VictorJuiz/thesis huggingface dataset:
Identification and characterisation of candidate monoclonal antibody Ebolavirus therapeutics
Keywords: ebolavirus
monoclonal antibodies

Multiple species of Ebolaviruses can cause outbreaks of devastating disease with high mortality. The 2014 outbreak in West Africa, focused attention on efforts to develop effective vaccines and therapies to save lives. Since then, vaccines and first generation therapies have been developed and approved for use. The only therapies to have shown any efficacy in human clinical trials are monoclonal antibodies (mAbs) targeting the Glycoprotein (GP) on the virus surface. However, they are limited in potency and breadth of activity as they target only Zaire ebolavirus (EBOV), yet Sudan ebolavirus (SUDV), Bundibugyo ebolavirus (BDBV) and Tai Forest ebolavirus (TAFV) also cause human disease. The aims of this thesis were to generate a panel of mAbs that could bind to GP from all species of Ebolaviruses that cause human disease, then to characterise the mAbs to select candidates to enter the pipeline of next generation therapies progressing to in vivo study. Using high throughput methods a panel of nineteen anti-GP mAbs were isolated, six of which could recognise GP from all four Ebolaviruses that have caused human disease. These mAbs were characterised in a range of in vitro assays focusing on their ability to neutralise pseudoviruses coated with Ebolavirus GPs. The panel of mAbs was subjected to a range of complementary biochemical assays to map their epitopes, and the epitope of one mAb, 11886, was characterised in more detail. 11886 is of interest to progress to in vivo study as it is able to neutralise all pseudoviruses so far tested and investigation of its epitope suggests that it binds a similar footprint to other broadly protective mAbs in the literature, but neutralises the virus via a different mechanism or mode of binding.
Christian building patronage in the cities of late antique and Merovingian Gaul, c. 300–751
Keywords: Merovingian
Christian patronage
late antiquity
Gaul

This is the first systematic investigation of the explosion in Christian building projects that transformed the cities of Gaul between the fourth and eighth centuries CE. Despite the disruption and simplification of society that accompanied the dissolution of Roman rule in this period, in many cases the extent and variety of such activity far surpassed what would have been necessary to endow Gallic cities with the essential Christian amenities. This study approaches this phenomenon through the lens of patronage, and in doing so addresses current debates regarding late antique urbanism, the chronology and pace of Christianisation, elite behaviour, the extent of episcopal power, and the nature of ‘barbarian’ kingship. It begins by sketching the parameters of urban and suburban Christian building patronage, acknowledging that while they intersected at times, four broad building categories can be distinguished: episcopal groups, the cult of saints, monasticism, and pastoral care. Through a series of case studies that illuminate the results of a broader quantitative analysis, this framework is then used to explore the motivations of the different patron groups who sponsored this building. Chapter three considers Gaul’s ecclesiastics and especially its bishops, chapter four the laity, and chapter five the region’s ruling families. Chapter six then examines the practice in the round, highlighting a number of overarching patterns of patronage across time, space, and patron group. While recognising that the prospect of divine intercession attracted donors at all social levels, this study emphasizes how urban and suburban Christian building patronage was a central component of elite competition in this period. The apparent rise and fall in the practice’s intensity thus reflects the response of the upper echelons of Gallic society to the evolving political and ideological significance of the region’s cities during the transition from late antiquity to the middle ages.
Host regulation of the legume-rhizobia symbiosis
Keywords: Legume
Resource allocation
Rhizobia
Symbiosis
Nitrogen

Leguminous plants host nitrogen-fixing bacteria, known as rhizobia, in specialised root nodules, providing them with carbon in return for nitrogen. However, plants face an investment dilemma, as they usually house multiple strains of rhizobia that can vary in their fixation ability. This thesis characterises the host plant response to poorly fixing strains and compares this across nodule types.
While plants are known to sanction non-fixing strains, non-fixers are rare in field settings, while intermediate fixers are common. We showed that pea (Pisum sativum) plants tolerated an otherwise isogenic intermediate fixer only when a better strain was unavailable. Nodules containing the intermediate fixer were large and healthy when the only alternative was a non-fixer. When a more effective strain was available, carbon transport to the intermediate fixer was decreased, nodules were smaller, with reduced nitrogen fixation, and contained fewer viable rhizobia. Flow cytometry showed that sanctioning hinders nodule development, as sanctioned nodules have fewer specialised nitrogen-fixing bacteroids. Furthermore, limited evidence of sanctioning was observed within mixed nodules, containing two strains, suggesting that poorly fixing strains may not be able to evade sanctioning by sharing a nodule with a better strain. This indicates that legumes can make conditional decisions at a per-nodule level, and possibly even within nodules, giving them remarkable control over their symbiotic partners.
We compared hosts with indeterminate (pea, Pisum sativum) and determinate (bean, Phaseolus vulgaris) nodules, to show that for strains differing only in nitrogen-fixation, the mechanism of host regulation was sanctioning (reducing resource allocation), rather than partner choice (forming fewer nodules). This opens avenues for further work investigating sanctioning mechanisms in both indeterminate and determinate nodules. Furthermore, indeterminate fixing nodules were largest when rare, showing an even finer level of host regulation.
These findings improve the understanding of how host plants manage their interactions with multiple symbiotic partners, which is of great importance when developing more effective rhizobia as alternatives to nitrogenous fertilisers.
Deux machina: a cross-disciplinary approach to artificial intelligence for regulatory understanding
Keywords: Non-Human Competence
Explicability
Regulation
Law
Judgement
Human Autonomy
Artificial Intelligence
Technology
Bias

Legal scholars, policymakers and artificial intelligence researchers disagree about how to typify and describe artificial intelligence; the goalposts are constantly shifting with the advancement of technology, but this is an ancillary matter. Definitions aside, sophisticated decision-making technology is widespread and influential, and a more important normative question needs answering: when should machines be used to make decisions? Since the law is premised on clear avenues of responsibility, rationality, and objective justifications for decisions, the prospect of complex, non-human decision-makers tendering inscrutable decisions with considerable utility but ineffable reasoning is a novelty without comparison in the realm of technology regulation. I contend that this novelty necessitates a deeper, contextual understanding of artificially-intelligent decision-making technology to provide a foundation for regulatory answers to the normative question and resolve ambiguity that pervades more general discussion. Meaningful answers cannot be obtained in the abstract and are tied to the domain in which machine decisions are made; broad doctrinal approaches that begin from the law, and take a technology-neutral approach to regulation, are thus inadequate. Medicine, a science and an art with a long history of integration of artificially-intelligent technology, provides a useful domain for close inquiry. Reliance on machine decision-making by physicians and patients in clinical medical contexts reveals important considerations that high-level discussions do not uncover; the most important of these is that data-driven machines reason in a manner that is alien to human reasoning, and this incongruity is the source of the unintelligibility described vaguely as the ‘black box’ of machine reasoning. Nonetheless, carefully designed machine reasoning is consistent, insightful, and useful, and should be constrained by predefined structural roles for machines, rather than human notions of explanation. Comprehensive, unambiguous understanding is a fundamental prerequisite to the regulatory prescription of suitable roles for machines, and understanding is what I provide here.
The applications of quantitative scanning transmission electron microscopy to the analysis of intracellular elemental distributions
Keywords: EDX
STEM
EELS

The scanning transmission electron microscope (STEM) is an extraordinarily powerful tool for materials characterisation. The wealth of signals available in the microscope mean that chemical and structural details may be probed simultaneously, and often at the atomic scale. Recent developments in quantitative STEM methods have brought about new capabilities for acquiring mass and compositional information. In particular, advances in the measurement of the high-angle annular dark-field (HAADF) signal means it is now possible to count atoms within individual nanostructures with extremely high precision. In parallel, new approaches for quantifying energy-dispersive x-ray spectroscopy (EDX) and electron energy loss spectroscopy (EELS) data afford new opportunities for the determination of elemental composition on an absolute scale.

Thus far, many of these emergent methods have seen little application outwith inorganic samples. This thesis aims to explore to what extent these advances can be applied in complex biological environments, with a particular focus on the measurement of intracellular elemental distributions. High-resolution imaging is first used to elucidate the nanoscale structure of two platinum-based chemotherapeutics. Similar methods are then used to identify single heavy atoms inside the cell bodies of dorsal root ganglia following Pt-drug administration. The use of quantitative HAADF STEM allows experimental measurements of atomic scattering cross- sections to be directly compared with those predicted from simulation. This ultimately confirms that the single atoms observed are indeed platinum, and allows the masses of small atomic clusters visualised in the cells to be measured.

In later chapters, it is further shown that quantitative STEM imaging may be combined with spectroscopy to measure EDX and EELS partial scattering cross-sections. These are acquired for several elements of biological significance, including calcium, sodium and potassium. Finally, spectroscopic cross-sections are applied in samples of peripheral nerve to quantify aggregations of calcium in the mitochondria, and to measure changes in intra-axonal sodium and potassium levels following treatment with a chemotherapeutic agent.
GABAN: ngarranga-birdyulang dhadharra ngawal murrungamirra
Keywords: post-traumatic theatre
Aboriginal
healing
Powerful Objects
experimental theatre
self determination
reimagine museum
systemic change
repatriation
theatre
Australia
anthropology
museum collection
First Nation
Indigenous
gaban
Wiradjuri
collection object

How can the power of objects in museum collections, their meaning and life, be worked with and revealed in a manner which is sensitive to the trauma of colonialism and its collecting practices for Indigenous peoples? How might experimental theatre and storytelling work to bring new insight to understanding the complexity and trauma of museums and their collections? How can museums reimagine their function, role and processes to care for and empower their collections?
This thesis embodies these questions by presenting a new theatre script GABAN and position paper along with associated writing, curated exhibitions and artworks. GABAN means strange in the language of Wiradjuri, the author’s matrilineal kinship group, and describes the experience of being in the museum today and realising the sheer mass of collections from Indigenous homelands. The facts of these collections, the conditions of their making and maintenance, speak to the injustice of colonialism and the continuing struggle for self-identity by Indigenous peoples. GABAN is an experimental story, ngarranga-birdyulang dhadharraa or post-traumatic theatre, driven by Indigenous methodologies to honour the agency of objects in museum collections and the lived experiences of Indigenous peoples navigating these institutions. It is told through characters which are embodiments of ngawal murrungamirra or Powerful Objects. The aim of writing GABAN was to create a fictional space in which to unpack the affects of the museum and reimagine how objects and human identities trapped within this system can speak their own narratives. Skirting the nirin or edge of the museum through new methods of storytelling, this thesis is a call for systemic change in cultural institutions, grounded in Indigenous ways of seeing and comprehending the world.
Investigation of plasticity mechanisms in shock-compressed matter via femtosecond x-ray diffraction
Keywords: twinning
shock waves
x-ray diffraction

The microstructural evolution of dynamically-compressed metals has been an area of active research for decades. This work uses a method of x-ray diffraction from highly-textured tantalum foils in order to identify plastic mechanisms mediating plastic deformations in shock-compressed tantalum. The obtained data provides evidence of shock-induced lattice rotations as well as the first in situ observation of shock-induced twinning. The study extends into an analysis of data capturing material as it returns to ambient conditions. It outlines a method of extracting time and depth-dependent strain profiles within the Ta target as the release wave travels back into the bulk of the sample. In agreement with molecular dynamics simulations, the lattice rotation and the twins that are formed under shock compression are observed to be almost fully eliminated by the rarefaction process. Finally, the investigation of thermal effects present during shock release is performed. Immediately after release, the temperatures of the samples are inferred from changes in the atomic lattice spacing which are the result of thermal expansion. It is found that simulations and experimental data suggest significantly larger temperatures of a material after its return to ambient condition than predicted by the theory of isentropic release.
Layered double hydroxide-based core-shells for CO2 adsorption and conversion
Keywords: layered double hydroxide
core-shell materials

This thesis discusses the development of novel layered double hydroxide-based (LDH-based) core-shells as CO2 adsorbents and as catalysts for the both the selective hydrogenation of CO2 to methanol and conversion to olefins.
Chapter 1 offers a brief introduction of LDHs as 2D anionic layered materials with versatile composition and wide application, and LDH based core-shell materials which can combine both advantages of inorganic cores and LDHs to display synergy effects. The background literature relating to CO2 adsorption, CO2 hydrogenation to methanol and CO2 conversion to olefins are introduced. The application of LDH and LDH-based core-shell materials in these fields is also presented and discussed.
Chapter 2 describes the synthesis and characterisation a series of zeolite@Mg2Al-LDH core-shell materials and the application of these materials as CO2 adsorbents. It was found that core-shells containing 5 wt% LDH exhibit the highest CO2 sorption capacity (5.75 mmol/g at 1 bar and 35 °C), better than most of the core-shell adsorbents and competing with some MOFs.
Chapter 3 systematically investigates the synthesis of mesoporous SiO2@CuxZnAl-LDH core-shells (mSiO2@CuxZnAl-LDH). The effect of metal solution addition rate, reaction pH, LDH content in the core-shell, copper loading of the LDH, concentration of reaction mixture, pre-treatment (aluminium nitrate wet impregnation) and the roles of the silica on the crystallinity, composition and morphology of core-shells are explored.
Chapter 4 focuses on the application of mSiO2@CuxZnAl-LDH for the selective hydrogenation of CO2 to methanol. The effect of copper loading and the effect of silica core on the catalytic activity was investigated using ES757@CuxZnAl LDH and mSiO2@Cu2ZnAl-LDH, respectively. ES757@Cu1.3ZnAl exhibits the best space time yield of methanol due to the highest copper metal nanoparticle surface. It was found that catalysts derived from ES757@Cu1.3ZnAl LDH and mSiO2@Cu2ZnAl LDH can outperform current industry standards for methanol production at a lower copper loadings.
Chapter 5 presents the design of zeolite@Cu1.3ZnAl-LDHs and their catalytic evaluation for the conversion of CO2 to olefins. Preliminary catalytic results were obtained, it was noted that the sodium in the reaction mixture modified the acidity of zeolite and changed the product selectivity. Alternatives to modify the acidity of catalyst were conducted which includes post-treatment with ammonium salt and sodium-free synthesis.
Structural, quantitative, and functional brain MRI findings in MOGAD: a comparison with NMOSD-AQP4 and MS
Keywords: MRI
MS
NMOSD
MOG-Ab
MOGAD
demyelinating disease
AQP4-Ab

In the past fifteen years two new antibody-mediated Central Nervous System (CNS) diseases, have been identified as distinct from multiple sclerosis (MS): Aquaporin-4-antibody (AQP4-Ab) and the more recently discovered myelin oligodendrocyte glycoprotein antibody-associated disorder (MOGAD). Although conventional brain MRI may help distinguish MS from antibody-mediated diseases, the use of quantitative and non-conventional imaging may give more pathological information and explain the clinical differences. This thesis comprises a clinical study, describing the main clinical characteristics of MOGAD, and a cross-sectional MRI study that compares structural, quantitative and functional brain MRI findings across MOGAD, NMOSD-AQP4, MS and healthy controls.
The principal clinical finding is:
• MOGAD patients have a good recovery from visual and physical disability compared to NMOSD-AQP4, although some of them can be left with sphincter, erectile dysfunction, and cognitive impairment.
The main MRI study findings are:
• In MOGAD most of the white matter lesions tend to resolve, but patients are left with grey matter damage, and this may be related to persistent white matter lesions. Despite the greater residual disability, NMOSD-AQP4 patients showed a relative sparing of deep grey matter volumes.
• Non-lesional tissue fractional anisotropy (FA) was only reduced in MS, although focal reductions were noted in NMOSD-AQP4 patients, reflecting mainly optic nerve and corticospinal tract pathways. In MOGAD there is no abnormal non-lesional tissue FA.
• Disability (EDSS) in NMOSD-AQP4 is associated with NAWM FA alone, with deep grey matter atrophy and female sex in MS, and with brainstem volume in MOGAD. Visual acuity was associated with optic chiasm volume in NMOSD-AQP4 disease and with thalamic volume and female sex in MOGAD.
• in MOGAD, despite the good visual recovery, and the absence of structural and microstructural tissue damage, there is a reduced functional connectivity in the primary visual cortex. In NMOSD-AQP4 there is a broader involvement of the large brain networks (visual, salience, sensorimotor, default mode network), possibly related to the higher level of disability (and tissue damage), while in MS, a preferential involvement of subcortical network was found (i.e., basal ganglia).
• Cognitive performance is influenced by fatigue and depression in MOGAD and NMOSD-AQP4 but not in MS. Low cognitive score is associated with low deep grey matter volume in MOGAD and MS, while is mainly driven by cortical volume in NMOSD-AQP4.
The clinical and MRI studies from this thesis, represent some of the earliest studies directed at better understanding the MRI changes behind the clinical recovery and outcome in MOGAD. The comprehensive clinical and MRI approach, investigating not only physical disability, but also the often-neglected cognitive function, added novelty to this body of work and can open to future larger studies.
Studies related to ammonia metabolism in mammalian tissues
Keywords: metabolism
tissues
ammonia
mammalian

The work reported in this thesis concerns the metabolism of ammonia in the liver and kidney of the rat. Glutamate dehydrogenase in the mitochondria of these tissues appears to be very close to equilibrium and thus ammonia is linked to a large number of other metabolites through the network of equilibrium enzymes in these tissues, These inter-relations and the factors influencing them in a number of different situations were studied.
Chapter I contains a historical introduction to the metabolism of ammonia and a discussion of the difficulties inherent in a study of its metabolism. Rapid freezing of tissues together with an enzymatic method for the determination of ammonia provide the best methods for the study of its in vivo metabolism. A very brief account of current knowledge concerning equilibrium enzymes is presented and the criteria necessary for establishing that the reaction of a given enzyme is close to equilibrium are discussed. As an arbitrary standard, it is proposed that the in in vivo mass action ratio should differ from the apparent equilibrium constant by no more than a factor of three before it may be considered to be ‘close to equilibrium’.
Continued in thesis ...
Lauchlin Macleane and his connexion with East India Company politics 1773-1778
Keywords: India
Lauchlin Macleane
British occupation
East India Company

As every writer of a thesis or academic work is indebted in one way or another to many people for the sources and, quite frequently, the shape and inspiration for his dissertation, the manner of expressing his gratitude to those concerned has been rendered by custom, the limits of language and the restraints of British formality to a recognised formula. Indeed, the formula is so well recognised that it seems to defeat its purpose, and the gratitude expressed often appears to be no more than an imposed exercise in manners, dispassionate and infinitely cold, The present writer, although constrained to follow custom, must therefore insist that he records his thanks with both sincerity and humility, and that all the defects in this thesis are attributable to him alone.
Above all others he is in the immeasurable debt of his Supervisor, Dr. Lucy Stuart Sutherland, C.B.E., The Principal of Lady Margaret Hall. But for her unfailing kindness, constant interest and painstaking guidance and criticism, this thesis would never have been started, let alone completed. Throughout its compilation Dr. Sutherland has always gone beyond the highest standards of supervision in order to throw light, either by discussion or written commentary, on innumerable matters concerned with the background or detail of the period. Móran taing a Dotair Liusaidh nic-Alasdair.