VictorJuiz/thesis huggingface dataset:
Molecular dynamics simulation studies of transmembrane signalling proteins

Receptor tyrosine kinases (RTKs) are a major class of cell surface receptors, important in cell signalling events associated with a variety of functions. High-throughput (HTP), coarse-grained molecular dynamics (CG-MD) simulations have been used to investigate the dimerization of the transmembrane (TM) domain of selected RTKs, including epidermal growth factor receptor (EGFR) and muscle-specific kinase (MuSK). EGFR activation requires not only a specific TM dimer interface, but also a proper orientation of its juxtamembrane (JM) domain. Phosphatidylinositol 4,5-bisphosphate (PIP2) is known to abolish EGFR phosphorylation through interaction with basic residues within the JM domain. Here, a multiscale approach was used to investigate anionic lipid clustering around the TM-JM junction and how such clustering is modulated by the mutation of basic residues. The simulations demonstrated that PIP2 may help stabilize the JM-A antiparallel dimer, which may in turn help stabilize TM domain helix packing of the N-terminal dimerization motif. A proximal TM domain residue has been implicated in the inhibition of ganglioside GM3 in phase-separated membranes. Here, CG simulations were used to explore the dynamic behaviour of the EGFR TM domain dimer in GM3-containing and GM3-depleted bilayers designed to resemble lipid-disordered (Ld) and phase-separated (Ld/Lo) membranes. The simulations suggest that the presence of GM3 in Ld/Lo bilayers can disrupt and destabilize the TM dimer, which helps to explain why GM3 may favour monomeric EGFR in vivo. To gain insights into the dynamic nature of the intact EGFR, a nearly complete EGFR dimer was modelled using available structural data and embedded in an asymmetric compositional complex bilayer, which resembles the mammalian plasma membrane. The results demonstrated the dynamic nature of the EGFR ectodomain and its predicted interactions with lipids in the local bilayer. Strong protein-lipid interactions, as well as lipid-lipid interactions, affect the local clustering of lipids and the diffusion of lipids in the vicinity of the protein on both leaflets.

Keywords: transmembrane
lipid
multiscale
RTKs
Molecular dynamics
juxtamembrane
EGFR
Advisor: Sansom, M
Trust and security risks in mobile banking

With the development and growth of mobile technologies, mobile phones enable users to perform a number of different tasks with their devices: from sending simple text messages, checking e-mails and browsing the internet, to running elaborated applications. Nowadays, the mobile phone platform creates great opportunities for businesses, especially due to its capabilities and population coverage: the number of mobile subscriptions approaches global population figures. In order to explore such opportunities, most banks have already launched their mobile applications and/or re-designed mobile version of their websites. One of the benefits of using mobile banking is the possibility for users to carry out bank transactions, such online payments or transfers, at anytime and anywhere. Expectations for the adoption of mobile banking were high; however, it represents about 20% of mobile phone users at the present. One factor has been recognised as being a strong reason for users not to adopt mobile banking: their concerns about security. This dissertation focuses on the relationship between the trust users have in mobile banking and the security risks that the use of mobile devices potentially pose. A questionnaire was created in order to gather users’ perception of security about mobile banking, and its results compared with recognised security issues.

Keywords: mobile apps
sense of trust
security
mobile banking
threats
Advisor: Flechais, I
Transfer from midwifery unit to obstetric unit during labour: rates, process and women's experience

Background
Midwifery units (MUs) provide midwife-led care for women at low risk of complications. They may be located on the same site as an obstetric unit (OU), in a hospital without obstetric services or separate from any hospital. In MUs, if unforeseen complications arise, transfer to an OU may be necessary.
Aim
To provide evidence to contribute to the improvement of the transfer process, help make transfer safer and less distressing for women, thereby improving the care and experience of women planning to give birth in MUs.
Methods
A structured literature review of existing evidence was followed by three integrated component studies using different methods. The content and quality of local NHS transfer guidelines were evaluated. Data from the Birthplace national prospective cohort study were analysed to estimate transfer rates, describe the transfer process and identify factors associated with transfer. The experiences of women transferred were explored in qualitative interviews.
Findings
Transfer is a common event, affecting around 25% of women planning birth in MUs, although rates in different units vary. Primiparous women are more likely to be transferred than women having a second or subsequent baby. The risk of transfer for primiparous women increases with increasing age; around 50% of women having their first baby aged 40 years or over are transferred.
Local NHS transfer guidelines are generally of poor quality and pay little attention to women’s experience.
Women interviewed after transfer report feeling unprepared for transfer. Sensitive care and clear communication from midwives during labour facilitate feelings of control in women and help women accept transfer as the right decision and not a 'negative' event. Transfer that is perceived by women as “too late” can have potentially serious and long-lasting negative effects.
Women’s experience of the transfer journey could be improved by the offer of choice in a number of areas which would help women feel 'cared for' rather than 'transported'. Having the MU midwife continue to care for the woman after transfer should be considered 'best practice'; where this is not possible a good handover is essential. Women who have experienced transfer should be offered the opportunity to talk to a midwife about their experience.

Keywords: Epidemiology
Birth centres
Qualitative Research
Midwifery
Transfer
Advisor: Fitzpatrick, R
Kurinczuk, J
Novel signalling pathways regulating epithelial-mesenchymal transition in bone metastatic prostate cancer

Prostate cancer (PCa) cells predominantly metastasize to bone and the complex crosstalk between PCa cells and osteoblasts (bone-forming cells) and osteoclasts (bone-destroying cells) leads to increased tumour growth and worsening of bone disease. Understanding the mechanisms of PCa bone metastasis can identify the aggressive fraction of PCa resulting in earlier intervention. The ability of PCa cells to express bone cell-specific features, termed osteomimicry, could potentially explain the osteotropic nature of PCa cells. The aim of this study was to determine the role of osteomimicry in the regulation of epithelial-mesenchymal transition (EMT) in bone metastatic prostate cancer cells.
It was demonstrated that the osteoblast-specific marker alkaline phosphatase (bone/liver/kidney) (ALPL) was overexpressed in bone metastatic (ARCaPM), compared to non-metastatic (ARCaPE), human PCa cells. Knockdown of ALPL resulted in decreased cell viability, increased cell death and a change from mesenchymal to epithelial morphology in ARCaPM and PC3 cells, and increased CDH1 expression along with decreased migration in ARCaPM cells. Treatment with extracellular ATP also resulted in decreased viability, increased expression of epithelial markers (CDH1, KRT14) and decreased expression of mesenchymal markers (VIM, ZEB1), and reduced expression of ALPL in ARCaPM cells. Small RNA-sequencing identified microRNAs differentially expressed between ARCaPE and ARCaPM PCa cell lines: miR-373 expression was lower in ARCaPM compared to ARCaPE cells and its overexpression in ARCaPM cells resulted in a change to epithelial morphology, increased expression of the epithelial marker CDH1 and decreased expression of the mesenchymal markers VIM and ZEB1. Finally, the development of a high-throughput screening method to identify novel microRNA regulators of osteomimicry was described, which identified two microRNAs miR-199a-5p and miR-212 as positive regulators of ALP activity. Taken together, this thesis describes the identification of ALPL and ATP as novel regulators of epithelial-mesenchymal transition in PCa cells and high-throughput ALP-activity screening as a powerful tool to identify novel microRNA regulators of ALP expression.

Keywords: purinergic signalling
signal transduction
cancer
epithelial-mesenchymal transition
microrna
prostate
Advisor: Edwards, CM
Hamdy, FC
Special purpose quantum information processing with atoms in optical lattices

Atoms in optical lattices are promising candidates to implement quantum information processing. Their behaviour is well understood on a microscopic level, they exhibit excellent coherence properties, and they can be easily manipulated using external fields. In very deep optical lattices, each atom is restricted to a single lattice site and can be used as a qubit. If the lattice is shallow enough such that the atoms can move, their properties can be used to simulate certain condensed matter phenomena such as superconductivity. In this thesis, we show how technical problems of optical lattices such as restricted decoherence times, or fundamental shortcomings such as the lack of phonons or strong spin interactions, can be overcome by using current or near-future experimental techniques. We introduce a scheme that makes it possible to simulate model Hamiltonians known from high-temperature superconductivity. For this purpose, previous simulation schemes to realise the spin interaction terms are extended. We especially overcome the condition of a filling factor of exactly one, which otherwise would restrict the phase of the simulated system to a Mott-insulator. This scheme makes a large range of parameters accessible, which is difficult to cover with a condensed matter setup. We also investigate the properties of optical lattices submerged into a Bose-Einstein condensate (BEC). A weak-coupling expansion in the BEC-impurity interaction strength is used to derive a model that describes the lattice atoms in terms of polarons, i.e.~atoms dressed by Bogoliubov phonons. This is analogous to the description of electrons in solids, and we observe similar effects such as a crossover from coherent to incoherent transport for increasing temperatures. Moreover, the condensate mediates an attractive off-site interaction, which leads to macroscopic clusters at experimentally realistic parameters. Since the atoms in the lattice can also be used as a quantum register with the BEC mediating a two-qubit gate, we derive a quantum master equation to examine the coherence properties of the atomic qubits. We show that the system exhibits sub- and superdecoherence and that a fast implementation of the two-qubit gate competes with dephasing. Finally, we show how to realise the encoding of qubits in a decoherence-free subspace (DFS) using optical lattices. We develop methods for implementing robust gate operations on qubits encoded in a DFS exploiting collisional interactions between the atoms. We also give a detailed analysis of the performance and stability of the gate operations and show that a robust implementation of quantum repeaters can be achieved using our setup. We compare the robust repeater scheme to one that makes use of conventional qubits only, and show the conditions under which one outperforms the other.

Keywords: Quantum simulations
Optical lattices
Quantum information theory
Ultracold atoms
Polarons
Bose-Einstein condensation
Advisor: Jaksch, D
Stability of magnetic remanence in multidomain magnetite

If a rock is to retain a geologically meaningful magnetic record of its history, it is essential that it contains magnetic minerals which are capable of carrying stable magnetic remanence. Of the natural occurring magnetic minerals, magnetite is the most important because of its abundance and strong magnetic signature. The stability, i.e., the resistance to demagnetisation or reorientation, of magnetic remanence is related to grain size; in smaller grains the magnetic moments align to have single domain (SD) structures, in larger grains complex magnetic patterns are formed (multidomain (MD)). “Classical” domain theory predicts that SD remanence is stable, whilst MD remanence is not. However experimental evidence has shown that both SD and MD grains can have stable remanences.
In this thesis the origin of stable MD remanence is examined. There are two opposing theories; one suggests that the stability is due to independent SD-like structures, the other postulates that the stability is due to metastable MD structure. A series of experiments were designed to examine the stability using a selection of characterised synthetic and natural samples. Low-stress hydrothermal recrystallised samples where grown for this study.
For the first time, the stability of thermoremanence induced in hydrothermal crystals to cooling was examined. The results agree with previous observations for crushed and natural magnetites, and support kinematic models.
The behaviour of SIRM and thermoremanences in MD magnetite to low-temperature cooling to below the crystallographic Verwey transition at 120-124 K (Tv) and the cubic magnetocrystalline anisotropy isotropic point (Tk) at 130 K was investigated. On cooling through Tv, SIRM was observed to decrease and demagnetise, however thermoremanence was found to display a large increase in the magnetisation at Tv, which was partially re- versible on warming. The size of the anomaly is shown to be dependent on the temperature at which the thermoremanence is acquired, internal stress and grain size. The anomaly is attributed to the large increase in the magnetocrystalline anisotropy which occurs on cooling through Tv . It is postulated that low-temperature cycling demagnetisation is due to kinematic processes which occur on cooling between room temperature and Tk. Characterisation of low-temperature treated remanence and partially alternating field demagnetised remanence, suggest that the stable remanence is multidomain.
Low-temperature cooling of remanence in single sub-micron crystals was simulated using micromagnetic models. The models predict the observed anomaly for thermoremanence on cooling through Tv, and also the relative behaviour of SIRM and thermoremanence. The single domain threshold was calculated for the low-temperature phase of magnetite, and was found to be 0.14 microns, compared to 0.07 microns at room temperature.

Keywords: Verwey transition
multi domain magnetite
thermoremanence
micro magnetic modelling
Advisor: McClelland, E
Williams, W
Personal identity and the police occupation in South Africa

This thesis explores the question, 'Who do South African police officers think they are and how does this shape police practice?' Based on eight months of ethnographic fieldwork in Cape Town and the Eastern Cape province of South Africa in 2012/13, it is an exploration of the deep-seated perceptions, stories and imaginings that South African Police Service (SAPS) officers have of themselves, their occupation and their country, in the early twenty-first century. It unpacks how officers’ individual narratives shape, and are shaped by organisational narratives and forces, and how this interplay influences police practice in an unequal and violent young democracy.
The thesis suggests that a job in the SAPS is primarily just that, a job. It is a means to strive and survive in a country saturated in vulnerability and risk. Most officers join the organisation after other dreams have slipped out of reach. Once recruited they re-write their self-narratives to accommodate their new circumstances. Recruited from lineages long-oppressed, the meaning and income the job brings to their lives is usually more important to them than the work they carry out. As a result, they seek first to please their institutional overseers and ease the pressure of the job. This is achieved by enacting institutional performances that promote the idea that the SAPS is a rational, effective, evidence-based and rule-bound organisation made of up well trained officers performing common-sense crime prevention tasks, while hiding the darker side of police work. Using carefully choreographed performances, the SAPS and its officers present a strategically crafted façade behind which individual officers strive to secure their sense of self. When the façade is challenged, some resort to violence in an attempt to garner the respect they seek.

Keywords: personal identity
Criminology
law and order
crime
security governance
police
South African Police Service
police officers
Advisor: Loader, I
Steinberg, J
Vector host choice and the environmental context of mosquito-borne virus transmission

The present thesis explored ethological and geographical approaches for the investigation of vector-borne parasites. In the first part, the role of associative learning on vector preferences for hosts was investigated through a comprehensive series of behavioural experiments using the vector of dengue and yellow fever diseases, the mosquito Aedes aegypti. To this end, the possibility that the mosquitoes were able to associate unconditional stimuli with particular odours and visual patterns to which they were responsive was explored, but no evidence supporting the hypothesis that associative learning abilities are present in adults of this species was found. A critical review of the literature on learning in mosquitoes conducted afterward allowed the reinterpretation of findings in the field, narrowing the scope of evidence suggesting the existence of these cognitive abilities in some species.
In the second part of the thesis, the distribution and evolution of mosquito-borne viruses was investigated with the use of geo-coded environmental data and spatial statistics. Initially, the eco-climates associated with the distribution of Japanese encephalitis virus were described and modelled, allowing the production of a worldwide predictive map defining the probability of each region to develop this disease in the future. Predominating amongst those areas shown to be under high risk were the equatorial regions of South America and Africa. The methodology used to infer such patterns – non-linear discriminant analysis – was subsequently explored with a number of simulations. Overall, differences in the choice of parameters required for the analysis were shown to lead to differences in the final outputs produced, basically in those cases where the environmental range for which predictions are generated is not rigorously limited. Finally, eco-climate surrogates for the evolution of the Japanese encephalitis serocomplex were investigated, but the current environmental distances between the viruses did not seem to be associated with the events leading to their speciation.

Keywords: ethology
virus
mosquitoes
learning
Advisor: Randolph, S
Wyatt, T
Properties of tests for mis-specification in non-stationary autoregressions

We are interested in the stochastic properties, individual and joint, of mis- specification testing when the data are generated by an autoregressive process. Good mis-specification tests are invariant to the dynamic properties of the pro- cess summarized by its characteristic roots, and to irrelevant misspecifications. Invariance in parameter space obviates inference prior to mis-specification test- ing. This is important as the latter is used to validate the former. Mutual independence of the tests allows calibration of the overall significance level. Es- tablishing such results requires work on individual tests and on their stochastic interactions.
In Chapter 2, we derive the asymptotic distribution of two types of CUSUM of squares test, one implemented with standardized one-step-ahead OLS pre- diction errors and another implemented with OLS residuals. The latter is found to be valid in all but singular explosive cases, but the former only in purely non-explosive, or regular explosive cases with all roots in the explosive region of the parameter space; in Chapter 3, we show that a nuisance term arises in the mixed case. In Chapter 4, we derive numerically a finite sam- ple correction to render the tests implementable into software, and Chapter 1 contains two examples of applications.
In Chapter 5, we consider inference on the parameters associated with the stationary part of the process, together with tests for a unit root, lag length, variance constancy, and normality of the regression innovations. In character- izing the joint distribution of these tests, we rely on asymptotic theory, and show independence in the limit. A simulation experiment suggests that finite sample correlations between some of the tests are statistically significant but small. Asymptotically, then, control of the overall significance level of the test procedure is feasible, and there is no reason to discount inference for the use of these mis-specification tests in model selection.

Keywords: specification testing
autoregressions
Advisor: Nielsen, B
An analysis of the morality of intention in nuclear deterrence, with special reference to final retaliation

Quite apart from its apparent political obsolescence, the policy of nuclear deterrence is vulnerable to attack for its seemingly obvious immorality. Nuclear war is blatantly immoral, and nuclear deterrenec requires a genuine intention to resort to the nuclear retaliation which would precipitate such a war. Therefore, since it is wrong to intend that which is wrong to do, deterrence is immoral.
This thesis seeks to examine the nature of the deterrent intention as a means of verifying the soundness of the above deontological argument. This examination is carried out by first suggesting an acceptable notion of intention in general and then, after analysing the views of deterrent intention by other writers, proceeding to demonstrate the uniqueness of that intention. Having done this, and having explored the possibility that deterrence need not contain a genuine intention to retaliate, the thesis moves on to suggest and defend a moral principle which states that endeavours requiring the formation of an immoral intention may nevertheless be moral. Called the Principle of Double Intention (and based on the Principle of Double Effect), it offers a method for the moral assessment of agents who form immoral intentions within larger contexts. By applying this principle to nuclear deterrence, it is demonstrated that agents who undertake such a policy may be morally justified in doing so, provided certain conditions are met.
The thesis closes with a refutation of the objection that an agent cannot rationally form an intention (such as that required in deterrence) which he has no reason to carry out. By highlighting the objection's reliance on a claimed isomorphism between intention and belief, it is shown that the objection, while generally sound, does not apply to the special case of nuclear deterrence. The conclusion suggests a framework for disarmament which results in a deterrent force structure which is both strategically effective and morally acceptable.

Keywords: morality
nuclear deterrence
final retaliation
Advisor: Glover, J