VictorJuiz/thesis huggingface dataset:
'No matter how much or how little they’ve got, they can’t settle down': A social history of Europeans on the Zambian Copperbelt, 1926-1974
Keywords: Zambia
Copperbelt
Mining history
Labour history

This thesis traces the social history of the European community on the Zambian Copperbelt from the onset of copper mining in 1926 to the mid-1970s when a dramatic slump in the price of copper generated severe economic difficulties. There has been almost no academic work on the Copperbelt's European community and, in this respect, this thesis fills an important gap. However, a focus on the European community has a wider significance than filling this gap.
Although the Copperbelt has generally been understood in a national or regional context, this thesis argues that developments there are better understood by exploring how the Copperbelt was linked to other mining regions around the world; in Britain, South Africa, the US and Australia. The European community was largely composed of highly mobile, transient individuals, and the constant movement of people made and sustained transnational connections.
Mobility and transience are crucial to two of the main themes of this thesis: class consciousness and the importance of race. Class was a strong marker of identity for Europeans and a variant of 'white labourism' dominated life on the Copperbelt. Industrial unrest was a regular occurrence in the life of the European community as strikes and other disputes underpinned extraordinary levels of affluence. The frequency of industrial unrest diminishes the relevance of South Africa as a viable comparison, as does the relative lack of importance of race. This thesis argues that the predominant attitude of Europeans toward the African majority around them was one of indifference and that the importance of 'African advancement' has been overstated.
Archival collections in Zambia and Britain constitute the main sources for this thesis. These sources are supplemented with material from archives in South Africa and Netherlands, contemporary publications including newspapers, and interviews with former European residents of the Copperbelt.
Variation of stellar populations and dark matter with time and environment
Keywords: Galaxies

In this thesis, I probe the stellar and dark matter component of galaxies in order to infer their evolutionary histories. I am doing this by studying two distinct galaxy population samples: (i) a high redshift sample at z&Tilde;1, and (ii) a high density environment sample of galaxies in the nearby Coma cluster. By comparing these samples to a sample of galaxies in the local Universe in a low density environment, I infer variation in their properties as a function of time and environment.
For both samples, I create accurate dynamical models to infer the stellar Mass-to-Light ratios of the galaxies and their dark matter fractions. Furthermore, I model the stellar population of the galaxies using a full-spectrum technique while reproducing their star formation history in a non-parametric manner. In addition, I use IFS data for a subset of galaxies in the high density sample to create detailed dynamical models that strengthen the results found in that sample.
Based on the quantities derived from these analyses, I present results on the IMF normalisation and dark matter fraction of galaxies in both samples. Furthermore, I studied the scaling relations of these galaxies and compared them to that observed for the ATLAS3D sample, which serves as a low density sample of the Local Universe, to infer variation in galaxy properties as a function of time and environment.
Quasiparticle interference in strongly correlated electronic systems
Keywords: Quasiparticle interference
Quantum impurity physics
Strongly-correlated electron systems
Computational physics
Kondo effect

We investigate the manifestation of strong electronic correlations in the quasiparticle interference (QPI), arising from the scattering of conduction electrons from defects and impurities in an otherwise translationally-invariant host. The QPI may be measured experimentally as the Fourier transform of the spatial modulations in the host surface density of states that result, which are mapped using a scanning tunnelling microscope.
We calculate the QPI for a range of physically relevant models, demonstrating the effect of strong local electronic correlations arising in systems of magnetic impurities adsorbed on the surface of non-interacting host systems. In the first instance the effect of these magnetic impurities is modelled via the single Anderson impurity model, treated via numerical renormalization group (NRG) calculations. The scattering of conduction electrons, and hence the QPI, demonstrate an array of characteristic signatures of the many-body state formed by the impurity, for example due to the Kondo effect.The effect of multiple impurities on the QPI is also investigated, with a numerically-exact treatment of the system of two Anderson impurities via state-of-the-art NRG calculations. Inter-impurity interactions are found to result in additional scattering channels and additional features in the QPI.
The QPI is then investigated for the layered transition metal oxide Sr2RuO4, for which strong interactions in the host conduction electrons give rise to an unconventional triplet superconducting state at Tc &Tilde; 1.5K. The detailed mechanism for this superconductivity is still unknown, but electron-electron or electron-phonon interactions are believed to play a central role. We simulate the QPI in Sr2RuO4, employing an effective parametrized model consisting of three conduction bands derived from the Ru 4d t2g orbitals that takes into account spin orbit coupling and the anisotropy of the Ru t2g orbitals. Signatures of such interactions in the normal state are investigated by comparing these model calculations to experimental results. We also calculate the QPI in the superconducting state, and propose how experimental measurements may provide direct evidence of the anisotropy and symmetry of the superconducting gap, and thus offer insight into the pairing mechanism and the superconducting state.
Methods of classification of the cardiotocogram
Keywords: Systems Identification
Intrapartum Labour
Classification
Fetal heart rate monitoring

This Thesis compares CTG classification techniques proposed in the literature and their potential extensions. A comparison between four classifiers previously assessed - Adaboost, Artificial Neural Networks (ANN), Random Forest (RF), Support Vector Machine (SVM) - and two proposed classifiers - Bayesian ANN (BANN), Relevance Vector Machine - was conducted using a database of 7,568 cases and two open source databases. The Random Forest (RF) achieved the highest average result and was proposed as a benchmark classifier. The proposal to use model certainty to introduce a third, unclassified, class was investigated using the BANN. An increase in the classification accuracy was demonstrated, however the proportion of cases in the unclassified class was too great to be of practical value.
The information content of time series was explored using a Hidden Markov Model (HMM). The average performance of the HMM was comparable with the performance of the benchmark with a smaller distribution across validation folds, demonstrating that time-series information provides more stable estimates of class than stationary methods.
Finally a method of system identification was implemented. Significant differences between feature trends and histograms in low pH (&LT; 7.1) and healthy pH (≥ 7.1) cases were observed. These features were used as classifier inputs, and achieved performance similar to existing feature sets. When these features were aligned according the onset of stage 2 labour three unique trend patterns were discovered.
The right to be killed: reassessing the case for the moral right to voluntary active euthanasia
Keywords: Physician-assisted suicide
Moral philosophy
Autonomy
Medical ethics
Bioethics
End of life
Moral rights
Professional ethics
Right to die
Self-determination
Euthanasia
Paternalism
Voluntary active euthanasia
Death
Self-ownership
Dying

This thesis defends an individual's moral right to be aided in dying by a physician (that is, voluntary active euthanasia, or VAE), but departs significantly from the view in its favor generally accepted in the bioethics literature. The prevailing view appeals to both respect for an individual's autonomy and promotion of an individual's well-being as necessary conditions for a right to VAE, so as to justify the right only for those suffering grave illnesses and/or disabilities. The author argues that such a view is logically untenable; one or another aspect must be given up. Since invoking the premise that certain individuals would be better off dead necessarily relies on controversial assumptions about both the value of life and the nature and value of death, about which reasonable people disagree, it is the justification from an individual's best interest which must be excluded in a liberal society. The author endorses a self-determination justification for the right to VAE, but rejects understanding this in terms of respecting personal autonomy, instead making the case for a right to VAE grounded in self-ownership. The author’s main conclusion is that the right to VAE is a general right applying to all competent adults, not only those suffering grave illnesses or disabilities, or those whose choice for VAE is an exercise of autonomy. Moreover, by analyzing the basis of physician authority over prescription medicine and how this can be justified to a society of self-owners, she maintains that individuals have not only the right to choose VAE without state interference, but also the right to be provided VAE by doctors. Nevertheless, both rights are compatible with reasonable limitations to protect both the interests of VAE seekers and the rights of others.
Effect of reward on visual perceptual decision-making in humans and non-human primates
Keywords: perception
reward
cortex
neuroscience
vision
decision-making

When primates make decisions about sensory signals, their choices are biased by the costs and benefits associated with different possible outcomes. However, much remains unknown about the neuronal mechanisms by which reward information is integrated into the perceptual decision-making process. I used electrophysiological, psychophysical and imaging techniques to explore the effect of reward on sensory representations, whilst humans and monkeys made perceptual judgements about structure-from-motion (SFM) stimuli.
Electrical microstimulation of visual area V5/MT in the macaque monkey was used to bias perceptual judgements, under different available reward sizes for correct choices. The behavioural effect of microstimulation interacted with available reward, and, in the context of a drift diffusion model of decision-making, the results demonstrated that reward must influence sensory processing before visual signals and microstimulation signals are accumulated in sensorimotor areas. In a parallel human psychophysics experiment, viewers made decisions about SFM stimuli whilst their choices were biased towards one outcome or the other by unequal pay-offs. A full drift-diffusion model was fitted to human choice and reaction time data. There was a significant effect of reward on model drift rate, a parameter known to be dependent upon evidence represented in sensory brain regions.
A second set of experiments used magnetoencephalography (MEG) to explore activity in visual areas in human cortex and the effects of reward. Brain responses to retinotopic visual stimuli were localized with three different MEG source analysis methods, and localization accuracy was evaluated by comparison with fMRI maps obtained in the same individuals. The results demonstrated that the beamformer and minimum norm estimate (MNE) methods were most suitable for investigating early visual activity with MEG. Human brain activity was then recorded with MEG whilst viewers made perceptual judgements about SFM stimuli, under unequal pay-offs. The results revealed an effect of reward size on early MEG responses in the region of the occipital cortex and visual precuneus.
Taken together, the experiments presented in this thesis provide consistent evidence that information about reward can influence the processing of sensory information during perceptual decisions.
Agreement through opposition: political ideology and legislative constraint in the 'special relationships' of the United States
Keywords: United States foreign policy
British foreign policy
Political ideology
International relations theory
Legislative constraint

Since 1945 the United States (US) has constructed a global web of 'special relationships' with states that share its political values, economic philosophy, or security predicament. Whether we understand these countries as 'clients', 'tributaries', 'friends', 'allies' or 'subordinates', what sets these relationships apart is the remarkably high level of cooperation and the extent to which this has endured over the decades. One question rarely asked, however, is how we can explain variation in the level of cooperation in these relations over time. Each of the 'special relationships' of the US has waxed-and-waned over the years, but the sources of this variation have not been fully uncovered. In this thesis I argue that changes in domestic political variables within each of the allied states are responsible for the varying degrees of cooperation witnessed over time. Utilising the example of Anglo-American relations in the postwar period, supplemented by a large-n statistical study, I demonstrate how a focus on political parties as the optimal actors in studying international cooperation helps us to understand the effects of political ideology and legislative constraint in foreign affairs.
Structural characterisation of the interaction between Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) and their human ligands in severe malaria
Keywords: Malaria
Plasmodium Falciparum
CD36
PfEMP1
IgM

Sequestration of infected erythrocytes during P. falciparum infection can lead to severe malaria. PfEMP1 proteins are central to this process. Multimodular PfEMP1 proteins can bind to a variety of human ligands due to the presence of CIDR and DBL domains. CIDR and DBL domains are classified to three and six families respectively, with each thought to bind to unique human ligands. The interaction between PfEMP1 proteins and human ligands protects the infected erythrocytes against spleen-mediated destruction. Additionally, these PfEMP1 proteins undergo antigenic variation to evade immune surveillance. They also elicit immune suppression by binding to immunoglobulins within the circulatory system.
The work described here focuses on two interactions between PfEMP1 on the infected erythrocytes and their human ligands, the first involving CD36 and CIDR1α domains and the second involving human IgM and DBL domains. I have expressed and purified recombinant proteins involved in both interactions.
In this thesis, I have confirmed using a variety of biophysical methods that CIDR1α domains are able to bind CD36 in a 1:1 binding stoichiometry, and this accounts for the binding affinity of the full length protein. This interaction was not disrupted after performing deglycosylation procedures on CD36, allowing me to obtain stable complexes of these interacting partners for structural characterisation by crystallography. I have also confirmed the interaction between DBL domains and human IgM Fc region using similar biophysical methods. These experiments are important for paving the way towards further structural characterisation of these interactions that leads to sequestration. .
Information structure in Japanese: scrambling, topicalization and passives
Keywords: Corpus analysis
Discourse analysis
Word order
Givo´nian approach
Particles

The main purpose of this thesis is to shed new light on Japanese grammar under the framework of the Givónian approach, with special attention to OSV word orders and by-passives: scrambling (OACCSV), topicalization (OTOPSV), ni-passive (S NPNI V), and niyotte-passive (S NPNiyotte V). This approach measures the discourse status of a referent by utilizing anaphoric and cataphoric co-referencing relationships within the texts. However, it is conceivable that OSV word orders and by-passives are also influenced by multiple factors other than information structure. Specifically, previous studies point out the possibility that heaviness and animacy are relevant to this issue. Therefore, the present study performs the corpus analysis, taking three factors into consideration: heaviness, animacy, and information structure.
First, OSV word orders have proven to be influenced by information structure and heaviness. In terms of information structure, scrambling correlates 'topic shift' from the referent of the scrambled object to that of the subject. In contrast, topicalization interrelates with 'continuing topic' realized as the referent of the subject. In terms of heaviness, the direct object tends to be longer than the subject in OSV word orders. Yet, animacy has no influence on the choice of word orders.
Second, by-passives are affected by information structure and animacy. In terms of information structure, the ni- and niyotte-passives are selected in order to maintain the topic continuity by promoting the topical logical object to the grammatical subject. However, the ni-passive is relevant to global topic whereas the niyotte-passive is related to local topic. In terms of animacy, the ni-passive prefers animate subjects while the niyotte-passive tends to select inanimate subjects. Yet, heaviness is unrelated to the use of by-passives in Japanese.
In conclusion, the thesis provides a functional analysis of OSV orders and by-passives from a descriptive and empirical point of view by using a written Japanese corpus. The new data reported contribute to elucidating the argument encoding system of Japanese.
mTOR signalling and the regulation of Hoxp3 expression
Keywords: mTOR
FOXP3
metabolism
Immunology
T cell

Regulatory T-cells (Treg) are essential for the establishment of self-tolerance and they can be identified by the expression of FOXP3, the "master" transcription factor for the development of Treg. A number of essential signals, namely TCR engagement, TGFβ, as well as the inhibition of the kinase mTOR, have been shown to be crucial for the induction of FOXP3 in the peripheral immune system. Despite recent progress, the molecular mechanisms for induction of FOXP3 remains elusive due, at least in part, to the lack of a cell line that mimics the behavior of primary CD4+ T-cells.
Here we report the isolation of a clone B02 from the mouse lymphoma line EL4 that can be induced to express high levels of FOXP3 in up to 50% of the cells. Pharmacological inhibition of mTOR and EAA depletion synergized with TGFβ in the induction, and led to reduced activity of both mTORC1 and mTORC2, which seemed to independently contribute to the enhanced FOXP3 expression. Luciferase reporter assays using Foxp3 promoter and enhancer sequences indicated that the mTOR inhibition-mediated increase in FOXP3 expression resulted primarily from enhanced transcriptional activity.
In addition to the enhancement of FOXP3 induction, mTOR inhibition reduced the levels of IL-17A, presumably by SOCS-mediated inactivation of STAT3, which could also have accounted for increased Foxp3 transcription. Although the precise targets of mTOR inhibition involved in the regulation of FOXP3 expression have yet to be identified, both luciferase assays and mass spectrometry-based quantitative phospho-proteomics using SILAC labelled B02 cells, have identified promising candidates. This unique EL4 clone could represent a special resource for investigating the signaling events leading to the induction of FOXP3 as well as events downstream of FOXP3 expression.
Enhancement of lentiviral vector production through alteration of virus-cell interactions
Keywords: lentiviral vector
lentivirus
HIV
gene therapy
production

Gene therapy is the introduction or alteration of genetic material with the intention to treat disease. To support this aim, viruses have been modified, with elements linked to viral pathogenicity removed from their genome and replaced by the genetic material to be delivered. Gene therapy vectors based on lentiviruses have many advantages, such as the ability to transduce non-dividing cells and to target specific cell types via pseudotyping. They have been successfully used in ex vivo clinical trials for several haematopoietic stem cell disorders. Lentiviral vectors, however, suffer from substantially lower titres than the more popular adeno-associated virus (AAV)-based vectors and therefore have limited applicability for in vivo gene therapy which requires much greater quantities of virus.
The main aim of this thesis was to investigate strategies to improve lentiviral vector productivity during manufacture, in order to increase the likelihood of lentiviruses being adopted for disease treatment.
Initial experiments were based on the lentiviral vector manufacturing process currently being developed by the United Kingdom Cystic Fibrosis Gene Therapy Consortium for the generation of highly concentrated, purified lentivirus for clinical use. Supplementation of FreeStyle 293 Expression Medium used during upstream processing was attempted, but none of the assessed supplements led to significant increases in lentiviral vector production. Investigation into intrinsic immunity to viral infection indicated that over-expression of the protein kinase RNA-activated (PKR) led to lower production titres, but over-expression of its inhibitors was not successful at increasing titres. The focus then shifted to reducing, or 'knocking-down', inhibitory factors present in the host cells, which could adversely affect viral titres. Investigation of the published HIV-1 literature revealed a possible 152 candidate inhibitory factors described as having a negative impact on HIV-1 replication in the late stages of the life cycle of the virus. A novel siRNA screen was developed to assess the effect of ‘knock-down’ of inhibitory factors on lentiviral vector titre. Application of the screen to 89 candidate inhibitory factors identified nine genes which, when knocked-down, resulted in increased lentiviral vector production by more than 40%.
Further work will be necessary to understand the role of the inhibitory factors in lentiviral vector production, but novel cell lines in which genes encoding these factors have been permanently deleted from producer cells could lead to higher titres, reducing costs in the manufacture of lentiviral vectors and making in vivo gene therapy more feasible from a health economics perspective.