VictorJuiz/thesis huggingface dataset:
Modelling blood flow and oxygen transport in the human cerebral cortex
Keywords: flow simulation

Dementia, a stepwise deterioration of cognitive function, affects over 700,000 people in the UK, resulting in over 60,000 deaths and a cost of over £1.7 billion each year. It is believed to have a combination of vascular and degenerative origins and to have correlations with localised lesions, or infarctions, in the brains of affected patients. Mini-strokes are one of the causes for this disease as the presence of ischemia is highly related to the risk factors for dysfunction of the neurovascular unit. The underlying interacting mechanisms are, however, often very complex and they remain largely poorly understood.
The cerebral microvascular bed is highly irregular and localised variations in its structure are large. To capture these variations, statistical algorithms are required, rather than large volumes of expensive experimental data. Therefore, accurate modelling of blood flow and oxygen transport at the microvascular level is important in improving our understanding of the structure and function of the cerebral vasculature and hence of brain diseases.
A novel algorithm is proposed here to create artificial microvascular networks that match quantitatively experimental data previously obtained in human brain tissue. Blood flow and oxygen transport in the network and the tissue are analysed through both discretised and continuum transport models. By disabling flow sources, ischemic events can be simulated. Using multiple networks, the influence of individual network structures on the response to ischemia is analysed. The relationship between the discretised and continuum formulations of the model is quantified, providing a means for scaling up the model over multi length scales.
Finally, the phenomenon of microvessel collapse under ischemic conditions is examined and it is shown that this is fundamentally dependent upon the variability found at the network level, since it cannot be modelled by a continuum model. An initial infarction is also found to facilitate the occurrence of collapse events for most networks.
Under the hood: the mechanics of London's street gangs
Keywords: organised crime
urban violence
signaling theory
street gangs
juvenile deliquency

Based upon two years of ethnographic fieldwork in London, England, which incorporated nearly 200 interviews with gang members, gang associates, and police officers, among others, this thesis addresses three questions presently unresolved in the street gangs literature: What is the business of gangs? How are gangs organised? And how do gangs recruit? With regard the business of gangs, this thesis illustrates how recreation, crime, enterprise, and extra-legal governance represent sequential stages in the evolutionary cycle of London’s street gangs. Gang member testimony emphasises how gangs typically begin life as neighbourhood-based peer groups, but also how, in response to external threats and financial commitments, gangs grow to incorporate street-level drugs distribution businesses that very much resemble the multi-level marketing structure of direct-sales companies. People join gangs to make money, achieve status, and obtain protection. Gangs engage in turf wars, acquire violent resources, and develop hierarchical structures in order to maintain provision of these desirable goods and services. Gang organisation, in turn, becomes a function of gang business.
To better understand the nature and extent of gang organisation, this thesis moves on to discuss the presence of subgroups, hierarchy and leadership, pecuniary and non-pecuniary incentives, rules, responsibilities, and restrictions, and consequences for absconding within gangs. It further presents how, in order to convey reputation and achieve intimidation, gangs seek association with elements of popular culture that help promote their image. Finally, through the novel application of signalling theory to the gang recruitment process, this thesis demonstrates how gangs face a primary trust dilemma in their uncertainty over the quality of recruits. Given that none of the trust-warranting properties for gang membership can be readily discovered from observation, gangs look for observable signs correlated with these properties. Gangs face a secondary trust dilemma in their uncertainty over the reliability of signs because certain agents (e.g., police informants, rival gang members, and adventure-seekers) have incentives to mimic them. To overcome their informational asymmetry gangs thus screen for signs that are too costly for mimics to fake but affordable for the genuine article. The thesis concludes with a discussion of gang desistance and intervention in the context of escalating youth violence in London.
Contesting corporate social responsibility: public challenges to the modern corporation in the 21st Century 
Keywords: multinational corporations
corporate social responsibility

This thesis argues that corporations have outgrown the theoretical frameworks that were devised to explain their dynamics at the turn of the 20th century. Contemporary conditions result in crises of legitimacy between corporations and their public contexts. With their amplified scales of operation and wide-reaching physical, economic, political, and social consequences, corporations of the 21st century demand revised theoretical, legal, and pragmatic interpretations that are better suited to grappling with present-day dynamics and to addressing critical challenges. This research examines contemporary controversies between corporations and publics from a critical legal perspective. Analysis of corporate dynamics is informed by geographically oriented themes of space and scale, contingency and attribution, and materiality and risk as they bear relevance to theoretical and real enactments of the corporation. This thesis grounds its claims with reference to the Corporate Social Responsibility (CSR) discourse; taking advantage of its reach and popularity while maintaining enough distance to note its limitations and internal contradictions.
This thesis finds that the present-day account of CSR is originated and advanced by an ideological orientation that is universalizing, materialist, positivist, formalist and rationalist. Such an orientation is confronted and contested in this work by a more critical rationality that is concerned with power dynamics, as well as questions of agency and self-determination. This rationality is elaborated through four empirical chapters which find that: 1) appeals to a CSR agenda as an effective mechanism for addressing the corporation’s public impacts assumes the existence of a modern, liberal political context; 2) community ‘materiality’ presents an opportunity to bridge the notional public/private divide that is a core tenet of liberal theory; 3) the global corporation extends into plural territorialities and legal jurisdictions, and its public identity as interpreted through legal text sets the parameters for the accountability regimes devised to manage its impacts 4) pragmatist and aspirational legal agendas might be coordinated to advance issue-focused as well as case-based corporate liability reform. This work advances an account of the corporate-public relationship that carries relevance to a range of actors; corporations, public communities, policy makers and legal scholars. Each group has an integral part to play in addressing the challenges presented by the modern corporate arrangement and devising regimes that contain its public implications.
Between ‘prophet’ and ‘professional’: imagery and identification amongst beginning teachers in Lebanon
Keywords: teacher motivation
teaching
articulation power
beginning teachers
portraits
Lebanon
images
teacher education
teacher identity

This study explores the motivations, perceptions, and imagery of beginning teachers in Lebanon. It foregrounds the importance of ‘images’ as potentially useful conceptual tools for understanding the developing identities of beginning teachers.
The research consists of in-depth, semi-structured interviews in which student-teachers are encouraged to reflect on their own and other people’s views and perceptions about teaching. The thesis places the students-teachers’ personal portraits of teaching within broader cultural-historical representations of teachers in Lebanon and examines how the student-teachers deal with such representations while still in training.
The core research questions focus on the participants’ motivations as well as the underlying cultural, social, and political factors that influence their views and perceptions about teaching. The research questions were designed to explore the various images of teachers and teaching that the students draw on in their personal portraits. Biographical information as well as students’ experiences at the time of training were explored for this purpose.
The findings suggest that student-teachers’ developing identities emerge through their identification with competing images and representations of teaching and teachers. These images cut across various contexts, temporalities, and imagined settings in the student-teacher portraits, linking personal, educational and professional experiences. Many of the images synthesized large amounts of experiences and knowledge about teaching and contained gendered, religious, affective and interpersonal dimensions. Finally, the thesis offers a new way of conceptualizing images. This study hopes to help teacher education programs gain greater insight into beginning teachers’ thinking, motivations and developing identities.
The futurity compact:
Keywords: justice
time
generations
intergenerational

This thesis is about justice between people born at different times: the way in which they interact and the extent to which those interactions can be a matter of justice. Its principal aims are: to present certain theories that describe what justice over time might look like; to present certain theoretical problems for this subject; and to understand the impact of these problems upon these theories.
The thesis draws mainly upon: the work of David Hume, John Rawls and David Gauthier as sources of certain social contract theories; and the work of Wilfred Beckerman, Gustaf Arrhenius and Derek Parfit for certain problems faced by these theories. The central argument of the thesis is that the theoretical obstacles to the application of justice thrown up by the temporal dimension are not as significant as they might appear. In particular, there are good reasons to believe that social contract theories are more susceptible to intertemporal extension and less encumbered by temporally-related problems than previously thought. The conclusion of the thesis is that, issuing from a clearer view of certain theoretical obstacles to their inclusion, there is significant potential for future people to be considered within the scope of justice over time as described by certain social contract theories and that present people have self-interested reasons to take this project seriously.
Statistical mechanics of nucleic acids under mechanical stress
Keywords: Single Molecules
Theoretical Physics
Biophysics
Biomaterials
supercoiling
Computer Simulations
Statistical Mechanics
DNA

In this thesis, the response of DNA and RNA to linear and torsional mechanical stress is studied using coarse-grained models. Inspired by single-molecule assays developed over the last two decades, the end-to-end extension, buckling and torque response behaviour of the stressed molecules is probed under conditions similar to experimentally used setups. Direct comparison with experimental data yields excellent agreement for many conditions. Results from coarse-grained simulations are also compared to the predictions of continuum models of linear polymer elasticity.
A state diagram for supercoiled DNA as a function of twist and tension is determined. A novel confomational state of mechanically stressed DNA is proposed, consisting of a plectonemic structure with a denaturation bubble localized in its end-loop. The interconversion between this novel state and other, known structural motifs of supercoiled DNA is studied in detail. In particular, the influence of sequence properties on the novel state is investigated. Several possible implications for supercoiled DNA structures in vivo are discussed. Furthermore, the dynamical consequences of coupled denaturation and writhing are studied, and used to explain observations from recent single molecule experiments of DNA strand dynamics.
Finally, the denaturation behaviour, topology and dynamics of short DNA minicircles is studies using coarse-grained simulations. Long-range interactions in the denaturation behaviour of the system are observed. These are induced by the topology of the system, and are consistent with results from recent molecular imaging studies. The results from coarse-grained simulations are related to modelling of the same system in all-atom simulations and a local denaturation model of DNA, yielding insight into the applicability of these different modelling approaches to study different processes in nucleic acids.
The structure, function and specificity of the Rhodobacter sphaeroides membrane-associated chemotaxis array
Keywords: Bacterial chemotaxis
Cell signalling
Rhodobacter sphaeroides

Bacterial chemotaxis is the movement of bacteria towards or away from chemical stimuli in the surrounding media. Bacteria respond to chemotactic signals through chemoreceptors which bind specific ligands and transduce signals through a modified two-component system. Typical chemoreceptors bind a ligand in the periplasm and signal across the inner membrane to the cytoplasmic chemosensory array through the inner membrane. Bacterial chemoreceptors must integrate multiple signals within an array of different receptor homologues to a single output. Chemoreceptors act cooperatively to allow a rapid signal spread across the array and large signal gain. Chemoreceptors adapt to a signal by chemical modification of their cytoplasmic domains in order respond across a wide range of effector concentrations. How bacterial chemoreceptors transduce signals through the inner membrane, integrate multiple effector responses, signal cooperatively and adapt to result in a single output signal is not currently fully known. In Rhodobacter sphaeroides, additional complexity arises from the presence of multiple homologues of various chemotactic components, notably the array scaffold protein CheW. Decoding this signalling mechanism and heterogeneity involved in this system is important in decoding the action of a biological system, with implications for biotechnology and synthetic biology.
This study used the two model systems Escherichia coli and R. sphaeroides to analyse the mechanism of signalling through bacterial chemoreceptors. Rational design of activity-shifting chemoreceptor mutations was undertaken and these variants were analysed in phenotypic and fluorescence localisation studies. Molecular-dynamics simulations showed an increase in flexibility of chemoreceptors corresponds to a decrease in kinase output activity, which was determined by the computational tracking of bacteria free-swimming in media. Fluorescence recovery after photobleaching was used to show that this increase in flexibility results in a decrease in binding of receptors to their array scaffold proteins. A two-hybrid screen also suggested that inter-receptor affinity is also likely to decrease. These results show that signalling through chemoreceptors is likely through a mechanism involving the selective flexibility of chemoreceptor cytoplasmic domains.
Analysis of R. sphaeroides chemoreceptors and CheW scaffold proteins in E. coli showed that it should be possible to design, from the bottom-up, a functional bacterial chemotaxis system in order to analyse individual protein specificity. Expression of R. sphaeroides MCPs in this E. coli system show the reconstitution of a chemotactic array, but not one capable of signalling specifically to proposed attractants. Results gained from this system suggest the R. sphaeroides CheW proteins are not homologous and their differential binding affinities may allow array activity 'fine-tuning'.
Assessment of local networking strategies to enhance clinical research capacity in Zambia
Keywords: Networking
Online Platforms
Clinical Research
Capacity Building
Zambia

Well conducted clinical research leading to the generation of evidence based guidelines, in low- and middle-income countries has been viewed as the means of making significant improvements to global health. This is because these are the regions that bear the highest burden of disease and premature death. Several efforts over the past two decades have therefore focused on research capacity strengthening initiatives as a way of increasing the amount of clinical research conducted in these regions. The aim of this study was to evaluate if setting up a local online network and holding a skills sharing workshop would raise the knowledge and confidence of researchers in Zambia and enhance their capacity to conduct independent clinical research. This was a before and after study that involved open discussions about clinical research in Zambia through a local online platform (the Zambian Clinical Research Forum), on the Global Health Network. A total of 19 members took part in the study, 12 of whom were emerging researchers and 7 established researchers. In addition to the discussions, a one-day research skills sharing workshop was conducted after the period of the discussions that brought together those who were interested in the conduct of clinical research in Zambia. Structured questionnaires were used as the assessment tool and administered before and after the online discussions and at the workshop. The Zambian Clinical Research Forum stimulated discussions between emerging and established researchers on the conduct of clinical research in Zambia and resulted in an increase in the research self-confidence of the emerging researchers as opposed to that of the established researchers. The conduct of the one-day skills sharing workshop also enabled the sharing of information, skills and experiences based on the conduct of clinical research in Zambia. Participation in the online discussions however did not illicit a demonstrable change in the reported behaviour of the members in conducting clinical research related tasks. Furthermore, the discussions and interactions on the online platform were not continued beyond the study period. These findings indicate that the development of future network-based capacity building initiatives in Zambia should be underpinned by clear and achievable objectives that could drive the participation of those involved. There could also be a need to incorporate capacity building initiatives such as online platforms within the regular conduct of clinical research rather than as isolated ventures. This could be considered in Zambia by embedding such an online platform in institutions that can support this initiative and stimulate participation amongst their members.
Lifescapes of a pipedream: a decolonial mixtape of structural violence & resistance along the Chad-Cameroon oil pipeline
Keywords: resource extraction
human geography
political geography

People's narratives, interpretations and understandings of the Chad-Cameroon Oil Pipeline and pipeline actors emphasise the uneven exercise of power through which structural violence is effected and experienced. The complexity of the processes of structural violence along with local socio-political context and peoples' dynamic understandings thereof play major roles in shaping resistance practices, in complex ways in Kribi and Nanga-Eboko. Working from these narratives, I offer a theoretical re-articulation of structural violence as (i) tangible through the body, (ii) historically compounded, (iii) spatially compressed and (iv) enacted in a globalised geopolitical nexus by actors who are spatially nested within a racialised and gendered hierarchy of scale. Drawing from critical interdisciplinary work on violence, my theory of a triad of divergent, often interrelated and co-existing, distinguishable indexes of structural violence includes: infra/structural violence, industrial structural violence and institutionalized structural violence. The particular processes and mechanisms of uneven power within structural violence, local socio-political contexts and the epistemologies through which power is conceived (in this case I consider epistemologies of la sorcellerie, or witchcraft) inform resistance practices; I illuminate key operations (within geographies characterised by high levels of infra/structural violence) within the spatial practices of power that influence the tendency for resistance struggles to be quiet, spontaneous and/or labour-based. I conclude with a discussion of the political and intellectual value of academic work on life and being amid structural violence, emphasising the need to move beyond the invisible/visible dichotomy that has often informed intellectual work on structural violence.
Extending and combining single-molecule fluorescence methods to study site-specific recombination
Keywords: single molecule
TFM
FRET
recombinase

Förster resonance energy transfer (FRET) has become an important tool for studying biochemical reactions at the single-molecule level, despite its increasing maturity there is an on-going effort to improve and expand the technique. This thesis presents methods for extending conventional two-colour single-molecule FRET measurements; by expanding the range and applicability of single-molecule fluorescence methods a greater variety of biological reactions can be studied, in greater detail than previously possible.
To circumvent the complexities of multi-colour FRET measurements and extend the range of observable distances I developed and characterised a new single-molecule fluorescence method termed tethered fluorophore motion (TFM). TFM is based on the existing technique of tethered particle motion (TPM) which relies on Brownian motion of a particle, attached to a surface by DNA, to probe the effective length of the DNA tether. TFM takes this concept and applies it at the single-fluorophore level, allowing simultaneous measurement of other fluorescence observables such as FRET and protein induced fluorescence enhancement (PIFE).
Having developed TFM I combined it with FRET to study site-specific recombinase proteins at the single-molecule level, in greater detail than possible by either technique alone. Studying the model tyrosine recombinase Cre, I extend and clarify previous ensemble observations regarding the order of DNA strand exchange, as well as uncovering a previously unobserved complex conformation and molecular heterogeneity. Finally, I used TFM-FRET to study the more complex XerCD recombination system and its interaction with the DNA translocase FtsK. I made observations, for the first time, of synaptic complex formation and of recombination at the single-molecule level, and these suggest intriguing and unexpected intermediates in the recombination reaction. I also combine TFM with PIFE to investigate the mechanism of DNA looping by FtsK.
The introduction of TFM, and its combination with other fluorescence techniques, allows observation of complex protein-DNA interactions from a variety of perspectives and will help expand the repertoire and applicability of single-molecule biophysical experiments.