VictorJuiz/thesis huggingface dataset:
Does sleep protect against oxidative stress?

Sleep is a vital behaviour, and despite spending one third of our lives asleep, we are yet to define its function. A proposed function connects sleep and the build-up of reactive oxygen species (ROS) in the brain, suggesting that sleep is needed as antioxidant defence mechanism. Indeed, ROS accumulation is implicated with prolonged waking, and artificial increase of ROS in the brain can induce sleep in animals. Using the fruit fly Drosophila melanogaster, investigated sleep’s possible role as an antioxidant defence. Acting as a ROS sensor in sleep-promoting dorsal fan-shaped (dFB) neurons is the potassium channel Shaker’s b subunit Hyperkinetic (Hk). Oxidization of its cofactor NADPH causes conformational changes of the channel and thereby modulates dFB neuron activity. dFB neurons could thus act as an early-alert system for rising ROS levels in the brain.
Here, I analysed the sleep pattern, learning and lifespan of short-sleeping Hk mutants, and found severe deficits in learning as well as a drastically shortened lifespan. Learning, additional to sleep duration, was rescued by reinstating Hk into dFB neurons. Lifespan was affected independently of sleep duration, as pan-neuronal Hk expression was required to rescue lifespan.
Introduction of the ROS-limiting alternative oxidase (AOX) into mitochondria of flies affected sleep duration and architecture similarly to Hk mutants. However, learning and lifespan remained unaffected, showing that flies were healthy despite severely shortened sleep duration. Furthermore, AOX expression in Hk mutants rescued learning, suggesting that learning deficits after chronic sleep deprivation are caused by an accumulation of ROS. Lifespan on the other hand seemed to be affected by loss of Hk regardless of sleep state or AOX expression, showing its dependence on functional Hk itself.
Summarizing, ROS plays an important role in the induction and regulation of sleep, and symptoms of chronic sleep deprivation can be counteracted via regulation of ROS production.

Advisor: Miesenboeck, G
Towards a methodology for prospective governance in quantum computing technologies

This thesis investigates the value and effectiveness of anticipatory governance techniques in a new technology – in this case, quantum computing. It contributes a novel framework to encourage more widespread institutionalisation, translational capability, and ease of use for such anticipatory governance methods.
Novel technologies frequently have (and indeed are expected to have) societal impact – quantum computing is one such technology. However, technologies that can have societal impact need to both merit and retain societal trust – such trust is predicated upon reliable and responsible methods of development, which enable publics to be assured of both specific and systemic trustworthiness. These concepts are closely allied to governance – but in the case of fast-developing technologies, there is often not yet any ‘traditional’ form of governance such as regulation. Traditional forms of governance are generally reactive, waiting for harm to occur before being framed. This is contrasted with ‘anticipatory’ governance, which seeks to mitigate potential negative outcomes by involving stakeholders in developmental processes, empowering researchers and developers to reflect on potential outcomes and consequences, and enabling them to respond in ways that can reduce harmful societal impacts.
This thesis has investigated these topics through qualitative case studies and analysis in three key domains for quantum computing – industry, academia, and policy. The work has engaged with leaders and significant figures across these sectors, drawing out themes that are specific to quantum computing as well as those that are commonly encountered across computer science disciplines, and some that are found in all novel technologies. As a result of these investigations, it has developed a Framework that can be used for anticipatory governance purposes across research, industry, and in policymaking. The thesis closes by describing how the Framework has been demonstrated and evaluated in numerous contexts; addressing and elaborating on some of the persistent underlying themes that have emerged through the work; and suggesting avenues for further research.

Keywords: responsible innovation
quantum computing
assessment framework
qualitative research
Advisor: Jirotka, M
Building on Bildung in the 20th century – individual and institutional learning in Wittgenstein and Hesse

This thesis will undertake a comparison of the figurative use of “games” in Philosophische Untersuchungen by Ludwig Wittgenstein and Das Glasperlenspiel by Hermann Hesse. Both works use “games” as an analogy to explore language use as a collective activity. ‘Bildung’ for the purposes of this thesis denotes the authors’ shared interest in how a good education should not only consist in applying oneself to scholarly study but also personal, moral development. I argue that ‘Sprachspiele’ and the ‘Glasperlenspiel’ are literary devices that the authors use in contrasting but complementary ways to explore the following questions: how do we help people to learn to think for themselves (to become well-rounded, independent thinkers) within an institutional environment that is necessarily conformist? How can students be taught to think for themselves, while also encouraging them to have the humility to listen to the opinions of others? The fact that games involve an element of freedom and spontaneity, while also being confined within rules that govern what can and cannot be done, means that the authors’ analogies were carefully chosen. This tension between freedom and rules within games reflects a tension at the heart of Bildung, identified by Georg Bollenbeck as dual process of ‘bilden’ and ‘sich bilden’ (whereby an individual is moulded by external forces, but also retains agency within their learning journey). By reading Wittgenstein and Hesse alongside one another, I would like to consider the question: If we were to think of our academic forms of life as a game, how might that change the way we think about what we do?

Keywords: institutions
German literature
pedagogy
education
philosophy
Bildung
Advisor: Morgan, B
Phenotyping C9-ALS/FTD iPSC-derived cortical neurons

The GGGGCC hexanucleotide expansion in the C9orf72 gene (C9-HRE) is the most frequent genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). C9-ALS/FTD describes the condition in which patients suffer from both ALS and FTD, which are described as the degeneration of motor or cortical neurons, respectively. While the molecular phenotype caused by the C9-HRE is relatively well established in motor neurons, little work has been done to understand the molecular effect of the C9-HRE on cortical neurons.
This study aims at furthering our understanding of the molecular impairments caused by the C9-HRE in patient cortical neurons. To this end, I differentiated C9-ALS/FTD-patient induced pluripotent stem cells (iPSCs) into cortical neurons. In these cells, I measured stress granule formation, autophagic flux, ER stress, excitability, Ca2+ signalling, and mitochondrial integrity and function, which are pathways that are commonly affected in C9-HRE-carrying motor neurons.
I found no evidence of altered stress granule formation, autophagic flux, and ER stress in C9-iPSC-derived cortical neurons. Furthermore, I discovered changes in excitability, excitation latency, and cytosolic Ca2+ clearance after glutamate and KCl stimulation due to changes in GluA1 expression in cortical neurons. In addition, C9-iPSC-derived cortical neurons displayed mitochondrial impairments. The mitochondrial membrane potential was reduced causing increased mitophagy which results in a reduction in mitochondrial mass. The mitochondrial fission apparatus was downregulated, and the anterograde axonal transport machinery was overexpressed. Mitochondrial respiration remained unaltered in patient cortical neurons. Together this data suggests the C9-HRE causes a distinct phenotype in iPSC-derived cortical neurons, stressing the need to study the FTD pathomechanism in the respective cell type. The molecular early-disease phenotype of C9-FTD includes impairments in excitability and mitochondrial processes. This study serves as a foundation for future FTD research using iPSC-derived cortical neurons.

Keywords: C9-ALS/FTD
amyotrophic lateral sclerosis
neurodegeneration
FTD
iPSC-derived cortical neurons
C9orf72
frontotemporal dementia
ALS
Advisor: Talbot, K
Dafinca, R
Climate risk scenario analysis and the role of central banks and supervisors in safeguarding financial stability in the net-zero transition

In response to a growing awareness that climate change and the associated net-zero transition may impact financial stability, academics, financial institutions (FIs), central banks and supervisors (CB&S) have been developing a suite of scenarios and analytical tools to assess climate-related financial risks. This DPhil contributes to the field of climate finance with: (i) a more systematic understanding of the evolving role of CB&S in setting climate-related financial regulation, as well as wider policy challenges involved in navigating the transition (Paper I); (ii) the development of an empirically grounded bottom-up climate stress testing approach – TRISK - to assess transition risks and the distributional consequences for financial institutions’ portfolios to scale up capabilities in forward-looking scenario analysis for risk management purposes (Paper II); and (iii) a taxonomy framework for assessing the suitability and credibility of scenarios within financial decisions to advance the understanding of the wider limitations, uncertainties, and trade-offs inherent in climate scenario risk analysis (Paper III).

Advisor: Caldecott, B
Farmer, D
Apoptosis-induced loss of CD43 from T cells promotes efferocytosis


The rapid and efficient phagocytic clearance of apoptotic cells by efferocytosis is a critical process for maintaining tissue homeostasis and immune function. T cells undergo apoptosis during thymic education and in the periphery, and require rapid clearance. CD43 is a bulky and heavily-glycosylated transmembrane protein highly expressed on the T cell surface. The function of CD43 in immune responses is mostly attributed to its anti-adhesive properties that negatively regulate cell-cell interactions. However, how CD43 might be modulated during cell apoptosis and whether such potential modulation might influence efferocytosis are not known. In this study, I demonstrate that CD43 is promptly and selectively eliminated from the human T cell surface during apoptosis, and the removal is mediated by the ADAM10 sheddase, whose activation is associated with surface-exposed phosphatidylserine that flips from the inner to outer leaflet of the plasma membrane. I established a novel efferocytosis assay and used this to show that CD43 removal increases the uptake of apoptotic T cells in an ADAM10-regulated manner. These findings present a novel regulatory pathway for CD43 expression and reveal CD43 as a ‘don’t eat me’ barrier for efferocytosis with implications for developing therapeutic strategies against pathological conditions that are associated with efferocytosis.

Keywords: macrophage
efferocytosis
apoptosis
ADAM10
T cell
CD43
Mucin
Advisor: Sattentau, Q
Dushek, O
Spatial and temporal variability in the Uranian atmosphere

VLT/MUSE, HST/STIS and HST/WFC3 observations of Uranus in the visible/near-infrared were employed to probe spatial and temporal variability within its atmosphere. A Minnaert analysis of Uranus’ north polar hood reveals a temporal brightening of this feature, predomi- nantly caused by physical changes within the atmosphere, as opposed to any brightening effects caused by changes in viewing geometry as Uranus’ orbit progresses towards northern summer solstice in 2030. A reduction in the temporal rate of brightening was also provisionally ob- served. The holistic aerosol model [Irwin et al., 2022] was applied to latitudinal retrieval analyses on the three datasets, determining an increase in the integrated opacity (τ), and a re- duction in the imaginary refractive index spectrum (ni) longwards of 0.6 μm, of the 1 – 2-bar haze (aerosol-2) layer north of ∼40°N to be the predominant cause of the hood’s brightening. The single-scattering albedo of the aerosol-2 layer in the 60 – 70°N latitude band at 0.8 μm is observed to increase from ∼0.958 ± 0.002 in 2012, to ∼0.973 ± 0.002 in 2015, and to ∼0.9918 ± 0.0002 in 2021 from HST/STIS and VLT/MUSE retrieval analyses. Between the 2012 and 2015 STIS observations, the average increase in τ2 was 1.09 ± 0.08 at 0.8 μm, a ∼33% increase. An average increase in τ for the deep haze (aerosol-1) layer north of ∼45°N of 0.6 ± 0.1 at 0.8 μm (∼56% increase), and an average decrease in polar cloud-top methane (CH4) VMR from 40 – 80°N of 0.0019 ± 0.0003 (∼10% decrease) were also found between 2012 and 2015. A further reduction in polar cloud-top CH4 was found from analysis of the 2021 VLT/MUSE observation contrary to Sromovsky et al. [2019]’s conclusion of a general latitudinal stability. The 1 – 2-bar haze layer altitude is observed to be very stable, provid- ing evidence for it lying within a region of static stability [Irwin et al., 2022]. The results were found to be consistent with a temporal slowing of a stratospheric meridional circulation exhibiting downwelling at the poles.

Keywords: atmospheric retrieval
radiative transfer
polar hood
Uranus
atmosphere
atmospheric physics
Advisor: Irwin, P
Understanding the role of Toll signalling in Drosophila midgut stem cell proliferation.

The intestinal epithelium is a site of complex interaction between microbiome, epithelial cells, and the immune system through a multidirectional crosstalk achieved using signalling molecules and metabolites secreted by the microbiome and host cells. This cross talk maintains epithelial turnover and the gut microbial population while integrating nutrient absorption and host defence. In this context, innate immune pathways have been extensively studied to understand their role in the maintenance of microbial and epithelial homeostasis and to study the response against infections and stress. In mammals, Toll-Like Receptors (TLRs) have been widely researched for their role in maintaining the commensals and influencing the epithelial regeneration. However, the complexity of mammalian systems and inability to standardize the models makes it challenging to study interactions of TLRs with different pathways in the gut. The immune and developmental pathways involved in epithelial plasticity are evolutionarily conserved. Therefore, using Drosophila melanogaster as a model organism, we aim to understand the role of Toll signalling in regulating epithelial turnover during infection. To this end, we used a constitutively active form of Toll receptor to mimic Toll activation. Our results reveal that, the canonical Toll pathway was involved in the intestinal stem cell (ISC) proliferation. It also led to the enteroblasts getting blocked from differentiating and/or (mis)differentiating that caused accumulation of esg+ cells in the gut resulting in dysplasia. We found that the Jun N-terminal kinase (JNK) pathway was acting downstream of Toll in mediating Toll-induced dysplasia. Moreover, the developmental pathway Notch, had a potential antagonistic role upstream or in parallel to the Toll pathway. Taken together our results place Toll as the signalling element to integrate epithelial renewal and immune response.

Keywords: notch signalling
microbiome
toll signalling
gut immunology
dysplasia
immunofluorescence
intestinal stem cells
innate immunity
drosophila
JNK signalling
Advisor: Ligoxygakis, P
“Girls should be ready for anything”: time, learning and aspiration among hostel girls in Lahore  

This thesis explores the lives of a group of young, middle-class women living in a privately-run girls’ hostel in Lahore. The key question that this thesis seeks to address is the meaning of this stage in the lives of young women. A temporary period of accommodation in an urban hostel while studying is increasingly conceptualised as part of the life course for middle-class young women, bracketed by childhood in the natal household and married, virilocal adulthood. What does it mean to move to the city alone as a young Pakistani woman, and how do these women understand the experience of being a ‘hostellite’?
Based on nearly nine months of close-range participant observation, I tell the stories of some of the women who lived alongside me in the hostel. I describe how the journeys they make from rural areas to the city become conceptualised as journeys from asynchronous cultural ‘backwardness’ to a distinctively gendered and classed modernity, embodied in bodily techniques, cultural competencies and practices of consumption. Against global narratives celebrating the liberatory potential of education and work for supposedly constrained and oppressed Muslim women in the Global South, my thesis shows the pressure placed upon these subjects in the process of becoming groomed, as they experience hardship, humiliation and loneliness and learn to cultivate endurance (bardasht) and patience (sabr) as key attributes of hostellite life.
In this thesis I reflect critically upon the ethical and methodological decisions that have influenced my research practice, particularly in the context of the Covid-19 pandemic. I seek to show how these issues have influenced my research and writing, and how questions of absence, incompleteness and ethical refusal have shaped my thesis.

Keywords: girls
hope
hostel
migration
adolescence
aspiration
women
Pakistan
uncertainty
Imagining Germany abroad, c. 1920-1950. Women writers, photographers, exiles, Nazis

This thesis explores the lives of a small selection of individual German women who pursued professions as writers, journalists, or photojournalists, and whose work saw them spend significant periods of time abroad between 1920 and 1950. These women were unalike in important ways: they held diverging political beliefs, pursued different personal and professional goals, and travelled abroad in contradictory directions. At the same time, they shared a strong sense of independence and individuality, unanimously considered themselves to be modern women, and were each committed to their own imagined version of the German nation.
I argue that centring the individual and subjective experiences of these heterogeneous women highlights the extent to which they remoulded abstract cultural frameworks, especially gender and national identity, first and foremost to suit their own purposes. Those purposes varied widely, but in their shared insistence on individuality, independence, and social relevance, they revealed themselves to be part of a fluid and emerging cohort of emancipated women who were aware of being unconventional, but who nonetheless had a wide range of complex possible life paths to choose from. Their loyalty to imagined versions of German modernity was paramount to their otherwise malleable sense of nationhood because it created openings they might not have found otherwise and bestowed external meaning on their choices. They thus often looked towards the future more than they did the past. At the same time, that the lives these women chose to live were available to them was due to their privileged social background and liberal education more than to contemporary events.
The research project is important, because it probes the complex relationship between individuals and their wider cultural context without flattening out either personality or agency. Especially in the case of Nazi Germany, the question of how cultural context and individual subjectivities intersect is one that continues to excite scholarly interest.

Keywords: Nazi Germany
subjectivity
gender
Weimar Republic
Advisor: Stargardt, N
Generalisation and expressiveness for over-parameterised neural networks

Over-parameterised modern neural networks owe their success to two fundamental properties: expressive power and generalisation capability. The former refers to the model's ability to fit a large variety of data sets, while the latter enables the network to extrapolate patterns from training examples and apply them to previously unseen data. This thesis addresses a few challenges related to these two key properties.
The fact that over-parameterised networks can fit any data set is not always indicative of their practical expressiveness. This is the object of the first part of this thesis, where we delve into how the input information can get lost when propagating through a deep architecture, and we propose as an easily implementable possible solution the introduction of suitable scaling factors and residual connections.
The second part of this thesis focuses on generalisation. The reason why modern neural networks can generalise well to new data without overfitting, despite being over-parameterised, is an open question that is currently receiving considerable attention in the research community. We explore this subject from information-theoretic and PAC-Bayesian viewpoints, proposing novel learning algorithms and generalisation bounds.

Keywords: generalisation bounds
expressiveness
over-parameterised networks
A fluid-solid coupled heat transfer methodology as applied to rotating cavities

Conjugate heat transfer (CHT), which captures the thermal interaction between the fluid and solid domains, is important for an accurate computational aerothermal analysis when there are temperature dependent fluid domain physics. In the rotating cavities in compressor internal air systems, there is a need to understand the unsteady buoyancy-driven flow and heat transfer so that the disk radial expansion (and hence change in blade tip clearance) throughout the flight cycle can be predicted. Despite the inherently conjugate nature of rotating cavity flows, coupled analyses are rare due to the challenges of using CHT with unsteady methods.
In this thesis, it is shown that it is necessary to use wall-resolved large eddy simulation (LES) to accurately capture the fluid domain flow structures, and to use CHT to capture the interaction of the wall heating conditions and the cavity aerodynamics. The main challenge in LES-CHT is that the timescale in the solid is significantly larger than in the fluid. Many current state-of-the-art methods try to address this by accelerating the solid domain timescale to achieve a temporally converged solution, before switching to a non-accelerated solid solution that is assumed to be correct. However, this is not the case - it is demonstrated in a simplified conduction analysis that these current time domain CHT methods still introduce a long-lasting error in the solid domain temperature.
As a result, a new multiscale framework for LES-CHT has been developed, building on an existing closely coupled methodology. Non-local interactions from coherent low frequency temperature fluctuations are calculated with a time-spectral solid domain solution and turbulent higher frequency fluctuations are accounted for using a wall transfer function approach, reformulated to simplify its application. This is the only framework that can consistently deal with the fluid-solid timescale disparity and capture all timescales of wall temperature fluctuation.
The novel framework is used in first-of-their-kind LES-CHT computations on rotating cavities, evidencing framework efficacy and providing further evidence of the previously observed issues with other LES-CHT methods. An examination of the effect of CHT on the flow structures within the rotating cavity found that thermally induced near-disk vortical instabilities are seen to only form when there is strong local heating. This effect has not been previously observed and illustrates the value of the multiscale framework for deriving new insights into heat transfer in gas turbines.

Keywords: computational fluid dynamics
turbulence modelling
rotating cavities
conjugate heat transfer
large eddy simulation
Advisor: He, L