VictorJuiz/thesis huggingface dataset:
The role of innate lymphoid cells in intestinal inflammation

A breakdown of intestinal homeostasis due to dysregulated immune responses against intestinal bacteria underlies the pathogenesis of inflammatory bowel disease (IBD) in genetically susceptible individuals. Amongst mucosal immune cells, innate lymphoid cells (ILCs) are a heterogeneous group of cells whose functions in pathogenic inflammatory processes in the intestine are beginning to emerge from experimental murine models. However, less is known about the role of ILCs in chronic intestinal inflammation in humans.
In this thesis, human ILCs were examined in the context of IBD and potential mechanisms by which these cells may contribute to IBD pathogenesis were investigated. We identified phenotypically and functionally distinct ILC1, ILC2 and ILC3 populations in the human intestinal lamina propria and peripheral blood and found that ILCs enriched for expression of IL-17A and IFNγ accumulated in the inflamed intestine, potentially through increased in situ proliferation and chemokine-mediated recruitment from blood. Based on their in situ localization, we investigated potential functional interactions between ILCs and CD4+ T cells and found that a proportion of human ILCs in peripheral blood and the intestinal lamina propria expressed HLA-DR and co-stimulatory molecules. ILCs were capable of taking up and processing protein antigen at levels equivalent to B cells, but in contrast to monocytes, antigen-pulsed ILCs failed to activate antigen-specific memory CD4+ T cells in vitro. Reciprocal activation between ILCs and monocytes enhanced the antigen-presenting potential and bactericidal capacity of myeloid cells and induced upregulation of co-stimulatory ligand expression by ILCs. This innate activation loop resulted in an augmentation of CD4+ T cell activation.
These findings extend our knowledge of the complex interactions between human ILCs and other key immune cell populations, and suggest mechanisms by which rare ILCs may contribute to the pathogenesis of IBD by augmenting myeloid cell and CD4+ T cell responses.

Keywords: Inflammatory bowel disease
Innate lymphoid cells
Advisor: Uhlig, H
Powrie, F
IRF5 in defining inflammatory macrophages: studies in vitro and in vivo

Macrophages are an integral part of the innate immune system and key players in pathogen clearance and tissue remodelling. Both functions are accomplished by a heterogeneous network of diverse macrophage populations that display pro- and anti-inflammatory properties. Understanding the molecular pathways that control this heterogeneity should provide abundant scope for the generation of more specific and effective therapeutics.
Previously, our laboratory identified the transcription factor interferon regulatory factor 5 (IRF5) as the master regulator of the pro-inflammatory phenotype in human in vitro differentiated macrophages. Here, we show that murine macrophages with pro-inflammatory capacities in vitro and in vivo are also characterised by high levels of IRF5. IRF5 is upregulated in vitro in response to inflammatory stimuli such as GM-CSF and IFN-γ and in a subset of in vivo macrophages in the arthritic knee joint during the model of antigen-induced arthritis (AIA). IRF5 is also expressed in other myeloid cells in vivo, especially in Ly6Chi monocytes and to a lesser extent in dendritic cells and neutrophils.
We furthermore explored the role of IRF5 and IRF5-expressing macrophages in acute inflammation using two different models, AIA and acute lung injury, which are characterised by an extensive initial influx of neutrophils. Mice lacking IRF5 display reduced disease severity and decreased signs of inflammation in both models. Specifically, far fewer neutrophils accumulate at the site of inflammation. We investigated the molecular mechanisms underlying this phenomenon and discovered that IRF5-/- mice produced reduced levels of chemokines important for neutrophil recruitment, such as CXCL1. These studies extend our knowledge of the IRF5 expression pattern in vivo and suggest that in addition to the previously proposed role of IRF5 in chronic inflammation, it also has an important function in orchestrating initial acute responses. Thus, IRF5 blockade may be beneficial for both acute and chronic inflammation.

Advisor: Udalova, I
The politics of implementing e-government for development: the ecology of games shaping property tax administration in Bangalore city, India

The recent global diffusion of information and communications technologies (ICTs) has raised expectations for technological change to support socio-economic progress and political reform in the developing as well as the developed world. Particularly prominent is the promise of ICT platforms and applications that enable innovations in electronic government (e-government), since their implementation and use in the public sector are often linked to organizational and administrative reforms.
Much has been written about e-government within a growing stream of literature on ICT for development, generating countervailing perspectives where optimistic, technocratic approaches are countered by far more sceptical standpoints on technological innovation. This body of work is not without its limitations: a large proportion has been anecdotal in its style and overly deterministic in its logic, with far less being empirical, and there is a tendency for models offered up by scholarly research to neglect the actual attitudes, choices and behaviour of the wide array of actors involved in the implementation and use of new technology in real organisations.
To address these shortcomings, this research sought to focus on an empirical case study surrounding the implementation and use of an electronic property tax collection system in Bangalore, India between 1998 and 2008. Early work reinforced the need to move beyond technologically deterministic explanations of the project, prompting the study to draw on the theoretical perspective of the 'Ecology of Games' which (being close to theories of New Institutionalism) recognises the importance of a multitude of diverse motives and individualistic behaviour as key factors influencing organisational reform and institutional change.
This thesis thus contributes not just to an understanding of the role of ICTs in administrative reform in development, but towards an emerging body of research that is critical of managerial rationalism for an organization as a whole, and sensitive to an ecology of actors and motivations within the organisation. The core research findings of the work question the received wisdom prevalent in current political and development discourse that all actors on such projects, operating within a given game arena or game ecology possess a global, rational perspective on the role of technology, both in government and within their particular domain specialism; suggesting that both scholars of e-government and top management would do well to recognise and seek to understand the complex web of varying actor interests and motivations inherent within ICT-fordevelopment projects.

Keywords: Ecology of Games
Strategic Choice Architecture
Political Game Theory
Behavioural Economics
Design-Actuality Gap Model
Advisor: Dutton, B
Gooptu, N
Eschatology, crusade and reform in English historical writing, c.1180-c.1220

The extraordinary proliferation of historical writing in late twelfth-century England has attracted much comment, but defies straightforward explanation. As such, this thesis makes no attempt at an all-encompassing elucidation of this diverse range of texts; it seeks instead to study one feature of some of the chronicles produced at this time, just as other studies have illuminated, for instance, the concern for administrative history shared by a number of chroniclers. The feature in question is a marked eschatological awareness. We may identify three factors that contributed to this. First, the fall of Jerusalem and the crusading movement spurred several chroniclers to relate events to the broader arch of Christian history. Against this same backdrop the distinctive Calabrian thinker Joachim of Fiore constructed a radical revision of the Augustinian theology of history; but to contemporaries he presented a simplified though no less influential scheme of history according to which the reign of Antichrist would shortly begin. This was demonstrably an influence on several English chroniclers, who reported his ideas with considerable interest. Joachim was also influential on the papacy: Innocent III co-opted his ideas to propound the crusading and reformist goals that he shared with, and had probably absorbed from, a group of contemporary Parisian theologians, of whom Peter the Chanter was the most important. The reform movement, which rapidly transcended its scholastic origins, was also reported with great interest by English chroniclers, and informed their writing as much as Joachim's ideas had; the two were arguably different sides of the same coin. It is with these various interrelated developments in late twelfth-century Europe, and their impact upon contemporary English historiography, that the present thesis is concerned.

Advisor: Sharpe, R
Terahertz cavity cooling for cuprate superconductors

Optical cooling is a well-established class of methods for reducing the temperature of a wide variety of atomic, mechanical and condensed matter systems. In this thesis, we demonstrate that it may be possible to cool the fluctuations of the Josephson phase in a cuprate single crystal by the application of coherent terahertz radiation. Such cooling strengthens the superconducting state as measured by switching current distribution, and may lead to an enhancement of the transition temperature Tc
We develop a parametric cooling scheme for bilayer cuprates in which intense terahertz driving produces a modulation in the dielectric material properties. This modulates the coupling between interlayer and intralayer Josephson plasmons which we exploit to upconvert thermal fluctuations of the Josephson phase and reduce their effective temperature. We quantify this as the suppression of the fluctuations in both position and momentum quadratures, and additionally via simulated switching current measurements. We predict a reduction in temperature of 30% given realistic material parameters, and identify the cuprates YBCO and TBCCO-2201 as candidate materials in which this effect may be observed experimentally.
With a view to developing cavity cooling schemes, we study the coupling between the Josephson modes and the electromagnetic modes of an external cavity. Following a review of the literature, we examine in detail a specific microcavity array geometry which is expected to provide a large coupling through minimisation of the mode volume. Numerical calculations using finite element methods and an effective dielectric model suggest that strong coupling with g / ωp &Tilde; 0.2 can be achieved using this geometry.

Advisor: Jaksch, D
In vitro, in silico and in vivo studies of the structure and conformational dynamics of DNA Polymerase I

DNA polymerases are a family of molecular machines involved in high-fidelity DNA replication and repair, of which DNA polymerase I (Pol) is one the best-characterized members. Pol is a strand-displacing polymerase responsible for Okazaki fragment synthesis and base-excision repair in bacteria; it consists of three protein domains, which harbour its 5’-3' polymerase, 3’-5’ exonuclease and 5’ endonuclease activities.

In the first part of the thesis, we use a combination of single-molecule Förster resonance energy transfer (smFRET) and rigid-body docking to probe the structure of Pol bound to its gapped-DNA substrate. We show that the DNA substrate is highly bent in the complex, and that the downstream portion of the DNA is partly unwound. Using all-atom molecular dynamics (MD) simulations, we identify residues in the polymerase important for strand displacement and for downstream DNA binding. Moreover, we use coarse-grained simulations to investigate the dynamics of the gapped-DNA substrate alone, allowing us to propose a model for specific recognition and binding of gapped DNA by Pol.

In the second part of the thesis, we focus on the catalytically important conformational change in Pol that involves the closing of the ‘fingers’ subdomain of the protein around an incoming nucleotide. We make use of the energy decomposition method (EDM) to predict the stability-determining residues for the closed and open conformations of Pol, and test their relevance by site-directed mutagenesis. We apply the unnatural amino acid approach and a single-molecule FRET assay of Pol fingers-closing, to show that substitutions in the stability-determining residues significantly affect the conformational equilibrium of Pol.

In the final part of the thesis, we attempt to study Pol in its native environment of the living cell. We make use of the recently developed method of internalization by electroporation, and optimize it for organically labelled proteins. We demonstrate the internalization and single-molecule tracking of Pol, and provide preliminary data of intra-molecular FRET in Pol, both at the single-cell and single-molecule levels. Finally, by measuring smFRET within an internalized gapped-DNA construct, we observe DNA binding and bending by endogenous Pol, confirming the physiological relevance of our in vitro Pol-DNA structure.

Keywords: single-molecule spectroscopy
in-cell FRET
single-molecule FRET
Advisor: Kapanidis, A
Efficiency and other-regarding preferences in information and job-referral networks

In this thesis I study how networks are formed and I analyse the strategies that well-connected individuals adopt in public good games on a network.

In chapter one I study an artefactual field experiment in rural India which tests whether farmers can create efficient networks in a repeated link formation game, and whether group categorisation increases the frequency of in-group links and reduces network efficiency. I find that the efficiency of the networks formed in the experiment is significantly lower than the efficiency which could be achieved under selfish, rational play. When information about group membership is disclosed, in-group links are chosen more frequently, while the efficiency of network structure is not significantly affected.

Using a job-referral network experiment in an urban area of Ethiopia, I investigate in chapter two whether individuals create new links with the least connected players in the network. In a first treatment, competition for job-referrals makes it in the player’s interest to link with the least connected partners. In this treatment, links to the least connected players are significantly more likely than links to better connected individuals. In a second treatment, connections only affect the welfare of the new partner. Choosing the least connected player minimises inequality and maximises aggregate efficiency. This may motivate other-regarding players. In this treatment, however, links to least connected partners are not significantly more likely than links to other players.

In chapter three I explore the characteristics that individuals value in the people they approach for advice. Using cross-sectional data on cocoa farmers in Ghanaian villages and a matched lottery experiment, I find an association between the difference in the aversion to risk of two farmers and the probability that one farmer is interested in the advice of the other farmer.

In chapter four I study a one-shot public good game in rural India between farmers connected by a star network. Contributions by the centre of the star have a larger impact on aggregate payoffs than contributions by the spoke players. I use the strategy method to study whether the centre of the star contributes more than the average of the spokes. In selected sessions, I disclose participants’ expectations about the choices of the centre of star. I find that the centre player contributes just as much as the average of the spokes, and that he is influenced by the expectations that other players hold about his decisions.

Keywords: lab-in-the-field experiment
public goods
social networks
other-regarding preferences
Advisor: Fafchamps, M
Abeler, J
Three-dimensional aligned fibrillar scaffolds -- fabrication and characterization

Aligned fibrillar scaffolds (AFSs) have been widely studied for their application in regenerative medicine, providing possible transplantable tissue replacements for nerve, spinal cord, tendon, ligament, muscle, etc. However, researches in AFSs are technically challenging mainly due to the complex fabrication and characterization processes, especially when the AFSs are made to be fully three-dimensional (3D). As the structure is linked to the quality and function of the engineered tissue product, there is an urgent need for novel techniques to characterize AFSs non-invasively and non-destructively and to link their characteristics to their functions and outcome.

In this thesis AFS fabrication and characterization were explored. By combining second harmonic generation (SHG) imaging, multiphoton microscopy (MPM), and various image processing tools, the whole process of 3D tissue characterization could be achieved in a non-invasive, precise, and quantitative way. A proof-of-concept AFS with blended fibers made of polycaprolactone and porcine gelatin was used to demonstrate the feasibility of implementing such a strategy. The data indicated that, in terms of scaffold characterization, the proposed MPM method was capable of measuring the porosity of homogenous scaffolds precisely from deconvolved 3D images. Furthermore, the method could also be used to illustrate the orientation of the aligned nanofibers. Next, when SH-SY5Y neurons were cultured on the AFS, the MPM imaging was capable of evaluating the cell viability ratio, cell-localization in AFS, and neurite outgrowth. This provided guidance for selecting the alignment method for AFS functional recovery. Lastly, when employing this non-invasive imaging-based characterization method, it was possible to illustrate the relationship between the alignment of collagen arrays in decellularized corneal stroma and the transparency. In summary, the proposed strategy can provide some essential scaffold/tissue properties (such as alignment of fiber, porosity of scaffold, and cell viability ratio) quantitatively and non-invasively, which will help both scaffold processing design and characterization.

Keywords: electrospinning
multiphoton
second harmonic generation
Advisor: Ye, H
Cui, Z
The impact of international actors on domestic agricultural policy : a comparison of cocoa and rice in Ghana

The global financial and food crisis of 2007 and 2008 was followed by a surge in foreign interest and investment in African agriculture. Renewed global interest in African agriculture was also accompanied by an increase in international efforts to influence domestic agricultural policies, including in Ghana. In the context of an increasingly globalised food regime and integrated commodity markets, this thesis answers the question: to what extent do international actors impact domestic agricultural policies in Ghana?
Policy ‘impact’ is understood as the marked influence that international actors have on policy goals and the resources, institutions, and knowledge used for achieving them. This thesis compares case studies of cocoa and rice policy over two different periods in Ghana’s recent history (1983-1995 and 2003-2012) to understand how international actors use their power and resources to impact agricultural policies. The comparison of cocoa and rice policy is used to address two gaps in existing literature by examining how the impact of international actors relates to: 1) the political economy for a specific crop; and 2) the interaction between actors at international, national and local levels. Findings from the comparative analysis are then used to test existing theories for how international actors influence government policy in Africa more generally. In particular, findings provide new insights into how the impact of international actors on African agricultural policies is strongly associated with the effect of policy decisions on the longer-term political economy for a particular crop.

Advisor: Mustapha, A
Absolute distance interferometry capable of long-term high frequency measurements of fast targets

This thesis presents two novel absolute distance measurement techniques which expand the recently developed dynamic frequency scanning interferometry method [1][2][3]. Preliminary work to improve the frequency referencing of the techniques will also be reported.
The first method was developed to eliminate gaps in the distance measurement which were present in previous approaches and is referred to as continuous frequency scanning interferometry (continuous FSI). This technique has been successfully demonstrated on stationary targets at a range of 2.5–5 m and moving targets at speeds around 2 mm/s and 8 mm/s.
The second method is referred to as enhanced continuous FSI (enhanced CFSI). It addresses one of the main limitations of the continuous FSI technique by greatly increasing the allowable target motion speed. Proof of principle measurements of enhanced continuous FSI have been performed at speeds of up to 16 mm/s and are presented here.
The improved frequency referencing technique uses an optical nanofibre to perform saturated absorption spectroscopy of acetylene-13. The equipment, experimental procedure and preliminary results are presented.

Keywords: absorption spectroscopy
laser interferometry
absolute distance measurement
metrology
Advisor: Reichold, A
Ultrasound segmentation tools and their application to assess fetal nutritional health

Maternal diet can have a great impact on the health and development of the fetus. Poor fetal nutrition has been linked to the development of a set of conditions in later life, such as coronary heart disease, type 2 diabetes and hypertension, while restricted growth can result in hypogylcemia, hypocalcemia, hypothermia, polycythemia, hyperbilirubinemia and cerebral palsy. High alcohol consumption during pregnancy can result in Fetal Alcohol Syndrome, a condition that can cause growth retardation, lowered intelligence and craniofacial defects. Current biometric assessment of the fetus involves size-based measures which may not accurately portray the state of fetal development, since they cannot differentiate cases of small-but-healthy or large-but-unhealthy fetuses.

This thesis aims to outline a set of more appropriate measures of accurately capturing the state of fetal development. Specifically, soft tissue area and liver volume measurement are examined, followed by facial shape characterisation.

A number of tools are presented which aim to allow clinicians to achieve accurate segmentations of these landmark regions. These are modifications on the Live Wire algorithm, an interactive segmentation method in which the user places a number of anchor points and a minimum cost path is calculated between the previous anchor point and the cursor. This focuses on giving the clinician intuitive control over the exact position of the segmented contour.

These modifications are FA-S Live Wire, which utilises Feature Asymmetry and a weak shape constraint, ASP Live Wire, which is a 3D expansion of Live Wire, and FA-O Live Wire, which uses Feature Asymmtery and Local Orientation to guide the segmentation process. These have been designed with each of the specific biometric landmarks in mind.

Finally, a method of characterising fetal face shape is proposed, using a combination of the segmentation methods described here and a simple shape model with a parameterised b-spline meshing approach to facial surface representation.

Keywords: Live Wire
shape model
Feature Asymmetry
analytic signal
monogenic signal