C