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A low-loss SiN integrated platform for visible photonics
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Characterising the spatial heterogeneity of ventricular electrophysiology under physiological and long QT conditions
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Asymptotic geometric and probabilistic properties of Teichmüller space
Get PDFTeichmüller spaces play a pivotal role in the study of dynamics, geometric group theory and conformal geometry. In this thesis we study several geometric and probabilistic aspects of these spaces.
We begin by showing that, while not hyperbolic, Teichmüller space with the Teichmüller distance is statistically hyperbolic with respect to harmonic measures generated by nonelementary measures with finite first moment.
Points in the Teichmüller space of a surface 𝘚 can be interpreted as conjugacy classes of discrete faithful representations of the fundamental group of 𝘚 on the group of isometries of the hyperbolic plane, PSL(2,ℝ). For a given measure on the fundamental group of S, this characterization gives us associated measures on uniform lattices on PSL(2,ℝ). It is a long standing conjecture that the harmonic measures associated to these random walks have dimension strictly smaller than one whenever the measure is admissible and has finite first moment. In this thesis we prove that the conjecture is true outside of a compact subset of the Teichmüller space. Furthermore, we give some sharp bounds for the growth of the drift of the associated random walks in terms of the Teichmüller distance. One key argument is an adaptation of Gouëzel's pivoting techniques to actions of a fixed group on a sequence of hyperbolic metric spaces.
Two commonly studied compactifications of Teichmüller spaces of finite type surfaces are the Gardiner-Masur compactification and the Teichmüller compactification. We finish by showing that these two compactifications are related, proving that the former is finer than the latter. This allows us to prove, among other results, that the Gardiner-Masur compactification is path connected and that its Busemann points are not dense. We also determine for which surfaces the two compactifications are isomorphic, and we show that some horocycles diverge in the Teichmüller compactification based at some point. As an ingredient in one of the proofs we show that the extremal length is not 𝐶² along some paths that are smooth with respect to the piecewise linear structure on measured foliations
‘How Do You Want to Do This?’: Dungeons & Dragons as transformative fantasy
Get PDFThis thesis examines Dungeons & Dragons (D&D) as a source of transformative fantasy. It explores the processes by which D&D players creatively revise, reimagine, and rebel against the conventions of fantasy that are condensed and handed to them by the D&D game text. Approaching fantasy as both a literary and transmedial phenomenon using Helen Young’s term, ‘fantasy genre-culture’, which places fantasy’s ‘textual practices within a wider set of social processes that include not only Fantasy conventions, but the behaviours of authors and audiences, the ideological arguments that circulate around the texts, and the meaning and location of Fantasy within a political economy’, this thesis argues that D&D is capable of encompassing many of the above aspects of genre-culture. It also allows players to react to these different discursive aspects of fantasy through play. Utilising Jessica Hammer’s framework of primary, secondary, and tertiary authorship in her work ‘Agency and Authority in Role-playing ‘Texts’’, this thesis examines how each of D&D’s author figures – the game designers, the Dungeon Master/Game Master, and the player – interact and respond to fantasy genre-culture, working to preserve and/or contribute new meanings to the communal definitions and conventions of fantasy. I examine examples taken from actual play media, to demonstrate instances where D&D gameplay has either reacted to canonical fantasy texts such as The Lord of the Rings and Harry Potter, or produced revisionist approaches to fantasy’s prevalent textual conventions, such as race. It is often through a direct confrontation with rules – generic convention preserved and reduced down into inflexible game rubric – that a challenge to fantasy’s ‘stereotypical’ mould occurs.
In particular, I argue that the contemporary context of D&D – that is, the advent of D&D actual play as a form of fantasy media, in which D&D games are broadcast and consumed as their own fictional fantasy narratives – means that the texts and meanings produced by DMs and players, as secondary and tertiary authors, have a greater sway over fantasy genre-culture than ever before. These once fannish, amateur, and often private contributions to genre-culture are now public and professional, while often retaining their transformative approach to fantasy. My chapters close-read examples from D&D paratexts and tie-in novels published by Wizards of the Coast, alongside actual play texts such as Critical Role, Dimension 20, and The Black Dice Society
An empirical study of Chinese large listed family firms: financial performance and R&D investment strategy
Get PDFThe aim of this thesis was to critically examine ‘large’ listed family firms (FFs) in China in terms of the role of family involvement (i.e., ownership and control) and the moderating effect of firm size within large listed FFs’ short-term financial performance and R&D investment strategy for the longer term. The focus of this study was on a dataset of 654 Chinese listed FFs (including 490 large-sized FFs) from 2021. The results suggest that family ownership played a significant and positive role in large listed FFs’ financial performance; but within the sample, firm size had no moderating effect on the relationship. Family CEO presence was also significantly, but negatively, associated with financial performance. In terms of long-term strategic performance, family ownership had a significant but negative impact on risky R&D investment; as firm size increased, such a significant impact was not found. Furthermore, family CEO presence was insignificantly and positively associated with R&D investment. However, as firm size increased, the impact of family CEO presence on R&D investment became significant and positive.
These findings highlight the complexity of large FFs across different sizes and the need to consider multiple factors when weighing financial performance and R&D investment. Theoretically, this study contributes to agency theory, the stewardship perspective, the socioemotional wealth (SEW) theory and the institution-based view (IBV) in exploring the impact of family shareholdings and family CEO presence on large listed FFs’ financial performance and R&D investment. Additionally, these findings could potentially contribute to practitioner decisions, especially for large listed FFs. Overall, this study contributes to a comprehension of the dynamics within FFs and provides insights into potential areas for future research
Simulation, fabrication and characterisation of III-V photodetectors
Get PDFPhotonic Integrated Circuits (PICs) are set to revolutionise optical communication and sensing technologies by enabling the integration of optical interconnects directly into electronic chips, which can significantly reduce the power required to transmit data. Currently, electrical interconnects suffer losses ranging from 50% to 80% due to thermal dissipation, which can be mitigated with existing Mach-Zehnder optical modulators that are already on the market. These modulators are millimetre-scale devices, consuming energy in the picojoule per bit range. However, by leveraging devices in the micrometre to nanometre scale, power consumption can potentially be reduced by a factor of 1,000, achieving levels in the attojoule per bit range [1]. A key challenge in the development of PICs is the integration of efficient and high-performance devices such as photodetectors, particularly those based on III-V semiconductors for near-infrared (NIR) applications, onto silicon platforms.
This thesis explores the integration of III-V nanowire photodetectors on silicon substrates using Template-Assisted Selective Epitaxy (TASE), a technique that offers precise control over nanowire placement and geometry, making it highly suitable for PIC applications. The research presented herein covers the entire spectrum of work from simulation to fabrication, followed by a detailed electrical and optical characterisation to evaluate device performance.
This project began with device simulations using the Sentaurus TCAD software, with which a comprehensive study of III-V materials was conducted. The heterostructure (n-InP/i-InGaAs/p-InP) emerged as the most suitable material combination for photodetectors' optical performance optimisation, outperforming simpler heterostructures such as pure InP and InGaAs. A secondary study examined the effects of mid-bandgap traps within the devices, and showed how the variability in current-voltage (I-V) curves is highly dependent on the position and concentration of these defects, highlighting their significant impact on device characteristics. The simulations were then used to analyse the electrical behaviour of the fabricated devices and address the observed variability in their I-V characteristics.
Following the simulation phase, photodetectors were fabricated with a focus on optimising critical steps such as material growth and doping techniques. The electrical characterisation of these devices revealed substantial variability in I-V characteristics across different devices, a consequence largely attributed to the crystallographic orientation of the silicon substrate used in their fabrication. This variability presents significant challenges for achieving reliable comparisons between devices, highlighting the need for meticulous control over fabrication steps and the importance of selecting the appropriate substrate to achieve consistent and reliable device performance.
The following optical characterisation aimed to study the influence of design variations on device responsivity after light-coupling through a waveguide, marking a step toward their integration into a full optical link. However, the high variability found in the electrical characterisation led to a shift in focus for this work. The subsequent optical study, where the devices were optically characterised at low temperatures for potential use in quantum technologies, a thermal anomaly was observed in which measurements on a 300 nm wide device, down to 5 K, showed an unexpected increase in dark current below 200 K. This was explained through the presence of defects in the devices. An optical anomaly was also observed, requiring further research and explanation which is outside the scope of this thesis.
The findings of this work provide important insights into the challenges and potential solutions for integrating III-V photodetectors into silicon-based PICs, contributing to the advancement of optical communication
A Foucauldian genealogical analysis of backward design
Get PDFThe aim of this research was to understand how “backward design” emerged to shape the beliefs, attitudes, and practice of educators. Using Foucauldian genealogical analysis, this study looks at key educational figures and movements in the United States (Ralph W. Tyler, Hilda Taba, and Grant Wiggins and Jay McTighe) to trace the ideas and practices that have shaped the curriculum process of backward design. Their seminal works are historized in relation to the economic, social, and political power dynamics that were a feature of their respective eras. Historizing their work aids in uncovering the sometimes incompatible conceptualizations of learning underlying backward design and how these conceptualizations reshaped behaviorist objectives-based curriculum design in response to social, economic, and/or political problems that education was tasked to solve.
Through the genealogical method, the rationality of the conceptualization of backward design, and previous iterations of it, are called into question and the subjugated knowledges and practices underlying these conceptualizations are unearthed. Bringing these subjugated knowledges and practices to the surface, uncovers the episteme many teachers are currently functioning within. The unsurfacing enables us to resist the dominance of backward design and consider alternative ways to frame our understanding of learning, assessment, and curriculum making. Genealogy shows that approaches to curriculum design, learning, teaching and assessment, were not always done this way, and so do not have to be done this way.
This research contributes to understanding how Foucauldian genealogy can be used as a research methodology. It also contributes to understanding how educational developments come into being, challenging ideas of linear progression and conceptual purity. Finally, this research contributes to educational theory by exploring theorists as the point of analysis of power. This study sees educational theorists as agents within a regime of truth that reorganizes existing knowledges to conform to the episteme of their time
Ultrasound-guided perineural injection of the tibial nerve in the horse versus a blind technique
Get PDFBackground: Proficiency in performing tibial perineural analgesia is an essential skill for clinicians carrying out lameness examinations in horses, allowing accurate localisation of the source of pain. Blind tibial perineural analgesia, however, often fails to provide reliable and prompt onset of analgesia despite the superficial location of the tibial nerve. The most common causes of failure include erroneous subcutaneous injection without penetration of the superficial crural fascia, erroneous intramuscular injection of the lateral deep digital flexor muscle or intravascular injection of the caudal root of the saphenous and caudal femoral veins. To overcome these difficulties ultrasound (US)-guided techniques for tibial perineural analgesia have recently been described and evaluated in cadaver studies but data supporting the use of US-guided tibial perineural analgesia clinically remains.
Objective: To compare US-guided and blind tibial perineural analgesia techniques in lameness investigation.
Materials and Methods: This study describes a randomised, prospective clinical trial. All cases were horses presented for lameness investigation which required tibial perineural analgesia. The cases were randomly assigned to US-guided or blind tibial perineural analgesia. Perineural analgesia was performed at the caudomedial aspect of the distal crus, about 10 cm proximal to the tuber calcanei between the common calcaneal tendon and the lateral deep digital flexor muscle. Injections were performed with the limb bearing weight and using mepivacaine hydrochloride 2% (w/v). Blind tibial perineural injections were performed after the nerve had been palpated with the limb in a non-weightbearing position. US-guided injections were performed using an 8-12 MHz linear transducer which was placed in a transverse orientation; the needle was inserted caudal to the nerve and redirected during injection to allow distribution of the anaesthetic agent around the nerve (single skin penetration). Onset of tibial perineural analgesia was assessed by testing loss of skin sensation at the medial and lateral heel bulbs, which were selected as autonomous zones (dermatomes) of the tibial nerve and following a review of the literature. Loss of skin sensation was assessed by measuring the mechanical nociceptive threshold (MNT) of each skin location using a hand-held algometer with a 1 mm diameter pin. A MNT value of 25 Newton (N) would indicate complete loss of skin sensation (MNT values for this specific pin had been previously validated). Skin sensation was assessed, prior to injection and then at four intervals postinjection (10–15, 20–25, 30–35 and 40–45 minutes). At each recording, 3 measurements were performed for each skin location and the mean value was used for analysis. The time taken to perform each injection technique and any adverse reactions were recorded (e.g. horse that snatched the limb away or kicked out). Summary statistics were performed to examine differences between groups. The frequency of skin desensitisation was compared between groups using a Fisher's exact test and the length of time taken to perform injections was compared using a Mann–Whitney U test.
Results: Sixteen US-guided and 11 blind injections were included in the study. All cases undergoing US-guided injection lost skin sensation, whereas this occurred in only one case receiving the blind injection. The US-guided group had a significantly higher probability of skin sensation loss (p < 0.001), although the injection technique took significantly longer to complete compared to the blind group (p < 0.001). No adverse reactions were noted with either perineural injection technique.
Conclusions: The US-guided technique described here resulted in a significantly higher percentage of cases with tibial nerve analgesia compared to cases undergoing the blind technique. No differences in patient tolerance and operator safety were observed between the injection techniques. The US-guided technique was straightforward to perform and resulted in complete tibial nerve analgesia within 30-35 minutes in all patients. The findings of this study suggest that the US-guided technique, therefore, should be used instead of the blind technique during lameness investigation when possible
Optimising radiotherapy outcomes for patients with head and neck cancer
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Elucidating BCR-mediated regulation of FOXO1 in chronic lymphocytic leukaemia: a role for deubiquitinase proteins?
Get PDFThe B-cell receptor (BCR) activity in chronic lymphocytic leukaemia (CLL) cells is vital for disease progression, driving cell survival, proliferation, and chemoresistance. Forkhead box protein O1 (FOXO1), a transcription factor widely considered as a tumour suppressor in B-cell malignancies, is inactivated downstream of BCR activation. Previously, we demonstrated that FOXO1 expression is significantly upregulated in lymph node (LN) biopsies of poor prognostic CLL patients. However, FOXO1 cytoplasmic localisation and deregulation of FOXO target genes, including cyclin-dependent kinase inhibitor 1A (CDKN1A), cyclin-dependent kinase inhibitor 1B (CDKN1B), and cyclin D1 (CCND1), may suggest functional inactivity of FOXO1 in these CLL patients. This finding indicates that FOXO1 possesses tumour-suppressive function in CLL cells. Aligning with previous studies, our data demonstrated that FOXO1 is an effector of BCR crosslinking in vitro, promoting FOXO1 inactivation and nuclear exclusion through phosphatidylinositol 3-kinase (PI3K)/ protein kinase B (AKT)-dependent phosphorylation of FOXO1. This was further confirmed using the Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib, which restored FOXO1 nuclear localisation and subsequently increased FOXO1 DNA binding and transcriptional activities, as indicated by the modulation of FOXO target genes, including the upregulation of Bcl-2-binding component 3 (BBC3) and the downregulation of cyclin D2 (CCND2). Furthermore, the levels of phosphorylated and total FOXO1 protein were transiently upregulated upon BCR crosslinking, peaking at 30 minutes and sustaining up to 2 hours. Therefore, we investigated FOXO1 regulation upon BCR crosslinking in relation to post-translational modifications involving the ubiquitination-proteasome system (UPS) pathway, particularly deubiquitinase (DUB) proteins.
Little is known about the role of individual DUB family members in CLL. Our analysis revealed that expression levels of DUB proteins in patient CLL cells were largely upregulated, including the expression of ubiquitin-specific protease 7 (USP7) and ubiquitin-specific protease 9, x-linked (USP9x). FOXO1 co-immunoprecipitation (co-IP) demonstrated USP7 interaction with FOXO1 in primary CLL cells and cell lines. The FOXO1-USP7 interaction was largely unaffected by BCR crosslinking, while inhibition with ibrutinib increased this interaction, suggesting that the PI3K/AKT pathway may play a role beyond modulating FOXO1 phosphorylation, potentially including modulation of FOXO1 interaction with DUB proteins. Treating CLL cells with the pan-DUB inhibitor PR-619 downregulated AKTˢ⁴⁷³ and FOXO1ᵀ²⁴ phosphorylation. However, USP7 inhibitors (P5091 and HBX19818) and the USP9x inhibitor (WP1130) were largely less effective at inhibiting the PI3K/AKT pathway. This suggests that DUB proteins have a regulatory role in the activity of the PI3K/AKT signalling pathway, but the inhibition of an individual DUB protein was not sufficient to exert a significant effect on PI3K/AKT activity. Additionally, the inhibitors induced the accumulation of MEC1 cells in the G0/G1 phase but did not impact cell proliferation. The combination of ibrutinib and DUB inhibitors enhanced CLL response to ibrutinib, leading to a greater reduction in cell viability, proliferation, and cell cycle accumulation at the G0/G1 phase.
DUB inhibitors or knockdown (KD) of USP7 or USP9x demonstrated no effect on total FOXO1 protein expression, while FOXO1 transcriptional activity was increased in MEC1 cells by HBX19818 or USP7/USP9x KDs, as indicated by the upregulation of FOXO target genes, including CDKN1B and BBC3. This effect was further enhanced by the combination of HBX19818 with ibrutinib. The nuclear localisation of FOXO1 while only modestly regulated by the inhibition of DUB proteins, particularly PR-619 and HBX19818 was enhanced when combined with ibrutinib. Additionally, USP7 or USP9x KD alone or in combination with ibrutinib increased FOXO1 DNA binding activity. This suggests that a reduction of USP7 interaction with FOXO1 may facilitate the promotion of FOXO1 to its DNA binding site, resulting in increased FOXO1 transcriptional activity.
Proteome and subsequent co-IP analysis of FOXO1 novel interactors revealed an interaction between FOXO1 and the E3 ligase tripartite motif containing 21 (TRIM21), with TRIM21 being predominantly cytoplasmic. TRIM21 KD resulted in a reduction of total FOXO1 and FOXO1 nuclear localisation, suggesting that FOXO1 is a substrate of TRIM21, which plays a role in regulating FOXO1 stability, localisation, and potentially its activity.
Our findings suggest that unleashing FOXO1 anti-tumour activity by simultaneously inhibiting BCR-mediated phosphorylation and USP7 deubiquitination of FOXO1 may present an alternative therapeutic strategy for CLL patients
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