VictorJuiz/thesis huggingface dataset:
Integrations and introgressions: a viral and genetic history of the human genome
Keywords: archaic introgression
population genetics
human evolutionary genetics
HERV-K (HML-2)
Africa
human endogenous retroviruses

The human genome combines archaic relics which have been obtained through two biological vehicles: viral infection and interbreeding. In this thesis I explore detection methods that search for the products of these biological processes, starting with some of the oldest fossils in our genome: viruses. I examine the most recently active endogenous retrovirus (ERV) family in humans: human endogenous retrovirus-K (HERV-K), human mouse mammary virus-like 2 (HML2), also known as HK2. I collaboratively developed and benchmarked the software STEAK for detecting mobile element and retroviral integrations in high-throughput sequencing data. Using STEAK on 70 whole genome sequences (WGS), I show that all polymorphic HK2 integrations found in Europeans are also present in African populations and estimate that HK2 activity stopped prior to the emergence of modern humans. The second half of this thesis investigates the outstanding question, did archaic and modern humans admix in Africa? Non-African populations today carry 1-5% of Neanderthal and/or Denisovan admixture. However, it remains unclear whether archaic introgression is present in African populations. I use WGS simulations to assess a current archaic reference-free method, S*, under different demographic models varying in divergence dates, admixture dates, and admixture proportion. I show that in the absence of an archaic reference and an obscure demographic history, S* results must be interpreted with caution given its sensitivity to demographic processes. Using S* and Sprime on African WGS, I find that putatively introgressed regions detected by both methods are notably long and old haplotypes. I show with D-statistics that African populations such as the San share excess derived alleles with Denisovans but not with Neanderthals. These analyses collectively support a model where interbreeding took place between an ancestral human population and other archaic hominins within Africa. Overall, this thesis elucidates the relationship between the human genome and the archaic sequences it hosts.
Focused ultrasound: a non-invasive brain stimulation modality
Keywords: Ultrasound
Brain stimulation
Neuromodulation

Non-invasive brain stimulation techniques allow for excitation or inhibition of neural activity via externally applied stimuli. Recently, ultrasound (US) has been shown to stimulate neurons with better spatial localisation than existing electrical stimulation modalities. We present a review of the literature in both the central and peripheral nervous systems demonstrating a range of effects from de novo action potential generation in isolated cell preparations to cognitive responses in humans. However, several questions remain before the technique can become widespread. These include: methods to accurately model, and deliver, transcranial US to specific brain targets; the safety of the approach from both a mechanical and thermal standpoint; elucidation of the fundamental mechanisms through which acoustic perturbations result in nervous system modulation; and the development of monitoring techniques to confirm US focusing in vivo as well as to detect the induced effects. In this thesis, we focus on the delivery and safety aspects. We present numerical simulations using k-Wave and experimental measurements demonstrating focusing to areas of the visual cortex using ex-vivo human skulls with single-element transducers. We show that targeting of many areas can be achieved without the use of lenses or arrays. Furthermore, we conduct an in-depth safety review detailing the parameter spaces over which studies have been conducted and highlighting any damage areas. In current human studies the technique appears to be safe with minimal, if any, side effects. Finally, we report findings from a human pilot study with the aim of modulating sites within the visual cortex. We present direct evidence of strong non-specific auditory activation following bursts of US confirming previous animal studies. These effects can confound US neuromodulation trials and demands further attention before US can realise its potential as both a scientific instrument to probe brain function and as a therapeutic modality to modulate brain activity.
The involvement of hypoxia in APOBEC-mediated mutagenesis in multiple cancers
Keywords: Computational Biology
Mutational Signatures
Genomics
Hypoxia
Cancer

Mutational signatures have been studied to associate mutations to their originating causes. One such signature is that of the APOBEC family of proteins. APOBEC proteins are normally involved in innate immunity, playing a role in the defence against foreign genetic material by inducing mutations in single-stranded DNA and RNA. APOBECs have recently been associated to mutations in the genomes of multiple human cancers. The regulation of APOBEC genes is currently poorly understood, especially in the context of cancer. Recent evidence suggests that certain APOBEC genes can be upregulated in immune cells exposed to hypoxia. I explore this path further by studying the association between hypoxia and APOBEC expression and activity in cancer using RNA-Seq, mutation, and amplification data from 6723 patients in 13 cancer types. My results show evidence of correlation between hypoxia and APOBEC gene expression as well as mutagenic activity, specifically APOBEC3A and 3B. I also show that APOBEC3B is involved in pathways that overlap with those associated with hypoxia, contrary to the other APOBEC family members. Finally, I provide a comparison of the methods used to evaluate the APOBEC mutational signature. Overall, this study provides preliminary evidence for the association between APOBEC and hypoxia. It also raises many questions, but it provides solid grounds for future studies to be conducted in more depth about this topic.
Made in the media: actresses, celebrity and the periodical press in the late eighteenth century
Keywords: Media
Periodicals
Theatre
Celebrity
Actresses
Newspaper

This thesis examines the periodical culture that operated in late eighteenth-century Britain (predominantly though not exclusively in London) and the ways in which it made the female ‘stars’ of the stage. I propose that actresses’ celebrity was in part made in the media; the press coverage they received has not had the same attention as their treatment through other media, such as the memoir or portraiture. Through a combination of literary and cultural analysis, this thesis examines the ‘media texts’ that circulated in the periodical press about three contemporaneous actresses: Sarah Siddons, Elizabeth Farren and Mary Wells.
Three central questions drive this thesis. What role did the periodical press play in the development of actresses’ celebrity in the late eighteenth century? What rhetorical strategies were used in the newspapers to represent actresses’ public identities and how did these verbal images correspond with other media? How did readers and subjects engage with news media as a shared space for shaping celebrity identities?
In exploring answers to these questions this work aims to contribute to the ongoing reevaluation of the centrality of media in early celebrity and to an understanding of the daily, weekly and monthly circulation of motifs that created and sustained celebrity identities. It also makes the case that an emergent celebrity culture in this period was shaped in and through an exploration of gendered (female) performance and the limits of its agency.
Part I describes the media landscape in relation to the stage. Chapter 1 describes the ways in which the stage represented newspapers and their reception. Chapter 2 turns to the ways in which newspapers represented the stage. Part II offers case studies. Chapter 3 argues that the press treated ambivalently Sarah Siddons’s background as a stroller. Chapter 4 focuses on the kind of ‘credit’ newspapers accorded Elizabeth Farren’s portrayal of the character of the ‘lady’ on and off stage. And Chapter 5 demonstrates that, despite her close association with newspapers, Mary Wells failed to secure the kind of celebrity she craved through the press.
Ḥisba and Maṣlaḥa as political thought: Fadlallah and Khomeini compared
Keywords: sovereignty
Ayatollah Khomeini
Iranian Revolution
Ayatollah Fadlallah
hisba
maslaha

This dissertation explores how ethical and political concepts inform and bolster theories of sovereignty in modern Islamic political thought. Commanding right and forbidding wrong, as an ethical-social concept, and maṣlaḥa, as a political concept, are intimately connected in Muslim formulations of state and good governance in the modern period. In other words, when mobilised together, the two constitute a comprehensive claim to sovereignty; where commanding right and forbidding wrong addresses social ethics related to sound public and private conduct, maṣlaḥa is used for legal decisions and national interest. Placing Ayatullah Muḥammad Ḥusayn Faḍlallah (d. 2010) in conversation with Ayatullah Rūḥallah Mūsavī Khumaynī (d. 1989) demonstrates most clearly the spectrum of debate on these concepts as they relate to sovereignty in Shi‘i political thought. On the one hand, Fadlallah developed his ideas on sovereignty primarily within the precarious political environment during and after Lebanon’s Civil War, when a strong centralised state was absent, and in which he promoted a politically integrous and ethically just community. Khomeini, on the other hand, wrote from within a centralised and secular monarchy, and subsequently from exile, to promote an Islamic state with juridical rule. This work examines how both scholars linked commanding right and forbidding wrong with maṣlaḥa to themes of law, the public-private spheres, gender, and state. Doing so, I demonstrate how and why these two concepts are appealing for contemporary Islamic politics and in which ways they are effective weapons for politics and sovereign claims.
Transcriptional regulation at the angiogenic sprout
Keywords: Sprouting angiogenesis
ATAC-seq
Endothelial cells
HLX regulation
Zebrafish
MEF2 transcription factors

Angiogenesis, the formation of new blood vessels from existing ones, depends on very precise spatio-temporal gene expression patterns in different sub-types of endothelial cells. These patterns are controlled by pro-angiogenic stimuli but the transcriptional mechanism by which these stimuli induce specific gene expression in endothelial cells is not well understood. In this thesis I identify and characterize a novel sprouting-specific enhancer upstream of the angiogenesis-specific H2.0-like homeobox protein (HLX/hlx) gene. This conserved enhancer, termed HLX-3/hlx-3, is able to direct gene expression specifically and selectively to angiogenic endothelial cells in both transgenic zebrafish and mice during physiological and pathological angiogenesis. Analysis of the transcription factor binding sites within the HLX-3/hlx-3 enhancer reveals a requirement for myocyte enhancer factor-2 (MEF2) family members for enhancer activity. Endothelial-specific Mef2A/C knockout results in reduced sprouting in the mouse retina, confirming an important role for MEF2 factors in the regulation of both Hlx and sprouting angiogenesis more generally. Further, I use the hlx-3:GFP transgenic zebrafish line to generate a genome-wide map of accessible chromatin regions from isolated sprouting cells, and compare them to arterial and venous endothelial cells. My results demonstrate that accessible chromatin is not sufficient to reliably predict enhancer activity patterns, and that within the endothelial-lineage, regulatory elements are constitutively open irrespective of the sub-endothelial cell type. Interestingly, despite these observations, binding motifs for MEF2C and angiogenic-associated transcription factors are enriched in sprouting endothelial cells. These results provide novel insights into the transcriptional regulatory landscape of endothelial cells and confirm the importance of MEF2 factors during angiogenesis.
The impact of iron technology on the economy of the Aegean and Cyprus from 1200-850 BCE
Keywords: iron
Early Iron Age
metalworking
bronzeworking
apprenticeship
forge
iron working
Greece
Late Bronze Age
iron knives
metals
ironworking
smith
Cyprus
ingot
metallurgy
apprentice
metal trade
billet
blacksmith
smelting

The thesis investigates the development of ironworking industries in the Aegean and Cyprus during the Early Iron Age, covering the crucial years from the twelfth to the ninth centuries BCE. It advocates for a move away from pan-Mediterranean models that rely on a centre of ‘innovation’ from which the technology radiated to new regions via itinerant craftsmen. It argues instead for the development of models based on region-specific cultural and economic factors that influenced iron production and use. This comparative method reveals that the iron industries of the Aegean and Cyprus developed along separate trajectories.
This thesis shows that iron objects were locally produced in the Mycenaean sphere during the Late Bronze Age. The Aegean did not depend on itinerant craftsmen from Cyprus to stimulate ironworking, but it was instead a local tradition that continued through the end of the palatial period in the Peloponnese. Iron spread throughout the Aegean in the ensuing century, with each region adapting objects to iron according to how it was valued. In the Peloponnese, iron was suitable for practical implements immediately, while Attica, Crete, Euboea, and the islands emphasised a high value ornamental purpose in mortuary display. By the 10th century, the standardisation of burial rituals during the Protogeometric integrated iron into general use across the Aegean. It became a widely produced, moderately valued metal for daily use implements like tools, as well as a regular part of mortuary display.
In Cyprus, ironworking sprang up rapidly across the island, and without a Bronze Age tradition. It began as part of a package that included the arrival of Urnfield-type goods from the Aegean, iron being the more appropriate than bronze for items such as knives, daggers, fibulae, obeloi. Iron was applied in two spheres immediately, to tools of practical use and to high value mortuary display items. Local production due to the lack of ore sources in favour for a copper-smelting by-product method remains debatable, but Cypriot smiths were capable of mass-producing a series of knives. The iron industry did not disrupt but developed alongside the Early Iron Age investments made in the copper industry.
Studying partially ordered systems using stochastic differential equations
Keywords: Stochastic Differential Equation
Brownian Motion

This thesis looks at two different problems in the field of partially ordered systems - modelling biopolymers on multiple scales as well as modelling two-dimensional nematic liquid crystal wells - and seeks to gain insight using stochastic differential equations, through mathematical analysis and numerical simulations.
In the field of biopolymers, we generalize existing models for a coarse-grained polymer to multiple resolutions, which allows for faster computations while maintaining a high level of detail in regions of interest. This is done for two bead spring models; the Rouse model, which does not account for hydrodynamic interactions, as well as the bead-spring model with hydrodynamic interactions. For both models mathematical analysis is done to find expressions for global statistics to derive scaling laws for the models. This is implemented by generalizing existing algorithms using a multi-resolution approach which utilizes multiple spatial and temporal scales. These simulations show that the scaling laws for multiple resolutions match expected analytic results through simulations. For the Rouse model, a model for the binding of a protein to DNA is introduced, along with a mechanism for changing resolutions along the filament on-the-fly. Within reasonable error, the results for the chain in multiple resolutions matches the chain modelled entirely in high-resolution.
The work on nematic liquid crystals is concerned with a stochastic dynamics model of nematic liquid crystals contained within a square well, looking at their behaviour under Brownian motion using the Gay-Berne potential. In particular, we are interested in the parameter regimes which are responsible for different types of steady states to form in the system and whether steady states suggested by continuum modelling are stable.
Transcriptional and epigenetic mechanisms of promiscuous gene expression by thymic epithelial cells
Keywords: Thymic epithelial cells
Promiscuous gene expression
Thymus
Central tolerance
Immunology

The thymus is the primary lymphoid organ responsible for the generation and selection of a T-cell repertoire that is able to respond to foreign antigens whilst remaining tolerant to self. For the purposes of T-cell central tolerance induction thymic epithelial cells (TEC) express almost all protein coding genes in a process termed promiscuous gene expression (PGE), which is partly under the control of the Autoimmune Regulator (AIRE). Many aspects of the molecular mechanisms underlying PGE in TEC remain unclear. It has not yet been conclusively established whether PGE within single mTEC is a stochastic or coordinated process. The mechanisms that target AIRE to tissue-restricted genes (TRGs) are also incompletely defined, with previous studies suggesting that interaction partners of AIRE may localise AIRE to repressive epigenetic marks associated with TRGs in TEC. The first part of this study examines the transcriptional patterns associated with PGE in single mTEC. Analysis of the transcriptomes of 6,894 single mTEC revealed 50 robustly defined co-expression groups supporting the hypothesis that PGE in individual mTEC is a highly ordered process. The second part of this study addresses the role of a putative AIRE interaction partner, Chromodomain-helicase-DNA-binding protein 4 (CHD4), in TEC biology. Using a variety of cellular and molecular tools, CHD4 was demonstrated to play important roles in TEC development, architectural organisation and function. In particular, CHD4 was found to cooperate functionally with AIRE to induce the promiscuous expression of AIRE-induced TRGs found in particularly repressive chromatin contexts and was consequently required for proper T-cell central tolerance induction.
Aerosol effects on microphysical processes and deep convective clouds
Keywords: Microphysics
Aerosols
Atmospheric physics
Deep convection
Numerical weather prediction
Climate modelling
Weather modelling
Aerosol–cloud interactions
Deep convective clouds
Convection
Microphysical processes
Tracking
Python
Cloud tracking
Clouds
Convective clouds
Numercial modelling
Cloud physics
Cloud ice
Thunderstorms
Mixed-phase clouds
Aerosol indirect effect
Cloud microphysics

Aerosol–cloud interactions are an essential feature of the Earth’s climate system. How- ever, aerosol effects on deep convection are highly uncertain. Different conceptual models for the effects of aerosols on deep convective clouds have been proposed, and assessments based on both models and observations show a wide range of results. This thesis aims at unravelling the cloud microphysical pathways involved in these interactions using a hier- archy of different model simulations and novel analysis tools. A detailed pathway ana- lysis based on microphysical process rates for individually tracked clouds is developed and applied to idealised supercell simulations with three different microphysics schemes in a cloud-resolving model (CRM). This reveals both consistent responses between the schemes, e.g. a suppression of warm rain formation and elevated freezing, and signific- ant differences between the schemes due to the definition of hydrometeor classes and microphysical processes. The cloud tracking framework tobac is developed to provide a consistent way to perform analyses resolving the time evolution of individual clouds in a wide range of datasets. Its application is demonstrated for both CRM simulation results and geostationary satellite data. The cloud tracking and the pathway analysis are combined to investigate deep convective clouds in a large case study simulation and their aerosol response for two different CRMs. Separating the tracked clouds into different categories and compositing along a relative time axis allows for a detailed assessment of the cloud microphysics that resolves the time evolution of the clouds. Despite some similar aerosol responses like a suppression of warm-rain formation and surface precipit- ation, the analyses highlight significant differences in the cloud types and cloud evolution simulated by the two models, especially regarding the mixed- and ice-phase processes. The detailed investigation of the microphysical evolution of individually tracked clouds reveals important pathways for aerosol effects on deep convective clouds and substantial uncertainties that arise from the representation of microphysical processes in numerical models.
Origen and prophecy
Keywords: Origen
prophecy
exegesis
free will
allegory
prediction

This thesis is an attempt to understand prophecy in the thought of Origen of Alexandria.
There is no speculative theological work of Origen (or, indeed, of any other Church writer of his period) on prophecy as a theological category in its own right. Yet prophecy lies at the heart of Christian understandings of the world, as a topic which intersects with all of the most complex questions of theological philosophy – free will, foreknowledge, eschatology, soteriology, cosmology. To understand the thought of Origen, who is frequently characterised as the first systematic theologian, we must have some understanding of his concept of prophecy.
The overall argument of the thesis is that Origen was the first Christian writer to attempt to unite disparate notions of prophecy – as future-telling, ethical instruction, and mystical revelation – in order to counter the challenges to Christianity put forward both by breakaway Christian movements and by Jewish and pagan critics. To do so I propose a new framework for understanding how Origen thought about prophecy. I argue that Origen understood prophecy as tripartite in the same way in which he understood scripture as tripartite: that is, as a layered phenomenon of ‘somatic’ or bodily readings, ‘psychic’ or moral readings, and ‘pneumatic’ or spiritual readings. In demonstrating this tripartite structure, I make the case that prophecy and exegesis are, in Origen’s thought, mirror-images of one another, reflected in the mirror of Christ.