VictorJuiz/thesis huggingface dataset:
Translational profiling of motor neurons with C9orf72 mutations under acute oxidative stress

Keywords: amyotrophic lateral sclerosis
stem cell model
cellular stress
C9orf72
translating ribosome affinity purification (trap)
motor neuron disease
translatome

Amyotrophic lateral sclerosis (ALS) is the most common adult-onset motor neuron disease (MND) with a median survival of 30 months from disease onset and no cure available. Mutations in the gene C9orf72-SMCR8 complex subunit (C9orf72) are the most common cause of ALS in populations of European genetic heritage. Previous studies suggest that RNA processing, global translation and stress granule (SG) dynamics are dysregulated in C9orf72-ALS, which might alter the profile of translating mRNAs (translatome) in motor neurons. To test this hypothesis, I employed translating ribosome affinity purification (TRAP) to obtain the parallel transcriptome and translatome of human induced pluripotent stem cell-derived motor neurons (iPSC-MNs) from patients with C9orf72 mutations and healthy controls. I examined their expression profiles both at baseline and after transient oxidative stress. While minimal differences were present in the transcriptome and translatome at baseline and immediately after stress, 68 differentially expressed genes (DEGs) were identified in the translatome 2 h after stress removal. Functional over-representation analysis showed that they were enriched in synaptic transmission, small GTPase-mediated signalling transduction, and neuron projection. Two of the downregulated DEGs, unc-13 homolog A (UNC13A) and purine rich element binding protein A (PURA), have been previously associated with ALS. Further characterisation of the acute stress response in iPSC-MNs revealed that transient oxidative stress exacerbated or induced some key molecular phenotypes related to C9orf72-ALS. Additionally, the mutant iPSC-MNs exhibited a gradual and persistent decrease in the signal of a cell viability assay, in contrast to the control group. No differences were found between the two groups in global translational activity or SG dynamics. Preliminary investigation into the subcellular distribution of UNC13A and PURA transcripts suggested potential dysregulation in nucleocytoplasmic redistribution and sequestration by SGs in C9orf72-ALS iPSC-MNs, although further experimentation is needed to reach a definitive conclusion.
Everyday betrayal, relentless hope: political life in a Lebanese city 
Keywords: uprising
clientelism
political anthropology
Tripoli
Islamism
Lebanon

This work is an exploration of the limits of resistance within oppressive contexts. It is based on an ethnography of the Lebanese city of Tripoli, which is associated with Islamism, soaring poverty rates, and an extractive clientelist political system that has remained unchanged for decades. Tripolitans who are actively resisting oppression use repertoires of action that inadvertently entrench the oppressive status quo. The first is that Tripolitans cultivate intimacy and conviviality with the ruling class, which the latter then use to exploit the former in the name of friendliness and familiarity. The second is the hustler mentality of Tripolitans, which promotes a dream of quick, easy transformation, but in reality contributes to overwhelming exhaustion and further reliance on clientelist networks. The third is the constant possibility that Tripolitans will engage in violence against structures of oppression, which in the end is contained and resolved by these structures themselves.
The thesis explores Tripolitan aspirations and their aftereffects during three key political ruptures in Tripoli’s recent past: a sectarian civil conflict (2008-2014), a Salafi-jihadist wave of radicalisation (2013-2015), and a secular uprising (2019), during which Tripolitans took radical action to change their political conditions but were unable to realise a political transformation. I view this outcome as nourishment of an ever-present, well recognised, and domesticated state of deadlock that, at the same time, Tripolitans continue to vehemently oppose. In discussion with literature on hope and resistance, I argue that resistance and complicity with oppressive political states are not contradictory processes, but are rather nestled closely together. This situation creates an anxious sense of stagnation where subjects constantly navigate the tension between hope and acquiescence. The thesis focuses on what is lost and gained by living in such anxious and unforgiving state of being.
Powerline communication and demand side management for microgrids
Keywords: demand-side management
microgrid
smart grid
powerline communications

Motivation: The greatest challenge for microgrid deployment is making energy affordable, especially in remote low-income communities. This thesis answers the following research question:

Can digital communication reduce the price of electricity for an islanded low voltage microgrid and if so, can broadband powerline communications meet microgrid control requirements?

Approach: This study conducts a cost-benefit analysis of the addition of a field area network to a microgrid. Broadband powerline communication is selected as a candidate technology and tested on various microgrid networks to determine its suitability.
Results: The main contributions of this study are:

A demand-side management strategy and unsubsidised cost reflective tariff structure for rural microgrids in the developing world.

A cost-benefit analysis that shows the addition of a low bit rate, medium latency communication system (1 kbps per customer, 100 ms) may reduce the levelized cost of energy by 32%.

A performance evaluation of broadband HomePlug powerline communications for microgrids which shows the Homeplug AV2 has a range of 600 m and functions well on complex radial distribution networks.

Conclusion: Investment in a minimally capable communication system has significant economic benefit to both customer and utility by enabling smart grid services such as automatic meter reading and demand side management. Since communication technologies share similar bit rate and latency capabilities and are similarly priced, the technology choice is driven more by microgrid geography, complexity, availability and reliability. Powerline communications require no additional cable, but boast reliability similar to dedicated cable solutions. The HomePlug AV meets bit rate and latency requirements, is affordable, reliable, simple and widely available around the world. This study concludes it is a solid candidate for low voltage islanded microgrids.

The material presented in this thesis has been published or submitted for publication in an abbreviated format in the following publications:
D. Neal et al, "Demand side energy management and customer behavioral response in a rural islanded microgrid," in IEEE PES/IAS PowerAfrica, 2020.
D. Neal, D. Rogers and M. McCulloch, "A Techno-Economic Analysis of Communication in Islanded Microgrids," unpublished. Submitted Oct 2023 to Elsevier Renewable and Sustainable Energy Reviews.
D. Neal, D. Rogers and M. McCulloch, "Broadband Powerline Communication for Low-Voltage Microgrids," unpublished. Submitted Oct 2023 to IEEE Transactions on Power Delivery.
Proud humility: paradoxes of self-representation in Huguenot memoir
Keywords: Louis XIV
early modern
life-writing
Huguenots

This thesis makes a contribution to early modern trauma theory and life-writing studies. I use memoirs written by French Protestants after the 1685 Revocation of the Edict of Nantes to explore the emotional impact of migration in the late seventeenth and early eighteenth centuries. In the past, some Huguenot historians have taken such ‘ego-documents’ as entirely veridical and factual accounts, whereas I engage with the metaphors and intertextual references employed by the writers. The present work can thus be situated within the growing field of Huguenot memoir scholarship. The central argument of this thesis is that memoir-writing offered refugees a space in which they could explore challenging moments in their pasts. In order to address the variety of post-Revocation experiences encountered by early modern Huguenots, each chapter of this thesis deals with a distinct ‘case study’ of sorts. I first look at writing by women who were imprisoned following initial unsuccessful attempts to escape France. I then focus on how galley slavery was depicted by Protestants who had close contact with its horrors. Finally, I explore memoirs whose contents concentrate on the difficulties of adapting to new cultures. Each of the authors whose works are examined in this thesis had their own personal concerns, but across the range of writings, some common strategies emerge for dealing with common issues. I engage with archival material and contemporary publications from the Grand Siècle to develop as full as possible an understanding of the authors’ worldviews, arguing that religious doctrine could be a source of both solace and stress. Throughout, I highlight what life-writing can reveal about inner, emotional worlds. I thus establish narrative as an important tool for Huguenots dealing with trauma in the early modern period.
A diagrammatic approach to networks of spans and relations
Keywords: classical mechanics
quantum mechanics
quantum computing
string diagrams
diagrammatic methods
Lagrangian relations
symplectic geometry
category theory

In this thesis we exhibit nondeterministic semantics for various classes of circuits. Motivated initially by quantum circuits, we also give nondeterministic semantics for circuits for classical mechanical systems and Boolean algebra. More formally, we interpret these classes of circuits in terms of categories of spans or relations: in less categorical terms these are equivalent to matrices over the natural numbers or the Boolean semiring. In the relational picture, we characterize circuits in terms of which inputs and outputs are jointly possible; and in the spans picture, how often inputs and outputs are jointly possible. Specifically, we first show that the class of circuits generated by the Toffoli gate as well the states |0⟩, |1⟩, √2|+⟩ and their adjoints is characterized in terms of spans of finite sets. We also give a complete axiomatization for these circuits. With this semantics in mind, we discuss the connection to partial and reversible computation. Shifting to the phase-space picture we also characterize circuits in terms of how they relate abstract positions and momenta. We show how this gives a unifying relational semantics for certain classes circuits for classical mechanical systems, as well as for stabilizer quantum circuits
Formation and collapse of non-wetting cavities in soft porous media
Keywords: capillarity
phase separation
soft porous media
phase-field method

Various biological and chemical processes lead to the nucleation and growth of non-wetting fluid bubbles within the pore space of a soft porous medium, such as the formation of gas bubbles in liquid-saturated sea-bed sediments, or biomolecular condensates in the cellular matrix. The non-wetting nature of these bubbles makes it energetically costly for them to invade the narrow pore throats between solid. If the solid skeleton is sufficiently soft and/or the confining stress is sufficiently low, non-wetting bubbles can instead displace solid to form macroscopic (open) cavities. An increase in the confining stress can suppress the formation of cavities and even trigger the collapse of existing cavities, forcing the non-wetting fluid into the pore space. A quantitative understanding of the total volume of non-wetting cavities, their size distribution, and their formation and collapse are important for the macroscopic mechanics of this three-phase system, and its interactions with the surrounding environment. Here, we consider this process through the lens of phase separation, where thermomechanics govern the separation of the non-wetting phase from a fluid--fluid--solid mixture. We construct a novel phase-field model informed by large-deformation poromechanics, in which two immiscible fluids interact with a poroelastic solid skeleton. Our model captures the competing effects of elasticity and fluid--fluid--solid interactions (capillarity). We complement our theory with a series of simple experiments, using a packing of hydrogel beads as an example soft porous medium. As model problems, we consider the spontaneous formation of multiple cavities from an initial distribution of non-wetting fluid in the pore space, and the deformation-driven collapse of cavities due to the application of a fluid-permeable piston. We study our model in a 1D setting, via numerical simulation, linear stability analysis, and analytical solution of a reduced model. We identify the key parameters that control cavity formation, and the characteristic size of resulting cavities. We also investigate the confining stress required to trigger cavity collapse, and explore the reversibility of cavity formation and collapse under fluctuating confining stress. We complement our theory with a series of simple experiments, using a packing of hydrogel beads as an example soft porous medium.
Towards a methodology for prospective governance in quantum computing technologies
Keywords: responsible innovation
quantum computing
assessment framework
qualitative research

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.
Building on Bildung in the 20th century – individual and institutional learning in Wittgenstein and Hesse
Keywords: institutions
German literature
pedagogy
education
philosophy
Bildung

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?
Phenotyping C9-ALS/FTD iPSC-derived cortical neurons
Keywords: C9-ALS/FTD
amyotrophic lateral sclerosis
neurodegeneration
FTD
iPSC-derived cortical neurons
C9orf72
frontotemporal dementia
ALS

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.
Apoptosis-induced loss of CD43 from T cells promotes efferocytosis

Keywords: macrophage
efferocytosis
apoptosis
ADAM10
T cell
CD43
Mucin

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.
Spatial and temporal variability in the Uranian atmosphere
Keywords: atmospheric retrieval
radiative transfer
polar hood
Uranus
atmosphere
atmospheric physics

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.