VictorJuiz/thesis huggingface dataset:
Influenza A virus: host restriction of the viral polymerase and a mechanism for vRNP nuclear export
Keywords: viral polymerase
Influenza virus
vRNP
host restriction
nuclear export protein NEP
PB2 627

Most avian influenza viruses do not replicate efficiently in human cells. This is partly due to the low activity of the RNA polymerase of avian influenza viruses in mammalian cells. However, an E→K adaptive mutation at residue 627 of the PB2 subunit of the polymerase increases the activity of avian-derived virus polymerases in mammalian cells. In contrast, purified viral polymerases containing either PB2 627E or PB2 627K show comparable levels of activity in transcription assays that do not require ribonucleoprotein (RNP) assembly. To reconcile this conflict, a nucleoprotein(NP)-independent cell based transcription/replication assay was used to assess viral polymerase activity. This indicated that PB2 627E polymerase inhibition in mammalian cells is independent of NP expression, but is dependent on the length of the viral RNA template. In addition, restriction of PB2 627E polymerase could be overcome by mutations to the viral RNA template promoter sequence. Taken together, these results suggest that PB2 627 affects interaction between the viral RNA promoter and the viral polymerase in human cells. Due to influenza viruses replicating and transcribing their genomes within the nucleus of infected cells, progeny virus production is dependent on the nuclear export of genomic RNA, in the form of viral ribonucleoprotein complexes (vRNPs). This function is carried out by the viral nuclear export protein (NEP) but the mechanism whereby this process is regulated remains unclear. Experiments measuring NEP nuclear export demonstrate that phosphorylation of a highly conserved serine-rich motif specifically up-regulates nuclear export of NEP in a manner that is conserved across viral genera. Further biophysical investigations revealed that modification of this site alters the backbone dynamics of NEP, shifting it towards an extended state that has the potential to be preferentially recognised by the cellular nuclear export machinery.
The role of the Leishmania mexicana amastigote flagellum in parasite-host interactions
Keywords: Ciliary trafficking
Electron microscopy
Parasite-host interactions

Cilia and flagella are important organelles with roles in motility and signalling across eukaryotes. Leishmania species possess both a motile 9+2 flagellum and an immotile 9+0 flagellum in different lifecycle stages. While several roles have been defined for the motile promastigote flagellum, the importance of the amastigote flagellum has long eluded understanding, but recent evidence suggests a potential role for this organelle in parasite-host interactions.
In this thesis, serial block-face scanning electron microscopy and transmission electron tomography were used to build comprehensive high-resolution models of Leishmania mexicana amastigotes within parasitophorous vacuoles and to precisely define parasite-host connectivity. This provided previously unavailable three-dimensional insight into both parasite and host structures and allowed us to propose a model of amastigote positioning during vacuole maturation. Analysis of the connectivity between the amastigote flagellum and the PV membrane identified membranous extensions of the flagellar membrane as well as evidence suggestive of vesicular trafficking.
In pursuit of functional insight into the amastigote flagellum, we assessed null mutants of components of the BBSome trafficking complex, and of the kinetoplastid-specific trafficking protein, KHARON1, for their ability to infect and replicate within macrophages to determine whether a correctly populated flagellar membrane is required for survival within the intracellular environment. Intriguingly, while KHARON1-null amastigotes were unable to survive within macrophages and exhibited a failure of cytokinesis as well as a cell-shape defect, knockout of individual BBSome components did not significantly impair survival of intracellular amastigotes.
This thesis offers insight into the complexities of intracellular survival and provides evidence which ties in with the emerging field of flagellar vesicles as a delivery mechanism for virulence factors, and has thus contributed to the complex body of evidence towards finally defining the role of the Leishmania amastigote flagellum.
Data-driven approaches enabling the design of community energy systems in the Global South
Keywords: energy access
participatory design
user-centered design
Kenya
rural electrification
service value method
representative load profiles
co-design
clustering analysis
daily electricity consumption

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.
Work, domination, and contemporary republicanism
Keywords: Workplace democracy
Domination
Republicanism
Work

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.
Epistocracy and constitutions
Keywords: Epistemic Democracy
Constituent Assemblies
Epistocracy
Democratic Theory

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.
Organising climate change adaptation
Keywords: Ghana
Climate Change
Adaptation Planning
Organisational Theory
Adaptive Capacity
Robust Action
Agriculture
Pakistan
Implementation
Social Network Analysis
Adaptation
Nepal

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.
Shadow of a taxman: how, and by whom, was the Republican government financed in the Irish War of Independence (1919-21)?
Keywords: Michael Collins
Fundraising
Eamon de Valera

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.
Geothermal urbanism: making the elemental explicit in Reykjavík
Keywords: place
Iceland
geopower
Reykjavik
urbanism
elementality
geothermal
energy
non-representational
dwelling
more-than-human

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.
Out-of-equilibrium replication and the amplification of chirality
Keywords: Out-of-equilibrium
Systems chemistry

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.
Time and being in being and time
Keywords: time
being
intelligibility
non-intelligibility
Heidegger

This thesis is about the relationship between time and being, and in particular, Martin Heidegger’s account of that relationship in Being and Time. It elaborates two central claims, in both exegetical and substantive terms, each of which challenges a dominant view of Heidegger’s work. First, most readers of Being and Time have focused upon what it says about being, and taken its claims about time as secondary. I challenge this view, arguing that for Heidegger, time is interrelated to being such that one cannot clarify the sense of the latter without first clarifying the sense of the former. I advance a novel conception of time, which I take to be the one Heidegger was working towards. Second, a prevailing interpretation of Being and Time holds that the issue at stake in Heidegger’s project is intelligibility. To be, the view goes, is to be intelligible or meaningful. Against this, I argue that the non-intelligible plays a privileged role in Heidegger’s account of what one is asking after, in asking after being.
The thesis proceeds in four chapters. In chapter 1, I investigate the connection between time and the traditional conception of being, developing in the process an account of Heidegger’s term “presence-at-hand” which shows how concerns about time frame Heidegger’s approach to the question of the meaning of being. In chapter 2, I challenge the completeness of the dominant view that for Heidegger being is the intelligibility of what is, arguing that Dasein’s fundamental disclosure of being does not procure entities at all, but a “non-intelligible” sheer presence. In chapter 3, I develop the problem with the traditional conception of time in the context of its incompatibility with Dasein’s disclosure (using Husserl’s phenomenology of time-consciousness to illustrate that the difficulty lies in successfully articulating time’s dynamism, or “flow”), as well as discussing how the dominant reading of Heidegger’s “primordial temporality” falls short in this regard. Finally, in chapter 4, I provide an interpretation of Heidegger’s primordial temporality which resolves that problem, showing how Dasein’s “ecstatic” structure is able to articulate time’s dynamism, and how as such primordial temporality grounds those other temporal characters constitutive of practical and reflective comportment.
Philosophy and religion: the hermeneutics of Paul Ricoeur
Keywords: Schleiermacher
Heidegger
Hermeneutic Philosophy
Philosophical Hermeneutics
Gadamer
Hermeneutics
Ricoeur
Biblical Hermeneutics
Revelation
Parables
World of the text
Metaphor

During the 1970s, the French philosopher Paul Ricoeur carried out two separate projects that came to be known as his philosophical hermeneutics and biblical hermeneutics. Until now, these two bodies of work have been perceived as broadly independent from one another. The current study sets out to offer a re- appraisal of Ricoeur’s hermeneutical outlook from this period, and to determine the role of religious reflection in it. By focusing on Ricoeur’s publications from 1968 to 1979, it is initially observed that his hermeneutics presents striking similarities with the, so called, Romantic model of the 19th century. Part 1 of the thesis therefore considers Ricoeur’s critique of the hermeneutical tradition and how, from the outset, he aligns his own research with the ‘universal’ principles of Friedrich Schleiermacher. It is specifically shown that Ricoeur appropriated from Schleiermacher the belief that only through a back-and-forth movement between general philosophical theory and regional interpretation can hermeneutics become a serviceable tool for the human sciences. It is further contended that, following this ‘general-regional’ outlook, Ricoeur’s hermeneutics took shape through a ‘constructed opposition’ between philosophical and biblical hermeneutics. Part 2 of the thesis provides a detailed examination of the individual investigations that Ricoeur carried out during the 1970s, in particular highlighting how his explorations of polysemy, metaphor and poetic language brought together the study of “language as discourse” and biblical exegesis. It is hoped that, by exposing the relationship between these two competing facets of Ricoeur’s hermeneutics, this research allows for a more widespread re-appraisal of the compatibility between contemporary philosophy of language and biblical textuality.
Logical factorisation machines: probabilistic boolean factor models for binary data
Keywords: Data Mining
Machine Learning
Genomics
Latent Variable Models

Logical Factorisation Machines (LFMs) are a class of latent feature models, that aim to decompose binary matrices, tensors or higher-arity relations into an approximate logical product of low rank, binary matrices. These products are defined through the use of logical operators instead of arithmetic operations. The resulting factor matrices contain interpretable patterns that lend themselves to the discovery of hidden causal structure.
We frame LFMs as probabilistic generative models and derive sampling based posterior inference. Despite full uncertainty quantification, the inference procedure scales to Billions of data points which is possible through exploitation of the logical structure in the factor conditionals.
OrMachines are a particularly interesting subset of LFMs, where a single latent cause is sufficient to explain an outcome. They represent a probabilistic approach to the well-studied problems of Boolean Matrix Factorisation and Boolean Tensor Factorisation.
The proposed model and inference procedure yield decompositions of higher accuracy than the existing techniques throughout a wide range of conditions. Real-world examples include single-cell genomics, cancer genomics, relational and spatio-temporal data. We propose several extensions, including hierarchies of OrMachines for data integration and a Bayesian nonparametric approach to infer the latent dimensionality.
LFMs with less established logics, their relationships and interpretation are considered. While the latent structure in many of these models is inherently difficult to recover, we demonstrate that certain LFMs can provide complementary representations and reveal new findings. A fast and flexible implementation is introduced and publicly available on GitHub.