VictorJuiz/thesis huggingface dataset:
Inscribing manumission in the Hellenistic world

This thesis is a study of Greek manumission inscriptions, their contexts and their functions. In total, more than 2,000 documents on stone recording the release of enslaved persons have been identified at dozens of sites across the Greek world. The majority of these cluster around the central and northern Greek mainland, and belong to the second and first centuries BCE. The procedures recorded are often cloaked in religious forms, and attest to the involvement of civic institutions. The primary aim of this study is to come to a better understanding of the motivations behind this peculiar epigraphic phenomenon.
The Introduction outlines some of the key conceptual and legal problems involved in the freeing of slaves, and provides an overview of the scholarship on manumission in ancient Greece. Chapter 1 sets some parameters for defining a manumission inscription, and for identifying shared cultural features in the practice and recording of manumission across the sites which produced these inscriptions. Chapter 2 explores the performances of the act of manumission which lie beneath our epigraphic texts, revealing the ceremonies and procedures, as well as the locations and the occasions at which Greek slaveowners effected the release of their slaves. Chapter 3 provides an overview of the documentary habits which accompanied the epigraphic evidence, and probes the extent to which the inscriptions themselves were considered valid and consultable documents. It concludes with a summary of the physical aspects of these inscriptions: the material upon which they were inscribed, their appearance and legibility, and their relationship with other epigraphic genres, are crucial factors to understanding the purpose of these objects. Chapter 4 details the multifunctionality of manumission inscriptions: in line with recent approaches to a variety of epigraphic documents, which have stressed both the practical and symbolic elements of Greek inscriptions, I argue that documents of manumission also served a number of overlapping purposes. Alongside the traditional explanations of their functions as being those of proof and publicity, they can be interpreted as reflecting certain values and ideals belonging to the individuals and communities which produced them. Chapter 5 is a case study of the manumission inscriptions from Seleukid Iran, which are broadly contemporary with our evidence from the Greek mainland, but present some interesting particularities.

Keywords: epigraphy
Manumission
Ancient Greece
Hellenistic period
Advisor: Crowther, C
A sociodemographic study of only-children and only-child fertility

This thesis explores only-child fertility from a sociodemographic perspective across three main chapters. The first substantive chapter examines trends in the proportion of women with an only-child across 125 countries, from 1920-79 birth cohorts, with combined data from different sources. The results show that the prevalence of only-child fertility has increased across the globe. However, as overall fertility reaches below-replacement, trends become more heterogeneous, and factors beyond a country’s cohort fertility rates and mean ages at childbearing become more important in dictating these prevalences. The second substantive chapter, with data from four countries in the first two waves of the Generations and Gender Surveys, explores fertility intentions and the realisation of those intentions in Eastern and Western Europe for a first and second child with the use of probit models with sample selection. The results show that while people seem to consider families and friends’ opinions, as well as what they believe to be the pros and cons of having a child when forming their fertility intentions, the actual realisation of intentions is more strongly guided by their perceived financial and physiological conditions for having and raising a child. The chapter further discusses differences between Eastern and Western Europe, and between those having a first and second child. The final substantive chapter explores behaviour differences between only-children and children with siblings in the British context with data from the Millennium Cohort Study. Results of a series of logistic models for children aged 3-14, show that only-children have higher odds of presenting abnormal peer behaviours, but fared better than children with siblings in conduct scores. However, the conduct score advantage for only-children disappears when only firstborns or only children with a resident father are considered.

Keywords: demographic transition
cross-country
only-children
Advisor: Monden, C
Unravelling the genetic and molecular mechanisms of the left-right patterning genes Pkd1l1 and Pkd2

Pkd1 and Pkd2 encode the polycystin proteins which underlie human ADPKD, a major cause of end stage renal failure. Recently, by analysing the Pkd2lrm4 mouse, a previous member of the lab provided evidence that loss of ciliary PKD2 underlies kidney cyst formation. Furthermore, the Pkd2lrm4 mouse highlights a requirement for PKD2 in nodal cilia for correct L-R patterning. However, we are yet to fully understand its cilia-specific role and the mechanisms controlling its ciliary trafficking and entry. PKD1L1 (a PKD1 Paralog) functions with PKD2 in the embryonic node to allow correct L-R patterning and its expression and localisation during this process remain to be fully characterized.
By generating endogenously tagged alleles of PKD1L1 and PKD2, I have investigated their localisation and co-localisation, in the embryonic node during L-R determination. Using these tagged alleles, Pkd1l1mTFP1 and Pkd2mNG, I have been able to evaluate their localisation in Pkd2-/- and Pkd1l1-/- embryos respectively. Enabling us to further understand the role of their co-localisation, and assess the co-dependent relationship between PKD2 and PKD1L1 for ciliary localisation. Using Pkd2lrm4/lrm4 samples, I have been able to identify a selection of candidate interacting proteins that may be involved in trafficking to cilia and ciliary entry of PKD2.
The work in this thesis provides a new insight into the genetic and molecular mechanisms involved with the polycystins, and their roles in left-right pattern determination.

Keywords: Pkd1l1
left-right patterning
nodal cilia
development
polycystins
Pkd2
Advisor: Norris, D
Whitby, M
Transcriptional changes and regulation of voltage gated calcium channels across human stem cell differentiation

Human neural development comprises a phase during which a risk for psychiatric conditions such as schizophrenia is established. Robust evidence has linked voltage-gated calcium channels (VGCCs) to psychiatric illness. However, the biology of VGCCs in the context of human neural development, and particularly the prenatal stages, has not been sufficiently studied. This thesis examines the transcriptional regulation of VGCCs in a model system of neural development, the differentiation of human induced pluripotent stem cells (hiPSCs) into neurons. By applying bioinformatics tools to hiPSC and hiPSC-derived neuron data from dozens of donors, I characterized changes in the abundance and splicing of VGCCs across hiPSC differentiation into neurons. Additionally, motif-based bioinformatics tools were applied to identify candidate regulators of VGCC splicing and abundance. The analyses revealed that as hiPSCs differentiate into neurons, VGCC transcript levels robustly increase. The alternative splicing of CACNA1C, CACNA2D1, and CACNA2D2, including a cell state-specific switch in the utilization of Exons 21 and 22 in CACNA1C, were identified. Analyzing the regions of interest using two different bioinformatics tools identified a binding site for BRUNOL4 and BRUNOL5 upstream of CACNA1C Exon 21, which showed neither evolutionary conservation nor acceleration; and a binding site for HNRNPL near CACNA2D2 Exon 26 showing evolutionary acceleration in primates. Finally, transcription factor (TF) footprinting analyses of ATAC-seq data identified candidate TFs that might regulate multiple VGCC loci, several of which are expressed more highly in human fetal compared with postnatal brain development, including KLF7 and TCF4. Altogether, the results provide a foundation for future research investigating the functions of the identified RBPs and TFs in VGCC transcriptional regulation. The findings also indicate that hiPSCs possess the potential for providing insights into the changes that occur in VGCC transcription and putative mechanisms of VGCC regulation in human neural development and different cell states.

Keywords: transcription factors
voltage gated calcium channels
differentiation
alternative splicing
human induced pluripotent stem cells
Advisor: Harrison, P
Tunbridge, E
On the ecology and behaviour of the African elephant

In the last decade many protected elephant populations in Africa have shown signs of overpopulation due to range decrease. Woodland and forest devestation by elephants has posed a dilemma for the administrators of the National Parks who wish to maintain habitat diversity and species abundance with the minimum of human interference. Crucial decisions on whether to cull elephants or not need to be based on exact knowledge of rates of habitat change and elephant population dynamics.
[Abstract continued in thesis]

Advisor: Owen, J
Chiral biotransformations of cyclic nitrile compounds

The aim of this thesis was to improve the understanding of how bacteria (in particular Rhodococcus rhodochrous LL100-21) use enzymatic reactions to biotransform nitrile compounds. Particular emphasis was given to some compounds of potential interest to the pharmaceutical industry.
Due to the difficulty in selectively converting one cyano group of a polynitrile by conventional chemical techniques, regioselectivity of Rhodococcus rhodochrous LL100-21 was investigated using (cyanomethyl) benzonitrile compounds. Depending on the induction/growth conditions and the position of ring substitution of the substrate, different products were obtained following the biotransformation. For example, bacteria grown/induced on propionitrile or benzonitrile converted the substrate 2-(cyanomethyl) benzonitrile to 2-(cyanophenyl) acetic acid- with a 64 % yield compared to the starting substrate. Conversely, bacteria grown on acetonitrile converted the same substrate to a mixture of amide intermediates but at very low yield. Furthermore, the aliphatic cyano group of 2-(cyanomethyl) benzonitrile was preferentially hydrolysed. In the case of 3- and 4-(cyanomethyl) benzonitrile, the aromatic cyano group was converted to the acid thereby suggesting ring substitution was an important factor in the biotransformation.
Initial rate studies were undertaken in order to greater understand the biotransformations. The results suggested that steric hindrance influenced the reaction. Furthermore, when there was a cyano or bromo group in the ortho position of the aromatic ring it was found that there was an in increase in the initial rate of hydrolysis, suggesting these groups also affect the enzymatic reaction.
In addition, PCR and Southern blot techniques were used to investigate the presence of nitrile hydrolysing enzymes in a range of bacteria.
Mid infrared spectroscopy was carried out to study the enzyme kinetics involved in nitrile biotransformations permitting, for the first time, nitrile biotransformations to be monitored in real-time. This opens up React IR MP as a useful technique for studying a wide range of biocatalytic processes in real-time. Bioconversion of prochiral nitriles was also undertaken using Rhodococcus rhodochrous LL100-21. The results suggested that the bacterium could biotransform these nitriles and, with further chemical rearrangement, could yield novel compounds of interest to the pharmaceutical industry.
Finally, the biotransformation of benzonitrile was undertaken in the presence of hydroxylamine (NH2OH), which is more nucleophilic than water. Interestingly, when bacteria were grown on benzonitrile (to induce the nitrilase enzyme) the hydroxylamine competed with the water and the novel product, benzohydroxamic acid, was foiuied. Furthermore, the abiotic control afforded another product benzamide oxime.

Advisor: Knowles, C
Motives beyond markets: state ownership, stranded assets, and decarbonisation in the power sector

State-owned enterprises (SOEs) will play a central role in the decarbonisation of the global economy. They are also the dominant type of actor in the power sector by both installed power generation capacity and investment, with China accounting for the largest share. Despite their obvious prominence, SOEs remain an understudied element in climate policy analysis, design and implementation. The papers in this thesis begin to address this research gap, focusing on state- owned power companies (SPCs). The three papers employ, respectively, comparative case study analysis, a modified version of discounted cash flow analysis, and microsimulation techniques. Together, they make some initial progress towards more explicit integration of SOEs and government shareholders into climate policy research. Paper 1 develops a framework for analysing how SPCs’ characteristics and the context in which they operate affects their response to government interventions. It finds that SPCs can, under certain circumstances, be more effective conduits for climate policy than private companies, and that market-wide policies may have less effect on SPCs than on their privately-owned counterparts. Paper 2 adapts and extends traditional stranded asset analysis to consider cases in which the asset owners are SOEs, focusing on coal power in China. It concludes that new coal power investments by Chinese SOEs are unlikely to deliver positive economic returns, and that dispatchable renewable power will soon be economically competitive as an alternative even without accounting for the social cost of carbon. Paper 3 simulates the effect of thermal coal phase-out in China on employment and tax revenue in the thermal coal value chain. The results show that delaying coal phase-out cannot prevent losses in employment and tax revenue in China’s coal sector from being realised, and that these losses are both geographically concentrated and associated with a small number of large SPCs. Overall, this thesis demonstrates the importance of explicitly accounting for SOEs both in formulating climate policies and analysing their effects.

Keywords: just transition
state-owned enteprise
carbon neutrality
climate policy
decarbonization
stranded assets
coal power
China
coal phase-out
What actually happened? Novel econometric methods to improve estimates of climate impacts and policies

Climate change is one of the most crucial societal challenges of the 21st century, affecting a wide range of social, economic, and environmental aspects of modern society. To design and implement policies that can deal with the climate challenge requires an accurate and robust understanding of the physical impacts of climate change as well as understanding the potential impacts of different policy instruments, their limitations, as well as their successes and failures in the past. Despite this necessity, there remains substantial empirical uncertainty around the effectiveness of policy approaches both in the context of mitigation and adaptation. In this doctoral thesis, I present a total of five papers that advance the field of impact estimation in the context of climate change. By using and developing novel econometric methods, I show how existing gaps in this literature can be addressed. In Paper 1, I develop a novel statistical test to illustrate the impact that outlying observations have on regression coefficients of econometric climate impact estimates. In Paper 2, I use these methods and advance climate impact estimates further by presenting a first set of economic climate damage projections that incorporate the effects of extreme weather events and adaptation. While current climate and weather impact data collection approaches focus on manual bottom-up database records, Paper 3 uses machine learning algorithms to predict the occurrence of weather impact events reliably without manual input or on-the-ground knowledge. In Paper 4, I operationalise an alternative way to empirically evaluate policy, which is used in Paper 5 to identify the effects of 10 distinct road transport mitigation policies in the EU15. Overall, I argue that when econometric methods are specified correctly, are applied to the most pressing research questions, and make use of appropriate data then using these methods can allows us to direct adaptation funding more efficiently, track Loss and Damage events around the world, and allow policy-makers to focus on those policy packages that have the largest chance of making a difference.

Keywords: climate change
climate impacts
econometrics
economics
Advisor: Hendry, D
Hepburn, C
Essays on voluntary disclosure, information uncertainty and investment

This thesis consists of three studies contributing to voluntary disclosure, information uncertainty and investment.
The first study investigates whether and how voluntary disclosure affects the earnings announcement premium (EAP). Using S&P500 index additions as an exogenous source of variation to voluntary disclosures, we test the effect of guidance on information risk and investor attention as drivers of the EAP. We document a significantly positive (negative) effect of raised (lowered) guidance on the EAP reconciling attention-based and risk-based explanations. Disentangling direct and mediated effects, we find a positive direct effect of raised guidance on the EAP (attention channel) and a weaker countervailing negative indirect effect of raised guidance on idiosyncratic risk (risk channel). Lowered guidance has an unambiguously negative direct and indirect effect. Using high-frequency data we further confirm the effect of voluntary disclosure on both sources of the earnings announcement premium.
The second study investigates the effect of firm-level idiosyncratic uncertainty on voluntary disclosure. Using a novel dataset of consumer transaction data to measure idiosyncratic uncertainty, this study finds that idiosyncratic uncertainty reduces managers’ propensity to make voluntary capital expenditure forecasts and that the negative effect of idiosyncratic uncertainty on disclosures is weaker in periods of declining performance compared to growing performance. This study also shows that managers place more weight on their private information with an increase in idiosyncratic uncertainty and rely less on market signals, suggesting that they have more internal information under uncertainty in periods of declining performance. Additional analyses confirm this finding by showing that idiosyncratic uncertainty has a less negative impact on planned capital expenditures in periods of declining performance compared to periods of growing performance.
The third study compares the public and private firms’ investment under uncertainty. Using a novel dataset of consumer transaction data to measure firm-specific fundamental performance uncertainty, this study finds that in the presence of high uncertainty, private firms are likely to invest more compared to their public peers. Moreover, when operational volatility is high, public firms’ profitability increases with the additional capital expenditure investment; however, private firms’ profitability decreases with their additional capital expenditure investment. These empirical findings show that public firms’ information environment enables public firms access additional information to resolve uncertainty during investment decision making. Additional analysis shows that the information advantage of public firms may spillover to private firms in industries with high presence of bellwether public companies.

Advisor: Wilson, M
Amel-Zadeh, A
Multiparametric characterisation of peripheral immunity in recipients of checkpoint immunotherapy across a large patient cohort

Immune checkpoint blockade (ICB) has revolutionised the treatment of metastatic melanoma (MM) which was historically resistant to conventional therapies, yet only a minority of patients experience durable clinical benefit. Dissecting peripheral immune responses to ICB may discern predictive markers of clinical outcome. However, infection with human cytomegalovirus (CMV) can have profound effects on immunity and the extent to which this affects the peripheral immune response to ICB is unclear. Using an agnostic transcriptomic and cytometric assessment of peripheral immune ICB responses across a large cohort of MM patients, I identify dynamic changes in immune composition, activation and adaptive immune cell repertoires. I also determine the contribution of CMV to these changes and describe predictors of clinical outcome.
Firstly, I identify CD8+ T-cells as being the most responsive cell type to ICB treatment and that responses in other peripheral blood mononuclear cell subsets are secondary to CD8+ T-cell ICB response. Next, I find that only B-cell proportion and subset composition are sensitive to ICB treatment. This includes a transient depletion of B-cells and an induction of antibody-secreting cells which associate with clinical outcome. I then characterise these changes and determine that these ICB-mediated effects are largely dependent on CD8+ T-cell activation and production of B-cell chemoattractant CXCL13. Finally, I describe the effects of ICB and CMV on corresponding B-cell receptor and T-cell receptor repertoires. Significantly, I find that B-cells undergo accelerated class switch recombination and somatic hypermutation following ICB, whilst MAIT cells are depleted and associate with clinical outcome. Although CMV infection is a major determinant of MAIT cell changes following ICB, all other identified ICB-mediated effects are independent of CMV serostatus.
In this thesis I present novel findings surrounding B-cell and T-cell responses to ICB treatment and identify predictive markers which may have clinical utility in monitoring patient treatment responses as well as guiding treatment stratification. My observations demonstrate that the response to ICB is multifaceted, involving a coordinated interaction between different cell subsets, driven by CD8+ T-cells. Notably, B-cells cannot be assumed to play a bystander role and my work highlights the importance of B-cell:CD8+ T-cell interactions in the response to ICB and long-term clinical benefit.

Keywords: T-cells
CMV
melanoma
B-cells
MAIT cells
immune checkpoint blockade
Advisor: Fairfax, B
Middleton, M