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Ultrafast Dynamics of Antiferromagnets
Full text linkWith the increasing global demand for high-speed and energy-efficient computing, conventional electronic and magnetic devices are nearing their fundamental performance limits. Although discovered in the 1930s, antiferromagnets were long overlooked in favour of ferromagnets. However, the intrinsic properties of antiferro- magnets make them particularly well suited to meet the performance and scalability requirements of next-generation magnetic technologies. The ultrafast timescales of antiferromagnets are particularly attractive for future memory and logic devices that must operate at speeds beyond the capabilities of conventional ferromagnetic devices. In a broader context, antiferromagnets have the potential to overcome bottlenecks in modern computing architectures by enabling higher data throughput, lower latency and improved energy efficiency. Atomistic modelling is a vital tool to capture the ultrafast dynamics observed within antiferromagnets, offering valuable insights into the fundamental mechanisms driving their responses to external stimuli. This approach significantly enhances our understanding of complex antiferromagnetic systems and phenomena that are often difficult to study experimentally. In this thesis, I present a detailed investigation into the dynamics of antiferromagnetic MnPt to a spin-orbit torque, with the dynamics compared to those of ferromagnetic and ferrimagnetic MnPt. Iridium Manganese (IrMn) is then modelled, and the three antiferromagnetic phases are simulated under an ultrafast laser pulse. Polygranular disordered IrMn is then coupled with a ferromagnetic layer to investigate an alternative method of setting the exchange bias. Subsequently, disordered IrMn is coupled with a ferrimagnetic layer to explore how the exchange bias can be controlled and manipulated. This work provides a comprehensive understanding of the ultrafast dynamics and coupling behaviour of antiferromagnets, relevant as antiferromagnets transition from passive to active elements in the next generation of spintronic devices
Reconstructing the Holocene evolution of glaciers in the Olivares Basin (33°S), Chile
No full textAndean glaciers are critical water resources, yet their future evolution under climate change remains uncertain. Reconstructing past glacier change is essential for understanding glacial sensitivity to climate, but records of postglacial evolution in the Central Chilean Andes, particularly between 33°S–35°S, remain sparse. This gap is striking given the significant glacier losses already documented in the Maipo River Basin, including rapid recession in the Olivares Basin (33°S), where satellite imagery shows terminus retreat of 0.5–2.5 km since 1973.
To understand recent changes in the context of long-term postglacial change, I present a reconstruction of Holocene glacier evolution in the Olivares Basin. Geomorphological mapping, derived from remote sensing and field surveys, was used to produce a basin-wide inventory of glacial landforms. Within the Salto del Olivares sub-basin, cosmogenic 36Cl whole rock exposure age dating of samples from moraines M2 and M3 yielded a Gaussian weighted mean age of 9.59 ± 2.25 ka (n = 7), constraining the early Holocene glacier extent. These results are then synthesised into a broader reconstruction of postglacial change between the early Holocene and recent decades. This was then used to constrain the results of numerical simulations of glacier evolution, which indicates that early Holocene climatic conditions were between 0.75–1.25°C colder and 40–60% wetter than today. The combined geomorphological, geochronological, and modelling evidence reveals that early Holocene glacier retreat was punctuated by climatically driven readvances, producing several overrun terminal moraines at Salto del Olivares. In contrast, observations since 1955 demonstrate sustained terminus recession, consistent with anthropogenic climate forcing. These results highlight the sensitivity of the Olivares Glaciers to precipitation, a pattern echoed elsewhere in the Andes. These results further indicate that when in equilibrium with climate, these glaciers occupy a broad area of near-zero mass balance, implying their persistence depends on limited but sustained perennial accumulation
CCL5 modifications using chemical biology tools for the dissection of the molecular function of endogenous CCR5
No full textThe C-C chemokine receptor 5 (CCR5) is a 7-transmembrane G-protein coupled
receptor primarily involved in the immune response, but its multifaceted properties
have been linked with many diseases. CCR5 expression has been reported on cancer
cells, influencing cancer progression, by affecting cell proliferation and metabolic-
reprogramming. These findings have been used to repurpose CCR5 antagonist
(Maraviroc) to target cells within the tumour microenvironment, but so far with not
much success. Since little is known about the molecular cell biology mechanisms
driving endogenous CCR5 activity in cancer cells, further investigations are required
before targeting CCR5 for cancer therapy.
We use a range of biological approaches and the development of chemical tools to
understand the presentation and mechanistic functioning of CCR5 on prostate cancer
(PCa) cells. Our findings confirm endogenous expression of CCR5 on PCa cells but
reveal alternative receptor presentation compared to previously studied transfected
and primary immune cells. We also demonstrate that CCR5 interaction with its
agonists on PCa cells do not trigger receptor internalisation, but induce activation of
downstream signalling pathways that leads to cell functional effect with the release of
chemokines. However, conventional tools are not sufficient for understanding the role
of low expressing endogenous CCR5. In order to define the alternative behaviour of
CCR5 on PCa cells, we have optimised the use of organocatalyst-mediated protein
aldol ligation (OPAL) and Conjugate addition/ring expansion (CARE) chemistry to
develop novel chemokine analogues and chemically modified CCL5 derivatives to
isolate agonist-bound receptor complexes, probe for CCR5 activation, and potentially
lead to chemokine-based therapeutics.
Overall, findings from my thesis expose unique functional characteristics of CCR5 in
cancer cell lines, inferring a cell-type-dependent behaviour for this receptor. Therefore,
understanding the factors that govern CCR5 behaviour could inform strategies to
target CCR5 for cancer therapies
Chewing Over the Evidence: Palaeogenomic insights into prehistoric technology, populations and microbiomes from ancient chewing gum
No full textLate Quaternary Palaeoenvironmental Reconstruction of Wadi Trubah in Western Saudi Arabia
No full textWhile research into Quaternary environmental changes has taken place in the Central, Eastern, and southern regions of the Arabian Peninsula (AP) within Saudi Arabia, little paleoenvironment research has yet to be carried out in the western part of the AP, this is, even though the western part of Arabia is uniquely different from the eastern and central areas regarding climate and geology. Western Arabia is also critical in understanding past human migrations from Africa and the archaeological record of Arabia. To address the project's aims in reconstructing Late Quaternary environmental changes in wadi activity in the western region of Saudi Arabia and their relationship to regional environmental changes on the AP, a multiple methods approach using luminescence dating of the Wadi sedimentary archive, particle size analysis, and remote sensing was applied to map, understand, and model the fluvial drainage network. This research revealed the occurrence of major wet phases in the western part of the AP, which are MIS 9, 7, 3, and 1, which align with wet periods in other areas of the AP. Interestingly, no wet phase during MIS 5 has been found in the selected study area, indicating a need for further research.
Remote sensing has assisted in delineating the extensive stream network, which used to be active during intense precipitation during pluvial periods due to the combined climate wind systems of the Indian Ocean Monsoon and the North African Summer Monsoon. Regarding palaeolakes, the research mapped 231 ancient lakes in the Harrat region, 93 interdune palaeolakes, and 4806 archaeological sites, which themselves suggest that Wadi Trubah had a favourable climate condition for human settlements
Developing and Characterising Novel Drosophila Models of Invasive Colorectal Cancer
No full textColorectal cancer is the fourth most common cancer in the UK, with incidence continuing to increase amongst younger adults. It accounts for 10% of cancer mortality and the majority of these deaths follow metastasis.
We use the Drosophila midgut to model human colorectal cancer by inducing stem cells to form tumours by driving mutations in Apc and Ras (AR) commonly seen in human colorectal cancers. While we do not observe metastasis in this model, we found that overexpression of the EMT transcription factor Snail in Apc-Ras-Snail (ARS) flies increases tumour growth and invasion and permits secondary tumour formation. In this project, my aim was to screen other genes expected to increase tumour growth and invasion to look for novel metastatic models and to develop our understanding of our existing models.
As part of this screen, I knocked down ImpL2, the Drosophila homologue of a mammalian gene involved in insulin signalling in the AR and ARS models. Knock down of ImpL2 in AR flies led to increased tumour growth and invasion and further investigation showed that ImpL2 acts as a tumour suppressor in this model. Furthermore, I found that ImpL2 levels are reduced in ARS clones and my results suggested that these reduced ImpL2 levels contribute to the increased tumour growth seen in ARS flies. ImpL2 knockdown was not sufficient for metastasis formation, despite the increased tumour burden and invasion. This suggests that comparison between AR, ARS and AR ImpL2 knockdown flies may help understand how Snail overexpression causes metastasis.
Finally, I characterised ImpL2 expression in wild-type flies and cancer models. This showed activity in three signalling pathways, the WNT, ERK and Pi3K pathways, is required for ImpL2 expression. Genetic perturbations of each pathway suggested that ImpL2 is not blocking growth via Pi3K or insulin receptor signalling
Backpack Production: An exploration of independent production techniques in no-budget contemporary cinema
Full text linkThis reflective thesis investigates the practice and implications of "backpack production", a mode of solo-operated filmmaking characterised by minimal collaboration and streamlined equipment use. Through a practice-based research framework, the study interrogates the creative, logistical, and cognitive dimensions of independent, no-budget narrative cinema. The research is anchored by the development, production, and analysis of a short film, Lost Inside, alongside exploratory test footage and a comprehensive literature review. Drawing inspiration from filmmakers such as Robert Rodriguez, Chloé Zhao, and Sean Baker, the study explores the creative autonomy and technical freedoms afforded by solo production while critically examining the drawbacks, such as cognitive overload, diminished creative input, and technical compromises. The findings reveal that while backpack production fosters flexibility and intimate storytelling, it often constrains complexity and collaboration, suggesting that its value may be greatest for emerging filmmakers or for projects seeking a highly personal artistic voice. The study advocates for hybrid workflows that retain the benefits of solo operation while strategically integrating collaborative support in key production areas
Investigations into the reduction of soft tissue artefacts using projection of markers and microwave imaging
Full text linkMovement analysis is a widely applied clinical tool for the diagnosis of neurological and musculoskeletal pathologies and in the evaluation of surgical interventions. The clinical gold standard for movement analysis is skin-mounted marker-based systems, whose clinical usability in computing the underlying movement of bones are impeded by soft tissue artefacts (STA). STA are discrepancies in bone movement calculated from skin-mounted markers, and are caused by the interposition of soft tissues.
Multibody kinematic optimisation (MKO) methods are the most widely applied solution to reduce STA. However, the efficacy of MKO methods varies between subjects and investigated motions, with most MKO methods not validated on participants with higher body mass index (BMI) scores.
This thesis proposes a practical solution to reduce the deleterious effects of STA. Two novel marker projection schemes, wherein the markers are projected onto the bone surface, are proposed. The projection schemes are validated on a dataset containing both skin-mounted marker trajectories and reference kinematics, of participants with varying BMI scores performing a wide variety of movements. Additionally, a novel imaging modality for biomechanics, microwave imaging, is investigated to project the markers onto the bone surface during both static and dynamic motion. The feasibility of this application of microwave imaging is investigated using both human models and tissue-mimicking phantoms.
Our results indicate that the projection schemes reduce errors in rotations most affected by STA, and also improves the quality of computed kinematics for all subjects and investigated motions. Additionally, the location of the bone can be detected using microwave imaging and a wearable system, in both static and dynamic situations. Our findings underscore the efficacy and generalisability of our multidisciplinary solution to reduce the effects of STA on computed kinematics, and represent a potential solution to improve the clinical usability of skin-mounted marker-based data
Pathological Aggregation of Cystatin C and α-Synuclein in Neurodegenerative Disease
No full textNeurodegenerative diseases are chronic conditions that progressive dysfunction in cognition, muscle control, and speech, driven by neuronal death and malfunction due to protein misfolding and aggregation. Current treatments are limited, and understanding the aggregation pathways involved is key to developing more effective therapies. This thesis investigates two such aggregation systems with strong associations to disease.
The first part focuses on cystatin C aggregation in Bunina bodies, observed in amyotrophic lateral sclerosis (ALS). Extensive attempts at optimising expression and purification of recombinant cystatin C from E. coli are shown, followed by in vitro aggregation assays. Cystatin C aggregation is induced in conditions similar to cytosol, where Bunina bodies form, by disrupting two structurally critical disulfide bonds. Kinetic analysis suggests a proline-isomerisation step during the aggregation process, as seen in other cystatins. Additionally, preliminary nuclear magnetic resonance (NMR) data hints at a potentially unreported binding interaction between cystatin C dimers and RNA. In vivo
overexpression of fluorescently-tagged cystatin C in mammalian cells produces Bunina body-like inclusions, which appear to be actively transported toward the nucleus via the microtubule network.
The second part explores α-synuclein aggregation on POPG lipid membranes, modelling Lewy body formation in Parkinson’s disease. This system has previously informed Parkinson’s drug development, including an ongoing phase II clinical trial, which heavily supports its disease relevance. This study shows that fully helical α-synuclein remodels POPG membranes into long cylindrical micelles, which form an inter-connected network, spaced 10-20 nm apart, consistent with a double-anchoring mechanism for α-synuclein reported in the literature. After prolonged incubation, a rapid structural transition from α-helix to β-sheet occurs, supporting a hypothesis of amyloid structural propagation along the micelle surface, providing a mechanism for accelerated aggregation and lipid sequestration by α-synuclein amyloids in Parkinson’s disease
Mulvaney: A practice-based enquiry into how an original verse play dealing with current political concerns might be created for contemporary theatre
No full textThis submission comprises an example of creative practice in writing verse drama dealing with contemporary settings and political concerns for mainstream theatre performance in England, together with an examination of the challenges this posed and the theoretical research and creative practice that resulted in the decisions made.
The project arose from the perception that the most urgent political issue of the time was the rise of “post-truth” populism in most major liberal democracies, and that verse drama offered the form most suited to its full dramatic interrogation. This arises from the form’s ability to depict how the presentation of that movement’s charismatic central figures relies heavily upon their construction of personae and idiolects, personal styles of discourse that deliberately challenge or break the conventions of more politically orthodox forms, how these personae and idiolects then try to create alternative realities, facts and modes of discourse in which they can dominate, and how the battle for dominance within and against these modes forms a central conflict they create.
The resulting play, Mulvaney, is written in a conventional five act structure using a combination of heroic couplets and iambic pentameter with some short sections in prose. The accompanying commentary examines the justification for the use of verse in addressing this subject matter and in contemporary theatre more generally. In so doing it identifies in particular how verse rhythm and form and their variation can depict the idiolect of a character, how the strict verse forms adopted for the play and the characters’ exploitation and control of those forms can convey personality, and how the competition between characters to dominate the formal patterns created can be used as an expressive device in depicting the dynamics between them.
Detailed examination of the recent work of two poet-playwrights, Tony Harrison and Simon Armitage, identifies important examples of analogous technical devices which were further evolved in the creation of the play for these expressive purposes. A detailed account of the genesis of the play and the results of practical trials in the form of workshop performances of sections from it provides an account of the evolution of these techniques and their disposition in the play.
The result is an example of creative practice embodying verse techniques which derive from the examples identified in the work of Armitage and Harrison, but differ materially from them in the manner in which they are used, and extend and refine these techniques further in the depiction of dynamics between characters by their competition for control and dominance within the formal patterns of the verse. This is accompanied by a detailed examination of those techniques and the process of their evolution within a project dominated by considerations of dramatic effectiveness
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