VictorJuiz/thesis huggingface dataset:
Engineering rhizobacteria as synthetic biology chassis

In the next half-century the world will face an enormous food deficit due to a raising birth rate and longer life-spans of the global population. By 2050 there will be 9.5 billion people in the world who will require a 69% increase from current total food calories to prevent global starvation. Widespread hunger and starvation are linked directly to the productivity of crop growth and productivity in agriculture, especially in the third world. By 2030, Areas such as sub-Saharan Africa and Australia are predicted to have a 37% and 48% decrease in crop productivity respectively due to global warming. The first ‘Green Revolution’ increased the world’s crop output by an order of magnitude using synthetic nitrogen fertilisers derived from the Haber-Bosch process. A process which last year yielded 180 million tonnes of ammonia, 82% of which was used for the manufacture of nitrogenous fertilisers. Global usage of synthetic nitrogenous fertilisers is increasingly unsustainable and a new approach to increasing crop productivity is required to face the ever-increasing food demands over the next 30 years. In this project we have contributed to the engineering of biofertilisers and plant growth promoting rhizobacteria that could alleviate the use of inorganic fertilisers and chemicals and serve as an economically viable alternative in developing countries. Synthetic biology tools and techniques are employed to engineer two model rhizobacteria. Azorhizobium caulinodans ORS571 and Azospirillum brasilense FP2, two nitrogen-fixing and known plant-associative rhizobacteria, are used as chassis. A suite of synthetic biology tools are characterised for the two rhizobacteria species as exemplars of the toolkit being used for the engineering of other significant rhizobacteria. Advanced logic-gate based genetic circuitry is developed to yield functional genetic circuits that can be engineered with characterised plant growth promotion (PGP) effectors to yield agriculturally-relevant phenotypes. A suite of these PGP mechanisms including auxin biosynthesis, phosphate solubilisation and antifungal compound (DAPG) biosynthesis, are built and characterised in both rhizobacterial strains
The novel implementation of a CRISPR interference technology (CRISPRi) is demonstrated in both chassis. Genomic targeting of dCas9 is implemented to control the ammonia assimilation pathway of A. brasilense FP2 with the effect of significant ammonia release into growth media. This work builds the foundations for the future engineering of both logical genetic circuitry and the CRISPRi system with an input from a unique associative crop plant signal. This will allow a rhizosphere-specific phenotypic switch of the rhizobacteria from a fast-growing competitive state to a plant beneficial ammonia secreting state.

Advisor: Poole, P
Data-driven approaches enabling the design of community energy systems in the Global South

This thesis answers the primary research question:
What techniques can be developed to address the challenges of context specificity and replication at scale in the design of electricity access systems suitable for rural, low-income communities in the Global South?
This is addressed through two sub-questions:
1. To build electricity access systems that are suitable for specific contexts, how can we take account of end-user needs, aspirations, and context in the design process?
2. To support replication of electricity access systems at scale, how can we use time series electricity demand data coupled with demographic data to estimate electricity demand for these communities?
Five techniques are developed. The first is the Service Value Method, which gathers and integrates end-user needs, aspirations, and context into engineering design practice. It incorporates data-gathering methods suitable for Global South contexts.
The remaining four techniques relate to how electricity and demographic data can be used to estimate electricity demand for new communities, supporting replication of systems at scale. Time series electricity data are linked to household demographic data, and exploited to estimate a) daily electricity consumption (relevant for battery-charging systems), and b) daily load profiles (relevant for micro-grids). For each demand metric, the approach is to retain the variation in electricity use for each household across different days.
Throughout this thesis a case study from Kenya of lighting electricity data from households using two solar nano-grids is used to demonstrate these techniques. Results from the case study, comprising a dataset of household lighting electricity data, and the typical use patterns derived from them, contribute to demand estimation research for these contexts.

Keywords: energy access
participatory design
user-centered design
Kenya
rural electrification
service value method
representative load profiles
co-design
clustering analysis
daily electricity consumption
Advisor: McCulloch, M
Characterising early human lympho-myeloid haematopoietic progenitors and their relationship with acute myeloid leukaemia stem cells

Haematopoiesis is a quintessential cellular hierarchy, with the haematopoietic stem cell having the ability to produce all blood cells. Downstream of the stem cell are multiple progenitor populations with increasing lineage-restriction. However, our knowledge of the progenitors that produce the lymphoid and myeloid lineages remains incomplete. Furthermore, in acute myeloid leukaemia there is a differentiation arrest at the lympho-myeloid progenitor stage, with the development of a progenitor-like leukaemia stem cells. A thorough comparison of the progenitor-like leukaemia stem cell with normal stem and progenitor cells is yet to be completed.
Presented here is a comprehensive study of the lympho-myeloid progenitors in both normal and leukaemic haematopoiesis. Firstly, the normal lympho-myeloid progenitors were fully characterised, both functionally and transcriptionally. Extensive single-cell analysis allowed the heterogeneity and continuum underlying lympho-myeloid differentiation to be uncovered. Although the majority of single-cells generated only one mature lineage, rare multi-lineage single-cells were detected.
The lympho-myeloid progenitors were then studied in acute myeloid leukaemia. It was demonstrated that there is often an expansion of the lympho-myeloid progenitors, which develop leukaemia-propagating ability. Transcriptionally, it was seen that the leukaemia stem cells displayed dysregulated expression profiles, whilst retaining some resemblance to the normal progenitors. A set of genes upregulated in the leukaemia stem cell was identified, and it was proposed that six of these genes may play a role in leukaemogenesis.
Studying both normal and leukaemic haematopoiesis is essential in advancing the treatment of acute myeloid leukaemia. Firstly, a more thorough understanding of the process of normal lympho-myeloid differentiation may aid the development of differentiation therapies. Secondly, by identifying functionally relevant markers of the leukaemia stem cell, treatments targeting the apex of the leukaemic hierarchy may be developed. And through the eradication of the leukaemia stem cell, we may truly eliminate the leukaemic disease.

Advisor: Vyas, P
Mead, A
Work, domination, and contemporary republicanism

Republicanism - in particular the 'Roman' or 'neo-Roman' republicanism of Philip Pettit and Quentin Skinner - has brought notions of domination and power to the forefront of political philosophy. Its proponents argue that non-domination is a radical ideal, one that is demanding and practical, and which can ground an effective and open-ended "normative and institutional research program". I hope to show that non-domination in the sense envisioned by most mainstream republicans is indeed a radical ideal, but one that requires much more substantial change than many of those republicans envision. Specifically, this thesis intervenes in ongoing debates within and around contemporary republicanism about the demands of non-domination when it comes to the organisation of work. It has both a critical and a constructive element. Where they pay attention to the organisation of work at all, the typical republican strategy involves little more than strong workplace regulation and some very limited mechanisms of worker voice. This set of proposals is coupled with tentative support for a universal basic income, or other ways of lowering the exit costs of any given job. After defending the application of personal accounts of domination to the world of work, I critically assess this mainstream republican approach to the workplace before arguing in favour of two broad strategies that better satisfy a commitment to non-domination: the pursuit of workplace democracy and the reduction of work. I argue that both strategies ought to be cornerstones of an anti-domination approach to the workplace, whether from a republican perspective or not.

Keywords: Workplace democracy
Domination
Republicanism
Work
Advisor: Frazer, E
Epistocracy and constitutions

Recently, some political commentators and academics have suggested that we should replace democracy with ‘epistocracy’, or rule by the competent. Drawing on historical case studies in Britain, India and the United States, the first part of this thesis sheds light on the use of franchise restrictions, legislative office qualifications, and indirect elections as epistocratic mechanisms concerned with competence in the legislative assembly. The second part of the thesis offers a normative critique of each of these mechanisms, demonstrating why these would be either self-defeating or simply futile from an epistemic perspective.

Keywords: Epistemic Democracy
Constituent Assemblies
Epistocracy
Democratic Theory
Advisor: Frazer, E
Organising climate change adaptation

Current efforts by nation-state governments to organise adaptation in developing countries are characterised by a broad concern with defining, measuring and governing adaptation efforts, with surprisingly little on how these efforts are organised and implemented through the different participant organisations. In this thesis, I develop an organisation-centred perspective based on the three distinct and relatively independent literatures of climate change adaptation, organisation theory and network analysis to study the emerging adaptation initiatives in developing countries. I use the term ‘organising adaptation’, to focus analytical attention on the organisational architectures and linkages that are critical, to develop coordinated responses, and to move forward from policy and plans to practical action. I present my results in four empirical papers from a detailed study of organising climate change adaptation in the agriculture sector in Ghana, supplemented with analysis from Nepal and Pakistan. I adopt a ‘granular’ and ‘nested’ design, backed by extensive empirical field data to analyse the effect and connectedness of key organisations in adaptation from local to national planning levels. The results show that the planned structures take on an organisational form composed of many component organisations (I refer to them as ‘meta-organisation’), but these structures are out of alignment with the requirements needed to address challenges posed by climate change. The component organisations in turn form implicit sub-groups (I refer to them as organisation-communities) and take on specific roles that are asymmetric and the challenges are often articulated in way that conflicts with, or thwarts, other capacity, leading to gaps in potential adaptation action. The findings of the papers emphasise that organisations and their relationships matter greatly but that it is also important to examine how these organisations work and what they do within the wider networks involved in adaptation.

Keywords: Ghana
Climate Change
Adaptation Planning
Organisational Theory
Adaptive Capacity
Robust Action
Agriculture
Pakistan
Implementation
Social Network Analysis
Adaptation
Nepal
Advisor: Thornton, T
Ventresca, M
Gaussian process arc lengths, functional regression and applications

This thesis presents novel functional regression methods for non-linear data and develops core Gaussian Process theory for arc lengths. The need for richer functional regression methods and theory around Gaussian Process arc lengths is established in the introduction.
Chapter 1 commences with the requisite background material and Chapter 2 works through the fundamentals of probability, highlighting key messages with a worked example. Gaussian Processes are introduced in Chapter 3, developing the core theory needed to extend the functional methods outlined in Chapter 4 and to prepare for considering the arc length dis- tribution of Gaussian Processes.
Three novel Gaussian Process functional regression models are introduced in Chapter 5, building upon existing models and furthering the probabilistic approach to functional regression, namely the Gaussian Process Functional Index Model, the Gaussian Process Functional Additive Model and the Gaussian Process Functional Generalised Additive Model. In each model a kernel function is derived whilst outlining inference and prediction. It is clearly demonstrated that the functional regression models out perform their competitors on synthetic examples.
In Chapter 6, the arc length distribution of a Gaussian Process is de- rived. By tackling the arc length integrand, a novel approach to the one dimensional arc length mean is presented. This equips us with the tools to approximate the arc length of a vector Gaussian Process. We derive the arc length distribution for a prior and posterior Gaussian Process in terms of its kernel functions and hyperparamaters.
Chapter 7 signals a return to functional regression where two challenging real world functional data sets are tackled. The novel Gaussian Process methods provide competitive results in a number of cases, supporting the potential for the new methods.
The thesis concludes with a vision for future work.

Advisor: Osborne, M
Roberts, S
Shadow of a taxman: how, and by whom, was the Republican government financed in the Irish War of Independence (1919-21)?

The Irish War of Independence (1919-21) was a guerrilla war between the IRA, loosely under the command of the underground Irish republican government known as Dáil Éireann, and the forces of the British government in Ireland. Eager to project itself as a legitimate government, the Dáil decided to raise funds by selling war bonds. These bonds promised a return to subscribers only when British forces had left Ireland and an independent Irish Republic was internationally recognised. Known as the National Loan and External Loans, these bonds raised £370,165 in Ireland and nearly $6m in America. This thesis explores the funding of Dáil Éireann during the Irish War of Independence, showing how its funds were solicited, collected, transmitted and safeguarded, as well as who the subscribers were and what might have influenced their subscriptions.
Section I explores the Dáil’s fundraising in Ireland, while Section II covers the funds collected overseas. Chapter 1 introduces the National Loan, placing it in the context of previous nationalist fundraising in Ireland. Chapter 2 explores the organisational structure that underpinned the loan campaign and chapter 3 analyses the ways in which the loan was promoted. Using previously unknown archival material, chapter 4 investigates the identities of its subscribers. Section II begins with chapter 5, which gives an overview of the history of Irish nationalist fundraising in America. Chapter 6 outlines the organisational landscape in which the First External Loan was promoted. Its promotion is covered in chapter 7, and chapter 8 looks at the internal dynamics of the External Loan organisation. In chapter 9, attention is paid to the identities of subscribers to the First External Loan. Chapter 10 then focuses on the Dáil’s Second External Loan, relating it to the Anglo-Irish peace negotiations. Finally, chapter 11 explores the Dáil’s fundraising in Argentina.

Keywords: Michael Collins
Fundraising
Eamon de Valera
Advisor: O'Rourke, K
Paseta, S
Geothermal urbanism: making the elemental explicit in Reykjavík

This research explores the distinct places shaped by human processes and proximity to geothermal heat. It underlines the concept of elementality as critical for understanding energy, the urban, and everyday life. Advancing from the rematerialistion of geography it draws upon approaches to other geo urban phenomena through relational and more-than-human terms. This has emphasised networked, assembled, and processual understandings; through which a distributed agency concerning the human and non-human alike has been utilised to foreground a geologic vitality. With a focus on Reykjavík in Southwest Iceland, attention is turned to the sites of infrastructures, architectures, and human bodies. It examines the distinct materialities of Reykjavík's geothermal urban environ; their relational properties, elemental capacities, and the palpable affective sense of place that arises as the geothermal is articulated through the urban form. It engages a more-than-representational methodology: utilising video, photography, and interviews with Reykjavík's inhabitants. Field materials provide a detailed illustration of the city's emergent geothermal urban lifeworld. As 'surfacing', geothermal urbanism is revealed as a geosociotechnical process. As 'atmospheric', it is experienced as gathered, elementally infused, and palpable. As 'affective', the geothermal urban is understood as embroiled with an embodied geothermal elementality, tracking the processual and the atmospheric. These findings culminate in a necessary revision of the geothermal field from an exclusively chthonic entity; extended beyond the subterranean into the urban, and understood as atmospheric and affective. Additionally, a discrete geothermal form of geopower is identified. This advances a non-carbon geologic agency, intersecting the geological and the affective. Geothermal urbanism is established as requiring a geosociotechnical ontology, an elemental epistemology, and characterised by distinct practices of embodied dwelling.

Keywords: place
Iceland
geopower
Reykjavik
urbanism
elementality
geothermal
energy
non-representational
dwelling
more-than-human
Advisor: McCormack, D
Greenhough, B
Malarial molecular chaperones of the Plasmodium falciparum infected erythrocyte

Resistance to common antimalarials is growing, resulting in the need to develop new therapeutics with the aim of disease elimination. Here we present the malarial molecular chaperones of the Plasmodium falciparum infected erythrocyte as potential drug targets and provide structural information for structure-based drug design. The parasite exports a single Hsp70 into the erythrocyte, PfHsp70-x, which has been linked to virulence. PfHsp70-x colocalises in J-dots with two parasite Hsp40 proteins – PFA0660w and PFE0055c. PFA0660w is a specific stimulator of PfHsp70-x whilst PFE0055c can also stimulate the activity human chaperones.
In this thesis, it was shown that PfHsp70-x is important in the parasite’s response to heat shock at certain stages of the intraerythrocytic life cycle. The ATPase domain of PfHsp70-x was structurally determined using X-ray crystallography and a unique druggable pocket was discovered. Numerous commercially available Hsp70 inhibitors were found to successfully inhibit the basal and/or the Hsp40 stimulated activity of PfHsp70-x. A combination of X-ray crystallography, biochemical assays and biophysical methods were employed to characterise the interaction of PfHsp70-x with PFA0660w and PFE0055c to understand the specificity of stimulation.
The role of PfHsp70-x in protection and proliferation of the parasite, alongside the inhibition of PfHsp70-x by available Hsp70s inhibitors, demonstrates the possibility of repurposing chaperone inhibitors as antimalarials. Differential interactions of PfHsp70-x with its cochaperones provide a route for specifically targeting PfHsp70- x as Hsp70 proteins require stimulation by a Hsp40. The work presented here characterises just a part of a wider network of chaperones likely formed of parasite proteins and hijacked human chaperones.

Advisor: Vakonakis, I
Out-of-equilibrium replication and the amplification of chirality

This thesis explores physical autocatalysis, or the replication of supramolecular aggregates of surfactants such as micelles. There is a focus on the out-of-equilibrium and non-linear behaviours that can be extracted from a process of physical autocatalysis and which characterise lifelike dynamics and properties.
Chapter 2 describes a study of reversibly-formed surfactants which form micelles within a dynamic combinatorial library. Though the system does not demonstrate a process of replication, the study of surfactants containing reversibly-formed bonds is of use towards the design of an out-of-equilibrium replicator. Thus, Chapter 3 describes the development of a physical replicator constructed by thiol-disulfide exchange which can persist, out-of-equilibrium, by the consumption of a chemical fuel, mimicking dissipative biological structures.
The second half of this thesis introduces an ambitious design for a process of physical autocatalysis with amplification of chirality. Chapters 5 and 6 detail two experimental attempts. Chapter 5 describes the study of a chiral surfactant constructed by a native chemical ligation reaction, which shows interesting differences in reactivity between homogeneous and biphasic reaction conditions. However, a process of replication is not observed, nor the amplification of chirality. A more successful system is the study in Chapter 6 on the formation of a chiral surfactant based on the autocatalytic reaction studied in Chapter 3. An interesting sense of asymmetry is established; the chiral surfactant appears to be autocatalytic and partitions into a precipitate of enhanced ee and a solution phase of diminished ee.

Keywords: Out-of-equilibrium
Systems chemistry
Advisor: Fletcher, S
Kukura, P
Situation awareness in medical practice

Situation awareness (SA) is a cognitive skill which has been studied extensively in military and industrial settings. Recent studies have shown that errors in SA commonly underpin adverse incidents in healthcare but there is little data to improve our understanding of how to measure or improve SA in clinical settings.
The aim of this thesis was to draw attention to the importance of SA in healthcare and to provide insights into how we might better train multidisciplinary teams in acute care settings. Error in healthcare and research into SA were reviewed and a novel, holistic method for the analysis of the role of SA in the evolution of error in an acute care setting was devised. A systematic review of tools for the measurement of non-technical skills (NTS) was undertaken and this informed a study to assess the reliability and usability of such tools in the measurement of SA. The final study involved the analysis of a variety of different techniques for the measurement of SA in teams from adult intensive care (AICU).
The results revealed that SA errors were present in 96% of serious incidents in a large teaching hospital in the NHS. Challenges were highlighted in the measurement of NTS in healthcare including: 76 measurement tools, revealed by the systematic review, with great variability in quality of design and psychometric testing; low levels of reliability amongst expert raters using these tools and limited evidence of validity for direct and indirect measures of SA in simulated scenarios for teams from AICU.
This work has revealed that SA errors are common in acute care settings and that there are significant challenges in the reliable measurement of SA. Future work should focus on improving measurement of SA and intelligent targeting of teamwork training which highlights the importance of SA and forms part of a system wide safety strategy in the NHS.

Advisor: Vincent, C
Young, D