VictorJuiz/thesis huggingface dataset:
The bioenergetics of paracoccus denitrificans

This thesis concerns the mechanism of oxidative phosphorylation, with special reference to the bacterium Paracoccus denitrificans.
A new method using affinity chromatography is described for the separation of vesicles of different membrane orientation.
The working hypothesis is the chemisosmotic theory of Mitchell with its emphasis on the transmembrane proton motive force made up of a membrane potential and a transmembrane pH gradient. The 3 experimental systems used ape bovine heart submitochondrial particles, chromatophores from the photosynthetic bacterium Rhodospirillum rubrum and phosphorylating vesicles from P. denitrificans.
From the uncoupling obtained with various ions added to the P. denitrificans particles it is concluded that the transmembrane distribution of weak bases and permeant anions permits a determination of the protonmotive force.
A flow-dialysis method has been developed to measure the steady-state transmembrane distribution of weak bases and anions in a determination of the protonmotive force. This method successfully overcomes problems which arise with the techniques previously used for these measurements.
Under the experimental conditions used to determine the extent of oxidative phosphorylation (the phosphorylation potential) no transmembrane pH gradient was detectable, and the protonmotive force could be accounted for completely by the membrane potential. A method using ion-selective electrodes was developed to provide a continuous determination of this membrane potential.
In all 3 systems the proton motive force determined by the above methods was found to be significantly lower than that required by the chemiosmotic hypothesis. A simple modification of the chemiosmotic hypothesis is proposed. This new concept is based on electrodic theory. It is shown to be useful in explaining results reported in the literature (from both photosynthetic and respiratory systems) which appeared to be at odds with the chemiosmotic theory in its usual form.

Advisor: John, P
Ferguson, S
Variant surface glycoprotein synthesis and cell cycle progression in Trypanosoma brucei

The unicellular eukaryote Trypanosoma brucei causes African Sleeping sickness and multiplies extracellularly in the bloodstream of the infected host. The parasite evades antibody-mediated lysis by switching its Variant Surface Glycoprotein (VSG) coat. Blocking VSG synthesis results in an abrupt growth inhibition and a precise pre-cytokinesis cell cycle arrest, with an accumulation of cells with two nuclei and two kinetoplasts. Additionally, induction of VSG RNAi triggers a global block in translation, which is not due to a general decrease in transcript levels. The mechanism behind this translation arrest was investigated. It was observed that it correlated with a decrease in polysomes, indicating that translation was blocked at the level of initiation. It was also shown that the VSG RNAi-triggered growth inhibition was reversible, which suggests that this is not a lethal phenotype.
The VSG221 RNAi-induced growth arrest could be alleviated if a second different VSG (VSG117), which was not recognised by the VSG221 RNAi, was expressed immediately downstream of the promoter of the active VSG221 Expression site. Further, it was possible to delete the telomeric VSG221 in these VSG double-expressors, leaving the cells completely reliant on the second complementing VSG117 gene. VSG117 expressed from a promoter-adjacent position in the active Expression site was shown to form a functional surface coat that protected the parasites from complement-mediated lysis in vitro.
Transiently transfecting cells with anti-VSG221 morpholino oligonucleotides allowed us to specifically block translation of VSG221 mRNA without degrading it. This resulted in a pre-cytokinesis cell cycle arrest similar to that induced by VSG221 RNAi. This indicates that the VSG RNAi-triggered growth inhibition was due to a lack of VSG protein or its synthesis rather than the ablation of the abundant VSG mRNA. In addition, it was shown that blocking VSG synthesis reduced the rate of surface VSG internalisation in cells that were stalled precytokinesis, but had no effect on other endocytic markers. These experiments give us further insight into the importance of the protective VSG coat for pathogenicity in T. brucei.

Keywords: Trypanosoma brucei. Variant Surface Glycoprotein
cell cycle
Advisor: Rudenko, G
Connecting man and nature: philosophical meanings of Zhu Xi's poetry

My thesis closely analyzes the shi poetry of the Song dynasty philosopher Zhu Xi (1130-1200). I look at its deep structure, especially the tensions embedded therein between literature and philosophy, and between his inner mind and the external world, manifested in ways different from what he taught in his philosophical works. Although his poetry itself is not considered to be aesthetically outstanding, I suggest that it is crucial to a better understanding of the evolution of Zhu’s philosophical project on the relationship between humans and the natural world. Zhu Xi wanted to establish and defend a coherent and practical self-cultivation theory, which would enable people to recognize the dao through daily experiences. Nevertheless, in his poetry production, he was facing a long-entrenched influential poetic tradition with its emphasis on the outer world described by embellished words and spontaneous overflow of emotions, while leaving an open end for the meanings or less discriminatively appealing to the Daoist or Buddhist idea of transcendence, the logic of which fundamentally contradicts that of daoxue construction. This made it impossible to achieve the dao in a this-worldly fashion. The contradiction had to be reconciled by Zhu Xi in his poems, an issue that he actually wrestled with throughout his life. Consequently, the style of Zhu Xi’s poetry was differentiated from both that of other Neo-Confucians and indeed that of any other poets in Chinese history. In his poetic texts, the tension between the outer world, inner emotions and philosophical inclination is more intensified, and the exploration of the relationship between man and nature more focused and conscious. In this thesis, I present an aesthetic world of Zhu Xi beyond all his ambiguous philosophical discussions, unfavorable comments on poetry, and his profoundly contradictory attitudes towards versifying.

Keywords: Zhu Xi
chinese poetry
Neo-Confucianism
Advisor: Ditmanson, P
Meyer, D
Volume holographic infra-red filters in iron doped lithium niobate

Two collimated laser beams, wavelength O-514 μm are overlapped within a crystal of heavily iron doped lithium niobate to form a one-dimensional volume holographic grating, a few mm long, designed to behave as a highly selective filter at near infra-red wavelengths. A novel recording geometry is described and a variety of diagnostic experiments are undertaken to determine the main characteristics of the grating. A filter fabricated using this method is used to obtain single mode operation from a 1-55 μm semiconductor laser.
The historical survey of holography contained in chapter one emphasizes the dynamic properties and applications of photorefractive recording materials. Standard results of two mathematical theories, kinematic and coupled-wave, are used in chapter two to predict the properties of a Bragg grating when replayed with infra-red light. Chapter three details the recording materials suitable for an infra-red filter, followed by a discussion on the concept of 'scaling'. The recording mechanism of iron doped lithium niobate, including its fixing and erasure process, is presented in chapter four as a basis for selecting the most advantageous crystal characteristics. Mathematical models describing the complex dynamic recording process in iron doped lithium niobate are introduced in chapter five. A novel recording geometry involving the use of two prisms is critically described in chapter six, from initial conception to final implementation. The performance of the grating as an infra-red filter is assessed in chapter seven by measuring the angular response of the transmitted and diffracted beams at a wavelength of 1-152 microns. Chapter eight discusses the applications for volume holographic filters, with particular reference to one example. In chapter nine general conclusions are drawn and future directions for research are suggested. A number of appendices are also included.

Advisor: Paige, E
Solution reactivity studies of group 15 Zintl ions

The reactivity of group 15 Zintl ions, E73– (E = P, As), towards a number of transition and post-transition metal reagents has been studied. The synthesis and characterisation of the resulting novel cluster anions are described herein.
The reactions of E73– with [Cu5(mes)5], MPh2 (M = Zn, Cd) and InPh3 yielded the Cu–Cu bridged species [Cu2(E7)2]4– (E = P, As), the group 12 bridged cluster anions [M(E7)2]4– (M = Zn: E = P, As; M= Cd: E = P), and the In-functionalised Zintl ions [E7InPh2]2–, respectively.
P73– and As73– have been found to react with a number of metal salts, namely [M(nbe)3][SbF6] and MCl (M = Ag, Au), InCl3, TlCl and MI2 (M = Sn, Pb). These reactions formed the Ag–Ag and Au–Au bridged complexes [M2(HP7)2]2– (M = Ag, Au), the In-bridged species [In(E7)2]3– (E = P, As), the Tl-derivatised Zintl ions [TlE7]2– (E = P, As), and the sixteen vertex cluster anions [ME15]3– (M = Sn, Pb; E = P, As).
The reactivity of P73– towards a series of group 8 compounds has also been studied. The reactions of P73– with FeCl2 and [Ru(PPh3)3Cl2] produced [M(HP7)2]2- (M = Fe, Ru). NMR studies showed that these species can be deprotonated to form [M(P7)2]4– (M = Fe, Ru). These Fe and Ru complexes are isoelectronic with ferrocene. In addition, P73– reacts with [Ru(COD)(η3-CH2C(CH3)CH2)2] to form [(C4H7)P7Ru(COD)]2–.
Both P73– and As73– undergo transition metal mediated activation reactions in the presence of [Co(PEt2Ph2)(mes)2], yielding [Co(η5-P5){η2-HP2(mes)}]2– and [Co([η3-As3){η4-As4(mes)2}]2–, respectively.

Keywords: Zintl ions
clusters
Advisor: Goicoechea, J
At-sea behaviour in marine birds: a life-history perspective

Recent bio-logging technology and associated techniques have uncovered the distribution, behaviour, and phenology of marine predators at remote locations, providing us with insights of not only scientific merit, but also in terms of conservation and management. This thesis explores the at-sea behaviour of marine birds using field studies and ethoinformatic approaches by using multiple data loggers, focusing on four species of free-ranging seabirds breeding in the UK. Key findings and conclusions are:
Extending travel distance in central place foragers in the wild is associated with higher prey quality as estimated by an indirect method based on dive profiles. This result is consistent with a prediction of optimal foraging theory, but my results show empirically that seabirds are able to increase reward with distance at the extended scale of the marine environment.
Razorbills Alca torda are capable of adjusting their foraging behaviour in response to proximate environmental conditions. The potential mechanisms underlying this adaptive behaviour are independent of breeding stage, but the magnitude of flight orientation is scale-dependent. These results suggest that Razorbills are capable of optimising their foraging adaptively, possibly reading cues from the environment or conspecifics.
Diving behaviour in sympatric Atlantic Puffins Fratercula arctica and Razorbills is very similar, in contrast to the predictions of the competitive exclusion principle. They are likely to be near carrying capacity for the location and this may explain why Skomer’s Razorbill population is declining while its puffin population is stable.
Differences in foraging trip duration of chick-rearing Manx Shearwaters Puffinus puffinus reflect differences in resource allocation between provisioning offspring and self-feeding. I developed a model based on patch quality and travel time to show that birds should use bimodal foraging trip durations to optimise feeding rates for their offspring.
Individual reproductive performance in Manx Shearwaters can be predicted from previous breeding phenology and is linked to differences in overwintering behaviour patterns. This carry-over effect reveals the existence of a trade-off between current parental investment and future reproductive performance.

Keywords: wildlife telemetry
bio-logging
seabirds
Advisor: Guilford, T
Transcriptional regulators of arterial-specific endothelial and mural cell development

The vertebrate vasculature is formed by populations of endothelial and mural cells that arrange into functionally and molecularly distinct arterial, venous and capillary beds. Although a number of signalling pathways and transcriptional regulators have been implicated in these processes of vascular differentiation, a clear picture of how arterial-specific gene regulation is achieved is yet to emerge. In this study I have investigated the transcriptional regulation of arterial identity from two different directions: characterisation of enhancers to identify the transcription factors that bind and direct arterial specification; and direct study of the function of one particular transcription factor expressed specifically in the arterial vasculature.
I have identified a novel gene enhancer that directs arterial-specific expression of Flk1 (Vegfr2) in transgenic mouse and zebrafish models. Dissection of inputs from individual transcription factor binding sites within this enhancer shows a requirement for Gata factors for enhancer function in endothelial cells, whereas arterial-specification is directed by Rbpj-mediated repression of enhancer activity in veins. This work demonstrates that Flk1 expression in arterial endothelial cells is downstream of the Notch/Rbpj pathway, and also describes a novel transcriptional mechanism of arterial differentiation.
In parallel, I have uncovered a novel role for the transcription factor Tbx2 in the regulation of arterial mural cell identity. Histological analysis demonstrates the previously unreported expression of Tbx2 exclusively in mural cells of peripheral arteries and microvessels, and genetic deletion experiments in mice suggest a role for Tbx2 in mural cell recruitment, survival, proliferation, and differentiation upstream of Notch3 and Pdgfrβ.
Together, these results contribute valuable insights into our understanding of the establishment of vascular identity by identifying novel transcriptional regulators of arterial fate in both endothelial and mural cells.

Keywords: Enhancer
Vascular Biology
Transcription Factor
Developmental Biology
Advisor: De Val, S
Capital and development in social and cultural contexts

Non-economic factors like culture and politics, as well as the socio-economic background, matter significantly in directing economic development endeavours towards social wellbeing. Therefore, the current narrow definition of economic development must be extended to include overall wellbeing. As one of the primary forms of physical capital constituting a regional economy, transport investments have played a significant role in development plans. Given that accessibility to social infrastructure is a basic need, certain levels of infrastructure are essential. How these investments have an impact on different groups of individuals has kept many scholars busy for a long time. However, the economic spillover effects of these investments into female labour markets have remained largely unexplored. Situating the implications of development initiatives, including transport investments, for female labour markets in social and cultural contexts requires an integrated view of the regional economy. Although economic geography and existing development theories provide extensive conceptual models to elucidate the links between transport, labour markets and culture, the methodological implications are obscure; hence, the empirical evidence remains weak.
This thesis explores the economic and non-economic dynamics of regional economies to clarify the links between transport infrastructure, labour markets, and social and cultural conditions. In particular, the association between female labour forces and development efforts, in the form of transport infrastructure development, is conceptually and empirically examined. This thesis conducts a case study on Turkey. With the extensive infrastructure investment that has been made since 2002 and the extremely low rates of female labour force participation (around 25%), compared to EU-15 and OECD averages of around 65%, Turkey serves as an illuminating case.
Theoretically, the study shows that the focus of transport economics on the economic growth effect of investments is not consistent with current efforts to extend economic development objectives: transport research requires a broader view to assess its development implications. The study demonstrates how the interactions between the economic, physical, political, cultural and socio-economic attributes of regions significantly affect how individuals benefit from the investments. The overarching policy implications of the study are useful for regional development policy with a gender focus: complementary policy interventions in human capital development and the consideration of social and cultural attitudes should strengthen the positive impacts of physical investments on female labour markets.

Keywords: gender
development
Turkey
female labour force
transport
mobilities
southeastern Anatolia
Advisor: Banister, D
Wojcik, D
Collectins and innate immunity in the lung

This thesis examines the role played by the lung collectins, surfactant proteins A and D (SP-A and SP-D) in innate immunity in the lung. The generation of SP-A and SP-D deficient mice has confirmed the important part played by these innate immune molecules in the defence of the lung against infection and in the control of inflammation. SP-A deficient mice are susceptible to infection with a range of microbes. The critical role played by SP-D in controlling inflammation in the lung has been convincingly demonstrated in the SP-D deficient mouse which shows a chronic low grade lung inflammation and the spontaneous development of emphysema. The thesis examines the in vivo activity of recombinant forms of surfactant proteins, in particular a recombinant fragment of surfactant protein D, in the control of lung inflammation using SP-D deficient mice as a model of emphysema. Murine models of allergic inflammation to fungal and common house dust mite allergens were employed to assess the efficacy of recombinant collectins in modulating allergic processes in vivo.
The animal models employed and the generation and structural characterisation of recombinant SP-Dare described in the first sections of the thesis. SP-A and SP-D are known to bind to fungal aeroallergens and to allergens of the common house dust mite. Therapeutic testing of the recombinant fragment of surfactant protein D was carried out in mouse models of allergy against allergens of the common house dust mite Dermatophagoides pterynossinus and those of the fungus Aspergillus fumigatus. Exogenously administered collectin reduced serum eosinophilia, IgE and specific IgG 1 levels as well as airway hyperresponsiveness to challenge with both fungal and house dust mite allergens.
Further characterisation of the lung phenotype of the SP-D deficient mouse and the use of replacement therapy in correcting the phenotype revealed that SP-D deficient mice have an increased burden of apoptotic and necrotic inflammatory cells in the alveolar space. Treatment of these mice with a recombinant fragment of surfactant protein D led to a marked reduction of the number of apoptotic and necrotic alveolar macrophages in the alveolar space and a partial resolution of the inflammation and excess production of surfactant phospholipids. These results indicate the critical role played by SP-D in regulating inflammation in the lung and the efficacy of a recombinant fragment of SP-D in reducing inflammation in the SP-D deficient lung. Finally the results of a pilot investigation into the levels of SP-Din a population of intubated neonates is presented. The clinical implications of the findings of the thesis are discussed in chapter four, focussing on the therapeutic potential of the recombinant fragment of SP-D to reduce inflammation in neonatal chronic lung disease, cystic fibrosis and adult emphysema.

Advisor: Reid, K
A study of collision cascade collapse in Cu³Au

This thesis describes an ion irradiation study of ordered Cu3M/sub>Au. Argon, Copper and Krypton ions of 50 and 100keV were implanted to nominal doses of 1011 ions cm-2 both at room temperature and at liquid helium temperature. The damage induced at low temperature was observed in-situ and after subsequent warming to room temperature.
The collapse of collision cascades to vacancy dislocation loops was observed to occur with moderately high probability under all irradiation conditions at low temperature, with no subsequent increase in the number of loops on warming. Comparison of the collapsed fraction of cascades at low temperature with that produced by room temperature irradiation revealed that the collapse process is more efficient in the latter case. An increase in collapse probability with ion mass was also observed, although no dependence on ion energy was found over the range investigated.
Quantitative analysis of the disordered zones which result in ordered Cu3Au at individual cascade sites revealed that cascades which had collapsed to loops generally produced larger disordered zones. Additionally, increases in disordered zone size with ion mass, ion energy and irradiation temperature were identified. The observation that disordered zone sizes exceed the theoretically predicted cascade dimensions for the case of the highest energy density in this study (50keV Kr) is interpreted as evidence for leakage of energy from the cascade region to the surrounding lattice.
A model is proposed which attributes the observed cascade collapse behaviour to vacancy migration during the cooling of the cascade region being systematically directed toward its centre, and accounts for the observed disordered zones in terms of extensive atomic rearrangement during the cooling. The major factors identified as controlling this vacancy and atomic motion are the initial spatial distribution of energy and vacancies within the region, and the rate at which the region cools.

Advisor: Jenkins, M
English, C