VictorJuiz/thesis huggingface dataset:
Characterisation of two putative rhomboid proteases in Shigella sonnei physiology and pathogenesis.

Shigella sonnei is a human-specific pathogen and a major cause of bacillary dysentery. Rhomboids are evolutionarily conserved serine intramembrane proteases that control a variety of important cellular processes, including regulating apoptosis in mammals, development in Drosophila, and invasion of eukaryotic parasites. However, functions of bacterial rhomboids remain largely unexplored.
This work identified two active rhomboids: GlpG and Rhom7, in S. sonnei. Rhom7 possesses a novel domain composition among rhomboids characterised so far, consisting of seven transmembrane domains (TMDs) and a putative C-terminal WD40 domain. However, neither the 7th TMD nor the C-terminal domain is required for the proteolytic activity of Rhom7. To identify physiological substrates of GlpG and Rhom7, the cleavage propensity of TMDs derived from all predicted type I & III membrane proteins in S. sonnei were assessed. Candidate substrates were further validated by testing the cleavage of the full-length substrates by GlpG and/or Rhom7, revealing that HybA and FdoH are physiological substrates for GlpG, and that HybA and FdnH are substrates for Rhom7 but only when Rhom7 is expressed from a plasmid.
Further analyses of these substrates revealed that they are all components of multi-protein respiratory complexes (HybA from hydrogenase-2, FdoH from formate dehydrogenase-O, and FdnH from formate dehydrogenase-N). I propose that their cleavage by rhomboids follows a ‘complex protection’ model, which states that only the uncomplexed substrates are cleaved by rhomboids, while the substrates residing in their native complexes are protected. As rhomboids are known to display propensity to cleave TMDs with low helical stability. I proposed that discrimination of uncomplexed and complexed substrates is likely to be mediated by the presence of helix-destabilising residues in the substrate TMDs, which render uncomplexed substrates prone to rhomboid cleavage while the stability of substrate TMDs is maintained by packing with TMDs from their binding partner(s) in the complex. Consistent with that, we identified helix-destabilising proline residues in HybA, FdoH, and FdnH. Moreover, substitutions of these residues with alanine abolished rhomboid cleavage regardless of complex integrity. These findings lead to the proposal that rhomboids might act as a quality control mechanism scrutinising membrane complex integrity, whose role might only become important under stresses.

Advisor: Exley, R
Tang, C
Flexoelectricity and multi-dimensional structures for liquid crystal photonics

The investigations carried out in this thesis involve the characterization and the manipulation of dielectric and flexoelectric phenomena in liquid crystalline systems. The first half of the thesis considers the flexoelectric effect in achiral and chiral nematic liquid crystals (LCs). These chapters demonstrate a new approach to measure the sum of the flexoelectric coefficients in achiral nematic LCs confined to hybrid aligned and planar-aligned geometries. The importance of ionic effects was considered, and the experimental and theoretical findings highlight the covariance between the ionic concentration and the flexoelectric coefficients.
Observations of the flexoelectro-optic (FEO) effect in chiral nematic LCs were carried out by first inducing a uniform lying helix (ULH) alignment so that an electric field could be applied perpendicular to the helical axis. A polymer templating method was implemented initially, which was found to enhance the FEO tilt angle compared with that observed following a bulk polymerization technique, but was inferior to the electro-optic response measured prior to the polymerization process.
Using an alternative approach, an in-situ direct laser writing (DLW) technique was employed to confine the polymer network to localised regions (polymer walls) within the device. Encouragingly, the ULH alignment was spontaneously formed when periodic polymer walls were written in the nematic phase (induced by applying a relatively large electric field to the device so as to unwind the helical structure) and spaced at the order of the device thickness. Fabrication of polymer walls in the chiral nematic phase was also investigated where it was found that the quality of the alignment was lower than that observed for polymer walls written in the nematic phase.
The second half of the thesis demonstrates the manipulation of electro-optic phenomena by exploiting the dynamic aberration correction element inherent in the DLW facility. It is shown that electrically tunable defects can be formed from two-dimensional polymer structures written in topologically discontinuous states. Three-dimensional polymer structures were also created in the form of arrays of pillars, polymer helices and polymer knots. In the final experimental chapter, results are presented that demonstrate the creation of reconfigurable optical elements based upon these polymerizable LC devices, whereby a simple emoticon is used to show how different features can be made to appear and disappear at specific applied voltages.

Keywords: Polymer Structures
Chiral Nematics
Topological Defects
Reconfigurable Optical Elements
Aberration Correction
Two-Photon Photopolymerization
Two-Photon Absorption
Adaptive Optics
Electro-Optic Response
Liquid Crystals
Uniform Lying Helix
Direct Laser Writing
Polymer Templates
The Flexoelectric Effect
Image Analysis
Flexoelectricity
Advisor: Elston, S
Applications of interferometric scattering microscopy (iSCAT) to single particle tracking in model and cell membranes

We have employed Interferometric Scattering (iSCAT) microscopy-based Single Particle Tracking (SPT) to study lipid dynamics of on model membranes and plasma membranes. This novel imaging technique offers high localization precision (~ 101 nm) and temporal resolution (< msec), together with tunable Signal-to-Noise Ratio.
In the Materials and Methods, we describe our custom iSCAT setup. Also, an advanced analysis pipeline for SPT data is introduced, to estimate camera blurring and localization error effects in SPT data, and to statistically evaluate the most likely model of particle diffusion dynamics.
In Chapter 3, we show the results of SPT experiments on gold nanoparticle-tagged lipids on model membranes. In slow sampling rate experiments (100Hz), the effects of localization error are not very pronounced, and vice versa in high sampling rate (2kHz) experiments. These experiments, corroborated by Fluorescence Correlation Spectroscopy (FCS) measurements, show that gold-tagged lipids are much slower compared to fl uorescent-dye tagged ones. This effect was attributed to the crosslinking potential and large size and of the gold tag.
In Chapter 4, the effects of crosslinking are explored. Streptavidin and a monovalent version thereof ("Flavidin") are used to tag biotinylated lipids, and their dynamics analyzed through iSCAT-SPT and FCS. Both techniques show how tetravalent Streptavidin-tagged particles are ~ 2 times slower than Flavidin- tagged ones. Detection of 2 kDa polymer-conjugated lipids was also achieved with iSCAT.
Chapter 5 is focused on the results of gold-tagged saturated lipids tracking on epithelial cell membranes. Their hopping diffusion behaviour was analyzed, and the diffusion in the confinement areas was found to be much slower than what previously reported.
In conclusion, iSCAT-SPT is a very valuable technique in the study of mem- brane biophysics, which has helped us uncover some details on the effect of tag crosslinking, and promising details on the diffusion of lipids on cell membrane. Future developments in technology and analysis methodology will provide more insights in single molecule dynamics on membranes.

Keywords: Single Particle Tracking
Fluorescence Correlation Spectroscopy
lipid diffusion
lipid membrane
Ptk2 cells
Interferometric Scattering Microscopy
Advisor: Eggeling, C
Kukura, P
Interplay between LARP1 and MYC - a two-way regulation?

There is increasing evidence that several steps of carcinogenesis including initiation, progression and chemotherapy resistance are regulated by post-transcriptional mechanisms. One such example is the RNA-binding protein LARP1 which has been shown to drive tumorigenesis and is highly expressed in several epithelial cancers, where it correlates with poor prognosis. Interestingly, there is huge overlap between the transcriptome of MYC and the interactome of LARP1. In this project, I investigated whether there was co-regulation between MYC and LARP1, which could explain the mechanism through which LARP1 promotes cancer progression.
In order to determine whether MYC drives the transcription of LARP1, siRNA knockdown of MYC was conducted in the cisplatin-resistant ovarian cancer cell lines OVCAR-3 and OVCAR- 8. While there are numerous ChIP- and RNA-seq datasets available suggesting a strong regulatory mechanism of MYC in various cell lines, only a modest change in LARP1 levels was observed after MYC depletion. To investigate whether MYC directly binds to the LARP1 promoter, chromatin immunoprecipitation was performed and analysed by qPCR. Indeed, MYC strongly binds the long isoform of LARP1, compared to IgG control. The knockdown experiment was repeated with a LARP1 targeting siRNA to analyse a potential stabilisation of MYC by LARP1. Upon LARP1 depletion, there was no significant effect on MYC levels or localisation, assessed by western blot and immunocytochemistry.
While MYC had a modest impact on LARP1 expression, this thesis did not demonstrate a direct regulation of MYC by LARP1. Future work will elaborate on the idea that LARP1 regulates the translation of MYC target genes and is therefore a regulator of the ‘MYC signal’. Should this prove to be the case, this could evolve as another option to target the – currently – ‘undruggable’ MYC. Finally, this interaction would implicate LARP1 as a promising target for rational drug design in MYC driven cancers.

Advisor: Blagden, S
Towards a psychology of surveillance: do ‘watching eyes’ affect behaviour?

Surveillance matters. Chapter 1 shows we are today watched more closely than at any time in modernity. Philosophers have long speculated that just feeling watched might change our behaviour, but empirical evidence for this is limited. This thesis extends the evidence by exploring ‘the watching eyes effect’ – a phenomenon identified by psychologists which suggests that the presence of pictures of eyes can trigger us to feel more watched and act more prosocially. The research presented also tests the effect of the ‘mere presence’ of a camera. In Chapter 1 we see that there is significant evidence that we are hypersensitive to gaze and feeling watched. However, a laboratory study reported in Chapter 2 finds no effect of eye cues or the presence of a camera on prosociality. In Chapter 3 a systematic review of the available watching eyes literature develops the hypothesis that if, as others suggest, watching eyes cue us to feel watched and worry about our reputation we might find they have more consistent effects on antisocial behaviour. A meta-analysis of 15 experiments supports this contention, finding a 35% reduction in antisocial behaviour when eye cues are present. Seeking to explore this further, Chapter 4 reports three studies finding that eye cues (or a camera) do not reduce antisocial behaviour in the laboratory. Chapter 5 reports the results of a field study finding consistent reductions in crime at 9 locations where signs are erected – three of which are statistically significant with crime falling 27%, 100%, and 100%. Chapter 6 reports a carefully designed large-scale field experiment in the London Borough of Ealing. Unexpectedly, over the twelve months after we put the signs up there was no cycle crime for 6 months preventing meaningful assessment of the signs’ effectiveness. In concluding, we consider the possibility that our laboratory studies show participants don’t feel watched in the presence of eye cues or a camera – that the watching eyes effect is the result of false positives and publication bias. However, noting Chapter 1’s evidence for our hypersensitivity to surveillance, and our findings in Hereford this investigation concludes that perhaps more consistent watching eyes effects can be found in the field than in the laboratory. In the end, having synthesised the psychological and interdisciplinary evidence for surveillance effects and added its empirical findings to the canon, this thesis advances us towards a psychology of surveillance, and points the way to further research.

Advisor: Dutton, K
Fox, E
The dysfunctional family in contemporary (post-1990) French and American films and novels

This thesis explores a question which runs through contemporary fiction: what is the weight of the family of origin once children have become adults? It does so by examining the families in six different works: Un Conte de Noël by Arnaud Desplechin, Le Skylab by Julie Delpy, Rien ne s'oppose à la nuit by Delphine de Vigan, The Savages by Tamara Jenkins, August: Osage County by John Wells and We Were the Mulvaneys by Joyce Carol Oates. My approach in this thesis is pluridisciplinary both in terms of my primary and secondary material. I use films and novels, and, while I rely on traditional film and literary criticism, I also borrow concepts and ideas from psychology, psychoanalysis, sociology, and anthropology. Concepts drawn from these fields shed light on issues and dynamics that might otherwise go unnoticed. Each chapter has a different approach: 'Home' argues that the childhood home is especially significant as the place which physically embodies the family, 'The Reunion' demonstrates how family reunions uncover the family system which characters operate within, 'Meals' offers a reading of family dynamics through an examination of the representation of family meals, while 'Secrets and Traumas' argues that family secrets and traumas affect family dynamics, and offer keys to individual characters' psyche. Throughout the thesis I observe the ways in which families can become dysfunctional, and the effects of these dysfunctions on its members. I do so by exploring themes such as cross-generational transmissions, the relationships which exist between different members of the family, and how the family can be a locus of trauma. The analysis sees two recurring questions emerge: what makes someone part of a family, and whether the family is a ‘trap’ or a ‘refuge’. Throughout these explorations, the question is one of identity: how is one's identity shaped by their family, and is it possible to forego or escape family transmission.

Keywords: Family therapy
Family
Advisor: Kemp, S
Marcus, L
Quantum cascade laser spectroscopy: from trace gas detection to nonlinear optics

Quantum cascade lasers (QCLs) are high power, narrow linewidth mid-IR lasers that are increasingly popular for trace gas sensing and nonlinear spectroscopy. This thesis demonstrates QCL based spectroscopic techniques for multi-species detection, nonlinear optics and trace gas detection, highlighting the versatility of these lasers. Firstly, a Fabry-Perot QCL (FP-QCL) operating at 5.3 μm was used to perform multi-mode absorption spectroscopy (MUMAS) for sensing of NO and H2O. The laser provides a spectral coverage of ca. 50 cm-1 with a time resolution down to the ms timescale. It also exhibits a frequency resolution of &LT; 50 MHz, limited by the longitudinal mode linewidth. This was the first demonstration of MUMAS with QCLs.
Secondly, the optical purity of a single mode distributed feedback (DFB) QCL operating at 5.3 μm was determined using Lamb-dip spectroscopy and by analysing the frequency noise power spectral density (PSD). Both methods revealed the linewidth of the device is ca. 500 kHz, which can be reproducibly broadened up to ˜&Tilde;8 MHz by applying broadband uncorrelated radio-frequency current perturbations.
Thirdly, the DFB-QCL was used in combination with an external cavity (EC) QCL to study the evolution of velocity selected coherent signals in vibrationally excited NO. The coherent signatures showed lifetimes up to 378 ± 23 ns. Maximum population transfer to the v = 1 level was achieved after pumping for 10 ± 0.5 μs, and the decay time of post-pumping coherent transient signals was 5.7 ± 0.3 μs at a pressure of 3 mTorr. The collisional relaxation rate of the coherent systems was determined for various buffer gases, reaching (4.28 ± 0:13) ×104 s-1 mTorr-1 with CO2.
Lastly, a DFB-QCL was used to demonstrate intracavity Faraday modulation spectroscopy (INFAMOS), a technique for the sensitive and selective detection of radicals, using NO as a test molecule. A model that predicts the INFAMOS lineshape was presented, and the sensitivity for the detection of NO was 0.21 ppbv Hz1/2, corresponding to a minimum detectable rotation angle of 0.16 nrad Hz1/2, at a total pressure of 412 Torr. Optical saturation effects were observed and included in the INFAMOS model.

Advisor: Ritchie, G
The P-TECH model: an embedded case study of digital inequalities and private sector involvement in U.S. public education

Amidst a rapidly changing educational landscape that is increasingly becoming corporatised, technology companies and wealthy techno-venture-philanthropists have demonstrated significant interest in education reform. According to the 2012 American Revolution 2.0 report, the US K-12 education market is valued at over $2.2 trillion. The emphasis placed on 21st century skills and the continued fiscal starvation of public education has enabled technology companies to entrench themselves in education. Technical catalysts for education reform including affordable hardware such as Chromebooks and cloud computing with Google’s G-Suite have been the primary methods for technological integration in public schools. What is distinct about the contemporary reform movement is that it is being led and shaped by Silicon Valley values and interests. I refer to this contemporary movement as technocratic corporate reform.
Encapsulating the trends and characteristics of the technocratic corporate reform is IBM’s Pathways in Technology Early College High School (P-TECH) model. The model, first implemented in 2011, is a STEM-focused six-year high school model built around a public-private partnership between industry, school districts, and community colleges. Notably, it was designed to serve marginalised students by providing the opportunity to earn an associate’s degree at no cost. P-TECH serves as the focus of this study.
This research entails a mixed-methods embedded case study research design examining three P-TECH model schools across the country. It includes 60 in-depth interviews with private partners, educators, and students across each school, participant observations, and a multi-level social network analysis of the P-TECH network. It employs a unique theoretical framework that combines the political economy of communication and cultural studies perspectives. By adopting both perspectives this research is able to capture what is happening in education at the macro and micro scales. Utilising theories of digital capitalism and Pierre Bourdieu’s theory of social reproduction this study provides an analysis of the underlying values, interests, and aims of P-TECH and its implications for the K-12 system. The micro level analysis unveils the ways in which P-TECH is influencing students’ identities and aspirations. It outlines the unintended consequences of this and the subsequent risk of reproducing the very inequalities the model was created to ameliorate. This thesis ultimately maps how the US K-12 education system is being reimagined and restructured according to the agenda of technology elites.

Keywords: Education
Cultural capital
Political economy
Social capital
Social Network Analysis
Digital inequalities
Communication
Public private partnerships
Advisor: Eynon, R
Meyer, E
The post-apartheid politicisation of the South African Broadcasting Corporation

This dissertation draws on concepts from political science, sociology, media studies, organisational studies, and psychoanalysis to describe and explain the manifestations and process of politicisation of the South African Broadcasting Corporation (SABC) after the end of apartheid (1993-2013) through the lens of organisational culture. It is based on ethnographic fieldwork conducted between 2005 and 2011, including six months participant observation in seven SABC newsrooms and 117 in-depth interviews with journalists and managers.
The study links an intra-organisational analysis of journalistic practice with the macro-level of the political field and the micro-level of individual actors. It explores in detail the unconscious processes inscribed in the SABC's culture and subcultures, as well as their interplay, before approaching the understudied problem of agency in newsrooms, in particular agency-as-resistance to politicisation.
The thesis makes three main contributions to the literature: (1) The most in-depth empirical account of the SABC's politicisation to date, and an example of an African public broadcaster in a post-authoritarian environment. Findings challenge conventional explanations for the failures of public broadcasting transformations by showing that politicisation is far more than a top-down phenomenon, and that organisational culture shapes susceptibility to it profoundly. (2) A systematic and chronological analysis of drivers, enablers and inhibitors of politicisation, highlighting the multi-causality and multi-directionality of the process. This contests the over-reliance on structural explanations in political science by emphasising culture and subjectivity, e.g. by introducing the concept of 'anticipatory politicisation'. (3) A conceptual framework that integrates group relations theories with Bionian concepts and Lacanian discourse theory to shed light on individual agency in the context of collective unconscious processes. Findings are of interest to scholars working on the SABC or media in transition, on politicised organisations, organisational culture, or agency.

Keywords: Self-censorship
Group relations
Politicisation
Discourse theory
Lacan
South African Broadcasting Corporation
Organisational culture
Organisational ethnography
SABC
Journalism
Advisor: Born, G
Cheeseman, N