VictorJuiz/thesis huggingface dataset:
Know what? New lenses on productive knowledge shed light on long run development, structural change, job switching and the transition to the green economy
Keywords: structural change
green economy
economic complexity
job transitions
knowledge

Tracing back to Adam Smith, scholars have emphasised the importance of knowledge and its profound implications for prosperity. However, measuring and analysing something as intangible and multifaceted as the knowledge collectively held and used within society has, not surprisingly, proved challenging.
This thesis advances quantitative empirical approaches for analysing productive knowledge within socio-economic systems and applies these methodologies to shed new light on (i) long run regional development and structural change (ii) labour market segregation and job switching, and (iii) the transition to the green economy.
This thesis shows that across a range of different contexts, from US regional development in the 19th century to modern-day labour markets, what places and people know matters. Measuring the type of knowledge concentrated in US states sheds new light on structural change, the decline of rust-belt states, and the reversal of patterns in income convergence. Similarly, measuring the type of knowledge held by individual workers in different occupations provides new insights on the division of labour, job transitions and future career prospects. Moreover, measuring the type of knowledge embedded within countries turns out to be particularly informative of a nation’s likelihood of success in the green economy – and its potential for green diversification in the future.
This thesis also reveals distinct segregation in societal knowledge across places and people. Such divisions could matter more than we realise. For example, the segregation of productive knowledge across US states could play a role in undermining the nation’s capacity for inclusive growth. The segregation of skills and productive capabilities across the US labour force could exacerbate the distributional consequences of labour market shocks. And moreover, the segregation across nations’ capacities to both participate and benefit from the transition to the green economy could slow or even create barriers to progressing one of the most important socio-economic transitions of our time. While this thesis has advanced new ways to identify these divisions in knowledge, further work is required to better understand their implications -- and what can be done.
Finally, this thesis suggests that future improvements in what places and people know will need to become less incremental and more transformational, if we are to successfully address the ‘twin challenges’ of poverty alleviation and climate change in the 21st century. Learning how to both navigate and drive the process of transformational change in productive capabilities could be the type of knowledge that matters more than anything else.
Does not compute: social dissonance in England's computing education policy
Keywords: digital skills
Michel Foucault
computing education
educational policy
primary school
England

The new computing component of England’s National Curriculum was promoted as an effective and egalitarian way to provide young people with the skills, knowledge, and ways of thinking necessary to participate in an increasingly digitalised world, both as citizens and as potential tech entrepreneurs or computer scientists. What policymakers did not adequately account for was how state schools would interpret this new policy, the impact it might realistically have on young people’s relationship with modern digital technologies, and whether there might be a mismatch between the pro-technology narratives represented in this curriculum and the everyday beliefs and experiences of teachers and young families.
England is at an important turning point as it haltingly transitions from its manufacturing roots to a digitalised knowledge society, with a growing nostalgia for its former position as an imperialistic power of world-leading technological advancement. Through this study I will unveil the power relationships and shared socio-cultural knowledge behind the computing education policy’s creation and its implementation. I will do this by answering the following research questions: 1) How are teachers translating the computing education policy into practice and why? 2) In what ways are the computing education policy influencing students' understanding of and disposition towards digital technology and why? and 3) What does the computing education policy – and teachers’ and students’ response to it – say about the incongruity between public policy around digital technology and people’s real-world experiences and understandings of it?
Using teacher interviews, student writing and drawings, student interviews, extensive classroom observations, and policy analysis, this ethnographic case study of four primary school classrooms in the South of England will examine how the addition of computing to England’s National Curriculum came to pass and why it is not meeting its stated goals, before discussing what this means about past assumptions and future possibilities for young people’s engagement with and understanding of modern digital technologies in formal education settings. My study contributes a unique perspective of a single education policy as it passes through three different stages in its development and implementation, encountering and being shaped by the beliefs and values of several groups along the way. The results of this study inform our understanding of how power relationships function to define a policy’s purpose and value across different settings, demonstrating how the power to define equates to the power to shape reality.
Understanding drug resistance through computational models of the genotype-phenotype mapping
Keywords: Evolution
Mathematical Modelling
Bet-hedging
Genotype-Phenotype mapping
Drug Resistance

The emergence of drug resistance is ultimately driven by Darwinian evolution. These evolutionary dynamics are inherently two-tiered, with mutational processes at the genetic scale inducing variation in cellular phenotypes that are subject to natural selection. If we are to predict or reverse evolution, as we must to determine effective treatments for drug-resistant infections and cancers, then we must first understand the relationship between genetic and phenotypic change. This relationship, known as the genotype-phenotype (GP) mapping, is governed by a complex cascade of potentially stochastic molecular interactions that integrate genetic, epigenetic and environmental factors to determine cellular phenotype. In this thesis, we introduce abstract models of the GP-mapping to explore how its structure influences the evolution of drug resistance, and determines the efficacy of novel therapeutic strategies such as drug holidays or adaptive therapy. We begin by providing a comprehensive review of previous abstract modelling of the GP-mapping (Chapter 2). In Chapter 3, we demonstrate, by means of a fitness landscape model for the GP-mapping, that through careful selection of drug sequences evolution can be steered′sucht
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highlydrugresistantpopa̲tiondoes¬emer≥.InChapter4,we∫roduceanovelmodelfortheGP-mapπngwhere∈phe¬ypesaredeterminedbythes→ch∗icsiμlationofbistab≤chemicalreaction≠tworks(CRNs).Throughthismodelweexploretheevolutionarydynamicsofecologicalbet-hedging', a common driver of drug resistance wherein phenotypes are determined stochastically, demonstrating that the structure of the GP-mapping can slow the evolutionary loss of this trait, preserving the survival mechanism when harsh environments occur very infrequently. Thus, the capacity to steer the evolutionary loss of bet-hedging through drug holidays is dependent on the structure of the GP-map. In Chapter 5, the CRN model is extended to account for epigenetic inheritance and the potential for phenotypic memory in bet-hedging. Critically, we find that genetics, epigenetics and the GP-mapping interact non-additively to determine organismal fitness, indicating that evolution likely cannot be predicted without accounting for each of these biological processes. Finally, in Chapter 6, we explore how properties of the GP-mapping are manifested at the population scale and suggest experimental approaches to identify bet-hedging and phenotypic plasticity from population measurements. The implications of our results for the treatment of drug-resistant diseases are explored throughout.
Multicellular group formation in algae
Keywords: group formation
ecology
algae
multicellularity
Daphnia
aggregates
predators
clumps
social evolution

The evolution of multicellular organisms from single cells has puzzled scientists for centuries. Separating this problem into smaller steps has been illuminating. The first step is multicellular group formation and the second is group transformation into an obligate multicellular entity where cells are fixed in a multicellular lifestyle and cannot reverse back to being single cells. Relatedness among cells is known to be fundamental in this major transition to an obligate lifestyle, but the role of ecology has not been addressed to such an extent. For instance, in the ecological literature, predation is known to induce defensive group formation in freshwater algae, and this has been mainly investigated as a means of harvesting algae. However, the role of algal predation in the context of multicellularity and social evolution has not been investigated as much. I use the freshwater algae Chlorella sorokiniana, Chlorella vulgaris, and Scenedesmus obliquus exposed to the predators Ochromonas, Tetrahymena thermophila, and Daphnia magna, to address why and how algae form multicellular groups. Answering why algae form groups helps us illuminate the costs and benefits involved in this cooperative behaviour. Answering how these algae form groups helps us understand whether these algae are likely to make a transition to obligate multicellularity, since we know that all obligate multicellular organisms have evolved via cells remaining stuck to their parent cell after division, not by cell aggregation. We found that these three algal species form multicellular groups in response to the three different predators, and in three predator-prey combinations this multicellular group formation was induced just by predator cues. These multicellular groups formed via aggregation of single cells and by cells remaining attached to the parent cell after division. Also, multicellular groups could form between different algal species. This group formation is costly under conditions of limited resources in C. sorokiniana, and provides a benefit in terms of avoiding ingestion by small predators, such as Ochromonos danica, but not by the larger predator D. magna. The benefit of multicellular group formation in the latter case may be that cells in multicellular groups are better able than single cells to kill their predator once they are ingested. Finally, this group formation is reversible. These results indicate that our system has not made a major transition to obligate multicellularity, but has made the first step of facultative multicellular group formation. This facultative feature of our system has therefore been ideal in allowing us to reveal the costs and benefits of multicellular group formation.
On the origin, progression, and evolution of ovarian cancer
Keywords: Chemotherapy resistance
Tumour Evolution
Microscopic residual disease
Genetic Micro-heterogeneity
Ovarian Cancer

High-grade serous ovarian cancer (HGSOC) is amongst the deadliest of cancers. Despite decades of research on this disease, the exact mechanisms through which this carcinoma initiates, spreads, and relapses remain unclear. I believe the main reason behind this discrepancy between importance and available knowledge roots in the fact that currently available genomics methods are not sensitive enough for accurate study of limited amount of clinical materials.
To address this issue, I optimised a novel library preparation protocol called DigiPico to generate reliable next generation sequencing data from picogram quantities of DNA that can be obtained from 10-20 human cells. Moreover, I implemented DigiTitan and MutLX analysis algorithms to identify clone-specific copy number alterations and small nucleotide variations from DigiPico data. Validating MutLX algorithm using experimental and simulated data I demonstrated that DigiPico/MutLX is a uniquely sensitive, accurate, and reliable method for analysis of micro-heterogeneity in solid tumours.
Next, using DigiPico, I conducted the first accurate case study of genetic micro-heterogeneity on a collection of pre-chemotherapy tumour islets and post-chemotherapy microscopic residual disease (MRD) samples from one HGSOC patient. Analysing the results using DigiTitan and MutLX, firstly, I introduced tumour heterogeneity and genetic diversity as a hallmark of HGSOC. Secondly, based on new observations from this study, I challenged a pre-existing notion that mutations in TP53 gene are responsible for the initiation of HGSOC. I proposed that mutations in the regulatory regions that adversely affect the DNA repair machinery which can lead to subsequent large-scale genomic alterations precede the loss of TP53 function in the tumorigenesis pathway of HGSOC. Thirdly, comparing the somatic mutation load of pre-chemotherapy, MRD and recurrent tumours, I demonstrated that MRD harbours the least number of somatic mutations. Thereby, I hypothesized that MRD is likely to be composed of stem cell-like tumour cells that have survived the chemotherapy therefore suggesting that MRD is likely be the recurrence precursor. Lastly, I propose experimental approaches that are required to effectively validate or nullify these hypotheses.
Improving the prevention and outcomes of severe complications of pregnancy through international collaborative and comparative studies
Keywords: maternal obesity
abnormally invasive placenta
international comparison
postpartum haemorrhage
anaphylaxis

Background: International collaborations have been set up to complete combined and comparative studies to improve the evidence to support the prevention and management of severe and rare complications of pregnancy. The utility of such collaborative studies has yet to be tested. This DPhil aims to explore the utility of multinational studies of severe and rare complications of pregnancy.
Methods: Secondary analysis and primary data collection through an international collaboration (INOSS) were used to address four clinical research areas; extreme maternal obesity, massive transfusion in major obstetric haemorrhage, abnormally invasive placenta and anaphylaxis in pregnancy.
Results: A pooled analysis of two national studies of extreme maternal obesity enabled the examination of a rare exposure group (BMI ≥60 kg/m2). Nevertheless, the combination of two national studies did not allow the examination of the most uncommon outcomes, such as perinatal death or stillbirth. A comparison of five population-based studies of massive transfusion in obstetric haemorrhage showed that haemostatic features varied according to aetiology. It also demonstrated the large variation in blood products used between countries. A binational study on abnormally invasive placenta enabled the examination of the association between outcomes and an uncommon management in a rare complication of pregnancy. A prospective international study of a very rare complication of pregnancy, anaphylaxis, overcame the limitations of comparability and provided a more precise estimate of the causal agents and outcomes associated with this complication.
Discussion: Multinational studies are feasible and can be used to address a multitude of clinical questions. They provide the comparison of management across nations, which empowers countries to benchmark their clinical care against that of other countries. The pooling of data creates a unique examination of uncommon modalities of management and a rare exposure group. Prospective studies overcome comparability issues and provide a more robust pooled analysis.
The role of institutional investors in financing sustainable energy
Keywords: Sustainable energy
Institutional investors

In the COP 21 Paris Agreement, Parties agreed to hold the increase in the global average temperature to well below 2°C and to make finance flows consistent with a pathway towards low greenhouse gas emissions and climate-resilient development. The scale of investment needed in sustainable energy for this transformation is so large that it will, inevitably, have to rely in large part on mobilising private capital. A key potential source is the capital controlled by institutional investors. This thesis focuses on examining and improving the understanding of the role of institutional investors in financing sustainable energy, the barriers to investment, and how they may be surmounted.
One of the central contributions is the articulation of an original methodology and framework to understand and monitor what policy settings, financing instruments, risk mitigants and transaction enablers might be most effective and appropriate with regards to scaling up institutional allocations through a variety of principal investment channels. The thesis also examines the role of the debt capital markets, including the emergence of the ‘green bond’ market. I argue that if there is concerted attention by policy makers and market participants, the bond markets can be relied on as a critical foundation for mobilising institutional investors and raising part of the debt financing that will be needed for the transition to a low-carbon economy.
Underpinning the analysis is an empirical base of 110 examples of institutional investment in sustainable energy projects. It is hoped that this framework, along with the analysis, conclusions and policy recommendations, can assist in creating the fundamental settings needed to study how to scale up and mobilise greatly needed flows of this type of investment.
Diagram and dimension: visualising time in the drawings of Opicinus de Canistris (1296-c. 1352)
Keywords: historical horology
Avignon papacy
medieval diagrams
Opicinus de Canistris
calendars
medieval visual culture

This thesis focuses on the representation of time within the diagrams of Opicinus de Canistris, a cleric working in the scriptorium of the Avignon Papacy from 1329, who created a collection of fifty-two large, highly complex, unbound drawings (BAV, MS Pal. Lat. 1993). The intimidating volume and variety of information which each image displays, amalgamating amongst other elements maps, calendars, astrological tables and theological hierarchies, led their twentieth-century interpreters to conclude that Opicinus was insane. This has been to the detriment of a properly historicised interpretation of his drawings. The dissertation shows that the calendrical and cartographic features of these pictures are neither ornamental nor vague allegories of temporality and geography, but methodically constructed and meticulously measured instruments. By focusing on the calendars of the Palatinus, it demonstrates how Opicinus incorporated and creatively configured new sources, temporal and theological, derived principally from the Avignon papal court, into representations of time in order to create unique cosmologies which sought to visualise, and so better to comprehend, the metaphysical themes of time, space and God.
In addition to elucidating a selection of Opicinus’s neglected drawings, they are contextualised here in order to illustrate their value to the study of medieval visual culture. Their comparison to other sources made in Avignon shows how a particular type of diagram, which used technological renderings of time and space for an essentially theological purpose, was characteristic of the Avignon court. This indicates that Opicinus’s drawings, in their form and content, were made in response to a discussion at the court concerning the shape of the cosmos and the place of the Church within it. Their interpretation also contributes to larger questions concerning the changing perception of time and function of diagrams in the fourteenth century, whilst demonstrating how the history of technology can inform the study of visual culture.
Identification of inhibitors for a family of human oxoglutarate-dependent oxygenases
Keywords: ribosomal hydroxylase
lysine demethylases
KDM
epigenetics
oxygenases

The family of human iron- and 2-oxoglutarate - dependent oxygenases encompasses over 60 members and a subclass of the enzymes, containing Jumonji C (JmjC) domain, is directly involved in epigenetic control of gene transcription, through demethylation of methyl marks present on histone tails. Recently, JmjC-type enzymes, namely MINA53, NO66 and OGFOD, were identified as ribosomal protein hydroxylases (ROXs), broadening the known substrate set and indicating a function in the control of mRNA translation. Oxygenases are frequently implicated as key regulatory factors in various types of cancers and targeted inhibition of this class of enzymes can lead to suppressed cancer cell proliferation, opening an epigenetic avenue for therapeutic intervention by small molecules.
In order to identify novel chemical starting points for JmjC- type oxygenases we have profiled representative members of the family with two libraries of fragments by activity assays and used X-ray crystallography to explore the binding mode of identified inhibitors. The obtained X-ray crystal structure complexes with JARID1B demethylase represent 7 novel chemotypes exploring different regions of the catalytic binding site as well as a previously unidentified putative allosteric pocket. We have then focussed on the ribosomal hydroxylases NO66 and MINA53, and identified novel chemical lead compounds through a mass spectrometry based enzymatic activity assay and obtained X-ray crystal structure complexes with JARID1B demethylase of two active inhibitors of MINA53 and JARID1B (IC50 of 0.9-5 µM). The most active hydroxamic acid series has an IC50 of 900 nM towards JARID1B with a favourable selectivity profile and shows anti-proliferative effects in human myeloma cell lines.
We anticipate that our comprehensive set of fragment library activity data together with X-ray crystal structure complexes identified in this thesis can be used as starting points for further structure-based inhibitor development programs for JmjC- type oxygenases.