VictorJuiz/thesis huggingface dataset:
Molecular machinery and cell biology of sleep control

Sleep is vital and universal, yet its essential biological functions remain elusive.
The sleep homeostat tracks an internal process that generates sleep pressure during waking, which is then periodically discharged by initiating sleep. Understanding the molecular nature of sleep pressure and its regulation by the homeostat will help to elucidate the physiological variables linked to the essential function of sleep.
In Drosophila, rising sleep pressure increases the activity of sleep-control neurons projecting to the dorsal fan-shaped body (dFB). Sleep need is encoded in the intrinsic excitability of these neurons, which fluctuates because two potassium conductances, voltage-gated Shaker and the leak channel Sandman, are modulated antagonistically. Signalling cascades transducing sleep pressure into sleep must thus converge on the regulation of currents flowing through these two ion channels.
To obtain a comprehensive view of the molecular machinery operating within dFB neurons, I have characterised transcriptomes of single cells isolated from dissociated brains of rested and sleep-deprived flies. These studies revealed a mechanism of bidirectional control of mitochondrial dynamics and sleep in dFB neurons. Sleep loss selectively upregulates genes encoding mitochondrial proteins and alters mitochondrial dynamics in these neurons. Conversely, manipulating mitochondrial fission and fusion in dFB neurons affects sleep in opposing ways. Since mitochondrial dynamics reflect and influence ATP synthesis and ROS production, they suggest a causal link to cellular oxidative stress, which is recorded by Shaker's redox-sensitive β-subunit and converted to heightened neuronal excitability driving sleep.
At the synaptic level, sleep deprivation decreases the strength of dFB neuron output synapses, which release the (in the Drosophila CNS inhibitory) transmitter glutamate. The neurons are heterogeneous in the expression of an octopamine receptor, whose cognate monoamine calibrates sleep.
These studies, based on the first single-cell transcriptome of an animal’s sleep-control neurons in different conditions of sleep pressure, advance our understanding of how sleep-control is implemented in the brain.

Keywords: glutamate
dFB neurons
neuroscience
mitochondria
sleep control
sleep
drosophila
fruit fly
single-cell RNA-sequencing
transcriptomics
plasticity
mitochondrial dynamics
octopamine
Advisor: Miesenboeck, G
Development and characterisation of a novel vaccine for Bordetella pertussis (whooping cough)

Bordetella pertussis is the causative agent of pertussis (whooping cough) which is a respiratory infection, particularly dangerous for babies and young infants. Protection against pertussis relies on the induction of potent T-cell and antibody responses. Current acellular pertussis (aP) vaccines induce strong antibody responses and T-cell helper type 2 (Th2) response but are less effective at producing Th1-type immunity necessary for complete and fast bacterial clearance. Although, aP vaccines protect against severe disease, the vaccine-induced protection wanes over time, and despite high aP vaccination coverage in many developed countries, pertussis is a re-emerging disease.
In this thesis, I explored the use of replication-deficient adenovirus (Ad) and modified vaccinia virus Ankara (MVA) vectors as platforms for development of novel pertussis vaccines. Pertussis toxin (PT), fimbriae adhesins (Fim2, Fim3 and FimD), iron-binding proteins (IRP1-3 and AfuA) and adenylate cyclase toxin (ACT) were selected as vaccine candidate antigens. Our aim was to enhance Th1-type responses against B. pertussis and induce strong antigen-specific and neutralising antibodies that prevent lung (and nasal) colonisation of B. pertussis. I therefore evaluated the vaccines’ different immunisation regimens and their potential to mediate such immune responses in mice.
A single intramuscular immunisation with a number of the Ad vaccines induced partial protection in mice. These constructs encoded the full length of the catalytic S1-235 subunit of PT, Fim3, AC and RTX domains of ACT. In particular, the Ad RTX vaccine may have the potential to prevent pertussis infection as 60% of mice immunised with one dose of the vaccine were fully protected against lung infection. In addition, the Ad S1-235 vaccine generated a PT-specific Th1-type response. The results indicate the potential of viral vectored vaccines to prevent pertussis infection either on their own or as future studies may reveal, using them in combination with different types of pertussis vaccines.

Keywords: vaccine development
novel vaccine for pertussis
whooping cough
respiratory infection
vaccine
pertussis
viral vectored vaccines
Advisor: Rollier Weissenburger, C
Markey, K
Dold, C
Bolgiano, B
Counter-Contagion: The emergence, dissemination and continuing effects of a new apparatus of disease response, 1791- 1958

The question of how medical experts and the state respond to rapidly spreading infectious diseases has obvious relevance amidst the current Covid-19 pandemic. The question of when and where these responses actually emerged, however, is far less apparent and far more opaque. This project studies the actions, writings and careers of British experts as they respond to three historic diseases – cholera, plague and tuberculosis – that all posed profound threats to Britain and its colonial empire. Beginning at the end of the 18th century, this postcolonial historical geography of medicine attends to what Chris Philo calls the ‘stuff’ of medicine, with particular focus on the relation between theories of contagion and practices of disease control. I trace the emergence of these acts and ideas through intra-imperial networks, which I argue held colony and metropole together in a state of mutual interpolation and co-constitution. Through this tracing, I uncover a particular arrangement or dispositif of theories, practices, individuals and institutions that were brought together by a single, striking argument: that the spread of disease is a consequence of the disorder innate to racialised populations and their inherent propensity to breach social and spatial boundaries. This argument justifies an expert, interventionist response that seeks to control the spread of disease through the coercive implementation of lines, borders and boundaries to contain disorder. I name this expansive dispositif ‘counter-contagion’.
This project begins by analysing four key components that constituted counter-contagion: Benthamite interventionism, counter-insurgency, racial science and germ theory. While these individual components all arose in the 19th century, it took until the 1890s for all four components to finally come together. During the Third Plague Pandemic in Hong Kong and Bombay (Mumbai), these components were combined into an expert-led, interventionist response that fused the medical with the martial. This new response, and the experts who enacted it, became part of a broader dispositif of counter-contagion that gained institutional weight through the progressive wing of tropical medicine. This institutionalisation effectively embedded the logics of counter-contagion in progressive medicine in twentieth century Britain, with decisive and understudied effects on the medical profession, the political sphere and broader civil society.

Keywords: Historical geography
Contagion
NHS
Public health
Counter-insurgency
Infectious diseases
Advisor: Vasudevan, A
An evolving synthetic biological platform for alkane production

Fossil fuels are finite and polluting, but underpin almost every system and product we use in the modern world. Anthropogenic greenhouse gas emissions from fossil fuel combustion are the major driver of climate change, yet demand for these fuels continues to grow. Alleviating global reliance on fossil carbon, especially in the transport sector, demands a drop-in compatible substitute with comparable energy density and fuel chemistry to diesel, jet fuel, or gasoline. If derived from atmospheric carbon, such a fuel could be central to future low-carbon circular economies. Liquid biofuels, produced via industrial microbial fermentation, have similar characteristics to their petroleum counterparts with a much smaller carbon footprint.
Microbial biosynthesis of advanced biofuels is currently uneconomical, but has been improved by rational engineering efforts. The physiological complexity inherent in living systems often limits such approaches, but can be sidestepped by harnessing natural evolutionary processes to optimise cellular metabolism for production of valuable molecules.
This work presents a novel biosensor-based directed evolution system for improving biosynthesis of alkanes – straight chain hydrocarbons useful as biofuel – in the bacterium Acinetobacter baylyi ADP1: the “artificial evolution”, or Artevo, system.
By placing a growth-essential gene under control of genetic regulators sensitive to alkanes, the Artevo system links alkane productivity of the host cell to fitness. High producing cells grow faster and outcompete their neighbours, resulting in generational enrichment of high-performing alkane biosynthesis genes within a growing population.
The Artevo system can interrogate a small pool of diverse alkane biosynthesis genes and distinguish between them based on relative productivity, conferring a growth advantage to host cells with the highest alkane yields. This system consolidates screening, selection, and amplification of useful biosynthetic genes from potentially large libraries into a single platform, and could form the basis for future continuous directed evolution strategies as it is built in a naturally transformable and recombinant microbe.

Keywords: directed evolution
genetic engineering
molecular biology
biotechnology
energy
alkanes
synthetic biology
bioengineering
renewables
chemical engineering
biofuel
Advisor: Huang, W
Thompson, I
Information gathering and motivated decision making in health and disease

Almost every aspect of our lives involves making decisions. From deciding to get out of bed in the morning to saying "I do" at a long-awaited wedding. Humans, like animals, often try to optimise their decisions to maximise reward and avoid losses. Understanding the mechanisms and neural correlates of such behaviours can provide crucial insights into human cognitive and psychological functioning in health and disease. In this thesis, two common forms of motivated decision making are examined: i) decision making under uncertainty and information gathering, and ii) effort-based decision making (EBDM). Through behavioural experimentation, computational modelling, and neuroimaging analysis, I reveal novel mechanisms and brain networks involved in these forms of behaviour and investigate their clinical implication on affect and motivation. In addition to healthy humans, different groups of patients were investigated, including autoimmune limbic encephalitis (ALE), subjective cognitive impairment (SCI), and Alzheimer’s disease (AD). The results across these study groups converged to characterise two potentially dissociable psycho-cognitive-brain axes. The first draws a link between uncertainty processing, affect, and the hippocampus. The second highlights the relationship between apathy (reduced motivation), deficits in EBDM, and key functional brain networks such as default mode and fronto-parietal networks. The findings in this thesis thus highlight an experimental and mechanistic framework for investigating information gathering and EBDM, and provide insights into their clinical implications and associated brain networks.

Keywords: brain networks
hippocampus
effort-based decision making
depression
Alzheimer's disease
decision making
apathy
anxiety
uncertainty
information gathering
subjective cognitive impairment
limbic encephalitis
Advisor: Husain, M
Manohar, S
Molecular imaging of DNA damage repair

Nuclear imaging has the ability to non-invasively probe target expression, drug pharmacokinetics, and monitor treatment response. With many cancer therapies inducing DNA damage to overwhelm tumour cells into arrest, there has been a push to investigate the DNA damage response with regards to understanding the key proteins involved and the development of DDR inhibitors to enhance current DNA damaging therapies. The use of DDR inhibitor radiotracers with PET or SPECT could allow scientists to quickly collect information on tumour phenotype, DDRi drug interactions and pharmacokinetics, calculate levels of DNA damage as a result of previous therapies, and could ultimately improve patient stratification. With some key targets of the DDR such as γH2AX and PARP, already under investigation for nuclear imaging, this thesis aimed to investigate ATM as a potential new target for DDR nuclear imaging, as well as expanding the selection of PARPi radiotracers to allow imaging of tumours in the brain. This body of work highlights the key challenges faced in the chemistry and radiochemistry of developing new radiotracers and demonstrates the limitations of ATM as an imaging target. It is the hope that this research will pave the way for further development of ATMi radiotracers to verify whether ATM is a suitable molecular imaging target and to promote the development of BBB-penetrable PARPi tracers.

Keywords: molecular imaging
cancer
PARP
DNA damage response
radiofluorination
ATM
PET
Advisor: Cornelissen, B
Ryan, A
Blackford, A
Smith, G
Optimal investment, valuation and hedging under model ambiguity

In this thesis, we study several utility maximisation problems under model uncertainty, involving optimal investment, valuation and hedging.
We first derived martingale distortion representations for classical utility maximisation problems in a non-Markovian stochastic factor model, with power, logarithmic and exponential utilities.
We then study multiple priors power utility maximisation problems when the reference model is a non-Markovian stochastic factor model, and derive a BSDE representation of the value process, optimal strategy and least favourable model.
We also study a variational preferences logarithmic utility maximisation problem when the reference model is a non-Markovian stochastic factor model, and when the plausible models are penalised by an additive entropic penalty function. The robust problem is transferred to a classical utility maximisation problem with a power utility whose risk aversion is dependent on the model ambiguity aversion parameter. We then fully solve the robust problem and perform numerical tests comparing several classical and robust strategies for a Stein-Stein stochastic volatility model and for a Heston model.
Finally, we study robust exponential valuation and hedging problems in a basis risk model, using both the multiple priors approach and the variational preferences approach with a multiplicative penalty function. Specialising to a constant parameter basis risk model, the robust problems admit explicit or approximate solutions, thus we are able to conduct large-scale simulation based tests on performances of various pricing and hedging strategies.

Keywords: model ambiguity
basis risk
stochastic volatility
Advisor: Monoyios, M
Searching for axionlike particles with gamma-ray observations of blazars

Many theories beyond the Standard Model of particle physics predict the existence of axionlike particles (ALPs) that mix with photons in the presence of a magnetic field. Searching for the effects of ALP-photon mixing in astrophysical gamma-ray observations of blazars—jetted active galactic nuclei with their jets pointed towards us—has provided some of the strongest constraints on ALP parameter space so far. The focus of this thesis is a type of search where the magnetic field of the blazar jet itself, as opposed to the various other mixing environments usually used, is the dominant region for ALP-photon mixing. I show that mixing in jets can be important for an un-probed region of ALP parameter space at high masses (close to the ALP dark matter space), making them promising mixing environments for an actual search. In order to perform such a search, however, the modelling of the jet field structure, and the effects of photon-photon dispersion within the jet, must be understood. I develop a framework to investigate and address these challenges. This framework is then used to perform an ALP search. In previous searches, only individual sources have been analysed. I perform a search with a combined analysis of Fermi Large Area Telescope data of three bright, flaring flat-spectrum radio quasars. For the first time, I include a full treatment of photon-photon dispersion within the jet, and account for the uncertainty in the B-field model by leaving the field strength free in the fitting. Overall, I find no evidence for ALPs, but am able to exclude ALP masses, m ≲ 200 neV, and ALP-photon couplings, g ≳ 5 × 10^−12 GeV^−1, with 95% confidence. This is an improvement on previous gamma-ray constraints in this mass range. Finally, I develop a proof-of-concept for an ALP search based on population-level observations of blazars, as opposed to individual source spectra. From simulated number counts with and without ALPs, I show that this method could potentially allow couplings down to g ∼ 1 × 10^−12 GeV^−1 to be probed for masses m ∼ 10 neV.

Keywords: Beyond the Standard Model
Axionlike particles
Axions
Blazars
Gamma rays
Advisor: Cotter, G
Meyer, M
Aspect and event structure: the morphosyntax of Polish verbs from a cross-linguistic perspective

This thesis presents a detailed analysis of Polish verb stems from a cross- linguistic perspective, couched in the framework of Distributed Morphology (Halle and Marantz 1993 et seq.). Polish verbs are decomposed into a number of functional projections responsible for aspect (perfective vs. imperfective) and event structure (simple event vs. complex change of state). The first part of the thesis focuses on the morphosyntax of event structure. Polish is classified as a weak satellite-framed language in a tripartite version of Talmy’s typology (Acedo-Matellán, 2016). Just like Latin and Classical Greek, Polish has resultative prefixes, but no complex AP or PP resultatives. The properties of weak satellite-framed languages are captured by an M-Merger Parameter, which requires a non-branching resultative X/XP to incorporate into the verb at PF (Matushansky, 2006). The second part of the thesis turns to the morphosyntax of aspect, investigating the relationship between verbal affixes and the value of aspect in Polish and other Slavic languages. I discuss and dismiss proposals based on syntactic agreement (Biskup, 2019, 2022) and a semantic mapping from event structure to aspect (Klein, 1995; Ramchand, 2008a; Tatevosov, 2018, 2022). Instead, I develop a novel movement-based analysis, whereby vP-internal prefixes raise to AspP to license perfectivity. Special attention is paid to the function of secondary imperfective morphology, such s the suffix -yw. I argue that there is no such thing as a ‘secondary imperfective operator’ at the level of syntax/semantics, and that the secondary imperfective is a dissociated morpheme in the sense of Embick (1997), inserted only at PF. The emerging picture is consistent with a grammatical architecture in which morphology interprets the output of narrow syntax, but is not fully isomorphic with it. Morphological operations may filter out well-formed syntactic representations or insert morphemes that are absent from narrow syntax and LF.

Keywords: event structure
aspect
linguistics
syntax
Polish
Distributed Morphology
morphology
Russian
Slavic
The limit experience in modern French poetry and thought

The limit experience (l’expérience-limite or, in Georges Bataille’s formulation, l’expérience intérieure) is the experience of reaching a firm limit and yet transgressing it. It is thus co-implicated from the outset with an experience of limitlessness. Twentieth-century thinkers in pursuit of the limit experience, such as Maurice Blanchot, have tended to locate something of it in poetry. While critics have identified numerous limit crossings or aporias in literature more broadly, a dedicated structural analysis of poetry’s own liminality has not been proposed. This thesis therefore expands the thinking of the limit experience beyond its presumed borders, bringing it into connection with close readings of poems to develop an understanding of on what grounds, if any, poetry is a privileged site for the limit experience. Using notions of experience, experiment, exemplarity, induction, and accumulation to frame its approach to the research question, this thesis offers a theoretical contribution to the study of modern French poetry, deconstruction, post-structuralism, liminality, and post-Heideggerian poetics. It clearly elucidates the figure of the limit and that of experience, drawing significantly on the thought of Jacques Derrida. It advances that the limit experiences identified by critics in the literary realm are interconnected, and that they form a differential matrix. Then, through the analysis of a corpus of poems by twentieth-century writers Jacques Dupin and Louis-René des Forêts—and incorporating an awareness of poetry’s fine details, its internal patterns and forms, including doubling, metaphor, rhyme, enjambment, parallelism, hyperbaton, typography, metonymy, and chiasmus—this study suggests that the experience of poetry takes the form of a compressed, vibrating network of mobile limit experiences. The thesis’s primary claim is that poetry’s exemplary status within the thinking of the limit experience may derive from its experimental, multiplicitous, and differential structure. In this way, the thesis provides a literary-theoretical explanation for why poetry in particular has become a privileged site for the limit experience.
Using machine learning for dynamic resource orchestration & task scheduling, in a radio access network based edge environment

The evolution in mobile wireless communication generations, continues to gift the world with new telecommunication capabilities towards how people live and work. For instance, the roll out of the fifth generation (5G) promises a much-enhanced cloud-native application service, through improved communication speed, higher bandwidth, improved capacity for more connected devices and many more. These exciting new 5G features have given numerous vertical and horizontal industries a reason to explore different ways of delivering value, through emerging cloud-native applications that run on access devices (i.e. the Internet of Things (IoTs) and mobile devices). These cloud-native applications such Virtual Reality, Vehicle to everything communication (V2X), artificial intelligence, video analytics and so on however have strict performance requirements for extremely low latency (10 milliseconds and below) and higher bandwidth, that 5G alone cannot deliver. Unfortunately, the traditional cloud computing and radio access network setups do not sufficiently address these key communication needs which are crucial to the performance of these cloud-native applications. There is therefore an urgency to enhance and optimize the traditional mobile telecommunication network architecture, to meet these performance needs. This thesis seeks to demonstrate how we have developed a facility called Multi-Access Edge Computing with Cloud Radio Access Networks (MECRAN) to address this issue. MECRAN is based on the edge computing paradigm and uses machine learning to optimize the round-trip delivery of data at low latency, by dynamically scheduling cloud-native applications, to run in close proximity to a mobile user, at the edge of the radio access network.

Keywords: ceph
artificial intelligence
containers
task scheduling
mobile edge computing
cloud computing
energy reduction
federated cloud
mMTC
URLLC
5G
machine learning
cloud-based/ Centralized Radio Access Network (C-RAN)
multi-access edge computing
eMBB
MEC orchestration
Advisor: Wallom, D