VictorJuiz/thesis huggingface dataset:
Clinical and neuroimaging markers of prodromal neurodegeneration in rapid eye movement sleep behaviour disorder

Patients with rapid eye movement sleep behaviour disorder (RBD) have a high long-term risk of developing Parkinson’s disease or a related synucleinopathy. Their individual trajectories are enormously varied, however, causing considerable prognostic uncertainty. This thesis examined aspects of the clinical and neuroimaging phenotype of RBD patients which might shed light on the underlying neurodegenerative process and thereby contribute to future risk stratification.
We found that across a range of clinical prodromal features, RBD patients were at least as impaired as those with established Parkinson’s and that neuropsychiatric disorders were particularly prominent in RBD patients. Genetic, environmental and demographic factors differed between PD and RBD groups. In a multi-centre longitudinal analysis, the outcomes of simple in-clinic tests were shown to substantially affect the risk of phenoconversion. Using ioflupane SPECT, we found that 43% of RBD patients already had evidence of dopaminergic deficit, and that this declines by an estimated 7% per year. Neuromelaninsensitive and susceptibility weighted MRI of the substantia nigra revealed signal changes in RBD patients consistent with early neurodegeneration. A combination of these novel MRI markers accurately distinguished PD patients from controls, suggesting an ability to capture the hallmark pathological process.
We found that apathy was common and under-recognised in RBD patients and dissociable from other neuropsychiatric features. SPECT neuroimaging data revealed that apathy was correlated with serotonin levels in the dorsal raphe nucleus, but not with dopaminergic availability. We used an eye-tracking paradigm to show that reward sensitivity is blunted in RBD patients, but that this relates to dopaminergic decline rather than clinical apathy. Overall, our data indicate that RBD patients have extensive evidence of underlying neurodegeneration, which manifests as a clinical phenotype with unique characteristics, suggesting that RBD may represent the prodromal phase of a particular synucleinopathy subtype. Multimodal assessment with in-clinic measures, neuroimaging and biometric data has the potential to facilitate risk stratification on an individual basis and will be important in selecting high-risk RBD patients for neuroprotective clinical trials.

Advisor: Hu, M
Mackay, C
Husain, M
A comparative analysis of nuclear cap binding complex proteins Cbc1, Cbc2 and putative cap binding protein Cbc3 in fission yeast

Cap-binding complex (CBC) proteins Cbc1 and Cbc2 bind to the 7-methylguanosine (7mG) cap modification present at the 5’ end of RNA polymerase II transcripts and have been linked to a variety of functions in RNA regulation. Despite the finding that Cbc1 and Cbc2 bind the 7mG cap synergistically, there are also reports suggesting that CBC proteins can also act independently. Furthermore, recently a new cap binder, named Cbc3, has been discovered, with its function in the context of CBC yet to be discovered. In this thesis, S. pombe Cbc1, Cbc2 and Cbc3 are compared with respect to their co-transcriptional recruitment, interacting proteins, and the subsequent effect of their depletion on the transcriptome. Cbc1 and Cbc2 depletions resulted in diverging differential expression profiles and changes in RNA processing. Differences could not be attributed to transcriptional changes. A genetic screen showed that these genes also have diverging interactions with RNA surveillance factors. Interestingly, Cbc1 depletion, and not Cbc2, was found to rescue readthrough transcription associated with a Dhp1 temperature- sensitive mutation. This thesis thus provides data supportive of Cbc1 having a Cbc2- independent, anti-cleavage role. On the other hand, S. pombe Cbc3 was found to facilitate the recruitment of elongation factor Paf1 to protein-coding (pc) genes that are longer than ~500 bases. Furthermore, Cbc3 deletion resulted in a mild hindrance of RNA export. Taken together, my findings point to inherent CBC-independent functions for Cbc1 and Cbc2. While Cbc3 is important for transcription elongation and nuclear export, it is unlikely that it forms the basis of an alternative CBC.

Keywords: Cbc1
RNA
Cap binding complex
Cbc3
transcription
Cbc2
Advisor: Vasilieva, L
Investigation of the tumour vascular response to single and fractionated irradiation

The effect of radiation therapy on tumour vasculature has been a subject of debate over the years. Increased oxygenation and perfusion have been documented during radiation treatments. Conversely, death of irradiated tumour endothelial cells by apoptosis, predicted to impair blood flow, has been proposed as a major determinant of tumour control. To approach these contradictions, we used video 2-photon microscopy to study the vascular response to irradiation in two different murine tumour models: MC38, a highly vascularized model with many non-perfused vessels and B16F10, a moderately vascularized model, both grown in transgenic mice with endothelium marked by the fluorescent protein tdTomato. These tumours received either a single dose of radiation (15 Gy) or a fractionated dose (5 × 3 Gy). Unexpectedly, even these high doses led to little structural change of the perfused vasculature. However, non-perfused vessels and blind ends were substantially impaired after radiation accompanied by apoptosis of their endothelium. These changes did not alter perfusion of the less vascularized B16F10 tumour, but led to increased perfusion in the more vascular MC38 tumour. After irradiation, the proliferation of endothelial cells was blocked resulting in diminished numbers of sprouts. Further, endothelial cells from control and irradiated tumours were subjected to RNA sequencing, which confirmed that irradiation upregulates the expression of genes in apoptotic pathways as well as cell cycle regulation. We now explain how apoptosis of tumour endothelial cells after radiation is not detrimental to function, because the apoptosis occurs primarily in the endothelium of non-functional small or blunt end non-perfused vessels leaving the functional vessels intact

Keywords: radiation
tumour blood vessels
Advisor: Muschel, RJ
Markelc, B
Love in twentieth-century French thought: Sartre and Lacan

This thesis investigates the possibility of love in twentieth-century French thought, focusing in particular on Jean-Paul Sartre’s early philosophy and Jacques Lacan’s psychoanalysis. I explore the philosophical status and metaphysical (im)possibility of love to advance my central argument that Sartre’s impossible notion of en soi pour soi developed in L’Être et le néant (1943) resurfaces in Lacan’s later psychoanalysis, notably in Encore (1975), as jouissance féminine. Sartre argues in L’Être et le néant that love is impossible, that in their attempts to love one another, subjects are helplessly trying to become en soi pour soi, which is an impossible wish to become God himself. For Sartre, the subject needs to choose between love and freedom, and this choice is a false one since the subject is unquestionably condemned to his/her freedom. We appeal to F.W.J. Schelling’s speculative onto-theology to suggest that Sartre’s highly original arguments for the contents of pour soi rest on unstable metaphysical foundations, thereby allowing us to reinvest love with possibility once again. This move situates our turn to Jacques Lacan’s psychoanalysis, which is equally steeped in onto-theology. First, we show that Lacan’s intellectual strategy was to highlight the necessary but impossible dualism found in Sartre’s concept of en soi pour soi. We investigate Lacan’s many formulations of this dualism: knowledge and truth, conscious and unconscious, and Symbolic and Real, to show that these pairs are all different names for a similar dualism Schelling identified at the heart of God, qualified by Sartre as impossible. Therefore, we show how Sartre’s en soi pour soi is a convincing shorthand for Lacan’s central object of study. Second, we present and explain aspects of Lacan’s philosophical project to show how, for Lacan, the subject is marked by various pathologies. For Lacan, as for Sartre and Schelling before him, the subject is ontologically sick, and, by its very structure, the Oedipus complex produces subjects that are prey to a mental collapse at any moment. As a result, for Lacan, the subject has no choice but to identify with their potential madness that is a constitutive aspect of their subjectivity. Finally, in a similar vein, this thesis argues that love in the Lacanian schema is the subject’s mad wish to reunite en soi with pour soi, which is an always impossible yet necessary aspect of subjectivity.

Keywords: en soi pour soi
Sartre
Lacan
Schelling
Advisor: Howells, C
Pierre Bonnard: beyond visual perception

This thesis presents a new understanding of modern art history through the French artist Pierre Bonnard (1867-1947). Refuting the prevailing realist understanding of his work, it shows how Bonnard developed original strategies for expanding depiction beyond a transcription of the world as it appears to vision – an aim that was central to artistic innovation in the early twentieth century.

Keywords: Perceptualism
Modern painting
Representation
Pierre Bonnard
Modern art history
Advisor: Grootenboer, H
Self in mind: a pluralist account of self-consciousness

This thesis investigates the relationship between consciousness and self-consciousness. I consider two broad claims about this relationship: a constitutive claim, according to which all conscious experiences constitutively involve self-consciousness; and a typicalist claim, according to which ordinary conscious experiences contingently involve self-consciousness. Both of these claims call for elucidation of the relevant notions of consciousness and self-consciousness.
In the first part of the thesis (‘The Myth of Constitutive Self-Consciousness’), I critically examine the constitutive claim. I start by offering an elucidatory account of consciousness, and outlining a number of foundational claims that plausibly follow from it. I subsequently distinguish between two concepts of self-consciousness: consciousness of one’s experience, and consciousness of oneself (as oneself). Each of these concepts yields a distinct variant of the constitutive claim. In turn, each resulting variant of the constitutive claim can be interpreted in two ways: on a ‘minimal’ or deflationary reading, they fall within the scope of foundational claims about consciousness, while on a ‘strong’ or inflationary reading, they point to determinate aspects of phenomenology that are not acknowledged by the foundational claims as being aspects of all conscious mental states. I argue that the deflationary readings of either variant of the constitutive claim are plausible and illuminating, but would ideally be formulated without using a term as polysemous as ‘self-consciousness’; by contrast, the inflationary readings of either variant are not adequately supported.
In the second part of the thesis (‘Self-Consciousness in the Real World’), I focus on the second concept of self-consciousness, or consciousness of oneself as oneself. Drawing upon empirical evidence, I defend a pluralist account of self-consciousness so construed, according to which there are several ways in which one can be conscious of oneself as oneself – through conscious thoughts, bodily experiences and perceptual experiences – that make distinct determinate contributions to one’s phenomenology. This pluralist account provides us with the resources to vindicate the typicalist claim according to which consciousness of oneself as oneself – a sense of self – is pervasive in ordinary conscious experiences, as a matter of contingent empirical fact. It also provides us with the resources to assess the possibility that a subject might be conscious without being conscious of herself as herself in any way.

Keywords: consciousness
virtual reality
spatial cognition
self-representation
cognitive phenomenology
bodily ownership
self-consciousness
somatoparaphrenia
drug-induced states
Advisor: Davies, M
Koralus, P
Zahavi, D
Enforcing trust in quantum networks

The phenomenal progress in quantum technologies over the past decades has laid the groundwork for the construction of quantum networks, which will channel the power of quantum theory to guarantee secure and efficient communication, computation, and much more. This thesis studies the notion of trust in quantum networks. In our information age, protecting the security or anonymity of data is a key requirement. We investigate certain protocols that are fundamental to the operation and applications of quantum networks, and propose ways to test and analyse their security, in spite of adversarial intervention. Our focus is on practical methods of verifying the untrusted components, which could be incorporated into realistic networks in the near future.
To begin, we propose a protocol for authenticated communication of quantum messages, by verifying the entanglement required for quantum teleportation in an experimentally feasible way. We model the performance of our scheme in the presence of noise. Furthermore, we explore such an authenticated teleportation in the one-sided device-independent scenario, where some devices used for verification may be corrupted. We derive error-tolerant self- testing bounds and extend our results to a realistic experimental setting, demonstrating the compatibility of our protocol with state-of-the-art technology. We then study anonymity, an essential feature for communication across networks. Combining the power of classical and quantum subroutines, we build a practical protocol for anonymous communication of quantum messages, without the need to trust the players in our network, their computational power, or the entanglement they share. We end by considering the verification of graph states distributed across a network of possibly dishonest players, applying our scheme to specific graph states that are central to quantum communication and computation schemes.

Keywords: Quantum networks
Quantum cryptography
Quantum verification
Advisor: Vedral, V
Non-invasive quantification of cerebral oxygenation in ischaemic stroke using MRI

Measurements of oxygen availability can be used to distinguish regions of the brain that are at risk of permanent damage during and after ischaemic stroke. This has the potential to inform management decisions, or monitor progress after treatment.
Differences in the oxygenation of blood (quantified as oxygen extraction fraction [OEF]) cause changes in the rate of reversible transverse relaxation, as measured using asymmetric spin echo (ASE) magnetic resonance imaging (MRI). This relationship is described by the quantitative blood oxygen level dependent (qBOLD) signal model. A streamlined version of the qBOLD model has recently been used to measure OEF in healthy subjects, and to detect changes in related parameters in ischaemic stroke.
In this thesis, a Bayesian framework for inferring on a multiple-compartment qBOLD model is developed, and applied to simulated and in vivo data to estimate OEF and other parameters. This model is then used to test potential improvements to the already established streamlined qBOLD framework. The possibility of acquiring data without a fluid-attenuated inversion recovery (FLAIR) sequence is investigated, and the complications that arise when cerebrospinal fluid contributes to the qBOLD signal are described. Then, modifications to the model that account for the effect of diffusion, and of differences in blood vessel distributions, are tested using Monte Carlo simulations, and validated in healthy subjects. These are tested alongside changes to other acquisition parameters that could lead to more efficient data collection.
Finally, the qBOLD model is used to infer OEF in ischaemic stroke patients. It is shown that oxygenation differs between pathological regions, which suggests that this method could be usefully applied to stroke assessment in the clinic.

Advisor: Chappell, M
Blockley, N
The genetics of cranial sensory ganglia development and evolution

Vertebrates perceive the world through sensory neurons of their cranial nerves that connect primary sensory receptors to the brain. The bodies of these neurons are organized in cranial sensory ganglia (CSG) in the head. CSG are considered a vertebrate novelty and they develop from neurogenic placodes and neural crest. The genetic network underlying their early development has been relatively well studied and placodal cell homologs have been suggested in other chordates. However, knowledge has been lacking on the evolution of different ganglia and their neurons. Undertaking a comparative approach, cyclostomes and tunicates are used here to look into the molecular identity and evolution of CSG sensory cells. First, conserved pan-vertebrate markers of the ganglia are identified by exploring the expression and specificity of candidate genes in lamprey embryos. Two of these marker gene families are the starting ground for a comparative investigation of sensory cell types between vertebrates and other chordates. Conserved expression and regulation of the estrogen related receptor (ERR) between lamprey and gnathostomes is presented. It is revealed that a single ERR homolog acquired a role in the development of the vestibuloacoustic ganglion in early vertebrates. Invertebrate sensory expression highlights ERR as an ancient sensory cell marker in bilaterian animals, suggesting a mode of evolution at cell type level. The Hmx homeobox gene family is then identified to ubiquitously mark all CSG and possess conserved genomic architecture across vertebrates. A unique enhancer pair is reported, derived by tandem duplication, connected to ancestral regulation of expression in the central and peripheral nervous systems. Hmx expression and function in Ciona embryos, combined with vertebrate data, provide evidence of homology between CSG and tunicate sensory neurons. Finally, a review is carried out, discussing how placodal and CSG components gradually evolved and assembled under new genomic organization and control in vertebrates.

Advisor: Shimeld, S
Queer in the prison?: what does it mean to be 'out' inside?

There is growing criminological interest in marginalised genders and sexualities, and a developing literature exploring the experiences of lesbian, gay, bisexual and transgender (LGBT) prisoners. However, these nascent and interconnected fields of study are notably underdeveloped in the UK. Little is known about gender and sexuality orders in British prisons, and the experiences of LGBT people therein.
This thesis seeks to address these gaps through presenting and analysing rich, qualitative data. It draws on formal interviews with 60 prisoners and staff across one men’s and one women’s establishment, the analysis of relevant documents at these prisons, written correspondence with 67 prisoners, and 7 interviews with related professionals. Methodologically, this thesis provides insights into gathering data and upholding research ethics when researching LGBT inmates, and offers a detailed exploration of LGBT researcher positionality – a topic almost absent from British criminology.
This thesis emphasises the need for British prisons scholars to abandon the idea that men’s establishments hold all, and exclusively, male prisoners, while female establishments hold all, and exclusively, female prisoners. Prisoners with minoritised genders are not always easily discernable, sometimes actively concealing their identities, and at other times hidden by cisnormative assumptions. Likewise, some sexual minorities are more visible than others. Examining how prisoners construct and communicate gender and sexuality, this thesis demonstrates that being in prison can lead to shifts in identity through encountering different labels and entering same-sex relationships for the first time. The nature of romantic and/or sexual relationships, and staff responses to them, are explored in depth. Furthermore, this thesis demonstrates how broader horizontal relationships between prisoners, and vertical relationships with staff, affect how prisoners understand and present their gender and sexuality. It documents staff and prisoners’ support and subjugation of people who identify as, or are presumed to be, LGBT, and the active responses of prisoners to discrimination. Concluding by presenting its limitations, the thesis suggests avenues for much-needed future research.

Keywords: Lesbian
Queer
Bisexual
Gay
Transgender
Prison
LGBT
Jail
Advisor: Condry, R
Leaky hardware: modeling and exploiting imperfections in embedded devices

Embedded systems are found in many safety- and security-critical applications, and bring aspects of the physical world to the digital one and vice versa. However, imperfections in this hardware bridge can break the integrity of sensor inputs into an embedded device, causing it to act upon the wrong data. For instance, malicious electromagnetic transmissions can trick systems into inducing defibrillation shocks and raising the temperature of infant incubators, both with potentially severe health consequences.
Unfortunately, such attacks which alter sensor outputs without changing the property being measured itself have so far only been studied in an ad-hoc manner. In my thesis, I address this shortcoming in two ways. First, I create a taxonomy of these “out-of-band” signal injection attacks and defenses. Second, I propose a framework that quantifies security in their context through a system model, mathematical definitions, and an algorithm that can compare the “security level” of off-the-shelf systems.
In my thesis, I also investigate Field-Programmable Gate Arrays (FPGAs), which are available on public cloud infrastructures, and are also integrated in many consumer end-products, such as smartphones and laptops. As FPGAs are often used in sensitive applications, including genome processing, cryptography, and financial modeling, it is necessary to ensure that they can maintain the secrecy of the data that they process.
However, the confidentiality of FPGA data can be broken, as I demonstrate through three new sources of information leakage due to hardware imperfections. The first source exists between “long wires” within seven families of Xilinx FPGAs. I explain how to exploit long-wire leakage for covert- and side-channel attacks, both locally, and on two commercial FPGA clouds through novel ring oscillators structures that bypass currently-deployed countermeasures.
The second source of leakage operates even when different FPGA users are isolated to distinct dies of the same chip. These unintended interactions demonstrate that current FPGA architectures are not well-suited for multi-tenancy, despite the physical isolation of user logic. Finally, I show that assigning dedicated FPGAs to different users is still not enough to prevent cross-FPGA communication: shared Power Supply Units (PSUs) leak information between physically distinct FPGA, CPU, and GPU boards, which can be detected via means of a novel receiver design and classification metric.
Overall, in my thesis, I highlight that the underlying electrical properties of embedded devices often fall short of protecting the integrity and the confidentiality of the data that they process, and allow remote attackers to spoof sensor measurements or infer cryptographic keys and other types of data.

Advisor: Rasmussen, KB