VictorJuiz/thesis huggingface dataset:
'Bringing back golden Bangladesh': decentered regulation and the political economy of water pollution

This thesis examines the relationships between state, market, and society in shaping the political economy of water pollution regulation in Bangladesh, as well as the consequences of these relationships for the distribution of regulatory power. In Bangladesh, where severe industrial water pollution is a feature of daily life for millions, actors navigate intersecting processes that have become institutionalized over the past five decades since independence. As a country striving toward middle-income status after an era of instability, Bangladesh navigates a surge in its ready-made garments’ industry; the rising influence of transnational private governance programs; civil society discontentment; and judicial authorization of public interest litigation. The thesis extends Julia Black’s decentered approach (2001) to analysis in a way that is underexplored in the political economy literature. This thesis uses a qualitative methodology drawing on 140 semi-structured interviews using NVivo to organize and code; review of legal and policy documents; and statistical analysis of water pollution penalties from the Department of Environment.
I argue that regulatory power relations are distributed, contested, and pursued by contending actors and institutions, which are often examined in silos in the prevailing literature. I argue for conceiving of non-compliance as normalized, resulting from the Department of Environment’s retreatist approach and compelling antiregulatory state-market linkages. I further develop the concept of enforcement styles by considering varying levels of formalism, coercion, autonomy, and capacity dimensions through fines for polluters, and show penalties to be a contested arena for resistance, negotiation, and discretion. Further, I extend a political-strategic framework by applying the concepts of autonomy, fragmentation, and the public-private distinction to a historical analysis of how Bangladesh’s national government, private sector, and transnational private regulatory interests’ interface. Taken together, this intertwined decentered regulation-political economy approach positions regulation as dynamic and embedded in social relations, contributing to new understandings of the mechanisms by which regulatory power is exerted.

Keywords: pollution
Bangladesh
political economy
compliance
regulation
The role of chromatin remodeller ATRX in gene expression

ATRX is a chromatin remodeller involved in a wide range of nuclear processes, including transcription. Germline mutations in ATRX give rise to alpha- thalassaemia/intellectual disability X-linked (ATR-X) syndrome and downregulate alpha globin expression through a mechanism which is poorly understood. To understand how ATRX regulates gene expression, here I use alpha thalassaemia as an exemplar to study how ATRX loss downregulates alpha globin expression, which would provide insights into understanding the general gene regulation mechanism of ATRX. Specifically, I aim to recapitulate the alpha thalassaemia phenotype observed in ATR-X syndrome patients in an ATRX deficient erythroid cell system, and then to determine the molecular mechanisms that cause perturbed alpha globin expression.
To this end, an ATRX deficient CD34+ haematopoietic stem cell model was generated via CRISPR-Cas9. However, the cells did not show distinct alpha thalassaemia phenotype at the bulk level when differentiated into erythrocytes. Further gene expression analysis in single erythroid colony and single erythroid cell RNA-seq revealed that ATRX deficiency led to alpha thalassaemia in only a subset of cells. Differential gene expression analysis indicated the downregulation of alpha-like globin was likely associated with replicative stress/DNA damage, in particular the activated pATM-RNF168-ubiquitination pathway.
To validate the mechanisms, an erythroid progenitor cell line containing a dTAG-13 inducible ATRX degron system was generated, in which the alpha-like globin gene was tagged with a fluorescent reporter for the enrichment of the affected cell subpopulation. This cell model recapitulated the alpha thalassaemia phenotype and was used to investigate the function and gene regulation mechanism of ATRX. It has been shown that ATRX mainly regulates alpha globin expression at the basophilic erythroblast stage, and ATRX loss-induced alpha globin downregulation is not associated with DNA methylation.
As a prime candidate for causing replicative stress/DNA damage in the absence of ATRX, a putative G4 DNA-forming region ψζ VNTR in the alpha globin cluster was studied to explore its contribution to the gene regulation. It is demonstrated that ATRX binds to this region in a gene expression dependent manner. G4 stabilizer treatment downregulated α-globin gene expression and deletion of this region in erythroid cells abolished the effect of ATRX depletion on alpha globin expression, indicating ATRX regulates alpha globin expression through binding to the G-rich ψζ VNTR.

Keywords: transcription regulation
ATRX
G4 structure
DNA damage
Advisor: Gibbons, R
Higgs, D
Stimulus-secretion coupling in L cells and factors affecting secretion of glucagon-like peptide 1

Glucagon-like peptide 1 (GLP-1) is a hormone released from gut endocrine L cells in response to the arrival of nutrients and plays an important role in regulating glucose homeostasis. However, factors and pathways modulating the stimulus-secretion coupling of GLP-1 are not fully understood. Our group previously reported a significant increase in GLP-1 plasma levels from an Abcc5 knockout (Abcc5-/-) mouse model, but the mechanism responsible for this effect remains unknown. Additionally, Abcc5-/- mice generated by other groups have reported an accumulation of various glutamate-conjugated compounds in the brain and other tissues, which could be responsible for driving the altered metabolic phenotype of the Abcc5-/- mice and also potentially affecting their behaviour.
In this study, we first characterised the neurobehavioural phenotype of mice lacking the Abcc5 gene. We showed that Abcc5-/- mice displayed a neurobehavioural phenotype consistent with disruption of glutamatergic signalling such as increased startle reactivity, loss of pre-pulse inhibition, and a decreased conditioned fear response. Further electrophysiological evidence implicates that glutamate-gated ion channels, NMDA receptors, might be responsible for the neurobehavioural phenotype of the Abcc5-/- mice. We showed that inhibition of NMDA receptors in an L cell model cell line, GLUTag cells, by various methods resulted in a significant increase in the release of GLP-1.
Since native L cells are exposed to different pH conditions alongside the digestive tract, the effect of extracellular pH on GLP-1 secretion was also investigated using GLUTag and primary L cells. Stimulated release of GLP-1 was found to be pH sensitive and an extracellular acidic pH inhibited GLP-1 release in a proton concentration-dependent manner. The mechanism of pH-regulated GLP-1 secretion was explored further to identify the point of proton entry into the cell and possible proton targets within the cell. Importantly, the pH-dependent release of GLP-1 in response to stimulation occurred irrespective of extracellular sodium levels, while chloride and calcium ions prove to be pivotal for GLP-1 secretion. Furthermore, while the production and processing of GLP-1 remained unaffected by an extracellular acidic pH, exocytosis of GLP-1 was inhibited and significantly more secretory granules containing active GLP-1 were shown to be retained intracellularly. Overall, results from this study showed that the activity of peripheral NMDA receptors expressed in L cells and the modulatory effect of extracellular pH plays an important role in the stimulus-secretion coupling of GLP-1 in response to nutrients. These findings provide new target possibilities to stimulate endogenous secretion of GLP-1, a much sought-after therapeutic strategy, for the treatment of obesity and diabetes.

Keywords: diabetes
exocytosis
Abcc5
GLP-1 secretion
Advisor: de Wet, H
Heather, L
Suing for grace: the early modern rhetoric of petition

Early modern petition was both a secular and spiritual mode. It was a distinct epistolary form, and a type of prayer. Both secular and spiritual petition share the same function: a request. This dual meaning did not escape early modern writers, who frequently exploited it for rhetorical effect. The thesis explores how early modern writers elaborated on petitionary metaphor, and to what ends; it considers the transfer between the formal characteristics of petition and literary forms which drew upon these conventions.
The thesis compromises four chapters. Chapter One provides an example of real petitionary rhetoric in action in two petitions written in 1567 by John Appleyard of Bracon Ash (1529 - c.1574) to the Privy Council. The following chapters explore how early modern writers both employed, and put pressure on, the petitionary strategies Appleyard exemplifies. Chapter Two examines how Edmund Spenser exploits the connection between political, martial, religious, and romantic petition in the Amoretti. Paying greater heed to the political connotations of petition, especially in relation to the Smerwick massacre of 1580, enables a greater understanding of the Amoretti’s colonial context. Chapter Three compares how Donne uses religious metaphor to negotiate hierarchy and petition for access in his verse-letters with his petitions to God in the Devotions Upon Emergent Occasions. In the Devotions, in his withdrawal from the world in his illness, he seems to expose and dismantle the patronage process; yet simultaneously the text itself is embroiled in patronage negotiations. Chapter Four studies the ‘mock petition’ for the first time. Tracing the circulation of the Jacobean verse-libel ‘The Commons Petition to St Eliza’ reveals an emerging tradition of mock-petitions running from the Spanish Match crisis to the Long Parliament. They highlight the prevalence and increasingly dramatic political significance of petitions during this period, and concomitantly how petitions directly inspired poetry.

Keywords: Smerwick massacre
prayer
patronage
John Donne
John Appleyard
verse-libel
hierachy
Long Parliament
Edmund Spenser
Devotions Upon Emergent Occasions
religion
Spanish Match
Privy Council
rhetoric
sonnets
miscellany
epistolary
letter
meditation
Parliament
access
metaphor
Ireland
'The Commons Petition to St Eliza'
politics
form
Jacobean
poetry
satire
verse-letter
Amoretti
manuscript
petition
Advisor: McCullough, P
Reflections upon black hole accretion discs: advanced x-ray modelling and novel timing methods

The regions close to black holes (BHs) have the most extreme gravitational fields; therefore we are able to probe Einstein’s theory of gravity by studying how matter accretes onto these objects. The best data we have of black hole accretion comes from X-ray binaries (XRBs) within the Milky Way, which shine brightly in X-rays. The accretion discs are very small and therefore are unresolved in observations, so we have to study the properties of the X-ray point source in great detail to understand the structure of, and processes within, the accretion system. A key observational feature we observe is the reflection of high energy X-ray photons incident onto the accretion disc, which imprint characteristic features onto the observed X-ray spectrum such as the Fe Kα line.Relativistic distortions to the energies and arrival times of the reflected photons enable the mapping of the accretion region.
In this thesis I employ advanced techniques to model the reflection spectrum in observations of two BH XRBs, GRS 1915+105 and H1743-322. First, I study quasi-periodic oscillations (QPOs) in the observed X-ray flux from these systems. There are many theories to the origin of these signals, and these theories make different predictions of how the energy spectrum of the source is modulated over the course of a QPO cycle. I use novel Fourier domain timing techniques in order to phase-resolve the energy spectrum of the source over a QPO cycle, to look for these telltale modulation. I constrain modulations in the illumination of the accretion disc by the high energy X-ray photons, adding growing body of evidence that the QPOs have a geometrical origin.
I also present pioneering work testing a model able to constrain the mass-distance ratio of a BH,using the spectral shape and observed flux of the reflected X-rays to constrain the size and ionization state of the accretion disc. I performed a proof-of-principle test using observations of H1743-322, which I combined with a prior distance measurement to constrain the mass of the BH in this system for the first time. This demonstration shows how X-ray spectroscopy can be used to make mass measurements of the many BHs within the Milky Way which are too obscured for current optical techniques.

Keywords: accretion
black hole
astrophysics
x-ray reflection
x-ray timing
x-ray binaries
Advisor: Ingram, A
Fender, R
Characterising the cellular and molecular basis of age-related clonal haematopoiesis

Throughout life, tissue stem cells accumulate somatic mutations. Occasionally, a mutation may occur that confers a selective advantage leading to growth of an expanded clone. When this occurs in haematopoietic stem cells (HSC), this is called clonal haematopoiesis. Clonal haematopoiesis is common in healthy older people, and is associated with increased risk of haematological malignancy and other adverse outcomes. Surprisingly, most cases of clonal haematopoiesis are associated with mutations in just two genes, DNMT3A and TET2, which regulate DNA methylation. Mutations in these genes are often the first genetic event in myeloid and lymphoid malignancies and may be acquired many years before the onset of disease. The mechanisms by which mutations in DNMT3A and TET2 cause clonal expansion are poorly understood and no studies have analysed their consequences in humans with unperturbed clonal haematopoiesis.
This study characterises the cellular and molecular consequences of somatic DNMT3A and TET2 mutations in humans with clonal haematopoiesis. Blood and bone marrow samples were collected from a cohort of 195 individuals undergoing total hip replacement surgery. DNA sequencing identified 85 cases with clonal haematopoiesis with a similar profile of mutations to those in the general population. Most individuals had normal blood counts and bone marrow immunophenotyping showed that clonal haematopoiesis is usually associated with normal stem and progenitor frequencies.
I adapted the TARGET-seq method to develop a more sensitive method for combined single cell genotyping with whole transcriptome sequencing. The new TARGET-seq+ method detected more genes per cell with lower dropout rates and reduced technical variation. I applied TARGET-seq+ to 12,847 single cells from 10 samples with clonal haematopoiesis and 3 controls. DNMT3A and TET2-mutant haematopoietic stem and progenitor cells did not occupy novel transcriptional states, but intermingled with wild-type cells, showing they follow a common differentiation trajectory. Expansion of DNMT3A-mutant clones occurred mainly in HSC and the greatest clone size was reached in early multipotent progenitors. In contrast, TET2-mutant clones expanded later in differentiation with a transcriptional bias towards the myeloid lineage. These findings highlight distinct effects of DNMT3A and TET2 mutations on haematopoietic stem and progenitor cells and identify dysregulated pathways that may have a role in expansion of the mutant clone.

Keywords: scRNA-seq
somatic mosaicism
single cell
haematopoiesis
leukaemia
clonal haematopoiesis
Advisor: Vyas, P
Higgs, D
Psychophysical dissociation of phase and position cues for visual motion perception

Visual motion perception is essential for viewing and interacting with our environment. The motion of an object in the visual field can be described by the changes in the position of a feature over time (‘position cues’ in the spatial domain), or by changes in the phase of the spatial frequency components in the Fourier domain (‘phase cues’). This thesis investigates the relative extent to which people rely on these cues to infer movement in the visual scene.
I showed that apparent motion discrimination with phase cues and position cues can be psychophysically dissociated by temporal interval (Chapter 2), and spatial frequency (Chapter 3), and that displacement thresholds for position cues increase more rapidly with eccentricity than do phase cues (Chapter 3). When phase and position cues are conflicted, I demonstrated that these spatial frequency dissociations can predict reversals in reported motion direction, both with changing spatial frequency, and between foveal and peripheral viewing (Chapters 4 and 5). The reliance on position cues to infer motion correlates with the ability to discriminate shapes, such that when shape discrimination is impaired motion discrimination is reliant on phase cues, in both normal observers and in the scotoma of V1 lesioned patients (Chapter 6). This shows that the visual system treats phase and position cues as separate sources of information which could be analysed separately.
These psychophysical dissociations may reflect the properties of different detectors in the visual field. Correlations of models of cell density distributions with the displacement thresholds across eccentricity suggest that the pα and pβ retinal ganglion cells form the physiological substrates for the input to these phase and position systems respectively (Chapter 7).
This thesis presents a psychophysical dissociation between phase and position cues, and suggests that these cues are initially processed by separate systems, with distinct physiological substrates.

Keywords: cortical blindness
psychophysics
retinal ganglion cell distributions
reverse Phi
motion cues
blindsight
visual motion perception
motion illusions
Advisor: Smithson, H
Azzopardi, P
Reconstructing diet and pottery technology of the Early Bronze Age 'Kura-Araxes culture': a multi-analytical approach

The Kura-Araxes (KA) cultural phenomenon, dated to the Early Bronze Age (EBA, 4th and 3rd millennium, c. 3500-2500 BCE) is primarily characterised by the emergence of a homogeneous ‘material culture package’ in settlements across the South Caucasus (Georgia, Armenia, and Azerbaijan), as well as territories extending to the Levant and Ancient Near East. More specifically, one of the major EBA craft products associated with the KA corresponds to a homogeneous style of black-burnished pottery in the South Caucasus, known as Early Transcaucasian Ware and other synonymous terms in the literature.
An interdisciplinary approach is conducted on a wide selection of ceramic samples representing the KA culture, in order to reconstruct pottery technology, direct evidence of pottery use, and dietary practices. Archaeological sites and potsherd samples selected span eight coeval KA settlements across Armenia: Gegharot, Karnut-1, Margahovit, Mokhra-Blur, Norabak-1, Shengavit, Sotk-2 and Talin Tombs. The analysis of KA pottery is carried out using an integrated multi-analytical approach to contribute to our understanding of cultural attributes, through (1) chaîne opératoire, (2) pottery use and dietary inferences. Stereomicroscopy, thin-section petrography, and scanning electron microscopy-energy dispersive x-ray analysis (SEM-EDS) are employed in order to reconstruct pottery fabric pastes and the transmission of technology across coeval KA settlements. Additionally, absorbed lipid residues from pottery are analysed using gas chromatography mass spectrometry (GC-MS) and gas chromatography-compound-isotope-ratio mass spectrometry (GC-C-IRMS), to determine the organic products produced, consumed and to reconstruct pottery function and subsistence practices.
Results from petrographic analyses suggest a local household industry production, spanning diverse technological procedures in raw materials and manufacturing at each settlement (i.e., the use of volcanic ash, grog and igneous rock fragments). Results from organic residue analysis provide compelling evidence for a diversified diet across settlements, comprising plant processing, dairying, animal carcass fats and aquatic commodities. The remarkable preservation of diagnostic plant lipid biomarkers, notably long-chain fatty acids (C20 to C28) and n-alkanes (C23 to C33) in organic residues from sites in Armenia has enabled identification of the earliest processing of plants in ceramic vessels of the region. These findings expand our current interpretation regarding the nature and fabric of the prescribed EBA Kura-Araxes communities residing in Armenia, South Caucasus. It is hoped that, in the future, new evidence in pottery analyses framed with archaeological evidence will increase our current understanding of the Kura-Araxes cultural phenomenon and the overall socio-economic structure of EBA communities.

Keywords: Armenia
Kura-Araxes
petrography
diet
South Caucasus
Early Bronze Age
archaeology
lipid residue analysis
The composer and musical identities in nineteenth-century fiction

This thesis explores representations of the composer in nineteenth-century fiction, with a primary focus on fiction in English, discussing well-known novels such as George Eliot’s Daniel Deronda (1876) and George du Maurier’s Trilby (1894) alongside less familiar fictionalisations of composers, real and imaginary. It reveals the under-acknowledged breadth of musical-literary interactions throughout the century, showing fiction’s part in working out new conceptions of the composer’s role and identity, and the importance of the composer figure for authors as a point of aspiration and differentiation. After introducing a radical new Romantic mode of conceptualising music at the beginning of the century, the thesis uses fiction to trace this mode’s afterlife: how it was reshaped by new ideas about music and its relationship to identity, but also its persistence long after the end of the Romantic period in other arts. In writing about the composer, authors explore the attribution of meaning to music, engaging with the Romantic commonplace that music is ineffable. Perpetuating the idea that music stood for the unexplained or inexplicable, but also exposing the cultural construction of musical meaning, fictional representations of the composer are both idealistic and realistic. The chapters offer a range of approaches for understanding the composer’s construction in, and impact on, the literary text. They reveal fiction’s dialogue with ideas about the composer, from Romantic beginnings which exalted the composer as an artist, to fin-de-siècle fears about the composer as a mad, dangerous genius. The composer embodies questions about music’s relationship to national, racial, and gender identities, and activates an experimental approach to selfhood which anticipates modernist literary engagements with music. The persistence of the Romantic mode, this thesis suggests, consists in an unabating exchange between literature and music. Fiction not only reflects shared cultural understandings about music, but actively produces them.

Keywords: music in literature
nineteenth century fiction
nineteenth century music
nineteenth century literature